[Show abstract][Hide abstract] ABSTRACT: Background:
Primary hyperaldosteronism (PA), known as Mb Conn, is one of the most common forms of secondary hypertension in middle-aged adults. High plasma aldosterone has been associated with severe organ damage. The unilateral aldosterone-producing adenoma (lateralized disease) is a subtype of PA, which can be fully or partly cured by adrenalectomy.
Retrospective review of data from 50 patients who underwent adrenal venous sampling (AVS) was performed. Medical records, plasma renin and aldosteron, confirmatory tests and medical imaging (predominantly Computed Tomography and Magnetic Resonance Imaging) were available. Patients with lateralized disease (n = 39) underwent adrenalectomy and additional clinical data at least one year after surgery was recorded.
Age and gender were widely and equally distributed (median age = 51, age span = 28-73). Patients with lateralized disease had higher blood pressure (BP) and lower serum potassium compared to patients with bilateral hyperplasia. No difference regarding age and gender distribution was detected. Despite lateralized disease diagnosed from AVS, the medical images were normal in 10 patients (28%). Follow-up of 30 patients who underwent adrenalectomy showed that six patients were cured, 17 had better BP control, five patients had no effect and one patient had higher BP but decreased number of antihypertensive drugs.
PA is of equal prevalence in men and women, young and old individuals. The agreement between imaging modalities and AVS is limited, and the final diagnosis must rely on AVS. Patients prone for surgery had better BP control after adrenalectomy.
No preview · Article · Oct 2015 · Scandinavian journal of clinical and laboratory investigation
[Show abstract][Hide abstract] ABSTRACT: Calcium intake and absorption is important for bone health. In a randomized double-blind cross-over trial, we investigated effects of adding chymosin to milk on the intestinal calcium absorption as measured by renal calcium excretion and indices of calcium homeostasis. The primary outcome of the study was 24-h renal calcium excretion that is considered a proxy measure of the amount of calcium absorbed from the intestine. We studied 125 healthy men and women, aged 34 (25–45) years on two separate days. On each day, a light breakfast was served together with 500 ml of semi-skimmed milk to which either chymosin or similar placebo was added. Compared with placebo, chymosin did not affect 24-h urinary calcium, calcium/creatinine ratio, plasma parathyroid hormone, calcitonin or ionized calcium levels. However, during the first 4 h after intake of milk with chymosin, urinary calcium–creatinine ratio was significantly increased (17 %) compared with placebo. Stratification by daily calcium intake showed effect of chymosin in participant with a habitual intake above the median (>1,050 mg/day) in whom both urinary calcium and calcium/creatinine ratio were significantly increased compared with placebo. Effects did not depend on plasma 25-hydroxyvitamin D levels. Chymosin added to milk increases renal calcium excretion in the hours following intake without affecting plasma levels of calcium or calciotropic hormones. The effect most likely represents enhanced intestinal calcium absorption shortly after intake. Further studies are warranted on whether intake of milk-added chymosin may cause beneficial effects on bone. www.ClinicalTrials.gov no. NCT01370941.
No preview · Article · Dec 2014 · Calcified Tissue International
[Show abstract][Hide abstract] ABSTRACT: Background and Purpose
Both cerebral hypoperfusion and vascular risk factors have been implicated in early aging of the brain and the development of neurodegenerative disease. However, the current knowledge of the importance of cardiovascular health on resting brain perfusion is limited. The aim of the present study was to elucidate the relation between brain perfusion variability and risk factors of endothelial dysfunction and atherosclerosis in healthy aged subjects.
Thirty-eight healthy subjects aged 50–75 years old were included. Mean global brain perfusion was measured using magnetic resonance phase contrast mapping and regional brain perfusion by use of arterial spin labeling.
Mean global brain perfusion was inversely correlated with caffeine and hematocrit, and positively with end-tidal PCO2. Furthermore, the mean global brain perfusion was inversely correlated with circulating homocysteine, but not with asymmetric dimethylarginine, dyslipidemia or the carotid intima-media thickness. The relative regional brain perfusion was associated with circulating homocysteine, with a relative parietal hypoperfusion and a frontal hyperperfusion. No effect on regional brain perfusion was observed for any of the other risk factors. A multiple regression model including homocysteine, caffeine, hematocrit and end-tidal PCO2, explained nearly half of the observed variability.
