[Intrathecal chemotherapy for leptomeningeal metastases in patients with breast cancer]. / Intratekal'naya khimioterapiya pri leptomeningeal'nom metastazirovanii u bol'nykh rakom molochnoi zhelezy.

Leptomeningeal metastases are lesions of brain and/or spinal cord sheaths by tumor cells. They occur in 5% of patients with solid tumors, although autopsies reveal these lesions much more often (10-20% of cases). Leptomengeal metastases are an unfavorable prognostic factor. Despite the modern NCCN treatment standards, including intrathecal therapy (ITT), such patients receive only irradiation of the entire brain and/or spinal cord in most cases. OBJECTIVE: To evaluate the effectiveness of ITT in patients with leptomeningeal metastases in breast cancer. MATERIAL AND METHODS: Twenty-five patients with breast cancer and leptomeningeal metastases underwent intrathecal administration of methotrexate between 2016 and 2022. Intrathecal chemotherapy was administered through lumbar puncture. We performed an intensive course (intrathecal methotrexate 15 mg 2 times a week for 1 month (8 injections), then intrathecal methotrexate 15 mg 1 time a week (4 injections), and then 15 mg 1 time a month until progression or unacceptable toxicity). RESULTS: The median duration of ITT was 2.5 months. Complete neurological responses were observed in 3 out of 25 (12%) patients, partial neurological response - in 15 out of 25 (60%) patients, progression of neurological symptoms - in 7 (28%) patients. The number of complete cytological responses was observed in 6 out of 25 (24%) patients. The median overall survival after ITT was 6.7 months. CONCLUSION: Effectiveness of ITT is confirmed by higher quality of life (72% of patients), complete cytological responses (24%) and improvement in neuroimaging data. This is an important criterion for severe patients with limited treatment options. First-stage ITT before whole-brain irradiation is preferable, as this approach increases overall survival by 3 months. Undoubtedly, ITT is a treatment option that can be used in routine clinical practice for lesions of brain and spinal cord sheaths.

[Evaluation the effectiveness of immersive VR-assisted rehabilitation in a child with chemotherapy-induced neurological complication in acute lymphoblastic leukemia]. / Izuchenie vozmozhnosti reabilitatsii s pomoshch'yu virtual'noi real'nosti u rebenka s nevrologicheskim oslozhneniem, voznikshem na fone khimioterapii pri ostrom limfoblastnom leikoze.

Rehabilitation therapy is considered as an actual and complex system of knowledge, in which the main task is the development and implementation of new methods of rehabilitation. In present time, the most perspective rehabilitation program is utilizing virtual reality. A report was made with the utilization of rehabilitation therapy with virtual reality in a child with chemotherapy-induced neurological disorders in acute lymphoblastic leukemia. The child performed a set of exercises using fully immersive virtual reality. Over the course of rehabilitation positive dynamics was observed, namely increased muscle strength in the injured limb from 3 to 5 scores according to the Medical Research Council Weakness Scale. There was improved balance on the Berg Balance Scale from 35 to 42. In addition, there were increased range of active movements, partly restored biomechanics of gait with increased velocity by 2 times. According to the results of testing the psycho-emotional state using the Luscher color test and the graphic technique «Cactus¼ by M.A. Panfilova, self-esteem, the desire to succeed and independence were improved, the level of auto-aggression was decreased. The results show that rehabilitation using fully immersive virtual reality is probably a perspective tool in addition to traditional rehabilitation. It improves the neurological and psycho-emotional state, raises motivation of patients, which, in turn, helps to increase the effectiveness of rehabilitation therapy and speeds up the rehabilitation process.

[Improvement of measures to ensure safe working conditions for staff of the bureau of forensic medicine]. / Sovershenstvovanie meropriyatii po obespecheniyu bezopasnykh uslovii truda sotrudnikov byuro sudebno-meditsinskoi ekspertizy.

