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Biomedical subjects

S Ljunghall

Publications and source records attributed to S Ljunghall.

At least 181 records · Page 10Linked to original sources
PubMed1991

Thrombin increases cytoplasmic Ca2+ and stimulates formation of prostaglandin E2 in the osteoblastic cell line MC3T3-El.

Using microfluorometric analysis in individual, fura-2 loaded cells, we found that thrombin (0.1-10 U/ml) caused a dose-dependent (EC50 approximately 0.5 U/ml), rapid (within seconds), transient increase in cytoplasmic Ca2+ in the osteoblastic cell line MC3T3-El. The thrombin induced rise in cytoplasmic Ca2+ was not dependent on extracellular Ca2+ and was unaffected by indomethacin. In MC3T3-El cells, thrombin (0.3-10 U/ml) caused a rapid and dose-dependent (EC50 approximately 0.5 U/ml) stimulation of PGE2 formation. The calcium ionophore A23187 (2 mumol/l) also rapidly stimulated an increase in cytoplasmic Ca2+ and the formation of PGE2 in MC3T3-El cells. These data indicate that thrombin mobilizes Ca2+ from intracellular stores and that Ca2+ may serve as a second messenger in thrombin induced stimulation of PGE2 biosynthesis in osteoblasts.

Animals↗
PubMed1991

Cerebrospinal fluid calcium, parathyroid hormone, and monoamine and purine metabolites and the blood-brain barrier function in primary hyperparathyroidism.

Psychiatric disturbances are common in primary hyperparathyroidism (HPT), but their pathogenesis is essentially unknown. This study deals with cerebrospinal fluid (CSF) calcium homeostasis and its connection with parathyroid hormone (PTH), blood-brain barrier (BBB) function, and central monoamine and purine metabolites in patients with primary HPT. In 22 patients with primary HPT (serum calcium 2.85 +/- 0.21 mmol/l), the CSF concentrations of total and ionized calcium were higher (1.21 +/- 0.08 mmol/l, p less than 0.01, and 1.09 +/- 0.05 mmol/l, p less than 0.001, respectively) than in 11 normocalcemic reference subjects. The values correlated with serum calcium concentration (p less than 0.001) and CSF/serum albumin ratio, a measure of BBB permeability. The latter ratio was elevated in one-third of the patients with HPT, indicating BBB damage. CSF immunoreactive intact PTH was higher in the HPT patients than in the reference group (p less than 0.05), and serum and CSF PTH were positively correlated (p less than 0.05). The CSF levels of the monoamine metabolites 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) were lower, and the level of urate in CSF was higher, in the HPT patients than in the reference subjects, while there were no consistent differences in CSF hypoxanthine or xanthine. CSF 5HIAA correlated inversely with CSF ionized calcium (r = -0.42, p = 0.02). After parathyroid surgery, CSF calcium and urate decreased significantly and CSF monoamine metabolites increased slightly. The decrease in CSF ionized calcium correlated with the alleviation of psychiatric symptoms. The results indicate the importance of increased CSF calcium concentrations in patients with primary HPT and suggest a relation between central calcium regulation and central turnover of monoamines.

Blood-Brain Barrier↗
PubMed1991

Serum chloride in the differential diagnosis of hypercalcemia.

In hospitalized patients primary hyperparathyroidism (HPT) and neoplasms account for more than 90% of all hypercalcemias. Measurements of parathyroid hormone, particularly when combined with dynamic tests using calcitonin and EDTA have a high specificity and sensitivity in the differential diagnosis of hypercalcemia but are time-consuming and costly for screening purposes. Most chemical autoanalyzers beside serum calcium also measure serum chloride, phosphate and albumin. In order to evaluate how these simple variables could differentiate between HPT and hypercalcemia due to malignant disorders, 110 measurements from HPT subjects and 111 measurements from cancer patients with hypercalcemia were used. Serum chloride was best among the simple variables to separate the two disorders and classified 84% of the hypercalcemic subjects correctly. When serum phosphatase and albumin were added giving the formula (serum chloride-84) x (albumin-15)/phosphate, only 3% of the cancer and 4% of the HPT subjects were misclassified when borderline values (400-500) were excluded (5% of the sample). In conclusion, while other more sensitive and expressive tests exist to establish the cause of hypercalcemia the above mentioned formula is a cheap and easy screening test for a preliminary diagnosis.

