Vol 82, No 10 (2010)
- Year: 2010
- Articles: 16
- URL: https://journals.rcsi.science/0040-3660/issue/view/1741
Editorial
Innovations in the treatment of type 2 diabetes mellitus: use of incretins
Abstract
There is a new class of drugs used to treat diabetes mellitus (DM). It has come into existence after long-term studies of the fundamentally new hemostastic mechanism in glucose regulation via the gastrointestinal hormones incretins. With the advent of this class of drugs that minimize routine adverse reactions (weight gain, glycemic risk, nephro-, hepato-, and cardiotoxic effects, etc.), there is hope for a delay in the progressive increase of secretory function and β-cell mass, which is inevitable during standard treatment (which presages the eventual need to initiate insulin therapy 7-10 years after the onset of the disease). The mechanism of action of incretins is considered. The place of novel agents (glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) in the total pattern of treatment for type 2 DM, indications for and contraindications to their use, benefits versus traditional glucose-lowering therapy (the inestimable advantage of these drugs is no risk for hypoglycemia), and prospects for their future application are discussed.
Terapevticheskii arkhiv. 2010;82(10):5-10
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The level of circulating cytokines and chemokines in the preclinical and early clinical stages of development of type 1A diabetes mellitus
Abstract
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.
Terapevticheskii arkhiv. 2010;82(10):10-15
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Clinical and metabolic risk factors for cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus
Abstract
Aim: to study clinical and metabolic risk factors for cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus (T2DM).
Subjects and methods. One hundred and fifty-seven patients were examined. According to the results of ECG tests and cardiointervalography, the patients were divided into 2 groups: 1) 45 patients without cardiovascular autonomic neuropathy; 2) 112 patients with this condition.
Results. The T2DM patients with cardiovascular autonomic neuropathy significantly differed from those without autonomic disorders in DM duration, insulin level, insulin resistance indices (HOMA-IR, FIRI), atherogenicity coefficient, and high-density lipoprotein levels. The glycated hemoglobin level of more than 9% affected the values of autonomic ECG tests.
Conclusion. In patients with T2DM, the development of cardiovascular autonomic neuropathy is affected by not only the duration of DM and the decompensation of carbohydrate metabolism, but also by hyperinsulinemia and insulin resistance, the low level of high-density lipoproteins, and the high coefficient of atherogenicity.
Terapevticheskii arkhiv. 2010;82(10):15-19
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Chronic cerebrovascular diseases, metabolic syndrome, and the hemorrheological and hemostatic systems
Abstract
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.
Terapevticheskii arkhiv. 2010;82(10):19-24
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Poststroke somatic pathology in patients with a history of burdened alcohol abuse
Abstract
Aim: to study concomitant somatic pathology in brain stroke patients abusing alcohol before cerebral catastrophe.
Subjects and methods. Two groups were identified according to the results of examining 255 poststroke patients. A study group included 57 (22.4%) pre-stroke alcohol abusers; a control group consisted of 198 (77.6%) alcohol non-abusers.
Results. Among the study group patients, lacunar and hemodynamic pathogenetic subtypes of ischemic stroke were encountered 3 times more and 2 times less frequently, respectively, than in the control groups. After cerebral stroke, the study group patients had a clinical picture with a preponderance of diminished cognitive functions, as well as motor disorders mainly as hemiparetic syndrome. Assessment of the pattern of somatic pathology in both group patients revealed a predominance of myocardial infarction by almost 2-fold, hepatobiliary diseases by 4.7-fold, duodenal ulcer disease by 1.6-fold, and bronchopulmonary pathology by 2-fold among the study group patients. Arthrosis deformans and obesity were observed by 6.4 and 3.5 times more frequently, respectively. The incidence of cardiac disease and hypertension in the acute period did not differ greatly in the compared groups. No thyroid pathology was recorded in the study group. In this group, the poststroke period was generally severer or ran as a galloping type in one third of cases.
Conclusion. Somatic pathology aggravates the poststroke period, on the one hand, and it is decompensated in the presence of inadequate cerebral blood supply, on the other. Measures to compensate for neuropsychological disorders should be efficiently combined with rehabilitative actions on somatic pathology in poststroke patients with a history of burdened alcohol abuse.
Terapevticheskii arkhiv. 2010;82(10):24-28
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Affective disorders in acute myocardial infarction and possibilities of their correction with tianeptin
Abstract
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.
