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Safety and efficacy of adjuvant single-agent ifosfamide in uterine sarcoma

GYNECOLOGIC ONCOLOGY 2000年第2期78卷 221-227页

作者： Kushner, DM Webster, KD Belinson, JL Rybicki, LA Kennedy, AW Markman, M Cleveland Clin Fdn Dept Obstet & Gynecol Cleveland OH 44195 USA Cleveland Clin Fdn Dept Hematol & Med Oncol Cleveland OH 44195 USA Cleveland Clin Fdn Dept Biostat & Epidemiol Taussig Canc Ctr Cleveland OH 44195 USA

Purpose. The role of adjuvant therapy for completely resected uterine sarcoma continues to be debated. Previous chemotherapy trials have shown little, if any, advantage over surgery alone, with significant added toxicity. To our knowledge, the current study is the first to evaluate adjuvant ifosfamide in completely resected uterine sarcomas. Methods. Between 1992 and 1999, 13 consecutive patients with completely resected moderate- to high-grade uterine sarcoma received three cycles of adjuvant ifosfamide (1.5 g/m(2)/day x 3 days, repeated every 28 days). Mesna was given 30 min prior to infusion. Postinfusion mesna was administered to 10 of the patients in the outpatient setting utilizing a subcutaneous infusion pump. The remaining 3 patients received traditional intravenous mesna at 4 and 8 h after infusion. Results. The median follow-up of the patient population was 26 months. For early-stage patients (n = 10), the 2-year progression-free survival was 60%, with a median of 26 months. The 2-year overall survival was 100%, dropping to 67% at 3 years. Early-stage patients showed an advantage in both progression-free and overall survival. Early-stage patients with mixed mullerian tumor (MMT) had a significantly longer time to progression that those with leiomyosarcoma (LMS) (2-year progression-free survival of 100% versus 33%;P = 0.019). Three patients required dose reduction secondary to grade 2-3 toxicities (neutropenia x2, nausea and vomiting x1). All significant toxicity was eliminated with dose reduction. Conclusions. Adjuvant ifosfamide appears to be safe and well tolerated in patients with completely resected uterine sarcoma. It can easily be given in the outpatient setting if mesna is administered via a subcutaneous pump. Our data, consistent with previous studies in advanced sarcoma, suggest a potentially greater role for ifosfamide in MMT than in LMS. (C) 2000 Academic Press.

关键词：抗肿瘤药烷基化/治疗应用化学疗法辅助异环磷酰胺/治疗应用输注静脉内平滑肌肉瘤/药物疗法平滑肌肉瘤/病理学平滑肌肉瘤/外科学美司钠/治疗应用混合瘤苗勒/药物疗法混合瘤苗勒/病理学混合瘤苗勒/外科学肿瘤分期预防和防护用药/治疗应用横纹肌肉瘤/药物疗法横纹肌肉瘤/病理学横纹肌肉瘤/外科学肉瘤/药物疗法肉瘤/病理学肉瘤/外科学存活率分析子宫肿瘤/药物疗法子宫肿瘤/病理学子宫肿瘤/外科学成年人老年人女(雌)性人类中年人

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Chemoprevention of cancer: a controversial and instructive story

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BRITISH MEDICAL BULLETIN 1999年第3期55卷 593-599页

作者： Vainio, H Karolinska Inst Natl Inst Environm Med Div Hlth Risk Assessment S-17177 Stockholm Sweden

Increased intake of fruits and vegetables seems to be one of the simplest means of decreasing the risk for cancer. Cancer-preventive effects of fruits and vegetables have been observed in epidemiological studies, which could not, however, distinguish the effects of the various ingredients. Antioxidant defence has been proposed as a mechanism of chemoprevention, although inconclusive results have been obtained. The results of randomized intervention trials have shown that beta-carotene supplements are of limited value and may even be deleterious, Vitamins are a good marker of the ingestion of fruits and vegetables, and vitamin E (alpha-tocopherol) is a lipid-soluble antioxidant which can scavenge free radicals. It had no significant effect on the risk for lung cancer of long-term smokers in an intervention trial, but it decreased both the incidence of and mortality from prostate cancer;however, there was a 50% increase in the occurrence of cerebral haemorrhage among the men given vitamin E. Aspirin and aspirin-like drugs appear to decrease the risk for intestinal tumours;the mechanism of action appears to involve diminishing prostaglandin production due to inhibition of cyclooxygenases, Dietary fibre has been linked to a reduced risk for colorectal cancer in many observational studies, but opposite findings were reported recently. In order to resolve these paradoxes, we need to understand better the underlying biology, develop mechanistic hypotheses and test them in clinical trials in humans. Until that time, we should confine any premature enthusiasm for chemopreventive micronutrient supplementation.

