Method for prediction of clinical course of yersiniosis in children

FIELD: medicine.

SUBSTANCE: initial (3 to 12 day) assessment of clinical symptoms of disease (fever and exanthema) is combined with measuring blood serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and specific antibodies (AT) and if observing: - fever response for less than 2 days, exanthema duration for less than 1.5 days, the CRP value less than 7.5 mg/l, ESR less than 15 mm/hour; the IFN-γ level less than 75 pg/ml, circulating immune complex 0.115 optical density units and lower, and specific antibody production more than 8.32 log2, a chronic clinical course of yersiniosis is predicted; - fever response for more than 12 days, exanthema duration for more than 3 days, the CRP value more than 15 mg/l, ESR more than 30 mm/hour; the IFN-γ level more than 150 pg/ml, circulating immune complex 0.130 optical density units and higher, specific antibody production less than 7.32 log2, a severe yersiniosis with associating organ lesions is predicted; - fever response for more than 12 days, exanthema duration for more than 9 days, the CRP value more than 5 mg/l, ESR more than 50 mm/hour; the IFN-γ level less than 150 pg/ml, circulating immune complex 0.250 optical density units and higher, and specific antibody production more than 9.32 log2, clinical outcome of yersiniosis in a systemic disease is predicted.

EFFECT: prevention of a chronic and prolonged clinical course of the disease.

3 tbl, 3 ex

 

The invention relates to medicine, in particular the prognosis of infectious diseases, and in particular to methods of predicting the course of yersiniosis infection in children.

Yersinia infection (AI) or yersiniosis unite diseases caused Y.pseudotuberculosis and pathogenic representatives of Y.enterocolitica. The problem of yersiniosis is relevant in connection with disease, polymorphism of the clinical picture, frequency, chronicity and recurrence of infection from 3-11% to 55%. In the Russian Federation in recent years were registered of 5.92-7.07 cases flow yersiniosis infection, in particular pseudotuberculosis (APC) and intestinal yersiniosis (CI) per 100 thousand population, with more than 75% of children under the age of 14 years, there are still outbreaks in groups of children.

AI is characterized by a circular current, which can disrupt the development of the protracted course and recurrence, as determined by the biological properties of the pathogen, with antiparasitary stability, and features of immune reactivity.

For acute course of yersiniosis characterized by significant disease duration (up to 4-8 weeks) despite ongoing therapy, and when nonsmooth course of developing the exacerbation or relapse with disease duration from 3 to 6 months, which requires about what edenia long courses of treatment. It should be emphasized that the yersiniosis are characterized by lesions of various organs and body systems, ranging from abdominal pain syndrome, diarrhea, and exanthema, to hepatitis, arthritis and meningitis. The greatest difficulty of predicting outcomes and differential diagnosis are marked with nonsmooth period of yersiniosis, as these infections can be a trigger system or malignant diseases.

Polymorphism of the clinical picture of yersiniosis, palindrome variants infection, frequent exacerbations and tendency to recurrence (clinical course), chronicity of infection, and age characteristics of the child's body substantially hinder the timely and correct diagnosis and conduct adequate therapy of the disease [Beniowa S.N. et al., 2002; Bockemuhl J., 2004; Uchaikin V.F. et al., 2005; Chesnokova M.V., 2005; Chan, V.L., 2006; UMUC N, 2007].

At the present stage, much attention is paid to the study of pathogenesis yersiniosis infection [Malov I.V., 1998; Popova O.V., 2006; Kaverina J.V., 2008; Hoogkamp-Korstanje J.A., 1996; Kirveskari J. et al.,1999; Ruck-deschel K. et al., 1998; Andersson K. et al., 1999; T. Yao et al., 1999; Ebringer, A., Wilson, C., 2000; N. Sauvonnet et al., 2002; Silva E.E., 2003; De Boer E. et al., 2008], therefore, remain poorly studied immunological causes uneven flow of yersiniosis. The results do not create a single CT is ins causes of adverse clinical outcome and contradictory. Still not given full immunological characteristics of different variants of the course and outcomes of yersiniosis, not studied the factors affecting the nature of the immune response, there are no clinical and laboratory criteria indicating the possible development of complications of the disease.

Currently of particular concern for clinicians cause adverse effects yersiniosis infection, in particular chronization and the formation of immunopathological syndromes with outcome in systemic autoimmune process [Smirnov A.V., 2005; Uchaikin V.F. et al., 2005; Gazenko A.A., 2006; A. Saebo et al., 1994; Ackermann C. et al., 1997; Granfors K. et al., 1998; Ebringer, A., Wilson, C., 2000; Spieper J. et al., 2002; Jalava K. et al., 2006; O'connor S.M. et al., 2006], therefore, the prediction of outcome AI is relevant, especially in the acute phase of the disease when using correction causal and immunomodulatory therapy to prevent adverse outcomes.

