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Zhuravskii S.G.,St. Petersburg State Medical University
History of Medicine | Year: 2016

Russian archives retain three diary books by a renowned Russian physician S.P. Botkin (1832-1889), containing information relating to his service as Physician-in-Ordinary to the Tzar Family in 1872-1889. Botkin’s work notes provide an important source revealing the practical arrangement of the royal court medical care as pertaining to internal diseases and laboratory diagnostics. Their central theme is the health status of Alexander II (1818-1881) and his spouse, Empress Maria Alexandrovna (1824-1880), in the last decade of their life. The everyday professional life of a court doctor is described in great detail: circumstances of medical examinations, physical examination results, clinical summaries, pharmaceutical prescriptions, guidelines on clinical nutrition, mineral water intake, climate therapy. The archive of the “elite” inscriptions contained in the diary books tracks the origins of contemporary clinical pharmacology with its patient-centered approach. Throughout the pages of the source, the author reveals himself in the little-known capacity of an empirical clinical psychologist. Diary entries show understanding of the pathogenic importance of the psychological background against which the internal abnormality develops and are indicative of the compliance level among the august patients. A number of fragments of daily comments along with a detailed post-mortem report of Empress Maria Alexandrovna constitute a unique material for consideration of the topic of deontological aspects of the service of the physician-in-ordinary to the Imperial family. Botkin’s notes provide an invaluable source of specific information exposing some private facts of life of the Imperial family in the described period of time. A targeted scientific study of the documents enables to consider the august personages’ individual health status as an independent factor in the historical process. © Sergei G. Zhuravskii.


RESULTS: It was revealed that Reamberine increased efficacy of postoperative treatment. There were earlier (by 52.6% compared with control group) improvement of health including weakness disappearance, sleep and appetite recovery. Hemodynamic parameters were also improved (stabilization of blood pressure and pulse). It was observed earlier disappearance of pain and edematous syndrome (by 32.3%). There were also earlier postoperative wound healing (by 21.3%) and reducing of rehabilitation terms (by 72%, i.e. 2.1 ± 0.7 vs. 7.5 ± 0.9 days respectively).AIM: To study an efficacy of Reamberine in complex therapy in early postoperative period after knee-joint surgery.MATERIAL AND METHODS: It was analyzed treatment of 108 patients (47 men and 61 women) with degenerative diseases of knee-joint in postoperative period. Periarticular osteotomy of tibia and knee-joint replacement were performed. Patients were divided into 2 groups. Main group consisted of 43 patients who received Reamberine 400-800 ml with infusion rate 4-5 ml/min during 1-1,5 hours for 4-8 days postoperatively. Control group (65 patients) had conventional therapy with daily volume 400-800 ml.Цель исследования — изучение эффективности включения препарата реамберин в схему инфузионной терапии в раннем послеоперационном периоде при ортопедических операциях на коленном суставе. Для этого проведен анализ терапии 108 больных (47 мужчин и 61 женщина) с дегенеративно-дистрофическими поражениями коленного сустава, получивших хирургическое лечение (корригирующие околосуставные остеотомии большеберцовых костей и эндопротезирование коленного сустава). В соответствии с проводимыми схемами медикаментозного лечения пациенты были разделены на две группы: в основной группе (43 больных) в раннем послеоперационном периоде был назначен препарат реамберин: внутривенно капельно 4—5 мл/мин в объеме 400—800 мл, в течение 1,0—1,5 ч ежедневно на протяжении 4—8 дней после операции. Пациентам контрольной группы (65 больных) проводилась традиционная инфузионная терапия в суточном объеме 400—800 мл. Было выявлено, что включение реамберина в схему терапии в раннем послеоперационном периоде после корригирующих околосуставных остеотомий большеберцовых костей и эндопротезирования коленного сустава повысило эффективность лечения, что проявлялось в более раннем (на 52,6% по сравнению с данными контрольной группы) улучшении самочувствия (исчезновение слабости, восстановление аппетита, нормализация сна) и показателей гемодинамики (стабилизация артериального давления и пульса) и более быстром (на 32,3%) купировании болевого и отечного симптомов. В связи с этим у пациентов, получивших реамберин, отмечено более раннее (на 21,3%) заживление послеоперационной раны, что позволило быстрее (на 72%, т.е. 2,1±0,7 сут против 7,5±0,9 сут в контрольной группе) начать мобилизацию пациентов и, как следствие, сократить сроки восстановительного периода.


The N.N. Petrov Research Institute of Oncology, which has turned 90 years old, is the oldest oncological institution in Russia dealing with the etiology and pathogenesis of malignant tumors, developing new methods for the prevention, diagnosis, treatment and rehabilitation of cancer patients. On this path, especially for recent years, the institution achieved undoubted success in clinical and research work, introduced modern technologies, the results of using them enriched clinical practice.


