Biomedical subjects

S Ljunghall

Publications and source records attributed to S Ljunghall.

At least 253 records · Page 14Linked to original sources

PubMed1988

Reduction of blood pressure by treatment with alphacalcidol. A double-blind, placebo-controlled study in subjects with impaired glucose tolerance.

Disturbances of calcium or vitamin D metabolism have been suggested to be of pathogenetic importance both for hypertension and impaired glucose tolerance, two disorders that are commonly associated. In the present study 65 men, aged 61-65 years, with impaired glucose tolerance were enrolled in a prospective, double-blind, placebo-controlled study over 12 weeks evaluating the effects of 0.75 microgram alphacalcidol, a synthetic analog to the active metabolite of vitamin D. In the 26 patients with blood pressure greater than or equal to 150/90 mmHg before treatment a significant reduction (p less than 0.01) of both the systolic (SBP) and diastolic (DBP) blood pressure was found after therapy (from 171/95 to 150/88 mmHg). The effect was additive to concomitant antihypertensive treatment and was correlated (p = 0.03) to a reduction of serum levels of parathyroid hormone. Also in the whole group of patients given alphacalcidol blood pressure was moderately lowered from a mean of 152/87 +/- 22/10 (SD) to 143/84 +/- 17/8 mmHg. There were no relationships between the changes in body weight, blood glucose or insulin parameters and the changes in blood pressure during the trial. The findings are compatible with the concept that calcium metabolism influences blood pressure regulation and suggest that supplementation with a physiologic dose of active vitamin D could be beneficial for patients with high blood pressure.

Aged↗

PubMed1988

Cytosolic free calcium in platelets: relationships to blood pressure and indices of systemic calcium metabolism.

Relationships between cytosolic free calcium ([Ca2+]i) in platelets, indices of systemic calcium metabolism and blood pressure were examined in 86 subjects; 29 patients with untreated and 29 patients with treated essential hypertension, six patients with borderline hypertension and 22 healthy reference subjects. In order to analyse interactions between the variables, multivariate statistical analyses were employed. The patients with untreated hypertension had higher [Ca2+]i values in non-activated platelets (P = 0.04) and lower levels of plasma ionized calcium (P = 0.02) than the reference subjects. In multivariate models analysing platelet [Ca2+]i mean blood pressure (MBP), plasma ionized calcium, serum parathyroid hormone (PTH) and body mass index (BMI), the relationship between platelet [Ca2+]i and blood pressure was attenuated (P = 0.13), whereas the inverse relationships between plasma ionized calcium and MBP (P = 0.01) and between platelet [Ca2+]i and serum PTH (P = 0.06) seen in univariate analyses persisted. According to the multivariate models the [Ca2+]i value explained only 5% of the MBP variability. Thus, the data from this investigation do not support a close relationship between basal platelet [Ca2+]i and blood pressure. The inverse relationship between plasma ionized calcium and blood pressure, independent of platelet [Ca2+]i and serum PTH, suggests a direct interaction between plasma ionized calcium and blood pressure regulation.

Adolescent↗

PubMed1987

Bimodal regulation of secretion by cytoplasmic Ca2+ as demonstrated by the parathyroid.

Bovine parathyroid cells were used to study parathyroid hormone (PTH) release and the cytoplasmic Ca2+ concentration (Cai2+). When the extracellular Ca2+ concentration was decreased from 3.0 to 0.5 mM, perifused cells reacted with rapid stimulation of PTH release. However, a further reduction of extracellular Ca2+ to less than 10 nM resulted in prompt inhibition. Both effects were readily reversible. Using the intracellular Ca2+ indicator quin-2 also as a buffer for calcium it was possible to control Cai2+ within the 20-600 nM range. PTH release was found to increase with Cai2+ up to 200 nM but was gradually suppressed above this concentration.

Aminoquinolines↗

PubMed1987

Survival and renal function in untreated hypercalcaemia. Population-based cohort study with 14 years of follow-up.