There are several ways of predicting the course of yersiniosis in which the quality of the laboratory criteria of prediction are used, the T - and b-lymphocytes, completion of phagocytosis, the levels of immunoglobulins a and M (Popova O.V., Fomichev M.A., Gultyaev M.M. and other Th1/Th2 response in different types of flow yersiniosis infection // Medical immunology. - 2005. - Volume 7. No. 2-3. - S-121; Uchaikin V.F., Gordiets AV, Beniowa S.N. Yersini the PS in children // Publishing group GEOTAR-Media. - Moscow. - 2005. - S-77).

The disadvantage of this method is the possibility of forecasting the only form of the disease, and not the severity and duration of clinical symptoms; prognosis of exclusively intestinal yersiniosis, and only generalized and secondary focal forms of joint damage). In addition, to predict the variants of the disease should be long re-examination of patients in the dynamics of the disease in the acute phase and during the reverse development of symptoms. For example, completion of phagocytosis is necessary to study the dynamics of the disease, however, it is proved that the reduction of the absorption capacity of neutrophils does not affect the outcome of the disease. Thus, the presented methods do not provide accurate prediction of the disease.

The closest way of predicting the course of yersiniosis to the proposed method is used for prediction of the protracted nature of the current infection evaluation of immune status in the acute phase of the disease by determining the relative number of CD8+, CD20+, CD25+ and CD95+, levels of IgE, IFN-γ in the blood.

The use of this method allowed us to predict a protracted course yersiniosis infection already on the first survey (zeleznikow GF, Ivanov V.V., Vasjakina LI, Monakhov N.E. and other Immunological Crete the AI protracted course yersiniosis infection in children. Medical immunology. - 2001. Vol 3. No. 2. - S). However, this method was used only in patients with a prolonged course of the disease was based solely on laboratory criteria without taking into account the clinical picture in the initial stages and in the midst of illness, had a high cost, is not considered a reasonable criterion as the level protivoerosionnih antibodies (indicator-specific immune response, used for routine diagnosis of yersiniosis). Therefore, the described method does not provide the accuracy and availability forecasting yersiniosis.

To eliminate these drawbacks by using the method of the forecast of yersiniosis in children.

The technical result of this method is to improve the accuracy of prediction of the outcome of the disease through a comprehensive assessment of the clinical-laboratory indices in the decreed time.

This is achieved by the fact that in the known method, including assessment of laboratory performance: CIC (circulating immune complexes), interferon-γ (IFN-γ), according to the invention in children from 3 to 12 day of illness, assess the duration and severity of clinical symptoms: febrile reactions, exanthema and additionally determine the serum level of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), the products specification is specific antibodies (AT) and:

when febrile reactions less than 3 days duration exanthema less than 1.5 days, CRP less than 7.5 mg/l, the average sedimentation rate of less than 15 mm/h, the level of IFN-γ is less than 75 PG/ml, the CEC is not above 0,115 adepts and production of specific antibodies more 8,32 log2predict a chronic course of yersiniosis;

when febrile reactions over 12 days, the duration of exanthema more than 3 days, the CRP levels of more than 15 mg/l, the average sedimentation rate of more than 30 mm/hour, the level of IFN-γ than 150 PG/ml, CEC above 0,130 adepts and production of specific antibodies less 7,32 log2predict a severe course of yersiniosis with the development of organ lesions;

when febrile reactions over 12 days, the duration of exanthema over 9 days, the CRP levels of more than 7.5 mg/l, the rate ESR > 50 mm/h, the level of IFN-γ is less than 150 PG/ml, CEC above 0,250 adepts and production of specific antibodies more to 9.32 log2predict the transition yersiniosis in systemic disease.

The authors, doing professionally for many years the treatment of very severe forms of this infection in children, watched the cyclic period of three types of outcome. In each of these situations, watching the development of the clinical picture, laboratory analyzed the data and found that the chronicity of yersiniosis is formed with febrile reactions less than 3 days duration exanthema less than 1.5 days, CRP less than 7.5 the g/l, the average sedimentation rate of less than 15 mm/h, the level of IFN-γ is less than 75 PG/ml, the CEC is not above 0,115 adepts and production of specific antibodies more 8,32 log2;

severe course of yersiniosis with the development of organ injuries in febrile reactions more than 12 days characterized by duration exanthema more than 3 days, the CRP levels of more than 15 mg/l, the average sedimentation rate of more than 30 mm/hour; the level of IFN-γ than 150 PG/ml, CEC above 0,130 adepts and production of specific antibodies less 7,32 log2;

the transition yersiniosis in systemic disease in febrile reactions more than 12 days characterized by duration exanthema over 9 days, the CRP levels of more than 7.5 mg/l, the rate ESR > 50 mm/h, the level of IFN-γ is less than 150 PG/ml, CEC above 0,250 adepts and production of specific antibodies more to 9.32 log2.

These observations served as the basis for predicting outcomes when not yielded to the treatment of all forms of this disease.

