[Current trends in bladder cancer diagnosis].

In the Russian Federation, a proportion of bladder cancer in the overall structure of malignant tumors is about 2.8% and among oncological diseases of genitourinary system its incidence is second only to prostate cancer. Bladder cancer ranks as ninth most prevalent in males and as eighteens in females. The most important issue is to determine a recurrence rate of non-muscle invasive bladder cancer, which can reach 80%. In this regard, currently, all over the world much more attention is paid to studying and creation of early detection, including non-invasive, which will be reliable in the early stages. It can possibly lead to a reduction the number of cystoscopy and become as "golden" standard of non-invasive diagnosis bladder cancer.

[The role of telomerase activity in non-invasive diagnostics of bladder cancer].

PURPOSE: To evaluate the potentials of determining the telomerase activity (TA) in the cellular material of the urine for noninvasive diagnosis of bladder cancer (BC). MATERIALS AND METHODS: Evaluation of TA was performed in the urine of 48 patients with bladder cancer (study group) before and after transurethral resection of the bladder wall (n=38), an open resection of the bladder (n=4), and cystectomy (n=6). TA was also evaluated in 48 tumor tissue samples obtained from these patients during removal of the bladder tumor. Each sample of the tumor tissue was separated into two parts, one of which was subjected to histological examination, and the latter was used to determine the telomerase activity. In all cases, the diagnosis of bladder cancer was confirmed morphologically. Determination of TA in the samples was performed by the modified TRAP-method (telomerase repeat amplification protocol), RT-PCR, PCR, and electrophoresis. As a control, cell material of the urine and tissue in 12 patients with chronic cystitis was investigated. RESULTS: TA before surgery was found in 45 (93.75%) of 48 samples of cellular material of the urine from patients with suspected bladder cancer. BC was histologically verified in all patients in this group. In the postoperative period, TA was not observed in the 48 samples of cellular material of the urine from patients with BC. In the control group of patients with histologically verified cystitis, weak TA was determined only in one sample of cellular material of the urine. The analysis indicates statistically significant predominance of patients with bladder cancer in case of TA in the urine (P=0.001). TA was detected in all samples of tumor tissue. We also analyzed the dependence of TA levels in urine and tissue on the degree of BC differentiation. In patients with highly differentiated BC, mean AT in the cellular materials of the urine was 0,61% (n=15), in patients with moderately differentiated BC - 0.95% (n=23), in patients with low-grade bladder cancer - 1.33% (n=10); in other words, increase in the TA levels with decreasing the degree of differentiation was observed. This finding can be used in the prognosis of the course of disease based on determining the TA level in these patients. CONCLUSIONS: Preliminary data indicate the possibility of use of determining the TA in cellular material of the urine for the diagnosis and monitoring of bladder cancer recurrence.

A new method for registration of kinesthetic evoked potentials for studies of proprioceptive sensitivity in normal subjects and patients with organic lesions in the brain.

The proprioceptive sensitivity of healthy volunteers and convalescents after acute cerebrovascular episodes was studied by a new neurophysiological method for registration of kinesthetic evoked potentials emerging in response to passive 50(o) bending of the hand in the wrist joint with the angular acceleration of 350 rad/sec(2). Kinesthetic evoked potentials were recorded above the somatosensory cortex projection areas in the hemispheres contra- and ipsilateral to the stimulated limb. The patients exhibited significantly longer latencies and lesser amplitudes of the early components of response in the involved hemisphere in comparison with normal subjects. The method for registration of the kinesthetic evoked potentials allows a more detailed study of the mechanisms of kinesthetic sensitivity in health and in organic involvement of the brain.

[Antiapoptotic gene bcl-2 prevents cellular senescence program reactivation induced by histone deacetylase inhibitor sodium butyrate in E1A and cHa-ras transformed rat fibroblasts].

