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Biomedical subjects

L C Rump

Publications and source records attributed to L C Rump.

At least 19 recordsLinked to original sources
PubMed2006

Alpha(2A)-adrenoceptors regulate sympathetic transmitter release in mice kidneys.

BACKGROUND AND PURPOSE: In the present study, a rodent model was used to investigate whether the alpha(2A)-adrenoceptor (alpha(2A)) represents the presynaptic autoinhibitory receptor regulating sympathetic transmitter release in the kidney. Moreover, the potential role of alpha(2A) as a heteroceptor regulating adenosine triphosphate (ATP) release was tested. EXPERIMENTAL APPROACH: Kidneys from wild-type (WT) and alpha(2A)-knockout (KO) mice were isolated and perfused. Renal nerves were stimulated with platinum-electrodes. Endogenously released noradrenaline (NA) was measured by HPLC. The perfusion pressure was monitored continuously. KEY RESULTS: Renal nerve stimulation (RNS) induced a frequency (1,2,5,7.5,10,15 Hz)-dependent release of NA in WT mice (994+/-373, 2355+/-541, 6375+/-950, 11626+/-1818, 19138+/-2001 pg NA g(-1) kidney (means+/-s.e.m.)). There was a 2.7-fold (5 Hz) increase of NA release in alpha(2A)-KO mice. In WT animals alpha-adrenoceptor blockade by phentolamine increased RNS-induced NA release in a concentration-dependent manner up to 350% of control. No facilitation by phentolamine was observed in alpha(2A)-KO mice. Pressor responses to 1 Hz and 2 Hz were resistant to alpha(1)-adrenoceptor blockade (0.03 microM prazosin) but abolished by P(2) receptor blockade (5 microM PPADS). Blockade of alpha(2)-adrenoceptors (1 microM rauwolscine) increased these purinergic pressor responses to 296+/-112% (1 Hz) in WT but not in alpha(2A)-KO mice. Exogenous ATP (100 microM) increased basal but not RNS-induced NA release. CONCLUSIONS AND IMPLICATIONS: alpha(2A)-Adrenoceptor-activation inhibits NA and ATP release from renal sympathetic nerves. Pressor responses to RNS at higher stimulation frequencies (>2 Hz) are mediated by NA. At lower frequencies neuronally released ATP seems to be the predominant transmitter mediating renovascular resistance.

Adenosine Triphosphate↗
PubMed2006

Obstructive sleep apnoea and its therapy influence high-density lipoprotein cholesterol serum levels.

Recent studies suggest an association of obstructive sleep apnoea (OSA) with cardiovascular risk factors, such as dyslipidaemia. The present study analyses the effects of OSA and its therapy on serum lipid concentrations in 470 OSA patients in a single centre study. Multivariate regression showed a significant association between the apnoea-hypopnoea index and high-density lipoprotein cholesterol (HDL-C) serum levels (n = 366), independent of age, sex, body mass index, diabetes and lipid lowering medication. There were no independent associations with total cholesterol, triglyceride and low-density lipoprotein cholesterol serum levels. During follow-up (6 months) with effective bilevel or continuous positive airway pressure therapy in 127 patients (lipoproteins: n = 86) without change in their lipid lowering therapy, the mean HDL-C serum level increased significantly by 5.8% from 46.9+/-15.8 to 49.6+/-15.3 mg x dL(-1) (mean+/-SD). An independent relationship was found between the change of apnoea-hypopnoea index and the change of high-density lipoprotein cholesterol or triglycerides, respectively. All patients with abnormal serum lipid/lipoprotein levels improved significantly under bilevel or continuous positive airway pressure therapy. This study demonstrates an influence of obstructive sleep apnoea and its therapy on high-density lipoprotein cholesterol levels.

Analysis of Variance↗
PubMed2005

Dihydrotachysterol therapy for hypoparathyroidism: consequences of inadequate monitoring. Five cases and a review.

