Lege Artis Medicinae


FARKAS Katalin

SEPTEMBER 19, 2008

Lege Artis Medicinae - 2008;18(08-09)

[The microvascular bed is an anatomical entity, which constitutes of blood vessels smaller than 50 μm (i.e. arterioles, capillaries and venules), and its major function is the nutritive perfusion of organs and tissues. In search of cardiovascular diseases, there are growing evidences that impaired microcirculation plays an important role in the patophysiology of arterial diseases. Beside the well known consequence of diabetic microangiopathy in the development of diabetic complications, new data support the role of microcirculation in the pathogenesis of hypertension and atherosclerosis, as well. There are different non-invasive methods for the investigation of the microcirculation. Capillarmicroscopy, laser doppler flowmetry and transcutaneous oxygen pressure measurement are used not only in the scientific research, but also in the clinical practice. Laser doppler flowmetry gives us the possibility to assess microvascular endothelial function and other early microcirculatory disturbances. Capillarmicroscopy is particularly useful in the diagnosis of different autoimmune diseases. Transcutaneous oxygen pressure measurement is mostly used in the diagnosis of critical limb ischemia, because it has proven prognostic relevance. Vascular specialist should prescribe all investigations. General practitioners play key role in the early diagnosis of vascular diseases that can be achieved through the screening of patients at risk for vascular disease. In case of suspected vascular disease, the patient should refer to angiology outpatient clinic, to decide further investigations and prescribe therapy. The conservative treatment includes the complex cardiovascular risk management supplemented with medication, acting on the microcirculation.]



Further articles in this publication

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[The History of Prosthetics from the Beginning until Today]


Lege Artis Medicinae

[A single-step colonoscopic screening method of colorectal cancer - A methodological guideline of the College of Gastroenterology]

RÁCZ István

Lege Artis Medicinae



[The high world prevalence of cerebrovascular diseases, and the particularly bad morbidity rates of Hungary are well known. The physiological properties of the brain make stroke prevention outstandingly important. Effective prevention will be reflected in the reduction of the late complications that are otherwise common and expensive to treat. Because of the common simultaneous development of stroke, cardiovascular and peripheral vascular diseases, overall vascular disease prevention is preferred, even if the various vascular diseases manifest in different degrees in a patient. Hungarian data also indicate the high risk of recurrence of cerebrovascular diseases, therefore, the importance of secondary prevention is obvious. Large international studies have proven the strokepreventing effect, and, by a pleiotropic drug action, additional benefits, of the efficient treatment of blood lipid disorders. Consensus conferences in recent years defined clear and even stricter lipid-lowering target values, mostly to be reached by “double inhibition”, bile acid binding resins, fibrates and nicotinic acid derivatives, beside the most common statin treatment. Neurological and stroke departments and clinics play a pivotal role in vascular prevention.]

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[INTRODUCTION - The occurrence of an adenomatoid tumour is rare in the uterus; in the female genitals it is more common in the Fallopian tube, whereas in men it mainly arises from the epididymis. Though there are controversies, its mesothelial origin seems to be confirmed. Apart from their different sites of occurrence, the mesothelioma and the adenomatoid tumour are distinguished by the fact that the latter is always circumscribed and never turns malignant. CASE REPORT - Two cases of adenomatoid tumour of the uterus are reported which had clinically been thought to be leiomyomata. Both of them were adenoid in type, and stained positive for cytokeratin and vimentin as well as for a mesothelial marker, but were negative for CD-34, whereas some cells of the adenoid epithelium showed positivity with ethidiummonoazide staining. CONCLUSION - The poor and non-specific clinical symptoms and course of this tumour warrants the reporting of such cases.]

