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Biomedical subjects

K Moore

Publications and source records attributed to K Moore.

At least 127 records · Page 7Linked to original sources

8-Isoprostaglandin F2 alpha, a product of lipid peroxidation, increases portal pressure in normal and cirrhotic rats.

BACKGROUND & AIMS: The F2-isoprostanes are a recently described class of prostaglandins formed by free radical-mediated lipid peroxidation. 8-Isoprostaglandin F2 alpha (8-iso-PGF2 alpha), an F2-isoprostane, has previously been shown to be a potent renal vasoconstrictor acting via a thromboxane-like receptor. The aim of this study was to investigate whether 8-iso-PGF2 alpha increases portal pressure. METHODS: Livers from normal and bile duct-ligated cirrhotic rats were perfused, and portal pressure response to infused agonist was monitored continuously. RESULTS: Infusion of 8-iso-PGF2 alpha increased portal pressure in both groups, with a significantly greater response in cirrhotic rats. At a dose of 2.5 nmol/min, the mean portal pressure increased from a baseline of 8.2 +/- 0.6 to 9.8 +/- 1.3 mm Hg, whereas in cirrhotic animals, the increase was from 12.0 +/- 0.9 to 18.6 +/- 1.8 mm Hg. This response was completely blocked by SQ29548, a thromboxane receptor antagonist. A similar response pattern was observed with the thromboxane receptor agonist U46619. CONCLUSIONS: 8-iso-PGF2 alpha can increase portal pressure in cirrhotic rats. If extrapolated to patients with cirrhosis, lipid peroxidation secondary to alcoholic liver injury, sepsis, or other liver pathology may cause an acute increase in portal pressure such as that observed in acute liver injury.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Iodine released from the wound dressing Iodosorb modulates the secretion of cytokines by human macrophages responding to bacterial lipopolysaccharide.

Clinical data suggests that iodine released into the wound environment by Iodosorb may enhance the healing of chronic leg ulcers by a mechanism additional to its anti-bacterial activity. The macrophage is considered to play a central role in controlling wound healing and this study was designed to determine whether interaction with iodine could modulate macrophage cytokine output. The human macrophage cell line U937 was co-cultured with Iodosorb, Iodosorb conditioned medium or elemental iodine in the presence of optimal and sub-optimal stimulatory concentrations of bacterial lipopolysaccharide (LPS). The concentration of tumour necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) were assayed in the culture medium after 24 hr culture. Co-culture with 0.25% Iodosorb, Iodosorb conditioned medium or 20 micrograms/ml iodine enhanced TNF alpha secretion (48 +/- 3% cytotoxicity in L929 bioassay to 78 +/- 2% cytotoxicity, +/-SD) by U937 cells stimulated with sub-optimal concentrations of LPS (0.25 ng/ml) and inhibited secretion of IL-6 from cells stimulated with 10 ng/ml LPS (> 750 pg/ml to 267 +/- 52 pg/ml, +/-SD, n = 4). Immunohistological staining of sections prepared from biopsies of chronic leg ulcers indicated that the majority of macrophages present were negative for TNF alpha. Thus one potential mechanism of action of iodine released from Iodosorb used as a wound dressing is to provide a pro-inflammatory stimulus in the wound tissue by activation of the resident macrophage population. This would result in a localized production of pro-inflammatory cytokines and generate an influx of monocytes and T-lymphocytes into the wound that may trigger the wound into a healing phase.

Animals↗

Quantitation of 8-oxoguanine and strand breaks produced by four oxidizing agents.