BACKGROUND: The half synthetic Vitamin D analogue dihydrotachysterol (DHT) is widely used for hypocalcaemic hypoparathyroidism following surgical removal of parathyroids. Such treatment generally initiated by surgeons right after surgery has to be continued in clinical practice. Unfortunately, the required careful monitoring of calcium metabolism is often lacking and as demonstrated may lead to life-threatening conditions. PATIENTS AND METHODS: Here we report on five patients referred to our nephrology unit because of unknown impairment of renal function during therapy with DHT. All patients had clinical signs of hypercalcaemia. Since most symptoms are nonspecific they were not perceived by primary care physicians. In fact DHT treatment was continued for 4 - 50 years. In all cases calcium levels were determined after inadequate long intervals ranging from 3.08 to 4.97 mmol/l. Creatinine levels ranged from 277 to 365 micromol/l. All patients suffered from symptoms of severe hypercalcaemia, three of them needing intensive care unit treatment. RESULTS: All patients were treated effectively with a regimen consisting of intravenous saline, a loop diuretic, and application of bisphosphonates. As confirmed by renal biopsy persisting alleviation of renal function was due to calcifications. After discontinuation of DHT therapy patients were safely switched to shorter acting vitamin D derivates maintaining a normal calcium level. CONCLUSIONS: In comparison to short acting vitamin-D derivates hypercalcaemic episodes with DHT appear to last longer and may therefore occur with higher incidence. A future option could be the use of synthetic parathyroid hormone (s-PTH) recently shown to be safe and effective. Nevertheless a customized therapy and careful monitoring is indispensable in any case to prevent irreversible organ damage.

Aged↗
PubMed2005

Nephrolithiasis and hematuria--sometimes a stony road to diagnosis.

We report a case of a young man with a history of kidney stones. Occurrence of gross hematuria several months after the extracorporeal shock wave, lithotripsy (ESWL) treatment lead to hospitalization. By ultrasound and abdominal CT scan, the urologist could exclude post-renal causes of the gross hematuria and acute renal failure. After transfer to a department of nephrology hemodialysis was started, an immediate kidney biopsy was performed and prednisolone was administered on the same day. The kidney biopsy revealed an anti-glomerular basement membrane (GBM) disease. The renal function did not recover and the patient remained on hemodialysis. In the literature it has been hypothesized that ESWL-treated patients are prone to develop anti-GBM disease by liberation of glomerular basement antigen through the ESWL high energy shock waves. An additional hypothesis considering the higher susceptibility for anti-GBM disease among certain HLA-tissue types is discussed with regard to our case. Unfortunately, the prolonged track to diagnosis and delayed immunosuppressive treatment could not prevent poor clinical outcome. Although anti-GBM disease is a rather rare disease, it should be included as a differential diagnosis for hematuria--especially months after ESWL treatment. Otherwise early diagnosis may be missed and as in our patient immunosuppressive treatment will remain unsuccessful to recover renal function.

Adult↗
PubMed2004

[Renal function in hypertensive patients with obstructive sleep apnea].

BACKGROUND: Patients with hypertension often suffer from obstructive sleep apnea (OSA). In addition to hypertension several other risk factors (hypoxemia, hyperlipidemia, and increased sympathic nerve activity) may contribute to progressive renal dysfunction in OSA patients. The aim of this study was to compare renal function in OSA-patients with and without hypertension. METHODS: 81 consecutive patients (50 males, 31 females) were screened for sleep apnea. Parameters of renal function (serum creatinine, creatinine clearance, microalbuminuria), and of lipid and glucose metabolism were correlated to polysomnographic results. RESULTS: OSA (apnea/hypopnea index [AHI] > or = 5) was found in 57 of 81 patients. Mean AHI was 26.7 +/- 26.1. Hypertension (blood pressure > or = 140/90 mmHg or use of antihypertensive drugs) occurred in 63 of 81 patients. Serum creatinine in OSA patients was significantly higher than in patients without OSA (1.11 +/- 0.15 vs. 0.91 +/- 0.12 mg/dl, p < 0.001). Serum creatinine correlated significantly with AHI. Creatinine clearance was associated with age (r = -0.314; p = 0.014) and presence of OSA (r = 0.265; p = 0.093). No correlation was shown between hypertension and serum creatinine or creatinine clearance. Microalbuminuria was not associated with OSA. CONCLUSION: Our results suggest an independent association between OSA and impaired renal function. Further prospective studies will have to be done to elucidate the pathophysiological mechanisms.

