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Biomedical subjects

R Brunkhorst

Publications and source records attributed to R Brunkhorst.

At least 19 recordsLinked to original sources
PubMed1995

Pyruvate neutralizes peritoneal dialysate cytotoxicity: maintained integrity and proliferation of cultured human mesothelial cells.

Toxic effects of commercially available peritoneal dialysate (PD) fluid include damage to mesothelial cells (MC), causing a severely disturbed proliferation of cultured MC. We investigated the injury to the cell membrane (by release of lactate dehydrogenase, LDH), the proliferation (by cell counts and by 3H-thymidine incorporation), and optional the cytokine generation (by IL-1 receptor-antagonist production, IL-1 ra) of cultured human MC during the 48 hours after a 30 minute exposure to PD containing either 35 mmol/liter sodium lactate or sodium pyruvate. All solutions had a pH of 5.2 to 5.6 and were composed as standard PD. Glucose contents of 1.36 and 3.86 mmol/liter were tested. After exposure to the lactate-PD containing 1.36% glucose, LDH activity was increased by more than 30%, proliferation of MC was inhibited by more than 30%, and IL-1 ra production was reduced significantly when compared to pyruvate-PD and the control solution. After preincubation with 3.86% glucose containing PD, all negative effects became even more pronounced in the lactate group whereas the MC maintained their integrity, rate of proliferation and IL-1 ra release after pre-exposure to pyruvate containing PD. These results suggest that the acute toxic effects of commercially available PD on the integrity, proliferation and IL-1 ra production of MC can be avoided by the use of sodium pyruvate instead of sodium lactate.

Cell Division↗
PubMed1995

Pre-transplant hypertension: a major risk factor for chronic progressive renal allograft dysfunction?

Despite of advances in 1-year survival rates of renal allografts, no comparable achievements have been made in long-term graft survival. To identify risk factors for chronic progressive renal allograft dysfunction we conducted a retrospective study in 639 patients transplanted between 1983 and 1990. Graft function was assessed by the slope of individual 1/creatinine regression lines and chronic progressive graft dysfunction was defined as a slope of the 1/creatinine line of > 0.1 dl/mg/year, indicating a loss of glomerular filtration rate of > 10 ml/min/year regardless of the initial serum creatinine value. A number of possible risk factors were determined and analysed by linear regression analysis. One hundred and six patients (16.6%) showed chronic progressive graft dysfunction. No correlation was found between the rate of functional deterioration and the age and gender of the donor or the recipient, the blood group, the prevalence of hepatitis B or C, the number of blood transfusions, the total ischaemia time, or the number of kidneys from female donors grafted into male recipients. Chronic progressive graft dysfunction was associated with the number of HLA-B/DR mismatches (P = 0.04) and with a first acute rejection episode later than 60 days after transplantation (P < 0.001). Chronic progressive graft dysfunction also occurred in the absence of an acute rejection episode. Significantly (P < 0.001) more patients with chronic progressive graft dysfunction were hypertensive not only 12 months after transplantation, but also at the time of transplantation, indicating that hypertension may not only be secondary to deteriorating graft function, but that hypertension per se leads to graft damage and initiates chronic progressive graft dysfunction. All efforts should be made to control blood pressure adequately to improve long-term survival of renal allografts.

Adult↗
PubMed1995

Pyruvate anions neutralize peritoneal dialysate cytotoxicity.

A new peritoneal dialysate containing pyruvate anions was developed in order to avoid cytotoxic effect of conventional lactate-based dialysate. The dialysate has a final pH of 5.4 to 5.6 and is composed of 1.36-3.86% glucose-monohydrate; 132 mmol/l sodium; 1.75 mmol/l calcium; 0.75 mmol/l magnesium; 102 mmol/l chloride and 35 mmol/l pyruvate. For cytotoxicity testing peritoneal macrophages, and mesothelial cells (MC) were exposed to conventional lactate dialysate, and pyruvate dialysate. We investigated the O2- generation and cytokine synthesis after endotoxin stimulation in peritoneal macrophages and the proliferation of mesothelial cells of cultured human MC. After exposure to lactate dialysate O2- generation and cytokine synthesis in peritoneal macrophages and proliferation of mesothelial cells were inhibited when compared to solution containing pyruvate and the control solution. After preincubation with 3.86% glucose containing solutions, all negative effects became even more pronounced in the lactate group whereas after pre-exposure to pyruvate containing solution the toxic effects were absent. These results suggest that the acute toxic effects of commercially available peritoneal dialysates can be avoided by the use of sodium pyruvate instead of sodium lactate.

