RU2616326C1 - Method for diagnosing of chronic gastroduodenitis in children associated with exposure to technogenic chromium, nickel, manganese, chloroform and carbon tetrachloride - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: for diagnosis of chronic gastroduodenitis in children, associated with exposure to technogenic chromium, nickel, manganese, chloroform and carbon tetrachloride, blood sampling is carried out. In case of a high content of these metals in blood, compared to the reference level, functional and laboratory diagnostic indicators of a child are determined.

EFFECT: method makes it possible to diagnose chronic gastroduodenitis for children, associated with exposure to technogenic metals to prevent development of complications due to timely appointment of adequate therapy.

2 cl, 11 tbl

Description

The invention relates to the field of medicine, human ecology, toxicology, in particular, to methods for diagnosing the toxic effects of chromium, nickel, manganese and organochlorine compounds (chloroform and carbon tetrachloride) (hereinafter - CW), in the form of manifestation in children living under conditions of technogenic load habitat, chronic inflammatory and degenerative diseases of the gastrointestinal tract (hereinafter referred to as HVDZ GIT), namely: chronic gastroduodenitis (code, according to the International Classification of Diseases of the 10th revision - ICD-10: K-29.9).

The invention can be used for the early detection of chronic gastroduodenitis (hereinafter referred to as CGD) associated with exposure to these metals and ChOS when supplied with atmospheric air and drinking water, for subsequent targeted treatment and preventive measures for such children.

According to the classical definition, CGD is an inflammatory disease of the duodenal mucosa and the pyloric zone of the stomach (see Wikipedia).

In the framework of this decision, the term “Chronic gastroduodenitis associated with exposure to metals and organochlorine compounds” refers to a chronic recurrent disease accompanied by an inflammatory process and morphological rearrangement of the gastric mucosa and duodenum (focal or diffuse) according to the hypotrophic variant with hyposecretory, hypomotor-disturbing and autonomic dysfunction of the parasympathetic type.

The habitat of industrial cities is characterized by multi-media pollution with chemicals, including metals (an inhalation route of metal to the child’s body is more often possible), as well as organochlorine compounds (chloroform and carbon tetrachloride, which enter the body with drinking water).

Chronic inflammatory diseases of the gastrointestinal tract are the most common childhood diseases, in the structure of which gastroduodenal localization diseases predominate, the proportion of which is 58-65%. Detection of chronic diseases of the stomach and duodenum in children of regions of the Russian Federation has increased over the past 5 years by 48.2% and in the structure of pediatric gastroenterological pathology are recorded in 100-150 cases per 1000 children. New data have been obtained indicating that the pathological process in children has a combined nature of the lesion, spreading from the stomach to the duodenum.

в год.One of the reasons that determine the growth and formation of the characteristics of the course of chronic gastroduodenal diseases is the effect of hazardous chemical environmental factors, primarily metals (chromium, nickel, manganese) and organochlorine compounds. According to statistics in 2013-2014 Manganese and its compounds were among the leading air pollutants (exceeding MPC.s. by 5 or more times), and nickel and chromium were classified as stably present at the level of 1.3-1.5 MPCs.s. Among the main pollutants of drinking water, special attention is given to trihalomethanes (chloroform, carbon tetrachloride, etc.), which are stably recorded in 8-13% of drinking water samples at concentrations 2-8 times higher than hygienic standards. The danger of chronic exposure to contaminants, indicating the likelihood of damage to the gastrointestinal tract during multi-media intake (with drinking water and atmospheric air) for compounds of chromium ⁶⁺ , manganese by the total index, ranges from 1.41 to 3.65. A complex effect of chemical compounds (metals and organochlorine compounds) causes the occurrence of additional cases of diseases of the stomach and duodenum at the level of

in year.

Existing methods for diagnosing chronic gastroduodenitis do not take into account the influence of chemical risk factors on the occurrence and course of the disease, which limits their capabilities and does not adequately assess the severity of the process and the likelihood of its progression, the development of complications in older age groups and increases the risk of disability. In this regard, the scientific justification and development of diagnostic technology in children of CGD due to exposure to hazardous chemical factors is relevant.

A number of technical solutions are known from the prior art, which are methods for diagnosing CGD disease.

From RF Patent No. 2574914, a method is known for non-invasively diagnosing chronic gastroduodenitis in children, according to which the level of cationic antimicrobial β-2-defensin peptide in the feces is determined by enzyme immunoassay. When the concentration of the cationic antimicrobial peptide β-2-defensin is reached in the range from 31.2 ng / g to 87 ng / g, the presence of active chronic gastroduodenitis is diagnosed. When the concentration of the cationic antimicrobial peptide β-2-defensin is equal to or more than 87 ng / g, a high degree of chronic gastroduodenitis is diagnosed. The disadvantage of this method is that the method does not take into account the patient’s content of toxic metals and ChOS in biological media, the increased level of which causes an increase in the severity of the pathological process, and therefore, the proposed criteria will not adequately reflect the stage of the course of chronic gastroduodenitis under the conditions of multi-medium exposure to metals and HOS.

Also known is a method for the diagnosis of chronic gastroduodenitis and functional dyspepsia (RF Patent No. 2255337), including the study of clinical and laboratory parameters, while additionally determining the spontaneous adhesion of leukocytes and their sensitivity to cell adhesion modulators - phytohemagglutinin, theophylline, thymalin. With indicators of the functional activity of white blood cells within normal limits, a diagnosis of functional dyspepsia is established. With indicators of the functional activity of leukocytes exceeding normal limits, chronic gastroduodenitis is diagnosed.

The disadvantage of this known method is the use of complex invasive techniques. In addition, the above indicators are nonspecific and participate in the development of various pathological processes, which reduces the sensitivity and specificity of the method, and also complicates the interpretation of the results, reducing the degree of their reliability.

A known method for the diagnosis of chronic gastroduodenitis and functional dyspepsia (RF Patent No. 2270610), including gas chromatographic determination in the saliva of acetic, propionic and butyric acids, and at a concentration of any of the three acids: acetic acid is greater than 0.910 mmol / l, propionic acid is greater than 0.150 mmol / l, chronic oil production of greater than 0.013 mmol / l is diagnosed with chronic gastroduodenitis, and at acid concentrations of acetic in the range of more than 0.010 to 0.910 mmol / l, propionic up to 0.150 mmol / l, butyric to 0.013 mmol / l, functional dyspepsia is diagnosed.

The disadvantages of this method are the complexity of the study, which complicates the widespread use of the above method in practical use, as well as the inability to assess the degree of damage to the gastric mucosa.

A known method for determining the pathology of the gastroduodenal zone (RF Patent No. 2128335), including a crystallographic study with saliva NaCl, analysis of the results on the NaCl crystallization system and the magnitude of the morphotypes of liquid crystal structures, as well as a crystallographic study of exudate.

The disadvantages of this method are the complexity of the study and subjectivity in the interpretation of the results of the analysis, which reduces its reliability.

In USSR author's certificate No. 1409928, a method for diagnosing gastroduodenitis in children is described, according to which saliva is collected from a patient on an empty stomach, centrifuged for 10 minutes. at 3000 rpm, then determine the content of creatine, with a value of more than 73 μmol / l relative to the norm, conclude the presence of gastroduodenitis.

