Developing strategies for therapeutic angiogenesis: vascular endothelial growth factor alone may not be the answer.
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Angiogenesis Inducing Agents↗
Biomedical subjects
M J McCarthy
Publications and source records attributed to M J McCarthy.
Developing strategies for therapeutic angiogenesis: vascular endothelial growth factor alone may not be the answer.
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Angiogenesis Inducing Agents↗
Low atmospheric pressure is associated with rupture of abdominal aortic aneurysms.
INTRODUCTION: the rate of rupture of abdominal aortic aneurysms (AAAs) has been shown to have a seasonal variation with more ruptures occurring during the winter months. One of the main meterological changes between the seasons is a change in atmospheric pressure. The aim of this study was to investigate whether there was any relationship between atmospheric pressure and the incidence of AAA rupture. METHODS: all cases of ruptured AAA admitted to a single hospital over a ten year period were identified from hospital records. Daily atmospheric pressure readings from the nearest weather recording station to the hospital were obtained for the same period. Cases were only included if rupture could be confirmed by reviewing the patients case-notes. RESULTS: admission rates for ruptured AAA showed a monthly variation with the highest rate in December and the lowest in August. There was a statistically significant correlation between the number of cases admitted in any particular month and the mean atmospheric pressure for the previous month. Neither daily minimum, maximum or mean pressure, weekly mean pressure or daily pressure variability were significantly different between those days when a ruptured AAA was admitted and those when no ruptured AAA was admitted. CONCLUSIONS: low atmospheric pressure is associated with increased rate of AAA rupture. The method by which this change in pressure precipitates rupture cannot be determined from this study.
Aortic Aneurysm, Abdominal↗
Systemic diseases associated with various types of retinal vein occlusion.
PURPOSE: To investigate systemic diseases associated with various types of retinal vein occlusion. METHODS: We investigated prospectively in 1090 consecutive patients with retinal vein occlusion, almost all Caucasian (consistent with the racial pattern here), the prevalence of associated systemic disorders before or at the onset of various types of retinal vein occlusion. The patients were categorized into six types of retinal vein occlusion based on defined criteria: nonischemic and ischemic central retinal vein occlusion, nonischemic and ischemic hemi-central retinal vein occlusion, and major and macular branch retinal vein occlusion. The patients had a detailed ophthalmic and systemic evaluation according to our protocol. For data analysis, patients were divided into three age groups: young (younger than 45 years), middle-aged (45 to 64 years), and elderly (65 years or older). The observed prevalence rates of major systemic diseases were compared among central retinal vein occlusion, hemi-central retinal vein occlusion, and branch retinal vein occlusion using a polytomous logistic regression analysis adjusting for gender and age. Logistic regression adjusting for age and gender was also used to compare the observed prevalence of systemic disease between nonischemic and ischemic in central retinal vein occlusion and hemi-central retinal vein occlusion and between major and macular branch retinal vein occlusion. These observed prevalence rates were also compared with those expected in a gender-matched and age-matched control population from estimates from the US National Center for Health Statistics. RESULTS: There was a significantly higher prevalence of arterial hypertension in branch retinal vein occlusion compared with central retinal vein occlusion (P < .0001) and hemi-central retinal vein occlusion (P = .028). Branch retinal vein occlusion also had a significantly higher prevalence of peripheral vascular disease (P = .0002), venous disease (P = .011), peptic ulcer (P = .031), and other gastrointestinal disease (P < .0001) compared with central retinal vein occlusion. The proportion of patients with branch retinal vein occlusion with cerebrovascular disease was also significantly (P = .049) greater than that of the combined group of patients with central retinal vein occlusion and patients with hemi-central retinal vein occlusion. There was no significant difference in prevalence of any systemic disease between central retinal vein occlusion and hemi-central retinal vein occlusion. A significantly greater prevalence of arterial hypertension (P = .025) and diabetes mellitus (P = .011) was present in the ischemic central retinal vein occlusion compared with the nonischemic central retinal vein occlusion. Similarly, arterial hypertension (P = .0002) and ischemic heart disease (P = .048) were more prevalent in major branch retinal vein occlusion than in macular branch retinal vein occlusion. Relative to the US white control population, the combined group of patients with central retinal vein occlusion and patients with hemi-central retinal vein occlusion