Method for prediction of developing myocardial dysfunction in children with acute lymphoblastic leukaemia

FIELD: medicine.

SUBSTANCE: invention may be used to predict a developing myocardial dysfunction in the children with acute lymphoblastic leukemia (ALL) at different stages of polychemotherapy (PCT). The method involves the blood examination for the iron metabolism parameters, namely before the beginning of polychemotherapy (1) and after the induction of remission (2), blood serum ferritin, hepcidin and iron are evaluated in the patients; the derived values are inserted into the equations to calculate varying ECG, IMS, B(E-Ea) NT-pro-BNP after the completion of the intensive PCT course (3) and the total coefficient K is calculated by formula K=ECG3* IMS3* B(E-Ea)3* NT-pro-BNP3, wherein a probability of the myocardial dysfunction is stated by the total coefficient, namely: the coefficient K> 0.24 ensures predicting the developing cardiac complications, while K <0.24 show a lower risk of the cardiac complications.

EFFECT: possibility to detect a risk of the developing myocardial dysfunction accompanying the early PCT by the biochemical parameters, namely in terms of iron metabolism.

1 tbl, 1 ex

 

The present invention relates to medicine, namely to Pediatrics, Hematology and pediatric cardiology, and can be used to predict the development of dysfunction of the myocardium in children with ALL at different stages of chemotherapy.

To the socially significant diseases in children are leukemia, which, accounting for 30-35% of all malignant neoplasms are the second most frequent cause of death in children, second only to the injury (Maschan M.A. et al., 2006 [18]; Karachunskii A.I., 2011) [16]. Acute lymphocytic leukemia accounts for 80% of all leukemias in children (Rumyantsev et al., 2009) [24].

The most serious side effects of polychemotherapy is the development of cardiopathy, leading to the development of progressive myocardial dysfunction and severe heart failure. Contribution to the development of cardiac contribute held polychemotherapy, neoplastic process, against which develop anemia and, as a consequence, Himicheskaya hypoxia.

Anemia leukemia requires substitution gamecomponent therapy (Spichak I.I., 2009) [27]. With each dose of erythromyci the body receives 200-250 mg of iron (M.D. Cappellini, 2011) [1]. Iron loss from the organism occurs mainly through the gastro-intestinal tract: part stands out, along with bile, part - otterhouse epithelium. Also, iron is lost from the epithelium of the skin, hair, urine, and among women of reproductive age with menstrual blood loss. Special mechanisms that displays an excessive amount of iron in the body? there is not, therefore, repeated blood transfusion can lead to an overload of iron in the body (Ganz T., 2011) [4].

It is known that iron overload is a factor that significantly worsens the prognosis of cancer patients (Ruccione for K.S. et al., 2011) [11]. There is evidence that iron overload may not only increase the hepatotoxicity and increase the risk of infectious complications during chemotherapy, but also have a negative impact on survival (Novik A.V., 2009) [21]. Recent studies using MRI (Glanville J. et al., 2006; [5] Chacko J. et al., 2007; [2] E. Konen et al., 2007; [7]) indicate that between the first signs of iron accumulation in the liver and the emergence of iron in the myocardium may take a lot of time. Labile iron in plasma iron, non-transferrin, easy to grab for the tissues, including the myocardium, in which this substance catalyzes the formation of active forms of oxygen. The ability of the ferrous iron to give up electrons, and trivalent to accept electrons, makes it highly toxic, because it acts as a catalyst for the conversion of hydrogen peroxide to highly toxic freedoms is haunted hydroxyl radicals, possessing a damaging effect on cell membranes, proteins and DNA (Jomova K. et al., 2011) [6].

Thus, at present, one of the most important problems of Haematology in connection with the intensity of modern chemotherapy programs requiring massive blood transfusions is iron overload.

Early diagnosis of the initial manifestations of dysfunction of the left ventricle in children with ALL enables us to begin active therapy to prevent life-threatening complications.

In the daily practice of a physician for the diagnosis of cardiovascular diseases is used phonocardiography, electrocardiography (ECG). Method ECG accurate and sensitive, reflects the state of the heart muscle. According to the results of the ECG can detect diseases such as arrhythmia, heart attack, heart failure, heart defects (Okorokov A.., 2002) [23].

