| 1. |
- Almquist, Martin, et al.
(författare)
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Reproductive history, lifestyle factors and season as determinants for serum calcium concentrations in women.
- 2008
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68, s. 777-785
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Serum calcium concentrations have been associated with the risk of malignant disease, especially breast cancer. Thus, determinants of serum calcium concentrations, with special regard to risk factors of breast cancer, are of great interest. Material and methods. Previous studies have either been small or they have not focused on reproductive factors. The present study examined serum calcium concentrations in relation to reproductive history, selected lifestyle factors and screening season in a large population-based cohort study comprising 8,114 women. ANOVA followed by the Bonferroni t-test were used for comparison of means, and logistic regression and multiple regression analysis were used to test associations. Results. Serum calcium concentrations were lower in hormone replacement therapy users versus non-users (2.321 mmol/L versus 2.364; p<0.001) and in users of oral contraceptives versus non-users (2.304 versus 2.348; p<0.001). They were higher in peri-/postmenopausal versus premenopausal women (2.357 versus 2.319; p<0.001). Overweight and obese women had higher mean calcium concentrations (2.350 and 2.355) than women with body mass index between 20 and 25 (2.342; p<0.001). Serum calcium concentrations were higher in spring and autumn than in winter (2.352 and 2.353 versus 2.343; p = 0.002). Both younger (40-45 years) (2.334; p = 0.001) and older age groups (>55 years) (2.363; p<0.001) had higher mean calcium concentrations compared to those of women aged 45-50 years (2.320), even when adjusting for menopausal status, suggesting that age has an independent influence on calcium concentrations. Conclusions. It is concluded that reproductive factors such as menopausal status, use of oral contraceptives or hormone-replacement therapy, and age, BMI and season are associated with serum calcium concentrations.
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| 2. |
- Almquist, Martin, et al.
(författare)
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Serum calcium and breast cancer risk: results from a prospective cohort study of 7,847 women.
- 2007
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Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 18, s. 595-602
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Tidskriftsartikel (refereegranskat)abstract
- Experimental and epidemiological studies suggest that calcium-regulating hormones-parathyroid hormone (PTH) and vitamin D-may be associated with breast cancer risk. No prospective cohort study has investigated the association between pre-diagnostic calcium levels and subsequent risk of breast cancer. We have examined this in a cohort of 7,847 women where serum calcium levels and established risk factors for breast cancer had been assessed at baseline. During a mean follow-up of 17.8 years, 437 incident breast cancer cases were diagnosed. Incidence of breast cancer was calculated in different quartiles of serum calcium levels and a Cox's proportional hazards analysis was used to obtain corresponding relative risks (RR), with a 95% confidence interval (CI), adjusted for potential confounders. In premenopausal women, serum calcium levels were inversely associated with breast cancer risk in a dose-response manner. The adjusted RR (95% CI) of breast cancer was in the 2nd calcium quartile 0.91 (0.65-1.30), in the 3rd quartile 0.89 (0.60-1.31), and in the 4th quartile 0.56 (0.32-0.98), as compared to the 1st calcium quartile. In postmenopausal overweight women (BMI > 25), breast cancer risk was higher in calcium quartiles 2-4 as compared to the 1st quartile. Our findings may have implications for primary prevention of breast cancer and for the management of asymptomatic primary hyperparathyroidism.
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| 3. |
- Almquist, Martin, et al.
(författare)
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Serum calcium and tumour aggressiveness in breast cancer: a prospective study of 7847 women.
