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Biomedical subjects

P Moore

Publications and source records attributed to P Moore.

At least 109 records · Page 6Linked to original sources
PubMed1998

Rapid tryptophan depletion, sleep electroencephalogram, and mood in men with remitted depression on serotonin reuptake inhibitors.

BACKGROUND: In previous studies, depletion of brain serotonin by administration of a tryptophan-free amino acid drink (TFD) (1) temporarily reversed the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) in euthymic patients who had a history of major depression, and (2) enhanced rapid eye movement (REM) sleep in normal volunteers. In this study, we hypothesized that the TFD would not only increase depressive symptoms but also the propensity for REM sleep in euthymic patients treated with SSRIs. METHODS: Ten fully remitted, medicated male patients who had a history of major depressive episode ingested a 100-g TFD (the experimental dose) or a 25-g TFD (designed to be the control drink) in double-blind, random order on separate days. The effects were assessed with mood ratings, plasma tryptophan concentrations, and an all-night sleep electroencephalogram. RESULTS: The TFDs produced a dose-dependent reduction in plasma tryptophan concentrations, sleep latency, and REM latency, as well as increased REM percentage, REM minutes, REM density, and total sleep time. Neither strength of TFD altered mood to a clinically significant degree. CONCLUSIONS: Although the TFD affected plasma tryptophan concentrations and various sleep measures, our study did not confirm previous reports that TFD temporarily reversed the antidepressant effects of SSRIs in euthymic patients. Our patients, however, had been treated for a longer period with SSRIs and were more fully remitted at the time of the study. Our results suggest that TFD-induced relapse in SSRI-treated patients in remission decreases as a function of treatment duration, degree of remission, or both.

Amino Acids↗
PubMed1998

Anoxic injury of endothelial cells causes divergent changes in protein kinase C and protein kinase A signaling pathways.

Alterations in protein kinase C (PKC) and cAMP-dependent kinase have been documented in anoxic brain injury. However, the regulation of these signaling enzymes in the cerebrovasculature has not been explored. In this study, cultured brain endothelial cells exposed to anoxic injury (anoxia--20 min/reoxygenation--40 min) showed both a significant increase (p < 0.001) in PKC and decrease (p < 0.01) in cAMP-dependent kinase activity. Analysis of PKC by Western blot indicated an increase in kinase level in response to anoxic injury, whereas there was no change in the level of cAMP-dependent protein kinase, as measured by labeled cAMP binding. Inhibition of nitric oxide synthase did not affect these changes. Addition of the nitric oxide-releasing compound sodium nitroprusside caused a dose-dependent increase in the activity of both signaling systems in endothelial cells. These data demonstrate that anoxic injury of brain endothelial cells in culture causes significant and divergent changes in signaling kinase activity. Abnormalities in brain endothelial PKC and cAMP-dependent kinase could have important consequences for the blood-brain barrier in anoxic brain injury.

Animals↗
PubMed1998

Virtual electrode effects in defibrillation.

This modeling study demonstrates that a re-entrant activity in a sheet of myocardium can be extinguished by a defibrillation shock delivered via extracellular point-source electrodes which establish spatially non-uniform applied field. The tissue is represented as a homogeneous bidomain with unequal anisotropy ratios in the cardiac conductivities. Spiral wave re-entry is initiated in the bidomain sheet following an S1-S2 stimulation protocol. The results indicate that the point-source defibrillation shock establishes large-scale changes in transmembrane potential in the tissue (virtual electrodes) that are 'superimposed' over regions of various degrees of membrane refractoriness in the myocardium. The close proximity of large-scale shock-induced regions of alternating membrane polarity is central to the ability of the shock to terminate the spiral wave. The new wavefronts generated following anode/cathode break phenomena restrict the spiral wave and render the tissue too refractory to further maintain the re-entry. In contrast, shocks delivered via line electrodes establish, in close proximity to the electrode, changes in transmembrane potential that are of same-sign polarity. These shocks are incapable of terminating the re-entrant activation.

Anisotropy↗
PubMed1998

Lymphocyte subsets and CD45RA positive T-cells in normal canine cerebrospinal fluid.

