Induction therapy of AML with ara-C plus daunorubicin versus ara-C plus gemtuzumab ozogamicin: a randomized phase II trial in elderly patients.

BACKGROUND: Chemotherapy for elderly patients with acute myeloid leukemia (AML) results in a median overall survival (OS) of ≤ 1 year. Elderly patients often present with cardiac comorbidity. Gemtuzumab ozogamicin (GO) is active in elderly (≥ 60 years) patients with relapsed AML with low cardiac toxicity. PATIENTS AND METHODS: This randomized phase II study compared a standard combination of ara-C and daunorubicin (DNR; 7+3) versus ara-C plus gemtuzumab ozogamicin (7+GO) as the first course of induction therapy. Primary objectives were comparison of blast clearance on day 16, event-free survival (EFS), and remission duration. OS, complete remission (CR), and tolerability were secondary objectives. RESULTS: One hundred and nineteen patients with de novo AML, treatment-related AML, AML with a history of myelodysplastic syndrome (MDS), or high-risk MDS entered the study. Median age of 115 patients (intent-to-treat population) was 69 years. Protocol outlined a second course 7+3 for patients without blast clearance and two courses of high-dose ara-C consolidation upon CR. Both treatments were equally effective in blast clearance, CR, EFS, remission duration, or OS (median: 7+3, 9 months; 7+GO, 10 months). Induction death rate was higher in the GO group due to veno-occlusive disease. CONCLUSION: The study did not show significant superiority of 7+GO over standard 7+3.

A new auroral phenomenon, the anti-black aurora.

Black auroras are small-scale features embedded in the diffuse background aurora, typically occurring post-substorm after magnetic midnight and with an eastward drift imposed. Black auroras show a significant reduction in optical brightness compared to the surrounding diffuse aurora, and can appear as slow-moving arcs or rapidly-moving patches and arc segments. We report, for the first time, an even more elusive small-scale optical structure that has always been observed occurring paired with [Formula: see text] 10% of black aurora patches. A patch or arc segment of enhanced luminosity, distinctly brighter than the diffuse background, which we name the anti-black aurora, may appear adjacent to the black aurora. The anti-black aurora is of similar shape and size, and always moves in parallel to the drifting black aurora, although it may suddenly switch sides for no apparent reason. The paired phenomenon always drifts with the same average speed in an easterly direction. From the first dual-wavelength (427.8 nm and 844.6 nm) optical observations of the phenomenon recorded on 12 March 2016 outside Tromsø Norway, we show that the anti-black and black auroras have a higher and lower mean energy, respectively, of the precipitating electrons compared to the diffuse background.

Preparation and properties of sterically stabilized hexadecylphosphocholine (miltefosine)-liposomes and influence of this modification on macrophage activation.

The aim of the study was to investigate for the first time the preparation, physical properties and macrophage activating effect of sterically stabilized liposomes made from hexadecylphosphocholine (HPC, Miltefosine) using different poly(ethylene glycol) lipids for coating. We could demonstrate that it is possible to prepare different liposomal vesicle types (MLV, SUV and LUVET) without any problem and with a high stability in buffer (release of hydrophilic marker was < 5% after half a year) and in plasma (t1/2 up to several days). The preparation method, including size of polycarbon membrane filter used for the preparation of LUVETs had the main influence on vesicle size and size distribution. The addition of a charged lipid like DCP and different amounts of PEG-lipid up to 10% had no effect on size and stability of PEG-LUVETs. A comparison of activating potency of PEG-HPC-vesicles with commonly used HPC-liposomes was performed with mouse peritoneal macrophages. HPC-liposomes induced a clear release of NO and TNF from mouse peritoneal macrophages especially in a synergistical action with LPS. On the contrary the effect of PEG-liposomes was similar to control cells after a combined activation in vivo/in vitro. The reduced interaction of these liposomes with the MPS was also demonstrated by an unchanged carbon ink uptake after treatment of mice (i.p.) with liposomes prepared with and without PEG-lipid. PEG-HPC-liposomes combine the advantages of HPC, liposomes and PEG-coating, resulting in a promising preparation for treatment of mammary cancers.

Arterial distensibility, intima media thickness and pulse wave velocity after renal transplantation and in dialysis normotensive patients.

