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Biomedical subjects

S Ljunghall

Publications and source records attributed to S Ljunghall.

At least 127 records · Page 7Linked to original sources
PubMed1994

Cytoplasmic calcium regulation and the electrocardiogram in patients with primary hyperparathyroidism.

Primary hyperparathyroidism (HPT) is a disease caused by an abnormal cytosolic regulation of calcium concentration [Ca++]i leading to an increased secretion of parathyroid hormone and thereby increased levels of extracellular calcium. It is well known that the QT-interval measured at electrocardiography (ECG) is shortened in HPT subjects. Whether this is due to an abnormal intracellular handling of calcium also in the heart or to the raised extracellular calcium levels is not known. In order to study the extent to which the deranged extra- and intracellular levels of calcium in HPT patients were related to ECG characteristics, [Ca++]i was determined in vitro by microfluorometry in surgery-removed parathyroid cells at extracellular calcium concentrations of 0.5 mM and 30.0 mM and ECG was recorded preoperatively in 42 HPT patients and in 15 subjects operated on for atoxic goitre. Serum calcium and plasma-ionized calcium also were measured preoperatively. The QT-interval and ST-segment duration were both shortened in the HPT patients compared to controls (P < 0.001). [Ca++]i at 3.0 mM extracellular calcium divided by that at 0.5 mM was correlated to the QT-interval, when measured at the onset of the T-wave (QoT, r = 0.39, P < 0.03) and early diastolic phase (end of T-wave to onset of p-wave, r = -0.34, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Electrocardiographic changes during antihypertensive treatment with diltiazem in relation to the achieved serum levels of the drug.

Diltiazem is a calcium channel blocker with antihypertensive and antiarrhythmic actions. In the present study 24 hypertensive patients were treated with diltiazem (180-360 mg daily) for 6 months. The effects on the electrocardiogram (ECG) were studied and were related to the serum levels of diltiazem. Treatment with diltiazem induced a non-significant reduction in heart rate with 3 beats min-1 and decreased blood pressure (-11/-9 mm Hg, p < 0.001). The treatment also induced a prolongation of the PQ-interval (+1.4 cs, p < 0.02), a prolongation only being weakly related to the plasma levels of diltiazem (r = 0.28, not significant) and its metabolite MA (r = 0.37, p = 0.07). Neither was the induced increase in the QT-interval (+0.9 cs, p < 0.05), significantly related to the plasma levels of diltiazem. In conclusion, the plasma levels of diltiazem were not clearly related to the induced changes at the ECG during antihypertensive treatment.

Adult↗
PubMed1994

Relationship between abnormal regulation of cytoplasmic calcium and elevated blood pressure in patients with primary hyperparathyroidism.

Primary hyperparathyroidism (HPT) is characterised by a defective calcium sensitivity of the parathyroid glands. HPT is, furthermore, associated with a high prevalence of hypertension. In the present study BP was measured before operation, during surgery and after operation in 42 HPT patients and in 15 control subjects operated for non-toxic goitre. Parathyroid tissue was removed from all patients and the concentration of cytoplasmic calcium [Ca2+]i was determined in vitro in dispersed single cells by means of microfluometry at extracellular calcium concentrations of 0.5 mM and 3.0 mM. The SBP levels were found to be raised both before (158 +/- 23 (SD) mmHg vs. 144 +/- 24 mmHg in controls, P < 0.05), during surgery (maximal level 167 +/- 22 mmHg vs. 146 +/- 16 mmHg in controls, P < 0.01) and after operation (maximal level 180 +/- 26 mmHg vs. 148 +/- 20 mmHg in controls, P < 0.001) in the HPT subject when compared with controls. SBP during surgery was found to be related to the in vitro measured [Ca2+]i in the parathyroid cells at 3.0 mM extracellular calcium concentration or to the ratio of [Ca2+]i at 3.0 mM-0.5 mM (r = -0.25 and -0.27, respectively; P < 0.05). The degree of suppression of PTH release in vitro at 3.0 mM extracellular calcium was found to be related to both systolic and diastolic BP (r = 0.57 and r = 0.53, respectively; P < 0.05) before surgery. In conclusion, BP was found to be raised in HPT patients both before operation as well as during surgery and after operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

The cyclic-AMP antagonist adenosine-3',5'-cyclic monophosphosphorothioate, RP-isomer inhibits parathyroid hormone induced bone resorption, in vitro.

