Method for prediction of developing symptomatic epilepsy accompanying neuroinfections in children
SUBSTANCE: recent comatose condition is detected; magnetic resonance imaging shows centres of cerebral structural changes; electroencephalography shows epileptiform activity, diffuse sharp waves, spikes, reduced complexes, high-amplitude low activity paroxysmal events, frequent paroxysmal events of 'peak-slow wave' and 'spike-slow wave' complexes. The EEG also shows irritant activity, local transient high-frequency beta-activity, advanced transient low-amplitude and advance continuous long-term high-amplitude activity. The presence of an aetiological agent of the disease caused by tick-borne encephalitis or the presence of encephalitis of other and uncertain aetiology is stated. The derived data are scored depending on the presence, absence and manifestations thereof. The derived data are used to calculate linear classification functions and to detect the favourable (LCF1) outcome of encephalitis without symptomatic epilepsy (SE) progression and the unfavourable (LCF2) outcome of encephalitis with SE progression. If LCF1>LCF2, the encephalitis outcome without SE progression is predicted, while LCF2>LCF1 shows the unfavourable outcome with SE progression.
EFFECT: method provides more reliable assessment of the SE progression in encephalitis that is ensured by taking into account additional EEG data and calculating the linear classification functions.
The invention relates to medicine, namely to the prediction of symptomatic epilepsy (SE) in neuroinfections in children and can be used in clinical practice infectious disease specialists and neurologists to predict the development of SCS after suffering meningitis and encephalitis.
The term of neuroinfections refers to the group of infectious diseases with the invasion of the pathogen into the Central nervous system and clinical signs of damage of any of its departments: meningitis - with the defeat of hard and soft meninges, encephalitis - with the defeat of the brain.
The relevance of acute CNS is determined by the known weight of their current involvement in the epidemic of children in the younger age groups (up to 50%), frequent development of life-threatening cerebral and extracerebral complications and persistent residual effects, as well as the continuing high mortality (in different age groups when a number of nosological forms from 15% to 70%.
Encephalitis is one of the serious diseases in children and is 10 cases per 100,000 inhabitants in children (Koskiniemi M, Korppi M, Mustonen K, et al. Epidemiology of encephalitis in children: a prospective multicentre study Eur J Pediatr. - 1997. - Vol.156, No. 7. - P. 541-545). The consequences of encephalitis in violation of the motor, sensitive higher brain functions, the composition of Aut from 30% to 60% (Åsa Fowler et al., 2010). The recovery period after suffering encephalitis in children is 6-12 months (Åsa Fowler et al., 2010). In the recovery period affected the functions are restored, pathological syndromes regress. However, full recovery is rare, a number of pathological syndromes remain, though weakening in its severity. During this period, as a consequence of the disease, can be formed and SE (Åsa Fowler et al., 2010). Symptomatic epilepsy is a frequent and severe complication of encephalitis in children. SE, emerging in the long term to carry encephalitis, presents various forms of manifestations and degrees of severity: (1)focal symptoms with frequent and constant twitching of the muscles in tick-borne encephalitis, and, as a rule, (2) secondarily generalized seizures, reaching a frequency of several times a day, leading to a delay in brain development, the violation of personality traits. SCS may be resistant to treatment, and to have an aggressive course. This significantly reduces the level of life of patients undergoing encephalitis (E). The risk of developing solar cell is determined by a number of factors in the development and manifestations of the disease in the acute phase. Knowledge of risk factors for symptomatic epilepsy allows you to adjust the tactics of treatment and to reduce or pre order to prevent the development of this syndrome in children.
It is considered that the risk of SE increased in children with epileptic seizures during the acute period of the disease, and the severity of the condition treated at the intensive care unit (RTO) (Fowler A, Stödberg T, Eriksson M. Wickström R. Long-term outcomes of acute encephalitis in childhood paediatrics. - 2010. - Vol.26, No. 4. - P. 828-835.). B 30%-60% of cases in the acute phase E develop epileptic seizures (U. K. Misra et al. Seizures in viral encephalitis // Epilepsia. - 2008. - Vol.49(Suppl. 6). - P. 13-18). But in a significantly larger number of cases (90%) in the acute phase E are EEG changes as focal or generalized slow activity with the presence or absence of epileptiform discharges (Lahat E, Barr J, Barkai G, Paret G, Brand N, Barzilai A. Long term neurological outcome of herpes encephalitis Arch Dis Child. - 1999. - Vol.80, No. 1. - P. 69-71). So using only EEG data in the prediction of the development of SE in outcomes E seems to be ill-founded.
There is a method of predicting the course of encephalitis by registering and evaluating data on the age and level of C-reactive protein in the blood, cerebrospinal fluid lymphocytosis, presence of coma (A. Schmidt, R. BÜhler, K. MÜhlemann, C. W. Hess, M. G. Täuber. Long-term outcome of acute encephalitis of unknown aetiology in adults // Clinical Microbiology and Infection. - 2011. - Vol.17, No. 4. - P. 621-626). However, when using this method are not considered data MRI, EEG. The forecast evaluation is intended for adults and does not take into account the development of the SCS as the most severe and,in some cases, poorly-curable consequences of encephalitis.
There is a method of predicting the course of acute CNS in children by registering and evaluating data MRI and evoked potentials of the brain. In accordance with this method of prediction is determined by the outcome of the disease (Skripchenko N. In., Savin, M. C., Ivanova, P., Grigoriev S., a Method for predicting outcome of viral encephalitis in children. Patent No. 2372839). However, when using this method are not available approaches to assessing opportunities for the development of SCS.
