[Clinical features of temporal lobe epilepsy with involvement of the insular lobe]. / Klinicheskie osobennosti visochnoi epilepsii pri vovlechenii v protsess ostrovkovoi doli.

OBJECTIVE: To determine the clinical features of the course of the disease when the insular lobe is involved in the epileptic process. MATERIAL AND METHODS: A comparative analysis of the results of diagnosis and treatment of 55 patients with temporal lobe epilepsy and 46 patients with temporal plus epilepsy was carried out. The results of neuroimaging, clinical and EEG studies were compared. RESULTS: Autonomic paroxysms of nausea and hypersalivation, skin changes, simple motor seizures, emotional seizure and sensory paroxysms are the most reliable signs of the involvement of the insular lobe in the epileptic process in temporal plus epilepsy. For 'pure' temporal lobe epilepsy, cognitive paroxysms of the déjà vu and aura are common. When the insular lobe is involved in the epileptic process, the seizures have a reliably high frequency, polymorphism and are more complex by structure. CONCLUSION: Paroxysmal syndrome in temporal plus epilepsy with involvement of the insular lobe undergoes significant changes in the form of increased seizures and the appearance of specific seizures and characteristic polymorphism.

[A pharmacogenetic analysis of dopaminergic and opioidergic genes in opioid addicts treated with the combination of naltrexone and guanfacine]. / Farmakogeneticheskii analiz vliyaniya genov dofaminovoi i opioidnoi sistem na effektivnost' kombinirovannoi terapii naltreksonom i guanfatsinom bol'nykh opioidnoi zavisimost'yu.

AIM: To evaluate an effect of opioid receptor and dopamine system gene polymorphisms on the efficacy of combined treatment with oral naltrexone and guanfacine in a randomized double blinded double dummy placebo controlled clinical trial. MATERIAL AND METHODS: Three hundred and one patients with opioid dependence were randomized into 4 treatment groups: naltrexone 50 mg/day + guanfacine 1 mg/day (N+G); naltrexone + placebo guanfacine (N+GP); placebo naltrexone + guanfacine (NP+G); double placebo (NP+GP). The primary outcome was treatment retention. All enrolled participants were genotyped for polymorphisms in the following genes: mu- (OPRM1), kappa-opioid receptors (OPRK1), catechol-O-methyltransferase (COMT), dopamine receptors types 2 (DRD2) and 4 (DRD4), dopamine-beta-hydroxylase, and dopamine transporter (SLC6A3, DAT1) and alpha-2-adrenoreceptor (ADRA2A) a pharmacological target of guanfacine. RESULTS: The efficacy of the combination of naltrexone and guanfacine was comparable to naltrexone monotherapy. Regardless of treatment, several gene polymorphisms were associated with higher chance to complete the treatment program: allele Т DRD4 - 521 С/Т (rs1800955) (р=0.039; OR (95% CI)=3.7 (1.1-12.7); log-rank test: р=0.01); allele С DRD2 С957Т (rs6277) (р=0.03; HR=0.6 (0.34-0.95); genotype combination: DRD4 VNTR (LL) + OPRM1 A118G (rs1799971) (AA), р=0.051; DRD2 C957T (ТТ) + OPRM1 (rs1074287) (СС), р=0.025; DRD2 - 141С (II) + OPRM1 (rs510769) (АА), р=0.035; DBH Fau(СС) + OPRM1 (rs1074287) (СС), р=0.0497. Regardless of treatment several polymorphisms were associated with high risk of relapse: allele Т (rs510769) OPRM1 (р=0.053), allele А (rs1799971, A118G) OPRM1 (р=0.056), allele S exon III 48 bp DRD4 VNTR (р=0.001; HR=3.1 (ДИ 95% 1.57-6.18); genotype combinations: DRD4 - 521 С/Т (ТТ) + DRD2 Nco I (TT), р=0.026; DRD4 -521 С/Т (ТТ) + DRD2 -141 С (II), р=0.011; DRD4 - 521 С/Т (ТТ) + OPRM1 A118G (rs1799971) (AA), р=0.011; DRD2 Nco I(ТТ) + ADRA2A (СС), р=0.012; DRD2 Nco I(ТТ) + OPRM1 A118G (AA), р=0.02. The effects dependent on the treatment group were as follows: 1) in the N+G group, patients with the DRD4 -521 С/Т TT genotype had higher probability of completion of treatment program in comparison with other genotypes (CC and CT) (log-rank test: p=0.002); 2) in NP + GP group, patients with the OPRM1 rs510769 T allele had higher risk of relapse compared to the genotype GG (p=0.008) (FDR p<0.0125). CONCLUSION: The additive effect of opioid receptor genes and dopaminergic system genes on outcomes of treatment opioid dependence with oral naltrexone and guanfacine was shown. Pharmacological effects of naltrexone and guanfacine were associated with genetic variants of the DRD4 - 521C/T polymorphism, since its effect was shown only in the N+G group. The effect of the OPRM1 rs510769 polymorphism was demonstrated in the double placebo group that was associated with personality traits (temperament, character) and determined compliance. Genetic analysis is useful for determining potential responders to treatment of opioid dependence; genotyping can increase the efficacy of pharmacotherapy.

