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Biomedical subjects

S Ljunghall

Publications and source records attributed to S Ljunghall.

At least 217 records · Page 12Linked to original sources

Use of clodronate and calcitonin in hypercalcemia due to malignancy.

Increased bone resorption and increased renal tubular reabsorption of calcium are involved in the pathogenesis of hypercalcemia of malignancy. Clodronate and calcitonin inhibit bone resorption and have been used as therapy for malignancy-associated hypercalcemia. Both drugs induce significant reductions of serum calcium but the decrease is greater with clodronate, particularly when given intravenously. While the response to calcitonin generally is of short duration, clodronate can maintain normal serum calcium values over several weeks when oral administered. Thus, from the clinical point of view clodronate is a very useful adjunct to the available therapy.

Calcitonin↗

Intestinal oxalate and calcium absorption in recurrent renal stone formers and healthy subjects.

The fractional intestinal absorption of oxalate and calcium was investigated by isotope techniques in 20 normal subjects and in 12 idiopathic calcium oxalate stone formers. The greatest amount of 14C-oxalate was excreted during the first six hour period in controls as well as in stone formers. The stone formers had a greater intestinal uptake of oxalate (11 +/- 5.1%) than the controls (6.2 +/- 3.7%; p less than 0.01). There was no significant relationship between the fractional absorption of oxalate and the total urinary oxalate excretion. The stone formers also had a higher fractional uptake of calcium compared to the controls (55 +/- 11% vs. 47 +/- 9.1%; p less than 0.05). There was a positive relationship (r = 0.47) between the urinary excretions of calcium and oxalate in the stone formers. During these conditions no correlation could be demonstrated between the fractional absorptions of oxalate and calcium, neither in the stone formers nor in the controls. In conclusion, patients with recurrent formation of calcium oxalate containing stones appear to have an enhanced intestinal uptake of both oxalate and calcium. This disturbance could be of primary pathogenic importance for their stone forming propensity.

Adult↗

Reduction of blood pressure during long-term treatment with active vitamin D (alphacalcidol) is dependent on plasma renin activity and calcium status. A double-blind, placebo-controlled study.

Patients with essential hypertension, in particular those with low plasma renin activity (PRA), are reported to have lowered plasma-ionized calcium and elevated parathyroid hormone levels. In this study 1 microgram alphacalcidol (1 alpha-hydroxy-vitamin D3) was given in a double-blind, placebo-controlled fashion over four months to 39 subjects with mild to moderate hypertension. There was a significant rise in PRA in the treatment group when compared to placebo (P less than .05), but the mean blood pressure response was similar in the two groups. When the treatment group was divided according to pretreatment PRA it was, however, seen that subjects with low PRA displayed a reduction in diastolic blood pressure, whereas those with high PRA raised their blood pressure compared to placebo. Also subjects with low pretreatment values for plasma-ionized calcium and high levels of parathyroid hormone showed a reduction in diastolic blood pressure. This study supports the idea of a relationship between calcium metabolism and the renin-aldosterone system in essential hypertension and describes a beneficial effect of vitamin D supplementation on blood pressure in low-renin hypertension.

Blood Pressure↗

Metabolic effects of diltiazem and atenolol: results from a randomized, double-blind study with parallel groups.

In a randomized, double-blind study (n = 58) with parallel groups, the effects of diltiazem (mean dose 329 mg/day) and atenolol (mean dose 67 mg/day) on carbohydrate and lipoprotein metabolism in hypertensive patients were compared. The mean systolic blood pressure (SBP)/diastolic blood pressure (DBP) reductions in the supine position were similar and satisfactory, 9/11 and 11/9 mmHg during atenolol and diltiazem treatment, respectively. Insulin-mediated glucose uptake, measured with the euglycaemic insulin clamp technique, decreased during atenolol treatment, from 7.1 to 5.6 mg/kg per min (P = 0.05). but not during treatment with diltiazem (initial value 6.8, final value 6.7 mg/kg per min; P greater than 0.8). Treatment differences between groups were statistically significant (P less than 0.05). During atenolol treatment there was a slight but significant increase in plasma glucose in the fasting state (P less than 0.05) and at the end of an intravenous glucose tolerance test (IVGTT; P less than 0.01), and in plasma insulin at the end of IVGTT (P less than 0.05). Despite increased insulin resistance the increase in insulin response was small, suggesting inhibition of insulin release. The insulin peak was decreased by 13% during diltiazem treatment (P less than 0.05). The concentrations of very-low and low-density lipoprotein triglycerides increased, whereas high-density lipoprotein cholesterol decreased and low-density lipoprotein cholesterol was unaffected during atenolol treatment. In conclusion, there was no difference between the antihypertensive effects of atenolol and diltiazem, but atenolol decreased insulin sensitivity and altered the lipid profile, thus possibly increasing the risk of diabetes mellitus and theoretically reducing the benefits of blood pressure reduction with regard to risk of coronary heart disease.