关键词：消炎药非甾类/治疗应用抗氧化剂/治疗应用环加氧酶抑制药/治疗应用微量营养系/治疗应用肿瘤/病因学肿瘤/预防和控制预防和防护用药/治疗应用活性氧 β胡萝卜素/投药和剂量动物人类

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Prevention of sodium lauryl sulfate irritant contact dermatitis by Pro-Q aerosol foam skin protectant

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JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY 1999年第5期40卷 783-785页

作者： Patterson, SE Williams, JV Marks, JG Penn State Univ Milton S Hershey Med Ctr Coll Med Dermatol Sect Hershey PA 17033 USA Ferndale Labs Ferndale MI 48220 USA

Eczematous skin disease is a serious work-related illness. Since 1995, reimbursement by insurance companies for treatment of skin diseases has become the largest cost source in some countries. This study was a randomized controlled trial (N = 20) of the efficacy of Pro-Q, a skin protectant product, in the prevention of contact dermatitis from sodium lauryl sulfate and urushiol, the resinous sap of poison ivy and poison oak. Pro-Q was significantly effective in reducing the irritation from sodium lauryl sulfate but did not prevent the allergic reaction to urushiol.

关键词：投药皮肤气雾剂儿茶酚类/副作用皮炎刺激性/预防和控制皮炎职业性/病因学皮炎职业性/预防和控制皮炎毒漆树/预防和控制皮肤科用药/投药和剂量皮肤科用药/治疗应用洗涤剂/副作用二甲基聚硅氧烷类双盲法湿疹/化学诱导湿疹/预防和控制甘油/投药和剂量甘油/治疗应用刺激剂/副作用植物有毒预防和防护用药/投药和剂量预防和防护用药/治疗应用二甲聚硅氧烷/投药和剂量二甲聚硅氧烷/治疗应用十二烷硫酸钠/副作用毒漆树人类

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The role of glutamine in skeletal muscle ischemia/reperfusion injury in the rat hind limb model

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AMERICAN JOURNAL OF SURGERY 1999年第2期178卷 147-150页

作者： Prem, JT Eppinger, M Lemmon, G Miller, S Nolan, D Peoples, J Wright State Univ Sch Med Dept Surg Dayton OH 45409 USA

OBJECTIVES: Ischemia/reperfusion injury is a commonly occurring event with severe pathologic consequences. Reperfusion initiates both the local and systematic damage in part through rapid oxygen generation. The glutathione system is a major mechanism of reducing this oxidative stress. If this system can be maintained or augmented during this stress then less damage may occur. Glutamine provides the source of glutamate to this system and has been shown to preserve total glutathione levels after injury/ischemia to both hepatic and gut models. To test this effect, we looked at glutamine and its role in ischemia/reperfusion injury in a rat hind limb model. METHODS: Fifty male HSD/Holtzman rats weighing 350-400 g were randomized to receive glutamine (3% sol) or normal saline via intraperitoneal injections. The groups were then subjected to 2 hours of ischemia to their hind limbs using the Tourni-Cot method. Animals were then randomized to reperfusion groups of 30 minutes, 2 hours, and 4 hours. Muscle tissue assays were performed for lipid peroxidation (LPO), total glutathione (GSH), and myeloperoxidase (MPO). Peripheral blood was analyzed for creatinephosphokinase levels (CPK). RESULTS: Animals that received glutamine showed a general trend of less lipid peroxidation products than the normal saline groups. In animals that received glutamine and underwent 2 hours of ischemia and reperfusion times of 0 minutes, 30 minutes, and 2 hours, there were significantly less percent changes in lipid peroxidation products from controls (4.6% vs 48.2%, P <0.05), (18.9% vs 123%, P <0.05), (12.6% vs 115%, P <0.05). A general trend upward was noted in CPK levels in both groups. In animals receiving 2 hours of ischemia and 30 minutes of reperfusion, there was a significantly greater level of creatinephosphokinase (CPK) calculated as percent change from control in the normal saline group as compared with the glutamine group (209.2% vs 92.7%). Myeloperoxidase assay of muscle tissue revealed

