[Inflammation and vascular diseases].

Chronic venous disease and cardiovascular atherothrombotic diseases have a high prevalence worldwide. The aetiopathogenesis of both these vascular conditions may share certain aetiopathogenetic moments. Abnormal blood flow, altered intravascular tension, and subsequent endothelial dysfunction may all play an important role.

[Are proton pump inhibitors an effective and safe drug not only in the prophylaxis of gastrointestinal bleeding in antithrombotic treatment?].

Proton pump inhibitors (PPIs) are popular and widely used “gastroprotectives”. More than 10% of our population is treated. In addition to classical indications such as gastroduodenal peptic disease or gastroesophageal reflux disease, they are indicated for the reduction of hemorrhagic complications in the digestive tract during antithrombotic treatment.

[Diosmin/hesperidin: a cooperating tandem, or is diosmin crucial and hesperidin an inactive ingredient only?].

With the advent of novel monocomponent venoactive drugs containing the flavonoid diosmin, the need has arisen to answer the question of therapeutic equivalence of the widely used micronized purified flavonoid fraction (MPFF) contained in Detralex and of the currently introduced monocomponent venoactive drugs. Experimental work provides evidence that each of the two dominant components, i.e.

[Anticoagulant therapy in the elderly].

Elderly and fragile patients have a higher risk of atrial fibrillation, a higher risk of systemic embolism. They are therefore often candidates for long-term anticoagulation medication. At the same time, they have an increased risk of bleeding due to age and co-morbidities, which anticoagulation therapy necessarily potentiates.

[Mountain sickness].

Mountaineering brings many health risks, one of which is mountain sickness. Its mildest form - acute mountain sickness - is mainly characterized by subjective symptoms (headache, loss of appetite, insomnia, weakness, nausea and rarely also vomiting). Advanced and life-threatening forms are characterized by tissue edema - cerebral or pulmonary high altitude edema.

[Anticoagulant therapy in secondary prevention of coronary events].

Secondary prevention of atherothrombotic events is the domain of antiplatelet therapy and according to present risk is used one drug strategy or combination of acetylsalicylic acid with ADP receptor blockers. The importance of the combination of dual antiplatelet therapy together with xabans or dabigatran was investigated in 6 clinical trials. Only one of them (ATLAS ACS 2-TIMI 51) indicated that treatment with small dose of rivaroxaban (2 × 2.

[Extended options of anticoagulant treatment in thromboembolism].

Thromboembolic disease (TD) is a relatively common disease with acute risk of death and potential long-term consequences in term of postthrombotic syndrome or chronic pulmonary hypertension. Anticoagulant therapy is the basic therapeutic procedure; thrombolytic therapy and the introduction cava filter are appropriately indicated for individual cases. In past few years, new direct oral anticoagulant drugs (NOAC) have occurred - Xa factor or thrombin inhibitors which have demonstrated the same efficacy and even higher safety in comparison to conventional treatment.

[Pharmacogenetics in cardiovascular diseases therapy--treatment according guidelines or according the individual requirement?].

In clinical practice the individual response to a drug represents a great problem. Many of us experienced a situation when the drug effect declined or drug-related toxic reaction occurred. The typical example is the variation of optimal warfarin dosage.

Potent anti-ischaemic effects of statins in chronic stable angina: incremental benefit beyond lipid lowering?

Aims: The DoUble-blind Atorvastatin AmLodipine (DUAAL) trial investigated whether atorvastatin decreases ischaemia by a vascular benefit, independent of low-density lipoprotein cholesterol lowering, in patients with coronary artery disease (CAD), both alone and in combination with the traditional anti-anginal therapy, amlodipine.

Methods And Results: Randomized, double-blind, parallel-group, multicountry trial (2 weeks run-in and 24 weeks active therapy) comparing three treatments: amlodipine, atorvastatin, and amlodipine + atorvastatin; in 311 patients (78% male; mean age 62 years) with stable angina (≥ 2 attacks/week), CAD history, ≥ 3 transient myocardial ischaemia (TMI) episodes, and/or ≥ 15 min ischaemia on 48 h ambulatory electrocardiographic (AECG) monitoring. Efficacy variables were change in TMI by AECG, exercise ischaemia, angina diary data, and inflammatory biomarkers at Week 26.