We have investigated the role of apoptosis resistance gene bcl-2 in the activation of cellular senescence program induced by histone deacetylase inhibitor (HDACi) sodium butyrate (NaBut) in transformed rat fibroblasts. This study was conducted in a resistant to apoptosis induction cell line of rat embryo fibroblasts transfor- med by oncogenes E1A, cHa-ras and bcl-2 (ERasBcl). The parent cell line transformed with only EJA and cHa-ras (ERas) was used as a control. It has been found that NaBut reduces proliferation rate of ERasBcl cells significantly weaker than of ERas transformed cells, despite the fact that the G1 cell cycle arrest was observed in both cell lines. After NaBut treatment, hypertrophy of the apoptosis resistant transformants ERasBcl also was reduced compared to parent cell line ERas, due to less activation of mTORC1, which is known to control the synthesis of protein and ribosome biogenesis. The degree of mTORC1 activation was as.sessed by its target proteins phosphorylation: the ribosomal S6 protein and 4E-BP1--inhibitor of translation initiation factor eIF4E. Since cell senescence process may be associated with changes in autophagy regulation, we analyzed the dynamics of one of the main autophagosome formation markers--protein LC3. The accumulation of lipid-bound form LC3-II changes significantly in ERasBcl cells after NaBut treatment and has transient nature. The set of analyzed cellular senescence markers suggests that a high level of apoptosis resistance gene bcl-2 expression prevents the realization of tumor-suppressor senescence program induced by HDACi sodium butyrate treatment.

Study of exteroceptive suppression of voluntary muscular activity in healthy volunteers and patients with paroxysmal neuropathic pain.

The exteroceptive suppression of voluntary electromyographic activity of the masseter and temporal muscles was studied in healthy volunteers and patients with paroxysmal neuropathic pain (trigeminal neuralgia). The latent period of the exteroceptive suppression was prolonged and the duration of its late fragment was shortened in the patients in comparison with normal subjects. A short exteroceptive suppression period in patients with trigeminal neuralgia reflected deficient activity of inhibitory interneurons of the reflector loop and excessive activity of the antinociceptive system of the brain stem, while prolongation of the latent period reflected prolongation of inhibitory interneurons activation. A direct correlation between the degree of changes in the exteroceptive suppression parameters and pain intensity, evaluated by the patients by the visual analog scale, was detected.

[The psychophysiological features of nonepileptic paroxysmal disorders].

22 patients with panic disorder without agoraphobia, 19 patients with paroxysmal atrial fibrillation and 43 healthy control subjects with use clinic technique, psychometric, neuropsychological, neurophysiological methods (quantitative EEG and auditory event-related potentials P300) were examined. Patients with panic disorder was differed from patients with paroxysmal atrial fibrillation by higher level of anxiety and greater degree cognitive functions disturbances. In comparison with healthy control subjects at panic disorders increased of P300 peak amplitude and the spectral power of EEG beta and theta bands in the right hemisphere was observed, at paroxysmal atrial fibrillation--decreased of P300 peak amplitude and the spectral power of EEG beta band in the both hemispheres. Obtained data may indicate various origin mechanisms of paroxysmal states or neurotic condition (panic disorder) and psychosomatic (paroxysmal atrial fibrillation).

[Effects of long-term isolation and anticipation of significant event on sleep: results of the project "Mars-520"].

The purpose of the research was to study effect of long-term isolation on night sleep. The data were collected during international ground simulation of an interplanetary manned flight--"Mars-500". The polysomnographic recordings of six healthy men were performed before, four times during and after 520-days confinement. During the isolation sleep efficiency and delta-latency decreased, while sleep latency increased. Post-hoc analysis demonstrate significant differences between background and the last (1.5 months before the end of the experiment) measure during isolation. Frequency of nights with low sleep efficiency rose on the eve of the important for the crew events (simulation of Mars landing and the end of the confinement). Two weeks after the landing simulation, amount of the nights with a low sleep efficiency significantly decreased. Therefore, anticipation of significant event under condition of long-term isolation might result in sleep worsening in previously healthy men, predominantly difficulties getting to sleep.

Study of nociceptive flexion reflex in healthy subjects and patients with chronic neuropathic pain syndrome.

Nociceptive flexion reflex was measured in healthy subjects and patients with chronic neuropathic pain (diabetic distal symmetric sensorimotor polyneuropathy). The study of nociceptive flexion reflex revealed reduction of subjective pain threshold and reflex threshold in patients compared with healthy persons reflecting deficit of descending antinociceptive influences in the CNS.

[Telomerase activity, mTert gene expression and the telomere length in mouse mesenchymal stem cells in the late period after γ- and γ,n-irradiation and in the tumors developed from these cells]. / Aktivnost' telomerazy, ékspressiia gena mTert i dlina telomer v otdalennyi period posle γ- i γ,n-oblucheniia v mezenkhimal'nykh stvolovykh kletkakh myshi i v opukholiakh, obrazovavshikhsia iz étikh kletok.

