High risk pregnancies in hypopituitary women

BACKGROUND: Various short papers have suggested that pregnancies in women with hypopituitarism are high risk but no formal assessment of pregnancy outcome has yet been reported. METHODS: An audit was carried out concerning the outcome of 18 pregnancies in nine women who underwent ovulation induction in a single centre over 20 years. RESULTS: The live birth rate was 61%, miscarriage rate 28% and mid-trimester uterine death rate 11% with no survivors from four sets of twins. The Caesarian section rate was 100% and half of the live births were on or below the 10th centile for weight. One woman successfully breast-fed. CONCLUSIONS: Women with hypopituitarism have high-risk pregnancies, perhaps because of a uterine defect secondary to endocrine deficiency. Fertility treatment must strive for singleton pregnancies with application of particularly strict criteria to avoid twin pregnancies. Early elective Caesarian section is probably warranted in this group.     

The impact of hormonal therapy for infertility on the age at menopause

Objectives: To look for possible association between past history of ovulation induction and age at menopause. Design: Women attending our postmenopausal outpatient clinic were asked to fill questionnaires with demographic data, obstetrical history (including treatment for infertility), and medical details related to menopause. Patients: The study group (n=31) consisted of women with a history of ovulation induction, and a control group (n=200) included women who did not experience such intervention. Results: The age at the final menstrual bleeding was 46.4±5 in the study group, and 50±4 for the control group (P<0.001). This difference was most prominent for women who had induction of ovulation prior to age 35 years: they entered menopause at age 43.8±5 years. Smoking had a weak effect on the age at menopause (48.5±4 for current, vs. 49.9±4 for non- or past-smokers; P<0.03). Conclusions: This retrospective and preliminary study raises the question whether hormonal manipulations and ovarian over-stimulation during fertility treatments could be a risk factor for premature menopause.     

Induction of NO synthesis in macrophages by Newcastle disease virus is associated with activation of nuclear factor-{kappa}B

Newcastle disease virus (NDV) has received much attention recentlybecause of its non-specific immune stimulating potential andits various anti-tumor activities. Here we describe that NDVinduces synthesis of NO and causes an activation of nuclearfactor-kB (NF-kB) In murine macrophages. These reactions werepart of an activation process which included also stimulationof adenosine deaminase and inhibition of 5'-nucleotidase. NDV-mediatedNO synthesis and NF-kB activation were blocked by an antioxidant(butylated hydroxyanisole), by an inhibitor of protein tyrosinekinase (genistein) and of protein kinase A (H-89), but not byan inhibitor of protein kinase C (staurosporin). These datasuggest that signalling requirements of NF-kB activation andNO production in NDV-treated macrophages are similar.     

Induction of ovulation after gnRH antagonists

The gonadotrophin-releasing hormone (GnRH) antagonist binds competitively to the receptors and thereby prevents endogenous GnRH from exerting its stimulatory effect on the pituitary cells. This causes suppression of gonadotrophin secretion which occurs immediately after administration of the antagonist. When using GnRH antagonist in controlled ovarian stimulation, ovulation or maturation of the oocyte can, therefore, be induced by a variety of drugs, e.g. native GnRH, recombinant LH or short-acting GnRH agonists. Short-acting GnRH agonists were recommended for triggering ovulation in cases with a high risk of developing ovarian hyperstimulation syndrome (OHSS). Since it is evident that GnRH is required to initiate the LH surge and the oestradiol rise, a single administration of GnRH antagonist during the late follicular phase delays the LH surge. Studies showed that a single s.c. administration of 3 or 5 mg of Cetrorelix in the late follicular stage was sufficient to prevent the LH surge for 617 days. This phenomenon can be used in high responder patients who are prone to OHSS. The question whether this delay has any effect on oocyte quality and maturation still remains unanswered. Overall, there are four uses for GnRH antagonist: (i) using short-acting GnRH agonists for triggering ovulation in cases in which the GnRH antagonist is part of the protocol for ovarian stimulation. Recombinant LH and native LHRH could also be used as triggers of LH surge; (ii) delaying the LH surge in cases prone to OHSS by treatment with GnRH antagonist; (iii) to administer GnRH antagonist during the luteal phase to decrease the activity of corpora lutea; (iv) in polycystic ovarian disease with elevated LH the LH/FSH ratio can be corrected with the injection of GnRH antagonist prior to and during ovarian stimulation.     

