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J A Carcillo

Publications and source records attributed to J A Carcillo.

At least 19 recordsLinked to original sources
PubMed2001

Congenital surfactant protein B deficiency--emphasis on imaging.

BACKGROUND AND OBJECTIVES: Surfactant protein B deficiency has become increasingly recognized as a cause of severe prolonged respiratory distress. Little has been written about the imaging appearance and the role of imaging in diagnosis. MATERIALS AND METHODS: Three newborn infants with severe respiratory distress exhibited prolonged diffuse pulmonary opacification radiographically. RESULTS: Diffuse ground-glass opacity and markedly prominent interlobular septa suggesting alveolar proteinosis were present on early thin-section chest computed tomographic (CT) images. Fibrotic changes with prominent interlobular septal thickening were present on a later CT. Surfactant protein B deficiency was confirmed by alveolar lavage and peripheral blood DNA analysis. CONCLUSION: Thin-section chest CT imaging contributes important information when this diagnosis is considered.

Extracorporeal Membrane Oxygenation↗
PubMed2001

Interstitial brain adenosine and xanthine increase during jugular venous oxygen desaturations in humans after traumatic brain injury.

OBJECTIVE: Adenosine decreases the cerebral metabolic rate for oxygen and increases cerebral blood flow, and it may play an important role in cerebrometabolic and cerebrovascular responses to hypoperfusion after traumatic brain injury. Jugular venous oxygen saturation is monitored after traumatic brain injury to assess brain oxygen extraction, and desaturations may reflect secondary brain insults. We hypothesized that brain interstitial adenosine and related purine metabolites would be increased during jugular venous oxygen saturation desaturations (<50%) and determined associations between the purines, lactate, and glucose to assess the role of adenosine during secondary insults in humans. DESIGN: Study of critically ill adults with severe traumatic brain injury. SETTING: Adult neurointensive care unit. PATIENTS: We prospectively defined periods of normal saturation and desaturation in six patients after severe traumatic brain injury. INTERVENTIONS: During these periods, cerebral microdialysis samples of brain interstitial fluid were collected, and adenosine and purine metabolites were measured by high-pressure liquid chromatography. MEASUREMENTS AND MAIN RESULTS: Adenosine increased 3.1-fold and xanthine increased 2.5-fold during desaturation periods (both p <.05 vs. normal saturation period, signed rank). Adenosine, xanthine, hypoxanthine, and cyclic-adenosine monophosphate correlated with lactate over both study periods (r(2) =.32,.14,.31,.07, and.26, respectively, all p <.05, Pearson product moment correlation). CONCLUSION: The marked increases in interstitial brain adenosine that occur during jugular venous oxygen desaturations suggest that adenosine may play an important role during periods of secondary insults after traumatic brain injury. The correlation of these metabolites with lactate further suggests that adenosine is increased during periods of enhanced glycolytic metabolism.

Adenosine↗
PubMed2001

Increased adenosine in cerebrospinal fluid after severe traumatic brain injury in infants and children: association with severity of injury and excitotoxicity.