Employees of the Bureau of Forensic Medicine (BFM) are exposed to various harmful and dangerous workplace factors during their work. The objective of the study is to improve measures to maintain a safe epidemiological situation in the experience of the BFM of the Republic of Tatarstan based on the results of an online questionnaire survey of employees, which included parts on the assessment of health, working conditions, and morbidity, including tuberculosis. The detailed analysis of the responses made it possible to determine a set of measures to improve the BFM workflow and health status of employees.

[Russian version of the neurogenic bladder symptom score (NBSS)].

AIM: The Neurogenic Bladder Symptom Score (NBSS) is widely used now for the bladder symptoms assessment in neurogenic low urinary tract dysfunction. It is suitable for all patients, regardless of a bladder management method. NBSS contains 24 questions, which focus on incontinence, storage and voiding symptoms, urinary complicationsand life quality.With the permission of the authors (Dr.Welk et al.), NBSS had been translated into Russian according to the cultural and lingual adaptation algorithm. OBJECTIVES: Validate the Russian version of NBSS for multiple sclerosis patients. DESIGN, SETTING, AND PARTICIPANTS: The study included 80respondents: group A - 40 multiple sclerosis (MS) patients with neurogenic bladder, group B - 40 multiple sclerosis (MS) patients without bladder dysfunction, group C - healthy controls. All participants filled out the NBSS two times with an interval of two weeks. They also completed other measurement tools (IPSS,OAB Awareness Tool, WHOQOL BREF).Data were used to determine the internal consistency (Cronbachs alfa), external validity (Pearson correlation), and test-re-test reliability with interclass correlation coefficient. RESULTS: The mean of the NBSS total in the group A was 22.56+/-12.6, which significantly (p<0.001) exceeded score in comparable groups B (6.42+/-2.3) and C (5.31+/-1.9). The Cronbachs alfa of the total and the in continence, storage/voiding, and consequences domains was 0.939, 0,965, 0,801 and 0.712 respectively, which confirms the high internal consistency of the Russian version of the NBSS. External validity was verified by the relevant correlations with other questionnaires. Test-retest reliability was excellent. The interclass correlation coefficients were >0.85 (p<0.001) for all subdomains and the overall score. CONCLUSION: The Russian version of the NBSS demonstrated good validity and reliability and may be recommended for use in clinical practice.

[A clinical case of combined treatment of a patient with breast cancer and metastases to the brain and meninges].

The article describes a clinical case of successful chemotherapeutic and radiation treatment of a patient with breast cancer and metastases to the brain and meninges and with a pronounced neurological deficit. The patient underwent combined treatment (whole brain radiation with TBD of 30 Gy and local radiation of a metastasis with TBD of 15 Gy associated with capecitabine therapy) with continued administration of capecitabine until improvement. A partial metastasis reduction by 50% and complete regression of the neurological deficit were observed. Disease-free period was 1 year and 10 months, and the overall survival amounted to 2 years.

[Complex treatment of breast cancer patients with brain metastases].

Brain metastases in breast cancer develop for 24-32 months after the detection of the primary tumor. The study included patients with brain metastases who were divided into three groups: the first group--with early chemoradiotherapy (CRT) without induction chemotherapy (IC) by capecitabine; the second group--with delayed CRT with 4 or 8 courses of IC by capecitabine; the third group (a historical control) who received only whole brain radiation therapy. The median time to progression of intracranial metastases was 15.3, 12 and 5 months, respectively. The median time to the intracranial progression significantly less in the third group (5 months) compared with the first (15.3 months) (p = 0.0007) and the second (12 months) (p = 0.027) groups. The overall survival rate was 22.1, 15.1 and 6.8 months in three groups, respectively.

[Current possibilities of targeted therapy in the treatment of breast cancer with overexpression of HER-2/neu and metastatic lesions in the brain].

Targeted therapy (lapatinib and/or trastuzumab) in combination with chemotherapy (capecitabine) is highly effective in metastatic lesions of the brain in breast cancer patients with overexpress HER-2/neu. An objective response in the brain was achieved in 19 patients (55.9%). Complete regression was observed in 5 cases (14.7%), partial regression--14 (41.2%). Stabilization of tumor process in the brain was revealed in 12 patients (35.3%). There was marked improvement in the quality of life of the majority of patients due to the regression of symptoms and good tolerability of treatment.

