Ayhan Göçmen

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.

Long-term clinical course of patients with idiopathic pulmonary hemosiderosis (1979-1994): prolonged survival with low-dose corticosteroid therapy.

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease of unknown etiology characterized by recurrent episodes of pulmonary symptoms such as cough, hemoptysis, and dyspnea. Our study consisted of 23 patients: 12 males and 11 females with IPH. The diagnosis was based on history, presence of anemia, and characteristic chest X‐ray, and was confirmed by showing macrophages laden with hemosiderin in gastric washings or bronchoalveolar lavage and/or open lung biopsy. All but one patient were diagnosed in our department between 1979–1994.

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.

Percutaneous treatment of pulmonary hydatid cysts

PurposeTo evaluate the safety and efficacy of percutaneous drainage of pulmonary hydatid cysts.MethodsEleven pulmonary hydatid cysts in eight patients were drained percutaneously after 1–2 years of treatment with mebendazole (50 mg/kg/day). Percutaneous needle aspiration was carried out under ultra-sound (US) in six patients and computed tomography (CT) in two patients. Nine cysts were close to, and two cysts were distant from the thoracic wall. After aspiration, hypertonic (15%) saline solution was instilled for up to 35% of the estimated volume of the cyst and aspirated 5–10 min later. Follow-up ranged from 8 to 31 months (mean 16.3 months).ResultsNeither anaphylactic shock nor death occurred in any of the eight patients. One patient developed fever, ipsilateral hydropneumothorax, and contralateral pleural effusion. One patient suffered from fever, pneumothorax, and abscess and was treated surgically; one developed fever and dyspnea. The volume reduction during follow-up was 47%–93%. The cystic contents turned into a pseudotumor appearance with a thick irregular contour on CT and higher Hounsfield units. On US, the cysts showed a heterogeneous content with internal echoes representing detached and degenerated membranes, and the fluid content almost completely disappeared.ConclusionWe believe that percutaneous therapy of pulmonary hydatid disease is an effective alternative to surgical treatment in patients who have failed medical therapy.

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.

Hydatid disease in childhood: A retrospective analysis of 376 cases

During a 20‐year period, 376 children with hydatid disease were treated at Hacettepe University Ihsan Dog˘ramaci Childrens Hospital. There were 223 males and 153 females with a mean age of 8.9 ± 0.1 years. Hydatid cysts were localized in the lungs in 222 patients, in the liver in 56 patients, and in other organs in the remaining patients. Cough, fever, and abdominal pain were the most common symptoms. One hundred eight patients had medical, 182 patients had surgical, 73 patients had medical and surgical, and 4 patients had medical and percutaneous drainage treatment as the initial therapy.

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.

Hexachlorobenzene exposure and the proportion of male births in Turkey 1935-1990.

Hexachlorobenzene (C(6)Cl(6), HCB) is a chemical that has been associated with significant immediate and long term adverse health effects in humans. It has been associated with both porphyria cutanea tarda and spontaneous abortions among survivors of widespread exposure in the 1950s in southeastern Turkey. HCB binds to the Ah receptor, albeit with lower affinity than dioxin. Dioxin exposure has been reported to lower human secondary sex ratio, putatively through a male mediated effect. We therefore wished to evaluate the impact of the HCB environmental event on the sex ratio of the progeny of the survivors. We undertook an assessment of 1) the effects of HCB exposure on the proportion of male births of individual subjects who had survived, 2) variables that significantly predicted the proportion of males among these individuals, and 3) the trend of the population sex ratio born in Turkey from 1935 to 1990. Women known to have been exposed to HCB in the 1950s did not have offspring with a significantly different sex ratio when compared to control populations. However, subjects reporting exposure at the peak of the episode (1955-57) had a significantly lower lifetime proportion of males than those exposed at a later date. The lifetime reported spontaneous abortion rate of these women also significantly predicted the percent males per subject. The available national data demonstrated a significant reduction in the calculated proportion of males from 1935 to 1970 that stabilized from 1970 to 1990. These data indicate that HCB exposure that was sufficient to induce clinical porphyria cutanea tarda may also have reduced the proportion of males in subjects over their reproductive life-span. The HCB episode does not explain the pattern of the national trend from a population perspective.