29 research outputs found
Derivatives of triangular, Toeplitz, circulant matrices and of matrices of other forms over semirings
No full textMyroides odorarus another one from the new emerging pathogens in cystic fibrosis – case report
No full textНякои клинични и генетични фактори за тежка астма при деца в България
No full textЦЕЛ И ЗАДАЧИ
ЦЕЛ:
Целта на настоящата дисертация е да се опишат характеристиките на тежката астма при деца в България и да се установи ролята на основните четири от единичните полиморфизми на ADAM33.
ЗАДАЧИ:
1. Ретроспективно определяне на честотата на тежка астма сред пациентите, лекувани в Клиника по педиатрия, УМБАЛ „Александровска“ за период от 5 години (януари 2010-декември 2014).
2. Да се оцени честотата на придружаващите заболявания, които могат да се отразят върху контрола и тежестта на бронхиалната астма в тази ретроспективна кохорта (алергичен ринит, наднормено тегло, гастро-езофагеален рефлукс).
3. Да се оптимизират праймери за T1 (rs2280091, T/C), T2 (2280090, C/T), V4 (rs2787094, C/G) и S2 (rs528557, G/C) от единичните полиморфизми на ADAM33 за RT-PCR и изработване на протокол за работа с тях.
4. Да се подберат пациенти с бронхиална астма, както и съответна контролна група пациенти, при които да се извърши генетично изследване след получаване на информирано съгласие от родителите за проспективно проучване.
5. Да се анализира как тежестта на астмата при пациентите от проспективната кохорта се отразява на резултатите от функционално изследване на дишането и лабораторните показатели (диференциална кръвна картина, назална еозинофилия, общи и специфични IgE и Th17).
6. Да се определи разпределението на посочените полиморфизми в българските пациенти.
7. Да се установи влиянието на откритите полиморфизми за клиничния ход и контрола на бронхиалната астма при изследваните деца.
8. Да се определи разпределението на изследваните полиморфизми при пациентие, които остават с клинична тежка астма и след 5 годишно проследяване (януари 2014-декември 2019).
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SUMMARY.
Bronchial asthma (BA) affects about 15% of all children, which makes it the most common chronic lung disease in childhood, about 15-20% of asthmatics in the world have a severe clinical course. The aim of this PhD thesis is to describe the characteristics of severe asthma in Bulgarian children and to establish the role of the main four of the single polymorphisms for ADAM33. ADAM33 is the first one of the many genes connected with asthma predisposition. There are two parts of the study – retrospective and prospective. In retrospective study 1075 children (640 boys and 435 girls with average age 9,23 years) hospitalized in the ward for chronic lung diseases of the Clinic of Pediatrics, University Hospital "Alexandrovska" EAD due to exacerbation of bronchial asthma for the period from January 1, 2010 to December 31, 2014 are included. In cases with more than one hospitalization of the same patient for this period, his/her data are reported once. Retrospectively we found out that in the last decade there is a tendency for a relatively constant number of children with BA requiring hospital treatment in Bulgaria. We calculated the rate of severe bronchial asthma as 2.88% of children with asthma, requiring hospital treatment. Children with BA in Bulgaria in 20% have clinical symptoms of gastroesophageal reflux (GER). All children with severe asthma have additionally allergic rhinitis (AR). The use of LTRA as a control drug in asthma in children is prescribed mainly in children with concomitant AR. Children with BA are not in a higher percentage of overweight compared to the general population of children in Bulgaria. Additionally we have found that also accompanying AR and / or GER are more important for the severity of BA compared to overweight. Therefore, in cases with severe, non-controlled asthma sometimes adding therapy for AR and/or GER could be beneficial. Out of the children identified as one with severe asthma 20 children and their families agreed to participate in a prospective genetic study. Additionally, 59 children with bronchial asthma (not severe one) and 29 healthy children and their families were included after obtaining signed informed consent. The control group is smaller due to more difficult recruitment of children with signed informed consent, when the information obtained does not contribute directly to the children themselves. Allgroups are similar in sex and age distribution. For the genetic study we designed primers and probes for the 4 SNPs of ADAM33 (T1 (rs2280091, T/C), T2 (2280090, C/T), V4 (rs2787094, C/G) and S2 (rs528557, G/C)). During execution of this PhD thesis a protocol for each SNPs was optimized. There is a higher frequency of minor alleles for S2 (rs2787094) and V4 (rs528557) in children with asthma compared to healthy children in Bulgaria. The homozygotes on the minor allele for T2 (rs2280090) are found more in children with severe asthma than in other asthmatics. The same was noted for the minor T1 allele (rs2280091) of ADAM33. Minor alleles T2 and V4 are more common in children with a family history of asthma. Children with severe asthma have lower results in lung function test (FEV1, FVC, MMEF), higher numbers of peripheral and nasal eosinophilia, higher IgE levels and percentage of Th17, but none of these markers can serve as a prognostic factor for the persistence of the severity of bronchial asthma in children. About 40% of the children with mild to moderate asthma enter clinical remission within 5 years of follow-up, while children with severe asthma do not achieve complete clinical remission. The presence of 4 minor alleles of the studied polymorphisms is a risk factor for severe and persistent severe asthma, and four major alleles show a protective association for BA. All children with four major alleles on the studied SNPs in 5 years either enter in clinical remission or the severity of their asthma is extremely reduced. This study for the first time draws the attention of pediatricians, pediatric pulmonologists and allergists to the frequency and characteristics of severe asthma among children in Bulgaria. It further clarifies the importance and emphasizes the role of the minor alleles of ADAM33 polymorphisms in the persistence of the severity of bronchial asthma in childhood
Antimicrobial susceptibility of Pseudomonas aeruginosa before and after initiation of inhaled tobramycin in Bulgaria
Get PDFIntroduction: In aim to achieve better infection control and possible eradication of the pathogens involved in chronic infections of patients with cystic fibrosis (CF) scientists have developed a new way to administer antimicrobials – inhalation. The first and so far the only available inhalable antimicrobial in Bulgaria is inhaled tobramycin (TOBI), introduced in 2009.We aimed to evaluate the antimicrobial susceptibility of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients before and after initiation of TOBI in the regular treatment regimen.
