Method for early diagnosis of violation of children adaptation under chemical hazards of environmental factors

FIELD: medicine.

SUBSTANCE: areas highly exposed to harmful chemical agents are chosen. A random group of children without clinical signs of living in this territory is tested using chemical laboratory tests of blood to identify the content of chemical compounds, which are priority chemical environmental factors on the selected area of residence and clinical and laboratory studies are conducted to determine a set of laboratory indicators of adaptation system. Then using the results of the study the average values of chemical compounds in the blood are fixed and then they are compared to the background and average values for each of the above laboratory parameters are fixed and compared to the physiological norm; deviation of this value from the normal rate reveals children bodies response to chemical exposure. Next, a causal relationship is established between the level of content of chemical compound in the blood and the response of the child body through deviation of laboratory parametres from the norm using a logistic regression model. Using method based on analysis of odds ratios the maximally inactive level of marker of exposure and corresponding response marker based on the conditions are determined under which the odds ratio that characterises the degree of the connection between exposure to a chemical compound and the body's response will be greater than or equal to one; for this a model of dependence between the level of a marker of exposure and the specified index odds ratio is designed, the parametres of the model are determined and they reflect the change in the probability using which the value of the maximally inactive level of marker of exposure is calculated, i.e. maximum ineffective concentrations of chemical compounds. From the entire spectrum of defined concentrations of certain chemical compounds for each laboratory parametre of adaptation systems choose the smallest value that is accepted as the maximally inactive concentrations on a child adaptation system for a given chemical compound i. In future diagnosis of violation of adaptation of children living in the selected area is performed by comparing the content Ci of certain chemicals in their blood with previously established value of inactive concentration for this chemical compound; and if a ratio is a violation of adaptation is diagnosed.

EFFECT: method allows diagnosing violation of children adaptation under chemical hazards of environmental factors with high precision at an early preclinical stage, with simultaneous simplicity and accessibility for a wide practical application.

5 tbl, 2 dwg

 

The invention relates to medicine, in particular to methods of laboratory diagnostics of disorders of adaptation processes in children by establishing a causal link between a child's health status and the influence of chemical factors present in the territory of residence, and is intended for use in outpatient and clinical practice, the diagnosis at an early stage of the disorder in children in order to predict possible violations of health, and can also be used in the formation of sanitary measures for the prevention and elimination of harmful chemical substances that lead to the formation of the disorder in children.

To understand the substance of the question, you should explain the following.

Adaptation is the ability of the body to adapt to the existing conditions. But the adaptation is the condition of the body in conditions of excessive negative impact of environmental factors.

There are several systems of adaptation, the main of which are: oxidant (regulates the level of free radicals); neuroendocrine (regulates the education level of hormones in the endocrine glands); immune (adjust device to viral and bacterial pathogens); proliferation (f is Biologicheskie or abnormal division of cells).

Due to change of any external factors, in particular the emergence of harmful chemicals in the environment stay, or any manifestations of stress (psychological, physical, chemical), may fail in one or more systems of adaptation, i.e. there is a violation of adaptation, and therefore may be a manifestation of morbidity in children as the most sensitive contingent with not fully formed organism.

The state of adaptation in humans is characterized by four phases, plotted on figure 1 and figure 2: phase I - zone effective adaptation (within normal limits); phase II - area voltage adaptation (increased adaptation process in tone, first violations laboratory indicators at the upper limit of normal, there is no clinic); phase III - zone depletion adaptation (laboratory values violated the first clinical manifestations); phase IV - area breakdown of adaptation (violation of laboratory parameters and clinical signs).

When the child's residence in ecologically unfavorable territory, and therefore, when the harmful effects of chemical compounds on the body, phase I and phase II are shortened, and the transition from phase characterizing the rate (I), per phase, characterizing pathology (II-III), is faster and even abruptly. And given that the violation of adaptation is item the child leads to the formation of prenosological state, the early diagnosis of the disorder in children is a relevant and necessary.

