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Biomedical subjects

P E Norman

Publications and source records attributed to P E Norman.

At least 19 recordsLinked to original sources
PubMed2006

Predictors, consequences and costs of diabetes-related lower extremity amputation complicating type 2 diabetes: the Fremantle Diabetes Study.

AIMS/HYPOTHESIS: The aims of this study were to assess the incidence, predictors, consequences, and inpatient cost of lower extremity amputation (LEA) in a community-based cohort of type 2 diabetic patients. METHODS: Between 1993 and 1996, 1,294 patients with type 2 diabetes were recruited to the longitudinal, observational Fremantle Diabetes Study. LEAs and mortality from cardiac causes were monitored until 30 June 2005. Inpatient costs (in Australian dollars in year 2000), derived using a case-mix approach, were available for the period from 1 July 1993 to 30 June 2000. RESULTS: During follow-up 44 patients without LEA at baseline had a first-ever diabetes-related LEA, an incidence of 3.8 per 1,000 patient-years. Independent predictors of first-ever LEA included foot ulceration (hazard ratio [95% CI]: 5.56 [1.24-25.01]), an ankle brachial index < or =0.90 (2.21 [1.11-4.42]), HbA(1c) (increase of 1%: 1.30 [1.10-1.54]) and neuropathy (2.65 [1.30-5.44]). The risk of cardiac death was significantly increased in patients with LEA at baseline, although this was not an independent risk factor. The median (interquartile range) inpatient cost per LEA admission was 12,485 Australian dollars (6,037 Australian dollars-24,415 Australian dollars), with a median length of stay of 24 (10-43) days. CONCLUSIONS/INTERPRETATION: First-ever LEAs in type 2 patients were associated with poor glycaemic control, foot ulceration and evidence of microvascular and macrovascular disease. Patients with LEA were at increased risk of cardiac death. LEAs contribute disproportionately to diabetes-related inpatient costs.

Aged↗
PubMed2005

Enhanced antiplatelet effect of clopidogrel in patients whose platelets are least inhibited by aspirin: a randomized crossover trial.

OBJECTIVE: We aimed to determine whether adding clopidogrel to aspirin in patients at high risk of future cardiovascular events would suppress laboratory measures of the antiplatelet effects of aspirin; and have greater platelet inhibitory effects in patients with the least inhibition of platelets by aspirin. METHODS: We performed a randomized, double-blind, placebo-controlled, crossover trial, comparing clopidogrel 75 mg day(-1) versus placebo, in 36 aspirin-treated patients with symptomatic objectively confirmed peripheral arterial disease. RESULTS: The addition of clopidogrel to aspirin did not suppress platelet aggregation induced by arachidonic acid, urinary 11 dehydro thromboxane B2 concentrations, or soluble markers of platelet activation markers (P-selectin, CD40-ligand) and inflammation (high sensitivity serum C-reactive protein, interleukin-6). Clopidogrel significantly inhibited platelet aggregation induced by ADP (reduction 26.2%; 95% CI: 21.3-31.1%, P < 0.0001) and collagen (reduction 6.2%; 95% CI: 3.2-9.3%, P = 0.0003). The greatest inhibition of collagen-induced platelet aggregation by clopidogrel was seen in patients with the least inhibition of arachidonic acid induced aggregation by aspirin [lower tertile of arachidonic acid-induced platelet aggregation: 2.8% (95% CI: -0.8 to 6.3%) reduction in mean collagen-induced aggregation by clopidogrel; middle tertile: 4.0% (95% CI: 0.4-7.6%); upper tertile 12.6% (95% CI: 4.5-20.8%); P-value for interaction 0.01]. CONCLUSIONS: The greatest platelet inhibitory effect of clopidogrel occurs in patients with the least inhibition of arachidonic acid-induced platelet aggregation by aspirin. This raises the possibility that the clinical benefits of adding clopidogrel to aspirin may be greatest in patients whose platelets are least inhibited by aspirin. Confirmation in clinical outcome studies may allow these patients to be targeted with antiplatelet drugs that inhibit the ADP receptor, thereby overcoming the problem of laboratory aspirin resistance.

Adenosine Diphosphate↗
PubMed2004

Vitamin D, shedding light on the development of disease in peripheral arteries.

