Search

Baroreceptor activation therapy (BAT) has been available for several years for treatment of therapy-refractory hypertension (trHTN). This procedure is currently being carried out in a limited number of centers in Germany, also with the aim of offering a high level of expertise through sufficient experience; however, a growing number of patients who are treated with BAT experience problems that treating physicians are confronted with in routine medical practice. In order to address these problems, a consensus conference was held with experts in the field of trHTN in November 2016, which summarizes the current evidence and experience as well as the problem areas in handling BAT patients.

Conventional medical curricula present information pertinent to chronic inflammatory diseases, infectious diseases and transplantation, via systematic lectures and courses in medical specialties without any integrated approach. The authors report on a 3-week model course that attempts to provide students with an overview of clinical presentation, diagnostics, and therapy of representative disease entities with particular emphasis on the interdisciplinary approach to these problems in hospital practice. In addition to problem-based learning in small groups, the model course comprises interdisciplinary concept lectures, practical demonstrations of specific diagnostic procedures, and bedside teaching. In the meantime, the course "Problem-Based Learning--Inflammation and Transplantation" has been held twice successfully as a mandatory course in the clinical part of the curriculum at the Muenster Medical School.

Patients with chronic renal failure are characterized by a tonic elevation of sympathetic tone. This factor largely contributes to their increased cardiovascular risk. The increased sympathetic drive is caused by activiation of renal afferent fibers in the diseased kidneys. Therapeutic options for hypertensive patients with chronic renal failure with respect to their sympathetic overactivity are inhibitors of the renin-angiotensin-system and central sympatholytic drugs. The role of catheter-based renal denervation in these patients is currently under investigation.

This commentary summarizes the expert consensus and recommendations of the working group 'Herz und Niere' of the German Society of Cardiology (DGK), the German Society of Nephrology (DGfN) and the German Hypertension League (DHL) on renal denervation for antihypertensive treatment. Renal denervation is a new, interventional approach to selectively denervate renal afferent and efferent sympathetic fibers. Renal denervation has been demonstrated to reduce office systolic and diastolic blood pressure in patients with resistant hypertension, defined as systolic office blood pressure ≥ 160 mm Hg and ≥ 150 mm Hg in patients with diabetes type 2, which should currently be used as blood pressure thresholds for undergoing the procedure. Exclusion of secondary hypertension causes and optimized antihypertensive drug treatment is mandatory in every patient with resistant hypertension. In order to exclude pseudoresistance, 24-hour blood pressure measurements should be performed. Preserved renal function was an inclusion criterion in the Symplicity studies, therefore, renal denervation should be only considered in patients with a glomerular filtration rate 45 ml/min. Adequate centre qualification in both, treatment of hypertension and interventional expertise are essential to ensure correct patient selection and procedural safety. Long-term follow-up after renal denervation and participation in the German Renal Denervation (GREAT) Registry are recommended to assess safety and efficacy after renal denervation over time.

In patients with severe hypertension a search for a renal cause, particularly for a renal artery stenosis, needs to be undertaken with 24-hour blood pressure measurement, urinary examination, determination of renal function and duplex sonography of the kidneys.--Sympathetic hyperactivity, which is associated with an increased cardiovascular risk, may already be found in an early stage of renal diseases. There is evidence that administration of an ACE inhibitor or an angiotensin receptor antagonist (ARB) may induce a decrease of sympathetic hyperactivity as well as a reduced rate of adverse cardiovascular events in patients in renal failure.--In patients with renal disease and high proteinuria antihypertensive therapy with ACE-inhibitors or ARB delays the progression of chronic renal failure. Combined therapy of ACE-inhibitors plus ARB may reduce proteinuria more than that would be the case with either of these drugs alone. However, there is no evidence that combination of these two drugs improves renal function more than monotherapy.--Renal artery stenosis of70% should be treated by dilatation, if there is evidence of fibromuscular dysplasia. Dilatation and/or stent implantation in an atherosclerotic renal artery stenosis of70% should be performed if indicated by the patient's clinical state. i.e. severe hypertension has proved to be resistant to triple drug antihypertensive therapy or pulmonary edema has occurred frequently. Preservation of renal function by angioplasty of an atherosclerotic renal artery stenosis remains a challenge. However, exact criteria for such intervention need to be established. But so far there have not been adequate data from controlled prospective trials.