had a higher prevalence of arterial hypertension (P < .0001), peptic ulcer (P < .0001), diabetes mellitus (in ischemic type only, P < .0001), and thyroid disorder (P < .0001). The patients with branch retinal vein occlusion showed a greater prevalence of arterial hypertension (P < or = .005), cerebrovascular disease (P = .007), chronic obstructive pulmonary disease (P = .012), peptic ulcer (P < .0001), diabetes (in young only, P = .0005), and thyroid disorder (P = .003) compared with the US white control population. CONCLUSIONS: The findings of our study revealed that a variety of systemic disorders may be present in association with different types of retinal vein occlusion and in different age groups, and that their relative prevalence differs significantly, so that the common practice of generalizing about these disorders for the entire group of patients with retinal vein occlusion can be misleading. The presence of a particular associated systemic disease does not necessarily imply a cause-and-effect relationship with that type of retinal vein occlusion; the particular disease may or may not be one of the risk factors in a multifactorial scenario predisposing an eye to develop a particular type of retinal vein occlusion. Based on our study, we think that apart from a routine medical evaluation, an extensive and expensive workup for systemic diseases is unwarranted in the vast majority of patients with retinal vein occlusion.
Adult↗
Tie-1 receptor tyrosine kinase endodomain interaction with SHP2: potential signalling mechanisms and roles in angiogenesis.
The endothelial receptor tyrosine kinase plays an essential role in vascular development where it is thought to be required for vessel maturation and stabilization. The ligands responsible for activating Tie-1, its signalling pathways and specific cellular functions are however not known. As with some other receptor tyrosine kinases, Tie-1 is subject to extracellular proteolytic cleavage generating a membrane bound receptor fragment comprising the intracellular and transmembrane domains. Here we examine the signalling potential of this Tie-1 endodomain. We show that the Tie-1 endodomain has poor ability to induce tyrosine phosphorylation. However, on formation the endodomain physically associates with a number of tyrosine phosphorylated signalling intermediates including the tyrosine phosphatase and adaptor protein SHP2. The assembly of this multimolecular complex is consistent with the endodomain having a ligand-independent signalling role in the endothelial cell. The potential roles of ectodomain cleavage and cleavage activated signalling in regulating microvessel stability in angiogenesis, vessel remodelling and regression are considered.
Animals↗
Intermittent groin swelling following a polytetrafluoroethylene iliofemoral graft.
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Abscess↗
The Prince Edward Island Conceptual Model for Nursing: a nursing perspective of primary health care.
The philosophy of primary health care (PHC) recognizes that health is a product of individual, social, economic, and political factors and that people have a right and a duty, individually and collectively, to participate in the course of their own health. The majority of nursing models cast the client in a dependent role and do not conceptualize health in a social, economic, and political context. The Prince Edward Island Conceptual Model for Nursing is congruent with the international move towards PHC. It guides the nurse in practising in the social and political environment in which nursing and health care take place. This model features a nurse/client partnership, the goal being to encourage clients to act on their own behalf. The conceptualization of the environment as the collective influence of the determinants of health gives both nurse and client a prominent position in the sociopolitical arena of health and health care.
Family Nursing↗
Angiogenic revascularisation in ischaemic disease. Molecular techniques hold promise, though they are still some way off.
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Humans↗
Experience of supraclavicular exploration and decompression for treatment of thoracic outlet syndrome.
The purpose of this study was to assess the symptomatic outcome of patients with thoracic outlet syndrome who underwent decompression of the thoracic outlet. In our unit we prefer the supraclavicular approach, performing anterior scalenectomy with excision of fibrous bands or cervical ribs if present. Operative details were gained by theater logbook and case note review. Over a 6-year period, 31 patients (37 limbs) underwent thoracic outlet decompression. Of the 37 affected limbs, the indications for surgery were a combination of both neurological and vascular symptoms in 24 patients (65%), neurological symptoms in 24 (65%), and 4 patients (11%) had vascular symptoms alone. All patients were assessed for postoperative outcome either at out-patient clinics or by personal contact. From the results of this study we concluded that supraclavicular scalenectomy and cervical rib excision with selective first rib excision is a safe and effective procedure for most patients with thoracic outlet syndrome.
