The method of selection of pharmaceuticals for the treatment of hepatic encephalopathy

 

(57) Abstract:

The invention relates to medicine, in particular for gastroenterology, Hepatology and General medicine, and can be used for selection of pharmaceuticals for the treatment of hepatic encephalopathy. Explore the quantitative composition of short-chain fatty acid fraction C2-C6 with isomers in serum and feces. Determine the percentage of propionic acid, butyric acid, acetic acid total content C2-C4, the higher amount of acid containing 3-6 carbon atoms with isomers, the amount of isocyclic ISO+ISO+ISO and the percentage of isovalerianic acid in the total content C2-C6. Depending on the received indicators prescribed any drugs lactulose or drug from the group of hepatoprotectors, with a combined effect: sorption and hepatoprotective or hepatoprotective funds in the maximum therapeutic doses or medications that affect the stimulation of neutralization of ammonia in the liver and muscles, and/or drugs that bind NH3in the blood. The method allows for a differentiated approach to the treatment and individually to choose the best therapeutic option Lesa therapy, and can be used for differential treatment of hepatic encephalopathy.

Under hepatic encephalopathy (PE) is a potentially reversible disorder of brain function resulting from chronic liver failure and/or portlistener shunting of blood (W. Sherlock diseases of the liver and biliary tract", Chapter 7, "Hepatic encephalopathy", 100-119, Moscow, GEOTAR MEDICINE,1999).

Estimated pathogenetic mechanism PE associated effect of neurotoxins (e.g., ammonia (NH3), medium - and short-chain fatty acids (FFA, KGK) and others) coming into the Central blood flow in portosystemic shunts from the intestine, the production of false neurotransmitters from aromatic amino acids and increased GABAergic transmission of nerve impulses in the brain (W. Sherlock diseases of the liver and biliary tract", Chapter 7, "Hepatic encephalopathy", 100-119, Moscow, GEOTAR MEDICINE, 1999; Podymova C. D. “Heptagenia encephalopathy”, Russian journal of gastroenterology, Hepatology, Coloproctology, 1997, No. 1, I. VII, S. 88-91).

Of laboratory diagnostic methods of pathogenetic mechanisms of development of the PE the most common is definitely the com of this method is that that its level does not correlate with the stage of PE. In addition, venous ammonia level may be falsely increased muscle activity and renal failure, which reduces the specificity of this study in relation to PE. However, the normal concentration of ammonia is not a basis for excluding the diagnosis of PE (Naginsky M. Y. “Latent hepatic encephalopathy: how to help the patient, Clinical perspectives in gastroenterology, Hepatology, 2001, No. 1, S. 10-17; Sanjay Sandhir, MD, Frederick L. Weber, Jr, MD "Portal-Systemic Encephalopathy", Current Practice of Medicine, Jan 1999, No. 2, p.103-108).

Recently much attention is paid to the study of short-chain fatty acids (CGC) in serum as a diagnostic pathogenetic markers PE and markers, evaluating the effectiveness of treatment (Minushkin O. N., Arbatskaya M. D., Elizarova N. A. Short-chain fatty acids in the diagnosis of hepatic encephalopathy and evaluation of the effectiveness of the drug lactulose (Duphalac)// Clinical pharmacology and therapeutics, 2001, No. 10 (5), S. 9-13). However, no data have been used to justify differential treatment of PE.

Taking into account the pathogenetic mechanisms of the development of the PE the principles of treatment of PE vkluchat - nevsasyvaemye and not perevarivayutsya in the small intestine synthetic disaccharide lactulose (4-O- -D-galactopyranosyl-D-fructose), 2) a decrease in the degree of portal hypertension (aldosterone antagonists, antagonists, vasopressin, sandostatin), 3) improving the metabolism of liver cells (hepatic: silimar, legal, hepatosis and others), 4) promote neutralization of ammonia in the liver and muscles (L-ornithine, L-aspartate), 5) binding of endogenous neurotoxins in the blood (sodium benzoate, phenylacetate), 6) detoxifying infusion therapy (W. Sherlock diseases of the liver and biliary tract", Chapter 7, "Hepatic encephalopathy", S. 100-119, Moscow, GEOTAR MEDICINE, 1999; Naginsky M. Y., Podymova S. D., “HEPA-Merz (ornithine-aspartate) in the treatment of hepatic encephalopathy in liver cirrhosis”, Russian journal of gastroenterology, Hepatology, Coloproctology, 1999, No. 1, I. IX, S. 53-58). The choice of therapeutic management of PE is currently empirically excluding leading in each case the mechanism for the development of PE (e.g., increased formation of toxic metabolites in the gut, enhancing their absorption, strengthening reset them portosystemic shunts, reducing disposal of toxic metabolites by the liver and so on), as well as otsutstvovaly data does not exceed 60-70%.

We believe that the study of the content CGC directly to the site of their synthesis and absorption of metabolites in other biosubstrate (e.g., in serum) would allow for a differentiated approach to the treatment and individually to choose the optimal therapeutic effect. This problem has not previously been solved.

