[Cognitive disorders in the middle-aged population and cerebrovascular risk factors]. / Kognitivnye narusheniia u lits srednego vozrasta i faktory riska tserebrovaskuliarnykh zabolevanii.

AIM: To study the frequency of subjective and objective cognitive disorders in the middle-aged population and their associations with main and additional cerebrovascular risk factors. MATERIAL AND METHODS: The authors examined 169 men and 239 women aged 40-59 years. Medical history study, blood tests, electrocardiography, brachiocephalic and common femoral arteries scan, echocardiography, magnetic resonance imaging of the brain (MRI) were performed. Luria and Munsterberg tests were done to assess cognitive dysfunction. Affective disorders were assessed by the Hospital scale of anxiety and depression. RESULTS AND CONCLUSION: Absence of subjective (SCI) and/or objective (OCI) cognitive impairments was found in 26,5%; 10% had purely SCI, more than 35,7% of complaints were accompanied by deviations in neuropsychological test results (OCI+), over 25% had only OCI-. The average age of patients with OCI+ was higher than in the control group. In women, the frequency of SCI was twice as high and OCI less frequent as in men. Absence of cognitive impairment and SCI were observed more frequently in individuals with higher education. The prevalence of multiple white matter lesions (WML) in MRI was 36%. Multiple WML and atherosclerosis of major arteries were more common in OCI+ group (47%). Mild affective disorders were more frequent in the studied groups. Anxiety disorders were more common than depressive ones. The amount of patients with affective disorders was highest in OCI+. Therefore, SCI is a common phenomenon among people aged 40-60 years. The use of simple neuropsychological tests in screening examination allows to identify individuals who are most appropriate for active search for vascular risk factors. Anxiety and depressive disorders cause a significant proportion of SCI among middle-aged people and are an important additional target for therapeutic measures.

[Biomarkers and mechanisms of early vascular damage]. / Biomarkery i mekhanizmy rannego povrezhdeniia sosudistoi stenki.

AIM: To assess the association of classic vascular risk factors, indicators of cerebral arteries wall damage and stress induction, and their role in early vascular and brain damage in middle age subjects without vascular events. MATERIAL AND METHODS: 87 patients were evaluated (49 women, 38 men, mean age 51.2±6.5). The following vascular risk factors were assessed: hypertension, diabetes, total cholesterol and low density lipoproteins levels, obesity and smoking. Patients underwent ultrasound of neck arteries, brain MRI and laboratory testing of blood parameters, probably associated with vascular wall damage: CRP, TNF-α, sICAM-1, sVCAM, HIF1-α, NO, VAP-1, VEGF-A, VEGF-C, sVEGF-R1, sVEGF-R2, TGF-ß1, general antioxidant status. RESULTS AND CONCLUSION: Mediating role of stress parameters in risk factors formation, initiation and maintenance of mechanisms of vascular damage was demonstrated. Hypercortisolemia suggested the association with age, atheromatosis, local inflammatory reactions via the TGF-ß1-HIF-1-VEGF family, systemic inflammation response via CRP, and elevated epinephrine levels were associated with TNF-α-mediated systemic inflammation. The association of TNF-α and MRI signs of cerebral small vessel disease (SVD) in non-hypertensive patients may indicate that TNF-α-mediated inflammation and increased permeability of vessel wall is an independent cause and potential biomarker of early small vessel damage. Influence of hypertension on age-dependent SVD is probably maintained by local vascular wall damage mechanisms via the TGF-ß1-HIF-1-VEGF family. However, hypertension heterogeneity and association of early cerebral vessels damage with various protective reactions require further clarification of the conditions for using these parameters as possible biomarkers of early SVD.

[Identification of people at the latent stage of Parkinson's disease (the PARKINLAR study): first results and an optimization of the algorithm].