Adult↗
Variations on the slotted-tube resonator: rectangular and elliptical coils.
Two designs (one rectangular, one elliptical) are proposed as efficient alternatives to noncylindrical birdcage RF coils. These designs are based on the slotted-tube resonator and their performance relies on the natural current distribution in the conductors due to the eddy current effects at high frequencies. A Finite element method program, solving the full set of Maxwell's equations, has been employed to accurately characterize and optimize the field homogeneity of the proposed noncylindrical coils. The optimum configuration of each design is presented, taking into account the effect of the RF shield. The proposed designs are compared to several configurations presented in the literature. Two coils (one rectangular, one elliptical) have been constructed and tested in a 0.6 T imaging system. A rectangular coil has been built to operate at 300 MHz. MR images substantiate the usefulness of these coils.
Equipment Design↗
Angiogenesis and the atherosclerotic carotid plaque: an association between symptomatology and plaque morphology.
PURPOSE: Symptomatic carotid disease resulting from generation of thromboemboli has been associated with plaque instability and intraplaque hemorrhage. These features of the lesion could be influenced by the fragility and position of neovessels within the plaque. The purpose of this study was to determine whether any association exists between neovessel density, position, morphology, and thromboembolic sequelae. METHODS: Carotid endarterectomy samples were collected from 15 asymptomatic patients with greater than 80% stenoses and from 13 highly symptomatic patients who had suffered ipsilateral carotid stenotic events within 1 month of surgery. Both groups were matched for gender, age, risk factors, degree of carotid artery stenosis, and plaque size. Samples were stained with hematoxylin/eosin and van Geison. Immunohistochemistry was performed by using an endothelial specific antibody to CD31. Plaques were assessed for histologic characteristics, and neovessels were counted and characterized by size, site, and shape. RESULTS: There were significantly more neovessels in plaques (P <.00001) and fibrous caps (P <.0001) in symptomatic compared with asymptomatic plaques. Neovessels in symptomatic plaques were larger (P <.004) and more irregular. There was a significant increase in plaque necrosis and rupture in symptomatic plaques. Plaque hemorrhage and rupture were associated with more neovessels within the plaque (P <.017, P <.001) and within the fibrous cap (P <.046, P <.004). Patients with preoperative and intraoperative embolization had significantly more plaque and fibrous cap neovessels (P <.025, P <.001). CONCLUSION: Symptomatic carotid disease is associated with increased neovascularization within the atherosclerotic plaque and fibrous cap. These vessels are larger and more irregular and may contribute to plaque instability and the onset of thromboembolic sequelae.
Arteriosclerosis↗
Prevalence of true vein graft aneurysms: implications for aneurysm pathogenesis.
BACKGROUND: Circumstantial evidence suggests that arterial aneurysms have a different cause than atherosclerosis and may form part of a generalized dilating diathesis. The aim of this study was to compare the rates of spontaneous aneurysm formation in vein grafts performed either for popliteal aneurysms or for occlusive disease. The hypothesis was that if arterial aneurysms form a part of a systemic process, then the rates of vein graft aneurysms should be higher for patients with popliteal aneurysms than for patients with lower limb ischemia caused by atherosclerosis. METHODS: Infrainguinal vein grafting procedures performed from 1990 to 1995 were entered into a prospective audit and graft surveillance program. Aneurysmal change was defined as a focal increase in the graft diameter of 1.5 cm or greater, excluding false aneurysms and dilatations after graft angioplasty. RESULTS: During the study period, 221 grafting procedures were performed in 200 patients with occlusive disease and 24 grafting procedures were performed in 21 patients with popliteal aneurysms. Graft surveillance revealed spontaneous aneurysm formation in 10 of the 24 bypass grafts (42%) for popliteal aneurysms but in only 4 of the 221 grafting procedures (2%) that were performed for chronic lower limb ischemia. CONCLUSION: This study provides further evidence that aneurysmal disease is a systemic process, and this finding has clinical implications for the treatment of popliteal aneurysms.