Adult↗
PubMed2003

Leptospirosis--3 cases and a review.

Leptospirosis is an infectious disease of variable severity characterized by sudden onset of headache, myalgia and prostration. Although most common in the tropics, an increasing number of cases is reported in Europe and Northern America. Severe forms referred to as Weil's disease commonly involve kidneys, liver, lungs, CNS and heart and require early recognition and immediate initiation of adequate therapy. We describe 3 patients with Weil's syndrome from an urbanized region in Southern Germany, who developed renal and respiratory failure. PCR facilitated early diagnosis, and therefore, specific treatment before serological tests were positive. Illustrating the case histories, initial presentations and clinical courses, we point out difficulties with early diagnosis and treatment. Furthermore, we offer a comprehensive overview on leptospirosis with emphasis on renal involvement, current diagnostic tools and evidence-based therapy.

Adolescent↗
PubMed2001

Acetylcholine release in human heart atrium: influence of muscarinic autoreceptors, diabetes, and age.

BACKGROUND: An imbalance of sympathetic and parasympathetic drive to the heart is an important risk factor for cardiac death in patients with coronary heart disease, diabetes, and renal insufficiency. The amount of neurotransmitter released from peripheral autonomic nerves is modulated by presynaptic receptor systems. In analogy to alpha-autoreceptors on sympathetic nerves, muscarinic autoreceptors activated by endogenous acetylcholine may exist on parasympathetic nerves in the human heart. METHODS AND RESULTS: We developed a technique to study acetylcholine release from human atria and investigated muscarinic autoreceptor function. A pharmacological and molecular approach was used to characterize the subtype involved. Of the 5 muscarinic receptor subtypes cloned, only mRNA encoding for M(2)- and M(3)-receptors were detected. Potencies of several muscarinic antagonists against the release-inhibiting effect of the nonselective muscarinic agonist carbachol at the cardiac autoreceptor were correlated with published data for human cloned M(1)- through M(5)-receptors. CONCLUSIONS: This analysis clearly indicates that acetylcholine release in human atria is controlled by muscarinic M(2)-receptors. Blockade of these receptors by atropine doubles the amount of acetylcholine released at a stimulation frequency of 5 Hz. In atria of patients >70 years of age and patients with late diabetic complications, acetylcholine release is reduced. Locally impaired cardiac acetylcholine release may therefore represent a pathophysiological link to sudden cardiac death in elderly and diabetic patients.

Acetylcholine↗
PubMed2001

Contractile effects of tacrolimus in human and rat isolated renal arteries.

1. We tested the vasoactive properties of the immunosuppressive drug FK 506 (tacrolimus) in preconstricted rat and human isolated renal arteries in vitro. 2. In rat renal arteries, tacrolimus (3, 10 microM) showed a direct and dose-dependent contractile effect by maximally 23 microm (10% of the noradrenaline effect), which was only observed in the presence of intact endothelium. Moreover, a lower concentration of tacrolimus (1 microM) potentiated pressor responses to the sympathetic neurotransmitter noradrenaline but not to ATP in this species. ATP- (0.01-10 microM) induced vasodilation was not affected by tacrolimus (1 microM). 3. In contrast, in human interlobar arteries, tacrolimus failed to induce direct vasoconstriction and did not significantly potentiate constrictor responses to noradrenaline. Acetylcholine-(1 microM) induced vasodilation was much smaller in human than in rat renal arteries suggesting the lack of functional endothelium in the human preparation. 4. The findings suggest that tacrolimus releases an endothelium-derived constricting factor in rat renal arteries to increase vascular tone and to potentiate pressor responses to noradrenaline. In human interlobar arteries, this effect of tacrolimus is not observed probably because of the absence of functional endothelium or the necessary mediator mechanism.

Acetylcholine↗
PubMed2001

Glomerulosclerosis and progression: effect of subantihypertensive doses of alpha and beta blockers.