A method for differential diagnosis of chronic gastroduodenitis and functional dyspepsia in children who study clinical and laboratory parameters is known from the RF patent No. 225337, and spontaneous adhesion of leukocytes and their sensitivity to cell adhesion modulators — phytohemagglutinin (PHA), theophylline, thymalin are additionally determined. With indicators of the functional activity of leukocytes within normal limits: spontaneous adhesion of neutrophils 28.03 ± 2.0%; monocytes 30.04 ± 1.27%; lymphocytes 20.81 ± 0.97% and modulated neutrophil adhesion: PHA 31.02 ± 1.27%, theophylline 30.88 ± 1.07%, thymalin 32.66 ± 2.01%; monocytes: PHA 32.15 ± 1.11%, theophylline 31.02 ± 2.07%, thymalin 31.54 ± 1.21%, lymphocytes: PHA 23.05 ± 1.27%, theophylline 22.14 ± 1 , 12%, thymalin 21.98 ± 1.09% establish the diagnosis of functional dyspepsia. With indicators of the functional activity of leukocytes exceeding normal limits, chronic gastroduodenitis is diagnosed.

The disadvantage of this method is the non-specificity of the above indicators, which are involved in the development of many other various pathological processes, which reduces the sensitivity and specificity of the method, and also complicates the interpretation of the results when making a diagnosis.

Moreover, the known methods for the diagnosis of chronic gastroduodenitis associated with the effects of chromium, nickel, manganese and organochlorine compounds (chloroform and carbon tetrachloride) of technogenic origin were not identified from the prior art, therefore, it is not possible to choose the closest analogue to the claimed object.

The technical result achieved by the present invention is to create an informative and evidence-based method for the diagnosis of chronic gastroduodenitis in children associated with the effects of chromium, nickel, manganese, chloroform and carbon tetrachloride, anthropogenic origin, which allows subsequently to prescribe adequate therapy and prevent the development of complications.

The technical result achieved is achieved by the proposed Diagnostic Method for children with chronic gastroduodenitis associated with exposure to chromium, nickel, manganese, chloroform and carbon tetrachloride of technogenic origin, according to which a blood sample is taken from the child, the content of chromium, nickel, manganese, chloroform and carbon tetrachloride is established in it, and with an increased content of these metals in the blood, compared with the reference level of more than 2 times, as well as in the presence of chloroform and tetrachloride in the blood Thane above the lower limit of detection, determine the functional diagnostic indicators characterizing the child: the state of the autonomic regulation; functional status of the biliary tract; functional state of the liver; gastric acidity; the condition of the gastric mucosa and the duodenum; motor function of the stomach and duodenum, and also determine the level of the following laboratory diagnostic parameters in the blood serum of the child: pepsinogen I, pepsinogen II, dopamine, serotonin, cortisol, thyroid stimulating hormone TSH, antioxidant activity of AOA, glutathione peroxidase GlPO, malondialdehyde, malondialdehyde lipid hydroperoxides, ASAT aspartate aminotransferase, alkaline phosphatase, leukocyte phagocytic activity: absolute number of phagocytes, phagocytic number, phagocytic index, immunoglobulin A IgA and secretory immunoglobulin in sIgA saliva, and further, if the child shows deviations from the age-related physiological norm of at least 80% of the indicated functional and laboratory diagnostic parameters characterizing the presence of: dysregulation of the autonomic regulation in the form of a vagotonic initial vegetative tone and asymptaticotonic reactivity; functional disorders of the biliary tract as a hypomotor disorder of the gallbladder; low acidity of gastric juice; hypotrophy of the mucous membrane of the stomach and duodenum; increase in liver size and its reactive change, impaired motor function of the stomach and duodenum according to the hypomotor type with the presence of duodenogastric, duodeno-bulbar, bulbogastric refluxes, and in the presence of the following deviations of laboratory diagnostic parameters: excess of the pepsinogen II level exceeds the physiological norm by more than by 20%; cortisol by more than 10-15%; TSH by more than 10%; MDA more than 2 times; lipid hydroperoxides more than 1.5 times; ASAT more than 1.3 times; alkaline phosphatase more than 1.4 times; IgA more than 30%; as well as a decrease of the pepsinogen I level by more than 15% relative to the physiological age norm; dopamine more than 20%; more than 15% serotonin; AOA more than 1.5 times; GLPO more than 1.5 times; phagocytic number and phagocytic index more than 1.2 times; the absolute number of phagocytes is more than 1.3 times; sIgA by more than 30%, a child is diagnosed with chronic gastroduodenitis associated with exposure to chromium, nickel, manganese, chloroform and carbon tetrachloride of technogenic origin.

Functional diagnostic parameters are determined by instrumental methods: cardiointervalography, ultrasound scanning of the hepatobiliary zone and upper gastrointestinal tract, pH-metry, fibrogastroduodenoscopy.

, при этом ее прогнозный уровень к 2018 г. составил

. В ходе изучения структуры БОП установлено, что на долю хронического гастродуоденита приходится 21,9-30,7% всей патологии желудочно-кишечного тракта у детей.It should be noted that the incidence of the children's population (on the example of the territories of the Perm Territory) by diseases of the digestive system (hereinafter - BOP) over the past 15 years has increased 3.4 times and amounted to January 1, 2014

, while its forecast level by 2018 amounted to

. In the course of studying the structure of BOP, it was found that chronic gastroduodenitis accounts for 21.9-30.7% of the entire pathology of the gastrointestinal tract in children.

To understand the essence of the issue, it should be clarified that the problem of assessing the impact of industrial environmental pollution on the health of the child population is relevant for many countries of the world, including Russia. The children's population is a high-risk group, since children have a number of physiological characteristics, are characterized by the presence of critical periods of development, and greater sensitivity to the influence of toxic substances.

When exposed to chemical compounds, first of all, non-specific units of protective systems suffer, in particular, the immune and biochemical systems that ensure the maintenance of homeostasis. A set of biochemical reactions aimed at the metabolism and transformation of toxic compounds of exogenous origin determines the development of adaptive-compensatory processes. Violation of the coordination of the stages of biotransformation, being one of the general mechanisms of endogenous intoxication, helps to maintain inflammation and dysregeneration in gastroenterological diseases.

The mechanism of the damaging effect of metals: chromium, nickel, manganese, and HOS is complex and ambiguous. General pathomorphological mechanisms of their implementation are distinguished at the cellular-molecular levels: genotoxic, enzyme-toxic and membrane-toxic. The membrane concept is based on the premise that metals and HOS have strong prooxidant properties.

The development of CGD in children is accompanied by tissue damage due to excessive formation of reactive oxygen species in them, the main source of which in the gastroduodenal zone are polymorphonuclear leukocytes that infiltrate the mucous membrane of the stomach and duodenum. A decrease in the activity of the antioxidant defense system contributes to an increase in the activity of free radical processes and to an increased formation of toxic products that cause a membrane-destructive effect and release of inflammatory mediators. Lipid peroxidation is catalyzed by transition metal valence ions (nickel, chromium, manganese, etc.), which, against the background of a decrease in antioxidant protection, leads to an increase in the MDA level and a decrease in the fraction of reduced glutathione and, ultimately, leads to membrane pathological processes. The result of the membrane- and enzymatopathological action of metals is a violation of the function of mitochondria, leading to a decrease in macroerg production, a decrease in the activity of ATP-dependent enzyme systems. Metals are strong damaging agents for the epithelium of the small intestine, causing degradation and a chronic inflammatory process.