The authors first discovered the appropriateness and effectiveness of the simultaneous estimation of the duration of the two leading clinical symptoms of yersiniosis (fever and exanthema) in the early stages of the disease (3 to day 12), proved the importance of these symptoms to predict the outcome of disease.

The authors proved the need for a joint assessment of clinical symptoms, laboratory parameters and specific antibodies in combination with what radoccia cytokines in forecasting of yersiniosis.

Considering the fact that yersiniosis are characterized by palindromes picture of the disease, the gradual accession of symptoms, the most difficult is to establish the form and severity of the disease.

The authors found that the most important symptoms and syndromes are formed from 3 to 12 day of illness. The authors carried out a comparative analysis of the clinical course and laboratory data at moderate forms and severe disease, a similar analysis was performed for the outcomes of yersiniosis in systemic disease (see table 1). Because the greatest difficulty of diagnosis observed in nonsmooth period of yersiniosis, when the clinical picture, regarded as yersiniosis may be a mask rheumatism, tuberculosis, systemic vasculitis, JUHA, leukemia, in addition, these infections can be a trigger system or malignant diseases, the authors have developed a method of prediction of outcome AI. In the available literature, the authors found no criteria for determining the transition infection in systemic pathology.

Table 1
The duration of clinical symptoms of yersiniosis in various forms of disease
The duration of the clinically the ski symptoms in days (M±m)For AI
Patients endured moderate form of the disease (comparison group) n=45Patients with severe and organ lesions n=35Patients with outcome AI in systemic disease n=12
Fever7,3±0,41,43±0,8#37,8±6,2*
Intoxication9,1±0,8917,1±1,36#41,3±7,7*
Exanthema4,4±0,778,4±1,34#34,8±8,1*
Arthralgic5,1±1,25,1±1,237,8±4,9*
Diarrhea4,6±0,36,1±0,4#5,7±1,2
Vomiting3,1±0,45,1±0,51#3,5±0,93
Abdominal pain5,0±0,69,7±1,33#6,76±0,33
Deposits in the oropharynx6,1±0,48,8±0,89,3±0,7#
The lymphadenopathy15,4±1,918,2±2,332,4±3,3*
Hepatomegaly8,8±0,713,8±0,6#29,8±4,7*
Splenomegaly5,4±0,89,8±1,3#16,2±0,95*
* reliable contrast to patients with moderate and severe forms of the disease with at least p<0,05
# reliable contrast to patients with moderate form of the disease with at least p<0,05

As follows from the presented data in table 1, the most informative are: the duration of febrile reactions, exanthema and arthralgia are the ones supporting diagnostic clinical criteria that can reliably predict the transition of yersiniosis in systemic disease and to predict the possibility of severe yersiniosis infection with organ damage. The authors evaluated the various symptoms of AI: the severity of INTOX the requirements, the nature of the rash, the type of febrile reactions, the number of affected joints, the development of parenchymatous hepatitis, etc., however, the authors found that the most significant and informative are the duration of febrile reactions, exanthema. While other clinical criteria (such as intoxication syndrome, lymphadenopathy, hepato - and splenomegaly, diarrhea etc), though they have significant differences in duration depending on the form of the disease, but do not allow to predict and severe disease, and outcome in systemic disease.

To predict a chronic course of the infection, the authors compared the disease and laboratory parameters of children with mild and moderate forms of the disease with outcomes in complete recovery with patient data, perencevich light and moderate forms of the disease, but later in 6-9 months formed the chronic course of yersiniosis.

Table 2
Clinical symptoms of AI in different clinical outcome
The duration of clinical symptoms in days (M±m)For AI
Patients endured Srednyaya the e form of the disease (comparison group) n=45 Patients with mild forms of AI (the comparison group) n=16Patients with the formation of chronic AI currents n=24
Fever7,3±0,45,3±0,82,7±0,3*
Intoxication9,1±0,894,1±0,361,97±0,4*
Exanthema4,4±0,775,0±1,341,8±0,15*
Arthralgia5,1±1,24,2±0,93,1±0,4
Diarrhea4,6±0,36,1±0,43,1±0,5
Vomiting3,1±0,42,7±0,371,5±0,23
Abdominal pain5,0±0,64,7±1,04,3±0,32
Deposits in the oropharynx6,1±0,43.3V±0,53,9±0,7#
Lymphoedema the Atiyah 15,4±1,912,2±3,116,4±4,1
Hepatomegaly8,8±0,74,8±0,69,3±2,7
Splenomegaly5,4±0,80,0±0,00,0±0,0
* reliable contrast to patients with moderate and severe forms of the disease with at least p<0,05
# reliable contrast to patients with moderate form of the disease with at least p<0,05

As can be seen from table 2, in the case of outcome AI in chronic infection, also only the duration of fever and exanthema allow a high degree of confidence to predict the outcomes of the acute phase of yersiniosis.

