Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma.

We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34.8 months (range: 0.1-45.8). Investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib+BR, versus 14.3 months for placebo+BR (hazard ratio [HR] [95% CI], 0.206 [0.159-0.265]; P < 0.0001); 36-month PFS rates were 68.0% versus 13.9%, respectively. The results are consistent with the primary analysis findings (HR = 0.203, as assessed by independent review committee, with 17-month median follow-up). Median overall survival was not reached in either arm; HR (95% CI) for ibrutinib+BR versus placebo: 0.652 (0.454-0.935; P = 0.019). Minimal residual disease (MRD)-negative response rates were 26.3% for ibrutinib+BR and 6.2% for placebo+BR (P < 0.0001). Incidence of treatment-emergent adverse events (including grades 3-4) were generally consistent with the initial HELIOS report. These long-term data support improved survival outcomes and deepening responses with ibrutinib+BR compared with BR in relapsed CLL/SLL.

[Adult B-cell acute lymphoblastic leukemias: Conclusions of the Russian prospective multicenter study ALL-2009]. / Ostrye V-limfoblastnye leikozy vzroslykh: vyvody iz Rossiiskogo prospektivnogo mnogotsentrovogo issledovaniia OLL-2009.

AIM: To analyze the efficiency and reproducibility of the ALL-2009 protocol within the Russian prospective multicenter study based on different principles of cytostatic effects (non-intensive, but continuous cytotoxic treatment and a small number of allogeneic hematopoietic stem cells). SUBJECTS AND METHODS: The ALL-2009 (NCT01193933) study conducted in April 2009 to December 2016 included 194 patients (95 males and 99 females) aged 15 to 55 years (median age 28 years) with Ph-negative B-cell acute lymphoblastic leukemia (ALL). There was early pre-B-cell ALL in 54 patients, common ALL in 101, pre-B ALL in 39, initial leukocytosis in 9.4·109/l (0.4-899.0), lactate dehydrogenase in 901 IU (31-13 059), an initial central nervous system lesion in 17 (8.7%), mediastinal injury in 3 (1.5%), and splenomegaly in 111 (57.2%). The results of standard cytogenetic analysis are known in 113 (60.4%) patients. Normal karyotypes were detected in 49 (54.5%) out of the patients; t(4;11) in 9 (5.4%), t(1;19) in 2 (1.2%), and other karyotypic abnormalities in 53 (46.9%). Thirteen (7.8%) patients underwent allogeneic hematopoietic stem cell transplantation in first complete remission (CR); their proportion did not differ in the federal and regional centers. RESULTS: The frequency of CR achievement was the same in the federal and regional centers and generally amounted to 87.5%. Early (8.8%) and CR (9.6%) mortality rates remained high despite the low aggressiveness of cytotoxic action, necessitating the improvement of auxiliary treatment. The five-year overall survival (OS) rates vary considerably in the federal and regional centers (72.6 and 43.8%), the relapse-free survival (RFS) (70.2 and 53.4%) and recurrence risk (23.1 and 36.5%) are comparable. This suggests that the non-intensive, but continuous exposure principle built in the ALL-2009 protocol makes it possible to reproduce the envisaged treatment program and to achieve satisfactory results. CONCLUSION: The ALL-2009 protocol allows both the federal and regional centers to obtain the long-term results comparable with those of current foreign studies: OS (54.2%), RFS (56.5%); and relapse risk (35.4%). Multivariate analysis has identified age (over 30 years), initial leukocytosis (30·109/l and more) and t(4;11) among the main clinical prognostic factors. Gene mutation detection evaluated in a small number of patients (8/36) is not a poor prognostic sign. There is a need for further investigations with centralized evaluation of the mutation status of leukemic cells and the clearance of minimal residual disease.

Analysis of Photoprotection and Apparent Non-photochemical Quenching of Chlorophyll Fluorescence in Tradescantia Leaves Based on the Rate of Irradiance-Induced Changes in Optical Transparence.

