胃癌7号染色体长臂的杂合性缺失分析

目的:检测胃癌患者7号染色体长臂微卫星位点的杂合性缺失(loss of heterozygosity,LOH),以初步确定7号染色体长臂上与胃癌相关基因连锁最密切的微卫星多态位点及LOH的临床意义.方法:在70例原发性胃癌中应用多重PCR技术扩增覆盖整个7号染色体长臂的9个微卫星位点(平均遗传距离为10cm),聚丙烯酰胺凝胶电泳分离PCR产物,用GeneScan、Genotyper软件进行分析.结果:9个微卫星位点的LOH均可发生于原发性胃癌,总的LOH频率为34.3%(24/70),其中D7S486和D7S798位点的LOH频率较高,分别为24.0%(12/50)和19.2%(5/26);总的LOH频率随临床分期而显著增高(P=0.046),D7S486位点的LOH频率在淋巴结转移者显著高于无淋巴结转移者(P=0.015).结论:在7号染色体长臂D7S486和D7S798位点附近,可能存在与胃癌发展相关的抑癌基因.     

环氧化酶-2抑制剂联合顺铂治疗肺癌的实验研究

目的 探讨环氧化酶-2(COX-2)抑制剂尼米舒利(NIM)与化疗药顺铂(DDP)联合应用治疗肺癌的效应及可能机制。方法 应用MTT试验及流式细胞术分别检测NIM与DDP联用对人肺腺癌A549细胞增殖和凋亡的影响，裸鼠移植瘤实验检测NIM与DDP联用对A549细胞成瘤性的影响。结果 在一定浓度范围内NIM、DDP均可抑制A549细胞的生长，其抑制作用呈量一效关系。NIM(25umol／L)与DDP合用可增强对A549细胞生长的抑制作用，DDP浓度≥1mg／L时二者有协同或相加作用。NIM及DDP可有效诱导A549细胞凋亡，联用后凋亡率显著增加。裸鼠移植瘤体内实验显示NIM与DDP均可抑制移植瘤生长，联用后抑瘤率显著增高。结论 NIM与DDP联用对A549细胞、肺癌移植瘤有显著的协同抗肿瘤效应，该作用可能是通讨增强对A549细胞增殖的抑制以及诱导其凋亡来实现的。     

穴注野木瓜治疗腰椎骨质增生108例疗效观察

方法：采用肾俞穴位注射野木瓜注射液治疗腰椎骨质增生108例，并没针刺对照组52例进行临床对照观察。结果：穴位注射有效率98％，对照组有效率85％。结论：野木瓜注射波穴位注射治疗腰椎骨质增生有显著疗效。     

A double-blind randomised controlled trial of the effects of medroxyprogesterone acetate on bone density of women taking oestrogen replacement therapy

Objective To assess the effects of medroxyprogesterone acetate on bone density in women who have had a hysterectomy
Design Randomised, double-blind, placebo-controlled trial of medroxyprogesterone acetate 10 mg, 20 mg or placebo as an adjunct to oestrogen therapy.
Participants One hundred and twenty-three women, aged 18 to 45 years and currently receiving daily oestrogen, who presented at a university-based rheumatology practice.
Interventions The women were randomly assigned to receive either medroxyprogesterone acetate 10 mg, 20 mg or placebo daily beginning on day 15 of each month for one year. Forty-one women were randomised into each group.
Main outcome measure The primary outcome measurement was the percentage of change from baseline in bone mineral density of the lumbar spine (L2–L4). Secondary outcome measures included differences in femoral neck bone density, cholesterol and triglyceride levels between groups.
Results At one year, change in bone mineral density did not differ between either the treatment or placebo groups. Medroxyprogesterone acetate 20 mg and 10 mg led to statistically significant reductions in very low density lipoprotein cholesterol, total triglycerides, and very low density lipoprotein triglycerides when compared with placebo. Medroxyprogesterone acetate 20 mg also led to a statistically significant reduction in high density lipoprotein cholesterol, high density lipo-protein-2 cholesterol, and high density lipoprotein-2 triglycerides.
Conclusions Medroxyprogesterone acetate at either dose as an adjunct to oestrogen did not improve bone mineral density at one year when compared with placebo. Medroxyprogesterone acetate 10 mg may not adversely affect lipids. Medroxyprogesterone acetate 20 mg, however, did reduce high density lipoprotein cholestrol and therefore may increase cardiovascular risk.     

