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Biomedical subjects

F Kelly

Publications and source records attributed to F Kelly.

At least 19 recordsLinked to original sources
PubMed2005

Toroidal plasma rotation induced by the dynamic ergodic divertor in the TEXTOR tokamak.

The first results of the Dynamic Ergodic Divertor in TEXTOR, when operating in the m/n=3/1 mode configuration, are presented. The deeply penetrating external magnetic field perturbation of this configuration increases the toroidal plasma rotation. Staying below the excitation threshold for the m/n=2/1 tearing mode, this toroidal rotation is always in the direction of the plasma current, even if the toroidal projection of the rotating magnetic field perturbation is in the opposite direction. The observed toroidal rotation direction is consistent with a radial electric field, generated by an enhanced electron transport in the ergodic layers near the resonances of the perturbation. This is an effect different from theoretical predictions, which assume a direct coupling between rotating perturbation and plasma to be the dominant effect of momentum transfer.

Journal Article↗
PubMed2005

A survey of the causes of sudden cardiac death in the under 35-year-age group.

CRY (Cardiac Risk in the Young) is a registered Irish charity established by parents who are bereaved as a result of sudden cardiac death. The aim of this study is to establish the incidence and causes of sudden cardiac death in Dublin city in the 10-year period from 1st January 1993 to 31st December 2002. All sudden cardiac deaths in the under 35-year age group which were reported to the city coroner in the study period were examined. Details regarding age, sex, previous symptoms, investigations, circumstances of death and main pathological finding were recorded in each case. A total of 72 cases of sudden cardiac death in the under-35 year age group were reported. 52 were men. The median age was 26.5 years (range 12-34 years). The cause of death in 20 cases was reported as atherosclerotic Coronary Artery Disease. The second commonest cause of death (24% cases) was Hypertrophic Cardiomyopathy. Hypertrophic Cardiomyopathy was the commonest cause of death under the age of 25 years. Overall atherosclerotic coronary artery disease was the commonest cause of death in this group. The importance of Hypertrophic Cardiomyopathy is highlighted by the fact it was the commonest cause of death in the under 25-year age group. Screening those at high risk of sudden cardiac death especially the relatives of those affected by Hypertrophic Cardiomyopathy need to be discussed and implemented.

Adolescent↗
PubMed2004

Global expression profiling of strains harbouring null mutations reveals that the five rpf-like genes of Mycobacterium tuberculosis show functional redundancy.

SETTING: Aged, dormant cultures of Mycobacterium tuberculosis can be resuscitated by a secreted, proteinaceous growth factor from Micrococcus luteus, known as resuscitation-promoting factor (Rpf). M. tuberculosis contains five rpf-like genes, rpfA (Rv0867c), rpfB (Rv1009), rpfC (Rv1884c), rpfD (Rv2389c) and rpfE (Rv2450c), that bear significant similarity to Mi. luteus rpf, suggesting that these too may play a role in growth and/or reactivation from a quiescent state. OBJECTIVE AND DESIGN: Unmarked deletion mutants of each of the five rpf-like genes of M. tuberculosis H37Rv were constructed and their phenotypes and global gene expression profiles were assessed. RESULTS AND CONCLUSIONS: Deletion of any one of the rpf-like genes did not affect growth or survival of M. tuberculosis in liquid culture, but some alterations in colony-forming ability and colonial morphology were observed. Global gene expression profiling suggested that loss of rpfC affected the expression of the largest number of genes and there was a significant overlap in the differential gene expression profile of the rpfC mutant with those of the rpfB, rpfD and rpfE mutants. The expression profile of the rpfA mutant was notably less similar, but inverse associations with genes affected in the other mutants were observed. These results, together with those obtained by real-time, quantitative RT-PCR, suggest that the rpf-like genes serve wholly or partially overlapping functions in M. tuberculosis.

Bacterial Proteins↗
PubMed2000

Non-specific antiviral activity of antisense molecules targeted to the E1 region of human papillomavirus.

