Proliferative effects of combination estrogen and progesterone replacement therapy on the normal postmenopausal mammary gland in a murine model

OBJECTIVE: The aim of the study was to analyze the proliferative response of the normal mammary gland to combination hormone replacement therapy with estrogen and progesterone in a murine model of early versus late postmenopausal states. STUDY DESIGN: Ovariectomized mice were injected daily for up to 56 days with estrogen plus progesterone, starting at either 1 or 5 weeks after ovariectomy to simulate early and late menopausal periods, respectively. At various times after treatment, proliferation was analyzed by deoxyribonucleic acid histoautoradiography and whole-mount preparations. The induction of progesterone receptor by estrogen was also analyzed. To distinguish between estrogen- and progesterone-specific responses, we tested the effects of the antiprogesterone mifepristone (RU 486) and the antiestrogen ICI 182,780. RESULTS: The acute response to estrogen-progesterone therapy in the early postmenopausal period resulted in duct-end enlargement, ductal side branching, alveolar bud formation, and a 100-fold increase in epithelial cell proliferation. This was caused by the dominant effect of progesterone acting through the progesterone receptor. In the late postmenopausal period the acute response produced only duct-end enlargement; the 100-fold increase in epithelial cell proliferation resulted from the dominant effect of estrogen. After long-term treatment, both early and late postmenopausal glands exhibited similar morphologic features and a 9-fold higher steady-state proliferation rate than was found in control-treated groups. CONCLUSIONS: Starting combined estrogen and progesterone hormone replacement therapy in either early or late postmenopause produced a persistent, steady-state 9-fold increase in epithelial cell proliferation, which could be a contributing factor to increased breast cancer risk. The acute response in the late postmenopausal period mimics the hormonal response of the pubertal mammary gland, which in rodents is the stage most susceptible to carcinogen-induced mammary tumorigenesis. These observations raise questions about increased susceptibility of the late postmenopausal gland to carcinogenesis and a role for hormone replacement therapy in the promotion of tumorigenesis.     

Home treatment for women with stress urinary incontinence

Urinary incontinence is an unpleasant, unwanted and distressing problem that is common among women in the UK. A recent study (Hunskarr et al, 2004) estimated that 10 million women in the UK suffer with urinary incontinence. Stress urinary incontinence (SUI) is the most common form, affecting four million women. The International Continence Society defines SUI as 'the complaint of involuntary leakage [of urine] on effort or exertion, or on sneezing or coughing' (Abrams et al, 2002).     

Categorical versus dimensional models of mental disorder: the taxometric evidence

OBJECTIVE: To review studies of the categorical versus dimensional status of mental disorders that employ taxometric methodology. METHOD: A comprehensive qualitative review of all published taxometric studies of psychopathology. RESULTS: Categorical and dimensional models each receive well-replicated support for some groups of mental disorders. Studies favour categorical models for melancholia, eating disorders, pathological dissociation, and schizotypal and antisocial personality disorders. Dimensional models tend to be favoured for the broad neurotic spectrum--general depression, generalized anxiety, posttraumatic stress disorder--and for borderline personality disorder. CONCLUSIONS: Taxometric research clarifies the latent structure of psychopathology in ways that have implications for the classification, assessment, explanation and conceptualization of mental disorder.     

Forssman synthetase expression results in diminished shiga toxin susceptibility: a role for glycolipids in determining host-microbe interactions