Both intrinsic and extrinsic factors influenced global cerebral perfusion variation between subjects. Further, the results suggest that the inverse relation between homocysteine and brain perfusion is owing to other mechanisms, than reflected by asymmetric dimethylarginine, and that homocysteine may be a marker of cerebral perfusion in aging brains.
[Show abstract][Hide abstract] ABSTRACT: Agents blocking the renin-angiotensin-aldosterone system are frequently used in patients with end-stage renal disease, but whether they exert beneficial cardiovascular effects is unclear. Here the long-term effects of the angiotensin II receptor blocker, irbesartan, were studied in hemodialysis patients in a double-blind randomized placebo-controlled 1-year intervention trial using a predefined systolic blood pressure target of 140 mm Hg (SAFIR study). Each group of 41 patients did not differ in terms of age, blood pressure, comorbidity, antihypertensive treatment, dialysis parameters, and residual renal function. Brachial blood pressure decreased significantly in both groups, but there was no significant difference between placebo and irbesartan. Use of additional antihypertensive medication, ultrafiltration volume, and dialysis dosage were not different. Intermediate cardiovascular end points such as central aortic blood pressure, carotid-femoral pulse wave velocity, left ventricular mass index, N-terminal brain natriuretic prohormone, heart rate variability, and plasma catecholamines were not significantly affected by irbesartan treatment. Changes in systolic blood pressure during the study period significantly correlated with changes in both left ventricular mass and arterial stiffness. Thus, significant effects of irbesartan on intermediate cardiovascular end points beyond blood pressure reduction were absent in hemodialysis patients.Kidney International advance online publication, 26 March 2014; doi:10.1038/ki.2014.69.
Full-text · Article · Mar 2014 · Kidney International
[Show abstract][Hide abstract] ABSTRACT: Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF and cardiac output were measured in 31 healthy subjects 50-75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43·6 ml per 100 g min(-1) , 5·5 l min(-1) and 2·7 l min(-1) m(-2) , respectively, in males, and 53·4 ml per 100 g min(-1) , 4·3 l min(-1) and 2·4 l min(-1) m(-2) , respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0·22, P = 0·008) and furthermore lower in males than in females (8·6% versus 12·5%, P = 0·003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed a gender-related inverse association of increased low-to-high-frequency power ratio with CBF and fractional brain flow. The findings do not support a direct effect of cardiac function on CBF, but demonstrates gender-related differences in cardiac output distribution. We propose fractional brain flow as a novel index that may be a useful marker of adequate brain perfusion in the context of ageing as well as cardiovascular disease.
No preview · Article · Dec 2013 · Clinical Physiology and Functional Imaging
[Show abstract][Hide abstract] ABSTRACT: Unlabelled:
Use of hormonal contraceptives (HC) may influence total plasma concentrations of vitamin D metabolites. A likely cause is an increased synthesis of vitamin D binding protein (VDBP). Discrepant results are reported on whether the use of HC affects free concentrations of vitamin D metabolites.
In a cross-sectional study, plasma concentrations of vitamin D metabolites, VDBP, and the calculated free vitamin D index in users and non-users of HC were compared and markers of calcium and bone metabolism investigated.
75 Caucasian women aged 25-35 years were included during winter season. Compared with non-users (n = 23), users of HC (n = 52) had significantly higher plasma concentrations of 25-hydroxyvitamin D (25OHD) (median 84 interquartile range: [67-111] vs. 70 [47-83] nmol/L, p = 0.01), 1,25-dihydroxyvitamin D (1,25(OH)2D) (198 [163-241] vs. 158 [123-183] pmol/L, p = 0.01) and VDBP (358 [260-432] vs. 271 [179-302] µg/mL, p < 0.001). However, the calculated free indices (FI-25OHD and FI-1,25(OH)2D) were not significantly different between groups (p > 0.10). There were no significant differences in indices of calcium homeostasis (plasma concentrations of calcium, parathyroid hormone, and calcitonin, p > 0.21) or bone metabolism (plasma bone specific alkaline phosphatase, osteocalcin, and urinary NTX/creatinine ratio) between groups.
Use of HC is associated with 13%-25% higher concentrations of total vitamin D metabolites and VDBP. This however is not reflected in indices of calcium or bone metabolism. Use of HC should be considered in the interpretation of plasma concentrations vitamin D metabolites.