AIM: To work out an optimal algorithm to identify people at the latent stage of neurodegenerative process of «parkinsonian¼ type in the Russian population. MATERIAL AND METHODS: Authors launched a two-step study aimed at identifying people at the latent stage of Parkinson's disease (PD) in the Russian population - the PARKINLAR (PARKINsonism, LAtent stage, Russia). As the first step, we formed a group of «primary risk¼ by the identification in neurologically healthy people of at least one of the following confirmed PD risk factors: a) the substantia nigra hyperechogenicity (ultrasound screening was performed in 193 people); b) mutations in «parkinsonian¼ genes (genetic screening was performed in 29 relatives of PD patients from families with LRRK2, PARK2 and GBA mutations). Thereby, 37 people comprised the «primary risk¼ group, of whom 23 agreed to continue further examination (44±10.2 years). A matched group of people without the aforementioned primary biomarkers of PD served as control. As the second step, we undertook in the prescreened groups a complex of investigations assessing the presence of secondary («minor¼) biomarkers of PD: Sniffin' Sticks olfactory testing; color visual evoked potentials; analysis of goal-directed eye-head-hand movements with the use of a special neuro-cybernetic system; assessment of motor and non-motor symptoms with the use of UPDRS and NMSS scales. RESULTS: When comparing the «primary risk¼ group with controls, maximal differences in the occurrence of symptoms were seen for goal-directed eye movements (43.5% vs. 20.0%) and color vision (39.1% vs. 26.7%). Among these individuals, we found two people with 4 secondary biomarkers and one with 3, and no such observations in controls. People with the combination of a primary biomarker with several secondary biomarkers of PD comprised a group of «high risk¼ in our study. CONCLUSION: Optimization of this algorithm of population screening of people predisposed to the development of PD may be done by expanding the spectrum of biomarkers and assessing their validity in a long-term prospective observational study.

Draft Genome Sequence of Mycobacterium tuberculosis Strain E186hv of Beijing B0/W Lineage with Reduced Virulence.

We report a draft genome sequence of Mycobacterium tuberculosis strain E186hv, belonging to the Beijing B0/W lineage and isolated from a patient from Kurgan, Russia. This clinical isolate showed a reduced virulence phenotype unusual for this lineage and resistance to isoniazid, rifampin, ethambutol, pyrazinamide, and ofloxacin. We analyzed single nucleotide polymorphisms (SNPs) associated with virulence.

[Estimation of atherogenic immune complexes containing modified lipoproteins in complement fixation tests].

A method for determining atherogenicity of the immune complexes containing multiple modified low-density lipoprotein (mmLDL) in complement fixation test has been found. In the proposed method, the precipitate immune complexes containing mmLDL (IC mmLDL) was prepared from human serum by treating it with buffer (8.3% of th PEG 3350 and 3.3% PVP 12600 th in the ratio 1: 1.2) for 10 min at 23 °C. IC mmLDL aggregates were separated by centrifugation at 3100g for 10 min at 23 °C. The precipitate IC mmLDL was dissolved in buffer without PEG and PVP, cholesterol content and the degree of binding of guinea pig complement were measured. Atherogenicity of the IC mmLDL was registered as the ratio of the degree of complement binding to cholesterol in the the immune complexes.

[Current pharmacotherapy of overactive bladder in neurological patients].

The literature data on the urgent neurological problem - overactive bladder (OAB) are summarized. The OAB prevalence, current conceptions on the physiology and pathophysiology of urination and pathogenetic mechanisms of OAB development are presented. Main groups of pharmacological agents used in OAB treatment are described. Special attention is drawn to rationale of using anticholinergic (antimuscarinic) drugs. The authors present the results of their own comparative analysis on the efficacy and tolerability of these drugs in treatment of patients with cerebral vascular diseases including the use of solifenacin succinate (VESIcare).

[Impact of antihypertensive therapy on clinical status and quality of life in patients with initial manifestations of hypertensive encephalopathy].

AIM: To study the clinical and instrumental characteristics of hypertensive encephalopathy (HE) in early stages, as well as the time course of their changes during long-term antihypertensive therapy (AHT). SUBJECTS AND METHODS: Prior to and after 9-month AHT, 57 patients aged 50-70 years who had uncomplicated grades 1-2 arterial hypertension (AH) with grades I-II HE underwent comprehensive examination comprising the studies of cognitive functions, quality of life (QL), hemorheology, and hemostasis, duplex scanning of great and intracerebral vessels, echocardiography, 24-hour blood pressure monitoring, magnetic resonance imaging. RESULTS: Early-stage HE was characterized by more cerebral complaints, higher rates of hypertensive crises, a greater degree of psychoautonomic syndrome, and worse QL. Focal brain lesions were detected in 74%; left ventricular hypertrophy (LVH) was diagnosed in 61% of cases. All the patients were observed to have cognitive dysfunctions. AHT (amlodipine, lisinopril) produced a good antihypertensive effect and substantial improvements of the patients' cognitive functions, health status, and QL. LVH regression was achieved. CONCLUSION: HE is a clinical manifestation of damage to the brain as the principal target organ in AH and should be therefore kept in mind in estimating the cardiovascular risk. The diagnosis of HE requires the use of tests to evaluate cognitive functions.