The present invention is to provide a method of differential treatment of hepatic encephalopathy, widespread in therapy, gastroenterology, Hepatology practice with high accuracy verification etiopathogenetic mechanisms of PE in each case with low cost and a significant reduction in time to produce results, allowing time to start pathogenetic therapy of PE accounting leading etiopathogenetic link and increase the effectiveness of the treatment.

The invention is based on the identified logical fact, representing in fact the technical result consists in the fact that the concentration and quality of the short-chain fatty acids (KJC) (short-chain fatty kierunkowy, C5-valeric, ISO-isocaproate and C6-Caproic acid) fraction of C2-C6with isomers in serum and feces define the basic types of changes that require the appointment of certain pharmaceuticals and determine the effectiveness of treatment:

- When changing the qualitative composition CZK characterized by a moderate increase in the percentage of propionic and butyric acids and moderate decrease in the percentage of acetic acid in the total content C2-C4; moderate increases the amount of higher acids containing more than 3 carbon atoms with isomers (C3-C6) and the amount of isocyclic (ISO+ISO+ISO), a moderate increase in the percentage of separately isovalerianic acid (ISOs) in the total content C2-C6 serum and a significant increase in the percentage of the amount of the higher acids containing more than 3 carbon atoms with isomers (C3-C6)amount isocyclic (ISO+ ISO+ISO) and separately isovalerianic acid (ISOs) in the total content of C2-C6, when compared with normal p<0.05) in Calais.

The increase in the percentage of propionic acid (C3) is in the range from 8.1 to 8.9%; butyric acid (C4) from 5.6 to 6.0% is VNA amount of higher acids, containing more than 3 carbon atoms with isomers (C3-C6) from 24,9 to 26.9%, the amount of isocyclic (ISO+ISO+ISO) from 10.9 to 12.5%, the increase of the percentage of separately isovalerianic acid (ISOs) from 4.8 to 6.2% in the total content C2-C6. At Calais there is an increase in the percentage of the amount of the higher acids containing more than 3 carbon atoms with isomers (C3-C6) ranging from 52.7% to 56,7%, the amount of isocyclic (ISO+ISO+ISO) from 10.3 to 11.9% separately isovalerianic acid (ISOs) from 8.5 to 9.3% in the total content C2-C6 when compared with normal levels (p<0,05). In this case, the most effective therapy with the drug Duphalac (duphalac - nevsasyvaemye and namerevajushijsja in the small intestine synthetic disaccharide lactulose (4-O- -D-galactopyranosyl-D-fructose) from the group of synthetic polysaccharides (lactulose).

When you change the qualitative composition CZK characterized by a significant increase in the percentage of propionic (C3) and butyric (C4) acids, a significant decrease in the percentage of acetic acid (C2) in the total content C2-C4; a significant increase in the amount of higher acids containing more than 3 carbon atoms with isomers (C3-C6) and the amount of isocyclic (ISO + ISO + from the Argania C2-C6 serum; a significant increase in the percentage of the amount of the higher acids containing more than 3 carbon atoms with isomers (C3-C6), the amount of isocyclic (ISO+ISO+ISO) and separately isovalerianic acid (ISOs) in the total content C2-C6 in Calais (p<0.05 with respect to normal).

The increase in the percentage of propionic acid (C3) is in the range from 8.7 to 9.5 per cent; butyric acid (C4) from 6.0 to 6.4% decrease in the percentage of acetic acid (C2) from 85,3 to 84.3 percent in the total content C2-C4; increased levels higher amount of acids containing more than 3 carbon atoms with isomers (C3-C6) from 24.7 to 26.7%, amount of isocyclic (ISO+ISO+ISO) from 10.7 to 12.3%, and the increase of the percentage of separately isovalerianic acid (ISOs) from 4.6 to 6.0% in the total content C2-C6 serum. In Calais - increasing percentage of the amount of the higher acids containing more than 3 carbon atoms with isomers (C3-C6) is in the range from 51,9 to 55.9%, the amount of isocyclic (ISO+ISO+ISO) from 9.6 to 10.1% and separately isovalerianic acid (ISOs) from 8.1 to 8.9% in the total content C2-C6 (p<0.05 with respect to normal). In patients with baseline defined 2 type of change profiles KIK the most effective was the purpose of EET 2 phases: 1 phase - sorption of toxic metabolites in the gut, phase 2 - hepatoprotective activity) from the group of hepatoprotectors, with a combined effect: sorption and hepatoprotective;

- When changing the qualitative composition CZK characterized by a significant increase in the percentage of propionic (C3) and butyric (C4) acids and significant decrease in the percentage of acetic acid (C2) in the total content C2-C4; a significant increase of the percentage of the amount of the higher acids (C3-C6) containing more than 3 carbon atoms with the isomers, the amount of isocyclic (ISO + ISO + ISO), and a significant increase in the percentage of separately isovalerianic acid (ISOs) in the total content C2-C6 serum; with a slight increase in the percentage of the amount of the higher acids containing more than 3 carbon atoms with isomers (C3-C6), a slight increase of the percentage of the amount of isocyclic (ISO + ISO + ISO) and separately isovalerianic acid (ISOs) in the total content C2-C6 in Calais (p<0.05 with respect to normal).

