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Biomedical subjects

T Risler

Publications and source records attributed to T Risler.

At least 19 recordsLinked to original sources
PubMed1995

The renin-angiotensin system--a possible neuromodulator in the human retina?

Morphology studies imply a possible contribution of the renin-angiotensin system (RAS) to neurotransmission in the mammalian retina. To investigate further the functional role of the RAS in the visual system of humans, we tested the effects of the angiotensin-converting enzyme (ACE) inhibitor Captopril (Capt; 25 mg) on electroretinogram (ERG) recordings, the cone flicker threshold (CFT), the FM-28-HUE test, and the psychophysical rod threshold in healthy volunteers. The parameters of renin, angiotensin, and blood pressure were controlled. We obtained the following results. First, Capt induced a significant decrease in amplitudes of the scotopic b-wave, oscillatory potentials, and the a-wave. The latency of responses to 30-Hz flicker was increased. Second, the CFT was reduced to a lower intensity, whereas the final rod threshold remained unchanged. These results are in accordance with previous immunocytochemical and electrophysiological data. They cannot be explained exclusively by the observed changes in systemic blood pressure. We conclude that the RAS may possibly be involved in retinal neurotransmission in humans in addition to its vascular effects.

Administration, Oral↗
PubMed1995

Does L-arginine alter proteinuria and renal hemodynamics in patients with chronic glomerulonephritis and hypertension?

Endogenous nitric oxide (EDRF) plays an important role in the regulation of systemic and renal blood pressure by an alteration of vascular tone. To assess the effect of L-arginine (160 mumol/min i.v. for 3 hours), the precursor of EDRF, on blood pressure, protein-excretion and renal function (GFR = glomerular filtration rate, RPF = renal plasma flow) we performed a prospective, double blind, placebo controlled study. 18 patients with chronic glomerulonephritis (51.3 +/- 11.5 years), renal insufficiency (GFR < 65 ml/min) and hypertension were investigated for changes in GFR and RPF by continuous inulin- and PAH-clearances and for changes in permselectivity by determination of protein-excretion. L-arginine infusion results in a reduction of proteinuria (p < 0.05, t-test). There is no significant effect on renal hemodynamics and mean arterial pressure (MAP). Comparing the excretion of the endogenous proteins, only albuminuria is decreased significantly (p < 0.01), whereas IgG-excretion is reduced slightly (p < 0.05). This can be considered as an indicator of a special influence on the mesangial cells or the basement membrane of the glomerulum itself by EDRF. In conclusion L-arginine reduces protein-excretion without significant alterations in renal hemodynamics and so might prevent a decline in renal failure.

Adult↗
PubMed1995

Renal hemodynamics in essential hypertensives treated with losartan.

ACE-inhibitors are known to have special renal effects, i.e. they increase ERPF, decrease the filtration fraction and lower proteinuria. These effects can be due to a decrease in angiotensin II (AII) levels as well as an increase in bradykinin. New and more specific AII-receptor antagonists may help to distinguish between effects exerted by angiotensin II and those exerted by bradykinin. We investigated the effects of losartan in 9 patients with essential hypertension (sitting mean diastolic blood pressure 95-120 mmHg). Renal hemodynamics were measured by continuous inulin-and PAH-clearance (GFR and RPF) after stopping antihypertensive therapy for 1 week, followed by a 2-week placebo period and after a 4-week treatment phase with losartan (50 mg/die) followed by a therapy with an ACE-inhibitor (ramipril 5mg/die). Additionally, urine albumin excretion (UAE) was measured. Treatment of patients with essential hypertension with losartan resulted in a significant decrease of MAP after three weeks of treatment (121 +/- 8 mmHg under placebo and 114 +/- 10 mmHg under losartan; * = p < 0.05). MAP after four weeks of losartan treatment was 115 +/- 11 mmHg. Regarding changes in renal hemodynamics we could not demonstrate a significant change for neither losartan nor the ACE-inhibitor. Urine albumin excretion was reduced by both treatment regimens in correlation to the magnitude of blood pressure reduction. Our data indicate that losartan induced a significant reduction in MAP in patients with essential arterial hypertension with only moderate effects on renal hemodynamics.

Antihypertensive Agents↗
PubMed1994

Pharmacokinetics of torasemide and its metabolites in end-stage renal disease.

