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Biomedical subjects

C J Olbricht

Publications and source records attributed to C J Olbricht.

At least 37 records · Page 2Linked to original sources
PubMed1995

Minimally invasive diagnosis of renal artery stenosis by spiral computed tomography angiography.

We prospectively compared in a blinded fashion spiral computed tomography angiography (CTA) with arteriography in 62 consecutive patients with suspected renal artery stenosis (RAS). For CTA 150 ml of contrast material were injected intravenously. Arteriography was performed by DSA technique with selective catheterization of renal arteries. Of the 157 visualized renal arteries 155 could be evaluated with DSA and a total of 157 with CTA. Sensitivity of CTA for RAS > or = 50% was 98% and the specificity was 94%. Comparison of the grade of stenosis as evaluated by DSA versus CTA showed: identical gradation in 59 arteries (DSA > or = 50%/CTA > or = 50%), underestimation by CTA in one artery (DSA 50 to 75%/CTA < 50%), and overestimation by CTA in six arteries (DSA < 50%/CTA 50 to 75%). Factors that may contribute to these differences include impaired renal function and possibly "underestimation" of ostial RAS by arteriography. One artery not evaluable by arteriography showed a 70% stenosis by CTA. CTA showed no major side effects. We conclude that CTA has the same accuracy for the diagnosis of RAS > or = 50% as arteriography. However, CTA is only minimally invasive, safe, and causes less discomfort to patients.

Adult↗
PubMed1995

Removal of clodronate by haemodialysis in end-stage renal disease patients.

BACKGROUND: Clodronate is a potent calcium-lowering drug. The effect of haemodialysis on clodronate pharmacokinetics is unknown. METHODS: The removal of clodronate by haemodialysis was determined in 10 end-stage renal disease patients (ESRD). A 2-h infusion of 300 mg of clodronate was followed immediately by a 4-h haemodialysis. Vascular access was by AV fistula. A 1.5-m2 cuprophane hollow-fibre dialyser was applied. Blood flow was 205 +/- 15 ml/min, dialysate flow 523 +/- 29 ml/min. Clodronate was determined by high-performance liquid chromatography in total collected dialysate, and in blood before and after the dialyser at initiation, 2 h, and 4 h of HD. RESULTS: The initial predialyser serum concentration of clodronate was 13.6 +/- 4 micrograms/ml. It decreased to 4.9 +/- 0.5 micrograms/ml and 2.6 +/- 0.5 micrograms/ml at 2 h and 4 h respectively. The clearance of clodronate (86 +/- 10 ml/min) remained unchanged during HD. Clodronate in total collected dialysate per single 4-h HD was 105 +/- 16 mg (35% of injected dose). CONCLUSION: We conclude that clodronate is effectively removed from plasma by HD. The present data together with information provided by previous studies suggest that 300 mg of clodronate given as an 2-h infusion immediately prior to haemodialysis is an adequate dosage for ESRD patients.

Adult↗
PubMed1994

Interstitial nephritis associated with 5-aminosalicylic acid.

A patient with severe Crohn's disease was treated with 5-aminosalicylic acid (5-ASA). Following initiation of treatment, serum creatinine increased slowly from 105 to 530 mumol/l (creatinine clearance 16 ml/min). The diagnosis of an interstitial nephritis was made based on normal urinary findings and the renal biopsy histology of interstitial mononuclear infiltrates and normal glomeruli, 5-ASA was discontinued and serum creatinine decreased to 245 mumol/l (creatinine clearance 40 ml/min) during the following 3 months. Partial reversibility of renal failure following discontinuation of 5-ASA and the absence of other drugs possibly causing interstitial nephritis suggest a causal relationship between 5-ASA and interstitial nephritis.

Adult↗
PubMed1994

Effect of cyclosporin on kidney proteolytic enzymes in men and rats.