[Show abstract][Hide abstract] ABSTRACT: Recently introduced iterative reconstruction algorithms with resolution recovery (RR) and noise-reduction technology seem promising for reducing scan time or radiation dose without loss of image quality. However, the relative effects of reduced acquisition time and reconstruction software have not previously been reported. The aim of the present study was to investigate the influence of reduced acquisition time and reconstruction software on quantitative and qualitative myocardial perfusion single photon emission computed tomography (SPECT) parameters using full time (FT) and half time (HT) protocols and Evolution for Cardiac Software.
We studied 45 consecutive, non-selected patients referred for a clinically indicated routine 2-day stress/rest (99m)Tc-Sestamibi myocardial perfusion SPECT. All patients underwent an FT and an HT scan. Both FT and HT scans were processed according to our standard procedure with both ordered-subset expectation maximization (OSEM) + filtered back projection (FBP) reconstructions and a second reconstruction of HT scans was performed with the RR software producing three datasets for each patient for visual analysis (FT-OSEM, HT-OSEM, and HT-RR) and for quantitative analysis (FT-FBP, HT-FBP, and HT-RR). The datasets were analyzed using commercially available QGS/QPS software and read by two observers evaluating image quality and clinical interpretation. Image quality was assessed on a 10-cm visual analog scale score.
HT imaging was associated with loss of image quality that was compensated for by RR reconstruction. HT imaging was also associated with increasing perfusion defect extents, an effect more pronounced using RR than FBP reconstruction. Compared to standard FT-FBP, HT-RR significantly reduced left ventricular volumes whereas HT-FBP increased end-systolic volume. HT imaging had no effect on measured left ventricular ejections fraction or measures of reversibility. Image interpretation found a higher level of concordance between FT-OSEM and HT-RR than between FT-OSEM and HT-OSEM without any observable systematic effects.
Use of RR reconstruction algorithms compensates for loss of image quality associated with reduced scan time. Both HT acquisition and RR reconstruction algorithm had significant effects on motion and perfusion parameters obtained with standard software, but these effects were relatively small and probably of limited clinical importance. Although no systematic effects on image interpretation were observed, the influence on diagnostic accuracy remains to be determined.
No preview · Article · Aug 2013 · Journal of Nuclear Cardiology
[Show abstract][Hide abstract] ABSTRACT: External fractionated radiotherapy of cancer increases the risk of cardio- and cerebrovascular events, but less attention has been paid to the potential side effects on the arteries following internal radiotherapy with radioactive iodine (RAI), i.e. 131-iodine. About 279 per million citizens in the western countries are treated each year with RAI for benign thyroid disorders (about 140,000 a year in the EU), stressing that it is of clinical importance to be aware of even rare radiation-induced side effects. In order to induce or accelerate atherosclerosis, the dose to the carotid arteries has to exceed 2 Gy which is the known lower limit of ionizing radiation to affect the endothelial cells and thereby to induce atherosclerosis.
To estimate the radiation dose to the carotid arteries following RAI therapy of benign thyroid disorders.
Assuming that the lobes of the thyroid gland are ellipsoid, that the carotid artery runs through a part of the lobes, that there is a homogeneous distribution of RAI in the lobes, and that the 24 h RAI uptake in the thyroid is 35 % of the (131)I orally administrated, we used integrated modules for bioassay analysis and Monte Carlo simulations to calculate the dose in Gy/GBq of administrated RAI.
The average radiation dose along the arteries is 4-55 Gy/GBq of the (131)I orally administrated with a maximum dose of approximately 25-85 Gy/GBq. The maximum absorbed dose rate to the artery is 4.2 Gy/day per GBq (131)I orally administrated.
The calculated radiation dose to the carotid arteries after RAI therapy of benign thyroid disorder clearly exceeds the 2 Gy known to affect the endothelial cells and properly induce atherosclerosis. This simulation indicates a relation between the deposited dose in the arteries following RAI treatment and an increased risk of atherosclerosis and subsequent cerebrovascular events such as stroke.