The kinetics of irradiation-induced changes in leaf optical transparence (ΔT) and non-photochemical quenching (NPQ) of chlorophyll fluorescence in Tradescantia fluminensis and T. sillamontana leaves adapted to different irradiance in nature was analyzed. Characteristic times of a photoinduced increase and a dark decline of ΔT in these species were 12 and 20 min, respectively. The ΔT was not confirmed to be the main contributor to the observed middle phase of NPQ relaxation kinetics (τ = 10-28 min). Comparison of rate of photoinduced increase in ΔT and photosystem II quantum yield recovery showed that the former did not affect the tolerance of the photosynthetic apparatus (PSA) to irradiances up to 150 µmol PAR·m-2·s-1. Irradiance tolerance correlated with the rate of "apparent NPQ" induction. Considering that the induction of apparent NPQ involves processes significantly faster than ΔT, we suggest that the photoprotective mechanism induction rate is crucial for tolerance of the PSA to moderate irradiance during the initial stage of light acclimation (first several minutes upon the onset of illumination).

[Acute Ph-negative lymphoblastic leukemias in adults: Risk factors in the use of the ALL-2009 protocol]. / Ostrye Ph-negativnye limfoblastnye leikozy vzroslykh: faktory riska pri ispol'zovanii protokola OLL-2009.

AIM: to analyze well-known risk factors (RFs), such as age, immunophenotype, baseline leukocytosis, enhanced lactate dehydrogenase (LDH) activity, time to achieve complete remission, a risk group, and cytogenetic abnormalities) in patients with acute lymphoblastic leukemia (ALL) in the use of the ALL-2009 protocol. SUBJECTS AND METHODS: The protocol covered 298 patients (137 women (including 13 pregnant women) and 161 men) aged 15 to 55 years (median age 28 years) with Ph-negative ALL. The phenotype was unknown in 6 patients. Three (1%) were ascertained to have a biphenotypic variant. 182 (62.4%) patients were found to have B-cell ALL (early pre-B ALL (n=51); common ALL (n=92), and pre-B ALL (n=39); 107 (36.6%) patients had T-cell ALL (early T-ALL (n=56); thymic T-ALL (n=41), and mature T-ALL (n=10). According to the baseline clinical and laboratory parameters (leukocytosis of 30·109/l and more for B-ALL; and that of 100·109/l and more for T-ALL; phenotype В-I for B-ALL, phenotype Т-I-II-IV for T-ALL; LDH activity was more than twice the normal values; the presence of translocation t(4;11)), the high-risk group included most patients with B-ALL (n=110 (72.8%)) and T-ALL (n=76 (76%)). Thirty-five patients with T-ALL underwent autologous bone marrow transplantation (BMT). Allogeneic BMT was performed in 18 (7%) of the 258 patients who had undergone an induction phase. RESULTS: Five-year overall survival for all the patients included in the investigation was 59%; relapse-free survival was 65%, which was significantly different in the patients with B-ALL and in those with T-ALL: the overall survival rates were 53.3 and 67.5% (p=0.1); the relapse-free survival was 56 and 79% (p=0.005), respectively. Multivariate analysis including the well-known RFs demonstrated that the latter for T-ALL were of no independent prognostic value and only the patient's age was identified for B-ALL (p=0.013). CONCLUSION: A lower chemotherapeutic load and a small number of allogeneic BMTs did not affect total positive treatment results in adult patients with ALL, by complying with the principle achieving the continuity of cytostatic effects and by preserving the total cytostatic loading dose. The results of the Russian investigation casts some doubt on the necessity of using very intensive consolidation cycles and performing a large number of allogeneic BMTs in adult patients with ALL.

[Autologous hematopoietic stem cell transplantation as late high-dose consolidation in adult patients with T-cell lymphoblastic leukemias: Results of a Russian multicenter study].

