Ectopic pregnancy associated with fallopian tube adenocarcinoma
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01.01.2018 |
Levakov S.
Sheshukova N.
Bolshakova O.
Tigieva A.
Dobryakov A.
Obukhova E.
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Akusherstvo i Ginekologiya (Russian Federation) |
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0 |
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© Bionika Media Ltd. Background. Fallopian tube cancer (FTC) is an extremely rare, difficult diagnostic malignant disease of the female reproductive system. The world literature describes single cases of FTC concurrent with tubal pregnancy. Description. The paper describes a clinical case of diagnosed FTC after surgical treatment for tubal pregnancy. Patient P., aged 34 years, who had complained of vaginal bleeding and tensive pain in the right iliac region, was admitted to the Bakhrushins Brothers City Clinical Hospital. After complete clinical and laboratory examinations diagnosed right ectopic pregnancy, emergency surgical treatment was performed as laparoscopy and rightsided tubectomy. The postoperative period was uncomplicated; the patient was discharged home in satisfactory condition. Histological examination revealed the growth of well-differentiated fallopian tube adenocarcinoma and confirmed the diagnosis of ectopic pregnancy. The diagnosis was verified by immunohistochemical study Conclusion. Preoperative diagnosis of FTC is extremely difficult; therefore the elaboration of a clear algorithm for the diagnosis and treatment of this condition is one of the important tasks in gynecologic oncology.
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Giant ovarian mucinous cystadenoma in a 54-year-old woman
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01.01.2018 |
Chuprynin V.
Buralkina N.
Chursin V.
Asaturova A.
Katkova A.
Zhurba A.
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Akusherstvo i Ginekologiya (Russian Federation) |
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0 |
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© Bionika Media Ltd. Background. Ovarian cancer develops from benign tumors in 80% of cases during long-term follow-up. According to the literature, the incidence of giant ovarian cystadenoma is extremely low. There are difficulties in verifying these ovarian tumors. Description. The paper describes a rare clinical case of a 54-year-old patient with giant ovarian cystadenoma. It depicts the patient’s clinical, medical history, laboratory, and instrumental data and demonstrates the technical complexities of surgery and the features of postoperative management. Conclusion. The early diagnosis and timely treatment of ovarian tumors will be able to avoid technically difficult surgical interventions and to minimize postoperative complications, which will substantially improve the prognosis of the disease. Such operations should be performed by a surgeon having extensive surgical experience and high qualification.
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Serum level and gene polymorphism of interleukin-1?, and efficiency of infertility treatment by in vitro fertilization
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01.01.2018 |
Lapshtaeva A.
Evsegneeva I.
Novikov V.
Sychev I.
Karaulov A.
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Medical Immunology (Russia) |
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© 2018, SPb RAACI Search for novel prognostic criteria predicting successful in vitro fertilization remains a nonresolved problem at the present time. The aim of our study was to analyse a predictive role of IL-1? as an additional marker of pregnancy after in vitro fertilization (IVF). The study included 120 women with tubo-peritoneal infertility subjected to the IVF procedure. Retrospectively, two groups were formed of this cohort, dependent on efficiency of in vitro fertilization. Group I included 40 women with successful pregnancy whereas group II comprised 80 women with failed pregnancy. IL-1? concentrations in serum were detected by ELISA technique. A polymorphic rs1800587 marker at 5`UTR region has been amplified by PCR followed by Sanger sequencing. We have shown IL-1? hyperproduction in the women from group I. The women with effective IVF outcome exhibited positive correlation between IL-1? and luteinizing hormone, prolactin, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate levels. The women with ineffective in vitro fertilization have detected a negative correlation between IL-1? levels and anti-Muellerian hormone, a positive correlation of IL-1? with 17-hydroxyprogesterone. The women with T allele of the polymorphic rs1800587 marker at 5`UTR region have shown a 2.5-fold higher chance to become pregnant after IVF than the women carrying C allele (95% CI = [1.45-4.35], ? = 0.0009). The women with T/T genotype exhibited a positive correlation between IL-1? and estradiol, testosterone; the subjects with heterozygous C/T genotype showed correlation with estradiol, and those harboring C/C genotype exhibited correlation with follicle-stimulating hormone. The revealed changes suggest a potential involvement of IL-1? into regulation of cyclic processes in the ovary including ovulation. Moreover, IL-1? may participate in formation of pro-inflammatory environment for successful blastocyst implantation.
