Lviv Clinical Bulletin

7-11

Authors: M. A. Stanislavchuk, A. Al Salim

Objective. To establish the features of cardiac remodeling in patients with postinfarction cardiosclerosis and type 2 diabetes based on gene polymorphism leptin receptors LEPR Q223R. Materials and methods. The study involved 147 patients with stable coronary heart disease (CHD) with postinfarction cardiosclerosis (100.0 % of men aged 53.0 ± 7.83 years). Type 2 diabetes was detected in 64 (43.5 %) patients. CHD was established regarding the recommendations of the AHA/ACC (2014) and ESC (2013), verification of the diagnosis of type 2 diabetes was conducted under the existing criteria. Gene polymorphism LEPR Q223R determined by PCR mode Real­Time. Echocardiographic studies were performed in M­, B­ and D­mode on the ″Logic 500 Sono Series″ (General Electric, Korea). Results and discussion. In CHD patients with type 2 diabetes size of the left atrium was significantly higher than those in patients with CHD without diabetes. In men with postinfarction cardiosclerosis and type 2 diabetes was registered significantly higher myocardial mass, wall thickness, end systolic and diastolic dimensions than in patients without diabetes. In patients with CHD with type 2 diabetes final systolic size, end systolic volume, and end systolic extent index were significantly higher than in patients with CHD without diabetes. Presence of type 2 diabetes in patients with CHD was associated with the increase of end­diastolic volume, and left ventricular mass. In patients with postinfarction cardiosclerosis and type 2 diabetes was noted a significant worsening of cardiac systolic function: the degree of shortening of the anteroposterior size of the left ventricle (ΔS) in systole and ejection fraction were 7.4 and 6.6 % lower than in patients without diabetes. Among patients with CHD there were revealed 25.2 % homozygotes QQ, 42.4 % ­ QR ­ heterozygotes and 32.7 % ­ RR homozygotes. RR genotype was associated with a higher frequency of maladaptive remodeling type characterized by the dilation of the heart’s chambers and thinning of the myocardium walls, especially in patients with type 2 diabetes. The frequency of the eccentric hypertrophy in homozygotes RR was 77.0 % and was significantly higher than among carriers of allele Q (OR = 4.60, 95,0% CI 2.13­9.94), while the frequency of concentric left ventricular hypertrophy was significantly lower (2.3­2.5 times, p < 0.05). Based on the multiple linear regression analysis it was confirmed that the genotype RR gene LEPR Q223R is an independent predictor of decrease of ejection fraction in patients with CHD associated with Type 2 diabetes. Conclusions. Gene polymorphism of LEPR Q223R is a predictor of maladaptive type of cardiac remodeling in patients with postinfarction cardiosclerosis and type 2 diabetes.