关键词：肌酸激酶/血液疾病模型动物谷氨酸/代谢谷氨酰胺/投药和剂量谷氨酰胺/治疗应用谷胱甘肽/生物合成后肢/血液供给注射腹腔内缺血/代谢缺血/病理生理学脂质过氧化作用/药物作用肌骨骼/血液供给肌骨骼/药物作用肌骨骼/代谢肌骨骼/病理学中性白细胞/药物作用中性白细胞/病理学氧化性应激/药物作用氧化性应激/生理学过氧化物酶/代谢预防和防护用药/投药和剂量预防和防护用药/治疗应用随机分配大鼠近交系再灌注损伤/代谢再灌注损伤/病理生理学再灌注损伤/预防和控制单盲法时间因素动物男(雄)性大鼠

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Chemically assisted dissection of tissues: An interesting support in abdominal myomectomy

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JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS 2000年第1期191卷 65-69页

作者： Benassi, L Lopopolo, G Pazzoni, F Ricci, L Kaihura, C Piazza, F Vadora, E Zini, C Univ Parma Dept Obstet & Gynecol I-43100 Parma Italy Univ Parma Ear Nose Throat Dept I-43100 Parma Italy

Background: The aim of this study was to verify the efficacy of sodium-2-mercaptoethanesulfonate (mesna) in the chemical separation of tissues in abdominal myomectomies when used with the traditional mechanical separation techniques. Study Design: In a prospective, randomized study, 58 women under-went abdominal myomectomy. In 29 of these, we used mesna for highlighting and separating tissues, and in the other 29 we used saline solution for the same purposes. The variables evaluated included the number of myomas removed, the volume of the biggest myoma, and the total volume of the myomas removed in every intervention. We also recorded operating time, the length of hospital stay, the degree of procedure difficulty perioperative blood loss, operative complications, and cost. Results: The operation was significantly shorter in the mesna group (p < 0.05) even though the volume and the number of myomas were larger. The degree of difficulty evaluated by the surgeon at the end of every operation was not significantly different in the two groups. The reduction in hemoglobin 24 hours after operation was significantly less in the patients treated with mesna (p = 0.006), but this difference was probably altered by the increase in hematocrit levels. Conclusions: Because of its ability as a chemical dissector, mesna may be a useful aid in this type of benign gynecologic operation. Larger studies to confirm this are needed. (J Am Cell Surg 2000;191:65-69. (C) 2000 by the American College of Surgeons).

关键词：失血手术妇科外科手术血细胞比容平滑肌瘤/外科学住院时间美司钠/治疗应用前瞻性研究预防和防护用药/治疗应用子宫肿瘤/外科学成年人女(雌)性人类

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水飞蓟素治疗抗结核药物肝损害的疗效观察

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中国误诊学杂志 2008年第19期8卷 4609-4610页

作者：霍丽亚王松河南省南阳市中心医院感染疾病科 473009

我院2005—06/2007—06应用水飞蓟素治疗抗结核药物所致肝功能损害42例,取得良好效果,现报告如下。1对象和方法[第一段]

关键词：水飞蓟素/治疗应用预防和防护用药/治疗应用抗结核药/副作用肝疾病/化学诱导/药物疗法人类

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Is there any use for nontraditional or alternative therapies in patients with chronic liver disease?

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Current gastroenterology reports 1999年第1期1卷 50-56页

作者： Bass, N.M. Division of Gastroenterology UCSF Medical Center Rm Box 0538 San Francisco 94143-0538 CA United States

There has been a substantial increase in the use of so-called complementary and alternative therapies by patients with liver disease. Although many such modalities are available, herbal therapies are the most popular, and of these remedies, silymarin extracted from the milk thistle is most widely subscribed to as a remedy for liver diseases. Available evidence points to a potential, but unproven, benefit for this as well as other therapies based on free radical scavenger or antioxidant principles in treating patients with liver disease. These therapies deserve further investigation through experimental studies and well-controlled clinical trials. Benefits to patients from these therapies, especially to patients with established cirrhosis, are most likely to be modest and insignificant. Conversely, the hepatotoxic potential of some alternative treatments is well recognized. As practitioners educating and treating patients with liver disease, we are obliged to be informed about popular alternative therapies, understanding of our patients' need to be partners in their care, and open-minded to the possibility that some benefit may come from some therapies currently regarded as alternative. We need to be effective and tolerant in learning about which alternative treatments our patients are taking, so that we can monitor their effects if any and counsel appropriately against those that may cause harm.

关键词：补充疗法肝疾病/治疗预防和防护用药/治疗应用水飞蓟素/治疗应用治疗结果动物人类

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The role of folic acid in oral clefting.