AIM: Structural and mechanical properties of the arterial wall are altered in patients with renal failure. The ageing process of the arterial wall appears to be accelerated in patients with end-stage renal failure. The mechanisms responsible for reduced arterial compliance and distensibility in dialysis patients and renal transplant recipients without hypertension remain to be evaluated. METHODS: Thirty-five normotensive dialysis patients (D), 35 normotensive renal transplant recipients (T) and 35 healthy volunteers (N) matched for age, sex and blood pressure as controls were enrolled into the study. The arterial blood pressure of all patients was < 140/90 mmHg. The dialysis patients and renal transplant recipients were eligible for the study if the serum creatinine level was < 2 mg/dL. In all subjects, fasting concentrations of serum creatinine, total cholesterol, HDL-cholesterol, LDL-cholesterol and hemoglobin and glucose were determined at enrollment to the study. Blood pressure was measured using an automatic sphygmomanometer. Pulse wave velocity (PWV) was evaluated using non invasive automatic Complior device. The vessel wall properties of the left common carotid artery were studied using multigate pulsed Doppler system. With this method, the end-diastolic diameter (d) and the systolic increase of vessel diameter (distension DELTAd) were measured. From these data the relative systolic increase of vessel diameter (DELTAd/d) and the arterial wall distensibility coefficient (DC) were calculated. RESULTS: Systolic blood pressure (SBP) and central pulse pressure (CPP) were significantly higher in T than in D and N group, respectively 138 +/- 18 mmHg and 59 +/- 16 mmHg vs 128 +/- 13 mmHg and 49 +/- 12 mmHg and 132.12 mmHg and 51 +/- 10 mmHg. The d did not change significantly between all groups. The distension DELTAd was significantly lower in patients group D and T, respectively 466 +/- 38 microm and 511 +/- 37 microm than in controls. Similarly DELTAd/d was in these groups significantly lower than in healthy volunteers, respectively D 6.33 +/- 0.5%, T 6.9 +/- 0.4% vs N 9.15 +/- 0.5%. DC was also significantly lower in D and T than in N groups, respectively D 17.91 +/- 1.5 10-3/kPa and T 18.92 +/- 1.3 10-3/kPa and N 24.28 +/- 0.51-3/kPa. Significant differences were found in the increase of the intima-media thickness (IMT) of carotid artery for dialyzed patients and renal transplant recipients in contrast to the control group, but there were no differences between the patients. PWV in both patient groups was statistically significant higher than in control group correspondingly D 11.1 +/- 1.03 m/s and T 13.3 +/- 1.13 m/s, N 9.4 +/- 0.89 m/s. There was a significant correlation between the change of DC, PWV and CPP in T group (n = 35; r = -0.43; P < 0.01 and n = 35; r = 0.48; P < 0.05). In the T group also an important correlation between PWV and IMT complex (n = 35; r = 0.49, P < 0.001) was found. CONCLUSIONS: The elastic and structural properties of arterial wall in dialysis patients and renal recipients are decreased. End-stage renal disease accelerates arterial stiffening despite of arteriosclerosis and hypertension. Renal transplantation does not reverse loss of elastic and morphologic properties of arteries found in patients with end-stage renal insufficiency.

[Diagnosis and treatment of disordered acid-base balance]. / Diagnostik und Therapie von Störungen des Säure-Basen-Haushalts. Warum Patienten sauer werden.

Differential diagnosis in disordered acid-base homeostasis is usually possible by measuring the pH, pCO2, pO2 and bicarbonate concentration, and enables differentiation between respiratory alkalosis and acidosis, and metabolic alkalosis and acidosis. Compensatory counter-regulation (respiratory or renal) can make correct assessment of the primary disorder problematic. Treatment of the underlying disease, in particular the provision of adequate oxygenation in respiratory disorders is of the essence. In chronic forms of metabolic acidosis, for example in chronic renal insufficiency and elderly patients, bicarbonate substitution should be initiated in order to prevent the negative effects on various organ systems. Sodium bicarbonate formulations that can be assimilated from the small bowel are especially tolerable and suitable.