16-25

Authors: M. Abrahamovych, O. Abrahamovych, S. Tolopko, M. Ferko

Introduction. Engaging of the different organs and systems into the pathological process, including the organs of the respiratory system, interpretated as syntropic co­ and polymorbid lesions, including the most common ­ hepatopulmonary syndrome (HPS), in many cases determines the severity of the general condition of the cirrhotic patients, leads to a significant reduction of their life quality, disability, has a decisive prognostic value at all the stages of the treatment and is the leading cause of the death of the hepatological patients. Taking into the account the poor prognosis and high mortality (41.0 %) of the patients with the HPS, it is required the constant monitoring and paying the special attention of the physicians to such patients and also prescribing the adequate pathogenesis­based drugs to optimize the treatment. The aim of our study was to modify the treatment of the cirrhotic patients with the hepatopulmonary syndrome of different severity degrees on the base of clarifying the characteristics of their pathogenesis and to evaluate its effectiveness. Materials and methods. Into the study in randomized manner with the preliminary stratification by the presence of the HPS were involved 93 patients [26 women (28.0 %) and 67 men (72.0 %); aged 27 to 67 years, who were treated in Lviv Regional Hepatological Center during 2012­2015. To elucidate the pathogenesis of the HPS for appointing the most effective pathogenetically reasonable treatment, we have determined the content of some vasoactive humoral and metabolic factors, namely the endothelium­dependent (cyclic guanosine monophosphate (cGMP), endothelin­1 (E­1)), tumor necrotizing factor α (TNF α) and the indices of the renin­aldosterone system (renin, aldosterone) in the blood plasma of the patients by ELISA. Also there were examined the gas composition of the venous blood and the acid­base balance (ABB) state. To determine the effect of the mediators of the autonomic nervous system (ANS) on the vascular tone, we have assessed its state by the registration of the heart rate variability (HRV). After the treatment clinically and laboratory indices and life quality of the patients of the experimental group (EG) who were treated by the modified by us technique and of the control group (CG), where the patients received the standard treatment were evaluated. Results. During the study of some pathogenetic mechanisms of the HPS it was found the inverse correlative connection between the values of carbon dioxide partial pressure, bicarbonate, standard bicarbonate, bases excess in the blood and in the extracellular fluid and the severity of the HPS, which was manifested by the progressive metabolic acidosis that required the medical correction. With the growth of the severity of the respiratory lesions the levels of cGMP, E­1, TNF α, renin and aldosterone in the blood plasma of the cirrhotic patients were significantly (p < 0.05) increased, which made theim to be the criteria to justify the appointment of the pathogenetic treatment. During the diagnosis of the ANS state in the cirrhotic patients with the syntropic respiratory lesions using HRV registration we proved the overwhelming influence of the sympathetic part over the parasympathetic in the patients with the I degree HPS with the directly proportional increase of the neurohormonal effects according to its severity. The modified by us method of the treatment of the patients considering the investigated pathogenic mechanisms of the liver cirrhosis and the HPS, its severity, as well as the conventional one, gave the positive result, but by its quality parameters the conventional medical complex significantly yielded comparing to the modified by us algorithm. Statistical analysis of the questionnaires MOS SF­36 before and after the treatment indicated a significant (p < 0.05) improvement of the physical activity, vitality, mental and general health, reducing of the pain and the role of the emotional stress in disability, resulting into the improvement of the physical and mental status of the patients treated by the modified by us technique and shows its effectiveness. Conclusions. Investigations of the indices of ABB (carbon dioxide partial pressure, levels of bicarbonate, standard bicarbonate, bases excess in the blood and in the extracellular fluid) the endothelium­dependent (cGMP, E­1), TNF α and the indices of the renin­aldosterone system (renin, aldosterone), the state of the ANS and their dependence on the severity of the HPS substantiated the advisability of including into the medical complex of the patients with the I degree HPS in addition to the detoxification, diuretic and hepatoprotective treatment the electrolyte combined isotonic solution (sodium, potassium, magnesium, calcium chloride, acetate, malate) ­ 500.0 ml intravenously once a day, pentoxifylline ­ 1 tablet (100.0 mg) twice daily, spironolactone ­ 1 tablet (25.0 mg) twice daily, carvedilol ­ 1 tablet (3,125 mg) once a day; with the II degree HPS ­ 4.0% sodium bicarbonate ­ 100.0 ml intravenously once a day, sol. Pentoxifyllini 0.05% ­ 100.0 ml intravenously once daily, valsartan ­ 1 tablet (40.0 mg) once daily, spironolactone ­ 1 caps. (50.0 mg) twice a day; with the III degree HPS ­ 4.2% sodium bicarbonate ­ 100.0 ml intravenously once a day, sol. Pentoxifyllini 0.05% ­ 200.0 ml intravenously once a day with the transition to oral use – 1 tablet (100.0 mg) of pentoxifylline twice daily, enalapril ­ 1 tablet (5.0 mg) once daily, spironolactone ­ 1 caps. (100.0 mg) twice a day. Using the modified pathogenetic reasonable treatment in the cirrhotic patients taking into account the severity of the HPS allowed us to increase its efficiency by 13.7 % and to improve the physical activity, vitality, mental and general health, reduce pain and the role of the emotional problems in disability, leading to the improvement of physical and mental status of the patients.

