[Sleep disorders and fatigue in patients with different forms of myotonic dystrophy type 1]. / Narusheniya sna i utomlyaemost' u patsientov s raznymi formami miotonicheskoi distrofii 1-go tipa.

OBJECTIVE: To characterize sleep disorders in children and adults with different forms of myotonic dystrophy type 1 (DM1), to assess their impact on cognitive functions, excessive daytime sleepiness (EDS) and fatigue, to determine the relationship of EDS, fatigue, and sleep disorders with the quality of life of patients. MATERIAL AND METHODS: The study included 48 adults and 9 children with confirmed DM1. Patients underwent an assessment of clinical and anamnestic data, neurological, cognitive status, severity of EDS, fatigue, quality of life according to international scales and questionnaires. Polysomnography was performed to identify sleep disorders. RESULTS: Obstructive sleep apnea syndrome (OSAS) was found in 78% of children and 79.2% of adults. The severity of OSAS in adults, in contrast to children, was influenced by obesity (p<0.001), the severity of muscle weakness (p=0.033), especially the neck muscles (p=0.018). In patients with OSAS and nocturnal hypoxemia, an increase in the duration of the 1st stage of sleep (p=0.008) and in the microactivation index (p=0.005) was revealed. EDS and fatigue were present in 31 (64.6%) and 34 (70.8%) adults, respectively, in 9 (18.8%) they emerged at the onset of the disease. The greater severity of muscle symptoms, anxiety, depression contributed to increased fatigue in adults and the presence of obesity and type 2 diabetes mellitus contributed to EDS. Increased fatigue affects the quality of life to a greater extent than EDS and sleep disturbances. CONCLUSION: OSAS, the development of which is facilitated by the presence of muscle weakness and obesity, is the leading syndrome among the spectrum of sleep disorders in all age groups. Cognitive and emotional impairments are not the result of sleep apnea, but rather develop because of a primary CNS lesion. The presence of increased fatigue reduced the quality of life of patients.

Proactive anti-inflammatory therapy in the advanced stages of a new coronavirus infection. Main results of the inpatient phase of the COLORIT study (Colchicin vs. Ruxolitinib and secukinumab in an open, prospective, randomized trial in patients with novel coronavirus infection COVID-19).

Aim      To evaluate clinical efficacy of the proactive anti-inflammatory therapy in patients hospitalized for COVID-19 with pneumonia and a risk of "cytokine storm".Material and methods  The COLORIT study was a comparative study with randomization into 4 groups: colchicine (n=21) 1 mg for the first 3 days followed by 0.5 mg/day through day 12 or discharge from the hospital; secukinumab 300 mg/day, s.c., as a single dose (n=20); ruxolitinib 5 mg, twice a day (n=10); and a control group with no anti-inflammatory therapy (n=22). The effect was evaluated after 12±2 days of inpatient treatment or upon discharge, what comes first. For ethical reasons, completely randomized recruitment to the control group was not possible. Thus, for data analysis, 17 patients who did not receive any anti-inflammatory therapy for various reasons not related with inclusion into the study were added to the control group of 5 randomized patients. Inclusion criteria: presence of coronavirus pneumonia (positive PCR test for SARS-CoV-2 RNA or specific clinical presentation of pneumonia; IDC-10 codes U07.1 and U07.2); C-reactive protein (CRP) concentration >60 mg/l or its threefold increase from baseline; at least 2 of 4 symptoms (fever >37.5 °C, persistent cough, shortness of breath with inspiratory rate >20 per min or blood saturation with oxygen <94 % by the 7th-9th day of disease. The study primary endpoint was changes in COVID Clinical Condition Scale (CCS-COVID) score. The secondary endpoints were the dynamics of CRP and changes in the area of lung lesion according to data of computed tomography (CT) of the lungs from the date of randomization to 12±2 days.Results All three drugs significantly reduced inflammation, improved the clinical course of the disease, and decreased the disease severity as evaluated by the CCS score: in the ruxolitinib group, by 5.5 (p=0.004); in the secukinumab group, by 4 (p=0.096); in the colchicine group, by 4 (p=0.017), and in the control group, by 2 (р=0.329). In all three groups, the CCS-COVID score was 2-3 by the end of observation period, which corresponded to a mild process, while in the control group, the score was 7 (р=0.005). Time-related changes in CRP were significant in all three anti-inflammatory treatment groups with no statistical difference between the groups. By the end of the study, changes in CT of the lungs were nonsignificant.Conclusion      In severe СOVID-19 with a risk of "cytokine storm", the proactive therapy with ruxolitinib, colchicine, and secukinumab significantly reduces the inflammation severity, prevents the disease progression, and results in clinical improvement.

