Vol 82, No 10 (2010)

Aim: to study the level of circulating proinflammatory (IL-1α, IL-1β, IL-6, α-TNF, IFN-γ) and anti-inflammatory (IL-4, IL-10) cytokines and chemokines (IL-8, IL-16) in preclinical development of type 1A diabetes mellitus (T1DM) in children. Subjects and methods. An examination was made in 450 children who had normal blood glucose levels and a burdened history of positive or negative Langerhans islet autoantibodies (LIAA): IAA, GADA, and IA-2A over time until the clinical manifestations of DM1 emerged. The levels of the cytokines and chemokines were determined by ELISA and the titer of LIAA was by radioimmunoassay. Results. Long before T1DM was clinically diagnosed, most children with normal blood glucose levels and LIAA had elevated levels of the cytokines IL-1α, IL-6, and α-TNF and the chemoattractants IL-8 and IL-16 with lower IL-4 concentrations as compared with the similar indices in children without LIAA and controls. After the disease manifested, the magnitude of changes in the indices under study reduced in the majority of children with LIAA, which may suggest that the autoimmune process subsides after destruction of most β-cells. Conclusion. The elevated levels of IL-6, IL-16, α-TNF, and the chemokine IL-8 with the lower blood content of the cytokine IL-4 were long before the development of DM1 in children with normal blood glucose level in the presence of LIAA, which should be borne in mind while developing the immune mechanisms specifically directed against block, which participate by means of cytokines in β-cell destruction, as well as methods for preventing the development of T1DM in subjects with LIAA.

Aim: to study an association between metabolic syndrome and endothelial dysfunction as a regulator of hemorrheological and hemostatic processes in patients with chronic forms of cerebral circulatory insufficiency. Subjects and methods. Forty-six patients with chronic cerebrovascular diseases (CCVD) were examined; of them 23 patients were diagnosed as having metabolic syndrome (MS). Clinical manifestations and major hemorrheological and hemostatic parameters, such as platelet and erythrocyte aggregation, fibrinogen, hematocrit, von Willebrand factor, antithrombin III, intercellular adhesion molecules (IAM), etc., were estimated. Endothelial dysfunction was studied from the data of cuff test (CT). Results. MS promotes a higher degree of clinical symptomatology in patients with CCVD and more significant impairments in the hemorrheological and hemostatic systems. CT has shown that all the patients have an inadequate endothelial reaction - the antiaggregatory, fibrinolytic, and anticoagulant activities of the endothelium are lowered. There was endothelium-dependent hyperproduction of IAM. Conclusion. The found changes suggest that MS has a considerable impact on the formation of a significant procoagulant state of the hemorrheological and hemostatic systems in patients with CCVD.

Aim: to study the prevalence, pattern of and trends in affective disorders (AD) in patients with acute myocardial infarction (AMI) and to assess whether they might be corrected with the antidepressant tianeptin. Subjects and methods. The study enrolled 108 patients with AMI. To detect and evaluate affective spectrum disorders, all the enrolled patients were interviewed on days 2-3 of AMI, by using the screening questionnaire developed at the Moscow Research Institute of Psychiatry (MRIP), Russian Agency for Health Care, and 4-5 days and 2 and 6 months after the onset of AMI they underwent an in-depth psychopathological examination by a psychiatrist who applied the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). To correct affective symptomatology in some patients with verified depression, the antidepressant tianeptin was added to the conventional therapy for AMI on its days 5-7. Results. The screening questionnaire study revealed depressive spectrum disorders in 45.4% of the patients with AMI. The in-depth psychopathological examination confirmed the presence of AD in 40.7%. Mild and moderate depressive episodes were observed in 26.9% of the patients and adjustment disorders were seen in 13.8%. The sensitivity and specificity of the MRIP screening questionnaire for the diagnosis of depressive spectrum disorders in patients with AIM was 86.2 and 69.6%, respectively. The concomitant symptoms of anxiety were detected in 27.8% of the patients with AMI. The duration of a course of antidepressant therapy with tianeptin averaged 3.9±1.1 months. Six moths after AMI, the tianeptin group a showed significant reduction in HDRS scores by 50% (p = 0.0013) and in HARS scores by 52.7% (p = 0.0004) versus the baseline values. During a follow-up, there was no significant decrease in HDRS and HARS scores in a group of patients who refused antidepressant therapy. Conclusion. Affective spectrum disorders are most common in myocardial infarction (MI). The use of the MRIP screening questionnaire favors a more adequate diagnosis of depressive spectrum disorders in patients with AMI. Tianeptin therapy for AD concurrent with MI causes an evident reduction in psychopathological symptomatology and a statistically significant decrease in HDRS and HARS scores.

Until recently, erectile dysfunction (ED) has been considered to be psychogenic in nature in most cases. Advances in our knowledge about the physiology of erection and the pathophysiology of ED have clarified that it is due to organic causes in most cases. Atherosclerosis-associated intraorgan lesion is most frequently encountered. ED is closely related to common cardiovascular risk factors, such as diabetes mellitus, arterial hypertension, dyslipidemia, smoking, physical inactivity. Endothelial dysfunction is of great and universal importance for the genesis of cardiovascular diseases (CVD) and ED. As a manifestation of endothelial dysfunction, ED is an independent risk factor for CVD since vascular endothelial damage is one of the first stages of atherosclerotic plaque formation. ED is an early symptom that is suggestive of atherosclerotic lesion of arterial vessels, coronary arteries in particular. The first manifestation of atherosclerosis in the large arteries is frequently the life-threatening complications myocardial infarction or stroke, which underlines the importance of timely detection of early-stage vascular system lesions. Understanding ED of arteriogenic origin as an early sign of vascular lesion gives a clinician the unique chance to take preventive measures that can prevent complications of CVD.

