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Biomedical subjects

S Ljunghall

Publications and source records attributed to S Ljunghall.

At least 289 records · Page 16Linked to original sources

Serum osteocalcin in rheumatoid arthritis and other inflammatory arthritides: relation between inflammatory activity and the effect of glucocorticoids and remission inducing drugs.

Osteocalcin, a vitamin K dependent protein synthesised by osteoblasts, was measured in serum by radioimmunoassay in patients with rheumatoid arthritis (n = 36) and seronegative spondyloarthropathies (n = 23). The serum osteocalcin levels were decreased in both patient groups compared with the levels measured in age and sex matched healthy controls. We found no relation between serum osteocalcin and the disease duration or inflammatory activity of the patients who were without drug treatment at the first examination. After administration of glucocorticoids (20 mg prednisolone a day) circulating osteocalcin decreased significantly after one week of treatment. During gradual reduction of the steroid dosage osteocalcin returned to pretreatment values. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) did not influence circulating osteocalcin. During treatment with chloroquine or penicillamine serum osteocalcin increased significantly, concomitant with a reduction of the acute phase reactants. Controversy persists about the abnormality of bone turnover in rheumatic diseases, but our data suggest that the overall bone turnover is decreased in patients with rheumatoid arthritis and other inflammatory arthritides.

Adrenocorticotropic Hormone↗

Stimulation of parathyroid hormone secretion by EDTA infusion--a test for the differential diagnosis of hypercalcaemia.

A constant EDTA infusion of 24 mg/kg/h during 60-120 min was given to 26 patients with primary hyperparathyroidism (HPT), 8 patients with hypercalcaemia of other origin and 10 healthy control subjects. PTH and ionized calcium concentrations were measured at 5-10 min intervals. In all three groups the infusion caused a linear decrease in plasma ionized calcium. In both the HPT patients and the healthy subjects there was a prompt increase in the serum levels of parathyroid hormone (PTH) until a plateau was reached. The PTH response of the HPT patients appeared already within the hypercalcaemic range and the plateau value was attained at higher levels of PTH and ionized calcium than in the healthy subjects. The enhanced response distinguished half of the HPT patients with basal PTH values within the reference range from the healthy controls. The patients with nonhyperparathyroid hypercalcaemia displayed no increase in PTH values until the ionized calcium concentration was reduced far into or below the reference range. Thus the EDTA infusion permitted a complete differentiation between HPT and other causes of hypercalcaemia. In most cases an infusion over 30 min was sufficient for this purpose.

Adult↗

Psychiatric symptomatology in patients with primary hyperparathyroidism.

A retrospective investigation was made of the occurrence of psychiatric symptoms among 441 patients operated on for primary hyperparathyroidism in Uppsala in 1956-79, and of the relationship between such symptoms and age, sex and degree of hypercalcaemia. A follow-up, using a mailed questionnaire, was carried out 4-27 years postoperatively. Psychiatric symptoms were found in 23% of the patients (102/441). The patients with these symptoms had the same sex distribution and serum calcium levels as the other patients, but were significantly older. Severe symptoms occurred more frequently in older patients. Such symptoms were noted not only in patients with very high serum calcium values but also in association with mild or moderate hypercalcaemia. The most common symptoms were depressive and anxiety states, which occurred in 78 patients. Psychosis with hallucinations and paranoid ideas was found in four patients. Eight patients had an organic brain syndrome and a further 12 patients had minor cerebral impairment. At the follow-up half of the patients reported an improvement after the first postoperative year. Most of them considered that this improvement was sustained at the time of follow-up. This study indicates that psychiatric symptoms are common among patients with hyperparathyroidism and can occur even with moderate hypercalcaemia. Elderly patients seem to be more vulnerable and more often develop severe symptoms such as psychosis or organic brain syndrome.

Age Factors↗

Late results of operation for primary hyperparathyroidism in 441 patients.