Proactive anti-inflammatory therapy with colchicine in the treatment of advanced stages of new coronavirus infection. The first results of the COLORIT study.

Actuality The course of the novel coronavirus disease (COVID-19) is unpredictable. It manifests in some cases as increasing inflammation to even the onset of a cytokine storm and irreversible progression of acute respiratory syndrome, which is associated with the risk of death in patients. Thus, proactive anti-inflammatory therapy remains an open serious question in patients with COVID-19 and pneumonia, who still have signs of inflammation on days 7-9 of the disease: elevated C-reactive protein (CRP)>60 mg/dL and at least two of the four clinical signs: fever >37.5°C; persistent cough; dyspnea (RR >20 brpm) and/or reduced oxygen blood saturation <94% when breathing atmospheric air. We designed the randomized trial: COLchicine versus Ruxolitinib and Secukinumab in Open-label Prospective Randomized Trial in Patients with COVID-19 (COLORIT). We present here data comparing patients who received colchicine with those who did not receive specific anti-inflammatory therapy. Results of the comparison of colchicine, ruxolitinib, and secukinumab will be presented later.Objective Compare efficacy and safety of colchicine compared to the management of patients with COVID-19 without specific anti-inflammatory therapy.Material and Methods Initially, 20 people were expected to be randomized in the control group. However, enrollment to the control group was discontinued subsequently after the inclusion of 5 patients due to the risk of severe deterioration in the absence of anti-inflammatory treatment. Therefore, 17 patients, who had not received anti-inflammatory therapy when treated in the MSU Medical Research and Educational Center before the study, were also included in the control group. The effects were assessed on day 12 after the inclusion or at discharge if it occurred earlier than on day 12. The primary endpoint was the changes in the SHOCS-COVID score, which includes the assessment of the patient's clinical condition, CT score of the lung tissue damage, the severity of systemic inflammation (CRP changes), and the risk of thrombotic complications (D-dimer) [1].Results The median SHOCS score decreased from 8 to 2 (p = 0.017), i.e., from moderate to mild degree, in the colchicine group. The change in the SHOCS-COVID score was minimal and statistically insignificant in the control group. In patients with COVID-19 treated with colchicine, the CRP levels decreased rapidly and normalized (from 99.4 to 4.2 mg/dL, p<0.001). In the control group, the CRP levels decreased moderately and statistically insignificantly and achieved 22.8 mg/dL by the end of the follow-up period, which was still more than four times higher than normal. The most informative criterion for inflammation lymphocyte-to-C-reactive protein ratio (LCR) increased in the colchicine group by 393 versus 54 in the control group (p = 0.003). After treatment, it was 60.8 in the control group, which was less than 100 considered safe in terms of systemic inflammation progression. The difference from 427 in the colchicine group was highly significant (p = 0.003).The marked and rapid decrease in the inflammation factors was accompanied in the colchicine group by the reduced need for oxygen support from 14 (66.7%) to 2 (9.5%). In the control group, the number of patients without anti-inflammatory therapy requiring oxygen support remained unchanged at 50%. There was a trend to shorter hospital stays in the group of specific anti-inflammatory therapy up to 13 days compared to 17.5 days in the control group (p = 0.079). Moreover, two patients died in the control group, and there were no fatal cases in the colchicine group. In the colchicine group, one patient had deep vein thrombosis with D-dimer elevated to 5.99 µg/mL, which resolved before discharge.Conclusions Colchicine 1 mg for 1-3 days followed by 0.5 mg/day for 14 days is effective as a proactive anti-inflammatory therapy in hospitalized patients with COVID-19 and viral pneumonia. The management of such patients without proactive anti-inflammatory therapy is likely to be unreasonable and may worsen the course of COVID-19. However, the findings should be treated with caution, given the small size of the trial.

