Vol 82, No 12 (2010)
- Year: 2010
- Published: 15.12.2010
- Articles: 16
- URL: https://ter-arkhiv.ru/0040-3660/issue/view/1746
Editorial
Choice of treatment policy for hypertensive patients: its individualization, indications, and criteria
Abstract
Fundamental innovations in the study of the regulatory mechanisms of circulation in the past 20-30 years (evidence for the role of the endothelium in local hemodynamic control, the basic significance of the tissue link of the angiotensin mechanism (A-II) of not only as a vasoconstrictor, but also a trigger of a slow pressor component that remodels resistance bed arteries) have forced to revise the concept of the pathogenesis of hypertensive disease (HD) (essential hypertension) and confirmed its nosological isolation. The new refined and specified information on the pathogenesis of HD has shown to give doctors reliable landmarks to optimize drug therapy: 1) symptomatic for accelerated effective blood pressure lowering and 2) basic in order to eliminate endothelial dysfunction and to restore remodeled arteries and microcirculation.
Terapevticheskii arkhiv. 2010;82(12):5-10
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Impact of antihypertensive therapy on clinical Status and quality of life in patients with initial manifestations of hypertensive encephalopathy
Abstract
Aim. To study the clinical and instrumental characteristics of hypertensive encephalopathy (HE) in early stages, as well as the time course of their changes during long-term antihypertensive therapy (AHT).
Subjects and methods. Prior to and after 9-month AHT, 57 patients aged 50-70 years who had uncomplicated grades 1-2 arterial hypertension (AH) with grades I-II HE underwent comprehensive examination comprising the studies of cognitive functions, quality of life (QL), hemorheology, and hemostasis, duplex scanning of great and intracerebral vessels, echocardiography, 24-hour blood pressure monitoring, magnetic resonance imaging.
Results. Early-stage HE was characterized by more cerebral complaints, higher rates of hypertensive crises, a greater degree of psychoautonomic syndrome, and worse QL. Focal brain lesions were detected in 74%; left ventricular hypertrophy (LVH) was diagnosed in 61% of cases. All the patients were observed to have cognitive dysfunctions. AHT (amlodipine, lisinopril) produced a good antihypertensive effect and substantial improvements of the patients' cognitive functions, health status, and QL. LVH regression was achieved.
Conclusion. HE is a clinical manifestation of damage to the brain as the principal target organ in AH and should be therefore kept in mind in estimating the cardiovascular risk. The diagnosis of HE requires the use of tests to evaluate cognitive functions.
Terapevticheskii arkhiv. 2010;82(12):10-15
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Coronary artery necroses and calcification in chronic coronary heart disease
Abstract
Aim. To study some particularly inadequately studied mechanisms for the development of coronary artery calcification (CAC), which are unassociated with calcified atheromatous masses of atherosclerotic plaques.
Subjects and methods. Endarterectomized coronary artery (CA) segments obtained during aortocoronary bypass surgery were pathomorphologically studied in 150 patients aged 49-72 years with coronary heart disease (CHD). CAC was found in 92% of cases. Two types of CAC were identified: one of them was associated with calcified atheromatous masses of atherosclerotic plaques; the other was related to necroses in the fibrous plaque parts. The atheromatous masses exhibited calcareous deposits as fine-grained masses of small extent. In chronic CHD, morphological signs of instability of atherosclerotic plaques were observed in 23.3% of cases, these being associated with lamellar CAC in two thirds.
Conclusion. Calcification in the necrotic area of fibrous parts of stenotic plaques is typical of chronic CHD and is frequently attended by the development of large-focal calcareous deposits generally as laminas (lamellar calcification). Impaired transmural perfusion of plasma is noted to be involved in the development of necroses in stenotic CA atherosclerotic plaques.
Terapevticheskii arkhiv. 2010;82(12):16-18
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New aspects of using dihydropyridine calcium antagonists during coronary bypass surgery
Abstract
Aim. To study the contractile properties of the human radial artery (RA) and to provide a comparative clinical assessment of the results of autoarterial coronary bypass surgery (AACBS) using calcium antagonists (CA).
Materials and methods. Human RA smooth muscle samples (n = 49) taken at AACBS were experimentally studied. Mechanography was used to record the contractile responses of isolated smooth muscle samples to the contractile properties of a RA segment exposed to the liquid vasodilators nifedipine, papaverine, and sodium nitroprusside. The study enrolled 106 patients who had undergone surgical revascularization applying 2 autoarteries or more. Dihydropyridine CAs, such as adulat, norvask, and felodip, were administered by the developed protocol.
