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Biomedical subjects

R M Schaefer

Publications and source records attributed to R M Schaefer.

At least 19 recordsLinked to original sources
PubMed2000

[Extracorporeal renal replacement therapies in acute renal failure].

The most serious forms of acute renal failure (ARF) are nowadays encountered in the intensive care unit (ICU), where up to 25% of new patients are reported to develop ARF. Lethality rates may reach 50 to 90% when the ARF is part of a multiple organ dysfunction syndrome. A multitude of extracorporeal procedures have been introduced into intensive care medicine. Applied with adequate skills and experience, most of these techniques will suffice to replace excretory renal function. However, because of low efficacy arterio-venous procedures (CAVH and CAVHD) have been abandoned for the veno-venous, pump-driven techniques (CVVH and CVVHD). Up to now, there is no consensus whether continuous or intermittent renal replacement therapy is more advantageous. In many cases, oliguric patients with circulatory instability will be treated by CVVH, even though there is no prospective study to show that in terms of outcome continuous treatment is superior to intermittent hemodialysis. It is equally conceivable to treat such patients with daily, prolonged (intermittent) hemodialysis. Apparently, the dose of replacement therapy, be it continuous filtration (36 to 48 l/24 h) or intermittent hemodialysis (daily 3 to 4 h) with a target BUN of less than 50 mg/dl, is more important than the modality of treatment. Moreover, there is good evidence that the use of biocompatible membranes (no complement- or leukocyte activation) is preferable and that with high-volume hemofiltration bicarbonate-containing replacement fluids should be used. However, despite all the technical advances, we firmly believe that the skills and the experience of those physicians and nurses who actually perform renal replacement therapy in the ICU are more important than the modality of treatment applied.

Acute Kidney Injury↗
PubMed2000

Small proteoglycans of normal adult human kidney: distinct expression patterns of decorin, biglycan, fibromodulin, and lumican.

BACKGROUND: Among the members of the small leucine-rich proteoglycan family, decorin, biglycan, and fibromodulin have been proposed to be potent modulators of transforming growth factor-beta (TGF-beta) activity, thereby playing an important role in the pathogenesis of fibrotic kidney diseases. Furthermore, decorin expression influences the expression of p21WAF1/CIP1, which has been related to kidney hypertrophy and hyperplasia. However, none of the members of this proteoglycan family have been investigated in normal adult human kidney cortex, thus making it impossible to correlate disease-mediated alterations of their expression with the normal situation in vivo. METHODS: The chondroitin/dermatan sulfate proteoglycans, decorin and biglycan, and the keratan sulfate proteoglycans, fibromodulin and lumican, were investigated in normal human adult renal cortex by immunohistochemistry on the light and electron microscopic level and by in situ hybridization. Northern blot and reverse transcription-polymerase chain reaction (RT-PCR) methods were used to get an estimate of their expression in isolated glomeruli. Decorin excretion with the urine was measured by Western blotting. RESULTS: Two bands of decorin and a single band of biglycan mRNA were identified in Northern blots of isolated glomeruli. Amplification by RT-PCR was required to detect the signals for fibromodulin and lumican. All four proteoglycans were preferentially expressed in the renal interstitium with accumulations around tubules. Weak expression was found in the mesangial matrix. Biglycan was expressed by glomerular endothelial cells and, together with fibromodulin, was synthesized and deposited in distal tubular cells and collecting ducts. Immunogold labeling indicated the presence of the proteoglycans in the glomerular basement membrane, which was interpreted as a result of glomerular filtration. Indirect evidence suggested tubular reuptake of decorin after glomerular filtration. CONCLUSION: The data indicate that the different cells of the adult human kidney are characterized by a distinct expression pattern of the four small proteoglycans. It is suggested that these proteoglycans may have distinct pathophysiological roles depending upon whether they are expressed by mesangial cells, endothelial cells, epithelial cells, or cells of the tubulointerstitium.

Adult↗
PubMed2000

Effects of bicarbonate- and lactate-buffered replacement fluids on cardiovascular outcome in CVVH patients.