The late results of operation for primary hyperparathyroidism (HPT) were analyzed in 441 patients operated on 4 to 27 years earlier (mean follow-up time, 7.7 years). A conservative surgical approach was mainly used, attempting if possible to visualize all four parathyroid glands and extirpate only the enlarged glands. Subtotal resection was performed in patients with hyperplasia. The histopathologic diagnosis was adenoma in 77% and hyperplasia in 18%. In 5% of the patients, the histopathologic classification was uncertain. Hypercalcemia persisted after operation in 8% of all patients. This generally occurred because of an incomplete neck exploration or too limited a resection in the patients with hyperplasia. Recurrent hypercalcemia occurred in 16% of the patients operated on for hyperplasia and was noted 1 to 19 years after surgery. Recurrences were also seen in 3% of the patients with adenomas but not earlier than 9 years after the operation. These findings suggest that primary HPT may even in patients with adenomatous disease, sometimes affect all parathyroid glands. Nevertheless, it was obvious that most of the patients with adenomas would not have benefited from a more radical procedure. On the other hand, it was evidently important to obtain a correct histopathologic diagnosis intraoperatively so that patients with hyperplasia could be identified and adequatley treated.

Adenoma↗

Paradoxical effects of K+ and D-600 on parathyroid hormone secretion and cytoplasmic Ca2+ in normal bovine and pathological human parathyroid cells.

The effects of K+ and the Ca2+ channel blocker D-600 on parathyroid hormone (PTH) release and cytoplasmic Ca2+ activity (Ca2+i) were measured at different Ca2+ concentrations in dispersed parathyroid cells from normal cattle and from patients with hyperparathyroidism. When the extracellular Ca2+ concentration was raised within the 0.5-3.0 mM range Ca2+i increased and PTH secretion was inhibited. There was also a stimulatory effect of Ca2+ on secretion as indicated by a parallel decrease of Ca2+i and PTH release when extracellular Ca2+ was reduced to less than 25 nM. Addition of 30-50 mM K+ stimulated PTH release and lowered Ca2+i. The effect of K+ was less pronounced in the human cells with a decreased suppressability of PTH release. The Ca2+ channel blocker D-600 had no effect on Ca2+i and PTH release in the absence of extracellular Ca2+. However, at 0.5-1.0 mM Ca2+, D-600 increased Ca2+i and inhibited PTH release, whereas the opposite effects were obtained at 3.0 mM Ca2+. The transition from inhibition to stimulation occurred at a higher Ca2+ concentration in the human cells and the right-shift in the dose-effect relationship for Ca2+-inhibited PTH release tended to be normalized by D-600. It is suggested that K+ stimulates PTH release by increasing the intracellular sequestration of Ca2+ and that the reduced response in the parathyroid human cells is due to the fact that Ca2+i already is lowered. D-600 appears to have both Ca2+ agonistic and antagonistic actions in facilitating and inhibiting Ca2+ influx into the parathyroid cells at low and high concentrations of extracellular Ca2+, respectively. D-600 and related drugs are considered potentially important for the treatment of hyperparathyroidism.

Animals↗

Serum myoglobin concentrations are decreased by beta-adrenergic stimulation.

During infusion with adrenaline in healthy subjects there was a more than 50% reduction in serum myoglobin concentrations. This effect appeared to be specific for beta-adrenergic stimulation, since no changes were seen after prior IV beta-blockade with propranolol, nor did noradrenaline affect the serum myoglobin levels. Oral beta-blockade with propranolol raised the basal serum levels of myoglobin and enhanced the exercise-related rise in serum myoglobin concentrations during ergometer cycling to exhaustion. These observations thus indicate that the beta-adrenergic system affects serum myoglobin concentrations. This should be kept in mind in the evaluation of myoglobin measurements for clinical purposes, and might reflect a physiologically relevant mechanism.

Adrenergic beta-Antagonists↗

Acute effects of ethanol intake on the serum concentrations of parathyroid hormone, calcium and phosphate.

Several previous observations from animal and in-vitro studies indicate that both the acute and chronic ingestion of ethanol could affect calcium regulation but little data is available concerning the effects of ethanol in man. Twelve healthy male subjects drank 0.8 g ethanol/kg body weight in the form of whisky so that the serum ethanol concentrations reached an average of 17.4 +/- 2.5 (SD) mmol/l. At this time there were no significant differences for the serum concentrations of parathyroid hormone, calcium or phosphate. Thus, it appears that there is little acute effect on calcium homeostasis in man of a moderate rise of serum ethanol levels.

Adult↗

Serum osteocalcin levels in normal subjects and patients with primary hyperparathyroidism.

The serum concentrations of osteocalcin were measured by a radioimmunoassay method in 95 apparently healthy subjects of both sexes with ages from 20 to 80 years and in 16 patients with primary hyperparathyroidism. There were no differences for the values between healthy males and females before the age of fifty, whereas the levels were higher in postmenopausal females. The osteocalcin levels were inversely related to age in premenopausal females but not in elder females or in males. The serum osteocalcin levels were raised in patients with primary hyperparathyroidism but with a large overlap against normal values. In all groups there was a positive correlation with the serum alkaline phosphatases. Variations with age should be considered in the interpretation of measurements in females. Furthermore, the increase in the immediate postmenopausal period might have implications for postmenopausal bone loss.