[Management of patients with chronic renal failure]. / Die Früherkennung einer Niereninsuffizienz lohnt sich immer. Handeln Sie, bevor das Kreatinin ansteigt.

Terminal renal failure has an incidence of approximately 60 persons per million population, and is on the increase. Victims suffer from an appreciably compromised quality of life and life expectancy. The financial burden on the health service imposed by the need for renal replacement therapy (dialysis or renal transplantation) is considerable. To achieve a therapeutic impact, the underlying kidney disease, as well as the factors driving progression and injury need to be identified as early as possible. Of particular importance in this connection is the rigorous management of arterial hypertension with the use of ACE inhibitors, dietetic measures and normalization of hemoglobin levels.

Impaired flow-mediated vasodilation of the brachial artery in patients with primary hyperparathyroidism improves after parathyroidectomy.

OBJECTIVE: The endothelium is a newly recognised target tissue of parathyroid hormone (PTH). It is not clear whether hyperparathyroidism affects endothelial function and whether parathyroidectomy (Ptx) has an influence on arterial vessel wall properties. We studied brachial flow-mediated vasodilation (FMD) and brachial and carotid intima-media thickness (IMT) in patients with primary hyperparathyroidism (pHPT) before and after Ptx and in healthy controls. METHODS: 19 patients with pHPT (mean+SEM, age 45+/-4.7 years, PTH 238+/-52 ng/l) were studied. Diabetes, hypertension and vascular disease were excluded. Twenty healthy volunteers matched for age, sex and blood pressure served as controls. Enddiastolic diameter, FMD and nitroglycerine-induced (NMD) dilation of the brachial artery were measured by a multigate pulsed doppler system (echo-tracking), IMT was determined using automatic analysis of the M-line signal. Healthy volunteers where studied on one occasion, patients were studied at baseline and 6 months after Ptx. RESULTS: Six months after Ptx PTH had decreased to normal, blood pressure levels remained unchanged. Endothelium dependent FMD at baseline was impaired in patients compared to controls (4.7+/-1.2 vs. 18.2+/-3.7%, P<0.01), however, FMD improved significantly after Ptx (16.7+/-3.0%, P<0.01). Nitroglycerine-induced dilation, IMT and artery diameter were not different between groups and did not change after Ptx. CONCLUSIONS: Impaired endothelium dependent vasodilation in patients with primary hyperparathyroidism improves after successful parathyroidectomy. Endothelial dysfunction associated with primary hyperparathyroidism occurs without detectable structural wall alterations of the brachial artery and appears therefore to be an early and reversible arterial alteration.

A novel assay for determination of diadenosine polyphosphates in human platelets: studies in normotensive subjects and in patients with essential hypertension.

OBJECTIVE: Diadenosine polyphosphates (APnAs, n = 3-6) are a family of endogenous vasoactive purine dinucleotides which have been isolated from thrombocytes. Diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A) are more potent than diadenosine tetraphosphate (AP4A) and diadenosine triphosphate (AP3A) and cause skeletal muscle vasoconstriction in rats. Little is known about their physiological and pathophysiological significance in humans. The aims of the present study were to compare thrombocyte APnA concentrations in patients with essential hypertension (HYP) and in healthy normotensive humans (CON) using a novel quantitative assay and to assess a possible relationship between thrombocyte APnA concentrations and skeletal muscle vascular resistance. DESIGN AND METHODS: We describe a novel assay for quantification of APnAs in human platelets, involving platelet isolation from human blood, a solid-phase extracting procedure with a derivatized resin, desalting and quantitative determination of the substances with an ion-pair reversed-phase high-performance liquid chromatography (HPLC) system. The structural integrity of the isolated APnAs was confirmed by mixed assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) measurements and co-elution with added standards. The detection threshold for all four APnAs was 1 pmol/l and the inter-assay coefficients of variation were < 11% (n = 12). After venous blood sampling, mean arterial blood pressure (MAP) and forearm blood flow (FBF, using venous occlusion plethysmography) were measured in HYP and CON. Forearm vascular resistance (FVR) was calculated as MAP/FBF. significantly differ in platelet AP3A and AP4A content, but HYP had significantly higher thrombocyte concentrations of AP5A (56 +/- 7 versus 32 +/- 3 ng/microg beta-thromboglobulin, P = 0.003) and AP6A (10 +/- 1 versus 6 +/- 1 ng/microg beta-thromboglobulin, P = 0.015) than CON. HYP had significantly elevated FVR (50 +/- 6 versus 33 +/- 2 arbitrary units, P = 0.01) compared to CON. Significant correlations were found between AP5A and FVR (p = 0.38, P = 0.04) as well as between AP6A and FVR (p = 0.42, P = 0.02). In contrast, there were no significant correlations between APnAs and MAP. CONCLUSIONS: The study shows that thrombocyte concentrations of AP5A and AP6A are elevated in patients with essential hypertension. Vasoconstriction caused by release of AP5A and AP6A from thrombocytes may contribute to the increase of vascular resistance in hypertensive patients.