UTP evokes noradrenaline release from rat sympathetic neurons by activation of protein kinase C.

The pathway involved in UTP-evoked noradrenaline release was investigated in cultures of rat superior cervical ganglia. Northern blots revealed an age-related increase in levels of mRNA for P2Y6 receptors in cultures obtained at postnatal days 1 and 5, respectively, but no change in transcripts for P2Y1 and P2Y2. Likewise, UTP-evoked overflow of previously incorporated [(3)H]noradrenaline was six-fold higher in neurons obtained at postanatal day 5. Various protein kinase C inhibitors diminished UTP-, but not electrically, induced tritium overflow by > 70%, as did down-regulation of protein kinase C by 24 h exposure to phorbol ester. beta-Phorbol-12,13-dibutyrate and dioctanoylglycerol caused concentration-dependent increases in [(3)H] outflow of up to 6% of total radioactivity, and the secretagogue actions of these agents were reduced in the presence of protein kinase C inhibitors and in neurons pretreated with phorbol ester. Overflow evoked by dioctanoylglycerol was attenuated in the absence of extracellular Ca(2+) and in the presence of tetrodotoxin or Cd(2+). In addition to triggering tritium overflow, UTP reduced currents through muscarinic K(+) channels which, however, were not affected by phorbol esters. This action of UTP was not altered by protein kinase C inhibitors. These results indicate that P2Y6 receptors mediate UTP-evoked noradrenaline release from rat sympathetic neurons via activation of protein kinase C, but not inhibition of K(M) channels.

Stress factors acting at the level of the plasma membrane induce transcription via the stress response element (STRE) of the yeast Saccharomyces cerevisiae.

A variety of stress factors induces transcription via the stress response element (STRE) present in control regions of a number of genes of the yeast Saccharomyces cerevisiae. Induction of transcription involves nuclear translocation of the STRE-binding transcription activators Msn2p and Msn4p. The primary cellular events triggering this translocation are presently not well understood. In this investigation, we have observed that a number of factors acting at the level of the yeast plasma membrane, including the antifungal agent nystatin, the steroidal alkaloid tomatine, benzyl alcohol, a number of detergents and the plasma membrane H+-ATPase inhibitor diethylstilbestrol or mutations in the PMA1 gene encoding the plasma membrane ATPase, induce Msn2p nuclear accumulation and STRE-dependent transcription. At least some of the stress factors acting via STREs cause an increase in plasma membrane permeability, leading to a decrease in membrane potential, which might be a primary cellular stress signal. A decrease in internal pH triggered by permeabilization of the plasma membrane or a change in cAMP levels are at least not obligatory factors in intracellular stress signal transduction. The signal transduction pathway transmitting the signal generated at the plasma membrane to Msn2p is still unknown.

A search in the genome of Saccharomyces cerevisiae for genes regulated via stress response elements.

Stress response elements (STREs, core consensus AG4 or C4T) have been demonstrated previously to occur in the upstream region of a number of genes responsive to induction by a variety of stress signals. This stress response is mediated by the homologous transcription factors Msn2p and Msn4p, which bind specifically to STREs. Double mutants (msn2 msn4) deficient in these transcription factors have been shown to be hypersensitive to severe stress conditions. To obtain a more representative overview of the set of yeast genes controlled via this regulon, a computer search of the Saccharomyces cerevisiae genome was carried out for genes, which, similar to most known STRE-controlled genes, exhibit at least two STREs in their upstream region. In addition to the great majority of genes previously known to be controlled via STREs, 69 open reading-frames were detected. Expression patterns of a set of these were examined by grid filter hybridization, and 14 genes were examined by Northern analysis. Comparison of the expression patterns of these genes demonstrates that they are all STRE-controlled although their detailed expression patterns differ considerably.