The prior art a number of patents on methods for diagnosing disorders of adaptive processes in children:

- RF patent №2269131, publ. 27.01.2206, "a method for the diagnosis of disorders of the overall adaptation process newborns in the first days of life", according to which determine the level of functional activity of monocytes by asking spontaneous and stimulated NBT-test. Calculated diagnostic index (CRP.) as the ratio of the indices of the stimulated NBT-test to spontaneous. If CCP. greater than or equal to 1.5, judge the adequacy of the process of adaptation of the newborn, if the CCP. less than 1.5, diagnose violation of the early period of adaptation and exhaustion functionality at the level of macrophage immune system. The known method makes it possible to identify early, often preclinical signs of homeostasis and adaptive processes in the body of the newborn in the first days of life that allows you to choose timely tactics rehabilitation or ways immune.

- Patent of RF # 2274867, publ. 20.04.2006, "Method biochemical evaluation of adaptation cardiac activity in newborn infants", in which newborns investigate the serum of venous blood, Oprah is Elea activity myocardial isoform of creatine phosphokinase (MB-ck), the level of triglycerides (TG), low density lipoprotein (LDL) on 3-4 day life. When activity of MB-CPK from 9,9 to 13.7 IU/l, triglycerides from 2.8 to 4.8 mmol/l, LDL from 8.6 to 12.8 g/l diagnosed with severe disorder of cardiac activity. When values of MB-CPK from 6.5 to 8.1 U/l, triglycerides from 0.8 to 1.6 mmol/l, LDL from 3.9 to 4.7 g/l diagnosed favorable for an adaptation period of cardiac activity in newborns. The method is technically simple, reliable, allows you to enhance biochemical evaluation of adaptation cardiac activity and to judge the severity of myocardial damage in newborns in the first days of life.

- RF patent №2052195, publ. 10.01.1996, "a method for predicting the disorder of newborns from mothers with obesity", the implementation of which determine the expression of Fc receptors on macrophages blood, the number and size of the CEC and the increased expression of Fc-receptors at birth more than 2 times and its further reduction of 5-7 days more than 25%, the increase in the concentration of the CEC more than 0.6-0.9 g/l and the increase of the coefficient of 1.1, characterizes the size of the CEC, predict the adaptation.

However, all these known methods have the following disadvantages:

Newborns are originally in terms of a huge "stress".

All indicators are measured relative activities is but 3-4 adaptation stage, i.e. when clinical signs, within the physiological crisis of newborns.

Also known a method for the diagnosis of environmentally caused diseases in the population (Patent RF №2137422, publ. 20.09.1999,), which is characterized by the fact that the produce selection of the most sensitive groups of the population living in ecologically unfavorable areas, conduct medico-chemical study of their biological environments for metals, organic and inorganic compounds, which is the priority of environmental factors in the area of the surveyed population, clinical and laboratory examination of this population on common indicators and then - specific examination by defining specific indicators of health status change (if the reliability of differences of ≥95%) is characteristic for the effects of chemical compounds previously identified in medical and chemical research, and establish a correlation relationship between the results obtained at the medico-chemical, clinical laboratory and special examinations, the establishment of which is diagnosed environment-related pathology. The method provides high accuracy of diagnosis.

However, this known method also has its disadvantages and property named is: the impossibility of establishing the disorder at an early stage, because when implementing the known method definition are at the stage of having changes of laboratory parameters and clinical manifestations.

The technical result achieved by the invention, is to provide a detection with high accuracy disorder in children living in conditions of exposure to harmful chemical factors at an early preclinical stage, while the simplicity and accessibility for a wide practical application.

