RHEOPHERESIS IN THE TREATMENT OF AGE-RELATED MACULAR DEGENERATION.

PURPOSE: Evaluation of the long-term effect of rheopheresis treatment of dry form of age-related macular degeneration (AMD). MATERIALS AND METHODS: The treatment group consisted of 65 patients and 55 patients in the control group, with a minimum follow-up period of 60 months. The basic treatment consisted of 8 rheopheresis procedures, and the additional treatment (booster therapy) of 2 rheopheresis procedures 1.5-2 years after the basic treatment. We evaluated changes in best corrected visual acuity, anatomical effect, electrical activity of the retina, haematological, biochemical and immunological parameters. RESULTS: Rheopheresis treatment contributed significantly: 1) to stabilisation of best corrected visual acuity of the treated patients, which initially showed an insignificant increased during the 2-years follow-up period, and then slightly decreased. By contrast, visual acuity decreased in the control group, to an insignificant degree up to 4 years, then statistically significantly. 2) to an improvement of the morphological findings in 62.4% of treated patients compared to 7.5% in the control group, while disease progression to stage 3 (neovascular form of the disease or geographic atrophy) with a significant decrease of visual acuity occurred in only 7.1% of treated patients, versus 37.0% in the control group. 3) to regression, even to the attachment of drusenoid pigment epithelial detachment (DPED). To a reduction of the area of DPED in 80.4% of treated patients, in contrast with an steaincrease in the area of DPED in 47.1% of patients in the control group, and the development of new DPED in only 2 eyes of treated patients compared with 16 eyes of patients in the control group. 4) to a preservation of the integrity of the ellipsoid layer in the fovea in 68.2% of the treated patients, while by contrast we found a damaged ellipsoid layer in the fovea in 66.6% of the control patients. 5) to a stabilisation of the activity of ganglion cells, the pineal system and the activity of the central area of the retina, with eccentricity between 1.8° and 30° in the treated patients, compared to alteration in the control group manifested mainly after 3.5 years of the follow-up period. 6) to a statistically significant improvement in rheological parameters, thereby increasing flow in microcirculation and positively influencing the metabolism in the retina. Also to a positive effect on the classical, alternative and lectin pathway of complement activation, a reduction in the level of proprotein convertase subtilisin kexin 9 (PCSK9), and thus also the level of LDLcholesterol, and 7) Additional treatment with 2 RHF procedures (so-called "booster therapy") seems to be a safe and suitable method of prolonging the stabilisation phase, or even improving visual acuity, anatomical and functional findings. CONCLUSION: We demonstrated positive changes in anatomical, functional and humoral parameters upon rheopheresis treatment of AMD. Their correlation provides a real possibility to identify patients at risk and to manage an individualised regime of rheopheresis therapy. This method of treatment is effective and safe, with a low percentage of non-serious adverse effects.

Monitoring of up to 15 years effects of lipoprotein apheresis on lipids, biomarkers of inflammation, and soluble endoglin in familial hypercholesterolemia patients.

BACKGROUND: Lipoprotein apheresis (LA) is considered as an add-on therapy for patients with familial hypercholesterolemia (FH). We aimed to analyze the data collected in the last 15 years from FH patients treated with LA, to elucidate the benefit of this procedure with respect to plasma lipids, biomarkers of inflammation, and endothelial dysfunction and soluble endoglin. RESULTS: 14 patients (10 heterozygous FH patients (HeFH), 4 homozygous FH patients (HoFH)) were treated by long-term lipoprotein apheresis. Lipid levels were examined, and ELISA detected biomarkers of inflammation and soluble endoglin. Paired tests were used for intergroup comparisons, and a linear regression model served to estimate the influence of the number of days patients were treated with LA on the studied parameters. LA treatment was associated with a significant decrease of total cholesterol (TC), LDL-C, HDL-C, and apoB, in both HeFH and HoFH patients, after single apheresis and in a long-term period during the monitored interval of 15 years. Biomarkers of inflammation and endothelial dysfunction were reduced for soluble endoglin, hsCRP, and MCP-1, and sP-selectin after each procedure in some HeFH and HoFH patients. CONCLUSIONS: LA treatment up to 15 years, reduced cholesterol levels, levels of biomarkers related to endothelial dysfunction, and inflammation not only after each procedure but also in the long-term evaluation in FH patients. We propose that long-term LA treatment improves lipid profile and endothelial dysfunction in familial hypercholesterolemia patients, suggesting a promising improvement in cardiovascular prognosis in most FH patients.

