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K Derfler

Publications and source records attributed to K Derfler.

At least 37 records · Page 2Linked to original sources
PubMed1999

Extracorporeal immunoadsorption for the treatment of haemophilic patients with inhibitors to factor VIII or IX.

BACKGROUND AND OBJECTIVES: This article reviews the relevance of immunoadsorption in the treatment of haemophilic patients with inhibitors. MATERIALS AND METHODS: Immunosorba (sepharose-bound staphylococcal protein A) and Ig-Therasorb (sepharose-bound polyclonal sheep antibodies to human immunoglobulin) columns are suitable for the clinical use of immunoadsorption. They allow the processing of large plasma volumes (>7,000 ml) without relevant side-effects. RESULTS: A haemophilic patient was treated with the Malmö protocol, another was admitted with intracerebral bleeding. Immunoadsorption reduced the inhibitor titer by 70-90%. CONCLUSIONS: Immunoadsorption can be used in cases of acute bleeding, before surgery, acquired factor VIII (FVIII) antibodies, and before the start of immune tolerance therapy. We suggest the inclusion of this method in immune tolerance protocols in order to improve levels, recovery, and half-life of FVIII and to save concentrates.

Chromatography, Affinity↗
PubMed1999

Up-regulation of LDL-receptor expression by LDL-immunoapheresis in patients with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is characterized by an autosomal dominantly inherited deficiency of LDL-receptor expression on the cell surface, leading to excess plasma LDL-cholesterol and severe premature atherosclerosis. In patients with heterozygous FH, a major therapeutic objective of conventional drug therapy is to stimulate maximally the residual cellular capacity to produce LDL-receptors via inhibition of endogenous cholesterol synthesis. In contrast, LDL-immunoapheresis aims at reducing the plasma LDL-cholesterol level by extracorporeal elimination of LDL particles. The present study investigates whether LDL-immunoapheresis applied in addition to conventional drug therapy is able to further stimulate residual LDL-receptor expression capacity in patients with heterozygous FH via the withdrawal of external cholesterol supply, thereby exerting a second accessory lipid lowering effect. METHODS: LDL-receptor expression--calculated by transforming mean fluorescence intensities into numbers of antibody binding sites per cell (S/C)--was determined flow-cytometrically on peripheral blood monocytes before and after LDL-apheresis. For a comparison with the maximum obtainable receptor expression capacity, in vitro stimulation experiments under completely LDL deficient conditions were performed. RESULTS: Prior to LDL-apheresis, LDL-receptor density was comparable in patients (N = 7; 2014 +/- 359 S/C) and controls (N = 10; 1782 +/- 252 S/C). Under in vitro conditions LDL-receptor expression of controls exceeded that of patients with FH by 1.6 times. Immediately after apheresis, LDL-receptor expression significantly increased to almost the same level as obtained by in vitro stimulation (3640 +/- 423 S/C and 3632 +/- 572 S/C). The LDL-receptor expression in FH subsequent to LDL-apheresis exhibited two patterns of kinetics [Type 1: maximal receptor stimulation (288 +/- 70%; P < 0.07) already during apheresis; Type 2: highest receptor density 24 hours after treatment (149 +/- 11%; P < 0.01)]. CONCLUSIONS: These results demonstrate that despite drug therapy, LDL-apheresis significantly stimulates the residual LDL-receptor expression in FH via the reduction of available extracellular cholesterol resulting in delayed reappearance of hypercholesterolemia in between treatments.

Adult↗
PubMed1998

Immunoapheresis in paraneoplastic pemphigus.