OBJECTIVES: To measure adenosine concentration in the cerebrospinal fluid of infants and children after severe traumatic brain injury and to evaluate the contribution of patient age, Glasgow Coma Scale score, mechanism of injury, Glasgow Outcome Score, and time after injury to cerebrospinal fluid adenosine concentrations. To evaluate the relationship between cerebrospinal fluid adenosine and glutamate concentrations in this population. DESIGN: Prospective survey. SETTING: Pediatric intensive care unit in a university-based children's hospital. PATIENTS: Twenty-seven critically ill infants and children who had severe traumatic brain injury (Glasgow Coma Scale < 8), who required placement of an intraventricular catheter and drainage of cerebrospinal fluid as part of their neurointensive care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients ranged in age from 2 months to 14 yrs. Cerebrospinal fluid samples (n = 304) were collected from 27 patients during the first 7 days after traumatic brain injury. Control cerebrospinal fluid samples were obtained from lumbar puncture on 21 infants and children without traumatic brain injury or meningitis. Adenosine concentration was measured by using high-pressure liquid chromatography. Adenosine concentration was increased markedly in cerebrospinal fluid of children after traumatic brain injury vs. controls (p < .001). The increase in cerebrospinal fluid adenosine was independently associated with Glasgow Coma Scale < or = 4 vs. > 4 and time after injury (both p < .005). Cerebrospinal fluid adenosine concentration was not independently associated with either age (< or = 4 vs. > 4 yrs), mechanism of injury (abuse vs. other), or Glasgow Outcome Score (good/moderately disabled vs. severely disabled, vegetative, or dead). Of the 27 patients studied, 18 had cerebrospinal fluid glutamate concentration previously quantified by high-pressure liquid chromatography. There was a strong association between increases in cerebrospinal fluid adenosine and glutamate concentrations (p < .005) after injury. CONCLUSIONS: Cerebrospinal fluid adenosine concentration is increased in a time- and severity-dependent manner in infants and children after severe head injury. The association between cerebrospinal fluid adenosine and glutamate concentrations may reflect an endogenous attempt at neuroprotection against excitotoxicity after severe traumatic brain injury.

Adenosine↗
PubMed2001

Pediatric sepsis and multiple organ dysfunction syndrome.

Systemic inflammatory response syndrome may be viewed as the systemic expression of cytokine signals that normally function on an autocrine or paracrine level. Sepsis is defined as systemic inflammatory response syndrome caused by an infection. Multiple organ dysfunction syndrome may represent the end stage of severe systemic inflammatory response syndrome or sepsis. Many cells are involved, including endothelial cells and leukocytes and multiple proinflammatory and antiinflammatory mediators (cytokines, oxygen free radicals, coagulation factors, and so forth). Various pathophysiologic mechanisms have been postulated. The most popular theory is that the inflammatory process loses its autoregulatory capacity; however, microcirculatory dysregulation and apoptosis may also be important, and a new paradigm posits a complex nonlinear system. Many new treatments have been studied recently. The usefulness of immune modulating diets remains to be evaluated. Molecular immunomodulation is still of unclear value. The therapy of sepsis and multiple organ dysfunction syndrome remains mainly supportive.

Adjuvants, Immunologic↗
PubMed2001

Inhibition of adenosine deaminase attenuates endotoxin-induced release of cytokines in vivo in rats.

The purpose of this study was to investigate in vivo the effects of modulating the adenosine system on endotoxin-induced release of cytokines and changes in heart performance and neurohumoral status in early, profound endotoxemia in rats. Time/pressure variables of heart performance and blood pressure were recorded continuously, and plasma levels of tumor necrosis factor alpha (TNFalpha), interleukin 1-beta (IL-1beta), plasma renin activity (PRA), and catecholamines were determined before and 90 min after administration of endotoxin (30 mg/kg of lipopolysaccharide, i.v.). Erythro-9[2-hydroxyl-3-nonyl] adenine (EHNA; an adenosine deaminase inhibitor) had no effects on measured time-pressure variables of heart performance under baseline conditions and during endotoxemia, yet significantly attenuated endotoxin-induced release of cytokines and PRA. Pretreatment with the non-selective adenosine receptor antagonist DPSPX not only prevented the effects of EHNA but also increased the basal release of cytokines and augmented PRA. At baseline, caffeine (a non-selective adenosine receptor antagonist) increased HR, +dP/dtmax, heart rate x ventricular pressure product (HR x VPSP) and +dP/dtmax normalized by pressure (+dP/dtmax/VPSP), and these changes persisted during endotoxemia. Caffeine attenuated endotoxin-induced release of cytokines and augmented endotoxin-induced increases in plasma catecholamines and PRA. Pretreatment with propranolol abolished the effects of caffeine on heart performance and neurohumoral activation during the early phase of endotoxemia. 6N-cyclopentyladenosine (CPA; selective A1 adenosine receptor agonist) induced bradicardia and negative inotropic effects, reduced work load (i.e., decreased HR, VPSP, +dP/dtmax, +dP/dtmax/VPSP and HR x VPSP) and inhibited endotoxin-induced tachycardia and renin release. CGS 21680 (selective A2A adenosine receptor agonist) decreased blood pressure under basal condition but did not potentiate decreases in blood pressure during endotoxemia. CGS 21680 completely inhibited endotoxin-induced release of TNFalpha, augmented sympathetic activity and PRA, and increased +dP/dtmax and +dP/dtmax/VPSP in the absence and presence of endotoxin. The present study provides strong evidence that inhibition of adenosine deaminase reduces cytokine release in vivo without producing significant hemodynamic and cardiac effects during the early phase of profound endotoxemia in rats. The augmented neurohumoral activation induced by caffeine is associated with decreased cytokine release induced by endotoxin. Further studies are warranted to determine the impact of these effects on cardiac function and hemodynamics in the late phase of endotoxemia.