Cyclosporin (CsA) induces autophagolysosomes in proximal tubules. A major lysosomal function is degradation of cell proteins. Cathepsin B and L are marker enzymes for the activity of lysosomal protein degradation. Therefore we measured cathepsin activities in microdissected proximal tubule segments and urine from rats treated with CsA, 30 mg/24 h by gavage for 42 days. Cathepsin activity was increased in proximal tubule by 117% and in 24-h urine by 37% compared to controls. Unchanged values of serum cathepsin activity and of proteinuria excluded increased glomerular filtration or decreased tubular absorption as major source of urine cathepsins. Therefore urine cathepsin excretion reflected tubular cathepsin activity. Urine cathepsin excretion was also measured in patients without renal disease treated with CsA for multiple sclerosis (MS). It was increased by 59% in patients with CsA serum values > 120 ng/ml compared to MS patients without CsA or with serum CsA < 120 ng/ml. Urine cathepsin excretion increased linearly with serum CsA (P < 0.001). The data suggest that cathepsin activity is increased in proximal tubules of CsA-treated patients. Hence CsA may stimulate protein degradation in proximal tubules of men and rats.

Adult↗
PubMed1993

Glomerulonephritis associated with inflammatory demyelinating polyradiculoneuropathy: a case report and review of the literature.

A patient developed relapsing inflammatory demyelinating polyradiculoneuropathy associated with nephrotic syndrome. Renal biopsy showed focal-segmental glomerulosclerosis. The review of the literature disclosed that glomerulonephritis with and without nephrotic syndrome seems to be not uncommon in inflammatory demyelinating polyradiculoneuropathy, such as Guillain-Barré syndrome. membranous glomerulonephritis is the most frequent histologic diagnosis while minimal change nephropathy, 'acute glomerulonephritis' and postinfectious type glomerulonephritis are not often present. This is the first case of inflammatory demyelinating polyradiculoneuropathy associated with nephrotic syndrome due to focal-segmental glomerulosclerosis. Larger prospective studies are necessary and may contribute to the understanding of the pathogenesis of both, glomerulonephritis and inflammatory demyelinating polyradiculoneuropathy.

Adult↗
PubMed1993

Effect of low-molecular-weight dextran on proteolytic and nonproteolytic lysosomal enzymes in isolated segments of rat proximal tubule.

Dextrans undergo glomerular filtration and are taken up by endocytosis into lysosomes of proximal tubule cells. We measured the activities of the intralysosomal proteolytic enzymes cathepsin B and L and the nonproteolytic acid phosphatase in microdissected segments of rat proximal tubules by means of fluorescent ultramicroassays. Cathepsin activities were increased following dextran injection in a dose-dependent manner. Cathepsin stimulation was not dextran-specific since enhanced proximal albumin uptake also increased cathepsin activities. Acid phosphatase remained almost unchanged. We conclude that increased proximal tubule uptake of macromolecules is accompanied by a rather specific stimulation of proteolytic enzymes in the lysosomes. For proteins this constitutes an adequate response to increased protein uptake to maintain the steady state between uptake and catabolism of proteins in lysosomes. For the nondigestible dextran the cathepsin induction is an inadequate response. Since lysosomal cathepsins are involved in breakdown of intracellular proteins, it is conceivable that the increased activities reflect increased cellular autophagy leading to proximal tubule damage.

Acid Phosphatase↗
PubMed1993

Extracorporeal treatment of hypercholesterolaemia.

Extracorporeal removal of LDL cholesterol (LDL apheresis) has been carried out in patients with diet- and drug-resistant hypercholesterolaemia to prevent or to reduce coronary heart disease. Plasma separation is the first step in all five LDL-apheresis methods presently available. Plain plasma exchange and double-membrane filtration are unselective and remove HDL cholesterol and plasma proteins. Adsorption of LDL to dextran sulphate, to LDL antibodies, or precipitation of LDL by heparin at low pH are more selective. With all methods LDL cholesterol reduction per treatment is 60-70%. In most patients one treatment per week is sufficient to reduce mean LDL to 100-150 mg/dl. Minor side-effects occur in 10 +/- 5% of treatments. Major side-effects are rare. Long-term LDL apheresis increased survival in patients with homozygous familial hypercholesterolaemia. In heterozygous familial hypercholesterolaemia controlled studies regarding survival are not available. Uncontrolled trials indicate regression of coronary artery disease in heterozygotes with drug- and diet-resistant LDL cholesterol > 200 mg/dl. Hence, LDL apheresis is indicated in all patients with homozygous familial hypercholesterolaemia. LDL apheresis in heterozygous familial hypercholesterolaemia should be restricted to patients with diet- and drug-resistant LDL cholesterol > 200 mg/dl with coronary heart disease and/or other atherosclerotic vascular lesion.