- 2009
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Ingår i: European Journal of Cancer Prevention. - 1473-5709. ; 18, s. 354-360
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Tidskriftsartikel (refereegranskat)abstract
- Experimental, epidemiological and clinical studies suggest that calcium and/or its regulating hormones affect breast cancer risk. There has been no prospective cohort study investigating serum calcium levels and breast cancer aggressiveness, as determined by tumour histology and stage. Dichotomized prediagnostic serum calcium levels were investigated in relation to breast cancer aggressiveness as determined by grade (mitotic frequency, tubule formation, nuclear atypia) and stage (tumour size and axillary lymph node status). Cox's proportional hazards analysis and heterogeneity analysis were used to investigate the associations between low/high calcium and grade/stage in a prospective cohort study of 7847 women, out of whom 462 women were diagnosed with incident breast cancer during a mean follow-up of 17.2 years. All analyses were stratified for body mass index and menopausal status. Prediagnostic serum calcium levels in premenopausal women were positively associated with increased tumour aggressiveness as determined by a higher risk of nodal metastasis; relative risk (RR) for calcium above median as compared with calcium below median was 1.88 with a 95% confidence interval (CI) of 1.04-3.38. In overweight women, prediagnostic serum calcium levels were also associated with tumour aggressiveness, as determined by both a higher risk of nodal metastasis [RR (95% CI) 1.69 (0.95-3.02)] and severe nuclear atypia [RR (95% CI) 2.06 (1.10-3.86)]. Results also indicate that, in overweight women, calcium is positively associated with worse grade as determined by tubule formation and mitotic frequency. In conclusion, prediagnostic serum calcium levels are positively associated with increased tumour aggressiveness in premenopausal and/or overweight women.
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| 4. |
- Almqvist, Erik, et al.
(författare)
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Increase of bioavailable testosterone is associated with gain in bone mineral density after cure of primary hyperparathyroidism in postmenopausal women
- 2006
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 64:1, s. 58-62
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Tidskriftsartikel (refereegranskat)abstract
- Objective The recovery of bone mineral density (BMD) after surgical cure of primary hyperparathyroidism (PHPT) seems to be multifactorial and not just dependent on declining PTH. The aim of the present study was to evaluate the role of sex steroids in this context. Design and patients Thirty-six postmenopausal women with PHPT were examined before and 1 year after curative parathyroidectomy. Their mean age at inclusion in the study was 71.7 +/- 1.1 years (range 54-83). BMD was measured in hip and lumbar spine using dual energy X-ray absorptiometry. No patient received any replacement therapy with sex hormones or treatment with corticosteroids, oestrogen receptor modulators or bisphosphonates. Measurements Serum concentrations of oestradiol, testosterone, androstenedione, dehydroepiandrosterone sulphate, SHBG, PTH and calcium. Results Postoperative increase of free (bioavailable) testosterone was positively correlated to the change of BMD in the hip (P < 0.01), whereas the change of PTH in serum correlated to the change of BMD in the lumbar spine (P < 0.05). Multiple regression analysis showed that bioavailable testosterone was the most important determinant of change in BMD in both spine and hip (femoral neck: P < 0.05; Ward's triangle: P < 0.001; trochanter: P < 0.01; lumbar spine: P < 0.05). The increase of bioavailable testosterone after curative parathyroidectomy was related to declining SHBG. Conclusions An increase of bioavailable testosterone following surgical cure of PHPT is related to improvement of hip and lumbar spine BMD in postmenopausal women. This previously unknown hormonal interaction may also be important to other aspects of hyperparathyroidism.
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| 5. |
- Almqvist, Erik, et al.
(författare)
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Increased plasma concentrations of N-terminal pro-B-type natriuretic peptide in patients with mild primary hyperparathyroidism.
- 2006
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Ingår i: Clinical endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 65:6, s. 760-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Primary hyperparathyroidism (PHPT) is associated with heart disease. The aims of the present study were to evaluate how cardiac function and secretion of N-terminal pro-B-type natriuretic peptide (NT-proBNP) correlate in patients with mild PHPT, and how the plasma level of NT-proBNP is influenced by cure of the parathyroid disease. DESIGN AND PATIENTS: Forty-two patients with PHPT without symptoms of heart disease were examined before and 1 year after curative parathyroidectomy. MEASUREMENTS: Plasma or serum concentrations of NT-proBNP, calcium, PTH, creatinine, oestradiol, testosterone and SHBG were measured. Cardiac function was evaluated by equilibrium radionuclide angiography (ERNA). RESULTS: At baseline, NT-proBNP levels correlated negatively with systolic function [left ventricular ejection fraction (LVEF), P < 0.001]. Twelve per cent of the patients had NT-proBNP levels above normal reference values preoperatively. One year postoperatively, the corresponding proportion was 21%. The mean plasma concentration of NT-proBNP increased after parathyroidectomy (P < 0.01) in parallel with a dip in diastolic function (peak filling rate, P < 0.05) and a falling trend in systolic function (LVEF, P = 0.08). The postoperative percentage changes in circulating NT-proBNP and total oestradiol correlated positively (P < 0.05). CONCLUSIONS: Patients with mild PHPT and normal renal function may have high levels of circulating NT-proBNP despite the absence of symptomatic heart disease. Cure of the parathyroid disease is followed by a further increase in NT-proBNP secretion in parallel with ERNA measures, indicating subclinical changes in heart function. These results are in line with data indicating an association between PHPT and increased risk of premature death.
