Method of predicting exacerbations of chronic viral hepatitis b in teenagers

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, namely to hepathology and pediatrics. In order to predict exacerbations of chronic viral hepatitis B in teenagers, blood test is performed. By means of bioluminescent method determined is activity of lymphocyte enzymes in peripheral blood of patients: glucose-6-phosphate dehydrogenase (G6PDG) and lactate dehydrogenase (NADN-LDG), ratio of activities is calculated. If value of obtained index is equal or is higher than 1.15 exacerbations are predicted, if index value is lower than 1.15, absence of exacerbations is predicted.

EFFECT: method makes it possible to predict exacerbations of chronic viral hepatitis B in teenagers with clinical-biochemical remission with high accuracy.

4 ex, 2 tbl

 

The invention relates to medicine, namely to Pediatrics and Hepatology, and can be used to predict the clinical course of chronic hepatitis b (CHB) in adolescents.

A known method for predicting acute viral hepatitis by studies of bilirubin in serum and determining the level of serum iron at the peak of bilirubinuria and 7-10 days after it [3]. With increase of level of serum iron in comparison with the initial level predict exacerbation of viral hepatitis. The disadvantage of this method is the prediction of exacerbations only when the protracted course of acute hepatitis. In addition, the method requires repeated blood sampling.

The objective of the invention is the creation of informative method of early prediction of acute exacerbations of HBV in adolescents.

The task carried out due to the fact that using bioluminescent method to determine the enzyme activity of peripheral blood lymphocytes of patients: glucose-6-phosphate dehydrogenase (GPDH) and lactate dehydrogenase (NADH-LDH), calculate the ratio of the activities, and when the value of the resulting measure is equal to or more than 1,15, predict exacerbation, and when the value is less 1,15 predict the absence of attacks.

The value of 1.15 is obtained empirically on the basis of FOSS is the provision of the calculation and the nature of the flow CHB from the surveyed adolescents.

The value of the index, determined by the ratio of activities GFDG and NADH-LDH equal to or more than 1,15 shows a significant outflow of substrates with glycolysis reaction of the pentose-phosphate cycle, which reduces the level of anaerobic processes and reduces the functional activity of lymphocytes.

It is known that lymphocytes that implement basic functions of the specific immune response, are the main cells in the immunological system of supervision and take an active part in the system of anti-infective protection, including viral hepatitis b (HBV) [4]. From the level of functional activity of lymphocytes depends on the outcome of acute infectious diseases and nature of chronic infectious process. At the same time showed that the functional activity of lymphocytes is largely determined by the level of their metabolic processes [6]. Among the indicators, the most objectively reflect the basic parameters of intracellular metabolism, can be attributed dehydrogenase.

Glucose-6-phosphatedehydrogenase (EC 1.1.1.49) is involved in the dehydrogenation of glucose-6-phosphate and coenzyme NADP. Formed during the reaction of 6-phosphogluconic-δ-lactone is unstable and hydrolyzes either spontaneously or with the help of the enzyme 6-phosphogluconolactonase with the education 6-phosphogluconate [1]. GFDG catalyzes the initialization and key reaction in the pentose-phosphate cycle, which is a competitor of glycolysis for the substrate (glucose-6-phosphate). In normal share pentose-phosphate cycle in quantitative conversion of glucose usually small and varies depending on the functional state of the cells.

Lactate dehydrogenase (EC 1.1.1.27) - enzyme of glycolysis, catalyzes the reversible oxidation of lactate to pyruvic acid with participation as a coenzyme NAD+. Lactate dehydrogenase is a key position in the regulation of the cytoplasmic level of NADH/NAD and characterizes the level of the terminal reactions of glycolysis [1].

The method is as follows.

In children, adolescence, patients with CHB, collect venous blood from the cubital vein free current in heparinized tubes. Isolated lymphocytes. Centrifuged on a density gradient ficoll-urografin by the standard method A.Boyum (1968) [5]. Calculate the concentration of lymphocytes, for example, in the camera Goryaeva. When control of the morphological composition of leukocyte suspensions determine the purity of the output of lymphocytes, which is not less than 97%. 1 million allocated cells are used to determine the activities GFDG and NADH-LDH in lymphocytes of one of the known methods, for example, bioluminescent [2]. For this purpose, 150 ál of incubation is MESI, containing the appropriate substrate and cofactor, make 50 μl of the suspension of the destroyed cells. Specific values of the concentrations of substrates and cofactors, as well as pH-defined enzymes are presented in table 1.