Adenine↗
PubMed2001

Chronic type IV phosphodiesterase inhibition protects glomerular filtration rate and renal and mesenteric blood flow in a zymosan-induced model of multiple organ dysfunction syndrome treated with norepinephrine.

To examine the effects of chronic type IV phosphodiesterase (PDE4) inhibition on renal function and renal and mesenteric vascular resistance and blood flow in a sublethal model of multiple organ dysfunction syndrome (MODS) we used a prospective, randomized, controlled laboratory animal study. Twenty-eight rats had mini-infusion pumps placed to deliver vehicle or PDE4 inhibition with Ro 20-1724 at doses of either 0.3 or 2.0 microg/kg/min. Simultaneously, MODS was induced by intraperitoneal injection of zymosan (0.25 mg/g). Mean arterial blood pressure, heart rate, renal blood flow, and superior mesenteric blood flow (SMABF) were measured at 48 h. Renal vascular resistance (RVR), superior mesenteric artery vascular resistance (SMAVR), and glomerular filtration rate were calculated. A dose-response effect of norepinephrine was also evaluated at 48 h. Chronic Ro 20-1724 treatment prevented norepinephrine-induced vasoconstriction in control rats. Inhibition of PDE4 with Ro 20-1724 (2.0 microg/kg/min) increased urinary cAMP, and attenuated the increase in RVR and SMAVR (p < 0.05) and the decrease in RBF and SMABF (p < 0.05) that occurred from zymosan and norepinephrine. Glomerular filtration rate was also preserved (p < 0. 05), despite a reduction in blood pressure. Chronic PDE4 inhibition protects renal function and mesenteric perfusion during MODS by increasing cAMP in the presence and absence of catecholamines. Higher doses of PDE4 inhibition result in clinically tolerated decreases in mean arterial blood pressure, with improved end-organ function. Chronic PDE4 inhibition is protective, likely through cAMP-mediated attenuation of vasoconstriction.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Inhibition of cytokine release by and cardiac effects of type IV phosphodiesterase inhibition in early, profound endotoxaemia in vivo.

1. In rats, inhibition of type IV phosphodiesterase (PDE4) attenuates acute renal failure and early (hours) mortality induced by high-dose endotoxin. Because it is unlikely that protection of renal function accounts for improved early survivability, most likely PDE4 inhibition exerts multiple beneficial effects in endotoxaemia and the purpose of the present study was to test this hypothesis. 2. In study 1, we determined, in anaesthetized rats, the effects of endotoxin (30 mg/kg, i.v.) on cardiac performance parameters (heart rate (HR), ventricular peak systolic pressure (VPSP), maximum positive change in left ventricular pressure with respect to time (+dP/dt), maximum negative change in left ventricular pressure with respect to time (-dP/dtmax), ventricular end-diastolic pressure (VEDP), ventricular minimum diastolic pressure (VMDP) and HR-pressure product), plasma catecholamine levels, plasma renin activity (PRA) and plasma levels of inflammatory cytokines (tumour necrosis factor (TNF)-alpha and interleukin (IL)-lbeta). 3. In study 2, we determined, in anaesthetized rats, whether inhibition of PDE4 attenuates lipopolysaccharide (LPS)-induced changes in the aforementioned parameters of heart performance and neurohumoral status. We compared the changes in these parameters induced by endotoxaemia in animals treated with either RO 20-1724 (10 microg/kg per min; a selective PDE4 inhibitor) or its vehicle (DMSO; 1.35 microL/min). 4. At 90 min postadministration, endotoxin significantly increased HR and reduced -dP/dtmax and VEDP and caused a several-fold increase in plasma levels of TNF-alpha, IL-1beta, noradrenaline, adrenaline and PRA. RO20-1724 significantly blunted the endotoxin-induced reduction in -dP/dtmax and decreased endotoxin-induced increases in TNF-alpha and IL-1beta without significantly altering endotoxin-induced changes in HR, VEDP, catecholamine levels and PRA. 5. Results from these studies indicate that, in addition to preserving renal function, PDE4 inhibition attenuates inflammatory cytokine release caused by high-dose endotoxin and may have protective effects on diastolic function in early profound endotoxaemia.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Increases in bcl-2 protein in cerebrospinal fluid and evidence for programmed cell death in infants and children after severe traumatic brain injury.