In proliferating normal and tumor cells, the telomere length (TL) is maintained by high telomerase activity (TA). In the absence of TA the TL maintenance involves a mechanism of alternative lengthening of telomeres (ALT). The aim of this study was to investigate the level of TA, the mTert expression and TL in cultured normal and transformed by γ- and γ,n-irradiation mesenchymal stem cells (MSCs) from mouse bone marrow, in sarcomas that developed after the transplantation of these cells into syngeneic mice, and in fibrosarcoma cell lines obtained from these tumors to find out the role of AT or ALT in maintaining TL in these cells. During prolonged cultivation of normal and transformed under the influence of γ- (1 Gy and 6 Gy) and γ,n-irradiation (0.05 Gy, 0.5 Gy, and 2 Gy) MSCs from mouse bone marrow, a decrease in TA was detected in irradiated cells. Even deeper decrease in TA was found in sarcomas developed after administration of transformed MSCs to syngeneic mice and in fibrosarcoma cell lines isolated from these tumors in which TA was either absent or was found to be at a very low level. TL in three of the four lines obtained was halved compared to the initial MSCs. With absent or low TA and reduced TL, the cells of all the obtained fibrosarcoma lines successfully proliferated without signs of a change in survival. The mechanism of telomere maintainance in fibrosarcoma cell lines in the absence of TA needs further investigation and it can be assumed that it is associated with the use of the ALT. The detected decrease or absence of TA in transformed under the action of irradiation MSCs with the preservation or even an increase in the telomerase gene expression may be associated with the formation of inactive splicing variants, and requires further study. The obtained lines of transformed MSCs and fibrosarcomas with TA and without the activity of this enzyme can be a useful model for studying the efficacy of TA and ALT inhibitors in vitro and in vivo.

Cognitive functions and the state of nonspecific brain systems in panic disorders.

A total of 93 patients with panic disorders and 36 healthy control subjects were studied. Clinical-neurological, psychometric, neuropsychological, and neurophysiological (auditory cognitive evoked potentials) investigations were performed. Patients with typical panic disorders were characterized by increased levels of anxiety and depression, along with impairments to cognitive functions in the form of decreases in short-term memory and attention, as compared with healthy subjects. Patients with atypical panic disorders differed from patients with typical panic disorders in having lower levels of anxiety, more severe depression, and more marked cognitive disorders. As compared with healthy subjects, patients with atypical panic disorders showed reductions in the amplitude of the P300 evoked potential wave, while patients with typical panic disorders showed increases. It is suggested that changes in the amplitude parameters of the P300 wave are associated with dysfunction of the limbic-reticular structures of the brain in patients with panic disorders.

Clinical-psychophysiological studies of patients with panic attacks with and without agoraphobic disorders.

A total of 77 patients with panic attacks (PA) with and without agoraphobic disorders were studied, along with 28 healthy subjects. Use of clinical-neurological investigation methods was supplemented by psychological methods, EEG recordings, and auditory event-linked evoked potentials (EP). Patients with PA with agoraphobic disorders were found to be characterized by significant decreases in the power density of the alpha rhythm and increases in the power density of the beta rhythm in the right hemisphere, reflecting significant activation of the ascending mesencephalic reticular formation; the most characteristic feature in patients without agoraphobia was a significant increase in the power density of the theta rhythm in the temporal areas of the right hemisphere, reflecting increased activity in temporal-limbic structures. Patients with agoraphobia had lower EP P300 peak amplitudes, with more significant impairments to habituation, and more marked impairments of attention and higher levels of anxiety and depression as compared with patients without agoraphobia.

[EEG analysis of functional cerebral state during the inter-attack period in patients with vegetative crises (panic disorders)].

Compressive spectral EEG analysis of 30 patients with panic attacks and 24 healthy subjects was conducted. The patients had significantly lower mean total spectral density of a-band power and higher mean spectral density of beta and tau-band power in the right hemisphere vs. the controls. The results are interpreted as an increase in the activating effects of reticulothalamic (arousal 1 system) and temporolimbic (arousal 2) structures during the inter-attack period of panic disorders.

[The use of P300 event-related potentials in the evaluation of the effectiveness of therapy of episodic exertional headaches].

Fifteen healthy individuals and 17 patients with episodic exertional headaches were examined before and after treatment with citalopram using P300 event-related potentials. Unlike healthy controls, patients with headaches before treatment displayed an increase in P300 amplitude and the loss of its habituation, which correlated with a decrease in cognitive functions. The treatment lowered the degree of pain and vegetative syndromes, normalized P300 parameters, and improved cognitive functions. The use of P300 method may be an additional criterion of the effectiveness of therapy in patients with exertional headaches.