Reactive oxygen species, produced endogenously or by exposure to environmental chemicals and ionizing radiation, induce a wide range of DNA lesions. The variety of chemistries associated with different oxidants suggests that each will produce a unique spectrum of DNA damage products. To extend our efforts to relate genotoxin chemistry to DNA damage, we measured both strand breaks and 8-oxoguanine (8-oxoG) in DNA after exposure to gamma-radiation, Fe(II)-EDTA/H2O2, Cu(II)/H2O2, and peroxynitrite at concentrations approaching physiological relevance. We found that the ratio of 8-oxoG to strand breaks varied more than 10-fold depending on the oxidizing agent: approximately 0.4 for Cu(II)/H2O2 and peroxynitrite and approximately 0.03 for Fe-(II)-EDTA/ H2O2 and gamma-radiation. In the case of Cu(II)/H2O2, the relative proportion of 8-oxoG and strand breaks was found to vary more than 2-fold (0.14-0.37) for different Cu(II) concentrations, consistent with other studies. We were able to detect 8-oxoG formation by peroxynitrite by using low peroxynitrite concentrations in conjunction with a sensitive immunoaffinity/HPLC-ECD methodology. The level of 8-oxoG relative to strand breaks produced by peroxynitrite was higher than that produced by Fe(II)-EDTA/H2O2 and gamma-radiation, which is consistent with the altered reactivity or accessibility of a non-hydroxyl radical species produced by peroxynitrite.

Copper↗

Extra pontine myelinolysis in a tetraplegic patient: case report.

Hyposmolar hyponatremia (serum sodium < 130 mmol/l) is a common phenomenon in the spinal cord injury (SCI) patient population and in most cases, it is of relatively little consequence. However, rapid correction or over correction of hyponatremia (a change in serum sodium > 25 mmol/l within 48 h) has been linked to Central Pontine Myelinolysis (CPM) and Extra Pontine Myelinolysis (EPM), usually along with other recognized predisposing factors. We report the first case of isolated Extra Pontine Myelinolysis in an SCI patient without any of the recognized predisposing factors, following correction of hyponatremia. The signs and symptoms of Extra Pontine Myelinolysis were not very remarkable in our patient because of prior spinal cord injury. The diagnosis was confirmed by the typical finding of myelinolysis in the basal ganglion region on MRI. Hyponatremia occurs frequently in the SCI patient population, thus placing them at increased risk for Extra Pontine Myelinolysis. Therefore, we emphasize the importance of watching for this entity during the management of hyponatremia in the SCI patient population and recommend the use of MRI scans to confirm the clinical diagnosis.

Hallucinations↗

The hepatorenal syndrome.

1. The hepatorenal syndrome is the development of renal failure in patients with severe liver disease in the absence of any identifiable renal pathology. 2. Decreased glomerular filtration is caused by a reduction in both renal blood flow and the renal filtration fraction. These changes arise as a consequence of a fall in mean arterial pressure due to systemic vasodilatation, activation of the sympathetic nervous system causing renal vasoconstriction, and increased synthesis of several vasoactive mediators, which together modulate both renal blood flow and the glomerular capillary ultrafiltration coefficient, and thence filtration fraction. 3. Patients with liver disease developing renal failure should have hypovolaemia excluded by volume challenge, and all nephrotoxic drugs including diuretics should be stopped. Broad-spectrum antibiotics should be given for subclinical infection, which may be a treatable precipitant of renal failure in cirrhosis. Renal perfusion should be optimized by ensuring that the blood pressure and systemic haemodynamics are adequate, and that if renal venous pressure is elevated, due to tense ascites, it is alleviated. 4. The prognosis of hepatorenal syndrome is poor with a > 90% mortality. However, patients can and do recover from the hepatorenal syndrome, but only if there is a significant improvement of their liver function, or if they undergo liver transplantation.

Hepatorenal Syndrome↗

T lymphocytes and the lack of activated macrophages in wound margin biopsies from chronic leg ulcers.