Full-text · Article · Jul 2013 · Annals of Nuclear Medicine
[Show abstract][Hide abstract] ABSTRACT: Measurements of cerebral blood flow (CBF) show large variability among healthy subjects. The aim of the present study was to investigate the relative effect of established factors influencing CBF on the variability of resting CBF. We retrospectively analyzed spontaneous variability in 430 CBF measurements acquired in 152 healthy, young subjects using (133)Xe single-photon emission computed tomography. Cerebral blood flow was correlated positively with both end-tidal expiratory P(CO(2)) (P(ET)CO(2)) and female gender and inversely with hematocrit (Hct). Between- and within-subject CO(2) reactivity was not significantly different. Including P(ET)CO(2), Hct and gender in the model reduced between-subject and within-subject variance by 14% and 13.5%, respectively. Within-subject variability was mainly influenced by P(ET)CO(2) and between-subject variability mostly by Hct, whereas gender appeared to be of little added value when Hct was also accounted for. The present study confirms large between-subject variability in CBF measurements and that gender, Hct, and P(ET)CO(2) explain only a small part of this variability. This implies that a large fraction of CBF variability may be due to unknown factors such as differences in neuron density or metabolism that could be subject for further studies.Journal of Cerebral Blood Flow & Metabolism advance online publication, 13 February 2013; doi:10.1038/jcbfm.2013.17.
No preview · Article · Feb 2013 · Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism
[Show abstract][Hide abstract] ABSTRACT: Autonomic and cardiac dysfunction is frequent in cirrhosis, and includes increased sympathetic nervous activity, impaired heart rate variability (HRV) and baroreflex sensitivity (BRS). Quantified (123)I-metaiodobenzylguanidine (mIBG) scintigraphy reflects cardiac noradrenaline uptake and in patients with cardiac failure it predicts outcome. In this study we aimed to investigate cardiac sympathetic function in cirrhosis by mIBG scintigraphy in relation to cardiovascular function. Ten patients with cirrhosis and 10 matched healthy controls participated in the study. Heart/mediastinum (H/M) ratios of mIBG uptake were calculated 15 and 230 minutes after intravenous injection of mIBG. Furthermore, washout rate (WOR) of mIBG was calculated. The patients underwent a liver vein catherization with determination of splanchnic and systemic haemodynamics and measurement of HRV and BRS. mIBG-scintigraphy revealed significantly increased WOR in patients with cirrhosis compared to controls (p<0.005), whereas H/M-uptakes were equal in the groups. Forty percent of the patients had reduced uptake of mIBG in the infero-lateral segment of the left ventricle. WOR correlated significantly with central circulation time, an estimate of central hypovolaemia (r=-0.64, P<0.05) and frequency-corrected QT(F) interval (r=0.71, p=0.01). Patients with cirrhosis had significantly decreased HRV and BRS correlating with indicators of abnormal cathecholamine up-take by mIBG although the catecholamine level was normal in the patients. In conclusion, in alcoholic cirrhosis, mIBG-scintigraphy reveals autonomic dysfunction and impaired myocardial distribution of sympathetic nervous activity. It is associated to indicators of central hypovolaemia, QT-interval, decreased HRV and BRS. Measurement of myocardial catecholamine-uptake by mIBG may add important information on autonomic and cardiac dysfunction in cirrhosis.
[Show abstract][Hide abstract] ABSTRACT: Pregnancy and lactation cause major changes in calcium homeostasis and bone metabolism. This population-based cohort study presents the physiological changes in biochemical indices of calcium homeostasis and bone metabolism during pregnancy and lactation
We describe physiological changes in calcium homeostasis, calcitropic hormones and bone metabolism during pregnancy and lactation.
We studied 153 women planning pregnancy (n = 92 conceived) and 52 non-pregnant, age-matched female controls. Samples were collected prior to pregnancy, once each trimester and 2, 16 and 36 weeks postpartum. The controls were followed in parallel.
P-estradiol (E2), prolactin and 1,25-dihydroxyvitamin D (1,25(OH)2D) increased (p < 0.001) during pregnancy, whereas plasma levels of parathyroid hormone (P-PTH) and calcitonin decreased (p < 0.01). Insulin-like growth factor I (IGF-I) was suppressed (p < 0.05) in early pregnancy but peaked in the third trimester. Postpartum, E2 was low (p < 0.05); prolactin decreased according to lactation status (p < 0.05). 1,25(OH)2D was normal and IGF-I was again reduced (p < 0.05). P-PTH and calcitonin increased postpartum. From early pregnancy, markers of bone resorption and formation rose and fall, respectively (p < 0.001). From the third trimester, bone formation markers increased in association with IGF-I changes (p < 0.01). Postpartum increases in bone turnover markers were associated with lactation status (p < 0.001). During lactation, plasma phosphate was increased, whereas calcium levels tended to be decreased which may stimulate PTH levels during and after prolonged lactation.