Vitamin D is generally associated with calcium metabolism, especially in the context of uptake in the intestine and the formation and maintenance of bone. However, vitamin D influences a wide range of metabolic systems through both genomic and nongenomic pathways that have an impact on the properties of peripheral arteries. The genomic effects have wide importance for angiogenesis, elastogenesis, and immunomodulation; the nongenomic effects have mainly been observed in the presence of hypertension. Although some vitamin D is essential for cardiovascular health, excess may have detrimental effects, particularly on elastogenesis and inflammation of the arterial wall. Vitamin D is likely to have a role in the paradoxical association between arterial calcification and osteoporosis. This review explores the relationship between vitamin D and a range of physiological and pathological processes relevant to peripheral arteries.

Animals↗
PubMed2004

Population-based study of carotid endarterectomy in Western Australia.

BACKGROUND: Previous studies reported an increase in the rates of operation following the publication of major trials that demonstrated the benefit of carotid endarterectomy in reducing stroke. The aim of this study was to determine whether carotid endarterectomy rates have continued to rise despite the reducing trend in most manifestations of atherosclerotic cardiovascular disease. METHODS: Record linkage was used to select patients who had a carotid endarterectomy during the interval from 1988 to 2001. Incidence rates were age-standardized and trends were examined with Poisson regression. RESULTS: The rate increased by 13.8 per cent per year between 1988 and 1998; however, from 1999 onwards the rate of carotid surgery fell by 15.8 per cent per year. In octogenarians, the rate increased steadily from 0.9 to 5.1 per 100,000 person-years between 1992 and 2000. The proportion of octogenarians also increased significantly from 0.9 per cent in 1988-1990 to 19.5 per cent in 2000-2001 (chi2=60.11, 4 d.f., P<0.001). CONCLUSION: For the first time a recent decline has been observed in the rate of carotid endarterectomy, most likely owing to a combination of the deceasing incidence of atherosclerosis and more widespread use of effective drugs in the treatment of cardiovascular disease. The rate and proportion of operations in patients aged 80 years or older has increased steadily.

Adult↗
PubMed2001

Long-term relative survival following surgery for abdominal aortic aneurysm: a review.

BACKGROUND: The literature reporting the long-term survival following surgery for abdominal aortic aneurysm (AAA) tends to be confusing. As a result, many clinicians looking after patients with AAA may be uncertain about the five-year survival of a given patient. This is in marked contrast to the situation for patients with malignant disease. With the current interest in population screening and endoluminal stenting for AAA, an understanding of long-term survival is increasingly important. METHODS: Thirty two publications in the English language over the last 20 years, containing data pertaining to five-year survival following routine elective surgery for AAA in unselected patients, were identified using Medline searches. RESULTS AND CONCLUSIONS: A range of important methodological differences were noted. The mean five-year crude survival was about 70% while the expected survival of a matched population was close to 80%. Survival was further reduced by about 10% in cases with significant coronary heart disease. Age alone is not a predictor of long-term relative survival with octogenarians who survive beyond 30 days surviving longer than an age-matched population.

Age Factors↗
PubMed2001

Initial results of ultrasound screening for aneurysm of the abdominal aorta in Western Australia: relevance for endoluminal treatment of aneurysm disease.