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Evaluation of the Efficiency of Lytic Mycobacteriophage D29 on the Model of M. tuberculosis-Infected Macrophage RAW 264 Cell Line
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01.01.2018 |
Lapenkova M.
Smirnova N.
Rutkevich P.
Vladimirsky M.
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Bulletin of Experimental Biology and Medicine |
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1 |
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© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Culture of mouse macrophages (RAW 264.7 ATCC strain) in wells of a 6-well plate was infected with M. tuberculosis in proportion of 15 mycobacteria per one macrophage and then treated with a lytic strain of mycobacteriophage D29. Antibacterial efficacy of mycobacteriophages was studied using D29 phage (activity 108 plaque-forming units/ml) previously purified by ion exchange chromatography. After single and double 24-h treatment, the lysed cultures of macrophages were inoculated onto Middlebrook 7H10 agar medium. The number of mycobacterial colonies in control and test wells (at least 3 wells in each group) was 300.178±12.500 and 36.0±5.4, respectively (p<0.01).
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Physical and computer-based modeling in internal temperature reconstruction by the method of passive acoustic thermometry
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01.01.2018 |
Anosov A.
Subochev P.
Mansfeld A.
Sharakshane A.
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Ultrasonics |
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1 |
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© 2017 Elsevier B.V. The purpose of this work was to investigate experimentally the capacity of passive acoustic thermometry (PAT) for the reconstruction of 1D, time-variable distributions of the internal temperature. Because in the PAT a noise signal is measured, a considerable integration time (about one minute) is required to attain an acceptable error level (0.5–1 K). To optimize the time, an algorithm was proposed to take account of the fact that the temperature satisfied the heat equation. The problem was reduced to that of determining two parameters (initial temperature and thermal diffusivity) of the object under study. The desired parameters were considered constant and were not determined anew after each measurement; instead, their values were refined using all the previous measurements. The proposed algorithm was tested experimentally (where the temperature was reconstructed in a model object, a slab of polytetrafluoroethylene) and investigated by means of computer modeling. The duration of one measurement was about 5.5 s. As a result, an error of the temperature reconstruction of about 0.5 K, acceptable for medical applications, was attained after 30–60 s (depending on the depth) from the beginning of the measurements. After that, temperature distributions can be reconstructed after each measurement without loss of the reconstruction accuracy. The proposed method can be used to control the temperature under a local hyperthermia, lasting 1 min and more, of the human body.
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Comorbidity between epilepsy and autism from the point of view of ontogenesis
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01.01.2018 |
Kuzmich G.
Sinelnikova A.
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Russkii Zhunal Detskoi Nevrologii |
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© 2018 ABV-Press Publishing House. All rights reserved. Early childhood autism, or autism spectrum disorders, is an extremely heterogeneous group of conditions that share similar symptoms of dysontogenesis. Epilepsy is the most significant comorbidity in autism. The present article covers various aspects of comorbidity between epilepsy and autism, described in the literature over the last 50 years. This review aims to analyze the development of epilepsy and autism during ontogenesis and to identify causal relationships between these diseases, considering the information on the two age peaks for epilepsy onset in patients with autism.
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From the history of public service of medical-social expertise in Russia
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01.01.2018 |
Puzin S.
Dmitrieva N.
Shurgaya M.
Solovyova N.
Filatkina N.