BACKGROUND: Bicarbonate-buffered replacement fluid (RF-bic) in continuous venovenous hemofiltration (CVVH) may be superior to lactate-buffered replacement fluid (RF-lac) in acute renal failure. In an open, randomized, multicenter study, we investigated the effects of RF-bic and RF-lac on cardiovascular outcome in patients requiring CVVH following acute renal failure. METHODS: One hundred seventeen patients between the age of 18 and 80 years were randomized to CVVH either with RF-bic (N = 61) or RF-lac (N = 56). Patients were treated with CVVH for five days or until either renal function was restored or the patient was removed from the study. Data were analyzed on day 5 or according to the "last observation carried forward" (LOCF) option. Adverse events were classified according to the WHO-Adverse Reaction Terminology system. RESULTS: Blood lactate levels were significantly lower and blood bicarbonate levels were significantly higher in patients treated with RF-bic than in those treated with RF-lac (lactate, 17.4 +/- 8.5 vs. 28.7 +/- 10.4 mg/dL, P < 0.05; bicarbonate, 23.7 +/- 0.4 vs. 21.8 +/- 0.5 mmol/L, P < 0. 01). The number of hypotensive crises was lower in RF-bic-treated patients than in RF-lac-treated patients (RF-bic 14 out of 61 patients, RF-lac in 29 out of 56 patients; 0.26 +/- 0.09 vs. 0.60 +/- 0.31 episodes per 24 h, P < 0.05). Nine out of 61 patients (15%) treated with RF-bic and 21 out of 56 patients (38%) treated with RF-lac developed cardiovascular events during CVVH therapy (P < 0. 01). A multiple regression analysis showed that the occurrence of cardiovascular events was dependent on replacement fluid and previous cardiovascular disease and not on age or blood pressure. Patients with cardiac failure died less frequently in the group treated with RF-bic (7 out of 24, 29%) than in the group treated with RF-lac (12 out of 21, 57%, P = 0.058). In patients with septic shock, lethality was comparable in both groups (RF-bic, 10 out of 27, 37%; RF-lac, 7 out of 20, 35%, P = NS). CONCLUSIONS: The results show that the administration of RF-bic solution was superior in normalizing acidosis of patients without the risk of alkalosis. The data also suggest that the use of RF-bic during CVVH reduces cardiovascular events in critically ill patients with acute renal failure, particularly those with previous cardiovascular disease or heart failure.

APACHE↗
PubMed2000

Reduced iopromide elimination in hemodialysis with cuprophan membranes.

PURPOSE: To evaluate the influence of different membrane materials on the efficiency of iopromide elimination. MATERIAL AND METHODS: Twenty stable patients with chronic renal failure after coronary angiography were investigated for contrast medium elimination during hemodialysis directly after contrast medium application. RESULTS: Clearance during hemodialysis with cuprophan membranes was 102 +/- 7 mg/ml in contrast to 153 +/- 4 mg/ml in polysulfone membranes. Elimination half-time was 94 +/- 5 min in cuprophan and 79 +/- 3 min in polysulfone membranes, and the elimination rate after 120 min was 59 +/- 2% and 66 +/- 1.5% respectively. Plasma clearance of iopromide was elevated in polysulfone membranes (188 +/-17 ml/min); however, not significantly different to cuprophane membranes (153 +/-11 ml/min). Accordingly, 24-h urinary iopromide excretion was reduced to 26 +/- 4 g/24 h vs. 32 +/- 7 g/24 h. CONCLUSION: Hemodialysis for iopromide elimination with polysulfone membranes is more effective than with cuprophan membranes.

Cellulose↗
PubMed2000

Pharmacokinetics of 1M gadobutrol in patients with chronic renal failure.