To improve the reliability of forecasting analyzed laboratory values, and emphasis was placed on such indicators as the level of CRP, ESR, CEC, products protivoerosionnih antibodies (table 3). Patients were examined in comparable terms.

Table 3
Laboratory to which iterei current TFP and CI in children 3-12 day disease (8,9±1.4 days)
Indicator (M±M)For AI
Patients with the formation of chronic AI currents n=24Patients with severe and organ lesions n=35Patients with outcome AI in systemic disease n=12
Examination periods (days of illness)6,7±0,928,3±1,129,1±1,3
CRP (mg/l)3,2±0,418,5±0,812,1±1,4#
ESR (mm/hour)10,3±2,138,8±3,762,2±1,2*
The level of specific antibodies (log2)10,12±1,15,67±1,711,46±0,98#
IFN-γ (PG/l)48±12212±28**96±30
CEC (adept)0,070±0,0010,143±0,0020,311±0,009*
* reliable is the one from patients with the formation of chronic diseases, at least p<0,05
# - significant difference between patients with severe and organ damage when at least p<0,05

As follows from table 3, selected laboratory criteria were the most informative for predicting outcomes. The method is as follows: after the hospitalization of a patient with suspected yersiniosis in the hospital from 3 to 12 day of the disease is clinical examination with compulsory determining age and sex of the patient, set the gravity of the breach of General condition, primarily assessed the severity and duration of febrile reactions, determine the location, nature and duration of the exanthema. Evaluated the degree of involvement in the pathological process of the joints and other organs and systems (CNS, cardiovascular and urinary systems etc). Performed routine laboratory examination with compulsory determination of the ESR, the CEC and the SLO. For further diagnosis of TFP and KI is serological survey in the reaction of indirect haemagglutination (rnga) to determine the production of specific antibodies, is then carried out immunological examination with determination of the level of IFN-γ and CEC, followed by an assessment of the results.

Use the top which method can prevent adequate therapy the development of severe forms of yersiniosis with organ damage (myocarditis, of cardiomyopathy, jade and so on), to predict the possibility of chronic and adverse clinical outcome. The results were obvious and have great clinical importance in the effectiveness of predicting the course and outcome of TFP and KEY.

By the proposed method predicted for AI in 132 children who were in hospital (see tables 1, 2, 3).

Severe AI diagnosed in 26,52% (n=35) children perencevich AI. According to the authors among organs and systems prevailed involvement in the pathological process of the heart in the form of cardiomyopathy 33% and myocarditis 8%, followed by kidney damage - 15%, pancreatitis and cholecystitis - 6%.

It is established that the kidney on the type of acute glomerulonephritis or interstitial nephritis developed mainly boys aged 4 to 10 years (78%), was accompanied by azotemia, oliguria, impaired concentration renal function, and edematous syndrome was minimally expressed. In 50% of patients with involvement in the pathological process of the kidneys was noted on the second wave of fever for 2-3 week of illness.

Myocarditis in the structure of yersiniosis were observed predominantly in girls 3-9 years of age (85%), was characterized by a significant and prolonged decrease in contractility, moderate rhythm and provodimost is, the increase in the activity of aspartate aminotransferase and lactate dehydrogenase; swelling within 4-5 days. It should be noted that all children with myocarditis long were outpatients with a variety of diagnoses, were hospitalized for 8-14 day in a serious condition. The use of this method of prediction has enabled a timely etiotropic and pathogenetic therapy and to prevent adverse outcomes.

Thus, this combination of clinical and laboratory criteria have not been applied previously to predict the course of pseudotuberculosis and Yersinia in children. It has been proved that this combination leads to accurate prediction of outcomes yersiniosis infection. The method is easily reproducible and inexpensive.

The proposed method of predicting the course of yersiniosis in children may be confirmed by the following specific examples.