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History of Medicine |
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© SN Puzin et al. In this article, we are looking at the stages of reorganisation of medical expert commissions into workplace health expert committees (WHEC). Classification of disability, according to which a disabled person could be assigned to one of three groups, is proposed. This classification regulated the criteria for the establishment of each group in accordance with the indications for employment. The Regulation on the WHEC, approved in 1942, practically became fundamental for all subsequent regulatory documents on the activities of the WHEC. According to this Regulation, the WHEC was able to grant certificates stating that the disability is related to being at the front. A new category of people with disabilities was created – the veterans of the Eastern Front of World War II. The Regulation on the WHEC, introduced in 1948, expanded the functions and powers of these services. The categories of people who had to be assessed by the WHEC were determined. Since 1955, the inpatient examination and the work of specialised (tubercular and psychiatric) WHEC have been organised. During 1956–1984 WHEC received the authority to set the time of the onset of disability to address the issue of pension benefits for people previously recognised as being disabled. The dates for the re-examination of people with disabilities were established. In 1956, a new Regulation on the WHEC was introduced. According to this document, as recommended by the WHEC, it was possible, in the absence of medical contraindications, for people with disabilities of all three groups to continue working, but under different conditions. During 1940–1960s, a new directive appeared – medical rehabilitation, the basic principle of which was specialised assistance to people with amputations, severe injuries of the skull, brain, spinal cord, and vertebral column. A foundation for the specialisation and improvement of expert doctors was created. The development of the state service of medical and social expertise was carried out in accordance with the new approaches of the World Health Organisation to the definition of disability, based upon the clinical and expert diagnosis of functional disorders and activity limitations.
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Efficacy and safety of afalaza in men with symptomatic benign prostatic hyperplasia at risk of progression: A multicenter, double-blind, placebo-controlled, randomized clinical trial
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01.01.2018 |
Pushkar D.
Vinarov A.
Spivak L.
Kolontarev K.
Putilovskiy M.
Andrianova E.
Epstein O.
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Central European Journal of Urology |
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1 |
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© 2018, Polish Urological Association. All rights reserved. Introduction In order to investigate the efficacy and safety of Afalaza in men with benign prostatic hyperplasia (BPH) at risk of progression, this multicenter, double-blind, placebo-controlled, randomized clinical trial was performed. Derived by technological treatment of antibodies to prostate-specific antigen (PSA) and endothelial nitric oxide synthase (eNOs), Afalaza was previously proved to modulate its molecular targets. The mechanism of action of the drug is associated with the modulating effect of the antibiodies (RA-Abs) on the molecular targets (PSA and eNOS) by way of conformational changes. Material and methods A total of 249 patients aged 45–60 years with BPH and moderate lower urinary tract symptoms (LUTS), total prostate volume (TPV) ≥30 cm3, Qmax 10–15 ml/s, and serum PSA<4 ng/ml were randomly assigned to receive either Afalaza (n = 125) or placebo (n = 124) for 12 months. Changes in BPH/LUTS symptoms (according to the International Prostate Symptom Score), Qmax, TPV, PSA, BPH clinical progression, occurrence of acure urinary retention (AUR) events or BPH-related surgery were estimated as the study endpoints. Results IPSS mean change was-3.7 ±3.0 (95% CI-4.3 to-3.2) after 12 months of Afalaza (vs.-2.9 ±2.4; 95% CI-3.3 to-2.4 in placebo; р = 0.02). Qmax growth was 2.5 ±4.3 ml/s (vs. 1.4 ±3.3 in placebo; p = 0.049), TPV reduced by 11.8 ±16.0% (vs. 6.5 ±14.7%; p = 0.01, and PSA remained unchanged. Afalaza therapy resulted in a significant decrease in the total sum of BPH progression symptoms (p = 0.01). The maximum effect of Afalaza was registered after 12 months without a tendency to form a ‘plateau’. During the study, no patients experienced AUR or BPH-related surgery. Conclusions A 12-month course of Afalaza therapy is effective and safe for patients with BPH. The results of end points measurements revealed asignificant advantage of Afalaza compared to placebo in the overall symptoms benefit and a decline in the risk of BPH progression. ClinicalTrials.gov: NCT01716104.
