Lviv Clinical Bulletin

14-20

Authors: Azhmi S., Serhiyenko V.

Introduction. Cardiovascular autonomic neuropathy (CAN) is a serious and common complication of type 2 diabetes mellitus (T2DM). Despite its relationship to an increased risk of cardiovascular mortality and its association with multiple symptoms and impairments, the significance of CAN has not been fully appreciated. CAN among T2DM patients may be accompanied by severe postural hypotension, decreased tolerance to the physical loadings, and cause the cardiac arrhythmias, ischemia of coronary vessels, ″silent″ myocardial infarction, sudden death syndrome. Although it is a common complication, the significance of CAN has not been fully appreciated and there are no unified treatment algorithms for today. It is obvious that the foreground should be the therapy aimed at lifestyle modification, reducing insulin resistance (IR), correction of hyperglycemia, dyslipoproteinemia (DLP), symptomatic treatment of concomitant diseases and syndromes. For DLP pharmacotherapy using statins, fibrates, bile acid sequestrants, nicotinic acid and its derivatives, products of long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFAs), or as an alternative-their combination with cholesterol absorption inhibitors. Statins are widely accepted as the first-line therapy of the atherogenic DLP, the effectiveness of its prescription was proved in several studies. However, the data about the ω-3 PUFAs effectiveness are incomplete, the future investigation are needed. The aim of this study was to investigate the blood lipid profile and IR parameters in patients with T2DM and CAN and the effects of simvastatin and ω-3 PUFAs prescription. Materials and methods. The study involved 219 patients with T2DM (101 women and 118 men, patients were aged between 50-59 years), among them: 1) 19 patients without CAN; 2) 44 – with subclinical CAN; 3) 156 (aged 50-59 years, disease duration 1-6 years, glycated haemoglobin A1c (HbA1c) level (7,1 ± 0,4) %) – with functional CAN. Control group – 15 healthy people of median age (51,9 ± 3,2) years. The concentration of glucose, HbA1c, immunoreactive insulin (IRI) in the blood were determinated, the insulin resistance index (HOMA-IR) was calculated. Lipid metabolism was assessed by the concentration of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) measurements and calculation of the atherogenic coefficient (AC). Among 156 patients with T2DM and functional CAN stage, 76 patients were allocated into four treatment groups: 1st group – 22 patients received standard hypoglycemic therapy and simvastatin 20 mg/day; 2nd group – 21 patients received standard hypoglycemic therapy and one capsule/day of the ω-3 PUFAs; 3rd group – 18 patients received standard hypoglycemic therapy, one capsule of the ω-3 PUFAs and simvastatin 10 mg/day; 4th group – control group received standard hypoglycemic therapy (n = 15). The duration of the study was 3 month. Results and discussion. Obtained results of our study could witness that the increase of IRI, HOMA-IR parameters in patients with T2DM and CAN was accompanied by growth of TC, TG, LDL-C, AC and decrease of HDL-C levels. The most pronounced changes were observed in patients with functional stage of CAN. The prescription of simvastatin was accompanied by a statistically significant decrease in TC, LDL-C, TG, IRI and increase in HDL-C levels (compared to control); statistically significant decrease in TC, LDL-C and IRI (compared to ω-3 PUFAs). ω-3 PUFAs are not contributing to changes in HbA1c, preprandial glucose, IRI and HOMA-IR; statistically significant reduced TG, AC and increased HDL-C levels. The combined prescription of simvastatin and ω-3 PUFAs contributed to the most positive, statistically significant changes in hyperinsulinemia/IR parameters and lipid metabolism, allowing to reduce the daily dose of simvastatin. Conclusions. Obtained results could witness that effects of combined simvastatin and omega-3 polyunsaturated fatty acids prescription are not connected with diabetes mellitus compensation state and are as a direct influence of this pharmacological agents on investigated parameters that justify the appropriateness of their prescription to patients with type 2 diabetes mellitus and functional stage of cardiovascular autonomic neuropathy.

25-31

Authors: Lypovetska S.