[Combination therapy at an early stage of the novel coronavirus infection (COVID-19). Case series and design of the clinical trial "BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)"].

The article focuses on effective treatment of the novel coronavirus infection (COVID-19) at early stages and substantiates the requirement for antiviral therapy and for decreasing the viral load to prevent the infection progression. The absence of a specific antiviral therapy for the SARS-CoV-2 virus is stated. The authors analyzed results of early randomized studies using lopinavir/ritonavir, remdesivir, and favipiravir in COVID-19 and their potential for the treatment of novel coronavirus infection. Among the drugs blocking the virus entry into cells, the greatest attention was paid to the antimalaria drugs, chloroquine and hydroxychloroquine. The article addresses in detail ineffectiveness and potential danger of hydroxychloroquine, which demonstrated neither a decrease in the time of clinical recovery nor any improvement of prognosis for patients with COVID-19. The major objective was substantiating a possible use of bromhexine, a mucolytic and anticough drug, which can inhibit transmembrane serin protease 2 required for entry of the SARS-CoV-2 virus into cells. Spironolactone may have a similar feature. Due to its antiandrogenic effects, spironolactone can inhibit X-chromosome-related synthesis of ACE-2 receptors and activation of transmembrane serin protease 2. In addition to slowing the virus entry into cells, spironolactone decreases severity of fibrosis in different organs, including the lungs. The major part of the article addresses clinical examples of managing patients with COVID-19 at the University Clinic of the Medical Research and Educational Centre of the M. V. Lomonosov Moscow State University, including successful treatment with schemes containing bromhexine and spironolactone. In conclusion, the authors described the design of a randomized, prospective BISCUIT study performed at the University Clinic of the M. V. Lomonosov Moscow State University with an objective of evaluating the efficacy of this scheme.

[Proactive anti-inflammatory and anticoagulant therapy in the treatment of advanced stages of novel coronavirus infection (COVID-19). Case Series and Study Design: COLchicine versus ruxolitinib and secukinumab in open prospective randomIzed trial (COLORIT)].

The article is devoted to the treatment of the new coronavirus infection (COVID-19) in the advanced stages of the disease. The types of response of the immune system to the viral load of SARS-CoV-2 with the start of the inflammation process are considered. The situation is analyzed in detail in which the growing autoimmune inflammation (up to the development of a "cytokine storm") affects not only the pulmonary parenchyma, but also the endothelium of the small vessels of the lungs. Simultaneous damage to the alveoli and microthrombosis of the pulmonary vessels are accompanied by a progressive impairment of gas exchange, the development of acute respiratory distress syndrome, the treatment of which, even with the use of invasive ventilation, is ineffective and does not really change the prognosis of patients with COVID-19. In order to interrupt the pathological process at the earliest stages of the disease, the necessity of proactive anti-inflammatory therapy in combination with active anticoagulation treatment is substantiated. The results of the first randomized studies on the use of inhibitors of pro-inflammatory cytokines and chemokines (interleukin-6 (tocilizumab), interleukin-17 (secukinumab), Janus kinase blockers, through which the signal is transmitted to cells (ruxolitinib)), which have potential in the early treatment of COVID- 19. The use of a well-known anti-inflammatory drug colchicine (which is used for gout treatment) in patients with COVID-19 is considered. The design of the original COLORIT comparative study on the use of colchicine, ruxolitinib and secukinumab in the treatment of COVID-19 is presented. Clinical series presented, illustrated early anti-inflammatory therapy together with anticoagulants in patients with COVID-19 and the dangers associated with refusing to initiate such therapy on time.

[Steroid pulse -therapy in patients With coronAvirus Pneumonia (COVID-19), sYstemic inFlammation And Risk of vEnous thRombosis and thromboembolism (WAYFARER Study)].

