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Biomedical subjects

C Davis

Publications and source records attributed to C Davis.

At least 19 recordsLinked to original sources
PubMed2006

Measurement of the Ec.m. = 184 keV resonance strength in the 26gAl (p, gamma)27 Si reaction.

The strength of the Ec.m. = 184 keV resonance in the 26gAl(p, gamma)27 reaction has been measured in inverse kinematics using the DRAGON recoil separator at TRIUMF's ISAC facility. We measure a value of omega gamma = 35 +/- 7 microeV and a resonance energy of Ec.m. = 184 +/- 1 keV, consistent with p-wave proton capture into the 7652(3) keV state in 27Si, and discuss the implications of these values for 26GAl nucleosynthesis in typical oxygen-neon white-dwarf novae.

Journal Article↗
PubMed2005

Inositols prevent and reverse endothelial dysfunction in diabetic rat and rabbit vasculature metabolically and by scavenging superoxide.

Endothelial dysfunction (ED) is an early feature of cardiovascular risk and diabetes. Hyperglycemia and hyperlipidemia are causative factors. Excessive endothelial mitochondrial superoxide (ROS) production with hyperglycemia and hyperlipidemia is a key mechanism. Inositol components of an insulin inositol glycan mediator, d-chiro-inositol (DCI) and 3-O-methyl DCI (pinitol), decrease hyperglycemia and hyperlipidemia. We tested whether these, myoinositol and dibutyryl DCI (db-DCI), would prevent or reverse ED in diabetic rats and rabbits. Oral inositols reduced hyperglycemia and hypertriglyceridemia with different potencies and prevented ED in rat aortic rings and mesenteric beds. Inositols added in vitro to five diabetic tissues reversed ED. Relaxation by Ach, NO, and electrical field stimulation was potentiated by inositols in vitro in rabbit penile corpus cavernosa. Inositols in vitro restored impaired contraction by the eNOS inhibitor l-NAME and increased NO effectiveness. DCI and db-DCI decreased elevated ROS in endothelial cells in high glucose and db-DCI reduced PKC activation, hexosamine pathway activity, and advanced glycation end products to basal levels. Xanthine/xanthine oxidase generated superoxide was reduced by superoxide dismutase or inositols, with db-DCI efficacious in a mechanism requiring chelated Fe(3+). Histochemical examination of rat aortic rings for protein SNO demonstrated a decrease in diabetic rings with restoration by inositols. In summary, inositols prevented and reversed ED in rat and rabbit vessels, reduced elevated ROS in endothelial cells, potentiated nitrergic or vasculo-myogenic relaxations, and preserved NO signaling. These effects are related to their metabolic actions, direct superoxide scavenging, and enhancing and protecting NO signaling. Of the inositols tested, db-DCI was most effective.

Animals↗
PubMed2005

Strange-quark contributions to parity-violating asymmetries in the forward g0 electron-proton scattering experiment.

We have measured parity-violating asymmetries in elastic electron-proton scattering over the range of momentum transfers 0.12 < or =Q2 < or =1.0 GeV2. These asymmetries, arising from interference of the electromagnetic and neutral weak interactions, are sensitive to strange-quark contributions to the currents of the proton. The measurements were made at Jefferson Laboratory using a toroidal spectrometer to detect the recoiling protons from a liquid hydrogen target. The results indicate nonzero, Q2 dependent, strange-quark contributions and provide new information beyond that obtained in previous experiments.

Journal Article↗
PubMed2005

Patients' perception of information about HAART: impact on treatment decisions.

The aim of this study was to profile patients' satisfaction with information they have received about HAART in relation to treatment uptake. As part of a prospective investigation into uptake and adherence to HAART, 115 participants, comprising predominantly gay men, completed validated questionnaires investigating their satisfaction with information relating to practical aspects and potential problems of HAART, perceptions of information from different sources and beliefs about HAART, following a clinically recommended treatment offer. There was a wide range of total satisfaction scores indicating variation in patients' information requirements. Those who declined HAART were less satisfied with the information they had received than those who accepted the treatment recommendation (p < 0.05). Lower levels of satisfaction were associated with stronger concerns about the potential adverse effects of HAART (p < 0.05). Furthermore, concerns about HAART were related to uptake of HAART with those declining treatment being significantly more concerned about potential adverse effects than those who accepted the treatment offer (p < 0.001). The most helpful sources of information were specialist HIV staff: hospital consultants, pharmacists and nurses, as well as other people with HIV. This study improves our understanding of how information about HAART is perceived by people faced with treatment decisions. It emphasizes the importance of providing information tailored to meet the needs of individual patients and address their specific concerns, in order to support informed decision making.

