Lipoprotein apheresis is an optimal therapeutic option to reduce increased Lp(a) levels.

BACKGROUND: Lipoprotein(a) (Lp(a)) is a genetic risk factor for cardiovascular disease (CVD) and is associated with the induction and sustaining of atherosclerotic cardiovascular diseases (ASCVD). Since 2008 Lp(a) along with progressive CVD has been approved as an indication for regular lipoprotein apheresis (LA) in Germany. The German Lipoprotein Apheresis Registry (GLAR) has been initiated to provide statistical evidence for the assessment of extracorporeal procedures to treat dyslipidemia for both LDL-cholesterol (LDL-C) and Lp(a). The GLAR now allows prospective investigations over a 5-year period about annual incidence rates of cardiovascular events. Here Lp(a) patients (LDL-C < 100 mg/dl; Lp(a) > 60 mg/dl or >120 nmol/l) showed the same reduction of major coronary (83%) and non-coronary events (63%) as had been formerly shown in the Pro(a)LiFe study. However, Lp(a) is not only an apolipoprotein(a) (apo(a)) and LDL-C containing particle, which is covalently bound to a LDL-C core by a disulphide bridge. The composition of this particle, inter alia containing oxidized phospholipids, gives pro-atherosclerotic, pro-inflammatory, and pro-thrombotic properties, inducing atherosclerotic processes mainly in the arterial wall. However, recent investigations have shown that a reduction of inflammatory settings without LDL-C or Lp(a) reduction may reduce ASCVD events. Lipoprotein apheresis (LA) could not only reduce LDL-C and Lp(a) in parallel, but also different inflammatory and coagulation parameters. In summary lipoprotein apheresis is not only anti-atherosclerotic, but also anti-inflammatory and anti-thrombotic and therefore an ideal treatment option with respect to the shown reduction of major adverse coronary events (MACE) and major adverse non-coronary events (MANCE) by reducing Lp(a) levels.

Current insights into the German lipoprotein apheresis standard: PCSK9-inhibitors, lipoprotein apheresis or both?

According to current European guidelines, lipid lowering therapy for progressive cardiovascular disease including cardiovascular events has to be focused on a target level for LDL-C. In contrast for Lp(a) a threshold has to be defined with respect to the method of measurement. However, due to new lipid lowering drug developments like PCSK9-inhibitors (PCSK-9-I) a therapeutic algorithm for patients with severe hypercholesterolemia or isolated Lipoprotein(a)-hyperlipoproteinemia with progressive cardiovascular disease may be necessary to manage the use of PCSK9-I, lipoprotein apheresis (LA) or both. The therapeutic approach for patients with homozygous familial hypercholesterolemia is unambiguous: In addition to LA, in order to improve LDL-C reduction, PCSK9-I could be applied. In patients with heterozygous familial hypercholesterolemia, PCSK9-I is to be applied first. If in addition to a pronounced LDL-C elevation, cardiovascular complications exist or if imaging techniques documented atherosclerotic changes pre-disposing for a cardiovascular event while LDL-C reduction is insufficiently reduced (LDL-C > 100 mg/dl (2.6 mmol/l)), LA treatment should then be applied as last resort. In patients with elevated Lp(a) concentrations (Lp(a) > 60 mg/dl (>120 nmol/l)) and established cardiovascular disease, therapy should rely primarily on LA methods. If in addition to high Lp(a) levels insufficiently treated LDL-C concentrations (LDL-C > 100 mg/dl (2.6 mmol/l)) exist, in rare cases PCSK9-I can supplement the lipid lowering concept.

[Tryptophan immunoadsorption for multiple sclerosis and neuromyelitis optica: therapy option for acute relapses during pregnancy and breastfeeding]. / Tryptophan-Immunadsorption bei Multipler Sklerose und Neuromyelitis optica : Therapieoption bei akuten Schüben in der Schwangerschaft und Stillphase.

