Macrophages, myofibroblasts and neointimal hyperplasia after coronary artery injury and repair

Macrophages participate in the restenosis process through the release of cytokines, metalloproteinases and growth factors. Studies of peritoneal granulation tissue suggest that macrophages may be precursors of myofibroblasts. This study examined the contribution of monocyte/macrophage lineage cells to neointimal cellular mass in a porcine model of thermal vascular injury. Thermal coronary artery injury caused medial smooth muscle cell necrosis and transformation of the media into an extracellular matrix barrier. The neointimal hyperplasia that developed over the injury sites was evaluated by light microscopy, electron microscopy and immunohistochemistry. At day 3, blood monocytes were adhered to the vessel wall and infiltrated the fibrotic media. At day 14, 42 +/- 3.9% of neointimal cells had a monocytic nuclear morphology and expressed macrophage-specific antigen SWC3 (identified by monoclonal antibody DH59B). Moreover, 9.2+/-1.8% of neointimal cells co-expressed SWC3 and alpha-smooth muscle actin and had ultrastructural characteristics intermediate between macrophages and myofibroblasts. At day 28, 10.5 +/- 3.5%, of cells expressed SWC3 and 5.2+/-1.8% of cells co-expressed SWC3 and alpha-smooth muscle actin. This study indicates that hematopoietic cells of monocyte/macrophage lineage abundantly populate the neointima in the process of lesion formation and may be precursors of neointimal myofibroblasts after thermal vascular injury. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Renal cell carcinoma may adapt to and overcome anti-angiogenic intervention with thalidomide

Objective To report on the failure of thalidomide to inhibit tumour growth in an animal model of human renal cell carcinoma (RCC). Materials and methods An orthotopic xenograft model of human RCC was used in which tumour cells were implanted in the left kidney of male 'severe combined immunodeficient' mice. Thalidomide was administered by intraperitoneal injection and after 34 days the mice were killed. The extent of tumour growth was compared in treated and untreated mice. Total RNA was extracted from both tumour-affected and contralateral kidneys, and analysed by reverse transcription-polymerase chain reaction for various genes implicated in angiogenesis and metastasis in RCC. Results Thalidomide failed to inhibit the growth of xenograft tumours. The expression of angiogenic genes, e.g. vascular endothelial growth factor and fibroblast growth factor type 2 (FGF-2) within normal and tumour-affected kidney tissue was not reduced by thalidomide. Intratumoral transcription Of beta(3)-integrin, a critical component of angiogenesis, was significantly increased in response to thalidomide treatment (P

An evaluation of tobacco brief intervention training in three Indigenous health care settings in north Queensland

Objective: To evaluate the pilot phase of a tobacco brief intervention program in three Indigenous health care settings in rural and remote north Queensland. Methods: A combination of in-depth interviews with health staff and managers and focus groups with health staff and consumers. Results: The tobacco brief intervention initiative resulted in changes in clinical practice among health care workers in all three sites. Although health workers had reported routinely raising the issue of smoking in a variety of settings prior to the intervention, the training provided them with an additional opportunity to become more aware of new approaches to smoking cessation. Indigenous health workers in particular reported that their own attempts to give up smoking following the training had given them confidence and empathy in offering smoking cessation advice. However, the study found no evidence that anybody had actually given up smoking at six months following the intervention. Integration of brief intervention into routine clinical practice was constrained by organisational, interpersonal and other factors in the broader socio-environmental context. Conclusions/implications: While modest health gains may be possible through brief intervention, the potential effectiveness in Indigenous settings will be limited in the absence of broader strategies aimed at tackling community-identified health priorities such as alcohol misuse, violence, employment and education. Tobacco and other forms of lifestyle brief. intervention need to be part of multi-level health strategies. Training in tobacco brief intervention should address both the Indigenous context and the needs of Indigenous health care workers.

Cholesterol-lowering therapy with pravastatin in patients with average cholesterol levels and established ischaemic heart disease: is it cost-effective?