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British journal of orthodontics 1999年第2期26卷 115-120页

作者： Hartridge, T. Illing, H.M. Sandy, J.R. Maxillofacial Unit Royal Devon &amp Exeter Hospital United Kingdom

The objective of this study is to describe the role of periconceptional folic acid supplementation and assess it's potential in the prevention of foetal abnormalities, and consists of a review of the literature undertaken using an electronic and hand search. This includes research trials and methodology associated with folic acid supplementation. It is recommended that all women planning to conceive should supplement their diet with folic acid in order to prevent abnormalities in neural tube development, particularly if there is a history of a previously affected pregnancy. There is increasing evidence that folic acid supplementation may, in addition, reduce the incidence of oral facial clefting. Further research with multi-disciplinary approaches in biochemistry, genetics, gene/environment interactions, and embryology are indicated.

关键词：唇裂/预防和控制腭裂/预防和控制营养保健品环境胎儿/药物作用叶酸/投药和剂量叶酸/治疗应用颌面畸形/胚胎学颌面畸形/遗传学颌面畸形/预防和控制神经管缺损/预防和控制预防和防护用药/投药和剂量预防和防护用药/治疗应用女(雌)性人类妊娠

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Effects of antihypertensive therapy on hypertensive vascular disease

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Current Hypertension Reports 2000年第3期2卷 280-288页

作者： Park, Jong Bae Schiffrin, Ernesto L. MRC Multidisciplinary Research Group on Hypertension Clinical Research Institute of Montréal Montréal QC H2W 1R7 110 Pine Avenue West Canada

Hypertension is associated with alterations in the structure, function, and mechanical properties of large and small arteries. Changes in the endothelium, smooth muscle cell, extracellular matrix, and possibly the adventitia, contribute to complications of hypertension. In large arteries, vascular hypertrophy is found, often with increased stiffness of media components. In small arteries, particularly in mild hypertension, rearrangement of smooth muscle cells around a smaller lumen without changes in media volume (eutrophic remodeling) occurs;in more severe hypertension, hypertrophic remodeling with increased vascular stiffness can be found. Vascular remodeling is accompanied by an increase in the extracellular matrix, particularly collagen deposition. Recent studies have demonstrated that vascular remodeling and endothelial dysfunction of small and large vessels may be normalized by treatment with some antihypertensive agents (angiotensin converting enzyme inhibitors, angiotensin AT1 receptor antagonists, and long-acting calcium channel blockers). Angiotensin converting enzyme inhibitors have now been shown to improve outcomes in hypertensive patients, an effect that may in part be related to the vascular protective effects reviewed here. Copyright © 2000 by Current Science Inc.

关键词：血管紧张素Ⅰ/拮抗剂和抑制剂血管紧张素转换酶抑制药/治疗应用抗高血压药/治疗应用动脉/药物作用小动脉/药物作用钙通道阻滞药/治疗应用胶原/药物作用弹性组织/药物作用弹性内皮血管/药物作用细胞外基质/药物作用高血压/药物疗法肥大肌平滑血管/药物作用预防和防护用药/治疗应用受体血管紧张素/拮抗剂和抑制剂治疗结果血管疾病/药物疗法人类

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Problems and approaches in investigating the role of micronutrients in the aetiology of cancer in humans

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BRITISH MEDICAL BULLETIN 1999年第3期55卷 600-618页

作者： Little, J Univ Aberdeen Dept Med & Therapeut Epidemiol Grp Aberdeen AB25 2ZD Scotland

Observational studies have provided leads regarding a number of micronutrients which may account for the apparent protective effects of high intakes of vegetables and fruit against many types of cancer. In general, these leads have not been confirmed by randomised controlled trials. This apparent conflict raises issues about the timing and duration of a critical period or periods during which micronutrient intake may influence the development of cancer, the dose, possible interaction between high doses of micronutrients and exposures conferring a high risk of cancer and gene-micronutrient interactions. When gene-environmental interaction exists, failure to take both of these sets of factors into account leads to bias in the estimation of disease risk. As a result of recent advances, it is now possible to take measures of genetic susceptibility into account. Therefore, in future studies, the opportunity should be taken to obtain DNA samples to determine genotypes for polymorphisms potentially affecting micronutrient metabolism.

关键词： 5 10-亚甲基四氢叶酸还原酶(FADH2) 芳基胺N-乙酰转移酶/遗传学结直肠肿瘤/酶学叶酸/遗传学疾病遗传易感性血色素沉着症/遗传学亚甲基四氢叶酸还原酶(NADPH) 微量营养系/代谢微量营养系/治疗应用肿瘤/遗传学肿瘤/代谢肿瘤/预防和控制氧化还原酶类/遗传学多态现象遗传预防和防护用药/代谢预防和防护用药/治疗应用研究设计人类

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