A decrease in total magnesium content is not a direct proof of a decreased magnesium ion concentration. It could reflect a phosphate alteration or an ATP metabolism disorder. Plasma phosphate levels are lower in spontaneously hypertensive rats (SHRs) than in Wistar-Kyoto rats (WKYs), and defects in membrane regulation or mitochondrial ATP synthase occur. Only sparse data exist concerning cellular magnesium and phosphate concentrations in hypertensive cells. In aortic smooth muscle cells from 10 SHRs of the Münster strain and 10 age-matched normotensive WKY rats, the intracellular phosphate and magnesium content was measured by electron probe X-ray microanalysis (Camscan CS 24 apparatus, Cambridge, U.K.). The Mg++ content was 0.09 +/- 0.15 g/kg dry weight in SHRs versus 1.15 +/- 0.10 g/kg dry weight in WKY rats (p0.01). Vascular smooth muscle phosphate content was 23.6 +/- 0.79 g/kg dry weight in WKY rats versus 15.81 +/- 1.22 g/kg dry weight in SHRs (p0.01). In aortic smooth muscle cells of one month old SHRs intracellular magnesium was measured as 1.05 +/- 0.08 versus 1.09 +/- 0.09 g/kg dry weight in WKYs. Intracellular phosphate concentration in one month old SHRs was 18.71 +/- 2.41 versus 21.36 +/- 1.25 g/kg dry weight in WKYs (eight animals in each group). Aortic smooth muscle cells of SHRs are caracterized by markedly lowered intracellular phosphate and magnesium concentrations, resulting in an altered ATP-metabolism, as described earlier. Possibly a membrane defect or a magnesium deficiency or disturbed magnesium channels are responsible for the early onset in the pathogenesis of primary hypertension.

Decisions about the management of patients with hypertension should not be based on the level of blood pressure alone but also on the presence of target organ damage. Apart of classical sites of target organ damage - kidney and heart - the assessment of functional and structural alterations of large arteries is of increasing clinical importance. Modern non-invasive procedures allow the assessment of large artery wall properties within the clinical routine. Hypertension associated large artery damage may present as structural and functional alterations. Structural alterations comprise intima-media thickening, plaque formation, stenosis of the artery and formation of aneurysms. Functional alterations comprise endothelial dysfunction and alterations of the mechanical properties of the arterial wall with increasing stiffness and loss of the Windkessel function. Loss of central artery elastic properties will ensue an early reflection of the pulse wave with a resulting increase in central systolic and central diastolic pressure. This causes an increase in left ventricular afterload and a reduction in diastolic perfusion of the myocardium. In the last decade the relevance of large artery structural alterations, endothelial dysfunction and arterial stiffness for the risk of cardiovascular morbidity and mortality in hypertensive patients could be demonstrated convincingly. Measurement of intima-media-thickness therefore is part of the standard evaluation of hypertensive patients. Because of the equal prognostic relevance of functional properties of the arterial wall, assessment of large artery functional alterations is helpful for the risk stratification of hypertensive patients. Modern antihypertensive drugs have favourable effects on arterial wall properties. Therefore, the quantification of large artery wall properties should be part of the management of hypertensive patients.

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.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 was140/90 mmHg. The dialysis patients and renal transplant recipients were eligible for the study if the serum creatinine level was2 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.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; P0.01 and n = 35; r = 0.48; P0.05). In the T group also an important correlation between PWV and IMT complex (n = 35; r = 0.49, P0.001) was found.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.