BACKGROUND: Approximately 25 % of women with multiple sclerosis (MS) suffer clinically relevant relapses during pregnancy. Almost all disease-modifying drugs are contraindicated in pregnancy. High-dose glucocorticoids have some serious risks, especially within the first trimester. Tryptophan immunoadsorption (IA) provides a safe option to treat MS relapses during pregnancy. OBJECTIVES: In this case series we describe for the first time the use of tryptophan IA for MS and neuromyelitis optica (NMO) relapses during pregnancy and breastfeeding. PATIENTS AND METHODS: In this study a total of 9 patients were retrospectively analyzed of which 7 patients received IA treatment during pregnancy, 2 during breastfeeding and 4-6 tryptophan IA treatments were performed per patient with the single use tryptophan adsorber. Primary outcome was symptom improvement of the relapse. RESULTS: In this study four patients with MS and one with NMO relapse during pregnancy were treated with IA without preceding glucocorticoid pulse therapy. The MS patients showed improvement in the expanded disability status scale (EDSS) by at least one point, the NMO patient showed significant improvement in visual acuity and two pregnant patients with steroid-refractory relapses showed clinically relevant improvement after IA. Of the patients two suffered from steroid-refractory relapses during breastfeeding and relapse symptoms improved in both cases after treatment with IA. All treatments were well tolerated and no serious adverse events occurred. CONCLUSION: Tryptophan IA was found to be safe, well-tolerated and effective in the treatment of MS and NMO relapses during pregnancy and breastfeeding, sometimes without preceding glucocorticoid pulse therapy. A binding recommendation is limited without prospective clinical studies.

Tryptophan immunoadsorption for the treatment of autoimmune encephalitis.

BACKGROUND AND PURPOSE: Detection of autoantibodies against neuronal surface antigens and their correlation with the pattern and severity of symptoms led to the definition of new autoimmune-mediated forms of encephalitis and was essential for the initiation of immunotherapies including plasma exchange. The elimination of autoantibodies using selective immunoadsorption (IA) is a pathophysiologically guided therapeutic approach but has not yet been evaluated in a separate analysis. METHODS: A retrospective analysis was performed of patients with autoimmune encephalitis who were treated with tryptophan IA in six neurological clinics between 2009 and 2013. The modified Rankin scale (mRS) was used to evaluate neurological status before and after IA. RESULTS: Data on 13 patients were documented. Twelve patients were positive for specific autoantibodies (NMDA-R, GABA, GAD, Lgl1). Patients received a series of a median of six IA treatments. Median mRS of all patients was 3.0 before IA and 2.0 after IA (P < 0.001). Eleven patients improved by at least one point in mRS after IA. CONCLUSION: For autoimmune-mediated forms of encephalitis rapid elimination of autoantibodies with selective IA seems to be an effective therapeutic option as part of multimodal immune therapy.

[Therapeutic apheresis for autoimmune encephalitis: a nationwide data collection]. / Therapeutische Apherese bei autoimmuner Enzephalitis: Eine bundesweite Datenerhebung.

BACKGROUND: The correlation between detection of autoantibodies and the pattern and severity of symptoms in patients with encephalitis was the crucial factor for the initiation of immune therapy. The elimination of autoantibodies using therapeutic apheresis by plasma exchange (PE) and immunoadsorption (IA) is a pathophysiologically guided therapeutic approach. The aim was to evaluate the current use of PE and for the first time also of IA for patients with autoimmune encephalitis. METHODS: A nationwide data collection was performed and the modified Rankin score (mRS) was used to evaluate the severity of neurological symptoms. RESULTS: Data of 31 treatment courses (30 patients and 1 relapse) were documented and 22 patients were positive for autoantibodies (NMDA-R, GABA, VGKC, Hu). In 23 cases PA was performed, tryptophan IA in 7 cases and in 1 patient both methods were applied. In 67 % of the treatment courses the mRS improved and the mean mRS of all patients was 3.2 before apheresis and 2.2 after apheresis (p < 0.05). All patients who were treated with IA improved clinically from a mean mRS of 3.9 before IA to 1.9 after IA (p < 0.01). CONCLUSIONS: For immune-mediated forms of encephalitis rapid elimination of autoantibodies with PA and IA seems to be an effective therapeutic option as part of a multimodal immune therapy and is already established in many clinics in Germany.

