THE RELATIONSHIP BETWEEN THE DURATION OF REMISSIONS AFTER THE ONSET, THE SEVERITY OF THE RELAPSES AGAINST THE BACKGROUND OF DIFFERENT DURATION OF THE RELAPSING STAGE AND THE NATURE OF THE PROGNOSIS IN SECONDARY-PROGRESSIVE MULTIPLE SCLEROSIS.

Work objective - to study the relationship between the duration of remission after the onset, the severity of relapses against the background of different duration of the relapsing stage (RS) and the nature of the prognosis in the secondary progressive multiple sclerosis (SPMS) using clinical and mathematical analysis. Patients with different prognosis for SPMS; neurological examination using The Expanded Disability Status Scale (EDSS); a survey method. Mathematical methods: 'contingency tables 2x2' (determining the significance of the connection between a pair of two indicators - different duration of remission after the onset and RS in four groups of patients), Yule's Coefficient of Association (determining the magnitude of differences between the group and the studied indicator), a permutation test (defining clinical indicators on RS, which significantly differed in mild and severe relapses). Pairwise comparison in four groups of patients with different duration of remission after the onset and RS in SPMS showed that long-term remission after the onset and prolonged RS delay the transition of RS into secondary progression (SP). Short duration of these indicators revealed the opposite prognostic tendencies, indicating the further progression of the disease. The presence of severe relapses on RS in SPMS is predominantly associated with unfavorable prognostic indicators on RS and indicates the initiation of the transition into SP. Accordingly, the duration of remission after the onset, the severity of relapses against the background of different durations of RS should be regarded as prognostic clinical markers that play a key role in the switch of RS to SPS in SPMS. The results obtained should be used to assess the current clinical situation and timely prescribe an appropriate pathogenetic therapy on RS.

[CLINICAL-MATHEMATICAL ANALYSIS OF INTERRELATIONS BETWEEN A CHARACTER OF THE PROGNOSIS AND PECULIARITIES OF ONSETS IN DIFFERENT TYPES OF MULTIPLE SCLEROSIS COURSE].

Aim of the study- to assess the prognostic value of indicators characterizing the course of the of multiple sclerosis onset (MS) using clinical-mathematical analysis. Patients with MS with different prognosis: good and uncertain for the relapsing-remitting type; uncertain and poor for progressive types of clinical course. A neurological examination using The Expanded Disability Status Scale (EDSS); a questionnaire method; determination of the Yule's coefficient of association (coefficient of colligation), the separating hyperplane method and the correlation analysis. The indicators of the onset with a high correlation, which have a prognostic value, are defined by means of the Yule's coefficient. To rank the onset indicators by the separating hyperplane method, its diagnostic weight was determined for different variants of prognosis in all types of MS. Correlation relations between the onset indices for each type of MS, were calculated and presented in a graphical form. The correlation analysis of the connections between these indicators is built according to a single algorithm that combines alternative programs of patterns of severe and mild onset, which can subsequently compete with each other for the final outcome of the disease. The results of the clinical-mathematical analysis of the onsets in different types of MS, with a high reliability, indicate a diagnostic informativity of the mentioned investigation methods for further prognosis of the MS disease type.

[ARCHITECTONICS OF THE NIGHT SLEEP BASED ON ITS POLYSOMNOGRAPHIC CHARACTERISTICS IN PATIENTS WITH MULTIPLE SCLEROSIS].

Aim of our study is to establish polysomnographic characteristics of nocturnal sleep in various forms of multiple sclerosis. Fifty eight patients with different clinical course of multiple sclerosis (MS) were included into the study. Disturbances of sleep architectonics were identified: representation of deep stages of NREM sleep, as well as REM sleep were reduced. Maintenance and continuity of sleep and its architecture were affected, leading to reduced sleep efficacy. Destabilization of sleep phases can be explained by activation of desynchronizing brain systems, leading to poor organization of NREM and REM sleep. These disorders were especially pronounced in patients with progressive course of MS. Thus, abovementioned sleep disorders can have prognostic value for predicting clinical course severity in patients with MS. Management of sleep disorders can improve quality of live in people with MS.

