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Carcinosarcomas are high-grade endometrial cancers which enclose mesenchymal and epithelial differentiated components. The vast majority of these cancers belong to the p53 abnormal molecular subgroup and usually come with an unfavorable prognosis. POLE mutant carcinosarcomas are a rarity and only make up about 5% of this histologic subtype. Recent literature even suggests that this number is still an overestimation and the result of misclassification of undifferentiated or dedifferentiated endometrial cancers. Here we present a case of a 56-years old patient diagnosed with carcinosarcoma of the uterus. Hysterectomy, bilateral salpingo-oophorectomy with pelvic lymph node staging was performed and complete molecular workup of the tumor revealed an abnormal p53 expression as well as a pathologic POLE mutation. NGS was performed separately on the epithelial and mesenchymal component of this high-grade cancer and both components shared two identical POLE mutations, a known pathologic mutation, and a variant of unknown significance (VUS). This finding hints to a clonal origin of both histologic components of this tumor and supports conversion theory as mechanism of carcinosarcoma emergence. The cancer was correctly staged as FIGO 2023 Stage IAmPOLEmut and according to ESGO-ESTRO-ESP guidelines adjuvant chemotherapy no longer considered and our patient entered follow-up after a detailed discussion.

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UNLABELLED: THE AIM of our research was to evaluate the impact of 8-week comprehensive rehabilitation programme on circulatory parameters, left ventricular (LV) function and functional capacity of patients after aortal (ao) and mitral (mi) heart defect surgery. PATIENT SAMPLE AND METHODOLOGY: The rehabilitation programme was completed by 54 patients (exercising, RHB+) following valve defect surgery (13 women/41 men), aged 27-83 (56 +/- 16) years. The majority were patients with aortal (ao) stenosis (39), the remainder had a combined ao defect (7), ao regurgitation (3) or mitral (mi) regurgitation (5). Myocardial revascularisation was concomitantly performed in 18 patients. There were 18 patients in the control group (non-exercising, RHB-). Patients from both groups were assessed before and after the rehabilitation with exercise echocardiography and spiroergometry to the individual maximum. The intervention group underwent the managed rehabilitation programme. The control group exercised individually. RESULTS: Reduction of the heart rate (HR) values at rest and on exercise and of the systolic and diastolic blood pressure (sBP, dBP) was observed in the exercising group. However, these changes were not statistically significant. The systolic, diastolic and global LV function parameters showed improvement although, once again, not statistically significant. Highly significant improvement in exercise tolerance (1.41 W/kg before and 1.67 W/kg after, p < 0.01) and peak oxygen consumption (20.0 ml/min/kg before and 23.6 ml/min/kg after, p < 0.01) were observed in the exercising patients. Improvement in functional and aerobic capacity in the control group was not statistically significant. The resting and exercise parameters (SF, sBP, dBP) have not changed either. CONCLUSION: The ambulatory rehabilitation programme was associated with improvement in circulatory response to exercise together with reduction in resting and exercise SF, sBP a dBP values. Tendency towards improvement in systolic, diastolic and global LV function parameters was observed even though not statistically significant in our sample. Unlike control group, the exercising group showed significant increase in exercise tolerance and aerobic capacity (p < 0.01). Managed rehabilitation programme enabled evaluation of the outcomes of the surgery, better education of the patients and optimal adjustment ofpharmacotherapy, the anticoagulation treatment in particular. We did not observe any adverse reactions or other complications associated with the exercise.