Long-term strategies for the treatment of Refsum's disease using therapeutic apheresis.

Refsum's disease is a rare autosomal recessive disorder of fatty acid metabolism. Poorly metabolized phytanic acid accumulates in fatty tissues, including myelin sheaths and internal organs, leading to retinitis pigmentosa, peripheral polyneuropathy, cerebellar ataxia, and renal, cardiac or liver impairment. Dietary restriction of phytanic acid in some cases is not sufficient to prevent acute attacks and stabilize the progressive course. Phytanic acid bound to large low density lipoproteins (LDL) and very low density lipoproteins (VLDL) molecules offers the possibility of extracorporeal elimination by lipid apheresis. We report on the long-term lipid apheresis treatment of four patients with severe Refsum's disease. Retinitis pigmentosa, peripheral polyneuropathy, cerebellar ataxia, anosmia, and sensorineural hearing loss were major symptoms exhibiting a progressive course. Lipid apheresis was performed for 5-13 years without severe complications. Maximum levels of phytanic acid before commencing chronic lipid apheresis were >300 mg/l. During steady state with lipid apheresis, mean phytanic acid before treatments was 87 mg/l and was reduced to 36 mg/l. Mean reduction rate was 59% per treatment. In all patients, abnormal motor nerve conduction velocity with signs of chronic denervation improved, morphological and functional stabilization of eye involvement was observed. Lipid apheresis prevented the extension of the disease to previously unaffected organs in three patients. Extracorporeal elimination of lipoprotein-phytanic acid complexes by lipid apheresis represents a pathophysiologically guided therapeutic approach, resulting in long-term improvement or stabilization of overall rehabilitation in patients with progressive Refsum's disease.

[Immunoadsorption for steroid-unresponsive multiple sclerosis-relapses: clinical data of 14 patients]. / Immunadsorption bei steroidrefraktärem Schub der Multiplen Sklerose : Klinische Erfahrungen bei 14 Patienten.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating immune-mediated disease of the central nervous system, often associated with relapses. Plasma exchange (PE) has become established as an escalation therapy for steroid-unresponsive relapses in national and international guidelines. PE is a non-selective apheresis method with elimination of the entire plasma with subsequent substitution. Selective extracorporeal elimination of autoantibodies and immune complexes with immunoadsorption (IA) is increasingly replacing PE for the treatment of autoimmune neurological diseases due to its equivalent efficacy and advantageous safety profile. The use of IA for MS still remains to become established. The aim of this retrospective investigation was to evaluate efficacy and safety of IA in patients with steroid-unresponsive relapses. PATIENTS AND METHODS: Fourteen patients with steroid-unresponsive MS relapses were retrospectively analysed. Patients received six IA treatments within 2 weeks using the single-use tryptophan adsorber. Peripheral venous access was used in 11 patients, and 3 patients needed a central line. The plasma volume treated was 2 l per IA. Efficacy criteria were improvement in symptoms of MS relapses which were measured with the Kurtzke scale (EDSS, FS) and visual acuity measurements for patients with optic neuritis. RESULTS: In 12 of 14 patients the major symptom of MS relapse improved to a clinically relevant extent after tryptophan IA; no patient got worse, corresponding to a response rate of 86%. Mean EDSS and FS in patients with spastic paresis (n=4) and dizziness (n=2) as well as mean visual acuity in patients with optic neuritis (n=8) significantly improved after IA. IA treatments were safe, with good tolerability, and no severe adverse events occurred. CONCLUSION: Immunoadsorption for the treatment of steroid-unresponsive MS relapses was safe and effective. The response rate was comparable to published results with PE. With IA, in contrast to unselective PE, administration of human plasma products is not necessary, avoiding associated risks.

