Method for predicting efficiency of interferonotherapy at chronic hepatitis b

FIELD: medicine, gastroenterology.

SUBSTANCE: one should detect TNF-α content in blood serum and IFN-γ synthesis by mononuclear cells in vitro before and 4.5 h after the first injection of interferon-preparation for a patient. At detecting TNF-α content in blood serum before injection not exceeding 59.31 pg/ml, and at the increase of TNF-α level after the first injection of interferon- being above 46.1 % and IFN-γ synthesis being above 70.25% against initial data one should predict high efficiency of interferonotherapy in the course of a 6-mo-long interferonotherapy. At TNF-α content in blood serum being above 74.51 pg/ml and increased TNF-α values not more than 24.9%, and IFN-γ - not more than 70% or their decrease after the first injection of interferon- it is possible to predict the absence of virological response, that is insufficient efficiency of interferonotherapy. Application of the method suggested enables to predict the results of interferonotherapy in case of chronic viral hepatitis B just after the first injection of interferon- preparation.

EFFECT: higher efficiency of prediction.

2 ex, 1 tbl

 

The invention relates to medicine, namely to a gastroenterologist.

The creation of a reliable prognostic criteria for the effectiveness of treatment of chronic viral hepatitis (hug) because of the high cost of antiviral drugs, in particular interferon is an important practical task. In addition, interferon therapy HCG even In circuits using active therapy gives not more than 40-50% of cases of virologic response, characterized by a large number of adverse effects [1].

A retrospective meta-analysis showed that the probability of response hug In the interferon therapy is correlated with some clinical, biochemical and serological characteristics. Favorable prognostic criteria for positive response to interferon therapy include: 1) low level of HBV-DNA in serum; 2) high levels of serum aminotransferases; 3) an active process detected by histological examination of the liver and limited fibrosis; 4) the short duration of the disease; 5) absence of other diseases and complications of the type of renal failure, HIV infection, HDV infection or immunosuppression [2-10].

As signs, conducive to the successful treatment are considered: young age of the patients, the HBV infection in adults, infection with wild virus strain (Nomologically cases), the normal level γ-glutamyltranspeptidase, heterosexual orientation of the patient, parenteral virus infection, no biochemical signs of cholestasis, mild autoimmune component of inflammation, female patients, the dose of injected interferon for at least 5 ME 3 times a week for a period of not less than 4 months. Cytolytic crisis that develops in a patient within the first 12 weeks of treatment with interferon, also is a harbinger of good response to treatment [11-18].

The success of the treatment is considered to be questionable in some cases with a set of characteristics specified opposite, as well as in patients with viral DNA and DNA polymerase without HBeAg and at a concentration of HBV DNA above 200 PG/ml Therapy with interferon-α because of low efficiency and a large number of adverse effects is not recommended for patients with normal level of serum aminotransferases, with end-stage liver disease or with severe comorbidity (failure of kidney function, severe immune deficiency. However, as rightly indicated, none of these factors or their combination did not predict remission in particular patient[6, 16, 19].

As you can see, most of the presented criteria are among the factors response belonging to the patient, and are mainly qualitative (is-h is t) parameters.

The disadvantages of this and other methods listed above prediction is clear:

- high cost and complexity of a method of determining the concentration of HBV DNA;

- absence for most of the criteria of signs, simultaneously taking into account the characteristics and patient, and virus;

- the ability to measure viral load to spontaneous fluctuations during the day, at different levels of physical activity, sun exposure, alcohol;

- underestimation of the form of HBV in a patient ("wild" or HBe-negative mutant)with different prognostic characteristics.

Some of the prognostic methods of the effectiveness interferonoterapii patients hug also have drawbacks. This is the difficulty of assessing the timing and routes of infection, the difficulty of assessing the degree of liver fibrosis (the need to perform invasive technique of liver biopsy), the time lag, the evaluation of such a prognostic indicator as cytolytic crisis.

The problem of development available for practical healthcare institutions in the method for predicting the effectiveness interferonoterapii in chronic viral hepatitis b, allowing to judge the probable results of the treatment after the first injection of interferon-α.

The essence of the method lies in the fact that serum and mononuclear cells of the peripheral the maternal blood, taken before and after the first introduction of patient drug interferon-α in therapeutic doses, respectively define the content of tumor necrosis factor-α (TNF-αand synthesis in vitro interferon-γ (IFN-γ) - secreted by cells in protein mediators of intercellular interactions, reflecting the severity of immune inflammation in the liver.