Adult↗

Effects of secretin on parathyroid hormone and calcium in normal subjects, patients with hyperparathyroidism and patients with gastrinoma.

In vitro studies have demonstrated that secretin can stimulate the release of parathyroid hormone (PTH), but reports concerning its effects on PTH and calcium in vivo are contradictory. To examine this question further, a bolus injection of secretin (75 IU) was given to 12 normal subjects and 10 patients with primary hyperparathyroidism (HPT). Six of the patients had multiple endocrine neoplasia and five had endocrine pancreatic tumours (EPT). Three normocalcaemic patients with EPT were also included in the study. The mean serum gastrin level rose significantly (from 19 to 40 pmol/l, p less than 0.01) within 15 min of secretin injection in the normal subjects. HPT patients without EPT had a somewhat higher mean basal level of gastrin (39 pmol/l, p less than 0.05 compared with controls), but it did not increase significantly after the secretin bolus. In six EPT patients the gastrin concentrations rose by more than 300 pmol/l. Although secretin had a biological capacity to release gastrin, it had no discernible effects on either serum PTH or serum calcium in any of the groups studied. Nor were any changes in PTH or calcium observed when secretin was given as a continuous infusion (3 IU/kg/h) over 90 min. Thus, our data do not support the concept that secretin, in vivo, is a secretagogue of PTH.

Adult↗

Effects of exogenous catecholamines and exercise on plasma magnesium concentrations.

Catecholamines and physical exercise are known to influence the metabolism of several minerals in man, but the effects on magnesium (Mg) have been scarcely investigated. In the present study, infusion of adrenaline (5 micrograms/min for 30 min followed by 10 micrograms/min for 30 minutes) significantly reduced the plasma Mg levels in healthy males. This effect was abolished by simultaneous infusion of propranolol. Noradrenaline had no such effect. In order to stimulate endogenous catecholamine release healthy males carried out physical exercise in four different ways: ergometer bicycling at maximum load until exhaustion with and without oral beta-blockade, ergometer bicycling with stepwise increasing load until exhaustion, isokinetic maximal exercise with one leg, with blood sampling both from the venous effluent of the exercising leg and the opposite resting arm and long-term (60 min) steady state ergometer bicycling at approximately 65% of estimated maximum capacity. During short-term (less than 20 min) intense exercise (i.e. experiments 1-3) the plasma Mg concentrations were increased. This was probably due to a reduction of plasma volume and to an influx of Mg to the vascular pool. During long-term steady state exercise (experiment 4) the Mg levels were not significantly affected but decreased during the first hour of recovery. These results suggest that both the beta-adrenergic system and muscular activity by itself affect Mg homeostasis.

Adult↗

Regional and systemic effects of short-term intense muscular work on plasma concentration and content of total and ionized calcium.

Isokinetic work with one leg was carried out with maximal force for 2 min by five healthy subjects. The concentrations of plasma total calcium and of ionized calcium in the effluent from the leg increased by a mean of 13.6 +/- 1.8% (SD) and 16.2 +/- 2.0%, respectively. The corresponding rises in the resting arm were 7.7 +/- 4.3% and 8.1 +/- 3.0%. There was a close correlation (r = 0.86; P less than 0.001) between the degree of exercise-induced acidosis and the rise in plasma ionized calcium. However, the calcium values normalized both in the leg and in the arm within 5 min after the exercise and were similar at the two measuring sites despite a lower pH in the leg sample. During work there was a reduction of the plasma volume of 11.2 +/- 6.0% in the regional (femoral) and 12.4 +/- 4.2% in the systemic (antecubital) sample (P less than 0.001 compared to baseline values for both measurements). When adjustments were made for the reduction in plasma volume as well as for acidosis it was evident that, despite the apparent increases in the calcium concentrations, there was a net reduction of the plasma ionized calcium content (the total amount of plasma ionized calcium). This decrease was significantly (P less than 0.05) more pronounced in the exercising leg than in the systemic circulation but the difference could largely be explained by higher calcium-lactate complex formation in the leg.

Adult↗

Family history of renal stones in recurrent stone patients.