Chlorides↗
PubMed1991

Blood pressure response during long-term treatment with magnesium is dependent on magnesium status. A double-blind, placebo-controlled study in essential hypertension and in subjects with high-normal blood pressure.

Both experimental and epidemiological studies support the idea of magnesium supplementation in essential hypertension. We added 15 mmol Mg to a free diet in 71 subjects with mild essential hypertension or a high-normal blood pressure in a double-blind, placebo-controlled study over 6 months. The treatment, which raised urinary magnesium excretion 30%, induced no general effects on the blood pressure. However, when the changes in blood pressure in the actively treated group were related to the pretreatment magnesium status, a correlation was found between pretreatment urinary magnesium excretion and the induced change in supine blood pressure (P less than .05) with a blood pressure reduction in subjects with a low pretreatment urinary excretion of magnesium, and a pressor effect in the subjects with the highest pretreatment levels of urinary magnesium. The induced change in blood pressure was furthermore found to be inversely correlated to the changes in serum magnesium and urinary excretion of sodium (P less than .03) induced by treatment indicating that both a direct calcium antagonist action of magnesium at the cellular level as well as a diuretic effect of the increased magnesium load might be involved in the blood pressure effects of magnesium. Pretreatment serum potassium concentration also appeared to be a predictor of the induced change in standing blood pressure (P less than .03). In conclusion, magnesium supplementation does not seem to be effective in unselected mild hypertensive subjects or in subjects with a high-normal blood pressure and can therefore not be generally recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1991

Effects of adrenaline and mental stress on serum digoxin concentration.

Physical activity and pharmacological stimulation of beta 2-adrenoceptors by salbutamol increase skeletal muscle digoxin binding with a secondary decrease in serum digoxin, possibly due to increased Na-K-ATPase activity. The present study was undertaken to examine if adrenaline (ADR) infusion and sympathoadrenal stimulation by mental stress affect the serum concentrations of digoxin and potassium. After 10 days on 0.50 mg digoxin orally, 35 healthy volunteers were investigated following 2 h of supine rest. They were divided into four groups: intravenous saline (placebo, n = 10). ADR infusion at the rates of 0.1 nmol kg-1 min-1 (ADR-L, n = 8), 0.4 nmol kg-1 min-1 (ADR-H, n = 7), or subjected to a mental stress [a color-word conflict test (CWT), n = 10]. Arterial blood samples were taken before and during the active period (50 min) and during the following 60 min (at rest) to analyze serum digoxin and potassium and plasma ADR and noradrenaline (NA). All variables were stable during placebo infusion. ADR infusions caused significant and dose-dependent decreases in serum digoxin (p less than 0.05 during ADR-L and p less than 0.001 during ADR-H) and serum potassium (p less than 0.05 and p less than 0.001, respectively). CWT, on the other hand, did not reduce serum digoxin and caused a slight decrease in serum potassium only in the poststress period. Thus, ADR caused dose-dependent shifts of digoxin and potassium, whereas mental stress failed to do so, possibly due to a modest ADR response and small increases in sympathetic nerve activity in skeletal muscle.

Administration, Oral↗
PubMed1991

Skeletal responsiveness to parathyroid hormone in healthy females: relationship to menopause and oestrogen replacement.