The method is as follows.

The criterion for inclusion is the availability of proven hepatitis (viral markers, including HBV-DNA, histology liver biopsy).

Exclusion criteria - related pathology (acute or chronic diseases in the acute stage), co-infection with viruses of D and C, HIV, alcohol and medication within 2 weeks prior to the survey.

The sampling of venous blood in patients spend in the morning, on an empty stomach and after 4.5 hours after the first injection of interferon on the "peak" of its therapeutic activity. The serum is separated by centrifugation. Mononuclear cells release on the density gradient of ficoll-urografin according to the method of Ferrante A. & Thoung Y.H. [20], the resulting population standardize (2×106cells in 1 ml) and incubated for 24 hours in culture medium RPMI-1640 with the addition of L-glutamine, 2% fetal calf serum and gentamicin in moist, enriched in CO2the atmosphere, pri° C. the Content of IFN-γ supernatant after centrifugation and TNF-α in the serum is determined by ELISA using the test-sets "Cytokine" (Russia). Spontaneous production of IFN-γ OLS healthy is 34,82±a 4.03 PG/2×106cells (fluctuations from 22,09 to 46,85), the content of TNF-α serum - 22,41±3,67 PG/ml (fluctuations from 10,82 to 34.0).

When the content of TNF-α in the serum, not exceeding 59,31 PG/ml, and a good response rate TNF-α and synthesis of IFN-γ cells in response to the first injection of interferon-α (increase of TNF-α 46,1% and IFN-γ more 70,25% from baseline levels) can predict virological response (respondentsa). When the content of TNF-α serum above 74,51 PG/ml in the case of limited or negative reaction of cytokines on the first injection of interferon-α (increase of TNF-α no more than 24.9 percent, IFN-γ no more than 70% or both drop), one should expect the absence of virological response (non-respondentsa).

During the development of the method was examined patients with hug Century After the examination prescribed therapy with interferon (intron a - "Schering-Plough" or IFN - Vector) at a dose of 5-6 million ME 3 times a week. Treatment for 24 weeks. After completion of therapy were analyzed its results on clinical, biochemical and is virusological indicators including testing for HBV-DNA. Patients were divided into 2 groups - "responders" (responders) with the disappearance of the DNA of the virus seroconversion, normalization of activity of Alat and "non-responders" (non-responders) with preservation of HBV-DNA, the absence of seroconversion and normalization or reduction of the initial high activity of Alat in the analyzed period. Conducted a retrospective analysis in both groups, assessing baseline spontaneous synthesis of IFN-γ OLS, the content of TNF-α in the serum and the dynamics of both cytokines during the first injection of interferon-α, which were compared with the results of the 6-month treatment of patients hug In preparations of interferon-α.

Results

In the group of 11 patients with the presence of virological response at 6-month interferon therapy (responders), including HBeAg seroconversion to anti-HBe, the synthesis of IFN-γ mononuclear cells was 19,06±3.04 from PG 2×106CL (fluctuations of 12.26 to 25,86) with significant (P<0,05) increase after the first dose of interferon to 32,45±4,11 PG/2×106class. the Average increase of the synthesis was 70,25%. The content of TNF-α in this group was 50,1±4,12 PG/ml (fluctuations from 40,89 to 59,31) before the first dose of interferon and 98,7±to 5.4 PG/ml (fluctuations from 86,63 to 110,77) after administration (P<0,05). The average increase in the content of the BUT-α was 96% with fluctuations of extreme values from 46.1% to 171%. In this group there were 7 patients infected with the mutant (NWO-DNA+, HBeAg-) and 4 infected with wild type virus (HBV-DNA+, HBeAg+).

In the second group of 8 patients with the same ratio of infection by virus types, but without virological response at 6-month interferon therapy (save HBV-DNA, the absence of seroconversion) synthesis of IFN-γ OLS (14,99±0,95 PG/2×106CL, fluctuating from $ 12.87 to 17.11 per bbl) was increased after the first injection of interferon-α marginally to 20,13±5,34 PG/2×106CL (fluctuations from 8.19 to 32,07) - an average of 34.3%. When variations are extreme values (in per cent from the level prior to the introduction) was determined from the reduction in the rate after the introduction of the drug to increase, but not exceeding 70%. The content of TNF-α in the serum of non-responders (85,4±4,87 PG/ml) with fluctuations from 74,51 to 96,29 PG/ml was significantly higher than that of responders. After the first dose of interferon-α was determined by the absence of any dynamics indicator TNF-α - 84,2±3,96 PG/ml (fluctuations from 75,39 to 93,05). The comparison of the extreme values of TNF-α after and before the introduction demonstrated the decrease or increase of not more than 24.9 percent (table).