BACKGROUND: Increased life expectancy in men during the last thirty years is largely due to the decrease in mortality from cardiovascular disease in the age group 29--69 yr. This change has resulted in a change in the disease profile of the population with conditions such as aneurysm of the abdominal aorta (AAA) becoming more prevalent. The advent of endoluminal treatment for AAA has encouraged prophylactic intervention and fueled the argument to screen for the disease. The feasibility of inserting an endoluminal graft is dependent on the morphology and growth characteristics of the aneurysm. This study used data from a randomized controlled trial of ultrasound screening for AAA in men aged 65--83 yr in Western Australia for the purpose of determining the norms of the living anatomy in the pressurized infrarenal aorta. AIMS: To examine (1) the diameters of the infra-renal aorta in aneurysmal and non-aneurysmal cases, (2) the implications for treatment modalities, with particular reference to endoluminal grafting, which is most dependent on normal and aneurysmal morphology, and (3) any evidence to support the notion that northern Europeans are predisposed to aneurysmal disease. METHODS: Using ultrasound, a randomized control trial was established in Western Australia to assess the value of a screening program in males aged 65--83 yr. The infra-renal aorta was defined as aneurysmal if the maximum diameter was 30 mm or more. Aortic diameter was modelled both as a continuous (in mm) and as a binary outcome variable, for those men who had an infra-renal diameter of 30 mm or more. ANOVA and linear regression were used for modelling aortic diameter as a continuum, while chi-square analysis and logistic regression were used in comparing men with and without the diagnosis of AAA. FINDINGS: By December 1998, of 19,583 men had been invited to undergo ultrasound screening for AAA, 12,203 accepted the invitation (corrected response fraction 70.8%). The prevalence of AAA increased with age from 4.8% at 65 yr to 10.8% at 80 yr (chi(2)=77.9, df=3, P<0.001). The median (IQR) diameter for the non-aneurysmal group was 21.4 mm (3.3 mm) and there was an increase (chi(2)=76.0, df=1, P<0.001) in the diameter of the infra-renal aorta with age. Since 27 mm is the 95th centile for the non-aneurysmal infra-renal aorta, a diameter of 30 mm or more is justified as defining an aneurysm. The risk of AAA was higher in men of Australian (OR=1.0) and northern European origin (OR=1.0, 95%CL: 0.9, 1.2) compared with those of Mediterranean origin (OR=0.5, 95%CL: 0.4, 0.7). CONCLUSION: Although screening has not yet been shown to reduce mortality from AAA, these population-based data assist the understanding of aneurysmal disease and the further development and use of endoluminal grafts for this condition.

Age Distribution↗
PubMed2001

Does the Mediterranean paradox extend to abdominal aortic aneurysm?

BACKGROUND: We sought to test, in men undergoing ultrasound screening for abdominal aortic aneurysms (AAA) in Western Australia, clinical impressions that the prevalence of AAA is high in Dutch migrants and low in migrants from Mediterranean countries. METHODS: In a population-based trial, men undergoing screening for AAA completed a questionnaire covering their place of birth, smoking habits and consumption of alcohol, meat, fish, salt and milk. We examined the variation by place of birth in the mean, median, 95th and 99th centiles of infrarenal aortic diameter and the prevalences of AAA defined by criteria of 30 mm, 50 mm and by the 95th and 99th centiles, in men born in Australia, of aortic diameter adjusted for height. FINDINGS: Overall, 12,203 (70.5%) of the 19 583 men took up the invitation to undergo ultrasound screening. The prevalence of AAA defined by absolute diameter was higher than average in men born in The Netherlands or Scotland (more of whom had ever smoked or smoked currently) and lower in men of Mediterranean origin (more of whom drank alcohol currently). There were no consistent relationships with simple dietary data. Correction of aortic diameter for height eliminated the significant heterogeneity in prevalence of large AAA, although a threefold variation in prevalence of AAA exceeding the 95th centile of height-adjusted diameter in Australian men persisted. INTERPRETATION: In our cohort of men, which is subject to both 'healthy migrant' and 'survivor' effects, if it exists at all, any 'Mediterranean paradox' for AAA is more modest than that for coronary disease.

Aged↗
PubMed2000

Screening for abdominal aortic aneurysm: lessons from a population-based study.

OBJECTIVES: To test the acceptability of screening and to identify modifiable risk factors for abdominal aortic aneurysm (AAA) in men. DESIGN: A trial of ultrasound screening for AAA in a population-based random sample of men aged 65-83 years, and a cross-sectional case-control comparison of men in the same sample. PARTICIPANTS: 12,203 men who had an ultrasound examination of their abdominal aorta, and completed a questionnaire covering demographic, behavioural and medical factors. MAIN OUTCOME MEASURES: Prevalence of AAA, and independent associations of AAA with demographic, medical and lifestyle factors. RESULTS: Invitations to screening produced a corrected response of 70.5%. The prevalence of AAAs (> 30 mm) rose from 4.8% in men aged 65-69 years to 10.8% in those aged 80-83 years. The overall prevalence of large (> 50 mm) aneurysms was 0.69%. In a multivariate logistic model Mediterranean-born men had a 40% lower risk of AAA (> 30 mm) compared with men born in Australia (odds ratio [OR], 0.6; 95% CI, 0.4-0.8), while ex-smokers had a significantly increased risk of AAA (OR, 2.3; 95% CI, 1.9-2.8), and current smokers had even higher risks. AAA was significantly associated with established coronary and peripheral arterial disease and a waist:hip ratio greater than 0.9; men who regularly undertook vigorous exercise had a lower risk (OR, 0.8; 95% CI, 0.7-1.0). CONCLUSION: Ultrasound screening for AAA is acceptable to men in the likely target population. AAA shares some but not all of the risk factors for occlusive vascular disease, but the scope for primary prevention of AAA in later life is limited.