Blood Component Removal↗
PubMed1992

Long-term experience with extracorporeal low-density lipoprotein cholesterol removal by dextran sulfate cellulose adsorption.

Patients with familial hypercholesterolemia have a high incidence of coronary heart disease due to diet- and drug-resistant, elevated low-density lipoprotein cholesterol (LDL-C). Five patients with familial hypercholesterolemia and diet- and drug-resistant LDL-C greater than 230 mg/dl were treated by LDL apheresis using dextran sulfate cellulose adsorption (Liposorber System LA-15, Kaneka). Plasma separation was by 0.5-m2 polysulfone hollow fiber filter. Two columns containing 150 ml of dextran sulfate cellulose alternately adsorbed LDL and were regenerated by 4.1% saline. The five patients received a total of 360 treatments at 7-day intervals. The treated plasma volume per session was 4.1 +/- 0.4 l. Postapheresis values compared with preapheresis were: total cholesterol, 40%; LDL-C, 28%; VLDL-C, 65%; HDL-C, 95%; triglycerides, 70%; white blood cells, 116%; platelets, 87%; C3 complement, 79%; fibrinogen, 64%; albumin, 94%. The decrease in HDL-C per treatment was not significant. The safety parameters showed only slight changes. The initial LDL of 436 +/- 172 mg/dl decreased to mean pre-apheresis levels of between 150 and 100 mg/dl. The anti-atherogenic HDL increased in three and remained unchanged in two patients. Adverse events like hypotension, angina pectoris, and technical problems occurred in 11 of the 360 treatments. Long-term treatment of patients with diet- and drug-resistant familial hypercholesterolemia by extracorporeal dextran sulfate cellulose adsorption is effective and safe.

Adult↗
PubMed1992

Renal hypertrophy in streptozotocin diabetic rats: role of proteolytic lysosomal enzymes.

Renal protein mass increases in diabetic renal hypertrophy. Accretion of protein may be the result of increased protein synthesis and/or decreased protein degradation. The lysosomal proteases, cathepsins B and L, are key enzymes in cellular protein catabolism. To evaluate the role of protein degradation in diabetic renal hypertrophy, the activities of cathepsins B and L were measured in microdissected proximal tubule segments and in kidney cortex homogenates. In rats four and ten days following induction of diabetes by streptozotocin, the kidney weight was increased and the cathepsin activities were reduced in proximal tubule segments. Treatment with insulin prevented both changes. The liver weight in diabetic rats was decreased and the activity of cathepsins B and L was increased, while the activity in kidney cortex was reduced. This excluded that diabetes per se may be accompanied by decreased cathepsin activities independent of organ hypertrophy. Renal hypertrophy as a cause rather than as the consequence of reduced cathepsin activities was excluded by the finding of unchanged cathepsin activities in proximal tubule segments from rats with compensatory renal hypertrophy four days and ten days following unilateral nephrectomy. Decreased activities of cathepsins B and L may reflect decreased intracellular protein degradation. Decreased protein breakdown in proximal tubules may contribute to diabetic renal hypertrophy. In agreement with this interpretation are the results from rats six months following induction of diabetes. Renal hypertrophy is complete at that time. No further accretion of protein occurs and the cathepsin activities in the proximal tubule were not different from controls.

Animals↗
PubMed1992

Kidney transplantation in Alport's syndrome: long-term outcome and allograft anti-GBM nephritis.