172 persons with mild to moderate hypercalcaemia were followed up for 14 years. Life-table analyses showed that, among persons aged 70 years or less at the time of detection of the hypercalcaemia, survival was lower in the hypercalcaemic group than in a normocalcaemic age and sex matched control group. No such difference was found among older persons. The lower survival was related to degree of hypercalcaemia, and this held true when systolic and diastolic blood pressure, serum glucose, serum uric acid, and serum cholesterol were taken into account in a multivariate analysis. The lower survival seemed to be due mainly to deaths from diseases of the circulatory organs. No person with normal renal function at the beginning of the study period had a more than marginally raised serum creatinine at follow-up.

Actuarial Analysis↗

PubMed1987

Reduction of serum parathyroid hormone levels during sympathetic stimulation in man.

The parathyroid glands contain sympathetic nerve endings and the parathyroid cells are endowed with beta-adrenergic receptors. The physiological role of the sympathoadrenal system for the secretion of parathyroid hormone (PTH) has, however, not been clarified. Using the technique of lower body negative pressure (LBNP), which is an established method to achieve sympathetic nerve activation, it was found in 17 healthy subjects that the venous serum levels of PTH were reduced by 7% within 20 min [from 0.79 +/- 0.12 (SD) to 0.74 +/- 0.11 arbU/l, p less than 0.01, paired t test]. The reduction corresponds to 30% of the maximal suppressibility of PTH by induced hypercalcemia or following parathyroidectomy when studied with the same PTH assay and with the short time period involved. After cessation of LBNP the PTH levels returned to baseline within 20 min. There were no concomitant changes of the plasma ionized calcium concentrations. The findings are compatible with a role for the sympathetic nervous system in the physiologic regulation of the secretion of PTH.

Adult↗

PubMed1987

Hyperparathyroidism presenting as the first lesion in multiple endocrine neoplasia type 1.

In a study of 16 different families, 55 persons were considered to be affected by the syndrome of multiple endocrine neoplasia type 1 (MEN-1). Serum calcium measurements were available for all but six patients, long deceased, and hypercalcemia was invariably present. All but four of these patients have been subjected to surgery, and hyperparathyroidism was verified in each case. In all the patients studied, hyperparathyroidism was apparently the first manifestation of the MEN-1 syndrome. Pituitary tumors were detected in 23 patients, and there was evidence of pancreatic lesions in 32. Although either the pituitary or pancreatic manifestations dominated clinically in some patients, hyperparathyroidism was invariably present when sought. Measurement of serum calcium in asymptomatic relatives at risk for MEN-1 disclosed no case of hyperparathyroidism in children below the age of 18, whereas half of all screened persons between the ages of 18 and 30 were found to have hyperparathyroidism. In some, the serum calcium values were only marginally or even intermittently elevated. It is concluded that since hyperparathyroidism is apparently the first lesion in MEN-1, screening for this syndrome should primarily be directed toward the diagnosis of hyperparathyroidism. The temporal relationships suggest that hyperparathyroidism could be a prerequisite for the other types of endocrine neoplasms in the MEN-1 syndrome.

Adolescent↗

PubMed1987

Patients with primary hyperparathyroidism operated on over a 24-year period: temporal trends of clinical and laboratory findings.

Temporal trends of clinical and laboratory data of 441 patients operated upon for primary hyperparathyroidism (HPT) during 1956-1979 were analysed retrospectively. There was a marked increase in the number of operations for HPT during that time period, from 32 during 1956-1964 to 326 in 1970-1979. In parallel there was a decrease in the proportion of patients with classical manifestations of HPT such as renal stones or bone disease, the latter being on the whole rarely seen in this population. The increased number of operations was instead largely attributable to the more frequent diagnosis of HPT in patients with vague psychiatric or neuromuscular symptoms or with no clinical manifestations; the majority of these persons were older women, the proportion of operations in women 45 years of age or older, increasing from 56% during 1956-64 to 71% during 1970-79. The increased number of operations for HPT during the last decades should be mainly the consequence of a greater awareness of the disease.

Adenoma↗

PubMed1987

Clinical studies of calcium metabolism in essential hypertension.

