Biomedical subjects
Publications and source records attributed to J Hradec.
A case of patient with choriocarcinoma, most likely of ovarian origin, with lung metastasis is presented. The disease manifested by recurrent embolism into peripheral arteries. Publications on this topic are reviewed.
This first Czech version of guidelines formulated by the working group of mentioned medical associations is based on current literature and international guidelines. They are aimed mainly on clinical medicine and on incorporation of this treatment into the health care system according to WHO recommendations. They should serve to the treatment of tobacco dependence at any level: during any contact with the smoking patient (short intervention), in specialised centres or for the health care providers or health system itself.
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Number of patients with chronic heart failure is increasing in all developed countries. The reasons are both, the improving prevention and treatment of deadly cardiovascular diseases, like acute myocardial infarction or stroke, and the increasing life expectancy. The cardiovascular mortality has declined by 30% and the average life expectancy has increased by 4 years also in the Czech Republic during the last 15 years. The prevalence of heart failure is about 1.5% in a general population, which means that there is about 150,000 patients in the Czech Republic. The annual incidence is about 0.4%, which means that there is about 40,000 new patients in the Czech Republic every year. The prevalence is increasing with age significantly. With respect to the ageing of the population it is expected that number of heart failure patients will be increasing. Based on the results of big clinical trials the treatment of heart failure has changed significantly. ACE inhibitors and beta-blockers became the first choice treatment improving not only symptoms but also mortality. In spite of all the progress in pharmacotherapy the prognosis of heart failure is still bad. Over 40% of patients will die within 4 years after making the diagnosis of heart failure and one-year mortality of patients with advanced heart failure (NYHA class IV) is over 50%. Therefore, a research of new therapeutic possibilities is still continuing. At present, a clinical significance of different devices, like biventricular cardiac pacemakers (cardiac resynchronization therapy) or implantable cardioverter/defibrillators in heart failure treatment is studied. A gene and cell therapy represents a great hope for heart failure treatment in future.
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OBJECTIVE: It has been repeatedly proven that statins improve endothelial function in isolated hypercholesterolaemia but there is far less evidence in the case of combined hyperlipidaemia. Studies assessing the effects of fibrates on endothelium have been neglected. Therefore, we conducted a trial in which the effects of fenofibrate and atorvastatin monotherapy on both endothelium-dependent vascular reactivity and biochemical parameters were compared in patients with combined hyperlipidaemia. METHODS: 29 otherwise healthy males (aged 47.4+/-7.8 years) with combined hyperlipidaemia (total cholesterol 7.55+/-1.20 mmol/l, triglycerides 5.41+/-4.54 mmol/l) were included into the randomised, single-blind, cross-over study to receive either 200 mg of micronised fenofibrate or 10 mg of atorvastatin daily--each of the drugs for a period of 10 weeks. Analysed biochemical parameters were as follows: serum total-, LDL- and HDL-cholesterol, apolipoproteins A-I and B, triglycerides, fibrinogen, uric acid, C-reactive protein (CRP), insulin, and homocysteine. Endothelial function was investigated by duplex Doppler ultrasonography at the brachial artery. Two indices of endothelial-dependent postischaemic changes were used - the recently introduced index of peak blood flow (PBF) representing the level of reactive hyperaemia and traditional flow-mediated dilatation (FMD). RESULTS: We observed a small improvement in FMD after both fenofibrate and atorvastatin (from 2.26% to 2.98% and 2.87%, respectively; NS). PBF increased from 448 ml/min to 536 ml/min after fenofibrate (P=0.04) and to 570 ml/min after atorvastatin (P=0.03). The effects of both fenofibrate and atorvastatin on endothelial function did not differ significantly (P-values of 0.82 and 0.47 for FMD and PBF, respectively). Significant correlations (P<0.01) between the changes of vascular reactivity and biochemical indices were found between FMD and CRP (r=-0.60) and between both FMD and PBF, and insulinaemia (r=-0.48 and -0.56, respectively) only during treatment with fenofibrate. CONCLUSIONS: Both fenofibrate and atorvastatin significantly improved endothelium-dependent vascular reactivity without mutual difference. The PBF was superior to FMD for the detection of this improvement. The beneficial effect of both drugs did not correlate with the change of lipid profile during therapy. The improvement of vascular reactivity during treatment with fenofibrate (opposed to atorvastatin) was related to the reduction of indirect marker of chronic vessel wall inflammation and of insulin resistance. The PBF was more reproducible than FMD because of considerably lower intra-subject variability.
