Building capacity for cardiovascular nursing research in Canada.
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Canada↗
Biomedical subjects
H M Arthur
Publications and source records attributed to H M Arthur.
Inducible expression of human endoglin during inflammation and wound healing in vivo.
OBJECTIVE: Because angiogenesis and inflammation are intimately associated and endoglin is required for angiogenesis, we wished to determine whether it also plays a role in inflammation. METHODS: Using an immunohistochemical approach, we examined spatial and temporal changes in endoglin expression during inflammation and angiogenesis. RESULTS: We found low levels of endoglin expression in quiescent endothelium in a range of normal adult human tissues. However, constitutive levels of expression are higher in dermal capillaries surrounding hair follicles and in alveolar capillaries as well as in the high endothelial cells of lymph tissue. During inflammatory disease, endoglin expression is strongly upregulated and is consistently associated with an infiltrate of inflammatory cells. For the first time, we have determined the relative changes in endoglin expression from the normal quiescent state through the inflammatory changes and angiogenesis that occur during dermal wound healing in vivo using a timed human wound healing model. Endoglin expression increases rapidly, reaching a peak of expression co-incident with maximal T cell infiltrate and persisting at an elevated level for at least 28 days in both activated and proliferating endothelial cells. CONCLUSION: Enhanced endoglin expression is not limited to angiogenesis, it is also associated with inflammation.
Adult↗
Outcomes and costs of coronary artery bypass grafting: comparison between octogenarians and septuagenarians at a tertiary care centre.
BACKGROUND: Decision-making related to coronary artery bypass grafting (CABG) in elderly patients is hampered by inadequate outcome data. We compared the clinical outcomes of octogenarians with those of septuagenarians who underwent CABG. Our secondary objective was to compare the costs associated with CABG in these groups. METHODS: We conducted a retrospective database review of patients 70 years of age and older who had undergone CABG at a regional cardiac surgical centre in Hamilton, Ont., between July 1, 1997, and Apr. 30, 2000. A total of 1034 patients were divided into 3 age groups: young septuagenarians (aged 70-74 years), old septuagenarians (aged 75-79) and those 80 and older. Costs were determined in a subset of 773 patients with the use of a case-costing system for cardiac surgery developed at our institution. RESULTS: The 3 groups were similar with respect to sex distribution and preoperative risk factors. Urgency scores at referral differed significantly between the groups, with the young septuagenarians demonstrating the lowest risk (mean score [and standard deviation] 4.48 [1.3] in that group, 4.28 [1.4] in the old septuagenarian group and 4.11 [1.2] in the octogenarian group). The rates of all complications combined were similar between the 3 groups (27.1%, 28.1% and 29.6% in the young and old septuagenarian groups and the octogenarian group respectively). There were no significant differences between the 3 groups in the mean number of grafts per patient (3.0, 3.1 and 3.0 respectively), the rate of postoperative death (3.3%, 5.7% and 4.2%), the mean length of stay (11.7, 13.4 and 12.6 days) or the incidence of postoperative myocardial infarction (4.5%, 3.4% and 4.2%). The total cost of CABG per patient did not differ significantly between the 3 groups. INTERPRETATION: Given that patients who are accepted for CABG represent a selected population, our findings suggest that, with careful triage, CABG in octogenarians is as safe as, and no more costly than, CABG in septuagenarians.
Age Factors↗
Reduced incidence and severity of collagen-induced arthritis in mice lacking IL-18.
We have recently reported the presence and a potential proinflammatory role of IL-18 in the synovium of patients with rheumatoid arthritis. To obtain direct evidence that IL-18 plays an influential role in articular inflammation, we investigated the development of collagen-induced arthritis in a strain of mice lacking IL-18 (IL-18(-/-)) of DBA/1 background. IL-18(-/-) mice developed markedly reduced incidence of arthritis compared with heterozygous or wild-type mice. Of the IL-18(-/-) mice that developed arthritis, the severity of the disease was significantly reduced compared with the intact mice. This was accompanied by reduced articular inflammation and destruction evident on histology. IL-18(-/-) mice also had significantly reduced Ag-specific proliferation and proinflammatory cytokine (IFN-gamma, TNF-alpha, IL-6, and IL-12) production by spleen and lymph node cells in response to bovine type II collagen (CII) in vitro compared with wild-type mice, paralleled in vivo by a significant reduction in serum anti-CII IgG2a Ab level. Treatment with rIL-18 completely reversed the disease of the IL-18(-/-) mice to that of the wild-type mice. These data directly demonstrate a pivotal role of IL-18 in the development of inflammatory arthritis and suggest that antagonists to IL-18 may have therapeutic potential in rheumatic diseases.