A known method for predicting the development of SE in acute CNS in children by taking into account clinical indicators (Åsa Fowler et al., 2010). In this way shall record only two clinical settings: the presence of seizures in the acute phase of the disease, and the severity of the disease, the characteristic of which is the presence of the patient in the ICU.
When this method is not taken into account the volume of brain lesions using a variety of neuroimaging methods, it is not considered an etiological factor of the disease and EEG data.
Closest to the present invention is a method of prognosis of SE in children who had encephalitis, based on clinical-encephalographic and virological data (Chen YJ, Fang PC, Chow JC. Clinical characteristics and prognostic factors of postencephalitic epilepsy in hildren J Child Neurol. - 2006. - Vol.21, No. 12. - P. 1047-51.). The authors propose to predict the development of SCS by taking into account the development in acute epileptic status, whether EEG medlennovolnovoj activity and multifocally spikes and the development of encephalitis herpes simplex virus. The disadvantage of the described method is that the authors take into account only neurophysiological, virological data and the presence of epileptic status, while unaccounted for are the severity of the clinical manifestations in the form of length of stay in the ICU or the duration of coma, and the degree of structural damage of the brain. This may lead to underestimation of the severity of functional disorders of the Central nervous system in the study during the acute period of the disease. In addition, the use of functional indicators in encephalitis without assessing the severity of clinical disorders and neuroimaging data do not provide sufficient accuracy of symptomatic epilepsy.
The technical result achieved by the invention is to improve the accuracy of the forecast of the development of SE in children through assessment of coma and structural brain lesions on MRI.
This result is achieved by the fact that in the known method, including determining whether the etiologic agent of the disease agent, Agov brain on MRI, the presence of coma, evaluation on the encephalogram epileptiform activity additionally, the EEG registration is carried out in the first 5 days after the release of the child from a coma or in the first 10 days of illness in cases without comatose state, evaluate the encephalogram irritative activity and the data obtained are building linear classification functions that are specific to favorable (LCF) outcome of encephalitis without the development of SCS and unfavorable (LCF 2) the outcome of encephalitis with the development of the AOC by the formulas:
LCF = -12,1-0,1∗X1+10,1∗X2-1,9∗X3+5,3∗X4+8,4∗X5
LCF = -20,1-0,5∗X1+4.0∗X2+2,1∗X3+8,2∗X4+10,9∗X5
X1 - the presence of a coma in the days, 0 - no coma;
X2 - lesions on brain MRI scans showed no foci is estimated at 0 points; the presence of foci - 1 point;
X3 - epileptiform activity on EEG: no - 1 point; diffuse sharp waves - 2 points; sharp waves, spikes, reduced complexes, high-amplitude paroxysmal slow activity - 3 points; frequent paroxysms complexes "spike-slow wave", "spike-slow wave") - 4;
X4 - irritative activity on EEG: no - 1 point; a local non-permanent high-frequency beta activity - 2 points; common volatile low-amplitude high-frequency activity - 3 points; common long in scampitella high-frequency activity - 4 points;
X5 - causative agent the causative agent of the disease: encephalitis, caused by the tick-borne encephalitis virus - 1 point; encephalitis other and unknown etiology - 0 points;
and when LCF>LCF predict the outcome of encephalitis without the development of SCS and when LCF>LCP - an unfavorable outcome of encephalitis with the development of a solar cell.
The result of many years of experience in the treatment of acute forms neyroinfektsionnyh diseases, such as encephalitis, meningitis, we often noted the occurrence of severe consequences in the form of neurological complications. We found that symptomatic epilepsy is a frequent and severe complication of encephalitis in children, up to a lethal outcome. Analyzing the flow patterns of the AOC and the results of treatment in the recovery period after suffering encephalitis in children, the authors became apparent need for early prediction to select the correct tactics of treatment. In the process of analysis of numerous clinical, instrumental and laboratory data were found most informative, relevant for predicting outcomes encephalitis indicators, ensuring the accuracy of the prediction in the early stages of the disease, which formed the basis of the invention. We have shown that in children with severe CNS infection the presence of EEG indicators not only epileptiform but irrit the positive activity in the first 5 days after coming out of his coma or in the first 10 days of illness in cases without comatose state was the most unfavorable in the prediction of the development of SE. Earlier registration of the EEG of children in a coma, did not allow to judge about the real bioelectric activity, as the patients were sufficient sedative and miorelaksantnoe therapy.
We established that consideration of the duration of coma, rather than the usual duration of stay of children in the intensive care unit, characterized the true severity of the condition in the acute phase. The duration of stay in the ICU, in some cases, was associated with somatic complications and did not have sufficient correlation with the severity of the patients.
The authors first established that in the presence as the causative agent of neuroinfections of tick-borne encephalitis virus increases the risk of SE that is associated with the possibility of the formation of chronic tick-borne encephalitis. Less of a role in the risk of developing SE in our observation played herpes simplex viruses and herpes viruses 6 are of the type that appears to be associated with a sufficiently prompt and adequate conducted by us anti-herpes therapy.
The authors first established that a comprehensive analysis taking into account the gravity of the clinical-neurological disorders, the prevalence of structural CNS changes on MRI, the severity of functional impairments according to EEG increases the accuracy of the forecast of the development of the AOC which stood at 88.9% and exceeds the accuracy of the other known methods.