BACKGROUND: Uremia is characterized by inadequately increased sympathetic activity. Sympathetic overactivity is involved in the genesis of hypertension in uremia, but its potential role on progression has not been well investigated. To address this issue, the effect of subantihypertensive doses of an alpha blocker and a beta blocker, and their combination on renal morphology and on albuminuria were investigated in the model of the subtotally nephrectomized rat. METHODS: Male Sprague-Dawley rats were subjected to surgical ablation (SNX) or sham operation (sham). Three days after surgery groups were treated either with phenoxybenzamine (PBZ, 5 mg/kg body weight/day), metoprolol (MET, 150 mg/kg body weight/day) or their combination (PBZ 2.5 mg/kg body weight/day + MET, 50 mg/kg body weight/day). Renal morphology was evaluated after 12 weeks by quantitative histology, immunohistochemistry, and electron microscopy. Urine albumin excretion and kidney endothelin-1 (ET-1), platelet-derived growth factor (PDGF), and transforming growth factor-beta (TGF-beta) mRNA expression were assessed. RESULTS: Systolic blood pressure was significantly higher in all SNX groups compared with sham-operated controls with no difference in the SNX groups. The number of glomeruli per left kidney was reduced from 30,904 +/- 3212 to 17,480 +/- 2341 by SNX (-43.5%). Mean glomerular volume increased from 2.63 +/- 0.7 in untreated sham operated to 4.11 +/- 0.48 microm 3 x 10(6) in untreated SNX (56.3%). The glomerulosclerosis index did not change in SNX + PBZ rats, but was significantly lower in SNX + MET (0.56 +/- 0.14) and particularly SNX + PBZ + MET rats (0.49 +/- 0.11) than in untreated SNX (0.74 +/- 0.24). Glomerular capillary length density (LV) as a sensitive index of capillary obliteration was significantly lower in SNX and almost normalized in the three intervention groups. The same was true for the mean podocyte number per glomerulus. Glomerular ultrastructure in SNX was largely preserved by all treatments. The albumin excretion rate was significantly higher in untreated SNX than in sham; it was significantly lower in all treated SNX groups. CONCLUSION: The beneficial effect of non-hypotensive doses of alpha and beta blockers and their combination on renal morphology and albuminuria in the model of renal ablation argue for a blood pressure-independent role of sympathetic overactivity in the genesis of progression. In addition, the beneficial effect of adrenergic receptor blockade indicates that a substantial part is not mediated by sympathetic cotransmitters such as adenosine 5'-triphosphate (ATP) and neuropeptide Y (NPY).

Adrenergic alpha-Antagonists↗
PubMed2001

Neurovascular contact of the brain stem in hypertensive and normotensive subjects: MR findings and clinical significance.

BACKGROUND AND PURPOSE: About 20 years ago, a theory was put forward that neurovascular contact of the root entry zone (REZ) of the ninth and 10th cranial nerve is responsible for elevated blood pressure in patients with essential hypertension. To test this hypothesis, we used MR tomography and MR angiography to evaluate the presence and degree of neurovascular contact of the REZ of the ninth and 10th cranial nerves in patients with essential hypertension as compared with patients with renal parenchymal hypertension and normotensive healthy volunteers. METHODS: Patients with essential hypertension (group 1; n = 33), renal parenchymal hypertension (group 2; n = 30), and normotensive healthy volunteers (group 3; n = 25) underwent high-resolution (axial and coronal) brain stem MR imaging and MR angiography. The images were interpreted consensually by two radiologists who were blinded to the patients' hypertensive status. Neurovascular contact was graded as vessel contact without associated brain stem deformity (grade I), vessel contact with associated brain stem deformity (grade II), or vessel contact with associated deformity and displacement of the brain stem (grade III). RESULTS: Neurovascular contact of the REZ of the ninth and 10th cranial nerve on the left side was found in 48.5% in group 1, in 26.7% in group 2, and in 48.0% in group 3. The rate of neurovascular contact on the right side was 24.2%, 13.3%, and 40.0%, respectively. chi(2) analysis showed no statistical difference between the groups. CONCLUSION: Neurovascular contact is not more frequent in patients with essential hypertension than in normotensive control subjects or in those with secondary hypertension; therefore, MR imaging cannot aid patient selection for neurosurgical vascular decompression.

