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Biomedical subjects

E I Gusev

Publications and source records attributed to E I Gusev.

At least 19 recordsLinked to original sources

Population pharmacokinetic modelling of carbamazepine in epileptic elderly patients: implications for dosage.

BACKGROUND: Proper use of antiepileptic drugs in the elderly involves knowledge of their pharmacokinetics to ensure a patient-specific balance between efficacy and toxicity. However, populations of epileptic patients on chronic carbamazepine (CBZ) therapy which have been studied have included data of relatively few elderly patients. AIMS: The aim of the present study was to evaluate the population pharmacokinetics of CBZ in elderly patients on chronic monotherapy. METHODS: We have used the non-parametric expectation maximization (NPEM) program in the USC*PACK collection of PC programs to estimate individual and population post-induction pharmacokinetics of CBZ in epileptic elderly patients who received chronic CBZ monotherapy. Age-related changes of CBZ population pharmacokinetics were evaluated from routine therapeutic drug monitoring (TDM) data of 37 elderly and 35 younger patients with epilepsy. As a 'historical control' we used previously published population modelling results from 99 young epileptic patients on chronic CBZ monotherapy. In that control group, TDM was performed in the same pharmacokinetic (PK) laboratory, using the same sampling strategy as in the present study, and the same PK population modelling software was used for data analysis. RESULTS AND CONCLUSIONS: A poor correlation was found between daily CBZ dose and serum concentrations in the elderly patients (r=0.2, P=0.25). Probably statistically significant difference in the median values of the CBZ metabolic rate constant (P<0.001) between elderly and relatively young epileptic patients was found. Our results showed that age-related influences in CBZ pharmacokinetics in elderly patients should be considered in the optimal planning of CBZ dosage regimens. Most elderly patients with epilepsy will usually need CBZ dosages lower than those based on the median population PK parameter values obtained from younger patients. The present population model is also uniquely well suited for the new 'multiple model' design of dosage regimens to hit target therapeutic goals with maximum precision.

Adult↗

[Space and time organization of perception in patients with chronic cerebral vascular insufficiency].

According to A.A. Ukhtomsky, chronotope is defined as a complex of time and space relations between subjects and events that surround human organism. Perception of chronotope by an individual is measured by individual minutes (IM), each minute being measuring in mind, and individual decimeters (ID) depicted by an individual as a line. In case of their simultaneous measuring, IM and ID chronotope is registered. Perception of chronotope has been studied in 31 women and 7 men with chronic cerebral vascular insufficiency and compared to the data obtained earlier in the group of young healthy people used as controls. In patients, giving short measure of time that was not treatment-depended, mismatch of spatial and temporal indices of chronotope measuring and influence of gender were observed.

Adolescent↗

[Batroxobin in patients with ischemic stroke in the carotid system (the multicenter study)].

A randomized placebo-controlled study has been carried out in 3 Moscow hospitals. A sample included 90 patients who survived hemispheric ischemic stroke caused by pathology in the internal carotid artery 72 h before the treatment. Forty-five patients were given standard (basic) therapy and 45 patients received adjuvant batroxobin intravenously by 1,0 ml (10BU) drops on day 1, 3 and 5 and by 0,5 ml (5BU) drops on day 7 and 9 after admitting in a hospital. Assessment of the patients' state was conducted before the treatment, on day 3, 6 and 15. The European Stroke Scale was used to measure severity of clinical symptoms. The results suggest efficacy of batroxobin the use of which provides rapid good results, especially improvement in movement disorders. The use of this drug is accompanied by defibrinating effect. The drug is well tolerated.

Batroxobin↗

[Risk factors of osteoporosis in women with multiple sclerosis].

Multiple sclerosis (MS) is a progressive disease that leads to early disability of young adults at a reproductive age. Motor disturbances caused by progressive pyramidal deficit and cerebellar dysfunction, accompanied by ataxia with frequent falls, and early decrease of physical activity are risk factors of osteoporosis in MS patients. A relapsing-remitting course of the disease with frequent attacks demands multiple courses of steroid therapy. Long-term steroid treatment causes bone loss and development of secondary osteoporosis. We have shown that reduced bone mineral density (BMD) in lumbar spine and femoral neck is associated with high level of EDSS score caused by the combination of moderate pyramidal and cerebellar dysfunction. An additional risk factor of osteoporosis in MS patients is low body weight. The glucocorticoid therapy does not exert a negative impact on BMD in lumbar spine and femoral neck in patients with MS.

Adult↗

[The possibilities of adaptation of patients with multiple sclerosis: the results of clinical and psychological study].