Karonova T.,St. Petersburg State Medical University | Micheeva E.,St. Petersburg State Medical University | Belyaeva O.,St. Petersburg State Medical University
Aging | Year: 2013

It was suggested that glucose metabolism and body fat content depend on serum levels of 25-hydroxyvitamin D [25(OH)D]. We studied 320 healthy women at late reproductive age of 40 to 52 years old (mean age 46.1±4.5) from St. Petersburg (North-West region of Russia). 25(OH)D levels were from 19.4 to 134.0 nMol/L (mean 52.9±22.7). Vitamin D deficiency (lower than 50 nMol/L) and insufficiency (50-75 nMol/L) was revealed in 59.1% and 27.8% of women, respectively. The study showed that low 25(OH)D levels were associated with obesity (r=-0.35, p<0.01), increased plasma glucose levels after OGTT (r=-0.31, p<0.01) and decreased insulin sensitivity index (r=-0.28, p<0.01). We found that 25(OH)D levels below 50 nMol/L were associated with obesity risk (OR 2.25[1.05-3.95], CI 95%) but not with risk of impaired glucose metabolism (1.07[0.54-2.12],CI95%). Our results showed that vitamin D insufficiency is highly prevalent in the population of healthy women. Low 25(OH)D levels correlated with high body fat, glucose levels and decreased insulin sensitivity. We conclude that vitamin D deficiency is a potential risk factor for obesity and development of insulin resistance leading to diabetes type 2. © Grineva et al.


Reck M.,Lung Clinic Grosshansdorf | Reck M.,German Center for Lung Research | Kaiser R.,Boehringer Ingelheim | Mellemgaard A.,Herlev University Hospital | And 11 more authors.
The Lancet Oncology | Year: 2014

Background: The phase 3 LUME-Lung 1 study assessed the efficacy and safety of docetaxel plus nintedanib as second-line therapy for non-small-cell lung cancer (NSCLC). Methods: Patients from 211 centres in 27 countries with stage IIIB/IV recurrent NSCLC progressing after first-line chemotherapy, stratified by ECOG performance status, previous bevacizumab treatment, histology, and presence of brain metastases, were allocated (by computer-generated sequence through an interactive third-party system, in 1:1 ratio), to receive docetaxel 75 mg/m2 by intravenous infusion on day 1 plus either nintedanib 200 mg orally twice daily or matching placebo on days 2-21, every 3 weeks until unacceptable adverse events or disease progression. Investigators and patients were masked to assignment. The primary endpoint was progression-free survival (PFS) by independent central review, analysed by intention to treat after 714 events in all patients. The key secondary endpoint was overall survival, analysed by intention to treat after 1121 events had occurred, in a prespecified stepwise order: first in patients with adenocarcinoma who progressed within 9 months after start of first-line therapy, then in all patients with adenocarcinoma, then in all patients. This trial is registered with ClinicalTrials.gov, number NCT00805194. Findings: Between Dec 23, 2008, and Feb 9, 2011, 655 patients were randomly assigned to receive docetaxel plus nintedanib and 659 to receive docetaxel plus placebo. The primary analysis was done after a median follow-up of 7·1 months (IQR 3·8-11·0). PFS was significantly improved in the docetaxel plus nintedanib group compared with the docetaxel plus placebo group (median 3·4 months [95% CI 2·9-3·9] vs 2·7 months [2·6-2·8]; hazard ratio [HR] 0·79 [95% CI 0·68-0·92], p=0·0019). After a median follow-up of 31·7 months (IQR 27·8-36·1), overall survival was significantly improved for patients with adenocarcinoma histology who progressed within 9 months after start of first-line treatment in the docetaxel plus nintedanib group (206 patients) compared with those in the docetaxel plus placebo group (199 patients; median 10·9 months [95% CI 8·5-12·6] vs 7·9 months [6·7-9·1]; HR 0·75 [95% CI 0·60-0·92], p=0·0073). Similar results were noted for all patients with adenocarcinoma histology (322 patients in the docetaxel plus nintedanib group and 336 in the docetaxel plus placebo group; median overall survival 12·6 months [95% CI 10·6-15·1] vs 10·3 months [95% CI 8·6-12·2]; HR 0·83 [95% CI 0·70-0·99], p=0·0359), but not in the total study population (median 10·1 months [95% CI 8·8-11·2] vs 9·1 months [8·4-10·4]; HR 0·94, 95% CI 0·83-1·05, p=0·2720). Grade 3 or worse adverse events that were more common in the docetaxel plus nintedanib group than in the docetaxel plus placebo group were diarrhoea (43 [6·6%] of 652 vs 17 [2·6%] of 655), reversible increases in alanine aminotransferase (51 [7·8%] vs six [0·9%]), and reversible increases in aspartate aminotransferase (22 [3·4%] vs three [0·5%]). 35 patients in the docetaxel plus nintedanib group and 25 in the docetaxel plus placebo group died of adverse events possibly unrelated to disease progression; the most common of these events were sepsis (five with docetaxel plus nintedanib vs one with docetaxel plus placebo), pneumonia (two vs seven), respiratory failure (four vs none), and pulmonary embolism (none vs three). Interpretation: Nintedanib in combination with docetaxel is an effective second-line option for patients with advanced NSCLC previously treated with one line of platinum-based therapy, especially for patients with adenocarcinoma. Funding: Boehringer Ingelheim. © 2014 Elsevier Ltd.