In order to evaluate changes in lymphocyte subpopulations of cerebrospinal fluid (CSF) cells in neurological diseases, normal control data have to be established. In this study we evaluated CSF samples from 65 dogs of both sexes and various breeds with an age range between 5 months and 6 years, and 20 one-year-old healthy inbred Beagles. For comparison, blood samples from 10 healthy dogs were examined. 14 different antibodies against leukocyte surface markers were used. The subpopulations were evaluated using flow cytometry (FACS) and immunocytochemistry. It could be shown that lymphocyte populations in CSF differ from peripheral blood in a few subsets. A relatively high degree of individual variation was found, not only in dogs of different breeds and ages, but also in the inbred Beagle population. These large individual variations suggest that repeated paired CSF-blood samples during the course of neurological disease should be examined within the same individual to obtain meaningful results. CD3+ and CD4+ T-cells were significantly lower in normal CSF. Of great interest is the fact, that T-cells, characterized by double staining CD3/CD45RA are present in variable numbers in normal CSF. In other species they are known to be naive or resting T-cells. CD4/CD45RA positive cells seem to be an important subpopulation of these CD45RA positive T-cells. Furthermore, by far more CD11b positive lymphocytes were observed in the CSF than in the peripheral blood and these are not large granular lymphocytes. The present study shows that systematic FACS analysis of CSF is feasible in larger animals such as dogs.

Animals↗
PubMed1998

Production and purification of recombinant protective antigen and protective efficacy against Bacillus anthracis.

Recombinant protective antigen (rPA), expressed by Bacillus subtilis WB600 (pPA 101), has been purified to homogeneity and the protective efficacy against a Bacillus anthracis challenge has been investigated. rPA was fractionated from culture supernatant fluid by ammonium sulphate, followed by anion exchange chromatography using DEAE Streamline, anion-exchange chromatography on FPLC MonoQ HR 10/10 and finally, gel filtration chromatography on FPLC Superose 12 HR 10/30, to yield 7 mg rPA per litre of culture. The protective efficacy of rPA against an airborne challenge with the AMES strain of B. anthracis was determined in the presence of the adjuvants, alhydrogel and Ribi, and compared to that achieved by the current UK human vaccine in guinea pigs. rPA combined with the Ribi adjuvant was found to provide 100% protection against challenge.

Adjuvants, Immunologic↗
PubMed1998

Characterisation of gastro-enteritis-associated adenoviruses in South Africa.

OBJECTIVE: To analyse adenovirus (Ad) numbers and types associated with paediatric gastro-enteritis in South Africa. SETTING: Gauteng, 1994-1996. METHODS: A total of 234 paediatric diarrhoeal stool samples were screened for Ad using commercial enzyme-linked immunosorbent assays (ELISAs). Adenoviral isolates were typed, where possible, using restriction enzyme analysis. RESULTS: Ad was detected in 23 (9.8%) specimens, of which 8 (34.8%) were found by subgroup F-specific ELISA to contain Ad40 or 41. Six of these isolates were typed and 2 could not be typed. Of the remaining 15 specimens, 2 isolates had restriction profiles that did not correspond with known Ads, while 2 were identified as Ad31 and 1 as a subgroup C Ad. The remaining 10 specimens negative for Ad40/41 were non-cultivable and could not be typed. CONCLUSIONS: The high percentage of non-cultivable Ads other than Ad40/41 is unusual, and may possibly indicate the prevalence of hexon variants of Ad40/41 or of emerging Ad types in South Africa.

Adenovirus Infections, Human↗
PubMed1997

Isolated left superior vena cava to the left atrium with situs solitus and dextrocardia: extracardiac repair facilitated by juxtaposition of the atrial appendages.

We describe an extremely unusual case, with isolated left superior vena cava to the left atrium, normal intracardiac anatomy, and left juxtaposition of the atrial appendages. Surgical repair was performed without cardiopulmonary bypass by anastomosing the left superior cava to the superior aspect of the right atrial appendage, and was facilitated by the ectopic location of the appendage.

Abnormalities, Multiple↗
PubMed1997

Production of neurotoxic factors by brain endothelium in Alzheimer's disease.

The cerebral vasculature is central to the maintenance of the neuronal microenvironment. We have previously demonstrated that brain microvessels in Alzheimer's disease produce high, potentially toxic, levels of nitric oxide. It is our hypothesis that neuronal injury in Alzheimer's disease occurs because an abnormal endothelium secretes factors that are toxic to neurons. In this study, we report that inhibition of protein kinase C in endothelial cells causes release of a factor that is toxic to neurons in vitro. Our results demonstrate that this endothelium-derived toxic factor is soluble, heat-labile, susceptible to proteolysis, and loses activity with repeated freeze-thawing. The molecular weight of this putative protein is between 10 and 50 kDa, and 8 hours are required after protein kinase C inhibition to detect the endothelium-derived toxic factor in the media. Finally, the endothelium-derived toxic factor kills neurons within 2 hours, suggesting that cell death occurs via necrosis, not apoptosis. These data support the notion that endothelial cells can create an injurious microenvironment for neurons by producing molecules with noxious properties. Altered/dysfunctional endothelial cells in the cerebral microcirculation could be a novel, unexplored source of neurotoxic factors in Alzheimer's disease.

Alzheimer Disease↗
PubMed1997

Reduction of bovine immunoglobulin contamination from monoclonal antibodies by SOURCE 15PHE chromatography.

