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A randomised trial of differentiated prednisolone treatment in active rheumatoid arthritis. Clinical benefits and skeletal side effects

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ANNALS OF THE RHEUMATIC DISEASES 1999年第11期58卷 713-718页

作者： Hansen, M Podenphant, J Florescu, A Stoltenberg, M Borch, A Kluger, E Sorensen, SF Hansen, TM Univ Copenhagen Hvidovre Hosp Dept Rheumatol Copenhagen Denmark Univ Copenhagen Herlev Hosp Dept Rheumatol & Radiol DK-2730 Herlev Denmark Natl Univ Hosp TTA Rigshosp Dept Internal Med Copenhagen Denmark Univ Copenhagen Bispebjerg Hosp Dept Rheumatol Herlev Denmark

Objectives-To study benefits and skeletal side effects of carefully monitored prednisolone treatment in patients with active rheumatoid arthritis. Methods-One hundred and two patients with active rheumatoid arthritis were randomly allocated to treatment with disease modifying anti-inflammatory drug (DMARD) alone or DMARD and prednisolone in a one year follow up study. Prednisolone was given in a dose regimen adapted to the disease activity of the individual patient. The mean dose was 6 mg and the mean cumulated dose was 2160 mg. Patients were followed up with disease activity parameters, radiograph of the hands (Larsen score), and bone mineral density (BMD) of the lumbar spine, distal forearm and hand. At one year 26 patients had withdrawn from the investigation leaving 76 patients for evaluation. Results-The results showed that disease activity in the prednisolone treated group was reduced within two weeks. In the DMARD alone group disease activity was gradually reduced over months. At six months there was no difference between the groups as evaluated by an improvement score using a number of ACR criteria. Prednisolone in the present set up was not able to protect significantly against radiological disease progression, although there was a trend towards less progression in Larsen score in the prednisolone group, a matter that was further underlined in an intention to treat analysis. BMD data revealed a significant reduction in spinal BMD in the prednisolone group, whereas prednisolone seemed to have a protective effect against bone loss in the hand and distal forearm. Conclusions-This study does not allow any firm conclusions for or against the treatment of rheumatoid arthritis with prednisolone. The data suggest that the beneficial effects of prednisolone are not as clear cut in established rheumatoid arthritis as in early disease. Furthermore the data indicate that treatment in the chosen relatively low dose does not provide sufficient control of disease. On the

关键词：消炎药/治疗应用关节炎类风湿/药物疗法骨密度/药物作用用药计划表药物疗法联合糖皮质激素类/治疗应用纵向研究泼尼松龙/治疗应用成年人老年人老年人 80以上女(雌)性人类男(雄)性中年人

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Two-dose versus monthly intermittent preventive treatment of malaria with sulfadoxine-pyrimethamine in HIV-seropositive pregnant Zambian women

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JOURNAL OF INFECTIOUS DISEASES 2007年第11期196卷 1585-1594页

作者： Hamer, Davidson H. Mwanakasale, Victor MacLeod, William B. Chalwe, Victor Mukwamataba, Doreen Champo, Davies Mwananyanda, Lawrence Chilengi, Roma Mubikayi, Lwambwa Mulele, Chikuli Kabika Mulenga, Modest Thea, Donald M. Gill, Christopher J. Trop Dis Res Ctr Kitwe Zambia Ndola Cent Hosp Kitwe Zambia Mines Hosp Kitwe Zambia Africa Malria Network Trust Dar Es Salaam Tanzania

Background. Intermittent preventive treatment of malaria during pregnancy (IPTp) reduces placental infection, maternal anemia, and low birth weight (LBW). However, the optimal dosing regimen in settings in which human immunodeficiency virus (HIV) is highly prevalent among pregnant women remains controversial. Methods. We conducted a randomized, double-blind, placebo-controlled study of IPTp comparing the standard 2-dose sulfadoxine-pyrimethamine (SP) regimen with monthly IPTp among a cohort of HIV-positive pregnant Zambian women. Primary outcomes included placental malaria (by smear and histology) and maternal peripheral parasitemia at delivery. Results. There were no differences between monthly IPTp (n = 224) and standard IPTp (n = 232) in placental malaria by histopathology (26% vs. 29%;relative risk [RR], 0.90 [95% confidence interval {CI}, 0.64-1.26]) or placental parasitemia (2% vs. 4%;RR, 0.55 [95% CI, 0.17-1.79]). There also were no differences in maternal anemia, stillbirths, preterm delivery, LBW, or all-cause mortality of infants at 6 weeks. Conclusions. In an area of mesoendemicity in Zambia, monthly SP IPTp was not more efficacious than the standard 2-dose regimen for the prevention of placental malaria or adverse birth outcomes. IPTp policy recommendations need to take into account local malaria transmission patterns and the prevalence of HIV. Trial registration. ClinicalTrials. gov identifier: NCT00270530.