[Stabilization of remission in patients with opioid dependence with naltrexone implant: a pharmacogenetic approach]. / Stabilizatsiia remissii u bol'nykh opiinoi narkomaniei implantom naltreksona: farmakogeneticheskii aspekt.

AIM: To evaluate the effect of opioid receptor genes and dopamine system genes polymorphisms on treatment outcomes of opioid dependence with implantable and oral naltrexone. MATERIAL AND METHODS: Authors carried out a randomized double-blind, double-dummy, placebo-controlled clinical trial. Three hundred and six patients with opioid dependence were randomized into 3 equal treatment groups. The first group received implantation of 1000 mg naltrexone every 2 months during 6 months + oral naltrexone placebo; the second group - placebo implant every 2 months + oral naltrexone (50mg/day) and the third group - placebo implant + oral naltrexone placebo. It was genotyped polymorphisms in the following genes: mu-opioid receptor (OPRM1), kappa-opioid receptor (OPRK1), catechol-O-methyltransferase (COMT), dopamine receptors types 2 (DRD2) and 4 (DRD4), dopamine-beta-hydroxylase, and dopamine transporter (DAT1). RESULTS: Regardless of treatment several polymorphisms of these genes were associated with high risk of relapse: an allele L (2R) DRD4 120bp (p=0.05; OR (95% CI)=3.3(1.1-10.1)); an allele С DRD2 NcoI (р=0,051; OR (95% CI)=2,86 (1,09-7,52)); the genotype 9.9 DAT VNTR 40bp (р=0,04; OR (95% CI)=1,4 (1,3-1,5)); on the contrary, (СС+СТ)-(ТТ)) variants of OPRK1-DRD2Ncol increased a chance to complete treatment program (р=0,004; OR (95% CI)=7.4 (1.8-30.4)), Kaplan-Meier survival analysis (р=0,016). The probability of completing treatment program by the carriers of these variants was higher in the oral naltrexone group (p=0.016), lower in the double placebo group (p=0.015), but did not influence on treatment outcomes in the naltrexone-implant group. CONCLUSION: Naltrexone-implant is a highly effective medication for treatment of opioid dependence and its effectiveness exceeds that of oral naltrexone and placebo. The study has shown the joint influence of opioid receptor genes and genes of dopaminergic system on treatment outcomes of opioid dependence. Genetic analysis is useful for determining potential responders to naltrexone treatment of opioid dependence.

[The dependence of the inflammatory reaction on the properties of mycobacterium tuberculosis and the course of specific pulmonary process].

The systemic analysis of the inflammatory process in untreated patients with newly diagnosed infiltrative-destructive tuberculosis has been performed in the context of host mycobacterium interaction. Variability of acute phase proteins (APP) reflecting mobilization of nonspecific protective systems of the body did not depend on cytotoxicity of Mycobacterium tuberculosis (MBT). In 87.5% of patients the dependence between effectiveness of antitubercular chemotherapy (for three months) and combination of MBT characteristics and initial APP levels was found. Patients with effectiveness of therapy, which was inadequate to MBT cytotoxicity, were characterized by its dependence on the APP level and MBT sensitivity to antitubercular agents. Results of multifactorial analysis of parameters reflecting intensity of the inflammatory response, pathological process in the lungs, and characteristics of MBT suggest that the overall result of the host-pathogen interactions primarily depend on adequateness of protective systems of the body

[Surgical resection in combination with stereotaxic cryodestruction in patients with supratentorial gliomas in functionally significant areas of the brain: possibilities of using combined surgical treatment and its results].

