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Biomedical subjects

R Klingel

Publications and source records attributed to R Klingel.

At least 19 recordsLinked to original sources
PubMed2005

[Monitoring of the heparin therapy during acute haemodialysis].

Anticoagulation during renal replacement therapy is recommended to avoid thrombosis of the filter devices and to maintain the blood flow. However, in the case of multiorgan failure and sepsis, an imminent bleeding complication in patients with acute renal failure may cause the need for an extracorporeal circulation without anticoagulation. The most common drug used in renal replacement therapy is the unfractionated heparin (UFH). With low molecular weight heparin (LMWH) good experiences are reported, too. Based on the level of evidence from clinical studies plasma measurement of heparin is indispensable for patients with renal insufficiency. The activated whole blood clotting time (ACT), the activated partial thromboplastin time (aPTT), and the determination of the anti-factor Xa activity (anti Xa) with chromogenic substrates are available as routine as well as as point-of-care tests. To monitor plasma levels of LMWH the anti Xa assay serves exclusively as a suitable monitoring. The anti Xa assay using chromogenic substrates is the most specific and valid one for monitoring heparin therapy. In lack of large controlled studies for the anticoagulation therapy and its monitoring with the anti Xa test in acute renal failure, the current experiences are based on the results of chronic renal replacement therapy.

Anticoagulants↗
PubMed2004

Bilirubin-adsorption in 23 critically ill patients with liver failure.

PURPOSE: Previous studies suggest that high levels of bilirubin exert cytotoxic, neurotoxic and encephalopathic effects that themselves may lead to further deterioration of liver function and multiorgan failure. Although extracorporeal BA is not a causal therapy, there are case reports of clinical benefits of BA. The present retrospective study investigated the clinical utility and effectiveness of BA in 23 patients with liver failure. METHODS: Twenty-three patients (61+/-11 years) with excessive hyperbilirubinemia (>25 mg/dL) after liver transplantation (n=7), partial liver resection (n=12) and others (n=4) were treated with BA (3.6 liters plasma per BA, BR350, Asahi) and followed for 45+/-8 days. RESULTS: A mean of 6.6 treatments (3-16) were performed per patient. On average, a single BA treatment reduced bilirubin-levels from 31+/-12 to 23.7+/-9 mg/dL (p<0.001). Levels of bile acid were reduced from 41.8+/-6 to 33.5+/-5 mg/dL. The 30-day mortality was 50%. BA was able to halt and stabilize the progressive increase in bilirubin levels in all patients. In contrast to survivors, non-survivors were characterized by a repeated rapid rise in bilirubin levels after cessation of BA treatment. CONCLUSIONS: BA is able to stabilize or decrease bilirubin levels in patients with liver failure. Our experience suggests that BA is a safe and promising short-term treatment option for patients with acute deterioration of hepatic function.

Adsorption↗
PubMed2003

Membrane differential filtration is safe and effective for the long-term treatment of Refsum syndrome--an update of treatment modalities and pathophysiological cognition.

Refsum's disease is a complex and difficult to diagnose storage disease caused by complex autosomal recessive peroxisomal disorder in which mutations of phytanolyl/pristanoyl-CoA-hydroxilase are the main cause. Poorly metabolised phytanic acid (PA), pristanic acid (PrA) and picolenic acid (PiA) accumulates in fatty tissues, myelin sheaths, heart, kidneys and retina, leading to retinitis pigmentosa, peripheral dissociative polyneuropathy, cerebellar ataxia ("sailors" walk), renal, cardiac and liver impairment. 65% of plasma PA and PrA is localized within VLDL, LDL and HDL lipoprotein particles. Dietary restriction of PA is mostly not sufficient to prevent acute attacks and stabilize the progressive course. LDL and VLDL bound PA/PrA can be effectively eliminated from plasma with extracorporal LDL-apheresis using membrane differential filtration. Mostly additive malnutrition will become worse the clinical picture. Latest experience with black cumin oil (nigella sativa) in a dose of 3 g/day shows a support and a regression of some malnutrition effects in PA restricted dietary and a supportive effect to MDF.

Blood Component Removal↗
PubMed2003

Successful removal of pathogenic autoantibodies in pemphigus by immunoadsorption with a tryptophan-linked polyvinylalcohol adsorber.