Animals↗
Women and heart disease: the treatment may end but the suffering continues.
Though heart disease is the number one health problem among women, men continue to represent the majority of those in cardiac rehabilitation for secondary prevention. Research has shown that conventional rehabilitation programs do not meet the needs of women recovering from cardiac events. Women's primary rehabilitative need may be support, particularly from women with similar experiences. Furthermore, the need for support in living with heart disease may persist beyond the in-hospital phase of recovery. The purpose of this study was to develop and implement a community-based communication and psycho-educational support group for women with heart disease. Participatory action research was the methodology selected. Two groups of women (n = 16) met monthly for 5 months to develop the program. Sessions were facilitated jointly by a nurse clinician and a nurse-researcher. Between sessions, participants kept diaries of their experiences. Data consisted of videotapes and transcriptions of the sessions, field notes, and the women's diaries and final evaluation. Initial analysis revealed that the value of the group for the women was threefold: it helped them to cope with their emotional reactions, offered social support, and helped them to manage their health problem. Iterative analysis unveiled a meta-paradigm consistent with the concept of suffering. The apparent overall benefit of a community-based psycho-educational support group for women with heart disease is acknowledgement and sharing of suffering, something that cannot readily occur in women's other life arenas.
Adaptation, Psychological↗
Effect of a preoperative intervention on preoperative and postoperative outcomes in low-risk patients awaiting elective coronary artery bypass graft surgery. A randomized, controlled trial.
BACKGROUND: In publicly funded health care systems, a waiting period for such services as coronary artery bypass graft surgery (CABG) is common. The possibility of using the waiting period to improve patient outcomes should be investigated. OBJECTIVE: To examine the effect of a multidimensional preoperative intervention on presurgery and postsurgery outcomes in low-risk patients awaiting elective CABG. DESIGN: Randomized, controlled trial. SETTING: A regional cardiovascular surgery center in a tertiary care hospital, southwestern Ontario, Canada. PATIENTS: 249 patients on a waiting list for elective CABG whose surgeries were scheduled for a minimum of 10 weeks from the time of study recruitment. INTERVENTION: During the waiting period, the treatment group received exercise training twice per week, education and reinforcement, and monthly nurse-initiated telephone calls. After surgery, participation in a cardiac rehabilitation program was offered to all patients. MEASUREMENTS: Postoperative length of stay was the primary outcome. Secondary outcomes were exercise performance, general health-related quality of life, social support, anxiety, and utilization of health care services. RESULTS: Length of stay differed significantly between groups. Patients who received the preoperative intervention spent 1 less day [95% CI, 0.0 to 1.0 day] in the hospital overall (P = 0.002) and less time in the intensive care unit (median, 2.1 hours [CI, -1.2 to 16 hours]; P = 0.001). During the waiting period, patients in the intervention group had a better quality of life than controls. Improved quality of life continued up to 6 months after surgery. Mortality rates did not differ. CONCLUSION: The waiting period for elective procedures, such as CABG, may be used to enhance in-hospital and early-phase recovery, improving patients' functional abilities and quality of life while reducing their hospital stay.
Anxiety↗
Endoglin, an ancillary TGFbeta receptor, is required for extraembryonic angiogenesis and plays a key role in heart development.
Endoglin (CD105) is expressed on the surface of endothelial and haematopoietic cells in mammals and binds TGFbeta isoforms 1 and 3 in combination with the signaling complex of TGFbeta receptors types I and II. Endoglin expression increases during angiogenesis, wound healing, and inflammation, all of which are associated with TGFbeta signaling and alterations in vascular structure. The importance of endoglin for normal vascular architecture is further indicated by the association of mutations in the endoglin gene with the inherited disorder Hereditary Haemorrhagic Telangiectasia Type 1 (HHT1), a disease characterised by bleeding from vascular malformations. In order to study the role of endoglin in vivo in more detail and to work toward developing an animal model of HHT1, we have derived mice that carry a targeted nonsense mutation in the endoglin gene. Studies on these mice have revealed that endoglin is essential for early development. Embryos homozygous for the endoglin mutation fail to progress beyond 10.5 days postcoitum and fail to form mature blood vessels in the yolk sac. This phenotype is remarkably similar to that of the TGFbeta1 and the TGFbeta receptor II knockout mice, indicating that endoglin is needed in vivo for TGFbeta1 signaling during extraembryonic vascular development. In addition, we have observed cardiac defects in homozygous endoglin-deficient embryos, suggesting endoglin also plays a role in cardiogenesis. We anticipate that heterozygous mice will ultimately serve as a useful disease model for HHT1, as some individuals have dilated and fragile blood vessels similar to vascular malformations seen in HHT patients.
