Early diagnostic technique for pulmonary artery thromboembolia. RU patent 2513845.
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| Method for diagnosing septic process and predicting septic complications development in children / 2248572 Method involves determining plasminogen/plasmin, α2-macro-globulin, α1-antitripsin content at the first, third, fifth and tenth day. The plasminogen/plasmin level being equal to 66-74 mcmole/l or 100-120 mcmole/l, α2-macro-globulin level of 2.7-3.0 mcmole/l, α1-antitripsin content of 2.38-3.2 mcmole/l, systemic inflammatory response to purulent infection, light severity degree endotoxicosis is diagnosed and favorable disease outcome is predicted. The plasminogen/plasmin level being equal to 50-65 mcmole/l or 125-160 mcmole/l, α2-macro-globulin level of 2.3-2.6 mcmole/l, α1-antitripsin content of 3.3-4.0 mcmole/l, sepsis with organ and system dysfunction, moderate severity degree endotoxicosis is diagnosed and septic complication availability and lingering disease development course is predicted. The plasminogen/plasmin level being equal to 39-40 mcmole/l, α2-macro-globulin level of 1.58-2.08 mcmole/l, α1-antitripsin content of 5.0-6.2 mcmole/l, severe sepsis, septic shock, severe degree endotoxicosis is diagnosed and unfavorable disease outcome is predicted. |
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| Method for predicting unfavorable result of metastatic peritonitis / 2251700 In patients one should study the content of lactoferrin in peritoneal exudates during the 1st d of postoperational period and at decreased value being below 3500 ng/ml on should predict unfavorable result. The suggested method provides correction of possible postoperational complications that deteriorate the flow of peritonitis and lead to lethal result. |
| Method for diagnosing endotoxicosis condition in cows suffering from acute pyocatarrhal endometritis / 2252418 Method involves determining low and middle molecular mass substances content in blood plasma and erythrocytes and general blood plasma albumin concentration. Integral index is calculated on basis of obtained values using formula II=100*S238-298(plasma)/S238-298(erythrocytes)*GAC, where S238-298(plasma) and S238-298(erythrocytes) are the low and middle molecular mass substances content in blood plasma and erythrocytes, respectively, determined from area of figures restricted by spectral curves in wavelength range of 238-298 nm and abscissa axis (conditional units2); GAC is the general blood plasma albumin concentration (g/l). The value being from 2.1 to 3.0, the first endotoxicosis degree is diagnosed. The value being from 3.1 to 4.5, the second endotoxicosis degree is diagnosed. The value being from 4.5 to 6.0, the third endotoxicosis degree is diagnosed. The value being greater than 6.0, the fourth endotoxicosis degree is diagnosed. The normal value is equal to 0.5-2.0. |
| Method for evaluating inflammatory process activity in infantine osteomyelitis cases / 2252419 Method involves separating blood serum proteins into fractions, determining albumins and alpha-2-globulins content and controlling their content changes during the disease development process. Gamma-globulin content is determined in per cent ratio with respect to total protein quantity. Then, changes in the fractions content are controlled from the first to the third week. Albumin content being in norm and alpha-2-globulins content becoming greater to the end of the first week by 30-50% when compared to normal value and dropping to norm at the second week end and gamma-globulin content increasing from norm by 10-30% to the second or the third week, high inflammatory process activity is to be diagnosed. Albumin content dropping by 10-30% from normal value at the second week, alpha-2-globulins content growing by 10-20% of norm and gamma-globulin content dropping by 30-50% at the second or the third week when compared to norm, low inflammatory process activity is to be diagnosed. |
FIELD: medicine.
SUBSTANCE: early diagnosis of pulmonary artery thromboembolia in the presence of the clinical signs of potential pulmonary artery thromboembolia PATE (tachypnea, tachyrhythmia, thoracodynia, bloody expectoration) is ensured by measuring blood serum fibrin D-dimer. If the fibrin D-dimer content is less than 0.5 mg/l, suspended PATE is discarded. If the blood plasma fibrin D-dimer content is 0.5 mg/l and more, an additional enzyme immunoassay is used to measure blood serum interleukin-6, and if the derived concentration is 21.3 pg/ml and more, pulmonary artery thromboembolia is diagnosed.