BACKGROUND: Autoantibodies against the glycoproteins desmogleins 1 and 3 which are components of the desmosomal adhesion complex have been shown to be responsible for the loss of epidermal adhesion characteristic of pemphigus. Elimination of these antibodies should clinically improve the pathology of this group of severe autoimmune blistering skin disorders. OBJECTIVES: To gather information about the efficacy of immunoadsorption in the reduction of pathogenic serum autoantibodies against desmogleins 1 and 3 and to evaluate the clinical benefit of immunoadsorption in the treatment of pemphigus. PATIENTS AND METHODS: Nine patients with pemphigus and detectable circulating desmoglein antibodies were included in this open trial. Two immunoadsorption treatments separated by a 48-h interval were performed per patient. Anti-desmoglein 1 and 3 antibodies in the patients' sera were monitored by enzyme-linked immunosorbent assay and indirect immunofluorescence before and following each immunoadsorption. In addition, the efficacy of the tryptophan-linked polyvinylalcohol adsorber in removing antidesmoglein antibodies was directly evaluated. RESULTS: IgG antibodies against desmogleins 1 and 3 were effectively eliminated from the patients' plasma upon passage through the adsorber and levels of serum autoantibodies were significantly reduced by immunoadsorption. A single immunoadsorption treatment led to a reduction of antidesmoglein autoantibodies of about 30%. Clinically, mucosal and cutaneous lesions improved allowing for a reduction of the systemic immunosuppressive treatment with glucocorticoids. CONCLUSIONS: Immunoadsorption with tryptophan-linked polyvinylalcohol adsorbers holds promise as a highly effective and safe adjuvant therapeutic regimen in pemphigus.

Autoantibodies↗
PubMed2002

[Rheophoresis. A systematic approach to therapy of age-related macular degeneration (AMD)?].

BACKGROUND: Choroidal microcirculation is impaired in age-related macular degeneration (AMD), and leads to deposition of lipids and proteins in Bruch's membrane. Rheophoresis can improve choroidal microcirculation by eliminating high molecular weight, rheologically relevant plasma proteins. The objective of this post-certification study was to analyse the effect of rheophoresis in 10 AMD patients. PATIENTS AND METHODS: A total of 6 patients with early AMD and 4 with late AMD in one eye (initial visual acuity equivalent 0.2-0.8) received rheophoresis treatment 10 times over an 18-week period. Visual acuity and color vision were determined initially and after 3, 5 and 12 months and fluorescein angiography was performed. RESULTS: Patients with early AMD showed improvement of visual acuity (2 lines on ETDRS charts) in 2 out of 6 cases and a stable visual acuity in 4 out of 6 cases 1 year after rheophoresis, whereas patients with late AMD showed improvement of visual acuity (2 lines on ETDRS charts) in 1 out of 4 cases and a stable visual acuity in 3 out of 4 cases. In red-free fundus photography, a reduction in drusen size and number could be observed in 4 out of 10 cases. CONCLUSION: The results of this investigation seem to be in accordance with data from previously published controlled clinical trials. Recommendations for the indication of rheopheresis for AMD should be further defined and evaluated within the framework base of a multicentric cooperative study.

Aged↗
PubMed2002

Intraindividual comparison of two extracorporeal LDL apheresis methods: lipidfiltration and HELP.

Low density lipoprotein (LDL) apheresis is an effective treatment option for patients with severe hypercholesterolemia not adequately responding to diet and drug therapy. Membrane differential filtration (MDF), synonymous with double filtration plasmapheresis (DFPP), here named Lipidfiltration, and heparin-induced extracorporeal LDL-precipitation (HELP) are two of the five methods available for extracorporeal LDL apheresis. In this prospective investigation 6 patients with severe LDL-hypercholesterolemia and CAD were treated in a cross-over design with Lipidfiltration at two stages of technical development and HELP to compare the efficacy of these two LDL apheresis methods with respect to lowering and modifying plasma lipids and rheologically relevant plasma proteins, especially fibrinogen. In total, 44 LDL apheresis sessions were investigated. In weekly intervals, patients were treated with consecutive LDL apheresis sessions with either Lipidfiltration and HELP, treating identical plasma volumes. In one part of the investigation Lipidfiltration was performed with the novel Lipidfilter EC-50, combined with a newly developed blood and plasma therapy machine allowing optimized plasma heating. The results showed that the reduction rates of LDL-cholesterol, lipoprotein(a) and triglycerides were essentially identical for both methods. Also pretreatment levels of total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol were not significantly different in both treatment groups. Both methods lead to a significant reduction of serum lipoproteins, especially for LDL-cholesterol, which was decreased by 61.4% with Lipidfiltration (treated plasma volume: 2998 ml) and 61.3% with HELP (treated plasma volume: 3013 ml). With respect to Lipidfiltration LDL-cholesterol reduction was more efficient with the novel Lipidfilter EC-50. Mean pretreatment HDL cholesterol concentrations remained unchanged. Comparing Cascadeflo AC-1770 with the novel Lipidfilter EC-50 reduction rates of HDL-cholesterol (17.4% versus 6.4%) and total protein (17.9% versus 7.8%) were significantly reduced. Lipidfiltration and HELP both resulted in a reduction of plasma viscosity and hemorheologically relevant plasma proteins, like fibrinogen.