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the role of molecular genetic alterations in sensitivity of the adjuvant intravesical therapy for non-muscle invasive bladder cancer
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01.01.2018 |
Mikhaylenko D.
Sergienko S.
Zaborsky I.
Safiullin K.
Serebryany S.
Safronova N.
Nemtsova M.
Kaprin A.
Alekseev B.
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Onkourologiya |
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1 |
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© 2018 ABC-press Publishing House. All rights reserved. Bladder cancer (BC) is represented by non-muscle-invasive forms at the stage Ta, T1, CIS (NMBC) in 75 % of cases. The gold standard of treatment of NMBC patients is transurethral resection, but its implementation does not always allow the patient to be relieved of the recurrence of the disease. In this regard, patients with a low risk of progression after transurethral resection are administered by intravesical chemotherapy, with high risk (T1G2/3) – using instillation with BCG (Bacillus Calmette–Guerin) vaccine. Searching of NMBC markers for laboratory diagnostics, which would help to determine sensitivity or resistance to the planned type of adjuvant therapy remains an actual problem. The data published mainly in the last 5–7 years about genetic predictors of the response to adjuvant chemotherapy and, to a greater extent, immunotherapy with BCG vaccine, are reviewed in this work. Allele combinations in the genes involved in immune response, xenobiotic biotransformation and other loci that are associated with the response to the adjuvant NMBC therapy in meta-analyzes are systematized. Also, expression profiles of mRNA, microRNA and proteins, as well as panels of methylated loci associated with the effectiveness of chemotherapy and immunotherapy of NMBC are considered. It was demonstrated that the somatic mutations sequencing in the primary tumor and the total mutational load using high-throughput sequencing technologies (NGS) identified a number of potential prognostic markers. Perhaps, the mutational load will be more widely used as a highly informative predictor of immunotherapeutic effect in BC: BCG therapy of NMBC and BC targeted therapy using the inhibitors of immune control points, after the standardization of the analysis. This review is intended to oncologists, geneticists, molecular biologists, urologists, pathologists and other specialists working in the field of molecular genetics in oncological urology.
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Application of nanoscale polymer colloid carriers for targeted delivery of the brain-derived neurotrophic factor through the blood-brain barrier in experimental parkinsonism
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01.01.2018 |
Kapitonova M.
Alyautdin R.
Wan-Syazli R.
Nor-Ashikin M.
Ahmad A.
Norita S.
Dydykin S.
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Bulletin of Russian State Medical University |
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© 2018 Istituto Superiore di Sanita. All Rights Reserved. Parkinson disease is one of the common age-related motor neurodegenerative diseases, in which dopamine neurons degeneration is considered to be pathognomic for the development of motor disfunction. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which is considered to be a key regulator of neuronal plasticity. BDNF, being a large molecule, does not pass through the blood-brain barrier (BBB). Synthetic polymer nanoparticles (NP), covered by surfactant, provide the phenomenon of “Trojan hoarse” and enable BDNF to penetrate into the brain tissue. For modelling of parkinsonism we used an intraperitoneal (i.p.) injection of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which was injected to the C57BL/6 mice with subsequest treatment with normal saline (group 1), BDNF (group 2), nanoparticulate BDNF (group 3) and surfactant-coated nanoparticulate BDNF (group 4). After 90 min, 24 hours, 72 hours and 7 days manifestations of parkinsonism were evaluated using behavioural tests of open field, rota-rod, assessment of the tremor, length of the body and pace. At the end of experiment the brain was sampled for histological evaluation of changes in the striatum and midbrain and concentration of BDNF in the brain tissues. The results of the experiments demonstrated that nanoparticulate BDNF covered with surfactant significanltly reduced rigidity of the skeletal muscles, oligokinesia and tremor, and also significantly increased BDNF concentration in the brain tissues.
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Belief in a just world, national identity, and military attitudes: The case of Syria war
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01.01.2018 |
Nevryuev A.
Gulevich O.
Nekrasova E.
