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Biomedical subjects

P Moore

Publications and source records attributed to P Moore.

At least 271 records · Page 15Linked to original sources

Echocardiographic guidance for transcatheter coil embolization of congenital coronary arterial fistulas in children.

Congenital coronary arterial fistulas are rare anomalies that have traditionally been managed by surgical ligation. However, in recent years endovascular therapy has been employed with encouraging results. Between 1993 and 1996, we performed transcatheter coil embolization of coronary arterial fistulas to the right atrium or ventricle in four children ranging in age from 4.5 to 9.8 years. Cardiac and coronary arterial anatomy were diagnosed correctly on the preoperative echocardiogram in all patients, including the origin, course, and termination of the fistulas. The fistula was occluded completely in three of the patients, whereas trivial residual flow remained in the fourth. Transesophageal echocardiography was useful for monitoring the embolization procedure. In one of the patients, the fistula reopened while the child was on overnight heparin, although the magnitude of flow was less than that before the embolization. At follow-up ranging from 10 to 43 months, there was no flow through the fistula in any patient. We present our experience with these patients, with a focus on the importance of echocardiographic evaluation before, during, and after transcatheter therapy of coronary arterial fistulas.

Child↗

Acute pulmonary embolism in a neonate: precipitation during cardiac catheterization and successful treatment.

This report illustrates the rare occurrence of a pulmonary embolus in a neonate during cardiac catheterization. The patient was a term newborn who underwent repair of obstructed infradiaphragmatic total anomalous pulmonary venous connection. Postoperative risk factors for pulmonary embolism included severe pulmonary hypertension unresponsive to nitric oxide therapy, an indwelling venous catheter, and young age. Successful management was achieved by initial mechanical fragmentation with streptokinase infusion and monitoring by serial lung perfusion scans.

Acute Disease↗

Cerebral microvessels in Alzheimer's have reduced protein kinase C activity.

Protein kinase C (PKC) is an important intracellular signalling enzyme. Numerous studies have suggested that alterations in this enzyme occur in aging and dementia. The objective of this study was to examine PKC in the cerebral microcirculation in aging and Alzheimer's disease. PKC activity, amount, and isoform distribution were analyzed in microvessels from adult and aged rodents as well as from Alzheimer patients and nondemented elderly controls. PKC activity was lower in Alzheimer vessels than in vessels from control brains, despite the presence of similar levels of PKC enzyme. In contrast, both activity and enzyme levels in young and aged rats were comparable. The beta-isoform was present in both rat and human microvessels and there were no age- or disease-related alterations. The loss in activity in cerebromicrovascular PKC in Alzheimer's suggest that perturbations in phosphorylation signalling cascades may exist at the Alzheimer blood-brain barrier.

Aged↗

Effect of sleep deprivation on neuroendocrine response to a serotonergic probe in healthy male subjects.

Neuroendocrine responses to stimulation with a selective serotonin reuptake inhibitor (citalopram) were measured to investigate the effects of all-night sleep deprivation on serotonergic function in healthy male subjects (n = 7). We studied citalopram-stimulated prolactin and cortisol plasma concentrations in a placebo-controlled cross-over protocol following sleep and sleep deprivation. Citalopram infusion (20 mg i.v. at 14:20-14:50 h) after a night of undisturbed sleep prompted robust increases in both plasma prolactin and cortisol concentrations. Following a night of sleep deprivation, by contrast, the citalopram-induced prolactin response was blunted, but the cortisol response was not significantly altered. This differential response pattern relates to the distinct pathways through which serotonin may activate the corticotrophic and the lactotrophic systems. While an unchanged cortisol response does not indicate (but also does not refute the possibility of) an altered serotonergic responsivity following sleep deprivation, the suppressed prolactin response could reflect a downregulation of 5-HT1A or 2 receptors. An alternative, not mutually exclusive, explanation points to the possibility that sleep deprivation activates the tubuloinfundibular dopaminergic system, the final inhibitory pathway of prolactin regulation.

Adult↗

Generation and functional characterisation of canine bone marrow-derived macrophages.

A culture of bone marrow cells from the femurs of canine pups at high concentrations of fetal calf serum under non-adherent conditions allowed the proliferation and differentiation of mononuclear phagocyte lineage cells, as evidenced by morphology and CD14 expression. Cells from other lineages progressively diminished in numbers. Cells collected between 12 and 19 days of culture expressed an array of macrophage activities including ingestion of opsonised erythrocytes, generation of superoxide, up-regulation of procoagulant activity and synthesis of tumour necrosis factor (TNF) upon appropriate stimulation. TNF production was enhanced when the cultures were simultaneously stimulated with canine recombinant, or supernatant-derived, interferon-gamma. In contrast, low levels of inducible nitric oxide (NO) synthase were expressed by only a minority of stimulated macrophages, and nitrite could not be detected in the medium. Therefore, canine macrophages generated by this novel culture system resemble human macrophages in their inefficient and restricted generation of NO upon appropriate stimulation.