RATIONALE AND OBJECTIVES: To investigate the pharmacokinetics of 1M gadobutrol as a new neutral MR contrast agent in patients with impaired renal function. METHODS: Twenty-one patients with impaired renal function and any indication for a contrast-enhanced MRI were enrolled into this prospective study and classified in two subgroups according to their creatinine clearance (group 1, 30-80 mL/ min; group 2, 30 mL/min or less, not requiring dialysis). Eleven patients were assigned to the lower dose of 0.1 mmol Gd/kg and 10 patients to the higher dose of 0.3 mmol Gd/kg. To calculate pharmacokinetic parameters, urine and venous blood samples were drawn at baseline and up to 72 hours for group 1 and 120 hours for group 2 after administration of gadobutrol. RESULTS: The predominant extracellular distribution of gadobutrol at steady state did not change according to the degree of renal impairment. The mean elimination half-life of gadobutrol increased to 7.4 +/- 2.6 hours (0.1 mmol/kg) and 5.4 +/- 1.5 hour (0.3 mmol/kg) in group 1 and to 17.9 +/- 6.2 hours (0.1 mmol/kg) and 20.4 +/- 16.9 hours (0.3 mmol/kg) in group 2, compared with 1.5 hours in healthy volunteers. The relation between serum (tbeta) and urine (t(elim)) elimination half-lives, as well as total serum and renal clearance, indicated renal elimination as the main pathway of elimination. The recovery of gadobutrol in the urine of group 1 was complete within 72 hours for both dosage levels. Patients with severe renal impairment showed a mean recovery of 80.1% (0.1 mmol/kg) and 85.3% (0.3 mmol/kg) within the observation period of 120 hours. CONCLUSIONS: The half-life of gadobutrol is prolonged in patients with impaired renal function, but elimination by means of the kidneys is the predominant route.

Case-Control Studies↗
PubMed2000

Iron metabolism in rhEPO-treated hemodialysis patients.

A number of factors have been shown to limit the response to recombinant human erythropoietin (rhEPO). One major factor appears to be an inadequate iron supply to the bone marrow. Erythropoiesis is dependent upon a continuous supply of iron to the bone marrow. The rate at which iron can be drawn from existing stores may easily limit the rate of delivery for hemoglobin synthesis. This may result in "functional iron deficiency" which is distinct from "absolute iron deficiency" caused by depletion of iron stores. At present there are three main parameters available to clinicians wishing to monitor iron status in their patients: serum ferritin and transferrin saturation (TFS), which are indirect measurements, and the percentage of hypochromic red cells, which directly reflects marrow iron status. Ferritin levels should be measured before starting rhEPO therapy to ensure adequate iron stores (> 200 microg/l), and when patients move from the correction phase to the maintenance phase of therapy (have stores become depleted during the correction phase?). In addition, ferritin levels can give an indication of iron overload following excess parenteral iron administration. The TFS represents a balance between iron supply by the stores and demand by bone marrow. A saturation below 20% probably indicates iron-deficient erythropoiesis. However, this is an indirect measure of marrow iron supply and wide fluctuations have been observed when determined at different time points. The percentage of hypochromic red blood cells is measured by flow cytometry and a hypochromic subpopulation of more than 10% (normal percentage > 2.5%) indicates iron-deficient erythropoiesis. However, not all departments have access to the required equipment. The aim of iron supplementation is to provide sufficient iron for the correction phase and replace iron losses (1,500 - 3,000 mg/year in hemodialysis patients) during the maintenance phase of rhEPO therapy. This amounts to a daily iron need in the range of 5-7 mg, which is well above the normal dietary intake and absorptive capacity of the human intestine. Therefore there is a need for intravenous iron, in particular when the patient ha absolute or functional iron deficiency, is in tolerant of oral iron, or is not complying we with the oral regimen.

Enzyme Inhibitors↗
PubMed2000

Prevalence of hepatitis G in patients on chronic hemodialysis.

Hepatitis G virus (HGV) is a newly described RNA virus from the family of flaviviridae. It is closely related to the hepatitis C Virus (HCV) but is more common than HCV among healthy blood donors. The pathogenicity of HGV in immunosuppressed patients such as those undergoing hemodialysis is unclear. We measured the incidence of HGV in 105 patients undergoing hemodialysis in a chronic outpatient hemodialysis facility. HGV-RNA was detected using a RT-PCR method with primers directed against the 5' non-coding region and the NS5a gene of HGV. Nine (8.6%) patients were HGV RNA positive, eleven (10.5%) were anti-HCV positive, three (2.9%) were positive for hepatitis B surface antigen. Four patients were positive for both HGV and HCV; three of them had normal liver enzymes while one showed elevated ALT levels but no other signs of exacerbation of preexisting hepatitis. The prevalence of HGV among dialysis patients is comparable to that of HCV. The transmission route for HCV is nosocomial transmission during dialysis, whereas HGV shows both ways of transmission: blood transfusion mediated by a high prevalence of HGV among healthy blood donors and nosocomial transmission. HGV appears to play a minor role in acute hepatitis, even in immunosuppressed patients.