Echocardiography (ECHO KG) ultrasound examination of the heart. Using this method it is possible to accurately consider the condition of the heart muscle and valves, to estimate the speed of the blood in the cavities of the heart. The study is absolutely painless, requires no special training, is conducted in the outpatient setting (Okorokov A.N., 2002) [23]. In recent years there has been increased attention to the study of diastolic function of the myocardium, change the texts which are the earliest in the pathophysiology of cardiac hemodynamics (Gosev SF and co-authors., 2007)[15].

With the rapidly approaching death of cardiomyocytes is primarily due to the development of systolic forms of cardiac activity. Slow-onset degenerative changes are accompanied by damage to the myocytes and interstitial (Mazur N.A., 2001) [17], which manifests diastolic disturbances and eventually leads to the appearance of clinical symptoms of diastolic heart failure (Galderisi M, 2005) [3]. Diastolic LV dysfunction is the inability of the left ventricle to take blood under low pressure and be filled without a compensatory increase the pressure in the left atrium (Little W.C. et al., 1995) [8]. By definition DF myocardium you can evaluate the efficiency and in the early stages to identify side effects of various drugs in children. Study and evaluation of diastolic function are widely applied in various clinical situations in childhood and represent an early assessment of the disturbances of the heart and prognosis, as well as provide an indication of the effectiveness of therapy. In foreign and domestic scientific literature in recent years, there are many works studying the possibility of using various diplomaticheskii estimation parameters of diastolic LV function.

For a highly informative, sensitivity is determined as being aparameters includes the index of the stiffness of the myocardium, indicator(E-EA) (Mironov S.A., 2009; [19], Ovchinnikov A.G. et al., 2009; [22] Savisko A.A. et al., 2011; [26]). The increase of these indicators reflects the impaired LV relaxation and indicates reduced elasticity of the myocardium. The stiffness index of the myocardium was calculated as the ratio of the half-time of exile (ET) to the time of maximum flow rate (ATE). Doppler time indicator(E-EA), MS - the time interval between the beginning of the peak early diastolic LV filling (E) and peak amplitude of the reflected signals of the motion corresponding to early diastolic filling of the left ventricle (EA) (Nelson POSTGRADUATE and co-authors., 2012) [20].

Proven highly informative natriuretic peptides in the diagnosis of cardiac dysfunction, even with minimal clinical manifestations (Mair J, 2002) [9]. Natriuretic peptide hormones are involved in many pathological processes, including development-related diseases of the cardiovascular system. BNP (brain natriyureticeski peptide) is neurohormone synthesized in the myocardium of the ventricles, secreted into the bloodstream in response to dilation of the ventricles of the heart and increased load pressure (My G.W., 2006; [10], Weber M. et al., 2006). [12]. Doppler time indicator(E-EA), MS - the time interval between the beginning of the peak early diastolic filling L Is (E) and peak amplitude of the reflected signals movement, appropriate early diastolic filling of the left ventricle (EA)is one of the most regular and early signs of development of heart failure (Andreev D.A., 2003; [13] Sarashina I.A., 2003; [30] Chumanov V.I. et al., 2006; [31] sherbatuk O.V. et al., 2007 [32]). The activation of natriuretic peptides in heart failure is associated with deterioration of intracardiac hemodynamics, namely with increasing pressure in the Atria and the ventricles, and their tension with increasing venous return to the heart, and with increased activity of neurohormones. When epidemiological studies had found a link between the severity of heart failure of different etiology and maintenance of NT-proBNP in plasma, which allowed us to consider its concentration as a "laboratory test" myocardial dysfunction (Mair J, 2002) [9].

While the effectiveness of treatment of cardiac complications depends on early diagnosis of the disease, time of beginning treatment, and therefore the problem of forecasting the development of cardiac complications is always relevant to practitioner.

Earlier joint work (Savisko A.A. et al., 2011; [26] Teplyakova DU et al., 2011 [29]; Tarasova N.E. et al., 2012 [28]; Nelson POSTGRADUATE et al., 2012 [20]) were determined optimal positive criteria for Doppler indices is diastolicheskoe dysfunction, such as the index of the stiffness of the myocardium, the time index In(E-VA); and a precursor of brain natriuretic peptide NT-proBNP as informative markers of cardiac complications. The excess values of the optimal positive criterion allows us to state the development of the early dysfunction of the myocardium.

