Method for diagnosing atrophic gastritis cases

FIELD: medicine.

SUBSTANCE: method involves making pepsinogen 1, gastrin and Helicopter pylori infection marker combinations analysis and making input of the obtained results into data processing means comprising operation system, means for receiving, transmitting and processing data. The mentioned data processing means is usable for comparing the measured concentration value of a substance under study to a threshold value associated to the substance under study and producing information as a response to comparison results and additionally to other entered data. A set and software are used for implementing the method.

EFFECT: high accuracy in identifying cancer cases at initial disease stages.

16 cl, 1 dwg

 

The technical field

The present invention relates to a method for assessing the status or condition of the gastric mucosa, in particular to a method for the diagnosis of changes associated with a high risk on the gastric mucosa, in particular, atrophic gastritis, the patient. In this way the patient is determined by the specific concentration of the analyzed compounds, namely the concentration of pepsinogen I, the concentration of gastrin (preferably, gastrin-17), and the concentration or presence of a marker of Helicobacter pylori, and optionally, the concentration of pepsinogen II, and data processing tools are used to process the received data and for information, for example, in the form of diagnosis or suggestions for further treatment or research.

Background of the invention

Although the rate of new cases of stomach cancer and has decreased in recent years, gastric cancer still represents one of the most common malignant diseases. In Finland recorded approximately 250 to 300 new cases of cancer per one million people per year. In the age group of people over the age of 50 years, estimated to occur 2350 cases of cancer of the stomach, which is about 3 averages for this age group population (Finnish Cancer Registry - The Institute for Statistical and Epidemiological Cancer Rsearch 1993). In addition to Finland, the high incidence of gastric cancer exists in Iceland, South America and, in particular, in Japan and China.

The prognosis of gastric cancer is usually unreliable, and specific treatment does not exist. Currently, the only successful treatment of gastric cancer is its early detection and complete surgical removal.

Stomach cancer does not necessarily give any symptoms in its early stages. Later symptoms naturally delays the phase of treatment of the patient. On the other hand, clinical data on early-stage gastric cancer are often nonspecific. The main method of diagnosis for gastric cancer is currently the gastroscopy and biopsy, cell and aspiration Cytology associated with them. Because routine gastroscopy is carried out in order to check symptoms, such as pain in the upper abdomen, or bleeding of the gastrointestinal tract, symptomatically gastric cancer detected in this way is often at a late stage and is therefore inoperable. Are also attempts to improve primary diagnosis using various immunological methods, but rather specific immunological methods had not been developed.

The main purpose of which is finding the means with the help of which it would be possible to identify in the General population simply and with reasonable expenses of those persons who may be suffering from stomach cancer in its early stages. Once identified, these individuals should be directly studied by gastroscopy. At the same time can be identified by those who show precancerous changes of the stomach, which should be monitored.

Gastric cancer may be preceded by a number of different diseases or conditions of the stomach (the so-called precancerous condition), which are chronic atrophic gastritis, pernicious anemia, stomach ulcers, polyps of the stomach and the disease Minetree (giant hypertrophic gastritis). Clearly identifiable changes in the mucous membrane represent dysplasia and adenoma. These States are associated with approximately 4-5-fold increase in cancer risk compared with the General population. It is established that in almost all cases the risk is mediated through chronic atrophic gastritis.

Chronic gastritis means long-term inflammatory condition of the gastric mucosa. The disease can roughly be divided into the so-called superficial and atrophic form. When superficial gastritis infiltration of inflammatory cells, the concentration of which varies under the surface epithelium. The case when the inflammation progresses and diffuses between specific secretory glands of the stomach, is defined as chronic atrophic gastritis. In this case, the normal structure of the glands of the mucous membrane of the stomach, at least partially replaced by metaplastic changes. The relative risk of gastric cancer in patients suffering from atrophic gastritis in the main part of the stomach, according to the estimates, which are obtained from the statistics of cancer in Finland, approximately 4-5-fold more compared with persons with healthy mucosa. In addition, there is a risk of the disease pernicious anemia due to deficiency of internal factors and impaired absorption of vitamin B12. In acute atrophy of the antrum, the risk increases even 18 times. If atrophic changes appear both in the antrum and in the main part (pangastrit), the risk may increase even up to 90 times (Sipponen P, Kekki M, Haapakoski, J. Ihamuki, T & Siurala, M (1985) Gastric cancer risk in chronic atrophic gastritis: statistical calculations of crosssectional data. Int. J. Cancer 35:173-77).