Adult↗
PubMed2000

Extracorporal therapy with AN69 membranes in combination with ACE inhibition causing severe anaphylactoid reactions: still a current problem?

The negatively charged membrane AN69 is known to evoke anaphylactoid reactions both without and with concomitant ACE inhibition. Underlying reasons are mainly the induction of bradykinin release due to the negatively charged membrane and the reduced degradation of bradykinin due to ACE inhibition. This complication has been reported repeatedly, but anaphylactoid reactions still occur in clinical practice. We recently had to treat two patients who suffered anaphylactoid reactions during extracorporal therapy with an AN69 membrane and simultaneous ACE inhibition. The first incident occurred in a patient on hemodialysis, the second was in a patient on continuous venovenous hemofiltration. An anaphylactoid reaction induced by an AN69 membrane during continuous, extracorporal treatment in combination with ACE inhibition has not been reported so far. Our report intends to serve as a reminder that the potentially lethal combination of AN69 membranes with ACE inhibitor treatment should be avoided.

Acrylic Resins↗
PubMed1999

Hypochromic red blood cells and reticulocytes.

The management of recombinant human erythropoietin (rHuEPO) treatment in hemodialysis patients requires close monitoring of iron status, because the pharmacologically stimulated erythropoiesis is particularly dependent on a continuous supply of iron. Parameters commonly measured to assess iron status are serum ferritin and the transferrin saturation. Both are indirect measures of iron availability for hemoglobin synthesis and frequently do not permit an assessment of the adequacy of iron supply to the erythron. Using flow cytometry, cell volume and hemoglobin concentration can be measured in individual red blood cells and reticulocytes. Based on these techniques, two parameters have proved to be particularly useful in identifying iron-deficient erythropoiesis. (a) The percentage of hypochromic erythrocytes (defined as red blood cells with a hemoglobin concentration of less than 28 g/dl) has been shown to detect insufficient marrow iron supply with a fairly good accuracy. (b) More recently, determination of the content of hemoglobin in reticulocytes (CHr) has been suggested by a number of authors to be even more sensitive in detecting iron-deficient erythropoiesis. For those who have access to an H*3 hematology analyzer, both indices can be determined at the time of a routine blood count at a minimal incremental cost.

Anemia, Iron-Deficiency↗
PubMed1999

Hypochromic red cells and reticulocyte haemglobin content as markers of iron-deficient erythropoiesis in patients undergoing chronic haemodialysis.

BACKGROUND: In patients on chronic haemodialysis, because of a non-specific increase in serum ferritin, iron deficiency may be overlooked leading to failure of erythropoietin treatment. A reticulocyte haemglobin content < 26 pg and a percentage of hypochromic red cells > 2.5 have been proposed as markers of iron-deficient erythropoiesis in such subjects, but it is unclear which parameter is superior. METHODS: We measured haematocrit, reticulocyte haemglobin content, ferritin and the percentage of hypochromic red cells over 10-150 days in 36 chronic haemodialysis patients in a university hospital. Transferrin saturation was also measured in a subset of 25 patients; iron deficiency was defined as a transferrin saturation < 15%. RESULTS: The diagnostic sensitivity and specificity of a reticulocyte haemoglobin content < 26 pg in detecting iron deficiency were 100% and 73% respectively, compared with 91% and 54% for a percentage of hypochromic red cells > 2.5. Paradoxical reticulocyte haemglobin concentrations occurred on follow-up in five patients receiving 4000 U erythropoietin per haemodialysis (HD). In three patients, reticulocyte haemglobin content exceeded 26 pg despite a persistent lack of iron. In a fourth, iron gluconate (62.5 mg i.v./HD) increased transferrin saturation to 27% and reduced the percentage of hypochromic red cells from 12 to 4, while reticulocyte haemglobin remained > 30 pg. In the final patient, iron gluconate increased transferrin saturation from 8 to 30% and reduced the percentage of hypochromic red cells from 40 to below 5, but reticulocyte haemglobin content remained < or = 26 pg throughout. CONCLUSIONS: The reticulocyte haemglobin content is superior to the percentage of hypochromic red cells in detecting iron deficiency in haemodialysis patients.