Table 1
EnzymeThe substrate, mmCofactor, mmThe PH of the buffer
GFDGGlucose-6-phosphate - 1,5NADP - 0,0259,8
NADH-LDHPyruvate - 0,25NADH - 0,0057,0
Note: an environment with a pH of 9.8 prepared in Tris-HCl buffer (ICN Biomedicals Inc., USA); pH 7.0 - K+, PA+phosphate buffer (the buffer is prepared from a2NRA4and NaH2PO4(Reakhim, Russia).

After incubation of samples tested at 37°C for 30 minutes for GFDG or 5 minutes for NADH-LDH to 200 μl of the incubation mixture are added 50 μl of playmonopolyonline (FMN) in a concentration of 1.5×10-5M, 50 μl of 0.0005% myristic aldehyde and 10 ál of enzyme system NADH: Flexibilityto-Liu is iterate (all reagents bioluminescent system diluted in 0.1 M +Ka+phosphate buffer with pH 7.0). After mixing bioluminescent reagents and incubation of the sample with biochemiluminescence, for example, the brand "BL-8803", measure the luminescence. Given that the cell has a certain number of substrates for the various metabolic reactions, including those catalyzed by the studied enzymes, identify indicators, conventionally called the "substrate background of enzymes". The determination performed in the same conditions as for the above dehydrogenases, but in the incubation mixture instead of the appropriate substrate contribute buffer. In the result of measuring luminescence on bioluminometer get the relative values of activity of the investigated enzymes. To obtain the absolute value of the activity construct graphs of the intensity of bioluminescence on the concentration of NADPH and NADH (calibration). For this, 200 µl of a standard solution of NADPH or NADH in the range of 10-9-10-4M contribute in the cell of bioluminometer containing FMN, maristany aldehyde and NADPH: Flexibilityto-luciferase in the concentrations specified above, then measure the intensity of bioluminescence. Due to the wide range of pH buffers used for determining the dehydrogenase activity and pH-dependence of bioluminescence fermentat the ate system of luminous bacteria, the calibration graphs are built on the basis of the corresponding buffer. The enzyme activity was calculated according to the formula A=Δ[C]×V/T

where A is the activity of dehydrogenase, E 1×104lymphocytes (1E=1 μmol/min [1]);

Δ[C] is the difference of concentrations OVER(f)N in samples of "enzyme" and "background of the enzyme", umol;

V - volume of sample, ml;

T is the incubation time, minutes

Then calculate the ratio of activities GFDG and NADH-LDH (GFDG/NADH-LDH). The value of the derived indicator that is equal to or more than 1,15, shows the development of deterioration, and the value of the parameter is less than 1,15 - about the lack of aggravation.

This method was tested on 34 adolescents, patients with CHB. All patients adolescents at admission to hospital and dynamics through 6 months were examined using conventional laboratory methods of examination. Held: the analysis of peripheral blood, the biochemical analysis of blood to determine the concentration of total bilirubin and its fractions, thymol turbidity tests, alanine transaminase (ALT), aspartic transaminase (ACT) and alkaline phosphatase. Using enzyme immunoassay in serum were determined by specific serological markers HBsAg and anti-HBcIgG. Using the method of polymerase chain reaction in patients was determined by a DNA virus of hepatitis C. the Activity GFDG and NADH-LDH in the blood lymphocytes of adolescents with CHB were determined using biolu inessential method.

According to the results of biochemical blood analysis found that in 22 children and adolescents within 6 months there was no exacerbation of CHB (ALT activity and ACT were within the normal range), 12 - in the range from 3 weeks to 6 months developed exacerbation of CHB (with the re-examination detected increased activity of transaminases in the serum).

All patients found the coincidence of prediction made by the proposed method (table 2).