Results. Adalat experimentally showed a pronounced dose-dependence of vasodilation and long-term aftereffects, which allows the CA to be regarded as the most attractive agent for the intraoperative preparation of an autoarterial shunt.
Conclusion. The systemic use of a dihydropyridine CA in a clinical trial could reduce the incidence of early autoarterial conduit dysfunction and improve prognosis in the patients.
Terapevticheskii arkhiv. 2010;82(12):19-22
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Impact of Gly389Arg 1-adrenoceptor polymorphism on the risk of chronic heart failure, the nature of its course, and on the efficiency of its treatment with carvedilol
Abstract
Aim. To study в1-adrenoceptor gene (ADRB1) polymorphism on the development and course of chronic heart failure (CHF) and on the efficiency of its treatment with the в-adrenoblocker carvedilol in patients with coronary heart failure.
Subjects and methods. Two hundred and twenty-six patients (149 males and 77 females; mean age 55.9±5.8 years) with CHF, who received continuous basic therapy: angiotensin-converting enzyme inhibitors, a diuretic, an aldosterone antagonist, digoxin, and a в-adrenoblocker, were examined; 68 patients were given for 24 weeks carvedilol (its starting dose was 3.125 mg twice daily with its further adjustment until an individually tolerable dose was achieved). Genotypes were identified by the restriction fragment length polymorphism analysis of polymerase chain reaction products. A control group comprised 136 subjects (63 males and 73 females; mean age 55.9±5.8 years) without signs of cardiovascular disorders, as evidenced by the examination.
Results. In patients with CHF, the Gly allele of the Gly389Arg polymorphic locus of the ADRB1 gene in homozygous state was associated with the high individual risk for CHF, the severity of its clinical manifestations and the nature of its course while carriage of the Arg allele of the Gly39Arg polymorphic locus manifested itself as a protective factor. During long-term carvedilol therapy, CHF patients with the Arg/Arg genotype of the ADRB1 gene were observed to have a more pronounced decrease in the functional class of heart failure, a significant increase in left ventricular ejection, and a decrease in left ventricular end-systolic and end-diastolic sizes as compared with patients with the Gly/Arg genotype.
Conclusion. There were associations of the polymorphism of ADRB1 gene (the Gly39Arg polymorphic locus) with the development and severity of CHF and with the efficacy of therapy with в-adrenoblocker carvedilol.
Terapevticheskii arkhiv. 2010;82(12):22-28
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Effect of lornoxicam on inflammatory markers in patients with non-ST-segment elevation acute coronary syndrome
Abstract
Aim. To evaluate the clinical efficacy, safety, and effects of the nonsteroidal anti-inflammatory drug lornoxicam on inflammatory markers in non-ST-segment elevation acute coronary syndrome (NSTEACS).
Subjects and methods. Eighty-five patients with NSTESCS were enrolled in a prospective randomized study. They were divided into 2 groups: 1) patients received lornoxicam (8 or 12 mg/daily) for 15 days in addition to standard treatment and 2) controls. Cardiovascular outcomes and the levels of C-reactive protein (CRP), IL-6, and IL-10 were determined.
Results. The lornoxicam group exhibited a significant reduction in CRP and a decrease in IL-6. There was also a significant increase in IL-10 levels in this group. A 6-month follow-up indicated a significant reduction in the number of cardiovascular events (nonfatal myocardial infarction, unstable angina, coronary death).
Conclusion. Lornoxicam reduces the risk of poor cardiovascular outcomes in patients with NSTEACS and the levels of inflammatory markers.
Terapevticheskii arkhiv. 2010;82(12):28-32
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FLT3 and NPM1 gene mutations in patients with acute myeloid leukemias and the impact of FLT3-ITD mutations on the survival of patients with a normal karyotype
Abstract
Aim. To estimate the extent of FLT3 and NPM1 gene mutations and the impact of mutations of FLT3-ITD on the survival of patients with acute myeloid leukemias (AML).
Materials and methods. The nucleus-containing cells of bone marrow and blood were studied in 43 patients with AML. Polymerase chain reaction analysis of total genomic DNA was applied.
Results. Mutations of FLT3-ITD, FLT3-TDK, and the NPM1 gene were found in 16 (37.2%) patients. A total of 19 mutations were revealed. There were 8 mutations of FLT3-ITD, 5 of FLT3-TKD, and 6 in the NPM1 gene. Single damages to genes were detected in 13 patients: FLT3-ITD in 6 (13.9%), FLT3-TKD in 4 (9.3%), and NPM1 in 3 (7%). Three (7%) patients exhibited 2 mutations simultaneously: in the NPM1 and FLT3-ITD in 2 (4.7%) and in the NPM1 gene and FLT3-TKD in 1 (2.3%). In AML patients with a normal karyotype and the FLT3-ITD-/NPM1- and FLT3-ITD+/ NPM1- genotypes, median overall survival was 17.3 versus 8 months (p = 0.069); and event-free survival (EFS) was 11 versus 5 months (p = 0.026). Univariate analysis established the negative impact of FLT3-ITD mutation on EFS.