Progressive heterogeneity of myocardial perfusion in heart transplant recipients detected by thallium-201 myocardial SPECT.

UNLABELLED: Progressive graft atherosclerosis is a serious complication in long-term survivors after heart transplantation. Coronary angiography is insensitive with regard to the early and characteristic alterations. We evaluated the progression of these abnormalities and the influence of former rejection episodes. METHODS: Early after transplantation, 43 patients (34 men, mean age 53.7 +/- 10.7 yr) underwent stress and redistribution 201Tl myocardial SPECT after treadmill exercise. Twenty patients were followed-up to the second postoperative year, and 13 patients to the third postoperative year. Thallium-201 distribution and kinetic abnormalities were documented in a scheme enclosing 20 myocardial segments. Additionally, a score was developed that measured the degree of inhomogeneity of 201Tl distribution and the severity of perfusion defects, respectively. RESULTS: Regarding scintigraphy, pathologic results could be found in 40% of segments (redistribution, 25%; reverse redistribution, 30%; persistent defects, 49%). Score values in heart transplant recipients differed significantly from normal controls (p < 0.001) and were comparable to patients with single vessel disease of their native hearts. Thallium-201 inhomogeneity in recipients after treatable rejection episodes did not differ from results in recipients without any biopsy-proven rejection. The follow-up of cardiac transplant patients revealed a significant increase of score values up to the third year after transplantation (p < 0.02), despite reproducible normal angiography. There was no direct correlation between score values and IVUS results, although there was a parallel trend in 10 of 12 follow-ups. CONCLUSION: Despite normal coronary angiography, 201Tl myocardial SPECT frequently revealed pathologic results in heart transplant recipients. Scintigraphic results did not correlate with intimal thickening of epicardial coronary arteries accessible to intravascular ultrasonography in the early phase after transplantation. The presented score of inhomogeneity might reveal progressive disease possibly caused by small vessel alterations.

Alterations in calcium and magnesium content of red cell membranes in patients with primary hypertension.

A cellular calcium-magnesium antagonism seems to be involved in the pathogenesis of primary hypertension. Total plasma, intracellular, and membranous calcium (Ca) and magnesium (Mg) contents were determined in 39 untreated patients with essential hypertension (EH) and 40 normotensive healthy subjects (NT). Membranous and intracellular measurements were performed in erythrocytes. Ca and Mg contents were measured by atomic absorption spectroscopy and membrane protein was determined according to Bradford's method as a membranous reference. There was no significant difference in plasma Ca (NT: 2.60 +/- 0.15 v EH: 2.64 +/- 0.17 mmol/L) and Mg concentrations (NT: 0.83 +/- 0.12 v EH: 0.87 +/- 0.14 mmol/L) in the studied groups. Intracellular Mg (NT: 1.72 +/- 0.15 mmol/L v EH: 1.64 +/- 0.19 mmol/L) and Ca (NT: 2.06 +/- 0.20 mmol/L v EH: 2.10 +/- 0.24 mmol/L) contents were also not significantly different between groups. Membrane Ca content was significantly increased in the EH group (2.23 +/- 0.32 micromol/g membranous protein) compared to controls (1.05 +/- 0.30 micromol/g membranous protein, P < .01). On the contrary, membranous Mg content was significantly decreased compared to controls (0.31 +/- 0.09 v 0.50 +/- 0.10 mmol/g membranous protein content, P < .01). The Ca/Mg ratio in membranes was significantly increased in EH as compared to healthy subjects (P < .01) and correlated to mean arterial blood pressure values (r = 0.47, P < .01). We conclude that the membranous alterations of Ca and Mg metabolism, shown by increased Ca/Mg ratio in red cell membranes of hypertensive subjects, may play a role in the pathogenesis of primary hypertension.