Table 2
The prognosis of acute exacerbations of HBV
No.Will/will not be exacerbationsThe ratio of activities GFDG and NADH-LDH
1will exacerbation12,31
2will exacerbation18,47
3will exacerbation1,19
4will exacerbation1,60
5will exacerbation1,56
6will exacerbation44,15
7will exacerbationto 2.29
8will exacerbation27,42
9will exacerbationof 3.77
10will exacerbation1,76
11will exacerbation1,24
12will exacerbation30,51
13no exacerbation0,15
14no exacerbation1,13
15no exacerbation0,14
16no exacerbation0,00
17no exacerbation1,14
18 no exacerbation0,79
19no exacerbation0,00
20no exacerbation0,35
21no exacerbation0,14
22no exacerbation1,06
23no exacerbation0,22
24no exacerbation0,27
25no exacerbation1,05
26no exacerbation0,77
27no exacerbation0,39
28no exacerbation0,10
29no exacerbation0,11
30no exacerbation 0,89
31no exacerbation0,00
32no exacerbation0,04
33no exacerbation1,03
34no exacerbation1,04

Clinical example 1. Patient B., age 9 (no history 128), was on routine examination in children infectious diseases ward of the MUSES GKB №20 of them. Iserson Krasnoyarsk with a diagnosis of chronic viral hepatitis b inactive. The child was in the dispensary for 3 years in a medical office hepatocyte MUSES GKB №20 of Krasnoyarsk. From the anamnesis it is known that the girl's mother is also sick with chronic viral hepatitis C. When entering the children's infectious diseases unit, the girl had no complaints.

The results of biochemical tests: bilirubin total of 14.6 µmol/l, ALT of 0.5 mmolc/l (within normal limits), ACT 0.24 mmol×h/l (within normal limits).

In the study of peripheral blood lymphocytes bioluminescent method and the proposed method found that the ratio of activities GFDG and NADH-LDH amounted to 0.14 (example No. 15 of table 2), indicating that nuutste aggravation.

For outpatient examination of the patient in the clinical study of the EMC Hepatology center after 6 months, the activity of ALT ACT was within normal limits.

Clinical example 2. Patient R., age 16 (no history 539)were on treatment at the children's infectious diseases ward of the MUSES GKB №20 of them. Iserson Krasnoyarsk with a diagnosis of chronic viral hepatitis with moderate activity. From the anamnesis it is known that the child received a transfusion of blood at the age of 5 years in connection with surgery. The child is in the dispensary for 5 years in the medical Cabinet of the MUSES GKB №20 of Krasnoyarsk. An examination in an outpatient office hepatocyte identified hyperferritinemia, and the child was sent to the hospital to clarify the nature of the liver and the decision of a question on tactics of treatment. When admitted to hospital, the patient complained of recurrent pain in the abdomen. During the inspection revealed a modest increase in liver (1/3-2 cm-2 cm).

The results of biochemical tests: bilirubin total 11 µmol/l (normal up to 20 µmol/l), ALT 1,6 mmolc/l (above the norm 2.3 times), ACT 0,99 mmol×h/l (slightly above normal).

In the study of peripheral blood lymphocytes under the proposed method found that the ratio of activities GFDG and NADH-LDH amounted to 1.13 (example No. 14 of the who L.2), that indicates no deterioration.

In the control of biochemical analysis blood was decreased bilirubin concentrations and normalization of indicators ALT ACT. On the 23rd day of hospital stay the patient was discharged.

For outpatient examination of a patient in an outpatient office hepatocyte after 6 months, the activity of ALT ACT was kept at normal parameters.

Clinical example 3. Patient D., age 11 (no history 438), was on routine examination in children infectious diseases ward of the MUSES GKB №20 of Krasnoyarsk with a diagnosis of chronic viral hepatitis In, with a minimal degree of activity. The patient is observed for 2 years in medical office hepatocyte MUSES GKB №20 of Krasnoyarsk with a diagnosis of chronic viral hepatitis C. an examination in an outpatient office hepatocyte identified hyperferritinemia, and the child was sent to the hospital to clarify the nature of the liver and the decision of a question on tactics of treatment.