Adult↗
PubMed2005

Improving uptake of cervical cancer screening in women with prolonged history of non-attendance for screening: a randomized trial of enhanced invitation methods.

OBJECTIVE: To compare the effectiveness and cost-effectiveness of three methods of inviting women with a long history of non-attendance to undergo cervical screening. METHODS: Randomized controlled trial and cost-effectiveness analysis. In all, 1140 women were identified from routine NHS screening records as having no smear for at least 15 years and randomly allocated to receive a telephone call from a nurse, a letter from a well-known celebrity (Claire Rayner) or letter from the local NHS Cervical Screening Commissioner. Uptake of screening was measured using routine data and attributed to interventions if occurring within three months. Uptake was compared with a control group. Costs of carrying out the interventions were noted from the perspective of the NHS and cost-effectiveness, as cost per additional attender, calculated. RESULTS: Uptake following all interventions was low: telephone call (1.4, 95% confidence interval [CI] 0.38-3.6%); celebrity letter (1.8, 95% CI 0.57-4.0%); commissioner letter (4.6, 95% CI 2.5-7.7%); control group (1.8, 95% CI 0.57-4.0%). There were no significant differences between groups. Telephone intervention was not possible in a quarter of women whose numbers were unlisted. Telephone intervention was the most expensive and least effective of the interventions. The commissioner letter yielded an additional attender within three months at an incremental cost of 23.21 pounds compared with taking no action. CONCLUSIONS: Neither a telephone call from a nurse nor a letter from a celebrity to encourage attendance for cervical screening were effective or cost-effective in women with a prolonged history of non-participation in the screening programme. A letter from the local cervical screening programme commissioner resulted in a small, non-significant increase in uptake. The low cost and ease of implementation of this intervention supports further research into its use in routine practice.

Adult↗
PubMed2004

Predicting outcome in ex-premature infants supported with extracorporeal membrane oxygenation for acute hypoxic respiratory failure.

OBJECTIVE: To identify predictors of outcome in ex-premature infants supported with extracorporeal membrane oxygenation (ECMO) for acute hypoxic respiratory failure. METHODS: Retrospective review of ex-premature infants with acquired acute hypoxic respiratory failure requiring ECMO support in the United Kingdom from 1992 to 2001. Review of follow up questionnaires completed by general practitioners and local paediatricians. RESULTS: Sixty four ex-premature infants (5-10 each year) received ECMO support, despite increased use of advanced conventional treatments over the decade. The most common infective agent was respiratory syncytial virus (85% of cases). Median birth gestation was 29 weeks and median corrected age at the time of ECMO support was 42 weeks. Median ECMO support duration was relatively long, at 229 hours. Survival to hospital discharge and to 6 months was 80%, remaining similar throughout the period of review. At follow up, 60% had long term neurodisability and 79% had chronic pulmonary problems. Of pre-ECMO factors, baseline oxygen dependence, younger age, and inpatient status were associated with non-survival (p < or = 0.05). Of ECMO related factors, patient complications were independently associated with adverse neurodevelopmental outcome and death (p < 0.01). CONCLUSIONS: Survival rates for ex-premature infants after ECMO support are favourable, but patients suffer a high burden of morbidity during intensive care and over the long term. At the time of ECMO referral, baseline oxygen dependence is the most important predictor of death, but no combination of the factors considered was associated with a mortality that would preclude ECMO support.

Acute Disease↗
PubMed2003

Pyk2 regulates multiple signaling events crucial for macrophage morphology and migration.