The increase in the percentage of propionic acid (C3) is in the range from 8.4 to 9.2 percent; butyric acid (C4) from 6.2 the levels of the sum of the higher acids (C3-C6), containing more than 3 carbon atoms with isomers from 25.4 to 26.8%, the amount of isocyclic (ISO+ISO+ ISO) from 11.3 to 12.6%, the increase of the percentage of separately isovalerianic acid (ISOs) from 5.6 to 6.6% in the total content C2-C6. At Calais there is an increase in the percentage of the amount of the higher acids containing more than 3 carbon atoms with isomers (C3-C6) ranging from 45,3 to 49.1%, increase of the percentage of the amount of isocyclic (ISO+ISO+ISO) from 7.4 to 8.6%, isovalerianic acid (ISOs) from 5.3 to 6.7% in the total content C2-C6 (p<0.05 with respect to normal). When the identified source 3 type of changes in the composition KIK the most effective was the purpose hepatoprotective funds in high therapeutic doses (silimar, cars) (cars, silimar - drugs group of hepatoprotectors, causing physico-chemical stabilization of cell membranes of hepatocytes, has a stimulating effect on the biosynthesis of structural elements of cells, antioxidant and antitoxic action (Reference Vidal Moscow, Attraversare, 2002)).

- When changing the qualitative composition CZK characterized by a slight increase in the percentage of propionic (C3) and butyric (C4) acids and ntnm the increase of the percentage of the amount of the higher acids, containing more than 3 carbon atoms with isomers (C3-C6), the amount of isocyclic (ISO + ISO + ISO) and a slight increase of the percentage of separately isovalerianic acid (ISOs) in the total content C2-C6 serum; a slight increase in the percentage amounts of the higher acids containing more than 3 carbon atoms with isomers (C3-C6), a slight increase of the percentage of the amount of isocyclic (ISO+ISO+ISO) and separately isovalerianic acid (ISOs) in the total content C2-C6 in Calais (p<0.05 with respect to normal).

- The increase in the percentage of propionic acid (C3) is in the range from 8.2 to 9.0%; butyric acid (C4) from 5.7 to 6.1% and a decrease in the percentage of acetic acid (C2) from 86,7 up to 85.7% in the total content C2-C4; increased levels higher amount of acids containing more than 3 carbon atoms with isomers (C3-C6) by 23.5 to 24.9%, the amount of isocyclic (ISO + ISO + ISO) from 9.3 to 10.5%, the increase of the percentage of separately isovalerianic acid (ISOs) from 4.6 to 5.6% in the total content C2-C6. In Calais - increasing percentage of the amount of the higher acids containing more than 3 carbon atoms with isomers (C3-C6), is in the range from 45,2 Oh acid (ISOs) from 5.2 to 5.8% in the total content C2-C6 (p<0.05 with respect to normal). When the identified source type 4 changes in the composition KIK the most effective was the purpose of L-ornithine, L-aspartate (HEPA-Merz), from a group of drugs that act on the stimulation of neutralization of ammonia in the liver and muscles, sodium benzoate, phenylacetate, from a group of drugs binding NH3in the blood and/or sodium benzoate, phenylacetate.

These changes in the qualitative composition CZK in serum and feces are evaluated in the aggregate.

Normal serum indicators of the relative content of acetic range from 89,6% to 90.8%, propionic from 6.9% to 7.3% and butyric acid from 2.5% to 2.9% in the total relative content2-C4; the percentage amount of the higher acids containing more than 3 carbon atoms with isomers (C3-C6), from 15.2 to 16.4%, the percentage amount of isocyclic (ISO+ISO+ISO) from 3.3 to 4.7%, the share of isovalerianic acid is 1.7-2.1% in the total content of C2-C6. In Calais - indicators percentage amount of the higher acids containing more than 3 carbon atoms with isomers (C3-C6), range from 42,1 to 45.1%, the percentage amount of isocyclic (ISO+ISO+ISO) from 6.4 to 7.2%, the share of isovalerianic acid sostav the changes in the qualitative composition KIK and treatment of PE drugs specified pharmgroup allows you to use these indicators CZK as predictors of response to therapy. The result that can be achieved with the implementation of the method is to achieve the most effective therapy for PE.

In our work studies were performed in 230 patients with chronic hepatitis b cirrhosis of the liver with the syndrome of hepatic encephalopathy at the time of treatment with drugs of different pharmgroup evaluating the effectiveness of treatment, a retrospective analysis of quantitative and qualitative content KIK with isomers, depending on the effectiveness of treatment, assessing the effectiveness of treatment when prescribing pharmaceuticals depending on the spectrum CZK.

The method is as follows.

Patient for differential selection of pharmaceuticals for the treatment of PE produced a blood from a vein and collection of faeces. The blood is centrifuged to obtain serum. Serum and Kale to explore quantitative and qualitative content of short-chain fatty acids determine the relative content of higher acids containing more than 3 carbon atoms with isomers (C3-C6), the total content of satisloh, the relative content of isovalerianic acid in the total content C2-C6. In addition, serum determine the relative content the project make a conclusion about the type of changes in the qualitative composition KIK and base the choice they (as described above).