Intracellular Mg++ concentrations in smooth and striated muscle cells in spontaneously hypertensive rats.

Decreased intracellular Mg++ concentrations seem to be involved in the pathogenesis of primary hypertension. Of special interest is the smooth muscle cell with its electrolyte metabolism in primary hypertension, but also heart muscle cells and their Mg++ concentrations are of growing interest. Therefore, in aortic smooth muscle cells and striated heart muscle cells (left ventricle) from 20 spontaneously hypertensive rats (SHR) of the Münster strain and 20 normotensive Wistar-Kyoto rats (WKY), the intracellular Mg++ content was measured. The electron probe x-ray microanalysis technique was used to determine intracellular Mg++ concentrations under nearly in vivo conditions in aortic cryosections 3 microm thick and striated heart muscle cells 4 microm thick (Camscan CS 24 apparatus). Vascular smooth muscle Mg++ content was 36.4 +/- 3.1 mmol/kg dry weight in SHR versus 48.6 +/- 3.7 mmol/kg dry weight in WKY (P < .001). In striated heart muscle cell Mg++ concentrations, there was no significant difference in SHR and WKY (79.9 +/- 5.6 versus 80.3 +/- 5.9 mmol/ kg dry weight). In conclusion, the present study revealed that genetic hypertension in the spontaneously hypertensive rat is accompanied by significantly decreased intracellular Mg++ concentrations in vascular smooth muscle cells. In striated heart muscle cells, Mg++ content was not significantly different in SHR and WKY. Mg++ handling is different in vascular smooth muscle and striated heart muscle cells in WKY and SHR (P < .01).

Studies on flow-mediated vasodilation and intima-media thickness of the brachial artery in patients with primary hyperparathyroidism.

The endothelium is a newly recognized target organ of parathyroid hormone (PTH) and may contribute to its effects on vascular tone and blood pressure regulation. Flow-mediated vasodilation (FMD), brachial and carotid intima-media thickness (IMT) were studied in patients with primary hyperparathyroidism (pHPT) and controls to evaluate endothelial function and structural arterial vessel wall alterations. Sixteen patients with pHPT (mean +/- SEM, age 44 +/- 5 years; PTH 229 +/- 72 ng/L; serum calcium 3.0 +/- 0.06 mmol/L; serum phosphate 2.0 +/- 0.2 mg/L) and 16 normocalcemic control subjects matched for age, sex, and blood pressure were included. Diabetes, hypertension, and vascular disease were excluded in both groups. End-diastolic diameter, flow-mediated (FMD) and nitroglycerin-mediated (NMD) dilation of the brachial artery were measured by a multigate pulsed Doppler system (echo-tracking). IMT was determined using automatic analysis of the M-line signal. Endothelium-dependent FMD was impaired in patients compared to controls (4.6 +/- 1.6% v 19.2 +/- 3.9%, P < .001). NMD (23.8 +/- 3.1% v. 22.4 +/- 2.8%, P = NS), carotid and brachial IMT (0.60 +/- 0.04 mm v 0.64 +/- 0.06 mm, P = NS, and 0.46 +/- 0.04 mm v 0.47 +/- 0.08 mm, P = NS, respectively) and artery diameters were not different. Endothelium-dependent vasodilation is impaired in patients with primary hyperparathyroidism despite normal IMT. Endothelial dysfunction may contribute to increased cardiovascular morbidity and mortality in pHPT.

Membrane, intracellular, and plasma magnesium and calcium concentrations in preeclampsia.

