Ugur Ozcelik

Mutations in SLC34A2 Cause Pulmonary Alveolar Microlithiasis and Are Possibly Associated with Testicular Microlithiasis

Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by the deposition of calcium phosphate microliths throughout the lungs. We first identified a PAM locus by homozygosity mapping to 4p15, then identified, by a candidate-gene approach, the gene responsible for the disease as SLC34A2 (the type IIb sodium-phosphate cotransporter gene), which is involved in phosphate homeostasis in several organs. We identified six homozygous exonic mutations in the seven unrelated patients with PAM we studied. Three of the mutations were frameshifts, one was a chain termination, one was an amino acid substitution, and one was a deletion spanning the minimal promoter and the first exon. Absence of functional protein product of the gene is compatible with calcium phosphate deposition in alveolar airspaces. We show that impaired activity of the phosphate transporter is presumably responsible for the microliths and that PAM is a recessive monogenic disease with full penetrance. Testicular microlithiasis (TM) is a disease that is more common than PAM. It is often associated with cancer and infertility. Since the gene we identified is also expressed in testis, we searched for mutations in subjects with TM. In 2 of the 15 subjects with TM we studied, we identified two rare variants, one synonymous and the other noncoding, that are possibly associated with the condition.

Effects of claritromycin on inflammatory parameters and clinical conditions in children with bronchiectasis.

Background:  The effects of the macrolides cannot be ascribed to their antibacterial action alone. Their immunoregulatory and anti‐inflammatory functions are significant too. They are frequently used in the treatment of diffuse panbronchiolitis and cystic fibrosis (CF).

High resolution CT in children with cystic fibrosis: correlation with pulmonary functions and radiographic scores

OBJECTIVE To compare the high resolution CT (HRCT) scores of the Bhalla system with pulmonary function tests and radiographic and clinical points of the Shwachman-Kulczycki clinical scoring system. METHODS HRCT of the chest was obtained in 40 children to assess the role of HRCT in evaluating bronchopulmonary pathology in children with cystic fibrosis (CF). The HRCT severity scores of the Bhalla system were compared with chest radiographic and clinical points of the Shwachman-Kulczycki scoring system and pulmonary function tests. Only 14 of the patients older than 6 years cooperated with spirometry. RESULTS HRCT scores correlated well with radiographic points (r = 0.80, P<0.0001) and clinical points (r=0.67. P<0.0001) of the Shwachman-Kulczycki system, FVC (r = 0.71 P = 0.004) and FEV1 (r = 0.66, P = 0.01). Although radiographic points correlated significantly with FVC (r = 0.61, P = 0.02) and FEV1 (r = 0.56, P = 0.04), HRCT provides a more precise scoring than the chest X-ray. CONCLUSION The HRCT scoring system may provide a sensitive method of monitoring pulmonary disease status and may replace the radiographic scoring in the Shwachman-Kulczycki system. It may be helpful especially in follow-up of small children too young to cooperate with spirometry.

Treatment of Hydatid Disease

Hydatid disease caused by Echinococcus granulosus presents medical, veterinary and economic problems worldwide. Hydatidosis can be treated by medical, surgical and percutaneous modalities. Benzoimidazole carbamates are effective against E. granulosus. Although mebendazole, the first benzoimidazole used, has some beneficial effects on the disease in selected patients, it has also been associated with treatment failure in some cases, perhaps because of its poor absorption. Albendazole, a more recently developed benzoimidazole, is more effective than mebendazole. Praziquantel, an isoquinoline derivative, has recently shown value in the treatment of human echinococcal disease and its use in combination with albendazole is recommended in some patients. Ultrasound guided cyst puncture is another choice of treatment which has been used successfully in selected patients, although anaphylactic and allergic reactions due to spillage of the cyst contents have occurred. Surgical therapy in echinococcal hydatid disease is indicated for large cysts with multiple daughter cysts, superficially located single liver cysts which have a risk of rupture, complicated cysts such as those accompanied by infection, compression or obstruction, and cysts located in vital organs or which are exerting pressure on adjacent vital organs. However, surgical therapy carries high risk of mortality, morbidity or recurrence. Therefore, medical therapy may be an alternative option in uncomplicated cysts and in patients at high risk from surgery. The adjuvant use of drugs with surgery and percutaneous treatment can also be recommended for some patients.

