Vol 83, No 7 (2011)

Articles
Nine-year experience in the treatment of patients with diffuse large B-cell lymphosarcoma
Magomedova A.U., Kravchenko S.K., Kremenetskaya A.M., Zvonkov E.A., Baryakh E.A., Mangasarova Y.K., Kaplanskaya I.B., Samoylova R.S., Vorob'ev I.A., Obukhova T.N., Karagyulyan S.R., Shulutko E.M., Galstyan G.M., Mar'in D.S., Gabeeva N.G., Vorob'ev A.I., Magomedova A.U., Kravchenko S.K., Kremenetskaya A.M., Zvonkov E.A., Baryakh E.A., Mangasarova Y.K., Kaplanskaya I.B., Samoilova R.S., Vorobiev I.A., Obukhova T.N., Karagyulyan S.R., Shulutko E.M., Galstyan G.M., Maryin D.S., Gabeeva N.G., Vorobiev A.I.
Abstract
Aim. To ascertain indications to standard (CHOP-21/R-CHOP-21) and intensive (mNHL-BFM-90) treatment in patients with diffuse large B-cell lymphosarcoma (DLBCL) with involvement of lymphoid organs. Material and methods. The trial, performed from January 2002 to December 2010, enrolled 139 DLBCL patients with affected lymph nodes (LN), tonsils, spleen, bone marrow (BM). The diagnosis was made according to WHO criteria. The patients were examined according to the protocol of lymphoproliferative diseases. Biopsy material from all 139 patients was studied immunohistochemically on paraffin blocks (LN, tonsils, spleen, BM) using a wide panel of antibodies. The same examinations of BM were made in all 18 cases of BM involvement. Cytogenetic examination was performed in 106 patients: 48 standard cytogenetic tests, 139 - FISH for t (14;18) as well as rearrangement of locus 3q27. Patients with a poor prognosis (n = 86, 61.8%) received intensive therapy according to mNHL-BFM-90 program. The signs of a poor prognosis were the following: massive tumor (tumor size more than 7.5 cm), invasion into the adjacent organs or tissues, stage III-IV disease by Enn-Erbor, high concentration of LDG. Patients without a poor prognosis (n = 53, 38.2%) received standard treatment CHOP-21 (n = 28) or R-CHOP-21 (n = 25). Results. A complete remission without recurrences was achieved in all 53 patients without signs of unfavourable prognosis (100%). Overall 5-year survival was 96%, 2 patients died in remission of other causes. Of 86 patients with a poor prognosis a complete remission was achieved in 64 (74.4%) patients. Overall and recurrence-free 5-year survival was 65 and 86%, respectively. Conclusion. Standard treatment provided long-term complete remission in all the patients without poor prognosis. Intensive (mNHL-BFM-90) treatment produced the best results in generalized lesion without BM involvement. Overall 5-year survival was 84% in these patients and 12% in patients with BM involvement.
Terapevticheskii arkhiv. 2011;83(7):5-10
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Pilot results of therapy of adult Ph-negative acute lymphoblastic leukemia according to the protocol of Research Group of Russian Hematological Centers ALL-2009
Parovichnikova E.N., Klyasova G.A., Isaev V.G., Sokolov A.N., Kokhno A.V., Troitskaya V.V., Mavrina E.V., Khodunova E.E., Ustinova E.N., Gribanova E.O., Kravchenko S.K., Ryzhko V.V., Kaporskaya T.S., Baranova O.Y., Bondarenko S.N., Nizametdinova A.S., Kondakova E.V., Ryl'tsova T.V., Alufer'eva A.N., Samoylova O.S., Skamorina O.P., Gavrilova L.V., Pristupa A.S., Vopilina N.A., Konstantinova T.S., Kryuchkova I.V., Anchukova L.V., Tikunova T.S., Kaplanov K.D., Lapin V.A., Tumakov V.A., Kozmina M.N., Chernysh S.A., Podol'tseva E.I., Kulikov S.M., Davidyan Y.R., Savchenko V.G., Parovichnikova E.N., Klyasova G.A., Isaev V.G., Sokolov A.N., Kokhno A.V., Troitskaya V.V., Mavrina E.V., Khodunova E.E., Ustinova E.N., Gribanova E.O., Kravchenko S.K., Ryzhko V.V., Kaporskaya T.S., Baranova O.Y., Bondarenko S.N., Nizametdinova A.S., Kondakova E.V., Ryltsova T.V., Aluferieva A.N., Samoilova O.S., Skamorina O.P., Gavrilova L.V., Pristupa A.S., Vopilina N.A., Konstantinova T.S., Kryuchkova I.V., Anchukova L.V., Tikunova T.S., Kaplanov K.D., Lapin V.A., Tumakov V.A., Kozmina M.N., Chernysh S.A., Podoltseva E.I., Kulikov S.M., Davidyan Y.R., Savchenko V.G.