Animals↗
Development and testing of a new hostility scale.
Evidence suggests that assessment of global type A behaviour as a coronary risk factor may not be the most fruitful strategy because some components, particularly hostility, may be more harmful than others. Measurement of hostility has been primarily through two types of instrumentation: the Type A Structured Interview (SI) and the Cook-Medley (Ho) scale. Deficiencies in the measurement of hostility have resulted from a lack of conceptual clarity because definitions of hostility have been blurred by overlap with the concepts of anger and aggression. The main objective of this study was to develop and test an instrument that focuses hostility on attitude rather than emotion or behaviour. Psychometric properties of the Hostile Attitude Scale (HAS) were Cronbach's alpha, 0.80, and correlation of 0.56 with the Ho scale and 0.43 with the SI. In a clinical investigation that used the HAS, SI and Ho scale, all measures were significantly correlated with angiogram outcome, although the strongest relationship was with the HAS. Hostile attitude alone (HAS) accounted for 6% of explained variance in angiogram outcome based on regression analysis. The HAS is offered as a short, easily administered measure of hostility, with particular emphasis on cognitive aspects of the construct.
Coronary Disease↗
Cynical hostility was associated with increased risk of mortality and MI.
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Journal Article↗
Effects of protein restriction in early life on growth and function of the gastrointestinal tract of the rat.
BACKGROUND: Undernutrition during early life may have both immediate and later consequences. This study was undertaken to measure the long-term effects of perinatal undernutrition on the growth and function of the gastrointestinal tract. METHODS: Pregnant rats were assigned to one of four groups that received isocaloric diets restricted in protein during pregnancy or lactation and during both or neither. Thereafter, their pups were followed until aged 1 year. RESULTS: At 21 days the body weights of the young of those born of dams with postnatal protein restriction were halved, with comparable reductions in the weights of the stomach and caecum, compared with those of control animals. The lengths of the small and large intestines and mucosal weights of the foregut were also significantly reduced. Lactase activities were significantly increased and sucrase and maltase activities significantly reduced. By 42 days all the effects were less marked, and at 1 year the dimensions of the organs of the gastrointestinal tract and the composition and enzyme levels of the mucosa were all insignificantly different relative to body weight. CONCLUSIONS: Prenatal protein restriction alone had no significant long-term negative effects on body weight, growth, or mucosal hydrolase activity of the gastrointestinal tract. Postnatal protein restriction had a marked effect on these indices in early life and delayed the changes in mucosal hydrolases usually seen at weaning. In contrast with other organs and their functions, long-term growth of the gut and activity of small intestinal hydrolases are preserved in the face of perinatal protein restriction.
Animals↗
Human milk IgA concentrations during the first year of lactation.
AIMS: To measure the concentrations of total IgA in the milk secreted by both breasts, throughout the first year of lactation, in a cohort of Gambian mothers of infants at high risk of infection. SUBJECTS AND METHODS: Sixty five women and their infants were studied monthly from the 4th to 52nd postpartum week. Samples of milk were obtained from each breast by manual expression immediately before the infant was suckled. Milk intakes were measured by test weighing the infants before and after feeds over 12 hour periods; IgA concentrations were determined by enzyme linked immunosorbent assay. RESULTS: A total of 1590 milk samples was measured. The median (interquartile range) concentration of IgA for all samples was 0.708 (0.422-1.105) g/l; that in milk obtained from the left breast was 0.785 (0.458-1.247) g/l, and that in milk obtained from the right breast was 0.645 (0.388-1.011) g/l (p < 0.0001). There was no significant change in milk or IgA intakes with advancing infant age, but there was a close concordance of IgA concentrations between the two breasts, with "tracking" of the output of the left and right breasts. There was a significant (p < 0.01) negative correlation between maternal age and parity, and weight of milk ingested by infants. During the dry season (December to May) the median (interquartile range) IgA concentration was significantly higher at 0.853 (0.571-1.254) g/l than during the rainy season (June to November), when it was 0.518 (0.311-0.909) g/l (p < 0.0001). CONCLUSIONS: Sustained IgA secretion is likely to protect suckling infants from microbial infection.