This technical result is achieved by the proposed method for early diagnosis of disorders of adaptation in children exposed to harmful chemical environmental factors, according to which produce the selection of ecologically disadvantaged areas with high exposure to harmful chemical factors, a random group of children without clinical manifestations, living in this territory, the number of which corresponds to a representative sample, perform chemical laboratory blood tests on the content of chemical compounds, which is the priority chemical environmental factors on the selected area, and also conduct clinical and laboratory research on determining the combination of laboratory indicators of system adaptation: for oxidant - level antioxida is based activity in the blood, the content of malondialdehyde in blood; for neuroendocrine level of thyroid-stimulating harmone in the blood; immune - concentration of serum immunoglobulins A, M, G; indicators of phagocytic activity; cell proliferation - level carcinoembryonic antigen in serum, according to a study set for a selected group of children the average content of chemical compounds in the blood, compare them with the background and set the average values for each of the above laboratory parameters, and compare the latter with the data of the physiological norm and deviation of the metric from the norm reveal the response of the organism of children to chemical substances, then establish a causal relationship between the levels of chemical compounds in the blood is a marker of exposure and the response of the child's body through abnormalities in laboratory parameters from the norm is a marker of response, using a logistic regression model, then the method is based on the analysis of odds ratios, determine the maximum inactive level of the marker of exposure and corresponding token response based on the conditions under which the ratio of the odds that characterize the strength of connection between exposure to chemicals and the response body will be more or ravensdene, to do this, build a model of dependence between the level of a marker of exposure and the specified index odds ratio, determine the parameters of the model, reflecting the changing nature of probability, through which calculate the maximum inactive level of the marker of the exposure, i.e. the maximum inactive concentrations of chemical compounds, and to establish the adequacy of the model used, and therefore, reliability of the obtained data, use the procedure dispersion analysis based on the calculation of the Fisher criterion and the coefficient of determination, taking into account that differences considered statistically significant with p≤0,05, that you are carrying out determination when building the model, 95% confidence limits - upper and lower and scope of the obtained models is the interval between the minimum and maximum experimental values, the value of the corresponding upper 95%confidence boundary of the resulting model corresponds to the minimum valid concentration of a chemical compound, and the value corresponding to the lower 95%confidence boundary of the resulting model, adequate maximum inactive concentrations of chemical compounds, further, the spectrum of the established concentrations of certain chemical compounds decadeago laboratory indicator systems adaptation choose the smallest value which is taken for maximum inactive concentrationsystem adaptation of the child for a given chemical compound i and a diagnosis of the disorder in children living in the selected site, produce in the future by comparing the contents of Ciin their blood definite chemical compound i with previously established for this chemical compound i most inactive concentrationwhen the ratio isdiagnose the adaptation.

The technical result is achieved due to the following.

Due to the fact that in biological media in children living in ecologically unfavorable territory, determine both the content of chemically harmful substances typical for this area, and these clinical and laboratory indicators of system of adaptation, it becomes possible to compare these values with the aim of determining the influence of chemical substances on laboratory indices (body systems).

The setting for all the children surveyed, a correlation between the level of laboratory performance and the level of toxic chemical compounds in the body provides reception zelot the th picture of the effects of toxic substances in the environment in a certain concentration on the adaptive processes of the child's body, and in addition, allows to obtain the tokens prenosological change adaptation.

The definition of the mathematical model of functional dependencies: content of chemical compounds in the blood of the body is a laboratory measure of blood allows you to quickly find the most inactive concentration of chemical compounds in the blood by determining the mathematical dependence of maximum concentrations of chemical compounds in which statistically on the physiological level does not change this laboratory indicator. This concentration is the maximum inactive concentration of a certain chemical compounds in the blood.

Next, choosing from a total number of identified concentrations of certain chemical compounds for each laboratory indicator systems adapt the smallest value is provided by the establishment of such maximum inactive concentrationsystem adaptation of the child for a given chemical compounds i, in which guaranteed there are no abnormalities in all laboratory parameters characterizing the system adaptation. And use this value in practice makes it easy to diagnose the disorder in children under certain techno is i.i.d. chemical factors by setting the concentration (content) of a chemical compound in the blood of a child and pre-clinical stage to make a forecast about the deviation of the adaptive processes of the child's body. All this allows to carry out the proper amount of adequate therapy in the earlier period, without disruption of adaptation.

