PubMed Health⌕ Search

Biomedical subjects

C Cave

Publications and source records attributed to C Cave.

11 recordsLinked to original sources
PubMed2001

Mechanisms of human neutrophil oxidant production after severe injury.

BACKGROUND: The purpose of this study was to determine the mechanisms of enhanced oxidant production after severe injury. METHODS: Neutrophils were harvested from patients within 24 hours of admission who had an injury severity score greater than 16. Nonadherent and adherent neutrophil oxidant production was measured after N-formyl-methionyl-leucyl-phenylalanine (fMLP) stimulation. Translocation of cytochrome b558 and cytosolic components p47phox and p67phox were determined by oxidation-reduction spectroscopy and immunoblotting, respectively. Flow cytometry measured integrin expression. Integrin and p47phox colocalization was examined by confocal microscopy. RESULTS: Eighteen patients were studied within 15 +/- 1.4 hours. Four women and 14 men suffered a blunt injury and had a mean injury severity score of 22 (range, 16 to 34). Nonadherent patient neutrophils showed a decrease in fMLP-stimulated oxidant production, whereas adherent neutrophil oxidant production was increased in both the vehicle control and fMLP-stimulated groups. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase components p47phox and cytochrome b558 were mobilized to the plasma membrane, whereas p67phox showed minimal change. Integrin CD11b a chain showed a significant increase in expression. Confocal microscopy showed colocalization of p47phox and a chain CD11b on the plasma membrane of patient neutrophils. CONCLUSIONS: Colocalization of NADPH oxidase components and integrins may regulate the enhanced oxidant production in human neutrophils after severe injury.

Adolescent↗
PubMed2001

CXCR2 regulation of tumor necrosis factor-alpha adherence-dependent peroxide production is significantly diminished after severe injury in human neutrophils.

BACKGROUND: Primed neutrophils are thought to play a key role in inflammatory pathology. We have shown though in vitro studies that interleukin (IL)-8 and growth-related oncogene-alpha (GROalpha) (CXCR2-specific chemokines) regulate the respiratory burst via the CXCR2 receptor. We have also shown in vivo, CXCR2 receptors are down-regulated in severely injured patients. Our hypothesis is that regulation of the respiratory burst by CXCR2 is lost after severe injury. METHODS: Patient neutrophils were studied within 24 hours of admission to the hospital; excluded were severe head injury and patients with Injury Severity Score < 16. Patient and normal neutrophils were isolated by Ficoll-Hypaque centrifugation after dextran sedimentation. Neutrophils were plated with buffer, 50 nmol/L IL-8 or GROalpha on fibronectin-coated plates for 15 minutes, then stimulated with 10 ng/mL of TNFalpha. CXCR2 expression was measured by flow cytometry. Receptor function was assessed by calcium mobilization. RESULTS: One female and 10 male patients with an average age of 37 +/- 3 and Injury Severity Score of 24 +/- 5 suffered blunt injury. CXCR2 showed a 32% +/- 7% loss, whereas CXCR1 showed 15% +/- 6% reduction. GROalpha stimulation of patient neutrophils showed 60% +/- 16% decrease in calcium mobilization, whereas IL-8 showed no decline. At 40 minutes, IL-8 and GROalpha significantly inhibited TNFalpha adherence-dependent peroxide production in normal neutrophils (35% +/- 4% and 45% +/- 3%, respectively; p < 0.05). Both IL-8 and GROalpha lost the ability to suppress the respiratory burst in severely injured patients, but GROalpha had a significantly greater loss of this suppression (p = 0.004). CONCLUSION: IL-8 and GROalpha lose the ability to regulate the TNFalpha-induced respiratory burst. This may contribute to neutrophil dysregulation after injury and result in organ injury.

Adult↗
PubMed1999

Preferential loss of CXCR-2 receptor expression and function in patients who have undergone trauma.