Changes in intracellular calcium and magnesium concentrations seem to be involved in the pathogenesis of preeclampsia, whereas the role of cell membranes has not been studied in detail yet. To investigate the changes in calcium and magnesium metabolism in normal pregnancy and preeclampsia, plasma, intracellular, and membrane calcium and magnesium concentrations were determined in a clinical study. Twenty-five control, 18 untreated healthy pregnant, and 16 nulliparas preeclamptic women were investigated. Plasma, cellular, and membrane (erythrocytes) calcium and magnesium contents were measured by atomic absorption spectroscopy. Plasma and intracellular magnesium concentrations were significantly lower in the healthy pregnant group and the preeclamptic group as compared to controls (P < .01). In erythrocyte membranes magnesium content was found significantly decreased in the preeclamptic women as compared to healthy subjects (P < .001). There was a significant decrease in the plasma calcium concentration in the preeclamptic group compared to controls or healthy pregnant women (P < .05). Membranous calcium content was significantly increased in the preeclamptic group versus controls or healthy pregnant women (P < .001) and an inverse correlation with membranous magnesium content was found (r = -0.79,P < .01). Lowered plasma, intracellular, and membrane magnesium concentrations in preeclampsia may contribute to the development in hypertension in pregnancy. In addition, a disturbed calcium homeostasis is observed in preeclampsia.

Flow-mediated vasodilation and distensibility in relation to intima-media thickness of large arteries in mild essential hypertension.

Whether endothelial dysfunction in essential hypertension is a cause or a consequence of structural vessel wall alterations is not known. The purpose of the present study was to compare flow-mediated vasodilation and mechanical vessel wall properties of large arteries between never treated mild essential hypertensive patients with normal intima-media thickness (IMT) and those exhibiting intima-media thickening. We measured brachial and carotid artery diameter and distension by Doppler frequency analysis of vessel wall movements in M-mode in ten essential hypertensive patients with normal carotid artery IMT (HYP1), in ten patients with increased IMT (HYP2), and in 13 normotensive control subjects (CON). Thereafter, we measured changes in brachial artery (BA) diameters during distal reactive hyperemia after 4 min of forearm occlusion. Nitroglycerin-mediated vasodilation was measured to assess endothelium-independent vasodilation, and BA blood flow was estimated using a pulsed Doppler system. Intima-media thickness of the carotid arteries was examined by high resolution B-mode ultrasound. IMT was 0.66 +/- 0.02 mm in the HYP1 group, 0.84 +/- 0.03 mm in the HYP2 group (P < .01 v HYP1, P < .01 v CON), and 0.71 +/- 0.04 mm in the CON group. Forearm occlusion was reduced in both the HYP1 group (3.4% +/- 3.6%, P < .01 v CON) and the HYP2 group (6.4% +/- 1.5%, P < .05 v CON) when compared with the CON group (16.5% +/- 2.8%). Nitroglycerin-mediated vasodilation and BA blood flow were not different between study groups. BA distension (as well as carotid artery distension) was significantly lower in the HYP1 group (52 +/- 6 microm, P < .05 v CON), but not in the HYP2 group (72 +/- 10 microm) when compared with the CON group (88 +/- 13 microm). The data suggest that endothelial dysfunction and reduced distensibility of large arteries in patients with essential hypertension occur in the absence of structural vessel wall alterations.

Decreased membrane Mg2+ concentrations in a subgroup of hypertensives: membrane model for the pathogenesis of primary hypertension.

Intracellular Mg2+ measurements were performed in erythrocyte membranes of 18 untreated normotensive and 19 untreated essential hypertensive patients. Mg2+ concentrations were determined by atomic absorption spectroscopy using a Video 12 apparatus. The results show that in patients with essential hypertension total Mg2+ content in erythrocyte membranes was significantly decreased as compared with the control group (0.28 +/-0.05 v 0.52+/-0.15 mmol/g membrane protein; mean+/-SD, P < .001). Additionally, plasma and free intracellular Mg2+ content of lymphocytes and platelets showed no significant difference in normotensives and hypertensives. Lowered total membrane Mg2+ concentrations in a subgroup of primary hypertensives may contribute to the development of this disorder, perhaps due to different buffering or membrane transport systems.

Vessel wall alterations in patients with renal failure.