Adult↗
PubMed1999

Zinc protoporphyrin and percentage of hypochromic erythrocytes as markers of functional iron deficiency during therapy with erythropoietin in patients with advanced acquired immunodeficiency syndrome.

BACKGROUND: We assessed zinc protoporphyrin (ZPP) and the percentage of hypochromic erythrocytes in patients with advanced acquired immunodeficiency syndrome (AIDS) treated with recombinant erythropoietin (rhEPO). METHODS: Patients received 150 IU rhEPO subcutaneously every second day for 10 days, and 150 IU rhEPO plus 62.5 mg of intravenous iron every second day for an additional 10 days. RESULTS: Before rhEPO therapy, ZPP was at 64.3 +/- 27.3 micromol/mol heme and the percentage of hypochromic erythrocytes was elevated at 9.7%, indicating mild functional iron deficiency. Ferritin was 1,002 +/- 956 microg/L, with transferrin saturation of 19.1 +/- 9.7%. Under rhEPO alone, ZPP rose to 80.1 +/- 21.6 micromol/mol heme and the percentage of hypochromic red cells rose to 22.9 +/- 4.7%; ferritin fell to 705 +/- 601 microg/L and transferrin saturation fell to 12 +/- 6.3%. When rhEPO was supplemented with iron, ZPP fell to 70.4 +/- 20.5 micromol/mol heme, the percentage of hypochromic red cells fell to 14.7 +/- 3.4%; ferritin was unchanged at 771 +/- 62 microg/L and transferrin saturation rose to 20.5 +/- 5.5%. CONCLUSIONS: In contrast to ferritin and transferrin saturation, ZPP and the percentage of hypochromic erythrocytes effectively detect the functional iron deficiency under rhEPO therapy in advanced AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Efficiency of 1-year treatment with fluvastatin in hyperlipidemic patients with nephrotic syndrome.

The influence of fluvastatin, a liver-selective, competitive inhibitor of the 3-hydroxymethyl-glutaryl-coenzyme A reductase, on the lipoprotein metabolism was investigated in 9 patients with nephrotic syndrome. All patients had biopsy-proven renal disease as cause of their nephrotic syndrome and exhibited severe hyperlipidemia [baseline: serum cholesterol 358 +/- 46 mg/dl (9.3 mmol/l), low-density lipoprotein cholesterol 236 +/- 18 mg/dl (6.1 mmol/l), triglycerides 333 +/- 28 mg/dl (3.8 mmol/l), and lipoprotein Lp(a) 46 +/- 11 mg/dl]. After 1 year of 40 mg of fluvastatin, significant reductions of total cholesterol by 31% to 242 +/- 26 mg/dl (6.3 mmol/l) and low-density lipoprotein cholesterol by 29% to 162 +/- 12 mg/dl (4.2 mmol/l) were observed. Furthermore, triglyceride values were also lowered significantly by 19% to 268 +/- 21 mg/dl (3.1 mmol/l). Lipoprotein Lp(a) and high-density lipoprotein-cholesterol remained unchanged by fluvastatin. These improvements in lipid profile were maintained during the entire follow-up period of 1 year. There were no adverse events, and the slight increase in serum creatinine observed during the study was considered to be due to the primary renal disease. In conclusion, long- term administration of fluvastatin in patients with nephrotic syndrome appears to be an effective and safe treatment of the hyperlipidemia associated with this disorder.

Adult↗
PubMed1999

Suppressed activities of cathepsins and metalloproteinases in the chronic model of puromycin aminonucleoside nephrosis.