Prediction of long-term prognosis of age-related macular degeneration treated by hemorheologic therapy using baseline laboratory indicators - Experimental-clinical model.

BACKGROUND + OBJECTIVE:Age-related macular degeneration (AMD) is the most common cause of practical blindness in people over 60 years of age in industrialised countries. We formulated a hypothesis that a group of initial laboratory parameters would be suitable for prediction of prognosis of AMD, allowing for individual modifications in treatment intensity. PATIENTS AND METHODS: 66 patients with dry form of AMD were treated using rheohaemapheresis with an individual follow-up period of more than 5 years. The patients' initial laboratory data was split in two subgroups based on treatment success and analysed using discriminant analysis (analysis of the linear and quadratic models using the automated and interactive step-wise approach) by means of the Systat 13 software. RESULTS: Prediction of prognosis based on the initial laboratory parameters was correct in 79% of unsuccessfully treated patients, allowing for early detection of high-risk patients. With the use of a quadratic model, the prediction was correct in 100% of unsuccessfully treated patients and in 75% of successfully treated patients. CONCLUSION: Implementation of discriminant analysis is a promising method for prediction of prognosis, especially when the patient is at risk of AMD progression, which allows for early and more intensive monitoring and treatment.

Antioxidant defense system in familial hypercholesterolemia and the effects of lipoprotein apheresis.

Oxidative stress is thought to play an important role in the pathogenesis of disorders associated with atherosclerosis. Alpha-tocopherol is considered to be an effective lipophilic antioxidant, which protects lipid membranes against peroxidation and thus prevents cell damage by reaction with free radicals. However, measurement of alpha-tocopherol concentration in serum does not reflect the content of α-tocopherol in membranes whereas erythrocyte alpha-tocopherol may be good indicator of antioxidative status. Therefore a simple isocratic reversed phase HPLC method has been developed and validated for the determination of alpha-tocopherol in human erythrocytes in a clinical setting. The content of alpha-tocopherol in human erythrocyte membrane and lipoperoxidation were studied in patients with severe hypercholesterolemia treated by lipoprotein apheresis. The group of hypercholesterolemic patients (n = 14) treated by lipoprotein apheresis was compared to healthy adult normolipidemic controls. After lipoprotein apheresis, the content of in membrane alpha-tocopherol did not change significantly despite decreased tocopherol in serum and lipoprotein fractions. We observed significantly decreased lipoperoxidation as revealed by serum TBARS, representing end products of lipid peroxidation, which increased from third day afterwards and remained significantly higher in comparison to controls until the next LDL-apheresis. We conclude that aggressive lipid lowering procedure with lipoprotein apheresis was associated with favorable transient decrease of lipoperoxidation. Simultaneously the cell membrane bound antioxidative defense mechanisms as reflected by the content of alpha-tocopherol in human erythrocyte membrane where not depressed in spite of its decreased plasma lipid carrier. Another variables involved remain to be investigated.

Familial hypercholesterolemia in the Czech Republic: more than 17 years of systematic screening within the MedPed project.

