Age-Based Percentiles of Measured Mean Arterial Pressure in Pediatric Patients in a Hospital Setting.

Objectives: To develop and validate age-specific percentile curves of measured mean arterial pressure for children in a hospital setting.

Design: Retrospective observational study of electronic records.

Setting: Tertiary care, freestanding pediatric hospital in Seattle, WA.

Interaction of Critical Care Practitioners With a Decision Support Tool for Weaning Mechanical Ventilation in Children.

Background: There is evidence that ventilator weaning protocols provide benefit to children receiving mechanical ventilation, but many protocols do not include explicit instructions for decreasing ventilator support from maximal settings. We evaluated care provider opinions on ventilator weaning recommendations made by a computerized decision support tool.

Methods: Recommendations for ventilator adjustment were generated using a computerized decision support tool based on the ARDSNet protocol using data from children with acute hypoxemic respiratory failure admitted to the pediatric ICU (PICU).

Short-Term Adverse Outcomes Associated With Hypoglycemia in Critically Ill Children.

Objectives: Previous studies report worse short-term outcomes with hypoglycemia in critically ill children. These studies relied on intermittent blood glucose measurements, which may have introduced detection bias. We analyzed data from the Heart And Lung Failure-Pediatric INsulin Titration trial to determine the association of hypoglycemia with adverse short-term outcomes in critically ill children.

An Elevated Low Cardiac Output Syndrome Score Is Associated With Morbidity in Infants After Congenital Heart Surgery.

Objectives: To evaluate an empirically derived Low Cardiac Output Syndrome Score as a clinical assessment tool for the presence and severity of Low Cardiac Output Syndrome and to examine its association with clinical outcomes in infants who underwent surgical repair or palliation of congenital heart defects.

Design: Prospective observational cohort study.

Setting: Cardiac ICU at Seattle Children's Hospital.

Effects of exendin-4, a glucagon like peptide-1 receptor agonist, on neutrophil count and inflammatory cytokines in a rat model of endotoxemia.

Background: Sepsis remains a major cause of morbidity and mortality. A variety of strategies targeting modulation of the pro-inflammatory response associated with early sepsis have been reported without clinical success. GLP-1 enhances glucose-stimulated insulin secretion.

Two pediatric cases of variant neurogenic stress cardiomyopathy after intracranial hemorrhage.

Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy, is an acquired form of left ventricular systolic dysfunction seen in the setting of physiologic stress and the absence of coronary artery disease. It is thought to be caused by excessive sympathetic stimulation. It is well described in the adult literature associated with subarachnoid hemorrhage where it is known as neurogenic stress cardiomyopathy (NSC), but few such pediatric cases have been reported.

Long-term dexmedetomidine use and safety profile among critically ill children and neonates.

Objective: To determine whether long-term dexmedetomidine dosing is associated with lower opioid and benzodiazepine use without risk of significant hemodynamic changes and/or withdrawal.

Design: Retrospective, observational study.

Setting: PICU, cardiovascular ICU, and neonatal ICU in a single, tertiary care, academic children's hospital.

Repeated lentivirus-mediated granulocyte colony-stimulating factor administration to treat canine cyclic neutropenia.

Cyclic neutropenia occurs in humans and gray collie dogs, is characterized by recurrent neutropenia, and is treated by repeated injections of recombinant granulocyte colony-stimulating factor (rG-CSF). As dose escalation of lentivirus may be clinically necessary, we monitored the outcome of four sequential intramuscular injections of G-CSF-lentivirus (3 × 10(7) IU/kg body weight) to a normal dog and a gray collie. In the normal dog absolute neutrophil counts were significantly increased after each dose of virus, with mean levels of 27.

Sustained glucagon-like peptide 1 expression from encapsulated transduced cells to treat obese diabetic rats.

Obesity and type 2 diabetes (T2D) are two prevalent chronic diseases that have become a major public health concern in industrialized countries. T2D is characterized by hyperglycemia and islet beta cell dysfunction. Glucagon-like peptide 1 (GLP-1) promotes β cell proliferation and neogenesis and has a potent insulinotropic effect.

Prolonged survival and improved glycemia in BioBreeding diabetic rats after early sustained exposure to glucagon-like peptide 1.

Background: Type 1 diabetes (T1D) in both humans and BioBreeding (BB) rats is an autoimmune disease that results in complete destruction of islets and insulin dependency for life. Glucagon-like peptide 1 (GLP-1) promotes beta cell proliferation and neogenesis and has a potent insulinotropic effect. We hypothesized that the expression of GLP-1 before disease onset would increase islet mass, delay diabetes and prolong survival of BB rats.