32-37

Authors: U. Abrahamovych, O. Abrahamovych, L. Tsyhanyk, O. Synenkyi, S. Guta

Introduction. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the chronic inflammation and multisystemic damages, accompanied by lesions in osteoarticular system, including secondary osteoporosis (OP) ­ an important risk factor for low­energy fractures. The most common noninvasive osteoporosis tests currently in use in Ukraine include ultrasound densitometry and X­ray densitometry (dual­energy X­ray absorptiometry (DXA) and hand bone X­ray densitometry). The objective is to compare diagnostic values of bone mineral density tests that employ ultrasound densitometry, X­ray osteodensitometry, and dual­energy X­ray absorptiometry in premenopausal women with SLE. Materials and methods. The study randomly included 51 women aged between 21 and 53 (mean age at the time of the study – 38.21 ± 1.66) which were diagnosed with SLE according to the criteria of the American College of Rheumatology (1982, 1997); all women at the time of the study were premenopausal. 100.0 % of the patients received methylprednisolone at a dose of 4.0 to 24.0 mg/day (average dose – 11.12 ± 0.81 mg/day) and calcium supplements at a dose of 1000.0 mg/day in combination with vitamin D at a daily dose of 400.0 IU. The average duration of treatment with glucocorticoids and calcium supplements corresponded to the average disease duration. Bone mineral density was assessed through calcaneus ultrasound bone densitometry performed with SONOST-2000 device (OsteoSys Co., Ltd, Seoul, Korea), hand bone X­ray densitometry performed with “ARM­Osteoloh” application, and dual­energy X­ray absorptiometry of lumbar spine and proximal femur performed with dual­energy X­ray absorptiometer (Stratos, France). Statistical analysis of the obtained results was carried out in MS Excel and IBM SPSS Statistics applications. Results and their discussion. The results of ultrasound densitometry among 51 patients with SLE were as follows: 13 (25.49 %) women were diagnosed with osteoporosis (average T­score ­(­2.77) ± 0.08); 26 (50.98 %) women were diagnosed with osteopenia (average T­score ­ (­1.81) ± 0.08), 6 of them (11.76 %) ­ with the first degree of osteopenia (average T­score ­ (­1.25) ± 0.04), 9 of them (17.65 %) ­ with the second degree of osteopenia (average T­score ­ (­1.74) ± 0.06), 11 of them (21.57 %) ­ with third degree of osteopenia (average T­score ­ (­2.17) ± 0.02); 12 (23.53 %) women had normal BMD (average T­score ­ (­0.7) ± 0.07). The results of hand bone X­ray densitometry among all patients with SLE showed changes in bone mineral density. 