Fetal jejunal atresia intrauterine volvulus

Peer Reviewe

Functional and molecular evidence for β(1)-, β(2)- and β(3)-adrenoceptors in human colon

1. Relaxation of carbachol pre-contracted human colonic muscle to (–)-isoprenaline was examined in circular, longitudinal and taenia coli preparations to determine the β-adrenoceptor subtypes involved. β(1)-, β(2)- and β(3)-Adrenoceptor mRNAs were also measured in colonic muscle and mucosa. 2. (–)-Isoprenaline caused relaxation of longitudinal smooth muscle preparations with pEC(50)=7.39±0.12, and this response was inhibited by both propranolol (0.1 μM, pK(B) 8.55±0.12) and the selective β(1)-antagonist, CGP 20712A (0.1 μM, pK(B) 8.80±0.20), while the selective β(2)-antagonist, ICI 118551 (0.1 μM) failed to inhibit isoprenaline relaxation consistently. 3. (–)-Isoprenaline caused relaxation of taenia coli with a pEC(50) of 6.70±0.17. Propranolol (0.1 μM), CGP 20712A (0.1 μM) and ICI 118551 (0.1 μM) inhibited the isoprenaline response with similar low affinities (pK(B) values 7.93, 7.71 and 7.54, respectively). Carbachol pre-contracted circular smooth muscle preparations failed to relax consistently to isoprenaline and these responses were not characterized. 4. β(1)- and β(2)-Adrenoceptor mRNAs were present in circular/longitudinal muscle samples and taenia coli samples, and lower levels were detected in mucosa. β(3)-mRNA was also present in both muscle preparations but was not detected in human colonic mucosa. 5. In summary, β(1)-adrenoceptors are the predominant subtype mediating isoprenaline-induced relaxation of the thin longitudinal smooth muscle of human colon, while β(3)-receptors do not appear to be involved in these responses. However, β(3)-adrenoceptors may play a role in relaxation of the taenia coli as conventional antagonist affinities are low. β(3)-Adrenoceptor mRNA was present in taenia coli and circular/longitudinal smooth muscle but absent from human colonic mucosa

Impact of Percutaneous Oestradiol Gels in Postmenopausal Hormone Replacement Therapy on Clinical Symptoms and Endometrium

OBJECTIVE: To compare the effects on endometrium, climacteric symptoms and the menstrual cycle, and the clinical and biological tolerance of two percutaneous oestradiol gels used as hormone replacement therapy. DESIGN: A large open randomised multicentre study. SETTING: France and Belgium. PARTICIPANTS: Two-hundred and fifty-four women with an intact uterus and who had experienced a natural menopause received either Oestrogel (n = 126) or Estreva, a new formulation of oestradiol gel (n = 128), (1.5 mg of oestradiol/day) for the 24 first days of each calendar month during six consecutive months. Nomegestrol acetate (Lutenyl), a norprogesterone derivative, was administered (5 mg/day) from day 11 to day 24 of each oestradiol cycle. MAIN OUTCOME MEASURES: Examination of endometrial biopsies taken before treatment and between days 18 and 24 of the last treatment cycle, climacteric symptoms assessed using a modified Kupperman index, control of menstrual cycle evaluated by diary cards, and clinical and biological tolerance. RESULTS: Both treatments lowered the frequency and intensity of hot flushes and the global Kupperman index. 96% of the cycles were followed by withdrawal bleeding. Breakthrough bleeding or spotting resulted in premature discontinuation of treatment in one volunteer. Mastodynia occurred in 20 women and contributed to the premature termination of treatment in three of them. Endometrial biopsies taken at the end of treatment showed identical histologies in both groups, with a secretory pattern in the majority of women, and absence of hyperplasia. CONCLUSIONS: This trial confirmed that, when the two oestradiol gels tested were administered cyclically with nomegestrol acetate to postmenopausal women, they were well tolerated, effective and suitable for the treatment of oestrogen deficiency syndrome