Lviv Clinical Bulletin

7-12

Authors: Chooklin S., Hranat O.

Introduction. The incidence of acute pancreatitis (AP) in the world has increased over the last years, mainly due to alcohol consumption. The increasing of the AP severity is characterized by pancreatic necrosis, local complications and systemic organ dysfunction and is about 20.0% of all cases of AP. Despite the successes of intensive care, early mortality from AP remains high. The main component in the pathogenesis of acute pancreatitis is the transition from local to the system inflammation that causes the increasing of the disease severity. Changes of microcirculation and endothelial dysfunction are an important step on the way from the mild to severe course of the disease. Aim. To determine the pathogenetic role of proinflammatory cytokines, adrenal molecules and E-selectin in the occurrence of vascular disorders and organ dysfunction in patients with acute necrotic pancreatitis. Materials and methods. The study involved 53 AP patients (28 – severe, 25 – mild). We measured interleukin-6, interleukin-18, ICAM-1 and E-selectin in the blood plasma. Flow in the visceral arteries was assessed with the help of the Doppler sonography. Organ dysfunction was evaluated on the SOFA scale. The severity of pancreatitis in patients was determined according to the criteria of J. H. C. Ranson. Results. Patients with AP during the hospitalization showed an increase of the levels of IL-6 and IL-18 in 12.11 and 2.02 times, respectively. However, a differentiated assessment of the individual forms of AP revealed a significant increase in both proinflammatory cytokines only in the case of acute necrotic pancreatitis, whereas IL-18 was not significantly elevated in patients with edematous pancreatitis. At the same time, the mean values ​​of IL-6 and IL-18 in patients with acute necrotic pancreatitis significantly exceeded the indicators of patients with pulmonary hypertension in 4.25 and 1.84 times, respectively. It has been established that proinflammatory cytokines mediate the damage of organs by their action on the endothelium of blood vessels and leukocytes by the increasing of the expression of adrenal molecules, which in turn leads to rolling, adhesion, aggregation and transmigration of leukocytes in the involved tissues. Cytokines stimulate endothelial cell membrane and cause the increased synthesis of selectin that bind to leukocytes through the appropriate receptors. This leads to roller leukocytes on the walls of postcapillary venules. The activation of intercellular adhesion molecules (ICAM) and vascular cell adhesion molecules (VCAM) on endothelial cells promotes the adhesion of leukocytes to vascular endothelium and their tissue transmigration. Inflammation cells respond to initial events by releasing enzymes and active forms of oxygen that cause damage of the tissues. Conclusions. It was determined that the levels of proinflammatory cytokines and adhesion molecules increase in the blood of AP patients. Their level correlates with the organ dysfunction and disturbances in splanchnic blood flow.

17-19

Authors: Denesiuk O.