[Left fouratrial heart. First clinical case].

The left three-atrial heart (LTH) is a rare congenital abnormality where the left auricle (LA) is divided into two chambers with an additional membrane. This article describes for the first time a clinical case of congenital heart defect with four atrial chambers. A 41-old man was hospitalized for newly diagnosed paroxysmal atrial fibrillation. On transthoracic echocardiogram (EchoCG), LA was considerably enlarged and divided into two equal interconnected parts with a membrane. Additional examination with contrast-enhanced EchoCG and computed tomography revealed two membranes dividing the LA into three chambers. Prediction for the patient was beneficial since there were no other developmental abnormalities of the heart, and the LA transmembrane pressure gradient (PG) was small. Data of literature on the incidence and prognosis of LTH are provided.

[Abdominal pain syndrome and quality of life in patients with cholelithiasis after cholecystectomy during a 10-year follow-up]. / Abdominal'nyi bolevoi sindrom i kachestvo zhizni u bol'nykh zhelchnokamennoi bolezn'yu posle kholetsistektomii pri 10-letnem nablyudenii.

AIM: To estimate the incidence of abdominal pain syndrome (APS) and to assess quality of life (QOL) in patients within 10 years after cholecystectomy (CE). SUBJECTS AND METHODS: This investigation is part of a long-term prospective follow-up study of patients after CE for cholelithiasis (CL). It enrolled 145 people: 30 (21.5%) patients with baseline asymptomatic CL and 115 (80.7%) with its clinical manifestations. The time course of changes in APS and QOL were analyzed. RESULTS: Over 10 years, all the patients showed a decrease in the incidence of APS from 84.1% (n=95) to 66.4% (n=75; p=0.004). In Group 1 (n=89), APS was at baseline detected in all the patients; 10 years later, its incidence declined to 67.4% (n=60; p < 0.001). Biliary pains were predominant; these had been identified significantly less frequently over the 10-year period in 47 (52.8%) patients; p<0.001). In Group 2 (n=24), pre-CE APS was generally detected in 6 (25%) patients; following 10 years, the incidence rates of pain significantly increased to 62.5% (n=15; p=0.035), among which there were predominant biliary pains (in 54.2%; p<0.001) and dyspepsia from 33.3% (n=8) up to 66.7% (n=16; p=0.039). QOL in the physical and mental health domains was found to decrease in both groups. CONCLUSION: Ten years after CE, the group with the baseline clinical manifestations of CL and poorer QOL showed a lower incidence of APS mainly due to the reduced incidence of biliary pains and the baseline asymptomatic group exhibited a rise in the incidence of APS due to the appearance of biliary pains and dyspepsia.

THE FREQUENCY OF DYSPEPTIC DISORDERS FOLLOWING CHOLECYSTECTOMY PATIENTS ACCORDING TO THE 10-YEAR STUDY.

AIM: To evaluate gastrointestinal symptoms during 10 years after cholecystectomy in patients with symptomatic and asymptomatic gallstone disease and to identify predictors of them. MATERIALS AND METHODS: The work is the part of a prospective long-term monitoring of patients with symptomatic (1) and asymptomatic (2) gallstone disease after cholecystectomy (CE). The study included 145 patients: 115 (80.7%) with initially symptomatic disease (1) and 30(21.5%) asymptomatic (2) disease. RESULTS: The frequency of heartburn increased from 15.9% to 63.7% during 10 years (p = 0.015) after CE especially in the group (1) (from 2.24% to 68.53% (p 0.037). The frequency of "bitter taste in the mouth" raised from 46.9% before the CE to 69.02% after CE (p < 0.001). The frequency of diarrhea increased from 0.88% to 38.2% in both groups. (p = 0.046). CONCLUSION: The frequency of heartburn, "bitter taste in the mouth", diarrhea increased in patients after 10 years in patients with symptomatic and asymptomatic gallstone disease after CE. A common risk factors are presence symptomps at baseline and the presence of these symptoms at the 6rst years after CE.

HEPATIC SARCOIDOSIS.