BACKGROUND: Paraneoplastic pemphigus was first described in 1990 in 5 patients with extensive mucocutaneous erosions, a distinct set of autoantibodies, and underlying neoplasia. Since then, patients described have been middle-aged, have suffered from prognostically unfavorable malignant neoplasms, and have responded poorly to immunosuppressive agents. OBSERVATION: A 16-year-old boy was examined with extensive oral erosions, halitosis that interfered with his quality of life, and rapid weight loss. The suspected clinical diagnosis of paraneoplastic pemphigus was confirmed by histopathological, immunofluorescence, and biochemical (eg, immunoblotting and immunoprecipitation) findings as well as by the demonstration of an inflammatory myofibroblastic tumor of the left retroclavicular region. Despite administration of corticosteroids, followed by excision of the neoplasm, clinical symptoms improved only slightly, and autoantibody titers decreased only marginally. We therefore initiated an immunoapheresis regimen with the use of sheep anti-human-IgG bead-formed agarose gel (Sepharose; Pharmacia Biotech Comp, Vienna, Austria), which led to the disappearance of circulating autoantibodies and the patient's recovery. CONCLUSION: Immunoapheresis may represent a novel therapeutic option for patients with paraneoplastic pemphigus who show little improvement after curative treatment of their neoplasms.

Adolescent↗
PubMed1998

Therapeutic efficiency of lipoprotein(a) reduction by low-density lipoprotein immunoapheresis.

This study was performed to investigate the effect of low-density lipoprotein (LDL) immunoapheresis on lipoprotein(a) [Lp(a)] reduction in patients with heterozygous and homozygous familial hyperlipidemia (N=16) and insufficient response to lipid-lowering agents. By desorption of approximately 5,700+/-500 mL of plasma, a mean reduction in total cholesterol of 62% (P < .001) and in LDL-cholesterol of 70% (P < .001) was achieved. Lp(a), which was elevated at study entry in seven of these patients (82.1+/-34.3 mg/dL; range, 48 to 148 mg/dL), was reduced during the initial LDL-apheresis procedure by 74.8%+/-14.1% (P < .001). Long-term apheresis treatment performed at weekly intervals resulted in an mean reduction in Lp(a) pretreatment values to 39.1+/-28.5 mg/dL (-54%; P < .001). Desorbed Lp(a) was measured at the waste of the columns for 31 apheresis treatments. Lp(a) concentration of the column waste was higher in patients with elevated serum Lp(a) pretreatment values as compared with those with Lp(a) serum values within the normal range (elevated Lp(a), 1,420+/-380 mg; without elevated Lp(a), 235+/-190 mg; P < .001). The rate of return of Lp(a) following apheresis treatment scheduled at weekly intervals was comparable to that of LDL-cholesterol.

Adolescent↗
PubMed1998

Decreased urinary apolipoprotein (a) excretion in patients with impaired renal function.

BACKGROUND: Plasma lipoprotein (a) [Lp(a)] levels are elevated in patients with kidney disease and are strongly associated with premature cardiovascular disease and stroke. METHODS: As the kidney is suggested to play an important role in apolipoprotein (a) [apo(a)] catabolism and as apo(a) fragments appear in urine, we determined plasma Lp(a) levels and urinary apo(a) excretion in relation to kidney function in a large cohort of renal patients. A total of 368 renal patients with normal or different degrees of impaired renal function and 163 healthy control subjects matched for age and sex were investigated. Plasma Lp(a) and urinary apo(a) were analysed immunochemically. RESULTS: Renal patients were found to have significantly elevated total cholesterol and low-density lipoprotein (LDL)-C values but lower high-density lipoprotein (HDL)-C values than control subjects. Plasma Lp(a) values were significantly higher only in patients with creatinine clearance < 70 mL min-1. There was a significant correlation between urinary apo(a) and plasma Lp(a) in patients and control subjects. Urinary apo(a) excretion was significantly lower in patients than in control subjects and showed no correlation with urinary protein excretion. CONCLUSION: Although it is unlikely that impaired renal excretion of apo(a) fragments largely contributes to increased plasma Lp(a) levels in patients suffering from impaired kidney function, these data suggest that urinary apo(a) excretion is significantly decreased in renal patients and that this might contribute to increased plasma Lp(a) levels in this patient group.

Aged↗
PubMed1998

Plasma immunadsorption treatment in patients with primary focal and segmental glomerulosclerosis.