Analysis of the existing scientific and methodological literature allowed us to identify general patterns and features of the mechanism for the implementation of the damaging effects of a number of metals and organochlorine compounds.

Nickel is an essential trace element from the group of metals, with the exogenous intake of which morphofunctional reactions are formed in the body, which are especially clearly detected in the gastrointestinal tract. Dystrophic changes in the epithelium of the apical divisions of the villi, stroma infiltration by plasma and lymphoid cells, an increase in the number of glycoproteins on the surface of the epithelium and goblet cells, an increase in the content of ribonucleic acids in the apical divisions of the villus epithelium occur. In the small intestine, pronounced proliferation of lymphohistiocytic elements in the stroma of the villi is detected.

Chromium is a microelement from the group of metals, with the exogenous intake of which the biological process of oxidation is substantially disrupted, tissue respiration is inhibited, leading to the suppression of energy metabolism in cells. The effect on the gastrointestinal mucosa contributes to the disruption of the secretory and motor functions of the stomach, inflammatory changes and the frequent development of gastroduodenitis, inhibition of acid-forming function with a slight change in pepsin formation is noted. In the bloodstream, chromium specifically binds to transferrin, which serves as a carrier not only of iron, but also of chromium, which leads to the development of anemia in patients with CGD.

Manganese is an essential metal, plays an important role in cell metabolism and the protection of cell membranes, is concentrated in mitochondria, while its highest concentrations are formed in enterocytes, liver, pancreas. With exposure to manganese, chronic gastritis with reduced gastric secretion, a violation of the protein-forming function of the liver, vitamin and carbohydrate metabolism (hypoglycemic effect) are observed.

Tetrachloromethane is an extremely hazardous chemical (hazard class 1). In the process of its metabolism in the endoplasmic reticulum and microsomes of liver cells, it forms even more toxic free radicals, as well as chloroform. The interaction of radicals with phospholipids of intracellular membranes initiates lipid peroxidation with the subsequent development of a chain reaction of free radical oxidation, which leads to a suppression of the activity of membrane-bound enzymes, disruption of their protein synthesizing activity, the release of cytosolic enzymes into the blood, destruction of nucleotides, decompartization of calcium, apoptosis and necrosis necrosis and necrosis . Metabolic transformations of carbon tetrachloride are the basis of hepatotoxicity.

The pathogenetic mechanism of the action of chloroform on the organs of the gastroduodenal zone is indirect, through a violation of neurohumoral regulation. At the same time, with chronic intake of chloroform into the body with drinking water, local inflammatory changes in the mucous membrane of the stomach and intestines are observed. The toxicity of chloroform is due to the action of intermediate products of its metabolism, the amount of which increases with the accelerated metabolism inherent in the children's body. Metabolites form covalent bonds with microsomal proteins and enzymes, which contributes to cell damage and death. It was shown that chlorine compounds are oxidized in the liver by cytochrome P-450 with the formation of strong reagents - digalocarbonyls, which are responsible for entero and hepatotoxicity.

That is why the development of a diagnostic method for children with CGD due to exposure to hazardous chemical factors is very important in terms of early detection of this pathology and subsequent preventive measures.

Due to the fact that the proposed method uses information about the content of chromium, nickel, manganese, chloroform and carbon tetrachloride in the blood of the child and the claimed specific functional and laboratory diagnostic indicators, in the aggregate characterizing a specific technogenic

the origin of chronic gastroduodenitis, the clinical significance of which has been proved by the method of correlation and regression analysis, provides additional information linkage of changes in these laboratory parameters with a certain, stated excess over the reference level, blood levels of these metals and cholesterol, which makes the proposed method accurate and reliable.

In addition, the test results showed that in order to establish an accurate diagnosis of the occurrence of CGD associated with the environmental toxic effects of these metals and ChOS of technogenic origin, it is enough for the child to deviate laboratory diagnostic parameters within the following limits:

- excess of the pepsinogen II level relative to the physiological age norm by more than 20%; cortisol by more than 10-15%; TSH by more than 10%; MDA more than 2 times; lipid hydroperoxides more than 1.5 times; ASAT more than 1.3 times; alkaline phosphatase more than 1.4 times; IgA more than 30%;

- reduction of the level of pepsinogen I relative to the physiological age norm by more than 15%; dopamine more than 20%; more than 15% serotonin; AOA more than 1.5 times; GLPO more than 1.5 times; phagocytic number and phagocytic index more than 1.2 times; the absolute number of phagocytes is more than 1.3 times; slgA more than 30%, which was confirmed by the model parameters. Moreover, it is enough that the deviations should be in an amount of at least 80% of the totality of the indicated functional and laboratory parameters. Studies have shown that a reliable correlation between the indicated laboratory parameters and the concentration of chromium, nickel, manganese in the blood is achieved only when the content is more than 2 times higher than the reference level and the presence of chloroform and carbon tetrachloride in the blood is higher than the lower detection limit (the detection limit in chemical analysis is the minimum content of the analyte in the sample, the signal from which can be reliably distinguished from the background. https://ru.wikipedia.org/wiki/).

At a lower concentration of these chemicals in the blood sample, a reliable relationship between this concentration and laboratory parameters for CGD has not been identified.

This, apparently, is due to the fact that these metals, when they are contained in the blood below this figure, have a damaging effect on the gastrointestinal tract only within the limits of a functional disorder of the stomach and duodenum (stage 1), without damage to the gastric mucosa, as in case of CGD.

The transition to the establishment of the above laboratory parameters and their deviation from the physiological norm is necessary if the child has changes in the following functional diagnostic indicators characterizing: impaired autonomic regulation in the form of a vagotonic initial autonomic tone and asymptaticotonic reactivity; functional disorders of the biliary tract as a hypomotor disorder of the gallbladder; low acidity of gastric juice; hypotrophy of the mucous membrane of the stomach and duodenum; an increase in the size of the liver and its reactive change, is a violation of the motor function of the stomach and duodenum according to the hypomotor type with the presence of duodenogastric, duodenobulbar, bulbogastric refluxes.

Thus, the proposed method allows to diagnose with sufficient accuracy CGD in children, due to the toxic effects of these metals and ChOS. All this will increase the effectiveness of the prevention and medical treatment of the disease in children with an accurate diagnosis, provide concrete planning of sanitary and hygienic measures to prevent and eliminate the effects of harmful chemicals that cause environmentally caused pathology in children.

Based on the foregoing, we can conclude that the technical result is achieved due to the totality of all operations of the proposed method, their sequence and modes of implementation.