The biological role of the protein tyrosine kinase, Pyk2, was explored by targeting the Pyk2 gene by homologous recombination. Pyk2-/- mice are viable and fertile, without overt impairment in development or behavior. However, the morphology and behavior of Pyk2-/- macrophages were impaired. Macrophages isolated from mutant mice failed to become polarized, to undergo membrane ruffling, and to migrate in response to chemokine stimulation. Moreover, the contractile activity in the lamellipodia of Pyk2-/- macrophages was impaired, as revealed by measuring the rearward movement toward the nucleus of fibronectin-coated beads on the lamellipodia in opposition to an immobilizing force generated by optical tweezers. Consistently, the infiltration of macrophages into a carageenan-induced inflammatory region was strongly inhibited in Pyk2-/- mice. In addition, chemokine stimulation of inositol (1, 4, 5) triphosphate production and Ca2+ release, as well as integrin-induced activation of Rho and phosphatidyl inositol 3 kinase, were compromised in Pyk2-/- macrophages. These experiments reveal a role for Pyk2 in cell signaling in macrophages essential for cell migration and function.

Actins↗
PubMed2003

Rapamycin causes down-regulation of CCR5 and accumulation of anti-HIV beta-chemokines: an approach to suppress R5 strains of HIV-1.

Propagation of R5 strains of HIV-1 on CD4 lymphocytes and macrophages requires expression of the CCR5 coreceptor on the cell surface. Individuals lacking CCR5 (CCR5 Delta 32 homozygous genotype) are phenotypically normal and resistant to infection with HIV-1. CCR5 expression on lymphocytes depends on signaling through the IL-2 receptor. By FACS analysis we demonstrate that rapamycin (RAPA), a drug that disrupts IL-2 receptor signaling, reduces CCR5 surface expression on T cells at concentrations as low as 1 nM. In addition, lower concentrations of RAPA (0.01 nM) were sufficient to reduce CCR5 surface expression on maturing monocytes. PCR analysis on peripheral blood mononuclear cells (PBMCs) showed that RAPA interfered with CCR5 expression at the transcriptional level. Reduced expression of CCR5 on PBMCs cultured in the presence of RAPA was associated with increased extracellular levels of macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta. In infectivity assays, RAPA suppressed the replication of R5 strains of HIV-1 both in PBMC and macrophage cultures. In total PBMC cultures, RAPA-mediated inhibition of CCR5-using strains of HIV-1 occurred at 0.01 nM, a concentration of drug that is approximately 103 times lower than therapeutic through levels of drug in renal transplant recipients. In addition, RAPA enhanced the antiviral activity of the CCR5 antagonist TAK-779. These results suggest that low concentrations of RAPA may have a role in both the treatment and prevention of HIV-1 infection.

Amides↗
PubMed2003

The role of inflammation in vascular injury and repair.

Inflammation plays a critical role in the vascular response to injury. In particular, mechanical injury using techniques such as balloon angioplasty and stenting results in complex inflammatory reactions which influence proliferation of vessel wall constituents such as endothelial cells, smooth muscle cells, and extracellular matrix proteins. Inflammatory cells are recruited to the injured vessel wall initially as a reparative mechanism; however, these same inflammatory processes are also pivotal in the development of restenotic lesions. Leukocytes serve as the primary inflammatory cells but we now know that platelets produce a number of important inflammatory mediators. This review describes the mechanisms that regulate endothelial cell migration, smooth muscle cell activation, and extracellular matrix protein production, all of which are key components in the inflammatory response to vascular injury.

Angioplasty, Balloon↗
PubMed2003

Measures of benefit for breast screening from the pathology database for Scotland, 1991-2001.

AIMS: To examine pathology characteristics of breast cancers detected by mammography screening over 10 years in Scotland, and compare the nature of cancer yields after different levels of very small invasive cancer at prevalence detection. METHODS: A pathology database of cancers from mammography screening of women aged 50-64 years invited every three years was used to assess the variation over time in annual yield of different invasive cancer sizes. Screening centres were compared for incidence screen yields, according to sizes, histological type, grade, and node status. RESULTS: There was a significant trend over time for increased detection of < 15 mm cancers among 2353 prevalence cancers, and a significant trend for increase in all size groups, < 10, 10-14, < 15, and >or= 15 mm, among 2245 incidence cancers. Based on individual screening centres, there was a significant negative relation between proportions of very small (< 10 mm) cancers at prevalence screens and of large (>or= 15 mm) cancers at incidence screens of the same "cohort" three years later. There was no significant relation on the same centre basis for worse pathology characteristics (histological no special type, high grade, and positive node status) in cancers detected in the same "cohort" three years later. CONCLUSIONS: Sensitive mammography screening has a significant effect on the nature of yields at subsequent screens. Length of screening interval and consistency in pathologist opinions are factors that account for lack of effect on incidence cancer qualitative pathology characteristics. These issues are relevant to the use of such characteristics as surrogate measures of service screening performance.