20 (39.22 %) women were diagnosed with osteoporosis (average T­score ­ (­3.03) ± 0.08); 23 (45.09 %) women ­ with osteopenia (average T­score ­ (­2.01) ± 0.08), 4 of them (7.84 %) ­ with the first degree of osteopenia (average T­score ­ (­1.2) ± 0.11), 19 of them (37.25 %) ­ with the third degree of osteopenia (average T­score ­ (­2.18) ± 0.03); 8 women (15.69 %) had normal BMD (average T­score ­ (­0.38) ± 0.01). The results of lumbar spine bone density test employing dual­energy X­ray absorptiometry (DXA) were as follows: 16 (31.37 %) patients with SLE were diagnosed with osteoporosis (average T­score ­ (­3.14) ± 0.13); 21 (41.18 %) patients were diagnosed with osteopenia (average T­score ­ (­1.56) ± 0.13), 10 of them (19.61 %) ­ with the first degree of osteopenia (average T­score ­ (­1.14) ± 0.03), 7 of them (13.73 %) ­ with the second degree of osteopenia (average T­score ­ (­1.70) ± 0.07), 4 of them (7.84 %) ­ with the third degree of osteopenia (average T­score ­ (­2.35) ± 0.03); 14 patients (27.45 %) had normal levels of BMD (average T­score ­ (­0.36) ± 0.15). The results of proximal femur bone density test employing DXA were as follows: only 12 (23.53 %) patients with SLE were diagnosed with osteopenia (average T­score ­ (­1.28) ± 0.08), 5 of them (9.80 %) ­ with the first degree of osteopenia (average T­score ­ (­1.03) ± 0.03), 3 of them (5.86 %) ­ with the second degree of osteopenia (average T­score ­ (­1.65) ± 0.04), 4 of them (7.84 %) ­ with the third degree of osteopenia (average T­score ­ (­2.05) ± 0.03); 39 patients (76.47 %) had normal levels of BMD (average T­score ­ (0.2) ± 0.14). The findings demonstrate direct correlation between T­score results obtained by ultrasound heel bone densitometry and T­score results obtained by lumbar spine DXA (r = 0.72, p < 0.001) as well as T­score results obtained proximal femur DXA (r = 0.38, p < 0.05). The findings also indicate direct relationship between the results of BMD tests employing hand bone X­ray densitometry and lumbar spine DXA (r = 0.56, p < 0.001) as well as proximal femur DXA (r = 0.37, p < 0.05). There is also direct correlation between the results of the BMD tests obtained by ultrasound heel bone densitometry and X­ray hand bone densitometry (r = 0.7, p < 0.001). Both ultrasound heel bone densitometry and X­ray hand bone densitometry identified 89.0 % of patients who had lowered BMD levels according to the results of lumbar spine DXA and 100.0 % of patients who had lowered BMD levels according to the results of proximal femur DXA (sensitivity – 0.89 and 0.1 respectively). Ultrasound densitometry demonstrated higher specificity compared to X­ray osteodensitometry: it identified 57.0 % of the patients who had normal BMD levels according to the results of lumbar spine DXA and 31.0 % of the patients who had normal BMD levels according to the results of proximal femur DXA (specificity ­ 0,57 and 0,31 respectively). X­ray osteodensitometry identified 29.0 % of the patients who had normal BMD levels according to the results of lumbar spine DXA and 21.0 % of the patients who had normal BMD levels according to the results of proximal femur DXA (specificity ­ 0,29 and 0,21, respectively). Conclusions. The study demonstrated that both ultrasound heel bone densitometry and X­ray hand bone densitometry are highly sensitive compared to dual­energy X­ray absorptiometry and acceptable methods for diagnosis of osteoporosis in patients with SLE.