Objective: To measure the cost-effectiveness of cholesterol-lowering therapy with pravastatin in patients with established ischaemic heart disease and average baseline cholesterol levels. Design: Prospective economic evaluation within a double-blind randomised trial (Long-Term Intervention with Pravastatin in Ischaemic Disease [LIPID]), in which patients with a history of unstable angina or previous myocardial infarction were randomised to receive 40 mg of pravastatin daily or matching placebo. Patients and setting: 9014 patients aged 35-75 years from 85 centres in Australia and New Zealand, recruited from June 1990 to December 1992. Main outcome measures: Cost per death averted, cost per life-year gained, and cost per quality-adjusted life-year gained, calculated from measures of hospitalisations, medication use, outpatient visits, and quality of life. Results: The LIPID trial showed a 22% relative reduction in all-cause mortality (P < 0.001). Over a mean follow-up of 6 years, hospital admissions for coronary heart disease and coronary revascularisation were reduced by about 20%. Over this period, pravastatin cost $A4913 per patient, but reduced total hospitalisation costs by $A1385 per patient and other long-term medication costs by $A360 per patient. In a subsample of patients, average quality of life was 0.98 (where 0 = dead and 1 = normal good health); the treatment groups were not significantly different. The absolute reduction in all-cause mortality was 3.0% (95% CI, 1.6%-4.4%), and the incremental cost was $3246 per patient, resulting in a cost per life saved of $107730 (95% Cl, $68626-$209881) within the study period. Extrapolating long-term survival from the placebo group, the undiscounted cost per life-year saved was $7695 (and $10 938 with costs and life-years discounted at an annual rate of 5%). Conclusions: Pravastatin therapy for patients with a history of myocardial infarction or unstable angina and average cholesterol levels reduces all-cause mortality and appears cost effective compared with accepted treatments in high-income countries.

Effects of the vasopeptidase inhibitor, omapatrilat, in 723 patients with coronary heart disease

Introduction Among individuals with a history of myocardial infarction (MI), higher levels of blood pressure (BP) are associated with increased long-term risks of death from coronary heart disease. Treatment with a BP-lowering regimen, based on omapatrilat may result in greater clinical benefits than treatment with a regimen based on a regular angiotensin-converting enzyme (ACE) inhibitor because of more favourable effects on the renin-angiotensin-aldosterone system. Methods Seven hundred and twenty-three clinically stable patients with a history of MI or unstable angina, and a mean entry BP of 134/77 mmHg, were randomised to six months treatment with omapatrilat 40 mg, omapatrilat 20 mg, or matching placebo. Results After six months, mean BP levels (systolic/diastolic) in the omapatrilat 40 mg group were reduced by 4.3/ 2.9 mmHg (95% confidence interval 1.3 to 7.2/1.2 to 4.6). Mean BP levels in the omapatrilat 20 mg group were reduced by 4.6/1.0 mmHg (1.6 to 7.6/-0.7 to 2.6) in comparison with the placebo group. Both doses of omapatrilat also produced significant decreases in plasma ACE activity and significant increases in levels of plasma renin activity, atrial natriuretic peptide, endothelin and homocysteine (p

Winter intervention against Aedes aegypti (Diptera : Culicidae) larvae in subterranean habitats slows surface recolonization in summer

At semiarid Charters Towers, north Queensland, Australia, the importance of Aedes aegypti (L.) in wells was assessed in relation to the colonization of surface habitats during the wet season. From April to July 1999, 10 wells (five positive for Ae. aegypti) were monitored to assess their status and larvae population numbers therein. All surface containers located within a 100 m radius of each well were removed, treated with s-methoprene or sealed to prevent the utilization of these containers by mosquitoes. These inner cores were surrounded by outer zones for a further 100 m in which surface containers were left untreated but all subterranean habitats were treated. Ovitraps were monitored monthly in the inner cores for 36 wk from August 1999 to April 2000 and differences in the proportions of ovitraps positive for Ae. aegypti and Ochlerotatus notoscriptus (Skuse) were analyzed by logistic regression. Analysis of the proportions of ovitraps positive for Ae. aegypti near positive wells indicated significantly greater colonization from November to March (the wet season), compared with those situated near Ae. aegypti negative wells. As Oc. notoscriptus were not produced from subterranean sites, comparisons of the proportions of ovitraps positive for Oc. notoscriptus in positive and negative inner cores provided an indication of the relative productivity of the uncontrolled surface containers in the outer zones. Differences in the utililization of ovitraps by Oc. notoscriptus among positive and negative cores were observed during only one month (March), when oviposition was greater in ovitraps in the negative cores, compared with the positive cores. Best subsets linear regression analysis of the proportion of ovitraps positive for Ae. aegypti against meteorological variables (rainfall, mean wind speed, mean relative humidity, mean minimum, and maximum temperature) during the week of ovitrapping indicated that minimum temperature and wind speed accounted for 63.4% of the variability. This study confirms that for semiarid towns such as Charters Towers, the practice of treating a relatively small number of key subterranean habitats during winter will significantly affect Ae. aegypti recolonization of surface container habitats during summer, the period of greatest risk for dengue.