From the patent literature known method for diagnosis of cardiotoxicity in patients negotiationscome lymphomas in the process of chemotherapy. According to the present method of conducting studies of the cardiovascular system: the ECHO-KG, daily ECG monitoring before and after chemotherapy. Additionally carry out the determination of leukocyte chemiluminescence, antipersonnel activity of plasma malondialdehyde source and in the process of chemotherapy, followed by assessment of the probability of development the degree of cardiotoxicity in patients depending on the degree of increasing the level of chemiluminescence, lipid peroxidation and reduced antioxidant protection.

(See the application for invention No. 2006109604, publ. 10.10.2007; CL G01N 33/48)

The disadvantages of this method is the following: it is used in patients with lymphoma, does not account for possible transfusion therapy transfusion and iron overload, and effects on the myocardium of toxic action.

For proto the Fe adopted our article "Evaluation of indicators of iron metabolism and dysfunction of the myocardium at different stages of chemotherapy in children with acute lymphoblastic leukemia / Petrasova, Adephagia, Avishalom etc. // pediatric diagnostics. - 2011. - V.3, №6. - C.11-17 [28].

In this work revealed that the syndrome of iron overload, defined in children with ALL with the help of research in serum iron, ferritin, combined with the formation of diastolic dysfunction of the myocardium and increase in the content marker of heart failure NT-proBNP.

However, diagnostically significant increase of indexes of diastolic dysfunction in carrying out dopplerechocardiography and precursor of brain natriuretic peptide detected in the blood of patients after intensive chemotherapy. This method does not allow to predict the development of dysfunction of the myocardium in the initial stages of chemotherapy for preventive (prophylactic) treatment measures that prevent the development of life-threatening conditions. These facts create the preconditions for finding new, available in pediatric practice indicators vysokonapryazhennyh with the early formation of cardiac complications in children with acute lymphoblastic leukemia when conducting chemotherapy, receiving blood transfusion.

The technical result of the invention is the possibility to detect in the initial stages PCT risk of dysfunction of the myocardium p. the biochemical parameters, namely indicators of iron metabolism.

This object is achieved in that a method for predicting the development of dysfunction of the myocardium in children with acute lymphoblastic leukemia (ALL) includes the study of blood indices of iron metabolism in the course of intensive polychemotherapy (PCT).

In accordance with the invention prior to chemotherapy (1) and after the induction of remission (2) determine the content of ferritin, hepcidin and iron in the serum of patients, substitute the identified values in the equations for calculating the changes of the ECG, EGM, IN(E-EA)NT-pro-BNP after intensive chemotherapy (3) and calculate total factor K by the formula K=ACG*IGM*(E-EA)3* NT-pro-BNP3, the probability of dysfunction of the myocardium is judged by the size of the total factor, namely, when the value of the coefficient K>0,24 predict the development of cardiac complications, when K<0.24 to low risk of cardiac events.

The change of parameters: ECG, EGM, Doppler index(E-EA)and the rate of increase of the precursor of brain natriuretic peptide NT-pro-BNP calculated from the following equations:

EKG=0,667629+(-0,000278)*ferritin+0,000399*hepcidin+(-0,000773)*jelezo+0,000552*ferritin+(-0,001144)*hepcidin+(-0,011576)*jelezo

The stiffness index myocard=0,25566+0,000527*ferritin+0,000281*hepcidin+0,005374*jelezo+(-0,000306)*ferritin+0,001773*hepcidin+(-0,002155)*jelezo

B(E-Ea)3=0,537484+(-0,000077)*ferritin+0,000073*hepcidin+0,006246*jelezo+0,000362*ferritin+(-0,001406)*hepcidin+(-0,000516)*jelezo

NT-pro-BNP3=0,244+0,0003*ferritin+0,0003*hepcidin+0,018*jelezo+(-0,0003)*ferritin+0,001*hepcidin+(-0,001)*jelezo;

where the numbers 1,2,3 denote the phases of the PCT.

ECG is the factor a high value (more than 0.7) indicates a high risk of developing electrocardiographic dysfunction of the myocardium at the 3rd stage of treatment, i.e. after conducting a PCT.

Similarly, IIMS and(E-EA)3 - estimated coefficients, also if the value is above 0.7 which speak of the risk of development of diastolic dysfunction at stage 3.