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Psikhologicheskii Zhurnal |
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© 2018 Russian Academy of Sciences.All rights reserved. In this study we investigated factors which predict attitudes toward different forms of Russian participation in Syrian conflict. Russian residents (N = 595) filled out the scales for belief in a just world, nationalism, patriotism, general military attitudes and attitudes towards different forms of Russian involvement in Syrian conflict. The results of the study have shown that just world belief predicts differ-ent forms of national identity-patriotism and nationalism. Patriotism, but not nationalism, is negatively correlated with general military attitudes. General military attitudes, in turn, are positively correlated with attitudes towards Russian military involvement in the conflict, but negatively correlated with the peaceful participation. The article contains new data on the links between national identity and the atti-tude toward war. Proposed assumptions about what the results may be related to. The main prospects for the development of this area of research are outlined.
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Comparison of the original (Plavix) and generic (clapitax) clopidogrel on platelet aggregation: Observational study
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01.01.2018 |
Skotnikov S.
Sizova Z.
Baglikov N.
Rozhnova G.
Novitsky N.
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Russian Journal of Cardiology |
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© 2018, Silicea-Poligraf. All rights reserved. Aim. To compare antiplatelet activeness of the original clopidogrel and its generic, and to evaluate the routine practice of antiplatelet drugs intake by clinically stable patients aiming prevention of atherothrombosis. Material and methods. Total number of patients that have been taking clopidogrel: 186, of those at outpatient stage 54 on original clopidogrel, the rest 132 on generic. Adenosindiphosphate-induced activeness was measured in two groups (n=57) taking consequently Plavix and Clapitax before replacement of the drug and 14 days after. Results. At interchange of the drug in group 1 (Clapitax to Plavix) and group 2 (Plavix to Clapitax) the grade of achieved effect remained, and in group 2 it showed additional non-significant decrease. Adverse events related to antiplatelet therapy were not registered. At in-patient stage, 117 patients had an interchange of the drug (incl. several times) of original clopidogrel to its various generics (n=65), and vice versa (n=52), that was related to a range of routine reasons, of those patient and relatives preferences, specifics of drug supply in a clinic. Conclusion. The found equal residual reactivity of the platelets after Clapitax and Plavix intake in two groups witness on therapeutical equivalence of the drugs.
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Diagnostic effectiveness of transforming growth factor beta 1 (TGF-β1) at adjustment of tacrolimus individual dose in pediatric liver recipients
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01.01.2018 |
Kurabekova R.
Tsiroulnikova O.
Gichkun O.
Pashkova I.
Olefirenko G.
Shevchenko O.
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Vestnik Transplantologii i Iskusstvennykh Organov |
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0 |
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© 2018 Russian Transplant Society. All Rights Reserved. Blood level of transforming growth factor beta 1 (TGF-β1) is associated with liver function and immune homeostasis, which suggests it as a potential biomarker for immunosuppressant tacrolimus dose requirement at liver transplantation (LT). Aim. To evaluate diagnostic efficacy of TGF-β1 blood level at determination of individual tacrolimus dose requirement in children at LT. Materials and methods. 89 children with end stage liver disease aged from 3 to 73 months were examined. Children underwent living related LT, then the recipients received 2–3 component immunosuppressive therapy, including tacrolimus. Blood concentration of tacrolimus and TGF-β1 was measured by ELISA. Results. TGF-β1 blood level in children before LT was significantly lower than in healthy children: 3.7 (1.3–8.4) and 19.3 (12.6–25.5) ng/ml, p = 0.001. A month after LT, its concentration increased to 8.1 (1.8–15.3) ng/ml (p = 0.02). A year after LT, the cytokine level remained higher than before transplantation: 6.6 (1.9–12.6) ng/ml, p = 0.01. TGF-β1 level did not correlate with tacrolimus blood concentration, determined 12 hours after the last administration of the drug, neither a month, nor a year after transplantation. At the same time, the cytokine level one month after LT was associated with a tacrolimus daily dose one year after the operation (r = –0.23, p = 0.04). In the recipients, who received smaller daily doses (0.4–2.5 mg) of tacrolimus, TGF-β1 level was higher than in those receiving large doses (3.0–6.0 mg) of the drug: 9.1 (2.6–16.2) ng/ml vs. 4.2 (1.3–9.2) ng/ ml, p = 0.04. Evaluation of diagnostic efficacy of the TGF-β1 level as a test for the detection of tacrolimus dose requirement showed that the area under the ROC curve (AUC) was 0.66 ± 0.07; 95% CI [0.53–0.79], the sensitivity and specificity of the test were 60 and 74% at threshold value 6.7 ng/ml. Relative risk of higher tacrolimus dose requirement was 3.14 ± 0.48; 95% CI [1.24–7.96]. Conclusion. TGF-β1 blood level in one month after LT less than 6.7 ng/ml is 3 times higher risk factor of tacrolimus dose requirement more than 3.0 mg per day. The likehood of the test is 66%, the sensitivity and specificity – 60 and 74%.