Lege Artis Medicinae



[Psoriatic arthritis is a destructive form of inflammatory arthritis that occurs in 10-30% of patients with psoriasis. Its prevalence is about 10.000 to 20.000 in Hungary. The pathogenesis includes both genetic and immunological factors. Average disease progression based on functional status is, on average, 0.05 HAQ score/year. The traditional disease-modifying antirheumatic drugs (DMARDs) are not always successful in controlling the disease and preventing joint damage. Based on the pathogenesis of psoriatic arthritis, several new drugs (anti-tumour necrosis factor alfa, or anti-TNF-α) have been introduced in the therapy, which have been found to be effective both in psoriasis and psoriatic arthritis. The development of the Biological Response Modifying Drugs (BRMDs) makes treatment possible for patients with the most serious, high activity disease, who are refractory to other therapy. There is no significant difference in efficacy among the different biological agents (etanercept, infliximab, adalimumab). The review presents the traditional DMARDs, as well as the indications, effectiveness, side effects and the national prescription regulations of the anti- TNF-alfa agents. Both DMARDs and TNF-α inhibitors can be safely used in psoriatic arthritis under strict specialist control.]

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[Current medical aspects of pantethine (in English language)]

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[Pantethine, the stable disulfide form of pantetheine, is the major precursor of coenzyme A, which plays a central role in the metabolism of lipids and carbohydrates. Coenzyme A is a cofactor in over 70 enzymatic pathways, including fatty acid oxidation, carbohydrate metabolism, pyruvate degradation, amino acid catabolism, haem synthesis, acetylcholine synthesis, phase II detoxification, acetylation, etc. Pantethine has beneficial effects in vascular disease, it able to decrease the hyperlipidaemia, moderate the platelet function and prevent the lipid-peroxidation. Moreover its neuro-endocrinological regulating role, its good influence on cataract and cystinosis are also proved. This molecule is a well-tolerated therapeutic agent; the frequency of its side-effect is very low and mild. Based on these preclinical and clinical data, it could be recommended using this compound as adjuvant therapy.]

Lege Artis Medicinae

[Experiences with rosuvastatine therapy]

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[A relative cardiovascular risk reduction of 25-35% has been reported in patients with high cardiovascular risk that have started statins directly after the cardiovascular events. A lot of patients fail to consistently take these medications as directed. In order to obtain further success, it is very important to improve the actual routine, especially because in the field of lipid-lowering we have new data and guidelines that strongly support our efforts in the right direc­tion. We report the results of our ten patients treated with rosuvastatin after myocardial infarction from our ALADDIN Study. In the period of six month of treatment with 40 mg rosuvastatin LDL-cholesterol decreased 55% (from 3.55±1.1 to 1.58±0.6 mmol/l, p<0.01), non-HDL-cholesterol decreased 52% (from 4.15±1.23 to 2.0±0.8 mmol/l, p<0.01), triglycerides -26% (from 1.63± 0.41 to 1.2±0.4 mmol/l) and hsCRP level decreased 61% (from 5.47±3.8 to 2.1±1.0 mg/l, p<0.01). The two years persistence in these patients were 100%. Our experience confirms that the daily use of a highly-efficient statin (rosuvastatin) has a beneficial effect on lipid parameters and also facilitates the attainment of target lipid levels and significant cardiovascular risk reduction. ]

Hypertension and nephrology

[The role of vitamin D receptor and the risk reducing effect of vitamin D receptor agonists in chronic kidney disease]