NT-pro-BNP3 - coefficient whose value is 0.7 and above indicates a high probability of development of heart failure in children with ALL to the end of PCT. This value, calculated using indicators ferrokinetic, by multiplying by the factor determined using the conducted regression analysis on the basis of a previously run analysis correlation, a correlation between cardiac complications and indicators of iron metabolism. They show the risk of disorders of the myocardium. In the present invention are expected to increase by biochemical parameters determined in the early stages of treatment, namely in terms of iron metabolism.

predelay in pre-course chemotherapy (1), and after completion of induction therapy (2) indicators of iron metabolism and getting a total price that is higher than 0,24, it is possible to predict the development of cardiac complications in children with acute lymphoblastic leukemia and start early preventive measures aimed at preventing the development of cardiovascular complications at the stage of completion of an intensive course of chemotherapy. However, if the ratio is below 0,24, additional preventive measures in this category of patients is not required.

Using the method of multiple regression (Borovikov V.) [14] was used to build the model for prediction of cardiac complications in children with ALL during an intensive course of chemotherapy taking into account the level of ferritin, hepcidin and iron in disease onset and after the induction of remission.

The model includes 4 equations showing ECG abnormalities (homotopie disorders of automaticity in the compartment with impaired repolarization of the myocardium), the increase of the stiffness index of the myocardium (>0.47 services. units), increasing the Doppler index(E-EA)(>28 MS) and growth precursor of brain natriuretic peptide NT-proBNP (>28 PG/ml).

To calculate the probability of developing cardiac complications in a patient-specific values of individual indicators ferritin, hepcidin and iron serum must be substituted into equation 4 and get 4 values of the coefficient for calculating the probability of the occurrence of cardiac events immediately following 4 signs you need to use the multiplication theorem of probability from the probability theory. Four values of the probabilities calculated by the four equations must be multiplied. If the result of the multiplication will be more 0,24 (0,7*0,7*0,7*0,7), this fact, taking into account all indicators indicates a high probability of cardiac complications during chemotherapy in a patient.

The values of the coefficients in equation multiple regression model to calculate the probability of developing cardiac complications are presented in table 7.1.

Table 7.1
The coefficients for the calculation of the probability model of development disorders myocardial function in children with ALL during PCT
BaselineConditional reductionThe ranking symptomThe coefficient ECG (K1)The coefficient of stiffness index infarction (K2)Factor(E-EA)(K3)The ratio of NT-proBNP (4)
Free--0,670,260,54 0,24
member of the equation
Ferritin 1AFAng/ml-0,00030,0005-0,000080,0003
Hepsidin 1A11ang/ml0,00040,00030,000070,0003
Iron 1AGAµmol/l-0,00080,0050,0060,02
Ferritin 1BFBng/ml0,0006-0,00030,0004-0,0003
Hepsidin 1BGBng/ml-0,0010,002 -0,0010,001
Iron 16GBµmol/l-0,012-0,002-0,0005-0,001

Tototal=K1*2*3*4,

Where K1possible development of ECG disorders, including homotopy disorders of automaticity and abnormalities of repolarization of the myocardium,

K2- possible increase of the stiffness index of the myocardium over 0.47 services. unit,

To3- increasing Doppler index(E-EA)more than 28 MS,

To4- the growth of the precursor of brain natriuretic peptide NT-proBNP over 28 PG/ml

K1=0,667629+(-0,000278)*ferritin+0,000399*hepcidin+(-0,000773)*jelezo+0,000552*ferritin+(-0,001144)*hepcidin+(-0,011576)*jelezo

K2=0,255366+0,000527*ferritin+0,000281*hepcidin+0,005374*jelezo+(-0,000306)*ferritin+0,001773*hepcidin+(-0,002155)*jelezo

K3=0,537484(-0,000077)*ferritin+0,000073*hepcidin+0,006246*jelezo+0,000362*ferritin+(-0,001406)*hepcidin+(-0,000516)*jelezo

K4=0,244+0,0003*ferritin+0,0003*hepcidin+0,018*jelezo+(-0,0003)*ferritin+0,001*hepcidin+(-0,001)*jelezo

The method is as follows. If diagnosed with acute lymphoblastic leukemia in a patient before the start of chemotherapy is determined by the level of si is orode blood ferritin, hepcidin and iron. After the induction of remission in a patient, you must re-determine the content of ferritin, hepcidin, iron serum.

