Borowitz D.,Childrens Hospital of Buffalo
Pediatric Pulmonology | Year: 2015
The gene that encodes for the cystic fibrosis transmembrane regulator protein (CFTR) was identified in 1989, yet major pathophysiologic questions remain unanswered. There is emerging evidence that CFTR is a bicarbonate channel, a driver of chloride-bicarbonate exchange and through its action on local pH, a regulator of other ion channels and of proteins that function optimally in a neutral environment. In both the respiratory and gastrointestinal (GI) tracts, bicarbonate drives ionic content and fluid on epithelial surfaces, allows mucins to unfold and become slippery, and contributes to innate immunity. In the GI tract bicarbonate neutralizes gastric acid to support digestion and absorption. When CFTR is dysfunctional, lack of bicarbonate secretion disrupts these normal processes and thus leads directly to the clinical symptoms and signs of CF. This article synthesizes evidence from cell, animal, and human investigations that support these concepts. Bicarbonate secretion does not seem to be the same in all tissues and varies with physiologic demand. Thus, tissue type and whether conditions are baseline or stimulated needs to be taken into account when evaluating the evidence concerning the role of bicarbonate in the pathophysiology of CF as a regulator of local pH. Basic and applied research that focuses on the role of CFTR-mediated bicarbonate secretion helps explain many of the diverse clinical manifestations that are CF. © 2015 Wiley Periodicals, Inc.
Nair J.,State University of New York at Buffalo |
Lakshminrusimha S.,State University of New York at Buffalo |
Lakshminrusimha S.,Childrens Hospital of Buffalo
Seminars in Perinatology | Year: 2014
Persistent pulmonary hypertension of the newborn (PPHN) is a syndrome of failed circulatory adaptation at birth, seen in about 2/1000 live born infants. While it is mostly seen in term and near-term infants, it can be recognized in some premature infants with respiratory distress or bronchopulmonary dysplasia. Most commonly, PPHN is secondary to delayed or impaired relaxation of the pulmonary vasculature associated with diverse neonatal pulmonary pathologies, such as meconium aspiration syndrome, congenital diaphragmatic hernia, and respiratory distress syndrome. Gentle ventilation strategies, lung recruitment, inhaled nitric oxide, and surfactant therapy have improved outcome and reduced the need for extracorporeal membrane oxygenation (ECMO) in PPHN. Newer modalities of treatment discussed in this article include systemic and inhaled vasodilators like sildenafil, prostaglandin E1, prostacyclin, and endothelin antagonists. With prompt recognition/treatment and early referral to ECMO centers, the mortality rate for PPHN has significantly decreased. However, the risk of potential neurodevelopmental impairment warrants close follow-up after discharge for infants with PPHN. © 2014.
Lehman H.K.,Childrens Hospital of Buffalo
Current Allergy and Asthma Reports | Year: 2015
Primary immune deficiencies are often associated with autoimmune disease due to the dysregulation of the immune system as a whole. In many immune deficiencies, lymphocytes may be present but dysfunctional, allowing for the development of excessive autoreactivity and resultant autoimmune disease. Autoimmune polyendocrinopathy candidiasis and ectodermal dystrophy, autoimmune lymphoproliferative syndrome, immunodyregulation polyendocrinopathy enteropathy X-linked, IL-10/IL-10 receptor deficiencies, and PLCG2-associated antibody deficiency and immune dysregulation are disorders in which autoimmunity is a hallmark of the clinical disease presentation. In contrast, adaptive and innate immune deficiencies, which are typically defined by their infectious susceptibilities, can be associated with variable rates of autoimmune manifestations, predominantly autoimmune cytopenias. This review describes the immune dysregulation and autoimmune manifestations that may be encountered in various immune deficiencies. © 2015, Springer Science+Business Media New York.
Cerny F.,Childrens Hospital of Buffalo
Pediatric Exercise Science | Year: 2013
In 1989 we knew that exercise, including regular prescribed physical activity, could be safely performed and described some of the physiological responses to exercise in patients with cystic fibrosis (CF). Also in 1989, the genetic defect causing cystic fibrosis (CF) was identified leading to improvements in treatment that greatly extended the life span for these patients. Increased understanding of the factors limiting exercise capacity and of the important role of regular exercise in slowing the progression of CF and in modulating some of the effects of the genetic defect on airway function has led to the consensus that regular exercise should be part of the standard of care for this disease. © 2013 Human Kinetics, Inc.
Frank J.S.,Spinal USA |
Gambacorta P.L.,Childrens Hospital of Buffalo
Journal of the American Academy of Orthopaedic Surgeons | Year: 2013
Intrasubstance anterior cruciate ligament (ACL) injuries in children and adolescents were once considered rare occurrences, with tibial eminence avulsion fractures generally regarded as the pediatric ACL injury equivalent. However, with increased single-sport focus, less free play, and year-round training at younger ages, intrasubstance ACL injuries in children and adolescents are being diagnosed with increased frequency. As in the adult, a knee devoid of ligamentous stability predisposes the pediatric patient to meniscal and chondral injuries and early degenerative changes. Management of ACL injuries in skeletally immature patients includes physeal-sparing, partial transphyseal, and complete transphyseal ACL reconstruction. Complications include iatrogenic growth disturbance resulting from physeal violation. Copyright 2013 by the American Academy of Orthopaedic Surgeons.