RU2664449C1 - Method for predicting the exacerbations of gastroduodenal ulcer associated with helicobacter pylori - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention relates to medicine and is intended to predict the exacerbation of gastroduodenal ulcer associated with Helicobacter pylori. Determine biochemical parameters of blood and PAF (platelet activating factor) and LT (leukotrienes) parameters. With an increase in the concentration in the gastric mucosa of the platelet activation factor from 9.12 pg/mg protein or more, leukotrienes from 4.68 ng/mg and more, correlating with the contamination of the mucous membrane with Helicobacter pylori, predict an exacerbation of gastroduodenal ulcer.EFFECT: method makes it possible to improve the accuracy of the prediction of exacerbations of gastroduodenal ulcer associated with Helicobacter pylori.1 cl, 12 dwg, 3 ex

Description

FIELD OF THE INVENTION

The invention relates to medicine, in particular, to a method for predicting exacerbation of gastric ulcer and duodenal ulcer associated with Helicobacter pylori and can be used in gastroenterology.

State of the art

A known method for the diagnosis of helicobacteriosis of the gastric mucosa in patients with peptic ulcer and gastric polyposis by examining the mucous membrane of the antrum, the percentage of plasmocytes (P) and lymphocytes (L) in relation to all leukocytes is determined morphometrically in the gastrobiopathy of the mucous membrane of the antrum of the stomach, infiltrating the mucous membrane of the stomach, after which the plasmolymphocytic index (PLI) is calculated by the formula: PLI = P / L and, when its value is 2.04 or less, n presence of Helicobacter pylori in the gastric mucosa, and when the value of 2.05 and above - lack heliobakternoy infection in the gastric mucosa (see Patent RU №2221244, IPC GO 1 N33 / 48, published 10.01.2004 r...).

The disadvantage of this method is its low efficiency in the diagnosis of heliobacteriosis of the gastric mucosa.

A known method for predicting the course of gastric ulcer and duodenal ulcer, including determining the serum ferritin content before treatment and 4-6 days from the start of treatment, while lowering its level to 280-350 ng / ml for gastric ulcer and to 360-400 ng / ml with peptic ulcer of the duodenum predict the course of peptic ulcer without exacerbations (see US Pat. RU No. 2241228, IPC G01N 33/68, publ. November 27, 2004).

The disadvantage of this method is its low efficiency of predicting the course of the disease.

A known method for predicting the course of gastric ulcer and duodenal ulcer associated with Heliobacter pylori by conducting a biochemical blood test, in this case, the titer of antibodies to Helicobacter pylori class IgG and IgA is determined and with a titer of each of them 1: 200 or more, the course of gastric ulcer is predicted and the duodenum associated with Helicobacter pylori, with exacerbations (see US Pat. RU No. 2269132, IPC G01N 33/53, publ. 04/20/2005 g).

The disadvantage of this method is its low accuracy in predicting the course of the disease.

The closest in technical essence and the achieved positive effect and adopted by the authors for the prototype is a method for diagnosing the course of peptic ulcer of the stomach and duodenum, including conducting biochemical blood tests, determining the activation factor of platelets and leukotrienes as a mediator of lesions of the digestive system (see Polonsky V. M. Platelet activating factor as a mediator of lesions of the digestive system // Ter. Arch. - 1990. - No. 8. - pp. 27-31).

The disadvantage of this method is the low accuracy of predicting exacerbation of peptic ulcer of the stomach and duodenum.

Disclosure of invention

The objective of the invention is to develop a method for predicting exacerbation of gastric ulcer and duodenal ulcer associated with Helicobacter pylori, with high accuracy in predicting exacerbation of gastric ulcer and duodenal ulcer.

The technical result, which can be obtained using the present invention, is reduced to high accuracy in predicting the exacerbation of gastric ulcer and duodenal ulcer associated with Helicobacter pylori.

The technical result is achieved using a method for predicting exacerbation of gastric ulcer and duodenal ulcer associated with Helicobacter pylori, including biochemical blood tests, determination of platelet and leukotriene activation factors, while in remission of gastric ulcer and duodenal ulcer with Helicobacter pylori and Helicobacter pylori - negative gastric and duodenal ulcers, determine inflammation of the gastric mucosa in the presence of Helicobacter pylori and with an increase in the concentration of inflammatory mediators in the mucous membrane of the stomach of platelet activating factors from 9.12 pg / mg protein or more, leukotrienes from 4.68 ng / mg protein or more, which correlate with colonization of the mucous membrane of Helicobacter pylori, they predict exacerbation of gastric ulcer and duodenal ulcer associated with Helicobacter pylori.