A survey was carried out on the family history of renal stones among 380 patients in an out-patient stone clinic, most of whom had experienced frequent recurrences. In 55.4% of patients at least one first-degree relative had experienced renal stones. A positive family history was more common in females (64.7%) than in males (51.0%) and was particularly apparent in those who had multiple recurrences. It was also significantly more common in female patients with evidence of renal tubular defects (incomplete forms of renal tubular acidosis). Among the ordinary stone patients 18% of the fathers and 8% of the mothers had also formed renal stones. The corresponding figures for female stone patients with renal tubular defects were 40 and 33% respectively. These findings indicate that tubular dysfunction could be an inherited trait that predisposes to the formation of renal stones. Hypercalciuria or hyperuricosuria was not over-represented among stone formers with a positive family history.

Acidosis, Renal Tubular↗

Allopurinol treatment of renal calcium stone disease.

Thirty-one calcium stone patients were treated with 300 mg allopurinol daily during a mean follow-up period of 2 years. They were also given advice on diet and fluid intake. The effects on the recurrence rate of stones were compared with the effects on the recurrence rate in 43 calcium stone patients who were given similar advice on diet and fluid intake but were not treated with allopurinol. In both groups there was a reduction in the recurrence rate but no difference between patients treated with allopurinol and the control group. Some patients with only hyperuricosuria prior to treatment seemed to benefit from allopurinol treatment, whereas those with hypercalciuria continued to form stones with the same frequency. Allopurinol treatment in calcium stone disease appears less effective than treatment with thiazides, magnesium hydroxide or orthophosphate.

Adolescent↗

Stimulus-secretion coupling of parathyroid hormone release: studies of 45Ca and 86Rb fluxes.

Pieces of rat parathyroid glands were used to study fluxes of 45Ca and 86Rb. The uptake of 45Ca increased with the extracellular Ca2+ concentration up to at least 5 mM. A rise of extracellular Ca2+ had dual effects on 45Ca efflux in terms of an initial stimulation and a subsequent inhibition. However, K+ depolarization neither affected the uptake nor the efflux of 45Ca indicating a lack of voltage-dependent Ca2+ channels. The depolarization obtained with exposure to Ca2+ cannot be attributed to a decreased K+ permeability, since the 86Rb concentrating ability diminished and the efflux of the isotope increased when parathyroid pieces were exposed to a raised Ca2+ concentration. A stimulation of 86Rb efflux by the Ca2+ ionophore A-23187 indicated that the parathyroid cells possess a K+ permeability activated by cytoplasmic Ca2+. It is suggested that Ca2+ fluxes through channels sensitive to activation by Ca2+ are important both for the membrane potential and the cytoplasmic Ca2+ activity.

Animals↗

The effects of methenamine-hippurate upon urinary risk factors for renal stone formation.

Among the various treatments for renal calcium stone disease, none has been documented to reduce urinary oxalate. Methenamine-hippurate (Hiprex) has been used extensively in the treatment of urinary tract infections and from micropuncture studies in the rat, using para-aminohippurate, it could be expected to reduce the renal secretion of oxalate. A daily dose of 3 g was given orally to 15 healthy subjects for 2 weeks. However, there was no net decrease in the urinary excretion of oxalate, but a risk index based on the urinary content of calcium, magnesium, oxalate, citrate and urine became reduced during treatment. The urinary inhibition of calcium oxalate crystal growth was unaffected. It is concluded that there may be a potential in methenamine-hippurate for the treatment of calcium stone disease, which can only be evaluated, however, by a clinical trial in stone patients.

Anti-Infective Agents, Urinary↗

Tubular proteinuria in renal calcium stone formers.

The incidence of tubular proteinuria measured as urinary excretion of beta 2-microglobulin was evaluated in 68 consecutive renal calcium stone formers, 14 of whom had impaired urinary acidification capacity. During normal conditions 13% of these stone formers had tubular proteinuria. There was no statistical difference in the incidence of tubular proteinuria between subgroups with proximal or distal acidification defects. During transient metabolic acidosis induced by an ammonium chloride load a pronounced increase in beta 2-microglobulin excretion was noticed in all patient groups but especially in those with urinary acidification defects. In stone formers with normal acidification capacity the degree of acidosis-induced beta 2-microglobulinuria was moderate but a small group of patients exhibited a large urine excretion of beta 2-microglobulin. This finding may reflect a latent tubular defect of importance for stone genesis.

Acidosis↗