The proposed method is as follows, in the specific example:

- choose environmentally disadvantaged areas based on high load of chemical factors in the habitat. As this site was selected by the city of Perm. It is characterized by the presence of environmentally harmful substances in the atmosphere and in surface water reservoirs, namely: heavy metals (copper, zinc, manganese, lead, Nickel, chromium), aromatic hydrocarbons (benzene, toluene, ethylbenzene, xylenes, phenol), saturated monohydroxy alcohols (styrene, methyl, propyl, butyl and isobutyl alcohols), aliphatic aldehydes (formaldehyde, acetaldehyde, propionic and butyric aldehydes), organochlorine compounds (chloroform, dichloroethane, trichloromethane, chlorobenzene, dibromochloromethane), aliphatic ketones (acetone). As priority factors in the implementation of the proposed method were selected metal - lead and organic substance - benzene, which adversely affect the health of children;

- select a random group of children living on this territory, in the amount of 950 people (representative sample) aged 3-7 years (this is the number of children line is only 10% of all children aged 3-7 years, living in the targeted area, and corresponds to the degree of reliability of more than 95%);

- conduct medical examination of selected children with the goal of establishing the absence of clinical manifestations, such as children check in the morning filter, and sick children (fever, catarrhal phenomena) are discarded;

- conduct chemical laboratory investigation of blood each child on the content of chemical compounds, such as metals, inorganic or organic compounds, which is the priority chemical environmental factors on the selected site. In our example, it is found in the blood levels of lead and benzene;

next in the blood of every child also define a set of laboratory indicators of system adaptation: for oxidant - level of antioxidant activity (JSC) in the blood, the content of malondialdehyde (MDA) in the blood; for neuroendocrine - the level of thyroid stimulating hormone (TSH) in the blood; immune - concentration of serum immunoglobulins A, M, G (IgG, IgM, IgA) and indicators of phagocytic activity; cell proliferation - level carcinoembryonic antigen (CEA) in serum; - the results of these studies establish for selected groups of children the average content of chemical compounds in the blood, compared soda is the content of lead with the reference values, and benzene content with the background, and set the average values for each of the above laboratory parameters and compare the latest data of physiological norm and deviation of the metric from the norm reveal the response of the organism of children on the effects of chemical compounds.

Data on the average results obtained by implementation of the specific example of implementation of the proposed method are given in tables 1 and 2.

Table 1
The content of chemical compounds in the blood of the children surveyed group (with probability: p=0.000÷0,007), mg/DM3
Chemical compoundAverageError
Lead0,1580,003
Benzene0,00320,00004

The data in table 2 show that reliably established the following:

- dysfunction of antioxidant protection of the organism, manifesting diverse changes: the decrease in antioxidant activity as decompos the tion in the depletion of antioxidant reserves in 27% and a compensatory increase in 63,1% as a manifestation of stress adaptation, while increasing the content of malonic aldehyde plasma 68.6% of children;

- stress adaptive mechanisms of the immune system by activation of the cellular link (percentage of phagocytosis, absolute phagocytosis, phagocytic number, phagocytic index in 6,9%, 40,2%, 10,8%, 18,7% children, respectively), the increase in the content of humoral factors (IgG, IgM, IgA at 19.7 percent, 6.6 percent and 20.5 percent respectively). Decompensation of the humoral response was detected in 20,4-10.7% of children by reducing the concentration of IgA and IgG in plasma. The decrease in the content of the percentage of phagocytosis - 9,8%, absolute phagocytosis - 7,8%, phagocytic number - 14.7% of children indicates a depletion of the cellular link;

