Vol 84, No 8 (2012)

The investigations conducted in the past decade have offered better insight into the basic mechanisms of chronic constipation (CC), among other things, its association with large bowel (LB) transit and anorectal function. Intestinal dyskinesia, slow transit of the intestinal contents (inert LB), and impaired defecation due to pelvic floor dyssynergia play a leading role in the pathogenesis of primary constipation. Its treatment should be similar to that for CC. Motility regulators correcting LB dyskinesia are given to treat functional constipation and constipation-predominant irritable bowel syndrome. Enteral pro-kinetic agents are effective in treating the inert LB. The possibilities of biofeedback therapy should be used to treat dyssynergic defecation.

Aim. To evaluate the efficiency and safety of combined drug therapy incorporating Ursofalk (Dr Falk Pharma GmbH, Germany) and a low-dose statin on the clinical course of the disease and blood lipid composition parameters in high-risk patients with abdominal ischemic disease (AID) and hepatic ischemic steatosis resulting from atherosclerotic lesion of the abdominal aorta (AA) and its unpaired visceral branches (UVB). Subjects and methods. One hundred and thirty-nine patients (95 (68.3%) men and 44 (31.7%) women, aged 18-87 years) with AID and ischemic hepatopathy were examined and treated. AID in the examinees was verified by color duplex scanning and computed tomographic angiography of AA UVB, as well as by X-ray contrast aortography. The patients were treated with Ursofalk 10-15 mg/kg/day in combination with atorvastatin 10-20 mg/day. Results. Due to the combination therapy, abdominal pains became less significant in the majority of patients and disappeared in some subjects. The same positive changes were also observed in the signs of intestinal dysfunction. There was an improvement in blood lipid composition parameters. No substantial weight changes were noted in the patients during the treatment. No adverse reactions occurred due to the combined use of Ursofalk and atorvastatin.Conclusion. It is reasonable to co-administer urosofalk and statins as an agent of hypolipidemic therapy in patients with AID concurrent with disseminated atherosclerosis and dyslipidemia that is accompanied by fatty infiltration of the liver with elements of fibrosis in 90% of cases and that is a pre-stage of steatohepatitis.

Aim. To study relationships between endothelial activation parameters and inflammatory activity markers in patients with rheumatoid arthritis (RA). Subjects and methods. Fifty-three RA patients aged 19 to 62 years were examined. A control group comprised 28 apparently healthy individuals. The markers of endothelial activation, the parameters of RA activity, and their relationship were studied. Results. There was an elevation in the level of interleukin-8 (IL-8) to 413 (295; 547) pg/ml as compared to the control group 208 (207; 212) pg/ml. In the RA group, the concentration of soluble vascular cell adhesion molecule 1 (sVCAM-1) increased up to 1929 (1297.6; 2739.6) ng/ml whereas in the control group it was 750 (734; 762) ng/ml (p<0.001). In the patients with RA, the concentration of von Willebrand factor antigen (vWFAg) reached 1.4 (0.8; 1.9) IU/ml; in the control group, it was 0.6 (0.3; 0.8) IU/ml. In the RA group, the level of desquamated endotheliocytes (DE) was higher than that in the control group. Positive correlations were found between the markers of vascular endothelial activation and those of inflammation. There was a positive correlation between C-reactive protein (CRP), rheumatoid factor (RF), sVCAM-1, and DE. Significant positive correlations were observed between DAS28 and the inflammatory markers RF and CRP (R=0.66; p<0.05 and R=0.4; p<0.05) and the endothelial activation markers sVCAM-1 and vWFAg (R=0.8; p<0.05 and R=0.3; p<0.05, respectively). Conclusion. The patients with RA had elevated IL-8, sVCAM-1, and vWFAg levels. Enhanced RA activity resulted in endothelial damage.