Introduction. One of the most actual problems of modern cardiology is the study of endothelial function, functional and structural changes in arteries, especially in patients with arterial hypertension (AH), the atherosclerotic process primarily affects the arteries of the elastic type (aorta) and slightly less – of the muscle type (brachial artery). Insufficient studies have been done to diagnose the endothelial function and arterial remodeling in the case of coronary heart disease (CHD), in particular with comorbid hypertension. Aim. To study the endothelial and functional-structural changes in blood vessels in patients with unstable angina (UA) with comorbid hypertension. Materials and methods. There were surveyed 143 men with UA and comorbid hypertension. The average age of the examined persons was 55.30 ± 0.63 years. Systolic blood pressure was 163.20 ± 1.50 mmHg, diastolic– 101.10 ± 0.67 mmHg. The duration of hypertension, according to information from the history, 9.62 ± 0.55 years. 60.1% of the surveyed previously had myocardial infarction (MI), 15.4% – two and more MI. The UA according to the classification of NYHA: II FC was diagnosed in 15.4%, and III FC – in 84.6%. Chronic heart aneurysm was in 11.2% of the patients, history of stroke was in 2.8%. Patients with neutropenia with comorbid hypertension had the following disturbances in rhythm and conduction of the heart: sinus tachycardia – in 14.0%, ventricular extrasystoles – in 4.9%, blockade of the left bundle branch of His – in 4.2 % Diagnostic constellation included: general analysis of blood and urine; coagulogram, determination of the levels of aspartate aminotransferase, alanine aminotransferase, bilirubin, creatinine, urea in blood, and for exclusion of the MI – sometimes the level of troponin I; ECG, echocardiography. To study the functional properties of the a. brachialis we have used dopplechocardiography. The initial diameter of the brachial artery, the reaction to hyperemia, which was treated as endothelium-dependent vasodilation, was determined. The test results were evaluated between the 30th and 90th seconds after the cuff was removed, which was previously applied over the shoulder and stopped the flow until the end of the 5th minute. Endothelial-independent vasodilatation was determined after 15-20 minutes of rest and taking nitroglycerin tablets. The diameter of the vessel was measured after 3 and 5 minutes. It was considered normal to increase the diameter of the brachial artery by 10.0% in 90.0 seconds during the reactive hyperemia and 20.0% in 5 minutes after taking nitroglycerin. The proposed study of the ratio of pulsed arterial pressure to shock volume, called the rigidity index of the aorta, was used to assess the overall arterial compliance. Results. It was found that in patients with unstable angina with comorbid hypertension increases the stiffness of the aorta, due to the increase in systolic, diastolic and pulse blood pressure. In these patients there is endothelial dysfunction with decreased endothelium-dependent and endothelium-independent vasodilation of the brachial artery, resulting in structural changes in the arteries. In patients with unstable angina, combined with hypertension, there were found the increased thickness of the intima-media complex, due to remodeling and changes in the structure of the brachial artery. Conclusions. In patients suffering from the unstable angina with the AH there was defined the increase of the index of rigidity of aorta, blood pressure, thickness of intima-media complex, decrease of the vasodilatation, remodeling and change in structure of the brachial artery that must be taken into account in the treatment algorithm.

23-28

Authors: Vares Ya., Gorak V., Filiplsky A.

Introduction. Frontal sinus fracture, despite rather low frequency of their occurrence, is one of the most complex problems of modern cranio-maxillofacial surgery, and strategies for their treatment are controversial. The complex anatomical structure of the sinus, the proximity of vital organs (brain, eyeball, nasal cavity), the need to attract the special diagnostic equipment, high risk of intra- and postoperative complications – only some factors that emphasize the severity of damage, determine its prognosis and require the multidisciplinary approach to the diagnostic and treatment process of the specified category of the patients. Frontal sinus fractures occur in 5.0-15.0 % of all cranio-maxillofacial injuries and may vary from isolated anterior table fractures to complex fractures involving the sinus, orbits, skull base and intracranial content. The aim of this work was to generalize the literature data and personal experience of the surgical treatment of patients with traumatic fractures of the frontal sinus. Materials and methods. The professional literary analysis reports and case histories of 18 patients (17 men and 1 woman aged 18-45 years) with the fractures of the frontal sinus that were treated in the department of maxillofacial surgery, neurosurgery and otorhinolaryngology of Lviv Regional Clinical Hospital and Lviv City Emergency Hospital during 2005-2011. Results. Among the most common complications of fractures of the anterior wall of the frontal sinus are aesthetic defects, paresthesia of the lobar region, chronic sinusitis. Fractures of the deeper structures, which are accompanied by the aggressive surgical tactics, can lead to persistent diplopia or loss of vision, threatening inflammatory complications in the form of meningitis and brain abscess. Computer tomography with three-dimensional reconstruction today is the standard in the diagnosis of fracture of the frontal sinus. Axial projections provide the information on the state of the anterior and posterior sinus walls, the coronal – allows the visualization of its bottom and the vaults of the ocular fossa, and the sagital – the nose-frontal cavity and the natural sinus duct visualization. Regardless of a severity of the trauma all fractures require a thorough diagnostics, including a multiplanar computed tomography and endoscopic revision of the sinus cavity, allowing to choose the most appropriate treatment strategy and to minimize the patient’s morbidity. Conclusions. Proposed by the World Association of cranio-maxillofacial osteosynthesis the science-based and clinically proven algorithms for the diagnosis and treatment of fractures of the frontal sinus allow to provide the quality medical care to patients under the conditions of any location and combination of traumatic injury.