Adult↗
Colour-coded duplex imaging and dependent Doppler ultrasonography in the assessment of cruropedal vessels.
BACKGROUND: It has been suggested that ultrasonography could replace diagnostic arteriography in the assessment of patients who present with leg ischaemia. This study investigated a group of consecutive patients who had femorodistal bypass and who were assessed before operation with colour-coded duplex and dependent Doppler insonation alone. METHODS: Thirty-seven consecutive patients with critical lower limb ischaemia underwent surgical exploration with a view to femorodistal bypass. Results of preoperative colour-coded duplex and dependent Doppler insonation were compared with intraoperative arteriograms and surgical findings. RESULTS: There was very good agreement between colour-coded duplex imaging and dependent Doppler insonation with intraoperative angiography and surgical findings in the prediction of the optimal run-off vessel (kappa = 1.0) and the site of the distal anastomosis (kappa = 0.85; 95 per cent confidence interval 0.71-1.0). There was also very good agreement between dependent Doppler insonation and intraoperative arteriography (kappa = 1.0) in predicting pedal arch patency and the predominant feeding vessel. CONCLUSION: Assessment of leg arteries before femorodistal bypass can be performed accurately with non-invasive colour-coded duplex imaging and dependent Doppler insonation alone, thus obviating the need for preoperative arteriography.
Adult↗
Infrainguinal revascularisation in the era of vein-graft surveillance--do clinical factors influence long-term outcome?
OBJECTIVES: To investigate the variables affecting the long-term outcome of infrainguinal vein bypass grafts that have undergone postoperative surveillance. DESIGN: A retrospective analysis. PATIENTS AND METHODS: Details of 299 consecutive infrainguinal vein grafts performed in 275 patients from a single university hospital were collected and analysed. All grafts underwent postoperative duplex surveillance. Factors affecting patency, limb salvage and survival rates were examined. These factors were gender, diabetes, hypertension, aspirin, warfarin, ischaemic heart disease, run-off, graft type, early thrombectomy, level of anastomoses and indication for surgery. RESULTS: The 6-year primary, primary assisted and secondary patency rates were 23, 47, and 57%, respectively. Six-year limb salvage and patient survival were 68 and 45%, respectively. Primary patency was adversely influenced by the use of composite vein grafts. Early thrombectomy was the only factor that significantly influenced secondary patency. Limb salvage was worse in diabetic limbs, limbs with poor run-off and in grafts that required early thrombectomy. Postoperative survival was better in males, claudicants and in patients who took aspirin. CONCLUSIONS: Although co-morbid factors did not influence graft patency rates, diabetes did adversely effect limb salvage. This study, like others before it, confirms that aspirin significantly reduces long-term mortality in patients undergoing infrainguinal revascularisation.
Angioplasty↗
Potential roles of metalloprotease mediated ectodomain cleavage in signaling by the endothelial receptor tyrosine kinase Tie-1.
