Congenital diaphragmatic hernia is a defect in the diaphragm. The diaphragm, which is composed of... more Congenital diaphragmatic hernia is a defect in the diaphragm. The diaphragm, which is composed of muscle and other fibrous tissue, separates the organs in the abdomen from those in the chest. Abnormal development of the diaphragm before birth leads to defects ranging from a thinned area in the diaphragm to its complete absence. An absent or partially formed diaphragm results in an abnormal opening (hernia) that allows the stomach and intestines to move into the chest cavity and crowd the heart and lungs. This crowding can lead to underdevelopment of the lungs (pulmonary hypoplasia), potentially resulting in life-threatening breathing difficulties that are apparent from birth.
... aguda pedia´ trica Douglas F. Willson, MDa,Ã , Patricia R. Chess, MDb, Robert H. Notter, MD, ... more ... aguda pedia´ trica Douglas F. Willson, MDa,Ã , Patricia R. Chess, MDb, Robert H. Notter, MD, PhD b ... Findlay et al. [133] Lactantes (40) Aspiració n meconial Survanta Mejorıa de la oxigenació n, disminució n neumotó rax y ventilació n mecá nica Luchetti et al. ...
Neonatal-perinatal medicine fellows must achieve a meaningful accomplishment in scholarly activit... more Neonatal-perinatal medicine fellows must achieve a meaningful accomplishment in scholarly activity as part of their training. Despite the requirement for scholarly training in fellowship, there is a vanishingly small number of MD-only physician-scientists pursuing a research-oriented career. Recent neonatal trainees have identified several factors that preclude their careers in research-focused academic neonatology, including lower pay in academic positions, inadequate training in research techniques, and the perception that individuals in research careers have a poor work-life balance. High competition for limited pediatric research funds also contributes to a diminishing pool of physician-scientists in neonatology. This small number of physician-scientists is threatened by a high rate of attrition among physicians who enter this career path. In order to prevent further declines in the number of neonatal physician-scientists, we need improvements in funding and strong intra- and cross-institutional mentorship to foster individuals interested in a career as a physician-scientist.
CD40 is a 50 kDa transmembrane protein important for regulating B lymphocyte proliferation and di... more CD40 is a 50 kDa transmembrane protein important for regulating B lymphocyte proliferation and differentiation. This novel activation antigen is primarily expressed by hematopoietic cells including B lymphocytes, follicular dendritic cells, and monocytes. Recently, human fibroblasts from.a variety of tissues were shown to display CD40; however, its function was unknown. Cellular responses mediated by CD40 are naturally triggered by its counter‐receptor, the CD40 ligand, which is displayed on activated T cells, mast cells, eosinophils, basophils, and B lineage cells. This study investigated the functional significance of CD40 expression on periodontal fibroblasts, in the context of periodontal inflammation. The experiments reported herein demonstrate constitutive CD40 expression on cultured periodontal ligament (PDL) and gingival fibroblasts. Interestingly, cells of gingival origin displayed up to 13‐fold higher constitutive levels of CD40, versus fibroblasts from PDL. Interferon gamma (IFN‐γ) treatment enhanced CD40 expression on PDL and gingival fibroblasts, with up to 61‐fold induction of expression. Immunohistochemical staining was used to detect CD40 on fibroblastic cells in both normal and acutely inflamed gingival tissue. Expression of CD40 in inflamed tissue was significantly higher than in uninflamed tissue. Western blot analysis of anti‐CD40 triggered cells revealed the induction of tyrosine phosphorylation on a 50 kDa protein in PDL and gingival fibroblasts. These results indicate that CD40 is an active signaling conduit in periodontal fibroblasts. This concept was further substantiated by the fact that CD40 engagement stimulated interleukin 6 (IL‐6) production by gingival fibroblasts, but not periodontal ligament fibroblasts. Overall, these results demonstrate that CD40 on periodontal fibroblasts may functionally interact with CD40L‐expressing cells. This CD40/CD40L interaction can stimulate fibroblast activation and synthesis of the proinflammatory cytokine IL‐6. J Periodontol 1997;68:284–292.