Conclusion. The findings allow AML patients with a normal karyotype and the FLT3-ITD-/NPM1- genotypes to be identified as a poor prognosis group.
Terapevticheskii arkhiv. 2010;82(12):33-39
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Acute abdominal syndrome in blood system diseases
Abstract
Aim. To define an optimal diagnostic and therapeutic algorithm when the acute abdominal syndrome occurs in hematological patients.
Materials and methods. The results of 145 emergency surgeries made in 2006-2008 for acute abdominal syndrome were studied in patients with blood system diseases.
Results. Clinical manifestations of acute abdominal syndrome emerge in 1-1.4% of all the patients treated at the Hematology Research Center, Russian Academy of Medical Sciences. There is a need for surgery in 0.5-0.7% of all the patients admitted. In this group of patients, annual postoperative mortality is 12-16%.
Conclusion. The routine algorithm for a diagnostic search in hematological patients with acute abdominal syndrome can lead to both hyperdiagnosis and unwarranted surgery, and incorrect choice of expectant policy as well.
Terapevticheskii arkhiv. 2010;82(12):39-43
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Use of various nutritional support regimens in patients with transplanted hematopoietic stem cells
Abstract
Aim. To study the impact of modified nutritional support (NS) versus standard NS on therapy tolerability and posttransplantation in patients with oncohematological diseases.
Subjects and methods. Fifty-three patients, who had been diagnosed as acute myeloblastic (n = 19) or acute lymphoblastic (n = 16) leukemias, lymphomas (n = 10), and other oncohematological diseases (n = 8) and had received large-dose polychemotherapy followed by hematopoietic stem cell transplantation (HSCT), were prospectively examined.
The control group (n = 27) used standard NS (NS was prescribed when gastrointestinal (GI) events occurred; on day 1 after HSCT, the study group (n = 26) had modified NS added by glutamine dipeptide (0.57 g/kg/day). Energy demands were 35 kcal/kg/day; protein requirements were 1.5-1.7 g/kg/day. Artificial nutrition preparations were daily given through infusion pumps for 24 hours. In both groups, the criteria for NS discontinuation were natural assimilation of 60% of the required energy within 3 consecutive days or day 14 after HSCT when GI function was preserved.
Results. The patients receiving modified NS showed reductions in the incidence and severity of mucositis (p = 0.05), a less significant decrease in the laboratory and anthropometric indicators of nutritional status (p = 0.01), and a better hospital outcome on day 100 after HSCT (p = 0.01). There were no differences in the rate and severity of acute graft-versus-host reaction (p = 0.7%) and in one-year overall survival (p = 0.7%).
Conclusion. As compared with standard NS, modified NS enables a patient to sustain negative consequences of the conditioning regimen, HSCT in the early posttransplantation period.
Terapevticheskii arkhiv. 2010;82(12):43-47
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Study of bone marrow microvessel density is one of the diagnostic approaches in patients with Ph-negative chronic myeloproliferative diseases
Abstract
Aim. To define an association of bone marrow microvessel density (MVD) with histological properties (the magnitude of fibrosis and quantification of megakaryocytes (MGKC)) in patients with Ph-negative chronic myeloproliferative diseases (CMPD).
Subjects and methods. MVD was analyzed in 93 patients with different forms of CMPD, by estimating histological parameters. True polycythemia (TP) was present in 28 patients; 20 patients had essential thrombocythemia (ET), 36 had subleukemic myelosis, out them 6 were in a prefibrotic stage, and 9 with diagnosed post-TP(ET) myelofibrosis. The grade of myelofibrosis was estimated from the degree of bone marrow fibrosis as 0, 1, 2, and 3 and the clusters of MGKC were in accordance with degrees: 0, 1, and 2. MVD was studied from the absolute number of CD34-positive vascular structures.
