Search

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. [ABSTRACT FROM AUTHOR]

Copyright of Der Nervenarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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 (m RS) 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 m RS 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 m RS 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. [ABSTRACT FROM AUTHOR]

Copyright of Der Nervenarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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. J. Clin. Apheresis, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Copyright of Der Nervenarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of HNO is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Mapped geological units can be regarded as proxies standing for a complex series of subsoil geochemical and physical properties including the assigned radon activity concentration in soil gas, which is taken as best estimator of the regional geogenic radon potential. Areal distribution of measuring sites for soil gas in Germany is adapted to spatial variation of geology. A grid-based and distance-weighted interpolation procedure is applied, following geologically defined neighbourhood relations of measuring sites and accounting for isolated outcrops of known geology but without measurements. To investigate the statistical relationship between indoor radon, house type and building ground specifications, measurements of the indoor radon concentration have been carried out in more than 10,000 dwellings in different regions of Germany. Multiple regression analyses of variance reveal that besides region-specific geological properties and building characteristics, various house type and living style variables significantly contribute to the explained variance for ground floor radon concentrations. These parameters are also dominant in controlling the radon transfer relation from soil gas to indoor air. Risk prediction maps for radon in houses indicating the probability to exceed certain indoor threshold values can be useful especially for regions with no or only a few measurements of indoor radon. [ABSTRACT FROM AUTHOR]

Summary 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. [ABSTRACT FROM AUTHOR]

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The allele distribution of the Ha-ras gene on chromosome 11p was analysed by the restriction fragment length polymorphism of the enzymes Mspl/Hpall in 238 individuals. The investigation covered 116 patients with colorectal carcinoma and 122 patients with Crohn's disease, representing two patient populations with the same ethnic origin, one with a malignant and the other a benign disease of the same organ system. A total of 17 different alleles were detected belonging to the common, intermediate, and rare classes according to the original nomenclature of Ha-ras alleles. Patients with Crohn's disease showed no difference in the distribution of Ha-ras alleles when compared with expected frequencies. In patients with colorectal carcinoma, the frequency of rare alleles was significantly increased compared with the patients with Crohn's disease (chi 2 = 8.166; Fisher's exact test = 0.005) and with a reference population of 424 cancer free individuals (chi 2 = 49.312; Fisher's exact test = 0.000). Homozygosity was not detected for any rare allele. The occurrence of a rare Ha-ras allele was not linked to the location of the colorectal tumour. These results confirm the hypothesis that unique Ha-ras alleles represent an inherited factor which predisposes the development of colorectal cancer. [ABSTRACT FROM PUBLISHER]

The major form of autosomal dominant polycystic kidney disease (ADPKD) in humans is linked to the PKD1 gene on chromosome 16p. The identity of the gene and the underlying pathogenetic mechanisms are not yet defined. Cyst-lining epithelial cells derived from a polycystic kidney were successfully grown in culture and designated MZ-PKD-1 cells. By linkage analysis, the related pedigree of the nephrectomized patient could be linked to the PKD1 gene on chromosome 16p. Thus, these cells exhibit the genotype of a mutated PKD1 gene and represent an in vitro culture model for ADPKD involving chromosome 16p. The antigenic phenotype was characterized immunohistologically by epithelial differentiation antigens and markers of individual nephron segments. An essentially identical antigenic pattern of proximal tubular cells was observed both in vitro and in fresh frozen tissue. Electron microscopy showed the formation of a microvillous-like coating. During growth phases in vitro successive changes in the cell shape were observed. MZ-PKD-1 cells exhibited a limited lifespan ending in replicative senescence. Northern blot analysis of kidney-growth-related genes, c-myc, TGF-alpha, TGF-beta1, and EGF receptor revealed abundant expression of all of these genes in MZ-PKD-1 cells. [ABSTRACT FROM AUTHOR]