Antisense phosphorothioate oligonucleotides (ODN1 0x5 OMe) directed against the E1 start region of human papillomavirus 11 (HPV11) can inhibit papillomavirus induced growth of implanted human foreskin in a mouse xenograft model. Administration of a mismatch control oligonucleotide (ODN9 0x5 OMe), in which guanine was replaced with adenine in the same model, had no effect on papilloma induced growth. However, the apparent antiviral activity of ODN1 0x5 OMe was also shown in a lethal mouse cytomegalovirus (CMV) model, in which the oligonucleotides are not expected to have antisense activity. To understand the mechanisms of action of these oligonucleotides, a mismatch oligonucleotide (ODN61 0x5 OMe) was prepared which retained the CpG motifs of ODN1 0x5 OMe. This was tested in the mouse xenograft model and shown to have moderate inhibitory activity. As a definitive experiment, a comparison was made between the efficacy of the active oligonucleotide ODN1 0x5 OMe against two papilloma viruses HPV11 and HPV40. Both these viruses cause benign genital warts, but differ by four bases in their E1 sequence that was the target for ODN1 0x5 OMe. Papillomavirus induced growth in the mouse xenograft model was inhibited by ODN1 0x5 OMe in both cases, suggesting that oligonucleotide molecules have a non-specific antiviral activity that is not directly related to their antisense sequence.

Animals↗
PubMed2000

Neural dynamics of 3-D surface perception: figure-ground separation and lightness perception.

This article develops the FACADE theory of three-dimensional (3-D) vision to simulate data concerning how two-dimensional pictures give rise to 3-D percepts of occluded and occluding surfaces. The theory suggests how geometrical and contrastive properties of an image can either cooperate or compete when forming the boundary and surface representations that subserve conscious visual percepts. Spatially long-range cooperation and short-range competition work together to separate boundaries of occluding figures from their occluded neighbors, thereby providing sensitivity to T-junctions without the need to assume that T-junction "detectors" exist. Both boundary and surface representations of occluded objects may be amodally completed, whereas the surface representations of unoccluded objects become visible through modal processes. Computer simulations include Bregman-Kanizsa figure-ground separation, Kanizsa stratification, and various lightness percepts, including the Münker-White, Benary cross, and checkerboard percepts.

Attention↗
PubMed1999

Absence of cardiac valve dysfunction in obese patients treated with sibutramine.

OBJECTIVE: Serotonin-releasing agents prescribed as weight-loss medications have been implicated as a cause of acquired aortic and mitral valve abnormalities. Sibutramine hydrochloride (MERIDIA) is a serotonin and norepinephrine reuptake inhibitor with proven efficacy of weight reduction. The purpose of this study was to determine the incidence of cardiac valve disease in sibutraminetreated patients. RESEARCH METHODS AND PROCEDURES: Obese patients with type 2 diabetes mellitus enrolled in an ongoing double-blind, placebo-controlled, parallel-arm, 12-month study of sibutramine (followed by a 12-month open label extension) underwent transthoracic echocardiographic imaging and color Doppler interrogation for assessment of cardiac valve anatomy and function. RESULTS: A total of 210 patients were evaluated. Of these, 133 were receiving sibutramine (72 in the double-blind period), and 77 were receiving placebo. The mean+/-Standard Deviation age was 54+/-9 years, and the mean duration of treatment was 229+/-117 days (approximately 7.6 months). The prevalence of left-sided cardiac valve dysfunction was low and similar for the two treatment groups (sibutramine 3/133, or 2.3%; placebo 2/77, or 2.6%). All five cases were cases of aortic insufficiency; four were mild, one was severe (in a placebo patient). All three sibutramine cases were patients over age 50; two had a history of systemic hypertension. CONCLUSION: The prevalence of left-sided cardiac valve dysfunction was not higher than background in obese patients treated with sibutramine for an average of 7.6 months.

Adult↗
PubMed1999

Neural dynamics of binocular brightness perception.