BACKGROUND: In response to traumatic injury or infection, human neutrophils are directed to the site of injury or infection by CXC chemokines that signal via 2 receptors, CXCR-1 and CXCR-2. In vitro studies have shown preferential loss of CXCR-2 expression and function after exposure to interleukin 8, N-formyl-methionyl-leucyl-phenylalanine (fMLP), C5a, and tumor necrosis factor alpha. HYPOTHESIS: CXCR-2 expression and function are preferentially down-regulated in severely injured patients. METHODS: We studied 20 patients within 24 hours of admission to the hospital. Patients with head injuries were excluded. Injury Severity Scores (range, 1-50; mean, 35) were calculated for each patient. To determine expression of CXCR-1 and CXCR-2, flow cytometry was used. Intracellular calcium mobilization and neutrophil migration to 10 nmol of interleukin 8, growth-related oncogene alpha, and fMLP was measured to determine receptor function. RESULTS: Compared with CXCR-1, there is a greater loss of CXCR-2 receptor expression in the severely injured group (P = .01). Neutrophils from patients with Injury Severity Scores greater than 16 did not mobilize calcium in response to growth-related oncogene alpha. However, there was no loss of calcium mobilization to interleukin 8 or fMLP. Chemotaxis to various stimulants is decreased in all injury groups. CONCLUSIONS: CXCR-2 expression and function are preferentially down-regulated in severely injured patients. Our data suggest that there are multiple mechanisms, in addition to receptor down-regulation, that play a role in the loss of migration and calcium flux in human neutrophils after injury.

Adolescent↗
PubMed1998

Transcutaneous monitoring of blood gases: is it comparable with arterialized earlobe sampling?

Researchers are increasingly looking for reliable non-invasive methods of assessing blood gas concentrations, and several new techniques have recently become available. Values derived using arterialized earlobe samples have been found to be comparable with conventional arterial samples, and recent studies have compared transcutaneous blood gas analysis with the traditional arterial samples and found a reasonable level of agreement in particular for the partial pressure of carbon dioxide. There are no data comparing oxygen and carbon dioxide partial pressures (pO2, pCO2) derived from arterialized samples with one of the newer transcutaneous techniques. We therefore simultaneously studied arterialized earlobe blood gas samples and values for pO2 and pCO2 obtained by a transcutaneous monitor (TINA, Radiometer, Copenhagen) in 26 subjects with varying blood gas values. There was a close agreement between the two methods for assessment of pCO2 [mean difference (95% C.I.) between transcutaneous and earlobe values 0.25 kPa (-0.004, 0.5 kPa)], but not for pO2 [1.71 kPa (0.35, 3.07 kPa)]. Similarly, the limits of agreement were narrow for pCO2 compared to those for pO2 (-0.98, 1.47 kPa and -6.44, 3.02 kPa respectively). We conclude that transcutaneous measurement of pCO2 using the TINA is acceptable in the research setting, whereas assessment of pO2 cannot reliably be made using this technique.

Adult↗
PubMedDate not supplied

Passage of allophanoyl-gamma-lactones through the kidney.

In order to establish if allophanoyl-gamma lactones (B compounds) can pass through the kidney or if only the corresponding delta-hydroxybarbiturates (A compounds), formed by intramolecular alcoholysis, are able to do so, nine experiments were performed to study the urinary excretion of four different allophanoyl gamma-lactones B after administration to dogs. Excreted compounds were extracted, identified and quantised. From the amounts of unmodified administered lactones that were recovered, it is concluded that B compounds can pass through the kidney before isomerisation into the corresponding barbiturates A.

Animals↗
PubMedDate not supplied

Infective endocarditis and an embolomycotic aneurysm in a 25-month-old child.

Infective endocarditis in young children is uncommon, especially where there is no underlying structural heart disease. While septic embolization in adults occurs in up to 43% of the cases of endocarditis, there is little data on systemic embolization in cases of children. We present an unusual case of a 25-month-old child with infective endocarditis and an embolomycotic aneurysm treated by mitral valve replacement and aortoiliac reconstruction.

Aneurysm, Infected↗