The stages of the study:

1. Blood sampling is carried out veins of the child in the amount of 2.0 ml, centrifuged for 10 minutes at a speed of 3000 rpm to obtain serum.

2. The serum iron concentration is determined in 0.1 ml of serum by colorimetric method without deproteinization using a set of reagents "Iron-Vital"Vital Diagnostics, St. Petersburg, Russia.

3. The concentration of serum ferritin determine in 0.02 ml of serum enzyme-linked immunosorbent assay using test systems "Ferritin-ELISA-BEST" (Russia).

4. The concentration hepcidin determine serum in 0.05 ml of serum enzyme-linked immunosorbent assay using test systems "Hepcidin-25 (human)Peninsula Laboratories, USA.

5. Further in accordance with the invention for calculating the probability of developing cardiac complications in a patient-specific values of individual indicators ferritin, hepcidin and iron serum substitute in equation 4.

K1=0,667629+(-0,000278)*ferritin+0,000399*hepcidin+(-0,000773)*jelezo+0,000552*ferritin+(-0,001144)*hepcidin+(-0,011576)*jelezo

K2=0,255366+0,000527*ferritin+0,000281*hepcidin+0,005374*jelezo+(-0,000306)*ferritin+0,001773*hepcidin+(-0,002155)*VC is so

K3=0,537484(-0,000077)*ferritin+0,000073*hepcidin+0,006246*jelezo+0,000362*ferritin+(-0,001406)*hepcidin+(-0,000516)*jelezo

K4=0,244+0,0003*ferritin+0,0003*hepcidin+0,018*jelezo+(-0,0003)*ferritin+0,001*hepcidin+(-0,001)*jelezo

6. To calculate the probability of the occurrence of cardiac complications immediately by 4 features four values of the probabilities calculated by the four equations must be multiplied. Cobs.=K1*K2*K3*K4

7. If the total factor up to 0.24, it is taking into account all indicators indicates a high probability of cardiac complications in patients with PCT.

The proposed method in a comparative perspective examined a control group of 35 children, matched for age and sex, and the group of 24 children with acute leukemia, ages 3 to 17 years who are receiving treatment at the children's hospital GBOU VPO Rostov state medical University and the Department of Hematology and Oncology, chemotherapy GBU RO "Regional children's hospital. These children had been diagnosed with acute lymphoblastic leukemia (ALL). Children received polychemotherapy according to the Protocol ALL-MB-2008. The study was conducted in the following stages of chemotherapy: prior chemotherapy (1); after the induction of remission (2); after intensive chemotherapy (3). All surveyed held electrocardiography in 12 standard leads alone complex transtor the local Doppler echocardiography (DeJong).

The essence of the proposed method is illustrated in the following clinical example.

Child Days, 5 years. Diagnosis: Acute lymphoblastic leukemia, B-III-immunophenotype, L-1 type, standard risk Protocol (ALL-MB-2008). At the onset of disease (1) the iron content of the blood serum of 45.2 mmol/l, serum ferritin 927,4 PG/ml, hepcidin serum 95,7 ng/ml After the induction of remission (2) the iron content of the blood serum of 17.9 μmol/l, serum ferritin 1384,9 PG/ml, hepcidin serum 69,7 ng/ml.

EKG=0,667629+(-0,000278)*927,4+0,000399*95,7+(-0,000773)*45,2+0,000552*1384,9+(-0,001144)*69,7+(-0,011576)*17,9=0,89

The stiffness index myocard=0,255366+0,000527*927,4+0,000281*95,7+0,0005274*45,2+(-0,000306)*1384,9+0,001773*69,7+(-0,002155)*17,9=0,67

B(E-Ea)3=0,537484+(-0,000077)*927,4+0,000073*95,7+0,006246*45,2+0,000362*1384,9+(-0,001406)*69,7+(-0,000516)*17,9=1,1

NT-pro-BNP3=0,244+0,0003*927,4+0,0003*95,7+0,018*45,2+(-0,0003)*1384,9+0,001*69,7+(-0,001)*17,9=1,0

Cobs.=0,89*0,67*1,1*1,0=0,66

The forecast high risk of dysfunction of the myocardium after an intensive course of chemotherapy.