Example 1. Boy N., 16 years old, IB. No. 3562, IB. No. 5912. Admitted with complaints on febrile fever, abdominal pain, diarrhea, skin rash at 8 D.B. Sick with 18.09.2006, when there was a maculopapular skin rash, abdominal pain, loose stools, then joined a sore throat and temperature rise to 40°C. is Directed to hospitalization with a diagnosis of ARI, O. pharyngitis, ed suspected pseudotuberculosis and child hospitalized in infection the e branch, where can I get empiricheskoi parenteral antibiotic therapy: Cefotaxime 7 days, then Ceftriaxone for 7 days ciprofloxacin intravenous 5 days. Against this background, continued febrile fever, continued symptoms of intoxication, exanthema, arthralgia, muscle pain, hepatosplenomegaly, however, were stopped abdominal pain syndrome and diarrhea. Serologically confirmed intestinal yersiniosis O3 - titles in rnga with Y.enterocolitica O3 consistently 1:800 dated 28.10.2006, 1:400 dated 09.10.2006 and 1:200 from 16.10.2006. Therapy was continued chloramphenicol 7 days, then Tienam, given the lack of effect of antibiotic therapy, were appointed immunomodulators: cold Roncoleukin, Viferon-3 (consistently). In laboratory data were observed increase of liver enzymes, erythrocyte sedimentation rate accelerated to 65 mm/h, in the biochemical analysis of blood expressed dysproteinemia (albumin 36%, α2-globulins 16%, hypergammaglobulinemia - 26%), CRP levels of 15.5 mg/l, leukocytosis with stab shift, the emergence of anemia, high levels of circulating immune complexes (0,415 adepts), production of IFN-γ 95 PG/ml, the level of specific protivoerosionnih antibodies (11,32 log2). Excluded viral hepatitis, malaria, leptospirosis, brucellosis, hemorrhagic fever, herpes viral infection. Conducted the examination, in addition to existing criteria negl is Drago currents detected: hypertransaminasemia, hyperbilirubinemia; the level of alkaline phosphatase more than 800 units; ferritin level increased more than 4 times; lactate dehydrogenase increased tenfold; in kilogramme - histiocytoma-macrophage response (part of histiocytes and macrophages phagocytic normocytes, red blood cells neutrophils, pigment). Therefore, the patient was diagnosed infectiousbunny hemophagocytic syndrome as a result of intestinal yersiniosis O3. Timely diagnosis infectiousdesigner hemophagocytic syndrome in this patient using the proposed method of predicting the course of yersiniosis have been able to avoid unjustified continuation of yersiniosis and treatment of secondary hemophagocytic syndrome (extracorporeal detoxification methods) with good therapeutic effect. In the future, the boy was observed dispensary within two years of relapse and recurrence is not registered.

Example 2. Patient Olga, age 11, case history No. 1814. Ill sharply with rise in temperature to 39°C, headache and marked abdominal pain, outpatient observed as the patient with acute intestinal infection and was given symptomatic treatment. By the sixth day of illness continued high fever, joined vomiting persisted, abdominal pain, rash on the trunk and extremities as "gloves" and "socks". Hospitalized in FGU NEEDY on the eighth day of the disease in moderately grave condition due to symptoms of intoxication, drain exanthema, showed lymphadenopathy, hepatomegaly +3.0 cm relative to age norms, complained of palpitations. In the clinical analysis of blood leukocytosis up to 15×109/l), neutrophilia (82%) with band shift (13%), erythrocyte sedimentation rate accelerated to 45 mm/h, in the biochemical analysis of blood expressed dysproteinemia (albumin 36%, α2-globulins 16%), CRP 18 mg/l In the immunological marked reduction in the number of CD3+ (42%), CD4+ (34%), with a significant increase in the number of CD20+ cells (36%), IFN-γ 202 PG/ml, the CEC has 0.168 adepts, and the production of specific antibodies by this time the disease was inadequate - 5,32 log2. All this combined with a fever for 13 days, continuing exanthema 5 days allowed to suspect the girl has severe pseudotuberculosis with the development of organ lesions. The child had performed an EKG and ultrasound of the heart, which revealed severe conduction disorders (AV-blockade) and reduced contractility of the myocardium that necessitate massive kardiologicheskii therapy, but given the early diagnosis of organ lesions and adequate therapy (broad-spectrum antibiotics, intravenous immunoglobulins, cardiotropic), the disease had blagopriyatnykh. In the future, the girl was observed outpatient outpatient techniques of relapse and recurrence is not registered, diseases of the cardiovascular system is not detected. Final diagnosis: Pseudotuberculosis mixed option: essentilly and gastrointestinal options, a severe form of serologically.

Example 3. Ill Ivan, age 8, case history No. 1802, No. 2314, No. 47805. The boy fell ill acutely with fever up to 38.5°C, the occurrence of repeated vomiting and loose stools, hospitalized in the FSI NEEDY with a diagnosis of acute gastroenteritis in the first days of the disease in the state of moderate severity. At admission revealed the presence of soft maculopapular rash with thickening in the natural folds and around the joints, increase front - and zadnesheynyh lymph nodes up to 1.5 cm In clinical analysis of blood leukocytosis up to 12×109/ l, stab shift to 12%, erythrocyte sedimentation rate of 12 mm/h, in the biochemical analysis of blood expressed dysproteinemia (α1-globulins 8%, α2-globulins 16%), but CRP remained within the normal range of 4 mg/l In the immunological marked reduction in the number of CD3+ (43%), CD4+ (36%), with a significant increase in the number of CD20+ cells (31%) and high expression of markers negative cell activation CD95+ (31%), production of IFN-γ was insufficient 35 PG/ml, the levels of CEC remained low 0,075 adepts Immediately after admission the child received l is volicitin succinate intramuscularly at a dose of 50 mg/kg of body weight three times a day and means of pathogenetic therapy (antihistamines, prebiotics, sorbents, enzymes). The diagnosis of yersiniosis was confirmed on 4 D.B. high levels - to 9.32 log2protivoerosionnih antibodies to Y. enterocolitica 9. On the background of therapy after 36 hours, the temperature was normalized, the rash disappeared after 12 hours, the feeling was good, and the child's parents refused further therapy in the hospital and took the child home, although the short duration of the entire clinical picture combined with laboratory data allowed us to think about the possibility of prolonged or chronic infectious process. Later in the year the child was hospitalized three times in the clinic with complaints on a periodic rises in temperature, skin rashes, joint pain, which in combination with high titers of specific antibodies allowed us to detect it is a chronic disease requiring long-term therapy with four courses of antimicrobial therapy and two courses of immunomodulatory drugs. Thus, the final diagnosis was formulated: Intestinal yersiniosis 9 mixed form: essentilly, artrologicheskoy and gastrointestinal options, the intermediate form of serologically, a chronic course.