EFFECT: using the technique enables higher accuracy and information value of diagnosing pulmonary artery thromboembolia.
2 tbl, 2 ex
The invention relates to medicine and can be used for early diagnosis of pulmonary embolism (PE).
According to literary data, pulmonary embolism (PE) is one of the leading causes of death in the European countries and the USA, along with acute myocardial infarction and stroke and is detected at autopsy 12-15% of patients [1]. According to Frengenskoto research (USA) PE is 15.6% of all vnutrikorporativnoj mortality, among them at surgical patients 18%and 82% are patients with internal diseases [2]. In addition to the high incidence of pulmonary embolism is characterized diagnostic difficulties associated with nespecificescuu clinical symptoms. Overall, under-diagnostics of this disease, despite the introduction into the clinical practice of high-tech diagnostic methods, such as ventilation-perfusion scintigraphy lungs, computed tomographic pulmonary, direct pulmonary.
Today the laboratory tests in the diagnosis of pulmonary embolism are auxiliary. There are several ways of diagnosis of pulmonary embolism, based on the determination of molecular markers.
One of them is the method of preoperative diagnostics and prevention of hemocoagulation complications (RF Patent №2256913 published 20.07.2005). For early detection and prevention of thromboembolism in hip and knee joints conduct pre-operative determination of the level antitrombina III, intravenous sodium thiosulfate daily 10 ml, in addition spend cuff test, by the blood after imposition of the cuff and discharge pressures equal systolic, determine its level antitrombina III and in the absence of changes level relative to the source spend preoperative preparation with the introduction of sodium thiosulfate until improve antitrombina III during the cuff of the sample. This method allows you to monitor and modify the level of anti-thrombin III. The area of application of this method is limited to cases of preparation of patients for surgical treatment, and are not eligible for the diagnosis of pulmonary embolism in other clinical situations.
Known method for the diagnosis of pulmonary equity pulmonary artery in patients with diseases of cardiovascular system (Patent RF №2256913 published 20.07.2005). The method consists in the fact that immediately after the onset of clinical symptoms pulmonary equity pulmonary artery in the serum of the patient to determine the number of protein-bound hydroxyproline and at higher levels to 369,78 umol/l and above diagnosed embolism equity pulmonary artery. The method provides the possibility of early and accurate diagnosis of pulmonary equity pulmonary artery with a view to its timely treatment. This method has limitations: it is intended only for patients with diseases of cardiovascular system with localization of tromboembolia in equity pulmonary arteries.
Closest to the proposed method is the determination in blood of patients with low or moderate clinical probability of pulmonary embolism level of D-dimer, fibrin, one of the degradation products fibrinoguena. The increase in the concentration of more than 0.5 mg/l indicates spontaneous activation of fibrinolysis in response to venous thrombosis and is diagnostically significant for pulmonary embolism when clinical conditions. Normal levels of D-dimer, fibrin in plasma (less than 0.5 mg/l) allows you to better than 90% reject the assumption of pulmonary embolism [3]. However, the high value of D-dimer plasma (more than 0.5 mg/l) are not specific for PE and not allow us to diagnose the disease. This method has a high negative predictive value, but does not differentiate between PE and other diseases and conditions associated with increased levels of D-dimer, fibrin, such as deep vein thrombosis.
It is known that the development of pulmonary embolism associated with higher levels of some of proinflammatory cytokines [4, 5, 6].
The new technical task - improvement of the accuracy and usefulness of early diagnosis.
To solve the problem in the method of early diagnosis of pulmonary embolism, namely, that if the patient's clinical symptoms of pulmonary embolism determine the level of D-dimer, fibrin in the serum; provided that the level of D-dimer, fibrin above 0.5 mg/l, optionally using enzyme immunoassay determine the level of interleukin-6 in blood serum, and when it is the content of 21.3 PG/ml and above diagnosed with pulmonary embolism.
The method is as follows.