Adolescent↗
PubMed2000

Careful clinical monitoring in comparison to sequential Doppler sonography for the detection of acute rejection in the early phase after renal transplantation.

Acute rejection is the most frequent cause of early graft failure. There is unanimity that Doppler sonography is a helpful method for the detection of complications after kidney transplantation. In the past, the indication for renal biopsy relied mainly on clinical assessment, although this assessment has not been standardised. Therefore, we conducted this prospective study to compare the value of sequential Doppler measurements with a standardised clinical rejection score, based on renal function, weight gain, graft swelling and tenderness. Fifty-eight patients (37 males, 21 females, mean age 46 +/- 12 years) after kidney transplantation were consecutively enrolled into the study. Doppler investigations were obtained within the first 24 h after transplantation, followed by an interval of 48-72 h. At the same time, a clinical examination was scored by a transplant physician blinded to the Doppler results. Clinical score and Doppler results, both were referred to the histological results of renal biopsy. In 24 out of 58 patients 25 acute rejections occurred. In seven patients, acute rejection was superimposed on primary graft failure. The cut-off levels for rejection were set at RI > or = 0.80 and PI > or = 1.70 based on receiver-operator curves using data from 663 Doppler examinations. Sensitivity and specificity was 72% for RI, and 72% and 74% for PI, respectively. The calculation of the intraindividual increase (deltaRI > or = 3%, deltaPI > or = 10%) did not improve these values. The clinical score revealed a sensitivity and specificity of 82% and 87%, respectively. The combined analysis of Doppler indices and clinical score showed a sensitivity of 96% with a specificity of 66%. Careful clinical monitoring alone using a clinical score is an appropriate procedure with which to decide about renal biopsy. Our data show that Doppler sonography should be performed within the first 24 h after transplantation to evaluate graft perfusion and baseline values. Afterwards, it should be used when clinical signs of rejection occur to underline the decision for renal biopsy even in borderline cases.

Acute Disease↗
PubMed2000

Design of the prospective randomized study for the treatment of patients with thrombotic microangiopathy. PRODROMI Study Group.

In thrombotic microangiopathies hemolytic uremic syndrome and thrombocytopenic purpura, plasma exchange (PE) therapy using fresh frozen plasma is standard. In almost 20% of the patients, however, this approach is ineffective. This prospective, randomized study for the treatment of patients with thrombotic microangiopathies (PRODROMI) compares PE with fresh frozen plasma (A) and cryosupernatant (B). The participating centers were the University Clinics of Freiburg, Hamburg, Düsseldorf, Essen, Göttingen, Mannheim, Ulm, Jena, Tübingen, Würzburg, Kreiskrankenhaus Offenburg, Städt Klinikum Karlsruhe, and Horst-Schmidt Kliniken in Wiesbaden, Germany. Patients (18 to 80 years) were diagnosed by the individual centers based on clinical and laboratory findings (thrombocyte/fragmentocyte count, hemoglobin, serum creatinine, haptoglobin and lactate dehydrogenase levels; negative Coombs-test is obligatory). HIV infection, bone marrow, or solid organ transplantation were exclusion criteria. After written consent, patients were randomized in the A or B group. All patients received 1.5 mg/kg methylprednisolone as a basic therapy. The first PE always was performed with fresh frozen plasma (50 ml/kg). A minimum of 5 and a maximum of 10 PEs were required. Thrombocyte count above 150,000/microl was considered to be a successful therapy. Treatment failure was defined as not responding to 10 PE with a thrombocyte count above 150,000/microl or a fall below this value within 30 days after stopping PE. Patients with clinical and laboratory signs of thrombotic microangiopathy occurring later than 30 days after having stopped PE were considered to have a relapse. Primary endpoints were survival, intensity of required PE sessions (duration, volume, and number), and relapse rate. Follow-up of clinical outcome was 2 years; von Willebrand Factor (vWF), vWF-cleaving-protease activity, and Factor H were determined.

Adolescent↗
PubMed2000

Dihydropyridine calcium antagonists and renal function in hypertensive kidney transplant recipients.