Stimulation of osteoclastic bone resorption is mediated via the osteoblasts. In order to investigate the second messenger events that cause the osteoblasts to initiate bone resorption we have evaluated the effect of the cyclic AMP antagonist adenosine-3'5'-cyclic monophosphosphorothioate, Rp-isomer (Rp-cAMPS) on bone resorption in vitro, by measuring the release of prelabelled 45Ca from cultured neonatal mouse calvarial bones. Forskolin (FSK, at and above 10 nM), an agent that enhances cyclic AMP-formation, stimulated bone resorption in 96 h cultures. Addition of Rp-cAMPS to the incubation media dose-dependently inhibited bone resorption induced by FSK (0.5 microM), with total inhibition obtained at 30 microM Rp-cAMPS. Bone resorption stimulated by parathyroid hormone (PTH, 0.1-10 nM, 72 h) was also inhibited by Rp-cAMPS (30 microM), while bone resorption induced by 1.25(OH)2D3 (1-10 nM, 72 h) was unaffected by Rp-cAMPS. These data demonstrate that PTH and 1,25(OH)2D3 cause bone resorption via different mechanisms and that cyclic AMP is the major second messenger in PTH-induced bone resorption.

Animals↗
PubMed1993

Reverse transcription-polymerase chain reaction assay demonstrates that the 9-cis retinoic acid receptor alpha is expressed in human osteoblasts.

The 9-cis retinoic acid receptor (RXR) alpha, a co-regulator of the thyroid hormone and vitamin D receptors, has previously been shown to be expressed predominantly in metabolic organs such as the liver and the kidney. In this study we have used a reverse transcription polymerase chain reaction (RT-PCR) to examine the expression of retinoic acid (RA) nuclear receptors in primary human osteoblasts and in SaOS-2, a human osteosarcoma-derived cell line with osteoblastic characteristics. Our results demonstrate that human osteoblasts express RXR alpha, as well as the all-trans RA receptors (RAR) alpha, beta, and gamma. These data further establish bone as a major target for retinoids and suggest that RA can regulate vitamin D and thyroid hormone actions in osteoblasts.

Base Sequence↗
PubMed1993

Role of protein kinase C in bradykinin-induced prostaglandin formation in osteoblasts.

UNLABELLED: Bradykinin (1 microM, 5 min) induced translocation of protein kinase C (PKC) to the plasma membrane fraction in osteoblastic MC3T3-E1 cells. Bradykinin also enhanced the binding of phorbol 12,13-dibutyrate (PDBu) to intact cells, a measure of PKC activation. Addition of bradykinin (1 microM) to cells preincubated with [3H]PDBu (10 nM, 20 min) caused an increase in specific PDBu binding that was maximal after 5-10 min. The bradykinin-induced enhancement of PDBu binding was seen at 1 nM and was maximal at 10 nM. The bradykinin B1 receptor agonist des-Arg9-bradykinin (1 microM) did not enhance specific PDBu binding to intact MC3T3-E1 cells. PDBu at and above 3 nM stimulated the formation of prostaglandin E2 (PGE2) in MC3T3-EI cells. This stimulatory effect was seen after 15-20 min incubation. The Ca2+ ionophore A23187 at and above 1 microM induced a rapid (within seconds) burst of PGE2 formation in MC3T3-E1 cells. The effect of PDBu and A23187 on PGE2 formation was synergistic. The PKC inhibitor staurosporine (200 nM) inhibited basal as well as bradykinin-induced prostaglandin-formation in MC3T3-E1 cells. IN CONCLUSION: bradykinin enhances PKC activation in osteoblastic MC3T3-E1 cells. This kinase activation may be involved in bradykinin-induced prostaglandin formation.

Alkaloids↗
PubMed1993

Fracture of the distal forearm as a forecaster of subsequent hip fracture: a population-based cohort study with 24 years of follow-up.

OBJECTIVE: To determine the long-term risk of hip fracture following fracture of the distal forearm. DESIGN: Registry-based cohort study comparing patients with a fracture of the distal forearm with a population-based cohort. FRACTURE COHORT: All women and men above 40 years of age with a radiologically verified fracture of the distal forearm during a 5-year period, 1968-1972, in all 1,126 women and 212 men. CONTROL COHORT: An equal number of population-based, age- and sex-matched control persons selected from a population register. MEASUREMENTS: All cohort members were followed up individually through record linkage until the first hip fracture, emigration, death, or the end of 1991. The cohort members contributed a total of 40,832 person-years of observation, and altogether 365 cases of hip fractures were observed. RESULTS: Both women and men with a fracture of the distal forearm ran an increased risk of sustaining a subsequent hip fracture. The overall relative hazard for the women was 1.54 and for men 2.27. The increased risk in the women was independent of age at inclusion, but that in the men was more pronounced in the younger age groups. CONCLUSIONS: Patients with a fracture of the distal forearm run an increased risk of sustaining a subsequent hip fracture. They therefore appear to constitute a group in which appropriate prophylactic measures against osteoporosis and fractures should be considered.

