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Biomedical subjects

K H Neumann

Publications and source records attributed to K H Neumann.

At least 19 recordsLinked to original sources
PubMed2003

Plasma serotonin and histamine levels in hemodialysis-related pruritus are not significantly influenced by 5-HT3 receptor blocker and antihistaminic therapy.

BACKGROUND: Elevated plasma histamine levels are considered to play a part in the pathophysiology of hemodialysis-related pruritus. However, antihistaminic therapy often fails to provide sufficient relief. Elevated serotonin levels in patients on dialysis therapy have also been described but the effects of 5-HT3 receptor antagonists on hemodialysis-related pruritus remain controversial. METHODS: we conducted a study to determine plasma histamine and serotonin levels before and after treatment with 5-HT3 receptor antagonists (tropisetron 5 mg and ondansetron 8 mg) and an antihistamine (cetirizine 10 mg). Eleven hemodialysis patients with a history of pruritus participated in this study,10 healthy volunteers served as control group. RESULTS: Histamine and serotonin values were normal in patients and controls. Treatment with cetirizine did not significantly reduce histamine levels in patients or in controls. Tropisetron and ondansetron likewise did not alter serotonin levels in patients. Tropisetron treatment did not significantly change serotonin levels in controls. CONCLUSION: Histamine and serotonin are no major mediators of pruritus in hemodialysis patients. Elevated histamine levels are occassionally seen and may be due to the increased mast cell number found in a subgroup of hemodialysis patients. Our findings explain the only marginal relief of antihistamines and the controversial antipruritic effect of serotonin receptor antagonists in hemodialysis-related pruritus.

Adult↗
PubMed2003

[Diagnostics and therapy of diabetic nephrology].

In Germany, 36% of all new chronic dialysis patients have diabetic nephropathy. The majority are type 2 diabetics. Early intervention has the greatest effect. Incipient nephropathy can be diagnosed by evidence of microalbuminuria (30-300 mg albumin/g creatinine). Proteinuria on the standard test strip (>300 mg/g) indicates manifest nephropathy followed by progressive renal failure. Important cofactors for progression are hypertension, hyperglycemia, and smoking. Low normal blood pressure levels (<130/80 mmHg without and <125/75 mmHG with proteinuria) based on ACE inhibitors/AT1 blockers are the goal. Combination therapies are frequently necessary. This can often reverse microalbuminuria. Chronic renal failure requires special attention (e.g. bone metabolism, anemia, acidosis). Timely initiation of renal replacement therapy (GFR <15 ml/min) reduces morbidity and mortality. In addition to hemo- and peritoneal dialysis, early kidney and in individual cases of type 1 diabetes combined kidney/pancreas transplantation is appropriate.

Combined Modality Therapy↗
PubMed2001

Homocysteine lowering effect of different multivitamin preparations in patients with end-stage renal disease.

OBJECTIVE: Hyperhomocysteinemia occurs in nearly 100% of patients with end-stage renal disease (ESRD) and is associated with increased morbidity and mortality. Means to reduce elevated homocysteine concentrations is supplementation with folic acid, vitamin B6, and vitamin B12. However, doses of vitamins required for optimized treatment are subject of debate. Therefore, the effect of 2 different multivitamin preparations on the homocysteine concentrations in patients with ESRD were compared. DESIGN: Patients received 3 times per week either 2 tablets of preparation A (800 microg folic acid, 6 microg vitamin B12, 10 mg vitamin B6), 2 tablets of preparation B (160 microg folic acid, no vitamin B12, 10 mg vitamin B6), or placebo for a period of 12 weeks with control of total homocysteine (tHcy) levels at baseline, and at 4, 8, and 12 weeks. SETTING: The study was performed at the University Hospital of Magdeburg, Germany in patients with ESRD treated with chronic intermittent maintenance hemodialysis. RESULTS: Preparation A reduced the tHcy concentration significantly by nearly 50%, whereas preparation B did not change the tHcy concentration in comparison with placebo. However, tHcy was not normalized in the majority of patients receiving preparation A. CONCLUSION: The reduction of tHcy achieved by a multivitamin containing 800 microg folic acid was substantial and even higher than the reduction reported in supplementation studies using higher doses of folic acid alone. Nevertheless, hyperhomocysteinemia in ESRD patients appears relatively refractory to vitamin supplementation, in contrast with results obtained in healthy volunteers.