Sarcoidosis is a multisystemic disease of unknown origin characterized by the formation of non caseating granulomas. Thoracic involvement is the most common presentation; however, sarcoidosis can involve almost any other organ. Liver is one of the most frequently affected organs after lungs and lymph nodes. Microscopic hepatic involvement is common in these patients but is mostly clinically silent. specific symptoms include jaundice and pruritus, mostly from chronic cholestasis. In a significant portion of these patients, macroscopic findings can be detected by ultrasound examination ,abdominal CT or magnetic resonance imaging and these findings may easily be confused with other benign and malignant conditions of the liver. Liver biopsy is usually required to confirm the diagnosis. Not all cases of hepatic sarcoidosis require treatment. For symptomatic patients, the first line treatment includes corticosteroids or ursodeoxycholic acid.

FULMINANT PARACETAMOL HEPATITIS.

This article describes a clinical case of fulminant paracetamoly hepatitis a young woman of 33 years. Fulminant hepatitis has developed as a consequence of uncontrolled reception paracetamol-containing medicines for acute viral infection. Paracetamol poisoning conlirmed at autopsy.

[Long-term dynamics of gastrointestinal symptoms after cholecystectomy for the treatment of cholelithiasis].

The aim of the work was to analyse dynamics of gastrointestinal symptoms and risk factors at different periods after cholecystectomy (CCE) in patients with cholelithiasis (CL). It was a prospective open cohort observational study with interviewing the patients before, 6 and 36 months after cholecystectomy for the treatment of CL. The pain symptom of CL persisted in 65.9% of the patients till the 6th month after CCE and in 57.3% of the patients till the 36th month. The logistic univariant analysis showed high probability of persistence and/or appearance of biliary pain within 6 months after surgery in patients suffering biliary colic before it (OR = 5.3, p = 0.01) and having hereditary aggravation of CL (OR = 2.7, p = 0.38). The relationship between biliary pain and planned surgical intervention for the treatment of CL was documented 3 years after the operation (OR = 2.6, p = 0.018). Similar relationship was revealed after 6 and 36 months (OR = 3.8, p = 0.002). Biliary pain within 6 months after CL was an independent prognostic factor of its development within the next 3 years. Other increasingly severe gastrointestinal symptoms were heartburn, intolerance of greasy food, and disturbed intestinal passage as a result of biliary insufficiency or disordered intestinal motility. The above relationships between gastrointestinal symptoms may be used to predict their appearance within 6 months after CL.

[Cystatin C: a biological role and impaired secretion in viral hepatitis c and hepatic cirrhosis].

Cystatin C is a non-glycated cationic protein with a molecular weight of 13.3 kD, which belongs to the superfamily of cystatins; its basic function is to inhibit and regulate the activity of cysteine proteinase. In apparently healthy individuals, the extracellular concentration of cystatin C is shown to be substantially higher in serum than in urine and bile. The increased serum concentration of cystatin C has been found in the development of chronic viral hepatitis C, and hepatic cirrhosis in particular, which reflects the development of an inflammatory process and, evidently, the higher secretion of cystatin C by stimulated macrophages.

[Biliary tract in patients with chronic viral hepatitides].

AIM: To characterize motor-kinetic and inflammatory changes in extrahepatic biliary tracts and gallbladder in patients with chronic viral hepatitis (CVH). To ascertain whether there is a pathogenetic correlation between affection of the biliary system and viral infection. MATERIAL AND METHODS: The condition of the biliary tract was examined in 183 patients with CVH using fractionated duodenal tubing with biochemical tests and bacteriological investigation of bile, dynamic ultrasonic investigation. RESULTS: 69.9% patients were diagnosed to have dysfunction of the Oddi's sphyncter caused by its hypertonicity, 4.4% patients had hypotonic sphyncter. Hyper- and hypotonicity of the gallbladder were observed in 45.8 and 20.8% patients, respectively. Biliary dysfunction was associated with the process activity but not with a nosological form of the disease. Chronic acalculous cholecystitis was verified in 21.2% patients. CONCLUSION: Chronic HBV and HCV infections are accompanied with biliary dysfunctions associated with activity of inflammation in the liver. Oddi's sphincter dysfunction in CVH is a risk factor of gallbladder inflammation.