Forssman glycolipid (FG), the product of Forssman synthetase (FS), is widely expressed among nonprimate mammalian species. Here, we describe a molecular and genetic relationship between FG expression and Shiga toxin (Stx) susceptibility. We have isolated the FS cDNA from human, canine, and murine cells. Whereas the murine and canine FS genes express a functional enzyme, the human FS cDNA was found to express a protein that lacks FS activity, despite a high degree of sequence identity with the enzymatically active murine and canine FS genes. In order to examine the relationship between FG expression and Stx susceptibility, Vero cells were transfected with the three FS orthologues or a vector control. Complementation with the human FS cDNA had no effect on Stx susceptibility, whereas stable expression of the canine and murine FS resulted in markedly decreased susceptibility to toxin. Among individual cells, an inverse correlation between FG expression and Stx binding was demonstrated. Moreover, only strongly FG-reactive cells were capable of growing in the presence of Stx. These cells were found to have high levels of FG expression and a correspondingly diminished GbO(3) content. We conclude that expression of a functionally active FS modifies Stx receptor glycolipids to FG and results in markedly decreased susceptibility to toxin. We speculate that inactivation of the FS gene during primate evolution may account, at least in part, for the marked susceptibility of human cells to Stx.     

Host microenvironment in breast cancer development: epithelial-cell-stromal-cell interactions and steroid hormone action in normal and cancerous mammary gland

Mammary epithelial cells comprise the functional component of the normal gland and are the major target for carcinogenesis in mammary cancer. However, the stromal compartment of the normal gland and of tumors plays an important role in directing proliferative and functional changes in the epithelium. In vivo and in vitro studies of the murine mammary gland have provided insights into novel stroma-dependent mechanisms by which estrogen and progesterone action in the epithelium can be modulated by hepatocyte growth factor (HGF) and the extracellular matrix proteins, collagen type I, fibronectin and laminin. In vitro and in vivo studies of estrogen receptor positive, estrogen-responsive human breast cancer cells have also demonstrated that estrogen responsiveness of tumor cells can also be modulated by extracellular matrix proteins, collagen type I and laminin.     

粘连性肠梗阻腹腔镜微创综合治疗118例探讨

目的探讨结合腹腔镜微创综合治疗急性粘连性肠梗阻的方法。方法对1996年12月～2006年12月388例中的118例采用结合腹腔镜微创综合治疗急性粘连性肠梗阻的方法及效果进行回顾分析。结果结合腹腔镜微创综合治疗急性粘连性肠梗阻的方法疗效较好,118例全部治愈,其中术中中转开腹手术治疗16例,无死亡病例,无并发症出现。结论结合腹腔镜微创综合治疗急性粘连性肠梗阻的方法疗效好,能明显降低急性粘连性肠梗阻的死亡率及并发症。     

Prospective comparison of MRA with catheter angiography in the assessment of patients with aortoiliac occlusion before surgery or endovascular therapy

AIM: The purpose of this study was to evaluate the usefulness of gadolinium enhanced 3D magnetic resonance (MR) angiography (CE MRA) as an alternative to translumbar or brachial angiography in the pre-operative work-up of patients with aortoiliac occlusion. MATERIALS AND METHODS: Nineteen patients (14 men and five women; age range 45-77 years; mean 62 years), not suitable for perfemoral angiography (aortoiliac occlusion, n = 18; infected femoro-femoral graft with femoral artery pseudoaneurysm, n = 1), underwent pre-operative CE MRA and catheter angiography (translumbar, n = 5; brachial, n = 14). CE MRA was performed using a 3D fast spoiled gradient-recalled pulse sequence during the intravenous injection of 40 ml of gadolinium DTPA and a 32-s breath-hold. All patients subsequently underwent surgical (n = 13) or percutaneous transluminal (n = 6) treatment for their vascular disease. The accuracy of CE MRA was determined compared with the findings at catheter angiography taken as the gold standard. RESULTS: CE MRA gave accurate information about the occlusion, inflow and distal run-off in the majority of patients. CE MRA revealed occlusions with an accuracy of 94.7% in the aortic segment, 98.7% in the iliac segment, and 100% in the common femoral segment. The arterial segments distal to the common femoral artery were not completely visualized in four patients but CE MRA provided sufficient information to plan either surgical or percutaneous transluminal therapy in all but one patient. CONCLUSION: CE MRA is highly accurate in showing the presence and extent of aortoiliac occlusions. In our study group, CE MRA gave sufficient information in the pre-operative evaluation of aortoiliac occlusion.