Thus, these data indicate the novelty of the method, the non-obviousness of the presence of significant differences and eff is aktivnosti this predicting the course of yersiniosis in children that allows you to present this method as the application material to the invention and recommend it for use in outpatient and clinical practice.

Before the introduction in the work of the clinic intestinal infections FGU NIIDI the FMBA of Russia proposed a predictor of yersiniosis children do not have a clear clinical and laboratory criteria, allowing to assess disease progression (development of organ lesions, chronization, the outcome in systemic disease), similar to the way the authors are not found in the available sources of information.

Thereby is achieved a prediction form yersiniosis infection that allows you to optimize the etiopathogenetic therapy (antimicrobial and together with immunomodulating), and most importantly, to prevent the development of organ lesions (myocarditis, nephritis and chronic disease. The authors showed that only the combination of clinical and laboratory parameters ensures high efficiency of predicting the course and outcome of disease. The method is simple and easily reproducible.

A method for predicting the course yersiniosis infections in children by assessing laboratory performance: CIC (circulating immune complexes), interferon-γ (IFN-γ), characterized in that children from 3rd to 12th day of the disease, assess the severity and duration: legoredo the Oh reaction and exanthema, additionally determine serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), CIC (circulating immune complexes), interferon-γ (IFN-γ) and specific antibodies (AT) and when:
febrile reactions less than 3 days duration exanthema less than 1.5 days, CRP less than 7.5 mg/l, the average sedimentation rate of less than 15 mm/h; the level of IFN-γ is less than 75 PG/ml, the CEC is not above 0,115 adepts and production of specific antibodies more 8,32 log2predict a chronic course of yersiniosis;
febrile reactions over 12 days, the duration of exanthema more than 3 days, the CRP levels of more than 15 mg/l, the average sedimentation rate of more than 30 mm/h; the level of IFN-γ than 150 PG/ml, CEC above 0,130 adepts and production of specific antibodies less 7,32 log2predict a severe course of yersiniosis with the development of organ lesions;
febrile reactions over 12 days, the duration of exanthema over 9 days, the CRP levels of more than 7.5 mg/l, the rate ESR > 50 mm/h; the level of IFN-γ is less than 150 PG/ml, CEC above 0,250 adepts and production of specific antibodies more to 9.32 log2predict the outcome of yersiniosis in systemic disease.



 

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FIELD: medicine.

SUBSTANCE: invention concerns a kit of reagents for pancreatic α-amylase activity test including a reagent 1 containing sodium chloride, potassium sulphocyanate, sodium azide, water-soluble calcium salt, monoclonal salivary α-amylase antibodies (MAB), 2-morpholinoethanesulfonic acid (MES) and water, and a reagent 2 containing 2-chloring-4-nitrophenyl-4-O-β-D-galactopyranosylmaltoside (GalG2CNP), MES and water, differing by the fact that the reagent 1 in addition contains EDTA and bovine serum albumin (BSA), and as calcium salt, it contains calcium acetate, and the reagent 2 in addition contains EDTA and sodium azide in the proportions specified in the patent claim.

EFFECT: enhanced stability of the set of reagents with maintaining high accuracy and result reproducibility of the analysis.

1 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, namely to methods of predicting post-operational complications, namely to methods of predicting development of scars after previous acne. In order to predict scar development content of receptor antagonist of interleukin-1 (RAIL) is determined during 15 days after resolution of inflammatory process. Scarless development of process is diagnosed at level RAIL in peripheral blood serum after disease being within physiological norm (300-800 pg/ml). If level of RAIL is lower than said norm prediction of acne complication in form of skin scars is diagnosed. Possibility of development of hypertrophic scars is predicted if RAIL concentration is lower than 200 pg/ml.

EFFECT: method makes it possible to predict type of complications after previous acne, therefore correcting therapy carried out in due time can prevent risk of skin scar formation and improve patient's life quality.