Familial hypercholesterolemia (FH) is the most common autosomal dominant disorder. It is characterized by a decrease in LDL cholesterol catabolism and an early clinical manifestation of atherosclerotic vessel damage. The aim of the MedPed (Make early diagnosis to Prevent early deaths) project is an early diagnosis of FH patients in order to profit from early treatment and prevent cardiovascular events. Till November 30, 2016 The Czech National MedPed Database has registered 7,001 FH patients from 5,223 different families that is 17.4 % of expected patients in the Czech Republic considering 1:250 FH prevalence. The improvement in diagnostic accuracy, patient cooperation and above all familial cascade screening is enabled by FH mutation detection using the modern technology of next-generation sequencing. FH still remain undiagnosed even though the Czech Republic is one of the most successful countries with respect to FH detection. The opportunities of international collaboration and experience sharing within international programs (e.g. EAS FHSC, ScreenPro FH etc.) will improve the detection of FH patients in the future and enable even more accessible and accurate genetic diagnostics.

Lipoprotein apheresis in the treatment of dyslipidaemia - the Czech Republic experience.

In 1984, we started using therapeutic plasmapheresis (plasma exchange) as a method of extracorporeal lipoprotein elimination for the treatment of hypercholesterolemic patients. We evaluated the results of long-term therapy in 14 patients, 8 men and 6 women. The average age was 55.6+/-13.2 (range 28-70), median 59.5 years. 14 patients were diagnosed with familial hypercholesterolemia (FH): 5 homozygous, 9 heterozygous. Ten patients in the group were treated using immunoadsorption lipoprotein apheresis and 4 using hemorheopheresis. Immunoapheretic interventions decreased LDL-cholesterol (82+/-1 %), ApoB (73+/-13 %) and even Lp(a) by 82+/-19 %, respectively. Selected non-invasive methods are important for long-term and repeated follow-up. Carotid intima-media thickness showed improvement or stagnation in 75 % of the patients. Biomarkers of endothelial dysfunction such as endoglin (in the control group: 3.85+/-1.25 microg/l, in lipoprotein apheresis-treated hypercholesterolemic individuals 5.74+/-1.47 microg/l), CD40 ligand (before lipoprotein apheresis: 6498+/-2529 ng/l, after lipoprotein apheresis: 4057+/-2560 ng/l) and neopterin (before lipoprotein apheresis: 5.7+/-1.1 nmol/l, after lipoprotein apheresis: 5.5+/-1.3 nmol/l) related to the course of atherosclerosis, but did not reflect the actual activity of the disease nor facilitate the prediction or planning of therapy. Hemorheopheresis may improve blood flow in microcirculation in familial hypercholesterolemia and also in some other microcirculation disorders via significantly decreased activity of thrombomodulin (p<0.0001), tissue factor (p<0.0001), aggregation of thrombocytes (p<0.0001) and plasma and whole blood viscosity (p<0.0001). In conclusion, lipoprotein apheresis and hemorheopheresis substantially lowered LDL-cholesterol in severe hypercholesterolemia. Our experience with long-term therapy also shows good tolerance and a small number of complications (6.26 % non-serious clinical complications).

Omentin-1 plasma levels and cholesterol metabolism in obese patients with diabetes mellitus type 1: impact of weight reduction.

BACKGROUND: Omentin-1 is an anti-inflammatory adipokine produced preferentially by visceral adipose tissue. Plasma levels of omentin-1 are decreased in obesity and other insulin-resistant states. Insulin resistance contributes to the changes of cholesterol synthesis and absorption as well. The aim of this study was to characterise omentin-1 plasma levels in obese patients with diabetes mellitus type 1 during weight reduction, and to elucidate the relationship between cholesterol metabolism and omentin-1. METHODS: Plasma levels of omentin-1 were measured in obese type 1 diabetics (n=14, body mass index >30 kg m(-2), age 29-62 years) by enzyme-linked immunosorbent assay (BioVendor). Gas chromatography with flame ionisation detector (Fisons Plc.,) was used to measure squalene and non-cholesterol sterols-markers of cholesterol synthesis and absorption (phase I). Measurements were repeated after 1 month (phase II; 1 week of fasting in the hospital setting and 3 weeks on a diet containing 150 g saccharides per day) and after 1 year (phase III) on a diet with 225 g saccharides per day. RESULTS: Omentin-1 plasma levels were stable during phases I and II, but significantly increased (P<0.001) during phase III. Omentin-1 plasma dynamics were significantly associated with plasma levels of high-density lipoprotein (P=0.005) and triacylglycerols (P=0.01), as well as with lathosterol (P=0.03). CONCLUSION: Omentin-1 plasma levels significantly increased during the weight reduction programme. Omentin-1 plasma dynamics suggest a close relationship with cholesterol metabolism.