Blood Component Removal↗
PubMed2001

[Hemodynamic effects of pneumoperitoneum in lithotomy position].

AIM OF STUDY: The study investigates the haemodynamic effects of the varying intraabdominal pressures and patient positions during gynecological procedures employing pneumoperitoneum in lithotomy positions. METHODS: TEE was used to determine end-diastolic and end-systolic left ventricular surface areas and ejection fractions were calculated from these data. To evaluate intraabdominal volume shifts the diameter of the internal iliac vein was measured by mean of vaginal ultrasound. RESULTS: In the horizontal lithotomy position both LVEDA and LVESA increased when intraabdominal pressure increased by 10 and 15 mmHg, respectively. LVAEF significantly decreased when intraabdominal pressure increased by 15 mmHg. Also DVII decreased. In Trendelenburg position there was no change in LVEDA, LVESA, LVAEF and DVII. In Anti-Trendelenburg position LVEDA and LVESA decreased. However, LVAEF remained constant and DVII increased. CONCLUSION: The increase of the intraabdominal pressure in the lithotomy position results in an increase in intrathoracic volume and an decrease in LVAEF via elevation of the the lower extremities and compression of the splanchnic vessels. There are no changes in Trendelenburg position. However, in Anti-Trendelenburg position, gravity results in a decrease in intrathoracic blood volume. In the decreased, dilatated heart the increase in intrathoracic volume may increase myocardial wall tension and hence oxygen demand, ultimately leading to an acute heart failure. As a result laparoscopic procedures in horizontal lithotomy position should be avoided in patients with dilatative cardiomyopathy.

Adolescent↗
PubMed2000

Rheopheresis: rheologic, functional, and structural aspects.

Rheopheresis is a specific application of membrane differential filtration, synonymous with double filtration plasmapheresis for extracorporeal hemorheotherapy, eliminating an exactly defined spectrum of high molecular weight proteins from human plasma (e.g.: fibrinogen, alpha-2-macroglobulin, low-density lipoprotein cholesterol, IgM). This results in the improvement of blood flow and microcirculation initiated by lowering blood and plasma viscosity, and erythrocyte aggregation. In this context, microcirculation stands not only for the patency of small blood vessels, but for the complete interactive network between plasma, blood cells, the vessel wall, and cellular and extracellular compartments of the surrounding tissue. Insufficient tissue oxygenation leads to tissue damage, e.g., a microcirculatory disorder develops, creating acute as well as chronic symptoms. Therefore, impaired microcirculation has a rheologic, functional, and structural dimension with respect to involved organs or tissues. Rheopheresis represents a specific therapeutic approach with an acute rheologic as well as chronic functional and structural effects, which was confirmed in pilot and controlled clinical studies for several organ systems. Data from 2 controlled clinical trials are available for the safe and effective treatment in patients with age-related macular degeneration.

Adolescent↗
PubMed1996

Adult, fetal, and polycystic kidney expression of polycystin, the polycystic kidney disease-1 gene product.

The polycystic kidney disease-1 gene, which is mutated in the majority of patients with autosomal dominant polycystic kidney disease, has been identified. The protein encoded by this gene, polycystin, has no homology with any gene known thus far. To gain more insight into the function of polycystin, we raised antibodies against synthetic peptides and a fusion protein corresponding to the sequence of two different fragments of polycystin. Two of the antibodies were capable of immunoprecipitating an in vitro transcription and translation product corresponding to a fragment of polycystin. In the cyst-lining epithelium of polycystic kidney disease-1 patients, a strong staining was observed. In normal adult and embryonic kidney tissues, expression was seen in the epithelium of all tubular structures and in the glomerular parietal and visceral epithelium (podocytes), although the podocytes were mainly recognized on cryosections and not on paraffin sections. A double-labeled immunofluorescence with one of the polycystin antibodies and the monoclonal antibody 8G8 ascertained that within the glomerular tuft podocytes were recognized.