How does the visual cortex combine information from both eyes to generate perceptual representations of object surfaces? Important clues about this process may be derived from data about the perceived brightness of surface regions under binocular viewing conditions, including data about binocular brightness summation in response to Ganzfelds, the U-shaped data of Fechner's paradox that violates binocular brightness summation, and the effects of different combinations of monocular and binocular contours and surface luminance differences on threshold sensitivity to monocular flashes of light. How to reconcile these apparently contradictory data properties has been a severe challenge to previous models, and none has explained them all. The present article quantitatively simulates them all by further developing the FACADE vision model. Key model processes discount the illuminant and compute image contrasts in each monocular channel using shunting on-center off-surround networks; binocularly fuse these discounted monocular signals using shunting on-center off-surround networks with nonlinear excitatory and inhibitory signals; and use these binocularly fused activities to trigger filling-in of a binocular surface representation that represents perceived surface brightness. Previous models that have suggested explanations of subsets of these data are discussed.

Contrast Sensitivity↗
PubMed1999

The association of diet and thrombotic risk factors in healthy male vegetarians and meat-eaters.

OBJECTIVE: The aim of this study was to assess thrombosis tendency in subjects who were habitual meat-eaters compared with those who were habitual vegetarians. DESIGN: Cross-sectional comparison of habitual meat-eaters and habitual vegetarians. SETTING: Free living subjects. SUBJECTS: One hundred and thirty-nine healthy male subjects (vegans n = 18, ovolacto vegetarians n = 43, moderate-meat-eaters n = 60 and high-meat-eaters n = 18) aged 20-55 y who were recruited in Melbourne. OUTCOME MEASURES: Dietary intake was assessed using a semi-quantitative Food Frequency Questionnaire. The parameters of thrombosis were measured by standard methods. RESULTS: Saturated fat and cholesterol intakes were significantly higher and polyunsaturated fat (PUFA) was significantly lower in the meat-eaters compared with vegetarians. In the meat-eaters, the platelet phospholipids AA levels were significantly higher than in the vegetarians, but there was no increase in ex vivo platelet aggregation and plasma 11-dehydro thromboxane B2 levels. Vegetarians, especially the vegans, had a significantly increased mean collagen and ADP stimulated ex vivo whole blood platelet aggregation compared with meat-eaters. The vegan group had a significantly higher mean platelet volume than the other three dietary groups. However, meat-eaters had a significantly higher cluster of cardiovascular risk factors compared with vegetarians, including increased body mass index, waist to hip ratio, plasma total cholesterol (TC), triacylglycerol and LDL-C levels, ratio of TC/HDL-C and LDL-C/HDL-C and plasma factor VII activity. CONCLUSIONS: Consumption of meat is not associated with an increased platelet aggregation compared with vegetarian subjects.

Adult↗
PubMed1999

Effect of dietary alpha-linolenic acid on thrombotic risk factors in vegetarian men.

BACKGROUND: Vegetarians have lower platelet and plasma concentrations of n-3 polyunsaturated fatty acids (PUFAs) than do omnivores. We recently showed that male vegetarians have higher platelet aggregability than do omnivores. OBJECTIVE: We investigated whether male vegetarians (n = 17) who consumed an increased amount of dietary alpha-linolenic acid (ALA) showed any changes in their tissue profile of PUFAs, plasma thromboxane concentrations, platelet aggregability, or hemostatic factors. DESIGN: During the study, all subjects maintained their habitual vegetarian diets except that a proportion of dietary fat was replaced with vegetable oils and margarines that were provided. Initially, all subjects consumed a low-ALA diet (containing safflower oil and safflower oil-based margarine) for 14 d; they then consumed either a moderate-ALA diet (containing canola oil and canola oil-based margarine) or a high-ALA diet (containing linseed oil and linseed oil-based margarine) for 28 d. Blood samples were collected at day 0 (baseline), day 14, and day 42. RESULTS: Eicosapentaenoic acid, docosapentaenoic acid, total n-3 PUFAs, and the ratio of n-3 to n-6 PUFAs were significantly increased (P < 0.05), whereas the ratio of arachidonic acid to eicosapentaenoic acid was decreased (P < 0.05), in platelet phospholipids, plasma phospholipids, and triacylglycerols after either the moderate-ALA or high-ALA diet compared with the low-ALA diet. No significant differences were observed in thrombotic risk factors. CONCLUSION: ALA from vegetable oils (canola and linseed) has a beneficial effect on n-3 PUFA concentrations of platelet phospholipids and plasma lipids in vegetarian males.