Below are examples of differential treatment of hepatic encephalopathy, confirming the possibility of using this method, which is not limited to them.

Example 1

Patient A., aged 52. Diagnosis: Chronic hepatitis nutritional etiology, moderate activity in the stage of cirrhosis. Class child-Pugh. Portal hypertension stage 2 (spleen, varicose veins of the esophagus 2 tbsp.). Hepatic cell failure (hypolipemic and hypocholesterolemia). Hepatic encephalopathy stage 1.

Upon receipt complained of weakness, fatigue, decreased performance, heaviness in the right hypochondrium, insomnia at night.

From the anamnesis it is known that sick since 1998, when a sudden jaundice was hospitalized in CIB No. 2 on suspicion of acting viral hepatitis. There the diagnosis was made and was first diagnosed with cirrhosis of the liver. Since that time, annually held stationary examination and treatment, irregularly takes hepatoprotective drugs, verospiron. Abusing alcohol.

At survey: the state is relatively satisfactory, the consciousness of ESNET., the abdomen is soft, painless, liver enlarged, edge rounded, sensitive to palpation, spleen not palpated, physiological functions in normal, meningeal signs, FMN no abnormalities, tremor+.

The results of the survey: 1) complete blood count: HB - 134 g/l, er. - 4,63×10, leukocytes - 6,4×10, five - 3, SJ - 66, E. - 1, l - 19, m - 10, platelet - 344×10, ESR - 10 mm/h; 2) urinalysis: St.-yellow, full transparency, 1012, protein and glucose is absent, an epithelium flat - 1-3, leukocytes - 2-4 in the field of view; 3) in the biochemical analysis of blood there is a decrease in albumin levels (32,0 g/l) and total cholesterol (3.6 mmol/l) and increasing concentrations of ALT (112,5 u/l), ACT (154,8 u/l), GGT (308,7 u/l), the remaining parameters within normal values; 4) ECG: sinus rhythm, right, HR=76 min, EOS - horizontal position, diffuse changes of a myocardium; 5) chest x-ray: lung fields clear, the structural roots, sines free, the movable diaphragm, the heart and large vessels without features; 6) ultrasound of the abdominal organs, kidneys: conclusion: hepatomegaly due to the left lobe of the liver with diffuse changes of the liver, portal hypertension, splenomegaly; 7) esophagogastroduodenal and, superficial gastritis, Bulut; 8) psychometric testing: test connection numbers of Ratana patient completed for 57 seconds (taking into account the age factor), which corresponds to stage 1 of PSE.

The study CZK in peripheral blood serum: increased percentage of propionic acid (C3) of 8.4%; butyric acid (C4) - 5.7% and a decrease in the percentage of acetic acid (C2) - 85.9% in the total content C2-C4; increased levels higher amount of acids containing more than 3 carbon atoms with isomers (C3-C6) - 25.9 per cent, of the amount of isocyclic (ISO+ISO+ISO) of 11.7%, and the increase of the percentage of separately isovalerianic acid (ISOs) 5,5% the total content C2-C6. The study CZK in Calais: there is an increase in the percentage of the amount of the higher acids containing more than 3 carbon atoms with isomers (C3-C6), 54.7 per cent, of the amount of isocyclic (ISO+ISO+ISO) 11.1% and separately isovalerianic acid (ISOs) 8.9% in the total content C2-C6.

In the Department of gastroenterology held effective treatment using hepatoprotective (Silimar 140 mg/day), enzymatic means, blockers aldosterone with the inclusion in the scheme of duphalac (lactulose) 60 ml/day.

The efficacy results of study content CZK in serum and feces. The results of the study CZK in serum after treatment: there is a decrease in the percentage of propionic and butyric acids - 7.8% and 3.6% respectively and the increase of the percentage of acetic acid - 88,6% in the total content C2-C4; decrease the percentage of the amount of the higher acids containing more than 3 carbon atoms with isomers (C3-C6), 17.3%, amount of isocyclic (ISO+ISO+ISO) of 6.4%, and reduced the percentage of separately isovalerianic acid (ISOs) of 2.7% in total content C2-C6. The study CZK in the feces after treatment: the authors observed a decrease of the percentage of the amount of the higher acids containing more than 3 carbon atoms with isomers (C3-C6), 49.8% and the amount of isocyclic (ISO+ISO+ISO) 7.3% and separately isovalerianic acid (ISOs) of 4.7% in the total content C2-C6.

Example 2

Patient P., 33 years. Diagnosis: Chronic hepatitis nutritional etiology, moderate activity in the stage of cirrhosis. Class child-Pugh. Portal hypertension stage 2 (spleen, varicose expanded veins of an esophagus 1 tbsp.). Hepatic cell failure (hypoalbuminemia). Hepatic encephalopathy stage 1. Chronic nutritional pancreatitis outside of the limits at night, heartburn, weakness.