Methodology: We have determined the minimal inhibitory concentration (MIC) of 17 antimicrobials by the E-test (LIOFILCHEM) in sputa samples of 118 CF patients for the period of 2005–2014. The results were interpreted according to the annual Clinical and Laboratory Standards Institute guidelines.
Results: In the sputa of 70 patients a total of 102 P. aeruginosa isolates were found. Sixty-eight out of 102 (66.7%) were susceptible to all studied antimicrobials. We divided the isolates in two chronological groups: those collected before the introduction of TOBI as a regular treatment in 2009 and those collected after 2009. A significant reduction (p < 0,001–0,02) in susceptibility for the strains after 2009 was noted towards piperacillin (100% vs 50%), ceftazidime (100% / 77.3%), cefepime (97.9% / 68.2%), amikacin (100% / 63.6%), gentamicin (95.7% / 40.9%), tobramycin (93.6% / 59.1%) and ciprofloxacin (93.6% / 45.5%).
Conclusion: The introduction of inhaled tobramycin as a regular therapy for CF patients in Bulgaria lead to a significant change in antimicrobial susceptibility of CF P. aeruginosa
The role of improved molecular genetic testing in the diagnosis of cystic fibrosis – a case series
No full textAbstract Cystic fibrosis (CF) is diagnosed through a combination of clinical symptoms, a sweat test, and genetic analysis. Over the last five years, significant advances in cystic fibrosis treatment have been driven by a better understanding of the disease’s genetic basis. This has enabled the development of more sophisticated genetic tests, allowing for more precise treatment for each individual patient. We present a case series of children with clinical presentations suggestive of cystic fibrosis, ambiguous sweat test results, and previous “negative” genetic analysis results. More precise and advanced genetic testing revealed that all three patients carried two CF-causing mutations. In cases where there is high clinical suspicion, despite initial results indicating a negative outcome, we recommend the use of MLPA analysis for the detection of large deletions and insertions that cannot be detected by standard sequencing methods
Measuring the bronchial reversibility in asthmatic children - clinical value of different indices
No full textLangerhans-Cell Histiocytoses - Epidemiology, Classification, Clinical Features, Diagnosis, Complications, Treatment and Prognosis
No full textHistiocytoses comprise a group of diverse diseases of unknown etiology with various clinical presentation and evolution. The underlying pathology is characterised by accumulation and infiltration of variable numbers of cells of the monocyte-macrophage line in the affected tissues and organs. Histiocytoses are divided into three major classes: Langerhans cell histiocytosis (LCH), non- Langerhans cell histiocytosis, and malignant histiocytic disorders. The term LCH (also known in the past as histiocytosis X) encompasses the following rare diseases: Eosinophilic Granuloma, Hand-Schuller-Christian disease, Letterer-Siwe disease, Hashimoto-Pritzker disease, in which accumulation of pathologic Langerhans cells (LCs) leads to tissue damage. LCs usually reside in the skin and ensure protection against infections by destroying foreign substances. LC accumulation is caused by antigen stimulation and inadequate immune response. Thus, clinical LCH manifestations range from isolated disease with mono- or multifocal bone lesions to disseminated multisystem disease. LCH is a rare disease, affecting mainly children and young smokers, aged 20-50 years. Lung involvement in LCH usually presents as a mono-system disease and is characterized by Langerhans cell granulomas (LCG) infiltrating and impairing the distal bronchioles. The definite diagnosis is based on lung biopsy of CAT selected LCG areas. So far, there is no an effective treatment, but the better understanding of the mechanisms involved in the pathogenesis of the disease would help in the development of effective therapeutic strategies in the future