A combined method of surgical treatment of glial tumors of the brain is proposed for decreasing risk of complications. The method includes microsurgical ablation of the main volume of the neoplasm and stereotaxic cryodestruction of the residual part of the tumor. Combined surgical treatment was used in 12 patients. The results obtained show that the proposed method elevates the efficacy of surgical method, facilitates increased indices of survival rate and maintenance of quality of life of the patients at the tolerant level.

[The clinical laboratory comparison in the assessment of treatment prognosis in patients with infiltrative tuberculosis of lungs].

The comprehensive prospective examination of 66 patients with first established non-treated infiltrative tuberculosis of lungs was used to analyze the possibility of optimization of assessment of course of specific inflammatory process on the basis of levels of proteins-reactants of acute phase. The characteristics of dynamics of clinical roentgenologic data and terms of coming of abacillarization as a result of three months anti-tuberculosis therapy has been used as grouping factors. It is established that the constellation of 3 out of 12 basic (before treatment) analyzed level indicators are the most prognostic informative--haptoglobin, ceruloplasmin and blood albumin. Their combined application according the proposed decisive rule provides 90.6% of effectiveness of prognosis of the results of treatment in the discussed category of patients.

[Peculiarities of the circulating phagocytes functional activity in patients with different forms of drug-resistant pulmonary tuberculosis].

Functional activity of circulating phagocytes (macrophages--Ms and neutrophils--Ns) was studied in 30 patients with infiltrative (I) and 30 patients with fibro-cavernous (FC) pulmonary tuberculosis (PT). Difference of the functional activity of both types of cells depending on the PT form was revealed: more significant increase in the oxygen-depending activity in FCPT while bactericide potential estimated with a zymosane induced NST-test was more pronounced in IPT patients. These data correlate with the blood levels of neopterin and elastase, the markers of the M and N activity, respectively. Participation of intracellular ADA in realization of oxygen-depending processes was demonstrated. Results of the multivariant analysis of the whole complex of the studied phagocyte characteristics, reflect their different roles in ther pathological process a prevailing role of Ms in the firstly diagnosed acute tuberculosis process (IPT) and Ns in the chronic progressive process (FCT).

[Technique of stereotactic cryodestruction in management of patients with cerebral gliomas].

Aim of the study was to evaluate the safety and efficiency of stereotactic cryodestruction of supratentorial astrocytomas that were located deeply in the brain and/or within eloquent areas.We examined 74 patients aged 18-64 years with supratentorial gliomas of different grade located in deep or eloquent brain areas. All the patients underwent stereotactically guided cryodestruction of the tumor. The survival rate was evaluated by the Kaplan-Meier method. The chi-square method was used for comparative analysis of results of this study with available data from the literature. For the analysis of the prognostic importance of various factors the Cox proportional hazards model was applied. The average survival period was 12.4 months for glioblastoma (control group--6.4 months, p=0.04), and 46.9 months for anaplastic astrocytoma (control group--18 months, p=0.006). For patients with fibrillar-protoplastic astrocytoma the 5-year survival rate was 95.7%. The frequencies of complications did not exceed those of the routine surgical interventions in patients with brain tumors. We found that stereotactic cryodestruction as well the Karnofsky performance score were statistically reliable prognostic factors (p=0.0377 and p=0.0006, respectively), while the extent of cryodestruction and the residual tumor mass did not influence the survival rate. Stereotactic cryodestruction is a safe surgical procedure, which results in statistically significant improvement of survival in patients with supratentorial gliomas located within deep and/or eloquent areas of brain.

[Comparative significance of the biochemical markers of cell-mediated immunity in the diagnosis of tuberculous pleurisy].

The authors have compared the informative value of the tests determining the activity of adenosine deaminase (ADA) and the levels of interferon-gamma (INF-gamma) and neopterin in the diagnosis of pleural effusions of tuberculous (n = 67) and nontuberculous (n = 30) origin. The equally high diagnostic value has been found in the study of the activities of ADA (94.8%) and INF-gamma, which are markers of lymphocytic cellular immunity. There are great differences in the sensitivity of the neopterin test depending whether tuberculosis is isolated or complicates the course of tuberculosis of the lung or intrathoracic lymph nodes, which may be regarded as a reflection of the different status of macrophageal cellular immunity.