33-35

Authors: Dutka Ya.

Introduction. The problem of surgical treatment of patients with tumors of the extrahepatic bile ducts is one of the most important and complicated in the surgery of the hepatopancreatoduodenal zone and is of increasing interest to the researchers. The main method that gives a chance to cure cancer patients is the removal of a tumor supplemented with lymphadenectomy, but it can only be performed in 9,0-46,0% of patients. The volume of surgery depends on the localization of the tumor, the extent of its spread – local and regional. The average survival time of patients whose tumors can not be removed does not exceed 6-7 months, whereas after a radical intervention, the five-year survival rate of cancer of such patients is from 8.0 to 42.0%. Aim. To work out an effective algorithm for treating the patients with pulmonary embolism taking into account age and general condition, localization, distribution and stage of the tumor process. Materials and methods. The results of the examination and surgical treatment of 205 patients with pulmonary hypertension, which were treated in the clinic in the period from 1991 to 2012, were analyzed. Men were 99 (48.3%) at the age of 61.6 ± 9.7 years, women – 106 (51.7%) at the age of 62.7 ± 9.5 years. For all the patients there were done complete blood count blood and urinalysis, also the alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase and amylase, bilirubin and its fractions levels have been determined in serum. Among the instrumental examination ultrasonography, computed tomography, magnetic resonance imaging and endoscopic retrograde cholangiography methods to confirm the diagnosis of tumor of the biliary system were applied. The results of these surveys, as well as during the intraoperative audit, determined the tumor’s operability. The choice of the method of surgery was determined by the general condition and age of the patient, the localization of the tumor, the degree of its prevalence, the duration of jaundice, the severity of hepatic renal failure and concomitant diseases. Conservative treatment was used to prepare the patient for the surgical intervention, minimally invasive methods of treatment – endoscopic papilloprotectomy, endoscopic stenting and percutaneous throughheat drainage of bile ducts, radical and palliative operations, and intraarterial polychemotherapy. Radical operations were performed for 21.5% patients. While conducting palliative interference a preference was given to internal drainage of bile ducts. Results. It is established that the choice of the method of surgical intervention depends on the localization of the tumor, anatomical features, the stage of the process, previous operations on the bile ducts. Minimal invasive treatment methods – endoscopic stenting, endoscopic papilloprotectomy and percutaneous throughheat drainage with lesser risk for the patient may replace the palliative surgery in cancer patients with non-resection of extrahepatic bile ducts. In patients with nonresectable tumors of extrahepatic bile ducts, it is advisable to use palliative surgical treatment, which increases the rate of annual survival of patients to 63.6%. Conclusions. The required results allowed to differentiate and to individualize the choice of optimal tactics for the patients with tumors of extrahepatic bile ducts and at the same time to minimize a number of postoperation complications. On the basis of required data, the complex algorithm of treatment tactics for patients with tumor obstruction of this localization which consists of four stages has been proposed. The elaborated algorithm promotes the adequate therapeutic tactics and improves treatment outcomes in patients with tumors of extrahepatic bile ducts.

40-46

Authors: Katerenchuk I., Tsyhanenko I., Katerenchuk O.