AIM: To analyze the efficiency of the ALL-2009 protocol (ClinicalTrials.gov NCT01 193933) in patients with T-cell leukemias, particularly the role of autologous hematopoietic stem cell transplantation (auto-HSCT) after non-myeloablative BEAM conditioning, followed by maintenance therapy. SUBJECTS AND METHODS: Since 2009, the ALL-2009 study has enrolled 90 patients with T-cell acute lymphoblastic leukemia (T-ALL), the treatment results were assessed in 86 patients: 6 and 28 patients underwent allogeneic HSCT and auto-HSCT, respectively. A landmark analysis was used to compare survival rates in patients who had undergone auto-HSCT and in those who had not. For this, the median time from complete remission to the date of auto-HSCT was determined (the median was 6 months). Then to compare with the auto-HSCT group, only 27 patients who had been in complete remission for 6 months or more were included in a chemotherapy group. RESULTS: The achievement of complete remission in patients with thymic T-ALL (100%) was significantly higher than in those with early (85.7%) or mature (70%) variants. The patients with early and mature T-ALL as compared to those with thymic T-ALL showed high death rates in the remission induction (7.4 and 10% versus 0) and the patients with mature T-ALL had a.higher proportion of refractory forms (20% versus 0). The 5-year overall and relapse-free survival rates in all the T-ALL patients were 66 and 76%, respectively. After auto-HSCT, the risk of recurrence was 0% versus 21% after chemotherapy (p=0.03). The relapse-free survival rates significantly differed in the auto-HSCT and non-auto-HSCT groups: 100 and 66%, respectively (p=0.047). CONCLUSION: The long-term survival rates obtained during this multicenter study in the T-ALL patients treated according to the ALL-2009 protocol, the basis for which is the principle of continuity of cytostatic effects, are exclusively optimistic. Late consolidation with auto-HSCT following non-myeloablative BEAM conditioning, followed by maintenance therapy, considerably reduces the risk of recurrence.

Addition of ivabradine to ß-blocker improves exercise capacity in systolic heart failure patients in a prospective, open-label study.

INTRODUCTION: Difficulties initiating and uptitrating ß-blockers due to tolerability can complicate management of heart failure. Among other actions, ß-blockers reduce heart rate, which is an important cardiovascular risk factor in heart failure. A new therapeutic strategy is ivabradine, which reduces resting heart rate and is associated with improved outcomes. METHODS: A 5-month, prospective, open-label, nonrandomized single-center study was performed in 69 patients. All patients had chronic heart failure with left ventricular systolic dysfunction in sinus rhythm, each were initiated on 3.125 mg twice daily (bid) carvedilol alone (n = 36) or 3.125 mg bid carvedilol/5 mg bid ivabradine (n = 33), on top of background therapy including angiotensin-converting enzyme inhibitor (88%), diuretics (86%), antiplatelet agents (91%), and statins (90%). Dosages were uptitrated every 2 weeks to 25 mg bid carvedilol in both groups and 7.5 mg bid ivabradine maximum in the carvedilol/ivabradine group. Uptitration of carvedilol lasted 1.9 ± 0.4 months with carvedilol/ivabradine and 2.8 ± 0.6 months with carvedilol alone (P < 0.05). RESULTS: The patients receiving ivabradine had lower resting heart rate at 5 months (61.6 ± 3.1 versus 70.2 ± 4.4 bpm, P < 0.05). Adding ivabradine to carvedilol in patients with heart failure was associated with increases in the 6-min walk test and ejection fraction (all P < 0.05). Treatment tolerability was satisfactory. Patients receiving ivabradine and carvedilol had lower heart rates and better exercise capacity than those on carvedilol alone. CONCLUSION: Adding ivabradine to carvedilol in patients with chronic heart failure improves the uptitration of ß-blocker. The results merit further verification in a prospective double-blind study.