[Comparative clinical and anatomic characteristic of patients with patent foramen ovale in cryptogenic and noncryptogenic stroke].

In order to study anatomical and functional characteristics of patent foramen ovale (PFO) in patients with cryptogenic stroke and with other stroke subtypes we examined 56 stroke patients (male--35, female--21, age 46.7 +/- 16.5 years) with PFO and ischemic stroke. Diagnosis of PFO was made by transesophageal echocardiography (TEE), contrast transcranial Doppler monitoring (C-TCD), contrast transthoracic echocardiography (C-TTE). Group 1 was made up of patients with definite stroke cause (cardioembolic, lacunar, atherotrombotic) (n=40), and group 2--of patients with cryptogenic stroke (n=16). Patients in group 2 were younger than patients in group 1 (38.7 +/- 13.4 and 50.4 +/- 16.5 years, p < 0.05) and had slight neurological symptoms. These patients also more frequently had avalvular, or "window-like" anatomic types of PFO (2 [13%] and 4 [27%] patients, respectively), combination of large anatomic size (3 mm and larger) and functional level of PFO (3 degree of the right-to-left shunt by C-TCD) (p < 0.05).

[Pathogenetic significance of patent foramen ovale in patients with the determined cause of ischemic insult].

The prevalence of open oval window (OOW) in patients with different types of ischemic insult and the possibility of independent pathogenetic contribution of OOW to brain injury were evaluated by examining 85 patients (mean age 53 +/- 14 yr) with cardioembolic (CES), lacunar (LS), and other subtypes of ischemic insult. CT and MRT of the head, duplex scanning of head arteries, contrast transcranial monitoring middle cerebral arteries, standard and contrast transthoracic and transoesophageal echocardiography revealed OOW in 40% of the patients. It had small anatomic and functional size and a tunnel-like shape. The presence of an interatrial shunt was unrelated to the degree of neurologic deficit, the size and location of brain injuries, the number of ischemic foci. It is concluded that OOW has no pathogenetic significance of its own and makes no contribution to brain injury in stroke-affected patients.

[Paradoxical embolism in patients with ischemic stroke].

The present study included 84 patients with ischemic stroke of known and unknown etiology. The risk of paradoxical embolism (PE) was evaluated using contrast transthoracic echocardiography, contrast transcranial Doppler monitoring, and transoesophagal echocardiography. The majority 64%) of the patients with strokes of known etiology were found to be predisposed to PE because they had the patent interatrial foramen (PIF) and pulmonary shunt (51 and 13 respectively). PIF was of small functional and anatomical size. Predisposition to PE in most patients with cryptogenic stroke (94%) was due to the presence of PIF (in 88%) and was often the sole cause of the stroke. These patients frequently had the shunt of a large functional size.

Genetic analysis of mycobacterium tuberculosis strains isolated in Ural region, Russian Federation, by MIRU-VNTR genotyping.

SETTING: The Ural region in Russia is one of the areas most affected by a high incidence of tuberculosis (TB). Molecular epidemiological studies able to trace Mycobacterium tuberculosis transmission are of particular significance. OBJECTIVE: To characterize the population of M. tuberculosis strains circulating in the Ural region, to detect the predominant genotypes and to evaluate their phylogenetic relationship and epidemiological significance. DESIGN: Ninety-two M. tuberculosis clinical samples originating from the Ural region were genotyped using the MIRU-VNTR method. RESULTS: Two major phylogenetically distinct groups of isolates were identified: the W-Beijing family (54.3%) and a previously unreported cluster, named the Ural group (15.2%). Forty-seven different MIRU profiles were identified, including 38 unique (41.3%) and 54 isolates grouped into nine clusters (from 2 to 28 isolates in each cluster). Genetic diversity within the clusters was shown by additional sub-typing of M. tuberculosis isolates in nine additional QUB-VNTR loci. CONCLUSION: W-Beijing family isolates are associated with multiresistance to anti-tuberculosis drugs. It is possible that the strains of this family play a significant role in the spread of multidrug-resistant TB over the Ural region.