[P300 component changes of the auditory event-related potential in the patients with typical and atypical panic attacks].

84 patients with panic disorders and 36 healthy control subjects with use of clinico-neurologic technique, psychometric, neuropsychological and the neurophysiological method of auditory event-related potentials P300 were examined. Patients with panic disorders were characterized by the raised level of anxiety, depression and cognitive function disturbances in the form of decrease of short-term memory and attention insufficiency in comparison with the healthy control subjects. Patients with atypical panic disorders differed from the patients with typical panic disorders by lower level of anxiety, a greater degree of depression and more expressed cognitive function disturbances. In comparison with the healthy control subjects with atypical panic disorders the decrease of P300 peak amplitude was observed, with typical--its augmentation. It is supposed, that P300 peak change is bound to dysfunction of temporal-limbic-reticular brain structures.

[Changes in electrical brain activity in patients with panic disorders].

Brain electrical activity was recorded in 38 patients with typical and in 42 patients with atypical panic disorders, also in 30 normal controls. Compared to controls, patients both with typical and with atypical panic disorders differed significantly in reduced spectral power of the EEG alpha band in the right hemisphere. Moreover, in patients with typical panic disorders, the spectral power of the EEG beta1 band was increased in the frontal, temporal, central, and parietal areas of the right hemisphere. In patients with atypical panic disorders, the spectral power of the theta band was increased in the temporal areas of the right hemisphere. The changes in the EEG activity in patients with typical panic disorders are supposed to reflect an increase in activity of non-specific systems of the mesencephalic reticular formation, and the EEG changes in patients with atypical panic attacks may be associated with increased activity of the temporolimbic brain structures.

[New facts about pathogenesis of atrial fibrillation: correlation between changes in bioelectric brain activity and recurrence of atrial fibrillation paroxysms].

AIM: Determination of neurophysiological features of the disease course in patients with paroxysmal atrial fibrillation (AF); pathogenetic validation of use and assessment of therapeutic efficacy of clonazepam (an atypical agonist of benzodiazepine receptors) in combined antiarrhythmic therapy. MATERIAL AND METHODS: The study group consisted of 31 patients with paroxysmal AF free of severe organic changes of the myocardium with twice a week paroxysms, on the average, treated ineffectively with beta-adrenoblockers, amiodaron, sotalol, etacisine, allapinin or combination of the above drugs. A comparative group consisted of 10 patients with perpetual arrhythmia. Fifteen healthy subjects entered the control group. Electroencephalograms were made on the unit Brain Surfing (Russia). Compression-spectral analysis was conducted with utilization of Fourier's algorithm in different periods of the disease for calculation of the absolute (mcV2/Hz) spectral power of the teta- (4.0-7 Hz), alpha (8-13 Hz) and beta-rhythm (14-18 Hz). Clonazepam was given in a dose 1.5 mg/day in addition to insufficiently effective anti-arrhythmic therapy. Holter ECG monitoring was carried out initially and in therapy with clonazepam. RESULTS: The spectral power of alpha-, beta- and teta-rhythm of patients with paroxysmal AF exhibits significant cyclic fluctuations depending on the disease course period. In attack-free period AF patients differ from healthy subjects by a significant fall of spectral power of beta-rhythm indicating functional deficiency of the reticular formation in this disease. 0-24 hours before AF paroxysm spectral power of all the rhythms rose greatly reflecting marked functional disintegration of nonspecific brain systems realizing psychovegetative regulation. At AF paroxysm spectral power of alpha- and beta-rhythm significantly decreased while that of teta-rhythm grew (activation of the lymbic complex). 0-24 h after paroxysm spectral power of alpha- and beta-rhythm continued to fall, of teta-rhythm--sharply fell. Spectral EEG characteristics in this period maximally approached those of the control group. Clonazepam treatment decreased the paroxysms two times and more in 58.1% patients. Holter ECG showed associated reduction in the number of supraventricular extrasystoles by 81.9%. The compression-spectral ECG analysis revealed a 12% enhancement of beta-rhythm spectral power showing lessening of functional disintegration of nonspecific brain systems. CONCLUSION: The course of paroxysmal AF is characterized by functional disintegration of nonspecific brain systems (thalamo-cortical, lymbic and mesencephalic reticular formation) which is maximally evident before AF paroxysm and attenuates after it. Cyclic changes in functional activity are a neurogenic factor realizing readiness of the atria to fibrillation. An atypical agonist of benzodiazepine receptors clonazepam effectively influences neurogenic mechanisms provoking AF paroxysms.