[Russian experts' clinical guidelines for acute myeloid leukemia treatment in patients less than 60 years of age].

The purpose of the paper is to present Russian experts' consolidated opinion about acute myeloid leukemia (AML) treatment in adult patients aged less than 60 years. The guidelines have been elaborated having regard to foreign publications and Russian experience, on the basis of global and Russian clinical trials to treat AML and to define indications for allogeneic bone marrow transplantation in patients during first complete remission.

[The first results of treatment for adult acute myeloid leukemia according to the AML-01.10 protocol of the Research Group of the Hematology Centers of Russia].

AIM: To give the preliminary results of the AML-01.10 Russian multicenter randomized trial to treat adult acute myeloid leukemia (AML), the basic principle of which is to use high-dose anthracycline antibiotics in induction/consolidation. SUBJECTS AND METHODS: By December 2011, 145 patients with AML had been randomized from 18 hematology centers of 15 cities and towns of the Russian Federation; the median age of all the patients was 44 years. Seventy-one patients were analyzed in August 2011 (a 1.5-year follow-up). RESULTS: The efficiency of 2 courses 7+3 using high-dose daunorubicin (60 mg/m2 per administration) and continuous infusion of cytarabine during the second course was high and comparable with that in the use of a high-dose HAM protocol as a second induction course and can achieve a complete remission in 74.6%. The protocol toxicity evaluated from its early mortality (11.3%) and its death in complete remission (16.6%) was permissible, particularly by taking into consideration the multicenter pattern of the trial. At the completion of analysis, 53 (68.8%) out of the 77 patients on whom the data on their vital status were available were alive. In this follow-up period, the frequency of recurrences was 19.2% (10/52). Only 3 (4.2%) patients out of the 71 patients in whom the efficiency of the protocol had been completely evaluated underwent allogeneic bone marrow transplantation. CONCLUSION: The total high dose (720 mg/m2) of anthracycline antibiotics, which is used in the period of induction and consolidation, determines the long periods of myelosuppression and intercourse intervals. Protocol deviations (no course of consolidation therapy, lower-dose idarubicin during consolidation therapy, a course of low-dose cytarabine, between the courses of induction and consolidation chemotherapy, and very long intercourse intervals) were recorded in a total of 20 (28%) patients.

[First results of Ph-negative acute lymphoblastic leukemia therapy of adults according to the protocol of Research Group of Russian Hematological Centers ALL-2009].

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.

Effects of light environment on the induction of chlorophyll fluorescence in leaves: a comparative study of Tradescantia species of different ecotypes.

In this work, using a PAM-fluorimetry technique, we have compared effects of plant adaptation to the light or dark conditions on the kinetics of chlorophyll a fluorescence yield in Tradecantia leaves of several species (Tradescantia albiflora, Tradescantia fluminensis, Tradescantia navicularis, and Tradescantia sillamontana), which represent plants of different ecotypes. Two fluorescence parameters were used to assess photosynthetic performance in vivo: non-photochemical quenching (NPQ) of chlorophyll fluorescence (q(NPQ)) determined by energy losses in the light-harvesting antenna of photosystem 2 (PS2), and PS2 operating efficiency (Φ(PSII)). Comparative study of light-induced changes in q(NPQ) and Φ(PSII) has demonstrated that shade-tolerant Tradecantia species (T. albiflora Kunth, T. fluminensis Vell.) reveal higher capacities for NPQ and demonstrate slower transitions between the 'light-adapted' and 'dark-adapted' states than succulent species T. navicularis and T. sillamontana, which are typical habitats of semi-deserts. We analyze the photosynthetic performance of Tradescantia species in the context of their adaptabilities to variable environment conditions. The ability of shade-tolerant plants to retain a relatively long-term (∼40-60 min) 'memory' for illumination history may be associated with the regulatory mechanisms that provide the flexibility of photosynthetic apparatus in response to fluctuations of light intensity.