Pregnancy in homozygous familial hypercholesterolemia--Importance of LDL-apheresis.

INTRODUCTION: Rare cases of pregnancy in women with homozygous familial hypercholesterolemia (HFH) have been reported. HFH might pose significant risks for the mother and her fetus. Statins, the most potent agents for low-density lipoprotein (LDL) cholesterol reduction, are contraindicated; thus lipoprotein apheresis remains the only effective treatment. CASE REPORT: We report on a 34-year-old pregnant woman with HFH who was treated throughout the entire pregnancy by lipoprotein apheresis (immunoadsorption method). Increasing levels of LDL-cholesterol were stabilized at 9-10 mmol/L by lipoprotein apheresis (performed every 10 days). No complications were observed during the treatment procedures. Monitoring of the fetus revealed no impairment of the umbilical cord and blood flow in the uterine arteries, as well as no intrauterine growth retardation. The delivery was spontaneous and the child was breastfed for two months. CONCLUSION: Intensive treatment by lipoprotein apheresis is an effective and safe therapeutic strategy during pregnancy, even in severe cases of HFH, as it can stabilize progressively increasing lipoprotein levels and prevent severe complications.

Changes of the complement system and rheological indicators after therapy with rheohemapheresis.

INTRODUCTION: In the last 10 years, many studies have been published on the role of the complement system in microcirculation disorders. However, as for the changes of complement components after rheohemapheresis, there is still a lack of detailed data in the literature. Complement changes may play an important role in pathogenesis of some microcirculation disorders, such as age-related macular degeneration and acute hearing loss. The objective of this study was to investigate the effect of rheohemapheresis on the basic complement pathways. PATIENTS AND METHODS: 32 patients were treated with rheohemapheresis, including 16 patients (10 men and 6 women) for age-related macular degeneration (AMD), mean age 69.7 ± 6.06 years (range 62-87 years) and 16 patients (11 men and 5 women) aged 56.4 ± 11.5 (range 34-73 years) for acute hearing loss. RESULTS: Rheohemapheresis led to a significant drop of all three complement-activation pathways in both groups of patients. Moreover, complement factor H was also reduced. CONCLUSION: The observed reduction in all three basic complement activation pathways after rheohemapheresis could be clinically important. The search continues both to find substances which influence complement systems and to develop more effective new drugs that require less frequent administration and that provide improved intraocular therapy for AMD patients.

Effects of body weight reduction on plasma leptin and adiponectin/leptin ratio in obese patients with type 1 diabetes mellitus.

The aim of this study was to explore the changes in the adipokines leptin and adiponectin in obese patients with type 1 diabetes mellitus (T1DM) who underwent seven days of fasting and 21 days of low-calorie diet (LCD). The plasma leptin and adiponectin concentrations were measured in 14 obese patients with T1DM at baseline, immediately after 7 days of fasting, and after 21 days of LCD. 13 non-obese patients with T1DM were studied only after an overnight fasting. Bioimpedance technique was used for determination of body composition. Obese T1DM patients lost 6.0 kg (6.0; 6.8) (median, 25 %; 75 %) and decreased their fat tissue after fasting and LCD. Plasma leptin in obese T1DM was significantly higher than in non-obese T1DM patients: 9.10 (5.06; 25.89) vs. 1.71 (1.12; 7.08) microg . l(-1) and transiently decreased immediately after fasting: 3.45 microg . l(-1) (1.47; 7.00), (P<0.05). Adiponectin/leptin ratio in obese T1DM was significantly lower than in non-obese T1DM patients: 0.67 (0.57; 1.49) vs. 3.50 (2.46; 6.30) . 10(3) and transiently increased immediately after fasting: 2.22 (1.26; 3.24) . 10(3), (P<0.05). We conclude that obese patients with T1DM are characterized by hyperleptinemia that is reduced by prolonged fasting, but only slightly affected by low calorie diet.

