Genetic polymorphisms in dopamine-related genes and smoking cessation in women: a prospective cohort study

Background  

Genes involved in dopaminergic neurotransmission have been suggested as candidates for involvement in smoking behavior. We hypothesized that alleles associated with reduced dopaminergic neurotransmission would be more common in continuing smokers than among women who quit smoking.     

Apparent lack of synergism between heparin and dihydroergotamine in prevention of deep vein thrombosis after elective hip replacement: a randomised double-blind trial reported in conjunction with an overview of previous results.

We report the results of a double-blind, randomised trial of venous thrombosis (VT) prevention in 117 patients having elective hip replacement where low dose heparin alone (5,000 IU sodium heparin given subcutaneously [sc] 8 hourly until the seventh postoperative day) was compared with low dose heparin plus dihydroergotamine (DHE; 0.5 mg, given 8 hourly by sc injection). The trial end point consisted of VT discovered through bilateral ascending venography done routinely on the seventh postoperative day. VT developed in 34% of patients given heparin/DHE (95% confidence interval = 22% - 47%) compared with 24% in those given low dose heparin alone (95% confidence interval = 14% - 37%; p = 0.34), difference = 10% (95% confidence interval = -7% to +26%). Corresponding figures for the incidence of proximal (above-knee) thrombosis were 17% and 14% (95% confidence intervals = 8% - 29% and 6% - 25% respectively). These results are discussed in the context of a detailed overview of published evidence concerning VT prevention with heparin/DHE after hip replacement and we conclude it is unlikely that heparin/DHE is markedly superior to low dose heparin alone in this clinical setting.     

Advanced primary breast cancer: assessment at mammography of response to induction chemotherapy

The response to induction chemotherapy is an important prognostic factor in patients with nonmetastatic, locally advanced breast carcinomas. Assessment at mammography of the response of 60 breast cancers in 59 women was performed between 1974 and 1986. Responses were excellent in 13 tumors, moderate in 34, and poor in 13 (excellent moderate = 78%). Assessment of response of discrete masses in a fatty breast was easiest; assessment of response of tumor areas that were poorly defined-such as a focal area of architectural distortion or mass in dense breast parenchyma-was more difficult. Of 17 patients with excellent pathologic responses-that is, minimal or no residual tumor-15 (88%) had complete responses (no residual tumor) as determined with mammography, physical examination, or both. Mammography provides information complementary to physical examination and is essential in the accurate assessment of the response to chemotherapy of locally advanced breast cancer.     

Artificial insemination and in-vitro fertilization using donor spermatozoa: a report on 15 years of experience

Donor insemination (DI) using cryopreserved semen commenced at The Royal Women's Hospital in 1976. Over the next 15 years we performed 5953 treatment cycles to achieve 816 pregnancies (13.7% per cycle) and 706 live births. In-vitro fertilization (IVF) using donor spermatozoa commenced in 1986. Over the next 5 years we performed 303 treatment cycles for 185 couples. Including subsequent transfer of cryopreserved embryos, a total of 33% of couples achieved a successful pregnancy by IVF. Statistical analysis indicated that, for DI pregnancies, the most important semen variable was the percentage post-thaw motility, whilst for normal fertilization in IVF it was the pre-freeze motility. These results may be explained by the compensatory effects of post-thaw processing of spermatozoa for IVF, but not for DI in our clinic.      

Pharmacological modification of tremor and enhanced acoustic startle by chlordecone and p,p′-DDT

Pretreatment of rats with phenoxybenzamine (5 mg/kg; SC), an alpha adrenergic antagonist, decreased the peak tremor power and startle magnitude of rats subsequently given DDT (75 mg/kg; PO) or chlordecone (60 mg/kg; IP), without having a significant effect on control animals. Pretreatment with an intracerebroventricular injection of calcium (3.75 M in 5 l NaCl) decreased the peak tremor power due to subsequently administered DDT, while increasing the tremor response in rats later dosed with chlordecone. The effects of phenoxybenzamine are postulated to be due to a blockade of an excitatory influence of the adrenergic system. Calcium may decrease DDT-induced tremor by acting as a neuronal stabilizer. Potentiation of the tremorigenic effect of chlordecone by calcium may be due to increased levels of intracellular calcium, resulting in augmented release of neurotransmitters in chlordecone-exposed animals.     