Cardiovascular complications are a major cause of morbidity and mortality in patients with renal failure. Death due to myocardial infarction and to stroke is more frequent in hemodialysis patients than in the total population. These cardiovascular diseases are mainly the consequence of atherosclerosis and cause decreased life expectancy in patients with renal failure. Ultrasound techniques now make it possible to measure atherosclerotic lesions in big and medium-sized arteries. Thickening of the intima-media-complex is an early sign of atherosclerosis in these vessels. It reduces the distensibility of the arteries during systole. The distensibility of big and medium-sized arteries can be determined using ultrasound-doppler-techniques. In our studies, the intima-media-thickness of the carotid artery was significantly (p< 0.01) increased in patients with chronic renal failure (1.32+/-0.49 mm, n=28) as compared with aged-matched healthy control subjects (0.75 +/- 0.20, n= 29). The distensibility coefficient was higher (p< 0.05) in healthy controls (26 +/- 1.8 10(-3)/kPa, n= 12) than in patients with renal insufficiency (19 +/- 1.7 10(-3)/kPa, n = 12). This demonstrates increased stiffness of the vessel wall resulting in loss of Windkessel function and increased work load of the heart.

Studies on cardiac sympathovagal balance and large artery distensibility in patients with untreated essential hypertension.

BACKGROUND: Power spectral analysis of heart rate variability and arterial distensibility are non-invasive measures of cardiac autonomic modulation and mechanical vessel wall properties, respectively. The aim of the present study was to assess cardiac sympathovagal balance, carotid and brachial artery distensibility and a possible relation between these parameters in mildly hypertensive patients as compared to normotensive controls. METHODS: Total power (TP, 0.01 to 0.5 Hz) and spectral components (low frequency 0.04-0.15 Hz, mainly sympathetic cardiac modulation; high frequency 0.15-0.4 Hz, mainly vagal cardiac modulation) and cardiac sympathovagal balance (LF/LH ratio) of short term heart rate variability (ECG-recording) were calculated in 15 untreated essential hypertensive patients (HYP) and 15 age- and sex-matched healthy controls (CON). Brachial and carotid artery distensibility coefficient (DC) was measured with a multigate doppler system (echo-tracking). RESULTS: TP (ms2 x 10(-3)) (11.2 +/- 0.8 vs 13.6 +/- 0.9, P < 0.03), LF/HF ratio (1.07 +/- 0.08 vs 0.75 +/- 0.07, P < 0.01) and HF (ms2 x 10(-3)/%) (0.7 +/- 0.1/49 +/- 2 vs 1.3 +/- 0.2/58 +/- 2, P < 0.01/P < 0.01) were significantly reduced in HYP compared to CON subjects. LF (ms2 x 10(-3)/%) was 0.7 +/- 0.1/50 +/- 2 vs 0.9 +/- 0.1/41 +/- 2, P = 0.16/P < 0.01. Carotid artery DC (15 +/- 2 vs 26 +/- 2, P < 0.001) and brachial artery DC (4.7 +/- 0.6 vs 9 +/- 1.0, P < 0.001) were significantly reduced in HYP. There was a significant correlation between carotid DC and LF/HF (rho = -0.41, P < 0.03). CONCLUSION: The data shows reduced heart rate variability and altered cardiac sympathovagal balance as well as impaired arterial distensibility in untreated mildly hypertensive patients. The relative increase in sympathetic modulation and decreased carotid distensibility appear to be related.

Increased membraneous calcium concentrations in primary hypertension: a causal link to pathogenesis?

BACKGROUND: Disturbance in calcium metabolism has been suggested in the pathogenesis of hypertension, however, membrane calcium content in humans has not been studied in detail yet in primary hypertension. We compared plasma, intracellular and membrane calcium concentrations in erythrocytes of patients with essential hypertension and in healthy, normotensive control subjects to determine a possible alteration of membrane calcium in primary hypertension. SUBJECTS AND METHODS: Thirty-four never treated patients with essential hypertension were included and 34 healthy, age- and sex-matched volunteers served as controls. Atomic absorption spectroscopy was used for measurement of intracellular and membrane calcium content in erythrocytes and plasmalemmal preparations. RESULTS: Plasma and intracellular Ca(++) concentrations were not significantly different between hypertensives and controls (plasma: 2.59 +/- 0.18 vs2.50 +/- 0.16 mmol/l, intracellular: 1.89 +/- 0.20 mmol/l vs 1.97 +/- 0.24 mmol/l, NS resp., mean +/- s.e.m.). However, membrane calcium content was significantly higher in hypertensive patients compared to control subjects (2.38 +/- 0.28 micromol/g membraneous protein vs0.86 +/- 0.32 micromol/g membrane protein, P < 0.01). Membrane calcium content was correlated to mean arterial blood pressure (r = 0.59, P < 0.01). CONCLUSION: Membrane calcium content is significantly increased in patients with untreated primary hypertension and correlates to blood pressure levels. This data suggest, that an membrane mechanism may contribute to alterations in calcium metabolism and to the pathogenesis of primary hypertension.