Adult↗
PubMed1999

Acute inflammatory responses in the airways and peripheral blood after short-term exposure to diesel exhaust in healthy human volunteers.

Several epidemiologic studies have demonstrated a consistent association between levels of particulate matter (PM) in the ambient air with increases in cardiovascular and respiratory mortality and morbidity. Diesel exhaust (DE), in addition to generating other pollutants, is a major contributor to PM pollution in most places in the world. Although the epidemiologic evidence is strong, there are as yet no established biological mechanisms to explain the toxicity of PM in humans. To determine the impact of DE on human airways, we exposed 15 healthy human volunteers to air and diluted DE under controlled conditions for 1 h with intermittent exercise. Lung functions were measured before and after each exposure. Blood sampling and bronchoscopy were performed 6 h after each exposure to obtain airway lavages and endobronchial biopsies. While standard lung function measures did not change following DE exposure, there was a significant increase in neutrophils and B lymphocytes in airway lavage, along with increases in histamine and fibronectin. The bronchial biopsies obtained 6 h after DE exposure showed a significant increase in neutrophils, mast cells, CD4+ and CD8+ T lymphocytes along with upregulation of the endothelial adhesion molecules ICAM-1 and VCAM-1, with increases in the numbers of LFA-1+ cells in the bronchial tissue. Significant increases in neutrophils and platelets were observed in peripheral blood following DE exposure. This study demonstrates that at high ambient concentrations, acute short-term DE exposure produces a well-defined and marked systemic and pulmonary inflammatory response in healthy human volunteers, which is underestimated by standard lung function measurements.

Adult↗
PubMed1999

Interleukin-5 production by human airway epithelial cells.

Interleukin (IL)-5 is a pleiotropic cytokine that exhibits biologic activity on cells of diverse hemopoieitic lineages. IL-5 enhances mediator release from human basophils and plays a pivotal role in the chemoattraction, proliferation, differentiation, survival, and activation of eosinophils. Th2- and Tc2-like T cells, mast cells, basophils, and eosinophils are the known cellular sources of this cytokine. Using a sensitive and novel reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay system, we found that IL-5 messenger RNA (mRNA) was constitutively expressed in bronchial biopsies obtained from healthy individuals, and that the levels of IL-5 mRNA expression decreased 1. 5 h after exposure to 0.12 ppm ozone for 2 h. Because the oxidative effects of ozone are confined to the epithelial cell surface and it is known that ozone induces epithelial damage and shedding, we hypothesized that epithelial cells might be a source of IL-5 mRNA. We demonstrate here that both transformed human bronchial epithelial cell lines (A549 and 16HBE14o-) and primary human bronchial and nasal epithelial cells grown in culture constitutively express IL-5 mRNA, which is upregulated on stimulation with tumor necrosis factor (TNF)-alpha. Culture supernatants derived from A549 cells exposed to TNF-alpha and interferon-gamma demonstrated detectable levels of IL-5 protein, and immunostaining of bronchial biopsies obtained from healthy human airways revealed the presence of IL-5 protein localized to the bronchial epithelium. To our knowledge, this is the first report demonstrating IL-5 production by human airway epithelial cells. This observation provides further evidence for the role of airway epithelium in regulating airway immune responses, in particular enhancing chemotaxis, activation, and survival of eosinophils, which could play an important role in the pathogenesis of bronchial asthma.

Adult↗
PubMed1998

The incidence of modular tibial polyethylene insert exchange in total knee arthroplasty when polyethylene failure occurs.