BACKGROUND: In primary focal and segmental glomerulosclerosis (FSGS) renal prognosis is poor if no remission of proteinuria can be obtained by treatment. In some patients a permeability factor, responsible for damaging the glomerular epithelial cell and detectable by an in vitro test (GVV-test), seems to be present in the serum. METHOD: We determined the effects of an immunadsorption treatment (IAT) on proteinuria and glomerular permselectivity (using a neutral dextran and dextransulfate-sieving technique to assess glomerular size and charge selectivity) in five patients with FSGS in the native kidneys and three patients with recurrence of FSGS after kidney transplantation. Furthermore, we performed the GVV-test using sera obtained from the patients before and after therapy. RESULTS: IAT reduced proteinuria by more than 50% in four patients, all of whom had an improvement in glomerular-size selectivity. Charge selectivity was better preserved after therapy in three out of these four subjects. The GVV-test prior to IAT was positive in two patients who also responded clinically to therapy. After IAT the GVV-test was negative in all patients, indicating an elimination of the proteinuric factor in the two previously positive patients. CONCLUSION: We conclude that a positive GVV-test before treatment makes a favourable response of IAT on proteinuria likely in patients with FSGS. If a reduction of proteinuria can be obtained by IAT this is due to an improvement in glomerular size and/or charge selectivity.

Adolescent↗
PubMed1998

Urinary apolipoprotein (a) excretion in patients with proteinuria.

Increased plasma lipoprotein (a) (Lp(a)) levels are strongly associated with premature cardiovascular disease and stroke. Recently we, as well as other groups, found that apolipoprotein (a) (apo(a)) fragments appear in the urine of healthy individuals, and that renal transplant patients with impaired renal function excrete fewer apo(a) fragments into their urine compared with controls. As the excretion mode of apo(a) is presently unknown, we determined plasma Lp(a) levels and urinary apo(a) excretion in relation to kidney function in 58 proteinuric patients and 58 healthy controls. For the first time, urinary apo(a) excretion was related to apo(a) isoforms. Plasma Lp(a) values were higher in the proteinuric patients compared with the controls, independent of their renal function. The patients with low-molecular-weight apo(a) isoforms had higher Lp(a) plasma levels, whereas the patients with high-molecular-weight apo(a) isoforms had lower Lp(a) plasma levels. Urinary apo(a) showed a very similar pattern to that of plasma Lp(a), being significantly higher in patients with low-molecular-weight isoforms as compared with patients with high-molecular-weight isoforms. Urinary apo(a) excretion was significantly decreased in the patient group when compared with healthy controls. There was a close correlation (P < 0.001) between the plasma Lp(a) and urinary apo(a) excretion in both the patient group and the control group. Urinary apo(a) excretion did not correlate with protein excretion, creatinine clearance or plasma creatinine levels. We conclude that urinary apo(a) excretion correlates with plasma Lp(a) and Lp(a) isoforms, and that proteinuric patients excrete significantly less apo(a) into their urine than healthy controls, a factor that might contribute to increased plasma Lp(a) levels in these patients.

Adult↗
PubMed1997

Malposition of central venous catheters. Incidence, management and preventive practices.

INTRODUCTION: Proper placement is an essential prerequisite for the use of central venous catheters. Our study was undertaken to determine the incidence of aberrant locations dependent on different anatomic approaches for various types of central venous catheters and to elucidate failures and pitfalls of preventive practices. METHODS: 2580 percutaneously inserted lines (including 538 tunneled devices and 112 implantable Port-A-Caths) introduced by Seldinger's technique were reviewed for inadvertent malpositioning. RESULTS: Primary misplacement was evident on 47 occasions (1.82%), 38 times into large venous tributaries of the superior vena cava. 3 aberrant locations involved a persistent left superior vena cava, two catheters were placed into minor intrathoracic veins and in 3 patients inadvertent arterial cannulation occurred. The frequency of malpositioning was related to the anatomic approach and the catheter type used, but not to the physician's experience. Respective incidences were 4.12% for the left internal jugular access, but were lower for the right internal jugular (1.1%) and the right (1.01%) and left (0.89%) supraclavicular approach. Misplacement was more frequent with soft silicone catheters (2.53%) than with semi-rigid catheters (0.79%). All malpositions but one were detected on chest X-ray. DISCUSSION: Our data suggest that the incidence of catheter malposition depends on the site of insertion, the type of material used, but not on the experience of the physician who inserted the catheter. Scrupulous use of preventive practices reduces the frequency of malpositioned catheters, but physicians must keep in mind potential pitfalls. Injection of radioopaque contrast medium into the catheter during control chest X-ray should be done even with opaque catheters.