OBJECTIVES: To determine whether bcl-2, a protein that inhibits apoptosis, would be increased in cerebrospinal fluid (CSF) in infants and children after traumatic brain injury (TBI) and to examine the association of bcl-2 concentration with clinical variables. STUDY DESIGN: Bcl-2 was measured in CSF from 23 children (aged 2 months-16 years) with severe TBI and from 19 children without TBI or meningitis (control subjects) by enzyme-linked immunosorbent assay. CSF oligonucleosome concentration was also determined as a marker of DNA degradation. Brain samples from 2 patients undergoing emergent decompressive craniectomies were analyzed for bcl-2 with Western blot and for DNA fragmentation with TUNEL (terminal deoxynucleotidyl-transferase mediated biotin-dUTP nick-end labeling). RESULTS: CSF bcl-2 concentrations were increased in patients with TBI versus control subjects (P =.01). Bcl-2 was increased in patients with TBI who survived versus those who died (P =.02). CSF oligonucleosome concentration tended to be increased after TBI (P =.07) and was not associated with bcl-2. Brain tissue samples showed an increase in bcl-2 in patients with TBI versus adult brain bank control samples and evidence of DNA fragmentation within cells with apoptotic morphology. CONCLUSIONS: Bcl-2 may participate in the regulation of cell death after TBI in infants and children. The increase in bcl-2 seen in patients who survived is consistent with a protective role for this anti-apoptotic protein after TBI.

Adolescent↗
PubMed2000

Intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 are increased in the plasma of children with sepsis-induced multiple organ failure.

OBJECTIVES: To determine concentrations of circulating adhesion molecules endothelial (E)-selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 in children with sepsis-induced multiple organ failure (MOF), and to determine associations among increased concentrations of these circulating adhesion molecules and important outcome measures. DESIGN: Prospective study. SETTING: University pediatric intensive care unit. PATIENTS: A total of 77 consecutive children with sepsis and 14 acutely ill children without sepsis. INTERVENTIONS: Plasma E-selectin, ICAM-1, and VCAM-1 concentrations and organ failure index (indicating number of failed organ systems) were determined in 77 children on days 1 and 3 of sepsis, and in 14 control children on pediatric intensive care unit day 1. Multivariate logistic regression analysis was used to determine associations between adhesion molecule concentrations and clinically relevant outcome measures. MEASUREMENTS AND RESULTS: Plasma concentrations of E-selectin, ICAM-1, and VCAM-1 were increased in children with sepsis vs. control on day 1 (p < .05). Plasma VCAM-1 (but not ICAM-1 or E-selectin) was increased in children with more than three organ failures vs. children with less than three organ failures (p < .05). Plasma ICAM-1 and VCAM-1 (but not E-selectin) concentrations independently predicted number of organs failed and development of more than three organ failures. Plasma ICAM-1 and VCAM-1 also predicted mortality and development of sequential (pulmonary/hepatic/renal) MOF (p < .05). CONCLUSIONS: The pronounced and persistent increase in plasma VCAM-1 and ICAM-1 that occurs in children with sepsis and persistent MOF may indicate a phenotypic change in endothelium toward a more proinflammatory state. Alternatively, the source for these adhesion molecules may be activated leukocytes and other cell types. Future studies are required to determine the role of ICAM-1 and VCAM-1 in the pathogenesis of sepsis-induced MOF.