One of the primary reasons for utilizing modular tibial polyethylene inserts (MTPI) at the time of total knee arthroplasty is to have the ability to simply exchange the polyethylene at the time of revision surgery when polyethylene failure has occurred. During a 2-year period from January 1993 to December 1994, 62 revision total knee arthroplasties were reviewed from five different institutions in North America, which were performed secondary to modular tibial insert failure. In 55 cases (88.7%), significant scoring and/or damage to the femoral and/or tibial components occurred necessitating revision of one or both components. This series does not support the premise that polyethylene exchange is common at the time of revision surgery for MTPI failure. Of the patients 88.7% had MTPI failure resulted in femoral and/or tibial component revision secondary to surface damage to the femoral component and/or tibial component baseplate. In order to avoid femoral and tibial component wear secondary to MTPI failure, early recognition is necessary to allow the much simpler operation consisting of polyethylene liner exchange only.

Aged↗
PubMed1998

User perspective on needs and satisfaction with mental health services. PRiSM Psychosis Study. 8.

BACKGROUND: Measurement of the impact of different types of service provision on the views of service users is important in planning mental health services. METHOD: Needs (met and unmet) and satisfaction with services, were assessed. People with psychosis (n = 131) were interviewed before (Time 1) and after (Time 2) the introduction of two community mental health services in south London. One was intensive, with two specialist teams, the other standard. Outcomes were compared at Time 2, controlling for the Time 1 values. RESULTS: Overall, 70% of needs were met and mean satisfaction was between 'mixed' and 'mainly satisfied'. There was evidence for higher met needs in the intensive sector, but no evidence for lower unmet needs in the intensive sector or for differences in satisfaction. The additional needs met by the intensive service were associated with aspects of basic living situation. Satisfaction was negatively correlated with both unmet and met needs. CONCLUSIONS: Both services were reasonably successful, with little difference from the user perspective. The intensive service provided benefits in terms of met needs, but this has to be balanced against a possible increase in unmet needs.

Community Mental Health Services↗
PubMed1998

The history of the United States Navy flight surgeon/naval aviator program.

Early in the history of aviation the need for a special kind of physician who could understand the physical and psychological problems encountered by flyers was well recognized. These physicians were called flight surgeons. In 1922, RADM W. A. Moffett, USN, the first Chief of the Bureau of Aeronautics and the "Father of Naval Aviation," called for a group of Navy medical officers to be trained as flight surgeons. He believed that all Navy flight surgeons should be trained as pilots "primarily in order that they may experience the emergencies and conditions that arise in flying." This article traces the history of the Navy flight surgeon/naval aviator. It chronicles the evolution of the Navy's flight surgeon/naval aviator program from the World War I doctor who flew seaplanes at a Naval Air Station in Italy to the present day flight surgeon/naval aviator who flys operational and test aircraft as a research pilot.

Aerospace Medicine↗
PubMed1997

Short-term ozone exposure upregulates P-selectin in normal human airways.

Short-term exposure to ambient levels of ozone induces neutrophilic bronchitis. To investigate the early events contributing to inflammatory cell recruitment in the airways we exposed 12 healthy nonsmoking volunteers to 0.12 ppm ozone or filtered air for 2 h on two separate occasions. Spirometry and fiberoptic bronchoscopy were performed immediately and at 1.5 h after the two exposures, respectively. Total protein, albumin, and total and differential cell counts were performed on the bronchial wash and BAL fluid. Bronchial biopsies were embedded in glycol methacrylate and immunostained for inflammatory cells, including neutrophils, mast cells, total T-cells (CD3), T-cell subset CD8, and leukocyte endothelial adhesion molecules, including VCAM-1, ICAM-1, E-selectin, and P-selectin. No significant changes were observed in FEV1, FVC, or any inflammatory indices in the bronchial wash and BAL fluid. In addition, no significant differences were seen in inflammatory cell numbers or percentages of vessels expressing VCAM-1, E-selectin, or ICAM-1 in the biopsies. The percentage of vessels expressing P-selectin increased significantly after ozone exposure: p = 0.016; median (IQR), 28.76 (26.36-36.94) versus 47.06 (38.14-56.86)%. The upregulation of P-selectin could signify an early inflammatory response to ozone such as margination and rolling of the neutrophils on the vessel wall prior to transendothelial migration.

