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DISCUSSION QUESTIONS OF BRONKHIAL ASTHMA IN CHILDREN

N.A. Geppe I.M. Sechenov
First Moscow State Medical University



In the article the questions about classification, assessment of severity and the way of therapeutic tactics during the bronchial asthma in pediatric patients are opened.
Key words: bronchial asthma, classification, monitoring criteria.



Bronchial asthma is a heterogeneous condition, which is based on chronic persistent inflammation and structural changes occurring with occasional periods of exacerbations, during which are mostly pronounced the clinical symptoms and deteriorations of lung function. Improving the understanding the state of bronchial asthma, changes in the lungs, their impact on the mechanics of breathing and also new data on changes in immunity, the formation of inflammation, irreversible damages of lungs accompanied by changes in the definition and classification of asthma pharmacotherapy and clinical management.

Connection of exacerbations with allergens, the similarities with anaphylaxis, immunological and genetic studies have led to the consideration of asthma as an allergic disease. For the basis of the definition of asthma at 60 years was taken such cardinal sign as reversible obstructive airway disease. Further emphasis was placed on airway hyperresponsiveness as features that are commonly found in asthma. But the sign was not specific as a number of people with a clinical picture of asthma may be normal or increased bronchial reactivity in the absence of asthma.

New data on the role of chronic inflammation in the development of the disease have shown that in sensitive persons this inflammation causes symptoms that are usually combined with widespread but variable, airway obstruction, which is reversible, either spontaneously or under the influence of therapy. To the International Report on the diagnosis and treatment of asthma (GINA), this provision was included in the definition of asthma [11]. The basis for the modern definition and understanding of asthma is formed by three components — chronic inflammation, reversible obstruction and increased bronchial reactivity. [12] They also represent a pathophysiological basis of symptoms origin as- wheezing, breathlessness, chest tightness, cough and sputum production — by which doctors clinically diagnosticate disease. In the definition which is represented in the National Program «Bronchial asthma in children. The strategy of treatment and prevention» [2], there is an allergic nature of the disease, in which sensitizations to allergens and the continuing impact leads to the clinical manifestations of asthma through the development of airway inflammation, reversible obstruction and increased bronchial reactivity. But it is known that there are cases of asthma with non-allergic airway inflammation.

These non-allergic mechanisms are currently poorly understood. The severity of inflammation determines the severity of clinical symptoms, their variability, fetchers of manifestation of each individual patient. Among patients with bronchial asthma distinguish the features of the flow in the individual cohorts caused predominant influence of various trigger factors, which in combination with a hereditary predisposition creates certain phenotypes, the degree of bronchial hyperresponsiveness and obstruction. The problem of asthma in children is extremely urgent. In 2011, at the meeting of the UN on Noncommunicable Diseases attention was focused on increasing the threat of asthma and other non-communicable diseases for the global health, social welfare and economic development.

From the moment of creation of the first guidelines on asthma the aim was to minimize symptoms, improve lung function and prevent exacerbations [11]. Due to the importance of determining the prospects of the patient and the lack of a clear correlation between inflammation, lung function and symptoms in clinical studies and clinical practice drew attention to the assessment of «asthma control.» The recommendations of the leading experts were focused on harmonizing the definition of asthma and asthma control and balance creation in the information gaining for the possibility of comparing different studies. Members of the European Respiratory Society (ERS) and the American Thoracic Society (ATS) in 2008 had published the results of a Cochrane review of randomized controlled studies between 1998 and 2004 yy., the containing of the words «asthma control», «asthma severity» or «aggravation» [3].