Results. In patients with TP, fibrosis was defined as grade 0 and 1 in 23 (82%) and 5 (18%) cases, respectively. The content of reticulin fiber was in the normal range in 19 (95%) of the 20 patients with ET. The clusters of MGKC of grades 1 and 2 showed an even distribution among patients with ET and those with TP. Fibrosis was absent in all the patients (n = 6) with prefibrotic-stage primary myelofibrosis (PMF). The patients with PMF had high MVD values [6.5 (range 2.8-22)] than those with TP [4.0 (range 1.76-10.2)] or ET [3.7 (range 2-8.5)] and the controls [3.2 (range 2-4.1)] (p < 0.001) confirming that angiogenesis is uninvolved at the onset of disease in patients with ET and those with TP. The patients with prefibrotic-stage PMF had higher values [6.0 (range 4.8-10.6)] than those with ET [3.7 (range 2-8.5)] (p < 0.001). This suggests that angiogenesis is an early sign preceding the development of fibrosis.
Conclusion. Bone marrow angiogenesis assessment (from MVD measurements) may be an additional criterion for the diagnosis of disease evolution and an additional criterion between ET and PMF in a prefibrotic stage.
Terapevticheskii arkhiv. 2010;82(12):47-51
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The survival and sequestration of transfused donor platelets in cytostatic cytopenias
Abstract
Aim. To study the survival and sequestration of transfused donor platelets labeled with 51Cr in patients with acute leukemia (AL).
Subjects and methods. Seven donor volunteers and 39 patients with different forms with AL at various stages of polychemotherapy (PCT) were examined. Cytostatic therapy was accompanied by 51Cr-labeled platelet concentrate (PC) transfusions. The patients were on appropriate high-dose (HD) PCT.
Results. The duration of donor platelet circulation was 8-10 days in healthy individuals. No platelet hypersequestration was recorded in both the spleen and the liver. Donor platelet survival was shorter in all patients with in a state of cytostatic cytopenia. There was an inverse correlation between the degree of circulation shortening and some clinical and hematological parameters (the bone marrow level of blastemia and blastosis, the XIIa-dependent fibrinolysis parameters). Four variants of radioactivity trends above the spleen and liver were identified. The findings suggest that there is platelet hypersequestration in the spleen, liver, and both organs. In some patients, the above both organs are uninvolved in the hypersequestration processes and the possible mechanism for increased consumption of transfused donor platelets, which is associated with recovery of the HD PCT-damaged vascular endothelium is considered.
Conclusion. Shortening of transfused donor platelet circulation was found in relation to the level of blastosis. The described procedure may be used as one of the additional methods for evaluating the efficacy of donor PC transfusion and for specifying the pathogenesis of thrombocytopenias in AL patients on programmed HD PCT. A procedure is proposed to time the circulation of 51Cr-labeled platelets, by assessing deposit phenomena and estimating the level of their sequestration in the spleen and liver for the prediction of the efficiency of TC transfusions.
Terapevticheskii arkhiv. 2010;82(12):51-56
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Pharmacogenetic criteria for the efficacy of basic anti-inflammatory therapy for rheumatoid arthritis
Abstract
Aim. To analyze the prognostic value of detection of allelic variants of the promoter regions of cytokine genes in patients with rheumatoid arthritis (RA) with varying efficiency of basic anti-inflammatory therapy (BAIT).
Subjects and methods. Eighty-nine patients with a valid diagnosis of RA, of them there were 79 females and 10 males (mean age 52.5±13.1 years), were examined. The patients received BAIT with methotrexate in a dose of 10.0-17.5 mg/week (77.5%) or with sulfasalazine in a dose of 2.0 g/day (22.5%) for 24 weeks. The efficiency of BAIT was evaluated using the European League Against Rheumatism (EULAR) criteria (DAS28) following 24 weeks. A high therapeutic effect was stated when DAS28 decreased by more than 1.2 scores. Changes in DAS28 by less than 0.6 scores were regarded as ineffective BAIT. Cytokine gene polymorphisms were studied by restriction analysis of amplification products. The following polymorphic sites in the interleukin genes: FNOA at positions C-863A, G-308A, G-238A, IL-1BT-31C, IL-4 C-590T, IL-6 G-174C, and IL-10 C-592A, were explored.
Results. The IL-6 G-174G genotype associated with the high production of this proinflammatory cytokine and the IL-IB C-31C genotype associated with the low production of interleukin-1в (IL-1в) were most frequently encountered in a group of patients with the high efficiency of BAIT (22 and 24.7%). At the same time the C allele associated with the low production of IL-6 and the IL1B T-31C genotype associated with the high production of this cytokine were most frequently detected at position of G-174C of the promoter regions in the IL-6 gene in patients unresponsive to BAIT (32 and 36%).
Conclusion. The allelic variants of the promoter regions of the IL-6 G-174G, IL-1B C-31C, IL-4 C-590T, and IL-10 C-592A can be genetically prognostic factors of formation of the high efficiency of BAIT.
