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| 3. |
- Andren, Bertil, et al.
(författare)
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The influence of body composition on left ventricular mass and other echocardiographic and Doppler measurements in 70-year-old males
- 1995
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Ingår i: Clinical Physiology. - 0144-5979 .- 1365-2281. ; 15:5, s. 425-433
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Tidskriftsartikel (refereegranskat)abstract
- Heart morphology and function are often related to body size. The most common way to standardize for body composition is to divide these measures by body surface area (BSA). It has, however, been suggested that left ventricular mass (LV mass) ought to be indexed for height and that cardiac output is influenced by the body fat distribution.As part of a health screening programme of 70-year-old males in Uppsala, Sweden, 100 consecutive men were investigated with echocardiography and Doppler with regard to cardiac morphology and function. These measures were related to an evaluation of body composition using an X-ray method (dual energy X-ray absorptiometry).Lean body mass was strongly related to BSA and body weight (r=0.90 and 0.89, respectively; P<0.001), and to a lesser degree to height (r=0.70, P<0.0001). In the healthy part of the population (n=39), relationships between LV mass on the one hand and lean body mass, BSA and height on the other were seen (r=0.51, 0.51 and 0.50, respectively; P<0.01). Stroke volume calculated according to Teichholtz (but not when calculated with Doppler) showed a significant correlation to lean body mass (r=0.38, P<0.05). Also, left ventricular diameter and the thickness of the free wall were related to lean body mass (r=0.40 and 0.39, respectively; P<0.05). All of the evaluated relationships were generally weaker and in most cases no longer significant when evaluated in the part of the population with diseases known to affect the heart.No significant correlations were seen between the size of the left atrium, septal thickness or indices of diastolic function (E/A-ratio, isovolumic relaxation time, deceleration time) and the indices of body composition. No measures of cardiac morphology and function were significantly related to the amount of body fat or body bone.LV mass, stroke volume and left ventricular diameter were found to be correlated with lean body mass, but not with the amount of fat, in healthy 70-year-old males.
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| 11. |
- Brändström, Helena, et al.
(författare)
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Regulation of osteoprotegerin mRNA levels by prostaglandin E2 in human bone marrow stroma cells.
- 1998
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 0006-291X. ; 247:2, s. 338-41
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Tidskriftsartikel (refereegranskat)abstract
- The recently cloned osteoclastogenesis inhibitory factor, or osteoprotegerin (OPG), has been shown to be a potent inhibitor of osteoclast formation. The inhibition is believed to be mediated through specific binding of OPG to a cell surface ligand on osteoblastic stromal cells. In this report we have studied the effect of the bone resorbing agent prostaglandin E2 (PGE2) on OPG mRNA levels in primary cultures of human bone marrow stroma cells (hBMSC). PGE2 dose- and time-dependently down-regulated the mRNA levels of OPG, as measured by RNAse protection assay. After 4 hours of stimulation with 1 microM PGE2, OPG mRNA levels were significantly decreased. The inhibitory effect was seen at and above 1 nM of PGE2. To elucidate whether the OPG mRNA levels are regulated via the proteinkinase A and/or the proteinkinase C pathways we stimulated cells with either forskolin (FSK) or phorbolic ester (PDbu) respectively. FSK (10 microM) decreased OPG mRNA levels to 50 % of control, whereas PE (10 nM) upregulated the mRNA levels to 250 % of control. These data show that PGE2 down-regulates the expression of OPG mRNA in hBMSC, probably via an increase in cAMP. This mechanism might be involved in PGE2-induced bone resorption.
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| 12. |
- Brändström, Helena, et al.
(författare)
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Tumor necrosis factor-alpha and -beta upregulate the levels of osteoprotegerin mRNA in human osteosarcoma MG-63 cells.
- 1998
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 0006-291X. ; 248:3, s. 454-7
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Tidskriftsartikel (refereegranskat)abstract
- Osteoprotegerin (OPG) is a recently cloned soluble member of the tumor necrosis factor receptor family. OPG has been shown to inhibit osteoclast recruitment by binding to OPG-ligand, an osteoclast differentiating factor on osteoblastic stromal cells, thereby blocking osteoclastogenesis. In this report we have examined the effect of tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor-beta (TNF-beta) on OPG mRNA levels in the human osteosarcoma cell line MG-63. We demonstrate that both TNF-alpha and TNF-beta dose- and time-dependently upregulate the mRNA levels of OPG. The effect is significant at and above 5 pM of TNF-alpha and 1 pM of TNF-beta. The stimulatory effect on OPG mRNA levels in MG-63 cells was detected after 2 hrs of incubation with TNF-alpha or TNF-beta. These data demonstrate that the expression of OPG in osteoblasts, with subsequent effects on osteoclastogenesis, is regulated by TNFs.