The pharmacokinetics of torasemide, a new loop diuretic, as well as its active metabolites M1 and M3, and its inactive main metabolite, M5, were studied in 12 patients with end-stage renal failure during single i.v. (n = 6) or single oral (n = 6) dosing of 200 mg torasemide, and during chronic oral treatment for 9 days (n = 12). The elimination half-life (t1/2) of torasemide was unchanged in renal failure, whereas t1/2 of the torasemide metabolites M1, M3, and M5 were markedly prolonged. However t1/2 as well as the area under the plasma level time curve of torasemide and its metabolites were unchanged during chronic compared to acute administration. The results of this study suggest that despite the increased half-life of torasemide metabolites M1, M3 and M5 in end-stage renal failure patients, no accumulation of the parent drug torasemide and its metabolites during chronic dosing is demonstrable.

Diuretics↗
PubMed1994

Comparative long-term experience with immunoadsorption and dextran sulfate cellulose adsorption for extracorporeal elimination of low-density lipoproteins.

Two low-density lipoprotein (LDL) apheresis methods allowing a specific extracorporeal removal of atherogenic lipoproteins from plasma were compared concerning their efficacy and safety in the long-term therapy of severe familial hypercholesterolemia. Five patients were treated with immunoadsorption (IMA) at weekly intervals over 3 years each, and three patients received weekly therapy with dextran sulfate cellulose adsorption (DSA) for up to 2 years. The mean plasma volume processed per session to decrease total cholesterol to a target level of 100-150 mg/dl at the end of LDL apheresis was significantly lower in DSA than in IMA: 143% vs. 180% of the individual plasma volume. Both LDL apheresis procedures achieved a mean acute reduction of plasma LDL cholesterol by more than 70%. The average interval concentrations of plasma LDL cholesterol obtained without concomitant lipid-lowering medication were 151 +/- 26 mg/dl compared to 351 +/- 65 mg/dl at baseline in the IMA-treated patients and 139 +/- 18 mg/dl compared to 359 +/- 48 mg/dl at baseline in the DSA-treated patients. Two patients from the DSA group died after 2 years of study participation due to a stroke and a sudden cardiac death several days after the last plasma therapy. Treatment-related side effects were infrequent. Long-term therapy with IMA and DSA was associated with symptomatic improvement of coronary artery disease and mobilization of tissue cholesterol deposits. Analysis of coronary angiograms after 3 years of weekly LDL apheresis with IMA revealed in five patients nearly identical atherosclerotic lesions without definite regression or progression.

Adult↗
PubMed1994

Do different dialysis-membranes affect beta 2-microglobulin kinetics during chronic hemodialysis?

Hemodialysis is not an absolute prerequisite for the formation of beta 2-microglobulin amyloidosis, but it enhances the progression of this complication related to long-standing renal failure. Thus the clearance and turnover of beta 2-microglobulin seems to play a major role in this disease. In a prospective multicenter study the beta 2-microglobulin clearance was studied in 87 patients starting hemodialysis. Serum samples were taken prior to and after the first dialysis session and also before and after dialysis at 4, 6, 12, 16, 26 and 52 weeks. Patients were either treated by cuprophane or a polyacrylonitril membrane. At the start, the mean serum beta 2-microglobulin level was about 18 mg/L in patients treated with a cuprophane membrane, but the levels increased after hemodialysis and reached a plateau, which was always higher than in those treated with polyacrylonitril, which cleared beta 2-microglobulin from the serum. However, after 12 months the difference was no longer significant. Thus beta 2-microglobulin excretion during dialysis differs between the two membranes, but seems to lose its significance for the beta 2-microglobulin serum level in chronic hemodialysis treatment.

Acrylic Resins↗
PubMed1994

[Therapy of primary chronic glomerulonephritis].

Primary chronic glomerulonephritis may emerge clinically as acute nephritis, the nephrotic syndrome as well as asymptomatic hematuria and proteinuria. Therapeutic consequences still depend on the morphological diagnosis. In cases of minor proteinuria [< 3,5 g/24 h] immunosuppressive therapy is not superior to symptomatic therapy. In patients with nephrotic syndrome immunosuppressive therapy depends on the morphological diagnosis. Glucocorticoids are the therapy of choice in minimal changes glomerulopathy and should be tried in focal segmental sclerosing glomerulonephritis. Steroids may be tried in pure mesangial as well as in IgA and IgM nephropathy. Especially Ponticelli claims significant therapeutic success in patients with membranous glomerulonephritis treated with Prednisolone and Chlorambucil. Failures and relapses may be treated with Cyclophosphamide, Chlorambucil or Cyclosporin A. Anticoagulants may be advantageous in the therapy of membranoproliferative glomerulonephritis.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Acute and chronic effects on cholesterol biosynthesis of LDL-apheresis with or without concomitant HMG-CoA reductase inhibitor therapy.