The aim of this work was to give a clear definition of control, severity, aggravation for future researches and clinical practice in patients older than 6 years. Asthma control means the reduction or elimination of various forms of asthma through therapy and includes two components: on the one hand, the level of clinical control of asthma, which is estimated by such appearance as symptoms and includes the ability of the patient to daily life activities and to optimum quality of life development, on the other — reducing the risk to the patient of such outcomes as aggravation, poor control, the progressive decline in lung function, side effects of therapy. Some of these future risks may be as a result of lack control of the underlying in the base process. This is a cumulative term which was proposed in the global assessment of symptoms, use of bronchodilators, pulmonary function status, the frequency/severity of exacerbations. For today there is no clear definition and criteria of asthma control, so the criteria used vary widely in the different studies. The modern clinical and research definition of «severe asthma» and «mild asthma» are focused primarily on the intensity of treatment required [3,12]. This view differs from the previously published definitions of severity [11], in which the severity of disease activity was defined that is presented in the form of clinical signs before treatment. It is noted that there is no gold standard definition of asthma control, there is no single key point, which may be recommended to evaluate the response to treatment. For comparison in the studies the «global assessment of the doctor» is used, «but it also is not an absolute standard [8].

At present times, there are no clear guidelines haw integrate the two components — real control and future risks — to the overall assessment of asthma control. Perhaps, the patient will be able to give their own assessment of the level of «control.» However, it will depend on its ability to determine the optimum change associated with therapy, which may be much different from the medical conclusions [3], especially in pediatrics. As evaluation of parents so assessment of older child is not always objective. Asthma control is proposed to be considered as «the scale» as a scale or in the time [3]. In the past, the level of control is often viewed with the use of semi-quantitative descriptions («total», «good», «bad») or relative terms, ranging from the «best achievable» or «optimal» at one and of observation and through the «suboptimal» to «undesirable» or «unacceptable» — on the other one. However, these descriptions require the engage of arbitrators, therefore long-lasting or common measurements are preferred. If a more precise description is necessary, it must be based on clinically important positions. The main goal for control evaluation — it is a patient.

However, the level of control may be appropriate for one patient and not acceptable to the other or to the physician. In each case, the «acceptability» in the present status of the patient must be balanced with the future risk of poor control or side effects associated with treatment. The data of evaluation of patients and their parents need to be supplemented by objective changes. The proposed ranking on «controlled», «partly controlled» or «out of control» [12] also raises questions in accordance with the lack of validity and age characteristics. Moreover, the level of control can be varied in a relatively short period of time (days to weeks) in response to allergens actions or infectious factor or in response to treatment. And control is generally proposed to estimate the period of 1 to 4 weeks [6] that does not reflect the whole picture of the dynamics of the disease.

The severity of bronchial asthma is also used to describe the severity of the clinical status or the intensity of asthma symptoms or exacerbations. According to modern views severity is defined as the difficulty in controlling of bronchial asthma by treatment. In patients not receiving glucocorticosteroid therapy severity was divided into four groups by the level of severity of symptoms, control and variability of lung function such as — intermittent and mild persistent, moderate persistent and severe persistent [12]. After exclusion of such modifying factors as poor adherence to treatment, smoking, comorbid disease severity reflects the desired level of treatment and activity status of the underlying disease during treatment, which may depend on the underlying phenotype, environmental factors and associated diseases. Because the evidentiary basis is insufficient to the clinical characteristics of the patient who is treated exactly in the decision to focus on the future treatment or predict easy or difficult it will be to achieve a good control when a certain treatment will be initiated, proposed maintaining the previous determination of the gravity «no treatment» [3]. It has been 15 years past when by the initiative of the Chairman of the Russian Respiratory Society Ac.A.G. Chuchalin by the leading Russian pediatricians was developed the first National Programme «Bronchial asthma in children. Strategy of Treatment and Prevention» (1997).