In order to directly evaluate the role of parathyroid hormone (PTH) and its interaction with oestrogens for postmenopausal bone loss, studies were performed where synthetic human (1-38) PTH was infused s.c. over 24 h in 15 healthy females. Measurements were made of serum electrolytes, PTH and biochemical indices of bone turnover: serum osteocalcin and alkaline phosphatase and fasting urinary hydroxyproline and calcium. During the infusion of PTH there were significant increases of serum calcium (15%), fasting urinary calcium (55%) and hydroxyproline (80%) but a reduction of the serum osteocalcin concentrations (15%). There were significant relations between the calcaemic response and the increases of urinary calcium and hydroxyproline and the two latter were also closely related. There was, however, no correlation between the responses to PTH for the formative vs the resorptive indices. Postmenopausal women displayed greater increases of serum calcium and fasting urinary hydroxyproline indicating greater skeletal sensitivity to exogenous PTH. Following treatment with oestrogens the indices of skeletal responsiveness were reversed towards the premenopausal values. The findings demonstrate that during short-term infusion of PTH there is a dissociation between bone resorption and formation and, furthermore, that the menopause is associated with an enhanced skeletal sensitivity for PTH.

Adult↗
PubMed1991

Cardiovascular risk factors in primary hyperparathyroidism: a 15-year follow-up of operated and unoperated cases.

The need for treatment of mild and apparently asymptomatic primary hyperparathyroidism (HPT) is questioned, but a raised incidence of cardiovascular disease has been regarded as evidence in favour of surgery. While it is well known that several risk factors for cardiovascular disease (hypertension, hyperlipidaemia and diabetes mellitus/impaired glucose tolerance) are overrepresented in HPT, it is not known whether surgery provides long-term normalization in these respects and reduces the risk of premature death. In a 15-year follow-up of a cohort of 172 subjects in whom mild hypercalcaemia was initially detected during a health screening, it was found that 56 subjects had died. 17 individuals had been operated on for HPT, 47 individuals were persistently hypercalcaemic, while 45 subjects had serum calcium within the normal range (seven individuals were lost to follow-up). There had been no significant differences in blood pressure between these groups of mildly hypercalcaemic patients and age- and sex-matched controls at the initial screening, but at follow-up blood pressure was significantly higher not only in subjects with persistent hypercalcaemia, but also in those who had been successfully operated on for HPT. Neither of the hypercalcaemic groups showed any significant deviations from the controls with regard to indices of lipid or glucose metabolism. These findings suggest that there is no simple cause-and-effect relationship to account for the propensity toward high blood pressure in primary HPT. Consequently it cannot be assumed that surgery for HPT will eliminate the increased risk of cardiovascular disease in patients with mild HPT.

Cardiovascular Diseases↗
PubMed1991

Vasoactive intestinal polypeptide stimulates parathyroid hormone release by interaction with cyclic adenosine monophosphate production of bovine parathyroid cells.

Influence of vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene-related peptide, and substance P was investigated on dispersed parathyroid cells of adult cattle. At a physiological concentration of extracellular calcium, vasoactive intestinal polypeptide stimulated the parathyroid hormone release in a dose-dependent manner, whereas no effects were noted for the other peptides. The dependency of PTH secretion upon extracellular calcium was shifted to the right by vasoactive intestinal polypeptide at 10(-6) mol/l, with a tendency for greater effects at low (0.5 mmol/l) than high concentrations (2.0-3.0 mmol/l) of the cation. Vasoactive intestinal polypeptide significantly enhanced cAMP release of the parathyroid cells, whereas no influence was noted on cytoplasmic calcium or pH within the cells. The results suggest that vasoactive intestinal polypeptide stimulates the PTH release by interaction with cAMP production of the parathyroid cells. This effect may contribute to the development of hypercalcemia in patients with neuroendocrine tumours secreting vasoactive intestinal polypeptide.

Animals↗
PubMed1991

Values of intact serum parathyroid hormone in different stages of renal insufficiency.