A complex clinical and psychological examination of three groups of patients with stable neurological deficit (113 subjects, 77 men and 76 women, aged from 19 to 67 years) included those with multiple sclerosis (MS), chronic cerebral vascular disorders and chronic dorsopathy with illness duration 5-7 years has been carried out. Neuropsychological status and quality of life were assessed using the following tests: Medical Outcomes Study Short Form 36 Health Survey (SF-36); the method of E.B. Fantalova "Level of Ratio of "Values" to "Availability" in Different Life Spheres", Integrative Anxiety Test, Manual for the Constructive Thinking Inventory, Coping test (Lazarus), Beck depression scale. In total, 42 traits on 6 tests have been studied. The study was conducted before and after treatment (21 +/- 2 days). The results revealed that patients with chronic neurological disorders, in particular with MS, often had subclinical depression, which negatively influenced the disease course, and needed treatment. A high level of anxiety was found in MS patients that was related to situational social defensive reaction. Low ability to positive reevaluation of life situations, one of the causes of anxiety states, was observed in all the groups, especially in MS. In MS patients, their real state was not consistent with their perception of this state. They also were featured by personal superstitious thinking. Most of the patients with MS had a good constructive thinking, preserved ability to emotional and behavioral self-control that indicated favorable prognosis in future complex rehabilitation. After the course of symptomatic vascular and metabolic therapy, with the exception of antidepressants and neuroleptics, the appearances of depression and anxiety as well as expression of social defensive reactions and situational phobic component of anxiety were decreased that suggested the necessity of inclusion of individual psychotherapy as a part the complex rehabilitation therapy.

Adaptation, Psychological↗

[The results of longitudinal use of copaxone and betaferon in Moscow Multiple Sclerosis Center: issues of efficacy and adherence to therapy].

In last decades, practical neurologists are able to use DMT in multiple sclerosis (MS) in every day practice. This paper presents data of 3-year study of DMT (copaxone and betaferon) treatment of 280 patients with definite diagnosis of multiple sclerosis (MS), 166 patients regularly receiving DMT (104--copaxone and 62--betaferon) for, at least, 3 years. Clinical symptoms of the patients, reasons of treatment withdrawal (48--copaxone and 31--betaferon) and the features of MS course after the withdrawal are analyzed. Patients who received betaferon previously had more severe MS course with frequent relapses, half of them had secondary progressive MS course (SPMS) with relapses. This made impossible a direct comparison of the data of two treatment groups. Treatment with copaxone reduced 5 times annual relapse rate, from 1.45 before DMT to 0.27 during these 3 years (p < 0.001), and this reduction remained stable. For 36 months, 40.4% of patients were relapse-free though all of them had, at least, one relapse per year before the treatment. No EDSS progression was observed in 80% of these patients. Treatment with betaferon caused the reduction of relapse rate from 1,84 to 0,69 per year (2.7 times), 8 patients (26%) with previously active RMS being relapse-free for 36 months. In 31 patients with SPMS, the reduction of relapse rate was also significant, from 1.89 to 0.49 (3.8 times, p < 0.001). Twenty-two patients (71%) with previous SPMS did not have EDSS progression for 36 months that indicate the positive effect of the therapy. Side-effects were moderate and were not the main cause of the treatment withdrawal. The latter was caused mainly by clinical un efficacy, most frequently by the increase of EDSS due to transformation of the MS course to SPMS without relapses and poor understanding by the patient of the goals and the possibilities of DMT. These facts stress the significance of improving compliance, motivation and adherence to DMT in everyday neurological practice.

Adjuvants, Immunologic↗

[The peculiarities of formation and approaches to the treatment of chronic fatigue syndrome in young patients with focal brain damage].

Chronic fatigue (CF) is a syndrome manifesting in cases with focal brain damage. It is frequent in multiple sclerosis (MS) and encephalopathies (post-traumatic, cerebrovascular, etc). Treatment of this syndrome remains problematic. The study aimed to analyze the genesis of CF in patients with different non-active neurological diseases with brain damage and possibility of its treatment with the complex drug fezam (piracetam plus cinnarizin) in dosage 2 capsules 3 times per day. Before the treatment, all the patients had CF, which was directly associated with severity of depression in patients with encephalopathies. In MS patients, changes in the valuable-and-sense sphere that plays a significant role in human behavior and activity underlying self-regulation in critical situations were found. Neuropsychological data revealed that in patients with encephalopathies psychological and behavioral aspects were more significant in regard with CF genesis than in patients with MS. Fesam caused significant decrease of the CF severity, which was more prominent in the MS group, while in another group it was associated with a decrease of depression severity. Mild side-effects were observed in 6 patients (12%) and appeared mainly as sleep disorders. This trial allows recommending Fezam for complex treatment of CF syndrome in MS and in combination with psychocorrective medicines in cases of encephalopathies.

Adult↗

[Semax in prevention of disease progress and development of exacerbations in patients with cerebrovascular insufficiency].

One hundred and eighty-seven patients with different stages of cerebrovascular insufficiency (CI) have been examined. A diagnosis of CI was based on the results of neurological and neuropsychological study, ultrasonic dopplerography, rheo- and encephalography, electrocardiography, brain MRI and eyegrounds examination. Neurological scales were used for neurological status assessment and further data processing. The study aimed at evaluation of tolerability and clinical efficacy of the medication and complications in CI course. Semax treatment resulted in significant clinical improvement, stabilization of the disease progress and reduced a risk of stroke and transitory ischemic attacks in the disease course. The drug is featured by minor percent of side-effects and is well tolerated by patients, including those of older age groups.