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Primary screening in vitro and study on the mode of action of oracin in Ehrlich ascites carcinoma cells have been performed. The measure of the cytotoxic effect was the degree of inhibition of 14C-adenine and 14C-valine incorporation into TCA insoluble fraction of Ehrlich ascites carcinoma (EAC) cells. The inhibitory effect was characterized by IC50 values. The biosynthesis of nucleic acides indicated by the incorporation of 14C-adenine was more sensitive (IC50 = 66 micromol/ l) than the biosynthesis of proteins indicated by the incorporation of 14C-valine (IC50 = 196 micromol/l). To elucidate the biochemical mode of action, the effect of oracin on dynamics of biosynthesis of macromolecules indicated by the incorporation rate of [14C] labeled precursors (adenine, thymidine, uridine, valine) into appropriate macromolecules of EAC cells was studied. Oracin inhibited incorporation of all four precursors into the trichloracetic acid - insoluble fraction of Ehrlich ascites cells. The extent of inhibition was dependent on both time and drug concentration. We found that oracin inhibited activity of topoisomerase II by 100% at concentration 5 to 15 micromol/l.

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Development of amino acid solutions for i.v. use proceeds worldwide, the main stimulus being the expanding physiological and pathophysiological findings of specific effects of some amino acids and their metabolism and the need to improve intensive metabolic care. New Czech preparations in this respect are the series of NEONUTRINS 5%, 10% and 15% (Infusia Ltd. Horátev). They are modern preparations which meet the pretentious criteria of contemporary amino acid solutions (balanced ratio of all essential, semiessential and assisting amino acids, a high content of essential and branched-chain amino acids, amino acids with specific pharmacodynamic effects). In a multicentre open clinical study the authors assessed the tolerance, safety and efficacy of NEONUTRIN 15% in 82 patients requiring total parenteral nutrition on account of catabolic states of different etiology. The preparation was administered repeatedly in an all-in-one mixture (together with glucose and lipid emulsions) by means of a central venous catheter. A total of 801 doses was administered. The trial provided evidence of very good tolerance and safety of the preparation with a practically zero incidence of undesirable effects. The follow-up of basic indicators of nitrogen metabolism confirmed also the efficacy of NEONUTRIN 15% in comprehensive treatment of patients (stabilization of nitrogen balance in the acute stage of a disease, normalization of the plasmatic aminogram).

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BACKGROUND: The use of hypertonic-hyperoncotic solutions (HHS) is a modern method of volume restoration in hypovolaemias of different etiology. The objective of the present work was to evaluate the effectiveness and safety of the hypertonic-hyperoncotic plasma expander Tensitone (7.5% NaCl in 6% dextran 70, Infusia a.s., CR) in patients with a massive acute blood loss. METHODS AND RESULTS: In a multicentre clinical study the authors investigated the effect of a rapid infusion of a small volume of tensitone (4 ml/kg) on the restoration of basic haemodynamic parameters, diuresis and the general condition of 81 patients with massive traumatic or peroperative haemorrhage. As compared with the effect of standard volume expanders (N = 34), Tensitone had a markedly more rapid and more pronounced effect on the normalization of the blood pressure (p < 0.01), heart rate (p < 0.05), central venous pressure and diuresis (p < 0.01). The haemodynamic effects of Tensitone are almost immediate (rise of blood pressure within 10 minutes) while they are at the same time sufficiently protracted (for at least 2 hours). The tolerance and safety of treatment were very good, more serious undesirable effects (thrombophlebitis) were recorded only in 3.6% of the patients. CONCLUSIONS: Tensitone is an effective and safe preparation for rapid small volume resuscitation. Its use is consistent with modern trends in intensive care and acute medicine.

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BACKGROUND: Postsynaptic alpha 1 adrenoceptor blockers are considered suitable drugs for modern vasodilatatory treatment of chronic heart failure. Therefore new analogues of these substances with more favourable characteristics than those of their main representative, prazosin are sought. The objective of the present work was to evaluate the therapeutic effect and tolerance of the original alpha 1-adrenoceptor blocker metazosin developed in the Research Institute for Pharmacy and Biochemistry (VUFB). METHODS AND RESULTS: In a multicentre clinical trial metazosin (tablets à 10 mg), 10-20 mg/day, were added to standard treatment of 56 patients of both sexes suffering from chronic congestive heart failure, for a period of eight weeks. The administration of metazosin led to rapid improvement of subjective complaints (in particular dyspnoea) as well as objective symptoms of peripheral congestion, to a significant (p < 0.05) regression of X-ray signs of pulmonary congestion and a slight (but statistically significant--p < 0.05) increase of the ejection fraction and cardiac output. After two months treatment the functional degree of severity of insufficiency according to the NYHA classification decreased from 2.7 to 2.2. Metazosin did not induce tachycardia and was well tolerated by the patients. CONCLUSIONS: Metazosin (Kenosin) tablets is a suitable supporting drug in the comprehensive treatment of chronic cardiac failure, in particular if refractory to treatment.