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| 18. |
- Frost, Anders, et al.
(författare)
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Interleukin-13 inhibits cell proliferation and stimulates interleukin-6 formation in isolated human osteoblasts.
- 1998
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 83:9, s. 3285-9
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-13 (IL-13) is a recently identified cytokine that is secreted by activated T cells and regulates inflammatory responses. We have investigated the effects of IL-13 on isolated human osteoblast-like cells (hOB). IL-13 dose-dependently (1-100 pmol/L) reduced the incorporation rate of [3H]thymidine in hOB cells by more than 50%. Using a cell metabolic assay as well as direct cell counting, we found that treatment with IL-13 lead to a decrease in hOB cell number. The effect was both time and dose dependent, and after 12 days of culture, treatment with IL-13 (0.1 nmol/L) caused a 70% decrease in the number of cells. Also, IL-13 increased the levels of IL-6 messenger ribonucleic acid in hOBs, as measured by ribonuclease protection assay, and stimulated secretion of IL-6 into culture supernatants. In conclusion, IL-13 inhibits cell proliferation and increases IL-6 formation in human osteoblasts. Our findings suggest that IL-13 may cause bone loss due to impaired osteoblastic growth and IL-6-induced osteoclast recruitment.
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| 26. |
- Holm, G, et al.
(författare)
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Renewal of the Journal
- 2001
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Ingår i: JOURNAL OF INTERNAL MEDICINE. - 0954-6820. ; 250:1, s. 1-2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 27. |
- Hvarfner, Andreas, et al.
(författare)
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Calcium metabolic indices, vascular retinopathy, and plasma renin activity in essential hypertension
- 1990
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Ingår i: American Journal of Hypertension. - 1941-7225. ; 3:12 Pt 1, s. 906-911
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Tidskriftsartikel (refereegranskat)abstract
- The interplays between calcium metabolic indices, retinal vascular status, plasma renin activity and blood pressure were examined in 67 patients with untreated essential hypertension. There was an inverse relationship between plasma ionized calcium and blood pressure (P = .002), whereas albumin-modified total serum calcium was directly related to blood pressure (P = .02). The plasma cyclic AMP level (P = .05) and the 24 h urinary excretion of cyclic AMP (P = .03) were also positively associated with blood pressure. Patients with vascular retinopathy had lower plasma ionized calcium concentrations (P = .01) and higher 24 h urinary cyclic AMP excretions (P = .05) than those without such changes, even when the differences in blood pressure, age, sex and body mass index were taken into account in analyses of covariance. Plasma renin activity did not interfere with the relationships between calcium metabolic indices and blood pressure, nor were there any associations between the renin status and the calcium metabolic indices. These findings suggest that a low concentration of plasma ionized calcium is an independent risk factor for vascular disease.
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| 29. |
- Hvarfner, Andreas, et al.
(författare)
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Indices of mineral metabolism in relation to blood pressure in a sample of a healthy population
- 1986
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Ingår i: Acta Medica Scandinavica. - 0001-6101. ; 219:5, s. 461-468
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Tidskriftsartikel (refereegranskat)abstract
- Indices of mineral metabolism in blood and urine were analysed in relation to blood pressure in 97 healthy subjects aged 16-82 years. In a multivariate analysis, after allowing for the effects of sex, body mass index (BMI) and age, there was an inverse relationship between plasma level of ionized calcium and mean blood pressure (MBP) (beta = -50.0 mmHg/mmol/l P-ionized calcium, p = 0.0005). In univariate analyses MBP also showed statistically significant inverse relationships with plasma ionized calcium, serum phosphate and renal threshold concentration of phosphate; positive relationships to MBP were found for fasting urinary excretion of calcium and cyclic adenosine monophosphate. However, when examined multivariately, only the relation between MBP and plasma ionized calcium persisted. This study supports previous findings of an inverse relationship between blood pressure and serum ionized calcium and extends the observations to the physiological range. It is further evident from this study that BMI and age should be taken into account in analyses of the relationship between blood pressure and mineral metabolism.
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| 30. |
- Hvarfner, Andreas, et al.
(författare)
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Interactions between indices of calcium metabolism and blood pressure during calcium infusion in humans
- 1989
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Ingår i: Journal of Human Hypertension. - 1476-5527. ; 3:4, s. 211-220
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 31. |
- Joborn, H, et al.