In the practical implementation of the proposed method, the following operations are carried out in the following sequence:

1. Choose an ecologically unfavorable territory for a high load of chemical environmental factors. Moreover, the specified territory is chosen in relation to the child population aged 8-12 years, living in this territory, which is characterized by:

- An increased incidence of children (above regional and / or average Russian) gastroduodenal pathology (ICD-10: K-29.9). To form the indicated contingent of children, a retrospective analysis of the actual incidence of the gastrointestinal tract according to the appeal for medical care is carried out. There is a group of children aged 8-12 years (the most vulnerable age group for the primary manifestation of the studied nosological form) with a frequency of seeking medical help two or more times a year;

- air pollution (on the example of metals) and drinking water supply (on the example of organochlorine compounds) in concentrations exceeding hygiene standards and determining the main contribution to the formation of an unacceptable risk of gastrointestinal diseases; At the same time, the study of the quality of atmospheric air and drinking water is carried out in accordance with the Decree of the Government of the Russian Federation of 02.02.2006 No. 60 "Regulation on the conduct of socio-hygienic monitoring as amended on 09/04/2012,

- the presence of an unacceptable risk (HI> 1.0) of the development of a gastrointestinal pathology associated with aerogenic exposure of these metals and oral exposure to cholesterol, the effect of which underlies the formation of CGD. The risk assessment for the development of this disease (ICD-10: K-29.9) is carried out according to a standardized method in accordance with the “Guidelines for assessing public health risk from exposure to chemicals that pollute the environment” (R 2.1.10.1920-04);

2. To substantiate the markers of negative effects characterizing the risk-associated pathomorphosis of CGD disease, biomedical studies are carried out, including a complex of clinical (analysis of heredity, medical history, clinical features), functional, instrumental (cardiointervalography, ultrasound of the hepatobiliary zone and upper gastrointestinal tract , pH-metry, fibrogastroduodenoscopy (FGDS), laboratory (biochemical, immunological, enzyme immunoassay, immunogenetic), chemical-analytical study (content of manganese, chromium, nickel, chloroform, carbon tetrachloride in the blood).

3. For each child, a blood sample is taken from the generated sample and the contents of chromium, nickel, manganese, chloroform and carbon tetrachloride are established in it.

4. With an increased content of these metals in the blood, compared with the reference level more than 2.0 times, and also with the presence of chloroform and carbon tetrachloride in the blood above the lower limit of determination, functional diagnostic indicators are determined by instrumental methods, characterizing: the state of autonomic regulation; functional state of the hepatobiliary tract; functional state of the liver; gastric acidity; the condition of the gastric mucosa and the duodenum; motor function of the stomach and duodenum.

5. A study is also carried out to determine the level of the following laboratory diagnostic indicators in the blood serum of a child: pepsinogen I, pepsinogen II, dopamine, serotonin, cortisol, TSH, AOA, HLPO of blood serum, MDA, lipid hydroperoxide, ASAT, alkaline phosphatase; phagocytic activity of blood leukocytes; immunoglobulin A in saliva (sIgA) and in serum (IgA).

6. Establish deviations from the norm of the specified functional and laboratory diagnostic indicators characterizing the presence of:

- Violations of autonomic regulation by the type of vagotonic initial autonomic tone and asympathicotonic reactivity;

- functional disorders of the biliary system as a hypomotor disorder of the gallbladder;

- low acidity of gastric juice;

- malnutrition of the mucous membrane of the stomach and duodenum;

- increase in the size of the liver and its reactive change,

- impaired motor function of the stomach and duodenum in the hypomotor type with the presence of duodenogastric, duodenobulbar, bulbogastric refluxes;

if there is an excess relative to the physiological age norm of the level:

- pepsinogen II more than 20%;

- cortisol by more than 10-15%;

- TTG by more than 10%;

- MDA more than 2 times;

- lipid hydroperoxides more than 1.5 times;

- ASAT more than 1.3 times;

- alkaline phosphatase more than 1.4 times;

- IgA by more than 30%;

and decreases relative to the physiological age level

- pepsinogen I more than 15%;

- dopamine more than 20%;

- serotonin more than 15%;

- AOA more than 1.5 times;

- GLPO more than 1.5% times;

- phagocytic number and phagocytic index more than 1.2 times;

- the absolute number of phagocytes is more than 1.3 times

- sIgA more than 30%;

7. If the child has deviations from the norm of at least 80% of the number of specified functional and laboratory diagnostic indicators, the child is diagnosed with chronic gastroduodenitis associated with exposure to chromium, nickel, manganese, chloroform and carbon tetrachloride of technogenic origin.

The physiological levels are used as criteria for assessing deviations of laboratory parameters: reference levels are used for the content of chromium, nickel, manganese (N. Tits, 2003), and for the content of cholesterol - the detection limit in accordance with the method for determining cholesterol in the blood (MUK 4.1.2115- 06 "Determination of the mass concentration of chloroform, 1,2-dichloroethane, carbon tetrachloride in biological media (blood) by gas chromatographic analysis of equilibrium vapor").

The main research methods in the implementation of the proposed method were:

- sanitary-hygienic: a comparative analysis of the results of monitoring observations; spatio-temporal analysis in a GIS environment using the Ecolog UPRZA program, version 3.0 and Ecolog-Srednye - 15 models of 3 elements on a site of 65,000 points; calculation of hazard coefficients and index for 5 components (Guidelines for assessing the risk to public health from exposure to chemicals polluting the environment: Guidelines 2.1.10.1920-04.M .: Federal Center for State Sanitary and Epidemiological Supervision of the Ministry of Health of Russia, 2004. 143 p.); epidemiological methods using one-dimensional statistical analysis and the construction of a trend model with dynamic exponential smoothing (Chetyrkin EM Statistical forecasting methods. M: Statistics. 1977. 356 p.);

- diagnostic: clinical (analysis of heredity, medical history, clinical features), functional and instrumental (cardiointervalography, FGDS, pH-metry, ultrasound scanning); laboratory (general clinical - hematological indicators; biochemical - indicators of oxidative-antioxidant processes, enzymatic activity, inflammatory reactions (in blood serum); immuno-allergological - indicators of cellular, humoral, specific immunity; immunoenzymatic - indicators of the exchange of neurotransmitters, thyroid hormones) (Medical laboratory technologies and diagnostics: a reference book. Medical laboratory technologies in 2 volumes / Edited by A.I. Karpishchenko. St. Petersburg: Intermedika, 2002. 408 p.);

- chemical-analytical methods of investigation (gas chromatography on a gas chromatograph Chromatec-Crystal-500, mass spectrometry with inductively coupled plasma on an Agilent 7500 cx mass spectrometer).

To prove the validity of the diagnostic indicators used in the proposed method, a correlation analysis was used between the obtained functional and laboratory diagnostic indicators and the content of chromium, nickel, manganese, chloroform and carbon tetrachloride in the child’s blood using the logistic regression model, according to which the probability of a negative change in the response marker of the body is calculated ( the above diagnostic indicators) when exposed to an exposure marker (decree OF DATA toxicants). The identification and assessment of the relationship between changes in indicators in children and the concentration of these toxicants in the blood is performed based on the calculation of the odds ratio indicator (OR) and its confidence interval (DI). The criterion for the presence of the relationship "concentration of chromium, nickel, manganese, chloroform and carbon tetrachloride - response indicator" is OR≥1. The justification of response markers is based on the evaluation of the parameters of the dependence of the odds ratio on the concentration of these metals and the presence of COS in the blood, described by the regression model as an exponential function. The Fisher test (F) is used as a criterion for testing statistical hypotheses. Differences are considered statistically significant with a probability of p≤0.05.