Adult↗
PubMed1994

Laboratory control of minimal heparinization during haemodialysis in patients with a risk of haemorrhage.

For patients undergoing dialysis with a high risk of haemorrhage there is no standardized procedure for anticoagulation during extracorporeal circulation. Minimal heparinization with a dose equivalent to half that used for chronic haemodialysis was employed in 49 patients (125 haemodialyses) performed after operative interventions (83.3%), after haemorrhagic events (5.2%) and after invasive investigations (11.5%). Using a biocompatible membrane and a low molecular weight heparin (bolus dose 500-1300 U; continuous infusion 100-400 U) it was possible to complete haemodialysis in 74 cases (Group 0) without clots appearing in the venous bubble trap of the tubing system. In 30 cases (Group 1) only small clots were detected at the end of haemodialysis, and in 13 cases (Group 2) larger clots (exceeding a diameter of 1 cm) were found. In eight cases (Group 3) partial or complete clot formation occurred in the tubing. No haemorrhagic complications were observed. Anti-Xa activity, thrombin-antithrombin III complex (TAT) and D-dimer were determined before haemodialysis, 2 h after the start of haemodialysis and on completion of the procedure. The anti-Xa activities ranged between < 0.2 and 0.56 U/ml. In contrast, at 2 h there were significant differences (P < 0.05) in the TAT concentrations between Group 0 and the other groups, as well as between Group 1 and Group 2 and 3. Significant differences (P < 0.05) in D-dimer levels occurred only at the end of haemodialysis. Minimal heparinization in haemodialysis is a practicable alternative in patients with a high risk of haemorrhage and extended coagulation monitoring is helpful in adjusting heparin dosage.

Adult↗
PubMed1993

[Minimal heparinization in dialysis patients with increased risk of bleeding].

In 78 patients (47 men, 31 women; mean age 53 [22-78] years) 174 dialyses were undertaken within one week of a bleeding episode or a diagnostic or therapeutic procedure which may cause bleeding. Minimal anticoagulation with low molecular weight heparin (LMWH) was the aim, using a biocompatible dialyser. During the dialysis coagulation was controlled by global tests (Quick value/international normalized ratio [INR], partial thromboplastin time, thrombin time, antifactor Xa activity), by molecular markers of clotting activity (thrombin-antithrombin III complex [TAT], D-dimers), as well as measurement of elastase (elastase-alpha 1-protein inhibitor complex). The LMWH dosage averaged 932 units as an initial bolus and 234 units/h as a continuous infusion. In the group of chronic dialysis patients (n = 72) this meant (standard heparin units = 2/3 LMWH units) a reduction to 45 +/- 11% from the previously used routine heparin dosage for a 4-hour dialysis. All dialyses were completed without bleeding complications. Considerable clotting formation in the extracorporeal circulation occurred in 11 dialyses (6.3%). TAT, D-dimer and elastase values proved to be suitable for determining individual clotting activity and for reducing anticoagulation to the minimum.

Adult↗
PubMed1993

alpha GalNAc is essential for recognition of Exo-1 epithelial antigen by mouse monoclonal antibody Pa-G-14.

Mouse monoclonal antibody Pa-G-14 detects Exo-1, an antigen whose expression is regulated in the processes of epithelial-cell differentiation and transformation. The epitope recognized by Pa-G-14 is present both in glycosphingolipids and in mucin glycoproteins. To characterize the specificity of Pa-G-14, immuno-thin-layer chromatography, biochemical, and enzymatic treatment of glycosphingolipid extracts from human pancreas were used. The antibody bound to all blood-group-A substances; alpha GalNAc, but not fucose, was essential for reactivity. In ELISA, Pa-G-14 also reacted with ovine and bovine submaxillary mucins but not with porcine submaxillary mucin. Binding to ovine submaxillary mucin was resistant to neuraminidase treatment. In solid-phase absorption assays on synthetic carbohydrate structures, Pa-G-14 recognized broadly blood group A, Tn and sialyl-Tn. Using immuno-electron-microscopic techniques, reactivity with all Golgi cisternae and mucin droplets of mucous cells in ovine submaxillary gland was demonstrated. All these assays indicate that Pa-G-14 shows a novel specificity, since it binds blood group A, Tn and sialyl-Tn, the common structural feature of these epitopes being the presence of a terminal alpha GalNAc sugar unit.