Cell Division↗
PubMed1994

Low-dose prednisolone/chlorambucil therapy in patients with severe membranous glomerulonephritis.

Because of the high rate of spontaneous remission, treatment of membranous nephropathy with prednisolone and chlorambucil is still controversial. The aim of this study was to give this therapy only to those patients at risk of developing renal insufficiency and to test the efficacy of a low-dose therapeutic regimen. Seventeen patients with more than 10 g protein excretion per day (mean 16.9) and/or a deterioration in renal function (mean serum creatinine, 162 mumol/l) were included. Serum total protein, serum lipids, proteinuria, serum creatinine, and blood pressure were measured, along with the diuretic and antihypertensive medication. The observation time before the start of treatment was 27 +/- 27 months. Steroids were given during months 1, 3, and 5 (methylprednisolone 3 x 500 mg intravenously) prednisolone 0.5 mg/kgBW daily per os for 1 week, then tapered by 0.1 mg/kg BW/week for 1 month). Chlorambucil was given during months 2, 4, and 6 at a dose of 0.12 mg/kgBW daily. At the end of treatment proteinuria had significantly decreased (mean of all patients, 7.8 +/- 1.4 g/d) in all patients. Six months after the end of treatment proteinuria was significantly lower than at baseline in 14 of 17 patients. Hypoproteinemia and hyperlipidemia had improved; diuretic and antihypertensive medication were reduced. Elevated serum creatinine decreased in 7 of 9 patients (pretreatment, 227 +/- 39 mumol/l; 6 months, 176 +/- 28 mumol/l). Nonresponders with respect to serum creatinine responded with respect to proteinuria. Regarding adverse effects, two patients complained of dyspepsia while taking steroids; during chlorambucil treatment two patients experienced nausea and lack of appetite, and one developed leukopenia (1600/microliters).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

On the specificity of assays to detect circulating immunoglobulin A-fibronectin complexes: implications for the study of serologic phenomena in patients with immunoglobulin A nephropathy.

Immunoglobulin A (IgA)-fibronectin complexes have been proposed as specific serologic markers of IgA nephropathy. They have been detected by the use of ELISA composed of an immobilized antifibronectin antibody (or albumin as a negative control) and an enzyme-conjugated anti-IgA antibody (antifibronectin capture assay). By the use of this type of assay, plasma samples from 32 normal controls, 38 IgA nephropathy patients, and 81 patients with other types of glomerulonephritis were analyzed. Extinction values in IgA nephropathy patients were higher (P = 0.06) than in patients with other glomerulonephritis types and significantly higher than in normals. Markedly lower values were obtained when the plates were coated with albumin. However, when the antifibronectin antibody was replaced by normal IgG or F(ab')2 fragments, almost identical extinctions were measured. The use of different antifibronectin antibodies, IgG, ELISA plates, or blocking regimens did not modify these results. Extinction values could not be suppressed by the addition of exogenous fibronectin. Similar extinctions were observed when plasma samples were replaced by physiologic concentrations of fibronectin-free IgA. Extinction values measured in the plasma samples correlated significantly with IgA concentrations in plasma as analyzed by nephelometry. A collagen binding assay, a second type of assay used to measure IgA-fibronectin complexes, also allowed the detection of fibronectin-free IgA, and again, extinctions measured in plasma could not be suppressed by exogenous fibronectin. In conclusion, both antifibronectin capture ELISA and collagen binding assays do not specifically detect only IgA-fibronectin complexes, but also total plasma IgA, which is frequently, but nonspecifically, elevated in IgA nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Lack of clinical evidence for a specific HIV-associated glomerulopathy in 203 patients with HIV infection.