The orphan receptor tyrosine kinase Tie-1 is expressed predominantly in endothelial cells. Expression of this receptor is increased in physiologic angiogenesis and pathologic situations including tumor growth and arteriovenous malformations. Tie-1 is essential for vascular development where it acts in later stages of angiogenesis to suppress endothelial activation and stabilize the newly formed vessel. Stimulation of protein kinase C in endothelial cells results in endoproteolytic cleavage of Tie-1, releasing the extracellular ligand-binding domain of the receptor. We show that this is mediated by a metalloprotease. Immunoprecipitation and immunoblotting of lysates prepared from human placentas confirm that Tie-1 truncation occurs in vivo. We propose cleavage of this receptor may be a mechanism for inducing vessel destabilization by preventing ligand-activated signaling through Tie-1. Using an antibody that recognizes the carboxy terminus of the intracellular domain, we show that the Tie-1 endodomain formed on cleavage persists as a cell-associated fragment for several hours. Subcellular fractionation reveals this tyrosine kinase containing receptor fragment to be localized in the membrane fraction of the cell. Immunoprecipitation with antibodies recognizing phosphotyrosine demonstrates that cleavage of Tie-1 stimulates association of newly generated endodomain with cellular phosphoproteins. Furthermore, there was a marked induction of tyrosine phosphorylation of several proteins after PMA-induced endodomain generation. These data indicate that ectodomain cleavage may be a mechanism for down-regulating ligand-induced signaling through Tie-1 while activating an alternative ligand-independent signaling pathway in endothelial cells. Ectodomain cleavage occurs in some other receptor tyrosine kinases. We suggest that rather than solely being a means of down-regulating receptor activity, ectodomain cleavage may be a novel way for a receptor to switch between two alternative signaling pathways.
Cells, Cultured↗
The endothelial receptor tyrosine kinase tie-1 is upregulated by hypoxia and vascular endothelial growth factor.
The receptor tyrosine kinase tie-1 is essential for angiogenesis where it appears to have a role in vessel maturation. Here we have examined the effects of hypoxia and vascular endothelial growth factor (VEGF) on the level of tie-1 protein expressed in bovine aortic endothelial cells. Both hypoxia (2% O2) and VEGF were found to increase tie-1 in a time-dependent manner. Hypoxic induction was direct and effects of hypoxia and VEGF were not additive. Experiments with actinomycin D indicate that these activators regulate tie-1 at the transcriptional level.
Animals↗
Bilateral infrainguinal vein grafts and the incidence of vein graft stenosis.
OBJECTIVES: To elucidate the incidence of significant vein graft stenosis in patients who have undergone bilateral infrainguinal vein grafts. MATERIALS: Between 1987 and 1996, 22 patients were identified from our vascular studies database as having undergone bilateral infrainguinal vein bypass grafting. METHODS: Data was obtained from the vascular studies database and by case note review. All patients had been part of a vein graft surveillance programme. RESULTS: Of the 22 patients with bilateral vein grafts, eight were excluded from further analysis because one or more of their grafts failed within 30 postoperative days. In the remaining 14 patients (28 vein grafts) there were 15 primary vein graft stenoses. Six patients (43%) had bilateral vein graft stenoses, which is significantly higher (p = 0.0008) than the predicted value of 9%, for developing bilateral vein graft stenoses. For those patients who developed a vein graft stenosis in their first grafted limb (9/14), 67% (6/14) subsequently developed a vein graft stenosis in their second grafted limb. CONCLUSION: Patients who develop vein graft stenosis in one limb are at a greater risk of developing a contralateral vein graft stenosis if that limb is grafted. This may well be due to individual vein morphology or unidentified systemic factors that play a role in the aetiology of vein graft stenosis.
Aged↗
At what peak velocity ratio value should duplex-detected infrainguinal vein graft stenoses be revised?
OBJECTIVES: To determine the peak velocity ratio (PVR) threshold at which to intervene and correct duplex detected vein graft stenoses. DESIGN: Prospective study. MATERIALS: Infrainguinal vein grafts in patients attending the vascular studies for routine postoperative surveillance. METHODS: Colour duplex detected stenotic vein graft lesions with a peak velocity ratio (PVR) between 2.0 and 2.9 were identified and monitored by serial duplex scans performed monthly for 3 months and then at 3-monthly intervals thereafter. At the end of the study period, the outcome of these lesions were analysed. RESULTS: Thirty-eight lesions were identified from 32 grafts. Of these lesions, sixteen (42%) resolved, 11 (29%) remained stable and 11 (29%) progressed to a PVR of > or = 3.0 and underwent angioplasty. There were no occlusions in any of the grafts during the period of study. CONCLUSIONS: Colour duplex detected vein graft stenoses with a PVR of less than 3.0 can be treated expectantly if grafts with stenoses with a PVR 2.0-2.9 are scanned every month for at least 3 months after detection.
Angioplasty, Balloon↗