Glomerulosclerosis and tubulointerstitial fibrosis are the hallmarks of chronic renal diseases. In the present study, we have investigated the potential involvement of various proteinases in these alterations in the model of puromycin aminonucleoside (PAN) nephrosis. Two groups of male Wistar rats were given either three or seven injections of PAN (2.0 mg/100 g body weight) over a 4- and 12-week period, respectively. The two control groups received saline injections. Activities of cathepsins (B, H and L) were determined in isolated glomeruli and proximal tubules. Moreover, collagenase-like and gelatinase-like activities were analyzed in isolated glomeruli. Three weeks after weekly PAN injection, the rats developed heavy proteinuria (140.8+/-22.0 vs. 13.5+/-3.29 mg/day; p<0.001), and at week 11 protein excretion reached 606.6+/-23.00 vs. 22.8+/-1.5 mg/day. Renal morphology revealed minimal glomerular mesangial changes at the 4th week after PAN administration. At the 12th week a marked mesangial matrix accumulation as well as severe tubulointerstitial infiltration and fibrosis associated with tubular dilation and atrophy were observed. Glomerular cathepsins B, H, and L and gelatinase-like activities decreased at the 4th week after the first PAN injection and remained at this low level throughout the entire study period. Glomerular collagenase-like activity decreased at the 4th week (p<0.05) and was still mildly lower than that of the control group at the 12th week, but without significance. In the isolated proximal tubules, the activities of cathepsins B, H, and L showed the same pattern of decreases as those found in the glomeruli over the whole experimental period. Taken together, our data in the model of chronic PAN nephrosis suggest that the suppressed activities of cathepsins as well as the decreased gelatinase- and collagenase-like activities participate in the accumulation of extracellular matrix and thereby may contribute to the development of glomerulosclerosis and tubulointerstitial fibrosis.

Animals↗
PubMed1999

Clearance of iopromide during haemodialysis with high- and low-flux membranes.

PURPOSE: The present clinical trial addressed the clearance of the contrast medium iopromide, a middle-sized molecule, during dialysis with high- and low-flux membranes. MATERIAL AND METHODS: Twenty chronic haemodialysis patients without residual renal function were dialysed either with low-flux haemophan or high-flux polyamide directly after application of the contrast medium. Iodine concentrations were determined by radiofluorescence methods. RESULTS: Plasma concentrations of iodine before dialysis ranged between 1.1 and 3.9 mg/ml. The mean clearance rates for both membranes were comparable (110+/-1.4 ml/min high-flux and 108+/-1.9 ml/min low-flux), the sieving-coefficient was 0.83 for both membranes. After three hours of dialysis, 58% (high-flux) and 62% (low-flux) of iopromide was removed, half time of elimination was reached after 140+/-16 min (high-flux) and 122+/-11 min (low-flux). CONCLUSION: Our results demonstrated that elimination of iopromide is not dependent on the pore size of the membrane during dialysis. Due to higher blood flow rate, we found a higher elimination rate and a reduced half-time of elimination than prior investigations.

Contrast Media↗
PubMed1999

Does early anemia correction prevent complications of chronic renal failure?

Anemia is a common complication of chronic renal failure (CRF). With the availability of recombinant human erythropoietin (rhEPO) over the last decade, much progress has been made in the management of anemia in patients with end-stage renal disease (ESRD) [Eschbach 1995, Gimenez and Scheel 1994, Muirhead et al. 1995, Winearls 1995]. The clearest benefit of rhEPO in ESRD is a substantial reduction in transfusion dependency, which reduces the need for hospital admission and the risk of viral transmission. Improvements in hemostasis and a decrease in human leucocyte antigen (HLA) antibodies have also been reported. Beneficial effects of rhEPO on the cardiovascular system in ESRD include regression of left ventricular hypertrophy (LVH), improvement of angina, and a modest increase in aerobic work capacity. Treatment of anemia with rhEPO has also been shown to improve cognitive function, socialization and quality of life in dialysis patients, although this has not led to better vocational rehabilitation or employment status. It has also been reported that a lower hemoglobin (Hb) content is an independent risk factor for increased mortality in hemodialysis patients [Harnett et al. 1995]. Clearly, therefore, treatment of anemia associated with ESRD is required and beneficial. The optimum treatment of anemia prior to dialysis, however, is still a matter for debate.

Anemia↗