Adult↗
PubMed1996

Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS)

BACKGROUND: Vitamin E (alpha-tocopherol) is thought to have a role in prevention of atherosclerosis, through inhibition of oxidation of low-density lipoprotein. Some epidemiological studies have shown an association between high dietary intake or high serum concentrations of alpha-tocopherol and lower rates of ischaemic heart disease. We tested the hypothesis that treatment with a high dose of alpha-tocopherol would reduce subsequent risk of myocardial infarction (MI) and cardiovascular death in patients with established ischaemic heart disease. METHODS: In this double-blind, placebo-controlled study with stratified randomisation, 2002 patients with angiographically proven coronary atherosclerosis were enrolled and followed up for a median of 510 days (range 3-981). 1035 patients were assigned alpha-tocopherol (capsules containing 800 IU daily for first 546 patients; 400 IU daily for remainder); 967 received identical placebo capsules. The primary endpoints were a combination of cardiovascular death and non-fatal MI as well as non-fatal MI alone. FINDINGS: Plasma alpha-tocopherol concentrations (measured in subsets of patients) rose in the actively treated group (from baseline mean 34.2 micromol/L to 51.1 micromol/L with 400 IU daily and 64.5 micromol/L with 800 IU daily) but did not change in the placebo group. Alpha-tocopherol treatment significantly reduced the risk of the primary trial endpoint of cardiovascular death and non-fatal MI (41 vs 64 events; relative risk 0.53 [95% Cl 0.34-0.83; p=0.005). The beneficial effects on this composite endpoint were due to a significant reduction in the risk of non-fatal MI (14 vs 41; 0.23 [0.11-0.47]; p=0.005); however, there was a non-significant excess of cardiovascular deaths in the alpha-tocopherol group (27 vs 23; 1.18 [0.62-2.27]; p=0.61). All-cause mortality was 36 of 1035 alpha-tocopherol-treated patients and 27 of 967 placebo recipients. INTERPRETATION: We conclude that in patients with angiographically proven symptomatic coronary atherosclerosis, alpha-tocopherol treatment substantially reduces the rate of non-fatal MI, with beneficial effects apparent after 1 year of treatment. The effect of alpha-tocopherol treatment on cardiovascular deaths requires further study.

Coronary Artery Disease↗
PubMed1996

Range of motion in total knee replacement.

This is a multicenter prospective clinical study using a modified Knee Society scoring system which evaluated the effect of age, gender, weight, preoperative range of motion and knee score, previous surgery, and modification of the posterior femoral condyle geometry on postoperative range of motion. The primary outcome variable was change in flexion. The data were collected from 5 surgeons using a single total knee system. The current study has 621 patients enrolled, of which 282 total knee replacements have followup of 12 months and 86 have followup of 24 months. Multivariate analysis was used to evaluate the data. The variables listed were examined as to their relationship to changes in flexion. Patients were divided into 3 groups: preoperative flexion less than 90 degrees, 91 degrees to 105 degrees, and greater than 105 degrees. When comparing the patients with preoperative motion less than 90 degrees to those with motion greater than 105 degrees, the first group improved 26 degrees more than the latter. They also improved 12 degrees more than the midrange group. The midrange group improved 14 degrees more than the upper range group. These values are all adjusted to eliminate differences due to the other variables. None of the other variables showed a significant correlation with the flexion outcome. To analyze the knee score, the group was also divided into 3 groups: preoperative score less than 27, 28 to 40, and greater than 40. The preoperative knee score was the best predictor of the postoperative knee score. The patients with preoperative knee scores below 27 improved 16 points more than those in the 27 to 40 range and 33 points greater than the greater than 40 group. To analyze functional evaluation, the patients were divided into 3 groups based on preoperative score: less than 40, 41 to 50, and greater than 50. Those in the less than 40 group improved 14 points more than the midrange group and 35 points more than the greater than 50 group. Analysis of delta range of motion and delta pain showed similar results. Age, weight, previous open surgical procedure, and altered femoral component contour, did not seem significantly correlated with changes in postoperative flexion. The best predictors of postoperative clinical results are the preoperative scores.

Aged↗