To determine the acute and long-term effects of low density lipoprotein (LDL) reduction on cholesterol biosynthesis, we studied changes in the cholesterol precursors mevalonic acid (MVA) and lathosterol in patients with heterozygous familial hypercholesterolemia undergoing LDL-apheresis. Long-term LDL-apheresis in eight patients resulted in slight but insignificant increases in plasma MVA levels and lathosterol/cholesterol (L/C) ratios over 18 months. In short-term studies, six patients not on drugs and six patients treated with lovastatin or pravastatin had blood taken immediately before and after LDL-apheresis, and afterwards on days 1, 2, 3, 5, and 7. Plasma L/C ratios and MVA concentration did not change significantly on the first day after LDL-apheresis in those not on statin therapy (1.11 +/- 0.08 vs. 1.40 +/- 0.18, and 9.2 +/- 1.3 vs. 9.1 +/- 0.6 ng/ml, respectively) but increased in the statin-treated group (from 0.78 +/- 0.09 to 1.55 +/- 0.21, P = 0.003 and from 5.0 +/- 0.7 to 11.0 +/- 1.6 ng/ml, P = 0.008, respectively). There was no clear correlation between the changes in either of these precursors and the extent of reduction of total cholesterol by LDL-apheresis, but there was a strong inverse correlation with the post-apheresis LDL-cholesterol level (r = -0.77, P = 0.002 for L/C ratio; r = -0.75, P = 0.003 for MVA). Post-apheresis changes in L/C ratio and MVA were mutually correlated (r = 0.68. P = 0.01). We conclude that LDL-apheresis stimulates cholesterol biosynthesis transiently despite concomitant therapy with an HMG-CoA reductase inhibitor, the degree of stimulation being inversely related to the level to which the LDL-cholesterol was reduced.

Adult↗
PubMed1992

[Proteinuria and atherogenic risk].

The relationship between blood-lipid levels and severity of proteinuria was examined retrospectively in 30 patients (12 males, 18 females; mean age 39 [18-58] years). All patients had histologically confirmed glomerulonephritis (minimal change: n = 7, perimembranous: n = 8, focal sclerosing: n = 6, rapid progressive: n = 3, mesangio-proliferative: n = 4, membrano-proliferative: n = 1, diabetic glomerulosclerosis: n = 1). None was taking lipid-lowering drugs. Patients were classified according to the degree of proteinuria. In group 1 (proteinuria less than 5 g/d, n = 13) the LDL-HDL ratio averaged 4.4; in group 2 (proteinuria 5.0-10.0 g/d, n = 10) the average ratio was 8.8, and in group 3 (proteinuria greater than 10.0 g/d, n = 7) 13.3. Total cholesterol concentration also rose with increasing proteinuria (to 300 +/- 87 mg/dl, 375 +/- 168 mg/dl and 464 +/- 143 mg/d, respectively). The size of the LDL-HDL ratio and the level of total cholesterol did not correlate with the degree of excretory renal failure. These results point to an impressive correlation between the degree of proteinuria and the level of LDL-HDL ratio as a measure of atherogenic risk for a given patient.

Adult↗
PubMed1992

Pharmacokinetic and blood pressure effects of carvedilol in patients with chronic renal failure.

The pharmacokinetic and acute systemic haemodynamic effects of a single oral dose of 50 mg carvedilol has been studied in 24 hypertensive patients with chronic renal failure. The patients were stratified into 3 groups according to the creatinine clearance: I 51-90 ml.min-1; II 26-50 ml.min-1; III 4-25 ml.min-1. The area under plasma level time curve AUC, the elimination half-life t1/2, the maximum plasma concentration Cmax, the time to peak concentration tmax were not significantly different between groups, whereas the amount of unchanged drug or metabolite excreted in urine Ae and the renal clearance CLR of carvedilol and its metabolites M2, M4, M5 were significantly decreased in Group III. Blood pressure and heart rate decreased in all 3 groups of patients after acute administration of 50 mg carvedilol. Mild adverse effects were reported in 6 patients. Despite a decrease in the renal clearance of carvedilol and of its metabolites with decreasing kidney function, its main pharmacokinetic parameters remained unchanged. The present results suggest that the dose of carvedilol need not be reduced in hypertensive patients with chronic renal failure.

