Method of estimating nephrotoxic impact of roentgenopaque preparations

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, namely to radionuclide diagnostics. Radionuclide rhinoscintigraphy with 99mTc-pentatech is carried out. Indices of filtering and avacuatory kidney functions are determined twice: before and 2-3 days after procedure with introduction to patient of reontgenopaque compound. Determined are slight disturbance of filtering function of kidney with less than 15% of initial value reduction of glomerular filtration, moderate disturbance of filtering function of kidney with from 15 to 30% of initial value reduction of glomerular filtration rate and expressed disturbance of filtering function of kidney with higher than 30% of initial value reduction of glomerular filtration rate. Less than 6 min from initial value increase of period of radiopharmpreparation semiejection is estimated as slight disturbance of evacuatory function of kidneys, from 6 to 15 min - as moderate disturbance of evacuatory function of kidneys and more than 15 min as expressed disturbance of evacuatory function of kidneys.

EFFECT: method ensures objective estimation of nephrotoxic impact of definite reontgenopaque compound and possibility of timely administering adequate therapy.

6 dwg, 6 ex

 

The invention relates to medicine, namely to radionuclide diagnostics.

There is a method of evaluation of the nephrotoxicity of radiopaque substances, which consists in measuring the level of serum creatinine before and after contrast administration [1, 2] or by calculating creatinine clearance [1, 3]. The disadvantage of this method is that the concentration of creatinine in serum, along with the functional activity of the kidneys, affect the volume of circulating plasma [4], the possible errors of metabolism, creatinine, inaccuracy when measuring levels in the blood samples [5] and other factors [6]. In addition, significantly increased the concentration of creatinine in serum he begins to secretariats in the tubules, causing the overstatement glomerular filtration when calculating it on the clearance of endogenous creatinine [7].

At the same time to study the function of the urinary tract for a long time and are widely used radionuclide methods. In particular, radionuclide renascentia allows not only to estimate glomerular filtration, tubular secretion, urodynamics, state parenchyma and the blood supply to the kidneys, the topography of the entire body and its individual parts [8], but also allows to detect renal dysfunction at the initial stages of the disease, when other method the diagnosis is still uninformative. Method physiologic, relatively simple to implement, is well tolerated by patients, vysokoproizvodi and can be used in the process of monitor observations.

Adequate prototype of the proposed method in the analysed literature was not found.

The aim of the invention is to provide objective assessment of nephrotoxic effects of certain radiopaque compounds and the timely appointment of adequate therapy.

This goal is achieved technical solution representing the way to assess nephrotoxic effects of radiopaque compounds by conducting patients radionuclide renascentia with99mTC-pentathol twice: before exposure (baseline) and after 2-3 days afterwards. According to the results of renascentia calculate the indicators of filtration and evacuation of kidney function before and after Radiocontrast studies. By comparing the original data and results of renascentia received after radiological research, assess the degree and nature of the nephrotoxic effects of certain contrasting connections as follows.

On the basis of the values of obtained parameters define a minor breach of the filtration function of the kidneys by reducing the rate of glomerular fil the radio less than 15% of the initial value moderate violation of the filtration function of the kidneys by reducing glomerular filtration rate from 15% to 30% from the original values and expressed violation of the filtration function of the kidneys by reducing glomerular filtration rate more than 30% from the original values, and increased half-life of the radiopharmaceutical less than 6 min from baseline values assessed as a minor breach of the evacuation function of the kidneys, from 6 to 15 min as moderate and more than 15 min as severely impaired evacuation of renal function.

New in the proposed method is twofold conducting patient radionuclide renascentia (before and after introduction of a radiopaque agent) and quantification of changes in rates of filtration and evacuation of the kidney under the influence of contrasting connections. On the basis of the magnitude of change in glomerular filtration rate and half-life of the radiopharmaceutical from the kidney to determine the degree of disturbance of the functional activity of the kidneys as "slight", "moderate" or "marked".

The essential features of the method showed in the inventive combination of new properties that are not explicitly derived from the prior art in this field and are not obvious to the expert.

Identical set of features not found in the patent and scientific IU izinski literature.

This invention can be used in scientific research for a comparative evaluation of the nephrotoxicity of different contrast agents, as well as in practical health care for the timely appointment of adequate therapy in the presence of nephrotoxic effects during patient diagnostic procedures with the use of radiopaque compounds.

Based on the foregoing should be considered as the invention with the relevant conditions of patentability of "Novelty", "Inventive step", "Industrial application".