Several authors described a high incidence of proteinuria with frequent progression to nephrotic syndrome and/or renal failure in patients with HIV infection. Though renal histological changes were rather non-specific, the existence of a specific, HIV-associated glomerulopathy was postulated. We repeatedly investigated proteinuria and serum creatinine in 203 HIV-infected patients. One hundred and twenty-two patients (group 1) had early stages of the disease without opportunistic infections, 81 suffered from acute opportunistic infections (group 2). In patients with a positive qualitative test (Combistix), quantitative measurement (Biuret) for proteinuria was carried out; when proteinuria was greater than 0.5 g/24 h, SDS gel electrophoresis was performed. None of the patients of group 1 had a proteinuria greater than 0.5 g/24 h or an elevated serum creatinine. Eleven of 81 patients from group 2 had a proteinuria between 0.5 and 3 g/24 h; one further patient of group 2 developed a transient proteinuria of 7.7 g/24 h. Only three of the proteinuric patients showed a glomerular pattern in SDS gel electrophoresis, all three during acute CMV or EBV infections. Fourteen of 81 group 2 patients showed a transient elevation of serum creatinine (x +/- SD of the maximum serum creatinines: 225.3 +/- 163 mumol/l), most during pentamidine therapy for Pneumocystis carinii infection; one patient treated with high-dose acyclovir had to be temporarily dialysed. In the investigated 203 HIV patients no nephrotic syndrome and no sustained elevation of serum creatinine greater than 200 mumol/l was observed. All cases of proteinuria and elevation of serum creatinine were associated with severe opportunistic infections and the administration of potentially nephrotoxic antibiotics.

Adolescent↗
PubMed1992

Present status of kidney transplantation.

Kidney transplantation today is the method of choice to treat end-stage renal disease (ESRD) in more than 50% of the ESRD-population. Due to major improvements in surgical handling, immunosuppressive therapy, and infection control, the one-year survival for patients and first grafts has reached nearly 90% in the recent years. In contrast no comparable achievements have been made in long-term graft survival. A constant number of grafts is lost yearly after the first postoperative year. In addition an increasing number of well functioning grafts is lost due to the death of the recipients caused mainly by cardiovascular and malignant disorders. The extension of kidney transplantation to all suitable recipients is nearly exclusively hampered by the organ shortage, which is further enhanced by failing grafts. This urges us to further improve the prognosis for patient and graft. This must include organ sharing on the basis of improved HLA-typing to achieve highly compatible grafts. The tools for differential diagnosis of acute and chronic graft dysfunction have to be improved. New immunosuppressive agents with higher immunosuppressive power and specificity but fewer nephrotoxic, metabolic and hemodynamic side effects are required at least for chronic rejection. The risk of infectious and malignant complications must be limited.

Cadaver↗
PubMed1991

Cyclophosphamide pulse therapy in Wegener's granulomatosis.

Twenty-three patients with Wegener's granulomatosis, 15 with daily oral cyclophosphamide therapy and eight with intravenous cyclophosphamide pulse therapy, were studied retrospectively. All patients had involvement of the kidneys and systemic symptoms. Mean monthly cyclophosphamide dose was 1.0 g in the pulse group and 2.7 g in the daily treated group. In all patients remission could be achieved. During 207.5 months of daily oral therapy the following complications were observed: leukopenia, necessitating dose reduction in seven patients, severe infection in one patient, relapses in three patients. During 103 months of intravenous pulse therapy one patient developed leukopenia. No patient had a severe infection. Two relapses were seen. Our data suggest that cyclophosphamide pulse therapy is an effective treatment strategy in patients with Wegener's granulomatosis and kidney involvement. It offers the chance of bladder protection and marked total dose reduction, possibly decreasing the risk of malignancies.

Administration, Oral↗
PubMed1991

Hypertension as a possible complication of recombinant human erythropoietin therapy.

The analysis of the hemodynamics accompanying correction of renal anemia by rhEPO shows that--although they behave qualitatively as in nonuremic anemic patients--cardiac output and peripheral resistance may change inadequately and thereby cause a rise of blood pressure. The underlying mechanisms are not yet fully understood but to a great part may be related to preexisting pathology due to a history of longlasting hypertension. In some patients the development of hypertension may only represent a temporary phenomenon of hemodynamic dysregulation. To avoid cardiovascular complications the following should be considered: Patients with a history of hypertension, even if they are normotensive in the anemic state, are at a higher risk of developing hypertension during therapy with rhEPO. Hypertensive complications may be rare events when anemia is corrected slowly. In case of the development or aggravation of hypertension a reduction of the target hematocrit is indicated.