Brand new is that in the stepwise discriminant analysis, the authors obtained a statistically significant (p<0.001) and informative formulas linear classification functions, which have included the most relevant for predicting outcomes encephalitis indicators, namely: the presence of a coma, the prevalence of lesions on MRI, the presence of epileptiform activity on EEG, the presence of irritative activity on EEG, causative agent the causative agent of the disease
The highest sensitivity of the method in predicting outcomes of encephalitis without SE 93%, lower sensitivity in predicting adverse outcomes encephalitis with the development of SE - 81,8%. High enough informative ability of the method in predicting adverse outcomes encephalitis (81,8%) allows to carry out directed by duration and volume of neurometabolic therapy to reduce the risk of development of a solar cell.
The method is as follows: after the hospitalization of a patient with suspected encephalitis is clinical and neurological examination to determine the severity of the condition, the duration of stay in a coma (days), clarification etiological factor for the of Alemania. To clarify the prevalence, nature of focal lesions is performed brain MRI.
In parallel with clinical and MRI studies during the first 5 days after the release of the child from a coma or in the first 10 days of illness in cases without comatose state conduct EEG research in standard leads in the first days of the disease.
After screening klinicheskogo, MRI and neurophysiological examination is the encoding used signs proposed in the formula. Carry out the calculation on the calculator. The amount received by the formulas LCF and LCF compared between them and the outcome is determined by the largest absolute value of one of the LCF, i.e. when LCF>LCF predict a favorable outcome of encephalitis without the development of SE, when LKFK<LCF - adverse with the development of a solar cell.
The effectiveness of this method of prediction can be confirmed by the following examples.
Example 1. Baby M, 1 year. The diagnosis of CMV encephalitis, severe. Symptomatic epilepsy. Your child is sick on the background of subfebrile temperature, the emergence of liquefied stool up to 3 times a day, vomiting after eating 1-2 times a day. On day 3 of illness deterioration in the form of a rise in temperature to 38.2°C, against which he developed generalized tonic-clonic seizures within 2 mine is, kupirovalsa yourself. The child urgently hospitalized at children's hospital No. 5 with a diagnosis of acute gastroenteritis, febrile convulsions. From the anamnesis of life it is known that a child from 1 pregnancy on a background of toxicosis 1 trimester, ureaplasmosis (mother received treatment during pregnancy), childbirth 1 term, cry baby immediately, weight at birth, 4840, length 56 cm, Apgar 8/9 points. Breastfed up to 3 months. In the first year of life 6 times suffered acute respiratory viral infection, not surveyed. Grafted on an individual schedule. Heredity is not burdened. On the first day of hospital stay was noted deterioration of the child in connection with the development of Epictetus on the background subfebrile body temperature. In neurological status: level of consciousness - stun (X1=0), the smoothness of the nasolabial folds to the right, voluptas, language in oral cavity in the midline, muscle tone S>D, deep reflexes in the extremities caused by expansion of reflexogenic zones S>D. Meningeal symptoms negative. CT of the brain on day 3 of illness data for volumetric education brain is not received, there are signs of cerebral oedema (X2=0). On EEG on day 3 of illness - expressed human BEA with the presence medlennovolnovoj, epileptiform and irritative activity. To stabilize the state of the Aulnay performed lumbar puncture: lymphocytosis 6/3 lymphocytic. protein 0.06 g/l Data for meningitis is not received. From the cerebrospinal fluid by polymerase chain reaction (PCR) of selected DNA cytomegalovirus (X5=0). In order to relieve apistatus child transferred on a ventilator with medical sedation. the use of muscle relaxants. For background purposes Depakine at a dose of 15 mg/kg/day. seizures do not occur, the child excubitor, but after 12 hours again series secondarily generalized seizures with focal component, requiring repeated for mechanical ventilation, use 2 anticonvulsant drug. From the first days of hospitalization, the child received zovirax 10 mg/kg/time, after establishing etiological factor cytotec 2 mg/kg/single No. 3, dexason 1 mg/kg/day. 5 days, Depakine syrup with 3 days of the disease at a dose of 15 mg/kg/day. with further dose titration to 40 mg/kg/day., from the 11th day of illness - Finlepsin 5 mg/kg/day., diacarb, asparkam, course aktovegin/No. 10, cytoflavin, pantogram in a dose of 50 mg/kg/day., elcar oral dose of 100 mg/kg/day. Recovery of neurological status were gradually: apistatus docked to the 10th day of illness, gamecentral was maintained for 10 days with a gradual regression. On MRI on the 20th day of the disease the pathological lesions and lesions of the changes in the brain tissue was not detected. Mixed hydrocephalus substitution type (X2=0). When re-EEG study on day 10 bole is neither revealed moderate breach medlennovolnovoj activity without irritation (X4=1), focal seizures and apicomplexa (X3=1). To predict the possible development of SCS was calculated by formulas.
In this case, it is obtained that LCF>LCF, therefore, was predicted a favorable outcome. In follow-up observation of the child noted absence seizures within 1.5 years after discharge from the hospital, made the abolition of anticonvulsant therapy under the control routine EEG, seizures do not occur.
The above example shows that, despite the severity of the disease in the acute period, the calculation based on the proposed formula was predicted favorable outcome of the disease, which was confirmed in further clinical and instrumental data.