Intact serum parathyroid hormone (PTH) values were determined in 136 patients consulting the out-patient clinic for renal medicine and in 36 patients on maintenance hemodialysis in order to reveal the extent of parathyroid involvement in different stages of renal insufficiency. Elevated PTH values were found in 53 of the conservatively treated patients and in all but 4 of those on hemodialysis. Serum creatinine values and the duration of uremia correlated significantly to serum PTH, and multivariate analyses revealed that these variables were of dominating importance in determining the extent of PTH elevation. The negative relationship between PTH and plasma ionized calcium indicated maintained calcium regulation of hormone release from the parathyroid, although a relative secretory autonomy seemed to develop in parallel with the functional renal impairment. It is concluded that measurements of intact serum PTH values can demonstrate parathyroid hypersecretion in early renal insufficiency and constitutes a useful tool in the management of patients with renal disease.

Adolescent↗
PubMed1991

Reduction in serum alkaline phosphatase levels by treatment with active vitamin D (alphacalcidol) in primary and secondary hyperparathyroidism and in euparathyroid individuals.

Raised levels of alkaline phosphatases (ALP) are seen in conditions with a high bone turn-over, such as in primary and secondary hyperparathyroidism (HPT). To study the effects of active vitamin D treatment on ALP, alphacalcidol (1-alpha-hydroxyvitamin D3), was given to patients with primary HPT as well as HPT secondary to chronic renal failure and also to healthy, euparathyroid subjects. Oral alphacalcidol (1 microgram daily) significantly reduced serum ALP (3.2 +/- 1.1 to 2.8 +/- 1.2 mu kat/l, p less than 0.05) in a 6-month double-blind, placebo-controlled study in patients with mild primary HPT, and alphacalcidol given intravenously to uremic subjects induced a reduction in serum ALP levels (3.5 +/- 3.1 to 2.6 +/- 1.7 mu kat/l, p less than 0.05) during a 4 months' study. A reduction in serum ALP was also seen in the euparathyroid subjects (2.4 +/- 0.77 to 2.2 +/- 0.64 mu kat/l, p = 0.03). This study indicates that treatment with active vitamin D is effective in reducing the increased bone turnover seen in subjects with both primary and secondary HPT.

Aged↗
PubMed1991

Potassium and blood pressure.

The relationships between serum potassium and urinary excretion of potassium and blood pressure were determined in an unmedicated adult population with a wide range of blood pressure (mean arterial blood pressure 100-130 mm Hg, n = 71). Inverse correlations between both serum potassium concentration and urinary excretion of potassium and standing (but not supine) mean blood pressure were seen (r = -0.41, p less than 0.005 and r = -0.33, p less than 0.01 respectively). These relationships persisted also when the influences of age, sex, obesity and kidney function were taken into account in a multiple regression analysis. The present observation is in accordance with previous reports of an association between potassium metabolism and blood pressure.

Aged↗
PubMed1991

No major metabolic alterations accompany the hypotensive effect of active vitamin D.

A hypotensive effect of active vitamin D treatment (alphacalcidol 1 mg daily) has previously been reported in three double-blind, placebo-controlled studies over 4-6 months in subjects with mild primary hyperparathyroidism (HPT), intermittent hypercalcemia and essential hypertension. The commonly used antihypertensive drugs, thiazides and betablockers, both induce impairments in both glucose and lipid metabolism and the thiazides are known to cause an elevation of serum urate. The effects of vitamin D treatment on these metabolic variables were recorded in these studies. Alphacalcidol did not induce any changes in fasting glucose HbA1c or insulin, serum triglycerides, cholesterol or serum urate in any of the treated groups. Neither was HDL cholesterol affected, except for a rise seen in the HPT subjects. It is therefore concluded that no major metabolic alterations in glucose or lipid metabolism or serum urate accompany the hypotensive effect of vitamin D.

Aged↗
PubMed1991

Short-term effects of pamidronate on biochemical markers of bone metabolism in osteoporosis--a placebo-controlled dose-finding study.