From the anamnesis it is known that the patient long-term abuse of alcohol in large quantities. For the first time similar complaints appeared in 2000, but he was tested and was not treated. The doctor asked in the fall of 2001, when I first was diagnosed with cirrhosis of the liver. Twice a year is held stationary examination and treatment, outpatient not treated.

At survey: the state is relatively satisfactory, clear consciousness, no edema, vesicular breathing, wheezing no heart tones are muffled, rhythmic, pulse rate=82 min, BP=130/80 mm RT.art., the abdomen is soft, painless, liver enlarged, edge rounded, dense, sensitive to palpation, spleen not palpated, physiological functions in normal, meningeal signs, FMN no abnormalities, tremor+.

The results of the survey: 1) complete blood count: HB - 123 g/l, er. - 3,84×10, leukocytes - 7,1×10, five - 2, SJ - 65, BC - 1, HP - 21, m - 10, platelet - 337×10, ESR - 12 mm/h; 2) urinalysis: St.-yellow, transparency, incomplete, 1009, protein and glucose is absent, the flat epithelium - a single in sight, leukocytes - 2-4 in the field of view; 3) in the biochemical analysis of blood marked decrease in the level of albumin (33,0 g/l), and; ) ECG: sinus rhythm, right, HR=76 min, EOS - vertical position, moderate signs of left ventricular hypertrophy, diffuse changes of a myocardium; 5) chest x-ray: lung fields clear, the structural roots, sines free, the movable diaphragm, the heart and large vessels without features; 6) ultrasound of the abdominal organs, kidneys: conclusion: hepatomegaly due to the left lobe of the liver with diffuse changes of the liver, portal hypertension, splenomegaly, chronic pancreatitis; 7) esophagogastroduodenoscopy: conclusion: varicose expanded veins of an esophagus 1 tbsp., peptic esophagitis, cardia insufficiency, superficial gastritis; 8) psychometric testing: test connection numbers of Ratana patient was performed for 48 seconds, which corresponds to stage 1 of PSE.

The study CZK in peripheral blood serum: there has been a significant increase in the percentage of propionic acid (C3) is 9.1%; butyric acid (C4) is 6.2% and decreasing the percentage of acetic acid (C2) - 84.7% of the total content C2-C4; increased levels higher amount of acids containing more than 3 carbon atoms with isomers (C3-C6) - 25.7%, and the amount of isocyclic (ISO+ISO+ISO) - 11,5%, and so the Study CZK in Calais: there is an increase in the percentage of the amount of the higher acids, containing more than 3 carbon atoms with isomers (C3-C6) - 53.9%, of the amount of isocyclic (ISO+ISO+ISO) - 9.8% and separately isovalerianic acid (ISOs) - 8.5% in the total content C2-C6.

In the Department of gastroenterology held effective treatment using Hepatosan (0.8 g/day), enzymatic means, blockers aldosterone.

The effectiveness of therapy in relation to PSE confirmed by clinical data and results of psychometric testing and the results of the study content CZK in serum and feces. The study CZK in peripheral blood serum after treatment: there is a significant decrease in the percentage of propionic acid (C3) was 7.2%; butyric acid (C4) - 3.2% and the increase of the percentage of acetic acid (C2) - 89.6% of the total content C2-C4; decrease the percentage of the amount higher, containing more than 3 carbon atoms with the isomers of the acids (C3-C6) - 17,5%, the amount of isocyclic (ISO+ISO+ISO) is 6.2%, and reduced the percentage of separately isovalerianic acid (ISOs) is 2.6% the total content C2-C6. The study CZK in the feces after treatment: there is an increase in the percentage of the amount of the higher acids containing more than 3 atoms of carbon is isovalerianic acid (ISOs) - 9.3% in the total content C2-C6.

Example 3

Patient S., 46 years old. Diagnosis: chronic hepatitis nutritional etiology, moderate activity in the stage of cirrhosis. Class child-Pugh. Portal hypertension stage 2 (spleen, varicose veins of the esophagus 2 tbsp.). Hepatic cell failure (hypolipemic and hypocholesterolemia). Hepatic encephalopathy stage 1.

Upon receipt complained of decreased performance, weakness, fatigue, discomfort in the right hypochondrium, drowsiness.

From the anamnesis it is known that for 4 years seeing a gastroenterologist about liver cirrhosis, chronic pancreatitis. During this time, twice held stationary examination and treatment, however, supportive treatment is not received. In recent weeks, notes the deterioration of health. Abusing alcohol.

At survey: the state closer to a satisfactory clear consciousness, pastos stop, vesicular breathing, wheezing no heart tones are muffled, rhythmic, HR=86 min, BP=110/60 mm RT.art., the abdomen is soft, painless, liver enlarged, edge rounded, sensitive when PAL is sociology, tremor +.

