Publications by authors named "Laurence Jewell"

Background: After resuscitation, asphyxiated neonates often develop poor cardiac function with hypotension, pulmonary hypertension and multiorgan ischemia. In a swine model of neonatal hypoxia-reoxygenation, effects of epinephrine, dobutamine and milrinone on systemic, pulmonary and regional hemodynamics and oxygen transport were compared.

Design: Controlled, block-randomized study.

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Background: Neonatal asphyxia may lead to the development of ischemia-reperfusion induced intestinal injury, which is related to oxygen-derived free radical production. N-Acetylcysteine (NAC) is a thiol-containing antioxidant which increases intracellular stores of glutathione.

Objectives: Using a swine model of neonatal hypoxia-reoxygenation, we examined whether administration of NAC after resuscitation improved intestinal perfusion and reduced intestinal damage.

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Neonatal asphyxia can result in poor perfusion, vasoconstriction, and decreased oxygen delivery in the intestine. Milrinone increases myocardial contractility and causes peripheral vasodilatation. We examined the dose-response of milrinone on the intestinal circulation, oxygen metabolism, and injury in a newborn piglet model of asphyxia-reoxygenation.

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Introduction: This study investigated the role of a novel nutrient-rich preservation solution in alleviating intestinal ischemia-reperfusion (IR) injury in a large animal model.

Materials And Methods: Porcine intestines were treated in vivo with the following intraluminal flush solutions: group 1, none; group 2, University of Wisconsin solution; group 3, an amino acid-based solution, previously shown to be effective in reducing IR injury in rodent models. Intestinal ischemia was induced in vivo for 60 min, followed by 180 min reperfusion.

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Objective: Neonatal asphyxia causes cardiogenic shock and pulmonary hypertension with decreased brain perfusion. We examined the dose-response of milrinone on systemic, pulmonary, and carotid circulations in a model of neonatal hypoxia-reoxygenation.

Design And Setting: Controlled, block-randomized study in a university research laboratory.

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Objectives: We examined the effects of 18%, 21% or 100% oxygen on the recovery of the heart and kidneys in a short-term survival model of neonatal hypoxia-reoxygenation (HR).

Design: Controlled, block-randomized animal study.

Setting: University animal research laboratory.

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Museums and pathology collections around the world represent an archive of genetic material to study populations and diseases. For preservation purposes, a large portion of these collections has been fixed in formalin-containing solutions, a treatment that results in cross-linking of biomolecules. Cross-linking not only complicates isolation of nucleic acid but also introduces polymerase "blocks" during PCR.

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Extensive collections of formalin-fixed paraffin-embedded (FFPE) tissues exist that could be exploited for genetic analyses in order to provide important insights into the genetic basis of disease or host/pathogen cointeractions. We report here an evaluation of a 44 SNP multiplex genotyping method, multiplex PCR with minisequencing (MPMS), on 92 DNA extractions performed on six archival FFPE samples of variable DNA quality, which date between 9 and 25 years old. On the three extracts with highest quality, we found the assay efficiency to be near 100%.

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Neonatal asphyxia may lead to cardiac and renal complications perhaps mediated by oxygen free radicals. Using a model of neonatal hypoxia-reoxygenation, we tested the hypothesis that N-acetylcysteine (NAC) would improve cardiac function and renal blood flow. Eighteen piglets (aged 1-4 days old, weighing 1.

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Background: A recent study from our laboratory documented significant improvements in post-transplant viability in an experimental model of intestinal transplantation when a novel, nutrient-rich preservation solution was used during cold storage. The current study investigated the relationship between energetic/oxidative stress responses and fundamental kinase signaling events during the period of organ storage. This relationship may be a key factor contributing to improved graft viability after storage in a nutrient-rich preservation solution.

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Objective: To compare mesenteric blood flow, oxidative stress, and mucosal injury in piglet small intestine during hypoxemia and reoxygenation with 21%, 50%, or 100% oxygen.

Summary Background Data: Necrotizing enterocolitis is a disease whose pathogenesis likely involves hypoxia-reoxygenation and the generation of oxygen-free radicals, which are known to cause intestinal injury. Resuscitation of asphyxiated newborns with 100% oxygen has been shown to increase oxidative stress, as measured by the glutathione redox ratio, and thus may predispose to free radical-mediated tissue injury.

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Background: Graft injury incurred during periods of cold storage remains a factor affecting the success of small bowel (SB) transplantation. No one preservation solution, including the gold standard University of Wisconsin (UW) solution, has been able to maintain graft integrity for storage periods paralleling that of other commonly transplanted intra-abdominal organs. We investigated the role for the luminal administration of preservation solutions in a small animal model, documenting significantly improved graft quality.

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Background: Povidone-iodine (PI) (Betadine, Purdue Fredrick Co., Norwalk, CT) is used during pancreas transplantation to provide duodenal decontamination without any intestinal complications.

Methods: This study assessed the combined effect of a luminal pretreatment with PI followed by a proven amino acid (AA)-rich preservation solution on small bowel (SB) storage quality.

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The mucosal layer is the initial site of small bowel (SB) graft injury sustained during cold storage. Vascular administration of preservation solutions alone is unable to prevent ischemic injury of this layer during clinically relevant storage periods. The SB is unique in that it possesses both a vascular and a luminal route by which preservation solutions can be administered.

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Background: Glutamine (gln)-supplemented University of Wisconsin (UW) solution improves overall small bowel (SB) preservation. Sustained gln metabolism in a system devoid of hepatic detoxification will necessarily result in the accumulation of pH active end products leading to nonphysiologic pH shifts. We hypothesized that simultaneous addition of N,N-bis[2-hydroxyethyl]-2-aminoethane sulfonic acid (BES), a known buffering agent, would potentiate the beneficial effect of gln supplementation by addressing the fundamental metabolic principle of pH homeostasis.

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