The invention will be clear from the following description and proposed to him the drawings.

Figure 1 presents renascentia patient P. before (a) and after (b) contrast coronaroventriculography (CVG): compared with the original data in the early stages after CVG is a slight decrease in the filtration function of the right kidney.

Figure 2 presents renascentia patient Hours before (a) and after (b) contrast coronaroventriculography: compared with the original data in the early stages after CVG is a moderate decrease in the filtration function of the left kidney.

Figure 3 presents renascentia patient X. before (a) and after (b) contrast coronaroventriculography: cf is the ranking with the original data in the early stages after CVG is decreasing filtration function of the left kidney.

Figure 4 presents renascentia patient, before (a) and after (b) contrast coronaroventriculography: compared with the original data in the early stages after CVG is a slight violation of the evacuation function of both kidneys.

Figure 5 presents renascentia patient P. before (a) and after (b) contrast coronaroventriculography: compared with the original data in the early stages after CVG is moderate violation of the evacuation function of both kidneys.

Figure 6 presents renascentia patient C. before (a) and after (b) contrast coronaroventriculography: compared with the original data in the early stages after CVG is severely impaired evacuation function of the right kidney.

The method is as follows.

Radionuclide dynamic renal scintigraphy performed with the patient sitting or lying down. The detector gamma camera set close to the back of the patient so that in the field of view was the heart and kidneys. For a study of special patient preparation is required. Radiopharmaceuticals, DTPA (99mTC-Pentateuch, "diamed"), Technetium-99m is injected at a dose of 30-40 MBq (of 0.8-1.0 MCI) and the amount to 1-1 .5 ml of the Recording continues for 20 min, mode 1 frame/60 C. For calculation of the rate of glomerular f is litraly additionally write two more frame duration 10-60 with each. The first frame of the recorded activity of the syringe before injection, and the last activity in the syringe after injection.

The result of this study is to obtain a series of scintigrams with the image of the kidneys in different time intervals. On native scientifico chosen area of interest region of both kidneys, heart and background and build curves "activity-time."

To quantify renascentia use the following key indicators:

GFR (ml/min) glomerular filtration rate (total and separately for each of the kidneys);

T1/2(min) half-life period of the indicator, i.e. the time for which there is a twofold reduction of the maximum activity over the region of the kidneys, reflects excretory function (separately for left and right kidney).

Example 1.

Patient P., 58 years old, medical history, No. 872, was on inspection and treatment at the Department of heart failure with 09.02.2006, 22.02.2006, with a primary diagnosis of ischemic heart disease, angina III-IV FC. Atherosclerosis of the aorta, stenosing atherosclerosis of the coronary arteries. Condition after mammomonogamus bypass anterior descending artery (2004). Atherosclerotic cardiosclerosis. HK-I, NYHA II. Background: hypertension I, III stage, risk 4. Accompanying diseases: chronic bronchitis, the remission phase. Atherosclerosis of the carotid arteries./p>

Biochemical blood test: creatinine - 79,1 mmol/L.

To determine the patency of the shunt and the further tactics of treatment of the underlying disease, the patient was assigned to conduct 14.02.06, the radiopaque coronaroventriculography (CVG).

To CVG (13.02.06 g) the patient was held radionuclide renascentia kidney99mTC-pentathol. According to the obtained data (Fig 1, a) violations of filtration and evacuation functions of the kidney have been identified: total GFR was 110,5 ml/min, the left kidney of 55.5 ml/min, right kidney - 55,0 ml/min; half-life period of the indicator of the left kidney was of 7.8 min, the right kidney is 6.2 minutes

48 hours after Radiocontrast procedure, the patient was re-held radionuclide renascentia without changes to the conditions of the study. According to the results (figure 1, b) found a slight decrease of the filtration function of the left kidney: total GFR was to 103.9 ml/min, left kidney - 55,0 ml/min, right kidney - 48,9 ml/min Evacuation function of the kidneys is moderately deteriorated (half-life period of the indicator of the left kidney was 15.4 min, right kidney - min 15,2), but its performance remained within permissible limits. Thus, the total GFR kidney after administration of contrast agent declined by 6%and GFR right kidney by 11% compared what Yu with an initial value.

Example 2.

Patient Hours, 50 years history No. 686, were examined and treated at the cardiac unit with 03.02.2005, 21.02.2005, with a primary diagnosis of ischemic heart disease, angina and II, respectively. Paroxysmal form of atrial fibrillation. HK-I. Background: hypertension II. Accompanying diseases: peptic ulcer, the remission phase.