The objective of this study was to characterize the leucocyte infiltrate which accumulates at the margin of chronic wounds. These leucocytes are a rich source of cytokines and growth factors, and an inappropriate function of these cells may contribute to the maintenance of wound chronicity. The leucocyte populations were stained immunohistochemically with monoclonal antibodies specific for surface receptors which give an indication of cellular function. Wound margin biopsies taken from chronic leg ulcers exhibited a localized infiltrate of CD45+ leucocytes associated with vascularized tissue in the dermis adjacent to the wound margin. Lymphocytes were identified in highest numbers in this area and CD45RO+ T lymphocytes predominated over B lymphocytes, which were either absent or present in very low numbers. In the majority of chronic wounds examined, CD4+ T lymphocytes were present in greater numbers than CD8+ T lymphocytes with a mean (+/-SD) ratio of CD4+:CD8+ of 1.5 +/- 0.6. CD68+ macrophages were identified in all layers of the dermis at the chronic wound margin. In 60% of wounds examined, macrophages were negative for the activation associated markers CD16 (Fc gamma III receptor) and CD35 (C3b receptor). In those biopsies where CD16 and CD35 positive macrophages were observed these were preferentially located in the perivascular regions. These data indicate that as monocytes extravasate into chronic wound tissue they may be subjected to microenvironmental influences which either suppress or do not induce macrophage activation. Suppression of macrophage activation may lead to an inappropriate cytokine/growth factor secretion and contribute to the maintenance of wound chronicity.

Antigens, CD↗

The treatment of conduct disorder: perspectives from across Canada.

OBJECTIVE: To provide a synopsis of treatment programs for conduct-disordered children in Canada. METHOD: Five groups of authors from British Columbia, Ontario, Quebec, and New Brunswick describe their approaches to the treatment of children with conduct disorder. RESULTS: All programs emphasize the needs to use multimodal treatment schemes, including day and short-term residential care, and to base programs on identified factors associated with the development of conduct disorder. CONCLUSION: Specific forms of treatment of conduct disorder are promising but are often hampered by social and political agendas.

Adolescent↗

Comparing the tensile strength of brackets adhered to laser-etched enamel vs. acid-etched enamel.

This study compared the tensile bond strength of brackets adhered to laser-etched enamel with that of brackets adhered to acid-etched enamel. Forty extracted, intact bovine teeth were treated with either 37 percent phosphoric acid for 15 seconds or neodymium:yttrium-aluminumgarnet laser on black-ink-coated enamel. After thermocycling, tensile stress was applied to the bonded specimens at a 0.1 millimeter/minute orosshead speed. A t-test comparison of means showed a significant difference between the laser-etched and acid-etched teeth, with the acid-etched teeth demonstrating significantly more tensile bond strength at a 95 percent level of significance.

Acid Etching, Dental↗

Bile acids, oxidative stress, and renal function in biliary obstruction.

Renal dysfunction occurs in patients with biliary obstruction. Plasma accumulation of bile acids and oxidative stress have been proposed as contributory factors. Bile acids can alter the renal handling of electrolytes and water by blocking the Na(+)-H+ antiport in the tubule. Oxidative stress, defined as an imbalance between radical generating systems and radical scavenging systems giving rise to free radical induced tissue damage, occurs in patients with liver disease. Bile acids cause oxidative damage to tubular cell membranes by stimulating the generation of oxygen free radicals from mitochondria, as well as promoting their release from neutrophils and macrophages. Oxidative stress can promote the formation of a variety of vasoactive mediators including endothelin-1, cysteinyl leukotrienes, as well as the F2-isoprostanes, endogenous products of lipid peroxidation. These mediators can each affect renal function directly by causing renal vasoconstriction or decreasing the glomerular capillary ultrafiltration coefficient, and thus reduce glomerular filtration rate. Collectively, these factors contribute to the onset of renal failure in patients with biliary obstruction.

Animals↗

Relationship between traditional quality indicators and perceptions of care.

A study was undertaken to examine the relationships between patient's perceptions of care received, nurses' perceptions of care delivered, and traditional measures of nursing care quality. Findings suggest that traditional quality indicators used in hospitals across the country have little in common with either patients' or nurses' perceptions of quality of care.

Attitude of Health Personnel↗

Research utilization by nurse managers: current practices and future directions.