Alterations of plasma calcium and intracellular and membrane calcium in erythrocytes of patients with pre-eclampsia.

BACKGROUND: Changes in plasma and intracellular calcium levels have been suggested in the pathogenesis of pre-eclampsia, however, membrane calcium content has not been studied so far. We compared intracellular and membrane calcium concentrations in erythrocytes of women with pre-eclampsia, healthy pregnant woman and controls to determine a possible alteration of membrane calcium in pre-eclampsia. SUBJECTS AND METHODS: Eighteen untreated, healthy pregnant woman and 16 pregnant nulliparous women with manifest pre-eclampsia were included, 25 healthy, age-matched woman served as controls. Atomic absorption spectroscopy was used for measurement of intracellular and membrane calcium content in erythrocytes and plasmalemmal preparations. RESULTS: Plasma Ca++ concentrations were significantly lower in pre-eclamptic women (1.96 +/- 0.15 mmol/l, P < 0.01, mean +/- s.e.m.) compared to healthy controls (2.43 +/- 0.14 mmol/l) or women with uncomplicated pregnancies (2.20 +/- 0.10 mmol/l). Intracellular Ca++ concentrations were not different between groups, however, membrane Ca++ content was significantly increased in the pre-eclamptic patients (1.23 +/- 0.36 micromol/g membrane protein, P < 0.01) compared to control subjects (0.83 +/- 0.16 micromol/g) and healthy pregnant women (0.77 +/- 0.13 micromol/g). CONCLUSION: Membrane calcium content is significantly increased in pre-eclamptic women despite low plasma Ca++ concentrations. This finding suggests an altered membrane ion transport and may be of importance for the pathogenesis of pre-eclampsia.

A longitudinal study of vessel wall properties in normotensive and hypertensive renal transplant recipients.

The mechanisms responsible for reduced arterial distensibility in renal transplant recipients remain to be evaluated. The present longitudinal study was aimed to evaluate the effect of hypertension on the evolution of vessel wall properties in renal transplant recipients. The mechanical properties of the common carotid artery were determined in 24 normotensive and 24 treated hypertensive renal transplant recipients 6-12 weeks after transplantation. The measurements were repeated after 2 years. Arterial distension was determined by using a multigate pulsed Doppler system, blood pressure (BP) was measured by a mercury sphygmomanometer. BP was 127 +/- 3/80 +/- 2 mm Hg at entry and 133 +/- 3/82 +/- 2 mm Hg after 2 years in the normotensive group, 146 +/- 4/90 +/- 3 mm Hg at entry and 145 +/- 3/87 +/- 2 mm Hg after 2 years in the hypertensive group (P < 0.01, normotensives vs hypertensives). The distensibility coefficient (DC) decreased significantly after 2 years in the hypertensive group (DC 18.3 +/- 1.3 10(-3)/kPa before, 15.1 +/- 1.2 10(-3)/kPa after 2 years, P < 0.05) whereas no significant change was observed in the normotensive group (DC 19.0 +/- 1.4 10(-3)/kPa before, DC 17.8 +/- 1.3 10(-3)/kPa after 2 years, NS). There was a significant correlation between the change of the distensibility coefficient after 2 years and mean arterial pressure (n = 48, r = 0.42, P < 0.01). The results show that the decrease of arterial distensibility after 2 years is accelerated in hypertensive renal transplant recipients despite effective anti-hypertensive treatment. Since BP levels were not different at entry into the study and after 2 years, differences in distending pressure along cannot explain the more pronounced decrease of arterial distensibility over time in hypertensive renal transplant recipients.