- improving the content of total content of serum immunoglobulin IgE (above the physiological level 57.4% of the children, while its mean value was 153,0 IU/ml, p=0.000 (at a rate of not more than 50 IU/ml-for-age)) indicates nonspecific sensitization of the organism, which can be regarded as a voltage adaptation of the immune system;

content carcinoembryonic antigen exceeded the limits of physiological norm at 3.2% of children, and the average value was 2.08 ng/ml (at a rate of not more than 5.0 ng/ml), indicating that the increased proliferative activity;

- the average content of thyroid-stimulating hormone in the examined children was 2.5 mkme/ml (at a rate of not more than 4.0 mkme/ml), indicating that the voltage mechanismo the neurohumoral regulation. Thus was revealed the response of the organism of children on the effects of chemical compounds with increased activity of the major adaptive systems, and in some children identified decompensation adaptive response in terms of the impact of anthropogenic chemical factors;

next perform mathematical modeling of causal relationships between levels - the content of chemical compounds in the blood is a marker of exposure and the response of the child's body through abnormalities in laboratory parameters from the norm is a marker of response. Dependency marker of exposure token response" described using a logistic regression model (1):

where p is the probability of rejection of the token response from the physiological norm when exposed to a marker of exposure,

x - level marker of exposure,

x0- maximum inactive level of the marker of exposure,

b0b1the parameters of the mathematical model, reflecting the changing nature of probability;

- using the method odds ratio, maximum inactive level of the marker of exposure x0and the corresponding magnitude of the response was determined on the basis of the conditions under which the indicator of the odds ratios (OR), characterizing the strength of connections between exposure to chemical compounds and ototo the body, is greater than or equal to one. And the condition OR<1 indicates no communication response with exposure time. To determine the maximum inactive level in the body marker of exposure have built a model of dependence between the level of a marker of exposure and the ratio of chances, which is described by an exponential function (2):

where a0, a1the model parameters determined by the regression analysis, reflecting the changing nature of probability;

- after determining the model parameters, compute x0according to the formula:

next inspect the adequacy of the model, which is carried out using the procedure of dispersion analysis based on the calculation of the Fisher test (F) and determination coefficient (R2). Differences are considered statistically significant when p<0,05. When building mathematical models carry out the determination of the 95% confidence limits - upper and lower and scope of the obtained models. For the scope of the model take the interval between the minimum and maximum experimental values. The value of the corresponding upper 95%confidence boundary of the resulting model corresponds to the minimum valid concentration of a chemical compound, and the value matching the I lower 95%confidence boundary of the resulting model, adequate maximum inactive concentrations of chemical compounds. The data obtained in the mathematical treatment, are shown in table 3.

Table 3
The model parameters according to negative changes in laboratory parameters of adaptive systems on the level (concentration) in blood lead (p=0.000) and benzene (p=0.000)
Marker of exposure (chemical compound)The marker effect (negative changes in laboratory parameters)The model parametersR2FThe concentration of chemical compounds, mg/DM3
b0b1
Increased CEA in serum-11,120,26106,270,093
3,11is the
LeadReduced Phagocytosis abs.-of 10.720,1233,550,095
4,22
The reduction in the percentage of phagocytosis-7,500,1346,800,122
3,02
Increased CEA in serum-260,90,54387,90,0029
2,12
The increase in total IgE in serum -KZT 205.70,57449,70,0034
0,34
Increased IgA in serum0,4672,050,1349,130,0096
Reduction of IgG in serum-43,420,0724,720,0160
1,51
Reduction of IgM in serum-68,730,0725,820,0101
0.58
BenzeneIncrease Δ in urine -198,20,851717,30,0035
1,82
Reduction of hemoglobin in the blood-674,50,43242,810,0062
3,11
Decrease in white blood cell count-61,00,0516,230,0114
2,04
The increase of MDA in plasma-235,80,65638,70,0027
1,07
The reduction in the percentage of phagocytosis in blood-273,70,882244,20,0028
2,37