Adult↗
PubMed1997

Impairment of citrate metabolism in acute hepatic failure.

AIMS: To compare the utilization of citrate employed as anticoagulant in patients with acute hepatic failure and subjects with normal liver function. PATIENTS AND METHODS: Three patients in acute hepatic failure and normal renal function were studied during therapeutic plasma exchange with citrate containing fresh frozen plasma. Six patients receiving immunapheresis or LDL-apheresis anticoagulated with citrate served as controls. Determinations of serum citrate concentrations, of ionized calcium and blood pH were performed before, during, and after the extracorporeal treatment. Total body clearance and elimination half life were calculated in a two compartment model. RESULTS: Preinfusion citrate levels were higher in the patients with acute hepatic failure than in the controls (n.s.). The citrate level rose to 1.73 +/- 0.2 mmol/l in the liver patients versus 0.99 +/- 0.1 mmol/l in the healthy subjects (p < 0.03). Total body clearance was markedly reduced in patients with acute hepatic failure (3.31 +/- 0.03 ml/kg/min) as compared with the controls (6.34 +/- 0.16 ml/kg/min) (p < 0.02), the elimination half life (t/2 k1e) was prolonged (49.7 +/- 5.4 vs. 32.9 +/- 1.02 min, p < 0.05). In the controls blood pH rose from 7.4 +/- 0.01 to 7.45 +/- 0.01 (p < 0.05) after citrate infusion, whereas in the liver patients no rise in pH was observed, again reflecting the impairment of citrate metabolism. Ionized calcium was lower in the patients with acute hepatic failure at the beginning (1.01 +/- 0.05 vs. 1.21 +/- 0.04 mmol/l, p < 0.05) and the end (0.68 +/- 0.02 vs. 0.93 +/- 0.04 mmol/l, p < 0.05) of the citrate infusion. CONCLUSIONS: Citrate metabolism is severely impaired and the plasmatic calcium stores are reduced in acute hepatic failure and, thus, the risk of adverse effects is high. Therapeutic infusions of citrate should be restricted in patients with acute hepatic failure and, if necessary, therapy should be closely monitored by repeated measurements of ionized calcium to avoid the development of potentially hazardous hypocalcemia.

Adolescent↗
PubMed1997

LDL-apheresis significantly reduces urinary apo(a) excretion.

Increased plasma Lp(a) is an established risk factor for atherosclerosis. We recently described the presence of apo(a) fragments in urine and the significant correlation between urinary apo(a) concentrations and plasma Lp(a). Here we investigated urinary apo(a) in patients suffering from familial hypercholesterolaemia (FH), treated with LDL apheresis. Before treatment, plasma Lp(a) levels and urinary apo(a) normalized to creatinine were > 2-fold increased in FH patients (P < 0.0001) as compared to controls. LDL-apheresis led to a reduction of plasma Lp(a) by 75% and a concomitant immediate reduction of urinary apo(a) by 45%. We conclude that a steady state condition for urinary apo(a) is rapidly achieved via LDL-apheresis.

Adult↗
PubMed1997

Lipoprotein pattern in end-stage renal disease and following successful renal transplantation.