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Lung transplantation for idiopathic pulmonary arterial hypertension: Perioperational features
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01.01.2018 |
Poptsov V.
Spirina E.
Pashkov I.
Belikova A.
Oleshkevich D.
Latipov R.
Tsirulnikova O.
Epremian A.
Shigaev E.
Gautier S.
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Vestnik Transplantologii i Iskusstvennykh Organov |
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© 2018 Russian Transplant Society. All Rights Reserved. Lung transplantation (LT) for idiopathic pulmonary arterial hypertension (IPAH) now is the only radical treatment of this disease. Aim: to analyze own experience of performing LT in patients with IPAH. Materials and methods. 8 adult IPAH patients, who underwent LT between 2014 and october 2018, were included. In 7 of 8 patients undergoing bilateral lung transplantation on intraoperative venoarterial extracorporeal membrane oxygenation (VA ECMO) with prolongation into the postoperative period. Results. VA ECMO support was prolonged into postoperative period 6 and 7 days respectively in 2 (25,0%) patients and 3 days in 6 (75,0%) patients. Hospital mortality in IPAH patients was 1. Conclusions. Own experience demonstrates that LT is an effective method of treatment in patients with IPAH. Hospital, 1- and 3-year survival rates for the patient collective were 87.5, 75.0 and 75.0% respectively.
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Heart transplantation waiting list of V.I. Shumakov National medical research center of transplantology and artificial organs. Trends from 2010 to 2017
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01.01.2018 |
Gautier S.
Poptsov V.
Koloskova N.
Zakharevich V.
Shevchenko A.
Muminov I.
Nikitina E.
Kvan V.
Halilulin T.
Zakiryanov A.
Golts A.
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Vestnik Transplantologii i Iskusstvennykh Organov |
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© 2018 National Research University Higher School of Economics. All Rights Reserved. The aim: to analyze the waiting list for heart transplantation from 2010 to 2017 and to characterize recipients with chronic heart failure III–IV NYHA Class. Methods. The study comprised 997 patients (139 [14%] females and 858 [86%] males) included in the waiting list for heart transplantation the period from January 2010 to December 2017. The average age of patients on the waiting list was 49.0 ± 12.0 (from 10 to 78 years). Before making a decision on inclusion in the waiting list, all patients underwent clinical and instrumental examination, including general clinical studies, echocardiography, measurement of central hemodynamic parameters using a Swan–Gans catheter, computer and/or magnetic resonance imaging of the chest, abdominal and brain. Results. Heart transplantation was performed on 728 patients (99 females – 13.6% and 629 males – 86.4%) including 18 children aged 12 to 17 years (14.18 ± 2.07 years). Mortality in the waiting list in 2010 was 16.1%, compared with 3.2% in 2017.
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The effects of angiotensin-converting enzyme inhibitors in heart recipients: A single center experience
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01.01.2018 |
Shevchenko A.
Faradzhov R.
Izotov D.
Koloskova N.
Nikitina E.
Gichkun O.
Orlov V.
Tunyaeva I.
Mironkov B.