The results of biochemical tests: bilirubin total of 13.4 µmol/l, ALT 0,76 µm×h/l (above the norm), ACT of 0.39 mmol×h/l (within normal limits).

In the study of peripheral blood lymphocytes under the proposed method found that the ratio of activities GFDG and NADH-LDH was 18,47 (sample No. 2 of table 2), indicating that the development is of ostrinia.

On the 16th day of hospitalization the patient was discharged. However, in outpatient examination in an outpatient office hepatocyte 6 months again marked increase in ALT activity and ACT 1.3 times.

Clinical example 4. Patient B., 15 years old (no history 108), was on the examination and treatment at the children's infectious diseases ward of the MUSES GKB №20, Krasnoyarsk with a diagnosis of chronic viral hepatitis b with a high degree of activity. From the anamnesis it is known that the child is observed since 2008 dispensary Cabinet of the MUSES GKB №20 of Krasnoyarsk with a diagnosis of chronic viral hepatitis B. During routine examination, the child was registered with increased ALT activity, and the boy was sent to the hospital.

The results of biochemical tests: bilirubin total of 19.6 µmol/l, ALT 5.2 mmol×h/l (above the norm 7.7 times), ACT 1.2 mmol×h/l (above normal in 2 times).

In the study of peripheral blood lymphocytes under the proposed method found that the ratio of activities GFDG and NADH-LDH was 44,15 (sample No. 6 in table 2), indicating the development of an exacerbation.

On the 28th day of hospital stay the patient was discharged. However, in ambulatory patient in a clinical study after 6 months again marked increase in ALT activity and ACT in 1.6.

The technical result of the proposed method:

probably the th forecast exacerbations of HBV in adolescents with clinical and biochemical remission;

- single fence venous blood;

- high level of coincidence of the forecast.

The proposed method allows to adjust the plan and tactics of treatment on the stages of the dynamic observation and can be recommended for use in clinical practice.

Sources of information

1. Birch CT, Korovkin B.F. Biological chemistry. - M.: Medicine, 1998. - 704 S.

2. Savchenko A.A., Suntsova LN. Highly sensitive determination of the activity of dehydrogenases in peripheral blood lymphocytes of human bioluminescent method // Laboratory work. - 1989. No. 11. - P.23-25.

3. Tomica G.S., Mediannikov O.Y a Method for predicting acute viral hepatitis // Patent RF №2188429 C2, G01N 33/68, G01N 33/84, BIPM No. 6, 27.02.2002.

4. Khaitov R.M P.M., Ignatieva GA, Sidorovich I.G. Immunology. - M.: Medicine, 2000. - 432 S.

5. Boyum A. Isolation of lymphocytes from blood and bone marroow // Scand. J. Clin. Lab. Invest - 1968. - Vol.21 (Suppl. 97). - P.77-80.

6. Jacobs S.R., J.C. Rathmell Lymphocyte selection by starvation: glucose metabolism and cell death // Trends Immunol. - 2006. - Vol.27, No. 1. - P.4-7.

A method for predicting exacerbations of chronic viral hepatitis b in adolescents by examining the blood, characterized in that by using a bioluminescent method to determine the enzyme activity of peripheral blood lymphocytes of patients: glucose-6-phosphate dehydrogenase (GPDH) and lactate dehydrogenase (NADH-LDH), calculate the ratio of activities and p and the value of the derived indicator, equal to or more than 1,15, predict exacerbation, and when the value is less 1,15 predict the absence of exacerbations.



 