The role of VEGF in the diabetic patients undergoing endovascular therapy of symptomatic aortic valve stenosis.

The aim of this study was to explore changes in plasma vascular endothelial growth factor (VEGF) in aged patients who undergone transcatheter aortic valve implantation or balloon angioplasty for the treatment of aortic stenosis. Plasma VEGF was measured in subjects with diabetes mellitus type 2 (DM) (n=21, age 79.2+/-1.6 years) and in non-diabetic subjects (non-DM) (n=23, age 84.4+/-0.7 years), using an ELISA kit. Before the procedure plasma levels of VEGF were significantly lower in DM than in non-DM patients (P<0.05). Plasma VEGF significantly increased in both groups (DM and non-DM) 24 h (387+/-64 vs. 440+/-30 pg/ml, P<0.05) and 72 h (323+/-69 vs. 489+/-47 pg/ml, P<0.05) after the endovascular procedure. However, the VEGF in DM patients was significantly lower compared to non-DM subjects up to one month after the endovascular procedure (283+/-47 vs. 386+/-38 pg/ml, P<0.05). We conclude that increased plasma VEGF in aged patients associates with atherosclerotic aortic valve stenosis. In spite of that plasma VEGF in DM was constantly significantly lower than in non diabetic patients, both before and after the endovascular procedure, possibly reflecting a disturbance of angiogenic/anti-angiogenic balance in diabetes.

Lipoprotein-associated phospholipase A2 mass level is increased in elderly subjects with type 2 diabetes mellitus.

OBJECTIVE. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is extensively expressed by advanced atherosclerotic lesions and may play a role in plaque instability. We selected a group of elderly subjects that underwent transcatheter aortic valve implantation (TAVI) or balloon angioplasty (BA) and separated them into two groups, diabetic and nondiabetic, to compare the level of Lp-PLA2 mass between them. METHODS. 44 patients aged 79.6 ± 5.6 years with symptomatic severe aortic valve stenosis underwent TAVI (n = 35) or BA (n = 9). 21 subjects had confirmed type 2 diabetes mellitus. Lp-PLA2 mass was measured using an enzyme-linked immunosorbent assay kit (USCN Life Science, China) before and 3 days after the procedure. RESULTS. Lp-PLA2 mass was significantly elevated in this population (1296 ± 358 ng/mL before TAVI; 1413 ± 268 ng/mL before BA) and further increased after TAVI (1604 ± 437 ng/mL, P < 0.01) or BA (1808 ± 303 ng/mL, P < 0.01). Lp-PLA2 mass was significantly increased on the diabetic group before these interventions. CONCLUSION. Lp-PLA2 may be a novel biomarker for the presence of rupture-prone atherosclerotic lesions in elderly patients. Levels of Lp-PLA2 in diabetic patients may accompany the higher amount of small dense LDL particles seen in these subjects.

[Opinion of the Czech Atherosclerosis Society's committee (CSAT) on the ESC/EAS guidelines related to the diagnostics and treatment of dyslipidemias issued in 2011]. / Stanovisko výboru CSAT k doporucením ESC/EAS pro diagnostiku a lécbu dyslipidemií z roku 2011.

This position statement of the Executive Committee of the Czech Society for Atherosclerosis (CSAT) summarizes the most important aspects and novelties of the latest European guidelines for the management of dyslipidemia. In particular the position statement comments on: cardiovascular risk stratification, indications for plasma lipid and lipoprotein levels assessment as well as target lipid values, evaluation of current options for both lifestyle and pharmacological treatment of lipid metabolism disorders and, also, recommendation for laboratory monitoring of patients treated with lipid lowering agents. The statement deals with actual concepts of management of dyslipiemia in everyday practice, e.g. therapy of dyslipidemia in special patients´ groups. This statement does not replace the latest guidelines but focuses on the changes from the former guidelines for dyslipidemia management, published by CSAT in 2007.