Next, from the whole range of concentrations of certain chemical compounds (separately for lead and separately for benzene) for each laboratory indicator systems adaptation (last column of table 3) choose the smallest (minimum) value, which is taken for maximum inactive concentrationsystem adaptation of the child for a given chemical compound i. From table 3 it can be seen that there is a connection between changes in laboratory parameters from higher concentrations of lead and benzene in the blood. For these compounds the selected minimum value from a number of non-performing concentrations (lead - 0,093 mg/DM3benzene - 0,0027 mg/DM3), in which the most sensitive statistically significant relative to physiological levels (standards) are changing the level of CEA in the serum for lead and the MDA level in plasma for benzo is and. These concentrations of contents contaminant (lead and benzene) in the blood are most inactive concentrations exceeding the level which will cause disruption of the processes of adaptation.

Just establish the dependence of the effects of other harmful chemical compounds on laboratory indicators of system adaptation, establish the most inactive concentration. This maximum inactive concentration characterizes the boundary of the influence of chemical factors on the transition of adaptive processes in children from the zone of effective adaptation (figure 1 and figure 2) in the zone of stress adaptation.

- A diagnosis of the disorder in children living in the selected site, produce in the future by comparing the contents of Ciin their blood chemical compound (i) with the previously established for this chemical compound most inactive concentration,

and with a ratio ofdiagnose the adaptation. That is, in an inpatient or outpatient basis take the blood sample from the child, determine its content of harmful chemical compounds, and on a scale previously established maximum inactive concentration for that chemical compounds is diagnosed in a child possibly the ity of the disorder or its absence. Moreover, this examination can be made at an early stage.

For evidence of the impact of benzene and lead was the diagnosis of the disorder from other children (healthy without clinical manifestations) (comparison group) aged 3-7 years, living on the territory of Kungur district of the Perm region (outside of man-made chemical factors), for violations of adaptive processes of the body. This made the blood and determine its content of chemical compounds of lead and benzene. The data obtained are given in table 4.

Table 4
The content of chemical substances in the blood of children in the comparison group
(p=0.000÷0,007 mg/DM3)
Index
AverageError
Lead0,0850,003
Benzene0,00000,0000

Next, we identified the main laboratory indicators of adaptive systems in the blood of children. The data are given in table 5.

Table 5Laboratory parameters of children in the comparison groupLaboratory indicatorThe physiological normAverageSTD. reject.ErrorThe number of children with off. from Fiziol. rules %The significance of differences
with Fiziol. norm (p)belowaboveAntioxidant
the activity of plasma, %36,2-38,6of 37.86,3421,3333,06,70,000Malonic dialdehyde plasma, umol/cm31,82-2,52,010,2570,1280,068,60,000IgG, g/DM3Age9,71/td> 1,5670,281the 10.1the 11.6OKIgM, g/DM3Age1,390,3200,0562,3of 5.4OKIgA, g/DM3Age1,100,3520,0677,33,1OKIgE total, IU/mlAge48,9202,03436,2120,057,40,000The percentage of phagocytosis, %Age51,4038,3866,543the 3.84,6OKAbsolute phagocytosis, 109/DM3 Age3,010,8340,1766,415,7OKPhagocytic number $ Age1,10,2910,05714,710,8OKPhagocytic index $ Age1,980,2830,0550,013,7OKKEA (carcino-embryo. the antigen, ng/ml0-5,00,520,5430,1100,00,0OKTSH (thyroid stimulating hormone) mkme/ml0,3-4,01,20,2450,1670,00.0OK/table>

Comparison of data in table 1 with the data in table 4 show that most of the surveyed children living on the territory of the impact of anthropogenic chemicals in the Perm region, was characterized by a high content of benzene and lead in the blood that exceeds almost twice the value of the content of these compounds in the blood of children in the comparison group (whose concentration contaminant - chemical compounds do not exceed the permissible level), not subjected to excessive pressures pollution of the environment.