Aim. To determine a relationship between matrix metalloproteinase-9 (MMP-9) activity and its tissue inhibitors TIMP-1 and 2, tumor necrosis factor-α (TNF-α), bone mineral density (BMD), and bone exchange in chronic obstructive pulmonary disease (COPD). Subjects and methods. Seventy-six patients with COPD and 20 healthy volunteers were examined using dual-energy X-ray absorptiometry n the lumbar spine (LII-LIV) and femoral neck (FN). The serum levels of MMP-9, TIMP-1 and TIMP-2, TNF-α, and Β-Crosslaps (ΒCL) were measured. Results. There was a higher MMP-9 level in COPD than that in the controls ((383.8±54.2 and 137.6±31.4 pg/ml, respectively; p<0.01). The levels of TIMP-1 and TIMP-2 were not different from those in the control group. An inverse correlation was found between forced expiratory volume in one second (FEV1) and MMP-9 concentration (r= -0.59; p=0.002) and a positive correlation with smoking index (r=0.47; p=0.04). There was an inverse correlation between MMP-9 concentration and BMD in both LII-LIV and FN (r= -0.67; p<0.001 and r= -0.61; p<0.01, respectively) and a direct correlation with ΒCL (r=0.53; p=0.04). An inverse correlation was established between TNF-α and T index in both LII-LIV (r =-0.54; p<0.01) and FN (r= -0.48; p<0.01). At the same time, the level of TNF-α directly correlated with the bone resorption marker ΒCL (r=0.53; p=0.002) and MMP-9 (r=0.57; p=0.003). Conclusion. Elevated MMP-9 levels may play an important role in type I collagen degradation, giving rise to enhanced bone resorption in COPD.

Aim. To retrospectively evaluate the immediate and delayed effects of the abnormally hot summer of 2010 on the course of cardiovascular disease (CVD). Subjects and methods. The study enrolled 188 patients with CVD, who had visited a polyclinic for advice in the past 2 weeks of January 2011. In addition to general clinical examination, all the patients were proposed to fill out the Hospital Anxiety and Depression Scale questionnaires concerning their quality of life, by applying the visual analog scale during their visit and (retrospectively) in the abnormal hot period (AHP). The questions were concerned with the location of the patient during the heat wave, his/her health status, the duration of a working day, the number of hypertensive crises (HC), calls to medical emergency teams (MET), and visits to a doctor, the pattern of therapy, etc. The authors estimated the following outcomes (endpoints): acute myocardial infarction, acute cerebrovascular accident, admissions for CVD, MET calls, the number of disability days, HC, and unplanned visits to the doctor, which occurred during the heat wave or in the period September to December 2010. Results. There was a worse quality of life during AHP. The patients living in the green zone (of a city, town, or a rural area) better experienced the abnormal heat. Male sex and overweight were associated with better abnormal heat tolerance; high anxiety, age, and living on high floors were with its worse tolerance. Conclusion. It is necessary to conduct large-scale prospective randomized studies, the results of which will yield objective information, which will be able to give patients scientifically sound recommendations how to behave during AHP.

Aim. To define the efficiency of the GMALL 2002 program for the treatment of patients with T-cell lymphoblastic lymphomas (T-LBL). Subjects and methods. Twenty-five patients with a verified diagnosis of T-LBL were examined. Male/female ratio was 19:6; median age was 33 (range 16-67) years. There was a preponderance of patients with the generalized stages of the diseases: 2, 5, and 18 with Stages II, III, and IV, respectively. Mediastinal lesion was found in 20 (80%) of the 25 patients. Their treatment was performed according to the GMALL 2002 program and similar CHOP courses. Analysis was made in 2 groups that were not different in their clinical and morphological characteristics. Group 1 consisted of 17 of the 25 patients treated according to the GMALL programs; Group 2 comprised 8 patients who had similar CHOP and other chemotherapy regimens. Results. In Group 1, 15 (88%) patients achieved a complete clinical and hematological remission and 2 (12%) patients died in the first stages of the treatment. No relapses were noted. The median survival had not been achieved; 5-year overall survival was 88±8%. In Group 2, three patients were alive; 2 completed their treatment; 5 (63%) patients died from treatment failures. The median survival was 23±18%; 5-year overall survival was 45%. Conclusion. The findings suggest that the GMALL 2002 programs are highly effective in treating patients with T-LBL at the first stage of treatment.