Introduction Coronavirus pneumonia not only severely affects the lung tissue but is also associated with systemic autoimmune inflammation, rapid overactivation of cytokines and chemokines known as "cytokine storm", and a high risk of thrombosis and thromboembolism. Since there is no specific therapy for this new coronavirus infection (COVID-19), searching for an effective and safe anti-inflammatory therapy is critical.Materials and methods This study evaluated efficacy and safety of pulse therapy with high doses of glucocorticosteroids (GCS), methylprednisolone 1,000 mg for 3 days plus dexamethasone 8 mg for another 3-5 days, in 17 patients with severe coronavirus pneumonia as a part of retrospective comparative analysis (17 patients in control group). The study primary endpoint was the aggregate dynamics of patients' condition as evaluated by an original CCS-COVID scale, which included, in addition to the clinical status, assessments of changes in the inflammation marker, C-reactive protein (CRP); the thrombus formation marker, D-dimer; and the extent of lung injury evaluated by computed tomography (CT). Patients had signs of lung injury (53.2 % and 25.6 %), increases in CRP 27 and 19 times, and a more than doubled level of D-dimer (to 1.41 µg/ml and 1.15 µg/ml) in the active therapy and the control groups, respectively. The GCS treatment group had a more severe condition at baseline.Results The GCS pulse therapy proved effective and significantly decreased the CCS-COVID scores. Median score difference was 5.00 compared to the control group (р=0.011). Shortness of breath considerably decreased; oxygen saturation increased, and the NEWS-2 clinical status scale scores decreased. In the GCS group, concentration of CRP significantly decreased from 134 mg/dl to 41.8 mg/dl (р=0.009) but at the same time, D-dimer level significantly increased from 1.41 µg/ml to 1.98 µg/ml (р=0.044). In the control group, the changes were nonsignificant. The dynamics of lung injury by CT was better in the treatment group but the difference did not reach a statistical significance (р=0.062). Following the GCS treatment, neutrophilia increased (р=0.0001) with persisting lymphopenia, and the neutrophil/lymphocyte (N/L) ratio, a marker of chronic inflammation, increased 2.5 times (р=0.006). The changes in the N/L ratio and D-dimer were found to correlate in the GCS pulse therapy group (r =0.49, p=0.04), which underlined the relationship of chronic autoimmune inflammation with thrombus formation in COVID-19. No significant changes were observed in the control group. In result, four patients developed venous thromboembolic complications (two of them had pulmonary artery thromboembolism) after the GCS pulse therapy despite the concomitant antiplatelet treatment at therapeutic doses. Recovery was slower in the hormone treatment group (median stay in the hospital was 26 days vs 18 days in the control group, р=0.001).Conclusion Pulse therapy with high doses of GCS exerted a rapid anti-inflammatory effect but at the same time, increased the N/L ratio and the D-dimer level, which increased the risk of thromboembolism.

[Results of Open-Label non-Randomized Comparative Clinical Trial: "BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)].

Introduction The aim of this study was to assess the efficacy and safety of a combination of bromhexine at a dose of 8 mg 4 times a day and spironolactone 50 mg per day in patients with mild and moderate COVID 19.Material and methods It was an open, prospective comparative non-randomized study. 103 patients were included (33 in the bromhexine and spironolactone group and 70 in the control group). All patients had a confirmed 2019 novel coronavirus infection (COVID 19) based on a positive polymerase chain reaction (PCR) for SARS-CoV-2 virus RNA and/or a typical pattern of viral pneumonia on multispiral computed tomography. The severity of lung damage was limited to stage I-II, the level of CRP should not exceed 60 mg / dL and SO2 in the air within 92-98%. The duration of treatment is 10 days.Results The decrease in scores on the SHOKS-COVID scale, which, in addition to assessing the clinical status, the dynamics of CRP (a marker of inflammation), D-dimer (a marker of thrombus formation), and the degree of lung damage on CT (primary endpoint) was statistically significant in both groups and differences between them was not identified. Analysis for the group as a whole revealed a statistically significant reduction in hospitalization time from 10.4 to 9.0 days (by 1.5 days, p=0.033) and fever time from 6.5 to 3.9 days (by 2.5 days, p<0.001). Given the incomplete balance of the groups, the main analysis included 66 patients who were match with using propensity score matching. In matched patients, temperature normalization in the bromhexine/spironolactone group occurred 2 days faster than in the control group (p=0.008). Virus elimination by the 10th day was recorded in all patients in the bromhexine/spironolactone group; the control group viremia continued in 23.3% (p=0.077). The number of patients who had a positive PCR to the SARS-CoV-2 virus on the 10th day of hospitalization or longer (≥10 days) hospitalization in the control group was 20/21 (95.2%), and in the group with bromhexine /spironolactone -14/24 (58.3%), p=0.012. The odds ratio of having a positive PCR or more than ten days of hospitalization was 0.07 (95% CI: 0.008 - 0.61, p=0.0161) with bromhexine and spironolactone versus controls. No side effects were reported in the study group.Conclusion The combination of bromhexine with spironolactone appeared effective in treating a new coronavirus infection by achieving a faster normalization of the clinical condition, lowering the temperature one and a half times faster, and reducing explanatory combine endpoint the viral load or long duration of hospitalization (≥ 10 days).