Administration, Oral↗
PubMed1992

Renal hemodynamics and reduction of proteinuria by a vasodilating beta blocker versus an ACE inhibitor.

The effects of a nonselective beta-adrenergic blocking drug with beta-2 agonist activity (dilevalol 200 mg) on proteinuria and renal hemodynamics were evaluated in a double-blind crossover study versus an ACE inhibitor (enalapril 5 mg) in eight patients with glomerulonephritis, moderate renal function impairment and proteinuria greater than 1 g/24 hr. Patients were studied after a one week placebo phase while off all other medications, except steroids in a few cases, and after three weeks of treatment. A 10-day placebo washout perod was included between the various drug treatments. During each period renal hemodynamics were measured by clearance techniques, and urinary protein excretion as well as fractional clearance of albumin and IgG were determined. Both drugs reduced mean arterial pressure and proteinuria to a similar extent [mean arterial pressure: placebo 108 +/- 13 mm Hg; dilevalol 103 +/- 11 mm Hg (P less than 0.05); enalapril 103 +/- 12 mm Hg (P less than 0.05); protein excretion: placebo 5.1 +/- 4.2 g/day; dilevalol 3.3 +/- 3.0 g/day (P less than 0.05); enalapril 2.8 +/- 2.8 g/day (P less than 0.05)]. The antiproteinuric effect was greater with enalapril than dilevalol. Dilevalol reduced GFR [baseline inulin clearance: 73.3 +/- 38 ml/min/1.73 m2; after dilevalol: 63.3 +/- 28 ml/min/1.73 m2 (P less than 0.05)] and the decrease of proteinuria correlated positively with the reduction of GFR. Enalapril did not significantly lower the GFR (inulin clearance during enalapril 66.8 +/- 23 ml/min/1.73 m2) and the reduction of proteinuria did not correlate with the lowering of the GFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Renal haemodynamics and organ damage in young hypertensive patients with different plasma renin activities after ACE inhibition.

We describe our observations concerning differences in two groups of young hypertensive patients according to their renin activities after ACE inhibition. Seventeen of these patients (age 26 +/- 7 years), so far untreated, were investigated prospectively for hormone levels (renin, aldosterone, vasopressin), microalbuminuria, renal haemodynamics (inulin and PAH clearance) and signs of organ damage (echocardiography, fundoscopy). Secondary forms of hypertension were excluded by routine methods, including angiography. We differentiated two groups of young hypertensive patients. Group 1 (n = 9) had a false positive captopril test with elevated renin activities after ACE inhibition with captopril (8.4 +/- 5 ng/ml per hour) compared to group 2 (renin activity: 2.2 +/- 1.3 ng/ml per hour) or an increase of greater than 400% of renin activity after ACE inhibition. Baseline renin activities and sodium excretion did not differ between the groups. Group 1 also showed significantly greater GFR, FF, and microalbuminuria, as well as signs of organ damage, with left ventricular hypertrophy and hypertensive changes in fundoscopy. There were no differences between the groups concerning mean arterial blood pressure and duration of hypertension. In conclusion, we were able to demonstrate that patients with highly stimulated renin activities showed signs of visceral organ damage and renal hyperfiltration compared to the normal renin activity group after ACE inhibition. Investigations of the renin-angiotensin-aldosterone system with ACE inhibitors might constitute a helpful indicator of renal changes and organ damages in young hypertensive patients.

Adult↗
PubMed1992

Noninvasive procedures for diagnosis of renovascular hypertension in renal transplant recipients--a prospective analysis.