If the patient's clinical signs indicating the probability of pulmonary embolism (tachypnea, tachycardia, chest pain, hemoptysis) determine the level of D-dimer, fibrin in plasma. If the value of the content of D-dimer, fibrin less than 0.5 mg/l suspected of pulmonary embolism reject. When the content of D-dimer, fibrin 0.5 mg/l and higher additionally determined by immune-enzyme analysis of the levels of Il-6 in blood serum, and when its concentration 21,3 PG/ml and above diagnosed with pulmonary embolism.
What's new is that to implement the process determine the level of interleukin-6 in blood serum and when its concentration 21,3 PG/ml and above diagnosed with pulmonary embolism.
These distinctive features is not known in the medical-scientific and patent literature. Thus, the proposed method meets the criterion of "novelty".
The set of distinctive features is not obvious to a person skilled in the art. Thus, the proposed method meets the criterion of "inventive step"
This method is passed the clinical tests in the clinical base of Khakass state University. NF Katanov - the Republican clinical hospital named. G-Ya Remiszewski. Thus, this solution meets the criteria of the invention "industrially applicable".
The method is based on analysis of clinical observations 33 patients with suspected pulmonary embolism. As a method for verifying the availability of tromboembolia in the pool pulmonary artery used spiral computed tomographic the pulmonary (SKT-pulmonary). In 19 patients with a diagnosis of pulmonary embolism was confirmed by the data of spiral CT-angiography, 14 rejected. All 19 patients with pulmonary embolism (PE), confirmed data SKT-angiography, was attended by clinical signs indicating the probability of pulmonary embolism (tachypnea (100%), tachycardia (93%), pain in chest (53%), hemoptysis (5%)). The level of D-dimer in all patients with pulmonary embolism (PE) exceeded the threshold value of 0.5 mg/L. All patients by enzyme immunoassay determined the levels of Il-6 in blood serum. The average values of these indices in patients depending on the availability of pulmonary embolism are shown in table 1 (Annex 1). Thus was determined the threshold level of interleukin-6 for the diagnosis of pulmonary embolism - 21,3 PG/ml
The proposed method is tested on the analysis of the results of clinical observations in 10 patients with suspected pulmonary embolism. All patients enrolled in the radiology Department with suspected pulmonary embolism. Table 2 presents the results of the validation of the proposed method in the group of patients with suspected pulmonary embolism. Verification of the results of the studies were carried out using spiral computer tomography when performing indirect angiography (SKT-pulmonary), which allowed to visualize the presence of thromboembolic. When using the proposed method for the diagnosis of pulmonary embolism in 6 patients had installed the disease, 4 patients decided to lack of pulmonary embolism. Diagnosis of pulmonary embolism was confirmed in the future (according to SKT-angiography) in 5 patients, and in 1 case the diagnosis of pulmonary embolism was rejected. 4 patients using the proposed method of pulmonary embolism was not diagnosed, further study (SKT-pulmonary) suspected of pulmonary embolism was rejected in 3 cases, and in 1 case of identified direct signs of pulmonary embolism in the form of tromboembolia in the upper lobe of the lung artery on the right. Thus, when using a new method for the diagnosis of pulmonary embolism received 5 true positive, 3 true-negative, 1 false positive and false negative 1 result. Thus, the new method has a sufficiently high sensitivity (83%), specificity (75%) and precision (75%) in the diagnosis of pulmonary embolism.
Example 1. Patient Zh., 48 years old, case history №110/12, date, 30.03.11 Was admitted to the hospital with complaints sharply developed shortness of breath, dizziness. In the collection of anamnestic data revealed the presence of coronary artery disease. Clinically established tachycardia and symptoms of deep vein thrombosis leg, at the time of inspection tachypnea (NPV=18), tachycardia (heart rate=108), AD=95/65. The level of D-dimer 0,67 mg/L.
The diagnosis of pulmonary embolism?
Study according to the proposed method. In this patient are anamnestic and clinical features of pulmonary embolism, a high level of D-dimer, fibrin - 0,67 mg/L. According to the proposed method is additionally determined the content of Il-6 in blood serum is by enzyme immunoassay. The level of interleukin-6 was 31.4 PG/ml as the level of interleukin-6 in the patient's serum exceeded 21,3 PG/ml, the conclusion about the presence of pulmonary embolism.