Thus, the virologic response to monotherapy with interferon-1 patients with chronic viral hepatitis b (if the infection as wild-type virus and virus-mutant) should be expected if before treatment, the content of TNF-α in the serum of patients does not exceed 59,31 PG/ml, but increased after the first dose of interferon-α 46.1% from the level before the introduction, and the synthesis of IFN-γ OLS after the first injection of interferon-α increases more than 70,25% of the rate of synthesis of the cytokine to introduction.

Negative (only biochemical) response to monotherapy with interferon-α patients with chronic hepatitis b with retention after 6 months of treatment with DNA-HBV, HBsAg and/or HBeAg (non-respondentsa) can be predicted when the level of serum TNF-αexceeding 74,51 PG/ml, reducing its number after the first injection of interferon-α or increase, but not in excess of 24.9 percent from levels before the introduction, and also by reducing the synthesis of IFN-γ mononuclear cells after injection of the first dose of the drug or its increase, but not more than 70% of the level prior to the introduction of interferon-α.

Table
Indicators of IFN-γ and TNF-α patients hug In depending on the results of the 6-month interferonoterapii
The studied parameter The group surveyed
respondersnon-responders
Spontaneous synthesis of IFN-γ OLS prior to the first injection of interferon (PG/2×106CL)19,06±3.04 from

(of 12.26-25,86)
14,99±0,95

(12,87-17.11 per bbl)
Spontaneous synthesis of IFN-γ OLS after the first injection of interferon (PG/2×106CL)32,45±4,11*

(23,26-41,64)
20,13±5,34

(8,19-32,07)
The content of TNF-α in the serum prior to the first injection of interferon (PG/ml)50,1±4,12

(40,89-59,31)
85,4±4,87**

(74,51-96,29)
The content of TNF-α in the serum after the first injection of interferon (PG/ml)98,7±5,4*

(86,63-110,77)
84,2±3,96

(75,39-93,05)
Note: * - P<0.05 to and after the first injection of interferon-α;

** P<0,05 in the two groups of responders and non-responders.

Clinical examples

Example 1. Patient A., 42 years. Case history No. 1688. Was in the gastroenterological Department of the regional hospital 2 through April 20, 1998.

Diagnosis. Chronic viral hepatitis b, replicative phase of HBV infection, moderate activity.

Complaints n is recurrent pain in the right hypochondrium, bloating, bitter taste in the mouth, fatigue.

Anamnesis. Suffered injecting drug addiction, using the same syringe with a partner who was a carrier of HBsAg. The last 10 years, drugs are not used.

Objectively. The condition is satisfactory. The skin and mucous regular color. On the chest a single telangiectasia, heart sounds, rhythmic, slightly muffled. Heart rate and blood pressure in the normal range. In the lungs vesicular breathing. The abdomen is soft, slightly painful in the right hypochondrium. The size of the liver by karlovu: 15×10×8 see the consistency of the liver dense, smooth. Spleen not palpated.

General blood and urine tests within normal limits. Bilirubin 13,67 Ámol/l Alat 174 units/l, AST 114 units/l, GGT 27 units/l, alkaline phosphatase 100 units/l Prothrombin index 90%. Total protein 79 g/l, albumin 56%, globulins: α - 16%, β - 10%, γ - 18%. Blood glucose of 5.5 mmol/l Thymol test 9,8% Serum iron 30,5 Ámol/L.

Viral markers: HBsAg (+)anti-HBs (-), anti-HBc total (+), HBeAg (-), anti-HBe (+), HBV-DNA (+), anti-HCV (-).

Ultrasonography. Liver: right lobe 162 mm, left - 100 mm, echo is increased. Intrahepatic ducts are not expanded. Portal vein 11 mm, splenic - 7 mm Choledoch 7 mm. Gall bladder 68×26 mm; wall hardened, thickened, without concretions. Pancreas: head 30 mm, the body 18 mm, tail 20 mm, the fabric is somewhat heterogeneous, echogen what the terrain is moderately increased. Spleen 127×48 mm, fabric uniform.