Breast Neoplasms↗
PubMed2002

Is there a dose response relationship for clodronate in the treatment of tumour induced hypercalcaemia?

Eighty-six patients with tumour induced hypercalcaemia were randomised to 600, 900, 1200 or 1500 mg of intravenous clodronate, according to post hydration serum calcium levels. Sixty-seven were evaluable for response. The overall response rate was 49.3% (95% CI: 36.8-61.8) with no significant difference in response rates, i.e. achievement of normocalcaemia at days 6-9 (corrected serum calcium < or =2.6 mmol l(-1)) across all groups.

Adult↗
PubMed2002

The effect of an experimental infection of the nematode Heterakis gallinarum on hand-reared grey partridges Perdix perdix.

We compared 26 hand-reared grey partridges given an experimental infection of the caecal nematode Heterakis gallinarum with 26 uninfected ones. Under laboratory conditions after 91 days, there were no measurable clinical effects of the infection. We found no effect of treatment on the amount of food eaten or on caecal dropping production. However, treated birds, in particular females, developed slightly lower body mass (around 2%) compared to the controls. At post-mortem examination, we found a positive relationship between breast muscle mass and the number of worms collected from the caeca of treated birds. Treated birds with no worms when examined had smaller breast muscle mass (4.6%) compared to the uninfected control birds. These results are largely different to those found in a similar study that documented significant negative impacts on most of these factors in 8 infected birds compared to 6 controls. Its findings were used in a published model to support a hypothesis that H. gallinarum maintained in the environment by common pheasants, the primary host for this worm, could negatively affect wild grey partridge productivity and survival. In the same model our data would not support this hypothesis. Possible explanations for the different results from the 2 experiments are discussed. Together they suggest that only in certain, as yet unidentified circumstances, could experimental H. gallinarum infections have deleterious effects on hand-reared grey partridges.

Animals↗
PubMed2002

Fryns syndrome: a surviving case with associated Hirschsprung's disease and hemidiaphragmatic agenesis.

Fryns syndrome is a rare autosomal recessive disorder of multiple congenital abnormalities. Major diagnostic criteria include congenital diaphragmatic hernia, distal limb and nail hypoplasia and abnormal facies. More than 70 cases have been reported since the first report in 1979, 86% of which have been associated with an early lethal outcome. We report the case of a survivor who also has associated Hirschsprung's disease. On review of previously reported cases, defects of neuronal migration may be more common than previously recognized. The diaphragmatic hernia was repaired in two stages with a silastic patch followed by a reversed latissimus dorsi muscle flap.

Abnormalities, Multiple↗
PubMed2002

Laparoscopic microsurgical anastomosis of the blocked, solitary post-ectopic Fallopian tube: case report.

The surgical options for the management of ectopic pregnancy include linear salpingotomy or salpingectomy. If salpingotomy is performed, subsequent tubal blockage may result and if this occurs in a solitary Fallopian tube then assisted reproductive technology is recommended as the treatment of choice. We describe a case report detailing the application of laparoscopic microsurgical tubal reanastomosis in two patients with post-ectopic blockage in a solitary Fallopian tube. Both patients conceived post-operatively and subsequently delivered term pregnancies. Laparoscopic microsurgery offers an alternative to assisted reproductive technology in patients with post-ectopic tubal obstruction in a single Fallopian tube.

Adult↗
PubMed2001

A dual role for the zebrafish unplugged gene in motor axon pathfinding and pharyngeal development.