Introduction. The role of serum uric acid (SUA) in the process of atherosclerosis and atherotrombosis is controversial. Epidemiological studies have recently shown that SUA may be a risk factor for cardiovascular diseases and a negative prognostic marker for mortality in subjects with pre-existing heart failure. Aim. To study out disturbances of cardiohaemodynamics, heart rhythm, lipid, purine metabolism and systemic inflammation and efficiency of their correction in patients with postinfarction cardiosclerosis, associated with hyperuricemia. Materials and methods. 147 patients, (59.2 ± 0.8) years old, with postinfarction cardiosclerosis were included in this study. They were divided into 2 groups depending on presence of hyperuricemia. The I group included 106 patients with high SUA (0.59 ± 0.06) mmol/l and II group – 41 patients with normal level of SUA (0.32 ± 0.05) mmol/l. Comparable evaluation of cardiohaemodynamics, heart rhythm disturbances, lipid and purine metabolism’s violation and systemic inflammation were performed. According to program of treatment patients with high SUA, were divided in 4 groups: I – 30 patients, whom standard treatment was prescribed, II – 25 patients, who received eprosartan 600 mg instead of ACE-inhibitor, III – 25 patients, whom fenofibrate 200 mg additionally was given, IV – 26 patients, who received combination of eprosartan and fenofibrate. Echo, Holter ECG monitoring, markers of systemic inflammation (C reactive protein (CRP), Interleukin 1 (IL1), tumor necrosis factor α (TNF α)), lipidiogram were assessed before treatment and after 6 months. Results. Elevated SUA level was associated with progression of postinfarction heart remodeling: increasing of left ventricle mass index (LVMI (220.9 ± 6.9) g/m2)) and violation of its geometry, particularly, concentric hypertrophy (56.6 %), eccentric hypertrophy (40.6 %) with diastolic dysfunction. SUA levels correlated significantly with mitral A wave velocity (r = 0.61, p < 0.01), E wave deceleration time (r = 0.26, p < 0.01), E/A ratio (r = 0.21, p < 0.05). Heterogenity of ventricular repolarization, decrease of time indexes of heart rate variability, as well as high grade premature ventricular complexes were observed in these patients. The correlation between elevated levels of CRP and SUA (r = 0.7, p < 0.01), TNF α (r = 0.8, p < 0.01), IL-1 (r = 0.7, p < 0.01) were found, confirming the direct role of SUA in inflammation. Complex treatment with eprosartan provided significant regress of left ventricle hypertrophy (LVMI was decreased to 14.3 g/m2 and increasing of ejection fraction from (46.2 ± 1,2) to (52.4 ± 1,1) %, normalization of circadian index, heart rate, complete recovery from ventricular tachycardia, reduced quantity of ventricular premature beats on 64.0 %, reduced duration of Q-T and its dispersion on 21.1 % and increased heart rate variability. Target levels of blood pressure were achieved in 85.7 % patients. Usage of fenofibrate provided reduction of total cholesterol by 21.1%, triglycerides – 44.2 %, low density lipoprotein – 30.1 %, SUA – 37.5 %, CRP – 71.2 %, TNF α – 69.0 %, IL-1 – 47.1 % and an increase of high density lipoprotein – 30.7 %. Conclusions. The combined therapy with eprosartan and fenofibrate is an adequate means for hypertension control, correction of dislipidemia, hyperuricemia and inflammation, prevention of heart remodeling in patients with postinfarction cardiosclerosis, associated with hyperuricemia. It was associated with improvement of heart rate variability indexes as well as with decrease of incidence of life-threatening arrhythmias.

39-43

Authors: Kiladze N., Chanishvili N., Shulaia T., Bendeliani Z., Zaichenko Y.

Introduction. The questions of treatment of chronic skin purulent infections are extremely important due to their wide spread, severe clinical course of some nosological forms, development of resistance to the traditional means, and growth of undesirable side effects of antibiotic therapy. Chronic suppurative skin diseases connected with skin appendages are disorders of common occurrence and a major constituent of pyodermas. They still remain a problem due to their chronic character and difficulty of treatment, as well as its large impact on patients’ quality of life. Due to the chronic course of the disease, treatment is long lasting, and often ineffective because of resistance to antibiotics therefore it is desirable to provide the treatment with effective alternatives to commonly used antibiotics to reduce the resistance and obtain a highly specific agent which is able to destroy bacteria effectively. In the same time across the world a growing number of scientists are noting the promising positive results of phage therapy and its advantages, especially in the treatment of chronic cases. The aim of this communication, which is a continuation of previously presented research, is to report the data and results of treatment of some common chronic suppurative skin disease with phages. Materials and methods. In the present investigation were included 87 males aged 18 to 56 with chronic folliculites (n=52), syccosis (n=30) and folliculitis et perifolliculitis capitis abscendens et suffodiens, Hoffmann (n=5), in all cases was approved prevalence of staphylococcal flora and all of them were treated before with antibiotics, but unsuccessfully. The treatment was provided with pyophages produced by Giorgi Eliava Institute (Tbilisi, Georgia) which include Staphylococcus aureus, Streptococcus (different cultures), Escherichia coli (different serotypes), Psedomonas aeruginosa, Proteus vulgaris, mirabilis. Taking into consideration deep locations for treatment was chosen mesotherapy technique – phage solution was injected by dermal nappage, papula and point by point technique in all damaged areas. In each case the frequency of procedures was usually once in 3-4 days until healing, the process took about one month. In patients with folliculitis full recovery was achieved in all cases, but they were still under observation up to 2 months in order to avoid relapses. In the cases of folliculitis et perifolliculitis capitis abscendens et suffodiens Hoffmann treatment was started with М. Jessner’s peeling followed by intralesional injections into buggy nodules and sinus tracts and dermal nappage, papula and point by point technique in all damaged areas. Patients were treated within three weeks once in three days with following break of 7 days, after the course was repeated. In all 5 cases the final results were positive. The cosmetic defect in the form of a fibroid growth was still present, but after the course of treatment the laboratory data confirmed the absence of pathogenic flora in correlation with marked clinical improvement. Conclusions. Рhage therapy has a long history and phages potential for treating infectious diseases has been pursued since their discovery, but still there are many important questions that must be decided before their wide therapeutic use in different clinical fields. Their benefits are undeniable, this therapy may replace or augment the conventional antibiotic therapy, help eliminate antibiotic resistance of bacterial strains and they give a real chance for patients suffering from chronic infections caused by antibiotic-resistant bacteria. The experience in phage the- rapy may become very important with the rapidly-increasing spread of antibiotic-resistance bacterial infections which are difficult to treat now. There is a need to develop phage therapy of purulent skin diseases, but more research is needed to understand the bacteria-bacteriophage interactions in the skin community to obtain comprehensive knowledge on different pathogenic flora.