Adult↗

Serum electrolytes and parathyroid hormone in patients in a coronary care unit.

A prospective study was carried out in 499 patients admitted to a coronary care unit (CCU) in order to evaluate the incidence of clinically significant electrolyte disturbances. Low serum potassium values (less than 3.6 mmol l) occurred in 7% of the CCU patients and low serum magnesium values (less than 0.70 mmol l-1) in 6%. Few patients had low values of both these ions (1.9%). In 49 patients the contents of these electrolytes in muscle biopsies were similar to the values of control subjects and were unrelated to treatment with diuretics. Serum calcium was determined in 444 of the patients and was above the reference range in 11 (2.5%). If we consider their concomitant parathyroid hormone (PTH) values, primary hyperparathyroidism was likely to occur in at least seven patients (1.5%). Patients with acute myocardial infarction (AMI) had mean PTH and electrolyte values similar to those of individuals without this disease. In conclusion, the present study indicates that clinically important disturbances of magnesium, potassium or calcium homeostasis are rare among unselected patients admitted to a CCU.

Adrenergic beta-Antagonists↗

Dietary habits in renal stone patients compared with healthy subjects.

The dietary habits of renal calcium stone patients were investigated both by dietary history and by 4-day food records and compared with the dietary habits of control subjects, matched on the basis of age, sex, social and professional status. The method using 4-day records seemed to be more precise, judged by the correlation to the urinary output of nutrients. There was no difference in the daily intake of major nutrients between stone formers and controls, but a higher ingestion of vitamin C in controls and a larger consumption of alcohol among stone formers. In contrast to some epidemiological evidence, there were no significant differences in consumption of animal protein when stone formers were matched for social class. Despite a similar total intake of calcium, the stone formers excreted more calcium in the urine, probably reflecting a higher intestinal absorption of calcium. There seem to be only marginally different dietary habits between stone formers and carefully matched control subjects. Differences in the urinary output of minerals and electrolytes are mainly due to variations in gastrointestinal uptake.

Adult↗

Treatment with active vitamin D (alphacalcidol) in patients with mild primary hyperparathyroidism.

The parathyroid gland possesses receptors for 1,25-dihydroxyvitamin D3, the active metabolite of the vitamin D system, and in vitro experiments have shown that 1,25-dihydroxyvitamin D3 can inhibit the secretion of PTH. In this study 31 subjects who had displayed persistent mild hypercalcemia for 14 years and presumably had mild primary hyperparathyroidism (HPT) were challenged with 1.0 microgram alphacalcidol (1 alpha-(OH)-vitamin D3) over 6 months in a double-blind, placebo-controlled study. Before initiation of therapy, the hyperparathyroid subjects showed lower serum levels of 1,25-dihydroxyvitamin D in relation to PTH or calcium when compared with age- and sex-matched controls. Treatment induced a slight rise in serum calcium (0.05 mmol/l), but no significant decrease of the PTH levels. Eighteen of the subjects thereafter entered an open study with a higher dose of alphacalcidol (2.0 micrograms) over 1 year. Although this high dose induced a marked rise in serum calcium (0.17 mmol/l), there was only a transient reduction of the PTH levels. Thus, during long-term condition there was an escape from the suppressive action of the elevated calcium concentrations and no evidence of a specific inhibition of PTH secretion by a small oral dose of active vitamin D.