Treatment of diabetic rats with encapsulated islets.

Immunoprotection of islets using bioisolator systems permits introduction of allogeneic cells to diabetic patients without the need for immunosuppression. Using TheraCyte immunoisolation devices, we investigated two rat models of type 1 diabetes mellitus (T1DM), BB rats and rats made diabetic by streptozotocin (STZ) treatment. We chose to implant islets after the onset of diabetes to mimic the probable treatment of children with T1DM as they are usually diagnosed after disease onset.

G-CSF-lentivirus administration in rats provided sustained elevated neutrophil counts and subsequent EPO-lentivirus administration increased hematocrits.

Background: Towards gene therapy treatment of patients with neutropenia, characterized by neutrophil counts < 500 cells/microl, we investigated the ability of lentivirus vectors to provide sustained granulocyte colony-stimulating factor (G-CSF) delivery and to permit transgene expression from a second virus administration in a preclinical rat model.

Methods: Rats were injected intramuscularly (IM) with 24 x 10(6) and 9 x 10(6) infectious units (IU) of a VSV-G-pseudotyped self-inactivating (SIN) lentivirus encoding rat G-CSF cDNA and containing cPPT and PRE elements. To determine the effectiveness of a second virus administration treated rats and a naïve rat received erythropoietin (EPO)-lentivirus IM.

An adult dog with cyclic neutropenia treated by lentivirus- mediated delivery of granulocyte colony-stimulating factor.

Cyclic neutropenia occurs in humans and gray collie dogs, is characterized by recurrent neutropenia, and is treated by daily injections of recombinant granulocyte colony-stimulating factor (G-CSF). After showing that canine recombinant G-CSF increased neutrophil counts in an affected dog, we administered intramuscularly 2 x 10(9) infectious units (IU) of a lentiviral vector encoding canine G-CSF cDNA. Elevated, therapeutic neutrophil production was obtained for nearly 18 months.

Sustained elevation of neutrophils in rats induced by lentivirus-mediated G-CSF delivery.

Background: Patients with severe chronic and cyclic neutropenia, characterized by neutrophil numbers <500 cells/microl, are treated daily with recombinant granulocyte colony-stimulating factor (G-CSF). As an alternative delivery approach we investigated the ability of lentivirus vectors to provide sustained G-CSF expression.

Methods: Fischer rats were injected intramuscularly (IM) with vesicular stomatitis virus G (VSV-G)-pseudotyped lentivirus pRRL-CMV-G-CSF-SIN that encoded rat G-CSF cDNA regulated by the human cytomegalovirus (CMV) promoter and incorporated a self-inactivating (SIN) construct in the 3' long terminal repeat (LTR).

Continuous pentobarbital infusion in children is associated with high rates of complications.

Purpose: To evaluate the incidence and severity of complications related to continuous pentobarbital (PB) infusion for sedation in the Pediatric Intensive Care Unit (PICU).

Materials And Methods: We conducted a retrospective, chart review study. All patients admitted to the PICU from January 1997 through June 1998 who received continuous IV PB infusion for sedation (n = 8) were included.

Long-term erythropoietin gene expression from transduced cells in bioisolator devices.

Recombinant erythropoietin (EPO) is widely administered for long-term treatment of anemia associated with renal failure and other chronic diseases. The ability to deliver EPO by gene therapy would have clinical and economic benefit. We compared autologous and allogeneic transduced primary vascular smooth muscle cells for their ability to provide sustained EPO gene expression when encapsulated in TheraCyte devices implanted subcutaneously (SQ) or intraperitoneally (IP) in rats.

Treatment of canine cyclic neutropenia by lentivirus-mediated G-CSF delivery.

Cyclic neutropenia is a rare disease that occurs both in humans and gray collie dogs and is characterized by recurrent severe neutropenia leading to bacterial infections and shortened life expectancy. Daily injections of recombinant granulocyte colony-stimulating factor (rG-CSF) are effective in shortening the period of severe neutropenia and reducing infections. After demonstrating that rG-CSF induced elevated neutrophil production in an affected dog, cytokine administration was stopped and 109 infectious units (IUs) of a lentivirus pseudotyped with vesicular stomatitis virus G protein (VSV-G) encoding canine G-CSF cDNA was administered intramuscularly.