An example of a specific implementation of the proposed method:

1. The method was tested on an environmentally unfavorable territory of the city of Chusovoy Perm Territory. In the course of studying the structure of diseases of the digestive system (BOP), it was found that CGD accounts for 21.9-30.7% of the entire pathology of the gastrointestinal tract in children. The city of Chusovoy was characterized by the most unfavorable situation regarding the incidence of CGD children from 12 industrially developed regions of the region, and the lowest incidence rate was in the city of Kungur.

до

и с 2005 г. превышала среднекраевой в 1,2 раза.The incidence of children in the city of Chusovoy HGD over the past 15 years has increased from

before

and since 2005, it exceeded the regional average 1.2 times.

The data of field observations indicate the excess of hygienic standards in the atmospheric air of residential buildings on manganese, nickel, chromium at the level of 1.3-1.5 MPC.s. Estimated concentrations of pollutants in residential areas are 1.8-2.2 MPC.s. At the same time, about 1.5 thousand children are in the exposure zones.

Sources of drinking water supply for the population of Chusovoy are surface water bodies. The results of monitoring observations of the quality of drinking water indicate that hygienic standards have been exceeded for the predominantly chloroform content of up to 2.5-2.8 MAC (maximum up to 5.3-7.3 MAC) and carbon tetrachloride - up to 2.1 MAC. The proportion of non-standard samples is 52.5% -100%.

The calculation of the hazard coefficients and index during chronic multi-media exposure with atmospheric air and drinking water by the studied chemical factors revealed an unacceptable risk of damage to the central nervous system (CNS) and hepatobiliary system, dysfunctional disorders of which initiate the development of gastrointestinal tract gastrointestinal tract exceeding an acceptable level (HQ = 1) in 27 -44 times for metals and 2.4 times for HOS. The simultaneous receipt of these contaminants increases the risk of damage to critical systems (HI = 29-46). Share contribution of metals - 95%, HOS - 5%.

2. To justify in children diagnostic indicators for the diagnosis of CGD associated with exposure to chromium, nickel, manganese and organochlorine compounds (chloroform and carbon tetrachloride), an anamnestic, clinical, functional, instrumental and laboratory examination was performed. The observation group consisted of 320 people aged 8-12 years with a previously established diagnosis - upper gastrointestinal tract disease (ICD-10: K-29.9) without exacerbation (49% of boys and 51% of girls) living permanently in the selected territory of the Perm Territory (g Chusovoy). The comparison group consisted of 230 children aged 8-12 years (46% of boys and 54% of girls) with a preliminary diagnosis of upper gastrointestinal tract disease (ICD-10: K-29.9) in the remission period, living in conditions of sanitary and hygienic well-being (g Kungur).

When analyzing medical and social questionnaires, there were no significant differences between groups by social indicators.

3. A comparative assessment of the content of toxicants in the blood of children with CGD living under various environmental conditions of exposure to metals and organochlorine compounds showed that carbon monoxide (in 86% of cases) and chloroform (77%) are determined in the blood of children in the observation group (0.0001≤ p≤0.002), not identified in the blood of children of the comparison group (table 1).

Statistically significant differences were found in the concentration of chromium, nickel, manganese in the blood of children with CGD of the sample under study relative to indicators in children of the comparison group. The excess ratio was from 2.3 to 5.4 times (p = 0.0001). Identification and evaluation of the parameters of the dependence “dose of the pollutant - concentration of the toxicant in the biological environment” allowed us to obtain adequate models of the dependence (F≥3.96, p≤0.05) between the daily dose of metals and organochlorine compounds and their concentration in the blood of children, described by linear equations (F = 17.54-1323.17, R ² = 0.42-0.71, p = 0.0001) (table 2).

Studies have shown that the clinical manifestations of gastrointestinal tract CTD in children of the observation group do not correspond to classical concepts: with an increase in the level of biomedical contamination, the severity of subjective gastroenterological symptoms decreases (odds ratio OR = 2.83-4.20; confidence interval DI = 2.1-4 ,8). Only 5.8 8 ± 1.19% of the children in the observation group had a combination of 6 or more pathognomonic gastrointestinal symptoms, and in the comparison group such a combination was noted in every fifth child (OR = 4.41 DI = 3.1-5.8 )

In the clinical picture of gastrointestinal tract gastrointestinal tract gastrointestinal tract in children of the observation group (p <0.0001), signs of endogenous intoxication (OR = 2.89, DI = 2.1-4.0), autonomic dysfunctions (OR = 1.44, DI = 1) prevail , 1-2.5), lesions of the cardiovascular system (OR = 1.84, DI = 1.2-3.8), proliferation of lymphoid tissue (OR = 2.16, DI = 1.5-3.6 )

In the observation group, the complex of symptoms characterizing the defeat of the hepatobiliary system was recorded 2 times more often (p≤0.05) than in the comparison group (OR = 2.03, DI = 1.3-3.8), liver enlargement and tightening - 1.5 times (OR = 2.04, DI = 1.2-3.6), characteristic etiological factors (infectious, hereditary, psychosomatic; OR = 4.44, DI = 3.1-5, 8) (tables 3-6).

External environmental factors (p≤0.003) relative to the comparison group are more likely to be triggers of gastrointestinal tract gastrointestinal tract gastrointestinal tract in children of the observation group: living in central areas (OR = 4.59, DI = 2.5-5.8), proximity to industrial residence enterprises (OR = 2.89, DI = 2.0-3.8), the absence of health-improving activities and good rest (OR = 3.99, DI = 2.6-4.7).

4. Further, in order to establish the reliability of the diagnosis of CGD associated with exposure to chromium, nickel, manganese and organochlorine compounds: chloroform and carbon tetrachloride, of technogenic origin, according to the proposed method, all children underwent the following examinations:

- determination of functional diagnostic indicators characterizing: the state of autonomic regulation; gastric acidity; the condition of the gastric mucosa and the duodenum; functional state of the hepatobiliary tract; functional state of the liver; motor function of the stomach and duodenum.

A study was also carried out to determine the level of the following laboratory parameters in the child's blood serum: pepsinogen I, pepsinogen II, dopamine, serotonin, cortisol, TSH, AOA, serum GLPO, MDA, lipid hydroperoxide, alkaline phosphatase, phagocytic activity of cells, immunoglobulin A (IgA) and secretory immunoglobulin in saliva (sIgA).

If the child has deviations from the norm of at least 80% of the number of the indicated functional and laboratory diagnostic indicators characterizing the presence of: violations of autonomic regulation in the form of a vagotonic initial autonomic tone and asymptaticotonic reactivity; functional disorders of the biliary tract as hypomotor disorders of the gallbladder; low acidity of gastric juice; hypotrophy of the mucous membrane of the stomach and duodenum; increase in the size of the liver and its reactive change; violations of the motor function of the stomach and duodenum according to the hypomotor type with the presence of duodenogastric, duodenobulbar, bulbogastric refluxes; as well as in the presence of the following deviations of laboratory parameters: excess of the pepsinogen II level by more than 20% relative to the physiological age norm; cortisol by more than 10-15%; TSH by more than 10%; MDA more than 2 times; lipid hydroperoxides more than 1.5 times; ASAT more than 1.3 times; alkaline phosphatase more than 1.4 times; IgA more than 30%; and a decrease in this case relative to the physiological age norm of the level of pepsinogen I by more than 15%; dopamine more than 20%; more than 15% serotonin; AOA more than 1.5 times; glutathione peroxidase more than 1.5 times; phagocytic number and phagocytic index more than 1.2 times; the absolute number of phagocytes is more than 1.3 times; sIgA more than 30%; then a child is diagnosed with chronic gastroduodenitis associated with exposure to chromium, nickel, manganese, chloroform and carbon tetrachloride of technogenic origin.