Comparison of data in table 2 with the data in table 5 show that most of the children surveyed a group of Perm revealed changes in laboratory parameters, indicating the disruption of the processes of adaptation, whereas the children in the comparison group adaptive reactions are effective adaptation (zone effective adaptation figure 1 and figure 2). For example, children in the comparison group adverse change in the level of antioxidant activity is registered by a 3.0-6.7% of children with lower average content of malonic aldehyde plasma, indicating that effective adaptation of the antioxidant system. The average level of CEA in children comparison group in 4 times lower than the average level of the subject group, indicating the absence of tension ProLife the exploring activity.

To prove the feasibility of assigning method were taken blood samples from 30 children living in the city of Perm and not included in the study group, to identify content in a sample of lead and benzene. In 84% of children have lead levels exceeded the preset maximum inactive concentration (0,093 mg/DM3), and 50% benzene content exceeded the preset maximum inactive concentration (0,0027 mg/DM3). These children underwent in-depth clinical and laboratory examination, which revealed the following: in 20 children by increasing antioxidant activity was established voltage antioxidant regulation against the background of increased MDA in plasma, 16 children average CTA equaled 2.10 ng/ml, which proves the validity of the proposed method.

Thus, the proposed method allows for early preclinical stage to identify the adaptation of children in a particular area by simple operations. It is accurate, reliable, affordable, and can be widely recommended for use in outpatient and clinical practice.

The method of early diagnostics of disorders of adaptation in children exposed to harmful chemical environmental factors, characterized by the fact that produce the selection of environmentally becomes obolochnoy areas with high exposure to harmful chemical factors, the random group of children without clinical manifestations, living in this territory, the number of which corresponds to a representative sample, perform chemical laboratory blood tests on the content of chemical compounds, which is the priority chemical environmental factors on the selected area, and also conduct clinical and laboratory research on determining the combination of laboratory indicators of system adaptation: for oxidant - level of antioxidant activity in the blood, the content of malondialdehyde in blood; for neuroendocrine level of thyroid-stimulating harmone in the blood; immune - concentration of serum immunoglobulins a, M, G; indicators of phagocytic activity; cell proliferation - level carcinoembryonic antigen in serum, according to a study set for a selected group of children the average content of chemical compounds in the blood, compare them with the background and set the average values for each of the above laboratory parameters, and compare the latter with the data of the physiological norm and deviation of the metric from the norm reveal the response of the organism of children to chemical substances, then establish a causal link between the level - provide the eat, chemical compounds in the blood is a marker of exposure, and the response of the child's body through abnormalities in laboratory parameters from the norm is a marker of response, using a logistic regression model, then the method is based on the analysis of odds ratios, determine the maximum inactive level of the marker of exposure and corresponding token response based on the conditions under which the ratio of the odds that characterize the strength of connection between exposure to chemicals and the body's response will be greater than or equal to one, to build a model of dependence between the level of a marker of exposure and the specified index odds ratio, determine the parameters of the model, reflecting the nature of the change the probability by which calculate the maximum inactive level of the marker of the exposure, i.e. the maximum inactive concentrations of chemical compounds, and to establish the adequacy of the model used, and therefore, reliability of the obtained data, use the procedure dispersion analysis based on the calculation of the Fisher criterion and the coefficient of determination, taking into account that differences considered statistically significant at p<0,05, that you are carrying out determination when building the model, 95% confidence limits - ver the it and the bottom and scope of the obtained models - the interval between the minimum and maximum experimental values, the value of the corresponding upper 95%confidence boundary of the resulting model corresponds to the minimum valid concentration of a chemical compound, and the value corresponding to the lower 95%confidence boundary of the resulting model, adequate maximum inactive concentrations of chemical compounds, then the spectrum of the established concentrations of certain chemical compounds for each laboratory indicator systems adapt choose the smallest value which is taken for maximum inactive concentrationsystem adaptation of the child for a given chemical compound i and a diagnosis of the disorder in children living in the selected site, produce in the future by comparing the content Withiin their blood definite chemical compound i with previously established for this chemical compound i most inactive concentrationand with a ratio ofdiagnose the adaptation.