Association between cardiac energy metabolism and gain of left ventricular mass in Fabry disease.

Left ventricular (LV) hypertrophy is the hallmark of cardiac involvement in Fabry disease (FD). However, its pathogenesis is not clearly understood as pathologic substrate accumulation represents only 1-2% of the total cardiac mass. Abnormal myocardial energy metabolism has been previously demonstrated in different forms of cardiomyopathies.

Fabry disease: progression of nephropathy, and prevalence of cardiac and cerebrovascular events before enzyme replacement therapy.

Background: In Fabry disease, progressive glycolipid accumulation leads to organ damage and early demise, but the incidence of renal, cardiac and cerebrovascular events has not been well characterized.

Methods: We conducted a retrospective chart review of 279 affected males and 168 females from 27 sites (USA, Canada, Europe). The pre-defined study endpoints included progression of renal, cardiac and cerebrovascular involvement and/or death before the initiation of enzyme replacement therapy.

Onset and progression of the Anderson-Fabry disease related cardiomyopathy.

Background: Cardiac involvement is responsible for substantial morbidity and mortality in Anderson-Fabry disease (AFD). We sought to document its onset and progression in a population of male and female AFD patients.

Methods: We performed a cross sectional echocardiographic study of a cohort of 177 male and female AFD patients with subsequent longitudinal follow-up of 76 patients (38 males and 38 females; mean follow-up 4.

The pharmacology of multiple regimens of agalsidase alfa enzyme replacement therapy for Fabry disease.

Purpose: This 10-week study was conducted to determine the pharmacokinetics of varying doses of agalsidase alfa and evaluate the effect of dose and dosing frequency on plasma Gb3 levels.

Methods: Eighteen adult male Fabry patients, naive to enzyme replacement therapy, were randomized to one of five regimens: 0.1, 0.

Agalsidase-beta therapy for advanced Fabry disease: a randomized trial.

Background: Fabry disease (alpha-galactosidase A deficiency) is a rare, X-linked lysosomal storage disorder that can cause early death from renal, cardiac, and cerebrovascular involvement.

Objective: To see whether agalsidase beta delays the onset of a composite clinical outcome of renal, cardiovascular, and cerebrovascular events and death in patients with advanced Fabry disease.

Design: Randomized (2:1 treatment-to-placebo randomization), double-blind, placebo-controlled trial.

A nationwide blood spot screening study for Fabry disease in the Czech Republic haemodialysis patient population.

Background: Fabry disease (FD) is a genetic disorder characterized by accumulation of trihexosylceramide in lysosomes of various tissues leading to multiorgan manifestations, including progressive renal disease. Previous screening studies have shown that a non-neglectable proportion of haemodialysis(HD) patients have unsuspected FD. An extensive FD screening study, the largest to date, has been conducted in HD patients in Czech Republic.

Fabry disease: guidelines for the evaluation and management of multi-organ system involvement.

Fabry disease is an X-linked metabolic storage disorder due to the deficiency of lysosomal alpha-galactosidase A, and the subsequent accumulation of glycosphingolipids, primarily globotriaosylceramide, throughout the body. Males with classical Fabry disease develop early symptoms including pain and hypohidrosis by the second decade of life reflecting disease progression in the peripheral and autonomic nervous systems. An insidious cascade of disease processes ultimately results in severe renal, cardiac, and central nervous system complications in adulthood.

Increased carotid intima-media thickness in the absence of atherosclerotic plaques in an adult population with Fabry disease.

Aim: Fabry disease is considered primarily as a progressive small vessel disease, with ischaemic degenerative lesions involving the kidneys, brain and heart. Macrovascular involvement in male patients includes an accelerated wall hypertrophy of the radial artery and a thickening of the intima-media of the common carotid artery. The aim of this study is to evaluate the prevalence and severity of carotid artery atherosclerosis in hemizygous and heterozygous patients with Fabry disease, compared with a matched control population.