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Several clinical studies have compared the anti-ischaemic properties of trimetazidine used as monotherapy with those of standard anti-anginal therapy. In the treatment of uncontrolled angina pectoris, the addition of a metabolic agent such as trimetazidine to existing therapy with a haemodynamic agent would appear to confer advantages over the addition of a second haemodynamic agent. Here we report the results of three studies conducted in Poland, the Czech Republic and Hungary that provide additional evidence for the beneficial effects of combining trimetazidine with a conventional haemodynamic agent such as beta-blockers, long-acting nitrate or calcium channel blockers. This combination provided significant benefits in terms of improved exercise capacity and decreased number of angina attacks along with a good tolerability profile.
A group of 13 acromegalic patients was treated with lanreotide for 18 months and followed-up echocardiographically; these patients showed significant correlations between the decrease of both growth hormone (GH) and insulin-like growth factor-1 and the decrease of left ventricular mass index. This documents a regression of left ventricular hypertrophy in acromegaly after lanreotide treatment, the degree of which is dependent on the magnitude of the decrease of GH and insulin-like growth factor-1 serum levels.
The multiplicity of phosphatidylcholines is caused by the presence of different pairs of fatty acids in their individual molecular species and at least 27 miscellaneous fatty acids were identified in phosphatidylcholines in the serum of healthy individuals by combined gas-liquid chromatography and mass spectrometry in our present experiments. A method is described for the separation and quantitation of molecular species of phosphatidylcholine in human serum. Total phosphatidylcholine is isolated from lipids extracted from the serum with chloroform-methanol (2:1) by reversed-phase liquid-liquid extraction and subjected to reversed-phase high-performance liquid chromatography with a discontinuous descending gradient of water. Separation is monitored by fluorometry (340/460 nm) and absorption at 205 nm, if required. Up to 25 different molecular species of phosphatidylcholine may be quantified with a satisfactory reproducibility (+/-5-8%). Data on the distribution of individual molecular species in phosphatidylcholine of 53 normal serums are presented. The method may be used for quantitation of these phospholipids also in other biological materials (cell lines, leukemic cells from patients), and on a micropreparative scale to isolate individual compounds. The speed of separation as well as a satisfactory reproducibility are its principal advantages.
The aim of this study was to evaluate the efficacy and tolerability of valsartan, a new angiotensin II receptor antagonist, versus atenolol in the treatment of severe primary hypertension. A total of 103 adult out-patients were randomised to receive either valsartan 160 mg or atenolol 100 mg once daily for 6 weeks. If necessary, additional blood pressure (BP) control could be provided as add-on therapy. Both valsartan and atenolol decreased mean sitting diastolic BP (DBP) and mean sitting systolic BP (SBP): least squares mean change from baseline in DBP; valsartan, -20.0 mm Hg; atenolol, -20.4 mm Hg: in SBP; valsartan, -30.0 mm Hg; atenolol, -25.5 mm Hg. There was no statistically significant difference between the treatment groups. Add-on hydrochlorothiazide (HCTZ) 25 mg was required by 97.2% of patients receiving atenolol and 83.6% of patients receiving valsartan; additional verapamil SR 240 mg was also required by 58.3% of patients receiving atenolol and 64.2% receiving valsartan. Valsartan was well tolerated, with a comparable incidence of treatment-related adverse experiences in both groups. In conclusion valsartan 160 mg is as well tolerated and effective as atenolol 100 mg in lowering BP in severely hypertensive patients.