Helicobacter pylori is a gram-negative spiral-shaped bacterium that develops in the mucous membrane in the immediate vicinity of the superficial epithelial cells of the mucous membrane of the stomach and in between cells. Apparently, acteria is passed from one person to another through the mouth. The impact of bacteria on the mucous membrane of the stomach is an inflammatory reaction, which is mediated, in addition, by release of substances are strong mediators of inflammation. After the acute phase inflammation is transformed into chronic gastritis. In patients with chronic gastritis, in 70-90% of cases set Helicobacter pylori infection (Calam, J (1994) Helicobacter pylori (Review) Eur. J. Clin. Invest 24: 501-510). Since Helicobacter pylori infection and chronic gastritis in the stomach are closely interrelated, it is assumed that this bacterial infection can be one of the etiological factors in the development of gastric cancer. For this reason, it is possible that the destruction of the bacteria Helicobacter pylori in the early stages of infection may prevent the development of atrophy associated with chronic gastritis, and thus, reduce the risk of cancer and the risk of gastric ulcers and duodenal ulcers.

Publication WO 96/15456, which is incorporated into this description by reference, describes a method of screening for the risk of cancer by determining the concentrations of the analyzed compounds of pepsinogen I and gastrin-17 from the serum sample of the patient. In accordance with the specified publication concentrations, determined in this way are then compared with a threshold value and with reference spaceneedle each of the analyzed compounds. The value of the concentration of pepsinogen I in serum below the threshold value for the level of pepsinogen I in combination with the value of the concentration of gastrin-17 above the upper reference limit indicates severe atrophy in the main part of the stomach. The level of gastrin-17 in serum below the threshold for gastrin-17 in combination with the value of the level of pepsinogen I is above the threshold value for the level of pepsinogen I, on the other hand, indicates atrophy of the antrum. In the case when the level of pepsinogen I in serum is below the threshold value for the level of pepsinogen I and gastrin-17 is at the lower limit of the reference value, it is an indication of acute atrophy of the stomach as a whole, i.e. atrophic pangastritis accordance with a possible option described implementation of these studies can be combined with the study of antibodies to Helicobacter pylori.

In accordance with the specified publication WO, the method can be supplemented with so-called studies of protein stimulation, according to which the blood sample is taken on an empty stomach in the morning, after which the patient eats enriched protein standard food, and blood samples are selected in 15 minute intervals for two hours. The maximum increase becomes noticeable after about 20 m the chickpeas. When atrophy is localized in the antrum, in this study will be greatly reduced reaction. When atrophy localized in the main part of the stomach, the reaction is normal or elevated, while atrophy of the mucous membrane generally leads to a reduced response.

Publication WO 00/67035, which is incorporated into this description by reference, describes a method for assessing the risk of stomach ulcers and duodenal ulcers by quantitative determination of the concentration of pepsinogen I in serum and gastrin-17 in the serum. In accordance with this method, if both the measured values in the serum levels of pepsinogen I and gastrin-17 are high, above the upper limit of their respective reference values, or the value of the level of pepsinogen I, serum exceeds the upper limit reference value, in combination with the value of gastrin-17 within the reference range or below its threshold value, it is an indication of increased risk of gastric ulcers and duodenal ulcers. In this area known methods for measuring different concentrations of the analyzed compounds and are also commercially available kits for this purpose. Some examples of ways to implement the above definitions describe what s in the publication WO 96/15456.

The invention

The present invention is to provide a method for assessing the condition of the gastric mucosa, in particular, for the diagnosis of changes in the mucous membrane of the stomach, such as atrophic gastritis, the patient, by analyzing the level of the analyzed compounds of pepsinogen I (PGI), gastrin and marker for Helicobacter pylori infection, and the method includes

- measuring in a sample from the patient a concentration of pepsinogen I and gastrin, and, in addition, determining the concentration or presence of the marker for Helicobacter pylori (Hp-token);

introduction data thus obtained, analyzed for the specified connection, data processing tools, including the operating system, means for receiving and transmitting and processing data, and the means for processing is configured to implementation stages;

- comparison of measured values of concentrations for the analyzed compounds with a predetermined threshold value for the specified analyzed compounds to obtain a combination of the comparison results, which is specific for the studied patient, and generating information in response to the specified combination of comparison results, and optionally on other entries.

Means for processing the data may include a display, displaying the generated information. The generated information relates primarily to the diagnosis or proposal for treatment or additional studies and/or tests on the basis of the results of the comparison.

The present invention also aims to set and program product for a computer, particularly for use in the method according to the present invention.

The present invention is also directed to a kit containing a means for measuring in a sample the concentration of pepsinogen I and/or gastrin and/or means for determining the concentration or presence of a marker of Helicobacter pylori, and program product for a computer, embodied in the storage medium, readable by a computer and containing computer code designed to implement the steps of comparing the measured concentrations of the analyzed compounds with a predetermined threshold value for the analyzed compounds, combining the comparison results in a combination of comparison results and information in response to said combination, and optionally other data entered when performing the said code on the computer.