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| 6. |
- Birgander, Mats, et al.
(författare)
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Cardiac Structure and Function Before and After Parathyroidectomy in Patients With Asymptomatic Primary Hyperparathyroidism
- 2009
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Ingår i: The Endocrinologist. - 1539-9192. ; 19:4, s. 154-158
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary hyperparathyroidism (PHPT) is associated with cardiac disease and increased risk of all-cause and cardiovascular mortality. We investigated cardiac structural and functional parameters before and after successful parathyroidectomy in asymptomatic PHPT patients. Methods and Results: Forty-nine PHPT patients (age: 62.9 +/- 11 years, 5 men) and 48 healthy control subjects, matched for age, sex and smoking status were enrolled in the study. PHPT patients were examined preoperatively and 6 and 12 months postoperatively. Structural and functional cardiac parameters were assessed by transthoracic echocardiography. One year after parathyroidectomy left ventricular (LV) mass, left atrial size, LV enddiastolic and endsystolic diameters, LV posterior wall and interventricular septum diameter, and right ventricular enddiastolic diameter were all increased in PHPT patients, although not significantly. As an indication of worsened LV diastolic function, the heart rate adjusted Doppler-derived deceleration time of the transmittal E-wave increased among PHPT patients (276 +/- 82-303 +/- 54 milliseconds, P = 0.004). There was also deterioration of LV ejection fraction (from 62.7 +/- 7 to 59.9 +/- 7.8%, P = 0.868) and mean atrioventricular plane displacement (from 13.2 +/- 2 to 12.6 +/- 2 mm, P = 0.029). Conclusion: There were no significant differences in heart function between hyperparathyroid and control subjects, and 6 months after parathyroidectomy, there was no change in heart function in hyperparathyroid subjects.
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| 7. |
- Birgander, Mats, et al.
(författare)
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Postexercise Cardiac Performance Among Patients With Mild Primary Hyperparathyroidism
- 2009
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Ingår i: The Endocrinologist. - 1539-9192. ; 19:6, s. 263-266
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Tidskriftsartikel (refereegranskat)abstract
- Primary hyperparathyroidism (pHPT) is associated with cardiac disease. This prospective study was designed to investigate changes in cardiac function before and after parathyroidectomy. Resting and post exercise cardiac function was compared with matched control subjects. Fifty patients (mean age 62.9 +/- 11 years, 45 women) and 50 healthy control subjects, matched for age and sex were studied. Resting and postmaximum exercise echocardiography/Doppler examination were performed at baseline and 6 months after parathyroidectomy. pHPT patients were tested at baseline and 6 months postoperatively. Control subjects were tested only at baseline. Patients were divided into 4 subgroups based on median preoperative levels of PTH and calcium (Ca): high (up arrow) PTI4/ up arrow Ca, up arrow PTH/low (down arrow) Ca, up arrow Ca/ down arrow PTH, and down arrow PTH/ down arrow Ca. No significant difference between pHPT patients and control subjects regarding post exercise systolic function were detected, There was a tendency of lowed E/A among pHPT patients which was significant in subgroup down arrow PTH/ down arrow Ca (1.07 +/- 0.3). Subgroup up arrow PTH/ up arrow Ca showed a lower S/D compared with control subjects at baseline (1.28 +/- 0.3 vs. 1.48 +/- 0.3, P = 0.029). No significant changes regarding post exercise echocardiographic parameters reflecting cardiac function were detected 6 months after parathyriodectomy. Patients with asymptomatic pHPT showed a tendency of elevated filling pressures and signs of impaired diastolic function during exercise.
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| 8. |
- Birgander, Mats, et al.