The indicated changes in diagnostic indicators, expressed as a deviation from the norm of the above functional and laboratory indicators, were proved on mathematical models. The results are shown below.

During an ultrasound scan of the gastroduodenal region 3 times more often in the observation group relative to the comparison group, the presence of a moderate amount of fluid on an empty stomach in the stomach was detected as a sign of hypersecretion (33% and 11%, respectively, p = 0.003).

The physiological variant of the motor function of the stomach and duodenum was determined in children of the observation group 2 times less often (14%) than in the comparison group (28%, p = 0.03).

The dominant type of disturbances was the presence of refluxes (duodeno-gastric, duodeno-bulbar, bulbo-gastric), which were recorded in the observation group 1.5 times more often (p = 0.04) than in the comparison group (OR = 1.41- 1.52; DI = 1.12-3.87).

Causal relationships of increased blood manganese content with impaired motor function of the stomach and duodenum (R ² = 0.25-0.52; F = 46.5-119.18; p = 0.01-0.001) were established .

As a result of pH-metry in children of the observation group, significantly more pronounced secretory disorders of the hyperacidity type were found with a significant insufficiency of the neutralizing function of the antrum and fundus. The diagnosis of CGD in children aged 8-12 years of the observation group was established in 57% of cases, in children of the comparison group in 27.8% of cases (p≤0.002).

During FGDS, it was found that in children of the observation group, more pronounced and widespread inflammatory and degenerative changes in the mucous membrane were determined: superficial gastroduodenitis (78.6% in the observation group and 48.3% in the comparison group), granular gastroduodenitis (20.5 % and 13.7%), erosive esophagogastroduodenitis (19.7% and 3.4%), atrophic gastritis (5.4% and 0%), changes in the mucous membrane of the duodenum in children of the observation group were more often characterized by pronounced phenomena duodenostasis (15.6% and 3.7%). Granularity of the mucosa (8.3%), atrophy (5.6%), erosion and ulcers (19.5%) were found only in the observation group (p≤0.05).

Reliable relationships of the content of contaminants in the blood of children with the morphological parameters of the pathological process in the mucous membrane of the stomach and duodenum have been established. The increased content of manganese in the blood correlated with the frequency of detection of lymphonodular hyperplasia of the gastric mucosa (R ² = 0.67, p≤0.05), chromium - with destructive processes of the gastric mucosa and bulb of the duodenum (R ² = 0.42 ÷ 0.81, p = 0.012-0.0001). A relationship was found between an increase in blood levels of carbon tetrachloride, chloroform and nickel with the detection of bile in the stomach (R ² = 0.55-0.61, p = 0.0002-0.004).

The largest number of significantly significant differences in children of the observation group was found between the frequency of occurrence of endoscopic indicators and an increased level of cholesterol in the blood (p = 0.001-0.009), the frequency of endoscopic detection of inflammatory changes in the esophagus and the content of nickel in the blood (R ² = 0.41), antrum gastritis - with chromium (R ² = 0.44), common lesions of the stomach (fundus and antrum) - with the level of carbon tetrachloride (R ² = 0.37).

Connections between endoscopically established pyloric insufficiency and granular gastritis were noted with an increased concentration of chloroform and manganese in the blood (R ² = 0.61-0.64, p = 0.001-0.004).

It was found that the erosive process in the duodenum in the children of the observation group is associated with an increased content of carbon tetrachloride in the blood (R ² = 0.72, p = 0.008) (tables 7-9).

According to cardiointervalography (CIG), the predominant type of initial vegetative tone in children of the observation group was eutonia (in 50% of cases), but in 37.5% of children the vagotonic variant was established, which was 2 times higher than the comparison group (p = 0.035).

The magnitude of the variation range (Dx), which reflects the activity of the parasympathetic department of the autonomic nervous system, in children of the observation group is significantly higher than the physiological norm and the indicator of the comparison group, and the mode amplitude (AMo), which characterizes the activity of the sympathetic nervous system, is 1.3 times lower (p = 0.0001). In children of the comparison group, the stress index IN = 110.4 ± 12.8 cu, which indicated an adequate tension of adaptation mechanisms.

Direct reliable associations were revealed between the increased content of manganese in the blood and the development of the initial vagotonia and the asymptaticotonic type of autonomic reactivity (R ² = 0.37-0.42; F = 87.54-118.12; p = 0.01).

Laboratory features of gastrointestinal tract gastrointestinal tract were as follows.

A study of the activity of oxidative-antioxidant processes showed an increased formation of lipid peroxidation products (the level of lipid hydroperoxides and MDA in 41.4-55.0% of children in the observation group was up to 2 times higher than in children in the comparison group, (p = 0.001) against depletion of antioxidant defense processes (the level of HLPO and the integral indicator of total antioxidant activity in blood serum are reduced in 42.0-65.7% of children in the observation group with 9.7-18.2% in the comparison group, p = 0.0001-0.048 ) (table 10). Hyperproduction of active forms of oxygen and lipid peroxide by cells causes an imbalance of neurotransmitters and at the same time has a direct cytotoxic effect on the mucous membrane of the stomach and duodenum, which determines their disregulating effect on the secretory-motor function of the upper gastrointestinal tract.

A study of the state of neuroendocrine regulation showed the development of a syndrome of dysregulatory disorders. In children of the observation group, in relation to the indicators of the comparison group, manifestations of violations of the regulatory function of the hypothalamic-pituitary system were established: significantly increased serum cortisol level (759.4 ± 45.5 nmol / dm ³ , excess ratio 1.2 times, p = 0.001), a reduced level of dopamine (on average to 80.23 ± 1.62 pg / cm ³ , the reduction ratio of 1.2 times, p≤0.0001) and serotonin (on average to 0.18 ± 0.03 μmol / dm ³ , the reduction ratio of 5.8 times, p≤0.0001), an increased level of TSH (4.41 ± 0.21 μI / cm ³ , the ratio of excess 1.8 times, p≤0.007).

Activation of the adrenal cortex and the anterior pituitary gland and inhibition of the synthesis of central neurotransmitters has a stressful effect on the vegetative-visceral innervation and vascular endothelium, which results in impaired gastrointestinal motor function and a decrease in the production of protective factors by the gastric mucosa. A study of the activity of cytolysis and the state of cellular-humoral immunity indicates an increase in cytolytic activity (ACAT activity in 76% of children increased to 48.1 ± 4.06 U / dm ³ ), a decrease in the activity of nonspecific resistance factors (a decreased phagocytic number and phagocytic index in 42 , 2% and 34.2%, which is 3 times higher than in the comparison group, 0.001≤p≤0.003). In addition, signs of cholestasis were detected in the form of an increase in alkaline phosphatase activity in 54% of children up to 903.0 ± 31.40 U / dm ³ , p = 0.003).