Adult↗
PubMed1993

Insulin-like growth factor I enhances the formation of type I collagen in hydrocortisone-treated human osteoblasts.

We have studied the effect of insulin-like growth factor I (IGF-I) on the formation of osteocalcin and type I collagen in isolated human osteoblasts. IGF-I at and above 0.1 nM stimulated the formation of type I collagen as measured by the type I procollagen carboxyterminal peptide (PICP), in human osteoblasts, incubated for 72 hrs in serum free conditions. The secretion of osteocalcin was not affected by IGF-I while 1,25(OH)2vitamin D3 significantly enhanced the formation of osteocalcin. When human osteoblast-like cells were incubated with hydrocortisone (1 microM), a significant decrease in the release of both PICP and osteocalcin was seen. Addition of IGF-I to human osteoblasts also treated with hydrocortisone normalized the PICP-formation but did not affect the suppressed osteocalcin-formation. These data indicate that IGF-I reverses selective effects of hydrocortisone on bone.

Calcitriol↗
PubMed1993

Serum osteocalcin and fracture susceptibility in elderly women.

The purpose of this investigation was to evaluate the bone turnover by using bone metabolic markers in relation to previous fracture history and independent of bone mass. Patients and controls were recruited from a population-based study of 193 women, all living in the same city and aged 60, 70, and 80 years. The bone mineral content (BMC) was measured bilaterally in the distal forearm by single-photon absorptiometry (SPA). At the same time, serum samples were obtained for biochemical analysis. Of the 193 women, we identified 26 with at least one major fracture during the past few years. Each of these 26 women with a certified recent previous fracture was individually matched with a woman from the same study group of equal BMC and age but without a fracture history. In the two groups, the serum samples were analyzed for osteocalcin, C-terminal procollagen peptide (P1CP), alkaline phosphatase, bone-specific alkaline phosphatase, calcium, phosphate, and albumin. The serum concentration of osteocalcin was 20% lower in the women with a previous fracture than in the controls (P = 0.03). The other markers of bone formation gave similar values in the two groups. There was a significant correlation between the osteocalcin and P1CP concentrations (P = 0.001). Our findings indicate that the susceptibility to fractures independent of factors such as age and BMC may be related to a decreased bone turnover.

Absorptiometry, Photon↗
PubMed1993

On the diversity of insulin secretion and sensitivity in subjects with impaired glucose tolerance.

Insulin secretion and sensitivity are basic characteristics determining the glucose tolerance. The aim of this study was to investigate if derangements in these two main characteristics were generally found in subjects with impaired glucose tolerance (IGT). The early insulin response at the intravenous glucose tolerance test (IVGTT) in 42 subjects with IGT was found to be correlated to the glucose tolerance (r = -0.38, p < 0.01 vs, fasting glucose and r = 0.35, p < 0.02, vs the k-value of IVGTT) while fasting insulin was found to be closely correlated to insulin sensitivity, measured by the euglycemic clamp method (r = -0.83, p < 0.003, n = 11). Using data obtained at the IVGTT's in the IGT subjects, different patterns of insulin secretion were found representing different combinations of impairments in insulin secretion and sensitivity. However, in the majority of the IGT subjects a marked decrease in the early insulin response and a fasting hyperinsulinemia were found. The present study suggest such a characterization by the IVGTT to be of importance for a better understanding of the dynamic interplay between insulin secretion and sensitivity in IGT subjects.

Blood Glucose↗
PubMed1993

Determination of body composition--a comparison of dual-energy x-ray absorptiometry and hydrodensitometry.

Determination of body composition by dual-energy x-ray absorptiometry (DEXA) was evaluated in healthy men, by using underwater weighing (UWW), skinfold thickness measurement, and bioimpedance analysis. There were strong correlations between percent body fat obtained by all techniques, but DEXA gave significantly lower values (P < 0.001). The influence of differences in bone mineral density (BMD) on fat content determined by UWW was also studied. The individual differences between UWW and DEXA fat estimates were calculated and there was a negative correlation with BMD (r = -0.50, P < 0.05). There was also a negative correlation between body fat by UWW and BMD (r = -0.71, P < 0.01) in the subjects with lowest fat by DEXA, indicating that high or low BMD gave false values by UWW. In conclusion, DEXA and UWW provide complementary information and a combination of these techniques seems to offer new opportunities in evaluations of body composition.

Absorptiometry, Photon↗
PubMed1993

On the relationships between mineral metabolism, obesity and fat distribution.