 

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2 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: invention concerns a method for prediction of the efficacy of Infliximab inclusion in a conventional therapy of the patients with rheumatoid arthritis (RA). A patient's peripheral blood is examined for total lymphocyte content (TLC) expressing TNF-α-CD120a receptors, for levels of spontaneous and stimulated production of tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). It is followed by calculating indexes of PHA action on PBMC (peripheral blood mononuclear cells) TNF-α and IL-6 production by formulae respectively: IA1=Ast/Asp, IA2=Bst/Bsp, where IA1 is an index of PHA action on PBMC TNF-α production; Ast is a level of stimulated TNF-α production, pg/ml; Asp is a level of spontaneous TNF-α production, pg/ml; IA2 is an index of PHA action on PBMC IL-6 production; Bst is a level of stimulated IL-6 production, pg/ml; Bsp is a level of spontaneous IL-6 production, pg/ml. Provided IA1≤2.4 and IA2≤1.6 and TLC≥6% simultaneously, the high efficacy of Infliximab inclusion in the therapy of the RA patients is predicted.

EFFECT: invention allows reliable prediction of the efficacy of Infliximab inclusion in the conventional therapy of the RA patients.

1 ex

FIELD: medicine.

SUBSTANCE: method starts with blood sample alkalisation with 10% sodium hydroxide to pH 8-10; dichlorobromomethane is recovered from the sample by hexane extraction; the extract is separated centrifugally at 7000-7500 rpm and analysed with gas chromatography in a partition gas chromatograph with an electron capture detector, while dichlorobromomethane is measured by a calibration diagram.

EFFECT: high sensitivity and accuracy of the method for blood dichlorobromomethane measurement.

1 ex, 5 tbl

FIELD: medicine.

SUBSTANCE: excitory cells of the immune system are recovered that is followed with primary incubation of the cells with an investigated substance to produce a primary-incubation supernatant or mixed cells and supernatant; secondary incubation of the target cells with the supernatant or mixed cells and supernatant wherein the secondary-incubation target cells are understood as human tumour cells or cell lines of an oncogenetic origins; the target cells are analysed where the analysis is specified in a group including an expression analysis of specific proteins and an apoptosis and/or necrosis analysis.

EFFECT: improvement of the method.

14 dwg

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, namely to orthopedics. In order to estimate state of bone tissue in case of immobilisation osteoporosis in a laboratory animal examined are homogenates: bone, muscular, bone marrow of any extremity and peripheral blood. Biochemical and integral parametres are determined. Five factor variables F1-F5 are calculated using values of biochemical and integral parametres, constant values of factor coefficients of biochemical parametres and free coefficients. After that calculated is the value of discriminant function, whose value is used to estimate bone state as normal or conclusion about presence of immobilisation osteoporosis is made.

EFFECT: method increases accuracy and efficiency, has high stability of immobilisation osteoporosis recognition.

1 ex, 3 tbl

FIELD: medicine.

SUBSTANCE: blood plasma is analysed for cytochrome oxidase activity, erythrocyte 2,3- biphosphoglycerate and lactic acid concentrations. It is followed by calculating an oxygenation coefficient K by formula: K=(C1+C2):A, where C1 is the erythrocyte 2,3- biphosphoglycerate concentration, mol/l; C2 is the erythrocyte lactic acid concentration, mol/l; A is plasma cytochrome oxidase activity, mol/l. The K value withint 1.0 <K≤3.0 enables to diagnose tissue hypoxia, while in case of the K values being 3.0<K≤5.0 cardiovascular hypoxia is diagnosed. If the oxygenation coefficient is 5.0 and more, blood hypoxia is diagnosed.

EFFECT: use of the method enables the differential diagnostics of blood, tissue and cardiovascular hypoxia.

3 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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