CD40 is an important signaling and activation Ag found on certain bone marrow-derived cells. Rece... more CD40 is an important signaling and activation Ag found on certain bone marrow-derived cells. Recently, CD40 also has been shown to be expressed by mesenchymal cells, including human fibroblasts. Little is known about the role of CD40 in fibroblasts. The current study investigates the hypothesis that CD40 expressed on lung fibroblasts is an activation structure and mechanism for interaction with hemopoietic cells. Communication between resident tissue fibroblasts and T cells is necessary for normal wound healing, and can be pathologic, resulting in tissue fibrosis. Signaling through CD40 with soluble CD40 ligand stimulated fibroblast activation, as evidenced by mobilization of nuclear factor-kappaB and by induction of the proinflammatory and chemoattractant cytokines IL-6 and IL-8. IFN-gamma-primed lung fibroblasts costimulate T lymphocyte proliferation utilizing CD40, but not the well-studied costimulatory molecules B7-1 and B7-2. Data reported herein support the hypothesis that cognate interactions between tissue fibroblasts and infiltrating T lymphocytes, via the CD40/CD40L pathway, augment inflammation and may promote fibrogenesis by activating both cell types.
A premature neonate with supraventricular tachycardia was treated prenatally and postnatally, wit... more A premature neonate with supraventricular tachycardia was treated prenatally and postnatally, without significant signs of congestive heart failure. Enteral feeding was initiated after 48 hours of age. The infant developed fatal, fulminant necrotizing enterocolitis 28 hours after starting feeds.
Bronchopulmonary dysplasia (BPD), initially described 40 years ago, is a dynamic clinical entity ... more Bronchopulmonary dysplasia (BPD), initially described 40 years ago, is a dynamic clinical entity that continues to affect tens of thousands of premature infants each year. BPD was first characterized as a fibrotic pulmonary endpoint following severe Respiratory Distress Syndrome (RDS). It was the result of pulmonary healing after RDS, high oxygen exposure, positive pressure ventilation, and poor bronchial drainage secondary to endotracheal intubation in premature infants. With improved treatment for RDS, including surfactant replacement, oxygen saturation monitoring, improved modes of mechanical ventilation, antibiotic therapies, nutritional support, and infants surviving at younger gestations, the clinical picture of BPD has changed. In the following pages, we will summarize the multifaceted pathophysiologic factors leading to the pulmonary changes in "new" BPD, which is primarily characterized by disordered or delayed development. The contribution of hyperoxia and hypoxia, mechanical forces, vascular maldevelopment, inflammation, fluid management, patent ductus arteriosus (PDA), nutrition, and genetics will be discussed.
Congenital diaphragmatic hernia is a defect in the diaphragm. The diaphragm, which is composed of... more Congenital diaphragmatic hernia is a defect in the diaphragm. The diaphragm, which is composed of muscle and other fibrous tissue, separates the organs in the abdomen from those in the chest. Abnormal development of the diaphragm before birth leads to defects ranging from a thinned area in the diaphragm to its complete absence. An absent or partially formed diaphragm results in an abnormal opening (hernia) that allows the stomach and intestines to move into the chest cavity and crowd the heart and lungs. This crowding can lead to underdevelopment of the lungs (pulmonary hypoplasia), potentially resulting in life-threatening breathing difficulties that are apparent from birth.
... aguda pedia´ trica Douglas F. Willson, MDa,Ã , Patricia R. Chess, MDb, Robert H. Notter, MD, ... more ... aguda pedia´ trica Douglas F. Willson, MDa,Ã , Patricia R. Chess, MDb, Robert H. Notter, MD, PhD b ... Findlay et al. [133] Lactantes (40) Aspiració n meconial Survanta Mejorıa de la oxigenació n, disminució n neumotó rax y ventilació n mecá nica Luchetti et al. ...
Neonatal-perinatal medicine fellows must achieve a meaningful accomplishment in scholarly activit... more Neonatal-perinatal medicine fellows must achieve a meaningful accomplishment in scholarly activity as part of their training. Despite the requirement for scholarly training in fellowship, there is a vanishingly small number of MD-only physician-scientists pursuing a research-oriented career. Recent neonatal trainees have identified several factors that preclude their careers in research-focused academic neonatology, including lower pay in academic positions, inadequate training in research techniques, and the perception that individuals in research careers have a poor work-life balance. High competition for limited pediatric research funds also contributes to a diminishing pool of physician-scientists in neonatology. This small number of physician-scientists is threatened by a high rate of attrition among physicians who enter this career path. In order to prevent further declines in the number of neonatal physician-scientists, we need improvements in funding and strong intra- and cross-institutional mentorship to foster individuals interested in a career as a physician-scientist.
