Cystic fibrosis presentation in del. F508 and p. Tyr109Glyfs compound heterozygote CFTR state: a case report.

The diagnosis of cystic fibrosis (CF) is commonly confirmed by molecular genetics with the presence of specific mutations of cystic fibrosis transmembrane conductance regulator (CFTR) gene. We report a case of cystic fibrosis (CF) in a 15-year-old female patient who is a compound heterozygote for CFTR gene, with delta F508 and Tyr109Glyfs mutations detected. This is the first detailed description of such a case in the medical literature. The primary CF presentation occurred at the age of 9 in the form of gastrointestinal symptoms including greasy, bulky, and foul-smelling stool. The patient exhibited delayed growth, with her height and weight being below the 5th centile for age according to the World Health Organization growth curves. Pancreatic enzyme supplement treatment was started immediately, alongside high-fat and high-calorie diet, resulting in patient's recovery and development. DNA analysis of CFTR gene demonstrated the presence of del. F508 mutation and a rare combining deletion and insertion mutation p. Tyr109Glyfs. The combination of the two mutations is very rare in CF patients and is therefore valuable to document this case in order to provide information on disease progression, therapy options, and outcomes. With standard treatment and early diagnosis, the patient is currently doing well and is not restricted by the disease in her daily and sports activities.

ACUTE RESPIRATORY DISTRESS SYNDROME IN A FOUR-YEAR-OLD BOY WITH DIABETIC KETOACIDOSIS - CASE REPORT.

- Among many disease states as known initiators of acute respiratory distress syndrome (ARDS), diabetic ketoacidosis (DKA) is the rarest one. We present a 4-year-old boy with DKA as the first manifestation of insulin-dependent diabetes mellitus who developed ARDS, required tracheal intubation and mechanical ventilation, and survived without significant sequels. To improve survival of patients with ARDS as a complication of DKA, physicians should be aware of this rare pulmonary complication and its appropriate management.

[Which tuberculin skin test hyperreactive child should be treated with -our experience]. / KOJIM PPD-HIPERREAKTORIMA TREBA DATI PROFILAKSU - NASA ISKUSTVA.

Since persons with latent tuberculosis infection (LTBI) represent a huge reservoir of potential tuberculosis (TB) disease, accurate diagnosis and treatment of LTBI is essential for TB control and eradication. The aim was to assess the diagnostic value of determination of interferon-gamma release assay in school children with hyperreactive tuberculin skin test (TST) reaction. A total of 120 BCG-vaccinated children were investigated due to a hyperreactive TST results. The QuantiFERON-TB Gold In-Tube test (QFT-GIT) was performed. Fifteen children (12.5%) had positive QFT-GIT and 105 (87.5%) children had negative QFT-GIT. There was no statistically significant difference in TST reaction (21.5 mm u QFT+ vs. 20.9 mm u QFT-group, p=0.458). The children with positive QFT-GIT had a statistically higher level of interferon-gamma (IFN-γ) than children with negative QFT-GIT. There were no statistically significant differences in concentrations of IFN-y either basic or upon stimulation with mitogen phytohemagglutinin. After isoniazid prophylaxis QFT-GIT remained positive in two children (p=0.019). In a difficult procedure for diagnosing LTBI in BCG-vaccinated children determination of IFN-γ could be the key factor in making decision whether to use preventive therapy or not.

[Treatment of empyema thoracis in children]. / Lijecenje empijema prsista u djece.

Empyema, an accumulation of infected fluid in the thoracic cavity, is commonly secondary to bacterial pneumonia in children. Despite the high prevalence and availability of many medical treatment options, there is no general consensus on the optimal management approach, which would lead to full and rapid recovery. Especially, there are the big differences in treatment options for the child with empyema. Regardless of the differences in the procedures, the ultimate outcomes are good. This article reviews the current literature and discusses the important considerations in managing these patients. This paper describes thoracoscopic and open thoracic surgery procedures in children. The authors present their own observations based on years of experience in the treatment of thoracic empyema.