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Vestnik Transplantologii i Iskusstvennykh Organov |
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© 2018 Russian Transplant Society. All Rights Reserved. Aim. To study the effect of ACE inhibitors (ACEI) in heart recipients on the prognosis and myocardial remodeling. Materials and methods. Three hundred and eighty-six patients who received orthotopic heart transplantation (HT) were consequently enrolled to the study from February 2009 to November 2016. Results. Thirty days after the HT, ACEIs were assigned to 141 recipients. Arterial hypertension was diagnosed in all cardiac recipients who received ACEI and among 48 patients (19.5%) from non-ACEI group. Patients receiving ACEI had significantly better event-free survival than control group (p = 0.045) during the follow-up for 1361,6 ± 36,9 days. Left ventricle (LV) end-diastolic dimension did not change over the time in both groups, whereas LV posterior wall thickness in non-ACEI group significantly increased from 1.35 ± 0.03 cm to 1,23 ± 0.05 cm (p < 0.05). Conclusion. Cardiac recipients who received ACE inhibitors had better survival and less transplant left ventricle progression, that could reflect beneficial effects of renin-aldosterone-angiotensin system inhibition after heart transplantation.
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The preferable binding pose of canonical butyrylcholinesterase substrates is unproductive for echothiophate
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01.01.2018 |
Zlobin A.
Zalevsky A.
Mokrushina Y.
Kartseva O.
Golovin A.
Smirnov I.
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Acta Naturae |
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1 |
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© 2018 Park-media, Ltd. In this paper, we, for the first time, describe the interaction between the butyrylcholinesterase enzyme and echothiophate, a popular model compound and an analogue of the chemical warfare agents VX and VR, at the atomistic level. Competition between the two echothiophate conformations in the active site was found using molecular modeling techniques. The first one is close to the mode of binding of the substrates of choline series (butyrylcholine and butyrylthiocholine) and is inhibitory, since it is unable to react with the enzyme. The second one is characterized by a significantly worse estimated binding affinity and is reactive. Thus, echothiophate combines the features of two types of inhibitors: competitive and suicidal. This observation will help clarify the kinetic reaction scheme in order to accurately assess the kinetic constants, which is especially important when designing new butyrylcholinesterase variants capable of full-cycle hydrolysis of organophosphorus compounds.
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Efficacy of eradication therapy with stimbifid plus in experimental acute helicobacter pylori infection in murinemodels and in volunteers
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01.01.2018 |
Chicherin I.
Pogorelsky I.
Darmov I.
Lundovskikh I.
Shabalina M.
Kolevatykh E.
Kozlov P.
Kornaukhov A.
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Infektsionnye Bolezni |
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0 |
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© 2018, Dynasty Publishing House. All rights reserved. Objective: to evaluate the possibility of creating a human model of acute Helicobacter pylori infection in healthy volunteers after infecting them with a mutant rifampicin-resistant strain of H. pylori KM-11 (Rif R ), to obtain evidence of H. pylori survival and invasion into the gastric mucosa, describe the symptoms, and assess the efficacy of H. pylori eradication therapy with Stimbifid plus. Materials and methods. In our experiments, we used conventional white mice of both genders weighing 18–20 g. The concentration of bifidobacteria, lactobacilli, and Escherichia (CFU) in animal faeces was determined by inoculating tenfold dilutions of biomaterial onto solid media and further counting of bacterial colonies grown after the incubation period. Microorganisms were cultivated in an anaerobic incubator and then identified by morphological evaluation and using biochemical identification kits. We created a murine model of H. pylori infection by oral administration of H. pylori KM-11 (Rif R ) suspensions to immunocompromised mice that had earlier undergone intramuscular administration of dexamethasone. For a human model of H. pylori infection, we selected healthy male volunteers. They took suspensions of H. pylori KM-11 (Rif R ) isolates in isotonic sodium chloride solution. Fecal specimens were collected from volunteers on daily basis during the entire follow-up period and then 2 weeks and 1 month after treatment completion. Fecal suspensions in isotonic sodium chloride solution were inoculated onto the selective hemin-containing solid media with rifampicin