Anemia↗
PubMed1990

Long-term effects of treatment with recombinant human erythropoietin on haemodynamics and tissue oxygenation in patients with renal anaemia.

Regional peripheral vascular resistance, transcutaneous oxygen pressure and blood pressure were studied in seven normotensive, chronically haemodialysed patients with renal anaemia before and after 3 and 12 months of rHuEpo therapy. Haematocrit increased from 21% to 33% within 3 months of commencing therapy, and remained stable throughout the following observation time. Though regional blood flow of the calf was markedly reduced after 3 and 12 months of rHuEpo compared to pretreatment values, transcutaneous oxygen pressure was significantly increased after 3 months and remained constantly elevated after 12 months. Mean arterial blood pressure increased significantly by 7.3 mmHg after 3 months of rHuEpo treatment but did not reach hypertensive values and was no longer different from pretreatment values 12 months after the start of rHuEpo. Results of peripheral haemodynamic studies were compared to those obtained by measurement of central haemodynamics in four further normotensive anaemic patients. In these patients cardiac output decreased, total peripheral vascular resistance increased and blood pressure increased slightly (by 5.5 mmHg) when a haematocrit of 37% was reached after 8 weeks of rHuEpo therapy. These effects were partly reversed when the maintenance haematocrit decreased to 32% (after 16 weeks of rHuEpo). In summary rHuEpo treatment induced a long-term increase of the total and regional peripheral resistance, an increase of blood pressure within the normal range, and a decrease in cardiac output. Despite these changes tissue oxygenation improved.

Adult↗
PubMed1990

Skin microcirculation and regional peripheral resistance in patients with chronic renal anaemia treated with recombinant human erythropoietin.

Skin microcirculation and regional peripheral resistance were studied in 14 patients with renal anaemia during therapy with recombinant human erythropoietin. Haematocrit was raised from 20.0 to 31.3% after 10-12 weeks of treatment and remained stable over another period of 12 weeks. Antihypertensive treatment had to be intensified in five patients. Regional calf blood flow decreased significantly; accordingly, calculated peripheral vascular resistance was increased by more than 100%. However, transcutaneous oxygen pressure (37 degrees C and 44 degrees C) increased significantly. The pathological vasoconstrictor response of skin capillaries was not influenced. There were no significant differences of any parameter between the patients requiring reinforced antihypertensive therapy and those with stable blood pressure. In conclusion skin oxygenation may be improved by erythropoietin treatment to a large extent despite an increase in calculated total limb vascular resistance.

Adult↗
PubMed1989

[Effect of captopril therapy on sodium and water excretion in patients with liver cirrhosis and ascites].

UNLABELLED: Ascites in patients with cirrhosis of the liver frequently is refractory to diuretic treatment. It was postulated that vasoconstriction of the renal cortex, mediated by activation of the renin-angiotensin-aldosterone-system (RAAS), may be one course of the disturbed sodium- and water-excretion in these patients. We therefore investigated in 14 cirrhotic patients with ascites under constant diuretic treatment the effects of low-dose captopril therapy on urinary sodium- and potassium-excretion, body weight, abdominal girth, serum-sodium, -potassium, creatinine-clearance, plasma-renin-activity (PRA), plasma-aldosterone (PA) and mean arterial pressure (MAP). After a control period of 4 days the patients received 2 x 6.25 mg/d captopril for 5 days and 4 x 6.25 mg/d for further 5 days. Treatment was followed by a second control period without captopril. PRA increased significantly after 2 days of captopril treatment. 2 x 6.25 mg/d captopril induced a significant increase in sodium excretion and a significant decrease of body weight. MAP decreased slightly but significantly without clinical signs of hypotension. 4 x 6.25 mg/d captopril resulted in a further reduction of body weight and a further enhancement of sodium excretion. Three days after withdrawal of captopril sodium output was significantly reduced again. CONCLUSION: In cirrhotic patients low-dose captopril seems to be efficient in the treatment of ascites resistant to diuretics without causing major side effects.

Adult↗