Thus, the role of pyloric helicobacter (PX) in triggering a cascade of inflammatory changes in the mucous membrane (CO) of the stomach and duodenum (duodenum) is currently proven, in 70-80% of cases the pathogenesis of chronic antral gastritis (XT) and duodenitis is associated with in 70% of gastric ulcer (UBI) and in 90-95% of duodenal ulcers (see Loginov A.S., Aruin L.I., Ilchenko A.A. Peptic ulcer and Helicobacter pylori: new aspects of pathogenetic therapy.- M ., 1993 .-- 230 p.). In the pathophysiology of inflammation caused by PC, an important role belongs to endogenous lipids, leading not only to damage to the cells of the integumentary - epithelial layer, but also to determining the effects of chemotaxis, hypersensitivity, cytotoxicity, etc. (see Polonsky V.M. Platelet activation factor as a mediator damage to the digestive system // Ter. arch. - 1990. - No. 8. - pp. 27-31), (see Braquet R., Touqui L., Shen T. Y. et a. Perspectives in platelet - activating factor research // Pharmacol. Rev. -1987. - Vol. 39. - P. 97-145.). Platelet activating factor (FAT), leukotrienes (LT), which are the products of the conversion of arachidonic acid (AK), pretend to be the main ulcerogenic factors, these mediators can be synthesized as the bacterium itself (see Denizot Y., Sobhani J., Rambaud I S. et al. Paf - acether synthesis by Helicobacter pylori // Gut. - 1990. - Vol. 31. - P. 1242-1245), as well as with a variety of cells - epithelial cells, basophils, neutrophils, mononuclear cells, eosinophils, macrophages , endotheliocytes, lymphocytes involved in the development of chronic inflammation of the stomach WITH and duodenum the presence of HRP, which show the relationship between bacterial seeding and an increase in the synthesis and release of FAT and RT during exacerbation of ulcer. FAT and RT indices with the main clinical and endoscopic criteria (age of patients, localization and size of ulcerative defects, severity and duration of the course of the disease) in HRP - positive and HRP - negative ulcers of the stomach and duodenum. It was shown that in patients with clinical remission of ulcer high concentrations of FAT and RT correlating with the seeding of HRP are predictive signs of future exacerbation, since the main mechanism of ulcerogenic action of FAT is a violation of microcirculation in the tissues of the gastrointestinal tract. FAT causes a dose-dependent slowdown of the mucous capillary blood flow, an increase in capillary permeability, which lead to hemoconcentration, aggregation and degranulation of neutrophils; under the influence of FAT, destruction of the surface coolant epithelium, expansion of the ventricular glands and the development of deep foci of necrosis also occur (see Dreyling KW, Нор U., Peskar, V.M. et al. Leukotriene synthesis by human gastrointestinal tissues // Biochim. Biophis. Acta - 1986 - Vo.l 878. P. 184-193.). The increase in vascular permeability caused by FAT leads to blood thickening and an increase in the hematocrit, resulting in an increase in blood viscosity, which is a decrease in local blood flow, especially in venules with the formation of stasis and thrombosis.

The essence of the method for predicting exacerbation of gastric ulcer and duodenal ulcer associated with Helicobacter pylori is as follows.

To perform a method for predicting an exacerbation of gastric ulcer (JAB) and duodenal ulcer (DC) associated with Helicobacter pylori, blood biochemical parameters and FAT and LT indicators are determined depending on the presence / absence of signs of infection of the gastric mucosa (SOF), an analysis of these indicators are carried out taking into account various criteria: age, localization, size of a peptic ulcer, severity and duration of the course of the disease, inflammation activity, dynamics during various options conservative treatment, while in the stage of remission of peptic ulcer of the stomach and duodenum with Helicobacter pylori - positive and Helicobacter pylori - negative ulcer of the stomach and duodenal ulcer, determine inflammation of the gastric mucosa in the presence of Helicobacter pylori and with an increase in the concentration in the mucous membrane of the stomach platelet activation factor from 9.12 pg / mg protein or more, leukotrienes from 4.68 ng / mg protein or more, correlating with seeding of the mucous membrane and Helicobacter pylori, predict an exacerbation of gastric ulcer and duodenal ulcer associated with Helicobacter pylori.

Brief description of drawings and other materials

Table 1 (see Fig. 1) provides a method for predicting exacerbation of gastric ulcer and duodenal ulcer associated with Helicobacter pylori, the distribution of patients with ulcer by age groups.