[First Experience of Clinical Application of LCZ696--an AT1-angiotensin Receptors and Neprilysin Inhibitor--in Patients With Chronic Heart Failure and Reduced Ejection Fraction].

UNLABELLED: Simultaneous inhibition of the renin-angiotensin-aldosterone system and the system of degradation of natriuretic peptides can potentially provide unique therapeutic effects in patients with chronic heart failure (CHF) with reduced ejection fraction (EF). Aim of this study was to assess tolerability of therapy with LCZ696--first representative of a class of inhibitors of angiotensin receptor and neutral endopeptidase neprilysin--and to study its pharmacodynamic effects. METHODS: We included into open uncontrolled study 30 patients with stable functional class II-III CHF and EF ≤ 40%. After 24-hour run-in period during which angiotensin converting enzyme inhibitors (ACEI) were withdrawn the patients were given LCZ696 (100 mg/day for 7 days followed by 200 mg/day for 14 days). Other CHF therapy remained unchanged. RESULTS: Transition from therapy with ACEI to LCZ696 was well tolerated. Three patients were excluded because of hyperkalemia ≥ 5mmol/l. After 21 days of treatment elevation of plasma biomarkers of inhibition of neprilysin and angiotensin receptors occurred: cyclic guanosine monophosphate, renin concentration and activity rose 1.38, 3.50, and 2.27 times from baseline level (p < 0.05 for all). After 7 and 21 days of LCZ696 administration we noted significant lowering of NT-proBNP; significant lowering of aldosterone and endothelin-1 in blood plasma, was observed on day 21. CONCLUSION: Administration of LCZ696 to patients with CHF with reduced ejection fraction (EF) was well tolerated and associated with potentially favorable for this category of patients dynamics of biomarkers.

[First Experience of Clinical Application of LCZ696 an AT1-angiotensin Receptors and Neprilysin Inhibitor in Patients With Chronic Heart Failure and Reduced Ejection Fraction].

Simultaneous inhibition of the renin-angiotensin-aldosterone system and the system of degradation of natriuretic peptides can potentially provide unique therapeutic effects in patients with chronic heart failure (CHF) with reduced ejection fraction (EF). Aim of this study was to assess tolerability of therapy with LCZ696 - first representative of a class of inhibitors of angiotensin receptor and neutral endopeptidase neprilysin - and to study its pharmacodynamic effects. METHODS: We included into open uncontrolled study 30 patients with stable functional class II-III CHF and EF less or equal 40%. After 24-hour run-in period during which angiotensin converting enzyme inhibitors (ACEI) were withdrawn the patients were given LCZ696 (100 mg/day for 7 days followed by 200 mg/day for 14 days). Other CHF therapy remained unchanged. RESULTS: Transition from therapy with ACEI to LCZ696 was well tolerated. Three patients were excluded because of hyperkalemia more or equal 5mmol/l. After 21 days of treatment elevation of plasma biomarkers of inhibition of neprilysin and angiotensin receptors occurred: cyclic guanosine monophosphate, renin concentration and activity rose 1.38, 3.50, and 2.27 times from baseline level (<0.05 for all). After 7 and 21 days of LCZ696 administration we noted significant lowering of NT-proBNP; significant lowering of aldosterone and endothelin-1 in blood plasma was observed on day 21. CONCLUSION: Administration of LCZ696 to patients with CHF with reduced ejection fraction (EF) was well tolerated and associated with potentially favorable for this category of patients dynamics of biomarkers.