Alterations in the metabolism of calcium and magnesium have been implicated in the pathogenesis of primary hypertension. Calcium influx across the external cellular membrane in smooth muscle cells and cardiomyocytes plays a crucial role in the control of cellular excitation contraction and impulse propagation. Intracellular calcium and magnesium concentrations are controlled by reversible binding to specific calcium binding proteins. The calcium and magnesium flux across the external membrane is regulated by a calcium pump (calcium-magnesium-ATPase), calcium channels and binding to the membrane. In cell membranes and in lymphocytes of essential hypertensives, our group showed increased calcium and decreased magnesium and an increased calcium/magnesium ratio in hypertensive cells. In this context, in aortic smooth muscle cells from 13 spontaneously hypertensive rats (SHR) of the Münster strain (systolic blood pressure 188.4+/-9.8 mmHg) and 13 normotensive rats (NT, systolic blood pressure 118.5+/-7.2 mmHg) aged 9 months, the intracellular calcium and magnesium contents were measured under nearly in vivo conditions by electron-probe microanalysis. Measurements were performed in aortic cryosections 3 microm thick. The calcium content was 124.7+/-4.5* mmol/kg dry weight in SHR versus 110.3+/-4.1 mmol/kg dry weight in NT (Means+/-SD, p0.01), the magnesium content was 35.5+/-3.9* in SHR versus 50.1+/-4.9 mmol/kg dry weight in NT /p0.01). The calcium/magnesium ratio was significantly increased in SHR versus NT (3.56+/-0.39* versus 2.23+/-0.27, p0.01). In hypertensive one month old animals the increase in the calcium/magnesium ratio was not as pronounced as in 9 month old animals. The calcium/magnesium ratio was measured 3.3+/-0.42 in SHR (n = 8) as compared to 2.51+/-0.39 in normotensive animals (n = 8, p0.01). Aortic smooth muscle cells from SHR are characterized by markedly elevated intracellular calcium and decreased intracellular magnesium contents compared with normotensive cells. The increased calcium/magnesium ratio in hypertensive cells may be a pathogenetic factor for the development of arteriosclerosis and hypertension.

Conventional medical curricula present information pertinent to chronic inflammatory diseases, infectious diseases and transplantation, via systematic lectures and courses in medical specialties without any integrated approach. The authors report on a 3-week model course that attempts to provide students with an overview of clinical presentation, diagnostics, and therapy of representative disease entities with particular emphasis on the interdisciplinary approach to these problems in hospital practice. In addition to problem-based learning in small groups, the model course comprises interdisciplinary concept lectures, practical demonstrations of specific diagnostic procedures, and bedside teaching. In the meantime, the course "Problem-Based Learning--Inflammation and Transplantation" has been held twice successfully as a mandatory course in the clinical part of the curriculum at the Muenster Medical School.

During the past two decades great progress was achieved with regards to short-term kidney graft survival. However, long-term graft survival did not improve similarly. Many factors contribute to chronic graft nephropathy eventually resulting in late graft loss, among these arterial hypertension is of major importance. In patients with chronic renal disease of diabetic and non-diabetic origin, angiotensin converting enzyme inhibitors have been convincingly shown to slow the progression of renal failure. The achieved nephroprotection correlates with the reduction of proteinuria by ACE inhibitor treatment. Also in renal transplant patients, ACE inhibitors have been shown unequivocally to reduce urinary protein excretion. The prevention of hyperfiltration, particular in the context of a reduced number of functional nephrons in patients with chronic graft nephropathy, could be important to prolong graft survival after renal transplantation. Moreover, ACE inhibitors may exert beneficial effects on immunologic processes contributing to chronic graft nephropathy. Many studies published in the last decade show convincingly that ACE inhibitors are safe and effective for the treatment of hypertension in renal allograft recipients. However, no data exist so far showing that ACE inhibitors are superior to other antihypertensive drugs in renal transplant patients and that they prolong graft survival. Studies investigating this issue are warranted. Apart from effects on the graft, ACE inhibitors may improve alterations of the cardiovascular system generally observed in renal transplant patients, such as structural alterations of large arteries, left ventricular hypertrophy, disturbed mechanical vessel wall properties and endothelial dysfunction. Therefore, angiotensin converting enzyme inhibitors could reduce cardiovascular morbidity and mortality in kidney transplant patients.