In table 2 (see Fig. 2), the same is the distribution of patients with ulcer according to the duration of the disease.

In table 3 (see Fig. 3), the same is the frequency of the main clinical symptoms of ulcer.

In table 4 (see Fig. 4), the same is the distribution of patients according to the types of ulcer course.

In table 5 (see Fig. 5), the same is the frequency of the location of the ulcer in patients with pulmonary ulcer in various parts of the stomach.

In table 6 (see Fig. 6), the same is the distribution of patients depending on the degree of activity of inflammation of the gastroduodenal CO.

In table 7 (see Fig. 7), the same is the distribution of patients with ulcer depending on the size of the ulcer defect.

In table 8 (see. Fig. 8), the same, - indicators of FAT in the coolant of patients with ulcer of various ages, depending on the infection with HRP.

In table 9 (see Fig. 9), the same, - indicators of FAT in the coolant PX - positive and PX - negative patients with pulmonary ulcer with different localization of ulcerative defect.

In table 10 (see Fig. 10), the same is the FAT content in the coolant of patients with ulcer, depending on the duration of the disease.

In table 11 (see Fig. 11), the same, - indicators of FAT in the coolant PX - positive and PX - negative patients with UJ with varying degrees of inflammation of the coolant.

In table 12 (see Fig. 12), the same is the correlation analysis between the indices of RT and MPO in the periulcerous CO of patients with UB.

The implementation of the invention

Examples of specific implementation of the method for predicting exacerbation of gastric ulcer and duodenal ulcer associated with Helicobacter pylori.

Example 1. To perform a method for predicting exacerbation of gastric ulcer (UB) and duodenal ulcer (DC) associated with Helicobacter pylori, blood biochemical parameters and FAT and RT indicators are determined depending on the presence / absence of signs of infection of the gastric mucosa (SOF) , the analysis of these indicators is carried out taking into account various criteria: age, localization, size of the ulcer, severity and duration of the course of the disease, activity of inflammation, dynamics during various arians of conservative treatment (see tab. 1, 2, 4, 5, 6, 7), for this purpose 49 people suffering from UBI were examined, men - 35, women - 14 and 50 people suffering from UBD - 47 and 3, respectively between the ages of 18 and 65 years and 15 people - made up the control group between the ages of 22 and 30 years, who had no history of gastrointestinal tract diseases and, during endoscopic examination, the gastroduodenal mucosa is characterized as practically unchanged. The studied patients are conditionally divided into three groups: from 18 to 35 years old, from 35 to 55 years old, from 55 and older (see table. 1) according to the duration of the disease, the patients are divided into three groups: the 1st is made up of persons with a prescription process up to 1 of the year; 2nd - from 1 year to 10 years; 3rd — patients suffering from ulcer over 10 years (see table. 2) In the biopsy samples of the coolant before and after conservative therapy, the concentrations of FAT, LTV ₄ , the sum of LTS ₄ , LTD ₄ , LTE _{4 are} determined. As a result of the surveys, it was found that 75% (37 people) of the patients were found to be infected with PX, 25% (12 people) were found to be PX - negative, while studying the nature of the distribution of patients depending on PX - status and localization of the ulcer defect, it was found that in the antrum all ulcers of the stomach turned out to be PX-associated (100% of cases), while in the body and corner of the stomach they were less so (respectively in 77% and 50% of cases), they establish that the highest percentage of PX-positive patients is observed in Group patients of young age (from 18 to 35 years) - 100%; close indicators (81%) were observed in patients over the age of 55 years; to a lesser extent, PCh patients were infected in the age category from 36 to 55 years. There was a correlation between the size of the ulcer defect and the HRP status of the coolant — smaller ulcers had a greater frequency of infection with HR, and it turned out that with a minimum (up to 1 year) duration of HRP disease, positive YAB is much less common than in groups of patients with a longer history of the disease (from 1 year to 10 years; over 10 years) - respectively in 56%, 86% and 88%. A comparative analysis of the results of the examination of patients with a history of bleeding showed that the largest number of cases of exacerbations of ulcer disease relates to the HRP-associated form. With PX - a negative form of ulcerative heart disease, gastrointestinal bleeding of varying severity was noted much less frequently in the anamnesis.

Determination of PAF, LTV _4, the sum of LTC4, LTD _4, LTE ₄ periultseroznoy CO at GU as a function of HRP - status of patients with the clinical criteria for the disease (Table 7, 8, 9, 10, 11, 12..).