Aged↗

Intestinal absorption of oxalate and calcium in patients with jejunoileal bypass.

Jejunoileal bypass (JIB) has been widely performed for treatment of excessive obesity. Formation of calcium oxalate stones is a common side effect. Since, under physiological conditions, the intestinal absorption of calcium and that of oxalate are interrelated, intestinal oxalate and calcium absorption were measured in the present study by isotope techniques in 19 JIB patients and 20 healthy controls. The JIB patients showed pronounced hyperoxaluria and markedly increased absorption of oxalate, with a urinary excretion of 14C-oxalate of 29 +/- 19% (controls 6.2 +/- 3.7%; p less than 0.001). There was a strong correlation between the intestinal absorption and urinary excretion of oxalate in the JIB patients (r = 0.72; p less than 0.001). Furthermore, their oxalate kinetics was altered, with continued urinary excretion of 14C-oxalate for up to 48 hours. The JIB patients also had reduced calcium absorption (36 +/- 9.1% vs. 47 +/- 9.0%; p less than 0.001) and patients with malabsorption of calcium and low urinary calcium had the highest intestinal absorption and urinary excretion of oxalate. It is concluded that hyperoxaluria in JIB patients is due to a significant extent to hyperabsorption of oxalate.

Adult↗

The relation between urinary tract infections and stone composition in renal stone formers.

During a seven-year period (1975-1981) a total of 1325 patients hospitalized for stone disease were studied as to the occurrence of positive urine cultures. Urinary stones from 535 surgically treated patients were analyzed with infrared spectrophotometry and the relationships between stone composition, level of surgery and bacteriological strains were studied. Positive urinary cultures were found in 34% of the surgically treated patients and in 21% of those not operated upon. Among the surgically treated patients with urinary tract infection (UTI) E. coli was the most frequent microorganism (35%), followed by Proteus (28%). Patients with Proteus infection had the highest frequency of UTI episodes, most of which occurred before hospitalization. There was a higher frequency of magnesium ammonium phosphate (MAP) calculi among patients with Proteus infection than among those with non-Proteus infection, in whom no difference in stone composition was found. Patients infected with E. coli had more phosphate-containing stones (CaP+MAP) than non-infected patients. The highest frequency of oxalate calculi (CaOx+CaOx/CaP) was found among patients without infection. No E. coli infections were seen in male patients with CaP and MAP calculi. MAP stones were most often found in the kidney and oxalate stones in the ureter.

Calcium Oxalate↗

Increased fracture risk in hypercalcemia. Bone mineral content measured in hyperparathyroidism.

In the present study, 39 women with mild hypercalcemia, which had been detected 18 years earlier during a health survey, and presumably caused by primary hyperparathyroidism (HPT), were investigated together with 34 age-matched controls. The bone mineral content (BMC) of the nondominant distal forearm was measured by single-photon absorptiometry, and the occurrence of fractures was recorded. Among women up to the age of 70 years, those with hypercalcemia had lower BMC than the controls (P less than 0.05), whereas among the older women, there was no difference. Twelve of the women with probable primary HPT had suffered a distal radius fracture as compared with 3 of the controls (P less than 0.05). Thus, also mild hypercalcemia is a risk factor for bone loss and distal forearm fractures. The findings constitute arguments in favor of early detection and treatment of primary HPT.

Aged↗

An association between mineral metabolism and the renin-aldosterone system in human hypertension.

In recent years abnormalities of calcium metabolism have been described in human hypertension. In this study, the relationships between indices of calcium metabolism and the renin-aldosterone system were studied in 39 subjects with untreated essential hypertension. No significant associations were found between the major determinants of calcium metabolism (plasma ionised calcium, parathyroid hormone and 1,25(OH)2-vitamin D) and the renin-aldosterone system. Serum magnesium was, however, positively correlated to plasma renin activity (PRA) (r = 0.38, P less than 0.05) while both 24 h urinary excretion of calcium and cAMP were found to be correlated to both PRA and urinary aldosterone in a positive way (r = 0.39-0.42, P less than 0.01 and r = 0.33-0.57, P less than 0.01, respectively). In this study there was no other evidence of any major influence of the renin-aldosterone status on the calcium balance in human hypertension. The urinary leak of calcium might be determined by the action of the renin-aldosterone system.