Abstract
Aim. To review results of 2-year experience in execution of the protocol on the treatment of adult acute Ph-negative lymphoblastic leukemia ALL-2009. Material and methods. Of 111 patients registered in the study from November 2008 to December 2010 the analysis covered 96 patients from 23 hematological centers in 18 towns of the RF. Results. Treatment according to the Protocol ALL-2009 resulted in achievement of a complete remission in 91.2% patients with low early lethality of 5.5%. Postremission lethality fell to 3.7% versus previous studies (22%). Overall 2-year survival and recurrence-free survival reached 77.6 and 78.4%, respectively. Detection of any chromosomic aberrations significantly affected recurrence-free survival: 74 vs 100% in patients with normal karyotype. Conclusion. Protocol All-2009 demonstrates high efficacy in moderate toxicity and good reproducibility in any hematologic center.
Terapevticheskii arkhiv. 2011;83(7):11-17
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Long-term results of HBV and HCV infection in patients with blood diseases
Garmaeva T.T., Kulikov S.M., Mikhaylova E.A., Gemdzhyan E.G., Gaponova T.V., Grumbkova L.O., Yaroslavtseva N.G., Tupoleva T.A., Somova A.V., Makarik T.V., Glinshchikova O.A., Fevraleva I.S., Sudarikov A.B., Filatov F.P., Savchenko V.G., Garmaeva T.T., Kulikov S.M., Mikhailova E.A., Gemdzhyan E.G., Gaponova T.V., Grumbkova L.O., Yaroslavtseva N.G., Tupoleva T.A., Somova A.V., Makarik T.A., Glinschikova O.A., Fevraleva I.S., Sudarikov A.B., Filatov F.P., Savchenko V.G.
Abstract
Aim. To specify trends in clinical and laboratory manifestations of virus hepatitis B and C (HBV and HCV) in patients with blood diseases from the moment of the first positive specific tests for HBV and HCV markers; to assess effects of HBV and HCV infection on efficacy of treatment of blood disease treatment, i.e. lifespan of patients with hematological diseases. Material and methods. The study enrolled 257 patients: 205 with acute leukemia - AL, 40 with lymphoproliferative diseases, 4 - with CML and 8 - others; 8 healthy bone marrow donors. The patients were admitted to Russian Hematological Research Center in 2004-2006. Follow-up median was 253 days. A total of 7800 biological samples were studied, among them about 4000 tests for HBV DNA and HCV RNA. Results. Positive tests for specific markers of HBV and HCV were absent only in 78 (29.4%) patients. Positive markers of coinfection were detected in 57 (32.8%) of 174 patients with HBV infection and in 81.4% of 70 patients with HCV infection. Probability of detection of HCV markers after positive tests for HBV markers and vice versa is about 3 times higher than probability of their isolated detection. Among patients infected with HBV symptoms of hepatitis B are likely to appear in 56% patients to day 500 of follow-up from the date of the first positive specific test. Median of the interval between the first positive test for HBV markers and probable clinical signs of hepatitis was 30 days. Among patients with HCV infection, 85% develop hepatitis to follow-up day 300 since the date of the first specific positive test. Almost 100% patients infected with two viruses develop hepatitis to follow-up day 600. Median of the interval between the first positive test for HBV and HCV markers and probable hepatitis picture was 47 days. Overall 3-year survival of AL patients was 40%, of patients with lymphoproliferative diseases - 58%. Overall 7-month survival was 75% in AA patients. HBV infection in patients with blood disease is associated with high risk of death, especially in AA and AL. Association between HCV infection and survival is not proved. Conclusion. A high rate of clinical realization of viral hepatitis B and C, especially in coinfection, calls for virological and clinical monitoring of patients with any positive test for HBV and HCV markers.