The effects of clofibrate on plasma glucose,lipoproteins, fibrinogen,and other biochemical and haematological variables in patients with mature onset diabetes mellitus

Summary We have studied the effects of clofibrate treatment on glucose tolerance and plasma insulin, plasma triglyceride, cholesterol and non-esterified fatty acid (NEFA) levels, and on various haematological variables (including plasma fibrinogen level, red cell flexibility, whole blood viscosity, and plasma -thromboglobulin level) in patients with mature-onset diabetes. Twenty-two patients (11 men and 11 women) were randomly allotted to treatment with clofibrate, 1 g twice daily, or a corn-oil placebo for 12 weeks, and then changed to the alternate medication for another 12 weeks. Half the patients took clofibrate in the first 12 weeks of the study, and half took the placebo. The patients stayed on their usual diet, and 13 also took tolbutamide before and during the trial. The trial was double-blind. At the beginning, middle and end of the trial fasting measurements were made, and plasma glucose, insulin, triglyceride, and NEFA concentrations were then measured repeatedly during the next 8 h (from 8.00 a. m. to 4 p. m.), to allow calculation of the mean 8-h concentration of these substances. In general, plasma concentrations of glucose, triglyceride, cholesterol, NEFA and fibrinogen were lower when the patients were taking clofibrate then when they were taking the corn-oil placebo, but higher when taking the placebo than at entry to the trial. We favour the explanation that clofibrate has lowered these concentrations, when compared with the placebo. The alternative interpretation, that 2 g per day of the placebo increases plasma concentrations of glucose, triglyceride, cholesterol, NEFA and fibrinogen, and that clofibrate has little effect, seems unlikely. The first interpretation, that clofibrate has a positive effect when compared with an inert placebo, has been adopted when interpreting the results. Clofibrate treatment led to a 15% lower fasting blood glucose level, and 11% lower mean 8-h glucose concentration than did placebo (p<0.01) but it did not significantly change plasma insulin concentration. The fasting and mean 8-hour concentrations of plasma triglyceride and fasting plasma cholesterol concentrations were reduced by clofibrate (by 44%, 33% and 10% respectively, p<0.05). Clofibrate decreased the fasting plasma NEFA level by 27% (p<0.01), and the mean 8-h plasma NEFA concentration by 23% (p<0.05). A weak relationship between the mean 8-h levels of plasma NEFA and plasma glucose (r=0.49, p<0.05) was consistent with the suggestion that the change in plasma glucose could, in part, be due to a change in NEFA concentration. The mean plasma fibrinogen concentration was decreased 23% by clofibrate (p<0.01). There was a positive correlation between the observed decrease during treatment and the baseline fibrinogen concentration (r=0.80, p<0.001), i. e. the greatest decrease occurred in those subjects with the highest plasma fibrinogen concentrations. Whole blood viscosity fell slightly, but erythrocyte flexibility was not significantly changed by clofibrate. The mean haemoglobin concentration and leucocyte count fell slightly during clofibrate treatment and the platelet count rose. -thromboglobulin was not affected. Clofibrate treatment was associated with rises in plasma albumin, urea, creatine kinase and aspartate aminotransferase, and falls in plasma bilirubin, -glutamyl-transpeptidase and alkaline phosphatase. Most of these changes occurred within the reference range.     

Cigarette tar yield and risk of upper digestive tract cancers: case-control studies from Italy and Switzerland.

BACKGROUND: Tobacco smoking is one of the main risk factors for oral, pharyngeal and oesophageal cancers in developed countries. Information on the role of the tar yield of cigarettes in upper digestive tract carcinogenesis is sparse and needs to be updated because the tar yield of cigarettes has steadily decreased over the last few decades. PATIENTS AND METHODS: We analysed two case-control studies, from Italy and Switzerland, conducted between 1992 and 1999, involving 749 cases of oral and pharyngeal cancer and 1770 controls, and 395 cases of squamous-cell oesophageal carcinoma and 1066 matched controls. Odds ratios (ORs) were estimated by unconditional multiple logistic regression models, including terms for age, sex, study centre, education and alcohol consumption. RESULTS: Based on the brand of cigarettes smoked for the longest time, the multivariate ORs for current smokers compared with never smokers were 6.1 for <20 mg and 9.8 for >or=20 mg tar for oral and pharyngeal neoplasms, and 4.8 and 5.4 for oesophageal cancer, respectively. For the cigarette brand smoked in the previous six months, the ORs for >or=10 mg compared with <10 mg were 1.9 for cancer of the oral cavity and pharynx and 1.8 for oesophageal cancer, after allowance for number of cigarettes and duration of smoking. CONCLUSIONS: The present study confirms the direct relationship between the tar yield of cigarettes and upper digestive tract neoplasms, and provides innovative information on lower tar cigarettes, which imply reduced risks compared with higher tar ones. However, significant excess risks were observed even in the lower tar category, thus giving unequivocal indications for stopping smoking as a priority for prevention of upper digestive tract neoplasms.     