During examination of the child after an intensive course of chemotherapy in a child identified symptoms of arterial dystonia, and the expansion of the heart to the left. ECG: Sinus tachycardia. Violation of intraventricular conduction. When assessing diastolic function of the myocardium of the left ventricle revealed an increase of the stiffness index of the myocardium (above optimum positive criterion ,47 c.u) - 0,7 used, increasing dopplerographical indicator(E-EA) (above optimum positive criterion 28 MS - 50 MS, the increase of the precursor of brain natriuretic peptide NT-proBNP (above optimum positive criterion 28 PG/ml) 169, 5mm PG/ml.

Conclusion. The forecast for the claimed method was confirmed.

Advantages of the method

1. The possibility of forecasting dysfunction of the myocardium in the conduct of chemotherapy in children with acute lymphoblastic leukemia.

2. Prediction of the outcome of the pathology on 3 parameters, taken twice.

3. For analysis requires a small amount of blood (2.0 ml).

4. Provides substantial assistance in the choice of tactics of conducting the patient. With a high probability of development of myocardial dysfunction (total factor up to 0.24) of the child should be included in the risk group for the development of cardiac complications.

5. Allows timely treatment and preventive measures and to improve the outcomes of dysfunction of the myocardium.

A method for predicting the development of dysfunction of the myocardium in children with acute lymphoblastic leukemia (ALL), including a study on blood indices of iron metabolism in the course of intensive polychemotherapy (PCT), characterized in that it is about the beginning of the PCT (1) and after the induction of remission (2) determine the content of ferritin, hepcidin and iron in the serum of patients, substitute the identified values in the equations for calculating the changes of the ECG, EGM, (E-EA), NT-pro-BNP after intensive chemotherapy (3) and calculate total factor K by the formula K=ECGS·IIS·(E-EA)3·NT-pro-BNP3,
where the change of parameters: ECG, EGM, Doppler indicator (E-EA), and the rate of increase of the precursor of brain natriuretic peptide NT-pro-BNP calculated from the following equations:
EKGS=0,667629+(-0,000278)·ferritin+0,000399·hepcidin+(-0,000773)··jelezo+0,000552·ferritin+(-0,001144)·hepcidin+(-0,011576)··jelezo;
The stiffness index of the myocardium 3=0,255366+0,000527·ferritin+0,000281··hepcidin+0,005374·jelezo+(-0,000306)·ferritin+0,001773·hepcidin+(-0,002155)·jelezo;
In (E-Ea)3=0,537484+(-0,000077)·ferritin+0,000073 ·hepcidin+0,006246·jelezo+0,000362·ferritin+(-0,001406)·hepcidin+(-0,000516)·jelezo;
NT-pro-BNP3=0,244+0,0003·ferritin+0,0003·hepcidin+0,018·jelezo+(-0,0003)·ferritin+0,001·hepcidin+(-0,001)·jelezo;
where the numbers 1, 2, 3 denote the stages of chemotherapy, the likelihood of dysfunction of the myocardium is judged by the size of the total factor, namely, when the value of the coefficient K>0,24 predict the development of cardiac complications, when K<0.24 to low risk of cardiac events.



 

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FIELD: medicine.

SUBSTANCE: method involves the blood serum analysis both by infrared spectroscopy, and by gas chromatography, and what is analysed by infrared spectroscopy is a blood sample to be dried, ground and suspended in Vaselin oil, then an IR spectrum of the prepared sample is recorded in the 1200-1000 cm-1, then the absorption band peak heights with maxima at 1170, 1165, 1160, 1150, 1140, 1130, 1125, 1100, 1070, 1050, 1040, 1025 cm-1 are measured, and the relations are calculated. These IR spectroscopy and gas chromatography data are used to draw a spectral characteristic curve as a function of the Fourier variable (p), and the maximum spectral characteristic as above +0.25 within the range of the Fourier variables 3.075 to 3.225, and/or provided the curve intersects the derived spectral characteristic of +0.65 within the range of the Fourier variables 6.2478 to 6.2495, and/or the curve does not intersect derived spectral characteristic of +0.65 within the range of the Fourier variables 6.2300 to 6.2440, vibration sickness is diagnosed.

EFFECT: method has high accuracy and requires no high material costs and allows diagnosing vibration sickness both in hospitals, and in clinics.

3 dwg, 3 ex

FIELD: medicine.

