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Biomedical subjects

M G Wyllie

Publications and source records attributed to M G Wyllie.

At least 19 recordsLinked to original sources
PubMed2004

Not all brands are created equal: a comparison of selected components of different brands of Serenoa repens extract.

Recommendations regarding the use of plant-derived medications for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) state that every brand should be fully evaluated and considered separately. Disparity between a number of brands in terms of their stated and actual doses has been recently highlighted. The aim of this study was to fully quantify the variation in Serenoa repens extracts (SrE) commercially available for the treatment of BPH-associated LUTS. To this end, 14 brands of SrE were compared. Concentrations of free fatty acids (FFAs), methyl and ethyl esters, long-chain esters and glycerides were assessed using liquid and gas chromatography. Many of the brands showed a significantly different proportional content which may have an impact on their clinical efficacy and safety. The high concentrations of FFAs in particular, which previous research has suggested as comprising the active agent of SrE for the treatment of LUTS, may influence the clinical benefit derived from each product. Our findings lend further weight to recommendations by the 5th International Consultation on BPH that plant-derived treatments should be analysed and considered as independent entities despite their common origin. Only extracts with demonstrated pharmacological activities and proven clinical efficacy should be considered for the treatment of patients with BPH.

Humans↗
PubMed2001

Directions in urological research and drug therapies.

This meeting report summarizes advances and notable developments in the pharmaceutical management of urological diseases presented at various sessions during the Annual Meeting of the American Urological Association held in Anaheim, California, June 2-7, 2001. More than 10,000 attendees drawn from clinical and preclinical research deliberated on the latest trends in surgical and pharmacotherapeutic management in diverse areas of urology. In particular, several forums were dedicated to reviewing scientific trends, emerging concepts and therapies in urological diseases, such as overactive bladder, erectile dysfunction and lower urinary tract symptoms, which are the focus of this report.

Journal Article↗
PubMed2000

Clinical trials design: protocols and endpoints.

Over the last decade there has been a proliferation in clinical trials to test agents for the treatment of erectile dysfunction (ED). Many aspects of clinical trials design and conduct and guidelines for future conduct have been the subject of a recent comprehensive review (Rosen R et al. In: Proceedings of the 1st International Consultation on Erectile Dysfunction 1999). The present article attempts to extend that analysis from trials that focus purely on symptomatic improvement of ED to trials relevant to the management of the ED patient in the community. Although the regulatory approval process accounts for the bulk of the clinical trials undertaken, studies are also initiated for concept testing, post-marketing surveillance and for promotional and/or pricing reasons. The trial design can be dependent on which of the above objectives is being served. However, there are also many common features that are summarized below; the major focus is placed on regulatory-standard or 'pivotal' studies. International Journal of Impotence Research (2000) 12, Suppl 4, S53-S58.

Clinical Trials as Topic↗
PubMed1999

alpha1-adrenoceptor selectivity: the North American experience.

OBJECTIVE: The recent publication of multicentre US studies raises the possibility that the response to tamsulosin is dose-related and less than maximum at 0.4 mg. The objective of the present study was to calculate pharmacologically equivalent, alpha-blocking doses of doxazosin and tamsulosin in a clinical setting and thereby to examine further the concept of 'uroselectivity' and 'prostate selectivity'. METHODS: Healthy male volunteers were monitored in controlled, crossover studies. The effects of placebo or alpha blocker on phenylephrine (PE)-induced urethral and vascular responses, were determined. These were related to plasma drug concentrations and used with in vitro radioligand binding data to derive receptor occupancy. RESULTS: Doxazosin effectively blocked PE-induced vascular and urethral changes over the dose range 1-16 mg. There was no evidence for target organ selectivity. The degree of blockade of the PE-induced responses by tamsulosin was highly dependent on the time of measurement, post drug administration. The degree of observed blockade with tamsulosin at 0.4 mg was substantially less than that observed at 0.8 mg tamsulosin and/or 1 mg doxazosin. CONCLUSIONS: These studies provide no evidence of prostate selectivity for tamsulosin. 0.4 mg tamsulosin is a sub-optimal blocking dose and is equivalent to 1 mg of doxazosin and terazosin (1-2 mg). It is recommended that future comparative studies on benefit/risk in patients should include a range of doses encompassing the ED50.

Adrenergic Antagonists↗
PubMed1997

Transforming growth factor beta 1 transduced mouse prostate reconstitutions: II. Induction of apoptosis by doxazosin.

BACKGROUND: To study the possible relationship between adrenergic activities and the pathogenesis of benign prostatic hyperplasia (BPH), we tested the effect of doxazosin, an alpha 1-adrenoceptor antagonist, on prostatic growth in vivo using a mouse model for BPH. METHODS: The mouse prostate reconstitution (MPR) model system with retroviral (BabeTGF-beta 1Neo) transduction of transforming growth factor beta 1 (TGF-beta 1) was used to induce focally hyperplastic BPH-like lesions and increase the number of catecholaminergic neurons. The mice were treated with daily intraperitoneal injections of doxazosin (3 mg/kg). RESULTS: Doxazosin caused a significant reduction in the wet weight of BabeTGF-beta 1-infected MPRs. The percent of PCNA-positive epithelial cells was similar in the doxazosin-treated and water only, control groups. There was a significant increase in the number of epithelial cells undergoing programmed cell death, apoptosis, in the doxazosin group (apoptotic index = 4.7 for doxazosin group vs. 3.1 for control group, P < 0.05). The doxazosin-induced apoptosis was more apparent in TGF-beta 1 transduced MPRs than BAG alpha control MPRs, and was not seen in the prostates of the adult male mice into which the MPRs were engrafted. CONCLUSIONS: Our data demonstrate a novel and potentially important biological activity of doxazosin in vivo in this mouse model of BPH.

Adrenergic alpha-Antagonists↗
PubMed1997

Prostatic alpha 1-adrenoceptors and uroselectivity.

BACKGROUND: alpha 1-adrenoceptor antagonists (blockers) are now commonly used in the treatment of the symptoms of lower urinary tract obstruction. Originally phenoxybenzamine, a non-selective antagonist at both alpha 1- and alpha 2-adrenoceptors, was used by Marco Caine. In an attempt to minimize side effects, selective alpha 1-antagonists, e.g. prazosin, were subsequently developed. More recently, agents such as alfuzosin, doxazosin, terazosin, and tamsulosin have been introduced and claims of "uroselectivity" and "prostate" selectivity have emerged. METHODS: This review attempts to put these claims into perspective and represents a comprehensive analysis of all pre-clinical and clinical data including several papers from the Japanese literature. An attempt is made to define what is meant by selectivity at various levels including the test tube, in the laboratory animal and, most importantly, in the clinical context of the whole patient. CONCLUSIONS: The conclusions are interpreted within the context of the subdivision of the alpha 1-adrenoceptor into alpha 1A, alpha 1B, and alpha 1D subtypes.

Adrenergic alpha-Antagonists↗