In the preparation of the National Program versions 1997, 2006, 2008, 2012 years were taken into account the recommendations of a joint report of the World Health Organization and the National University Heart, Lung, Blood (USA) GINA — «Bronchial asthma. Global Strategy» (1995–2010 yy.) and the European Respiratory Society and the best practices of a series of foreign countries for the treatment of bronchial asthma in children. The creation of pediatric program allowed to make the accent on the clinical variants of bronchial asthma course, in the first place, depending on the age as in young children, pre-school children, adolescents the disease has own features; on the characteristics of the immune system, the metabolism of medical preparations, routes of delivery, the mainstream approach to the diagnosis, treatment, prevention and education programs. It is emphasized that the variants of the current course are dependent on the interaction of genetic components and environmental factors, which forming in result the phenotypic features of bronchial asthma according to the age, date of onset and the variability of the underlying in the basis allergic inflammation in the bronchial tubes, etc. In the 2009–2010years the new regulations for the provision of health care to children and adults with pulmonary and allergic diseases have been prepared by the experts and approved by the Orders of the Russian Federation Ministry of Health and Social Development , in which great attention is paid to the BA as an outpatient so inpatient stages. From the practical point of view in the national practice is suitable classification of bronchial asthma in the first place by severity because of such approach provides the optimal selection of therapeutic activities and the plan of treatment of patients. Sometimes, it is very difficult to evaluate severity of bronchial asthma, especially in young children.
Therefore, almost all children with bronchial asthma are consulted and followed up by specialists. The definition of bronchial asthma severity before treatment is based on an evaluation of clinical and functional parameters and on the background of the treatment depends on the volume and effectiveness of therapy. For the clinician to determine the severity is the main idea because it determines the solution of the main problems of medical tactics and plan of the patient, as well as the ability to achieve control of short-term and long-term programs. According to the basic indicators of the severity of bronchial asthma (severity of daytime and nighttime symptoms, the frequency of use of short-acting bronchodilators and their efficacy, exercise tolerance, reduce of respiratory function, the variability of PEF) there are found mild, moderate and severe bronchial asthma. The course of bronchial asthma has undulation character. In the course of the disease the periods (phases) of recurrence and remission are underlined. In accordance with the absence of clear definitions in the literature of intermittent and persistent asthma, this characteristic is mainly associated with the recurrence of exacerbations and does not significantly affect the decision-making for today. To the intermittent variant belong rare episodes of wheezing which are disappearing spontaneously or with the use of bronchodilators. A persistent variant of asthma is often characterized by prolonged episodes of breathing difficulties that requires the regular use of bronchodilators. Apart from the variant the appointment of antiinflammatory therapy is needed to be considered, the duration of which will depend on the severity of asthma and the possibility of achieving control [12]. The severity of course can vary under the influence of conducted therapy, the recurrences become more rare (intermittent) and mild, which is also can be a criteria of effectiveness of the therapy.

According to the produced approaches in the national pediatric the classification of bronchial asthma according to it severity allow provision of selection of optimal therapy for practicing doctors in the different age periods, to maintain continuity in the transition to adult specialists and conduct adequate expert estimation. [12]

Bronchial asthma control was the key concept of «The global strategy of treatment and prevention of bronchial asthma», the revision of 2006 year, and is offered as a main criterion for evaluating of disease symptoms. However, it is needed to be marked that the criteria for control relate primarily to adults while defined from 6 years. Bronchial asthma is well controlled in condition of achieving and maintaining of the follows:
  • daytime symptoms twice a week or less (not more than once daily);
  • no activity limitations due to symptoms of bronchial asthma;
  • night symptoms 0–1 times a month (0–2 times a month, if the child is older than 12 years);
  • use of preparations of emergency treatment twice a week or less;
  • normal lung function (if it is possible to measure);
  • 1–2 exacerbation in the past year.

If we compare the data of control criteria with the original severity of asthma, so for severe asthma and even some patients with moderate to meet the criteria logic achieve control. For children with mild asthma the presence of night symptoms and the use of preparations for emergency treatment will characterize the uncontrolled course, requiring changes in therapy. According to the International Pediatric Consensus PRACTALL, children (especially preschoolers) can have 1–2 recurrences per year, and bronchial asthma can be treated in this way as a controlled in condition of absence of presents of non acute symptoms of disease presents [7]. Proposed levels of bronchial asthma control, reflecting the answer on conducted therapy in pediatrics can be used as a characteristic of the effectiveness of the therapy.