Pro-inflammatory markers are determined in biopsy specimens obtained from the edges of ulcerative defects and antrum of the CO of 49 patients with UBI aged 18 to 71 years. Studies show that FAT in infected patients with HRP significantly (* - p 0.05) exceeds those in the coolant of healthy people, while in PH - negative patients, FAT practically does not differ from the control group. The content of FAT in CO was studied taking into account the age of patients, for which they were divided into three groups: the first consisted of people under the age of 35 years, the second from 36 to 55 years old, the third group included people older than 55 years. As shown in table 8, the FAT indices in the ulcer margin in HRP - positive patients with ulcer of different ages were significantly higher (* - p. 0.05) control values and similar parameters of HRP - negative patients (** - p. 0.05); There were no significant differences between the FAT indices in different age groups (p _1-3 0.05), in the groups of HRP-negative patients, the FAT indices did not differ from the control group and were independent of age. Analysis of the distribution of patients depending on the size of the ulcer allowed three groups to be distinguished: 1st — ulcer defect no more than 1 cm; 2nd from 1 cm to 2 cm; 3rd — more than 2 cm. The FAT indices in HRP-positive patients significantly exceed those in healthy patients in all compared groups (* p _1-3 0.05), significantly differing in groups with minimum and maximum sizes (** p _1.3 0.05) ulcerative defects. In the group of HRP - negative patients, there was no significant difference in the FAT indices depending on the size of the ulcer defect. We studied the concentration of FAT depending on the localization of the ulcer defect: in the body (group 1), angle (group 2) and the antrum (group 3) (see table. 8). As shown in the table. 8 PAF content in the HRP - positive patients was significantly higher (* - p _1-3 0.05) the normal rates, regardless of the localization of ulcers. The FAT indices significantly increased from the body to the antrum, however, the difference between the groups turned out to be significant (** p _1.3 0.05) only for the 1st and 3rd groups of patients with PCh - positive UB. The indicated differences were not observed in groups of patients with HRP - negative ulcers.

Clinical examples of studies of a method for predicting exacerbation of gastric ulcer and duodenal ulcer associated with Helicobacter pylori.

The revealed patterns illustrate extracts from the case histories of patients with pulmonary ulcer.

Example 2. Patient E., 35 years old, medical history No. 7454, was treated in the clinic from 10/11/15 to 05. 11.15, with a diagnosis of gastric ulcer in the acute stage.

Complaints upon receipt of moderate pain in the epigastric region 30 minutes after eating, belching, nausea, weakness (see table Z. Suffers from YABZH for 8 years, exacerbations - 1 time in 1-2 years).

Objectively: the condition is satisfactory. Height 178 cm, body weight 75 kg. The tongue is lightly coated in white. Heart sounds are rhythmic, clean. Pulse 78 in 1 minute. HELL 120/80 mm. Hg. Art. In the lungs, vesicular breathing. The abdomen is regular in shape, soft, slightly painful in the epigastric region.

Complete blood count: HB 143 g / l, red blood cells 4.5 × 10 ¹² / l, white blood cells 6.3 × 10 ⁹ / l, ESR 7 mm / h. General urine analysis without pathology. Fractional study of gastric juice: basal flow rate of HCl -3.45 meq / hour; stimulated - 7.34 meq / hour.

Gastroduodenoscopy: the fiberscope is inserted freely, the esophagus and cardia are not changed. The stomach is of the usual form, in the lumen there is a moderate amount of mucus, the tone is ordinary. In the middle third of the lesser curvature of the stomach, a rounded ulcerative defect up to 0.8 cm in diameter with smooth edges and pronounced periulcerous inflammation is determined. The mucous membrane is hyperemic in the form of a “shaft” with sharply defined boundaries. The pylorus and bulb of the duodenum are not changed.

Histological examination of biopsy material: elements of detritus in the preparation presented. Severe stromal infiltration by polymorphonuclear leukocytes, plasma cells. There are areas of atrophy of the mucosa.

The concentration of FAT is 5.36 pg / mg protein, LTV ₄ -2.15 ng / mg protein, LTS ₄ D ₄ E ₄ - 9.24 ng / mg protein; the activity of myeloperoxidase (MPO) in the periulcerous region is 0.13 U / mg protein; antibodies in the blood serum (-).

The presented observation demonstrates moderate changes in the activity of the marker of neutrophilic infiltration, the levels of FAT and RT in HRP - negative UBI of the age group from 18 to 35 years. Against the background of the described characteristics, the development of the disease is characterized by a mild course, small sizes of the ulcer defect.

The following example shows a different course of HRP - associated UJ.

