Impaired type I and type III interferon induction and rhinovirus control in human cystic fibrosis airway epithelial cells

Rhinoviruses are important triggers of pulmonary exacerbations and possible contributors to long-term respiratory morbidity in cystic fibrosis (CF), but mechanisms leading to rhinovirus-induced CF exacerbations are poorly understood. It is hypothesised that there is a deficient innate immune response of the airway epithelium towards rhinovirus infection in CF.

Distinct patterns of inflammation in the airway lumen and bronchial mucosa of children with cystic fibrosis

Studies in cystic fibrosis (CF) generally focus on inflammation present in the airway lumen. Little is known about inflammation occurring in the airway wall, the site ultimately destroyed in end-stage disease.

Use of sputum eosinophil counts to guide management in children with severe asthma

Previous studies in adults with asthma incorporating the control of sputum eosinophils into management strategies have shown significant reductions in exacerbations. A study was undertaken to investigate whether this strategy would be successful in children with severe asthma.

Airway remodelling and its relationship to inflammation in cystic fibrosis

Pulmonary disease is the most important cause of morbidity and mortality in cystic fibrosis (CF). Most patients with CF die from respiratory failure with extensive airway destruction. Airway remodelling, defined as structural airway wall changes, begins early in life in CF but the sequence of remodelling events in the disease process is poorly understood. Airway remodelling in CF has traditionally been thought to be solely the consequence of repeated cycles of inflammation and infection. However, new evidence obtained from developmental, physiological and histopathological studies suggests that there might instead be multiple mechanisms leading to airway remodelling in CF including (1) changes related to infection and inflammation; (2) changes specific to CF as a result of CF transmembrane conductance regulator (CFTR) dysfunction in the airway wall, independent of infection and inflammation; and (3) protective responses to (1) and/or (2). Recent advances in bronchoscopic techniques have allowed airway mucosal (endobronchial) biopsies to be taken in children and even infants. Endobronchial biopsy studies may provide insight into the role and relative contribution of the different mechanisms of airway remodelling in CF, with the main limitation that they assess only changes in proximal large airways and not in peripheral small airways from where CF disease is thought to originate. Findings from biopsy studies could encourage the development of novel therapeutic strategies targeting structural changes in addition to infection and inflammation.

Associations between fluctuations in lung function and asthma control in two populations with differing asthma severity

Lung function is a major criterion used to assess asthma control. Fluctuation analyses can account for lung function history over time, and may provide an additional dimension to characterise control. The relationships between mean and fluctuations in lung function with asthma control, exacerbation and quality of life were studied in two independent data sets.

Dual origins of dairy cattle farming - evidence from a comprehensive survey of European Y-chromosomal variation

BACKGROUND: Diversity patterns of livestock species are informative to the history of agriculture and indicate uniqueness of breeds as relevant for conservation. So far, most studies on cattle have focused on mitochondrial and autosomal DNA variation. Previous studies of Y-chromosomal variation, with limited breed panels, identified two Bos taurus (taurine) haplogroups (Y1 and Y2; both composed of several haplotypes) and one Bos indicus (indicine/zebu) haplogroup (Y3), as well as a strong phylogeographic structuring of paternal lineages. METHODOLOGY AND PRINCIPAL FINDINGS: Haplogroup data were collected for 2087 animals from 138 breeds. For 111 breeds, these were resolved further by genotyping microsatellites INRA189 (10 alleles) and BM861 (2 alleles). European cattle carry exclusively taurine haplotypes, with the zebu Y-chromosomes having appreciable frequencies in Southwest Asian populations. Y1 is predominant in northern and north-western Europe, but is also observed in several Iberian breeds, as well as in Southwest Asia. A single Y1 haplotype is predominant in north-central Europe and a single Y2 haplotype in central Europe. In contrast, we found both Y1 and Y2 haplotypes in Britain, the Nordic region and Russia, with the highest Y-chromosomal diversity seen in the Iberian Peninsula. CONCLUSIONS: We propose that the homogeneous Y1 and Y2 regions reflect founder effects associated with the development and expansion of two groups of dairy cattle, the pied or red breeds from the North Sea and Baltic coasts and the spotted, yellow or brown breeds from Switzerland, respectively. The present Y1-Y2 contrast in central Europe coincides with historic, linguistic, religious and cultural boundaries.