[Assessment of a risk for postoperative infectious complications in patients with fibrocarvous pulmonary tuberculosis].

The paper analyzes whether it is possible to predict a risk for postoperative empyema, by studying a totality of characteristics of a patient, a pathological process, and the properties of MBT in 46 patients with progressive fibrocavernous tuberculosis. It also shows it actual to accomplish this task with a prediction accuracy of 89.5-100%, by simultaneously taking into account both the bacteriological properties of MBT (the magnitude of Mycobacterium tuberculosis excretion and viability) and different combinations of serum biological parameters that reflect the activity of an inflammatory process.

[The reentrant binomial model of nuclear anomalies growth in rhabdomyosarcoma RA-23 cell populations under increasing doze of rare ionizing radiation].

Distributions of nuclear morphology anomalies in transplantable rabdomiosarcoma RA-23 cell populations were investigated under effect of ionizing radiation from 0 to 45 Gy. Internuclear bridges, nuclear protrusions and dumbbell-shaped nuclei were accepted for morphological anomalies. Empirical distributions of the number of anomalies per 100 nuclei were used. The adequate model of reentrant binomial distribution has been found. The sum of binomial random variables with binomial number of summands has such distribution. Averages of these random variables were named, accordingly, internal and external average reentrant components. Their maximum likelihood estimations were received. Statistical properties of these estimations were investigated by means of statistical modeling. It has been received that at equally significant correlation between the radiation dose and the average of nuclear anomalies in cell populations after two-three cellular cycles from the moment of irradiation in vivo the irradiation doze significantly correlates with internal average reentrant component, and in remote descendants of cell transplants irradiated in vitro - with external one.

[Functional activity of phagocytes of bronchoalveolar lavage in patients with fibro-cavernosis and infiltrative pulmonary tuberculosis].

Functional activity of the bronchoalveolar lavage fluid (BALF) phagocytes was studied in 33 and 16 patients with fibro-cavernosis (FC) and infiltrative (I) pulmonary tuberculosis (PT), respectively. Complex examination of BALF, alveolar macrophages (AM) and neutrophils (N) sedimented from BALF revealed interrelationship between functional activity of the cells and the form of PT. Higher activities in BALF of neopterin and elastase mainly secreted by activated AM and N respectively, reflect a higher secretory activity of both types of cells in FC - PT. These patients are also characterized by more pronounced bactericide activity of Ns, which significantly correlates with adenosine deaminase (ADA) activity. It is suggested that changes in BALF of various biochemical parameters examined (neopterin, elastase, ADA and its isoenzymes, 2-deoxyADA) and bactericide activity of the sedimented cells represent are the consequences of differend sides of BALF phagocytes functioning. According to modem notions about the mechanisms of their regulation different intercellular relations are suggested in different form of PT.

[Characterization of destructive pulmonary tuberculosis (by the results of a clinicomathematical analysis)].

The results of examination of 56 patients with destructive pulmonary tuberculosis, which involved the study of biochemical parameters characterizing different stages of an inflammatory process, as well as clinical and X-ray findings were analyzed, by applying various multivariate statistical methods. This approach was shown to be promising for estimating the severity of the process and for specifying the stage of development of an inflammatory process in some patients.

[The use of nebivolol in menopausal women with hypertension]. / Vozmozhnosti ispol'zovaniia nebivolola u zhenshchin s arterial'noi gipertenziei i klimaktericheskim sindromom.

Nebivolol was given for 8 weeks to 34 menopausal women with grade 1 and 2 hypertension. Monotherapy was effective in 66,7% of patients, while in other patients combination with hydrochlorothiazide (12.5 mg) was required. The use of nebivolol was associated with decreased rate and severity of vasomotion reactions and thus with positive effect on menopausal syndrome. Nebivolol appeared to be safe and metabolically neutral.

[Use of olicard retard in patients with stable angina of low effort in an outpatient setting]. / Poliklinicheskii opyt ispol'zovaniia Olikarda retard u bol'nykh stabil'noi stenokardiei malykh napriazhenii.

Efficiency of olicard 40 retard monotherapy and its combination with beta-blockers and calcium antagonists was studied in 33 IHD patients with effort angina of functional class III. It was established that olicard retard is an effective antianginal drug pharmakinetics of which allows assignment of individual therapy of IHD outpatients.