Adolescent↗
PubMed1999

Inducible nitric oxide synthase is an endogenous neuroprotectant after traumatic brain injury in rats and mice.

Nitric oxide (NO) derived from the inducible isoform of NO synthase (iNOS) is an inflammatory product implicated both in secondary damage and in recovery from brain injury. To address the role of iNOS in experimental traumatic brain injury (TBI), we used 2 paradigms in 2 species. In a model of controlled cortical impact (CCI) with secondary hypoxemia, rats were treated with vehicle or with 1 of 2 iNOS inhibitors (aminoguanidine and L-N-iminoethyl-lysine), administered by Alzet pump for 5 days and 1. 5 days after injury, respectively. In a model of CCI, knockout mice lacking the iNOS gene (iNOS(-/-)) were compared with wild-type (iNOS(+/+)) mice. Functional outcome (motor and cognitive) during the first 20 days after injury, and histopathology at 21 days, were assessed in both studies. Treatment of rats with either of the iNOS inhibitors after TBI significantly exacerbated deficits in cognitive performance, as assessed by Morris water maze (MWM) and increased neuron loss in vulnerable regions (CA3 and CA1) of hippocampus. Uninjured iNOS(+/+) and iNOS(-/-) mice performed equally well in both motor and cognitive tasks. However, after TBI, iNOS(-/-) mice showed markedly worse performance in the MWM task than iNOS(+/+) mice. A beneficial role for iNOS in TBI is supported.

Animals↗
PubMed1999

Levels of antimicrobial molecules defensin and lactoferrin are elevated in the cerebrospinal fluid of children with meningitis.

OBJECTIVE: To measure levels of defensins and lactoferrin in the cerebrospinal fluid (CSF) of children with meningitis. STUDY DESIGN. Prospective descriptive study involving children undergoing lumbar puncture during evaluation for meningitis. METHODS: CSF concentrations of defensins and lactoferrin were determined using enzyme-linked immunosorbent assays on 19 children with bacterial meningitis, 31 children with aseptic meningitis, and 32 control children found to have normal CSF during evaluation for meningitis. Pertinent clinical and laboratory data were gathered on all children. RESULTS: CSF concentrations of both defensins and lactoferrin were elevated markedly in children with bacterial and aseptic meningitis, compared with control children. No control subject had detectable levels of defensins in the CSF. Lactoferrin was undetectable in the CSF of 31 of 32 control subjects. Defensin and lactoferrin levels were significantly higher in the CSF of children with bacterial meningitis than in those with aseptic meningitis. Defensin levels in the CSF of children with bacterial meningitis ranged from 128 ng/mL to 99 430 ng/mL with a mean of 30 311 ng/mL (SD +/- 28 865) and a median of 23 042 ng/mL. Defensin levels in the CSF of children with aseptic meningitis ranged from 0 ng/mL to 1675 ng/mL with a mean of 227 ng/mL (SD +/- 433) and a median of 23 ng/mL. A significant correlation was found between defensin levels in the CSF and the total leukocyte count and the absolute neutrophil count in the CSF of children with bacterial meningitis. Lactoferrin levels in the CSF of children with bacterial meningitis ranged from 184 ng/mL to 31 412 ng/mL with a mean of 13 209 ng/mL (SD +/- 9644) and a median of 10 382 ng/mL. Lactoferrin levels in the CSF of children with aseptic meningitis ranged from 0 ng/mL to 2715 ng/mL with a mean of 1042 ng/mL (SD +/- 878) and a median of 852 ng/mL. No correlation was found between lactoferrin level in the CSF and the total leukocyte count or the absolute neutrophil count in the CSF of children with bacterial meningitis. In our study population, the sum total of CSF defensins and lactoferrin was found to be highly sensitive and specific in delineating bacterial from aseptic meningitis when compared with standard CSF studies. CONCLUSIONS: Significant elevations of defensins and lactoferrin, indicative of endogenous local antimicrobial peptide and polypeptide release, are found in the CSF of children with meningitis. We speculate that elevations in these antimicrobial molecules may reflect the intensity of the host response. Defensins seem to parallel neutrophil activation more closely than lactoferrin. Cumulative levels of CSF defensins and lactoferrin clearly distinguished bacterial meningitis from aseptic meningitis and control patients. Further investigation is warranted to determine the usefulness of measuring defensins and lactoferrin as a diagnostic tool and therapeutic monitor in the evaluation of children with meningitis.