Terapevticheskii arkhiv. 2011;83(7):17-26
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Development of aceptic osteonecrosis during the treatment of acute lymphoblastic leukemia: review of the literature and original data
Baranova O.Y., Shirin A.D., Falaleeva N.A., Osmanov E.A., Baranova O.Y., Shirin A.D., Falaleeva N.A., Osmanov D.S.
Abstract
We report a case of aceptic osteonecrosis (AON) of the left hymerus epiphysis in programmed treatment of a male patient with lymphoblastic lymphoma to illustrate clinical, laboratory, epidemiological, pathogenetic, diagnostic and therapeutic aspects of AON in programmed therapy of acute lymphoblastic leukemia (ALL). We believe that AON is a rather frequent but often missed for early diagnosis complication of ALL treatment. Even a weak pain in bones and joints under mechanical load in patients on long-term treatment with glucocorticosteroids is an alarming symptom which may indicate a risk of an osteodestructive process and relevant diagnostic and therapeutic measures may be needed.
Terapevticheskii arkhiv. 2011;83(7):26-32
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Follow-up study of expression of Bcl-2, Bax, p53 and ACE in CD34+ cells of peripheral blood and bone marrow in acute leukemia patients in the course of induction chemotherapy
Khodunova E.E., Parovichnikova E.N., Gal'tseva I.V., Kulikov S.M., Isaev V.G., Savchenko V.G., Khodunova E.E., Parovichnikova E.N., Galtseva I.V., Kulikov S.M., Isaev V.G., Savchenko V.G.
Abstract
Aim. To determine unbalance in the system of programmed cell death in the cells CD34+ of the bone marrow (BM) and peripheral blood (PB) before and after cytostatic impact in acute leukemia (AL). Material and methods. Flow cytoflowmetry estimated expression of Bcl-2, Bax, p53 and ACE in the cells CD34+ of BM and PB from 10 AL (4 AML and 6 ALL) patients. PB and BM samples were studied before polychemotherapy (PCT) and in the course of induction treatment: on day +8, +21 (blood only), +36 - 38. Control group consisted of 4 BM donors. Results. The number of CD34+ cells expressing Bcl-2 in AL patients was 46,5 ± 9,35 % in BM and 39,4 + 10,8 % in PB, in healthy donors - 9 and 32,8 %, respectively. Bax expression in AL patients' cells CD34+ of BM versus this expression in donors was 3 times higher (36,7 ± 8,1 and 14,8%, respectively), of PC - 2 times lower (40,7 ± 6,59 and 75,8%, respectively). Expression of p53 in AL patients was 36,8 ± 9 % in BM and 26 ± 7,4 % in PB, in donors - 28,2 and 65 %, respectively. ACE expression on the cells CD34+ in AL patients in early disease was 62 ± 7,57 % in BM and 48 ± 8,1 % in PB, in donors - 40 and 85 %, respectively. Moreover, there were significant changes in expression of Bcl-2 in BM and Bax, ACE and p53 in PB in the cells CD34+ in AL patients during and after induction PCT. Conclusion. The above changes evidence for unbalance of pro- and antiapoptosis proteins of regulators in AL patients. PCT changes profile of expression of these proteins, but not to the level of healthy donors.
Terapevticheskii arkhiv. 2011;83(7):32-37
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Primary mediastinal (thymic) large B-cell lymphoma: review of the literature and original data
Kichigina M.Y., Tumyan G.S., Kovrigina A.M., Trofimova O.P., Larionova V.B., Chekan A.A., Bykov D.A., Osmanov D.S., Kichigina M.Y., Tumyan G.S., Kovrigina A.M., Trofimova O.P., Larionova V.B., Chekan A.A., Bykov D.A., Osmanov D.S.