The results of the survey: 1) complete blood count: HB - 112 g/l, er. - 3,47×10, leukocytes - 5,9×10, five - 1, SJ - 63, BC - 1, HP - 26, m - 9, platelet - 335×10, ESR - 15 mm/h; 2) a General analysis of urine: dark yellow, full transparency, 1014, protein and glucose is absent, an epithelium flat - 3-4, leukocytes - 4-6 field of view, mucus+; 3) in the biochemical analysis of blood there is a decrease in albumin levels (30.0 g/l) and total cholesterol (3.2 mmol/l) and increasing concentrations of ALT (97,3 u/l), ACT (167,8 u/l), GGT (317,4 u/l), the remaining parameters within normal values; 4) ECG: sinus rhythm, right, HR=88 per minute, EOS - horizontal position, diffuse changes of a myocardium; 5) chest x-ray: lung fields clear, the structural roots, sines free, the movable diaphragm, the heart and large vessels without features; 6) ultrasound of the abdominal organs, kidneys: conclusion: hepatomegaly with diffuse changes of the liver, portal hypertension, splenomegaly; 7) esophagogastroduodenoscopy: conclusion: varicose expanded veins of an esophagus 2 tbsp., superficial gastritis; 8) psychometric testing: test connection numbers of Ratana the patient has performed in 47 seconds, which corresponds to stage 1 PE.

Research (C3) - 8,6%; butyric acid (C4) - 6.3% and a decrease in the percentage of acetic acid (C2) - 85,1% in the total content C2-C4; increased levels higher amount of acids containing more than 3 carbon atoms with isomers (C3-C6) - 26.1 per cent, of the amount of isocyclic (ISO+ISO+ISO) - 11.9% and also increase of the percentage of separately isovalerianic acid (ISOs) - 6.1% in the total content C2-C6. The study CZK in Calais: a slight increase in the percentage of the amount of the higher acids containing more than 3 carbon atoms with isomers (C3-C6) - 47,1%, a slight increase of the percentage of the amount of isocyclic (ISO+ISO+ISO) - 7.4%, and also separately isovalerianic acid (ISOs) - 5.3% in the total content C2-C6.

In the Department of gastroenterology held basic therapy using hepatoprotectors (Silimar 420 mg/day), blockers aldosterone, enzymatic means, detoxification activities and cleansing enemas. After treatment, the positive dynamics, confirmed by clinical data and results of psychometric testing and the results of the study content CZK in serum and feces. The study CZK in peripheral blood serum after treatment: OIE percentage of acetic acid (C2) - 89.4% of the total content C2-C4; lowering the percentage of the amount of the higher acids containing more than 3 carbon atoms with isomers (C3-C6) - 17.4 per cent, the amount of isocyclic (ISO+ISO+ISO) is 6.7%, and reduced the percentage of separately isovalerianic acid (ISOs) - 2.7% in the total content C2-C6. The study CZK in the feces after treatment: there is a decrease in the percentage of the amount of the higher acids containing more than 3 carbon atoms with isomers (C3-C6) - 46,3%, a slight decrease of the percentage of the amount of isocyclic (ISO+ISO+ISO) - 6.8%, and also separately isovalerianic acid (ISOs) - 4.7% in the total content C2-C6.

According to our data, the effectiveness of the treatment of PE in a traditional choice of regimens was 72±4% in the subgroup of patients with the use of various pharmaceuticals. When differentiated treatment of PE, based on the assessment of changes in quality content CZK in serum and feces, the treatment efficiency was 89±3% (p<0,05).

Thus, the proposed method of differential treatment hepatic encephalopathy allows to achieve high accuracy verification etiopathogenetic mechanisms of PE in each case, has the bottom is but to start pathogenetic therapy of PE accounting leading etiopathogenetic link and increase the effectiveness of the treatment.