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1 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to neurosurgery. Values of 20 prognostic signs, which contain 12 anatomo-anthropometric parameters separately for men and women, 8 immunologic and immunogenetic indices, selected by methods of principal components and expert evaluation, are estimated. By Bayesian algorithm in Genkin-Gubler modification found are corresponding prognostic coefficients: for anthropometric parameters in men with body length: less than 168.6 cm equal +3, from 168.6 to 177.2 cm equal - 1, more than 177.2 cm equal 0; with body weight: less than 67.5 kg equal 0, from 67.5 to 85.9 kg equal - 1, more than 85.9 kg equal +4; with fat fold of hip: less than 8.4 mm equal +19, from 8.4 to 18.3 mm equal -6, more than 18.3 mm equal -6; with fat fold of chest: less than 8.0 mm equal +5, from 8.0 to 17.9 mm equal 0, more than 17.9 equal -3; with girth of shoulder: less than 27.9 cm equal +1, from 27.9 to 33.0 cm equal 0, more than 33.0 cm equal -1; with distal diameter of shoulder: less than 6.6 cm equal -9, from 26.6 to 7.4 cm equal +1, more than 7.4 cm equal +1; with transverse diameter of chest: less than 28.4 cm equal +2, from 28.4 to 33.3 cm equal -1, more than 33.3 cm equal +1. When values of Tenner's index are: less than 93.1 equal -7; from 83.7 to 93.1 equal +3, more than 83.7 equal +6; when values of index of relative width of shoulders is: less than 20.6 equal 0, from 20.6 to 23.5 equal -3, equal -3, more than 23.5 equal +6; when values of index of relative width of pelvis are: less or equal 15.9 equal +6, from 16.0 to 17.9 equal -5, more or equal 18.0 equal -2. When values of Ketle's index are: less than 18.5 kg/m2 equal 0, from 18.5 to 30.0 kg/m2 equal -1, from 25.0 to 30.0 kg/m2 equal -1, more than 30.0 kg/m2 equal +7; for anthropometric parameters in women: with body length: less than 156.5 cm equal 0, 156-165 cm equal 0, more than 164.7 cm equal -1; with body weight: less than 63.7 kg equal -1, from 63.7 to 83.8 kg equal - 1, more than 83.8 kg equal +3; with fat fold of shoulder on the front: less than 11.3 mm equal +1, from 11.3 to 20.6 mm equal -1, more than 20.6 mm equal +2; with fat fold of shoulder on the back: less than 19.6 mm equal +2, from 19.6 to 29.9 mm equal -1, more than 29.9 mm equal +1; with fat fold of hip: less than 14.5 mm equal+19, from 14.5 to 25.2 mm equal -2, more than 25.2 mm equal -11; with girth of hip: less than 55.7 equal +1, from 55.7 to 64.3 cm equal -3, more than 64.3 cm equal +14; with distal diameter of ankle: less than 5.8 cm equal -3, from 5.8-6.8 cm equal +1, more than 6.8 cm equal -1. When values of Rees-Eisenck index are: more or equal 107 equal -3, from 106 to 97 equal +2, less or equal 96 equal +4; when values of index of relative width of shoulders is: less than 20.6 equal +16, from 20.6 to 23.5 equal -5, more than 23.5 equal -6; when values of index of relative width of pelvis are: less or equal 15.9 equal+3, from 16.0 to 17.9 equal -2, more or equal 18.0 equal 0; when values of pelvic-shoulder index is: less or equal 69.9 equal 0, from 70.0 to 74.0 equal -1, more or equal 75 equal 0. When values of Ketle's index are: less than 18.5 kg/m2 equal +3, from 18.5 to 25.0 kg/m2 equal -2, from 25.0 to 30.0 kg/m2 equal-1, more than 30.0 kg/m2 equal +2. For immunologic and immunogenic parameters with relative content of CD3+: less than 67% equal 0, from 67 to 76% equal +1, more than 76% equal 0. With relative content of CD8+: less than 28% equal +4, from 28 to 40% equal -1, more than 40% equal -5. When values of immunoregulatory index (CD4+/CD8+) are: less than 1.2 equal -1, from 1.2 to 2.0 equal +2, more than 2.0 equal +3. When level of IgA is: less than 1.4 g/l equal -1, from 1.4 to 4.2 g/l equal 0, more than 4.2 g/l equal +6; when level of IgM is: less than 0.5 g/l equal 0, from 0.5 to 1.3 g/l equal 0, more than 1.3 g/l equal +1; when level of IgG is: less than 8.0 g/l equal -7, from 8.0 to 16.6 g/l equal 0, more than 16.6 g/l equal +6. When level of CIC is: from 0 to 100 c.u. equal 0, more than 100 c.u. equal +7; with HLA B27 phenotype: HLA B27(+) equal +7, HLA B27(-) equal -7, which are summed up, and if obtained value is +13 and higher, high degree of risk of developing fibrosis in epidural space is predicted, if value is 13 and lower - insignificant risk of development, in cases, when total prognostic coefficient is less than +13 and higher than -13 prognosis is estimated as indefinite.