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The authors discuss the diagnosis and treatment of acute myocardial infarct complications. They describe a rare combination of these complications: interventricular septum rupture and left ventricular aneurysm with envelope perforation, filled by a thrombus.

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The authors examined a group of hitherto not treated patients with primary hypertension and hypertrophy of the left ventricle. By means of echocardiography and isometric loading they investigated the effect of treatment on the left ventricular morphology and function. Despite long-term normalization of casual and loading values of the blood pressure the authors did not observe a significant regression of LV hypertrophy. The authors did not find a relationship between the casual blood pressure and weight of the left ventricle with exception of the diastolic pressure after a load. The indicators of diastolic function did not correlate with the weight of the left ventricle but with changes of the end diastolic volume and blood pressure.

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In a representative group of 10 conventional antihistaminic agents, a comparison of their H1-antagonistic efficacy was carried out in a series of pharmacological tests. A very good correlation of findings obtained under in vivo conditions in guinea-pigs (tests of detoxication of histamine and histamine aerosol) and a test in rats, which examined the influence on local changes induced by histamine in the dermal region, was demonstrated. No statistically significant correlation of in vivo findings and receptor binding studies on membranes of the rat brain (displacement of (3H)-mepyramine) was found. The tests based on displacement of (3H)-mepyramine are usable primarily for the needs of screening research. The predictive value of pharmacological findings obtained under in vivo conditions is substantially higher.

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In their generally designed presentation the authors focus on practical problems concerning indication, different stress modalities and projections, evaluation and interpretation of findings, as well as on technical novelties and their use. Only dynamic exercise echocardiography is being discussed. Currently available knowledge is assessed in the light of the authors' own experience. Problems of evaluation and interpretation are considered to be most intricate. In the authors' opinion, many technical problems which have prevented the routine use of the method in practice will be eliminated by introducing technical novelties such as digitalization of the display with image loop. Other innovations will certainly be used to advantage and render the method less demanding and far more widespread.

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Using two-dimensional echocardiography, the authors made a one-year investigation of left ventricular function in a group of patients after a first transmural myocardial infarction. They evaluated subjectively and quantitatively changes in the contractility and the development of the diastolic area of the left ventricle. They revealed a certain improvement of the contractility, probably as a result of the development of a collateral circulation and altered structure of the infarction focus associated with dilatation of the left ventricle by the Frank-Starling mechanism.

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The authors examined by echocardiography at rest and after exertion a group of 55 patients after a clinically confirmed first transmural infarction. They compared the echocardiographic findings with coronarographic ones. The finding at rest, as regards impaired mobility of the left ventricular wall, corresponded to the clinical finding and the coronarographic finding. By diagnosis of the extended asynergy of contraction during an isometric load it was not possible to differentiate the functional and organic cause of impaired mobility and thus to assess the extent of the coronary affection. The impaired mobility of the left ventricular wall is associated above all with the state of the blood supply rather than with the finding on the coronary artery.

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Drugs of the pizotifen type (pizotifen, cyproheptadine), possessing high H1-antihistamine and high antiserotonin activities in animal experiments, exert potent inhibitory actions on the passive cutaneous anaphylaxis (PCA) reaction in the rat. The drug pipethiadene, a 4,9-dihydrothieno(2,3-c)-2-benzothiepin derivative also belongs to this group. Selective histamine H1-antagonists alone are unable to cause pronounced reduction of the intensity of the PCA reaction in the rat, but in local reactions induced in rats by compound 48/80, histamine H1-receptors seem to play major role.

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