Cancer risk assessment for health care workers occupationally exposed to cyclophosphamide

In the present study a cancer risk assessment of occupational exposure to cyclophosphamide (CP), a genotoxic carcinogenic antineoplastic agent, was carried out following two approaches based on (1) data from an animal study and (2) data on primary and secondary tumors in CP-treated patients. Data on the urinary excretion of CP in health care workers were used to estimate the uptake of CP, which ranged from 3.6 to 18 g/day. Based on data from an animal study, cancer risks were calculated for a health care worker with a body weight of 70 kg and a working period of 40 years, 200 days a year (linear extrapolation). The lifetime risks (70 years) of urinary bladder cancer in men and leukemias in men and women were found to be nearly the same and ranged from 95 to 600 per million. Based on the patient studies, cancer risks were calculated by multiplication of the 10-year cumulative incidence per gram of CP in patients by the estimated mean total uptake in health care workers over 10 years, 200 days a year. The risk of leukemias in women over 10 years ranged from 17 to 100 per million using the secondary tumor data (linear extrapolation). Comparable results were obtained for the risk of urinary bladder tumors and leukemias in men and women when primary tumor data were used. Thus, on an annual basis, cancer risks obtained from both the animal and the patient study were nearly the same and ranged from about 1.4 to 10 per million. In The Netherlands it is proposed that, for workers, a cancer risk per compound of one extra cancer case per million a year should be striven for (target risk) and that no risk higher than 100 per million a year (prohibitory risk) should be tolerated. From the animal and the patient study it appears that the target risk is exceeded but that the risk is still below the prohibitory risk.     

成人大脑沟、回在MRI矢状图像上的定位研究

为给大脑占位性病变及脑功能的影像学研究提供断层解剖学依据,利用１５ 例头部矢状断层标本及相应脑片,颅脑ＭＲＩ矢状扫描图像研究了大脑沟、回在ＭＲＩ矢状图像上的定位。结果显示：扣带沟缘支和外侧沟后升支是识别中央沟的标志,若出现壁间回则更易识别中央沟;借外侧沟前水平支和前升支形成的“Ｙ”或“Ｖ”形外观,可识别中央前沟及额下回的眶部、三角部和岛盖部;侧副沟居海马结构下方,其下方为枕颞内侧回。选了８ 个典型矢状扫描层面详细介绍大脑沟、回的识别     

瘤苗联合当归多糖抗瘤的实验研究

以皮下接种5108肉瘤细胞的昆明鼠为荷瘤动物模型,用S180瘤苗和／或当归多糖（Ap）免疫治疗。结果,二者联用能显著增强荷瘤鼠的巨噬细胞介导细胞毒作用及NK活性。另外,Ap能显著增加初次免疫鼠血清中抗绵羊红细胞抗体滴度。提示,Ap能促进免疫功能,具有免疫佐剂活性。与瘤苗联用可提高瘤苗的主动免疫治疗效应。     

192例腰椎间盘突出症患者的诊断及手术治疗分析

目的：总结分析１９２例腰椎间盘突出症及侧隐窝狭窄伴黄韧带肥厚患者的诊断和手术治疗。方法：经临床检查明确定位、定性诊断,影像学检查证实,采用小切口半椎板或全椎板切除减压、突出椎间盘髓核切除手术治疗。结果：手术证实腰椎间盘突出症１８９例,侧隐窝狭窄伴黄韧带肥厚３例,术后随访６月－５年,优良率７９％。结论：临床检查是腰椎间盘突出症诊断的基础,影像学检查对进一步明确定位诊断和鉴别诊断是必要的。手术指征的严格把握是手术成功的关键。     

组合硬化剂治疗肾囊肿远期疗效观察

目的：研究组合硬化剂对家兔胆囊的硬化作用,观察治疗肾囊肿的远期临床疗效。方法：应用四环素与氟美松组合硬化剂注入家兔胆囊,与生理盐水和无水乙醇对比观察其对胆囊壁的作用;与无水乙醇对比观察介入硬化治疗肾囊肿的疗效。组合硬化剂治疗组４１例,男２３例,女１８例,年龄４３岁－７２岁;无水乙醇对对照组４０例,男２８例,女１２例,年龄４５岁－７０岁。     

Cardiac effects of contrast media in MR angiography: evaluation in an experimental model of myocardial ischemia

RATIONALE AND OBJECTIVES: The authors evaluated the cardiac tolerability of paramagnetic contrast agents for magnetic resonance (MR) angiography in an in vitro model of ischemic rat heart. MATERIALS AND METHODS: The left anterior descending coronary artery was temporarily occluded in a perfused rat heart model to induce cardiac ischemia and reperfusion. A dose of 0.4 mL of gadobenate dimeglumine, of gadopentetate dimeglumine, or of D-mannitol was injected directly into the aorta both during the ischemia and during the reperfusion period. The left ventricular pressure and heart rate were recorded. RESULTS: Myocardial ischemia resulted in decreased cardiac activity, with a reduction in left ventricular pressure and heart rate. A further decrease in cardiac activity was temporarily induced by injection of contrast medium during both the ischemic and early reperfusion phases. Less marked responses were induced by a hyperosmolal solution of mannitol. CONCLUSION: These results suggest that the transient cardiac effects induced by bolus injection of paramagnetic contrast medium may be regarded as the combined effects of the osmotoxicity of the contrast medium solution and the chemotoxicity of the contrast medium molecule.     