[The addiction of ephedrine like psychostimulators and use of nimotop for its correction]. / Zloupotreblenie éfedrinopodobnymi psikhostimuliatorami i primenenie preparata nimotop dlia ego korrektsii.

Twenty six patients, used home-made ephedrine like psychostimulators were examined. Nervous system pathology in these cases was characterized by short (several months) period of the pathological process formation, young patient's age, absence of family psychiatric history, pronounced systemic and multilevel affection of the organism, severity of psychic defects and patients disability. Electrophysiological study revealed essential changes of neurodynamics manifesting with insufficiency of non-specific activating brain system, diencephalic stem structure dysfunction, deep structure irritation that might correspond to clinical picture of multisystem CNS lesions. An involvement of limbic reticular structures in pathological process on the background of neurophysiological immaturity was detected as well. In patients disorders of brain homeostatic mechanisms and cognitive functions were also found. Deprivation of reactivity of upper-segmental autonomic system regulation can determine rigidity and pathological adaptation of such patients. Insufficiency of activating systems of reticular formation, arrhythmia, disturbances of cognitive functions and cerebral homeostasis dictate a need for nootropics prescription for these patients. Clinical experience justifies including drug nimotop in complex treatment and rehabilitation schemes.

Alexa dyes, a series of new fluorescent dyes that yield exceptionally bright, photostable conjugates.

Alexa 350, Alexa 430, Alexa 488, Alexa 532, Alexa 546, Alexa 568, and Alexa 594 dyes are a new series of fluorescent dyes with emission/excitation spectra similar to those of AMCA, Lucifer Yellow, fluorescein, rhodamine 6G, tetramethylrhodamine or Cy3, lissamine rhodamine B, and Texas Red, respectively (the numbers in the Alexa names indicate the approximate excitation wavelength maximum in nm). All Alexa dyes and their conjugates are more fluorescent and more photostable than their commonly used spectral analogues listed above. In addition, Alexa dyes are insensitive to pH in the 4-10 range. We evaluated Alexa dyes compared with conventional dyes in applications using various conjugates, including those of goat anti-mouse IgG (GAM), streptavidin, wheat germ agglutinin (WGA), and concanavalin A (ConA). Conjugates of Alexa 546 are at least twofold more fluorescent than Cy3 conjugates. Proteins labeled with the Alexa 568 or Alexa 594 dyes are several-fold brighter than the same proteins labeled with lissamine rhodamine B or Texas Red dyes, respectively. Alexa dye derivatives of phalloidin stain F-actin with high specificity. Hydrazide forms of the Alexa dyes are very bright, formaldehyde-fixable polar tracers. Conjugates of the Alexa 430 (ex 430 nm/em 520 nm) and Alexa 532 (ex 530 nm/em 548 nm) fluorochromes are spectrally unique fluorescent probes, with relatively high quantum yields in their excitation and emission wavelength ranges.

A stable nonfluorescent derivative of resorufin for the fluorometric determination of trace hydrogen peroxide: applications in detecting the activity of phagocyte NADPH oxidase and other oxidases.

The enzymatic determination of hydrogen peroxide can be accomplished with high sensitivity and specificity using N-acetyl-3, 7-dihydroxyphenoxazine (Amplex Red), a highly sensitive and chemically stable fluorogenic probe for the enzymatic determination of H2O2. Enzyme-catalyzed oxidation of Amplex Red, which is a colorless and nonfluorescent derivative of dihydroresorufin, produces highly fluorescent resorufin, which has an excitation maximum at 563 nm and emission maximum at 587 nm. The reaction stoichiometry of Amplex Red and H2O2 was determined to be 1:1. This probe allows detection of 5 pmol H2O2 in a 96-well fluorescence microplate assay. When applied to the measurement of NADPH oxidase activation, the Amplex Red assay can detect H2O2 release from as few as 2000 phorbol myristate acetate-stimulated neutrophils with a sensitivity 5- to 20-fold greater than that attained in the scopoletin assay under the same experimental conditions. Furthermore, the oxidase-catalyzed assay using Amplex Red results in an increase in fluorescence on oxidation rather than a decrease in fluorescence as in the scopoletin assay. In comparison with other fluorometric and spectrophotometric assays for the detection of monoamine oxidase and glucose oxidase, this probe is also found to be more sensitive. Given its high sensitivity and specificity, Amplex Red should have a broad application for the measurement of H2O2 in a variety of oxidase-mediated reactions and very low levels of H2O2 in food, environmental waters, and consumer products.