2 cl, 1 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: developing hypoxia in a pregnant woman of the third trimester of gestation is predicted by evaluating peripheral blood oxyhemoglobin (HbO2) and 2,3 diphosphoglycerate phosphatase (2,3DPG) concentrations. A discriminator (D) is calculated by formula D=+17.072·2.3DPG + (-0.041·HbO2), 2,3DPG - concentration, mol/l, HbO2 - amount, %. The D value within 97.09-112.37 enables to predict threatened hypoxia in a pregnant woman had an acute condition of herpes virus infection.

EFFECT: use of the method allows well-timed detection of a risk group and correct prediction of developing hypoxia.

2 ex

FIELD: medicine.

SUBSTANCE: threatened reduced erythrocyte oxygenation in a pregnant woman suffering an acute attack of bronchial asthma in the first trimester of gestation is predicted by evaluating oxyhemoglobin (HbO2) and 2,3 DPG (2,3 diphosphoglycerate phosphatase). This is followed by calculating a D discriminator value by formula D=18.05·2,3DPG + (-0.075·HbO2), and observing the D value within 88.66 to 102.42, threatened reduced erythrocyte oxygenation that leads to hypoxia is predicted.

EFFECT: use of the method enables predicting threatened reduced erythrocyte oxygenation in a pregnant woman with the acute attack of bronchial asthma.

1 ex

FIELD: medicine.

SUBSTANCE: differentiated detection large and small circulating immune complexes in blood serum is ensured by a follow-on examination of blood serum clarified by short centrifugation with a method of circulating immune complexes precipitation PEG -6000 of the end concentration 4 % and 6 %. Thereafter, the results are recorded by a turbidimetric method with using a microplate spectrophotometer in a two-wave mode: basic - 340 nm, reference filter - 620 nm. Duration of an incubation step at temperature +18-25°C is 15 minutes. Using the method enables higher effectiveness and reliability of determining the level of large circulating immune complexes, results reproducibility, as well as differential measurement of the level of small CIC which are a diagnostically significant indicator of human body immune responsiveness in many types of a pathology, decreased volume of analysed serums to 0.06 ml, and incubation duration to 15 minutes.

EFFECT: method is suitable for clinical screenings.

1 dwg, 1 tbl, 1 ex

FIELD: measurement equipment.

SUBSTANCE: invention refers to biophysics. In order to determine calcium concentration on the basis of discharged photoproteins, bioluminescent reaction of photoproteins and calcium ions is performed, intensity of the solution fluorescence is measured, calibration dependence of fluorescence intensity on calcium concentration in double logarithmic coordinates is built and logarithm value of calcium concentration is determined as per the logarithm of the measured fluorescence intensity. Fluorescence is initiated with the light source after bioluminescent reaction is completed. Fluorescence intensity is measured at the specified length of excitation and recording wave.

EFFECT: method allows determining calcium concentration in various media as per fluorescence intensity of discharged photoproteins, which allows performing continuous measurements of calcium concentration in "in vivo" system.

2 dwg, 6 ex

FIELD: medicine.

SUBSTANCE: invention describes a method of determining a bronchial asthma control ratio in the patients with prescribed a background anti-inflammatory therapy with a combination of inhaled glucocorticosteroids and (long-acting 32-agonist) that involves determining the BA control by GINA 2006 criteria; in addition, the method measuring peripheral blood CD 20+ lymphocytes, and if the CD 20+ cell count is 15 or lower, the clinical course of BA is considered to be controlled, and if the CD 20+ cell count exceeds 15 then the clinical course is uncontrolled.

EFFECT: method enables the objective determination of the bronchial asthma control ratio that is necessary for correction of the antiasthmatic therapy.

1 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: ploidy of peripheral blood cell is evaluated by a flow cytometry method. If observing aneuploidy, development of an intermittent or terminal stage of CRI is predicted.

EFFECT: method allows higher accuracy and reliability of the prediction of disease severity.

4 dwg, 2 ex

FIELD: medicine.

SUBSTANCE: patient's blood serum is examined for the contents of tissue inhibitor of matrix metalloproteinase (hTIMP-1). If the value hTIMP-1 is 138 ng/ml to 179 ng/ml in the female patients, and 138 ng/ml to 189 ng/ml in the male patients, the presence of early subclinical left ventricular myocardium affection in the patients suffering hypertension without ventricular hypertrophy is stated.

EFFECT: using the technique allows early diagnosing subclinical cardiac affection in the patients suffering hypertension without left ventricular hypertrophy.

4 ex, 4 tbl

FIELD: space engineering.