Does an apple a day keep the oncologist away?

BACKGROUND: Apples have commonly been described as a healthy food. To understand better their role on risk of cancer at several sites, we analyzed data from multicenter case-control studies conducted between 1991 and 2002 in Italy. PATIENTS AND METHODS: The studies included 598 patients with incident cancers of the oral cavity and pharynx, 304 of the oesophagus, 460 of the larynx, 1953 of the colorectum, 2569 of the breast, 1031 of the ovary and 1294 of the prostate. The comparison group included a total of 6629 patients admitted to the same network of hospitals as cases for acute, non-neoplastic diseases. Multivariate odds ratios (OR) were obtained with allowance for age, sex, study center, education, body mass index, tobacco smoking, alcohol drinking, total energy intake, vegetable consumption and physical activity. RESULTS: Compared with subjects reporting consumption of <1 apple/day, the ORs for > or =1 apple/day were 0.79 [95% confidence interval (CI) 0.62-1.00] for cancers of the oral cavity and pharynx, 0.75 (95% CI 0.54-1.03) for oesophagus, 0.80 (95% CI 0.71-0.90) for colorectum, 0.58 (95% CI 0.44-0.76) for larynx, 0.82 (95% CI 0.73-0.92) for breast, 0.85 (95% CI 0.72-1.00) for ovary and 0.91 (95% CI 0.77-1.07) for prostate. CONCLUSION: This investigation found a consistent inverse association between apples and risk of various cancers.     

阿哌沙班VS依诺肝素用于膝关节置换术后血栓预防（ADVANCE-2）：随机双盲试验

背景依诺肝素等低分子肝素是预防大关节置换术后静脉血栓形成的首选。阿哌沙班是一种口服活性的Xa因了抑制剂，在预防大关节置换术后静脉血栓形成方面可能有效，而且相对于依诺肝素来说，出血风险较低、用法也较简便。本研究评估选择性全膝关节置换术后上述药物的有效性和安全性。方法ADVANCE．2为多中心随机双盲III期研究，选择性双侧或单侧全膝关节置换术患者通过交互式中心电话系统进行分组，随机接受阿哌沙班2．5mg每天2次口服（1528例）或依诺肝素40mg每天1次皮下注射（1529例）。随机化方案由Brist01．MyersSquibb随机中心生成，按研究中心和单侧或双侧手术分层，区组大小为4。研究者、患者、统计专家、评判者和指导委员会不知道患者分组情况。阿哌沙班于手术伤口闭合后10～12小时使用，依诺肝素于术前12小时使用；两药均持续用药10～14天，按照计划用药结束时行双侧顺行性静脉造影。土要终点是治疗期间无症状和有症状的深静脉血栓形成、非致死性肺栓塞和全因死亡的复合指标。统计学计划要求在检验阿哌沙班的优效性之前达到非劣效；非劣效检验对意向治疗患者进行分析。本研究在CliniealTrials．gov备案，备案号NCT00452530。结果接受治疗的3057例患者（阿哌沙班组1528例、依诺肝素组1529例）中，1973例符合主要有效性分析的要求。阿哌沙班组976例和依诺肝素组997例中，报告主要终点的患者分别为147例（15％）和243例（24％）[相对危险度0．62（95％可信区间d为：0．51～0．74），P〈0．0001；绝对危险度下降9.3％（5．8～12．7）1。阿哌沙班组1501例和依诺肝素组1508例中，发生大出血或临床相关非大出血的患者分别为53例（4％）和72例（5％）（P=0．09）。解读全膝关节置换术后次日上午使用阿哌沙班2．5mg每天2次，是依诺肝素40mg／天简便而更有效的口服替代措施，且不会增加出血。