[Hematopoietic stem cell transplantation in children with primary immunodeficiencies]. / Transplantacija krvotvornih maticnih stanica u djece s primarnim imunodeficijencijama.

Hematopoietic stem cell transplantation is the optimal treatment for patients with primary immunodeficiencies. Best results are achieved with stem cells from a HLA-identical donor, but it is only possible in a small number of patients. Until recently, HLA-mismatched/haploidentical hematopoietic stem cell transplantation was reserved exclusively for patients with severe combined immunodeficiency (SCID). However, as there are many haploidentical donors, it has become the treatment of choice for many other severe primary immunodeficiencies. Apart from appropriate choice of the donor, treatment of infections and pre-transplantation patient conditioning have major impact on transplantation outcome in patients with primary immunodeficiencies.

Expression of chemokine receptor CX3CR1 in infants with respiratory syncytial virus bronchiolitis.

Respiratory syncytial virus (RSV) glycoprotein G mimics fractalkine, a CX(3)C chemokine, which mediates chemotaxis of leukocytes expressing its receptor, CX(3)CR1. The aim of this study was to examine the relationship between RSV infection and expression of perforin and IFN-gamma in CX(3)CR1-expressing peripheral blood CD8(+) T cells. Samples were collected from infants with RSV bronchiolitis, both in the acute and convalescence phase (n = 12), and from their age- and sex-matched healthy controls (n = 15). Perforin expression and IFN-gamma secretion in CX(3)CR1(+) CD8(+) T cells were assessed by four-color flow cytometry. The NF-kappaB p50 and p65 subunit levels were also determined as markers of RSV-induced inflammation. Study results showed perforin and CX(3)CR1 expression to be significantly lower in the convalescent phase of infected infants than in healthy controls. There was no significant difference in IFN-gamma secretion and NF-kappaB binding activity between two time-points in RSV-infected infants, or when compared with healthy controls. Infants with prolonged wheezing had lower acute-phase CX(3)CR1 levels in peripheral blood. These data indicate existence of an event persisting after acute RSV infection that is able to modulate effector functions of cytotoxic T cells, and also link disease severity with CX(3)CR1 expression.

Met-enkephalin effects on histamine-induced bronchoconstriction in guinea pigs.

We investigated the effects of the neuropeptide met-enkephalin on histamine-induced bronhoconstriction in an experimental model of asthma. Classic Konzett and Rössler's method of whole body plethysmography modified by Gjuris, was applied in the study. This method represents a standard experimental model of bronchoconstriction, suitable for the evaluation of peptide effects on the histamine-induced bronchoconstriction. The results of the measurements implicate a dose-related modulatory effect of met-enkephalin on the bronchoconstrictor action of histamine. Met-enkephalin doses of 1 mg/kg and 10 mg/kg, respectively, caused statistically significant reduction of the histamine-induced bronchoconstriction. Estimated ED50 dose was 0.235 mg/kg. Further studies are needed to define practical and therapeutical use of the presented observations in respiratory pharmacology.

Adherence ability of Pseudomonas aeruginosa strains isolated from patients with cystic fibrosis to two different epithelial cell lines.

The ability of 59 wild-type strains of Pseudomonas aeruginosa to adhere to the HeLa and Buffalo Green Monkey Kidney (BGMK) cells was investigated. Twenty strains were isolated from sputa of cystic fibrosis patients, while 19 strains were isolated from tracheal aspirates and 20 from bronchial secretions of patients without cystic fibrosis, and they were used as a control group of strains. The statistically significant difference between adherence ability of strains was observed (p < 0.01). While most of the tracheal and bronchial isolates were hyperadhesive (51-110 bacteria per cell) most of the cystic fibrosis isolates adhered poorly to the HeLa and BGMK cells (1-10 bacteria per cell). The bacterial binding to the cells was blocked when bacteria were incubated at 80 degrees C for 20 min before the adherence assay. These results indicate that alginate is not involved in the adherence of P. aeruginosa to the used epithelial cell lines, and, because of that, mucoid strains isolated from persistently colonized cystic fibrosis patients showed poor adherence ability.