A one-step fluorometric method for the continuous measurement of monoamine oxidase activity.

We have developed a one-step fluorometric method for the measurement of monoamine oxidase (MAO) activity in 96-well microplates with sensitivity 10-fold higher than the conventional spectrophotometric assay method. This assay is based on the detection of H2O2 in a horseradish peroxidase-coupled reaction using N-acetyl-3, 7-dihydroxyphenoxazine (Amplex Red), a highly sensitive and stable probe for H2O2. With a single sampling, this assay is useful for performing both end-point and continuous measurements of MAO activity. Using a commercially available enzyme, our assay allows the detection of MAO B activity as low as 1.2 x 10(-5) U/ml. When applied to crude tissue homogenates, we have been able to selectively detect both MAO A and MAO B from cow brain tissue with protein content as low as 200 microgram per sample. The potential applications of this assay include the measurement of MAO activity in normal and diseased tissues, blood samples, and other biological fluids and the screening of drugs for the treatment of MAO-mediated diseases.

Quenched BODIPY dye-labeled casein substrates for the assay of protease activity by direct fluorescence measurement.

We have prepared casein conjugates of two BODIPY dyes for use as fluorogenic protease substrates in homogeneous assays. Both conjugates are labeled to such an extent that the dyes are efficiently quenched in the protein, yielding virtually nonfluorescent substrate molecules. These fluorogenic substrates release highly fluorescent BODIPY dye-labeled peptides upon protease digestion, with fluorescence increases proportional to enzyme activity. These quenched substrates are suitable for the continuous assay of enzymatic activity using standard fluorometers, filter fluorometers, or fluorescence microplate readers using either fluorescein excitation and emission wavelengths to measure BODIPY FL casein hydrolysis or Texas Red wavelengths to detect proteolysis of BODIPY TR-X casein. Most current techniques for detecting protease activity, such as the fluorescein thiocarbamoyl casein (FTC-casein) protease assay, require extensive manipulation, including separation steps, and are therefore labor intensive and error-prone. In comparison, we found the BODIPY dye-labeled casein protease assays to be simple and precise and to have greater sensitivity and a broader dynamic range of detection than the FTC-casein assay. We were able to sensitively detect the activities of a wide variety of enzymes with these new substrates, including serine, acid, sulfhydryl, and metalloproteases. We also found the assay suitable for quantitating protease inhibitor concentrations and for real-time analysis of proteolysis.

[Electrical impedance tomography in pulmonology]. / Elektroimpedansnaia tomografiia v pul'monologii.

Application of a modern method of introscopy--electroimpedance tomography (EIT) for diagnosis of different types of lung diseases is described. The EIT system including measurement and collecting data devices, 16-electrodes array and IBM PC 486 computer was used. The results of analysis of electrotomograms have demonstrated that the EIT-system can be introduced for detecting abnormal lung fluid levels, pulmonary edema, diagnosis of lung cancer, emphysema, pleuritis, hydrothorax, sarcoidosis. The method provides high sensitivity to the changes in the body physiological state. Other advantages are: safety, fast measurements, ease of equipment transportation and maintenance, low cost.

[The direct and reverse processes of cholesterol and triglyceride transport in patients with Alzheimer's disease]. / Sostoianie protsessov priamogo i obratnogo transporta kholesterina i triglitseridov u bol'nykh bolezn'iu Al'tsgeimera.

Based on the investigation of 42 persons with Alzheimer's disease, it has been shown that in spite of absence of changes in the sum of apoB-containing fractions of lipoproteins a redistribution of their particles is observed suggesting adverse shifts in the processes of direct transport of lipids. These patients also manifest disturbances of the reverse transport of lipids which, fact is inferred from a perverted redistribution of particles of high-density lipoproteins.