Many factors can ultimately lead to an increased blood pressure and it is a generally accepted view that an increase in the active tension of arterioles reflects an increase of the free calcium concentration in the cytosol of the vascular smooth muscle cells. Only recently, however, has the possibility been considered that blood pressure regulation could be influenced by calcium homeostasis. A background for these studies has been provided by the epidemiological observations which link hypertension to a low dietary intake of calcium as well as experimental studies in animals, mostly rats, which have demonstrated that various disturbances of calcium metabolism are related to a raised blood pressure. This review is focused on clinical studies of a possible association between systemic calcium metabolism and the regulation of blood pressure.

Calcium↗

PubMed1987

Plasma potassium and phosphate concentrations--influence by adrenaline infusion, beta-blockade and physical exercise.

Infusion of adrenaline into healthy male subjects reduced the plasma concentrations of both potassium and phosphate to a similar extent, in a dose-dependent manner, an effect which was prevented by the administration of propranolol. Ergometer bicycling until exhaustion, which caused marked accumulation of lactic acid in the blood and reduction of pH, induced great elevations of both plasma potassium and phosphate with close relationships between the raised plasma concentrations and the reduction in pH, also during beta-blockade. However, longer-term aerobic exercise, without acidosis, also caused some rise of the potassium and phosphate concentrations. During recovery from anaerobic, but not from aerobic, exercise there was a rapid decrease of the plasma potassium levels while the phosphate values normalized gradually together with pH. From measurements of the ion concentrations both in the femoral effluent of one leg, which carried out maximal isokinetic work, and in the opposite antecubital vein it could be calculated that there was for potassium, but not for phosphate, a post-exercise uptake both in the exercised muscle and in the entire organism, indicating the participation of systemic factors.

Adult↗

PubMed1987

Clodronate treatment in patients with malignancy-associated hypercalcemia.

The possibility of reducing symptomatic hypercalcemia and of maintaining total serum calcium concentrations less than 2.8 mmol/l with clodronate (dichloromethylene bisphosphonate) was evaluated in 28 patients with various types of malignant tumors. Four episodes of hypercalcemic crisis with mean serum calcium concentrations of 4.43 mmol/l were controlled within 4-6 days of intravenous clodronate (4 mg/kg BW/day). This was accompanied by a moderate increase in serum creatinine values which, however, returned to pretreatment levels after therapy withdrawal in all but one case. Oral clodronate successfully reduced a mean serum calcium concentration of 3.16 mmol/l in 22 out of 25 patients after 3-12 days (800-3,200 mg/day). After reversal of the hypercalcemias oral clodronate controlled the serum calcium concentration for up to 42 weeks in six out of 15 patients After discontinuation of initial therapy five of seven recurrent hypercalcemias were successfully treated with oral or intravenous clodronate. Hypocalcemia and subjective side-effects were uncommon. It is concluded that clodronate is a valuable clinical tool in the management of patients with malignancy-associated hypercalcemia.

Administration, Oral↗

PubMed1987

Treatment with one-alpha-hydroxycholecalciferol in middle-aged men with impaired glucose tolerance--a prospective randomized double-blind study.

Experimental evidence suggests a specific role for the active metabolite of vitamin D (1,25(OH)2D3) in insulin secretion. In order to evaluate the possible clinical significance, 65 middle-aged men with impaired glucose tolerance, and normal serum levels of vitamin D metabolites, were enrolled in a three-month study where they were given either 0.75 micrograms alpha-calcidol (1 alpha(OH)D3) daily or placebo. Indices of glucose and lipid metabolism were evaluated before and after treatment. There were no significant changes during the trial neither for fasting blood glucose, hemoglobin A1c or for the intravenous glucose tolerance between the treatment and the placebo groups, nor were there any consistent changes in insulin values during the glucose tolerance test. Subjects treated with alpha-calcidol displayed a significant reduction in body weight with an average of 1.1 kg, while those receiving placebo lost no weight. Treatment did not affect the serum lipoprotein values. Thus, a modest dose of active vitamin D, which did not cause elevation of serum calcium, did not provide general improvement of glucose tolerance or of insulin secretion when given to patients with impaired glucose tolerance, but without vitamin D deficiency, over a three-month period.

Aged↗

PubMed1987

Blood pressure is lowered by vitamin D (alphacalcidol) during long-term treatment of patients with intermittent hypercalcaemia. A double-blind, placebo-controlled study.

