Immunohistochemical analysis of estrogen receptors in the urethra of sexually intact, ovariectomized, and estrogen-substituted ovariectomized sheep

INTRODUCTION AND HYPOTHESIS: Urinary incontinence is prevalent in postmenopausal women and spayed dogs and is associated with decreased estrogen plasma concentrations. The objective of the study was to investigate the expression of estrogen receptors (ER) in the urethra of sexually intact, ovariectomized, and estrogen-substituted ovariectomized ewes. METHODS: Paraffin cross-sections from each urethral quarter were immunohistochemically analyzed. The reactivity of ER was semiquantitatively assessed employing an immunoreactive score (IRS). RESULTS: In contrast to ERβ, ERα was identified in all urethral compartments; the highest IRS was detected in the epithelium of the distal urethra. The immunoreactivity and distribution of ERα did not differ among groups. Highly significant differences in ERα concentrations were observed between consecutive urethral quarters in each group. CONCLUSIONS: Neither ovariectomy nor ovariectomy and estrogen substitution seem to have a significant effect on overall urethral ERα concentration. The results demonstrate that the precise location of the investigated urethral part is crucial to the reliable evaluation or possible comparison of ERα concentrations

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Effects of tamoxifen and estradiol on estrogen binding sites in the urogenital tract: an experimental study in the rabbit

The aim of the study was to investigate the effects of estradiol and tamoxifen alone and in combination on the estrogen binding site status of the urogenital tract in the rabbit. Bilaterally ovariectomized rabbits were divided into four groups of six. Wereas the control group received no treatment, the remaining rabbits were treated with estrogen orland tamoxifen. Cytosolic and nuclear fractions were isolated from the uterus, vagina, urethra and urinary bladder and used for binding site assay, by radioligand binding. The total weight of the rabbit vagina and uterus was increased significantly by both estradiol, tamoxifen and the combination of the two. The total weight of the urethra was increased only in the combination group. The cytosol binding site was downregulated by estradiol, tamoxifen and combination in the uterus, and in the vagina. Cytosol binding site in the urethra was not detected. The combination of estrogen-tamoxifen markedly reduced the nuclear binding site in the urethra and decreased affinity of the nuclear binding sites in all three tissues. The data suggest that tamoxifen has a specific ability to modulate the transcriptional activity of the estrogen binding sites in the rabbit urogenital tract