Dietary Supplements↗
PubMed2000

Cardiac troponin T predicts mortality in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease have a high risk of premature death, mainly as the result of cardiovascular disease (CVD), which is not sufficiently explained by the conventional risk factors. We therefore prospectively investigated total mortality and cardiovascular events in 102 patients on hemodialysis and assessed the prognostic value of baseline disease status and laboratory variables including total homocysteine and cardiac troponin T. METHODS AND RESULTS: Patients were followed for 2 years or until their first event of CVD (for outcome variable cardiovascular events, n=33) or death (for outcome variable total mortality, n=28). Survival was computed by the Kaplan-Meier method. Cox proportional hazards model was used to determine independent predictors of CVD events or total mortality. Cardiac troponin T emerged as the most powerful predictor of mortality, resulting in an almost 7-fold risk increase at concentrations >0.10 ng/mL (hazard ratio 6.85, 95% CI 3. 04 to 15.45). Total homocysteine level greater than median was also associated with mortality (hazard ratio 2.44, 95% CI 1.10 to 5.40). These hazard ratios did not change substantially after adjustment for other risk factors. Significant predictors for CVD events were baseline diabetes, cerebrovascular disease, serum glucose, and triglycerides. After adjustment, only glucose and triglycerides remained significantly related to CVD events (hazard ratio with 95% CI 1.33 [1.12 to 1.57] and 1.14 [1.04 to 1.26], respectively, for a 1-mmol/L increase in concentration). CONCLUSIONS: We conclude that total homocysteine and particularly cardiac troponin T are important predictors of mortality in patients with end-stage renal disease, whereas other laboratory variables and baseline disease status have less prognostic value.

Cardiovascular Diseases↗
PubMed1999

Supplementation with vitamin B12 decreases homocysteine and methylmalonic acid but also serum folate in patients with end-stage renal disease.

Hyperhomocysteinemia is frequently found in patients with end-stage renal disease (ESRD). Plasma total homocysteine (tHcy) concentrations may be reduced by supplementation with folic acid or combinations of folic acid, vitamin B12, and vitamin B6. Supplementation studies with vitamin B12 alone in patients with ESRD have not yet been published. In this study, we investigated the effects of intravenous injection of cyanocobalamin (1 mg/wk for 4 weeks) in ESRD patients (N = 14) with low serum cobalamin concentrations (<180 pmol/L). All patients had elevated levels of plasma tHcy, methylmalonic acid (MMA), and cystathionine before supplementation. After supplementation, plasma tHcy and MMA decreased 35% and 48%, respectively; however, cystathionine levels were unchanged. The extent of the plasma tHcy reduction tended to be influenced by the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR). Serum cobalamin increased significantly upon supplementation, whereas serum folate levels were substantially reduced by 47%. In contrast, red blood cell (RBC) folate was unchanged. This study shows that vitamin B12 supplementation effectively decreases both MMA and plasma tHcy in ESRD patients with low B12 levels. Furthermore, it illustrates the close interrelation between vitamin B12 and folate metabolism.

Adult↗
PubMed1999

Short- and long-term effects of fish oil on proteinuria, morphology and renal hemodynamics in the Milan normotensive rat model of spontaneous glomerulosclerosis.