Forty nurse managers from seven hospitals were surveyed about barriers to utilization of research. The highest rated barriers were related to the acquisition and understanding of research; the lowest rated barriers pertained to the need for research as a basis for nursing practice. Managers with diploma and associate degree preparation and those in rural hospitals perceived themselves as having more barriers in research skills and awareness of research than did baccalaureate and master's prepared managers and managers in urban hospitals. Implications for nurse executives include support for research active environments and the time and education necessary for involvement in research and research utilization activities.

Humans↗

Advances in the generation of transgenic pigs via embryo-derived and primordial germ cell-derived cells.

The development of new technologies that would increase the efficiency for generation of transgenic livestock and would overcome some of the problems associated with random insertion of the transgene will greatly benefit animal agriculture. A potential alternative technology to pronuclear injection for the generation of transgenic pigs involves the isolation, culture and genetic manipulation of cell lines that can be reintroduced into the embryo for participation in the formation of the germ cells. We have isolated and cultured pig primordial germ cells (PGC) while maintaining them in an undifferentiated state as determined by morphology and alkaline phosphatase (AP) activity. More importantly, PGC-derived cells were stably transformed with the green fluorescent protein marker driven by the cytomegalovirus promoter. After visual identification of transgenic colonies, the pluripotential characteristics of the transgenic PGC-derived cells were tested by chimaera formation and to date we have identified, by genomic Southern blots, two chimaeric fetuses that contain tissues with the transgene incorporated into their chromosomes. To our knowledge, this is the first report of a chimaeric transgenic pig fetus obtained via a cultured cell line.

Animals↗

Functional heterogeneity of the hematopoietic microenvironment: rare stromal elements maintain long-term repopulating stem cells.

It has been hypothesized that distinct stromal cells from niches within the microenvironment that selectively regulate stem cell functions. To test this hypothesis, we derived a panel of matched stromal cell lines from murine fetal liver. The lines were immortalized with a retroviral vector encoding a temperature sensitive SV40 T antigen, to provide a snapshot of potential heterogeneity of the in vivo stroma compartment. All the stromal cell lines tested, supported the proliferation and differentiation of myeloid cells in Dexter type bone marrow cultures. Furthermore, RT-PCR analysis indicates that these lines are similar with respect to the production of an array of cytokines. However, the stromal cell lines differed markedly in their ability to maintain in vitro stem cells with in vivo repopulating capacity. Stem cell levels were measured in the competitive repopulation assay, following 3 weeks of coculture on individual stromal cell lines. Three classes of stromal cell lines were identified: (1) lines that did not support stem cells, (2) lines that sustained low levels of stem cells that often showed limited persistence in vivo, and (3) an infrequent line (1 out of 16 lines tested) that maintained high levels of primitive, long-term repopulating stem cells. This suggests that stromal cells that can support primitive stem cells are rare in the hematopoietic microenvironment. Taken together, these data substantiate the hypothesis that distinct stromal cells interact selectively with stem cells.

Animals↗

Effects of heterologous hematopoietic cytokines on in vitro differentiation of cultured porcine inner cell masses.

An exogenous supply of hematopoietic cytokines is essential for maintaining murine embryonic stem (ES) cells in a proliferative yet undifferentiated state. Recently, it was demonstrated that hematopoietic cytokines utilize the gp130 signal transduction pathway to maintain this phenotype, although their involvement toward maintaining porcine ES cell pluripotency has not been established. Therefore, the objective of this study was to determine the effectiveness of several heterologous hematopoietic cytokines at maintaining the isolated porcine inner cell masses (pICM) in an undifferentiated state. pICMs (day 7) were isolated by immunosurgery and cultured 4 days in one of six treatments: control medium, human leukemia inhibitory factor (hLIF; 1,000 mu/ml), human interleukin-6 (hIL-6; 100 ng/ml), hIL-6 + hIL-6 soluble receptor (hIL6 + sR; 100 ng/ml + 2.5 micrograms/ml), human oncostatin M (hOSM; 100 ng/ml), or rat ciliary neurotrophic factor (rCNTF; 100 ng/ml). All cytokines were prepared in Dulbecco's Modified Eagle's Medium/Ham's F-10 (1:1)-based medium. Morphology of pICMs was evaluated on a scale of 1 (fully undifferentiated) to 5 (fully differentiated) at 24-h intervals. Differentiation was significantly lower on day 2 for rCNTF vs. hLIF cultured pICMs (2.07 +/- 0.15 vs. 2.70 +/- 0.16; P < 0.05). Furthermore, addition of rCNTF gave the lowest overall mean differentiation score (2.53 +/- 0.15). However, none of the cytokines significantly delayed differentiation over controls for the 4-day culture period (P > 0.05). Since these heterologous cytokines were unable to inhibit differentiation, it is unlikely they will be beneficial towards isolating porcine ES cell lines under current conditions. Future work with homologous cytokines and dose effects may prove more beneficial.