CD40 is a 50 kDa transmembrane protein important for regulating B lymphocyte proliferation and di... more CD40 is a 50 kDa transmembrane protein important for regulating B lymphocyte proliferation and differentiation. This novel activation antigen is primarily expressed by hematopoietic cells including B lymphocytes, follicular dendritic cells, and monocytes. Recently, human fibroblasts from.a variety of tissues were shown to display CD40; however, its function was unknown. Cellular responses mediated by CD40 are naturally triggered by its counter‐receptor, the CD40 ligand, which is displayed on activated T cells, mast cells, eosinophils, basophils, and B lineage cells. This study investigated the functional significance of CD40 expression on periodontal fibroblasts, in the context of periodontal inflammation. The experiments reported herein demonstrate constitutive CD40 expression on cultured periodontal ligament (PDL) and gingival fibroblasts. Interestingly, cells of gingival origin displayed up to 13‐fold higher constitutive levels of CD40, versus fibroblasts from PDL. Interferon gamma (IFN‐γ) treatment enhanced CD40 expression on PDL and gingival fibroblasts, with up to 61‐fold induction of expression. Immunohistochemical staining was used to detect CD40 on fibroblastic cells in both normal and acutely inflamed gingival tissue. Expression of CD40 in inflamed tissue was significantly higher than in uninflamed tissue. Western blot analysis of anti‐CD40 triggered cells revealed the induction of tyrosine phosphorylation on a 50 kDa protein in PDL and gingival fibroblasts. These results indicate that CD40 is an active signaling conduit in periodontal fibroblasts. This concept was further substantiated by the fact that CD40 engagement stimulated interleukin 6 (IL‐6) production by gingival fibroblasts, but not periodontal ligament fibroblasts. Overall, these results demonstrate that CD40 on periodontal fibroblasts may functionally interact with CD40L‐expressing cells. This CD40/CD40L interaction can stimulate fibroblast activation and synthesis of the proinflammatory cytokine IL‐6. J Periodontol 1997;68:284–292.
CD40 is an important signaling and activation Ag found on certain bone marrow-derived cells. Rece... more CD40 is an important signaling and activation Ag found on certain bone marrow-derived cells. Recently, CD40 also has been shown to be expressed by mesenchymal cells, including human fibroblasts. Little is known about the role of CD40 in fibroblasts. The current study investigates the hypothesis that CD40 expressed on lung fibroblasts is an activation structure and mechanism for interaction with hemopoietic cells. Communication between resident tissue fibroblasts and T cells is necessary for normal wound healing, and can be pathologic, resulting in tissue fibrosis. Signaling through CD40 with soluble CD40 ligand stimulated fibroblast activation, as evidenced by mobilization of nuclear factor-kappaB and by induction of the proinflammatory and chemoattractant cytokines IL-6 and IL-8. IFN-gamma-primed lung fibroblasts costimulate T lymphocyte proliferation utilizing CD40, but not the well-studied costimulatory molecules B7-1 and B7-2. Data reported herein support the hypothesis that cognate interactions between tissue fibroblasts and infiltrating T lymphocytes, via the CD40/CD40L pathway, augment inflammation and may promote fibrogenesis by activating both cell types.
A premature neonate with supraventricular tachycardia was treated prenatally and postnatally, wit... more A premature neonate with supraventricular tachycardia was treated prenatally and postnatally, without significant signs of congestive heart failure. Enteral feeding was initiated after 48 hours of age. The infant developed fatal, fulminant necrotizing enterocolitis 28 hours after starting feeds.
Bronchopulmonary dysplasia (BPD), initially described 40 years ago, is a dynamic clinical entity ... more Bronchopulmonary dysplasia (BPD), initially described 40 years ago, is a dynamic clinical entity that continues to affect tens of thousands of premature infants each year. BPD was first characterized as a fibrotic pulmonary endpoint following severe Respiratory Distress Syndrome (RDS). It was the result of pulmonary healing after RDS, high oxygen exposure, positive pressure ventilation, and poor bronchial drainage secondary to endotracheal intubation in premature infants. With improved treatment for RDS, including surfactant replacement, oxygen saturation monitoring, improved modes of mechanical ventilation, antibiotic therapies, nutritional support, and infants surviving at younger gestations, the clinical picture of BPD has changed. In the following pages, we will summarize the multifaceted pathophysiologic factors leading to the pulmonary changes in "new" BPD, which is primarily characterized by disordered or delayed development. The contribution of hyperoxia and hypoxia, mechanical forces, vascular maldevelopment, inflammation, fluid management, patent ductus arteriosus (PDA), nutrition, and genetics will be discussed.
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