[Vitamin D3 is produced in the skin and is modified in the liver and kidney to the active metabolite form, 1,25-dyhydroxyvitamin D3 (calcitriol). Calcitriol binds to a nuclear receptor, the vitamin D receptor (VDR), and activates processes that bind to vitamin D. The classical effects of vitamin D receptor activator or agonist (VDRA) therapy for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease primarily involves suppressive effects on the parathyroid gland, and regulation of calcium and phosphorus absorption in the intestine an mobilization in bone. Several VDR agonists have been developed for the treatment of osteoporosis, hyperparathyroidism secondary to chronic kidney disease (CKD), and psoriasis. Secondary hyperparathyroidism (SHPT) is a common and serious consequence of CKD. SHPT is a complex condition characterized by a decline in 1,25-dihidroxi vitamin D and consequent VDR activation, abnormalities in serum calcium and phosphorus levels, parathyroid gland hyperplasia, elevated parathyroid hormone (PTH) secretion, and systemic mineral and bone abnormalities. There are three classes of drug used for treatment of SHPT (non-selective and selective VDR activators, and calcimimetics). Observational studies in hemodialysis patients report improved cardiovascular and allcause survival among those received VDRA therapy compared with those not on VDRA therapy. The survival benefits of selective VDRA paricalcitol appear to be linked to "non classical" action of VDRA, possibly through VDRA-mediated modulation of gene expression. VRDAs are reported to have beneficial effects such as anti-inflammatory and antithrombotic effects, inhibition of vascular calcification and stiffening, inhibition of vascular smooth muscle cell proliferation, and regression of left ventricular hypertrophy. VDRA are also reported to negatively regulate the renin-angiotensin system, which plays a key role in hypertension, myocardial infarction and stroke. Data from epidemiological, preclinical and clinical studies have shown that vitamin D and/or 25(OH) vitamin D deficiency is associated with increased risk for cardiovascular disease (CVD). The selective VDR agonists are associated direct protective effects on glomerular architecture and antiproteinuric effects in response to renal damage. Emerging evidence suggest that VDR plays important roles in modulating cardiovascular, immunological, metabolic and other function. Paricalcitol may prove to have a substantial beneficial effect on cardiac disease and its outcome in patients with CKD.]

Lege Artis Medicinae

[Anti-atherosclerotic effects of Ca-antagonists in the light of new clinical data]


[Based on in vitro and animal research, it has been found that calcium antagonist drugs are capable of inhibiting directly the atherosclerotic process. In spite of their advantegous antiatherosclerotic effect, the fast-release, first-generation dihydropyridines had an unfortunate effect on the number of newly developed myocardial infarctions and on cardiovascular mortality. New, controlled clinical studies have found long acting calcium antagonists to decrease significantly the progression of the atherosclerosis in the carotid artery - verified with B-mode ultrasound scans - and the appearance of cardiovascular clinical events, when either proven coronary sclerosis (PREVENT, CAPARES studies) or hypertension (INSIGHT, ELSA, VHAS) was present. If further clinical trials (CAMELOT, NORMALISE - now under way) justify these promising clinical data, then long-acting calcium channel blockers may become new and significant tools in the prevention of the progression and clinical complications of atherosclerotic disease.]

Lege Artis Medicinae



[Statins, specific inhibitors of the 3-hydroxy-3-methylglutaryl- coenzyme A (HMG-CoA), decrease significantly pathologically elevated cholesterol levels. The effectiveness and the side effects of the different analogs depend on their inhibitory potency, lipid solubility, active uptake into the liver cells and on the difference in their metabolism. The statins can be divided into three groups on the basis of their clinical effectiveness: the highly effective agents are rosuvastatin and atorvastatin; simvastatin exhibits an intermediate activity, while lovastatin, pravastatin and fluvastatin are the least active drugs. The main metabolic pathways of the statins are oxidation and glucoronidation and finally the spontaneous inactivation by lactone ring formation of the glucoronidated products. Gemfibrozil increases the plasma level of all statin analogs by inhibiting the activity of UGT1A1 and UGT1A3 isoenzymes of the UDPglucoronosyltransferase. Therefore, when a statinfibrate combination is needed, fenofibrate and bezafibrate are recommended, the metabolism of which are linked to other UGT isoenzymes. Similarly elevated plasma levels are produced by inhibiting the specific cytochrome isoforms participating in the oxidation of a particular statin. Severe side effects are rarely observed. The most frequent adverse reaction is the development of myopathy of various severity. Using various statins rhabdomyolysis occurred in 0.0-0.3 cases /100 000 statin prescriptions if the already withdrawn cerivastatin is not considered. The statin+gemfibrozil combination increases the number of rhabdomyolysis approximately tenfold. The long-term benefit of statin therapy far exceeds the risk of the treatment. For achieving very low lipid target values even the most effective statins must be used in high doses. Nevertheless, this goal cannot be reached in about 20% of the cases. High dose statin treatment should be administered with the gradual increase of the dose, tight control of the patients and by meticulously selecting the drugs given simultaneously. Further development can be expected from the application of agents with new mechanisms of action, such as the cholesterol uptake inhibitor ezetimibe.]