Exacerbations in clinical practice are the greatest risk to patients, creating anxiety in patients and their parents, determine the most financial cost and identified as events which are characterized by changes, differ from usual patient's status that go beyond the usual day-byday fluctuations of patient [9]. Different terms are used for exacerbations describing. For example, some studies have often used the term «acute severe bronchial asthma» instead of exacerbated or «asthma attack», «treatment failure.» To the «mild» exacerbations of bronchial asthma may be included episodes with FEV1 30% of predicted [14]. While under general settings, they should be regarded as extremely severe. In the clinical practice severity is recognized as episodes which are creating problems for patients and need to make changes in the treatment. These episodes vary different by its speed of onset (minutes or hours to 2 weeks) and term of relief, by their absolute severity and subjective tolerability.

Clinical characteristics which are causing acute distress and impairment for one patient and can be represented by the normal status for another. To severe exacerbations belong the events that require immediate actions on the part of the patient and the doctor to prevention of serious outcomes such as hospitalization or death from asthma. The most common criterion is the need for systemic corticosteroids (CS) for at least 3 days (tablets, suspensions, or injections) at the discretion of the doctor [4,10].

However, the administration of CS as a primary care by physicians has a low sensitivity. Asking for help or administration of CS can have subjective character. These actions are pretty much due to the adequacy of patient perception of such phenomena as obstruction.

Other authors include as criteria the emergency care and / or hospitalization, unscheduled visits to the doctor [10]. In Russia, the fact of hospitalization does not fully reflect the severity of an exacerbation.

Hospitalization of a child with bronchial asthma, especially in the early age, can be also connected with the need of status control of the child, the use of preparations or devices which are absent in the family, by additional diagnostic procedures. In many definitions, including lowering of PEF from 20% to 30%, as usual 2 days running, but sometimes it takes 1 day with a low PEF [4,10]. In some studies, the criteria were increased asthma symptoms or increased use of rescue medication — â2-agonists of short-action + PEF reduction [13].

Moderate asthma exacerbations are defined as events that cause problems for the patient, but are not heavy and require a change in treatment. These events are clinically defined as beyond the patient's usual day-to-day variations in asthma. Moderate exacerbations can be considered as those that require additional treatment (additional control therapy — oral corticosteroids / inhaled corticosteroids) for the prevention of severe exacerbation, an additional appointment to the IGCS â2-agonists of long-action / theophylline. For the modeodifficalt patients in the studies of which were the need to double or even greater increase in the dose of ICS in case of worsening asthma for reducing of probability of progression of severe exacerbation were examined [5]. It is obvious that in these situations the solution would be determined more by clinical criteria, but not only by change of medications.

In the studies review a number of criteria used for determination of mild exacerbation are included, for example 15% reduction in PEV in the morning, 20% reduction in clinic FEV1 [15] and/or an increase in the
use of preparations for emergency care [4]. Some experts believe that the definition of «mild» exacerbation cannot be used, because these episodes are in the range of changes for a particular patient, and they can
not be separated from a transient loss of bronchial asthma control by the modern methods of investigation.

However, in children, especially in infants and during the mild asthma exacerbations are often associated with viral infections and are fundamentally different by clinical manifestations from the normal status. There are no real methods for early objective definition of bronchial obstruction and its severity. The method of bronchophonograhy has been recently developed [1].

Many exacerbations in children treated with the use of Pulmicort suspension thought for nebulizer or by increasing of ICS dose more often than systemic corticosteroids. However, as long as there are no specific studies, they should be considered as moderate, while the administration of systemic CS — as sever [3]. As noted in the GINA, the determination scheme of controlled asthma is based on expert opinion, it is not validated, but correlates well with the control questionnaires, including the ACT.