Abstract
Aim. To study morphoimmunological and clinical features of primary mediastinal large B-cell lymphoma (PMLBCL). Material and methods. We analysed the results of biopsy material study and treatment of 86 PMLBCL patients, effects of different factors on the disease prognosis, efficacy of some therapeutic programs and overall therapeutic efficacy. Results. PMLBCL manifests mainly with massive lesions of anterior upper mediastinum with involvement of adjacent organs and tissues, absence of bone marrow involvement, frequent affection of CNS. Many primary patients have resistance to treatment, sensitive patients have no late recurrences. Conclusion. PMLBCL is an independent extranodal variant of non-Hodgkin's lymphoma with special clinical and morphoimmunological characteristics. Criteria are proposed for differential diagnosis of different variants of PMLBCL. New approaches to PMLBSL patients' management are outlined.
Terapevticheskii arkhiv. 2011;83(7):38-46
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Differential diagnosis of thymic hyperplasia and mediastinal tumor in patients with Hodgkin's lymphoma after chemotherapy
Moiseeva T.N., Al'-Radi L.S., Shitareva I.V., Shevelev A.A., Kostina I.E., Kravchenko S.K., Kremenetskaya A.M., Tsyba N.N., Moiseeva T.N., Al-Radi L.S., Shitareva I.V., Shevelev A.A., Kostina I.E., Kravchenko S.K., Kremenetskaya A.M., Tsyba N.N.
Abstract
Aim. To make differential diagnosis of thymic hyperplasia and mediastinal tumor after chemotherapy (CT) in patients with Hodgkin's disease (HD). Material and methods. The examination of 182 HD patients aged 16-71 years (median 28 years) included chest x-ray computed tomography (XCT) at baseline, during treatment, each 3 months, ultrasound investigation of the chest and abdominal cavity. All the patients received 6-8 courses of the treatment according to the program BEACOPP-14 followed by radiotherapy on the residual tumor in 137 patients, or not followed in 45 patients. Results. Soft tissue tumor in the anterior mediastinum was detected in 14 (31%) from 45 unirradiated patients (age 19-31 years, median 24 years) 1 to 10 months (median 3.5 months) after chemotherapy. The analysis of the data of ultrasound investigation and tomography identified a mediastinal lesion as thymic hyperplasia. The patients are now in remission with follow-up median 21 months (13-36 months). No recurrence was registered. Conclusion. Young HD patients with unirradiated mediastinum develop thymic hyperplasia in 31% cases within one year after chemotherapy. In view of this, detection of the lesion in the anterior mediastinum after CT demands complex examination for differential diagnosis of thymic hyperplasia with tumor recurrence to avoid unwanted intensification of the treatment.
Terapevticheskii arkhiv. 2011;83(7):47-50
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Optimization of regimes of mobilization of blood hemopoietic stem cells in patients with multiple myeloma
Pokrovskaya O.S., Mendeleeva L.P., Urnova E.S., Gaponova T.V., Gribanova E.O., Alekseeva I.V., Drokov M.Y., Kalinin N.N., Gretsov E.M., Klyasova G.A., Savchenko V.G., Pokrovskaya O.S., Mendeleeva L.P., Urnova E.S., Gaponova T.V., Gribanova E.O., Alekseeva I.V., Drokov M.Y., Kalinin N.N., Gretsov E.M., Klyasova G.A., Savchenko V.G.