Also the present invention is the creation of software for the computer, embodied the media, read by the computer, and contains the computer code designed to implement the steps of comparing the measured concentrations of the analyzed compounds with the corresponding threshold value referred to the analyzed compounds, combining the comparison results in a combination of comparison results and information in response to said combination, and optionally other data entered when performing the said code on the computer.

Detailed description of the invention

The method of comparing the measured value with a threshold value for the analyzed compounds is intended to establish whether the measured value for the level of the analyzed compounds greater, equal or smaller than the corresponding threshold value, and thus, to generate specific combinations of comparison results for the analyzed compounds, and on the basis of this combination will be generated for specific information and, for example, be displayed on the display.

Thus, in accordance with the present invention, for each patient, which explores the means for processing generates a specific set of comparison results, this set is obtained by comparing the measured value with a predetermined threshold value, the La analyzed compounds in any given order or simultaneously. In the context of the present invention under the patient refers to a mammal, e.g. a human or an animal, in particular a domestic animal such as a dog.

The present invention thus includes in the first stage, the method for identifying at least one marker of Helicobacter pylori, the level of pepsinogen I (PGI) and gastrin. The marker or indicator of Helicobacter pylori infection may therefore, in accordance with the present invention, to represent, for example, antibody to Helicobacter pylori, a level value which can be measured in a sample of bodily fluid. This sample is preferably a serum sample, but may also be a sample of saliva, urine or tears, for measuring, for example, values of antibodies, can be used commercially available kits. The threshold value for the level of antibodies to Helicobacter pylori can be easily determined by the person skilled in the art. In one of the embodiments of the present invention, the authors use a value of 30 EMU as a threshold to indicate the presence or absence of Helicobacter pylori infection. Specific antibodies to Helicobacter pylori can also be measured using Western blotting.

Another alternative is an assessment of the presence of Helicobacter pylori infection by detecting the presence of the antigen. T is some measurement can be carried out, for example, in the stool sample of the patient, and for this purpose are commercially available such tests and enzyme-linked immunosorbent assays (see, for example, Lancet 1999; 354, 30-33). You can also determine the presence of antigen in the patient's breathing, using well-known techniques for measuring the content of carbon dioxide, the formation of which of the labeled urea catalyzed by bacteria Helicobacter pylori, and systems for such analysis are also commercially available (for example, Heliprobe™ from the company Noster AB, Sweden). Another alternative is the presence of antigen in the sample biopsies taken during endoscopy of the stomach of the patient. When this alternative studies are either positive or negative with respect to the antigen and the presence of antigen is perceived as being an indication of an infection of Helicobacter pylori. The result is accordingly introduced into the data processing system using Boolean logic.

Of pepsinogen and gastrin preferably determined from a sample of bodily fluid, in particular from a sample of serum or urine sample, saliva or tears.

This method involves measuring the level of the analyzed compounds of pepsinogen I, but according to one of embodiments of the present invention, also who is one dimension, in addition, the concentrations of the analyzed compounds of pepsinogen II (PGII) and using relations PGI to PGII, instead of level PGI or in addition thereto, as the value, which is compared with a predetermined threshold value. Of pepsinogen I, and the level of pepsinogen I to II, tend to a linear reduction in the deterioration of atrophy of the mucous membrane of the main part of the stomach.

In the method according to the present invention, typically, the first uses a lower threshold for the level of pepsinogen I, which represents the "normal" threshold value for differentiating normal and atrophic mucosa of the main part of the stomach. In addition to this can be used a second, higher threshold level of pepsinogen I, such a higher value when the concentration of gastrin is its threshold limits, indicates only slightly stimulated the activity of gastrin, defining the threshold between neotropicheskii (including the body of the stomach gastritis (pepsinogen I is above the second threshold), and only slightly atrophic mucosa of the main part of the stomach (the level of pepsinogen I is below a second threshold) in combination with atrophy of the antrum. The specified second threshold value can be easily determined by the expert in Yes the Noi area.

The concentration of gastrin, and in particular gastrin-17, similarly decreases with worsening atrophy of the mucous membrane of the antrum. For gastrin can be used a threshold range. This range has a lower threshold limit value below which indicate atrophy, at least, antrum, and the upper threshold limit values above which may indicate normal neotropicheskii gastritis or atrophic mucosa of the main part of the stomach. Values in the range between the lower and upper value may indicate atrophy, at least, the field antrum or in combination with a high level of pepsinogen (above a second, higher threshold values) and also on neotropicheskii gastritis, as discussed above. In addition, the third threshold, the lower threshold for the level of gastrin, can be used to indicate normal mucosa, when the level of pepsinogen I is equal to or greater than the first threshold value.

Analyzed the connection gastrin can be a gastrin in General, that is, essentially, the amount of gastrin-34 and gastrin-17, but in accordance with the preferred embodiment of the present invention, the measured level of gastrin-17.