The method of selection of pharmaceuticals for the treatment of hepatic encephalopathy, namely, that explore the quantitative composition of short-chain fatty acid fraction C2-C6 with isomers in serum, feces, and when the change of the quantitative composition CZK characterized by the increase of the percentage of propionic acid in the range from 8.1 to 8.9%, butyric acid from 5.6 to 6.0% and the decline in the percentage of acetic acid from 86,4 to 85.4% in the total content C2-C4, increase the amount of higher acid containing 3-6 carbon atoms with isomers, from 24,9 to 26.9%, the amount of isocyclic ISO+ISO+ISO from 10.9 to 12.5% and the increase of the percentage of isovalerianic acid from 4.8 to 6.2% in the total content C2-C6 serum; increase the percentage of higher amount of acid containing 3-6 carbon atoms with isomers, ranging from 52.7 to 56.7%, the amount of isocyclic ISO+ISO+ISO from 10.3 to 11.9 per cent and the percentage of isovalerianic acid from 8.5 to 9.3% in the total content C2-C6 in Calais prescribed drugs lactulose; by changing the quantitative composition KIK, increasing the percentage of propionic acid from 8.7 to 9.5 per cent, butyric acid from 6.0 to 6.4% and reduced proh acids, containing 3-6 carbon atoms with isomers, from 24.7 to 26.7%, amount of isocyclic ISO+ISO+ISO from 10.7 to 12.3% and the increase of the percentage of isovalerianic acid from 4.6 to 6.0% in the total content C2-C6 serum; increase the percentage of higher amount of acid containing 3-6 carbon atoms with isomers, from 51,9 to 55.9%, the amount of isocyclic ISO+ISO+ISO from 9.6 to 10.1% and the percentage of isovalerianic acid from 8.1 to 8.9% the total content C2-C6 in Calais prescribe a drug from the group of hepatoprotectors, with a combined effect: sorption and hepatoprotective; by changing the quantitative composition CZK characterized by the increase of the percentage of propionic acid from 8.4 to 9.2%, and butyric acid from 6.2 to 6.6% and the decline in the percentage of acetic acid from 85,6 to 84,5% in the total content C2-C4, increase the amount of higher acid containing 3-6 carbon atoms with isomers, from 25.4 to 26.8%, the amount of isocyclic ISO+ISO+ISO from 11.3 to 12.6% and the increase of the percentage of isovalerianic acid from 5.6 to 6.6% in the total content C2-C6 serum; increase the percentage of higher amount of acid containing 3-6 carbon atoms with isomerate 5.3 to 6.7% in the total content C2-C6 in Calais appoint hepatoprotective funds in the maximum therapeutic doses; when the change of the quantitative composition CZK characterized by the increase of the percentage of propionic acid from 8.2 to 9.0%, butyric acid from 5.7 to 6.1% and a decrease in the percentage of acetic acid from 86,7 up to 85.7% in the total content C2-C4, increase the amount of higher acid containing 3-6 carbon atoms with isomers by 23.5 to 24.9%, the amount of isocyclic ISO+ISO+ISO from 9.3 to 10.5% and the increase of the percentage of isovalerianic acid from 4.6 to 5.6% in the total content C2-C6 serum; increase the percentage of higher amount of acid containing 3-6 carbon atoms with isomers, 45,2 to 46.3%, the amount of isocyclic ISO+ISO+ISO from 7.3 to 7.8% and the percentage of isovalerianic acid from 5.2 to 5.8% in the total content C2-C6 in Calais prescribed drugs that act on the stimulation of neutralization of ammonia in the liver and muscles, and/or drugs that bind NH3blood.



 

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FIELD: medicine, hepatology.

SUBSTANCE: one should detect the level of hepato-specific enzymes (HSE) in blood plasma, such as: urokinase (UK), histidase (HIS), fructose-1-phosphataldolase (F-1-P), serine dehydratase (L-SD), threonine dehydratase (L-TD) and products of lipid peroxidation (LP), such as: dienic conjugates (DC), malonic dialdehyde (MDA). Moreover, one should detect the state of inspecific immunity parameters, such as: immunoregulatory index (IRI) as the ratio of T-helpers and T-suppressors, circulating immune complexes (CIC). Additionally, one should evaluate the state of regional circulation by applying rheohepatography (RHG), the system of microhemocirculation with the help of conjunctival biomicroscopy (CB) to detect intravascular index (II). In case of increased UK, HIS levels up to 0.5 mcM/ml/h, F-1-P, L-SD, L-Td, LP products, CIC by 1.5 times, higher IRI up to 2 at the norm being 1.0-1.5, altered values of regional circulation, increased II up to 2 points at the norm being 1 point, not more one should diagnose light degree of process flow. At increased level of UK, HIS up to 0.75 mcM/ml/h, F-1-P, L-SD, L-TD, LP products, CIC by 1.5-2 times, increased IRI up to 2.5, altered values of regional circulation, increased II up to 3-4 points one should diagnose average degree of process flow. At increased level of UK, HIS being above 0.75 mcM/ml/h, F-1-P, L-SD, L-TD, LP products, CIC by 2 and more times, increased IRI being above 2.5, altered values of regional circulation, increased II up to 5 points and more one should diagnose severe degree of process flow.

EFFECT: higher accuracy of diagnostics.

3 ex

FIELD: medicine, infectology, hepatology.

SUBSTANCE: in hepatic bioptate one should detect products of lipid peroxidation (LP), such as: dienic conjugates (DC), activity of antioxidant enzymes, such as: catalase (CAT)and superoxide dismutase (SOD). One should calculate by the following formula: C = DC/(SOD x CAT)x100, where DC - the content of dienic conjugates, SOD - activity of superoxide dismutase, CAT - activity of catalase. At coefficient (C) values being above 65 one should predict high possibility for appearance of cirrhosis, at 46-645 - moderate possibility and at 14-45 -low possibility for appearance of cirrhosis.

EFFECT: higher accuracy of prediction.

3 ex

FIELD: medicine, clinical toxicology.

SUBSTANCE: at patient's hospitalization one should gather the data of clinical and laboratory values: on the type of chemical substance, patient's age, data of clinical survey and laboratory values: body temperature, the presence or absence of dysphonia, oliguria being below 30 ml/h, hemoglobinuria, erythrocytic hemolysis, exotoxic shock, glucose level in blood, fibrinogen and creatinine concentration in blood serum, general bilirubin, prothrombin index (PTI), Ph-plasma, the state of blood clotting system. The state of every sign should be evaluated in points to be then summed up and at exceeding the sum of points being above "+20" one should predict unfavorable result. At the sum of "-13" prediction should be stated upon as favorable and at "-13" up to "+20" - prediction is considered to be doubtful.