(författare)
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Serum electrolytes and parathyroid hormone in patients in a coronary care unit
- 1989
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Ingår i: Journal of Internal Medicine. - 1365-2796. ; 225:1, s. 9-14
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 41. |
- Lind, L, et al.
(författare)
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Fasting insulin, calcium metabolism and the electrocardiogram in hypertensive subjects
- 1992
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Ingår i: Journal of Internal Medicine. - 1365-2796. ; 232:4, s. 335-339
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Tidskriftsartikel (refereegranskat)abstract
- Changes in both calcium and insulin metabolism have been described in essential hypertension. Low levels of plasma ionized calcium (Ca2+) and high levels of insulin have previously been associated with vascular complications and coronary heart disease. In the present study, indices of calcium metabolism and fasting serum insulin were related to electrocardiographic (ECG) variables in 58 patients with untreated hypertension. Fasting insulin was found to be related to heart rate (r = 0.47, P < 0.001), diastolic interval (r = -0.39, P < 0.004) and electrical axis (r = -0.29, P < 0.03) while Ca2+ was found to be correlated with the QRS amplitude (r = -0.32, P < 0.03) and diastolic interval (r = 0.37, P < 0.02). Furthermore, non-ionized serum calcium was correlated with the QRS duration (r = 0.36, P < 0.02), ST-segment interval (r = -0.49, P < 0.002) and QT interval (QoT, r = -0.42, P < 0.008). These correlations were still significant when the influences of age, sex, obesity, blood pressure and heart rate were taken into account in the multiple regression analysis. In conclusion, the present study demonstrates that calcium and insulin metabolism are related to several basic characteristic functions of the heart, such as the systolic and diastolic function, as well as to signs of left ventricular hypertrophy.
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| 42. |
- Lind, L, et al.
(författare)
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Hypertension in primary hyperparathyroidism in relation to histopathology
- 1991
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Ingår i: European Journal of Surgery. - 1102-4151. ; 157:8, s. 457-459
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 43. |
- Lind, Lars, et al.
(författare)
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Hypertension in primary hyperparathyroidism--reduction of blood pressure by long-term treatment with vitamin D (alphacalcidol) : A double-blind, placebo-controlled study
- 1988
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Ingår i: American Journal of Hypertension. - 0895-7061 .- 1941-7225. ; 1:4 Pt 1, s. 397-402
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Tidskriftsartikel (refereegranskat)abstract
- Patients with primary hyperparathyroidism (HPT) often have raised blood pressure but a simple cause-and-effect relationship has not been established. In 33 persons with probable primary HPT and mild hypercalcemia detected in a health survey, diastolic blood pressure (DBP) was significantly higher than among age- and sex-matched, normocalcemic, controls (89.4 +/- 9.8 (SD) v 85.2 +/- 8.9 mm Hg; P less than 0.05). Among the hypercalcemic individuals, DBP was, in a multivariate analysis, inversely related to the serum calcium and plasma-ionized calcium concentrations and to the serum levels of parathyroid hormone. A prospective, placebo-controlled, double-blind, study evaluating the effects of active vitamin D, alphacalcidol, (1 microgram daily) was carried out in the hypercalcemic patients over a six-month period. This treatment caused a slight further increase (0.05 mmol/L) of both serum calcium and plasma-ionized calcium concentrations. At the same time there was a significant reduction of DBP with a mean of 6.7 mm Hg compared with placebo (P less than 0.05). The hypotensive action of the vitamin D compound was inversely related to the pretreatment serum levels of 1,25(OH)2D3 and additive to concomitant, unchanged, antihypertensive medications. The negative correlation between serum calcium and blood pressure is similar to that obtained in normocalcemic individuals and suggests that raised blood pressure, at least in the milder forms of primary HPT, is only independently associated with the disease. Active vitamin D, although it raises serum calcium, can lower blood pressure also in hypercalcemic patients as previously demonstrated in normocalcemic individuals.
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| 44. |
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| 45. |
- Lind, L, et al.