A significantly reduced level of serum IgA was found, recorded in 29.0% and 35.4% of cases in the observation group at 10.4% and 3.9% of cases, respectively, in the comparison group (0.023≤p≤0.032), the reduction ratio was 1 2-1.3 times; elevated levels of IgE specific to the studied metals in 57-68% of cases in the absence of those in the comparison group (p = 0.0001).

In addition, 47% of children showed a decrease in sIgA content in saliva (up to 259.0 ± 14.06 mg / dm ³ , p = 0.0001), which is 2.0 times lower than the value of the comparison group.

Confirmation of a change in the state of the mucous membrane of all parts of the stomach and duodenum (tendency to develop hypotrophic processes) is an increase in the level of pepsinogen II by a factor of 2.0 relative to the physiological norm in 37% of cases in 12% of cases in the comparison group (p = 0.002) and a decrease in the level of pepsinogen I in 25% of cases with 3% of cases in the comparison group.

During the study, a relationship was found between the clinical manifestations of dysregulatory disorders of the motor-secretory function of the gastrointestinal tract with a predominance of parasympathetic influences; functional indicators of the failure of adaptive-compensatory mechanisms for maintaining homeostasis of vegetative-visceral innervation; indicators of the imbalance of oxidation-antioxidant processes, the development of cholestasis and increased cytolysis, decreased activity of non-specific resistance factors and increased sensitivity of the gastrointestinal mucosa with the content of carbon tetrachloride, chloroform, manganese, nickel, chromium in the blood (the probability of a change in indicators (P) is 0.58-0, 77, the Fisher test (F) - 8.08-422.06, the coefficient of determination (R ² ) - 0.10-0.89, p = 0.0001-0.04) (table 10).

Summarizing the results obtained during the study, in children with CGD and elevated blood levels of metals compared with the reference level (chromium at the level of 0.075 ± 0.005 mg / dm ³ , nickel - 0.056 ± 0.0036 mg / dm ³ , manganese 0.059 ± 0.008 mg / dm ³ ) and the presence of COS in the blood (carbon tetrachloride - 0.00003 ± 0.000002 mg / dm ³ , chloroform - 0.0008 ± 0.00005 mg / dm ³ ) the pathogenetic links of the modification of the pathological process were established. The increased content of manganese, carbon tetrachloride and chloroform has a negative effect on the central and autonomic nervous systems, which is manifested by an imbalance in the homeostasis of neurotransmitters (markers: decreased levels of serotonin, dopamine, cortisol, R ² = 0.36-0.89, p≤0.05) , with the development of 2 times more often astheno-neurotic and autonomic disorders, mainly according to the parasympathetic type (markers: vagotonic type of the initial vegetative tone with an asymptaticotonic variant of autonomic reactivity, disturbance of the head biorhythmics th brain according electroencephalography associated with an increased content of manganese; R ² = 0,36-0,42, p≤0,05).

Autonomic disorders with a predominance of parasympathetic influences in children are manifested by biliary dysfunction syndrome and increased activity in the blood serum of alkaline phosphatase (markers: hypotonic type of biliary dysfunctions according to ultrasound scans and increased activity of alkaline phosphatase associated with manganese in the blood; R ² = 0.52 -0.6, p≤0.05), the course of which is exacerbated by the direct effect of chloroform on liver cells with the subsequent development of a reactive inflammatory process and functional disorders of the biliary about the path of the hypomotor type (markers: reactive changes and an increase in the size of the liver according to ultrasound scans, increased activity of ASAT, R ² = 0.39-0.44, p≤0.05).

Vegetative disorders of the parasympathetic type in children with a high content of manganese in the blood cause a violation of the motor function of the stomach and duodenum with the development of refluxes and throwing the contents of the duodenum into the stomach (markers: impaired motor function of the stomach and duodenum, various reflux according to ultrasound scan, R ² = 0.25-0.52, p≤0.05).

Exposure to the gastric mucosa of bile acids leads to solubilization of the lipid layers of the surface epithelial membranes. Lecithin contained in bile is biotransformed into lysolecithin, which has a pronounced cytotoxic effect on the epithelium with the subsequent development of hypotrophic processes (markers: decreased pepsinogen I, activation of pepsinogen II, R ² = 0.21, p≤0.05).

The inflammatory process in the mucous membrane of the stomach and duodenum in children with a high content of metals is aggravated by a decrease in nonspecific resistance of mucous membranes to aggression factors caused by activation of free radical oxidation, suppression of antioxidant defense reactions and activation of cytolytic processes (markers: decreased sIgA in saliva, increased lipid hydroperoxides, MDA in blood serum; decrease in total AOA, serum HLPO; phagocytosis, IgA content, R ² = 0.33-0.68, p≤0.05).

Thus, the increased content of chromium, nickel, manganese in the blood and the presence of COS, due to exposure to atmospheric air at the level of 1.3-1.5 PDCs.s. and with drinking water at the level of 2.1-2.8 MAC, underlie the pathomorphism of CGD, which consists in the development of vegeto-visceral dysfunctions in the parasympathetic type and reactive changes in the liver, accompanied by motor disorders of the biliary tract in the hypotonic type, gastric motility and 12- duodenal ulcer according to the hyperkinetic variant; suppression of factors of nonspecific resistance and local immunity against the background of activation of cytolytic processes with the development of inflammatory and degenerative changes in the gastrointestinal mucosa, which is manifested in children by the development of chronic gastroduodenitis by hypotrophic type.

Thus, the study on mathematical models “exposure marker (indicated metals, ChOS) - the answer (deviations of diagnostic indicators) showed that for the diagnosis of children,“ Chronic duodenitis associated with exposure to chromium, nickel, manganese, chloroform and carbon tetrachloride of technogenic origin »A child must have a complex of the following indicators:

1. The increased content in the blood sample of these metals, compared with the reference level of more than 2.0 times and the presence in the blood of chloroform and carbon tetrachloride above the lower detection limit.

2. The presence of functional diagnostic indicators (fp), expressed in deviations from the physiological norm and characterizing:

2.1. violations of autonomic regulation in the form of a vagotonic initial autonomic tone and asymptaticotonic reactivity;

2.2. functional impairment of the biliary tract as a hypomotor disorder of the gallbladder

2.3. reduced acidity of gastric juice;

2.4. the presence of malnutrition of the mucous membrane of the stomach and duodenum;

2.5. an increase in the size of the liver and its reactive change;

2.6. violation of the motor function of the stomach and duodenum according to the hypotonic type with the presence of duodenogastric, duodenobulbar, bulbogastric refluxes;

3. The presence of laboratory diagnostic criteria (lp), expressed in deviations from the norm of the following laboratory indicators:

excess relative to the physiological age norm

3.1. pepsinogen II level by more than 20%;

3.2. cortisol levels of more than 10-15%;

3.3. TSH levels of more than 10%;

3.4. MDA more than 2 times;

3.5. lipid hydroperoxides more than 1.5 times;

3.6. ASAT more than 1.3 times;

3.7. alkaline phosphatase more than 1.4 times;

3.8. IgA more than 30%;

and decreases relative to the physiological age norm

3.9. pepsinogen I level by more than 15%;

3.10. dopamine more than 20%;

3.11. more than 15% serotonin;

3.12. AOA more than 1.5 times;

3.13. GLPO more than 1.5 times;

3.14. phagocytic number more than 1.2 times;

3.15. phagocytic index more than 1.2 times;

3.16. the absolute number of phagocytes more than 1.3 times

3.17. sIgA more than 30%;

The justification of the declared boundary limits of the content of toxicants and laboratory parameters relative to the physiological age norm was as follows:

- at a lower concentration of these toxicants in the blood sample, a reliable relationship between this concentration and the indicated functional and laboratory parameters (diagnostic criteria) was not detected.