The purpose of this study was to clarify the selectivity and specificity of noninvasive procedures for diagnosis of clinically suspected posttransplant renovascular hypertension. We prospectively investigated 25 renal transplant recipients with arterial hypertension and clinically suspected stenosis of the graft artery (8 female and 17 male patients; ages 45 +/- 15 years). We performed a captopril test with 25 mg captopril (n = 25), renography with technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) before and after angiotensin-converting enzyme (ACE) inhibition with determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) (n = 23) and color-coded duplex ultrasonography of the transplant kidney vessels (n = 24). Renal transplant artery stenosis (RTAS) was excluded by renal arteriography in 20 patients and by operative evaluation or clinical follow-up in 5 patients. We identified 4 patients with RTAS and renovascular hypertension. The noninvasive methods showed the following results (sensitivity/specificity): (1) captopril test: 75%/67%; (2) renography combined with ACE-inhibition: 75%/84%; and (3) color-coded duplex ultrasonography: 100%/75%. We conclude that in patients with clinical evidence of RTAS most noninvasive diagnostic procedures are not sufficiently accurate to exclude the diagnosis. Only color-coded duplex ultrasonography did not fail to detect all patients with RTAS and may act as a screening test. Intraarterial renal angiography remains the most reliable and as-yet indispensable diagnostic test for transplant recipients to rule out RTAS.

Adult↗
PubMed1992

Human cytomegalovirus in immunoglobulin A nephropathy: detection by polymerase chain reaction.

Human cytomegalovirus (HCMV) has been suspected to participate in the pathogenesis of IgA nephropathy (IgAN). However, with regard to the presence of HCMV in the renal tissue of IgAN, conflicting results have been reported using a variety of different techniques. Renal biopsies of 29 patients with IgAN, of 7 with focal segmental glomerulosclerosis (FSGS) and of 11 normal kidneys were analyzed for the presence of HCMV-DNA using the polymerase chain reaction. HCMV-DNA was detected by hybridization with digoxigenin-labelled probes in 14 of 19 analyzed frozen renal biopsies from patients with IgAN. However, only 1 of 17 renal biopsies of IgAN embedded in paraffin was positive for HCMV-DNA. Furthermore, HCMV-DNA was detected in 4 of 18 frozen normal kidneys but in none of the tissues from patients with FSGS. The present results provide further evidence of an association between the presence of HCMV in renal tissue and IgAN.

Adult↗
PubMed1992

Human cytomegalovirus in rejected kidney grafts; detection by polymerase chain reaction.

Human cytomegalovirus (CMV) infections are frequently associated with graft rejection in the immunosuppressed patients following organ transplantation. Thirty-four tissue samples from rejected kidneys and 18 samples from normal adult kidneys obtained from autopsies were investigated for the presence of CMV-DNA by the polymerase chain reaction (PCR) and by immunohistochemistry. DNA extracted from renal tissues after proteinase K digestion was specifically amplified in 32 cycles using primers which flank a 147 bp DNA fragment of the immediate early CMV gene and analysed by slot-blot hybridization with digoxigenin-labelled detection oligonucleotides. CMV-DNA was detected by PCR in a range from 0.1 fg up to 100 fg in 14 (41%) rejected kidney transplants. Comparative immunohistological analysis revealed presence of CMV in only three biopsies of these rejected kidneys. Furthermore, CMV-DNA was also found in four of 18 (22%) normal donor kidneys. These results reveal that CMV is often present in rejected kidneys and that the infection can be transferred from the donor to the recipient, since the normal adult kidney appears to be a frequent site of latency for CMV. No differences in local immunological changes, characterized by interstitial mononuclear leukocyte infiltration as well as by aberrant expression of HLA-class II antigens and of ICAM1 on proximal tubular epithelial cells, could be detected by further immunohistological analysis between grafted kidneys at late stage of rejection with and without CMV infection.

Adolescent↗
PubMed1992

In vivo clearance and elimination of nine marker substances during hemofiltration with different membranes.

The handling of low, middle and high molecular weight markers was examined in seven stable dialysis patients during hemofiltration with different membranes. Four membranes were examined in a randomized, crossover order (polysulfone, polyamide, AN69 polyacrylonitrile, Asahi polyacrylonitrile) by measuring plasma and dialysate concentrations of phosphate, creatinine, vitamin B12, beta 2-microglobulin, furanic acid, hippuric acid, retinol-binding protein, alpha-1-antitrypsin, and albumin. Sieving coefficients and plasma clearances of beta 2-microglobulin or retinol-binding protein were markedly or slightly lower during hemofiltration with the Asahi polyacrylonitrile membrane than with the other membranes (highest removal with polysulfone/AN69 polyacrylonitrile membranes). No differences of obvious clinical relevance could be seen between the four membranes. A high beta 2-microglobulin removal rate might be important to prevent dialysis-associated amyloidosis.

Aged↗