Acetylgalactosamine↗
PubMed1993

Expression of epithelial antigens EPM-1 and EXO-1 in normal, transitional, inflammatory and neoplastic colorectal mucosa.

EPM-1 (a high molecular weight glycoprotein) and EXO-1 (a carbohydrate epitope expressed on polar neutral glycolipids and mucins) are two developmental antigens of normal and neoplastic human epithelia and were characterised by monoclonal antibodies. Their distribution was investigated in normal and pathological human colorectal mucosa. In normal mucosa, EPM-1 and EXO-1 showed characteristic expression patterns. EPM-1 was differentially expressed along the crypt villus axis with maximum at the crypt basis. EXO-1 was present throughout the whole mucosa. The characteristic gradient of EPM-1 expression along the crypt axis in normal mucosa was no longer detectable in benign polyps. Intact gradient of EPM-1 staining discriminated between neoplastic changes of the benign adenomatous polyp and mucosal inflammation. Neoplastic mucosa in benign polyps and especially atypical glands in highly differentiated tumours showed essentially identical expression patterns. In colorectal carcinomas the overall reactivities for EPM-1 and EXO-1 were independently associated with the histopathological grade of tumour differentiation.

Antigens, Neoplasm↗
PubMed1993

Coexpression of extracellular matrix glycoproteins undulin and tenascin in human autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common entity of cystic diseases of the kidney leading to end-stage renal insufficiency. Changes in extracellular matrix (ECM) are regarded to be an important pathogenic factor connected with the genes assumed to be responsible for human ADPKD. In order to assess the biological significance of altered expression and deposition of ECM glycoproteins for human ADPKD at molecular levels fresh-frozen tissue from ADPKD kidneys, fetal kidneys and normal adult kidneys were comparatively tested by immunohistochemistry for the presence of multifunctional ECM glycoproteins undulin, tenascin and fibronectin, interstitial collagen types I, III and VI and intrinsic basement membrane components laminin and collagen type IV using monoclonal antibodies and polyclonal antisera. Studies were especially focused on ECM glycoproteins undulin and tenascin which in connection with interstitial collagens and fibronectin have specific structural and functional roles in tissue development and differentiation. Cultures of cyst-lining epithelial cells from two polycystic kidneys and autologous fibroblasts were investigated in vitro. By Northern blot analysis mRNA levels of undulin, tenascin and the ECM-regulating growth factor transforming growth factor-beta 1 (TGF-beta 1) were investigated. A strong increase of fibrogenesis was demonstrated in tissue architecture of polycystic kidneys. Immunohistochemically subepithelial fibrous tissue of cyst walls in ADPKD kidneys showed strong coexpression of both undulin and tenascin with marked intensity adjacent to cyst-lining epithelium. In contrast the normal adult human kidney and developmental stages of the fetal kidney showed expression patterns of undulin and tenascin which were significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Adhesion Molecules, Neuronal↗
PubMed1992

Expression of differentiation antigens and growth-related genes in normal kidney, autosomal dominant polycystic kidney disease, and renal cell carcinoma.

Cellular differentiation and mRNA levels of genes involved in kidney growth were investigated in normal kidney cells, cyst-lining epithelial cells of polycystic kidney disease, and renal carcinoma cells (RCC). All cells comparatively studied exhibited an antigenic phenotype of proximal tubular cells as shown by the expression of a panel of brush border membrane enzymes and kidney-associated cell surface antigens. The epithelial developmental antigen Exo-1 was expressed in 50% to 80% of cyst-lining epithelia in polycystic kidney tissue and in 20% to 30% of polycystic kidney cells cultured in vitro. Normal kidney cells and RCC were negative under identical culture conditions. The expression of antigen Exo-1 is associated with hyperproliferation in an epithelial tissue compartment composed of cells which have not yet reached their terminal differentiation state. Increased amounts of mRNA of the growth factor receptor system of epidermal growth factor (EGF) receptor and its ligand transforming growth factor (TGF)-alpha were associated with the malignant phenotype of RCC. Increased expression of EGF receptor and TGF-alpha, although less prominent, were also observed in polycystic kidney cells compared with normal kidney cells. In conclusion, the expression of Exo-1 in cyst-lining epithelial cells of autosomal dominant polycystic kidney disease (ADPKD) and the altered regulation of TGF-alpha and EGF receptor in these cells contribute to the hypothesis that hyperproliferation is an underlying pathogenic mechanism of ADPKD.

Antibodies, Monoclonal↗