Aim. To evaluate the efficacy and safety of Spiriva (thiotropium bromide 18 μg for inhalation via a HandiHaler device) in patients with chronic obstructive pulmonary disease (COPD) of all severities in routine clinical practice in Russia. Subjects and methods. The study enrolled 407 patients (68 women and 339 men) with COPD who used thiotropium bromide (Spiriva) for 8 weeks. Most (72.3%) of the patients were aged 50-70 years; active smokers were 64.9%; ex-smokers were 27%; smoking duration averaged 38.6 pack-years; Severe, moderate, very severe, and mild COPD was observed in 38.6, 37.3, 18.4, and 5.7%, respectively. By the start of the trial, 305 (74.5%) had received concomitant therapy. Results. After 8-week thiotropium bromide therapy, there was a significant increase in bronchial patency, as suggested by considerable increments in the postbronchial indices: forced expiratory volume in one second (FEV1) by an average of 290 ml (20.4%) of the baseline level during treatment and forced vital capacity (FVC) by 310 ml (12.1%). By the end of the trial, the mean increase in inspiratory capacity (IC) by 180 ml (8.07%) of the baseline value was indicative of decreased lung hyperinflation in the treated patients. The significant increment in mean FEV1, FVC, and IC was observed in patients with any severity of COPD. Conclusion. The RUSSE study has indicated that there may be very good results in patients with COPD of any severity and a steady-state positive effect just after 8-week thiotropium bromide treatment. This treatment improves bronchial patency and diminishes lung hyperinflation, thus improving the patients' health status and exercise endurance.

Aim. To define the risk factors and predictors of atherosclerosis progression leading to clinical worsening in patients with chronic lower extremity ischemia (CLEI). Subjects and methods: Two hundred and forty patients with lower extremity arterial (LEA) atherosclerosis were examined. All the patients underwent color duplex ultrasound scanning of the great arteries supplying blood to the brain and LEA. Later on an annual observation was made for 11 months to 11 years (mean 45.6 months). To evaluate the influence of various factors on the progression of LEA atherosclerosis, the authors estimated overall survival without progression of CLEI. Results. The one-year overall CLEI progression-free survival was 93.5% (SE = 0.016); 5- and 7-year survival was 66.9% (SE = 0.040) and 53.7% (SE = 0.054), respectively. Over 5 years, a clinically significant progression of CLEI was noted in 32% of the smokers and in 8% of the non-smokers, also in 26% of the patients with grade 1 or 2 hypertensive disease (HD) and in 43% of those with grade 3 HD. The overall CLEI progression-free survival did not depend on the severity of type 2 diabetes mellitus (patients with the severe course were excluded from the analysis). LEA atherosclerosis showed a significantly rapider progression in patients with increased common carotid intima-media thickness (IMT) (p = 0.004). During 5 years, CLEI progression occurred in 18% of the patients with an IMT of ≤ 1.0 mm and in 38% of those with an IMT of more than 1.0 mm, in 15% of the patients without hemodynamically significant stenosis (HDSS) of brachiocephalic arteries (BCA) and in 52% of those with HDSS of BCA, as well as in 20% of the patients without ischemic heart disease (IHD) and in 36% of those with symptoms of IHD. Conclusion. Smoking that increases the risk of CLEI progression by 2.1 times and severe hypertension are the most important factor influencing the progression of atherosclerosis. The IMT index is a universal predictor of progressive atherosclerosis. It may be presumed that there is a higher process development rate in the detection of HDSS of one of the arterial beds (LEA, BCA, and symptoms of IHD) at the first examination.

Aim. To study the specific features of porphyrin metabolic disturbances in cadmium poisoning. Material and methods. The paper describes a patient who has developed clinical and biochemical syndromes of acute porphyrinopathy after exposure to cadmium-containing paint the vapors. The levels of δ-aminolevulinic acid, porphobilinogen, coproporphyrin, and uroporphyrin in urine and those of coproporphyrin and protoporphyrin in feces were measured. The concentrations of lead, cadmium, and copper were determined in whole blood and urine; selective screening of amino acids for hereditary metabolic diseases was made. Results. The clinical signs of acute porphyrinopathy developed in the patient mimicked those of acute porphyries known by the current classification. The biochemical syndrome more corresponded to lead poisoning. However, the blood and urinary lead levels were not greater than the normal values, but the blood showed a 4-fold increase in cadmium, which seemed to induce porphyrin dysmetabolism.

The results of a study of the efficiency of treatment in patients with chronic hepatitis C conducted in a complex of multicenter clinical trials of the impact of various antiviral therapy regimens including the interferon genesis inductor cycloferon are reviewed. Four hundred and seventy-eight patients with hepatitis C virus infection were followed up. The study has demonstrated that the incorporation of cycloferon into the standard treatment regimen, which is manifested by the effect of drug synergism, by producing antiviral, immunomodulating, and antifibrotic effects, is a promising pharmacotherapy for chronic hepatitis C. This treatment is economically sound, reduces the incidence and degree of adverse reactions and increases the quality of life in the patients.