Immunological role of vitamin D at the maternal-fetal interface.

During pregnancy, immune activity is tightly regulated so that antimicrobial protection of the mother and fetus is balanced with the need for immune tolerance to prevent fetal rejection. In this setting, the maternal-fetal interface, in the form of the uterine decidua, provides a heterogeneous immune cell population with the potential to mediate diverse activities throughout pregnancy. Recent studies have suggested that vitamin D may be a key regulator of immune function during pregnancy, with the fetal-maternal interface representing a prominent target. Among its non-classical actions are potent immunomodulatory effects, including induction of antibacterial responses and modulation of T-lymphocytes to suppress inflammation and promote tolerogenesis. Thus, vitamin D may play a pivotal role in normal decidual immune function by promoting innate responses to infection, while simultaneously preventing an over-elaboration of inflammatory adaptive immunity. Research to date has focused upon the potential role of vitamin D in preventing infectious diseases such as tuberculosis, as well as possibly suppressing of autoimmune disease. Nevertheless, vitamin D may also influence facets of immune function not immediately associated with primary innate responses. This review summarises our current understanding of decidual immune function with respect to the vitamin D metabolism and signalling, and as to how this may be affected by variations in maternal vitamin D status. There has recently been much interest in vitamin D supplementation of pregnant women, but our knowledge of how this may influence the function of decidua remains limited. Further insight into the immunomodulatory actions of vitamin D during pregnancy will help shed light upon this.

Colposcopic management of high-grade referral smears: a retrospective audit supporting 'see and treat'?

OBJECTIVE: The National Health Service Cervical Screening Programme monitors the quality of colposcopy services through the annual KC65 returns. The 2002 returns demonstrated that Standard 7c, which specifies a biopsy rate > or = 90% at first colposcopy visit for high-grade referrals, was not met in the assessed 3-month period. This was investigated along with the other standards. METHODS: Retrospective colposcopy records were accessed for the 597 new referrals, excluding 10 pregnant patients, seen at the colposcopy clinic at the Royal Victoria Infirmary between 1 July 2001 and 31 December 2002, following an abnormal high-grade smear. Cytology and histopathology computer records were checked for confirmation. The results were assessed against the colposcopy standards applicable at that time and the revised standards (2004). RESULTS: Biopsies were taken from 94.47% (Standard > or = 90%) of women at index colposcopy visit including wire loop excision biopsies from 66.16% (87.97% of high-grade colposcopic appearances). Cervical intraepithelial neoplasia (CIN) on histology was found in 91.79% in the study group (Standard > or = 85%) and in 96.71% of index visit biopsies (Standard > or = 90%), meeting the applicable colposcopy standards. The revised 2004 standards specify a biopsy in > or = 95% of high-grade referrals and excision biopsies in 95% if colposcopic appearances are also high-grade, if colposcopy is low grade but the smear is severely dyskaryotic, or when the lesion extends into the canal. The positive predictive value of high-grade cytology for this entire group was 75.54% with CIN present in 90.95%. CONCLUSION: From this study it appears that high-grade cytology in this centre reliably indicates high-grade CIN. Therefore, in women referred for colposcopy following a high-grade smear, excision biopsies should be performed in a higher proportion at the first visit to comply with the revised standards.

Cellular proliferation in the female lower urinary tract with reference to oestrogen status.

OBJECTIVE: To assess cell proliferation throughout the tissues of the female lower urinary tract and to compare cell proliferation rates in women of varying oestrogen status. DESIGN: Prospective observational study. SETTING: A large teaching hospital. SAMPLE: Fifty-nine women undergoing surgery for urogynaecological conditions of whom 23 were premenopausal, 20 were postmenopausal and taking no oestrogen supplementation and 16 were postmenopausal and receiving some form of hormone replacement therapy. Biopsies were taken during surgery from the bladder dome, trigone, the proximal and distal urethra, vagina and vesico-vaginal fascia in the region of the bladder neck. METHODS: Formalin-fixed paraffin-embedded biopsies were labelled by an avidin-biotin technique with a monoclonal antibody raised against part of the nuclear matrix known as Ki-67 antigen. MAIN OUTCOME MEASURES: Ki-67 expression was assessed in the epithelial, subepithelial and muscle or deep fascial regions of all tissues and related to oestrogen status. RESULTS: Ki-67 expression was only found in high levels in biopsies containing squamous epithelia. Significantly higher levels of Ki-67 expression were observed in the tissues of oestrogen replete women in the premenopausal and hormone replacement groups, compared with postmenopausal women receiving no oestrogen supplementation. CONCLUSIONS: Squamous epithelia of the female lower urinary tract exhibit greater levels of cell proliferation in oestrogen replete as compared with oestrogen deficient women. As these same squamous epithelia also consistently express oestrogen receptors, the findings suggest a mechanism by which oestrogen exerts its effect on the lower urinary tract and also provide an explanation for the success of oestrogen in the treatment of some conditions causing lower urinary tract dysfunction in postmenopausal women.