The increased calcium requirements in early pregnancy are not completely offset by increased intestinal calcium absorption caused by high 1,25(OH)2D since changes in bone markers indicated a negative bone balance. The rise in bone formation in late pregnancy may be initiated by a spike in IGF-I levels. The high bone turnover in lactating women may be related to high prolactin and PTH levels, low E2 levels and perhaps increased parathyroid hormone-related protein levels.
No preview · Article · Aug 2012 · Osteoporosis International
[Show abstract][Hide abstract] ABSTRACT: There is a need for real-time non-invasive, continuous monitoring of cerebral blood flow (CBF) during surgery, in intensive care units and clinical research. We investigated a new non-invasive hybrid technology employing ultrasound tagged near infrared spectroscopy (UT-NIRS) that may estimate changes in CBF using a cerebral blood flow index (CFI). Changes over time for UT-NIRS CFI and 133Xenon single photon emission computer tomography (133Xe-SPECT) CBF data were assessed in 10 healthy volunteers after an intravenous bolus of acetazolamide. UT-NIRS CFI was measured continuously and SPECT CBF was measured at baseline, 15 and 60 min after acetazolamide. We found significant changes over time in CFI by UT-NIRS and CBF by SPECT after acetazolamide (P ≤ 0.001). Post hoc tests showed a significant increase in CFI (P = 0.011) and SPECT CBF (P < 0.001) at 15 min after acetazolamide injection. There was a significant correlation between CFI and SPECT CBF values (r = 0.67 and P ≤ 0.033) at 15 min, but not at 60 min (P ≥ 0.777). UT-NIRS detected an increase in CFI following an acetazolamide bolus, which correlated with CBF measured with 133Xe-SPECT. This study demonstrates that UT-NIRS technology may be a promising new technique for non-invasive and real-time bedside CBF monitoring.
Full-text · Article · May 2012 · Neurocritical Care
[Show abstract][Hide abstract] ABSTRACT: There is considerable evidence suggesting, that older antiepileptic drugs (AEDs) and some of the newer ones decrease bone mineral density (BMD). However, there is only limited and conflicting data concerning the effect of levetiracetam on BMD. In this cross-sectional study we analysed data from 168 adult consecutive outpatients treated with AEDs for more than 2 years, and who underwent measurement of the BMD. We compared the incidence of decreased BMD among the patients treated with 6 different AEDs: carbamazepine (CBZ), oxcarbazepine (OXC), valproic acid (VPA), lamotrigine (LTG), topiramate (TPM) and levetiracetam (LEV). Among the patients on monotherapy, reduced BMD was present significantly most often in patients treated with LEV and those treated with OXC. In the group of patients on polytherapy there was no significant difference in the incidence of low BMD among patients treated with various AEDs. Our data suggest that patients on long-term treatment with LEV have a higher risk for affection of bone density.
[Show abstract][Hide abstract] ABSTRACT: The hypothalamic-pituitary-adrenal axis is susceptible to programming during fetal development and may be linked to risk of disease later in life. In a former prospective study the cohort was divided into those born appropriate for gestational age (AGA) or small for gestational age (SGA; birth weight <10 percentile). In 52 adolescent boys (17.5 years) we assessed circulating androgen levels (T, Δ(4)-adione, DHEAS), overnight serum cortisol profiles (every 20 min), ACTH stimulation test (250 μg i.v.) and analysis of 24-hour urinary adrenal steroid excretion. Urinary excretion of adrenal androgen and cortisol metabolites were significantly lower in the SGA compared to the AGA group. Basal morning cortisol levels were lower in adolescents born SGA compared to those born AGA (365 mmol/l, interquartile range (IQR) 284-413 vs. 445 mmol/l, IQR 377-495, p = 0.04), but overnight cortisol profiles (AUC) did not differ. The ACTH test showed equally stimulated levels of cortisol for those born SGA and AGA. There was no difference in serum testosterone, dehydroepiandrosterone sulfate and Δ(4)-adione levels between the SGA and AGA subjects. This suggests impaired excretion of adrenal androgen and cortisol metabolites in young men born SGA compared to AGA. In conclusion, this study demonstrated subtle changes in adolescent adrenal function associated with birth weight.
No preview · Article · Jan 2011 · Hormone Research in Paediatrics