The presence of pulmonary embolism was confirmed by later studies. The patient is made SKT-pulmonary: SKT-angiography revealed thromboemboli in proximal arteries to the right, and tromboamboliy in segmental arteries of the lower lobe of the left. The patient is assigned thrombolytic and anticoagulant therapy.
Example 2. The patient that is, 51, is focused on an outpatient basis for excluding pulmonary embolism. Analysis of historical data revealed the presence of hypertension II century According to the clinical examination revealed shortness of breath, tachycardia (heart rate=105 per minute), respiratory rate of 14 per minute, the level of D-dimer, fibrin of 0.58 mg/L.
The diagnosis of pulmonary embolism?
Study according to the proposed method. The patient are some signs of pulmonary embolism (shortness of breath, tachycardia). The level of D-dimer, fibrin match of 0.58 mg/L. According to the proposed method was further defined the levels of Il-6 in blood serum, which was 13.2 PG/ml In accordance with the new method of diagnosis of pulmonary embolism in patients rejected, which was confirmed by further observations and research. According to SKT-angiography availability of thromboembolic in a small circle not confirmed the diagnosis of pulmonary embolism is cleared.
The positive effect of the proposed method is confirmed by the results of its application in 10 patients studied about suspected of pulmonary embolism.
Thus, the application of the proposed method will allow to increase the accuracy of the diagnosis of pulmonary embolism in the early stages of the disease, which will contribute to more timely appointment of treatment and preventive measures.
Sources of information
1. The Columbus Investigators. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism.//N. Engl. J. Med. - 1997. - Vol.337. - P. 657-662.
2. Klochkov N Analysis of deaths from pulmonary embolism arteries//Vesting. - 1994. - №5. - P.101-104.
3. P.S. Wells, D.R. Anderson, Rodges M. Evalution ofD-dimer in the diagnosis of suspected deepvein thrombosis//N. Engl. J. Med. - 2003. - Vol.349. - P. 1227-1235.
4. K.A. Zykov, V.P. Masenko, S.N. Tips, I.E. Chazov. Fractalkine - new marker of cardiovascular disease//Cardiological Bulletin. - 2008. -Volume 3, number 2. - P.34-37.
5. Vormittag R, Hsieh, Kaider A et al.. Interleukin-6 and interleukin-6 promoter polymorphism (-174 G>in patients with spontaneous venous thromboembolism.//Thromb Haemost. - 2006. - Vol.95, №5. - P.802-806.
6. YANG M., G. LIU, Y. SUN et al. Changes ofhomocystiene and interleukin -8 in patients with massive pulmonary embolism before and after thrombolysis therapy//J. Fore. - 2011. - Vol.22, no. 9. - P. 797-798.
Application
Table 1. The results of the research of the level of interleukin-6 and interleukin-8 in patients with suspected pulmonary embolism.
Table 2. Results validation of the proposed method in the group of patients with suspected pulmonary embolism.
Table 1 Group PEThere is no data for PE
The level of statistical significance of differences between groups, R.
Interleukin-6, PG/ml
28,1(21,3% to 34,3)
13,4(8,9% to 18,3)
0,046 Table 2The patient
The levels of Il-6 in blood serum, PG/ml
The presence of pulmonary embolism, according to the proposed method
Conclusion CT-angiography
№1 31,2 PE PE №2 24,5 no PE №3 41,3 PE PE №4 29,5 PE PE №5 54,2 PE PE №6 18,3 nono data for PE
№7 28,6 PEthere is no data for PE
№8 29 PE PE №9 15,2 nothere is no data for PE
№10 9,5 nothere is no data for PE
The method of early diagnosis of pulmonary embolism, which is that if the patient's clinical signs, indicates the probability of pulmonary embolism (tachypnea, tachycardia, chest pain, hemoptysis) determine the level of D-dimer, fibrin in the serum; in the content of D-dimer, fibrin less than 0.5 mg/l suspected of pulmonary embolism reject, and when the content of D-dimer, fibrin in the serum of 0.5 mg/l and above additionally determined by immune-enzyme analysis of the levels of Il-6 in blood serum, and when its concentration 21,3 PG/ml and above diagnosed with pulmonary embolism.