SUBSTANCE: what is presented is a method for assessing the suitability of a donor cornea for transplantation, including PCR diagnosis of infectious agents. Donor cornea tissue is examined for herpes virus (HSV1, 2, EBV, HHV-6, 7) DNA. If observing the presence of viral DNA in the donor cornea, it is considered to be unsuitable for transplantation.

EFFECT: method enables improving the effectiveness of penetrating keratoplasty and reducing a risk of developing transplant disease related to herpes infections.

1 tbl, 5 ex

FIELD: medicine, hepatology.

SUBSTANCE: one should detect the level of hepato-specific enzymes (HSE) in blood plasma, such as: urokinase (UK), histidase (HIS), fructose-1-phosphataldolase (F-1-P), serine dehydratase (L-SD), threonine dehydratase (L-TD) and products of lipid peroxidation (LP), such as: dienic conjugates (DC), malonic dialdehyde (MDA). Moreover, one should detect the state of inspecific immunity parameters, such as: immunoregulatory index (IRI) as the ratio of T-helpers and T-suppressors, circulating immune complexes (CIC). Additionally, one should evaluate the state of regional circulation by applying rheohepatography (RHG), the system of microhemocirculation with the help of conjunctival biomicroscopy (CB) to detect intravascular index (II). In case of increased UK, HIS levels up to 0.5 mcM/ml/h, F-1-P, L-SD, L-Td, LP products, CIC by 1.5 times, higher IRI up to 2 at the norm being 1.0-1.5, altered values of regional circulation, increased II up to 2 points at the norm being 1 point, not more one should diagnose light degree of process flow. At increased level of UK, HIS up to 0.75 mcM/ml/h, F-1-P, L-SD, L-TD, LP products, CIC by 1.5-2 times, increased IRI up to 2.5, altered values of regional circulation, increased II up to 3-4 points one should diagnose average degree of process flow. At increased level of UK, HIS being above 0.75 mcM/ml/h, F-1-P, L-SD, L-TD, LP products, CIC by 2 and more times, increased IRI being above 2.5, altered values of regional circulation, increased II up to 5 points and more one should diagnose severe degree of process flow.

EFFECT: higher accuracy of diagnostics.

3 ex

FIELD: medicine, infectology, hepatology.

SUBSTANCE: in hepatic bioptate one should detect products of lipid peroxidation (LP), such as: dienic conjugates (DC), activity of antioxidant enzymes, such as: catalase (CAT)and superoxide dismutase (SOD). One should calculate by the following formula: C = DC/(SOD x CAT)x100, where DC - the content of dienic conjugates, SOD - activity of superoxide dismutase, CAT - activity of catalase. At coefficient (C) values being above 65 one should predict high possibility for appearance of cirrhosis, at 46-645 - moderate possibility and at 14-45 -low possibility for appearance of cirrhosis.

EFFECT: higher accuracy of prediction.

3 ex

FIELD: medicine, clinical toxicology.

SUBSTANCE: at patient's hospitalization one should gather the data of clinical and laboratory values: on the type of chemical substance, patient's age, data of clinical survey and laboratory values: body temperature, the presence or absence of dysphonia, oliguria being below 30 ml/h, hemoglobinuria, erythrocytic hemolysis, exotoxic shock, glucose level in blood, fibrinogen and creatinine concentration in blood serum, general bilirubin, prothrombin index (PTI), Ph-plasma, the state of blood clotting system. The state of every sign should be evaluated in points to be then summed up and at exceeding the sum of points being above "+20" one should predict unfavorable result. At the sum of "-13" prediction should be stated upon as favorable and at "-13" up to "+20" - prediction is considered to be doubtful.

EFFECT: higher accuracy of prediction.

2 ex, 3 tbl

FIELD: medicine, juvenile clinical nephrology.

SUBSTANCE: disease duration in case of obstructive pyelonephritis should be detected by two ways: either by detecting the value of NADPH-diaphorase activity, as the marker of nitroxide synthase activity in different renal department and comparing it to established norm, or by detecting clinico-laboratory values, such as: hemoglobin, leukocytes, eosinophils, urea, beta-lipoproteides, lymphocytes, neutrophils, the level of glomerular filtration, that of canalicular reabsorption, urinary specific weight, daily excretion of oxalates, arterial pressure, and estimating their deviation against average statistical values by taking into account a child's age.

EFFECT: higher efficiency of detection.

7 dwg, 1 ex, 6 tbl

FIELD: clinical medicine, pulmonology.