Liver biopsy. Lobular structure saved. Portal tracts unevenly expanded with diffuse infiltration of lymphocytes, macrophages, fibroblasts. Infiltration seats penetrates through the edge of the plate, reaching the 3 zones of the lobules. Notes unevenly marked proliferation of the bile ducts. Lobular component is expressed on the territory of 2-3 hepatocytes. Fibrosis of the walls of the Central veins and small foci of sclerosis in the slice. Hepatocytes in the hydropic state, focal baloney and globular fatty dystrophy, private binucleate hepatocytes contain eosinophilic inclusions. Conclusion: chronic hepatitis of moderate activity. Index Knodes 9 points, the index Desmet 2 points.

Spontaneous synthesis of IFN-γ mononuclear cells prior to the first injection of intron a dose of 3 million intramuscularly ME was the value of 16,81 PG/2×106class. after the first injection - 17,20 PG/2×106CL Content of TNF-α in the serum before the first injection of interferon was 91 PG/ml, after administration - and 82.2 PG/ml.

The patient started treatment with intron And 5 million ME 3 times a week. Treatment endured hard - mentioned pain sustava feet, weakness in the legs, lower potency, depression. After 6 months showed normalization of activity of aminotransferases, however, remained the of n HBsAg and HBV-DNA in serum.

Thus, in a patient with A. absence of 6 months interferonoterapii virological response was defined baseline TNF-α blood 91 PG/ml, i.e. exceeding 74,51 PG/ml, reduced after the first injection of the intron And to 82.2 PG/ml and increased spontaneous synthesis of IFN-γ after the first injection of interferon with the value of 16,81 to 17,20 PG/2×106CL - less than 70%, which is broadly in line with the proposed criteria non-respondenta.

Example 2. Patient B., 37 years. Case history No. 6037. Was in the gastroenterological Department from 24 November to 22 December 1999.

Clinical diagnosis: chronic viral hepatitis b, replicative phase of infection, a high degree of activity. Complaints about significant fatigue, occasional dull pain and a constant heaviness in the right hypochondrium.

From the anamnesis. In 1982 he suffered acute viral hepatitis. In 1998, he called in Chechnya, where he stayed in difficult conditions for about 6 months. After returning, he began to mark fatigue, interesest sclera. For medical assistance only in November 1999.

Objectively. The condition is satisfactory. The skin and sclera slightly icteric. Heart, lungs - without a pathology. The abdomen is soft, moderately painful in the right hypochondrium. The liver stands out from the edge of the rib arc 2 cm, moderately p is now with a smooth surface. Sizes karlovu 14×10×8 see Palpated the lower pole of the spleen.

A General analysis of blood, urine, without deviation from the norm. Bilirubin 63,2 (direct - cent to 8.85) Ámol/l Alat 608 units/l, AST 255 units/l Total protein 82 g/l, albumin 50%, globulins: α - 20%, β - 8%, γ - 22%. GGT 110 units/l, alkaline phosphatase 318 units/l, LDH-539 units/l Prothrombin index 96%.

Viral markers: HBsAg (+)anti-HBs (-), HBeAg (-), anti-HBe (+), anti-HBc IgM (+), HBV-DNA (+), anti-HCV (-), anti-HDV (-).

Ultrasonography. Liver: right lobe 161 mm, left - 104 mm, echo is increased, the fabric diffuse heterogeneous. Intrahepatic ducts are not expanded. Portal vein 13 mm, splenic - 9 mm Choledoch 5 mm Gall bladder 56×21 mm, wall sealed, content homogeneous. Pancreas: head 26 mm, the body is 15 mm, the tail is 17 mm, the tissue is homogeneous, hyperechoic. Spleen 138×64 mm, fabric uniform. The splenic vein at the gate 10 mm

Liver biopsy. In portal tracts and pericentral areas there is abundant infiltration of plasma cells, lymphocytes, histiocytes, fibroblasts. There are manual and bridges necrosis. Pronounced lobular component. Meet metavolcanics hepatocytes. Portal tracts expanded, there are signs of portal fibrosis. Conclusion: chronic hepatitis with a high degree of activity. YOKE 14 points. Index Desmet 1 point.

The content of TNF-α savored the blood before the first dose reaferona (3 million ME, intramuscularly) was 59,12 PG/ml, after administration - 96,8 PG/ml Spontaneous synthesis of IFN-γ mononuclear cells before the first injection reaferona was 12,38 PG/2×106cells, after injection - 26,63 PG/2×106cells.