43-47

Authors: T. Butovа

Introduction. Postmenopausal women ­ one of the most critical periods in which modern woman spends a third of her life, and therefore the study of this problem is of particular interest. Today is proved the activity of steroidogenic ovarian function in postmenopausal women. It is known that one of the most biologically active forms of testosterone in men and women, which is formed from testosterone directly into the cells “respective authorities target” is dihydrotestosterone (DHT). It is also reported that testosterone may be involved in metabolic disorders glucose in healthy women and about the relationship between high levels of free testosterone incidence of type 2 diabetes mellitus (DM). The presence of the relative hyperandrogenemia may be related to the risk of cardiovascular diseases in postmenopausal women. However, despite the numerous studies of the peculiarities of androgens in the female body, until now this issue has not received its final decision. The aim of the study was to find out the features of the contents of DHT levels in postmenopausal women according to the comorbid diseases DM type 2 and hypertension (HT). Materials and methods. The study involved 137 females aged 45­60 years. Patients were stratified into three groups: 30 patients with type 2 DM (1st group), 34 patients with HT (2nd group), 42 patients with type 2 DM and HT (3rd group). Control of group ­ 31 postmenopausal women without the disease. In blood serum using ELISA methods were tested folitropin, DHT and concentration glucose and glycosylated hemoglobin (НbА1с). Results and discussion. Found that in patients with HT in postmenopausal was observed a statistically significant increase in the concentration preprandial glycemia and content НbА1с, DHT levels compared to women with postmenopausal without the disease. Joining hypertension in patients with type 2 DM accompanied by more pronounced, statistically significant increase of preprandial glycemia and НbА1с and most statistically significant DHT. Among indicators of glucose concentration, НbА1с DHT levels and there is a direct correlation, indicating a direct positive indicators of glucose dependence concentration in blood and the content НbА1с, DHT. Conclusions. In patients with HT in postmenopausal was observed a statistically significant increase in DHT concentrations in the blood compared to women with postmenopausal without the disease. At the same time in patients with type 2 DM, compared to patients with HT verified a clear increase in the content of DHT in the blood. Thus, to forecast the possibility of type 2 DM and comorbid HT during examination in postmenopausal women, should be considered the level of serum DHT.

53-59

Authors: S. Nyankovskyy, R. Furtak, M. Yatsula, O. Shpychka

Introduction. Respiratory system diseases were and continue to be a topical problem of the medicine overall and pediatrics in particular. Pneumonia is the most serious disease that kills children under 5 years old globally, taking about 1 million lives every year. Purpose of the study. To analyze the domestic and foreign literary sources of information dedicated to the role of pharmacogenetics in appearances of the severe forms and complications of pneumonia in children and also to describe a clinical case. Materials and research methods. Content­analysis, methods of systemic and comparative analysis, biblio semantic method of the actual scientific researches study about the role of pharmacogenetics in appearence of severe forms and pneumonia complications in children, analysis of a case of the disease of a particular patient who was under our observation. Source searching was done with the scientometric databases of medical information: PubMed­NC­BI, Medline, CochraneLibrary, EMBASE, ResearchGate using keywords: pneumonia, children, pharmacogenetics, xenobiotic biotransformation genes. In all, 41 sources in English, Russian and Ukrainian languages were analyzed. Results of the analysis. Pneumonia is an acute infectious inflammatory disease of the lung parenchyma, characterized by the infiltrative changes in lung tissue and respiratory failure. A lot of microorganisms can be a reason for pneumonia occurrence. Among the most common bacteria pathogens are: Streptococcus pneumoniae, Haemophilus influenzae type B, and among viruses it’s Human respiratory syncytial virus. Despite the timely diagnosis and an appropriate drug therapy the number of severe forms and complications of pneumonia is not being reduced. A lot of scientific studies of this topic during the last years are aimed at genetics exploration. Particularly, the area of pharmacogenetics is interesting and perspective part of it. About 50 % of adverse responses to drugs are caused by the genetic factors. Study of pharmacogenetic impact can serve as a basis for a creation of the individualized approach to the choice of treatment tactics and to the dosage regime. Genetic polymorphisms of xenobiotic metabolism determines the division of people into groups that differ in their ability to metabolize drugs from insufficient to ultrafast metabolisers. Genetic polymorphisms of xenobiotic metabolism can be the reason for occurrence of severe forms and complications of various diseases, including pneumonia in children. These genes include: glutathione transferases (GSTM), O­ and N­acetyltransferases (OAT, NAT1, NAT2) and others. Among the proteins which affect the speed of excretion of the pharmacological agents the special place belongs to P­glycoprotein, encoded by the gene MDR1. The research results of different authors showed that genetic polymorphism of MDR1 can be an important factor that determines the predisposition to various diseases and resistance to treatment. Conclusions. The researches of genes involved in the distribution, biotransformation and excretion of toxic products of decay of drugs, is a promising and important component of the pathogenesis and, accordingly, the diagnosis and treatment of pneumonia in children.