BACKGROUND/AIMS: A diet rich in polyunsaturated Omega3 fatty acids has been shown to modulate the course of several experimental models of renal disease. The short- and long-term effects of an 8% fish oil (FO) chow on proteinuria, renal blood flow and glomerular morphology were evaluated in Milan normotensive rats that spontaneously develop progressive glomerulosclerosis. METHODS: Eight rats each were pairfed FO- versus cholesterol-enriched or control diets for either 2 or 32 weeks. 4/48 animals died (2-week trial: 1 rat on the FO and 1 rat on the control diet; 32-week trial: 1 rat on the cholesterol and 1 rat on the control diet) and were excluded from all statistic analyses. RESULTS: After 2 weeks the renal blood flows were higher in the FO animals versus controls (8.75+/-2.19 vs. 6.87+/-1.91 ml/min/g, p<0.05), and the prostaglandin E2/thromboxane B2 ratio shifted towards the vasodilatative prostaglandin E2 (1. 76+/-0.18 vs. 0.91+/-0.19, p<0.05). During the long-term trial proteinuria in the FO animals progressed faster and to a higher level (176.5+/-32.2 vs. 82.7+/-36.7 mg/24 h at week 32, p<0.01). After 32 weeks the renal blood flow was significantly lower in th FO group 2.8+/-1.1 vs. 4.6+/-1.9 ml/min/g, (p<0.05), and the rats had an accelerated development of nephrosclerosis, with sclerotic lesions in 60.3+/-6.6% of the glomeruli as compared with 46.5+/-9.8% in the cholesterol and 39.8+/-5.9 in the control group (p<0.05). CONCLUSION: The short-time effects of FO on renal hemodynamics did not alleviate the progress of renal damage in Milan normotensive rats, but the morphologic and functional signs of injury were rather pronounced with FO feeding.

Animals↗
PubMed1999

Response of hyperhomocysteinemia to folic acid supplementation in patients with end-stage renal disease.

BACKGROUND: Elevated concentrations of homocysteine are associated with an increased risk for cardiovascular disease. Reasons for elevated homocysteine concentrations are folate or vitamin B12 deficiency, renal disease or genetic abnormalities. A high prevalence of hyperhomocysteinemia is found in patients with end-stage renal disease (ESRD). Since these patients are also at increased risk for vitamin deficiency, a supplementation study comparing two doses of folic acid was performed in patients with ESRD treated with maintenance hemodialysis or with peritoneal dialysis. PATIENTS AND METHODS: Patients undergoing hemodialysis (n = 70) or peritoneal dialysis (n = 12) were supplemented with 2.5 mg or 5 mg folic acid (three times per week after each dialysis treatment) for four weeks in a parallel study design. In 20 hemodialysis patients, the effect of folic acid withdrawal was observed after four weeks. RESULTS: Both supplementation schemes reduced homocysteine to a similar extent (35%) but did not normalize homocysteine concentrations in the majority of patients. Dialysis also had a strong homocysteine lowering effect. After supplementation, 74% of the hemodialysis patients had post-dialysis homocysteine concentrations within the reference range (<16 micromol/l). Homocysteine concentrations remained decreased in 20 patients four weeks after withdrawal of folic acid supplementation. CONCLUSIONS: It is concluded that supplementation with 2.5 or 5 mg folic acid has a similar effect on homocysteine concentrations to supplementation regimens using 15 mg folic acid supplements. In contrast to the effect of folic acid supplementation in subjects with normal renal function, folic acid supplementation does not normalize homocysteine concentrations in ESRD patients.

Adult↗
PubMed1998

Compositional and functional changes of low-density lipoprotein during hemodialysis in patients with ESRD.

BACKGROUND: This study focused on the effects of hemodialysis on the atherogenic properties of low density lipoprotein (LDL) in patients with end-stage renal disease (ESRD). The impact of cholesterol ester transfer protein (CETP) activity and lipolysis on LDL composition, particularly the changes during hemodialysis, was investigated. METHODS: Blood was drawn from 15 normotriglyceridemic (NTG) and 15 hypertriglyceridemic patients [HTG; triglycerides (TG) < 2.2 mmol/liter] before hemodialysis, during (1.5 hr after the beginning of anticoagulation) and at the end of treatment. In each sample, lipid values and CETP activity were measured. LDL was prepared and characterized by its components and diameters (2 to 16% PAGGE). To investigate the functional properties of LDL, fractions obtained from NTG and HTG patients were incubated with human skin fibroblasts and a cell line of murine macrophages (P388), and cholesterol ester formation rates were measured. RESULTS: In comparison to LDL from NTG patients at baseline, HTG-LDL were enriched in triglycerides (P < 0.02), depleted in cholesterol proportion (P < 0.01) and small in size (P < 0.001). These LDL induced the cholesterol esterification rates (50 micrograms/mL LDL-protein) in a twofold greater unsaturation in macrophages when compared to LDL from NTG patients (P < 0.04). The rates in fibroblasts were reduced by approximately half (P < 0.05). During hemodialysis, LDL were decreased in size (P < 0.001) and depleted in TG (P < 0.01), particularly in the hypertriglyceridemic state. Although CETP activity increased during hemodialysis (P < 0.001), the cholesterol content remained unchanged. When HTG-LDL obtained during hemodialysis were incubated with cells, esterification rates particularly in macrophages were markedly accelerated in comparison to the unmodified lipoprotein at baseline (P < 0.05). CONCLUSION: LDL from HTG patients with ESRD was TG-enriched, CH-depleted and smaller in size. As the intracellular esterification rates induced by LDL were related to the cellular uptake, these LDL were a superior substrate for murine macrophages with the tendency of intracellular accumulation, and an inferior substrate for fibroblasts suggesting a decreased uptake by the specific receptor pathway. TG-depletion of LDL during hemodialysis, particularly in HTG patients due to a lipase-mediated TG-hydrolysis, increased these effects in macrophages. We suggest that the alterations of LDL that occur during repeated hemodialysis in vivo could contribute to the high prevalence of premature atherosclerosis found in HTG patients with ESRD.