As described to enter the, methods for measuring the level of pepsinogen I, pepsinogen II and gastrin well known in this field. These measurements typically represent immunological methods using mono - or polyclonal antibodies to the indicated test compounds. Usable methods for detection include, for example, measurement of absorbance, fluorescence or luminescence. It is also possible the simultaneous measurement of all three of the analyzed compounds, for example, on the same microplate, in different holes or in the same hole that provides a particularly convenient way.

Values for the analyzed compounds, thus obtained, are then entered in the means for data processing, such as a terminal for data processing, which has the required operating system, which can be equipped with a means for data input and data output and which includes means for comparing the measured concentrations of the analyzed compounds with a predetermined threshold value for that analyzed compounds. Data can be entered using any terminal equipment for data processing, accompanied by an appropriate user interface, or by reading data from the device carrier for whom arenosa and data storage, or by receiving data from a data providing system using the data transmission and data networks such as the Internet.

Thus, the user interface is the means by which the user can communicate with the system, supplying information, and through which you are entering and checking data, and the generated information is reported or displayed or transmitted next, for storage or for printing on the printer.

The concept of threshold analyses, including the determination of the concentrations of the analyzed compounds, well known to specialists in this field and, as a rule denotes some value or set of values, is selected as the limit between the reference values (normal values) and abnormal values for this study. These thresholds are specific to each method and depend on the specificity and sensitivity of selected research method used to determine the concentrations of the analyzed compounds (see, for example, William J Marshall, Clinical Chemistry, Third Edition, 1995, Mosby).

The threshold values can be entered in the data processing system before entering the measured values for the analyzed compounds, or they can be pre-stored the data processing system. In accordance with the present invention also provides the use of thresholds in the process, when it is desirable to change the sensitivity or specificity sposobov accordance with the present invention, the means for processing performs the comparison operation, in accordance with which various measured concentrations of the analyzed compounds are compared with the corresponding threshold value or threshold range for the specified analyzed compounds, the results of the comparison are combined, and in response to a combination of comparison results and, additionally, on other or additional data or parameters entered in the means for data processing, information is generated, and this information can be displayed, for example, the display on the user interface.

The information generated by the means for processing data may take the form of diagnosis, displayed in a window on the display, or it may take the form of proposals for the treatment or proposals for additional studies or tests, displayed in the same or in another display window.

Thus, in accordance with the present invention, depending on the specific combination of the results obtained comparing the main diagnosis can be defined as "normal (SL is sista shell)", "atrophic gastritis of the main part of the stomach (optional, autoimmune type), "atrophic gastritis antrum and the main part of the stomach" (pangastrit), "atrophic gastritis of the antrum", or "neotropicheskii gastritis", and supplemented by information relating to the presence or absence of Helicobacter pylori infection.

The table below includes a specific combination of comparison results associated with different diagnoses, when the analyzed compounds are Hp-marker, such as Hp-antibody, pepsinogen I and gastrin.

In the table,

Hp-co indicates the threshold value for the marker Hp

P-coI means the first threshold for the level of pepsinogen I

P-coII means the second threshold value for the level of pepsinogen I

G-coI means the value of the lower threshold for gastrin

G-coII mean value of the upper threshold for gastrin.

The table shows that the level of the marker of Helicobacter pylori shares many specific combinations into two groups, where the measured analyze connections Hp marker are either above or below the threshold level of the marker Hp (Hp-co). When the level value Hp-marker is equal to or less than the threshold value level PGI equal to or higher than the value of the first threshold PG (P-coI), indicates the normal of the th mucous membrane, while, if the value of level PGI is below the specified threshold, the value of the gastrin level equal to or higher than the upper limit threshold for gastrin (G-coII), indicates atrophic gastritis of the main part of the stomach, and if this value is below the specified threshold, this indicates atrophic gastritis antrum/main part of the stomach, i.e. pangastrit. Instead of the terms "any value" for gastrin in the diagnosis of normal mucosa can also be applied third, the lowest threshold level of gastrin (G-coiii complexes), above which the concentration of gastrin should indicate the normal mucous membrane.

On the other hand, when the level value Hp is above its threshold and the value of the gastrin level is below the lower threshold limit (G-coI), this indicates pangastrit, if also the level of pepsinogen I is below the first threshold value, and indicates atrophic gastritis antrum, if the level of pepsinogen I is equal to the first threshold value or exceeds it. If the value of the gastrin level is within a threshold range (G-coI - G-coII) and the level of pepsinogen I is below the second threshold value (P-coII), this also indicates atrophic gastritis antrum, but when the level of pepsinogen equal to the second threshold value or exceeds, this indicates neotropicheskii gastritis. Finally, when the gastrin level is above the upper threshold limit (G-coII) and the level of pepsinogen I is equal to the first threshold value or greater, it indicates neotropicheskii gastritis, but when the level of pepsinogen is below the first threshold, this indicates atrophic gastritis of the main part of the stomach. In the above table, when it is rather the presence of the marker Hp, such as the antigen than the antibody concentration, the table includes only the option of the presence or absence of antigen in the sample.