[Hepatobiliscintigraphy in the diagnosis of obstructive jaundice].

The authors show the role of hepatobiliscintigraphy (HBSG) in cholelithiasis as a screening technique in evaluating the patency of the common bile duct, which allows cholecystectomy to be performed if there are normal values, without resorting to additional studies. They have reprospectively analyzed the results of clinical and instrumental studies in 101 patients with cholelithiasis and obstructive jaundice of various etiology in whom the diagnosis was verified by endoscopic cholangiopancreatography (ERCPG). The sensitivity, specificity, and diagnostic efficiency of the scintigraphic technique were 96.5, 36.3, and 86.1%, respectively. It is recommended that invasive diagnostic techniques, such as ERCPG and other direst X-ray contrasting methods, should be used after having a positive result of two techniques: ultrasonography and HBSG (in the above order).

[Specific features of impairment of systolic and diastolic left ventricular functions in patients with acute myocardial infarction complicated with pulmonary edema].

The purpose of the study was to investigate specific features of systolic and diastolic functions of the left ventricle (LV) in patients with acute myocardial infarction (AMI), complicated by acute left ventricular failure (ALVF) and to estimate their prognostic value. We examined 90 patients with AMI. The following types of left ventricular dysfunction were detected in patients with ALVF: systolic dysfunction (25%), restrictive filling pattern of mitral flow (11.7%), combined dysfunction (31.7%); whereas 31.7% of these patients had no severe dysfunction of LV. The presence of restrictive filling pattern affected negatively the course of AMI, development of complications, and processes of postinfarction remodeling.

[Fistulography in destructive pancreatitis in postoperative period].

Results of different x-ray methods applied in 151 patients early after operations for destructive pancreatitis were analyzed. The technique of fistulography is described. Plain roentgenography of the chest demonstrated changes in 77.4% cases, most often occurred disk-shaped atelectases and pleural effusion. Examination of the abdominal cavity revealed functional disorders in 69.8% cases, direct symptoms of purulent process -- in 52.9%, radiographic signs of aseptic sequestration -- in 47.1% patients. X-ray signs of purulent process in the retroperitoneal fat and aseptic sequestration of the infiltrate or fat are outlined. The value of fistulography for localization and determination of the shape of drained cavities, position of the drainage tubes in the cavity, condition of the adjacent tissue, progression of purulent process, adequacy of drain of the purulent cavities is shown. Based on the results of complex x-ray examination with ultrasound investigation and CT data, the indications to repeated procedure (surgery or additional drainage) were formulated in 82 (54.3%) of 151 patients.

[Our experience with the sentinel lymph node detection]. / Nase zkusenosti s detekcí sentinelové uzliny.

BACKGROUND: Axillary lymph node staging is the most powerful predictor of survival in breast cancer women. Sentinel lymph node biopsy (SLNB) is more accurate method in evaluation of axillary lymph node staging than complete axillary lymph node dissection (CALND) because of more precious histological and imunohistochemical assessment of the first draining lymph nodes. Furthermore, SLNB eliminates complications resulting from CALND. MATERIAL AND METHODS: SLNB is either performed using blue dye technique or using of combination of blue dye and radioguided technique. We prefer two days protocol in application of Tc 99 radiocolloid. There were used both techniques for detection sentinel lymph nodes and results were compared. RESULTS: There were performed 21 SLNBs using blue dye technique, Group A, and 20 SLNBs using combination of blue dye and radioguided technique, Group B, from October 2001 to November 2003. Sentinel lymph nodes were not detected in Group A in two cases, false negativity occurred two times in this group. Sentinel lymph nodes were detected in all cases in Group B and there was no false negativity present in this group. CONCLUSION: Combination of blue dye and radioguided technique is more precious in detection of sentinel lymph node than blue dye technique itself. Two days protocol of application of Tc 99 radiocolloid enables performing this method even in hospitals, where the Department of Nuclear Medicine is not available.

