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John McConnell

Publications and source records attributed to John McConnell.

At least 19 recordsLinked to original sources

The effects of 5alpha-reductase inhibitors on the natural history, detection and grading of prostate cancer: current state of knowledge.

PURPOSE: The Prostate Cancer Prevention Trial (PCPT) showed that the 5alpha-reductase inhibitor (5ARI) finasteride significantly decreased the 7-year period prevalence of prostate cancer vs placebo. However, Gleason score 7-10 tumors were significantly more common in the finasteride vs the placebo group. We considered data on the effects of 5ARIs on prostate cancer natural history and detection. MATERIALS AND METHODS: A detailed review was performed of the literature identified from the MEDLINE database examining the effects of 5ARIs on prostate cancer prevalence and tumor histopathology. RESULTS: In PCPT there were fewer biopsies performed for cause in the finasteride vs the placebo group and the proportion of high grade tumors in the treatment groups did not diverge with time. Given that finasteride has an effect on prostate specific antigen and prostate volume, which are key factors in triggering prostate biopsies, they may be significant confounders of Gleason score results. Prostate shrinkage in the finasteride treated group may minimize biopsy sampling error. Furthermore, histological studies have shown that 5ARIs have a significant effect on prostate architecture, which can make the interpretation of prostate specimens in men treated with 5ARIs difficult. Further evaluation of PCPT findings will help determine the true nature of these observations. CONCLUSIONS: 5ARIs decrease the risk of prostate cancer but also alter the detection of disease through effects on prostate specific antigen, and prostate volume and histology. The weight of evidence suggests an artifactual effect of finasteride on Gleason grading in the PCPT. The role of 5ARIs for prostate cancer chemoprevention needs further examination before it can be considered for wide recommendation.

Antineoplastic Agents↗

Grand round.

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Education, Medical, Continuing↗

Effects of low-dose continuous combined HRT on vascular function in women with type 2 diabetes.

BACKGROUND: Improvement in vascular endothelial function is widley cited as a beneficial effect of hormone replacement therapy (HRT). Women with type 2 diabetes (T2DM) are at increased cardiovascular risk and have impaired endothelial function. Any benefits of HRT on endothelial function in this group are of particular interest. OBJECTIVES: We assessed effects on vascular function of oral 17beta oestradiol (1 mg) and norethisterone (0.5 mg) in postmenopausal women with T2DM. DESIGN: Double-blind, randomised, placebo-controlled trial. ASSESSMENTS: Twenty-eight women had pulse wave velocity (PWV) and adhesion molecules VCAM-1 and ICAM-1 assessed before and after three months' treatment. Twenty-four women also had gluteal fat biopsy for assessment of resistance vessel function (using wire myography). RESULTS: HRT did not affect PWV, VCAM-1, ICAM-1 or carbachol response. Effects of L-NAME and indomethacin on carbachol sensitivity were similar in both groups. CONCLUSIONS: This HRT preparation had no detectable effect on these measures of endothelial function in women with T2DM.

Arteries↗