The above diagnoses may also be supplemented with information relating to the risk of developing gastric ulcers and duodenal ulcers (gastric and/or intestinal), as well as the associated risk factor, and also with a possible cancer risk, with an associated risk factor. Criteria for establishing the risk of ulcers or gastric cancer and duodenal ulcer, based on the measurement values of the levels of PGI and G-17 compared with their threshold and reference values have been described in WO 00/67035 and WO 96/15456 respectively. Various risk factors associated with ulcer and gastric cancer and duodenal ulcer described in detail, for example, in Gastroenterology Clinics of North America, Volume 29, No. 3 (2000), in particular on page 586, where various facto is s risk associated with normal, neotropicheskii, slightly, moderately and acute atrophic mucosa antrum and the main part of the stomach is described as for ulcers and cancer of the stomach and duodenum, in the form of a graph.

Other additional options that can be taken into account when forming the information to display, for example, in the form of a diagnosis may represent the patient's age, condition, for example, symptoms of reflux, dyspepsia, and/or anemia, or other symptoms and painful condition, in accordance with one of the embodiments of the present invention, considered symptoms or diseases can be introduced into the means for processing data as parameters Boolean logic.

The table above can be supplemented, for example, the threshold for age, in this case, for example, age above 45 years, in combination with dyspepsia in patients with Helicobacter pylori infection and neotropicheskii gastritis or atrophic gastritis of the main part of the stomach, in addition to the diagnosis related to the status of the gastric mucosa may lead to a proposal for treatment of the patient from infection of Helicobacter pylori.

In addition, for example, the diagnosis of atrophic gastritis of the main part of the stomach, optionally in combination with pernicio the Noah anemia, regardless of age, may cause the proposal for the study of serum vitamin B12 and homocysteine, and perhaps also the proposal to support the treatment of vitamin B12.

The present invention is also directed to a kit containing the means for measuring, in a sample, the concentration level of pepsinogen I and/or gastrin, and/or means for determining the concentration or presence of a marker of Helicobacter pylori. This set also contains a variety of tools, such as the reagents necessary for measuring the concentration or presence under consideration of the analyzed compounds, Packed in different containers, but contained in the same package. This kit can also contain instructions for use. In addition to this kit contains the software product for PC, embodied on a storage medium, readable by a computer and containing computer code that, when execution of the mentioned code on the computer ensures the implementation of the steps of comparing the measured concentrations of the analyzed compounds with a predetermined threshold value to obtain a combination of comparison results, together with additionally introduced other data form the basis for the information that should the result be generated. Software about the SPS computer may contain pre-stored threshold values for one or more of the analyzed compounds, which should be measured, or such values must be entered during use. When using a set concentration of at least one of the analyzed compounds, and the concentration of any other analyzed compounds, if required, measured using the same set, or using other means, or sets, are entered using this program on your computer.

The present invention also relates to a program product for a computer, embodied in the storage medium, readable by a computer and containing computer code designed to implement the steps of comparing the measured concentrations of the analyzed compounds, such as the analyzed compounds Hp-marker, PGI and gastrin, with its pre-defined threshold value to obtain combinations of comparison results to generate together with other optional data entered information in the performance of the mentioned code on the computer.

The drawing shows a chart relating to panel studies or "decision tree" in accordance with one of the embodiments of the present invention. Threshold values for each of the analyzed compounds are as shown in the diagram and described below. They are, as shown, to give an accurate diagnosis is s for the population on average. Of course, you can also use other more or less modified threshold value, if required in the methods used to determine the concentrations of the analyzed compounds, and/or if you want to change the sensitivity and specificity of the measurements.

The used sample is a blood serum sample, and gastrin is a gastrin-17 (G-17). When determining the level of pepsinogen I, serum threshold for atrophic gastritis is, in accordance with the preliminary research of the authors, 20-30 g/l depending on the specificity and sensitivity of the corresponding method under consideration, which corresponds to about 450-690 pmol/L. In this example, the authors used a value of 25 g/l as the first threshold for atrophic gastritis in the main part of the stomach or atrophic pangastrita. However, in accordance with the present invention, it is also possible to use the second value for PGI as a threshold to differentiate between atrophic gastritis in the antrum (with only a small atrophic gastritis of the main part of the stomach) and neotropicheskii gastritis, respectively, when the G-17 is within a threshold range for G-17. In the context of the present invention uh what about the second value is determined as the second threshold value. In this example, the authors use a value of 50 g/l for this second threshold value, this value is about two times larger than the first threshold value. If in addition, the measured concentrations of the analyzed compounds of pepsinogen II, the first threshold value for the relationship PGI to PGII may be, for example 2.5, for the second threshold, for example, about 5.