Alterations in calcium metabolism have been associated with cardiovascular risk factors. An altered binding of calcium to plasma proteins and raised levels of parathyroid hormone (PTH) have been described in morbid obesity. In the present study, indices of mineral metabolism were related to obesity (body mass index, BMI) and fat distribution (waist to hip ratio, w/h) in 194 subjects with a wide range of BMI and w/h. The ratio of total serum calcium to plasma ionized calcium (Ca2+) was found to be significantly correlated to both BMI (r = 0.20, P < 0.02) and w/h (r = 0.22, P < 0.005). Serum phosphate was also correlated to both of the indices of obesity in an inverse way (r = -0.24, P < 0.0008 for BMI and r = -0.33, P < 0.0001 for w/h). These relationships were still significant when the influences of age, sex and serum creatinine were included in the multiple regression analysis. This kind of analysis also disclosed that w/h was superior to BMI as a determinant of serum phosphate and the total calcium/Ca2+ ratio in serum. PTH was not significantly correlated to any of the indices of obesity. In conclusion, fat distribution rather than obesity per se was found to be associated with an altered mineral metabolism.

Adipose Tissue↗
PubMed1993

The risk of hip fractures in patients with primary hyperparathyroidism: a population-based cohort study with a follow-up of 19 years.

OBJECTIVE: To evaluate primary hyperparathyroidism (HPT) as a risk factor for hip fractures. DESIGN: A population-based, record-linked, prospective study with a mean observation time of 17 years (women) and 16.5 years (men). SETTING: A cohort obtained from a register of hospital admissions in the Uppsala Health Care Region, Sweden, 1965-1983. PARTICIPANTS: All patients (1373 women and 551 men) who were admitted to hospital with the diagnosis of HPT during the period. Comparisons were made with the entire background population. MEASUREMENTS: Cohort subjects were followed with regard to a first instance of hip fracture prior to or after the diagnosis of HPT. The observed number of cases was compared with that expected on the basis of person-years of observation and incidence rates in the background population. Analyses were made for cervical and trochanteric fractures, and for patients operated and not operated for HPT. MAIN RESULTS: (i) Women. During 23,341 person-years of observation, 67 cases of first hip fractures occurred, yielding a relative risk (RR) of 0.93 (95% confidence interval [CI] 0.72-1.19). The RR for cervical fractures was 0.77 (CI 0.54-1.06), and for trochanteric fractures 1.33 (CI 0.88-1.93). Operation for HPT did not influence the risk of hip fracture. (ii) Men. The total person-years was 9091. Eleven fractures were observed--compared with the expected 7.90 (RR 1.39; CI 0.69-2.50). Men operated for HPT had an increased risk for cervical hip fractures (RR 2.73; CI 1.18-5.39). Owing to the few fractures in this group (n = 8) the relevance of this is uncertain. CONCLUSIONS: This study indicates that HPT is not a risk factor for hip fractures in women.

Aged↗
PubMed1993

Maintained bone density at advanced ages after long term treatment with low dose oestradiol implants.

OBJECTIVE: To investigate whether the bone preserving effect of low dose oestrogen replacement therapy (20 mg oestradiol implanted subcutaneously every six months) persists during continuous long term treatment through advanced ages. DESIGN: Cross sectional clinical study of postmenopausal women treated with oestradiol implants as compared with nonusers matched for age. SETTING: Outpatient research unit at a university hospital. SUBJECTS: Thirty-five women with a mean age of 67 years (range 47-83 years) at the time of investigation who, after a prior hysterectomy, had been treated with oestradiol implants for climacteric symptoms for a mean period of 16 years (range 5.5-31 years). The results were compared with those in women matched for age and without any diseases or medications known to affect the bone metabolism. MAIN OUTCOME MEASURES: Bone mineral densities (BMD) in the distal forearm, vertebrae and hip analysed by study group, age and duration of treatment. RESULTS: Implant users had a median serum oestradiol concentration in the luteal range, 313 (range 126-1711) pmol/l, and premenopausal levels of follicle stimulating hormone (FSH). All women except one who were given the standard dose at the standard intervals had serum oestradiol levels below 650 pmol/l. Compared with nonusers, women treated with oestradiol implants had 20 to 25% higher BMD at all measurement sites: distal radius (P < 0.0001), lumbar vertebrae (P < 0.0002) and femoral neck (P < 0.0001). These differences also remained after adjustment for potential confounders (height, age at menarche, parity, smoking habits, physical exercise and education) (P < or = 0.01 at all sites). In a multiple regression analysis the negative effect of advancing age was more than compensated by the positive effect of increasing treatment duration with a higher BMD at all measurement sites in women with a longer as compared with shorter, duration of treatment; the regression coefficients were significant (P < 0.05) in the spine and hip measurements. CONCLUSIONS: Continuous long term treatment with low dose oestradiol implants yielding physiological levels of serum oestradiol preserves both compact and cancellous bone and the effect seems to persist into advanced ages without any inevitable age related bone loss.

Aged↗