Reversal of cardiovascular remodelling with candesart

Cardiovascular remodelling, defined as ventricular and vascular hypertrophy together with fibrosis, characterises hypertension following inhibition of the production of the endogenous vasodilator, nitric oxide (NO). This study has determined whether the cardiovascular remodelling following chronic NO synthase inhibition can e reversed by administration of the selective angiotensin II AT(1)-receptor antagonist, candesartan. Male Wistar rats were treated with L-nitroarginine methyl ester (L-NAME, 400 mg/l in drinking water) for eight weeks and with candesartan cilexetil (2 mg/kg/day by oral gavage) for the last four weeks. L-NAME-treated rats became hypertensive with systolic blood pressure increasing from 110 +/- 4 mmHg (control) to 170 +/- 10 mmHg. Rats developed left ventricular hypertrophy (control 1.70 +/- 0.06; L-NAME 2.10 +/- 0.04 mg/kg body wt) with markedly increased deposition of perivascular and interstitial collagen. Candesartan returned blood pressure, left ventricular weights and collagen deposition to control values. Echo cardiographic assessment showed concentric hypertrophy with an increased fractional shortening; this was reversed by candesartan treatment. Heart failure was not evident. In the isolated Langendorff heart, diastolic stiffness increased in L-NAME-treated rats while the rate of increase in pressure (+dP/dt) increased after eight weeks only; candesartan reduced collagen deposition and normalised +dP/dt. In isolated left ventricular papillary muscles, the potency (negative log EC50) of noradrenaline as a positive inotropic compound was unchanged, (control 6.56 +/- 0.14); maximal increase in force before ectopic beats was reduced from 5.0 +/- 0.4 mN to 2.0 +/- 0.2 mN. Noradrenaline potency as a vasoconstrictor in thoracic aortic rings was unchanged, but maximal contraction was markedly reduced from 25.2 +/- 2.0 mN to 3.0 +/- 0.3 mN; this was partially reversed by candesartan treatment. Thus, chronic inhibition of NO production with L-NAME induces hypertension, hypertrophy and fibrosis with increased toxicity and significant decreases in vascular responses to noradrenaline. These changes were at least partially reversible by treatment with candesartan, implying a significant role of AT(1)-receptors in L-NAME-induced cardiovascular changes.

Introducing OTseeker (Occupational Therapy Systematic Evaluation of Evidence): A new evidence database for occupational therapists

OTseeker (Occupational Therapy Systematic Evaluation of Evidence) is a new resource for occupational therapists that has been designed with the principle aim of increasing access to research to support clinical decisions. It contains abstracts of systematic reviews and quality ratings of randomized controlled trials (RCTs) relevant to occupational therapy. It is available, free of charge, at www.otseeker.com. This paper describes the OTseeker database and provides an example of how it may support occupational therapy practice.

Australian occupational therapists' use of an online evidence-based practice database (OTseeker)

Introduction: Online databases can support the implementation of evidence-based practice by providing easy access to research. OTseeker (www.otseeker.com), an electronic evidence database, was introduced in 2003 to assist occupational therapists to locate and interpret research. Objectives: This study explored Australian occupational therapists' use and perceptions of OTseeker and its impact on their knowledge and practice. Methods: A postal survey questionnaire was distributed to two samples: (i) a proportionate random sample of 400 occupational therapists from all states and territories of Australia, and (ii) a random sample of occupational therapists working in 95 facilities in two Australian states (Queensland and New South Wales). Results: The questionnaire was completed by 213 participants. While most participants (85.9%) had heard of OTseeker, only 103 (56.6%) had accessed it, with lack of time being the main reason for non-use. Of the 103 participants who had accessed OTseeker, 68.9% had done so infrequently, 63.1% agreed that it had increased their knowledge and 13.6% had changed their practice after accessing information on OTseeker. Conclusion: Despite OTseeker being developed to provide occupational therapists with easy access to research, lack of time was the main reason why over half of the participants in this study had not accessed it. This exploratory research suggests, however, that there is potential for the database to influence occupational therapists' knowledge and practice about treatment efficacy through access to the research literature.