[Toxicity of different treatment protocols for acute myeloid leukemias in adults: the results of four Russian multicenter studies].

AIM: To comparatively analyze the toxicity of 4 treatment protocols in patients with acute myeloid leukemia (AML), which were used in the Russian multicenter center in 1992 to 2009. MATERIALS AND METHODS: The information obtained in 4 Russian multicenter studies conducted in 33 hematology departments of 26 cities and towns of the Russian Federation in 1992 to 2009 was analyzed. Randomization was made in 243 patients with AML (median age 38 years) in 1992-1995, 396 patients (median age 39 years) in 1995-1999, 392 patients (median age 39 years) in 2001-2006, and 137 patients (median age 40 years) in 2006-2009. The analysis excluded patients with acute promyelocytic leukemias who were recruited in the AML-92 and AML-95 studies. These patients' statutory forms adequately filled in were 60-70% therefore toxicity was analyzed on the basis of the data of 631 patients. RESULTS: The baseline clinical and laboratory parameters in the patients enrolled in the studies in different years slightly differ in the count of leukocytes at the onset of the disease and in the level of lactate dehydrogenase (LDH): the recent studies revealed a larger number of high-risk group patients (leukocytes more than 30 10(9)(/l; LDH more than 500 units) possibly due to the later diagnosis of AML. During the studies, the number of complete remissions remained as before (55%) after the first course and increased from 65 to 78% after the second course using cytosine arabinoside in high doses. Despite treatment intensification, mortality in the induction period remained as before (19-21%). Remission mortality decreased from 18 to 10-13%. The long-term results of using the aggressive therapy did not differ from those obtained during the standard treatment protocols. The duration of leucopenia after standard induction courses during the all studies remained equal (17-19 days); the exclusion was a HAM course as the second induction course after which the duration of neutropenia was much more than that of the standard course (17 and 10 days, respectively). During the study years, there was an increase in platelet transfusion volumes (from 20 to 53 doses during the first course and from 7 to 28 doses during the second course) and a reduction in the percentage of severe hemorrhagic complications. The incidence of pneumonias remained at the same level (40-50%) during the induction courses and that of septic complications and necrotic enteropathy considerably decreased from 40-46 to 17-19%. The incidence of invasive aspergillosis during the current programs from AML treatment was 10% (two induction courses), that of invasive candidiasis was 4.7% (two induction courses). CONCLUSION; The long-term results of treatment for AML were virtually unchanged regardless significant therapy intensification. Mortality remained high during induction treatment and in the postremission period. Its cause is severe infectious complications developing during myelotoxic agranulocytosis. The results of the analysis provide the basis for developing a new AML treatment protocol that should take into account all the merits and demerits of the previous protocols and provide a toxicity-treatment efficiency balance.

[Reaction of the autonomic nervous system to carbon dioxide baths in patients with cardiovascular diseases].

Holter ECG monitoring was for the first time accomplished before, during, and several hours after a balneologic procedure (carbon dioxide bath) with simultaneous analysis of cardiac rhythm variability. Results of the study suggest the possibility of high-quality ECG monitoring n the course of balneologic treatment. Its data can be used to evaluate cardiac rhythm variability and estimate the degree of activation of sympathetic and parasympathetic components of the vegetative nervous system in patients with cardiovascular diseases in response to balneotherapeutic procedures.

[The results of a multicenter randomized trial on the treatment of acute myeloid leukemia of adults].