Serodiagnosis of Echinococcus spp. infection: explorative selection of diagnostic antigens by peptide microarray

BACKGROUND: Production of native antigens for serodiagnosis of helminthic infections is laborious and hampered by batch-to-batch variation. For serodiagnosis of echinococcosis, especially cystic disease, most screening tests rely on crude or purified Echinococcus granulosus hydatid cyst fluid. To resolve limitations associated with native antigens in serological tests, the use of standardized and highly pure antigens produced by chemical synthesis offers considerable advantages, provided appropriate diagnostic sensitivity and specificity is achieved. METHODOLOGY/PRINCIPAL FINDINGS: Making use of the growing collection of genomic and proteomic data, we applied a set of bioinformatic selection criteria to a collection of protein sequences including conceptually translated nucleotide sequence data of two related tapeworms, Echinococcus multilocularis and Echinococcus granulosus. Our approach targeted alpha-helical coiled-coils and intrinsically unstructured regions of parasite proteins potentially exposed to the host immune system. From 6 proteins of E. multilocularis and 5 proteins of E. granulosus, 45 peptides between 24 and 30 amino acids in length were designed. These peptides were chemically synthesized, spotted on microarrays and screened for reactivity with sera from infected humans. Peptides reacting above the cut-off were validated in enzyme-linked immunosorbent assays (ELISA). Peptides identified failed to differentiate between E. multilocularis and E. granulosus infection. The peptide performing best reached 57% sensitivity and 94% specificity. This candidate derived from Echinococcus multilocularis antigen B8/1 and showed strong reactivity to sera from patients infected either with E. multilocularis or E. granulosus. CONCLUSIONS/SIGNIFICANCE: This study provides proof of principle for the discovery of diagnostically relevant peptides by bioinformatic selection complemented with screening on a high-throughput microarray platform. Our data showed that a single peptide cannot provide sufficient diagnostic sensitivity whereas pooling several peptide antigens improved sensitivity; thus combinations of several peptides may lead the way to new diagnostic tests that replace, or at least complement conventional immunodiagnosis of echinococcosis. Our strategy could prove useful for diagnostic developments in other pathogens.

Multiple-breath washout measurements can be significantly shortened in children

Multiple-breath washout (MBW)-derived lung clearance index (LCI) is a sensitive measure of ventilation inhomogeneity in patients with cystic fibrosis (CF), but LCI measurement is time consuming. We systematically assessed ways to shorten LCI measurements. In 68 school-aged children (44 with mild CF lung disease) three standard nitrogen (N2) MBWs were applied. We assessed repeatability and diagnostic performance of (1) LCI measured earlier from three MBW runs and (2) LCI measured at complete MBW (1/40th of starting N2 concentration) from two runs only. Compared with the standard LCI from three complete MBW runs, the new LCI based on three N2MBW runs until 1/20th, or two complete runs until 1/40th, provided similar or better repeatability as well as sensitivity and specificity for CF lung disease. Alternative ways to measure LCI reduced test duration in children with CF by 30% and 41%, respectively. LCI measurements can be reliably shortened in children. These new MBW protocols may advance the transition of LCI from research into clinical settings.

[Case report: an exceptional case of a monozygotic thoracopagus parasiticus in a German Holstein calf]

A black and white German Holstein calf displayed a complex double malformation in shape of a thoracopagus parasiticus. By means of a molecular genetic investigation the genesis of the malformation from one zygote could be demonstrated. Both vertebral columns showed a pronounced lordosis, with the vertebral column of one animal ending in a rudimentary head. Close to this rudiment two derivates of branchial arches were found. The two thoracic cavities merged into one "thorax". In the shared thoracic cavity one heart was found. In its right atrium, a cherry-sized structure was found in which heart- and vascular smooth muscles were demonstrated histologically. The aorta split shortly after its origin to provide both animals with one aorta each. The larger pair of lungs was connected with a trachea leading to the head while the smaller pair of lungs originated from a trachea deriving from the rudimentary head. The diaphragm jejunum and split afterwards. The pedigree of the affected animal showed neither inbreeding nor any other affected animal.

The relationship between coagulation and the extend of surgery and postoperative infection in surgical infants below 6 months of age

AIM: First to assess coagulation changes after surgery in children below 6 months of age. Second to detect differences attributable to the extent of surgery and postoperative infection. MATERIALS AND METHODS: Blood counts, haemoglobin concentration (Hb), haematocrit (Ht), prothrombine time (PT), activated partial thromboplastine time (aPTT) and thrombelastography (TEG) were studied pre- and 2+/-1/2 d postoperatively. Patients were divided in 3 groups. I: minor surgery without access to the abdomen or thorax (n=51); II: abdominal or thoracic interventions (n=24); III: abdominal surgery with postoperative sepsis (n=11). RESULTS: Preoperative values of Hb, Ht and INR were related to the age of the infant. Postoperatively clot strength and formation rate increased in gr. I (p<0.05). In gr. II, clot formation was initiated earlier (p<0.05) even though PT decreased (p<0.05). In group III, patients postoperatively developed a tendency for hypocoagulability in all TEG-parameters, but not in plasmatic coagulation. Postoperative TEG measurements were significantly inferior in gr. III when compared to gr. I and II. CONCLUSION: Our findings suggest activation of whole blood coagulation in the uncomplicated postoperative period despite of a decrease in plasmatic coagulation. In sepsis, only thrombelastography, but not plasmatic coagulation was affected.