SUBSTANCE: device to sample a gas medium for a sorbent in a compartment of a manned spacecraft includes a bellows aspirator with a working volume of around 100 cm3 and a sampler with an absorber, arranged in the form of a sorbent-filled tube body made of stainless steel with the length of around 150 mm and inner diametre of not more than 6 mm, at the ends of which the thread is cut, onto which captive nuts are screwed - as plugs of duraluminium with a Teflon seal, joined with the absorber body by a flexible synthetic thread, and the tube ends are closed with a glass wool with Teflon limiters. Also there is a method provided to sample a gas medium for a sorbent in a compartment of a manned spacecraft by pumping of an examined air in the manned spacecraft through a previously prepared device. Besides, preparation includes thorough degreasing and washing of the inner surface of the tube with subsequent drying in the nitrogen atmosphere at 300°C prior to the sorbent charging into the absorber; removal of substances absorbed by a used sorbent by means of nitrogen blowdown via the sorbent and the sampler sealing.

EFFECT: accuracy and reliability of gas sampling for sorbents when used in conditions of a manned space flight.

4 cl, 1 dwg

FIELD: medicine.

SUBSTANCE: blood is examined. A hematocrit level (H), erythrocyte count (E), thrombocyte count (T) are determined. Said parametres are evaluated. In the event if they keep within the determined limits for the patients with acute coronary syndrome (ACS), then adenosine phosphate induced (ADP-induced) clotting time test samples are prepared. Citrated blood sample 0.4 ml is prepared of whole blood and divided on two samples 0.2 ml. Each of these samples is introduced in a measuring cell, recalcified at temperature 37°C for 2 minutes. Then a magnetic ball mixer is placed in each cell. The measurement is activated, and in three seconds the ADP solution 0.1 ml is introduced. After a clotting reaction, a process time duration is recorded separately for each sample. An arithmetical mean of the derived values is calculated (A). The derived values of each of said parameters are scored. Total score Σ=A+H+E+P shows the risk of recurrent thrombotic events. If Σ=4 points, the low risk is observed; the value Σ=5-6 points shows the medium risk, while Σ=7-10 points - the high risk.

EFFECT: method provides more objective risk evaluation of recurrent thrombotic events in the patients with ACS with its simplicity and low cost.

1 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: in a newborn baby on the first day of life content of transforming factor beta-1 (TGF-β1) in blood serum is determined and its level is used to diagnose severity of abnormality of postnatal myocardium remodeling.

EFFECT: method makes it possible to administer pathogenetic therapy in due time.

1 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, surgery, and can find of application when choosing a postoperative therapeutic approach in children with a surgical septic pathology. It involves a standard cell blood composition assay and leukogram description. A leukocyte-derived intoxication index (LII), a nuclear index (NI) and a blood leukocyte shift index (BLSI). The derived indexes are used to calculate an average total intoxication level (IL) daily. A toxicity level ΔIL is determined as a relation of a difference of daily actual and reference toxicity levels to the reference. The postoperative IL and ΔIL dynamics are compared for up to 5 days to the values derived as of the date of admission to hospital. Another surgical intervention is required if these values and their references are exceeded.

EFFECT: more accurate prediction of the clinical postoperative course in children with purulent-septic diseases due to analysing the intoxication and toxicity levels dynamics.

3 ex

FIELD: medicine.

SUBSTANCE: method for thrombocyte intravascular activation analysis involving blood sampling, blood cell fixation with ethylene-diamine-tetraacetic acid, centrifugation, and activated thrombocyte detection in the prepared plasma by maximum integrated optical density of all formed units, and if any observed, the intensity of thrombocyte intravascular activation is evaluated.

EFFECT: method provides higher accuracy of thrombocyte intravascular activation analysis.

3 ex

FIELD: medicine.

SUBSTANCE: method for prediction of clinical course of acute leukemia in children, characterised by the fact that peripheral blood is analysed for cell ploidy and kinetics by flow cytometry, and if observing aneuploidy and DNA index less than 1.19, unfavourable outcome is predicted.

EFFECT: method provides more accurate and reliable prediction of the clinical outcome.

3 dwg, 3 ex

FIELD: medicine.

SUBSTANCE: oxyhemoglobin and 2,3-diphosphoglyceratephophotase are evaluated in umbilical blood of newborns by a spectrophotometric method. The coefficient D is calculated by formula D=-1.858·HbO2+(+13.097·2.3DPG). If D is lower than -81.04, low oxygenation of arterial erythrocytes in newborns is predicted.

EFFECT: use of the method allows predicting a degree of oxyhemoglobin saturation of umbilical erythrocytes in newborns.

FIELD: medicine.

SUBSTANCE: invention relates to laboratory methods for blood analysis. Plasma is dropped in copper sulfate solution with density 1.023 g/cm3, not above, and time for drop falling on bottom of graduated cylinder with column height 243 mm is measured. The blood plasma density value is calculated by the formula:

wherein is the unknown blood plasma density (g/cm3); is copper sulfate solution density measured by areometer (g/cm3); t is average falling time of plasma drop in the copper sulfate solution (as seconds); 0.260130126 and 0.00290695 are correction coefficients. Temperature of plasma and copper sulfate solution is 20oC. Method is simple and suitable and allows carrying out analysis of small volumes of blood plasma and to reduce analysis time.

EFFECT: improved assay method.

2 ex

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