Rare association between cystic fibrosis, Chiari I malformation, and hydrocephalus in a baby: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Cystic fibrosis, an epithelial cell transport disorder caused by mutations of the cystic fibrosis transmembrane conductance regulator gene, is not generally associated with malformations of the central nervous system. We review eight previously published reports detailing an infrequent association between cystic fibrosis and Chiari I malformation.</p> <p>Case presentation</p> <p>To the best of our knowledge, our report describes only the ninth case of a baby presenting with a new diagnosis of cystic fibrosis and Chiari I malformation, in this case in a 10-month-old, full-term Caucasian baby boy from the United States of America. Neurosurgical consultation was obtained for associated developmental delay, macrocephaly, bulging anterior fontanel, and papilledema. An MRI scan demonstrated an extensive Chiari I malformation with effacement of the fourth ventricle, obliteration of the outlets of the fourth ventricle and triventricular hydrocephalus without aqueductal stenosis. Our patient was taken to the operating room for ventriculoperitoneal shunt placement.</p> <p>Conclusions</p> <p>It is possible that the cystic fibrosis transmembrane conductance regulator gene may play a previously unrecognized role in central nervous system development; alternatively, this central nervous system abnormality may have been acquired due to constant valsalva from recurrent coughing or wheezing or metabolic and electrolyte imbalances that occur characteristically in cystic fibrosis.</p

Modelling the Cost Effectiveness of Interventions for Osteoporosis: Issues to Consider

Expenditure on treating osteoporotic fractures and on preventative intervention is considerable and is likely to rise in forthcoming years due to the association between fracture risk and age. With funders such as the National Institute for Health and Care Excellence and the Pharmaceutical Benefits Advisory Committee explicitly considering cost-effectiveness analyses within the process of producing guidance, it is imperative that economic models are as robust as possible. This article details issues that need to be considered specifically related to health technology assessments of interventions for osteoporosis, and highlights limitations within the current evidence base. A likely direction of impact on cost effectiveness of addressing the key issues has been included alongside a tentative categorization of the level of these impacts. It is likely that cost-effectiveness ratios presented in previous models that did not address the identified issues were favourable to interventions

Expression and Distribution of Cystic Fibrosis Transmembrane Conductance Regulator in Neurons of the Human Brain

The importance of the molecule cystic fibrosis transmembrane conductance regulator (CFTR) is reflected in the many physiological functions it regulates. It is known to be present in epithelial cells of the lungs, pancreas, sweat glands, gut, and other tissues, and gene mutations of CFTR cause cystic fibrosis (CF). We studied the expression and distribution of CFTR in the human brain with reverse transcriptase polymerase chain reaction, in situ hybridization, and immunohistochemistry. This study demonstrates widespread and abundant expression of CFTR in neurons of the human brain. Techniques of double labeling and evaluation of consecutive tissue sections localized CFTR protein and mRNA signals to the cytoplasm of neurons in all regions of the brain studied, but not to glial cells. The presence of CFTR in central neurons not only provides a possible explanation for the neural symptoms observed in CF patients, but also may lead to a better understanding of the functions of CFTR in the human brain. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. (J Histochem Cytochem 57:1113–1120, 2009