OBJECTIVE: To investigate whether calcium antagonists are nephroprotective in hypertensive cyclosporine-treated renal allograft recipients. METHODS: We studied 50 hypertensive and 17 normotensive renal transplants (eight females, nine males; 14-54 years, mean age 38.8 +/- 3.5 years). Hypertensive patients were randomized to be treated with (+Ca; 11 females, 13 males; 20-65 years, mean age 43.1 +/- 3 years) or without (-Ca; 15 females, 11 males; 25-60 years, mean age 41.3 +/- 2.5 years) a calcium antagonist (nitrendipine or nifedipine). Additional antihypertensives were given stepwise according to a standardized protocol: beta1-adrenoceptor blocker, diuretic alpha1-adrenoceptor blocker or vasodilator. Data were analysed at 0, 1, 2 and 3 years on an intention-to-treat basis. RESULTS: Hypertensive patients had a higher body mass index at 0/3 years (23.7 +/- 0.6/25.1 +/- 0.6 kg/m2) than normotensive patients (22.2 +/- 0.6/22.1 +/- 0.7 kg/m2). During the study, blood pressure in normotensive transplants was always slightly, but not significantly, lower than that of transplants with treated hypertension. There was no difference between the groups (+Ca) and (-Ca). Cr51-ethylenediaminetetracetic acid (EDTA) clearance (0/2 years) was 58 +/- 4/57 +/- 6 ml/min in normotensives, 52 +/- 4/47 +/- 4 ml/min in hypertensives (+Ca) and 47 +/- 4/49 +/- 6 ml/min in hypertensives (-Ca). Proteinuria (0/3 years) was 0.16 +/- 0.04/0.15 +/- 0.02 g/24 h in normotensive, 0.26 +/- 0.08/0.23 +/- 0.05 g/24 h in hypertensives (+Ca) and 0.26 +/- 0.07/0.22 +/- 0.05 g/24 h in hypertensives (-Ca). CONCLUSIONS: Post-transplant hypertension is associated with higher body mass index and poor renal function. No difference in the course of Cr51-EDTA clearance, serum creatinine, proteinuria or blood pressure was observed between groups treated with or without calcium antagonists. Calcium antagonists and conventional antihypertensive treatment have the same nephroprotective effect in hypertensive renal transplants, when treatment is started 3 months after transplantation.

Adult↗
PubMed2000

Cortisol producing adrenal adenoma--a new manifestation of Gardner's syndrome.

INTRODUCTION: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder which typically presents with colorectal cancer in early adult life secondary to extensive adenomatous polyps of the colon. Gardner's syndrome is a variant of FAP in which desmoid tumors, osteomas and pigmented retinal lesions occur together with intestinal manifestations. The APC gene (adenomatous polyposis coli) at 5q21 is a tumor suppressor gene which is mutant in FAP. PATIENT: A 36 year old woman presented with a history of polyposis ventriculi, ovarian desmoid cysts, and disseminated desmoid tumors. Her familial history was unremarkable. On admission she complained weight gain, secondary amenorrhea, and episodes of hypertension followed by paroxysmal headache. RESULTS: Elevated urinary free cortisol (878 microg/24h), suppressed basal ACTH (< 5 pg/ml) and insuppressible serum cortisol after low dose dexamethasone (189 ng/ml) revealed adrenal Cushing's syndrome. Abdominal NMR showed an adrenal mass two centimeter in diameter with inhomogeneous contrast enhancement. Unilateral adrenalectomy was performed and an adrenal adenoma was diagnosed by histological criteria. For mutational detection DNA from peripheral blood leucocytes was extracted. A protein truncation test was performed, which revealed a termination mutation between codon 1099 and 1623 of the APC gene. Direct sequencing showed a point mutation in exon 15 of the APC gene at position 1542 (CAG --> TAG). This region is known to be altered in patients with extraintestinal manifestation of FAP. CONCLUSION: In patients with Gardner's syndrome adrenal tumors leading to hormonal excess should be considered. Whether mutations in the APC gene have implications in sporadic adrenal tumorigenesis needs to be proven.

Adenoma↗