Metformin & lifestyle intervention prevent Type 2 diabetes: lifestyle intervention has the greater effect

Diabetes mellitus is now occurring in epidemic proportions in many countries. Owing to the limited effectiveness of drug prophylaxis of diabetic complications after diabetes has developed, it may be more appropriate to investigate ways to prevent the onset of diabetes. A recent trial published by the Diabetes Prevention Programme Research Group investigated whether lifestyle changes or metformin were effective in delaying the onset of diabetes in subjects with impaired glucose tolerance. The goals of the intensive lifestyle intervention were to achieve and maintain a weight reduction of 7% through a low-calorie, low-fat diet and to engage in physical activity of moderate intensity, such as brisk walking, for at least 150 min/week. The effectiveness of the intensive lifestyle intervention on body weight was initially quite good but decreased over time. Metformin caused some weight loss but to a lesser extent than the intensive lifestyle intervention. Both therapies decreased the fasting plasma glucose levels to a similar extent initially. The intensive lifestyle intervention decreased plasma glycosylated haemoglobin levels to a greater extent than metformin. Both intensive lifestyle intervention and metformin reduced the incidence of diabetes, with the lifestyle intervention having the greater effect.

The Solomon Island: The limits of intervention

Binoy Kampmark Criticises the Basis of Australia's New Strategic Thinking for the Pacific Region

The genetics of coronary heart disease: the contribution of twin studies

Despite the decline in coronary heart disease in many European countries, the disease remains an enormous public health problem. Although we know a great deal about environmental risk factors for coronary heart disease, a heritable component was recognized a long time ago. The earliest and best known examples of how our genetic constitution may determine cardiovascular risk relate to lipoprotein(a), familial hypercholesterolaemia and apolipoprotein E. In the past 20 years a fair number of polymorphisms assessed singly have shown strong associations with the disease but most are subject to poor repeatability. Twins constitute a compelling natural experiment to establish the genetic contribution to coronary heart disease and its risk factors. GenomEUtwin, a recently funded Framework 5 Programme of the European Community, affords the opportunity of comparing the heritability of risk factors in different European Twin Registries. As an illustration we present the heritabilities of systolic and diastolic blood pressure, based on data from over 4000 twin pairs from six different European countries and Australia. Heritabilities for systolic blood pressure are between 52 and 66% and for diastolic blood pressure between 44 and 66%. There is no evidence of sex differences in heritability estimates and very little to no evidence for a significant contribution of shared family environment. A non-twin based prospective case/cohort study of coronary heart disease and stroke (MORGAM) will allow hypotheses relating to cardiovascular disease, generated in the twin cohorts, to be tested prospectively in adult populations. Twin studies have also contributed to our understanding of the life course hypothesis, and GenomEUtwin has the potential to add to this.

Heroin overdose: Research and evidence-based intervention

Drug overdose is a major cause of Premature death and morbidity among heroin users. This article examines recent research into heroin overdose to inform interventions that will reduce the rate of overdose death. The demographic characteristics of overdose cases are discussed, including factors associated with overdose: polydrug use, drug purity, drug tolerance, routes of administration, and suicide. Responses by heroin users at overdoses are also examined. Potential interventions to reduce the rate of overdose and overdose-related morbidity are examined in light of the emerging data in this field.