Example 2. Patient A., 3 months. Diagnosis. Herpetic meningoencephalitis. Symptomatic epilepsy. Ill sharply with rise of temperature up to 38.5, the appearance of loose stools, frequent regurgitation, recurrent vomiting. When admitted to hospital, the child's condition is moderate. In neurological status and focal meningeal symptoms are not identified. On the 2nd day got worse, it was noted the development of secondary generalized seizures with the development of a coma. In neurological status: the level of the new consciousness coma, large Fontanelle size of 2×2 cm will wybodaeth, not pulsing, smoothness nasolabial folds to the right, the eyes narrow, photoreactive absent muscle tone diffuse reduced tendon reflexes of the limbs low S>D, the symptom Babinski from 2 sides of the positive. On the severity of the condition the child was in the ICU for 10 days, coming out of his coma for 6 days (X1=5), IVL - 7 days. To stabilize the performed lumbar puncture: lymphocytosis 256/3 (182 - lymphocytes, 74 - neutrophils), protein 1.2 g/l, CSF PCR allocated DNA of herpes simplex virus type 1-2 (X5=0). CT brain in the acute period of the disease is swelling, a decrease in the density of the brain tissue in the temporal divisions on both sides (X2=1). When conducting EEG on day 2 after coming out of his coma revealed rough diffuse changes in the BEA brain with the presence of focal medlennovolnovoj, paroxysmal activity and expressed irritatio brain structures (X3=3, X4=3). From the first days of inpatient child receives zovirax/drip at a dose of 10 mg/kg/day. within 21 days, anticonvulsant therapy - Depakine 30 mg/kg/day., dexason 1 mg/kg/day.7 days, dehydration therapy, neurometabolic therapy: Actovegin No. 15, pantogram 50 mg/kg/day. - 1.5 months, elcar 100 mg/kg/day. - 1 month. When re-EEG studies remained the mind is i.i.d. disturbances BEA with the presence of focal medlennovolnovoj activity and mild symptoms of irritation of the brain structures. The series of MRI in the convalescence period conducted MRI brain: MP-picture implications of herpetic meningoencephalitis. Cystic glioznogo changes in the temporal lobes on both sides.
To predict the possible development of SCS was calculated by the formula:
Given that LCF<LCF, predicted an adverse outcome of the disease. At discharge from the hospital, the child in the neurological status is a hemiparesis on the left, in spite of anticonvulsant therapy, remain the focal twitching of the facial muscles without breaking the respiratory and cardiovascular activity. During the follow-up observation of the child noted the coarse delayed psycho-motor, speech development, remains a hemiparesis on the left, the child continues to receive combination anticonvulsant therapy on the background of intercurrent diseases marked focal seizures.
Thanks to the application of the proposed method will increase the accuracy of prediction of symptomatic epilepsy in neuroinfections in children. High informative ability of the method to predict the development of SCS increases forecast the development of the adverse outcomes SE, that allows to carry out voltage is allenou duration and volume of neurometabolic therapy to reduce the risk of development of SCS, accordingly, to reduce the duration of hospital stay of patients. This method can be widely used in clinical practice in infectious hospitals, neurology, intensive care units.
A method for predicting the outcome of neuroinfections in children with encephalitis, including determining whether the etiological agent of infection, foci of structural changes on brain MRI, the presence of a coma, evaluation on the encephalogram epileptiform activity, characterized in that it further registration of EEG carried out in the first 5 days after the release of the child from a coma or in the first 10 days of illness in cases without comatose state, evaluate the encephalogram irritative activity and the data obtained are building linear classification functions that are specific to favorable (LCF) outcome of encephalitis without symptomatic epilepsy (SE) and adverse (LCF) outcome of encephalitis with the development of the SCS according to the formula:
LCF=-20,1 to 0.5*X1+4,0*x2+2,1*X3+8,2*X4+10,9*X5
X1 - the presence of a coma in the days, 0 - no;
X2 - foci of structural changes on brain MRI: no 0 points, the presence of - 1 point;
X3 - epileptiform activity: no - 1 point; diffuse sharp waves - 2 points; sharp waves is, adhesions, reduced complexes, high-amplitude paroxysmal slow activity - 3 points; frequent paroxysms complexes "spike-slow wave", "spike-slow wave" - 4 points;
X4 - irritative activity on EEG: no - 1 point; a local non-permanent high-frequency beta activity - 2 points; common volatile low-amplitude high-frequency activity - 3 points; common long-term high-amplitude high-frequency activity - 4 points;
X5 - causative agent the causative agent of the disease: encephalitis, caused by the tick-borne encephalitis virus - 1 point; encephalitis other and unknown etiology - 0 points;
and when LCF>LCF predict the outcome of encephalitis without the development of SCS and when LCF>LCP - an unfavorable outcome of encephalitis with the development of the SCS.
SUBSTANCE: group of inventions relates to field of medicine and can be used for determination of presence of clinically relevant quantity of bacteria in donor blood or tissue. method of detecting bacterial contamination of donor blood, or blood product, or donor tissue from mammal-donor, preserved in liquid, consists in contact of sample to be analysed with a series of generic antibodies, which specifically bind with Gram-negative bacterial antigen and/or Gram-positive bacterial antigen, and detection of binding of the series with the sample. Presence of bacteria in quantity higher than 1×103 CFU of bacteria per ml of sample indicates unsuitability of donor blood, blood product or tissue for transfer to patient, with absence of said quantity of bacterial indicating suitability of donor blood, product or donor tissue for transfer to patient. Group of inventions also relates to version of said method.