Biochemical analysis of blood: urea - 7.4 mmol/l, creatinine - 98.6 mmol/L.

To determine further tactics of treatment of the underlying disease, the patient was assigned to conduct 10.02.05, the radiopaque coronaroventriculography (CVG).

To CVG (07.02.05,) the patient was held radionuclide renascentia kidney99mTC-pentathol. According to the obtained data (figure 2, a) violations of filtration and evacuation functions of the kidney have been identified: total GFR was 122,9 ml/min, left kidney, at 63.5 ml/min, right kidney - to 59.4 ml/min; half-life period of the indicator of the left kidney was of 12.3 min, right kidney and 15.3 minutes

After 72 hours after Radiocontrast procedure, the patient was re-held radionuclide renascentia without changes to the conditions of the study. According to the results (figure 2, b) evacuation kidney function has not changed (the half of the indicator of the left kidney represented 14.0 min, right on the key of 9.2 min). At the same time it was found moderately decreasing filtration function of the left kidney: total GFR was 109,1 ml/min, the left kidney is 50.2 ml/min, right kidney to 58.9 ml/min Thus, GFR left kidney after administration of contrast agent decreased by 21% compared with an initial value that corresponds to a moderate degree of violation.

Example 3.

Patient H., 66 years history No. 6969, 14.11. 2005 enrolled in the cardiac surgery Department with a primary diagnosis of ischemic heart disease, angina FC III. Stenosing atherosclerosis of the coronary arteries. Postinfarction cardiosclerosis. HK-I, NYHA III. Background: hypertension II, risk 2. Accompanying diseases: chronic bronchitis without exacerbation. Diffuse pneumovirus. Emphysema. Respiratory failure II Art. chronic pyelonephritis, latent. CRF 0. Dyscirculatory encephalopathy II Art.

Biochemical analysis of blood: urea - 6.1 mmol/l, creatinine - of 86.1 mmol/L.

To determine further tactics of treatment of the underlying disease, the patient was assigned to conduct 21.11.05, the radiopaque coronaroventriculography (CVG).

To CVG (18.11.05 g) the patient was held radionuclide renascentia kidney99mTC-pentathol. According to the obtained data (Fig 3, a) violations of the evacuation function of the kidney have been identified (the periods of the half-life of the indicator of the left kidney was 14.9 min, the right kidney was 13.8 min). Was a moderate decrease in the filtration function of both kidneys: total GFR was 90,5 ml/min, left kidney - 44,0 ml/min, right kidney - 46,5 ml/min

After 72 hours after Radiocontrast procedure, the patient was re-held radionuclide renascentia without changes to the conditions of the study. According to the obtained results (Fig 3, b) evacuation kidney function has not changed (the half of the indicator of the left kidney was 13.8 min, right kidney - 11.2 min). At the same time it was found a significant reduction in the filtration function of the left kidney: total GFR was 77.8 ml/min, left kidney - 30,4 ml/min, right kidney, with 47.4 ml/min Thus, GFR left kidney after administration of contrast agent decreased by 31% compared with an initial value, which corresponds to significant disturbance.

Example 4.

Patient G., 48 years old, medical history No. 2162, was on the examination and treatment in the cardiac unit with 30.03.2007, 08.05.2007, with a primary diagnosis of ischemic heart disease, angina FC III. Stenosing atherosclerosis of the coronary arteries. Postinfarction cardiosclerosis. HK-IIA.

Background: hypertension III, risk 4.

Accompanying diseases: atherosclerosis of the aorta and its branches. Cholelithiasis, the remission phase. Chronic pyelonephritis, the REM phase is hurt.

Biochemical analysis of blood: urea - 5.1 mmol/l, creatinine - 95,0 mmol/L.

To determine further tactics of treatment of the underlying disease, the patient was assigned to conduct 16.04.07, the radiopaque coronaroventriculography (CVG).

To CVG (13.04.07,) the patient was held radionuclide renascentia kidney99mTC-pentathol. According to the obtained data (figure 4, a) violations of filtration and evacuation functions of the kidney have been identified: total GFR was 112,0 ml/min, left kidney, with 56.8 ml/min, the right kidney is 55.2 ml/min; half-life period of the indicator of the left kidney was $ 14.4 min, right kidney and 10.8 minutes

48 hours after Radiocontrast procedure, the patient was re-held radionuclide renascentia without changes to the conditions of the study. According to the obtained results (figure 4, b) filtration function of the kidneys virtually unchanged (total GFR was 109,1 ml/min, left kidney at 53.4 ml/min, right kidney and 55.7 ml/min). At the same time it was found slightly expressed violation of the evacuation function of both kidneys: the half-life of the indicator of the left kidney was 18,8 min, right kidney to 15.0 minutes Thus, after introduction of a radiopaque substance was a minor breach of the evacuation function of both kidneys.