To compare the effects of two long-acting calcium antagonists of different types on cardiovascular stress responses in hypertension.One-hundred and forty-five patients with mild to moderate hypertension and a mean (+/- s.e.mean) age of 51 +/- 0.9 years received for 8 weeks the phenylalkylamine verapamil sustained release (240 mg) and the dihydropyridine amlodipine (5 mg) in a double-blind cross-over design, both after 4 weeks of placebo. Blood pressure, heart rate and plasma noradrenaline were monitored during 3 min of sustained isometric handgrip and 2 min of cold pressor.Blood pressure was equally reduced by both drugs. After 3 min handgrip, systolic blood pressure, heart rate and rate-pressure product were lower with verapamil compared with amlodipine. Verapamil attenuated the increases in systolic blood pressure (25 +/- 2 vs 30 +/- 2 mmHg, difference 4.6, 95% CI (1.0, 8.1), P0.01) and rate-pressure product (3.1 +/- 0.2 vs 3.6 +/- 0.3 x 10(3) mmHg x beats min(-1), difference 0.5, 95% CI (0.1, 0.9), P0.01) during handgrip compared with amlodipine. Similar results were observed during cold pressor. Plasma noradrenaline levels were lower with verapamil compared with amlodipine at rest and after both tests, but the increases in plasma noradrenaline were not significantly different.Verapamil is more effective in reducing blood pressure and rate-pressure product responses to stress compared with amlodipine. Although plasma noradrenaline is lower with verapamil at rest and after stress, the increase during stress is not different.

There is evidence that secondary hyperparathyroidism alters arterial vessel wall properties. However, it is unclear whether effects of parathyroid hormone (PTH) on the vascular wall are direct or permissive and related to hypertension and renal failure. To assess early direct effects of PTH on large artery wall properties isobaric distensibility (DC), pulse wave velocity (PWV) and intima-media thickness (IMT) were studied before and after parathyroidectomy (Ptx) in patients with primary hyperparathyroidism (pHPT).DC and IMT of the brachial and carotid artery were measured by echo-tracking and tonometry, PWV by the automatic Complior-device at baseline and 6 months after Ptx in 20 patients with pHPT (data mean +/- SEM, age 45+/-5 years, PTH 240+/-61 ng/l). Cardiovascular risk factors like diabetes, hypertension, renal insufficiency and hypercholesterolemia were excluded. Twenty healthy volunteers matched for age, sex and blood pressure served as controls.Six months after Ptx, PTH decreased to normal; however, blood pressure levels and vessel wall parameter remained unchanged. At baseline, there were no significant differences in brachial and carotid IMT (0.48+/-0.04 and 0.62+/-0.04 mm vs. 0.47+/-0.06 and 0.61+/-0.06 mm), radial and aortic PWV (9.1+/-0.4 and 9.9+/-0.7 m/s vs. 9.2+/-0.5 and 10.0+/-0.6 m/s), brachial and isobaric carotid DC (10.1+/-1.4 and 19.5+/-3.4 10(-3)/kPa vs. 9.1+/-0.9 and 20.4+/-3.2 10(-3)/kPa) or artery diameter between patients and controls.Structural and viscoelastic properties of large arteries are not disturbed and not influenced by parathyroidectomy in patients with early pHPT devoid of hypertension and renal disease. We conclude that increased PTH levels per se are not associated with alterations of mechanical arteriall wall properties; permissive factors like renal insufficiency may be necessary to mediate vessel wall alterations in patients with hyperparathyroidism.