Effect of low calorie diet and controlled fasting on insulin sensitivity and glucose metabolism in obese patients with type 1 diabetes mellitus.

Obesity in T1DM patients is associated with the components of metabolic syndrome. The influence of controlled fasting and low calorie diet (LCD) on insulin sensitivity and glucose metabolism was studied in 14 obese patients with type 1 diabetes mellitus (T1DM) (42.6+/-9.4 years, BMI 32.4+/-2.1 kg m(-2)). Insulin sensitivity in obese T1DM patients was measured using a hyperinsulinemic-euglycemic clamp before fasting, immediately after 7 days of fasting, and after 21 days of LCD. Glucose oxidation and non-oxidative glucose disposal were measured before and during the clamp by indirect calorimetry. In the control group of 13 of non-obese T1DM patients (36.9+/-13.9 years, BMI 22.6+/-2.1 kg m(-2)), only one hyperinsulinemic-euglycemic clamp was performed. Obese T1DM patients lost 6.1+/-1.1 kg after fasting and maintained reduction in body weight after 21 days of LCD. Fasting transiently reduced insulin-mediated glucose disposal in the clamp (from 9.69+/-1.48 to 6.78+/-1.21 mg min(-1) kg(-1), P<0.001). This was caused by reduced glucose oxidation after the fasting period (from 2.81+/-0.52 to 0.88+/-0.98 mg min(-1) kg(-1), P<0.001). We conclude that one week of fasting transiently decreased insulin-mediated glucose disposal in T1DM patients. This was caused by reduced glucose oxidation.

The decrease of mean platelet volume after extracorporeal LDL-cholesterol elimination.

OBJECTIVE: Mean platelet volume is arousing increasing interest as a new independent cardiovascular risk factor. Large platelets are likely to be more reactive. If mean platelet volume would drop after LDL-lowering therapy, decreased MPV could be one of the markers of successful therapy. Therefore, we investigated mean platelet volume after extracorporeal LDL-cholesterol elimination. METHODS: Mean platelet volume was investigated in patients with severe familial hypercholesterolemia long-term treated (3-12 years) by LDL-apheresis (immunoapheresis) or cascade filtration. Plasma was obtained by centrifugation. Adsorbers Lipopak 400 were used for immunoapheresis and filters Evaflux 4A were used for cascade filtration. 95 pair samples were measured (before and after the procedures) in a group of 12 patients--each patient 8 times in 4 years. RESULTS: Mean platelet volume before the procedures was 10.891 fl, CI 10.25-11.53. Mean platelet volume after the procedures decreased--10.478 fl, CI 09.84-11.11. The difference is statistically significant (p = 0.036). Mean platelet volume did not correlate with age, sex, platelet count, duration of therapy. At the same time, we used rheohemapheresis in the therapy of 40 patients with age-related macular degeneration. But mean platelet volume was not changed. CONCLUSION: Mean platelet volume is easily available and is often disregarded, and sometimes may suggest the need for a careful assessment in patients with familial hypercholesterolemia. Mean platelet volume could be one of the markers of therapeutic efficacy in patients with familial hypercholesterolemia treated by extracorporeal LDL-cholesterol elimination that is simple and inexpensive.

Rheohaemapheresis in the treatment of nonvascular age-related macular degeneration.