Anti-Infective Agents↗
PubMed1998

Quantification of G protein mRNA using reverse transcription and competitive PCR with a colorimetric microplate assay.

This paper reports an assay for the quantification of levels of specific mRNA for the alpha subunits of the inhibitory G proteins G alpha i-1, G alpha i-2, and G alpha i-3. The assay employs reverse transcription and competitive polymerase chain reaction (PCR) coupled to enzyme-linked oligonucleotide sorbent assay for differential detection and quantification of PCR products. The assay was conducted with conventional thermal block PCR cyclers as well as rapid air microcapillary cyclers. The detection stage consists of three steps using synthetic oligonucleotides, commercially available reagents and a conventional 96-well plate absorbance reader at settings of 450 and 630 nm. The assay is: (1) rapid, requiring about 3 h for quantification of PCR products; (2) safe, being non-radiometric; (3) relatively simple; (4) highly sensitive, being capable of detecting less than 10 initial copies of target cDNA; (5) precise, resolving two-fold differences in initial copy numbers of specific sequences as low as 10(-20) mol; (6) linear over a 3 log range, with two-fold differences in the quantity of cDNA producing consistent reductions in quantity of specific cDNA detected; and (7) reproducible, intra-assay and inter-assay coefficients of variation being 11.9 and 14.7%, respectively.

Animals↗
PubMed1998

Interstitial adenosine, inosine, and hypoxanthine are increased after experimental traumatic brain injury in the rat.

Adenosine is a putative neuroprotectant in ischemia, but its role after traumatic brain injury (TBI) is not clear. Metabolites of adenosine, particularly inosine and hypoxanthine, are markers of ischemia and energy failure. Adenosine triphosphate (ATP) breakdown early after injury and metabolism of cyclic adenosine monophosphate (cAMP) are potential sources of adenosine. Further delineation of the magnitude, location, time course, and source of production of adenosine after TBI is needed. We measured adenosine, inosine, and hypoxanthine in brain interstitial fluid after controlled cortical impact (CCI) in the rat. Rats (n = 15) were prepared for TBI induced by CCI. A microdialysis probe was placed in the cortex, and samples were collected every 10 min. After 3 h of equilibration, the catheter was removed, CCI was performed (4 m/sec, depth 2.5 mm), and the catheter was replaced. In the shams, the catheter was removed and replaced without CCI. The injury group included rats (n = 10) subjected to CCI. Within the injury group, the microdialysis probe was placed in the center of the eventual contusion (center, n = 5) or in the penumbral region (penumbra, n = 5). Purine metabolites were measured using ultraviolet-based high-pressure liquid chromatography. Adenosine, inosine, and hypoxanthine were dramatically increased after injury (61-fold, 37-fold, and 16-fold, respectively sham, all p < 0.05, two-way analysis of variance for repeated measures). No changes in cAMP were observed (p = 0.62 vs. sham). Adenosine peaked in the first 20 min and returned to near baseline 40 min, whereas inosine and hypoxanthine peaked at 30 min and remained increased for 40 min after CCI. Interstitial brain adenosine, inosine, and hypoxanthine were increased early after CCI in rats in the contusion and penumbra. ATP breakdown is a potential source of adenosine in this early period while metabolism of cAMP does not appear to play a role. Confirmation of these data in humans may suggest new strategies targeting this important metabolic pathway.

