Ian Z. MacKenzie

The usefulness of ultrasound assessment of amniotic fluid in predicting adverse outcome in prolonged pregnancy: a prospective blinded observational study.

Objective To determine whether a single ultrasound scan at or beyond 40 weeks of gestation to detect a single deepest pool of amniotic fluid <2 cm and amniotic fluid index (AFI) <5 cm is clinically useful in the prediction of subsequent adverse pregnancy outcome.

Validation of anti-vascular endothelial growth factor (anti-VEGF) antibodies for immunohistochemical localization of VEGF in tissue sections: expression of VEGF in the human endometrium

Transient transfection of COS‐1 cells followed by fixation, embedding in paraffin, and immunohistochemistry has identified anti‐vascular endothelial growth factor (anti‐VEGF) mouse monoclonal antibodies that efficiently immunostain VEGF in paraffin‐embedded tissue sections. Immunohistochemical localization of VEGF in 34 specimens of normal human endometrium that had been collected at different stages of the menstrual cycle was then performed. VEGF was present at all stages of the cycle, but both the pattern and the intensity of staining varied. Thus, VEGF expression occurred predominantly in the endometrial epithelium and while weak in the proliferative phase, was strong in the secretory phase. VEGF expression in the stroma was weaker than in the proliferative phase glands and did not change throughout the cycle. These findings are in agreement with reports of VEGF mRNA expression in the endometrium, but disagree with previous immunohistochemical studies that employed an immunohistochemically unvalidated antiserum. This study has shown that the commercially available anti‐VEGF monoclonal antibody M293 is excellent for the immunohistochemical localization of VEGF in paraffin sections.

Should tissue from pregnancy termination and uterine evacuation routinely be examined histologically

Objective To assess the value of routine histological examination of tissue samples collected at termination of pregnancy in the first trimester and emergency surgical uterine evacuation.

Regulation of the expression of the angiogenic enzyme platelet-derived endothelial cell growth factor/thymidine phosphorylase in endometrial isolates by ovarian steroids and cytokines.

The angiogenic enzyme platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) was strongly expressed in the endometrial glands in the luteal and menstrual, but not the proliferative, phases of the cycle. The converse was seen in the stroma, where expression was strong in the proliferative, but not the luteal or menstrual, phases. Inflammatory cytokines induced PD-ECGF/TP expression in primary cultures of human normal endometrial epithelial (NEE) and normal endometrial stromal cells. The profile of cytokine induction of PD-ECGF/TP was cell dependent. Thus, in NEE cells, PD-ECGF/TP expression was strongly induced by the combination tumor necrosis factor-a and interferon-gamma. In contrast, in normal endometrial stromal cells, interferon-gamma gave, by far, the strongest induction of PD-ECGF/TP. Expression of the enzyme was not regulated by ovarian hormones alone. Although treatment of NEE cells with a physiological concentration of progesterone (5 X 10[-8] M) or transforming growth factor-beta1 (10 ng/ml) alone had no effect on PD-ECGF/TP expression, when delivered together at the same dose they induced a 48-fold increase in expression. This expression correlates with cyclic changes in progesterone and transforming growth factor-beta1 levels in the uterus.

Progesterone inhibition in mid-trimester termination of pregnancy: physiological and clinical effects.

Summary. A double‐blind, placebo controlled clinical trial was conducted to assess the clinical and physiological effects of‘epostane’, a progesterone synthesis inhibitor, in mid‐trimester prostaglandin termination of pregnancy. Mean peripheral progesterone levels had fallen by 74% after 72 h in the patients treated wtih epostane. The mean induction abortion interval in the treatment group was 490 (SD 271) min, compared with 1432 (SD 640) min in the control group. Intrauterine pressure recording demonstrated increased sensitivity to prostaglandin E2 after epostane treatment but no change in oxytocin sensitivity. The clinical implications of facilitated induction of abortion are discussed.