In this example, the authors use the concentration of gastrin-17 in the serum obtained after protein stimulation, that is, gastrin-17 after a meal. The threshold range for "stimulated" levels of gastrin-17 (G-17st)generally is in the range from 5 to 10 pmol/l, with the lower limit at 5 pmol/l forms a lower threshold, the upper limit of 10 pmol/l upper threshold value, and the range in between the third threshold range. In addition, there is the lower threshold for the level of gastrin-17, 0.5 pmol/l, which is used to indicate normal mucosa with normal levels PGI (PGI ≥ 25 g/l). Appropriate values and ranges for restimulating level G-17 should be approximately half of the values shown for stimulated values. In this example, the authors use antibodies to Helicobacter pylori as Hp-token, and the authors found the, what is the appropriate threshold for the value of antibodies to Helicobacter pylori is approximately 30 AME

In accordance with the described embodiment, the means for processing data compares the measured level values Hp-Ab with a threshold value for the level of Hp-Ab, which is specified as equal to 30 AMA depending on the measured level values, which may be higher or equal to or lower than a predetermined threshold value, the means for processing performs in the first case, comparing the measured level of G-17st with its threshold range, and in the latter case, the means for data processing compares a level PGI with it the first threshold value.

If in the first case, the level of G-17st is either below the lower threshold or above the upper threshold, the means for data processing compares a level PGI with his first specified threshold value. When the level of G-17st is below the lower threshold and the level of PGI is below the value of the first threshold, the system for processing data to generate information related to the diagnosis of atrophic gastritis antrum and the main part of the stomach (pangastrit), but if the level of PGI is equal to or higher than the first threshold value is s, information will be associated with atrophic gastritis antrum.

When the level of G-17st is above the upper threshold and the level of PGI is below the first threshold level for PGI, the generated information will be associated with atrophic gastritis of the main part of the stomach, but if the measured level PGI is equal to or higher than the first threshold level for PGI, the generated information will be associated with neotropicheskii gastritis. The same diagnosis will be displayed if the measured level PGI is high and equal to or higher than the second threshold level for PGI, in combination with G-17st, which is in the threshold range. If, in turn, the measured level PGI is below the second threshold level PGI, the level of G-17st is within the threshold range, the displayed diagnosis will be a atrophic gastritis region of the antrum.

On the other hand, if the value of level Hp-Ab is lower or equal to its threshold value, the means for processing data compares the measured level values PGI with the first threshold level for PGI. In the case when the measured value of the level PGI is equal to or higher than the specified threshold value, the generated information is vasana diagnosed with normal mucosa at the level of gastrin-17st, higher than the third, the lowest threshold, which in this example is 0.5 pmol/L. However, if the specified measured value of the level PGI is below the first threshold value, the displayed information will be associated with a diagnosis of atrophic gastritis main part of the stomach, when the measured level of G-17st is equal to or higher than the upper threshold value, and diagnosed with pangastrit, when the level of G-17st is low, namely less than the upper threshold limit. In this case, atrophic gastritis of the main part of the stomach will be a disease of the autoimmune type.

As indicated previously, by introducing additional parameters into the data processing system and combining it with the generated information can be obtained for more information, for example, in the form of proposals for further treatment and/or additional studies, such as the proposal to conduct an endoscopy to determine the levels of vitamin B12 and homocysteine, and treatment aimed at the destruction of Helicobacter pylori infection.

The following examples illustrate the present invention without limiting it in any way. Measured the analyzed compounds are pepsinogen I in serum gastrin-17 in serum and antibodies to Helicobacter pylori; the threshold values are to the that shown in figure 1. Also the patient's age is included as a parameter, and the threshold is 45 years. Appropriate diagnosis is given in each example, together with additional proposals for research and treatment, when they can be applied.

EXAMPLE 1
The level of pepsinogen I, serum30 g/l
The level of gastrin-17st serum20 pmol/l
Antibodies to Helicobacter pylori10 EME
The age of the patient40 years

The proposed diagnosis: NORMAL

1) Atrophic gastritis no

2) H.pylori Infection no

3) No risk of cancer of the stomach and stomach ulcers and duodenal ulcers (gastric and gastro); risk factor IX.

Suggestions for further research and treatment:

It is not recommended any additional studies (e.g., endoscopy).

EXAMPLE 2
The level of pepsinogen I, serum20 g/l
The level of gastrin-17st serum20 pmol/l
Antibodies to Helicobacter pylori10 EME
Patient age40 years

The proposed diagnosis of ATROPHIC GASTRITIS of the MAIN PART of the STOMACH

1) Disease ulcer of stomach and duodenal ulcers (ulcers of the intestines and stomach) is unlikely.

2) Atrophic gastritis main part of the stomach, autoimmune type.

3) Increased risk of gastric cancer (a risk factor of 3-5X).