Adenosine↗
PubMed1998

Soluble adhesion molecules in CSF are increased in children with severe head injury.

Leukocyte-endothelial adhesion molecules, critical to the development of acute inflammation, are expressed in brain as part of the acute inflammatory response to traumatic brain injury (TBI). We measured the concentrations of the adhesion molecules P-selectin, ICAM-1, E-selectin, L-selectin, and VCAM-1 in ventricular cerebrospinal fluid (CSF) from children with severe TBI (Glasgow coma score < 8) and compared these findings with those from children with bacterial meningitis. P-selectin, an adhesion molecule associated with ischemia/reperfusion, was increased in children with TBI versus meningitis and control. Univariate and multivariate regression analyses demonstrated associations between CSF P-selectin and child abuse and age of < 4 years, and a significant, independent association between CSF intercellular adhesion molecule-1 (ICAM-1) and child abuse. These results are consistent with a specific acute inflammatory component to TBI in children. Future studies of secondary injury mechanisms and therapy after TBI should assess on the roles of P-selectin and ICAM-1 in injury and repair processes in brain after TBI.

Adolescent↗
PubMed1998

Plasma nitrite and nitrate concentrations and multiple organ failure in pediatric sepsis.

OBJECTIVE: To determine whether plasma nitrite and nitrate concentrations are associated with the development of sepsis-induced multiple organ failure. DESIGN: Prospective study. SETTING: University children's hospital. PATIENTS: Fifty-three consecutive children meeting criteria for sepsis and not receiving exogenous sources of nitric oxide. INTERVENTIONS: Plasma nitrite and nitrate concentrations were measured, and the number of organs failing was scored using an organ failure index on the first 3 days of sepsis. MEASUREMENTS AND MAIN RESULTS: Children with three or more organs failing on day 3 of sepsis had higher plasma nitrite and nitrate concentrations than children who had resolution of failure of three or more organs by day 3 of sepsis (days 2 and 3) and children who never had three organs failing in the first 3 days of sepsis (days 1, 2, and 3). Children who developed sequential pulmonary/hepatic/renal organ failure had significantly higher plasma nitrite and nitrate concentrations (days 1, 2, and 3). Nonsurvivors had significantly higher plasma nitrite and nitrate concentrations (days 2 and 3) than survivors. Plasma nitrite and nitrate concentrations on day 1 predicted the development of persistent failure of three of more organs and sequential multiple organ failure but not mortality. CONCLUSION: Increased plasma nitrite and nitrate concentrations are associated with the development of multiple organ failure in pediatric sepsis.

Adolescent↗
PubMed1998

Effect of the type IV phosphodiesterase inhibitor Ro 20-1724 on catecholamine-induced alterations in regional vascular resistance and regional blood flow.

Type IV phosphodiesterase inhibitors have been studied in multiple disease processes that commonly afflict patients who are treated with catecholamine infusions. To examine whether type IV phosphodiesterases alter catecholamine-induced changes in systemic and regional hemodynamic parameters, we examined the effects of Ro 20-1724 on rats during dobutamine, epinephrine, isoproterenol, and norepinephrine infusions. Twenty-six Sprague-Dawley rats received either Ro 20-1724 or vehicle. After central and regional hemodynamic monitoring was initiated, animals received increasing doses of two of the four catecholamines. In the absence of catecholamines, Ro 20-1724 infusion caused a significant increase in heart rate and a trend toward an increase in superior mesenteric artery blood flow. Ro 20-1724 attenuated the increase in blood pressure caused by epinephrine but had no effect on the dobutamine-, isoproterenol-, or norepinephrine-induced changes in blood pressure. Ro 20-1724 had no effect on catecholamine-induced changes in renal, carotid, and hindquarter vascular resistance but did attenuate the decrease in superior mesenteric artery vascular resistance caused by isoproterenol. Type IV phosphodiesterase inhibition in combination with catecholamines has no adverse effects on regional hemodynamics; however, it can inhibit the ability of epinephrine infusion to increase blood pressure.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