EFFECT: group of inventions provides increase of accuracy and acceleration of detection of presence of clinically relevant quantity of infecting bacteria in donor blood, blood products, or in donor tissue.
10 cl, 6 dwg, 9 ex
SUBSTANCE: method for elution is implemented as follows: 10% tularemic, plague or brucellosis magnetic immune sorbent (MIS) 0.1ml is incubated with microbial suspensions of tularemic, plague or brucellosis agents for 30 min; the supernatant is removed; the MIS is incubated with an eluting solution 0.5 ml for 10 min; the eluate pH is reduced to the physiological value; an indirect hemagglutination reaction or a latex agglutination reaction is carried out.
EFFECT: method enables eluting the pathogen from a magnetic immobilised matrix qualitatively to be analysed by serological responses and keeping the antibody functionally active on the magnetic matrix for re-use.
3 ex, 1 tbl
SUBSTANCE: method provides using a solid phase of an influenza virus vaccine for sensitisation, whereas antigen-antibody complexes formed by incubating the sensitised surface of an immunosorbent with a test serum containing the influenza virus antibodies are visualised by means of an optical contrast carbon-protein G conjugate for 10-15 minutes.
EFFECT: producing simple, high-sensitive, operative, clear and reliable diagnostic system for estimating a level of post-vaccine immunity to the influenza virus.
1 ex, 1 dwg
SUBSTANCE: method includes taking into account the following clinical, anamnestic and laboratory parameters (yes/no: presence of menorrhagias, presence of intrauterine surgery in anamnesis, carrying out myomectomy in hysteroscopy, level of alaninaminotransferase and asparagine aminotransferase in blood serum, content of lactobacilli in vaginal microbiocenosis, presence of enterobacteria in vaginal microbiocenosis, content of bifidobacteria in intestine microbiocenosis, presence of Staphylococcus aureus in intestine microbiocenosis, presence of fungi of species Candida in intestine microbiocenosis. data are processed. Each value is given a digital code, and they are substituted into a formula to calculate a risk of development of purulent-inflammatory complications in women with intrauterine pathology after hysteroscopy "Y", which represents the sum of values of codes of the analysed parameters. If the value Y>5, development of infectious-inflammatory complications is predicted. The method makes it possible to predict development of infectious-inflammatory diseases with accuracy up to 89%.
EFFECT: invention makes it possible to increase efficiency of predicting a risk of development of complications.
2 tbl, 2 ex
SUBSTANCE: characterised strain of influenza virus of subtype A/pochard/Siberia/249/08-MA H10N7 is isolated from cloacal elution of pochard and adapted to mice line BALB/c. The strain is deposited in the Collection of viral infections and rickettsioses of Federal budget institution of science "State Research Centre of Virology and Biotechnology "Vector" (under the registration number V-592). The strain has the high antigenic affinity for modern variants of influenza virus of subtype H10 and suitable for production of polyclonal serum for determining belonging of influenza virus to subtype H10, and can also be used as a control reference sample in assessment of specificity of the test systems based on PCR, it has lethality for mice.
EFFECT: possibility to use the strain for the study of antiviral preparations in vivo.
5 tbl, 3 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a subtype B of a human immunodeficiency viral strain, and can be used in virology, medicine and biotechnology. The presented type 1 IV735 human immunodeficiency viral strain is deposited in the State Collection of Viruses of Federal State Institution Ivanovsky Research Institution of Virology of the Russian Ministry of Healthcare and Social Development, No. 1189. The strain possesses a stable reproductive activity. An infectious titre makes 6 lg 50% tissue cytopathic dose.
EFFECT: strain is a handy natural model for studying an antiviral activity of chemopreparations of the new generation, as well as for creating a vaccine.
1 dwg, 3 tbl, 3 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutics. What is created is an immunologically relevant composition inducing an immune response on at least two strains and/or serotypes Streptococcus uberis, containing at least one recovered and/or recombinant protein having a specific amino acid sequence prepared by the method involving transformation of prokaryotic and eukaryotic cells or a microorganism, such as a bacterium, yeast, or fungi, by a nucleic acid construct coding the above protein, a recombinant nucleic acid molecule, a recombinant carrier and/or their immunologically relevant portion, derivative and/or analogue. A method for preparing the immunologically relevant composition. A method for identifying a protein of the bacterium Streptococcus uberis, that induces the immune response to at least two strains and/or serotypes Streptococcus uberis, involving the stages: a) identifying at least a portion of the secreted protein, superficially associated protein and/or protein min. 80% identical to a sequence of the bacterial virulence factor, b) selecting at least one protein identified at the stage a), which persists in at least two strains and/or serotypes Streptococcus uberis, c) determining an ability of at least one protein selected at the stage b) or its immunologically relevant portion, derivative or analogue to bind specifically the antibody and/or immune cells of an animal infected with the first strain and/or serotype Streptococcus uberis, and the antibody and/or immune cells of an animal infected with the second strain and/or serotype Streptococcus uberis. A method for inducing the immune response on at least two strains and/or serotypes Streptococcus uberis. And also a bovine mastitis diagnostic kit containing at least one protein having the specific amino acid sequence, the recombinant nucleic acid molecule, the recombinant carrier and the agents for detecting the antibodies.
EFFECT: using the invention enables inducing the immune response on at least two strains and/or serotypes Streptococcus uberis.