A simple and rapid method is described for the determination of total phosphatidylcholines in serum. Extracts of lipids are applied to octadecyl silica cartridges and phosphatidylcholines are eluted by methanol-acetonitrile mixtures containing choline. Quantitation of these compounds is performed by colorimetry of their complexes with erythrosin B. The method is sensitive down to approximately 10 microg, exhibits good reproducibility and may be used as a preliminary step for the separation of individual molecular species of phosphatidylcholines by high-performance liquid chromatography.
Three enzymes esterifying cholesterol with long-chain fatty acids were purified approximately 31,000-fold to apparent homogeneity from the cytosol of normal rat liver. The enzymatic activity was tested by incubation of active fractions with tritiated cholesterol and separation of newly formed esters from non-reacted cholesterol by a passage through silica gel cartridges with subsequent assay for radioactivity by liquid scintillation. For the purification of enzymes, active proteins were precipitated by (NH4)2SO4 to 35% saturation. The bulk of inactive proteins was removed by size-exclusion chromatography on TSK G3000 SW. The active fraction was subsequently separated on Separon HEMA BIO 1000 DEAE in gradients of 0-500 mM KCl into three enzymatic activities differing in their retention and these proteins were finally purified by affinity HPLC on columns of cholesterol immobilized on HEMA BIO 1000 E-H. Final purified enzymes showed the same single band in polyacrylamide gel electrophoresis corresponding to 16.5 kDa. Combination of individual enzymes did not increase the overall yield of cholesteryl esters but the reaction-rate was significantly accelerated. These proteins are apparently subunits of a larger complex (M(r) 65,000) that can be demonstrated by electrophoresis in the absence of 2-mercaptoethanol. Results presented in this paper indicate that because of good and rapid separation of active proteins, HPLC may be a method of choice for enzyme purifications.
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Captopril was the first oral inhibitor of the angiotension converting enzyme (ACE). Its introduction into clinical practice in 1981 was a great advance in the treatment of essential hypertension. In subsequent years a number of other ACE inhibitors was developed. They are nowadays, due to their favourable effects and good tolerance, basic antihypertensive drugs. They are indicated either as monotherapy or part of combined treatment, in particular in moderate to severe hypertension or when other antihypertensive drugs are ineffective, poorly tolerated or contraindicated. They are suitable also for hypertensive patients with left ventricular hypertrophy, cardiac failure, in diabetics and in dyslipoproteinaemia. Recent reports indicate that ACE inhibitors preserve the quality of life of hypertonic patients better than other hypotensive drugs. It seems that some can it, even improve.
Evidence has accumulated regarding acromegalic heart muscle disease which existence now appears to be unequivocal. We took an advantage of a large group of acromegalic patients being followed-up at our institution for a long time and have studied pattern, nature and reversibility of acromegalic heart disease. Its major manifestation is cardiac hypertrophy expressed especially as left ventricular hypertrophy. The cardiac hypertrophy is slowly reversible after normalization of plasma growth hormone levels due to successful treatment. This we have first suggested on the basis of a retrospective analysis of clinical and echocardiographic data in 78 patients with acromegaly and subsequently confirmed by a 10-year prospective follow-up of the original patient cohort. We have also showed that effective treatment of acromegaly with a new slow release somatostatine analogue lanreotide leads to regression of cardiac hypertrophy.
Two-dimensional and Doppler echocardiography have an important role in the management of patients with mitral balloon valvuloplasty (MBV). It is extremely useful in the selection of patients for the procedure, the prediction of its outcome, the assessment of the effect of MBV, the recognition of major complications and long-term follow-up of patients with the aim to recognize early restenosis. The authors report their own experience with long-term follow-up of the population of 55 patients after MBV.
A simple reversed-phase HPLC method has been developed for the determination of cholesteryl 14-methylhexadecanoate (CMH) in the blood serum. Lipids are extracted from 0.1 ml of blood serum and after centrifugation, the extract is chromatographed and individual cholesteryl esters, including CMH are separated and eluted with an acetonitrile-2-propanol mixture. The quantification of cholesteryl 14-methylhexadecanoate is precise and highly reproducible and the analysis may be completed within 35 min. The level of CMH in the blood of cancer patients appears to be a useful marker of malignant tumors.