Terapevticheskii arkhiv. 2010;82(10):28-33
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Role of obesity in the development of osteoarthrosis and concomitant diseases
Abstract
Aim. To specify the association between obesity and the frequency of concomitant states, fat metabolic disturbances, and progressive osteoarthrosis (OA) at various sites.
Subjects and methods: The study included 298 patients with manifest knee and hip osteoarthrosis in whom the body mass index (BMI) and waist and hip circumferences were measured calculating the waist-hip index. The association of these indices with the severity of OA and the development of concomitant states was analyzed.
Results. Both women and men were found to have overweight and first-second-degree obesity at equal ratios - 61.6 and 59%, respectively. There was an evident rise in the prevalence of cardiovascular diseases (arterial hypertension, coronary heart disease) and diabetes mellitus with a higher BMI. Stages II-III gonarthrosis was predominant (97.1%) in the obesity group (BMI 30.0-35.0 or greater). With a BMI of > 40, X-ray stages III-IV OA were revealed in 83.3% of the patients.
Conclusion. Our findings support the important role of obesity as a risk factor in the development of OA. Fat metabolic disturbances also make a considerable contribution in the development of concomitant states and in the progression of OA of both knee and hand joints.
Terapevticheskii arkhiv. 2010;82(10):34-37
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Cardiovascular diseases and erectile dysfunction
Abstract
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.
Terapevticheskii arkhiv. 2010;82(10):37-40
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The efficacy and safety of infliximab in patients with ankylosing spondylitis: results of an open-labeled multicenter study
Abstract
Aim. To evaluate the efficacy and tolerability of the anti-tumor necrosis factor-α infliximab in patients with active ankylosing spondylitis (AS) in a 54-week multicenter open-label study.
Subjects and methods. The study enrolled 42 patients with AS who continued to have an active phase of the disease despite that they had received standard therapy. All but one patient had signs of active spondylitis; peripheral arthritis was noted in 52%; enthesitis was seen in 79%. Infliximab was administered in a dose of 5 mg/kg as 2-hour intravenous infusions; the second and third infusions were injected 2 and 6 weeks after the first one; all further infusions were used at an interval of 6-8 weeks.
Results. Thirty-three (78.6%) of the 42 patients completed the trial. There was a considerable, at least 50%, improvement in the ASAS criteria in 84.8% of the patients who completed the trial. A substantial therapeutic effect was observed in the majority of patients just a week after the first infusion of infliximab. There was a statistically improvement in all the analyzed clinical effectiveness indicators, including the Bath AS Disease Activity Index (BASDAI); pain became less in the vertebral column and joints (on an average from 49.6 to 12.4 mm on the 100-mm visual analog scale); the level of C-reactive protein and the number of swollen and tender entheses were decreased. The patients' functional capacity improved considerably (the Bath AS Functional index (BASFI) decreased on average from 59.7 to 16.3 scores). Nine (21.4%) patients were withdrawn from the study ahead of time: 7 and 2 patients because of adverse reactions (AR) and contact loss, respectively. The most common ARs were airway infections (13.6%), hepatic dysfunction (12.0%), and herpes simplex virus infections (10.4%). Four patients developed the severest ARs (pulmonary tuberculosis, generalized psoriasis-like dermatitis, pneumonia, and abscess of the epithelial coccygeal tract); the outcome of all complications was good.
Conclusion. The results of the study suggest that infliximab has a high, rapidly occurring and stably preserving efficiency in most patients with active AS. The frequency and spectrum of ARs corresponded to the available data on the tolerability of infliximab.
Terapevticheskii arkhiv. 2010;82(10):41-46
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The efficacy of thiotropium bromide (Spiriva) in the treatment of patients with chronic obstructive pulmonary disease of varying severity: results of the Russian trial
Abstract
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.
Terapevticheskii arkhiv. 2010;82(10):46-51
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Metabolic syndrome and insulin resistance in patients with chronic hepatitis C
Abstract
Aim. To estimate the incidence and clinical value of metabolic syndrome, insulin resistance, and steatosis in patients with chronic hepatitis C (CHC) caused by its virus genotype 1.
Subjects and methods. One hundred and fourteen patients (67 men and 47 women; mean age 44.9±13.3 years) were examined.