PURPOSE: To evaluate the experience with rheohaemapheresis (RH) in the treatment of age-related macular degeneration (AMD). METHODS: Thirty-eight patients were each treated with 8 procedures of RH (14 males, 24 females). The control group consisted of 34 random patients (30 females, 4 males) with the dry form of AMD but not treated by RH. Our modification of the cascade method (named rheohaemapheresis) was used for plasma separation. After plasma separation (blood cell separator, Cobe Spectra, Denver, CO, USA), the separated plasma was pumped through a rheofilter (Evaflux 4A, Kuraray, Osaka, Japan) to remove lipoproteins and other high-molecular-weight rheologic factors. RESULTS: In treated patients, best-corrected visual acuity (BCVA) increased significantly from 0.61 (0.06-1.00) to 0.68 (0.35-1.00) after 2.5 years (p = 0.035). We found no significant changes or differences in scotopic activity, whereas cone response and paramacular activity in the more peripheral region between 14° and 22° of eccentricity were significantly higher in treated patients after 2.5 years. CONCLUSION: RH therapy favourably influenced BCVA. During 2.5 years after the therapy, no progression of dry to wet AMD was observed in our patients. RH reduced the area of drusenoid retinal pigment epithelium detachment (which increased during the natural course of dry form AMD). RH influenced rheological markers and probably improved metabolism in the affected retinal areas which lead to the aforementioned positive results.

[Current guidelines on the care of tunelized vascular catheters in patients on home parenteral nutrition]. / Péce o tunelizované zilní katétry u nemocných na domácí parenterální výzive podle soucasných doporucení

Home parenteral nutrition is the only option to provide nutrition in a number of patients. Care of venous entry, its management and treatment of complications resulting from its use importantly affect patient survival. Appropriate care of the catheter and the use of current knowledge may prolong the lifespan of the catheter, reduce patient morbidity and mortality and thus increase quality of life of patients who are dependent on home parenteral nutrition. The present paper summarizes recommendations for the care of long-term venous catheters.

Use of ultra high performance liquid chromatography-tandem mass spectrometry to demonstrate decreased serum statin levels after extracorporeal LDL-cholesterol elimination.

BACKGROUND: Using our statin analysis method, it was possible to uncover a significant drop in statin levels (atorvastatin, simvastatin, and metabolites) after extracorporeal LDL-cholesterol elimination (EE) in severe familial hypercholesterolemia (FH). The purpose of this work was to identify the mechanism underlying this drop and its clinical significance as well as to propose measures to optimize a pharmacotherapeutical regimen that can prevent the loss of statins. METHODS: Ultra High Performance Liquid Chromatography (UHPLC) connected to the triple quadrupole MS/MS system was used. Patients. A group of long-term treated patients (3-12 years of treatment) with severe FH (12 patients) and treated regularly by LDL-apheresis (immunoadsorption) or haemorheopheresis (cascade filtration) were included in this study. RESULTS: After EE, the level of statins and their metabolites decreased (atorvastatin before/after LDL-apheresis: 8.83/3.46 nmol/l; before/after haemorheopheresis: 37.02/18.94 nmol/l). A specific loss was found (concentration of atorvastatin for LDL-apheresis/haemorheopheresis: 0.28/3.04 nmol/l in washing fluids; 11.07 nmol/l in filters). To prevent substantial loss of statin concentrations, a pharmacotherapeutic regimen with a longer time interval between the dose of statins and EE is recommended (15 hours). CONCLUSIONS: A specific loss of statins was found in adsorbent columns and filters. The decrease can be prevented by the suggested dosage scheme.

Extracorporeal immunoglobulin elimination for the treatment of severe myasthenia gravis.

Myasthenia gravis (MG) is a neuromuscular disorder leading to fluctuating muscle weakness and fatigue. Rarely, long-term stabilization is not possible through the use of thymectomy or any known drug therapy. We present our experience with extracorporeal immunoglobulin (Ig) elimination by immunoadsorption (adsorbers with human Ig antibodies). Acetylcholine receptor antibodies (AChRAs) were measured during long-term monitoring (4.7 +/- 2.9 years; range 1.1-8.0). A total of 474 samples (232 pairs) were analyzed, and a drop in AChRA levels was observed (P = .025). The clinical status of patients improved and stabilized. Roughly 6.8% of patients experienced clinically irrelevant side effects. The method of Ig elimination by extracorporeal immunoadsorption (IA) is a clinical application of the recent biotechnological advances. It offers an effective and safe therapy for severe MG even when the disease is resistant to standard therapy.