On their way toward their synaptic targets, motor growth cones encounter multiple choice points, where they are confronted with trajectory choices. We have previously shown that the zebrafish unplugged gene acts as a somite-derived cue controlling pathway choice of primary motor axons. Here, we demonstrate that this trajectory choice is not exclusively controlled by a single unplugged-dependent process, but depends on the coordinated function of additional cues. We also show that secondary motor neurons, most similar to those in birds and mammals, depend on the unplugged gene to navigate a choice point, suggesting that primary and secondary motor neurons share common mechanisms controlling axonal path selection. Moreover, we show that the unplugged gene plays an additional role guiding secondary motor axons through a single segmental nerve. Finally, we report that unplugged larvae display a striking pharyngeal arch defect, consistent with a dual function of the unplugged gene in axonal guidance and cell motility.

Alleles↗
PubMed2001

Altered transcription in yeast expressing expanded polyglutamine.

Expanded polyglutamine tracts are responsible for at least eight fatal neurodegenerative diseases. In mouse models, proteins with expanded polyglutamine cause transcriptional dysregulation before onset of symptoms, suggesting that this dysregulation may be an early event in polyglutamine pathogenesis. Transcriptional dysregulation and cellular toxicity may be due to interaction between expanded polyglutamine and the histone acetyltransferase CREB-binding protein. To determine whether polyglutamine-mediated transcriptional dysregulation occurs in yeast, we expressed polyglutamine tracts in Saccharomyces cerevisiae. Gene expression profiles were determined for strains expressing either a cytoplasmic or nuclear protein with 23 or 75 glutamines, and these profiles were compared to existing profiles of mutant yeast strains. Transcriptional induction of genes encoding chaperones and heat-shock factors was caused by expression of expanded polyglutamine in either the nucleus or cytoplasm. Transcriptional repression was most prominent in yeast expressing nuclear expanded polyglutamine and was similar to profiles of yeast strains deleted for components of the histone acetyltransferase complex Spt/Ada/Gcn5 acetyltransferase (SAGA). The promoter from one affected gene (PHO84) was repressed by expanded polyglutamine in a reporter gene assay, and this effect was mitigated by the histone deacetylase inhibitor, Trichostatin A. Consistent with an effect on SAGA, nuclear expanded polyglutamine enhanced the toxicity of a deletion in the SAGA component SPT3. Thus, an early component of polyglutamine toxicity, transcriptional dysregulation, is conserved in yeast and is pharmacologically antagonized by a histone deacetylase inhibitor. These results suggest a therapeutic approach for treatment of polyglutamine diseases and provide the potential for yeast-based screens for agents that reverse polyglutamine toxicity.

Amino Acid Sequence↗
PubMed2001

Parainfluenza virus infections after hematopoietic stem cell transplantation: risk factors, response to antiviral therapy, and effect on transplant outcome.

Parainfluenza virus (PIV) infections may be significant causes of morbidity and mortality in patients undergoing stem cell transplantation, but data regarding their impact on transplant-related mortality is limited. This study sought to determine the risk factors of PIV acquisition and progression to lower respiratory tract infection, their impact on transplant-related mortality, and the effectiveness of antiviral therapy. A total of 3577 recipients of hematopoietic stem cell transplantation (HSCT) between 1990 and 1999 were studied. PIV infections occurred in 253 patients (7.1%); 78% of these infections were community acquired. Multivariable analysis identified the receipt of an unrelated transplant as the only risk factor for PIV acquisition; the dose of corticosteroids at the time of PIV infection acquisition was the primary factor associated with the development of PIV-3 pneumonia, both among allogeneic and autologous HSCT recipients. Both PIV-3 upper respiratory infection and pneumonia were associated with overall mortality. Pulmonary copathogens were isolated from 29 patients (53%) with pneumonia. Mortality was highly influenced by the presence of copathogens and the need for mechanical ventilation. Aerosolized ribavirin with or without intravenous immunoglobulin did not appear to alter mortality from PIV-3 pneumonia, nor did such therapy decrease the duration of viral shedding from the nasopharynx among patients with pneumonia. Corticosteroid administration thus drives the development of PIV pneumonia in a dose-dependent fashion, even among autologous HSCT recipients. Both upper and lower tract PIV infections are predictors of mortality after HSCT. Currently available antiviral therapy appears to be inadequate in reducing viral shedding or mortality once pneumonia is established. (Blood. 2001;98:573-578)

Adolescent↗