Results. There were high incidence rates of metabolic syndrome (47.2%) and insulin resistance (50%), in the genesis of which the host-virus interaction is discussed. There was an independent correlation of the insulin resistance and elevated leptin levels with abdominal obesity and hepatic steatosis; however, these indicators did not correlate with the stage of fibrosis. At the same time hepatic steatosis (found in 38% of the patients) and its degree correlated with the stage of fibrosis. Thirty-four of 66 (54.5%) patients receiving antiviral therapy achieved a stable virological response.
Conclusion. Obesity, hyperglycemia, and significant insulin resistance along with the stage of hepatic cirrhosis are independent cofactors that determine no treatment response.
Terapevticheskii arkhiv. 2010;82(10):51-56
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The risk factors and predictors of the clinically significant progression of atherosclerosis in patients with chronic lower extremity ischemia
Abstract
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.
Terapevticheskii arkhiv. 2010;82(10):56-60
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Autologous peripheral hemopoietic cell transplantation in the treatment of AL-amyloidosis
Abstract
Aim. To evaluate the efficiency of chemotherapy with standard doses of melfalan and dexamethazone versus autologous peripheral hemopoietic cell transplantation (auto-PHCT) in patients with AL amyloidosis and to reveal poor prognostic factors.
Subjects and methods. Of 36 patients diagnosed as having AL-amylodosis, 17 patients underwent auto-PHCT, 11 patients received chemotherapy only; 8 patients died prior to treatment.
Results. In patients with AL-amyloidosis after chemotherapy and autotransplantation, 3-year overall survival was 28 and 64%, respectively. Low somatic ECOG status and cardiac lesion were independent poor prognostic factors of the disease. The number of involved organs failed to affect overall survival.
Conclusion. Auto-PHCT may be proposed as first-line therapy for patients with AL-amyloidosis who have a somatic ECOG score of 0 to 2 and not more than 3 organs involved. Young patients who have a satisfactory somatic status and no benefit from autotransplantation may undergo auto-PHCT. It is expedient to use average-dose melfalan and dexamethasone when treating patients who are ineligible for high-dose chemotherapy.
Terapevticheskii arkhiv. 2010;82(10):61-64
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Clinical and biochemical syndromes of cadmium-induced acute porphyrinopathy
Abstract
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.
Terapevticheskii arkhiv. 2010;82(10):65-70
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Methylglyoxal is a test for biological dysfunctions of homeostasis and endoecology, low cytosolic glucose level, and gluconeogenesis from fatty acids
Abstract
If a lot of carbohydrates cannot be in vivo stored as glycogen, the synthesis of palmitic fatty acid (FA) from glucose and its adipocyte deposition as triglycerides are under way in phylogenesis. With impaired biological function of exotrophy (fasting, early postnatality, hibernation), the cells perform a reverse process - the synthesis of glucose from FA. Physiologically, the substrate of gluconeogenesis is acetyl-CoA that is converted by the malate → piruvate → glucose pathway in the glyoxalate cycle. Under the pathological conditions of hypoxia and energy deficiency, gluconeogenesis occurs without ATP consumption via the methylglyoxalate pathway (MGP) while using as a substrate of ketone bodies: butyric acid (butyrate) → β-hydroxybutyrate → acetoacetate → acetone → acetol → methylglyoxal (MG) → S-D-lactolglutathione → D-lactate → piruvate → D-lactate. Under physiological conditions, this pathway of gluconeogenesis does not work. The authors hold that gene expression and gluconeogenesis occur via the MGP when glucose levels are low in the cell cytosol (glycopenia) and FA cannot be oxidized in the mitochondria. Cytosol, intercellular medium, plasma show elevated levels of MG and D-lactate, to which it converts under the action of glyoxalases I and II. Glycopenia develops in fasting, diabetes mellitus, metabolic syndrome, renal failure, phenofibrate therapy, impaired function of exotrophy - excessive dietary intake of saturated and trans fatty acids. The chemical interaction of MG with amino acid residues of lysine and arginine leads to protein denaturation during carbonylation - glycosylation and impaired biological function of endoecology. The determination of plasma MG and D-lactate may be a test for glycopenia, compensatory activation of gluconeogenesis from FA or for the evaluation of endogenous intoxication.
Terapevticheskii arkhiv. 2010;82(10):71-77
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Efficiency of using cycloferon as part of combined therapy for chronic hepatitis C (a review of multicenter clinical trials)
Abstract
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.
Terapevticheskii arkhiv. 2010;82(10):78-78
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