EFFECT: method makes it possible in preoperative period of standard microdisectomies to determine degree of risk of developing fibrosis in epidural space after surgery of hernias of lumbar intervertebral discs and thus increase efficiency of its prevention.

3 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine and can be used for detecting efficiency of carrying out therapeutic or therapeutically-health-improving measures in passage of patient from pathogenesis to sanogenesis under influence of controlling therapeutic impacts. Measured are values of different diagnostic signs xi, which characterise vector of human organism state (VHOS) x=(x1,x2,…xm)T in m-dimensional phase space of states (PSS). For group of patients as a result of said signs xi measurement obtained is set of points in PSS in form of a "cloud", and for an individual patient carried are several repeated measurements, when patient is in approximately similar physiological conditions and obtained totality of measurements of xi (points in PSS) also, but already for an individual person forms a "cloud" in PSS, which occupies definite region of phase space, designated as quasiattractor (QA). Performed is calculation of parameters of obtained quasiattractor in PSS, namely: volume of Vg of m-dimensional parallelepiped, inside which QA is placed by formula: where values Di=(ximax-Ximin) represent dimensions of sides of parallelepiped with volume Vg, and coordinates Ximax represent extreme "right" point from the set in projection on coordinate axis xi and ximin - extreme "left" point from the same set of coordinates; coordinates of vector xc of the centre C of said m-dimensional parallelepiped from formula where xc=(x1c,x2c,…,xmc)T; index r of asymmetry is determined as a distance between coordinates of chaotic centre in PSS and stochastic centre xis. Said parameters QA for group of patients or for one patient - in case of repetition of measurements - are determined before beginning of carrying out therapeutic or therapeutically-health-improving measures and after expiry of certain time τ. By measurement of Vg, xc and r value conclusion about therapeutic impact efficiency is made. If changes ΔVg, Δxc Δr are small - less than 10% from initial value, decision about low efficiency of therapeutic measure is made.

EFFECT: method makes it possible to estimate quantitatively efficiency of carrying out therapeutic, training-health-improving and other measures, selecting as xi various diagnostic signs.

3 tbl, 5 dwg

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, in particular to low-invasive methods in surgical endocrinology. In order to diagnose pathologically changed parathyroid glands carried out are: fine-needle aspiration puncture biopsy under ultrasonic navigation; washing from aspiration needle with reagent; determination of parathyroid hormone are performed. Washing from needle is carried out with specially prepared "draining serum" from healthy donors with preliminarily known level of parathyroid hormone. Determination of parathyroid hormone level is performed by subtraction of mean arithmetic value of parathyroid hormone of "draining serum" from obtained value of parathyroid hormone in mixture of "draining serum" and contents of aspiration needle. Level of parathyroid hormone at which pathologically changed parathyroid gland is diagnosed is 65 pg/ml and higher or value, higher than is contained in blood serum of said patient.

EFFECT: method increases accuracy of diagnostics of pathologically changed parathyroid glands due to determination in obtained material of parathyroid hormone level with small trauma due to targeted aspiration of contents.

4 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, in particular to toxicology and pharmacology. Reduction of neurologic indices of nervous system functioning: behaviour (B), pharyngeal reflex (PR), tactile-pain sensitivity (PR), flexion reflex of hind limbs (FR), papillary reflex (PR), corneal reflex (CR) is estimated by four-point system. Index of severity of nervous system depression (ISNSD) is calculated by formula: ISNSD= 5*B+4*PR+3*PR+2*FR+2*PR+CR. If ISNSD value is higher than 55 points, state of nervous system functioning is estimated as being within physiological norm, from 46 to 55 points - torpor; from 36 to 45 points - spoor; from 26 to 35 points - moderate coma; from 18 to 25 points - deep coma, 17 points and lower - prohibitive coma.

EFFECT: method makes it possible to increase reliability of determining degree of nervous system depression in case of alcoholic intoxication.

2 tbl, 4 dwg, 4 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

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