Adult↗
PubMed1995

Prevention of glomerular hypertrophy and glomerulosclerosis in Milan normotensive rats by low-protein diet, but not by low-dose captopril treatment.

Milan normotensive rats, which spontaneously develop marked proteinuria (PU) and glomerulosclerosis (GS), were either kept on a normal-protein diet, a normal-protein diet with additional low-dose captopril (CAP), which did not affect blood pressure, or on a low-protein diet. After 8 months PU (79 +/- 25 mg/day) GS (3 +/- 2%) and total glomerular volume (TGV; 27.9 +/- 2.9 mm3/kidney) were significantly lower (p < 0.05) in the low-protein diet group than in both the normal-protein group (PU 583 +/- 210 mg/day, GS 12 +/- 5%, TGV 34.6 +/- 8 mm3/kidney) and the low-CAP group (PU 611 +/- 224 mg/day, GS 16 +/- 6%, TGV 41.8 +/- 8.6 mm3/kidney). In conclusion, the development of glomerular hypertrophy and GS in Milan normotensive rats was reduced by the low-protein diet, but not by low-CAP treatment.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

[Cyclophosphamide bolus therapy in lupus nephritis].

A pilot study of 21 patients (17 women; 4 men; mean age 35 [18-59] years), randomized into two groups, was undertaken to test how many cycles of intravenous pulse cyclophosphamide administration were required in lupus nephritis to achieve remission. It was planned that patients randomized to group A should be treated for 3 months, those in group B for over 12 months. In the first cycle the cyclophosphamide dosage was 500 mg/m2, in the subsequent cycles, 4 weeks apart, it was raised by 250 mg/m2 to a maximum of 1,000 mg/m2, if the WBC count was over 2,000/microliters. Three women in group B gave up treatment prematurely after 5-8 cycles, because a remission had occurred. In group A only one patient went into remission after only three cycles. Of the total of 18 patients in both groups whose data could be evaluated, 15 achieved remission after an average of 7.3 cycles and a cumulative total cyclophosphamide dosage of 9.3 g. The disease progressed in two patients, one died. No recurrence has so far been observed after a follow-up period of 1-41 months. Three patients had infections and two had developed leukopenia as side effects. Pulse cyclophosphamide has thus been shown to be an effective treatment in lupus nephritis, but it must be continued for more than 3 months.

Adolescent↗
PubMed1993

[Cyclophosphamide bolus therapy in lupus nephritis--status of the clinical study].

In order to establish a low-dose cumulative cyclophosphamide therapy for lupus nephritis, 21 patients were either randomized for at least 3 i.v. cyclophosphamide pulses until remission occurred or for 12 pulses. 18/21 patients developed a remission after an average of 7.3 pulses and a cumulative cyclophosphamide dose of 9.3 g. Side effects were only mild.

Cyclophosphamide↗
PubMed1992

Decrease in beta 1- and increase in beta 2-adrenoceptors in long-term follow-up after orthotopic cardiac transplantation.