48-52

Authors: Olіynyk O., Kіrda І., Voitsekhivska I.

Introduction. Influenza – an acute infectious disease of viral origin with a short incubation period, sudden onset and cyclical course that is characterized by severe toxicity and defeat of the upper respiratory tract and lungs. During the epidemic from 5.0 to 20.0 % of the population is ill, and particularly high incidence among children. The mor- tality rate of uncomplicated influenza is 0.01-0.2 %, but it increases sharply in the case of illness in frail persons and young children. The highest incidence occurs in children aged from 1 to 14 years, which is 4 times higher than in older people. At present the urgent problem is to improve the methods of effective prevention and treatment of viral infections in children, including through the use of appropriative dosage forms. Aim. To identify the main groups of drugs and conduct analysis of the current range of dosage forms that are most often recommended for the prevention and treatment of influenza in children. Materials and methods. In the process of study were used: the method of content analysis, the bibliographic method and generalization method. The objects of researches were the State Register of medicinal products, The State Form of medicines, clinical protocols and standards of care of influenza and acute respiratory infections. Results. To ensure the safety of pharmacotherapy in children extremely important is providing and availability of dosage forms of drugs for children. Today there are only 311 drugs in the form of granules, powders, tablets, syrups and suspensions from the total number of medicines, which are approved for children in Ukraine. Formulations for children in Ukraine are represented mostly by foreign manufacturers. The lack of children’s dosage forms of drugs leads to prescriptions medicines for children based on adult dosage forms (eg. tablets divided in half or crushed). It should be noted that in the most developed countries may not use solid dosage forms (tablets, capsules and pills) for children under 3 years. Results of content analysis of the State Register of medicinal products, clinical protocols and standards of care clarified that for prevention and treatment of influenza and acute respiratory infections in Ukraine are used 191 trade names of drugs in the form of 11 dosage forms. It was found that for prevention and treatment of influenza and acute respiratory viral infections (ARI) in children from the time of birth to 3 months are used 16 (8.38 %) names of drugs, for children aged from 3 months to 1 year are used 15 (7.85 %) names of drugs, for children aged from 1 to 6 years are used 19 (9.95 %) names of drugs, for children aged from 6 to 12 years are used 29 (15.18 %) names of drugs, and for children aged from 12 to 15 years are used 112 (58.64 %) names of drugs. According to results of the research the main bulk of medicines consist of the tablet dosage form (45.55 %), capsules (6.28 %) and powders (21.99 %), use of which for children aged up to 3 years is problematic. The most effective formulations for children (syrups, suppositories) comprise only 8.37 % of the required range of medicines. The analysis of the seventh issue of the State Form of drugs suggests that for prophylaxis and treatment of viral origin are used those antiviral drugs, belonging to 22 pharmacotherapeutic groups and comprise with about 135 trade names of medicines. Only three groups have the means to prevent and treat of influenza with amount of 9 trade names, and the only three trade names of medicines are produced in Ukraine. Antiviral drugs for systemic use belong to two classes: cyclic amines (rimantadine) and neuraminidase inhibitors (zanamivir and oseltamivir). Antiviral drugs of both classes are active against influenza viruses: cyclic amines (rimantadine), are active only against influenza A viruses, while neuraminidase inhibitors (zanamivir and oseltamivir) are active against influenza viruses A and B. On the base of virological surveillance data received during the last flu seasons, most of influenza viruses A (H3N2) are resistant to rimantadine, but sensitive to both neuraminidase inhibitors, and many of influen- za viruses A (H1N1) are resistant to oseltamivir, but sensitive to zanamivir and rimantadine. Analysis of the range of antiviral drugs indicates that only one product – oseltamivir can be used for treatment of influenza in children aged from one to five years. At the same time zanamivir is used for treatment of influenza in children older than 5 years, and rimantadine for treatment of children who are over 7 years. Conclusions. It was found that the list of regular use of antiviral drugs for prevention and treatment of influenza in children contains only three names. And only one drug – Oseltamivir can be used for treatment of influenza in children aged from one to five years. It was also found that the prevention and treatment of influenza and acute respiratory infections in children are used primarily tablets, capsules and other dosage forms for adults. Increasing efficiency of prevention and treatment of infection diseases in children needs improvement of drug administration methods by increasing the number of appropriate dosage forms.