RESUMEN
OBJECTIVES: To describe the health service attendance patterns of urban Aboriginal and Torres Strait Islander (Aboriginal) Australians and make comparisons with those of the general Australian population. DESIGN AND SETTING: General practitioner-completed survey of all attendances over two separate 2-week periods in 2006 at an urban Aboriginal health service in Canberra, which provides services for about 3500 patients per annum. MAIN OUTCOME MEASURES: Standardised attendance ratios (SARs) for a range of health problems, using patients attending Australian general practice for the same reasons as the reference population. RESULTS: Patients attending the Aboriginal health service were significantly younger than the Australian general practice patient reference population. The most common conditions managed were psychological, encompassing substance misuse; psychological problems accounted for 24% of all attendances. Patients attending the Aboriginal health service had higher rates of attendance for psychological conditions (SAR, 2.14; 95% CI, 2.01-2.28), endocrine conditions (SAR, 2.44; 95% CI, 2.29-2.60) and neurological conditions (SAR, 2.90; 95% CI, 2.71-3.09), as well as for circulatory, digestive and male and female genital conditions, than the reference population. Patients attending the Aboriginal health service had significantly lower attendance rates than the Australian population for respiratory illnesses, and conditions related to eyes or ears. CONCLUSIONS: At this urban Aboriginal health service, attendance patterns reflected complex health care needs that are different from those expected of a population of this age. Urban Aboriginal health service attendance appears to reflect significant ill health among the patients, aligning more with Aboriginal health statistics nationally rather than health statistics for urban non-Aboriginal Australians.
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Servicios de Salud Comunitaria/estadística & datos numéricos , Necesidades y Demandas de Servicios de Salud/tendencias , Nativos de Hawái y Otras Islas del Pacífico , Australia , Femenino , Humanos , Masculino , Población UrbanaRESUMEN
OBJECTIVE: Neutral endopeptidase (NEP, EC 3.4.24.11) metabolises endogenous vasoactive peptides that may protect against atherogenesis. Since NEP is found in the adventitia of arteries, we investigated the anti-atherogenic effects of chronic adventitial NEP inhibition. METHODS: Intimal hyperplasia of rabbit carotid arteries was induced by placement of soft, non-occlusive, peri-arterial silastic collars. NEP localisation was studied with autoradiography 7 and 14 days after collar placement. Vascular NEP was inhibited in vivo by local superfusion of one collared carotid artery with Candoxatrilat (50 pmol/h), for 7 days (n = 7). The contralateral collar was filled with saline vehicle. After 7 days, ring segments of collared and normal (proximal to the collar) arteries were obtained and in vitro functional measurements, immunohistochemical determination of the pro-atherogenic factor plasminogen activator inhibitor-1 (PAI-1), localization of macrophages and morphometric analyses were carried out. RESULTS: Vascular NEP radiolabelled substrate binding, mainly in the media, was increased by approximately 50% after 7 days (n = 5; p < 0.05) and by approximately 300% after 14 days of collar placement (n = 5; p < 0.05). Compared with normal artery segments from the same animal, vehicle-filled collared sections displayed significantly impaired vasorelaxation to acetylcholine (endothelium-independent vasodilatation was preserved), increased PAI-1 immunostaining, macrophage accumulation and intimal thickening. In Candoxatrilat-treated collared arteries, vasorelaxation to acetylcholine was improved, along with reductions in PAI-1 levels, macrophage numbers and intimal area (all p < 0.05). CONCLUSION: Enhancing the activity of local, endogenous peptides by adventitial inhibition of vascular NEP may protect against early atherogenesis. This is of particular relevance to using adventitial therapies to prevent intimal hyperplasia leading to restenosis.
Asunto(s)
Estenosis Carotídea/enzimología , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Células Endoteliales/enzimología , Neprilisina/antagonistas & inhibidores , Inhibidores de Proteasas/uso terapéutico , Túnica Íntima/enzimología , Acetilcolina/farmacología , Animales , Autorradiografía , Biomarcadores/análisis , Arterias Carótidas , Estenosis Carotídea/inmunología , Estenosis Carotídea/patología , Células Endoteliales/inmunología , Células Endoteliales/patología , Hiperplasia , Inmunohistoquímica/métodos , Macrófagos/patología , Masculino , Modelos Animales , Inhibidor 1 de Activador Plasminogénico/análisis , Conejos , Túnica Íntima/inmunología , Túnica Íntima/patología , Vasodilatadores/farmacologíaRESUMEN
OBJECTIVE: Elevated vascular plasminogen activator inhibitor-1 (PAI-1) levels are associated with atherosclerosis. In vitro, C-type natriuretic peptide (CNP) has anti-proliferative effects and inhibits the production of PAI-1 in cultured vascular cells. Whether CNP can affect PAI-1 in vivo, particularly in the setting of atherosclerosis, has not been reported. METHODS: Using the rabbit carotid arterial collar model of intimal hyperplasia (collar in place for 7 days), PAI-1 protein was compared in normal, vehicle (saline)-collared, and CNP-treated-collared arteries from the same animal. PAI-1 levels were measured by immunohistochemistry and densitometry and by Western blot. CNP was either infused into the peri-arterial space within one collar (10 fmol/h) or infused directly into the arterial lumen under one collar (100 pmol/h). In some rabbits (n=8), superoxide production in collared and normal artery segments was measured in vitro by chemiluminescence. RESULTS: PAI-1 was present throughout the vascular wall. Endothelial PAI-1 was elevated in saline-collared arteries (approximately 16%, P<0.05; n=7 rabbits) compared with normal carotid segments. The collar induced both a neointima that contained PAI-1 and the accumulation of macrophages in the adventitia. Peri-arterial CNP reduced PAI-1 (P<0.05) in the endothelium (33%), adventitia (47%) and neointima (39%), compared with levels in the contralateral, saline-collared carotid artery, while macrophage infiltration was reduced. Elevated superoxide production in collared arteries was not altered by chronic in vivo treatment with CNP (n=8). Peri-arterial CNP treatment did not reduce intimal thickening. Intra-luminal CNP (n=6) reduced endothelial, neointimal and total vessel (Western blot) PAI-1, macrophage accumulation, and intimal thickening (all P<0.05). CONCLUSIONS: CNP treatment of collared carotid arteries in vivo for 1 week suppressed endothelial and neointimal PAI-1, independently of intimal thickening. The CNP effects were not via superoxide. This is the first evidence that CNP inhibits activated PAI-1, in vivo.