Postinfectious Bronchiolitis obliterans in Children: Clinical and Radiological Profile and Prognostic Factors

Background: Postinfectious bronchiolitis obliterans (BO) designates a clinical syndrome of chronic airflow obstruction associated with inflammatory changes in the small airways. Objectives: The aim of this study was to determine the etiology, clinical and radiological features and define prognostic factors of postinfectious BO in children. Methods: We undertook a review of the medical records of 20 children with postinfectious BO, who were followed up between January 1994 and August 2001. Results: Postinfectious BO was diagnosed in 11 boys and 9 girls with a median age of 21.5 months (6–69 months) who were followed up for a median of 23 months. Cough and wheezing persisted since the initial lung infection in all patients. Postinfectious BO was diagnosed in an average of 6 months (1–42 months) after the acute illness. Adenoviruses were the most common etiologic agents identified serologically. The diagnoses of postinfectious BO was made by thoracic high-resolution computed tomography and clinical features. Corticosteroid therapy was used in 17 patients and supportive treatment was applied in all patients. Age at initial lung infection, gender, time of starting corticosteroid treatment, presence of bronchiectasis or atelectasis and etiologic agents identified on presentation did not predict severity in our study. Conclusions: Despite the prominent role of inflammation in the pathogenesis of postinfectious BO, the use of anti-inflammatory agents remains controversial. We could not identify any prognostic factors related to disease severity. In order to minimize associated complications, patients with postinfectious BO should be closely followed up and receive meticulous lung care.

Conservative Treatment of Empyema in Children

Seventy-two children with no underlying diseases were treated for empyema. Radical surgical approaches like decortication were necessary for only 3 children. In 66 children tube drainage was applied. Staphylococcus aureus was cultured or was shown in Grams stain in 32 (44%) and children with this microorganism had longer duration of tube drainage (p < 0.05). The period for normalization of chest X-ray was positively related with the age of the patient (p < 0.05). In 60 of 72 children, chest X-ray was normal after 3 months. Follow-up of the patients 18 months after the infection revealed that pulmonary radiograms were normal in all cases and pulmonary function tests were within normal limits in all of the tested children (n = 25). It is emphasized that avoiding major surgical approaches must be encouraged in childhood empyema.

Gorham-Stout Syndrome with chylothorax: successful remission by interferon alpha-2b.

Gorham–Stout syndrome is a rare disease and most often recognized in children and young adults. Chylothorax is a serious complication of Gorham–Stout syndrome. The treatment of either Gorham–Stout syndrome or chylothorax is still a dilemma. We described a 9‐year‐old girl with Gorham–Stout syndrome and chylothorax who was admitted to our hospital because of dyspnea, orthopnea, and bone pain, and treated with interferon alpha‐2b. Pediatr Pulmonol. 2009; 44:613–615.

Clinical features and treatment approaches in cystic fibrosis with pseudo-Bartter syndrome.

Abstract Introduction: Infants with cystic fibrosis (CF) are prone to develop episodes of hyponatraemic, hypochloraemic dehydration with metabolic alkalosis, which are biochemical hallmarks of the pseudo-Bartter syndrome (PB). Method: We reviewed the clinical and laboratory features and treatment aproaches of 29 children with CF and PB who were under follow-up in our institution from May 1992 to November 2003. Results: Of 241 patients with CF, PB was detected in 29 (12%) with a median age of 4 months at the time of the first attack. Most patients experienced vomiting, loss of appetite and dehydration during episodes of PB. All patients were managed with intravenous fluids and sodium chloride solutions. During follow-up, 12/29 cases required hospital admission for recurrent PB attacks. The oldest age at the time of the last attack was 48 months. Conclusions: CF should be considered in the differential diagnosis of metabolic alkalosis in young children. Vomiting and loss of appetite are important warning signs of possible PB in CF patients, particularly before 4 years of age. To prevent serious complications, it is crucial that parents and physicians recognise PB as early as possible.

Tracheomalacia and Bronchomalacia in 34 Children: Clinical and Radiologic Profiles and Associations with Other Diseases

We reviewed our experience on tracheomalacia (TM) and bronchomalacia (BM) in children who presented with chronic respiratory problems and evaluated their clinical and radiologic characteristics and their associations with other disorders. There were 26 males and 8 females with a median age of 9 months. The main symptoms were wheezing, persistent or recurrent pneumonia, and chronic cough. Atelectasis on chest radiograph was the most common sign. Of 23 children with TM, 1 had a double aortic arch, 1 had tracheoesophageal fistula, and 1 other had associated laryngomalacia. BM was found in 27 children and was predominantly seen on the right side. TBM was found in 16 cases (in an infant TBM was accompanied by pharyngeal dyskinesia and in another by laryngomalacia). Malacia disorders were associated with gastroesophageal reflux, cardiovascular anomalies, and tracheoeosophageal fistula. TM and BM should be considered in the differential diagnosis of children with chronic and recurrent respiratory symptoms. Early diagnosis of malacia disorders will prevent unnecessary use of antibiotics or antiasthmatic drugs, which are often abused to treat these children. In these patients, treatment for associated diseases should also be considered.

Study of 12 mutations in Turkish cystic fibrosis patients

67 unrelated cystic fibrosis (CF) patients were screened for some of the most common mutations of the CFTR gene. This analysis resulted in the identification of 34.6% of all CF alleles. The most common mutation is delta F508 (28.4%). Two other mutations account for a further 6.7% of the alleles (R347H: 3.0%; N1303K: 3.7%). 1677delTA, G542X, G551D, S549N/I, R553X, L558S, R334W, and R297Q were not detected.