Suggestions for further research and treatment:

Desirable endoscopy. It is recommended that the definition of the levels of vitamin B12 and homocysteine.

Replacement therapy with vitamin B12 if the B12 level below 170 pmol/L.

EXAMPLE 3
The level of pepsinogen I, serum20 g/l
The level of gastrin-17st serum5 pmol/l
Antibodies to Helicobacter pylori10 EME
Patient age40 years

The proposed diagnosis of ATROPHIC GASTRITIS ANTRUM/the MAIN PART of the STOMACH.

1) Disease ulcer of stomach and duodenum (intestine and stomach) is unlikely.

2) Increased risk of gastric cancer (a risk factor 3-90X).

Suggestions for further research and treatment:

Desirable endoscopy. It is recommended that the definition of the levels of vitamin B12 and homocysteine.

Vicarious terap what I vitamin B12, if the B12 level below 170 pmol/L.

EXAMPLE 4
The level of pepsinogen I, serum20 g/l
The level of gastrin-17st serum2 pmol/l
Antibodies to Helicobacter pylori80 AME
Patient age40 years

The proposed diagnosis of ATROPHIC GASTRITIS ANTRUM/the MAIN PART of the STOMACH.

1) Disease ulcer of stomach and duodenum (intestine and stomach) is unlikely.

2) Increased risk of gastric cancer (a risk factor 3-90X).

Suggestions for further research and treatment:

Desirable endoscopy. It is recommended that the definition of the levels of vitamin B12 and homocysteine.

Replacement therapy with vitamin B12 if the B12 level below 170 pmol/L. Should the treatment of H. pylori infection.

EXAMPLE 5
The level of pepsinogen I, serum30 g/l
The level of gastrin-17st serum2 pmol/l
Antibodies to Helicobacter pylori80 AME
Patient age40 years

The proposed diagnosis of ATROPHIC GASTRITIS ANTRAL DEPARTMENT IS LA.

1) High risk of ulcer disease of stomach and duodenum (intestine and stomach) (risk factor 10-20X).

2) Increased risk of gastric cancer (a risk factor 18X).

Suggestions for further research and treatment:

Desirable endoscopy. Should the treatment of H. pylori infection.

EXAMPLE 6
The level of pepsinogen I, serum30 g/l
The level of gastrin-17st serum8 pmol/l
Antibodies to Helicobacter pylori80 AME
Patient age40 years

The proposed diagnosis of ATROPHIC GASTRITIS ANTRUM.

1) High risk of ulcer disease of stomach and duodenum (intestine and stomach) (risk factor 10-20X).

2) Increased risk of gastric cancer (a risk factor 18X).

Suggestions for further research and treatment:

Desirable endoscopy. Should the treatment of H. pylori infection.

EXAMPLE 7
The level of pepsinogen I, serum60 g/l
The level of gastrin-17st serum8 pmol/l
Antibodies to Helicobacter pylori80 AME
Patient age/td> 40 years

The proposed diagnosis: NEOTROPICHESKII GASTRITIS.

1) Increased risk of disease ulcer of stomach and duodenum (intestine and stomach) (risk factor 10X).

2) Low risk of gastric cancer (a risk factor for 1-2X).

Suggestions for further research and treatment:

Endoscopy is not necessary. Should the treatment of H. pylori infection.

EXAMPLE 8
The level of pepsinogen I, serum50 g/l
The level of gastrin-17st serum20 pmol/l
Antibodies to Helicobacter pylori80 AME
Patient age40 years

The proposed diagnosis: NEOTROPICHESKII GASTRITIS.

1) Increased risk of disease ulcer of stomach and duodenum (intestine and stomach) (risk factor 10X).

2) Low risk of gastric cancer (a risk factor for 1-2X).

Suggestions for further research and treatment:

Endoscopy is not necessary. Should the treatment of H. pylori infection.

Antibodies to Helicobacter pylori
EXAMPLE 9
The level of pepsinogen I, serum20 g/l
The level of gastrin-17st serum20 pmol/l
80 AME
Patient age40 years

The proposed diagnosis of ATROPHIC GASTRITIS of the MAIN PART of the STOMACH.

1) Increased risk of gastric cancer (a risk factor of 3-5X).

Suggestions for further research and treatment:

Desirable endoscopy. It is recommended that the determination of vitamin B12 levels and homocysteine. Replacement therapy with vitamin B12 if the B12 level below 170 pmol/L. Treatment of H. pylori infection.

EXAMPLE 10
The level of pepsinogen I, serum50 g/l
The level of gastrin-17st serum20 pmol/l
Antibodies to Helicobacter pylori80 AME
Patient age50 years

The proposed diagnosis: NEOTROPICHESKII GASTRITIS.

1) Increased risk of disease ulcer of stomach and duodenum (intestine and stomach) (risk factor 10X).

2) Low risk of gastric cancer (a risk factor for 1-2X).