21 cl, 4 dwg, 7 tbl, 12 ex
SUBSTANCE: invention is a method of determining the nonspecific resistance of pathogenic microorganisms to antibiotics and the fact of the presence of bacterial biofilms on the basis of measurement of catalytic activity of phosphodiesterases cleaving the cyclic diguanosine monophosphate, with a threshold sensitivity of 50 pg/ml, comprising: 1) isolating the target-phosphodiesterase from lysed bacterial cells; 2) binding of phosphodiesterase with biotin-conjugated antibodies specific for non-catalytic domains of phosphodiesterase; 3) affinity purification of complexes formed by target-phosphodiesterase and biotin-conjugated antibody using paramagnetic particles containing neutravidin or its analogs that bind biotin; 4) interacting of the complexes of phosphodiesterase/biotin-conjugated antibody, immobilised on paramagnetic particles with complexes containing a-di-GMP in the form of G-quadruplex systems with intercalate dye, which is accompanied by decrease in the intensity while destruction of complexes of intercalate dye with c-di-GMP; 5) measurement of decrease of fluorescence upon hydrolysis with c-di-GMP and destruction of complex of c-di-GMP with intercalate dye, followed by quantitative estimation of the phosphodiesterase activity based on calibration curves made using known amounts of the recombinant enzyme of phosphodiesterase identical to the test target; 6) identification of increased level of phosphodiesterase activity detected by the test antibiotic-resistant bacterial strains capable of biofilm formation, as compared with the level of phosphodiesterase activity that can be detected for the control strains of bacteria of the same species not having the antibiotic resistance and the ability to form biofilms.
EFFECT: method enables to determine the nonspecific resistance of pathogenic microorganisms to antibiotics and to establish the fact of the presence of bacterial biofilms.
4 dwg, 5 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a subtype A human immunodeficiency viral strain, and can be used in virology, medicine and biotechnology. The presented type 1 IV742 human immunodeficiency viral strain is deposited in the State Collection of Viruses of Federal State Institution Ivanovsky Research Institution of Virology of the Ministry of Healthcare and Social Development of the Russian Federation, No. 1187. The strain possesses a stable reproductive activity. An infectious titre makes 6 lg 50% tissue cytopathic dose.
EFFECT: strain is a model for studying an antiviral activity of chemopreparations of new generation, as well as for creating vaccine preparations.
1 dwg, 3 tbl, 3 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a subtype A human immunodeficiency viral strain, and can be used in virology, medicine and biotechnology. The presented type 1 IV710 human immunodeficiency viral strain is deposited in the State Collection of Viruses of Federal State Institution Ivanovsky Research Institution of Virology of the Ministry of Healthcare and Social Development of the Russian Federation, No. 1188. The strain possesses a stable reproductive activity. An infectious titre makes 3.5-4.0 lg 50% tissue cytopathic dose.
EFFECT: strain is a model for studying an antiviral activity of chemopreparations of new generation, as well as for creating vaccine preparations.
1 dwg, 4 tbl, 3 ex
SUBSTANCE: invention refers to biology, medicine, nuclear magnetic resonance (NMR) diagnosing, and can be used for the qualitative assessment of the fat content of a long-length biological object, in particular human's. The method is implemented with the use of a magnetic resonant tomography scanner that provides a multilayer transversal body scanning from one end to the other, with the biological object movable discretely longitudinally at a pitch equal to a scanning layer thickness. The layer size is specified if providing a magnetic field uniformity within this layer. The NMR signal spectra are recorded in layers, and the NMR signal spectra received by the magnetic resonant tomography scanner are summed, while the qualitative assessment of the fat content in the biological object is made by water to fat peak relation in the summed spectra.
EFFECT: invention provides the express analysis and accuracy of the qualitative assessment of the fat content in the long-length biological object, such as a human by better tissue specificity, high sensitivity to recorded signal, high rate measuring and obtaining the spectroscopic data with the use of common typical tomography equipment without the need of MRT imaging, with obtaining the chemical shift data without using the gradient fields, provided the magnetic field uniformity space is inadequate for enclosing the entire biological object with relaxation in the requirements for the number and thickness of the scanned sections.
3 dwg, 1 ex
SUBSTANCE: invention relates to instrumentation and represents a method for magnetic-resonant shaping of images and a system for its implementation. At implementation of the method using a set of radio-frequency transmission coils, some number of B1 field mapping sequences, which is less than the number of coils of the set, is performed; a set of B1 field mapping data is obtained and sensitivities of coils in a basis of the obtained set of B1 field mapping data are determined; with that, the determined coil sensitivities are used for B1 shimming. As per some versions, the performed sequences of B1 field mapping are set by linear conversion as per a set of radio-frequency transmission coils for formation of a set of orthogonal virtual radio-frequency transmission coils and for selection of a sub-set from a set of orthogonal virtual radio-frequency transmission coils, which sets the performed B1 field mapping sequences.
EFFECT: increasing degree of homogeneity of transmitted field B1 either in a non-filled or in a filled state.
14 cl, 7 dwg
SUBSTANCE: method involves performing the magnetic resonance tomography of the right and left temporomandibular joint with the use of a standard coil for the cerebral examination at the magnetic field intensity of 3 T with the closed and wide open mouth. The joint is additionally examined with the sub-open mouth having the lower jaw dropped, but not put forward. The closed-mouth MRT is performed in an oblique sagittal and oblique frontal projection. The MRT is performed in a sagittal projection, if the mouth is opened wide or sub-opened. In each projection in each position of the joint, magnetic resonance tomography is performed for 1 minute at a section thickness of 2 mm and the section clearance of 0 mm.