The bisphosphonates are potent inhibitors of osteoclastic bone resorption that mainly have been used for treatment of hypercalcaemia secondary to malignancy. We have performed a controlled dose-finding study of oral pamidronate that was given to 60 patients with a history of fracture of the distal forearm, an enhanced bone turnover and a lowered bone mineral density. Different doses of pamidronate, 75 mg and 150 mg daily, or placebo were given to parallel groups. Fasting specimens of blood and urine were collected before the treatment period and at regular intervals. Oral pamidronate caused a dose-related reduction on the biochemical markers of bone resorption, i.e. fasting urinary calcium, hydroxyproline, pyridinoline and deoxypyridinoline that was seen already after the first week. The inhibition was evident during the treatment period and 4 weeks thereafter but not 12 weeks after cessation of therapy. Also the levels of serum osteocalcin, a marker of bone formation, were lowered during treatment with the higher dose.

Administration, Oral↗
PubMed1991

Hypertension in primary hyperparathyroidism in relation to histopathology.

Hypertension in primary hyperparathyroidism (HPT) was previously attributed to hypercalcemia per se or to impaired kidney function. Of 441 consecutive patients operated on for HPT over 24 years, 57% were hypertensive. Preoperative blood pressure remained fairly constant during the study period, despite otherwise markedly changing clinical picture with, latterly, more asymptomatic patients. The preoperative systolic blood pressure (SBP) was significantly correlated to both serum calcium (p less than 0.001) and serum creatinine (p less than 0.05), but not when the influence of age was taken into account in a multiple regression analysis. Other pathogenetic factors in hypertension were therefore probable. When the statistical analysis was adjusted for differences in age and serum calcium, blood pressure was lower in the HPT patients with parathyroid hyperplasia than in those with adenoma (153 +/- 31/90 +/- 14 vs. 163 +/- 29/91 +/- 14 mmHg, p less than 0.01 for SBP). The concept that parathyroid hyperplasia represents a mild (early) form of HPT that may precede adenoma formation is corroborated by our observations, which also indicate that there is no simple cause-and-effect relationship accounting for hypertension in primary HPT.

Adult↗
PubMed1991

Disturbance of basal and stimulated serum levels of intact parathyroid hormone in primary hyperparathyroidism.

In patients with primary hyperparathyroidism, measurements were made of basal and stimulated levels of intact parathyroid hormone (PTH). The basal PTH values were elevated in all but six of 89 patients and provided clear separation towards normal individuals (n = 75) and patients with hypercalcemia of other origin (n = 34). The PTH value correlated with the serum calcium concentration in hyperparathyroidism and with the weight of excised parathyroid adenomas but not with that of chief cell hyperplasias. A constant ethylenediaminetetraacetic acid infusion during 60 minutes of induced essentially linear reductions of plasma-ionized calcium concentrations, averaging 0.02 mmol/L/10 minutes, which were associated with swift, curvilinear, elevations of PTH levels that reached a plateau after 10 to 20 minutes. The increment in serum PTH level correlated with the basal PTH value both in patients with hyperparathyroidism and controls. However, in proportion to the much greater glandular mass in the patients with hyperparathyroidism, the secretion of PTH was relatively reduced. The findings support the value of the intact PTH assay in the differential diagnosis of hypercalcemia and show that PTH secretion in vivo is extremely sensitive to hypocalcemic stimulation, that the pathological parathyroid tissue in hyperparathyroidism is characterized by a reduction of hormone release per unit weight, and that the hormone secretion in hyperparathyroidism operates closer to its maximal capacity than under normal circumstances.

Adult↗
PubMed1991

[Primary hyperparathyroidism--a frequently overlooked cause of psychological symptoms].

Studies in recent years have demonstrated that nervous symptoms are common in hyperparathyroidism but that they are often overlooked even in very serious cases. The mechanisms behind the symptoms have to some extent been surveyed and show that operation, which normalizes the parathyroid function, also leads as a rule to considerable improvement of the patient's nervous symptoms.

Aged↗