Abstract
Aim. To determine an optimal cyclophosphamide dose in the mobilization scheme providing adequate collection of CD34+ cells in patients with multiple myeloma (MM), to optimize the time of initiation of granulocytic colony-stimulating factor (G-CSF) administration, to study effects of induction therapy schemes on results of mobilization and collection of CD34+ cells. Material and methods. Department of hemoblastoses chemotherapy and bone marrow transplantation of the Russian Hematological Center performed mobilization of autologous blood hemopoietic stem cells (BHSC) in 93 MM patients treated in 2001-2010. This was done with cyclophosphamide and G-CSF. The former was used in 59 cases in a dose 6 g/m2, in 34 cases - 4 g/m2. Results. Myelotoxic agranulocytosis after cyclophosphamide administration developed in all the patients and was observed for 3-10 days (median 5 days). Agranulocytosis ran without documented infections in 51 (54.8%) patients, with febril fever - in 42 (45.2%) patients. Cepticemia, pneumonia, necrotic enteropathy, stomatitis, herpetic lesion of the skin were registered in 9, 4, 11, 14 and 6 cases, respectively. Severe thrombocytopenia (< 30x109/l) occurred more frequently in administration of 6 g/ m2 cyclophosphamide. It was corrected with 2-5 transfusions of thromboconcentrates, only 1 transfusion was needed after the dose 4 g/m2. Collection of CD34+ cells started in leukocyte level over 3.5x109/l on mobilization day 12-20 (median day 15). The day of the first leukocytapheresis did not depend on the day of the first introduction of G-CSF. Duration of G-CSF administration was significantly shorter in the start of its use after leukocyte count decrease under 1.0x109/l. Conduction of 1 to 5 (median 2) leukocytapheresis was needed for collection of BHSC. Sufficient for 2 autotransplantations number of BHSC were stored in 90 of 93 patients. Cyclophosphamide administration in a dose 6 g/m2 allowed collection of cells sufficient for one autotransplantation for the first leukapheresis in 52 (88.1) patients. A total number of CD34+ cells over 4x106 cells/kg were collected in 56 (94.9%) patients. In administration of cyclophosphamide in a dose 4 g/m2 mobilization was effective in all 34 patients. The first leukapheresis provided sufficient for one autotransplantation number of cells in 29 (85.3%) patients. Conclusion. Administration of high cyclophosphamide doses in combination with G-CSF is an effective and safe method of BHSC mobilization providing collection of adequate number of CD34+ cells for double autotransplantation in 96.8% patients. Cost effective is the start of G-CSF administration in the fall of leukocytes under 1.0x109/l. Cyclophosphamide dose 4 g/m2 provides collection of CD34+ cells number sufficient for two autotransplantations in moderate thrombocytopenia and in less number of substitute transfusions in the absence of serious toxic complications.
Terapevticheskii arkhiv. 2011;83(7):50-57
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Extremely high concentration of mexotrexate in blood serum leading to development of acute renal failure in a patient with acute lymphoblastic leukemia after high-dose consolidation
Pimenova M.A., Sokolov A.N., Biryukova L.S., Ustinova E.N., Shaforostova I.I., Donskova I.A., Bogdanov R.F., Parovichnikova E.N., Savchenko V.G., Pimenova M.A., Sokolov A.N., Biryukova L.S., Ustinova E.N., Shaforostova I.I., Donskova I.A., Bogdanov R.F., Parovichnikova E.N., Savchenko V.G.
Abstract
Acute renal failure (ARF) is one of rare and severe methotrexate(MT)-induced complications in patients with acute lymphoblastic leukemia. A case of MT-induced renal dysfunction with an extremely high serum MT concentration is reported. This toxicity required conduction of hemodiafiltration for extracorporeal MT elimination. The presence of homozygous mutation of methylene-tetrahydrofolate reductase reflects an individual metabolism of MT and its renal clearance.
Terapevticheskii arkhiv. 2011;83(7):58-61
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A case of legionellesis pneumonia verified by isolation of legionella pneumophila serogroup 1 from bronchoalveolar lavage treated with levofloxacine and tigecycline
Galstyan G.M., Drokov M.Y., Katrysh S.A., Klyasova G.A., Gilyazitdinova E.A., Karpova T.I., Marakusha B.I., Tartakovskiy I.S., Galstyan G.M., Drokov M.Y., Katrysh S.A., Klyasova G.A., Gilyazitdinova E.A., Karpova T.I., Marakusha B.I., Tartakovsky I.S.
Abstract
A male patient received non-chemotherapeutic drugs which induced deep neutropenia complicated with sepsis, bilateral pneumonia, acute respiratory insufficiency. Artificial pulmonary ventilation was applied. The examination of bronchoalveolar lavage showed the presence of the culture L. pneumophila (serogroup 1) in a concentration 2x103 CFU/ml. Antibacterial therapy with levofloxacin in a dose 1000 mg/day was conducted. In a week not only L.pneumophila but also Acinetobacter baumanii was isolated from bronchoalveolar lavage. Tigecyclin was added to levofloxacin treatment. Two air cavities were found in the left lung. The treatment reduced the size of these cavities, infiltrative changes in the lungs and respiratory insufficiency regressed. The patient was discharged from hospital. This case is the first case in Russia of L.pneumophila isolation from bronchoalveolar lavage. The case is also characterized by use of tigecycline for treatment of combined legionella and akinetobacterial infection and cavities in the lungs in legionella pneumonia.
