Primary ciliary dyskinesia (PCD) is a hereditary disorder of mucociliary clearance causing chronic upper and lower airways disease. We determined the number of patients with diagnosed PCD across Europe, described age at diagnosis and determined risk factors for late diagnosis.Centres treating children with PCD in Europe answered questionnaires and provided anonymous patient lists.In total, 223 centres from 26 countries reported 1,009 patients aged <20 yrs. Reported cases per million children (for 5–14 yr olds) were highest in Cyprus (111), Switzerland (47) and Denmark (46). Overall, 57% were males and 48% hadsitus inversus. Median age at diagnosis was 5.3 yrs, lower in children withsitus inversus(3.5versus5.8 yrs; p<0.001) and in children treated in large centres (4.1versus4.8 yrs; p = 0.002). Adjusted age at diagnosis was 5.0 yrs in Western Europe, 4.8 yrs in the British Isles, 5.5 yrs in Northern Europe, 6.8 yrs in Eastern Europe and 6.5 yrs in Southern Europe (p<0.001). This strongly correlated with general government expenditures on health (p<0.001).This European survey suggests that PCD in children is under-diagnosed and diagnosed late, particularly in countries with low health expenditures. Prospective studies should assess the impact this delay might have on patient prognosis and on health economic costs across Europe.

Background-Patients with cystic fibrosis (CF) have significantly decreased plasma concentrations of nutrient antioxidant vitamins, especially of -carotene, which is thought to result from fat malabsorption and chronic pulmonary inflammation. The aim of this double blind, placebo controlled study was to investigate the eVect of oral -carotene supplementation for six months on clinical parameters. Methods-Twenty four patients with CF were randomised to receive -carotene 1 mg/kg/day (maximum 50 mg/day) for three months (high dose supplementation) and 10 mg/day for a further three months (low dose supplementation) or placebo. At monthly follow up visits the plasma -carotene concentration, total antioxidant capacity, malondialdehyde (MDA) as a marker of lipid peroxidation, and clinical parameters (ShwachmannKulczycki score, body mass index (BMI), height, and lung function (FEV 1 )) were assessed. The number of pulmonary exacerbations requiring antibiotic treatment (in days) three months before and during the study were evaluated. Results-The plasma concentration of -carotene increased significantly to the normal range during the three months of high dose supplementation (baseline 0.08 (0.04) µmol/l to 0.56 (0.38) µmol/l; p<0.001) but decreased to 0.32 (0.19) µmol/l in the period of low dose supplementation. Initially raised plasma levels of MDA fell to normal levels and the total antioxidant capacity showed a nonsignificant trend towards improvement during high dose supplementation. Antibiotic treatment decreased significantly in the supplementation group from 14.5 (14.9) days/patient during the three months before the study to 9.8 (10.3) days/ patient during high dose supplementation (p=0.0368) and to 10.5 (9.9) days/patient during low dose supplementation, but increased in the placebo group. The Shwachmann-Kulczycki score, lung function, and BMI did not show any changes in either of the treatment groups. No adverse events were observed during the study period. Conclusion-Oral -carotene supplementation in a dose of 1 mg/kg/day only was eVective in normalising the plasma concentration of -carotene and resulted in a decrease in pulmonary exacerbations. These data suggest that patients with CF may benefit clinically from supplementation with -carotene and further studies are warranted. (Thorax 2001;56:48-52)

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The human genome maybe limited to about 30000 genes whereas the human proteome may be represented by a rough estimate of one million proteins. A legion of proteins have been described and information about these structures are readily available in data banks. There remains, however, a large series of unknown or hypothetical proteins (HPs). Many of them have been predicted from nucleic acid sequences only and are therefore named predicted or HPs. Carrying out "protein hunting" by generating large maps of human cell lines, we aimed to find and identify HPs and provide an analytical tool thereof. Cell lysates from human bronchial epithelial, fibroblast, amnion, lymphocyte, mesothelial and kidney cell lines were prepared and proteins run on two-dimensional gel-electrophoresis (2DE) with in-gel digestion and mass spectrometrical analysis using the MALDI-TOF principle.16 HPs were found in these cell lines and some show cell-specific expressional patterns. HPs belong to several protein classes including structural, signaling, transcriptional/translational, chaperone-related and others. We furthermore provide analytical data i.e. pIs that were often different from predicted values in data banks.A list of HPs has been shown to really exist in several human cell lines thus contributing to knowledge on protein machineries and cascades. Observed and predicted pI values are given representing an analytical tool along with unambiguous identification of protein spots by mass spectrometry independent of antibody availability and specificity thus complementing established methods.

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