Aim. To evaluate the efficiency and safety of early combination therapy with sulfonylurea derivatives (SUD) and insulin sensitizers in patients with type 2 diabetes mellitus (T2DM). Subjects and methods. Forty patients (31 women and 9 men; mean age 57.7±0.9 years) with decompensated T2DM (НbА1с 8.16±0.27%), a mean body mass index of 32.7±0.7 kg/m2, who received glimepiride, were examined. The duration of T2DM was 3.3±0.4 years. The patients had concomitant cardiovascular diseases (CVD). Coronary heart disease and hypertensive disease (HD) were treated; the doses of the agents were not adjusted during the study. For T2DM compensation, all the patients were given insulin sensitizers (rosiglitazone 4 mg) in addition to glimepiride. The treatment lasted 24 weeks. Carbohydrate and lipid metabolic parameters, insulin resistance, body weight, structural and functional parameters, and heart rate were estimated before and after the treatment. Results. During the combination therapy, there were decreases in the level of НbА1с from 8.16±0.27 to 6.84±0.15%, fasting blood glucose from 8.89±0.35 to 6.77±0.16 mmol/l, postprandial blood glucose from 8.66±0.24 to 7.761±0.20 mmol/l, HOMA index from 5.88±0.70 to 3.75±0.44. The rate of hypoglycemic reaction reduced. Sugar-lowering therapy was observed to have, on average, a positive impact on blood lipid composition and cardiovascular parameters in the group. Echocardiography (EchoCG) identified a group of patients with negative cardiac structural and functional changes. Conclusion. The combination therapy with SUD and insulin sensitizers was stated to be effective in maintaining the reached blood glucose level, reducing the risk of hypoglycemic reactions, and positively affecting lipid metabolism. The therapy resulted in cardiovascular improvement only in patients without obvious signs of CVD while it caused negative EchoCG changes (transformation of concentric to eccentric left ventricular hypertrophy) in patients with a long-term (more than 7 years) history of HD and pronounced cardiac structural and functional alterations.

Aim. To evaluate the antidote properties of acizol in acute carbon monoxide poisoning (ACMP). Subjects and methods. The study included 70 patients with ACMP. Of them 35 patients received a package of medical measures, which involved 6% acizol solution injected in a dose of 1 ml on hospital admission and an hour later. The efficacy of acizol was evaluated using clinical and laboratory studies. Results. Just an hour after acizol injection, there was an average 2-fold reduction in the blood concentration of carboxyhemoglobin as compared to the baseline levels. Consciousness recovered 1.5 times more quickly than in the control group. The clinical efficacy of acizol was supported by positive laboratory tests. Conclusion. The use of acizol in ACMP assists in increasing the rate of detoxification and positively affects some blood laboratory parameters.

The active practical introduction of the achievements of genomics, proteomics, metabolomics, and bioinformatics brought about a fundamental change in views on the role and place of medicine in the structure of healthcare at the turn of the 1980s-1990s, by giving impetus to the development of the radically new health care area - preventive, predictive, and personalized medicine (PPPM). The main goals of PPM are to recognize disease signs at the stage of subclinical pathology with d the identification of targets suitable for drug-based prevention for drug-based prevention and to make pharmacorrection of the disturbances identified aimed at the drug-based prevention to promote the suppression of pathological process at the subclinical stage.

Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases, the incidence of which tends to grow steadily. The great social importance of diabetes mellitus is determined by disability and deaths from late vascular events. So the risk for cardiovascular disease (CVD) and the cardiovascular safety of glucose-lowering therapy for T2DM are a multidisciplinary and multi-faceted problem. Its solution requires a comprehensive approach to controlling the risk factors of CVD and assessing hypoglycemic therapy in the context of cardiovascular safety. The paper shows the bases of CVD pathogenesis and contains the results of numerous international clinical trials evaluating the efficiency and safety of current glucose-lowering therapy (metformin and cardioprotective drugs, the action of which is based on their incretin effect).