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Charron M.J.,Yeshiva University | Vuguin P.M.,Cohen Childrens Medical Center
Journal of Endocrinology

Glucagon action is transduced by a G protein-coupled receptor located in liver, kidney, intestinal smooth muscle, brain, adipose tissue, heart, pancreatic β-cells, and placenta. Genetically modified animal models have provided important clues about the role of glucagon and its receptor (Gcgr) beyond glucose control. The PubMed database was searched for articles published between 1995 and 2014 using the key terms glucagon, glucagon receptor, signaling, and animal models. Lack of Gcgr signaling has been associated with: i) hypoglycemic pregnancies, altered placentation, poor fetal growth, and increased fetal-neonatal death; ii) pancreatic glucagon cell hyperplasia and hyperglucagonemia; iii) altered body composition, energy state, and protection from diet-induced obesity; iv) impaired hepatocyte survival; v) altered glucose, lipid, and hormonal milieu; vi) altered metabolic response to prolonged fasting and exercise; vii) reduced gastric emptying and increased intestinal length; viii) altered retinal function; and ix) prevention of the development of diabetes in insulin-deficient mice. Similar phenotypic findings were observed in the hepatocyte-specific deletion of Gcgr. Glucagon action has been involved in the modulation of sweet taste responsiveness, inotropic and chronotropic effects in the heart, satiety, glomerular filtration rate, secretion of insulin, cortisol, ghrelin, GH, glucagon, and somatostatin, and hypothalamic signaling to suppress hepatic glucose production. Glucagon (α) cells under certain conditions can transdifferentiate into insulin (β) cells. These findings suggest that glucagon signaling plays an important role in multiple organs. Thus, treatment options designed to block Gcgr activation in diabetics may have implications beyond glucose homeostasis. © 2015 The authors Published by Bioscientifica Ltd. Source

Haemophilia is an inherited disorder of clotting factor deficiencies resulting in musculoskeletal bleeding, including haemarthroses, leading to orthopaedic complications. The pathogenesis of haemophilic joint arthropathy continues to be explored and there is evidence to suggest that iron, cytokines, and neo angiogenesis can initiate synovial and early cartilage damage resulting in molecular changes and the perpetuation of a chronic inflammatory state. This joint arthropathy has long term consequences for bone health resulting in chronic pain and quality of life issues in the individual with haemophilia. Haemarthroses can be prevented by the administration of clotting factor concentrates (prophylaxis). However, high costs and the need for venous access devices in younger children continue to complicate recommendations for universal prophylaxis. In patients who fail or refuse prophylaxis, procedures, such as synovectomy and arthroplasty, can provide relief from repeated haemarthroses. The optimal timing of these, however, is not well defined. Prevention of joint arthropathy needs to focus on prevention of haemarthroses through prophylaxis, identifying early joint disease through the optimal use of cost effective imaging modalities and the validation of serological markers of joint arthropathy. Screening for effects on bone health and optimal management of pain to improve quality of life are, likewise, important issues. © 2011 Blackwell Publishing Ltd. Source

Sood S.K.,Cohen Childrens Medical Center
Infectious Disease Clinics of North America

The diagnosis and management of Lyme disease in children is similar to that in adults with a few clinically relevant exceptions. The use of doxycycline as an initial empiric choice is to be avoided for children 8years old and younger. Children may present with insidious onset of elevated intracranial pressure during acute disseminated Lyme disease; prompt diagnosis and treatment of this condition is important to prevent loss of vision. Children who acquire Lyme disease have an excellent prognosis even when they present with the late disseminated manifestation of Lyme arthritis. Guidance on the judicious use of serologic tests is provided. Pediatricians and family practitioners should be familiar with the prevention and management of tick bites, which are common in children. © 2015 Elsevier Inc. Source

Abrams S.A.,Baylor College of Medicine | Schanler R.J.,Cohen Childrens Medical Center | Lee M.L.,Prolacta Bioscience | Rechtman D.J.,Prolacta Bioscience
Breastfeeding Medicine

Background: Provision of human milk has important implications for the health and outcomes of extremely preterm (EP) infants. This study evaluated the effects of an exclusive human milk diet on the health of EP infants during their stay in the neonatal intensive care unit. Subjects and Methods: EP infants <1,250g birth weight received a diet consisting of either human milk fortified with a human milk protein-based fortifier (HM) (n=167) or a diet containing variable amounts of milk containing cow milk-based protein (CM) (n=93). Principal outcomes were mortality, necrotizing enterocolitis (NEC), growth, and duration of parenteral nutrition (PN). Results: Mortality (2% versus 8%, p=0.004) and NEC (5% versus 17%, p=0.002) differed significantly between the HM and CM groups, respectively. For every 10% increase in the volume of milk containing CM, the risk of sepsis increased by 17.9% (p<0.001). Growth rates were similar between groups. The duration of PN was 8 days less in the subgroup of infants receiving a diet containing <10% CM versus ≥10% CM (p<0.02). Conclusions: An exclusive human milk diet, devoid of CM-containing products, was associated with lower mortality and morbidity in EP infants without compromising growth and should be considered as an approach to nutritional care of these infants. © Copyright 2014, Mary Ann Liebert, Inc. 2014. Source

Rohan A.J.,State University of New York at Stony Brook | Rohan A.J.,Cohen Childrens Medical Center
Journal of Perinatology

Objective:To examine the association of pain assessment scores achieved through regular reassessment practice, as required by the Joint Commission (JC), with painful events and the use of analgesics in premature, ventilated infants.Study Design:A cross-sectional study was performed in two tertiary level neonatal intensive care units. Pain was assessed at regular intervals at each center using validated multidimensional instruments in accordance with the JC standards.Result:Sample comprised 196 ventilated premature infant patient-days. Overall, 2% of scores suggested the presence of pain, and 0.1% of pain scores were associated with analgesia. Ventilated infants who were exposed to multiple pain-associated procedures in a day never demonstrated pain score elevations despite infrequent preemptive or continuous analgesic administration.Conclusion: Pain assessment scores achieved using regular reassessment processes were poorly correlated with exposure to pain-associated procedures or conditions. Low pain scores achieved through regular reassessment may not correlate to low pain exposure. Resources that are expended on regular reassessment processes may need to be reconsidered in light of the low yield for clinical alterations in care in this setting. © 2014 Nature America, Inc. Source

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