at a concentration of 160 µg·mL –1 . The results of this experiment (H. pylori colony count) were used to evaluate the efficacy of H. pylori eradication therapy with Stimbifid plus. Results. Both in vitro experiments and murine models demonstrated high anti-H. pylori activity of Stimbifid plus and its ingredients, restoration of the gastric microbiota, restoration of gastric colonization resistance, and eradication of H. pylori KM-11 (Rif R ). Self-infection with H. pylori KM-11 (RifR) caused acute infection in volunteers. The disease manifested with mild ailment, epigastric discomfort, belching, increased stool frequency, and changes in the color of stool. The detection of H. pylori KM-11 (Rif R ) in the faeces of volunteers and isolation of pure cultures prior to treatment initiation indicated bacterial adhesion to gastric mucosa and survival of microorganisms. Treatment with Stimbifid plus caused gradual decrease in the number of bacteria isolated from feces and their complete elimination by day 11 of therapy. All fecal specimens collected 2 weeks and 1 month after therapy completion from volunteers were negative for H. pylori KM-11 (Rif R ). None of the study participants required in-patient treatment. Conclusion. The results of our experiments obtained in both murine and human models of H. pylori infection will be used for more detailed assessment of this pathological process, clinical manifestations, impact of H. pylori virulence factors on the host, choosing new methods for the prevention and treatment of chronic gastritis caused by H. pylori, and monitoring the efficacy of eradication therapy.
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Photo dynamic adjuvant therapy in complex treatment of patients with portal cholangiocarcinoma
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01.01.2018 |
Zharikov Y.
Pozharskaya A.
Tupikin K.
Baidarova M.
Nikolenko V.
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Medical News of North Caucasus |
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0 |
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© 2018 Stavropol State Medical University. All Rights Reserved. The review presents the latest achievements in the field of complex adjuvant treatment of patients with portal cholangiocarcinoma. Modern data on the clinical efficacy and benefits of intraduct photodynamic therapy are presented.
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The impact of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty
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01.01.2018 |
Sychev D.
Levanov A.
Shelekhova T.
Bochkov P.
Denisenko N.
Ryzhikova K.
Mirzaev K.
Grishina E.
Gavrilov M.
Ramenskaya G.
Kozlov A.
Bogoslovsky T.
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Pharmacogenomics and Personalized Medicine |
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6 |
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© 2018 Sychev et al. Background: Non-vitamin K oral anticoagulants (NOACs) are commonly used for prophylaxis of venous thromboembolism (VTE) in orthopedic patients. Despite known safety and high potency of NOACs, potential interactions of NOACs with genetic polymorphisms are poorly understood. Dabigatran etexilate is one of the most commonly prescribed direct thrombin inhibitors for the prevention of VTE. The objectives of this study were to assess the effect of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) polymorphisms on dabigatran pharmacokinetics in patients after total knee arthroplasty. Patients and methods: A total of 60 patients, aged 37–81 years, who underwent surgery for knee replacement have been included in the study. VTE prophylaxis was conducted via administration of dabigatran etexilate 220 mg once daily. Genotyping for carrier state of polymorphic variants such as rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene was carried out using real-time polymerase chain reaction (PCR). We also measured the peak and trough concentrations of plasma dabigatran by using high-performance liquid chromatography (HPLC). Results: Our study revealed that TT genotype of rs1045642 polymorphism of the ABCB1 gene was associated with higher dabigatran equilibrium peak concentrations and the higher risk of bleeding than the presence of CC genotype (p<0.008). There was no statistically significant genotype-dependent difference in the trough concentrations between rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene. Conclusion: Our findings indicate that the polymorphisms of ABCB1 rs1045642 may have a prominent contribution to the safety of dabigatran in patients after knee surgery. Moreover, TT genotype may be associated with the higher risk of hemorrhagic complications in this population. There were no influence of polymorphism of ABCB1 rs4148738 and CES1 rs2244613 on dabigatran peak and through concentrations. Larger studies are needed to confirm our observations.
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