[Rheopheresis for recurrent sudden hearing loss : therapeutic options for patients refractory to infusion therapy]. / Rheopherese bei rezidivierendem Hörsturz : Therapieoption für Patienten nach erfolgloser Infusionstherapie.

BACKGROUND AND OBJECTIVE: For patients suffering from recurrent sudden hearing loss (SHL) that is refractory to infusion therapy, new therapeutic options must be established. PATIENTS AND METHODS: Patients suffering from recurrent and progressive SHL refractory to infusion therapy according to German guidelines were analysed retrospectively. After unsuccessful infusion therapy following the last onset of SHL, patients were treated with Rheopheresis twice. Hearing gain and recovery of speech discrimination were analysed. RESULTS: Twenty-five patients with a mean of 2.1+/-0.4 events of SHL within 30.0+/-21.6 months were examined. The patients' mean hearing loss before the first onset of SHL was 34 dB and was reduced by infusion therapy to 20 dB. With the second onset of SHL, hearing loss remained almost unchanged after infusion therapy. Patients showed a mean improvement of 20 dB after two consecutive Rheopheresis treatments. Forty percent showed complete remission of SHL, and a further 28% showed partial remission. CONCLUSION: Rheopheresis can efficiently improve the hearing of patients with recurrent SHL refractory to infusion therapy.

[Long-term treatment of refractory myasthenia gravis with immunoadsorption]. / Langzeitbehandlung der therapierefraktären Myasthenia gravis mittels Immunadsorption.

BACKGROUND AND OBJECTIVE: Myasthenia gravis in the majority of patients is a well treatable neurological autoimmune disorder with a prevalence of 60-150 per million. For the treatment of myasthenic crisis in the intensive care unit the use of therapeutic apheresis, e. g. immunoadsorption or plasma exchange, is well established due to its rapid therapeutic effect, whereas the necessity in long term treatment is still questioned. Aim of this retrospective cohort-study was the assessment of patients with refractory myasthenia gravis in Germany treated by regular immunoadsorption, the characterization of previous therapies and the efficacy of long-term treatment. PATIENT AND METHODS: In total 14 patients (9 women, 5 men, mean age: 40.5 years) were identified in Germany using regular therapeutic apheresis. 13 were treated with different modes of immunoadsorption (10 yen l-tryptophan-adsorption, 2 yen epitope-specific adsorption, 1 yen polyclonal sheep antibody on sepharose) and 1 with plasma exchange. Mean duration of standard treatment of myasthenia gravis before initiation of regular apheresis was 7.8 years. RESULTS: Average duration of analyzed apheresis treatment was 6.4 years, with a mean treatment-interval of 1.1 per week. Mean reduction rate of autoantibodies against acetylcholine-receptor-protein was 50-60 % per session. After initiation of immunoadsorption the mean time of hospitalisation decreased significantly by app. 60 %. In particular the number of myasthenic crises could be reduced by 89 % per year. Tolerability of immunoadsorption was very good, no severe adverse events occurred. CONCLUSION: In conclusion, for the treatment of the subgroup of myasthenia gravis patients becoming refractory to standard treatment immunoadsorption should be regarded as integral part of the therapeutic armamentarium to stabilize and optimize the state of neurologic rehabilitation. This evaluation should be also carefully considered by carriers of health care cost as currently best available evidence to decide on appropriate treatment regimens for these rare patients.

[Monitoring of the heparin therapy during acute haemodialysis]. / Uberwachung der Heparintherapie bei Akutdialysen.

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.

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.

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.

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.

[Rheophoresis. A systematic approach to therapy of age-related macular degeneration (AMD)?]. / Rheopherese Ein systemischer Therapieansatz für die altersabhängige Makuladegeneration (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.

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.

[Hemodynamic effects of pneumoperitoneum in lithotomy position]. / Hämodynamische Auswirkungen eines Pneumoperitoneums in Steinschnittposition.

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.

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.

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.