Adrenocorticotropic Hormone↗

[Functional brain activity in patients with Parkinson's disease during amantadin-sulfate therapy].

An investigation of bioelectrical brain activity in 32 patients with akinetic-rigid and trembling-rigid forms of Parkinson's disease was conducted before and after treatment with amantadin-sulfate on the basis of spectral-coherent EEG analysis. Comparing to controls, EEG deviations, mainly related to the main rhythm, were observed in 93.75% patients. Symptoms stabilization augmented EEG disorganization emerging in diffused spikes and sharp theta- and alpha-waves. The presence of paroxysmal activity in the form of synchronic bilateral groups of theta-waves and/or beta-waves was detected in 11 out of 32 patients, with paroxysmal activity of theta-waves being more evident in patients with a trembling PD form. In the group of patients with post treatment positive dynamics, EEG spectrum power increased in the range of alpha-beta-waves. Significant differences were mainly found in the range of beta-activity in frontal-parietal-occipital leads of the left hemisphere. The coherent analysis of EEG revealed that an amantadin-sulfate course resulted in normalization of space organization of biopotentials at the expense of a decrease of pathologically high indications of coherency for the majority of intra- and interhemisphere pairs of leads in alpha-, beta- and theta-ranges. In those regions, where the spectrum power increased in the same range, a significant decrease of the coherency indices was detected for inter hemispheric frontal-frontal, frontal-parietal and frontal-occipital leads and intracortical long connections of the left hemisphere. In amantadin-sulfate non-responders, the changes of EEG spectrum and coherency were insignificant.

Adult↗

Dialectics and implications of natural neurotropic autoantibodies in neurological disease and rehabilitation.

The role of natural idiotypic (Id-Abs) and anti-idiotypic (AId-Abs) autoantibodies against neuroantigens observed in different neurological disorders is not fully understood. In particular, limited experimental evidence has been provided concerning the qualitative and quantitative serological response after acute injuries of the central nervous system or during chronic mental diseases. In this study, we analyzed the specific Id-Abs and AId-Abs serological reactivities against 4 neuro-antigens in a large population of patients with ischemic stroke, schizophrenia, as well as healthy individuals. Patients with ischemic stroke were tested at different time points following the acute stroke episode and a correlation was attempted between autoantibodies response and different patterns of functional recovery. Results showed variable and detectable Id-Abs and AId-Abs in different proportions of all three populations of subjects. Among patients with different functional recovery after ischemic stroke, a difference in time-related trends of Id-Abs and AId-Abs was encountered. Our observations suggest that changes in the production of natural neurotropic Abs may engender a positive homeostatic, beside a possible pathogenic effect, in specific neurological disorders.

Aged↗

[Clinical features of an early stage of Parkinson's disease].

One hundred and forty-nine patients with Parkinson's disease (PD), mean age 66.3 years, have been examined. It was found that the early stage of the disease might include isolated depression, minimal movement disorders and functional compensation, the latter being observed during L-Dopa treatment. In general, the peculiarities of this stage comprise polymorphism of clinical symptoms, predominance of movement disorders over high mental dysfunctions and slow progression of pathological disorders with patient's adaptation to developing defect and reversibility of some dysfunctions under the treatment. The early stage was distinguished also by independence of high mental functions damage on movement disorders severity. More pronounced disturbances were detected in akinetic PD type in the presence of depression in the older patients. Depression may be a prodrome of movement disorders manifestation. The above peculiarities of the early stage are important for early PD diagnosis.

Adult↗

[Modeling of focal ischemia of the brain].

Methods of modeling and criteria of evaluating the pathological process in the central nervous system (CNS) as well as modern technologies of provoking the focal ischemia of the brain in experimental animals are under discussion. The results were analyzed comparatively from the viewpoint of efficiency and adequacy of certain models as well as of the clinical specificity of ischemic strikes in man and of set research goals. A literature analysis confirms that the existing arsenal of methodical schemes provides for choosing the most adequate model of focal ischemia of the brain and to ensure a cerebral infarction of a preset scope and localization; it makes possible also an objective evaluation of pathological processes occurring in the cerebral tissues both at the earliest stages of ischemic lesion and during a relatively long time period comparable with rehabilitation time period. Achievements in the sphere of experimental modeling of focal ischemia of the brain pave the way to further promotion of experimental therapy in acute stroke and open up new research priorities; it concerns primarily research of mechanisms timing the neurodegenerative process after ischemic stroke as well as searching-for and testing of means of stroke prevention and of patients' rehabilitation.

Animals↗

[A differentiated approach to Parkinson's disease treatment in early stage of the disease].

A conception of the approach to Parkinson's disease treatment at early stage, which could be realized in practice is suggested. The conception is based on the results of dopaminergic drugs treatment of 149 patients, aged 33-87 years. The patient's state was assessed by neurological examination and clinical scales with regard to different disease types, tremor and rigid, and levodopa doses--from moderate (up to 500 mg) to high (above 500 mg). A general treatment policy, including therapy directed to activation of regulatory and compensatory influences and differentiated usage of levodopa and combined therapy with levodopa and dopamine agonists, is presented.

Adult↗