化疗药诱导卵巢癌细胞凋亡的初步探讨

目的 观察人体内化疗药诱导卵巢癌细胞凋亡及其规律性。方法 采用末端脱氧核苷酰的转移酶方法,对９例卵巢癌腹水患者行腹腔化疗,观察不同时间腹水中卵巢癌细胞凋亡的动态变化,并应用免疫组化法动态检测腹水中肿瘤细胞增殖及Ｂｃｌ－２,Ｂａｘ基因表达。结果 发现化疗后,肿瘤细胞凋亡多在化疗后４８小时达高峰,与化疗前有显著差异（Ｐ〈０．０５）,至１２０小时,凋亡逐渐下降,部分病例降至治疗前水平,化疗后腹腔内肿瘤细     

Patterns of practice for acute myocardial infarction in a population from ten countries

Background: There is conclusive evidence from large scale randomized clinical trials (RCTs) that several treatments administered in the acute phase of a myocardial infarction (AMI) reduce mortality. However, only a minority of patients admitted with AMI receives at the appropriate treatments. Objectives: This study aims at (1) describe the utilization patterns for AMI; (2) determine the appropriateness of prescribing, measured as adherence to the ACC/AHA guidelines; and (3) determine which factors are associated with the administration of thrombolytic agents. Methods: The study was a multi-center survey carried out in ten countries (nine European and one Canadian province) over a 3-month period. Data were prospectively collected by clinical pharmacists. All consecutive patients admitted to the participating hospitals during the study period with a diagnosis of suspected AMI were included in the study. Rates of use were calculated as “overall utilization” and “adjusted utilization” (e.g., accounting for eligibility). Results: Data were available on 1976 patients from 56 participating centers. The mean age of the patients was 65 years (range 25–95, SD = 12.6) and 29.7% were women. Adjusted utilization rates were 63.7% for thrombolysis, 88% for aspirin, and 65.9% for β-adrenergic blocking agents. The most utilized thrombolytic agent was streptokinase (65.9%). The main reasons given by physicians for not administering thrombolysis was the delay from chest pain onset to admission. Patients admitted to teaching hospitals were less likely to receive aspirin than patients admitted to general hospitals (adjusted rate 90.1% vs 86%, P = 0.007), but they were more likely to undergo a primary invasive procedure (11.0% vs 2.5% P = 0.001). Multivariate analysis showed that age greater than 74 years, delay, prior myocardial infarction, and Killip scale were correlated with the non-utilization of thrombolysis. Conclusion: Recommended treatments are still underutilized in patients with AMI. Increased utilization is required, particularly for elderly people. There is a wide variability among hospitals with different affiliations (teaching vs non teaching), demonstrating the different patterns of practice in various settings. Received: 2 February 1998 / Accepted in revised form: 8 August 1998     

Cytotoxic constituents from the roots ofAnthriscus sylvestris

Activity-guided fractionation of the roots of Anthriscus sylvestris resulted in the isolation and characterization of five cytotoxic compounds, deoxypodophyllotoxin (1), falcarindiol (2), and angeloyl podophyllotoxin (5) from the hexane soluble fraction and morelensin (3), bursehernin (4) from the chloroform soluble fraction. It is the first report of the occurrence of compound 5 in nature.     

A systems approach to cancer therapy

Conclusion The molecules described herein as antiangiogenic agents and antimetastatic agents represent a wide variety of molecular structures with a wide variety of biological effects and targets. Most often these agents have been generally classified as antiangiogenic or antimetastatic by their effects in an in vitro bio-assay system. The diversity in this group of molecules gives strength to the potential of this approach in therapeutic applications. The biological and biochemical pathways involved in angiogenesis are numerous and redundant. It is likely that there are many angiogenic factors and many pathways of invasion, therefore it is likely that blockade of more than one pathway related to angiogenesis and/or invasion will be necessary to impact on the natural progress of a malignant disease.The vasculature forms the first barrier to penetration of molecules into tumors. Although the antiangiogenic agent treatments administered in this study did not inhibit angiogenesis in these tumors completely, the vasculature present in the treated tumors may be impaired compared to control tumors. Overall, therefore, the best speculation is that the main targets for the antiangiogenic agents are extracellular matrix processes and/or tumor endothelial cells and that inhibition and/or impairment of these non-malignant functions can improve therapeutic responses when used in combination with cytotoxic therapies. The incorporation of antiangiogenic agents and/or antimetastatic agents into therapeutic regimens represents an important challenge. The successful treatment of cancer requires the eradication of all malignant cells and therefore treatment with cytotoxic therapies. The compatibility of antiangiogenic therapy and/or anti-invasion agents with cytotoxic chemotherapeutic agents is not obvious [316].The goal of the addition of any non-cytotoxic potentiator to a therapeutic regimen is to take a good therapy and, without additional toxicity, push it to cure.Cyclophosphamide is a good drug against the Lewis lung carcinoma although no long-term survivors of animals bearing Lewis lung carcinoma are achieved with cyclophosphamide treatment alone. Adding antiangiogenic agents to treatment of this tumor with cyclophosphamide produced a cure rate of 40–50%, meaning that both the primary and metastatic disease has been eradicated in these animals. Cures were achieved only when the antiangiogenic treatments extended from days 4–18 post Lewis lung tumor implantation. The results obtained with the addition of antiangiogenic agents to cytotoxic anticancer therapies in in vivo models of established solid tumors have been very positive and provide direction for future clinical trials including these antiangiogenic agents. Two conclusions may be drawn. First, combinations of antiangiogenic and/or antimetastatic agents evoke a greater effect on tumor response to therapy than does treatment with single agents of these classes. Second, treatment with antiangiogenic agents and/or antimetastatic agents can interact in a positive way with cytotoxic therapies.