Abolition of hypertension-induced end-organ damage by androgen receptor blockade in transgenic rats harboring the mouse ren-2 gene

A sexual dimorphism in hypertension has been observed in both human and laboratory animal studies. The mechanisms by which male sex hormones regulate cardiovascular homeostasis are still not yet fully understood and represent the subject of this study. The possible involvement of androgen receptors in the development of hypertension and end-organ damage in transgenic rats harboring the mouse Ren-2 renin gene [TGR(mREN2)27] was studied. Male TGR(mREN2)27 rats were treated with the androgen receptor antagonist Flutamide starting at 4 wk of age. Also, an androgen receptor mutation (testicular feminization mutation [tfm]) was introduced in these rats by crossbreeding male TGR(mREN2)27 rats with tfm rats. The resulting offspring male rats that contain the tfm mutation are insensitive to androgens. Flutamide treatment or tfm mutation produced a significant attenuation of the development of hypertension. Besides a reduction in cardiac hypertrophy, urinary albumin excretion was blunted and no histologic characteristics of end-organ damage were observed in the kidney after Flutamide treatment. Testosterone levels increased 15-fold after Flutamide treatment and 2.7-fold by the tfm mutation. Also, plasma estrogens and luteinizing and follicle-stimulating hormones were significantly increased. Plasma renin concentrations and activity but not plasma angiotensinogen were reduced. Our results indicate that androgens contribute not only to the development of hypertension, but even more importantly to end-organ damage in TGR(mREN2)27 rats.     

Serum amyloid P component scintigraphy for diagnosis and monitoring amyloidosis

Serum amyloid P component is a normal plasma protein and a universal non-fibrillar constituent of amyloid deposits. Radiolabelled serum amyloid P component scintigraphy is a non-invasive and quantitative method for imaging amyloid deposits, which produces diagnostic images in most patients with systemic amyloidosis, and can be used repeatedly to monitor the course of the disease. The scintigraphy technique and biopsy histology are complementary, providing a detailed microscopic analysis and a quantitative whole body survey respectively. Clinically useful observations provided by the imaging method include different organ distributions of amyloid in different types of the disease, demonstration of amyloid in anatomic sites not available for biopsy, and evidence for rapid progression and sometimes regression of amyloid deposits with different rates in different organs. Labelled serum amyloid P component studies thus make a unique contribution to the diagnosis and management of individual patients with systemic amyloidosis, and to systematic studies of existing and novel therapies. The technique is available routinely for all known or suspected cases of amyloidosis in the NHS National Amyloidosis Centre at the Royal Free Hospital, but it has not been developed commercially.     

Clinicians' attitudes to clinical practice guidelines: a systematic review

OBJECTIVE: To systematically review surveys of clinicians' attitudes to clinical practice guidelines. DATA SOURCES: MEDLINE, HealthStar, Embase and CINAHL were searched electronically for English-only surveys published from 1990 to 2000. STUDY SELECTION: We included surveys with responses to one or more of seven propositions (see below). Studies were excluded if they had fewer than 100 respondents or if the response rate was less than 60%. RESULTS: Thirty studies included responses to one or more of the seven items, giving a total of 11 611 responses. The response rate for the included studies was 72% (95% confidence interval [CI], 69%-75%). Clinicians agreed that guidelines were helpful sources of advice (weighted mean, 75%; 66%-83%), good educational tools (71%; 63%-79%) and intended to improve quality (70%; 60%-80%). However, clinicians also considered guidelines impractical and too rigid to apply to individual patients (30%; 23%-36%), that they reduced physician autonomy and oversimplified medicine (34%; 22%-47%), would increase litigation (41%; 32%-49%) and were intended to cut healthcare costs (52.8%; 39%-66%). CONCLUSIONS: Surveys of healthcare providers consistently report high satisfaction with clinical practice guidelines and a belief that they will improve quality, but there are concerns about the practicality of guidelines, their role in cost-cutting and their potential for increasing litigation.