(författare)
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Indices of mineral metabolism in subjects with an impaired glucose tolerance
- 1990
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Ingår i: Experimental and Clinical Endocrinology. - 0232-7384. ; 96:1, s. 109-112
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Tidskriftsartikel (refereegranskat)abstract
- An altered mineral metabolism has been described both in insulin dependent and non-insulin dependent diabetes mellitus. In order to investigate if a disturbed mineral homeostasis was an early feature in the development of diabetes, 52 middle-aged men who all had recently developed an impaired glucose tolerance (IGT) were compared to healthy control persons. The IGT subjects showed higher levels of serum calcium (2.38 +/- 0.081 mmol/l (SD) vs 2.35 +/- 0.065 in controls) but similar levels of plasma ionized calcium indicating an increased protein binding of serum calcium in IGT. Serum magnesium was significantly lower in the IGT subjects (0.79 +/- 0.060 mmol/l vs 0.85 +/- 0.065, p less than 0.001) while serum phosphate was unaltered. This study demonstrates indices of an impaired mineral metabolism in IGT subjects similar in characteristics to what has previously been reported in manifest diabetes mellitus suggesting that an alteration of mineral homeostasis could be part of a primary event.
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| 46. |
- Lind, L, et al.
(författare)
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Influences of different antihypertensive treatments on indices of systemic mineral metabolism
- 1994
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Ingår i: American Journal of Hypertension. - 1941-7225. ; 7:4 Pt 1, s. 302-307
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Tidskriftsartikel (refereegranskat)abstract
- A negative calcium balance has previously been described in human hypertension with low levels of plasma ionized calcium (Ca2+) and an increased urinary excretion of calcium. The cause of this disturbance in mineral metabolism is not known, nor is it known if this derangement could be abolished if blood pressure is reduced by antihypertensive treatment. In the present investigation, the effects of antihypertensive monotherapy on serum and fasting urinary electrolytes were studied. For 3 to 6 months, 319 hypertensive patients entered 17 study groups, each group using one of the following antihypertensive drugs: dilevalol, metoprolol, antenolol, pindolol, propranolol, hydrochlorothiazide, bendrofluomethiazide, furosemide, spironolactone, doxazocine, prazocine, diltiazem, verapamil, nifedipine, isradipine, captopril, or lisinopril. Treatment with different beta-blockers, as well as diuretics, reduced the fasting urinary calcium excretion (P < .001). However, while the beta-blockers increased the proportion of the ionized form of calcium in blood (Ca2+) (P < .001), Ca2+ was further decreased by diuretic treatment (P < .05). Angiotensin converting enzyme inhibitors caused no major changes in mineral metabolism while of the calcium antagonists studied only verapamil raised the levels of Ca2+ (P < .01). No significant relationship between the changes in mineral metabolism and the reduction in blood pressure was observed in any of the treatment groups. Of the antihypertensive drugs used in the present study, beta-blockers appeared to reverse the basic abnormality with regard to calcium balance, suggesting that the activity of the sympathetic nerve system is involved in the disturbed calcium metabolism seen in hypertensive patients.
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| 47. |
- Lind, L, et al.
(författare)
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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
- 1989
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Ingår i: Diabetes Research (Edinburgh, Scotland). - 0265-5985. ; 11:3, s. 141-147
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 49. |
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| 50. |
- Lind, L, et al.
(författare)
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Serum calcium : a new, independent, prospective risk factor for myocardial infarction in middle-aged men followed for 18 years.
- 1997
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier BV. - 0895-4356 .- 1878-5921. ; 50:8, s. 967-73
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Primary hyperparathyroidism (HPT) is a disease characterized by hypercalcemia, and associated with an increased mortality in cardiovascular diseases. However, serum calcium levels within the normal range have not been evaluated as a prospective cardiovascular risk factor.METHODS: A cohort of males aged 50 (n = 2183) were investigated in 1970-1973 for serum calcium and known cardiovascular risk factors. They were then followed up over the next 18 years.RESULTS: During the follow-up period, 180 subjects experienced a myocardial infarction (MI). The serum calcium levels were significantly elevated at the baseline (2.37 +/- 0.09 SD versus 2.35 +/- 0.09 mmol/l, p < 0.03) in the subjects who developed a MI when compared with the rest of the cohort. Also blood pressure, body mass index (BMI), fasting insulin, serum cholesterol, serum triglycerides, and the atherogenic index were significantly elevated in the MI group (p < 0.01), while HDL-cholesterol was lower at the baseline investigation (p < 0.01). Cox's proportional hazard analysis showed that only serum calcium (p < 0.01), BMI (p < 0.0003), diastolic blood pressure (p < 0.0009), and the atherogenic index (p < 0.002) were significantly independent risk factors for MI. The range of serum calcium levels from the mean value, -2 SDs to the mean value +2 SDs corresponds to a variation in estimated risk for MI ranging from 0.06 to 0.15.CONCLUSIONS: Serum calcium was found to be an independent, prospective risk factor for MI in middle-aged males suggesting a role for extracellular calcium levels in the atherosclerotic process.
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