Ciuleanu T.,Institute of Oncology Ion Chiricuta | Stelmakh L.,St. Petersburg State Medical University | Cicenas S.,Vilnius University | Miliauskas S.,Lithuanian University of Health Sciences | And 5 more authors.
The Lancet Oncology | Year: 2012

Background: Erlotinib, docetaxel, and pemetrexed are approved for the second-line treatment of non-small-cell lung cancer (NSCLC), but no head-to-head data from large clinical trials are available. We undertook the Tarceva In Treatment of Advanced NSCLC (TITAN) study to assess the efficacy and tolerability of second-line erlotinib versus chemotherapy in patients with refractory NSCLC. Methods: TITAN was an international, randomised multicentre, open-label, phase 3 study that was done at 77 sites in 24 countries. Chemotherapy-naive patients with locally advanced, recurrent, or metastatic NSCLC received up to four cycles of first-line platinum doublet chemotherapy, after which patients with disease progression during or immediately after chemotherapy were offered enrolment into TITAN. Enrolled patients were randomly assigned (1:1) by a minimisation method to ensure balanced stratification, to receive erlotinib 150 mg/day or chemotherapy (standard docetaxel or pemetrexed regimens, at the treating investigators' discretion), until unacceptable toxicity, disease progression, or death. Patients were stratified by disease stage, Eastern Cooperative Oncology Group performance status, smoking history, and region of residence. The primary endpoint was overall survival in the intention-to-treat population. TITAN was halted prematurely because of slow recruitment. This study is registered with ClinicalTrials.gov, number NCT00556322. Findings: Between April 10, 2006, and Feb 24, 2010, 2590 chemotherapy-naive patients were treated with first-line platinum doublet chemotherapy, of whom 424 had disease progression and were enrolled into TITAN. 203 patients were randomly assigned to receive erlotinib and 221 were assigned to receive chemotherapy. Median follow-up was 27·9 months (IQR 11·0-36·0) in the erlotinib group and 24·8 months (12·1-41·6) in the chemotherapy group. Median overall survival was 5·3 months (95% CI 4·0-6·0) with erlotinib and 5·5 months (4·4-7·1) with chemotherapy (hazard ratio [HR] 0·96, 95% CI 0·78-1·19; log-rank p=0·73). The adverse-event profile of each group was in line with previous studies. Rash (98/196 [50%] in the erlotinib group vs 10/213 [5%] in the chemotherapy group for all grades; nine [5%] vs none for grade 3 or 4) and diarrhoea (36 [18%] vs four [2%] for all grades; five [3%] vs none for grade 3 or 4) were the most common treatment-related adverse events with erlotinib, whereas alopecia (none vs 23 [11%] for all grades; none vs one [<1%] for grade 3/4) was the most common treatment-related adverse event with chemotherapy. Interpretation: No significant differences in efficacy were noted between patients treated with erlotinib and those treated with docetaxel or pemetrexed. Since the toxicity profiles of erlotinib and chemotherapy differ, second-line treatment decisions should take into account patient preference and specific toxicity risk profiles. Funding: F Hoffmann-La Roche. © 2012 Elsevier Ltd.