There is epidemiologic evidence of a relationship between calcium deficiency and hypertension. The present study evaluated the effects of alphacalcidol, a synthetic analogue of active vitamin D, given to 29 patients with marginal, intermittent hypercalcaemia. Before therapy there was an inverse relationship between serum calcium levels and diastolic blood pressure (p less than 0.02). Treatment with 1 microgram alphacalcidol raised the serum calcium by 0.07 mmol/l during a 6-month, double-blind, placebo-controlled trial and caused a significant reduction of diastolic blood pressure by 9.2 mmHg compared with placebo (p less than 0.01). The study extends previous observations, in normocalcaemic subjects, of inverse relationships between serum calcium and blood pressure indicating a primary disturbance of calcium homeostasis in hypertension. The observation that a physiologic amount of active vitamin D has hypotensive effects agrees with such a concept and suggests a new principle for the treatment of hypertension.

Blood Pressure↗

PubMed1987

Dynamic tests of parathyroid function for diagnosis of primary hyperparathyroidism in malignancy.

Hypercalcaemia can be caused by malignant diseases as well as by primary hyperparathyroidism (HPT). The two disorders may occur together and an accurate discrimination between them is sometimes not possible from basal measurements of calcium and parathyroid hormone (PTH) concentrations. In primary HPT the regulation of PTH secretion is maintained, albeit the set-point is shifted to a hypercalcaemic value. Therefore, when serum calcium is lowered by ethylene diamine tetra-acetic acid (EDTA) infusions or calcitonin injections, patients with primary HPT display enhanced secretion of PTH already within the hypercalcaemic range, whereas parathyroid function remains suppressed in malignancy-associated hypercalcaemia. Tests based on this principle enable a specific identification of HPT. The present report describes eight hypercalcaemic patients with disseminated malignancy where HPT could be diagnosed by the use of such stimulatory tests.

Adenoma↗

PubMed1987

Prevalence of renal stones in 60-year-old men. A 10-year follow-up study of a health survey.

Information on the occurrence of renal stones was obtained in a health survey of 50-year-old men and at follow-up of the same group 10 years later. At the latter investigation, 338 of 1781 participants (19%) had a history of renal stone formation. In 47% there had been recurrences. For the individual there was a continuous risk of acquiring a first renal stone up to the age of 60. Approximately 0.5% of the entire unselected population experienced onset annually up to this age. Recurrent renal stones occurred primarily in those with a positive family history of stones or early onset of stones, as well as in those who previously had frequently formed stones. A carefully obtained clinical history should be useful in predicting recurrences in the individual stone former.

Follow-Up Studies↗

PubMed1987

Development of abnormal parathyroid cell function during monolayer culture and its relation to cellular hypertrophy and proliferation.

Primary cultures of adult bovine parathyroid cells grown for up to 8 days were used to study the relationship between regulation of parathyroid hormone (PTH) release, cytoplasmic Ca2+ (Ca2+i) and cell growth. Cell counting indicated that proliferation was inversely proportional to the seeding density. The culture was associated with cell enlargement without apparent relation to the proliferation rate. Moreover, flow cytometric analysis of the DNA distribution excluded that the hypertrophy was due to a high proportion of the cells being in the S and G2 stages of the cell cycle. With progressive time in culture there was a gradual deterioration of the ability of increasing concentrations of extracellular Ca2+ to suppress PTH secretion and raise Ca2+i. This functional dedifferentiation developed to the same extent despite considerable differences in proliferation rates. The data show that parathyroid cells in monolayer culture develop functional and some of the morphological characteristics of parathyroid cells from patients with hyperparathyroidism and that the functional abnormality seems to be related to hypertrophy but not to proliferation of the cells.

Animals↗

PubMed1987

Increased bone turnover during gonadotropin-releasing hormone superagonist-induced ovulation inhibition.