The impact of hormone replacement therapy on quality of life and willingness to pay

Objective To measure the gain in quality of life due to hormone replacement therapy for women with mild and severe menopausal symptoms.
Design Prospective study where data on quality of life and willingness to pay were collected by interview.
Setting Department of Gynaecology at Sodertalje Hospital near Stockholm.
Participants One hundred and four women aged 45 to 65 years treated for menopausal symptoms for at least one month.
Methods Quality oflife was measured by the time tradeoff and rating scale methods. The willingness to pay for hormone replacement therapy was investigated using the contingent valuation method.
Main outcome measures The quality adjusted life year weight measured with the rating scale and time tradeoff methods, and willingness to pay.
Results The increase in the quality adjusted life year weight due to hormone replacement therapy for women with mild symptoms was 0.26 according to the rating scale method and 0.18 according to the time tradeoff method. For women with severe symptoms the quality adjusted life year weight increased by 0.50 according to the rating scale method and by 0.42 according to the time tradeoff method. The mean willingness to pay for hormone replacement therapy per month was 2300 Swedish krone for women with mild symptoms and 4800 Swedish krone for women with severe symptoms (£1 = 10.3 Swedish krone).
Conclusions Hormone replacement therapy leads to a major improvement in quality of life for women with menopausal symptoms. Both for women with mild and severe menopausal symptoms the willingness to pay for the treatment also greatly exceeds the costs, indicating that hormone replacement therapy is economically beneficial for women with menopausal symptoms.     

The use of hormone replacement therapy in women with acute myocardial infarction: an audit of current practice

We undertook criterion-based audit of the current practice of prescribing hormone replacement therapy for women with acute myocardial infarction; the audit included 181 consecutive women admitted to one hospital with this diagnosis in one calendar year. The set standard was that, barring any contraindication, all postmenopausal women with acute myocardial infarction should be prescribed hormone replacement therapy before discharge from hospital. The evidence base of this standard derives from more than 30 epidemiological and clinical studies and a large body of biological data. Only 4.7% of the women were current users of hormone replacement therapy and the set standard was met in only 3% of eligible nonusers. Professionals caring for women who have had a myocardial infarction need to consider hormone replacement therapy as a secondary prophylaxis of myocardial infarction. Gynaecologists should liaise with colleagues in other specialties and general practice to ensure that information on the nongynaecological benefits of hormone replacement therapy is widely disseminated.     

Association of gestational diabetes with abnormal maternal vascular endothelial function

Objective To evaluate vascular endothelial function in isolated small arteries from women with gestational diabetes.
Methods Small subcutaneous arteries (mean luminal diameter ∼ 250μm) were dissected from biopsies obtained at caesarean section in 14 normotensive women with gestational diabetes and in 18 normotensive nondiabetic pregnant women. Vascular function was determined after mounting the arteries on a small vessel myograph.
Results Pre-constricted arteries from gestational diabetic pregnant women demonstrated poor relaxation to acetylcholine, an endothelium-dependent vasodilator (pEC₅₀, mean [SE], 6.98 [0.10] vs normal pregnant, 7.28 [0.08],   P < 0.03  ; % maximum relaxation, median [range], 88.2 [42.4–994] vs normal pregnant 94.2 [71.8–100.0],   P < 0.01  ). In the presence of indomethacin relaxation to acetylcholine was similar in both groups suggesting a deficiency in dilator prostaglandin synthesis in the arteries from the diabetic women. The nitric oxide synthase inhibitor N -monomethyl-L-arginine further reduced sensitivity of arteries to acetylcholine but to a similar degree in both normal pregnant and gestational diabetic women. Relaxation to sodium nitroprusside, an indicator of sensitivity of the vascular smooth muscle to nitric oxide, was similar in both groups.
Conclusions Maternal vascular endothelial dysfunction may contribute to the increased incidence of cardiovascular disorders in women with gestational diabetes.     