Objective: RheoNet-registry was established to record Rheopheresis safety and efficacy data. Registry outcome analysis reference controlled by results of clinical trials represents a direct transfer of evidence-based medicine into clinical practice. For AMD two controlled randomized clinical trials demonstrated that 8 to 10 Rheopheresis treatments given over 10-21 weeks promote sustained improvement of the natural course of the dry form of the disease. The US multicenter, double masked placebo controlled MIRA-1-trial is ongoing to evaluate safety and efficacy of Rheopheresis for the treatment of dry AMD with soft drusen. Methods: RheoNet-registry is regularly analysed for safety aspects of Rheopheresis in centers and clinics performing treatments. Efficacy for AMD can be evaluated by analysis of the clinical data provided by ophthalmologists, which are responsible for indication and follow-up examination. Results: In March 2004 in total 3,314 Rheopheresis treatments of 529 pts., including 365 pts. with AMD, 115 pts. with sudden deafness/tinnitus (SD/T), 9 with ischemic diabetic foot syndrome, and 12 with critical limb ischemia were recorded. Mean age of treated pts. was 66 years (73.5 years for AMD). In 5.49 of treatments (all diagnoses) adverse events were reported, but only in 1.84% needed intervention, temporary break or discontinuation of the treatment. 18% of pts. were 80 years or older, but did not exhibit increased incidence of adverse events. AMD in general has an increased risk of retinal hemorrhage. 2 cases of retinal bleeding were reported within an interval of 14 days after Rheopheresis, which both caused no irreversible visual impairment. Ophthalmological data of 165 eyes of 118 AMD patients could be analyzed for this registry update including 149 eyes (108 pts.) with dry AMD, VA > 0.1 and 16 eyes (10 pts.) with pigment epithelial detachment. Patients received in mean 8.7 Rheopheresis treatments. For eyes with dry AMD, mean change in ETDRS-VA after Rheopheresis compared to baseline was +0.9 lines. For the group with PED, ETDRS-line change was +0.3. Conclusions: Based on interdisciplinary cooperation and quality management Rheopheresis can be regarded as a safe ambulatory treatment for patients for patients with microcirculatory disorders such as AMD or SD/T. Current RheoNet update for the group of patients with dry AMD essentially resembling inclusion criteria of controlled clinical trials showed results which were in good accordance with study data. [ABSTRACT FROM AUTHOR]

Objective: Based on different methodology, five options of extracorporeal LDL apheresis are available, which fulfill quality standards of German reimbursement guidelines: HELP-apheresis, LDL-immunoadsorption, dextran sulfate adsorption (DSA), two hemoperfusion systems directly adsorbing lipoproteins from whole blood (DALI and a recently developed adsorber system based on dextran sulfate) and Lipidfiltration. To further characterize performance of Lipidfiltration the influence of two different anticoagulatory regimes was investigated, and an intraindividual comparison with DSA was made. Methods: 6 patients (mean age 52 ± 11 y) with coronary artery disease and severe hypercholesterolemia regularly treated with DSA were included. DSA was continued for 8 weeks, then all patients were treated by Lipidfiltration (lipidfilter EC50) randomly assigned to anticoagulation with either heparin (LF-H) or combined heparin bolus with citrate infusion (LF-C). After 8 weeks the patients were switched to the other anticoagulatory regime (LF-C/LF-H) for another 8 weeks. During each period pre- and postapheresis lipoproteins (ultracentrifugation), Lp(a), fibrinogen and hs-CRP (nephelometry), VCAM, ICAM, e-selectin (ELISA) were measured twice (after 4 and 8 weeks). Activated complement C3, PTT, and TAT were measured before, at 15 min, 1 hr, and after apheresis. Results: Basic conditions of pre-apheresis LDL-cholesterol (159 ± 20-176 ± 33 mg/dl), mean treated plasma volume (DSA 4,077 ml, LF-C 3,960 ml, LF-H 4,125 ml, [equivalent to 110-120% PV]), and treatment time (167-174 min) were not significantly different between the three treatment periods. LDL-cholesterol was effectively reduced with DSA, LF-C, and LF-H (-70 ± 7%, -67 ± 7%, -69 ± 7%, respectively). Reduction rates for Lp(a) were between 69-74% for all three modalities. Fibrinogen and e-selectin were more effectively reduced with LF, while DSA was more effective for hs-CRP, and less affected HDL-cholesterol and immunoglobulins. TAT generation during apheresis did not reveal significant differences between DSA, LF-H, and LF-C. Detectable C3a was lowest with DSA. Conclusions: Lipidfiltration and DSA exhibited essentially identical reduction of atherogenic lipoproteins after treatment of similar plasma volumes. Change of the anticoagulatory regime did not affect performance characteristics of Lipidfiltration. Overall detectable C3a was very low with DSA, which could be a potential advantage for the recently developed DSA-hemoperfusion sytem for lipid-apheresis. Increased reduction rate of fibrinogen with LF might be favourable in select patients. Clinical relevance of the observed elimination of hs-CRP, VCAM, ICAM, and e-selectin remains to be further elucidated. [ABSTRACT FROM AUTHOR]