Aged↗
PubMed2000

The influence of gender on outcome following peripheral vascular surgery: a review.

There is considerable evidence that outcome following intervention for coronary artery disease in women may be worse than it is for men. The influence of gender on outcome following peripheral vascular surgery has received less attention and is the subject of this review. The incidence of most vascular procedures in women is 20-40% that of men. Women appear to have a greater risk of dying following surgery for abdominal aortic aneurysm, a higher risk of stroke and death following carotid endarterectomy, and poorer patency rates following infrainguinal bypass. The causes may include delayed diagnosis and referral, increased co-morbidity and possibly the effect of smaller arteries in women.

Female↗
PubMed2000

Influence of gender on outcome from ruptured abdominal aortic aneurysm.

BACKGROUND: The aim of the present study was to compare outcomes following ruptured abdominal aortic aneurysm (AAA) in men and women. METHODS: Overall mortality from ruptured AAA was compared in men and women using the Western Australia Health Services Research Database. The linked chains of de-identified hospital morbidity and death records were selected using the ICD-9-CM (International Classification of Diseases - Clinical Modification) diagnostic and procedure codes pertaining to AAA. Cases were divided into three groups for analysis: patients who died without admission to hospital, those admitted to hospital with a ruptured AAA but who did not undergo operation, and patients who underwent operation for ruptured AAA. RESULTS: Ruptured AAA occurred in 648 men and 225 women over the age of 55 years during the decade 1985-1994. Only 50 per cent of women, compared with 59 per cent of men, were admitted to hospital. Of those admitted to hospital only 37 per cent of women underwent operation, compared with 63 per cent of men. The overall mortality rate from ruptured AAA was 90 per cent in women and 76 per cent in men (chi2 = 50.34, 1 d.f., P < 0.0001). Although women were, on average, 6 years older than men, this unfavourable pattern occurred across all age groups. CONCLUSION: Women with a ruptured AAA are more likely to die than men. More research is required to identify the causes of this sex difference.

Aged↗
PubMed2000

The potential for a selective screening strategy for abdominal aortic aneurysm.

OBJECTIVES: To investigate the feasibility of selective screening for abdominal aortic aneurysm (AAA) based on identification of a target group of manageable size defined by risk factors for AAA. SETTING: Male residents of Perth, Western Australia, aged 65-83 years, who participated in a randomised controlled trial of ultrasound screening for AAA. METHODS: Eligible men were identified from the electoral roll and invited to attend a screening clinic. Those who attended completed a questionnaire, had a limited physical examination, and underwent an ultrasound examination to identify the maximum diameter of the infrarenal aorta. Data on risk factors collected from the first 8995 men seen were used to calculate a multivariate risk score for the remaining 2755 men who were screened. Centiles of the risk score were used to define potential target groups for screening and the sensitivity and specificity of each of these selective screening strategies were calculated. We repeated the calculation separately for AAAs of at least 30 mm, 40 mm, and 50 mm in diameter. RESULTS: We found that screening half of the male population aged 65-83 years would find approximately 75% of AAAs, regardless of their size, whereas screening only current smokers in this population would find approximately 20% of AAAs. CONCLUSIONS: Selective screening for AAA using easily recognisable risk factors is feasible but is not worthwhile as approximately 25% ofclinically significant cases would be missed.

Aged↗
PubMed1999

The changes seen in balloon-injured porcine femoral arteries following sympathectomy.