Terapevticheskii arkhiv. 2010;82(12):56-61
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Long-term effect of 3-week intravenous б-lipoic acid administration in symptomatic diabetic polyneutropathy with clinical manifestations
Abstract
Aim. To estimate the late duration of the effect of 3-week intravenous б-lipoic acid (б-LA) administration.
Subects and methods. The study included patients with symptoms of myodiabetic polyneuropathy. The authors studied trends in neuropathic symptoms by the TSS scale and neuropathic deficit by the NIS-LL scale after 3-week intravenous a-LA (600 mg/day) administration. Control follow-up visits were made at weeks 8 and 30 of the study.
Results. In б-LA-treated patients, the mean TSS score dropped from 9.46±1.01 to 3.29±1.49 after intravenous б-LA administration and continued to decrease to 2.60±1.18 and 4.39±2.01 scores at follow-up weeks 8 and 30, respectively. In the placebo group, these were 9.78±1.23, 6.16±1.95, 6.52±1.61, and 7.36±1.31 scores at weeks 3, 8, and 30, respectively; p < 0.05). In the б-LA group, NIS-LL scores fell from 8.65±3.46 to 6.01±3.12 at therapy week 3, to 6.11±3.36, at week 8, and to 7.68±3.68 at week 30 and in the placebo group, these decreased from 8.35±3.84 to 7.81±3.51, 7.89±3.72, and 8.32±3.49 scores at weeks 3, and 8, respectively; p < 0.05).
Conclusion. Alleviated neuropathic symptoms persisted within 6 months after 3-week intravenous б-LA injection. Reduced neuropathic deficit did within 8 weeks after initiation of б-LA therapy.
Terapevticheskii arkhiv. 2010;82(12):61-64
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Use of melatonin in combined treatment for inflammatory bowel diseases
Abstract
Aim: to provide rationale for and develop treatment regimens using melatonin for inflammatory bowel diseases (IBD).
Subjects and methods. Prior to and 30 days after treatment, colonic mucosal biopsy specimens were studied by electron microscopy in 40 patients with Crohn's disease (CD) and ulcerative colitis (UC) in whom the diagnosis was verified by the examination and morphological study of the colonic mucosa. The patients were divided into 2 groups: 1) traditional pathogenetic therapy; 2) combined therapy using melatonin.
Results. Following 30-day therapy using melatonin, signs of inflammatory infiltration were absent in 77.8% of the patients with CD. Minor inflammatory infiltrates consisting mainly of lymphoid cells and solitary granulocytes persisted in the mucosa and submucosal layer in 44.4% of the CD patients receiving the therapy without melatonin. The surface of columnar cells exhibited villi in 77.8%; however, a brush border failed to form in all cells.
One month after therapy using melatonin, the ultrastructure of the colonic mucosa was normal in the patients with UC. Inflammatory infiltration and dystrophy were absent in 88.8% of cases. Small inflammatory infiltrates consisting of lymphocytes were seen in occasional mucosal portions in 50% of the melatonin-untreated patients with UC. There was focal plethora in the vessels.
Conclusion. The use of melatonin in combined therapy for IBD considerably improves the results of treatment and promotes a more complete ultrastructural recovery of the colonic mucosa.
Terapevticheskii arkhiv. 2010;82(12):64-68
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Evidence-based grounds of the efficacy of simvastatin (zocor): 15 years later
Abstract
The review describes the history of hypolipidemic therapy with statins. It gives the results of studies of the primary prevention of atherosclerosis and the treatment of hyperlipidemias with lovastatin, pravastatin, and fluvastatin. Emphasis is laid on trial data on the efficacy, tolerability, and safety of simvastatin (zocor). The results of studies, including regression ones, of this drug in different doses, controlled by biochemical, clinical, magnet resonance imaging, and ultrasonic data are summarized. There is a significant reduction in the risk of cardiovascular, coronary, and overall deaths and in that of stroke. There is evidence for the successful use of simvastatin (zocor) in combined therapy with fibrates, nicotinic acid, and ezetrol.
Terapevticheskii arkhiv. 2010;82(12):68-72
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Baroreflex sensitivity in patients with chronic heart failure: the clinical significance and impact of therapy
Abstract
The review deals with the baroreflex regulation of circulation in chronic heart failure (CHF). The pathophysiological aspects of development of dysfunction of the baroreflex clinically estimated from its sensitivity are presented; the clinical value of this indicator is discussed in relation to the etiology of the underlying disease and clinicohemodynamic status. Data on the impact of some components of current therapy for CHF and nondrug treatments on the values of baroreflex sensitivity are shown.
Terapevticheskii arkhiv. 2010;82(12):73-80
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