A decrease in total magnesium content is not a direct proof of a decreased magnesium ion concentration. It could reflect a phosphate alteration or an ATP metabolism disorder. Plasma phosphate levels are lower in spontaneously hypertensive rats (SHRs) than in Wistar-Kyoto (WKY) rats, and defects in membrane regulation or mitochondrial ATP synthase occur. Only sparse data exist concerning cellular magnesium and phosphate concentrations in hypertensive cells. In aortic smooth muscle cells from 10 SHRs of the Münster strain and 10 age-matched normotensive WKY rats, the intracellular phosphate and magnesium content was measured by electron probe X-ray microanalysis (Camscan CS 24 apparatus, Cambridge, U.K.). The Mg++ content was 0.90+/-0.15 g/kg dry weight in SHRs versus 1.15+/-0.10 g/kg dry weight in WKY rats (p0.05). Vascular smooth muscle phosphate content was 23.6+/-0.79 g/kg dry weight in WKY rats versus 15.81+/-1.22 g/kg dryweight in SHRs (p0.01). In seven animals, erythrocytic ATP content was 180.2+/-102 in SHRs vs. 432+/-72 micromol/L cells in WKY rats (p0.01). The Na+/K+-ATPase activity was significantly decreased in hypertensive animals as compared to controls (6.49+/-2.3 vs. 12.64+/-2.9 nmol inorganic phosphate/mg protein/min (p0.01)). Aortic smooth muscle cells from SHRs are characterized by markedly lowered cellular phosphate and magnesium concentrations and an altered ATP metabolism, possibly due to a membrane defect or a magnesium deficit in hypertensive cells.

Osteoporosis remains a major problem following kidney transplantation. Radiographic measures of bone mass are of limited predictive value after transplantation and are complicated by preexisting renal osteopathy. Quantitative ultrasound (QUS) is a new and non-invasive method to assess skeletal status, however, no data exist on ultrasonic bone parameter after kidney transplantation. We evaluated the potential use of this novel method in renal allograft recipients and studied the accuracy compared to normal controls.Thirty patients (NTP, age 47.5 +/- 13.0 years) were studied 4.8 +/- 3.2 years after transplantation. Twenty-five healthy control persons (CON) were matched for age and sex. The left and right os calcis were studied by QUS and speed of sound (SOS) and broadband ultrasound attenuation (BUA) were measured. Bone stiffness (BS) was calculated from these parameters and corrected for age (CBS). Differences between right and left os calcis were compared to CON to assess the side variability.Mean +/- SD BS was 75 +/- 22% compared to young adults, age-corrected CBS was decreased in NTP with 86 +/- 25% of normal, indicating a two-fold increased risk of fracture. SOS was 1525 +/- 47.7 m/s, BUA 105 +/- 22 dB/MHz. Mean difference between right and left os calcis was significantly higher in NTP than in CON (7.2 +/- 7.1% vs. 2.1 +/- 2.1%, p0.01). Limits of agreement of the measurements (MW of differences +/- 2 SD) according to a Bland-Altmann-type statistic were -16.9% and 20.7%. There was no correlation between CBS and age, cumulative steroid dose, parathyroid hormone concentrations or time after transplantation.Our data show altered bone structure expressed by low bone stiffness values measured by quantitative ultrasound in kidney transplant patients. However, because of relatively high inter-feet variance of QUS results we suggest measurement of both ossa calcis to minimize measurement error after transplantation.

Renovascular hypertension as a secondary form of hypertension can be improved or cured in many cases by interventional radiology or vascular surgery.The renin-angiotensin-aldosterone system and the development of hypertension are linked in renovascular hypertension.Early clinical symptoms are of special interest in diagnosing renovascular hypertension.Nowadays, angioplasty or stenting have mostly replaced surgery in view of treatment of renovascular hypertension.Renovascular hypertension, if diagnosed early, can be improved or cured in many cases regarding hypertension and/or renal insufficiency.