Prima is 5.

Patient P., 54 years old, medical history, No. 985, passed the examination and treatment in the Department of heart failure with 17.02.2005, 21.03.2005, with a primary diagnosis of ischemic heart disease, angina and II, respectively. Atherosclerosis of the aorta, stenosing atherosclerosis of the coronary arteries. Atherosclerotic cardiosclerosis. NK-0-I, NYHA I-II. Background: atherosclerosis of the carotid, femoral, iliac arteries, Leriche syndrome. Hypertension III, risk 3. Comorbidities: metatuberculosis pneumovirus. Gastritis, duodenitis, the remission phase.

To determine further tactics of treatment of the underlying disease, the patient was assigned to conduct 03.03.05, the radiopaque coronaroventriculography (CVG).

To CVG (02.03.05 g) the patient was held radionuclide renascentia kidney99mTC-pentathol. According to the data obtained (figure 5, a) violations of filtration and evacuation functions of the kidney have been identified: total GFR was 118,7 ml/min, left kidney - 57,7 ml/min, right kidney - 61,0 ml/min; half-life period of the indicator of the left kidney was of 14.3 min, right kidney and 11.8 minutes

48 hours after Radiocontrast procedure, the patient was re-held radionuclide renascentia without changes to the conditions of the study. According to the obtained results (figure 5, b) filtration function of the kidneys in practice the automatic has not changed (total GFR was 115,9 ml/min, the left kidney, with 56.8 ml/min, right kidney - 59,1 ml/min). At the same time it was found moderately severely impaired evacuation function of both kidneys: the half-life of the indicator of the left kidney was 28,0 min, right kidney compared with 26.4 minutes Thus, after introduction of a radiopaque substance was moderate violation of the evacuation function of both kidneys.

Example 6.

Patient S., 42 years old, medical history, No. 6787, was on the examination and treatment in the cardiac unit with 07.11.2005, 16.12.2005, with a primary diagnosis of ischemic heart disease, angina I FC. Stenosing atherosclerosis of the coronary arteries. Postinfarction cardiosclerosis. HK-I, NYHA II. Background: dyslipoproteinemia.

Accompanying diseases: osteochondrosis of the spine, the remission phase. Biochemical analysis of blood: urea - 4.8 mmol/l, creatinine - to 82.6 mmol/L.

To determine further tactics of treatment of the underlying disease, the patient was assigned to conduct 17.11.05, the radiopaque coronaroventriculography (CVG).

To CVG (16.11.05 g) the patient was held radionuclide renascentia kidney99mTC-pentathol. According to the data obtained (Fig.6, a) there has been a substantial violation of the filtration function of the left kidney: total GFR was 107,4 ml/min, left kidney - 43,4 ml/min, right kidney - 64,0 ml/min; detected NESN is a massive violation of the evacuation function of the right kidney: the half-life of the indicator of the left kidney was 14.6 min, right kidney - 21,0 minutes

After 72 hours after Radiocontrast procedure, the patient was re-held radionuclide renascentia without changes to the conditions of the study. According to the results (Fig.6, b) filtration function of the kidneys virtually unchanged (total GFR was 108,1 ml/min, the left kidney was 43.6 ml/min, the right kidney is 65.5 ml/min). At the same time it was found significantly expressed violation of the evacuation function of the right kidney: the half-life of the indicator of the left kidney was of 16.3 min, right kidney - 43,1 minutes Thus, after introduction of a radiopaque substance was revealed severely impaired evacuation function of the right kidney.

The proposed method allows high accuracy to determine the nature and extent nephrotoxic effects of radiopaque substances.

LITERATURE

1. Morcos S.K., H.S. Thomsen, Webb J.A. Contrast-media-induced nephrotoxicity: a consensus report. Contrast Media Safety Committee of European Society of Urogenital Radiology (ESUR). // Eur Radiol. - 1999. - Vol.9(8). - P.1602-1613.

2. Briguori C., Tavano D., Colombo A. Contrast agent-associated nephrotoxicity. // Prog Cardiovasc Dis. - 2003. - Vol.45(6). - P.493-503.