Simple questionnaires based on their own assessment of the patient (or by his parents) status, provide objective information about the level of bronchial asthma control in the ordinary work of the doctor. Asthma control test in children (The Childhood Asthma Test — ACT for children) is designed for children 4–11 years old. The kids version of ACT includes four questions that should answer the child, describing the symptoms of the disease at the current time (to facilitate the understanding of these issues have a clear visual support), and three questions for the parents in the previous 4 weeks. From the 12 years the adult asthma control test (ACT) is used. Asthma control test (ACT) and the children's version presented online in an interactive way (http://www.astmatest.ru). Today, the Russian validated questionnaires ACT, children ACT, ACQ5, TRACK are valid for sale. These questionnaires can identify patients with controlled or uncontrolled bronchial asthma course and with high sensitivity to evaluate a change of control of the disease over time.

TRACK (Test for Respiratory and Asthma Control in Kids) — a simple checklist of five questions that can help in the evaluation of the control of respiratory symptoms and bronchial asthma in patients aged from 2 months to 5 years, is filled by parent / guardian of he child, while the interpretation of the results represented by a medical worker. In the present questionnaire was reflected as an area of risk so the region of the everity of violations described in the major international guidelines for the treatment of bronchial asthma. Program of management of children with bronchial asthma provide a complex approach with the appointment of a wide range of activities to achieve a stable remission and quality of life for all patients, regardless of disease severity. The main directions of the program during the bronchial asthma in children include: eliminating the impact of causal factors (elimination); the development of individual plans of anti-inflammatory therapy; the development of individual plans for relief of exacerbations, the development of plans of rehabilitation and dispensary observation; education and training of sick children and the members of their families, prevention of disease progression [2]. Therapy is aimed at eliminating of bronchus mucous membrane inflammation, the reduction of bronchial hyperreactivity, reconstruction of bronchial obstruction and prevention of structural restructuring of the bronchial wall.

Delayed diagnosis and inadequate therapy are the main reasons of sever cause of disease and a poor prognosis during the bronchial asthma.

 The modern approach to the treatment is determined by the knowledge of algorithms of pharmacotherapy during the period of exacerbations and for prevention and also possible individualization taking into account the phenotype of bronchial asthma. The basis of bronchial asthma pharmacotherapy is the baseline (anti-inflammatory) therapy, which is defined as a regular long-term use of preparations arresting allergic inflammation in the airway mucosa. Basic therapy administrated individually according to the severity of the disease at the time of examination of the patient and corrected according to the achievable effect; the treatment of patient is determined by the patient's physician in accordance to the particular clinical situation and comorbidities. This is especially important in pediatrics. Symptoms of asthma, atopic dermatitis, allergic rhinitis, conjunctivitis are indicators of current allergic process and require an integrated approach.

During the pharmacotherapy of bronchial asthma the «step-by-step» approach which includes an increase or decrease in the amount of therapy depending on the severity of clinical symptoms is recommended. To the algorithm of pharmacotherapy during the mild asthma in the way of starting preparations the leukotriene receptors from 2 years are included, especially during the virus-induced asthma phenotype, where triggers are respiratory viruses, and during the combination of asthma and allergic rhinitis (montedukast one chewable tablet), inhalation of Cromones least 3–4 times a day. Alternative therapy includes low-doses of inhaled corticosteroids. During the development of persistent symptoms in the early years in the therapy the Pulmicort suspension from 6 months of age is used, beginning from the periods of exacerbations, which can be extended as a basic treatment and after the elimination of the symptoms of an exacerbation. In moderate and severe asthma, the inhaled corticosteroids (monotherapy) or in combination with â2-agonists for long periods are used as usual. Preference is given as initial therapy by the preparations with the fixed combination of corticosteroid and â2-agonist of long-action (fluticasone + salmeterol from 4 years, budesonide + formoterol from 6 years, beclomethasone + formoterol from 12 years). Combinations with antagonists of eukotriene receptors and theophyllineare are also possible. During the severe asthma the higher doses of ICS in the different combinations are used. During the poorly controlled course, starting from the moderate difficulties the rates the introduction of monoclonal IgE antibody is used. Etiopathogenetic method of treatment of bronchial asthma is allergen specific immunotherapy. In the complex treatment the non-drug treatments are needed to be in use, it concerns the methods which are focused on normalizing of breathing, training of effort tolerance, and hardening.