Alterations of arterial vessel wall function are associated with increased cardiovascular morbidity and can be measured by noninvasive ultrasound techniques. There is increasing evidence that hyperparathyroidism contributes not only to structural changes of the cardiovascular system but to disturbances in functional arterial vessel wall properties. It has been shown that elevated concentrations of parathyroid hormone are associated with decreased arterial distensibility and increased intima-media thickness in patients with renal insufficiency. A permissive role of parathyroid hormone in the pathogenesis of uremic vessel wall changes has been discussed. The endothelium is a newly recognized target organ of parathyroid hormone. In patients with primary hyperparathyroidism endothelial dysfunction has been demonstrated, that seems to be reversible after parathyroidectomy. Effects on arterial vessel wall function may contribute to increased blood pressure observed in hyperparathyroidism. The complex cardiovascular effects of parathyroid hormone and changes in vascular tone, arterial distensibility and endothelial function in hyperparathyroidism are discussed.

Cardiovascular events are the main cause of death in patients with end-stage renal disease. Functional and structural alterations of the arterial system substantially contribute to the high cardiovascular mortality in these patients. Structural alterations of the arterial wall comprise intima-media thickening and atherosclerotic plaque formation. Moreover, mechanical vessel wall properties of large arteries are significantly disturbed. This is already observed in young patients. Reduced arterial distensibility impairs large artery cushioning function. This results in increased ventricular afterload promoting left ventricular hypertrophy and in reduced coronary perfusion. After renal transplantation, structural alterations of the arterial wall and disturbed mechanical vessel wall properties persist. Moreover, renal failure is characterized by a severe impairment of endothelial function. Disturbed endothelial function results from reduced production of endothelium-dependent endogenous vasodilators and/or blunted vascular effects of these substances. Uremia is associated with the accumulation of an endogenous inhibitor of the endothelial nitric oxide synthase. Impaired endothelial function in renal failure promotes the progression of structural lesions of the arterial wall. Also in renal transplant recipients, substantially impaired endothelial function is observed despite correction of uremia. Hyperparathyroidism commonly observed in renal failure contributes to the disturbed functional vessel wall properties of large arteries. In patients with end-stage renal disease, decreased large artery distensibility is an independent risk factor for increased cardiovascular mortality. This may apply also to intima-media thickening and to impaired endothelial function.

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 Munster 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).

There are now numerous studies demonstrating that essential hypertension is accompanied by sympathetic activation. Using drugs which block cardiac sympathetic effects, it could be shown that a noticeable fraction of subjects with borderline hypertension had an increased sympathetic drive. A meta-analysis of studies on plasma noradrenaline levels as an indirect marker of sympathetic tone reported that noradrenaline concentrations were significantly elevated in patients with essential hypertension as compared with normotensive control subjects. In addition, it could be shown that the rate of noradrenaline spillover from sympathetic nerve terminals was sometimes increased in essential hypertension, particularly in young hypertensive subjects. Additional data have emerged by direct measurement of sympathetic nerve traffic to skeletal muscle circulation using a microelectrode technique. Most studies using this method have demonstrated increased sympathetic nerve activity in patients with essential hypertension. In contrast, patients with secondary hypertension did not differ from normotensive subjects. Taken together, the data available at present show that sympathetic activation is a specific feature of essential hypertension and that it may play a pathogenetic role in this disease.

A 49-year-old, otherwise healthy woman had recurrent fever and lymphadenopathy with leukopenia for nineteen years. Her symptoms prompted successless antibiotic therapy and extensive evaluations of fever of unknown origin. At admission there were several enlarged cervical lymph nodes and subfebrile temperatures.Neither laboratory findings nor imaging did show an infectious, rheumatologic or hematologic cause of her symptoms. Histopathological examination of an lymph node biopsy revealed histiocytic, necrotizing lymphadenitis (Kikuchi-Fusimoto disease) as the underlying disease.After spontaneous resolution without specific therapy the patient is now symptomless and well 9 months after diagnosis.Kikuchi-Fusimoto disease is a cause of benign and usually self-limiting lymphadenopathy. Clinicians and pathologists should be aware of this uncommon differential diagnosis since early histologic recognition will minimize potentially and unnecessary evaluations and treatments.