AIM: Systematization of the results of 20-year multicenter randomized trial of the efficacy of treatment of acute myeloid leukemia (AML) of adults; presentation of the design of the study of the strategy of consolidation and maintenance therapy after high-dose consolidation initiated in 2007. MATERIAL AND METHODS: Treatment outcomes on the protocol AML-01.01 are presented for 354 AML patients from 29 hematological centers located in 22 towns of Russia and 2 towns of Ukraine. The patients were randomized into 3 groups by variant of therapy: 124 patients (62 males and 62 females; age median 42 years) received 4 courses of 7+3+VP-16 and 5 courses of maintenance therapy (7+3 with thioguanin); 130 patients (65 males and 65 females, age median 41 year) received 2 courses of 7+3+VP-16, 2 courses 7+3, maintenance--5 courses 7+3 with thioguanin; 126 patients (57 males and 68 females, age median 40 years) were given 2 courses of 7+3+VP-16, 2 HAD courses, treatment discontinuation. RESULTS: A complete remission after the first course of 7+3+VP-16 was achieved in 55% patients, after the second course--in 30% after the course 7+3+VP-16 or 7+3 with mitoxantron, in 70%--after NAM. Overall and recurrence-free survival were 18 and 35%; 30 and 20%; 36 and 30%, respectively. There was no significant difference in efficacy of the treatment scheme. CONCLUSION: The multivariate analysis has shown that a leading factor having impact on treatment results was the number of randomized patients: the less patients were randomized, the worse were the results.

[Treatment of idiopathic thrombocytopenic purpura in adults: efficacy of domestic intravenous immunoglobulin in immune thrombocytopenia]. / Lechenie idiopaticheskoi trombotsitopenicheskoi purpury u vzroslykh: éffektivnost' otechestvennogo immunoglobulina dlia vnutrivennogo vvedeniia pri immunnykh trombotsitopeniiakh.

AIM: The study of effectiveness of intravenous immunoglobulin (IVIG) in therapy of idiopathic thrombocytopenic purpura (ITP) in adults. MATERIALS AND METHODS: High doses of IVIG (0.2-0.4 g/kg b.w. for 4-6 days) were given to 6 female patients aged 20 to 59 years (median--39 years) with immune thrombocytopenia. 4 patients had primary ITP resistant to glucocorticosteroids (GCS) and 1 female had chronic ITP treated by splenectomy without effect. 1 patient with rheumatoid arthritis developed severe thrombocytopenia combined with agranulocytosis when treated with nonsteroid antiinflammatory drugs. RESULTS: The response was observed in 5 of 6 patients (in 4 patients resistant to GCS and 1 RA patient). In 3 of them the effect was rated as excellent (platelets level > 150,000 per cubic millimeter), in 2 patients it was good (platelets count from 50,000 to 150,000 per cubic millimeter). Splenectomy was performed in 4 cases with ITP on day 8-14 after IVIG therapy. The 2- and 6-month follow-up evidenced for good results of the surgical treatment. The RA patient showed a stable rise of the blood count. Serious side effects of IVIG therapy were not registered. CONCLUSION: IVIG of Russian produce is effective in the treatment of drug-induced thrombocytopenia and ITP resistant to GCS.

[Change in certain physical characteristics of cells at various stages of the cell cycle]. / Izmenenie nekorotykh fizicheskikh kharakteristik kletok na raznykh stadiiakh kletochnogo tsikla.

Experiments on semisynchronized cultures of animal and plant cells, performed in our laboratory approximately 30 years ago, have demonstrated that there exist regular changes of certain physical parameters of the cells during the cell cycle. In particular on yeast cultures there has been observed the appearance of specific electron paramagnetic resonance (EPR) signals with simultaneous change of the static magnetic susceptibility of the cultures in the period immediately preceding the beginning of the intensive budding. On chlorella cultures grown at certain regimes of light and darkness it is possible to observe characteristic changes of the kinetics of the photoconduction signal at the frequency of 10 HHz (SHR-photoconduction). It can be conjectured that these effects are of a similar nature linked to some changes of the intracellular structures at certain stages of the cell cycle. The work performed much later makes it possible to link these changes to the appearance of spin, glass-like structures in macromolecular intracellular bodies.

[Role of cathepsin D in the appearance of micronuclei in lung cells of mice immunized with influenza vaccine]. / Rol' katepsina D v induktsii mikroiader v kletkakh legkikh myshei, immunizirovannykh vaktsinnym shtammom virusa grippa.