(författare)
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Relationship Between Mild Primary Hyperparathyroidism and Left Ventricular Structure and Diastolic Performance
- 2009
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Ingår i: The Endocrinologist. - 1539-9192. ; 19:4, s. 187-191
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Forskningsöversikt (refereegranskat)abstract
- Aim: This study aims to investigate cardiac structure and function in patients with asymptomatic primary hyperparathyroidism (pHPT) and if there is any relation to severity regarding serum levels of calcium (Ca) and parathyroid hormone. Methods and Results: We consecutively included 50 patients (mean age 62.9 +/- 11 years, 45 women) with clinically diagnosed pHPT. We prospectively recruited 50 healthy control subjects, matched for age and sex. Standard transthoracic echocardiographic examination was performed using the 4 standard views and structural parameters as well as left ventricular (LV) systolic and diastolic function was determined. Mean LV ejection fraction and atrioventricular plane displacement were on average normal and did not differ between patients and controls. However, pHPT patients had significantly greater LV mass (148 +/- 37 vs. 127 +/- 29 g, P = 0.002), LV end diastolic area (81 +/- 20 vs. 68 +/- 18 cm(2), p = 0.003), LV posterior wall diameter (8.9 +/- 1 vs. 8.1 +/- 1 min, P = 0.006), and LA size (21 +/- 3 vs. 19 +/- 2 mm, P < 0.001). A moderate to severe LV diastolic filling impairment was present in substantially more pHPT patients, compared with control subjects (36% vs. 4%, P < 0:001). Conclusion: Patients with asymptomatic pHPT showed LV structural changes and impaired LV diastolic function.
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| 9. |
- Johansson, Lovisa, et al.
(författare)
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Variation in the adiponutrin gene influences its expression and associates with obesity.
- 2006
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 55:3, s. 826-833
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Tidskriftsartikel (refereegranskat)abstract
- Adiponutrin is one of three recently identified adipocyte lipases. Surprisingly, these proteins also retain transacylase activity, a hitherto unknown pathway of triacylglycerol synthesis in the adipocytes. This may enable them to participate in both anabolic and catabolic processes. The adiponutrin gene (ADPN) is downregulated by fasting and upregulated by refeeding, suggesting a role in lipogenesis. Experiments in human adipocytes confirmed that the gene is upregulated in response to insulin in a glucose-dependent fashion. Obese subjects had increased levels of subcutaneous and visceral abdominal adipose tissue ADPN mRNA. Visceral ADPN mRNA expression was correlated to measures of insulin sensitivity (fasting insulin and homeostasis model assessment). We also studied genetic variation in ADPN and its relation to obesity, lipolysis, and mRNA expression. Two ADPN polymorphisms showed association with obesity. Carriers of the obesity-associated variants showed a lesser increase in the levels of adipose tissue ADPN mRNA and an increased basal lipolysis. Our results suggest that obese subjects that are insulin resistant and/or carriers of the obesity-associated ADPN alleles fail to upregulate the gene and that upregulation of adiponutrin may be an appropriate response to orchestrate energy excess.
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| 10. |
- Lantz, Mikael, et al.
(författare)
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Thyrostimulin (a TSH-like Hormone) Expression in Orbital and Thyroid Tissue.
- 2007
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1557-9077 .- 1050-7256. ; 17:2, s. 113-118
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate gene expression of thyrostimulin in orbital and thyroid tissue from patients with and without Graves' disease. Design: Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was used for detection of thyrostimulin gene expression in intraorbital adipose tissue from patients with severe ophthalmopathy and thyroid healthy controls in addition to thyrostimulin expression in normal thyroid tissue, multinodular goiter tissue, and Graves' thyroid tissue. Main Outcome: In intraorbital tissue, thyrostimulin expression was identified in both patients and controls with fluorescence intensities varying between 0.23 and 0.88 in patients and 0.29 and 8.9 in controls before treatment with DNase. The signal of thyrostimulin was weak or absent in intraorbital adipose tissue from patients with ophthalmopathy and thyroid healthy controls after treatment of samples with DNase. This was in contrast to the expression of the thyroid-stimulating hormone (TSH) receptor and the housekeeping gene cyclophilin A that were detected both before and after DNase treatment. Similar results were found when analyzing human and rat thyroid tissue. Conclusions: Neither did we demonstrate gene expression of thyrostimulin in intraorbital adipose tissue or in thyroid tissue, nor could we confirm earlier findings in rat thyroid tissue. Whether thyrostimulin is a regulator of thyroid function has to be further investigated in future studies.
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