Terapevticheskii arkhiv. 2011;83(7):61-65
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Nephropathy caused by non-amyloid organized and granular deposits as multiple myeloma syndrome
Rekhtina I.G., Golitsina E.P., Biryukova L.S., Rekhtina I.G., Golitsina E.P., Biryukova L.S.
Abstract
A rare variant of nephropathy in multiple myeloma (MM) is reported. Nephropathy is characterized basing on the study of nephrobiopsy with light, immunofluorescent and electron microscopy. A repeat biopsy of the kidney was made after achievement of a complete clinicohematological remission. A MM patient's nephrobiopsy in a picture of glomerulonephritis had 3 types of deposits: granular, irregular fibrils of 12 nm in diameter and microtubes organized in bunches 19 nm in diameter. Congo red test was negative, cryoglobulinemia was absent. Immunofluorescent test detected deposit of monoclonal IgG in the mesangium and glomerular basal membrane (GBM) corresponding to monoclonal type of monoclonal secretion. After treatment and achievement of remission, neither IgG no light chains were found in nephrobiopsy. Electron microscopy registered complete resorption of granular deposits and microtubes with formation of electron-transparent cavities. However, fibrils seen before treatment only in mesangium appeared in the above hollow cavities. The presence of such fibrils in the mesangium and GBM did not influence clinical picture of the disease. After achievement of remission the patient had no clinical and laboratory signs of nephropathy, only insignificant selective glomerular proteinurea was observed (0,5 g/l). Thus, granular deposits and microtubes contained paraprotein, they were completely resorbed after achievement of MM remission. Fibrils seem to have another genesis unrelated to monoclonal gammapathy.
Terapevticheskii arkhiv. 2011;83(7):65-68
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Hematologic disorders in celiac disease
Parfenov A.I., Parfenov A.I.
Abstract
Gluten-sensitive celiac disease (GSCD) belongs to systemic diseases one of manifestations of which may be various hematological disorders. Some patients with GSCD have blood changes, anemia in particular, which precede clinical symptoms of celiac disease. Anemia can arise as a result of disorders in iron, folic acid and/or vitamin B12 absorption. Celiac disease can be associated with thrombocytosis, thrombocytopenia, leucopenia, vein thrombosis, hyposplenism, immunoglobulin A deficiency. Patients with celiac disease have a high risk of lymphoma, especially of T-cell lymphoma associated with enteropathy, B-cell non-Hodgkin's lymphoma. Aglutenic diet, recovery of structure and function of the small intestine eliminate or attenuate hematological disorders associated with GSCD.
Terapevticheskii arkhiv. 2011;83(7):68-73
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Endothelial condition and hemostasis in acute leukemia
Tarasova L.N., Skol'skaya O.Y., Vladimirova S.G., Tarasova L.N., Skolskaya O.Y., Vladimirova S.G.
Abstract
The review presents modern conceptions of disturbances in endothelial lining of the vessels and plasmic hemostasis in patients with acute leukemia; different mechanisms of coagulation disorders in acute leukemia: effects of leukemic cells containing procoagulants, fibrinolytic and antifibrinolytic substances, of intensive chemotherapy and inflammation. All these impacts impair endothelial cells and trigger plasmic coagulation cascade; the initiator of coagulation is a tissue factor. Mechanisms of this process and statistics of thrombohemorrhagic complications in different variants of acute leukemia are outlined.
Terapevticheskii arkhiv. 2011;83(7):74-78
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Reforms of practical medicine in the course of the first scientific revolutions (the XVII century 1770s). Communication 1. Therapeutic-diagnostic Galen's conception and failure of its practical use
Stochik A.M., Zatravkin S.N., Stochik A.M., Zatravkin S.N.
Abstract
This communication outlines basic principles of Galen's therapeutic and diagnostic conception which dominated in medicine for 15 centuries, shows changes in the attitude of medical professionals to this conception as a result of discoveries of the first scientific revolution. Two leading trends in reforms of practical medicine in the XVII century are described.
Terapevticheskii arkhiv. 2011;83(7):78-80
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