Superactive stimulatory analogs of GnRH inhibit ovulation in women. This investigation was done to assess bone turnover during GnRH agonist-induced anovulation. Particular interest was directed to the effects of smoking, since smokers have an increased risk of osteoporosis. Fasting serum calcium, phosphate, PTH, and bone Gla-protein (osteocalcin) levels, as well as urinary calcium, cAMP, and hydroxyproline excretion and the renal tubular threshold for phosphate were determined before and after 6 months of GnRH superagonist contraceptive treatment in 47 women, 22 of whom smoked more than 10 cigarettes daily. Before treatment the women who smoked had significantly higher serum phosphate concentrations and lower serum PTH concentrations than the women who did not smoke. Fasting serum calcium and the urinary calcium to creatinine ratio increased after treatment in all women, especially in the nonsmokers. The nonsmokers also had more pronounced increases in serum phosphate and osteocalcin concentrations. A decrease in serum PTH during treatment was confined to the nonsmokers. These results suggest increased bone resorption and turnover during GnRH agonist-induced anovulation and indicate that smoking habits should be taken into account in the evaluation of bone disease.

Adult↗

PubMed1987

Parathyroid hormone release in vitro in hyperparathyroidism associated with multiple endocrine neoplasia type 1.

Hyperparathyroidism (HPT) in the syndrome of multiple endocrine neoplasia type 1 (MEN-1) exhibits a different picture regarding its propensity for recurrence compared with sporadic primary HPT. In order to shed further light on the MEN-1 syndrome an investigation in vitro was made of parathyroid hormone (PTH) release of dispersed parathyroid cell from 11 patients with parathyroid hyperplasia associated with MEN-1, 10 patients with single parathyroid adenomas, and 10 preparations of normal bovine parathyroid glands. The two patient groups had the same average serum calcium value prior to surgery. Immunoreactive concentrations of PTH were measured after 2-h incubations at extracellular calcium concentrations of 0.5-3.0 mmol/l. Compared with the normal bovine parathyroid cells, the cells of the MEN-1 patients had a reduced calcium sensitivity of the PTH release and secreted smaller amounts of hormone at both low and high extracellular calcium concentrations. A similar abnormality of the PTH release was found for the cells of the hyperplastic and adenomatous parathyroid glands. Although individual parathyroid glands were investigated in only three MEN-1 patients, the results suggested the secretory regulation to be less defective in the small glands of each patient. It is concluded that in patient groups matched for serum calcium, the parathyroid tissue of MEN-1 patients has an abnormality of the PTH release similar to that of parathyroid adenomas.

Adenoma↗

PubMed1987

Optimal discrimination of mild hyperparathyroidism with total serum calcium, ionized calcium and parathyroid hormone measurements.

The serum concentrations of calcium, albumin and parathyroid hormone (PTH) and the plasma levels of ionized calcium were determined in 124 healthy subjects, 89 patients with primary hyperparathyroidism (HPT), 23 of whom had the syndrome of multiple endocrine neoplasia type 1 (MEN-1) and 43 patients who had hypercalcaemia of other causes than HPT (non-HPT), in most cases due to widespread malignancies. The total serum calcium was corrected for the serum albumin concentration (CaM). Healthy females over the age of 50 had higher CaM, than younger females and the women of all ages also had, higher serum PTH levels than males. For all study groups both the intra- and inter-diurnal variations were small for all the studied variables. Discriminant function and optimal discriminatory limits were calculated with the help of computer programs. A consideration of all the individuals in the discriminant analysis, revealed that measurements of CaM alone separated most HPT patients both from the healthy subjects and from the non-HPT patients. However, when only those who had borderline values (defined as CaM between 2.45 and 2.75 mmol/l) were included it turned out that measurements of ionized calcium markedly improved the delineation of mild HPT from the healthy subjects and that, in addition, PTH measurements helped to exclude those with non-HPT hypercalcaemia. The optimal discriminatory levels of serum calcium were calculated as the levels which caused the minimum loss in terms of misclassification when attention was paid to the relative importance of false positive to false negative classifications and to the prevalence of HPT. The optimal discriminatory level for serum calcium for a weighting ratio between false positive to false negative of 1:1, and a prevalence of HPT of 1%, was calculated to be 2.68 mmol/l and for a prevalence of 50% 2.56 mmol/l. In the latter situation a weighting ratio of 10:1 for false positive to false negative gave a level of 2.63 mmol/l while a weighting ratio of 1:10 corresponded to an optimal discriminatory level of 2.47 mmol/l.

Adolescent↗