Aging↗
Relationship between functional exercise capacity and general quality of life in nonsurgical patients with lower-extremity peripheral arterial disease.
The purpose of this study was to examine the relationship between functional exercise capacity and general quality of life in patients with lower-extremity peripheral arterial disease (PAD) whose conditions are managed without surgical intervention and to establish new ways of measuring functional exercise capacity and general quality of life in this population. This descriptive survey examined 29 nonsurgical patients with lower-extremity PAD. Functional exercise capacity was measured with the 6-minute walk test. Quality of life was measured with the Medical Outcomes Study Short Form 36 (SF-36). All participants were either present or former smokers. Age ranged from 42 to 81 (M = 65). Walk test performance improved significantly from appointment 1 to appointment 2 (p = 0.01) but not from appointment 2 to appointment 3 (p = 0.9). All participants were able to finish all three walk tests for a total of 87 tests; however, in 30% (n = 26) of tests breaks were required because of leg pain. No one reported angina, and no syncope was observed. The SF-36 revealed significantly lower scores on the physical dimension scales and physical component summary (PCS) score in study participants as compared with a general population. Three physical dimension scales correlated significantly with walk test performance, as did the PCS score (r = 0.57, p = 0.001). In conclusion, functional exercise capacity correlated significantly with physical domains of general quality of life, whereas mental domains were unaffected. The 6-minute walk test was a safe, reliable measure of functional exercise capacity in the nonsurgical PAD population. By improving functional exercise capacity, physical abilities may improve. Thus the 6-minute walk test and SF-36 provide additional methods for objective measurement of the therapeutic impact of the nonsurgical management of PAD.
Activities of Daily Living↗
Effect of novel 1-alkyl-3-hydroxy-2-methylpyrid-4-one chelators on uptake and release of iron from macrophages.
The effect of several iron chelators on iron uptake and release by mouse peritoneal macrophages has been investigated. The 1,2-dimethyl (L1) and 1-ethyl-2-methyl (L1NEt) derivatives of 3-hydroxypyrid-4-one markedly enhanced iron mobilisation from macrophages pulsed with 59Fe-transferrin-antitransferrin immune complexes and were more effective than desferrioxamine, maltol, or mimosine. Release increased with increasing chelator concentration. None of the chelators donated significant amounts of iron to macrophages, and none showed any cytotoxic effect. The synthetic alpha-ketohydroxypyridine chelators may therefore be active in removing iron from the reticuloendothelial system as well as from hepatocytes, and indeed may be superior to desferrioxamine.
Animals↗
Regulation of the Escherichia coli uvrD gene in vivo.
The roles of two putative promoter sequences, P1 and P2, and a potential antiterminator sequence found in the uvrD control region were examined in vivo. Constitutive and SOS-induced levels of uvrD mRNA were determined by S1 mapping, and it was shown that the majority of uvrD transcripts are from P1, while P2 plays only a minor role. A series of increasing deletions from the 5' end of the uvrD gene was used to assay transcription in the promoterless vector pKO-1. Loss of just the -35 region of P1 was sufficient to switch off detectable transcription from both P1 and P2. Disruption of the antiterminator by site-specific mutagenesis had no effect on constitutive levels of transcription, but led to a significant increase over wild-type levels following SOS induction. This suggests that the attenuator comes into play following DNA damage to moderate the increase in UvrD protein synthesis.
Adenosine Triphosphatases↗
Microinjection of Escherichia coli UvrA, B, C and D proteins into fibroblasts of xeroderma pigmentosum complementation groups A and C does not result in restoration of UV-induced unscheduled DNA synthesis.
The UV-induced unscheduled DNA synthesis (UDS) in cultured human fibroblasts of repair-deficient xeroderma pigmentosum complementation groups A and C was assayed after injection of identical activities of either Uvr excinuclease (UvrA, B, C and D) from Escherichia coli or endonuclease V from phage T4. Under conditions where the T4 enzyme was able to induce repair synthesis in both XP complementation groups in agreement with earlier observations (de Jonge et al., 1985), no effect of the UvrABCD excinuclease could be observed either when the enzymatic complex was injected into the cytoplasm, or when it was delivered directly into the nucleus. In addition, no effect of the E. coli excinuclease was found on the repair ability of normal repair-proficient human fibroblasts. We conclude that the UvrABCD excinuclease may not work on DNA lesions in human chromatin.
Bacterial Proteins↗
Incest: a violation of trust.
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Adolescent↗
Functions of DNA helicases in the DNA metabolism of Escherichia coli.
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Adenosine Triphosphatases↗