Example 3. Patient P., 68 years old, medical history No. 4470, was in the clinic for treatment from 15. 10.15 to 21.11. 15 g. With a diagnosis of gastric ulcer in the acute stage. Antral erosive gastritis. Erosive bulbit.

Complaints: moderate pain in the epigastragal region of a constant nature, heartburn (see table. 3). Suffers from gastric ulcer 11 years. In the first 5 years, the disease was characterized by a mild course with an exacerbation duration of up to 30 days, a frequency of 1 time per year. Subsequently, exacerbations became more frequent - 3-4 times a year and expressed in symptoms, complete scarring of the defect was achieved after 45-50 days.

Objectively: the condition is satisfactory. Height -166 cm, body weight - 75 kg, tongue coated with white plaque. Heart sounds are clean, rhythmic. Pulse 80 in 1 minute. HELL 160/85 mm. Hg. Art. In the lungs, vesicular breathing. The abdomen is regular in shape, soft, with palpation moderately painful in the epigastric region. The liver is not palpable.

Complete blood count: HB -132 g / l, red blood cells - 3.7 × 10 ¹² / l, white blood cells - 6.9 × 10 ⁹ / l, ESR - 23 mm / h. Urinalysis - without pathology.

Fractional study of gastric juice: basal flow rate of HCl - 1.5 meq / hour; stimulated -3.86 meq / hour.

Gastroduodenoscopy: the fiberscope is inserted freely, the esophagus and cardia are not changed. The stomach is of normal shape, in the lumen there is an insignificant amount of mucus, the relief of the folds is ordinary. In the area of the angle of the stomach, a small round curvature is used to determine a deep rounded ulcerative defect up to 2.2 cm in diameter. The edges of the ulcer are even and clearly defined. The bottom of the defect is covered with a yellowish-gray coating. The mucous membrane surrounding the ulcer is edematous, hyperemic, rises above the rest of the departments in the form of a “roller”. The antrum mucosa is sharply hyperemic, edematous, and bleeds contact. The mucosa of the duodenum is hyperemic, on the back wall 3 flat erosion.

The concentration of FAT is 9.12 pg / mg protein, LTV ₄ is 4.68 ng / mg protein, LTS ₄ D ₄ E ₄ is 16.43 ng / mg protein; the activity of myeloperoxidase (MPO) in the periulcerous region is 0.13 U / mg protein; antibodies to HRP in serum (+).

Compared with the previous clinical example, in this case, a patient with an older age category of HRP - an associated stomach ulcer, has a higher neutrophilic infiltration index and significantly higher levels of PAT and RT, which is accompanied by a severe course of the disease, concomitant erosive lesions of the gastroduodenal mucosa, a large ulcer defect and a long period of its repair.

Thus, in the stage of exacerbation (remission) of peptic ulcer of the stomach and duodenum with Helicobacter pylori-positive and Helicobacter pylori - negative ulcers of the stomach and duodenum, inflammation of the gastric mucosa in the presence of Helicobacter pylori and with an increase in the concentration in the mucous membrane is determined mediators of platelet activation factor from 9.12 pg / mg protein or more, leukotrienes from 4.68 ng / mg protein or more, correlating with seeding of Helic mucosa bakter pylori predict aggravation of gastric ulcer and duodenal ulcer associated with Helicobacter pylori, as the results suggest the involvement of PAF and improve radiotherapy to the development of inflammation in patients with coolant HRP - positive gastric ulcer and acute gastric ulcer forecasting and duodenum.

The invention in comparison with the prototype and other known technical solutions has the following advantages:

- the ability to predict exacerbation of peptic ulcer of the stomach and duodenum associated with Helicobacter pylori;

- high information content;

- high diagnostic accuracy.

Claims (1)

A method for predicting exacerbation of gastric ulcer and duodenal ulcer associated with Helicobacter pylori, including biochemical blood tests, determination of platelet and leukotriene activation factor, characterized in that in the stage of remission of gastric ulcer and duodenal ulcer with Helicobacter pylori and Pylori-positive - negative ulcers of the stomach and duodenum determine inflammation of the gastric mucosa in the presence of Helicobacter pyl If and when the concentration of inflammatory mediators of platelet activation factor from 9.12 pg / mg protein or more, leukotrienes from 4.68 ng / mg protein or more, correlating with colonization of the mucous membrane of Helicobacter pylori, an exacerbation of peptic ulcer disease is predicted, peptic ulcer disease is predicted. the stomach and duodenum associated with Helicobacter pylori.

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