Method for predicting erosive ulcerating stomach lesions occurrence in the cases of hemorrhagic fever with renal syndrome

The invention relates to medicine, in particular to the pathology and gastroenterology.

It is known that in addition to renal injury in hemorrhagic fever with renal syndrome (HFRS) are often damaged gastric mucosa (GM). Morphological studies of the gastrointestinal tract in patients with HFRS reveal significant disturbances in blood circulation in the coolant, with subsequent degenerative and necrobiotic processes and the development of acute erosions and ulcers, often leading to fatal bleeding (Zelensky A.I., Kowalski G.S., Konstantinov A.A. and other Hemorrhagic fever with renal syndrome in the far East of the USSR /edited by Gostovarsko, A.a.konstantinova, Akerica. - Khabarovsk, 1979. - 112 C.). One of the main methods of assessment of proliferative processes and structural homeostasis of the gastric mucosa (GM) in various diseases, including hemorrhagic fever with renal syndrome, is counting positively stained nuclei of cells Ki-67 on 1800 cells with subsequent expression of interest, i.e. the calculation of the index of proliferation (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).

Also known scientific work, in which using morphometric mesh Avtandilov GG determine the relative activities the major amounts of microvessels in the mucosa proper coolant. (Avtandil, Medical morphometry: a Guide. M.: Medicine, 1990. - 384 S. Bogdanova A.L. Characteristics of chronic gastroduodenal pathology in children infected with Mycobacterium tuberculosis. author.... Kida. the honey. Sciences. Khabarovsk. 1999. - 23 S.)

Existing methods have the following disadvantages:

- evaluate and get the average relative volumes of micro-and stroma in GM without repair processes; not predicting the development of gastric lesions;

- estimate only and proliferative processes in the coolant in various diseases.

The objective of the invention is the prediction of erosive and ulcerative lesions in the gastric mucosa in HFRS by determining the index of Ki-67 positive nuclei of cells.

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

The results are presented in the table.

Frozen pieces of stomach or paraffin fragments coolant antrum in HFRS made histological sections with a thickness of 3-5 μm, stained with hematoxylin and eosin, pikrofusin by van gieson. For immunohistochemistry using paraffin sections, which is treated with monoclonal antibodies to Ki-67 (DAKO) streptovidin-Biotin method with subsequent visualization. Proliferative index was determined after viewing an average of 1800 cells. The index of Ki-67 positive nuclei of cells expressed as a percentage (%). The purpose of quantitative evaluation produce interest the determination of the specific amounts of stromal components of the coolant using the eyepiece measuring grid for citogeneticheskich studies with increasing 400 (Avtandil, Medical morphometry: a Guide. M.: Medicine, 1990. - 384). Significant differences in the selected group is determined by kriter the pits student.

In the midst of illness on day 2-3 of the disease HFRS count index of Ki-67 positive nuclei of cells in the biopsy of the coolant. When the index Ki-67 positive nuclei of cells from 6 to 16% predict occurrence of erosions and ulcers in the coolant, bleeding and hemorrhagic shock. Histologically observed: petechial hemorrhage and erosion, acute gastric ulcers. Dominated by degenerative changes and necrosis predominantly superficial epithelial structures. Gastric epithelium rollers and pit epithelium was represented by a high cylindrical cells with round nuclei, which are located in the basal part of the cell. The private layer of the mucous membrane were detected stromal edema, hyperemia, and stasis in the microvasculature, hemorrhage, polymorphonucleocytes infiltration. The bottom of acute erosions and ulcers were covered with mucus and fibrin, infiltrated PMN. In addition, it was revealed hyperemia of blood vessels stasis, sludge erythrocytes with microthrombi in the microvasculature of the stroma. The relative amounts of stroma and vessels in the mucosa itself was: 49 - 47% 24-27%, respectively. The index of Ki-67 positive nuclei of cells ranged from 6 to 16%.

When the index Ki-67 positive nuclei of cells 17-30% predicted erosions and ulcers in the coolant without the development of bleeding. Macroscopically in HFRS noted - single erosion, one sharp I had VA of the stomach. Histologically dominated by degenerative changes and necrosis predominantly superficial epithelial structures. The private layer of the mucous membrane were detected stromal edema, hyperemia, and stasis in the microvasculature, focal hemorrhage, polymorphonucleocytes infiltration. The bottom of acute acute erosions and ulcers were also covered with fibrin, infiltrated PMN. Marked hyperemia of the vessels, sludge erythrocytes with microthrombi in the microvasculature of the stroma. The relative amounts of stroma and vessels in the mucosa itself were: 46-44% 20-23%, respectively.

