Pavel Vyroubal

Fulminant hepatitis and death associated with disseminated varicella in an immunocompromised adult from the Czech Republic caused by a wild-type clade 4 varicella-zoster virus strain

Varicella zoster virus typically causes a benign disease in childhood called varicella (chickenpox) and can reactivate in adults as a dermatomally distributed, painful rash illness known as herpes zoster (HZ). Infection with VZV can however lead to severe complications in immunocompromised patients that can result in hospitalization and, occasionally, death. Here we describe a patient, who acquired primary VZV infection during a 3-week-long treatment regimen with corticosteroids. The disease took a fulminant course, leading to a liver failure and severe coagulopathy. The patient died 9 days following hospital admission, despite intensive antiviral and supportive treatment. Wild-type VZV DNA was detected from multiple samples from esophagus, liver and skin. Genotypic analysis based on single nucleotide polymorphism profiles in open reading frames (ORFs) 21, 22 and 50 identified this strain as a clade 4 isolate, which is typically found in tropical countries. This is the first description of a clade 4 strain from a patient in the Czech Republic.

Bioanalysis of PUFA metabolism and lipid peroxidation in coronary atherosclerosis

Twenty eight men (age 34-77 years) who underwent an elective coronary angiography for coronary artery disease (CAD), were studied. They were divided into group A (luminal narrowing < 50%; n = 11) and group B (luminal narrowing > 50%; n = 17). Capillary gas chromatography was used for determination of fatty acids. Retinol and alpha-tocopherol were analyzed by reversed-phase high-performance liquid chromatography (HPLC), other parameters were determined spectrofluorometrically and spectrophotometrically. Severe coronary atherosclerosis in group B was associated with higher serum low density lipoprotein/high density lipoprotein (LDL/HDL) cholesterol ratio, triacylglycerols, and phospholipids (P < 0.05). Erythrocyte membrane fatty acids C14:0, C16:1 and C22:6n3 were significantly higher in group B (P < 0.05). We found significantly higher plasma polyunsaturated fatty acids (PUFA) C18:3n6 in group B, whereas plasma linoleic acid was not changed significantly. There was a significant increase of IDL-C18:0, LDL-C14:0 and HDL-C22:6n3 PUFA in group B. We conclude that disturbances in saturated fatty acids (SUFA) and PUFA metabolism are associated with coronary atherogenesis. Such abnormalities may include enhanced extrahepatic transport of C14:0 SUFA via LDL and its incorporation into cell membranes, and enhanced clearance of anti atherosclerotic C22:6n3 PUFA via serum HDL.

Extracorporeal LDL cholesterol elimination (25 years of experience in CZ)

In the Czech Republic the therapy of severe familial hypercholesterolemia (FH) by extracorporeal elimination using LDL-apheresis (immunoadsorption) and hemorheopheresis is concentrated into one center. The authors evaluate the long-term therapy (3-12 years, median 7,25) in 12 patients with FH - 3 homozygous, 9 heterozygous; Fredrickson type IIa, IIb (treated: 9 by LDL-apheresis and 3 by hemorheopheresis). Immunoapheretic interventions decrease LDL-cholesterol, ApoB and even Lp(a) by about 82 +/- 1; 73 +/- 13; 82 +/- 19 %, respectively. Selected non-invasive methods are important for a long-term and repeated follow-up. Carotid intima-media thickness showed improvement or stagnation in 75% of the patients. The level of some adhesive molecules, cytokines, endoglin and some coagulation functions were measured, but no universally accepted biomarkers informing of the actual activity of the disease were found to predict and plan the therapy. A program for procedure planning with the use of Microsoft® Excel for Windows® was developed. In summary, LDL-apheresis and hemorheopheresis substantially lower LDL-cholesterol in FH. Our experience with long-term therapy also shows good tolerance and a small number of complications (5,6% of clinically irrelevant side-effects). Hemorheopheresis may improve blood flow in microcirculation in familial hypercholesterolemia and also in some other disorders of microcirculation.

Interrelationship between fatty acid composition, lipid peroxidation and alpha-tocopherol consumption post-LDL-apheresis treatment evaluated by liquid chromatography and gas chromatography

Abstract The performance of regular low-density lipoprotein (LDL)-apheresis (LA) permits the achievement of lower levels of LDL-cholesterol (LDL-C) and the related apolipoprotein B-containing lipoproteins. Consequently, the application of LA may offer opportunities to study the influence of rapid changes of lipid homeostasis upon particular atherogenic species. The purpose of the study was to analyze the interrelationship between fatty acid composition, lipid peroxidation, and alpha-tocopherol consumption post-immuno-LA (Sepharose 4b columns carrying an anti-apoprotein B antibody) in six hyperlipidemic patients (three men and three women, age 14–56 years) by liquid chromatography (LC) and gas chromatography (GC). Immediately after LA, we observed significantly decreased serum thiobarbituric acid-reactive substances (TBARS) and serum total Vitamin E ( P P P P =0.07), and was decreased in high-density lipoprotein (HDL) ( P P =0.01) and decreased in LDL ( P P =0.02), and non-significantly increased in LDL ( P =0.08). Analysis of long-term effects of LA upon lipid metabolism revealed that Vitamin E in serum and lipoprotein fractions, neither serum TBARS did change significantly. Plasma phospholipids significantly decreased ( P P P

Self-reported adherence by MARS-CZ reflects LDL cholesterol goal achievement among statin users: validation study in the Czech Republic

RATIONALE, AIMS AND OBJECTIVES Measuring self-reported adherence may contribute to minimizing the risk of therapy failure. Hence, the main aim of the study was to assess the psychometric properties of the Czech version of Medication Adherence Report Scale (MARS-CZ) and its appropriateness for use in long-term statin therapy where goal levels of low-density lipoprotein cholesterol (LDL-c) should be achieved. METHODS Anonymous structured interview was performed to determine self-reported adherence by MARS-CZ in outpatients chronically treated with statins. At the same time, medication records were reviewed for inclusion of patients into groups of those who achieved and do not achieved LDL-c goal according to cardiovascular risk level. Reliability and validity of MARS-CZ were tested as well as the relationship between adherence and LDL-c goal achievement was examined. RESULTS A total of 136 (86.6%) patients completed the interview; mean age was 66.1 years; 49.3% were male. The mean score of MARS-CZ was 24.4 and showed positive skewing. Satisfactory internal consistency (Cronbachs α=0.54), strong test-retest reliability (r=0.83, P<0.001; intra-class correlation=0.63, 95% confidence interval: 0.35-0.81) and positive correlation with eight-item Morisky Medication Adherence Scale (r=0.62, P<0.001) were indicated. Low validity values were found between MARS-CZ and 12-item Short Form Health Survey mental and physical subscales. MARS-CZ score significantly correlated with LDL-c goal achievement (P<0.05) when all patients who achieved LDL-c goal (35%) reported high adherence to statin. MARS-CZ score also correlated with cardiovascular risk level and doctors judgments on adjusting treatment targets for each patient. CONCLUSION This study proved MARS-CZ as an acceptable self-reported adherence measure. In routine clinical practice, MARS-CZ could be helpful to reveal medication non-adherence before the alteration of drug regimen and thereby contributing to enhancement of statin therapy management.