SUBSTANCE: one should carry out complex estimation of interleukin-1β) concentration in blood, saliva, bronchoalveolar liquid. Moreover, one should detect distribution coefficient (DC) for IL-1β as the ratio of IL-1β blood content to IL-1β salivary content. At increased IL-1β blood content by 10 times and more, by 2 times in saliva, unchanged level of bronchoalveolar IL-1β, at DC for IL-1β being above 1.0 one should predict bronchial obstruction. The method enables to conduct diagnostics of the above-mentioned disease at its earlier stages.

EFFECT: higher efficiency of prediction.

2 tbl

FIELD: medicine, diagnostics.

SUBSTANCE: the present innovation deals with genetic trials, with diagnostic field of oncological diseases due to analyzing DNA by altered status of gene methylation that take part in intracellular regulation of division, differentiating, apoptosis and detoxication processes. One should measure the status of methylation in three genes: p16, E-cadherine and GSTP1 in any human biological samples taken out of blood plasma, urine, lymph nodes, tumor tissue, inter-tissue liquid, ascitic liquid, blood cells and buccal epithelium and other; one should analyze DNA in which modified genes of tumor origin or their components are present that contain defective genes, moreover, analysis should be performed due to extracting and purifying DNA out of biological samples followed by bisulfite treatment of this DNA for modifying unprotected cytosine foundations at keeping 5-methyl cytosine being a protected cytosine foundation followed by PCR assay of bisulfite-treated and bisulfite-untreated genes under investigation and at detecting alterations obtained according to electrophoretic result of PCR amplificates, due to detecting the difference in the number and electrophoretic mobility of corresponding fractions at comparing with control methylated and unmethylated samples containing normal and hypermethylated forms of genes one should diagnose oncological diseases. The method provides higher reliability in detecting tumors, detection of remained tumor cells after operation.

EFFECT: higher efficiency of therapy.

1 cl, 3 dwg, 4 ex

FIELD: medicine, gastroenterology.

SUBSTANCE: one should carry out diagnostic studying, moreover, on the 5th -6th d against the onset of exacerbation in case of gastric and duodenal ulcerous disease one should detect the content serotonin, histamine and acetylcholine in blood, then during 2-3 wk one should conduct medicinal therapy to detect serotonin, histamine and acetylcholine level in blood again and at serotonin content being by 2-3 times above the norm, histamine - by 1.15-1.4 times above the norm and acetylcholine - by 20-45% being below the norm one should predict the flow of gastric and duodenal ulcerous disease as a non-scarring ulcer.

EFFECT: higher accuracy of prediction.

3 ex

FIELD: medicine.

SUBSTANCE: method involves taking blood from ulnar vein (systemic blood circulation) and from large vein of the injured extremity proximal with respect to lesion focus (regional blood circulation). Spontaneous NST-test value is determined and difference is calculated in systemic and regional blood circulation as regional-to-systemic difference. The difference value is used for predicting clinical course of pyo-inflammatory disease in extremities.

EFFECT: high accuracy of diagnosis.

4 cl, 2 tbl

FIELD: medicine, gastroenterology.

SUBSTANCE: one should introduce biologically active substance, moreover, in patient's blood serum one should detect the content of acetyl choline and choline esterase activity followed by 2-h-long intragastric pH-metry at loading with biologically active substance as warm 40-45%-honey water solution at 35-40 C, and at increased content of acetyl choline being above 1.0 mM/l, choline esterase being above 0.5 mM/l/30 min and pH level being 6.0-6.9 it is possible to consider apitherapy to be useful for treating ulcerous duodenal disease.

EFFECT: higher efficiency and accuracy of detection.

3 ex

FIELD: medicine, gastroenterology.

SUBSTANCE: it has been suggested a new method to detect pharmacological sensitivity to preparations as acidosuppressors. After the intake of the preparation a patient should undergo fibrogastroduodenoscopy 3 h later, then, through endoscopic catheter one should introduce 0.3%-Congo red solution intragastrically and the test is considered to be positive at keeping red color that indicates good sensitivity to the given preparation, and in case of dark-blue or black color the test is considered to be negative that indicates resistance to this preparation. The suggested innovation widens the number of diagnostic techniques of mentioned indication.

EFFECT: higher efficiency of diagnostics.

2 ex

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