EFFECT: higher accuracy of prediction.

2 ex, 3 tbl

FIELD: medicine, juvenile clinical nephrology.

SUBSTANCE: disease duration in case of obstructive pyelonephritis should be detected by two ways: either by detecting the value of NADPH-diaphorase activity, as the marker of nitroxide synthase activity in different renal department and comparing it to established norm, or by detecting clinico-laboratory values, such as: hemoglobin, leukocytes, eosinophils, urea, beta-lipoproteides, lymphocytes, neutrophils, the level of glomerular filtration, that of canalicular reabsorption, urinary specific weight, daily excretion of oxalates, arterial pressure, and estimating their deviation against average statistical values by taking into account a child's age.

EFFECT: higher efficiency of detection.

7 dwg, 1 ex, 6 tbl

FIELD: clinical medicine, pulmonology.

SUBSTANCE: one should carry out complex estimation of interleukin-1β) concentration in blood, saliva, bronchoalveolar liquid. Moreover, one should detect distribution coefficient (DC) for IL-1β as the ratio of IL-1β blood content to IL-1β salivary content. At increased IL-1β blood content by 10 times and more, by 2 times in saliva, unchanged level of bronchoalveolar IL-1β, at DC for IL-1β being above 1.0 one should predict bronchial obstruction. The method enables to conduct diagnostics of the above-mentioned disease at its earlier stages.

EFFECT: higher efficiency of prediction.

2 tbl

FIELD: medicine, diagnostics.

SUBSTANCE: the present innovation deals with genetic trials, with diagnostic field of oncological diseases due to analyzing DNA by altered status of gene methylation that take part in intracellular regulation of division, differentiating, apoptosis and detoxication processes. One should measure the status of methylation in three genes: p16, E-cadherine and GSTP1 in any human biological samples taken out of blood plasma, urine, lymph nodes, tumor tissue, inter-tissue liquid, ascitic liquid, blood cells and buccal epithelium and other; one should analyze DNA in which modified genes of tumor origin or their components are present that contain defective genes, moreover, analysis should be performed due to extracting and purifying DNA out of biological samples followed by bisulfite treatment of this DNA for modifying unprotected cytosine foundations at keeping 5-methyl cytosine being a protected cytosine foundation followed by PCR assay of bisulfite-treated and bisulfite-untreated genes under investigation and at detecting alterations obtained according to electrophoretic result of PCR amplificates, due to detecting the difference in the number and electrophoretic mobility of corresponding fractions at comparing with control methylated and unmethylated samples containing normal and hypermethylated forms of genes one should diagnose oncological diseases. The method provides higher reliability in detecting tumors, detection of remained tumor cells after operation.

EFFECT: higher efficiency of therapy.

1 cl, 3 dwg, 4 ex

FIELD: medicine, gastroenterology.

SUBSTANCE: one should carry out diagnostic studying, moreover, on the 5th -6th d against the onset of exacerbation in case of gastric and duodenal ulcerous disease one should detect the content serotonin, histamine and acetylcholine in blood, then during 2-3 wk one should conduct medicinal therapy to detect serotonin, histamine and acetylcholine level in blood again and at serotonin content being by 2-3 times above the norm, histamine - by 1.15-1.4 times above the norm and acetylcholine - by 20-45% being below the norm one should predict the flow of gastric and duodenal ulcerous disease as a non-scarring ulcer.

EFFECT: higher accuracy of prediction.

3 ex

FIELD: medicine.

SUBSTANCE: method involves taking blood from ulnar vein (systemic blood circulation) and from large vein of the injured extremity proximal with respect to lesion focus (regional blood circulation). Spontaneous NST-test value is determined and difference is calculated in systemic and regional blood circulation as regional-to-systemic difference. The difference value is used for predicting clinical course of pyo-inflammatory disease in extremities.

EFFECT: high accuracy of diagnosis.

4 cl, 2 tbl

FIELD: medicine, gastroenterology.

SUBSTANCE: one should introduce biologically active substance, moreover, in patient's blood serum one should detect the content of acetyl choline and choline esterase activity followed by 2-h-long intragastric pH-metry at loading with biologically active substance as warm 40-45%-honey water solution at 35-40 C, and at increased content of acetyl choline being above 1.0 mM/l, choline esterase being above 0.5 mM/l/30 min and pH level being 6.0-6.9 it is possible to consider apitherapy to be useful for treating ulcerous duodenal disease.

EFFECT: higher efficiency and accuracy of detection.

3 ex

FIELD: medicine, gastroenterology.

SUBSTANCE: it has been suggested a new method to detect pharmacological sensitivity to preparations as acidosuppressors. After the intake of the preparation a patient should undergo fibrogastroduodenoscopy 3 h later, then, through endoscopic catheter one should introduce 0.3%-Congo red solution intragastrically and the test is considered to be positive at keeping red color that indicates good sensitivity to the given preparation, and in case of dark-blue or black color the test is considered to be negative that indicates resistance to this preparation. The suggested innovation widens the number of diagnostic techniques of mentioned indication.

EFFECT: higher efficiency of diagnostics.

2 ex

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