The physiological effects of cigarette smoking have been widely studied; however, little is known about the effects of acute exposure to sidestream smoke (passive smoking). We examined the effects of sidestream smoke on muscle sympathetic nerve activity (MSNA) and forearm vascular resistance (FVR) at rest and during stressful stimuli, including the cold pressor test (CPT), sustained handgrip (SHG), and mental stress (MS).In 17 healthy nonsmokers, blood pressure (BP), heart rate (HR), forearm blood flow (venous occlusion plethysmography), FVR, and MSNA (obtained through direct intraneural recordings) were measured before and during inhalation of sidestream smoke in one session (n = 16) and before and during vehicle (air) inhalation in another session (n = 17) on a separate day. The order of sessions was randomized between subjects. Responses to CPT, SHG, and MS were measured before and after inhalation of smoke or vehicle (ie, twice during each session). After 15 minutes' exposure to sidestream smoke, plasma nicotine and carboxyhemoglobin levels increased to 0.77 +/- 0.11 ng/mL and 0.36 +/- 0.04% (mean +/- SEM, P.05), respectively. Sidestream smoke, but not vehicle inhalation, increased resting MSNA from 23 +/- 2 to 28 +/- 2 bursts/min (P.05). FVR increased with passive smoking, but this increase was not significantly different from the change in FVR with vehicle. Plasma norepinephrine and epinephrine, BP, and HR were not changed significantly by sidestream smoke. The responses of MSNNA, BP, HR, and FVR to the stressful stimuli were not potentiated by sidestream smoke, except for an increased BP response to the CPT (P.05).Acute short-term passive (sidestream) smoke exposure elicits a modest increase in MSNA in healthy non-smokers but does not change HR, BP, or FVR.

This is a case report of heparin-associated thrombocytopenia syndrome (white clot syndrome). An 81-Year-old patient was treated with sodium-heparin for proximal deep-venous thrombosis and pulmonary embolism. During administration of heparin, the platelet count decreased to a nadir of 27/nl on day 14 after initiation of this therapy. We also observed a recurrence of pulmonary embolism as well as arterial thromboembolism in the right arm and the right leg. After immediate discontinuation of heparin therapy and change of anticoagulation to oral anticoagulants with overlapping administration of a low molecular weight heparin and application of immunoglobulins, we observed total recanalization of the arterial occlusions, normalization of lung-perfusion scan and rapid recovery of the platelet count.

ObjectiveSystemic lupus is a chronic autoimmune disease characterised by its phenotypic heterogeneity. Neutropaenia is a frequent event in SLE occurring in 20%–40% of patients depending on the threshold value of neutrophil count. On a daily basis, the management of neutropaenia in SLE is difficult with several possible causes. Moreover, the infectious consequences of neutropaenia in SLE remain not well defined.Methods998 patients from the Lupus BioBank of the upper Rhein (LBBR), a large German and French cohort of patients with SLE, mostly of Caucasian origin (83%), were included in this study. Neutropaenia was considered when neutrophil count was below 1800×106/L. An additional analysis of detailed medical records was done for 65 LBBR patients with neutropaenia.Results208 patients with neutropaenia (21%) were compared with 779 SLE patients without neutropaenia. Neutropaenia in SLE was significantly associated with thrombocytopaenia (OR 4.11 (2.57–10.3)), lymphopaenia (OR 4.41 (2.51–11.5)) and low C3 (OR 1.91 (1.03–4.37)) in multivariate analysis. 65 representative patients with neutropaenia were analysed. Neutropaenia was moderate to severe in 38%, chronic in 31%, and both severe and chronic in 23% of cases. Moderate to severe and chronic neutropaenia were both associated with lymphopaenia and thrombopaenia. Chronic neutropaenia was also associated anti-Ro/SSA antibodies and moderate to severe neutropaenia with oral ulcers.ConclusionThis study is to date the largest cohort to describe neutropaenia in SLE. Neutropaenia displays a strong association with other cytopaenias, suggesting a common mechanism. Chronic neutropaenia is associated with anti-Ro/SSA antibodies with or without identified Sjögren’s disease.