Sokolov A.Y.,St. Petersburg State Medical University | Lyubashina O.A.,RAS Pavlov Institute of Physiology | Panteleev S.S.,St. Petersburg State Medical University
Journal of Headache and Pain | Year: 2012

Primary headaches are often associated with pain in the maxillofacial region commonly classified under the term "orofacial pain" (OFP). In turn, long-lasting OFP can trigger and perpetuate headache as an independent entity, which is able to persist after the resolution of the main disorder. A close association between OFP and headache complicates their cause and effect definition and leads to misdiagnosis. The precise mechanisms underlying this phenomenon are poorly understood, partly because of the deficiency of research-related findings. We combined the animal models of OFP and headache - the orofacial formalin test and the model of trigeminovascular nociception - to investigate the neurophysiological mechanisms underlying their comorbidity. In anesthetized rats, the ongoing activity of single convergent neurons in the spinal trigeminal nucleus was recorded in parallel to their responses to the electrical stimulation of the dura mater before and after the injection of formalin into their cutaneous receptive fields. Subcutaneous formalin resulted not only in the biphasic increase in the ongoing activity, but also in an enhancement of neuronal responses to dural electrical stimulation, which had similar time profile. These results demonstrated that under tonic pain in the orofacial region a nociceptive signaling from the dura mater to convergent trigeminal neurons is significantly enhanced apparently because of the development of central sensitization; this may contribute to the comorbidity of OFP and headache. © The Author(s) 2011.


Osinovskaya N.S.,St. Petersburg State Medical University
International Journal of Gynecological Pathology | Year: 2015

Uterine leiomyomas (ULs) are common benign tumors affecting women of different ethnicities. A large proportion of UL has mutations in MED12. Multiple and solitary ULs usually manifest with different severities, suggesting that their origin and growth pattern may be driven by different molecular mechanisms. Here, we compared the frequency and the spectrum of MED12 exon 2 mutations between multiple (n=82) and solitary (n=40) ULs from Russian patients. Overall, we detected MED12 exon 2 mutations in 51.6% (63/122) of ULs. The frequency of MED12 exon 2 mutations was almost two-fold higher in samples from the multiple UL patients than in those from the solitary UL patients – 61% (50/82) versus 32.5% (13/40). The increased MED12 exon 2 mutation frequency in the multiple ULs was not accompanied by significant alterations in the spectrum of mutation categories, which included missense mutations, deletions, splicing defects, and multiple (double/triple) mutations. Each mutation category had a unique mutation set, comprising both frequent and rarely encountered mutations, which did and did not overlap between the studied groups, respectively. We conclude that in contrast to the solitary ULs, the multiple ULs predominantly originate through MED12-associated mechanisms. The nature of these mechanisms seems to be similar in solitary and multiple ULs, as they contain similar mutations. In multiple UL patients, they are likely to be nonsporadic, indicating the existence of specific factors predisposing to multiple UL development. These data suggest that to clearly understand UL pathogenesis, solitary and multiple tumors should probably be analyzed as separate sets. ©2015International Society of Gynecological Pathologists


Mertz B.,University of Arizona | Struts A.V.,University of Arizona | Struts A.V.,St. Petersburg State Medical University | Feller S.E.,Wabash College | Brown M.F.,University of Arizona
Biochimica et Biophysica Acta - Biomembranes | Year: 2012

Rhodopsin has served as the primary model for studying G protein-coupled receptors (GPCRs)-the largest group in the human genome, and consequently a primary target for pharmaceutical development. Understanding the functions and activation mechanisms of GPCRs has proven to be extraordinarily difficult, as they are part of a complex signaling cascade and reside within the cell membrane. Although X-ray crystallography has recently solved several GPCR structures that may resemble the activated conformation, the dynamics and mechanism of rhodopsin activation continue to remain elusive. Notably solid-state 2H NMR spectroscopy provides key information pertinent to how local dynamics of the retinal ligand change during rhodopsin activation. When combined with molecular mechanics simulations of proteolipid membranes, a new paradigm for the rhodopsin activation process emerges. Experiment and simulation both suggest that retinal isomerization initiates the rhodopsin photocascade to yield not a single activated structure, but rather an ensemble of activated conformational states. This article is part of a Special Issue entitled: Membrane protein structure and function. © 2011 Elsevier Inc. All rights reserved.


Al-Shukri S.,St. Petersburg State Medical University
European Urological Review | Year: 2012

Neurogenic bladder is defined as dysfunction of the bladder due to damage to the central nervous system. Urination is under the control of a complex neural feedback system, involving the sacral micturition centre, the pontine micturition centre and the cerebral cortex and damage to any of these areas or the neural circuits connecting them, can result in bladder storage or voiding disorders. Because of the wide spectrum of damage and disease that can occur, the population of patients with neurogenic bladder is diverse. Methods used to evaluate patients with neurogenic bladder include post-void residual urine determination and urodynamic studies. Treatment aims to protect the upper urinary tractand treatment options include intermittent and indwelling catheterisation, drug interventions and botulinum toxin A. However, some drugs used in the treatment of neurogenic bladder are associated with poor patient compliance and significant side effects. This article outlines the management strategies that should be implemented when treating this diverse group of patients and discusses recent advancesin the treatment of neurogenic bladder. © TOUCH BRIEFIGS 2012.

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