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INVENTION
Patent of the Russian Federation RU2245104

METHOD FOR PREDICTING THE EROSION OF EROSIVE-CAUSULAR GAS DEFENSE IN HEMORRHAGIC FEVER WITH RENAL SYNDROME

The name of the inventor: Evseev AN (RU); Timoshin S.S.
The name of the patent holder: Far Eastern State Medical University
Address for correspondence: 680000, Khabarovsk, ul. M-Amursky, 35, FECU, OIS
Date of commencement of the patent: 2003.04.03

The invention relates to medicine, in particular to pathological anatomy and gastroenterology, and can be used to predict the development of erosive-ulcerative lesions of the gastric mucosa. The evaluation of proliferative processes is carried out by calculating the positive cell nucleus index (Ki-67). At the level of Ki-67 from 6% to 16% predict the development of erosive-ulcerative lesions with gastric bleeding and hemorrhagic shock, and at a level of Ki-67 from 17% to 30% predict the occurrence of erosive-ulcerative lesions without bleeding. The method allows to predict the occurrence of ulcers and erosions in hemorrhagic fever with renal syndrome.

DESCRIPTION OF THE INVENTION

The invention relates to medicine, in particular to pathological anatomy and gastroenterology.

It is known that along with kidney damage with hemorrhagic fever with renal syndrome (HFRS), damage to the gastric mucosa often occurs. Morphological studies of the gastrointestinal tract in patients with HFRS reveal severe circulatory disturbances in the coolant, followed by dystrophic and necrobiotic processes and the development of acute erosion and ulcers, often leading to fatal bleeding (Zelensky AI, Kovalsky GS, Konstantinov A A hemorrhagic fever with renal syndrome in the Far East of the USSR / Edited by GSKovalsky, AAKonstantinov, AKPiotrovich .- Khabarovsk, 1979. - 112 pp.). One of the main ways to evaluate the proliferative processes and structural homeostasis of the gastric mucosa (LMW) in various diseases, including HFRS, is the counting of positive-stained Ki-67 cell nuclei by 1800 cells with a subsequent percentage expression, that is, the calculation of the proliferation index (Hoshi T ., Sasano H, et al. Cell damage and proliferation in human gastric mucosa infected by Helicobacter pylori-a comparison before and after H pylori eradication in non-atrophic gastritis Hum Pathol 1999 Dec; 30 (12): 1412-7).

And scientific works are known in which, using the morphometric grid, Avtandilov GG Determine the relative volumes of microvessels in the mucous membrane of the coolant. (Avtandilov GG Medical morphometry: Manual, Moscow: Meditsina, 1990. - 384 pp. Bogdanova AL Characteristics of chronic gastroduodenal pathology in children infected with mycobacteria of tuberculosis., Author's abstract ... Candidate of Medical Sciences, Khabarovsk. 1999. - 23 seconds.)

The existing methods have the following drawbacks:

- average values ​​of relative volumes of microvessels and stroma in the coolant are estimated and received without taking into account the processes of reparation; Not predicting the development of lesions of the stomach;

- evaluate only proliferative processes in the coolant for various diseases.

The aim of the invention is to predict erosive and ulcerative lesions in the gastric mucosa at HFRS by determining the Ki-67 index of positive cell nuclei.

The results of histological studies of various coolants at HFRS in patients showed a direct relationship between the level of the Ki-67 index of positive cell nuclei in the coolant and the severity of the inflammatory process in the coolant and the appearance of acute erosions and ulcers with bleeding in HFRS.

The results are shown in the table.

From fresh-frozen pieces of stomach or paraffin-embedded fragments of the antiplaquial coolant in HFRS, histological sections 3-5 μm in thickness are made, stained with hematoxylin and eosin, picrofuxin according to Van Gieson. For the immunohistochemical study, paraffin sections are used which are treated with monoclonal antibodies to the Ki-67 antigen (DAKO) with streptovidin-biotin method followed by visualization. The proliferative index is determined after viewing an average of 1,800 cells. The Ki-67 index of positive cell nuclei is expressed as a percentage (%). For the purpose of quantitative estimation, a percentage determination of specific volumes of stromal components of coolant is made using an ocular measuring network for cytohistosterometric studies with an increase of 400 (Avtandilov GG Medical morphometry: Manual, Moscow: Meditsina, 1990. - 384). The reliability of the difference in the selected groups is determined by the Student's criteria.

At the height of the disease on day 2-3 of the HFRS disease, the Ki-67 index of the positive cell nuclei in the biopsy specimen from the coolant is counted. With the index of Ki-67 positive cell nuclei from 6 to 16% predict the occurrence of erosions and ulcers in the coolant, bleeding and development of hemorrhagic shock. Histologically, small-point hemorrhages and erosions, acute ulcers of the stomach were noted. Dystrophic changes and necrosis predominantly of superficial epithelial structures predominated. The epithelium of the gastric ridges and the pit epithelium were represented by high cylindrical cells with rounded nuclei located in the basal part of the cell. In its own layer of the mucous membrane, edema of the stroma, hyperemia and stasis in the microcirculatory bed, hemorrhage, polymorphic cell infiltration was revealed. The bottom of acute erosions and ulcers was covered with mucus and fibrin, infiltrated PMN. In addition, vascular hyperemia, stasis, erythrocyte sludges with microthrombi in the stromal microvessels were detected. The relative volumes of stroma and microvessels in the mucosa proper were 49 to 47% and 24 to 27%, respectively. The Ki-67 index of positive cell nuclei was from 6 to 16%.