EFFECT: method provides the comfortable and accessible procedure ensured by no need for using a device for holding the mouth open and a special coil for the temporomandibular examination.
SUBSTANCE: invention refers to medical instrument engineering, represents an integrated system for tracking an intervention device, e.g. a needle or a catheter in an intense magnetic field, and a method for making it, and is applicable in a magnetic resonance imaging (MRI) system for biopsy for the purpose of proper diagnosing of various oncologic diseases. The system comprises an elongated rod with a tip made of a Si-plate, as well as one or more passive LC-chains arranged at the tip section; the LC-chain is made in the form of an inductance-capacitance resonator and arranged above the Si-plate. The magnetic field of the MRI activates the LC-chain and makes it generate vibrations that leads to generation of the secondary magnetic field recognisable by an MRI assembly, so that the LC-chain, as well as the tip section are visible on the MRI imaging.
EFFECT: generating no local heat of the device, making the device visible on the MRI imaging, as well as preventing tissue deformities that provides higher accuracy of the device control.
10 cl, 6 dwg
SUBSTANCE: invention relates to spin magnetic resonance application. A method of performing nuclear magnetic resonance spectroscopy (NMR) a sample under investigation comprises generating nuclear spin magnetic resonance random emission radiations by placing the sample in a NMR magnetic environment; detecting spin resonance random emission radiations from the sample; converting the detected NMR signals for processing; correlating the converted NMR signals to obtain an NMR auto-correlation function; and obtaining spin resonance properties of the sample from the NMR auto-correlation function. To perform nuclear magnetic resonance imaging (MRI) of a sample under investigation, generation of nuclear spin magnetic resonance random emission radiations is performed in a MRI magnetic environment. In a second version of performing NMR, an NMR power spectrum is obtained from the converted NMR signals. Similarly, a second version of performing MRI, an MRI power spectrum is obtained from the converted MRI signals. A method of performing electron spin magnetic resonance (ESR) of a sample under investigation comprises generating spin magnetic resonance random emission radiations by placing the sample in an ESR magnetic environment; detecting spin resonance random emission radiation from the sample as source ESR signals; converting the ESR signals for data processing; correlating the converted ESR signals to obtain an ESR auto-correlation function; obtaining an ESR power spectrum from the ESR auto-correlation function and obtaining electron spin resonance properties or constructing electron spin resonance property images of the sample from the ESR auto-correlation function and/or ESR power spectrum. For the second version of ESR, the ESR power spectrum is obtained from the converted ESR signals and the ESR auto-correlation function is then obtained from ESR power spectrum.
EFFECT: use of the invention improves spectral resolution and safety for patients.
23 cl, 8 dwg
SUBSTANCE: invention refers to medicine, particularly to glioblastoma multiforme diagnostic technique by magnetic resonant tomography (MRT). The technique involves magnetic resonant tomography before and after intravenous administration of a contrast agent. The latter is presented by magnetic nanoparticles of ferric oxide stabilised by a biocompatible polymer and conjugated with monoclonal antibodies to the vascular endothelial growth factor. The particles have a hydrodynamic diameter of less than 150 nm. Magnetic resonant tomography is performed in the Susceptibility Weighted Imaging (SWI) mode providing the susceptibility weighted imaging of the examined region. Glioblastoma multiforme is detected by comparison results of the MR images before and after administration of the contrast agent as shown by low-brightness areas on the MR images.
EFFECT: technique provides higher reliability and information value of diagnosing by increasing a contrast value of the areas corresponding to glioblastoma tissues, its vessels and neoangiogenesis centres.
13 cl, 4 ex, 1 tbl, 1 dwg
SUBSTANCE: invention refers to medicine, namely traumatology, orthopaedics, and can be used for supporting treatment in large joint replacement. That is ensured by determining a volume of involved joint contracture six months before the operation. That is followed by X-ray and magnetic resonant examination of the involved and collateral joints to specify their state. Besides, a quality of the bone tissue is assessed by osteodensitometry. If observing changes in the bone tissue quality, the complex of the drug therapy is added with the preparations Bivalos and Calcemin. A pain syndrome intensity is assessed by the visual analogue scale three months before the operation. That is followed by the complex therapy aiming at optimising the state of extremity joints with added local injection therapy (LIT). That is ensured by preliminary exposing the biologically active periarticular zones in the proximal and distal direction from the involved joint to the focused infrared laser light. A mixture containing solutions of the therapeutic preparations: chondroprotectors, Contrykal, Lidocaine, vitamin B12 is injected into the same zones. Besides, Arthrofoon is administered for the whole preoperative period. If the pain syndrome intensity is less than 4 points, Arthrofoon is administered in a dose of 4 tablets a day. If the intensity value is more than 4 points, the preparation is administered in a dose of 8 tablets a day in a complex with a short course of a non-steroidal anti-inflammatory preparations and a chondroprotector. The replacement operation is immediately followed by fixing a collateral joint with an orthesis for the period of 3 months. The complex of the postoperative supporting therapy started three weeks after the operation is added with a single intravenous introduction of the preparation Aklasta, the preparation Arthrofoon in a dose of 4 tablets a day for three months, alpha calcidole and Calcemin continuously. A pectoral girdle of the extremities is reinforced by means of an individually specified set of therapeutic exercises and electric walking myostimulation. The LIT of the collateral joint is performed three months after the operation. If observing a degenerative process in the adjacent joints, the LIT is performed alternatively in these regions. Vasodilators, chondroprotectors, and the preparation Milgamma are administered with underlying LIT. If observing psychoemotional changes in the patient, the preparation Tenoten is additionally administered. A postoperative medication regimen, including the LIT is repeated 3-4 times every 6 months.