Introduction. For a long time, the main medication for treating and preventing of thrombotic complications was unfractionated heparin (UFH). However, despite its high efficiency, UFH has a number of disadvantages and side effects. Significant advantages over UFH are low molecular weight heparins or low molecular weight heparins (LMWH). LMWH is a product of enzymatic or chemical depolymerization of conventional heparin. The low molecular weight fractions of heparin obtained during the polymerization process have new pharmacodynamic properties. Today about 10 drugs of LMWH are used. They are obtained by various methods of depolymerization of UFH, resulting in fractions with a lower molecular weight (from 4000 to 6500 daltons). Aim. To review and analyze the current knowledge about the effectiveness and safety of use of LMWH for the treatment and prevention of acute coronary syndrome. Materials and methods. The content analysis, method of system and comparative analysis, the bibliosemantic method of study of actual scientific researches concerning the efficiency and safety of the use of LMWH for the treatment and prevention of acute coronary syndrome has been used. Comparison of the effectiveness of various preparations of low molecular weight heparins is carried out taking into account the results of multicenter studies. The results indicate that LMWH is an effective and safe remedy for the treatment of acute coronary syndrome and preventing coronary events in patients at different risk levels. LMWH are much less than UFH binding to plasma proteins that can neutralize their antithrombotic activity. The low affinity of LMWH to plasma proteins that neutralize heparin is due to their high bioavailability of low doses and greater predictability of anticoagulant response at high doses. LMWH have longer antithrombotic activity than UFH. While the half-life in blood plasma (T1 / 2) of UFH is, if judged by its activity against factor Xa, 50-60 minutes, T1 / 2 of LMWH after intravenous administration is within 1.5-4.5 hours. Significant duration of antithrombotic effect of LMWH allows them to be assigned once or twice a day. The bioavailability of most of the LMWH after deep subcutaneous injection is about 90.0%, whereas in case of UFH it is 15.0 – 20.0%. All of the considered features of pharmacokinetics and pharmacodynamics of LMFH suggest their undoubted advantage over UFH, which consists in the fact that with both – preventive and therapeutic purpose – subcutaneously constant dose can be administered. In addition, LMWH are resistant to inactivating of factor 4 of thrombocytes and do not increase their arrreation under the influence of various inductors. In the case of LMWH, the frequency of thrombocytopenia is much lower. Conclusions. LMWH is an effective and safe medication of the treatment of acute coronary syndrome and for the preventing of coronary events in patients at different risk levels.

54-61

Authors: Katerenchuk O.

Introduction. Heart failure is a clinical syndrome associated with the high rates of short-time and long-time mortality. The pathological role of several neurohumoral systems is well-established in heart failure progression. According to the data available from the basic experiments the role of the endogenous cannabinoid system in heart failure progression is considered. Aim. To make a review of literature and topical scientific sources regarding the possible pathological role of endogenous cannabioid system in heart failure syndrome. Materials and methods. Content analysis, method of system and comparative analysis, bibliosemantic method of research of actual scientific researches on the possible pathological role of endogenous cannabioid system in heart failure syndrome were used. Results. So we have found that several pathological processes in heart failure syndrome are the consequences of endogenous cannabinoid system influence on the hemodynamic. For the majority of patients with the end-stage heart failure a strong and progressive loss of appetite and weight are observed. There are no doubt that this fact can be explained by impaired liver function as the phenomena of “congestion liver,” but this is probably also due to the hyperactivation of endogenous cannabinoid system. As its known, the activation of cannabinoid system due to the activation of CB1 receptors causes an increase in appetite, changes in metabolism of adipose tissue and further leads to obesity. The drug rimonabant was studied as a central cannabinoid receptor blocker as blocking the CB1 receptors that results in the loss of appetite and weight. Heart failure is a condition associated with the hyperstimulation of cannabinoid receptors and/or the depletion of effects of the mediators on them, which leads to loss of appetite and weight. Heart failure is associated with the development of abnormal liver function, elevated liver enzymes and progressive fibrosis process in liver. Also the hyperactivation with further depletion of CB1 is strongly related with the progressive cirrhotic process in the liver as it was observed in several experiments on mice. Depression. For most patients with the high functional class of heart failure the development of depression is usually observed. According to the own observations, among the patients with heart failure NYHA I the depression rate is not more than 5,0 %, in NYHA II – 12,0 % in NYHA III – 40,0 %, in NYHA IV – up to 70,0 %. Theoretically, this could be due to hyperactivation and further depletion of CB1 stimulation in the central nervous system, as its known that stimulation of the CB1 causes euphoria, inhibition/depletion leads to depression. Pain. The acute decompensation of chronic heart failure does not often accompany the patients’ complaints on pain of muscular origin. CB1 receptor activation is known to lead to stable analgesia, inhibition/depletion – to the pain. Conclusions. The hyperstimulation with further depletion of CB1 receptors and mediators results in hypotension, bradycardia, depression, muscle pain and liver cirrhosis – that usually accompanies the decompensated and end-stage heart failure. Further discovering of CB1 exogenous agents acting on central nervous system and/or peripheral CB1 receptors can result in creating the new group of drugs in heart failure treatment.