Lipoprotein abnormalities are common in uremia and frequently persist after successful renal transplantation (RT). Based on the influence of immunosuppression on lipoprotein metabolism, this prospective study in 76 patients has been focused on lipoprotein pattern in end-stage renal disease and after successful RT during a follow-up period of 18 months. Additionally, the influence of different immunosuppressive regimes has been evaluated. Hyperlipidemia was present in 32% of the patients before and in 59% after grafting. Total cholesterol was 5.42 +/- 1.57 mmol/l (mean S D) before RT and continuously and significantly increased during the entire observation period, being highest 18 months after RT (6.8 +/- 1.63 mmol/l; p < 0.01). This was mainly due to an increase in LDL-cholesterol (before RT: 3.68 (1.41 mmol/l; 18 months after RT: 4.69 +/- 1.88 mmol/l; p < 0.05) while HDL-cholesterol values only slightly increased (before RT: 0.99 +/- 0.36 mmol/l; 18 months after RT: 1.13 +/- 0.3 mmol/l; p < 0.05). Changes in total HDL-cholesterol were mainly due to an increase in HDL 3, while HDL 2 moderately increasing remained at low concentrations. As corticosteroid dosage was substantially reduced during the entire observation period, other factors such as cyclosporin A have to be considered for hyperlipidemia in renal transplant recipients. The observation on LDL-cholesterol being highest 18 months after transplantation suggests lipid lowering interventions to be indicated and might improve long-term outcome in renal transplant recipients.

Adult↗
PubMed1996

Elevated lipoprotein(a) and increased incidence of restenosis after femoropopliteal PTA. Rationale for the higher risk of recurrence in females?

It has been shown that the incidence of recurrent stenosis following successful percutaneous transluminal coronary angioplasty (PTCA) is correlated with serum Lipoprotein(a) [Lp(a)] levels. The aim of the present study was to examine the influence of Lp(a) on restenosis after primary successful femoropopliteal PTA. One hundred and thirty nine consecutive patients with peripheral arterial occlusive disease (PAOD) and successful femoropopliteal PTA were studied. Follow-up included clinical examination and non-invasive laboratory testing (pulse volume recordings, ankle-brachial arterial pressure measurement) in every patient before and after 1, 3, 6 and 12 months following intervention. Duplex sonography was performed 1 year after PTA. Suspicion of restenosis (> or = 50% diameter reduction) was verified by angiography. Lp(a) was determined using ELISA technique (mg/dl). Twelve months after successful PTA no restenosis was found in 82 patients (59%: group A). The one-year recurrence rate of 41% (group B) was due to significant restenosis in 35 patients (25%) and reocclusion in 22 patients (16%). The corresponding mean values +/- S.E.M. for Lp(a) were as follows: group A, 28 +/- 5.3; group B 59 +/- 11 (P < 0.01). Women showed a higher frequency of recurrences (55%) versus men (30%, P < 0.01) also corresponding with a high Lp(a) level (51.8 +/- 8 versus 32.7 +/- 5; P < 0.05). Furthermore Lp(a) aggravated the well known increased risk for recurrence in multiple stenoses or occlusions of > or = 5 cm in length. There were no significant differences between groups A and B with respect to age, diabetes, hyperlipidaemia, obesity and cigarette smoking. The results support the view that Lp(a) is an independent risk factor for recurrence after PTA in the femoropopliteal area. It might also be a causal basis for the higher incidence of recurrences in female PAOD patients.

Aged↗
PubMed1996

Beneficial effect of renal transplantation on cognitive brain function.

Cognitive brain dysfunction is a common complication of end-stage renal disease. To investigate the cerebral effect of renal transplantation, we studied P300 event-related potentials--an objective marker of cognitive brain function--trailmaking test and Mini-mental state in 15 chronic hemodialysis patients and 45 matched healthy subjects. Before transplantation, patients showed prolonged P300 latency (364 vs. 337 ms, P < 0.01), smaller amplitude (15.2 vs. 19.1 microV) and scored lower (P < 0.05) in trailmaking test and Mini-mental state as compared to healthy subjects. Following renal transplantation (14 months), P300 latency decreased (337 ms, P < 0.01 vs. before) and amplitude increased (17.4 microV, P < 0.05 vs. before), indicating improved cognitive brain function. The trailmaking test and Mini-mental state tended to improve. Following transplantation, P300 findings, trailmaking test and Mini-mental state were not different from healthy subjects. Additional studies following erythropoietin treatment in 6 of the 15 hemodialysis patients revealed decreased (improved) P300 latency (351 vs. 379 ms before, P < 0.05) with further decrease following transplantation (341 ms, P = 0.06). Our findings indicate that cognitive brain dysfunction in hemodialysis patients may be fully reversed by successful renal transplantation.

Adult↗