[Clinico-neurophysiological features of the course of the disease in patients with paroxysmal atrial fibrillation].

The subjects of the study were 32 patients with paroxysmal atrial fibrillation (AF) and 19 ':ealthy individuals using a clinical and neurophysiological method of toposelective mapping of electroencephalogram (EEG). EEG was done during the inter-attack, pre-attack, and post-attack periods, as well as during a paroxysm. During the inter-attack period, the patients had a lower beta-rhythm power vs. the healthy controls, while there were no significant differences between them in the power of alpha- and beta-activity. Before an attack, the patients had a significant increase in beta, alpha-, and theta-range power, reflecting the intensification of the activity of the metaencephalic reticular formation, thalamocortical, and hypothalamosepto-hyppocampal systems, respectively. During an AF paroxysm, the activity of the thalamocortical and reticular systems was lowered, while the activity of the hypothalamo-hyppocampal system further increased. After an attack, the activity of all the mentioned systems went down to the initial state of the "optimal" brain functioning after an excessive excitation. It is assumed that generalized one-way direction of EEG changes before an attack reflects tensed functioning of practically all activation systems, which increases the probability of a "breakdown" in a form of an AF paroxysm. The data of the study evidence a cyclic character of the disease and stresses an important role in AF pathogenesis played by disturbances associated with the functional condition of non-specific temporal-limbic and reticular brain structures, especially in patients without organic myocardial alterations.

[Endovideosurgical methods at the treatment of patients with cholelithiasis].

Experience of 10,046 laparoscopic cholecystectomies is analyzed. The were 8097 female and 1949 male patients aged 13 to 93 years. Complicated cholelithiasis was seen at 4310 (42.9%) patients including 792 patients with acute inflammation of gallbladder, 2375--with chronic empyema, 1143--with gallbladder hydrops. Choledocholithiasis was diagnosed at 502 patients, Mirizzi syndrome--at 8, biliodigestive fistulas--at 12, cancer of gall bladder--at 5 patients. Mini-invasive endoscopic methods were used at all the patients, conversion to open surgery was necessary at 23 cases. Average time of surgery was 20-35 min, hospital stay--1-6 days. Intra- and postoperative complications were diagnosed at 86 patients among the first 3000 procedures. Among successive 7000 operations (after development of prophylactic complex) there were only 3 cases of trocar puncture infection. There were 2 cases of lethal outcome due to pulmonary embolism and pancreonecrosis.

[The modified method registration of kinesthetic evoked potentials and its application for research of proprioceptive sensitivity disorders at spondylogenic cervical myelopathy].

OBJECTIVE: To analyze the efficacy of modified (passive radiocarpal articulation flexion/extension) and «standard¼ (passive radiocarpal articulation flexion) methods of kinesthetic evoked potentials for proprioceptive sensitivity assessment in healthy subjects and patients with spondylotic cervical myelopathy. MATERIAL AND METHODS: The study included 14 healthy subjects (4 women and 10 men, mean age 54.1±10.5 years) and 8 patients (2 women and 6 men, mean age 55.8±10.9 years) with spondylotic cervical myelopathy. Muscle-joint sensation was examined during the clinical study. A modified method of kinesthetic evoked potentials was developed. This method differed from the "standard" one by the organization of a cycle including several passive movements,where each new movement differed from the preceding one by the direction. RESULTS AND СONCLUSION: The modified method of kinesthetic evoked potentials ensures more reliable kinesthetic sensitivity assessment due to movement variability. Asignificant increaseof the latent periods of the early components of the response was found in patients compared to healthy subjects. The modified method of kinesthetic evoked potentials can be used for objective diagnosis of proprioceptive sensitivity disorders in patients with spondylotic cervical myelopathy.

[Development of noninvasive bladder cancer diagnosis on basis of telomerase and it's subunits hTERT and hTR detection].

Telomerase activity (TA) and expression of genes coding it's subunits (hTERT and hTR) have been examined in tumor tissue and urine sediment samples taken from patients with bladder cancer (BC) using the modified TRAP assay (in the case of telomerase detection) and RT-PCR (in the case of hTERT and hTR expression). Results obtained in this study demonstrate possibility of noninvasive diagnosis of BC with sensitivity of 96% and specificity of 100% in the case of telomerase detection and with sensitivity of 80% and specificity of 100% in the case of hTERT detection in urine sediment samples.