Adult↗

Long-term treatment with active vitamin D (alphacalcidol) in middle-aged men with impaired glucose tolerance. Effects on insulin secretion and sensitivity, glucose tolerance and blood pressure.

There are specific receptors for the active metabolite of vitamin D on the pancreatic beta cells and severe vitamin D deficiency can inhibit insulin secretion. In the present study 14 middle aged men with impaired glucose tolerance and low glucose-stimulated insulin values received 2 micrograms alphacalcidol daily for 18 months. On treatment there was a transient increase of both the peak and the late insulin response to intravenous glucose while neither intravenous nor oral glucose tolerance were consistently altered. Nor was the peripheral insulin sensitivity, measured by the euglycemic clamp technique, significantly affected. In the untreated state there was a positive relationship (r = 0.77) between the tissue insulin sensitivity and the serum concentrations of 25-hydroxyvitamin D. There was also an inverse relationship (r = 0.61) between systolic blood pressure and the serum levels of 1,25-dihydroxy vitamin D. Although the subjects were normotensive and not overweight, treatment with alphacalcidol tended to lower both systolic (6 +/- 12 mmHg) and diastolic blood pressures (5.8 +/- 9.1 mmHg) and there was a small reduction (0.9 kg) in body weight. In conclusion, subjects with impaired glucose tolerance without vitamin D deficiency do not benefit from vitamin D supplementation, which however has some hypotensive action also in normotensive individuals.

Blood Glucose↗

Interactions between indices of calcium metabolism and blood pressure during calcium infusion in humans.

Calcium plays a central role in maintaining vascular tone. Recent studies indicate that there are continuous relationships between systemic calcium metabolism and BP, as over the whole range of normal and raised BPs there is an inverse correlation between plasma ionised calcium concentration and BP. Twenty-two subjects with normal or moderately elevated BP participated in the present study, undertaken to investigate the interactions between systemic calcium metabolism and BP during a two-hour constant-rate calcium infusion in the absence and in the presence of concomitant verapamil infusion. During the infusion there was an increase in plasma ionised calcium by 0.40 mmol/l, SBP rose by 14 mmHg, and DBP by 9.7 mmHg. Higher basal plasma ionised calcium and lower basal serum parathyroid hormone concentrations were associated with a more pronounced diastolic pressor response to the calcium infusion. A greater DBP increase was also accompanied by more pronounced parathyroid hormone suppression, determined as cyclic adenosine monophosphate excretion, and greater tissue uptake of calcium during the infusion. Conversely, higher basal BPs were associated with greater tissue calcium uptake during the infusions. This relationship was abolished when verapamil was present. The present findings extend the previous observations of continuous relationships between indices of calcium metabolism and BP and indicate that both a direct effect of the calcium ion and indirect effects, as evidenced by cyclic adenosine monophosphate excretion, affect the BP response to acute hypercalcaemia.

Adult↗

Self-rated psychiatric symptoms in patients operated on because of primary hyperparathyroidism and in patients with long-standing mild hypercalcemia.

Self-rated psychiatric symptoms were investigated in 30 patients referred for surgery because of primary hyperparathyroidism (HPT) (serum calcium, 2.87 +/- 0.21 mmol/L) in 38 subjects detected in a health screening, with 15 years of mild hypercalcemia and probable HPT (serum calcium, 2.66 +/- 0.09 mmol/L), and in 38 normocalcemic control subjects. The psychiatric symptomatology was evaluated by use of the Hopkins Symptom Checklist (HSCL-56), a self-rating symptom scale. The patients with verified HPT had the highest mean HSCL score, 89.1 +/- 20.1 before surgery, compared with 76.6 +/- 17.0 (p less than 0.01) in the health survey hypercalcemic patients and 73.8 +/- 16.0 (p less than 0.001) in the controls. The factors for anxiety, depression, and cognitive symptoms were the most pronounced in the HPT patients and were also increased among the mildly hypercalcemic persons of the health survey, compared with the controls. Somatic symptoms such as headache, back pain, chest pain, and weakness were equally common in HPT and in the controls, and measurements of isometric muscle strength of knee extension did not demonstrate reduction of muscle strength in the health survey hypercalcemic patients. Follow-up of the HPT patients 1 year after parathyroid surgery revealed a marked improvement in mental health (HSCL score 73.2 +/- 13.7, p less than 0.001). In the health survey hypercalcemic patients, neither the psychiatric symptomatology nor the muscle strength were influenced by 6 months of oral vitamin D therapy (alphacalcidol). The results demonstrate that psychiatric symptoms are experienced frequently by patients with HPT and minimum to moderate increases in the serum calcium level and that these disturbances are reversed by parathyroid surgery.