Suggestions for further research and treatment:

Desirable endoscopy. Treatment of H. pylori infection, if you have symptoms of dyspepsia.

EXAMPLE 11
The level of pepsinogen I, serum 20 g/l
The level of gastrin-17st serum20 pmol/l
Antibodies to Helicobacter pylori80 AME
Patient age50 years

The proposed diagnosis of ATROPHIC GASTRITIS of the MAIN PART of the STOMACH.

1) Increased risk of gastric cancer (a risk factor of 3-5X).

Suggestions for further research and treatment:

Desirable endoscopy. It is recommended that the definition of the levels of vitamin B12 and homocysteine. Replacement therapy with vitamin B12 if the B12 level below 170 pmol/L. Should the treatment of H. pylori infection, if you have symptoms of dyspepsia.

1. The way to assess the condition of the gastric mucosa, in particular, to diagnose changes in the mucous membrane of the stomach, such as atrophic gastritis, the patient, by analyzing the analyzed compounds of pepsinogen I (PGI), gastrin and marker of Helicobacter pylori infection, and the method comprises measuring in a sample from the patient a concentration of pepsinogen I and gastrin in addition to determining the concentration or presence of the marker for Helicobacter pylori (HP-marker), the introduction of data, thus obtained, analyzed for the specified compounds in the tool data, including the operating system means for receiving and transmitting, and processing data,and the said means of data processing is intended to implement the steps of comparing the measured concentration values for the analyzed compounds with a predetermined threshold value for the specified the analyzed compounds, to obtain a combination of the comparison results, which is uniquely defined for the studied patient, and generating information in response to the specified combination of comparison results, and optionally on other entries.

2. The method according to claim 1, wherein a marker of Helicobacter pylori is an antibody to Helicobacter pylori, the concentration of which is measured in the sample.

3. The method according to claim 1, wherein a marker of Helicobacter pylori is an antigen of Helicobacter pylori, the presence of which is determined in the sample.

4. The method according to any of the preceding paragraphs, in which the measured value of the gastrin level represents the level of gastrin-17 (G-17), in particular, the value of the level-stimulated gastrin-17 (G-17st), or as gastrin-17, and stimulated gastrin-17.

5. The method according to any of the preceding paragraphs, in which additionally measure the concentration of the analyzed compounds of pepsinogen II (PGII) and form the ratio of PGI/PGII for comparison.

6. The method according to claim 2, in which the analyzed compounds measured in the sample of bodily fluid, such as serum, urine, saliva or tears, especially in the blood serum sample.

7. The method according to any of the preceding paragraphs, in which the means of processing data includes a display screen, the generated information display of what is on the display.

8. The method according to any of the preceding paragraphs in which the generated information includes diagnostic information related to changes in the gastric mucosa.

9. The method according to any of the preceding paragraphs in which the generated information includes suggestions for further treatment or for additional research.

10. The method according to any of the previous PP and 9, which information indicates a risk of ulcer disease and/or cancer of the stomach and duodenum and additional associated risk factor.

11. The method according to any of the preceding paragraphs, in which the parameters enter additional data related to the patient's age, symptoms of reflux, dyspepsia and/or anemia in the patient.

12. The method according to any of the preceding paragraphs, in which process the data impose pre-defined thresholds for levels of PGI and gastrin and advanced levels of HP-marker and PGII, using the data entry and data storage media.

13. Set for use in the method according to claim 1, the kit contains means for determining in a sample the concentration of pepsinogen I and gastrin and the concentration or presence of the marker Helicobacker pylori, and program product for a computer embodied in a machine-readable carrier of information and that contains the computer code, execute steps of comparing the specific concentrations of the analyzed compounds with a predetermined threshold value for the specified analyzed compounds, combining the comparison results in a combination of comparison results and receipt of information in response to this combination, and optionally other data entered during execution of the specified code on the computer.

14. Set in item 13, in which the predefined thresholds mentioned the analyzed compounds are stored on a machine-readable storage medium containing a computer program for use with a computer program, for use in the method according to any of previous claims 1 to 12.

15. The computer-readable storage medium containing embodied therein program product for use in the method according to claim 1, containing computer code designed to implement the steps of comparing the measured concentrations of pepsinogen I and gastrin and the concentration or presence of the marker for Hellcobacker pylori in the sample from the patient with an appropriate threshold value for the analyzed compounds, combining the comparison results in a combination of comparison results and information in response to said combination and additionally on the other input when the execution of the mentioned code on the computer.

16. A machine-readable medium of clause 15, in which the said product also contains data for the predefined thresholds analyzed for these compounds for use in the method according to any of previous claims 1 to 12.



 

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47 cl, 1 tbl, 5 dwg, 6 ex

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4 ex, 2 tbl

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2 ex, 2 tbl

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1 tbl, 2 ex

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2 ex, 2 tbl

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