[Thrombolytic therapy of acute myocardial infarction in elderly patients. Immediate and long-term remote prognosis]. / Tromboliticheskaia terapiia ostrogo infarkta miokarda u bol'nykh pozhilogo i starcheskogo vozrasta: blizhaishii i otdalennyi prognoz.

AIM: To study effects of thrombolytic therapy in elderly patients. MATERIAL AND METHODS: One hundred twenty three patients with acute myocardial infarction were admitted within first 12 hours of myocardial infarction, 66 of them were subjected to thrombolytic therapy with streptokinase (group 1) while 57 were not because of contraindications (group 2). In group 1 age of 49 patients was 66-75 years, and that of 17 patients exceeded 75 years. RESULTS: In 24.2% of patients pain ceased during thrombolysis. This effect occurred less often in patients over 75 years of age. Reperfusion arrhythmias were registered in 15.1% of older patients. Patients of group 2 more often had acute left ventricular failure (47.4% vs. 18.2% in group 1, p=0.003). Rate of development of acute heart failure was higher in patients aged over 75 years (by 8% compared with younger patients in both groups). Chronic heart failure developed in 36.8% and 13.6% of patients in group 2 and 1, respectively (p=0.001). Rate of chronic heart failure in group 1 was lower than among total population of patients, subjected to thrombolytic therapy (13.6 and 26.5%, respectively, p=0.040). Rate of early angina and reinfarction was higher in group 1 than in group 2 (by 4 and 3%, respectively). In 12 months rate of angina was higher in group 1 compared with group 2 (83.3 and 52.6%, respectively, p=0.088). Among patients with heart failure in group 1 prevailed those with class I-II (p=0.175) while in group 2 there were more patients with class III-IV than class I-II heart failure. Rate of chronic heart failure among patients older than 75 years was by 13 and 22.8% higher, than in younger patients of groups 1 and 2, respectively. One year mortality was 9.1% in group 1 and 22.8% (p=0.019) in group 2. Mortality among patients over 75 years of age was higher in both groups especially in group 1 (by 13.5%).

Vinorelbine, epirubicin, and methotrexate (VEM) as primary treatment in locally advanced breast cancer.

PURPOSE: This phase II trial of VEM (vinorelbine + epirubicine + methotrexate) in the treatment of locally advanced breast cancer was conducted to obtain downstaging to allow surgery and breast conservation. PATIENTS AND METHODS: This multicenter study recruited 58 patients with locally advanced breast cancer (two patients ineligible); 56 were evaluable for response and tolerance. RESULTS: Downstaging was obtained in 77% of the patients with a pathological complete response (pCR) rate of 9%. At 33 months of follow-up, median survival has not been reached. Neutropenia grade 3-4 was reported in 31% of cycles with 3% of cycles with infection grade 3. Alopecia grade 3 was noticed for 71% of patients. CONCLUSION: VEM represents an effective regimen for patients with locally advanced breast cancer, allowing an important pCR. Moreover, this regimen appears to be particularly well tolerated.

[Characteristics of borderline modulation frequencies in the differentiation of tonal and amplitude-modulated stimuli following the removal of the inferior colliculus in rats]. / Kharakteristika granichnykh chastot moduliatsii pri differentsirovanii tonal'nogo i amplitudno-modulirovannykh stimulov posle udaleniia zadnego dvukholmiia u krys.

Elaboration of differentiation between sound stimuli was carried out in 15 laboratory rats. After bilateral ablations of auditory inferior colliculi the border frequency of stimulus amplitude modulation was determined for all rats when they still could differentiate between tonal and amplitude-modulated stimuli. Decrease in frequency of modulation by 2 Hz and more from the border frequency caused a complete loss of ability to differentiate. In all rats bilateral inferior colliculi ablations completely disturbed differentiation between tonal and amplitude-modulated signals with modulation frequency below 183-191 Hz (the range of border frequencies). The surgery however did not affect differentiation between tonal and amplitude-modulated signals with the modulation frequencies above 183-191 Hz. The data suggest that the functions of completion of coding of amplitude-modulated stimuli in the auditory system is strictly linked with definite structures.