On the basis that vasoconstriction may contribute to restenosis following angioplasty, the influence of lumbar sympathectomy on the morphometry of femoral arteries after balloon injury was examined in a pig model. Twenty-six juvenile pigs underwent balloon de-endothelialization of the right femoral artery followed by an open bilateral lumbar sympathectomy (n = 14) or a sham sympathectomy (n = 12). Four weeks later flow was measured in femoral arteries. Animals were then killed and the femoral arteries were perfusion-fixed and harvested. Sympathectomy resulted in a significant (P = 0.04) increase in flow in both the injured (right) and uninjured (left) femoral arteries. Sympathectomy did not inhibit intimal thickening following balloon injury: median (interquartile range) intimal area was 0.4 mm2 (0.3-0.9) in the sympathectomy group versus 0.5 mm2 (0.4-0.9) in the sham group. Sympathectomy did, however, result in a significant (P = 0.02) increase in the lumen area: 1.1 mm2 (0.8-1.8) versus 0.7 mm2 (0.6-0.9). Sympathectomy may reduce vasospasm following angioplasty with the potential for clinical benefit.

Animals↗
PubMed1998

Long term relative survival after surgery for abdominal aortic aneurysm in western Australia: population based study.

OBJECTIVE: To determine the long term relative survival of all patients who had surgery for abdominal aortic aneurysm in Western Australia during 1985-94. DESIGN: Population based study. SETTING: Western Australia. SUBJECTS: All patients who had had surgery for abdominal aortic aneurysm in Western Australia during 1985-94. MAIN OUTCOME MEASURES: Morbidity and mortality data of patients admitted and surgically treated for abdominal aortic aneurysm in Western Australia during 1985-94. Elective, ruptured, and acute non-ruptured cases were analysed separately. Independent analyses for sex and patients aged 80 years or more were also undertaken. Postoperative (>30 days) relative survival was assessed against age and sex matched controls. RESULTS: Overall, 1475 (1257 men, 218 women) cases were identified. The crude five year survival after elective surgery, including deaths within 30 days of surgery, was 79% for both men and women. When compared with a matched population the five year relative survival after elective surgery was 94.9% (95% confidence interval 89.9% to 99.9%) for men but only 88.0% (76.3% to 99.7%) for women. The five year relative survival of those aged 80 years and over was good: 116.6% (89.1% to 144.0%) compared with 92.4% (87.7% to 97.0%) for those under 80 years of age (men and women combined). Cardiovascular disease caused 57.8% of the 341 deaths after 30 days. CONCLUSION: In a condition such as abdominal aortic aneurysm, which occurs in elderly patients, relative survival is more clinically meaningful than crude survival. The five year relative survival in cases of elective and ruptured abdominal aortic aneurysm was better in men than in women. This is probably because of greater comorbidity in women with abdominal aortic aneurysm and this deserves more attention in the future. The long term survival outcome in octogenarians supports surgery in selected cases.

Age Distribution↗
PubMed1998

Vascular endothelial growth factor (VEGF) expression during arterial repair in the pig.

OBJECTIVES: Vascular endothelial growth factor (VEGF) is reported to be a potent and specific mitogen for endothelial cells (EC) and an inducer of angiogenesis in vivo. Originally called vascular permeability factor (VPF), VEGF also increases permeability of microvessels to circulating macromolecules. The aim of this study was to examine whether the VEGF gene was expressed in porcine arteries following denudation of EC. DESIGN: Experimental animal model with mechanical injury to large arteries. METHODS: The right iliac artery of juvenile pigs was de-endothelialised using an inflated balloon catheter. At a number of time-points after injury, these arteries were harvested together with uninjured contralateral arteries. Sections of arteries were used for RNA analysis by Northern blots and for protein localisation studies by immunohistochemistry. RESULTS: Two VEGF transcripts (2.0 kb, 4.5 kb) were markedly elevated in pig arteries soon after injury. Newly synthesised VEGF protein was located in smooth muscle cells (SMC) throughout the media of injured arteries. CONCLUSIONS: The elevated expression of VEGF by SMC in denuded porcine arteries is evidence that this cytokine plays a role in the injury response of large arteries. Since several biological activities have been identified for VEGF, the function of this cytokine in the arterial repair process remains to be determined.

Animals↗