Cardiac and vascular hypertrophy in Fabry disease: evidence for a new mechanism independent of blood pressure and glycosphingolipid deposition.

Objective: Fabry disease is an X-linked disorder resulting from alpha-galactosidase A deficiency. The cardiovascular findings include left ventricular hypertrophy (LVH) and increased intima-media thickness of the common carotid artery (CCA IMT). The current study examined the possible correlation between these parameters.

Early diastolic mitral annular velocity and color M-mode flow propagation velocity in the evaluation of left ventricular diastolic function in patients with Fabry disease.

Fabry disease is an X-linked genetic disorder characterized by progressive intracellular accumulation of neutral glycosphingolipids. Cardiac involvement is frequent and left ventricular (LV) diastolic dysfunction is present in most of the affected subjects. Pulsed-wave tissue Doppler echocardiography (PW-TDE) and color M-mode are new Doppler methods for LV diastolic function evaluation.

Fabry disease: percutaneous transluminal septal myocardial ablation markedly improved symptomatic left ventricular hypertrophy and outflow tract obstruction in a classically affected male.

Fabry disease (alpha-galactosidase A deficiency) is an X-linked recessive lysosomal storage disease in which left ventricular hypertrophy (LVH) is common, and if severe, may mimic hypertrophic obstructive cardiomyopathy. Alcohol-induced percutaneous transluminal septal myocardial ablation (PTSMA) has been used as a safe and effective method to alleviate LVH obstruction in patients with hypertrophic obstructive cardiomyopathy (HCM). We describe a case of a classically affected Fabry 53-year-old male with symptomatic HCM (NYHA class III with exertional angina) who was treated with PTSMA.

Relationship between X-inactivation and clinical involvement in Fabry heterozygotes. Eleven novel mutations in the alpha-galactosidase A gene in the Czech and Slovak population.

We have identified 21 different alpha-galactosidase A gene (GLA) mutations in 22 unrelated Czech and Slovak families with Fabry disease. Eleven of these mutations were novel (point mutations D93N, A135V, D155H, G171R, Q280K, G360S, Q330X, splicing errors c.194ins14, c.

Recurrence of Fabry disease as a result of paternal germline mosaicism for alpha-galactosidase a gene mutation.

We present two sisters with a severe form of Fabry disease, who both carry the same mutation in the alpha-galactosidase A (alpha-gal A) gene (Q330X). Each of the sisters developed renal failure in the third decade of life; the older sibling underwent renal transplantation at 40 years of age. The severe phenotype of the siblings correlates with results of the X-inactivation study: examination of methylation status in human androgene receptor (HUMARA) gene suggests preferential inactivation of the wild-type allele in both patients.

Comparison of early diastolic mitral annular velocity and flow propagation velocity in detection of mild to moderate left ventricular diastolic dysfunction.

Background: Pulsed wave tissue Doppler echocardiography (PW-TDE) and color M-mode are new Doppler methods for left ventricular (LV) diastolic function assessment. To date, few studies have compared the data obtained by these methods in the same series of patients and compared them to the current clinical reference method of detecting LV diastolic function.

Aims: To determine the utility of PW-TDE and color M-mode parameters in the assessment of LV diastolic function in the typical patient population encountered in daily clinical practice and to compare their discriminating power.

Medical treatment of myocardial ischemia in coronary artery disease: effect of drug regime and irregular dosing in the CAPE II trial.

Objectives: The Circadian Anti-ischemia Program in Europe (CAPE II) compared the efficacy of amlodipine and diltiazem (Adizem XL) and the combination of amlodipine/atenolol and diltiazem (Adizem XL)/isosorbide 5-mononitrate on exercise and ambulatory myocardial ischemia during regular therapy and after omission of medication.

Background: The optimal medical therapy for ischemia suppression and the impact of irregular dosing using agents with different pharmacologic properties has not been established in patients with coronary disease.

Methods: Patients with > or = 4 ischemic episodes or > or = 20 min of ST segment depression on 72-h electrocardiogram were randomized to amlodipine 10 mg once daily or diltiazem (Adizem XL) 300 mg once daily in a 14-week double-blind randomized multicountry study.