Started treatment with IFN at a dose of 6 million ME 3 times a week. On the first introduction (3 million ME) was noted chills, arthralgia, temperature rise up to 39°back To the time of discharge from hospital the drug is well-tolerated. At the control examination after 3 months being satisfactory, remains a two-fold increase in the activity of Alat. After 6 months of starting treatment: aminotransferase within normal limits, HBsAg (-)anti-HBs (+), HBeAg (-), anti-HBe (+), anti-HBc IgM (-), anti-HBc total (+), HBV-DNA (-). Thus, the patient hug In with pronounced activity of the process was achieved seroconversion, the disappearance of viremia and normalize the activity of cytolytic enzymes.

The given clinical example demonstrates that the patient B. formation after 6 months interferonoterapii virologic remission hug In the initial content of TNF-α serum was 59,12 PG/ml, i.e. less than 59,31 PG/ml and increased after the first injection of interferon with 59,12 up to 96.8 PG/ml by 63.7% (i.e. more 46,1%). Spontaneous synthesis of IFN-γ OLS prior to treatment in the dynamics of the first injection of interferon uvelichilis is more than 70,25% - on or 115.1%. Together, these data corresponded developed criteria respondenta.

The use of the proposed method will allow before treatment to identify differences in the synthesis of IFN-γ and the content of TNF-α and their different response to the first injection of interferon-αcharacteristic of virological or only for clinical and biochemical remission.

The study is safe, invasive intervention is limited to two drawing blood from a vein, is available for practical health care institutions, there are no additional costs for equipment and training, not time-consuming.

Sources of information

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2. Abdurakhmanov DT Chronic HBV infection // Clinical medicine. - 2002. No. 4. - P.20-26.

3. Coppens J.-P., Comu Century, Lens E. et al. Prospective trial of recombinant leukocytte interferon in chronic hepatitis B: A long-term follow-up study // J. Hepatol. - 1990. - Vol.11 (Suppl.1). - S126-S128.

4. Coopens J.-P., Comu, S., Lens E. et al. Low-dose recombinant interferon alpha in chronic hepatitis B: A long-term follow-up study // 17th International Congress of Chemotherapy. - Munich: Futuramed, 1991. - 1179(Abstr.).

5. Dooley J.S., G.L. Davis, Peters M et al. Pilot study of recombinant human alpha-interferon for chronic type B hepatitis // Gastroenterology. - 1986. - Vol.90 - P.150-157.

6. Hoofhagle J.H. Therapy of viral hepatitis // Digestion. - 1998. - Vol.59. - P.563-578.

7. Lau D.T.-Y., L. Comanor, Minor, J.M. et al. Statistical models for predicting a beneficial respons to interferon-α in patients with chronic hepatitis // B.J. Viral Hepatitis. - 1998. - Vol.5. - P.105-114.

8. Marcelin P., Boyer N., Loriot M.A. et al. Long term outcome after spontaneous or therapeutically induced loss of HbeAg in patients with chronic hepatitis B // J. Hepatol. - 1993. - Vol.18 (Suppl.1). - S24 (Abstr.).

9. Thomas H.C. Treatment of hepatitis B viral infection // Viral Hepatitis and Liver Disease / Zuckerman A.J., ed. New York: Alan R. Liss, 1988. - P.817-822.

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11. Ivanov, L.M., credeva NV, Nabatchikova G.B. and other long-term results of treatment of patients with chronic hepatitis b and C virus drugs // Kremlin medicine. - 2000. No. 1. P.47-48.

12. Viral hepatitis C. the clinical picture, diagnosis, treatment. - Schering-plough (USA). - P.37.

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A method for predicting the effectiveness interferonoterapii in chronic hepatitis b, including the use of interferon-α, characterized in that to determine the number of TNF-α in the serum and synthesis in vitro IFN-γ mononuclear cells (MNCs) in the peripheral blood before and after 4.5 hours after the first dose of interferon-αand, when identifying the content of TNF-α in the serum prior to the introduction of not exceeding 59,31 PG/ml, and increased after the introduction of interferon-α the levels of TNF-α more than 46.1% and synthesis of IFN-γ OLS more than 70,25% of baseline, predict virologic response during the 6-month interferonoterapii, and in identifying the content of TNF-α serum above 74,51 PG/ml, and the improvement after the first injection of interferon-α the levels of TNF-α no more than 24.9 percent, synthesis of IFN-γ OLS no more than 70%, or the reduction of both cytokines relative to baseline, predict the absence of a virologic response.



 

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SUBSTANCE: method involves studying lactoferrin content in blood serum and peritoneal exudates in postoperative period every day during the first three days. Lactoferrin concentration in blood serum being concurrently reduced by 0.02 mcmole/l or less and increasing lactoferrin concentration in peritoneal exudates by 0.04 mcmole/l or more, enteric detoxication is considered to be effective.