The positive correlation of micronuclei quantity appearance and catepsin D activation in mice cells after immunization by alive influenza vaccine was demonstrated. Activation of proteinase precedes chromosomal aberrations. Catepsin D activation is supposed to lead to proteolysis in achromatic apparatus which results in micronuclei formation.

[An assessment of the surgical and anesthesiological stress in cesarean section by studying the hypophyseal-adrenal system]. / Otsenka operatsionno-anesteziologicheskogo stressa pri kesarevom sechenii s pomoshch'iu issledovaniia gipofizarno-nadpochechnikovoi sistemy.

Cesarean section performed under endotracheal anesthesia is accompanied by a considerable stimulation of hypophyseal-adrenal system (HAS) manifested in the activation of adenohypophysis and adrenal cortex adrenocorticotropic function. Prolonged epidural anesthesia performed for the anesthesiological protection of pregnant women during abdominal delivery is characterized by optimal HAS hormonal levels at all the stages of anesthesia and surgery. Relative stability of HAS function and hemodynamic indexes indicates the adequacy of antinociceptive protection of the type of anesthesia under study.

[Regularity of changes in magnetic characteristics of Saccharomyces cerevisiae yeast cells at various stages of culture growth]. / Zakonomernosti izmeneniia magnitnykh kharkteristik kletok drozhzhei Saccharomyces cerevisiae na raznykh stadiiakh rosta kultury.

Correlation between cell cycle of the synchronous yeast culture and ESR signal intensity at g 2.2 and 77 K was studied. It was shown that the maximal intensity of ESR signal was reached 10-15 min before the beginning of intensive cell division. The ESR signal with g 2.2 (77 K) is caused by the spin-glass like structure. The "freezing" temperature of these spin-glasses was measured.

[Effect of combined oral contraceptives on the hypophyseo-thyroid and hypophyseo-adrenal systems in women with various anatomy of the thyroid gland]. / Vliianie kombinirovannykh oral'nykh kontratseptivov na gipofizarno-tireoidnuiu i gipofizarno-nadpochechnikovuiu sistemu zhenshchin s razlichnym anatomicheskim sostoianiem shchitovidnoi zhelezy.

PIP: Potential therapeutic effects of combined oral contraceptives (COC) rigevidon and ovidon (estrogen:gestagen ratio of 1:5) were studied in 97 women aged 19-35 years. With respect to the anatomical state of the thyroid, the patients were divided into two groups: group 1 included 42 women with normal thyroid function and group 2 included 55 women with euthyroid hyperplasia of the thyroid gland of stage I-II (the anatomical state of the thyroid gland was ranked according to the five-point Swiss scale adopted by WHO in 1975). All patients had a history of pregnancy, normal delivery, or abortion. The state of the pituitary-thyroid system was estimated by absorption of iodine isotopes in the thyroid tissue, and by the blood levels of thyrotropic hormone, thyroxine-binding globulin, thyroxine, and triiodothyronine. Activity of the pituitary- adrenal system was estimated by the blood levels of adrenocorticotropic hormone (ACTH) and cortisol. Blood samples were withdrawn 9 and 10 hours prior to the onset of COC administration, and after 24 and 48 weeks of COC use. The changes in the functional state of the pituitary- thyroid system in groups 1 and 2 were identical throughout the entire period of COC administration. Progressive increase in the levels of thyroxine and triiodothyronine was associated with inhibition of the thyrotropic function of the pituitary seen as decrease in thyrotropin levels. COC administration caused decrease in size of hyperplastic tyroid gland. Prior to COC administration, women in group 2 showed significant elevation of ACTH levels and marked decrease in ACTH levels and increase in cortisol levels in both groups. Normalization of the size of thyroid gland indicated that COC be used therapeutically in patients with thyroid hyperplasia.^ieng