Animals↗

Children's performance on "animal tests" of oddity: implications for cognitive processes required for tests of oddity and delayed nonmatch to sample.

To investigate the ontogenesis of oddity learning, children (16 to 102 months of age) and adults were tested on two versions of the oddity task using non-verbal procedures originally developed for monkeys. On the standard, "one-part" or "simultaneous" oddity task (Experiment 1), young children (16 to 74 months of age) performed more poorly than older children (81-102 months of age) who were as proficient as adults. The delayed mastery of one-part oddity contrasts to mastery, at much younger ages (3 to 4 years of age) of a similar, but two-part task, delayed non-match to sample (DNMS) (Overman, 1990). In Experiment 2, those children from the first experiment who had difficulty in learning the one-part oddity task were tested on a two-part oddity task, and a subset of the subjects was retested on the one-part oddity task, and, finally, given verbal instructions for the one-part oddity task. The two-part oddity task was mastered significantly more rapidly than the previous one-part task; however, children's performance dropped significantly when tested on the one-part oddity task, and finally, children rapidly mastered the one-part oddity task when given verbal instructions. The data suggested that (a) children used different strategies to solve the different versions of the oddity task, (b) the solution for the two-part-task appeared earlier in life than the solution for the one-part task and did not involve the use of the concept of "oddity relations", and (c) in tasks in which stimuli are shown twice, behavior may come under control of the absolute properties of the exemplar stimulus via a simple "win-shift" pattern of behavior. In contrast, in tasks in which all stimuli are presented simultaneously, behavior may be controlled by stimulus relations, the analysis of which has a protracted ontogenetic development.

Adult↗

Variability of post-void residual urine volume in the elderly.

Residual urine volume, though clinically important as a diagnostic tool, is reported to be variable and unreliable. Variability was examined among 14 geriatric patients, mean age 77 years. Residual urine was measured by ultrasound at three different times of day on each of two visits separated by 2-4 weeks. Results were examined by analysis of variance. Mean residual urine was 154 ml. Between-patient variability was large [standard deviation (SD) 246 ml]. There was no significant difference between values in men and women, nor between visits. Within-patient variability was large because of a large systematic variation with time of day (SD 128 ml), with greatest volumes in the early morning. The inherent, random variability of the measurement was much smaller than this (SD 44 ml). If the physiological factors causing the temporal variation could be controlled, more reproducible measurements would be possible.

Aged↗

The hepatorenal syndrome.

Hepatorenal syndrome may occur in any form of severe liver disease. It appears less common in children than adults, but still carries a poor prognosis. There are several factors involved in its aetiology, including a decreased renal perfusion pressure, activation of the renal sympathetic nervous system and increased synthesis of several vasoactive mediators, which may modulate glomerular filtration by acting as both renal vasoconstrictors and dynamic regulators of the glomerular capillary ultrafiltration coefficient, through their action on mesangial cells. This review will discuss the pathophysiology of the hepatorenal syndrome and some of the principles of management of patients with renal failure and severe liver disease. The role of renal support and liver transplantation will also be covered.

Adult↗