Animals↗

Prostacyclin production by human placental cells in short-term culture.

Human placentae of varying gestational ages have been cultured in vitro with little variation in cell type and pattern of growth found. Cell types found are similar morphologically and histochemically to those previously described. The biological specificity of the cells in culture was also confirmed by human placental lactogen production. Placental cells in culture appear to synthesize and release PGI2 which can be identified by gas chromatography-mass spectrometry. Production of PGI2 was routinely measured by radioimmunoassay (RIA) for 6-oxo-PGF1alpha and 13,14-dihydro-6,15-dioxo-PGF1alpha in culture supernatants. Good agreement was found between RIA and gas chromatography-mass spectrometry measurements. PGI2 production in culture was not affected by mode of delivery, and synthetic capability was found to increase with gestational age. Production of PGI2 by cells from preterm and term placentae was similar but significantly greater than that of first-trimester cells. As the proportion of PGI2 produced in culture supernatants as 13,14-dihydro-6,15-dioxo-PGF1alpha changed with time of incubation, it appears pertinent to measure this metabolite when assessing total PGI2 production. Synthesis of PGI2 wa inhibited by the cyclo-oxygenase inhibitors indomethacin and aspirin and PGI2 synthetase inhibitor 15 hydroperoxyarachidonic acid. However, in the culture system tranylcypromine, a putative specific inhibitor of PGI2 synthetase, produced weak inhibition only before becoming cytotoxic. The cell culture system appears to offer a reliable and reproducible means for measuring placental PGI2 production in vitro and in which to study factors controlling its production and metabolism.

Arachidonic Acids↗

The role of DNA polymerase in base substitution mutagenesis on non-instructional templates.

In vitro DNA synthesis on phi X174 or M13 templates with non-instructional lesions such as UV dimers or AP (apurinic/apyrimidinic) sites terminates one base before the site of the lesion when synthesis is catalyzed by T4 DNA polymerase or E. coli polymerase I. E. Coli polymerase I also produces termination bands at the site of AP lesions. Substitution of Mn2+ for Mg2+ and increasing the concentration of dNTP's results in elongation of the newly synthesized strand opposite the site of the lesion and beyond. Purine deoxynucleoside triphosphates are utilized for insertion opposite lesions to a greater extent than are pyrimidine deoxynucleoside triphosphates. Deoxy ATP is used almost exclusively for elongation opposite AP sites with pol I-Klenow fragment in the presence of Mg2+. We suppose that these results illustrate the previously observed greater affinity of polymerases under template-free conditions for purine nucleotides. We also suppose that the results can be used to account for mutagenic base selection on noninstructional DNA templates. If purines are preferentially selected by polymerases, then treatments which inactivate pyrimidines will lead to an excess of transitions whereas inactivation of purines will produce more transversions. Data in the literature support this hypothesis.

Bacteriophage phi X 174↗

A case study: oligonucleotide purification from gram to hundred gram scale.

This article describes the purification and scale-up of ISIS 2302, a 20-mer phosphorothioate oligonucleotide by anion-exchange (AX) chromatography. The key operating parameters were optimized at gram scale and further scaled up to hundred gram. SOURCE 30Q, a high efficiency polymeric chromatographic media was used for both the small and large-scale work. High length-based purity and yield were maintained at scale-up. This purification is one of the largest demonstrations of AX purification of phosphorothioate oligonucleotide.

Chromatography, Ion Exchange↗

Social competence and behavioral problems of pediatric survivors of burns.

Sixty children (35 boys, 25 girls) with burns were surveyed at least 1 year after burn injury to assess the behavior problems and difficulties with competency that they were having. The Child Behavior Checklist, the Youth Self Report, and the Teacher Report Form developed by Achenbach were administered to obtain standardized measures of behavior and competence. The mean values for these scales were in the normal range for each age and sex. However, the Child Behavior Checklist revealed a statistically significant (p < 0.05) increase in problems and decrease in competency for most age groups and both sexes when compared with the reference population. In contrast, the Teacher Report Form and the Youth Self Report revealed very few differences from the reference population. The burn size (15% to 20% total body surface area, 35% to 50% total body surface area, and > 70% total body surface area) did not account for any of the group differences. Further studies involving detailed clinical interviews and other standardized measures are needed to understand the discrepancies between the Child Behavior Checklist and the other scales.

Adolescent↗

Parental stress as a cause and effect of pediatric burn injury.

The current study reports assessments of stress for parents of children with acute burns at the time of hospital admission and during the first 5 years after injury. At each assessment, parents of children with burns report neither more nor less stress than a normal population. At the time of admission, parents of children with acute burns do not differ from the normal sample on any of the measures of parenting stress. Parents of recovering children with burns do report significant changes. They report significantly higher depressive symptoms at year 2 after the child's burn injury and lower than normal levels of depression in years 4 and 5 after the child's injury. During the recovery period, these parents also attribute their stress more often to the child with burns, whereas other parents more evenly divide blame among their children and their personal characteristics.

Acute Disease↗