At the Ki-67 index of positive cell nuclei, 17-30% predict the occurrence of erosion and ulceration in the fluid without the development of bleeding. Macroscopically in the coolant with HFRS there were - single erosions, one acute ulcer of the stomach. Histologically, dystrophic changes and necrosis predominantly of superficial epithelial structures prevailed. In their own layer of the mucous membrane, edema of the stroma, hyperemia and stasis in the microcirculatory bed, focal hemorrhages, polymorphic cell infiltration was revealed. The bottom of acute erosions and acute ulcers and was covered with fibrin, infiltrated PMN. There was hyperemia of the vessels, erythrocytes erythrocytes with microthrombi in the microvessels of the stroma. The relative volumes of the stroma and microvessels in the actual mucosa were 46-44% and 20-23%, respectively.

With the Ki-67 index of positive cell nuclei over 31% macroscopically, no hemorrhages, no single erosions, or acute gastric ulcers were detected in the coolant at HFRS. Histologically, focal dystrophic changes predominantly predominated in the surface epithelial structures. In its own layer of the mucous membrane, edema of the stroma, focal hyperemia and stasis in the microcirculatory bed, weak polymorphic cell infiltration was revealed. The relative volumes of stroma and microvessels in the actual mucosa were 43-40% and 17-19%, respectively.

Advantages of this method:

- the ability to predict the occurrence of ulcers and erosion in HFRS;

- the possibility of a rapid assessment of the coolant during HFRS during fence;

- the objectivity of quantitative criteria, which have a direct correlation with the histological changes in the wall of the coolant;

- low traumatism and simplicity of the procedure, since it does not require the sampling of many pieces of tissue, thus eliminating the risk of accidental damage to unchanged anatomical structures of the coolant.

Example 1. Patient O. 20 years old, a medical history of 276, was diagnosed with HFRS, medium-severe form, infectious-toxic shock, DIC-syndrome. OPN. Serozno-hemorrhagic pneumonia. Pulmonary edema. Edema of the brain.

When the endoscopic examination: multiple erosion and hemorrhages in the coolant, several acute ulcers in the antral and cardiac parts - acute erosive-ulcer hemorrhagic gastritis, in the 12-duodenal - acute serous-hemorrhagic duodenitis. The relative volumes of the stroma and microvessels in the actual mucosa were 48.4% and 24.3%, respectively. The Ki-67 index of positive cell nuclei was from 7.2%. Later the patient developed gastrointestinal bleeding. Hemorrhagic shock.

Histologically: hemorrhages, acute erosion and stomach ulcers. Dystrophic changes and necrosis predominantly of superficial epithelial structures predominated. The bottom of acute erosions and ulcers was covered with mucus and fibrin, infiltrated PMN. Outside erosions and ulcers, the epithelium of the gastric ridges and the pit epithelium were represented by high cylindrical cells with rounded nuclei located in the basal part of the cell. In its own layer of the mucous membrane, edema of the stroma, hyperemia and stasis in the microcirculatory bed, hemorrhage, polymorphic cell infiltration was revealed.

Example 2. Patient A. 21 years old, No. of medical records 280, was diagnosed with HFRS, moderate-severe, erosive gastroduodenitis. OPN, polyuria. The relative volumes of stroma and microvessels in the coolant were 45.4% and 21.2%, respectively, and the Ki-67 index of positive cell nuclei was 27%. There were erosive and ulcerative lesions of coolant in this patient, gastric bleeding did not develop.

Macroscopically in the coolant - small-point focal hemorrhages and single erosions, one acute ulcer of the stomach. Histologically, dystrophic changes and necrosis predominantly of superficial epithelial structures prevailed. In their own layer of the mucous membrane, edema of the stroma, hyperemia and stasis in the microcirculatory bed, focal hemorrhages, polymorphic cell infiltration was revealed.

Example 3. Patient M. 25 years old, No. 2060, entered the diagnosis: HFRS, medium-heavy form. OPN, polyuria. The relative volumes of stroma and microvessels in the mucosa proper were 41.2% and 18.2%, respectively, and the Ki-67 index of positive cell nuclei was 32%. The patient had no erosive-ulcerative lesions of the coolant. Macroscopically, no hemorrhage, no erosion, no acute stomach ulcers were detected in the coolant during HFRS. Histologically, dystrophic changes predominantly of the cover-pate epithelium predominated. In its own layer of the mucous membrane, edema of the stroma, focal hyperemia and stasis in the microcirculatory bed, weak polymorphic cell infiltration was revealed.

CLAIM

A method for predicting the occurrence of erosive and ulcerative lesions of the gastric mucosa in hemorrhagic fever with renal syndrome, which consists in evaluating the proliferative processes by calculating the positive cell nucleus index (Ki-67) and at a Ki-67 level of 6-16% Erosive-ulcerative lesions with gastric bleeding and hemorrhagic shock, and at a level of Ki-67 from 17 to 30% predict the occurrence of erosive-ulcerative lesions without bleeding.

print version
Date of publication 29.03.2007gg

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