Anti-glomerular basement membrane (anti-GBM) nephritis occurring in kidneys transplanted in patients with Alport's syndrome (AS) has been reported repeatedly. Therefore, we studied graft survival and course of renal function in all 30 AS patients grafted at Hannover Medical School and compared them with non-diabetic, age and sex matched patients, transplanted on the date closest to the transplantation of the AS patient. Serum creatinine, proteinuria, urinary sediment and anti-GBM antibodies were examined in all AS patients with functioning grafts. Cases of patient or graft loss in the AS group were analyzed retrospectively. One- and five-year patient survival was 100 and 91% in AS and 89 and 78% in controls (p > 0.05, respectively). One- and five-year first graft survival was 79 and 66% in both groups. Graft histology was available in 34 biopsies obtained from 21 kidneys in 15 AS patients. Anti-GBM nephritis was not detected in any of the biopsies. No graft was lost due to anti-GBM nephritis. Anti-GBM antibodies were detectable temporarily only in one AS patient. He also had linear IgG staining in his graft GBM, but no other signs of anti-GBM nephritis. We conclude that patient survival and graft survival in AS patients following kidney transplantation is not different from non-AS patients. Allograft anti-GBM nephritis is a rare complication in patients with Alport's syndrome.

Adult↗
PubMed1992

Distribution of cathepsins B and L in the kidney and their role in tubular protein absorption.

Intralysosomal proteinase activity, due to cathepsins B and L, was measured in microdissected segments of rat nephron, using Z-Phen-Arg-7-amido-4-methylcoumarin as the substrate. Cathepsin B was determined with Z-Arg-Arg-7-amido-4-methylcoumarin. The enzymes cleave on the carboxy side of arginine and release free 7-amino-4-methylcoumarin, which is highly fluorescent and can be measured at very low concentrations in small volumes. Enzyme activities were measured in three individual microdissected segments of the proximal tubule and in six different segments of the distal tubule. Experiments were performed in normal non-proteinuric rats and in several rat models of glomerular proteinuria. The distributions of cathepsin activities along the nephron were similar. In all groups, the convoluted part of the proximal tubule had enzyme activities three times higher than in the remaining segments of the nephron. In the last millimeter of the pars convoluta and in the pars recta of the proximal tubule, enzyme activities were two to three times higher in proteinuric animals. These findings suggest that in proteinuric animals the increase in the protein load delivered to the proximal tubules selectively stimulated cathepsin B and L activities in the last millimeter of the pars convoluta and in the pars recta of the proximal tubule, presumably because of an increase in protein uptake, and that cathepsins B and L participate in lysosomal digestion of protein reabsorbed from the glomerular ultrafiltrate via endocytosis.

Absorption↗
PubMed1991

[Pathophysiology and therapy of lipid metabolism disorders in kidney diseases].

Nephrotic syndrome, uremia, hemodialysis, peritoneal dialysis, and renal transplantation are accompanied by alterations in lipoprotein metabolism In nephrotic patients, total cholesterol, LDL, VLDL and triglycerides are elevated, while HDL may be increased, normal, or decreased. The pathophysiology includes increased hepatic synthesis of VLDL and cholesterol, decreased activity of lipoprotein lipase, and increased urinary excretion of HDL. The risk of coronary heart disease (CHD) is increased in nephrotic patients and elevated LDL-cholesterol may contribute to this risk. Cholesterol lowering diet and drugs are indicated. Presently, Lovastatin and Simvastatin are the most potent cholesterol lowering drugs in nephrotic patients with good evidence of long-term safety. Most patients with impaired renal function or on hemodialysis have moderate hypertriglyceridemia due to decreased lipoprotein lipase activity. HDL may be slightly decreased. Although the risk of CHD is increased in these patients, triglyceride lowering drugs are not indicated, since no benefit can be expected. Peritoneal dialysis is accompanied by elevated VLDL in addition to hypertriglyceridemia. Reabsorption of large amounts of glucose from peritoneal dialysis fluid increases the carbohydrate load and stimulates hepatic VLDL synthesis. Cholesterol lowering therapy may be advantageous, but the experience is very limited. Side effects of lipid lowering drugs may be aggravated in renal failure. Total cholesterol, LDL, VLDL, and triglycerides are elevated in 50% of patients following renal transplantation. Corticosteroids and cyclosporin are major causes of hyperlipidemia. Cholesterol lowering therapy is indicated since the incidence of CHD is increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