When diagnosing a child’s chronic gastroduodenitis associated with exposure to chromium, nickel, manganese, chloroform and carbon tetrachloride, it is concluded that this child needs specialized medical and preventive measures.

To justify the accuracy of the proposed diagnostic method, as well as to prove the significance of the symptom: “if the child has deviations from the norm of at least 80% of the number of specified functional and laboratory diagnostic indicators in accordance with the specified criteria, then the child is diagnosed with the presence of chronic gastroduodenitis associated with exposure to chromium, nickel, manganese, chloroform and carbon tetrachloride of technogenic origin ”, drug treatment was carried out - combined use of Drugs and physiotherapy indicated in table 11.

These drugs are aimed at the treatment of detected CGD associated with exposure to these toxicants.

It should be clarified that deviations from the norm of 80% of the number of specified functional and laboratory diagnostic criteria are: (6 f.p. + 17 hp) × 80/100 = 18.4 (round up to 19 deviations of the criteria, t .k. 80% or more) indicators with deviations in accordance with the specified criteria. Those. if a child has an increased content of these contaminants in the blood, the presence of 19 or more functional and laboratory diagnostic criteria, then the diagnosis is made: "CGD associated with exposure to chromium, nickel, manganese, chloroform and carbon tetrachloride of technogenic origin."

In addition, to prove the accuracy of the proposed method, drug treatment of children from the observation group (the first group) was carried out, in which 80% or more deviations from the norm from the number of declared diagnostic criteria were detected (i.e., in the amount of 19 or more deviations of diagnostic indicators ), as well as in children from the same group in whom such deviations were below 80% (second group) (i.e., less than 19 of these indicators with deviations). The treatment was carried out by the combined use of drugs and the physiotherapeutic method indicated in Table 11. These drugs and physiotherapy are aimed at treating and preventing the detected CGD associated with exposure to chromium, nickel, manganese, chloroform and carbon tetrachloride.

After this treatment, the children of the first group improved clinical, laboratory and functional indicators:

- reduction in the frequency and duration of relapse of the disease by 50%;

- a decrease in the content of chromium, nickel, manganese in the blood to a value of 1.0 or less than the reference concentration in 85% of children;

- a decrease in the content of chloroform and carbon tetrachloride to the lower limit of determination in all children;

- increase in serotonin to a physiological level in 85% of children

- reduction to the physiological age norm of pepsinogen II level in 75% of children; cortisol in 50%; TSH level in 45%; MDA in 85%; lipid hydroperoxides in 80%; ASAT in 25%; alkaline phosphatase in 30%; IgA in 45%;

- increase to the physiological age norm of pepsinogen II level in 57% of children; dopamine in 55%; serotonin in 47%; AOA in 87%; GLPO in 45%; phagocytic number and phagocytic index in 48%; sIgA in 67%;

- restoration to the physiological level of the initial vegetative tone (eutonia) and autonomic reactivity (sympathicotonic) in 55% of children from the total number of children with this deviation; gallbladder motility in 75%; gastric acidity in 36%; the state of the mucous membrane of the stomach and duodenum in 58%; the size of the liver in 17%; peristalsis of the stomach and duodenum in 25% with the elimination of duodenogastric, duodenobulbar, bulbogastric refluxes.

In children from the comparison group, no significant dynamics of the studied parameters was found.

Thus, the above studies have confirmed the accuracy of the diagnosis of the toxic nature of CGD in children.

The proposed method allows to evaluate the influence of adverse chemical factors of technogenic origin on the occurrence of CGD, in order to identify the contingent of children, for whom it is necessary to implement an additional specialized treatment and prevention program.

Claims (2)

1. A method for diagnosing in children chronic gastroduodenitis associated with exposure to chromium, nickel, manganese, chloroform and carbon tetrachloride of technogenic origin, characterized in that the child takes a blood sample, sets the content of chromium, nickel, manganese, chloroform and carbon tetrachloride and the increased content of these metals in the blood, compared with the reference level by more than 2 times, as well as in the presence of chloroform and carbon tetrachloride in the blood above the lower detection limit, determine the function national diagnostic indicators characterizing a child: state of autonomic regulation; functional status of the biliary tract; functional state of the liver; gastric acidity; the condition of the gastric mucosa and the duodenum; motor function of the stomach and duodenum, and also determine the level of the following laboratory diagnostic parameters in the blood serum of the child: pepsinogen I, pepsinogen II, dopamine, serotonin, cortisol, thyroid stimulating hormone TSH, antioxidant activity of AOA, glutathione peroxidase GlPO, malondialdehyde, malondialdehyde lipid hydroperoxides, ASAT aspartate aminotransferase, alkaline phosphatase, leukocyte phagocytic activity: absolute number of phagocytes, phagocytic number, phagocytic index, immunoglobulin A IgA and secretory immunoglobulin in sIgA saliva, and further, if the child shows deviations from the age-related physiological norm of at least 80% of the indicated functional and laboratory diagnostic parameters characterizing the presence of: dysregulation of the autonomic regulation in the form of a vagotonic initial vegetative tone and asymptaticotonic reactivity; functional disorders of the biliary tract as a hypomotor disorder of the gallbladder; low acidity of gastric juice; hypotrophy of the mucous membrane of the stomach and duodenum; increase in liver size and its reactive change, impaired motor function of the stomach and duodenum according to the hypomotor type with the presence of duodenogastric, duodenobulbar, bulbogastric refluxes, and in the presence of the following deviations of laboratory diagnostic parameters: excess of pepsinogen II level by more than 20 %; cortisol by more than 10-15%; TSH by more than 10%; MDA more than 2 times; lipid hydroperoxides more than 1.5 times; ASAT more than 1.3 times; alkaline phosphatase more than 1.4 times; IgA more than 30%; as well as a decrease of the pepsinogen I level by more than 15% relative to the physiological age norm; dopamine more than 20%; more than 15% serotonin; AOA more than 1.5 times; GLPO more than 1.5 times; phagocytic number and phagocytic index more than 1.2 times; the absolute number of phagocytes is more than 1.3 times; sIgA by more than 30%, a child is diagnosed with chronic gastroduodenitis associated with exposure to chromium, nickel, manganese, chloroform and carbon tetrachloride of technogenic origin. 2. The method according to p. 1, characterized in that the functional diagnostic parameters are determined by instrumental methods: cardiointervalography, ultrasound, scanning of the hepatobiliary zone and upper gastrointestinal tract, pH meter, fibrogastroduodenoscopy.