EFFECT: method provides optimising the effect of the surgical management and preventing developing complications both in the operated joint, and in the adjacent and symmetrical joints after the replacement, preventing developing instability of the endoprosthesis components, preventing developing or aggravating degenerative process in the symmetrical and adjacent joints that reduces a risk of the recurrent operations.
SUBSTANCE: technique consists in administering a hormonal preparation followed by magnetic resonance tomography. The hormonal preparation is presented by serotonin administered intravenously slowly or orally thereby promoting a stimulation of pancreatic secretion that leads to increasing a duct diameter, and observing an obstruction in the form of a tumour mass enables visualising and diagnosing the latter.
EFFECT: technique enables the adequate functional study of the pancreas, assessing tumour prevalence, the presence of other growths, providing a differential diagnosis of inflammatory and malignant growths of the pancreas.
2 dwg, 1 ex
SUBSTANCE: invention can be used for differential diagnostics of occluding-stenosing affection of the internal carotid arteries, caused by dissection with the forming intramural hematoma (IMH) or intra-arterial thrombosis of the internal carotid artery. Magnetic-resonance tomography of the neck region is carried out in modes of time-of-flight magnetic-resonance angiography (TF MRA), T1f/s and T2f/s. A zone of changed MR signal from the intramural hematoma (IMH) or intra-arterial thrombus (IAT) of the internal carotid artery is identified on one tomographic section in the axial projection. Intensity of the changed MR signal from IMH or IAT of the internal carotid artery (I1) and intensity of the MR signal from the pterygoid muscle from the same side (I2), are determined; an index of contrast (C) in the zone of the changed MR signal from the internal carotid artery in comparison with the MR signal from the pterygoid muscle from the same side is calculated on their basis by formula: C=(I1-I2)/I2. If the duration of clinical IMH or IAT symptoms is from 1 to 3 days, when the increased MR signal in the T2f/s mode with the contrast index in the range 3.666<C<4.180 is obtained, intra-arterial thrombosis is diagnosed, and if the decreased MR signal in the T2f/s mode with the negative contrast index in the range 0.070<C<-0.099 is obtained, dissection with the forming intramural hematoma is diagnosed. In the terms from 4 days to two months in the TF MRA mode with values of the contrast index in the range -0.006<C<0.13, and in the T1f/s mode in the range 0.3<C<1.89, intra-arterial thrombosis is diagnosed, in case of the increased MR signal in the TF MRA mode in the range 0.3<C<2.15, and in the T1 f/s mode in the range 0.98<C<3.23, dissection with the forming intramural hematoma is diagnosed.
EFFECT: method ensures accuracy of differential diagnostics of the said processes and unambiguous choice of a particular mode of magnetic-resonance angiography for diagnostics of IMH or intra-arterial thrombus in terms from the most acute period to two months.
2 tbl, 3 dwg, 2 ex
SUBSTANCE: invention refers to medical equipment, namely to devices for ultrasonic transurethral therapy of prostate. A sensor compatible with magnetic resonance equipment comprises an axially pivot ultrasonic element, a adjoining rod providing a support for the ultrasonic element and a possibility of pivoting motion together with it, fluid canals enclosed into the rod for the cooling and acoustic contact fluid circulation, an acoustic membrane fixed to enclose the ultrasonic element and retaining the acoustic contact and cooling fluid, and a rigid outer case attached to the acoustic membrane and configured to comprise the ultrasonic element and the rod, and to provide free rotation of the ultrasonic element and the rod in the case so that the ultrasonic element and the rod turns around the outer case and the acoustic membrane. When operating the sensor, it is positioned in a tubular passage so that the acoustically transparent membrane provides acoustic accessibility to a target along the whole circular length of the tubular passage; the target is exposed to the ultrasonic element through the acoustic membrane along the circle of the tubular passage, and the ultrasonic element is cooled down through the fluid canals integrated into the rod. A magnetic resonance visualisation system comprises a magnet generating a static magnetic field within an examination field, a high-frequency transmission coil configured to excite a magnetic resonance and to manipulate the magnetic resonance within the examination field and/or to obtain magnetic resonance data from the examination field, and a sensor.
EFFECT: using the invention enables relieving side effects and providing therapy without physical injuries of surrounding tissues.
14 cl, 10 dwg
SUBSTANCE: invention refers to medicine, namely to neonatology and neurology. During a 300-second slow sleep recording, transitory patterns are recovered on the EEG: frontal sharp waves of an average duration of 0.13 seconds, spike acute waves of an average duration of 0.045 seconds, high-amplitude PTӨ-waves of an average duration of 0.1 seconds, STOP-wave patterns of an average duration of 0.1 seconds. Indices (K) are calculated for each pattern in percentage, as a relation of the number of patterns of 300 seconds multiplied by its average duration to the recording duration (300 seconds). If K of the most patterns determined is less than 1, a physiologic norm is diagnosed; K falling within the range of 1-2 shows a moderate neurophysiologic immaturity; and if K is more than 2, major disturbances of the electrobiologic brain activity are stated.
EFFECT: method enables assessing the electrobiologic brain maturity of newborns of different gestational age that is ensured by determining and considering the transitory age-related patterns in the EEG.
4 dwg, 3 ex