Hormone replacement therapy with dydrogesterone and 17β-oestradiol: effects on serum lipoproteins and glucose tolerance during 24 month follow up

Objective To assess serum lipid and lipoprotein concentrations and oral glucose tolerance in postmenopausal women treated with 17β-oestradiol (2 mg/day) and cyclical dydrogesterone (10 mg/day for 14 days per 28 day cycle).
Design A 24 month prospective study of 29 women acting as their own controls. On-treatment samples were taken during the combined (oestrogen–progestogen) phase of therapy.
Setting Metabolic research unit in London.
Population Postmenopausal women with no previous exposure to hormone replacement therapy attending a menopause clinic in a London hospital.
Methods Fasting serum sampling and oral glucose tolerance testing.
Main outcome measures Serum lipids and lipoprotein concentrations and plasma glucose, insulin and C-peptide responses to an oral glucose load.
Results Restricting the analysis to the 17 women who completed the study, no effect was seen on serum triglyceride concentrations. There was a mean fall of 5.9% (95% CI 1.2 to −13.0) in concentrations of serum total cholesterol, reflecting the balance of a 10.7% fall (95% CI 4.3 to −25.8) in low density lipoprotein cholesterol concentrations and a 16.3% increase (95% CI 7.3 to −25.3) in those of high density lipoproteins. Fasting glucose concentrations and glucose tolerance test responses were unchanged. Fasting insulin concentrations fell substantially (–41.6%, 95% CI −23.4 to −59.8) with falls also being seen in insulin responses to glucose. Fasting C-peptide concentrations increased by 36.2% (95% CI 9.17 to 63.3), with no consistent effect on C-peptide responses to glucose.
Conclusions Dydrogesterone did not appear to oppose the potentially beneficial effects of oestradiol on insulin or either low or high density lipoproteins, making the combination with 17β-oestradiol a potentially useful option for postmenopausal women particularly those at risk of cardiovascular disease or diabetes mellitus.     

Increased levels of intercellular adhesion molecules and vascular cell adhesion molecules in pre-eclampsia

Objective To investigate the correlation between soluble forms of the intercellular adhesion molecule (SICAM-1) and vascular cell adhesion molecule (sVCAM-1) and the severity of pre-eclampsia or its possible consequences for fetal growth.
Design Prospective observational study.
Setting Institute of Medical Genetics, University of Oslo, Department of Medical Genetics and Haematological Research Laboratory, Ullevål University Hospital; and the Department of Obstetrics and Gynaecology, The National Hospital, Oslo, Norway.
Participants Seventy-six women with normotensive pregnancies and 157 women with pre-eclampsia divided into three subgroups: mild, severe and pre-eclampsia with fetal growth retardation.
Methods ELISA-measurements of plasma SICAM-1 and sVCAM-1 were performed in a group of healthy pregnant normotensive women and three groups of women with varying degrees of pre-eclampsia.
Results SICAM-1 concentrations were higher in the pre-eclampsia group compared with the control group, but this difference was not statistically significant. Plasma concentrations of sVCAM-1 were significantly greater ( P < 0.0001) in all pre-eclampsia subgroups (835.34, 855.25 and 964.05 ng/mL) compared with the control group (667.62 ng/mL). Within the pre-eclampsia group, plasma concentration of sVCAM-1 was significantly higher in the subgroup exhibiting fetal growth retardation ( P = 0.03) compared with mild pre-eclampsia.
Conclusion The observed increases in plasma concentrations of sVCAM-1 suggest that measurements of this adhesion molecule may be useful in monitoring pregnancies with respect to the development of pre-eclampsia or fetal growth retardation.