Total beta 1- and beta 2- subtype distribution were examined in right ventricular biopsies taken from 100 patients 1-60 months after orthotopic cardiac transplantation and from eight prospective transplant donor hearts serving as controls. The patients were classified into eight groups depending on the time after transplantation that the biopsies were taken: 1-3 (n = 15), 4-7 (n = 15), 8-11 (n = 6), 12 (n = 15), 24 (n = 15), 36 (n = 12), 48 (n = 12) and 60 months (n = 10). The non-selective beta-adrenoceptor antagonist (-)-[125I]-iodocyanopindolol (ICYP) was used as a radioligand to assess total beta-adrenoceptor density. The beta 1- and beta 2-subtype distribution was determined with a beta 1-adrenoceptor saturating concentration of the selective beta 1-adrenoceptor antagonist CGP 20712A (300 nmol/l). In transplant donor hearts the total beta-adrenoceptor density was found to be 70.8 +/- 7.1 fmol/mg protein including a beta 1:beta 2-adrenoceptor ratio of about 80:20%. Until 36 months after cardiac transplantation the total number of beta-adrenoceptors showed no significant change. A slight but insignificant decrease was observed after 48 (16.2%) and 60 (21.2%) months. In contrast, from 12 to 60 months after cardiac transplantation the beta 1:beta 2-adrenoceptor ratio was shifted significantly (66:33% to 61:39%) as compared with transplant donor hearts which was due to an increase in beta 2- and a decrease in beta 1-adrenoceptor number. Thus, the surgically denervated, transplanted human heart exhibits a beta 2-adrenoceptor up-regulation during long-term follow-up. It is suggested that this up-regulation of the beta 2-adrenoceptor subtype could be owing to an increased importance of circulating catecholamines in modulating positive chronotropic and inotropic effects.

Adult↗
PubMed1992

Mechanisms of ciclosporin A-induced vasoconstriction in the isolated perfused rat kidney.

Hypertension is a well-known side effect of ciclosporin A (CsA). In the present study the mechanisms of vasoconstriction in renal vessels were examined in the isolated perfused rat kidney. Kidneys were perfused with constant flow at a temperature of 37 degrees C with Tyrode's solution equilibrated with 95% O2/5% CO2. CsA was dissolved in ethanol. 500 and 2000 ng/ml increased resistance of renal vessels by 0.97 +/- 0.55 x 10(5) and 2.29 +/- 1.33 x 10(5) dyn s cm-5, respectively (mean values +/- SD, n = 12). The vasoconstriction developed gradually over 4 min. The vasopressor effect of CsA was not changed by saralasin (10(-6) M), nifedipine (10(-6) M) and ketanserin (10(-6) M), but was completely blocked by phentolamine and prazosin (each 10(-6) M). CsA-induced vasoconstriction was not prevented by perfusion with Ca(2+)-free solution containing 2 mmol EGTA. Similarly, pretreatment with reserpine to deplete sympathetic nerve endings from catecholamines did not affect CsA-induced vasoconstriction. The findings suggest that CsA-induced vasoconstriction is mediated by stimulation of alpha 1-receptors. Ca2+ influx does not play a role for CsA-induced vasoconstriction. Prolonged perfusion of rat kidneys with the vehicle cremophor EL elicits an irreversible increase in perfusion pressure.

Animals↗
PubMed1992

The physiological and pathophysiological basis of glomerular permeability for plasma proteins and erythrocytes.

The barrier function of glomerular capillaries in vivo, which prevents the leakage of plasma proteins and cellular elements, depends on the basic morphological and electro-chemical fine structure of the glomerular capillary wall, and on a functional barrier maintained by components obtained from blood, which effect the definitive barrier against the leakage of plasma proteins and cellular elements. The functional component of the barrier may explain the variability and some of the phenomena known as functional proteinuria. A certain size and number of morphological "defects" are thought to represent the normal condition, but under pathological conditions they may increase in size and number, resulting in a shift to an increasing permeability for higher molecular mass proteins; also an increase of the size and number of larger defects may enable more red cells to pass the barrier compared with the normal condition. These defects are different from the minimal glomerular lesions which are due to charge defects in the glomerular capillary membrane, primarily the lamina rara interna and the lamina rara externa of the basement membrane.

Animals↗