When the index Ki-67 positive nuclei of cells over 31% macroscopically in HFRS is not revealed no bleeding, no single erosion or acute gastric ulcers. Histologically, the predominant focal degenerative changes mostly superficial epithelial structures. The private layer of the mucous membrane were detected stromal edema, focal hyperemia and stasis in the microvasculature, weak polymorphonucleocytes infiltration. The relative amounts of stroma and vessels in the mucosa itself was: 43-40% and 17-19%, respectively.

The advantages of this method:

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

- the ability to quickly assess HFRS during sampling;

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

low - invasiveness and ease of the procedure, as it does not require sampling of the many pieces of fabric, this eliminates the risk of accidental damage to the anatomical structures of unmodified coolant.

Example 1. Patient O. 20 years, 276 medical history, was admitted with a diagnosis of HFRS, medium-severe, infectious-toxic shock, DIC. The ARF. Serous-hemorrhagic pneumonia. Pulmonary edema. Brain edema.

During endoscopic examination: multiple erosions and hemorrhages in the coolant, several acute ulcers in the antrum and cardia of acute hemorrhagic erosive and ulcerative gastritis, 12 duodenal ulcer - acute serous-hemorrhagic duodenitis. The relative amounts of stroma and vessels in the mucosa itself was: 48,4% and 24.3% respectively. The index of Ki-67 positive nuclei of cells ranged from 7.2%. Subsequently the patient developed gastrointestinal bleeding. Hemorrhagic shock.

Histologically: hemorrhage, severe erosion and ulcers of the stomach. Dominated by degenerative changes and necrosis predominantly superficial epithelial structures. The bottom of acute erosions and ulcers were covered with mucus and fibrin, infiltrated PMN. Outside of erosions and ulcers gastric epithelium rollers and patching apite the s was represented by a high cylindrical cells with round nuclei, located in the basal part of the cell. The private layer of the mucous membrane were detected stromal edema, hyperemia, and stasis in the microvasculature, hemorrhage, polymorphonucleocytes infiltration.

Example 2. Patient A. 21, No. 280 history, was admitted with a diagnosis of HFRS, medium-severe, erosive gastroduodenitis. ARF, polyuria. The relative amounts of stroma and microvessels in the coolant were: 45.4% and 21.2%, respectively, the index of Ki-67 positive nuclei of cells was 27%. Marked erosive-ulcerative lesions of the coolant in the patient, gastrointestinal bleeding developed.

Macroscopically in the coolant - focal petechial hemorrhages and single erosion, one acute gastric ulcer. Histologically dominated by degenerative changes and necrosis predominantly superficial epithelial structures. The private layer of the mucous membrane were detected stromal edema, hyperemia, and stasis in the microvasculature, focal hemorrhage, polymorphonucleocytes infiltration.

Example 3. Patient M 25 years old, no history of 2060, was admitted with a diagnosis of HFRS, medium-heavy form. ARF, polyuria. The relative amounts of stroma and vessels in the mucosa itself were: 41.2% and 18.2%, respectively, the index of Ki-67 positive nuclei of cells - 32%. The patient was missing erosive-ulcerative lesions of the coolant. Macroscopically in the coolant when the FSC is not revealed no hemorrhage, no erosion, no acute gastric ulcers. Histologically dominated by degenerative changes mainly cover-pit epithelium. The private layer of the mucous membrane were detected stromal edema, focal hyperemia and stasis in the microvasculature, weak polymorphonucleocytes infiltration.

A method for predicting the occurrence of erosive and ulcerative lesions of the gastric mucosa in hemorrhagic fever with renal syndrome, which consists in the fact that the assessment of proliferative processes by calculating the index of positive nuclei of cells (Ki-67) and at the level of Ki-67 from 6 to 16% predict the development of erosive and ulcerative lesions with gastrointestinal bleeding and hemorrhagic shock, and at the level of Ki-67 from 17 to 30% predict occurrence of erosive and ulcerative lesions without bleeding.