The presence of bovine immunoglobulin in cell culture media, and its nature as a polyclonal antibody, imposes increasing difficulties in resolution from the MAb intended for in vivo human applications. Particular difficulties are encountered when murine MAbs are the target antibody. This study presents model cases to simulate this problem, and suggests an efficient method for reduction of bovine IgG (BGG) from MAb preparations. Utilizing the new small particle size hydrophobic interaction chromatography resin, SOURCE 15PHE, up to complete resolution was achieved with a chimeric MAb. A 17-fold reduction of BGG was achieved with a murine MAb. In both cases, high recoveries of the MAb were obtained. The general applicability of the method is suggested.

Animals↗
PubMed1997

Fetoscopic and open transumbilical fetal cardiac catheterization in sheep. Potential approaches for human fetal cardiac intervention.

BACKGROUND: Shortening the prenatal disease course of severe aortic and pulmonary stenoses by balloon valvuloplasty may diminish their postnatal expression. The purpose of this study in fetal sheep was to assess the feasibility of fetoscopic and open transumbilical fetal cardiac catheterization guided by fetal transesophageal echocardiography to provide alternative approaches for human fetal cardiac intervention. METHODS AND RESULTS: We studied a total of nine fetal sheep (95 to 103 days of gestation; term = 145 to 150 days) and performed transumbilical fetal cardiac catheterization by a minimally invasive fetoscopic (n = 6) or an open fetal surgical approach (n = 3). Monitored by fetal transesophageal echocardiography, with an 8F or 10F, 10-MHz intravascular ultrasound catheter we placed guidewires and interventional catheters via the umbilical arterial route into the fetal heart. In three of the fetuses, we created supravalvar pulmonary artery stenosis by open fetal cardiac surgery After fetal and maternal recovery, we exteriorized these fetuses and performed open transumbilical fetal cardiac catheterization with successful pulmonary arterial angioplasty in two. Three fetuses survived fetoscopic transumbilical catheterization for 1 or 2 days and died most likely of blood loss after sheath dislodgment (n = 1) or removal (n = 2). By securing the sheath insertion site with a suture, we prevented sheath dislodgment and minimized bleeding during sheath removal in three fetuses. These fetuses then survived fetoscopic transumbilical fetal cardiac catheterization for 1 to 2 weeks before being killed. CONCLUSIONS: This study in fetal sheep demonstrates that fetoscopic and open transumbilical fetal cardiac catheterization are feasible and, guided by fetal transesophageal echocardiography, provide potential alternative approaches for human fetal cardiac intervention.

Angioplasty, Balloon↗
PubMed1997

Bidirectional cavopulmonary shunt in patients with anomalies of systemic and pulmonary venous drainage.

BACKGROUND: Bidirectional cavopulmonary shunt and Fontan repair are now commonly performed in patients with a variety of forms of complex single ventricle, including those with anomalies of systemic or pulmonary venous return. These anomalies are ideally dealt with during bidirectional cavopulmonary shunt, thereby minimizing the complexity of the eventual Fontan procedure. METHODS: Between March 1990 and December 1995, 36 patients with anomalous systemic or pulmonary venous drainage underwent bidirectional cavopulmonary shunt. A combination of anomalous systemic and pulmonary venous drainage was present in 12 patients, whereas 19 patients had anomalous drainage only from the systemic circulation and 5 patients had isolated anomalies of pulmonary venous return. Visceral heterotaxy syndrome was diagnosed in 18 patients. The median age at operation was 11 months, and bidirectional cavopulmonary shunt was the first surgical procedure performed in 10 of these patients. Techniques of repair are described. RESULTS: There were two early deaths and one bidirectional cavopulmonary shunt was taken down, for mortality and failure rates not significantly different than those for all patients undergoing bidirectional cavopulmonary shunt during this time period (n = 117). At a mean follow-up of 19.9 months, there have been three late deaths and 11 patients have undergone Fontan completion. Actuarial survival was 87% at 1 year and 81% at 3 years. Among all patients undergoing bidirectional cavopulmonary shunt during this time period, neither heterotaxy syndrome nor anomalies of systemic or pulmonary venous return were significantly associated with decreased survival or poor outcome. CONCLUSIONS: Bidirectional cavopulmonary shunt can be performed in patients with anomalous systemic or pulmonary venous drainage, including those with visceral heterotaxy syndrome, with morbidity and mortality rates that do not differ significantly from those achieved in all patients undergoing bidirectional cavopulmonary shunt. In this report, we describe our experience with this group of patients, primarily focusing on outcomes and technical issues that pertain to the use of bidirectional cavopulmonary shunt as a preparatory procedure for the extracardiac conduit Fontan operation.

Actuarial Analysis↗