3. McCullough P.A., Wolyn R, Rocher L.L. et al. Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. // Am J Med. - 1997. - Vol.103. - P.368-75.

4. Basics of Nephrology. // Edited Amoreena - M.: Medicine, 1972. - S.

5. Perrone R.D., N.E. Madias, A.S. Levey Serum creatinine as an index of renal function: new insights into old cncepts // Clinical Chem. - 1992. - Vol.38. - P.1933-1953.

6. K/DOQI Clinical practice guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Available at URL: http://www.nephro.ru/standard/doqi_ckd/g4.htm.

7. Papayan A.V., V. Arkhipov, Beresnev, E.A. Markers of kidney function and evaluating the progression of renal failure. // Therapeutic archive. - 2004. No. .4. - S-90.

8. Vesnina IV Radionuclide diagnostics in Nephrology and urology. // Lishmanov B, Chernov, I. (editors). Radionuclide diagnostics for practitioners. - Tomsk: STT, 2004. - S-181.

Method of assessment nephrotoxic effects of radiopaque agents, characterized in that conduct the radionuclide renascentia with99mTC-pentathol determine the performance of filtration and evacuation of the kidneys twice: before and 2-3 days after the procedure with the introduction of the patient radiopaque compounds and determine a minor breach of the filtration function of the kidneys by reducing glomerular filtration rate less than 15% of the initial value, moderate violation of the filtration function of the kidneys by reducing glomerular filtration rate from 15% to 30% from the original values and expressed violation of the filtration function of the kidneys by reducing glomerular filtration rate more than 30% from the original values, and the increase in period probiogen what I radiopharmaceutical less than 6 min from baseline values assessed as a minor breach of the evacuation function of the kidney, from 6 to 15 min as a moderate violation of the evacuation function of the kidneys and more than 15 min as severely impaired evacuation function of the kidneys.



 

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SUBSTANCE: claimed method includes administration of vaccine representing complex of heat shock protein and tumor peptide, isolated from subject tumor tissue, and radioactive preparation Oncofer. Oncofer is administered both during vaccination course and after vaccination.

EFFECT: stable antitumor immunity, enhanced tumor cell apoptosis and blocked blood supply due to alteration of erythrocyte properties in tumor caused by radioactive preparation and activation of clot formation in said vessels.

2 cl, 4 ex, 2 dwg

FIELD: medicine, neurology, neurosurgery.

SUBSTANCE: one should carry out electroencephalographic (EEG) investigation along with hyperventilation during 3 min at frequency being 18 breathings/min. At detecting epileptiform activity upon EEG it is necessary to introduce cereteck and diagnose epileptiform focus by the appearance of hyperperfusion area. The innovation widens the number of techniques for predicting epileptiform foci.

EFFECT: higher efficiency of diagnostics.

FIELD: medicine, hormones, chemistry of peptides.

SUBSTANCE: invention describes compound of the formula: cyclo-[{4-NH2-C2H4-NH-CO-O-)-Pro}-Phg-D-Trp-Lys-Tyr-(4-Bzl)-Phe] being not obligatory in protected form, or its pharmaceutically acceptable salt of complex. Compound possesses the inhibitory activity on release of the growth hormone and insulin.

EFFECT: valuable medicinal properties of peptide.

9 cl, 2 ex

FIELD: medicine, radiology, pharmacy.

SUBSTANCE: invention relates to roentgenology and designated for X-ray study of different organs. The proposed agent for contrasting in X-ray diagnosis comprises tantalate of at lest one element chosen from group comprising yttrium, lanthanum, cerium, praseodymium, neodymium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, lutetium or bismuth, polysaccharide and water. Also, agent can comprise pectin, xanthane resin, carragheenan as polysaccharide and, additionally, it can comprise methylparaben and propylparaben as a preserving agent. Also, invention proposes an agent for contrasting in X-ray diagnosis that comprises tantalate of at least one element chosen from group including yttrium, lanthanum, cerium, praseodymium, neodymium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, lutetium or bismuth, polysaccharide and water that comprises additionally barium sulfate. Invention provides effective carrying out X-ray analysis of some organs in the sparing regimen using region of low energy of X-radiation (about 35-45 keV), and to obtain the distinct image of organ to be contrasted in diagnosis of patients with big weight and, therefore, significant adipose layer.

EFFECT: valuable properties of agent.

6 cl, 15 ex

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