Tamoxifen induction of angiogenic factor expression in endometrium

Tamoxifen is the current therapy of choice for patients with oestrogen receptor positive breast cancer, and it is currently under evaluation as a prophylactic for women at high risk of developing the disease. However, tamoxifen is also known to induce proliferative changes in the endometrium increasing the risk of developing endometrial hyperplasia, polyps and carcinoma. Angiogenesis is an intimate part of this process. For this reason, we have examined the expression of several well characterized angiogenic factors, namely, acidic and basic fibroblast growth factor, thymidine phosphorylase, vascular endothelial growth factor and adrenomedullin in both normal and tamoxifen exposed pre- and postmenopausal endometrium. Vascular density and endothelial proliferation index were also quantified. We found increased expression of acidic and basic fibroblast growth factor and adrenomedullin after treatment with tamoxifen mainly in premenopausal tissue. Vascular density was significantly increased in pre- but not post-menopausal endometrium (P=0.0018) following tamoxifen treatment. These results support the notion that angiogenesis is integral to the response to tamoxifen exposure, and is a potential target with which to block these side effects of tamoxifen.

Cellular schwannoma of the vagina

Schwannomas of the female genital tract are rare, and an example in the vagina has not previously been reported. The case of a 37-year-old woman with a cellular schwannoma of the vagina is described and is accompanied by a review of schwannomas in the female genital tract.

1170 consecutive hysterectomies: indications and pathology.

Objective: An analysis of consecutive hysterectomies during 1997-99 exploring the relationship between histological findings, operation performed and clinical indication was conducted to observe any trends. Methods: A retrospective review of histology reports for hysterectomies performed in a large district teaching hospital. Results: The rate of hysterectomy for women aged over 25 years was 23 per 10,000 women. Menstrual disturbance including endometriosis was the indication in 45%, pelvic tumours including fibroids in 21%, prolapse in 17% and malignant or pre-malignant conditions in 15%; 1% were performed in relation to childbirth. 79% were total abdominal hysterectomies, 4% subtotal and 17% vaginal. 50% included removal of both ovaries and in 8% omentectomy was also performed. The uterus was histologically normal in 20% of abdominal hysterectomies, the rate rising to 70% for vaginal hysterectomies. Conclusions: The rate of hysterectomy has not changed over the past 15 years, despite the introduction of alternative medical and surgical therapies for managing menstrual problems and fibroids. There may have been a greater proportion performed for malignant and premalignant conditions and genital tract prolapse. There were fewer specimens with no evidence of pathology than is often suggested.

Assessment of abnormal bleeding in menopausal women: an update.

Peri and postmenopausal bleeding, with or without the use of hormone replacement therapy, is a common clinical problem. The exclusion of endometrial hyperplasia and carcinoma is the key issue in the evaluation of patients with abnormal uterine bleeding. Transvaginal ultrasound measurement of endometrial thickness has become a routine procedure and an initial investigation in patients with abnormal uterine bleeding. There is debate as to whether a cut-off of 5 or 4 mm endometrial thickness should be employed. If the endometrial thickness is above these values, polyps have been diagnosed or the patient is presenting with recurrent bleeding, endometrial disease has to be excluded by histological assessment. Outpatient aspiration curettage has superseded dilatation and curettage, which was previously considered to be the gold standard for obtaining endometrial tissue, and provides the same sensitivity in detecting endometrial disease. Hysteroscopy allows visualisation of the uterine cavity and the opportunity for targeted biopsy and removal of endometrial polyps.

Wnt-7a is upregulated by norethisterone in human endometrial epithelial cells: a possible mechanism by which progestogens reduce the risk of estrogen-induced endometrial neoplasia

Progestogens are added to oestrogen in hormone replacement therapy regimens to reduce the risk of endometrial cancer. We have performed in vitro studies analysing gene expression of isolated normal endometrial epithelia cells (NEE) treated with estradiol and the progestogen norethisterone acetate (NETA). We report here for the first time upregulation of the Wnt-7a gene by NETA in estrogen treated NEE. Wnt genes are a large family of developmental genes associated with cellular responses such as oncogenesis. We therefore suggest that upregulation of Wnt-7a may be associated with the antineoplastic effects of progestogens on the endometrium.