EFFECT: high quality of estimation.

2 tbl

FIELD: medicine.

SUBSTANCE: method involves determining plasminogen/plasmin, α2-macro-globulin, α1-antitripsin content at the first, third, fifth and tenth day. The plasminogen/plasmin level being equal to 66-74 mcmole/l or 100-120 mcmole/l, α2-macro-globulin level of 2.7-3.0 mcmole/l, α1-antitripsin content of 2.38-3.2 mcmole/l, systemic inflammatory response to purulent infection, light severity degree endotoxicosis is diagnosed and favorable disease outcome is predicted. The plasminogen/plasmin level being equal to 50-65 mcmole/l or 125-160 mcmole/l, α2-macro-globulin level of 2.3-2.6 mcmole/l, α1-antitripsin content of 3.3-4.0 mcmole/l, sepsis with organ and system dysfunction, moderate severity degree endotoxicosis is diagnosed and septic complication availability and lingering disease development course is predicted. The plasminogen/plasmin level being equal to 39-40 mcmole/l, α2-macro-globulin level of 1.58-2.08 mcmole/l, α1-antitripsin content of 5.0-6.2 mcmole/l, severe sepsis, septic shock, severe degree endotoxicosis is diagnosed and unfavorable disease outcome is predicted.

EFFECT: high accuracy of diagnosis.

5 tbl

FIELD: medicine, biochemistry.

SUBSTANCE: at testing one should precipitate high-molecular compounds with acetonitrile and register supernatant's spectral characteristics. Supernatant should be applied onto a paper filter, dried and put into solution containing aromatic aldehyde, acetone and concentrated hydrochloric acid taken at weight ratio of 70:5:1 to be kept for 2-3 min. Then it should be once again dried up to detect qualitative and semiquantitative content of oxidized tryptophan metabolites by intensity and chromatic shades. Moreover, by chromatic shades of yellow dyeing it is possible to detect the content of hydroxylated metabolites and by chromatic shades of violet dyeing - that of unhydroxylated ones.

EFFECT: higher significance of detection.

3 ex

FIELD: medicine, anesthesiology, resuscitation.

SUBSTANCE: in patients one should study the content of lactoferrin in peritoneal exudates during the 1st d of postoperational period and at decreased value being below 3500 ng/ml on should predict unfavorable result. The suggested method provides correction of possible postoperational complications that deteriorate the flow of peritonitis and lead to lethal result.

EFFECT: higher accuracy of prediction.

3 ex

FIELD: veterinary medicine.

SUBSTANCE: method involves determining low and middle molecular mass substances content in blood plasma and erythrocytes and general blood plasma albumin concentration. Integral index is calculated on basis of obtained values using formula II=100*S238-298(plasma)/S238-298(erythrocytes)*GAC, where S238-298(plasma) and S238-298(erythrocytes) are the low and middle molecular mass substances content in blood plasma and erythrocytes, respectively, determined from area of figures restricted by spectral curves in wavelength range of 238-298 nm and abscissa axis (conditional units2); GAC is the general blood plasma albumin concentration (g/l). The value being from 2.1 to 3.0, the first endotoxicosis degree is diagnosed. The value being from 3.1 to 4.5, the second endotoxicosis degree is diagnosed. The value being from 4.5 to 6.0, the third endotoxicosis degree is diagnosed. The value being greater than 6.0, the fourth endotoxicosis degree is diagnosed. The normal value is equal to 0.5-2.0.

EFFECT: high accuracy of diagnosis.

1 dwg, 1 tbl

FIELD: medicine.

SUBSTANCE: method involves separating blood serum proteins into fractions, determining albumins and alpha-2-globulins content and controlling their content changes during the disease development process. Gamma-globulin content is determined in per cent ratio with respect to total protein quantity. Then, changes in the fractions content are controlled from the first to the third week. Albumin content being in norm and alpha-2-globulins content becoming greater to the end of the first week by 30-50% when compared to normal value and dropping to norm at the second week end and gamma-globulin content increasing from norm by 10-30% to the second or the third week, high inflammatory process activity is to be diagnosed. Albumin content dropping by 10-30% from normal value at the second week, alpha-2-globulins content growing by 10-20% of norm and gamma-globulin content dropping by 30-50% at the second or the third week when compared to norm, low inflammatory process activity is to be diagnosed.

EFFECT: high accuracy and reliability of diagnosis.

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