[Pulmonary microscopic tumor embolism syndrome]

HISTORY: A 76-year-old woman and a 62-year-old man were both referred to our clinic because of an unexplained weight loss, increasing dry cough and shortness of breath. INVESTIGATIONS: Investigations revealed an adenocarcinoma of the colon with retroperitoneal, mediastinal and supraclavicular lymph node metastasis and poorly differentiated carcinoma of the prostate with extensive bone metastases. During their hospital stay both patients developed increasing shortness of breath and clinical signs of right heart failure. Echocardiography confirmed severe pulmonary hypertension and dilatation of the right ventricle in both patients. Despite the high degree of clinical suspicion CT scans of the thorax could not demonstrate pulmonary embolism. DIAGNOSIS, TREATMENT AND COURSE: During the following days the patients condition deteriorated further and both patients' died from irreversible right heart failure. Both autopsies showed extensive metastatic adenocarcinoma with marked angiosis carcinomatosa of the lungs with numerous occlusions of small arteries and arterioles and resulting cor pulmonale. Thrombotic pulmonary embolism could not be detected. CONCLUSION: In patients with malignant neoplasms, especially adenocarcinomas, dyspnea and signs of increasing pulmonary artery pressure, the possibility of a microscopic pulmonary tumor embolism should be considered after exclusion of more usual causes especially thrombotic pulmonary embolism. In selected cases a cytologic examination of blood aspirated from a wedged pulmonary artery catheter can be performed to prove angiosis is carcinomatosa.

Alterations of the thoracic spine in Marfan's syndrome

OBJECTIVE: The purpose of this study was to determine if the thoracic vertebral elements are altered in patients with Marfan's syndrome. MATERIALS AND METHODS: Thirty patients underwent helical CT of the thorax because of suspected thoracic aortic dilatation and acute dissection. Thirteen had Marfan's syndrome and 17 did not. Two reviewers, unaware of the final diagnosis, evaluated the images by consensus for laminar thickness, foraminal width, dural sac ratios, and vertebral scalloping for T2-T12. RESULTS: At T9-T12, dural sac ratios at the midcorpus level (p = 0.031) and foraminal width (p = 0.0124) were significantly greater in the patients with Marfan's syndrome than in the patients without. Dural sac ratios at lower endplate levels (p = 0.0685), laminar thickness (p = 0.951), and vertebral scalloping (p = 0.24) were not significantly greater in the patients with Marfan's syndrome than in the patients without. CONCLUSION: Because the phenotypic expression of Marfan's syndrome is variable, information on the spine from thoracic studies in combination with major criteria may be helpful clinically.

Locally generated particulate pollution and respiratory symptoms in young children

BACKGROUND: Particulate matter <10 mum (PM(10)) from fossil fuel combustion is associated with an increased prevalence of respiratory symptoms in children and adolescents. However, the effect of PM(10) on respiratory symptoms in young children is unclear. METHODS: The association between primary PM(10) (particles directly emitted from local sources) and the prevalence and incidence of respiratory symptoms was studied in a random sample cohort of 4400 Leicestershire children aged 1-5 years surveyed in 1998 and again in 2001. Annual exposure to primary PM(10) was calculated for the home address using the Airviro dispersion model and adjusted odds ratios (ORS) and 95% confidence intervals were calculated for each microg/m(3) increase. RESULTS: Exposure to primary PM(10) was associated with the prevalence of cough without a cold in both 1998 and 2001, with adjusted ORs of 1.21 (1.07 to 1.38) and 1.56 (1.32 to 1.84) respectively. For night time cough the ORs were 1.06 (0.94 to 1.19) and 1.25 (1.06 to 1.47), and for current wheeze 0.99 (0.88 to 1.12) and 1.28 (1.04 to 1.58), respectively. There was also an association between primary PM(10) and new onset symptoms. The ORs for incident symptoms were 1.62 (1.31 to 2.00) for cough without a cold and 1.42 (1.02 to 1.97) for wheeze. CONCLUSION: In young children there was a consistent association between locally generated primary PM(10) and the prevalence and incidence of cough without a cold and the incidence of wheeze which was independent of potential confounders.

Postmortem noninvasive virtual autopsy: extrapleural hemorrhage after blunt thoracic trauma

A 19-year-old man speeding recklessly along a highway caused a left-frontal crash with another car. After his vehicle came to a standstill, he climbed out of the wreck and crawled across the tarmac to the other side of the road, where he died several minutes after the accident and before the arrival of an ambulance. Postmortem multislice computed tomography (MSCT) demonstrated fractures of the first, second, and third ribs and scapula on the left, an extrapleural hemorrhage in the apical region of the left thorax, as well as a large amount of blood in the left thoracic cavity. These radiologic findings were indicative of a delayed rupture of a traumatic extrapleural hematoma into the pleural space. A traditional autopsy confirmed the very rare diagnosis of a traumatic extrapleural hemorrhage with a delayed rupture.