三氧化二锑诱导急性早幼粒细胞白血病细胞凋亡的研究

目的 研究锑剂三氧化二锑（Sb2O3)对早幼粒细胞白血病细胞株NB4凋亡的诱导作用，以寻求早幼粒细胞白血病治疗的新方法。方法 采用细胞生长曲线，形态学及硝基四氮唑蓝（NBT）还原试验，判定NB4细胞的生长，分化及功能。采用细胞周期分析和DNA电泳研究细胞凋亡。结果 Sb2O3能诱导早幼粒白血病细胞凋亡，且具有时间，剂量依赖性。结论 Sb2O3能有效地诱导早幼粒白血病细胞凋亡，提示锑剂诱导细胞半亡的疗法，有望成为临床治疗早幼粒细胞白血病的新方法。     

Consensus statement on the bio-safety of urinary-derived gonadotrophins with respect to Creutzfeldt-Jakob disease

Human transmissible spongiform encephalopathies (TSE) encompass a group of rare neurodegenerative diseases. In April 2004, a group of international experts and regulators met in Buenos Aires, Argentina, to review the safety and to reach consensus on the use of urinary-derived gonadotrophins with respect to TSE. Iatrogenic transmission of Creutzfeldt-Jakob Disease (CJD) from pituitary-derived gonadotrophins has been reported, no infectivity in urine has been demonstrated, and no definite cases of transmission via urine have been reported. It is currently not possible to monitor donor urine or finished product for the presence of prions. Therefore the assessment of risk has to be based on the likelihood of infection in urine, the source of the urine, and the capacity of the manufacturing process to remove any adventitious infection. Urine for the production of medicinal products should be obtained from sources that minimize the possible presence of materials derived from subjects suffering from human TSE. As no strong evidence for TSE infectivity in urine exists, it can be concluded that the risk of disease-generating prions and TSE infectivity being present in donor urine is low. Current evidence indicates that, with respect to the risk of TSE infection, urinary-derived gonadotrophins appear to be safe.     

Endocrinology: Randomized trial of misoprostol and cervagem in combination with a reduced dose of mifepristone for induction of abortion

Mifepristone (600 mg) in combination with a prostaglandin hasbeen demonstrated to be a safe, acceptable alternative to vacuumaspiration for induction of abortion in the first 9 weeks ofpregnancy. However, the efficacy and side-effects of differentprostaglandins used in combination with mifepristone have notbeen assessed in a randomized trial. In this study, 800 womenseeking an abortion at gestational age 63 days amenorrhoea wererandomized to receive either 0.5 mg gemeprost by vaginal pessary(group I) or 600 µg misoprostol (group II) by mouth –48h after taking 200 mg mifepristone by mouth. The side-effectsand number of complete abortions were used as measures of efficacy.There was no significant difference in the rate of completeabortion between group I [96.7%; 95% confidence interval (CI)94.9–98.5%, n = 391] and group II (94.6%; 95% CI 92.3–96.9,n = 386). It was not possible to assess the outcome with certaintyin the remaining 23 women. However, there were significantlymore ongoing pregnancies in the women who received misoprostolthan in those who received gemeprost (nine versus one, P <0.01) and in eight of these 10 women the gestation was >49days. Fewer women in group II required analgesia than in groupI (48 versus 60%, P < 0.001) although the number requestingopiate was similar in each group (6.9 versus 5.2%, P > 0.4).The incidence of nausea and vomiting after misoprostol (47.8and 21.9% respectively) was higher (P < 0.001) than aftergemeprost (33.9 and 12% respectively). The incidence of infectionand heavy bleeding was low in both groups (<2%) and onlyone woman required blood transfusion. We conclude that the recommendeddose of mifepristone and gemeprost can be reduced without impairingclinical efficacy in pregnancies up to 63 days amenorrhoea.Misoprostol is a safe alternative prostaglandin but has a higherincidence of ongoing pregnancies especially at gestation after49 days amenorrhoea.     

珍珠层水溶性提取物对人骨髓基质细胞成骨性分化的诱导作用

目的:探讨珍珠层水溶性提取物(WSM)对人骨髓基质细胞的诱导作用。方法:原代培养人骨髓基质细胞,条件培养基和WSM分别作用于第3代细胞,对照组不加处理因素。倒置显微镜观察细胞在施加处理因素后的生长状态;采用钙钴法染色检测AKP表达;应用RT-PCR方法检测BMP-2等生长因子表达;应用茜素红染色检测骨髓基质细胞的矿化结节形成情况。结果:施加处理因素第7d,WSM组、条件培养基组的BMP-2表达水平较对照组明显增加;WSM组及条件培养基组TGF-β1表达量较对照组相比未见差异。施加处理因素第7d,WSM组及条件培养基组骨髓基质细胞AKP染色明显,与对照组相比差异显著。每高倍视野阳性细胞数,条件培养基组、WSM明显多于对照组,差异具有显著性(P<0.01);加入处理因素18d,条件培养基组可见典型红色钙化结节形成,WSM组也可见到钙结节形成,但没有条件培养基组典型,对照组偶有零星钙化结节形成。结论:WSM可以促进体外培养的人骨髓基质细胞成骨性分化进程,具有一定的骨诱导作用。