Successful treatment of bronchial asthma is not possible without a partnership, a trust relationship between
the doctor, the sick child, his parents and family.


References
  1. Geppe N.A. Primenenie bronkhofonograficheskogo issledovaniya legkikh dlya otsenki effectivnosti terapii bronkhial'noi astmy I obstruktivnogo bronkhita u detei rennego vozrasta / Geppe N.A., Seliverstova N.A., Malyshev V.S. / / Zhurn. pediatrii im. G.N. Speranskogo— 2009 g.— T. 87, № 2. — S. 51—55.
  2. Natsionalnaya programma «Bronkhialnaya astma u detei. Strategiya lecheniya i profilaktika.» — M., 2008.
  3. A new perspective on concepts of asthma severity and control / Taylor D. R., Bateman E. D., Boulet L_P. [Et al.] / / Eur. Respir. J. — 2008. — Vol. 32. — P. 545—554.
  4. Budesonide and formoterol in a single inhaler improves asthma control compared with increasing the dose of corticosteroid in adults with mild_to_moderate asthma / Lalloo U. G., Malolepszy J., Kozma D. [Et al.] / / Chest. — 2003. — Vol. 123. — P. 1480—1487.
  5. Canadian Asthma Exacerbation Study Group. Doubling the dose of budesonide versus maintenance treatment in asthma exacerbations / FitzGerald J. M., Becker A. Sears M. R. / / Thorax. — 2004. — Vol. 59. — P. 550—556.
  6. Committee and Investigators. Stability of asthma control with regular treatment: an analysis of the Gaining Optimal Asthma control (GOAL) study / Bateman E. D., Bousquet J., Busse W. W. [Et al.] / / Allergy. — 2008. — Vol. 63. — P. 932—938.
  7. Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report / / Allergy. — 2008. — Vol. 63. — P. 5—34.
  8. Jones P. W. Interpreting thresholds for a clinically significant change in health status in asthma and COPD / P. W. Jones / / Eur. Respir. J. — 2002. — Vol. 19. — P. 398—404 /
  9. Lane S. An international observational prospective study to determine the cost of asthma exacerbations (COAX) / S. Lane, J. Molina, T. Plusa / / Respir. Med. 2006. — Vol. 100. — P. 434—450.
  10. Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial / O'Byrne P. M., Barnes P. J., Rodriguez_Roisin R. [Et al.] / / Am. J. Respir. Crit. Care. Med. — 2001. — Vol. 164. — P. 1392—1397.
  11. National Asthma Education and Prevention Program Expert Panel Report: 2. Guidelines for the diagnosis and management of asthma. Bethesda, MD: National Heart Lung and Blood Institute; 1997.
  12. National Heart Lung and Blood Institute National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. 2007 [Electronic resource]. — Access mode: http: //www. nhlbi.nih.gov/guidelines/asthma// — Title from screen.
  13. Risk factors of frequent exacerbations in difficult-to-treat asthma / Brinke A., Sterk P. J., Masclee A. A. M. [Et al.] / / Eur. Respir. J. — 2005. — Vol. 26. — P. 812—818.
  14. Rodrigo G. J. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta_analysis / G. J. Rodrigo, J. A. Castro_Rodriguez / / Thorax. — 2005. — Vol. 60. — P. 740—746.
  15. Zafirlukast improves asthma control in patients receiving highdose inhaled corticosteroids / Virchow J. C. Jr., Prasse A., Naya I. [Et al.] / / Am. J. Respir. Crit. Care Med. — 2000. — Vol. 162. — P. 578—585.

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