Adult↗

Relation of serum calcium concentration to metabolic risk factors for cardiovascular disease.

Data from a health screening survey with over 18,000 adult participants were used to determine the relations between serum calcium concentration and the cardiovascular risk factors hypertension, hyperglycaemia, and hyperlipidaemia. Blood pressure and serum glucose and cholesterol concentrations were all positively related to each other independent of age, sex, kidney function, and obesity. Similar relations between the risk factors were found in subjects with hypertension or hyperglycaemia independent of the degree of overweight. These results suggested that there might be a metabolic syndrome of cardiovascular risk factors. Serum calcium concentration was positively related to systolic and diastolic blood pressures and serum glucose and cholesterol concentrations. Thus a common feature in the syndrome is an increased serum calcium concentration. The relations between serum calcium concentrations and the cardiovascular risk factors were not limited to the upper parts of the distribution, being seen over a wide range. Changes in calcium metabolism seem to be related to a metabolic syndrome of hypertension, impaired glucose tolerance, and hyperlipidaemia.

Aged↗

Psychiatric symptoms and cerebrospinal fluid monoamine metabolites in primary hyperparathyroidism.

This prospective study included 32 patients with primary hyperparathyroidism (HPT). As compared with a healthy reference group, the patients had pronounced psychiatric symptomatology [CPRS score 17.2 +/- 9.0 (SD) versus 4.4 +/- 2.0], which was mainly affective in character. The severity of symptoms was not related to the serum calcium or parathyroid hormone concentrations. The majority of the patients had low CSF concentrations of monoamine metabolites (5-HIAA, HVA, and MHPG) and, in particular, those with the most severe psychiatric symptoms had low values for 5-HIAA. At follow-up, 1 year after parathyroid surgery, the patients displayed a clear improvement in mental health (CPRS score 4.4 +/- 3.0) together with an increase in CSF concentrations of 5-HIAA and HVA. The study demonstrates that significant psychiatric disturbances, which can be improved/normalized by surgery, are common in patients with HPT and are possibly related to changes in the central nervous system turnover of monoamines.

Aged↗

Maximal isokinetic muscle strength in patients with primary hyperparathyroidism before and after parathyroid surgery.

Primary hyperparathyroidism (HPT) is associated with symptoms of generalized fatigue and muscle weakness. The purpose of this study was to investigate muscular function in HPT quantitatively and to evaluate the effect of parathyroid surgery in this respect. The maximal isokinetic muscle strength (peak torque) of knee extension and flexion was measured with a Cybex-II dynamometer in 16 patients with primary HPT (mean serum calcium 2.81 +/- 0.14 mmol/l), four of whom had subjective impairment of strength, and in nine control patients submitted to hemithyroidectomy due to atoxic thyroid adenoma. Before surgery there was no significant difference in muscle strength between the two groups, neither was there any consistent relationship between the subjective feeling of muscular weakness and the measured peak torque. Seven months after surgery the HPT patients had increased their muscle strength by 8 per cent (P less than 0.05). The improvement was correlated with the pre-operative serum calcium levels (r = 0.56, P = 0.02) and was particularly seen in patients with pre-operative subjective muscular weakness. Patients with only slightly raised calcium values and without subjective muscular symptoms did not benefit clearly from surgery, compared with the controls. The study demonstrates that HPT patients, especially those with neuromuscular symptoms, can improve their muscle strength after parathyroid surgery.

Adult↗