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CD28-B7-mediated T cell costimulation in chronic cardiac allograft rejection -: Differential role of B7-1 in initiation versus progression of graft arteriosclerosis

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AMERICAN JOURNAL OF PATHOLOGY 2001年第3期158卷 977-986页

作者： Kim, KS Denton, MD Chandraker, A Knoflach, A Milord, R Waaga, AM Turka, LA Russell, ME Peach, R Sayegh, MH Harvard Univ Brigham & Womens Hosp Sch Med Lab Immunogenet & TransplantatRenal Div Boston MA 02115 USA Univ Penn Dept Med Philadelphia PA 19104 USA Univ Penn Inst Human Gene Therapy Philadelphia PA 19104 USA Pochon CHA Univ Pundang CHA Gen Hosp Dept Internal Med Pochon South Korea Parexel Int Waltham MA USA Bristol Myers Squibb Co Pharmaceut Res Inst Princeton NJ 08543 USA

Provision of adequate T cell costimulation is critical for the development of acute and chronic allograft rejection. We have previously reported that early blockade of CD28-B7 T cell costimulation prevents the development of graft arteriosclerosis, in the LEW into F344 rat cardiac transplant model. In this study, we used the same model to examine the requirement for CD28-B7-mediated T cell costimulation in the progression of established chronic rejection and examined the individual roles of B7-1 (CD80) and B7-2 (CD86) costimulatory molecules. Late blockade of CD28-B7 T cell costimulation by the fusion protein CTLA4Ig, which binds both CD80 and CD86, attenuated the development of transplant arteriosclerosis, mononuclear cell infiltration, and parenchymal fibrosis in this model. Selective blockade of CD80 using the mutant fusion protein Y100F mas as effective as CTLA4Ig in this regard. In contrast to CTLA4Ig, blockade of CD80 alone by Y100F was ineffective at preventing early graft loss and prolonging graft survival when given early after transplantation. This study is the first to demonstrate that late blockade of CD28-B7 T cell costimulation interrupts chronic cardiac allograft rejection, and it indicates the importance of continued T cell activation in this process. This study further defines functional differences between CD80 and CD86 costimulatory molecules in vivo.

关键词：抗原 CD 抗原 CD28/免疫学抗原 CD80/免疫学抗原分化/投药和剂量抗原分化/遗传学抗原分化/治疗应用 CD4阳性T淋巴细胞/药物作用 CD4阳性T淋巴细胞/免疫学颈动脉损伤/病因学颈动脉损伤/病理学细胞分裂冠状动脉疾病/病因学冠状动脉疾病/病理学冠状血管/病理学用药计划表纤维化/病理学移植物排斥/药物疗法移植物排斥/免疫学移植物排斥/病理学移植物存活免疫轭合物免疫抑制剂/投药和剂量免疫抑制剂/治疗应用淋巴细胞活化/药物作用突变心肌/病理学大鼠 Sprague-Dawley 时间因素移植同种血管内膜/病理学动物男(雄)性大鼠

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LONG-TERM PREDNISONE FOLLOWED BY THYMECTOMY IN MYASTHENIA-GRAVIS

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ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 1976年第MAY28期274卷 608-622页

作者： MANN, JD JOHNS, TR CAMPA, JF MULLER, WH UNIV VIRGINIA SCH MEDDEPT NEUROLCHARLOTTESVILLEVA 22904 UNIV VIRGINIA SCH MEDDEPT SURGCHARLOTTESVILLEVA 22904

The present series of thirty patients has led us to certain conclusions concerning the management and treatment of patients with myasthenia gravis. The use of cholinesterase inhibitors alone is reserved for those patients with purely ocular myasthenia whose deficits can be satisfactorily corrected with those agents. Some of those with ocular involvement may be disabled; and in light of our excellent results with that small group, as well as similar findings presented by Fischer et al., patients with disabling or refractory ocular myasthenia should be considered for treatment with prednisone. All other patients with myasthenia are given a course of oral corticosteroids (prednisone) initially at high doses, with subsequent tapering to maintenance, alternate-day low-dose therapy. Cholinesterase inhibitors are used as needed while the patient is receiving corticosteroids. We now anticipate that patients will exhibit sustained improvement within the first two weeks, reaching maximal improvement at about three months. Exacerbations of myasthenic weakness may occur in the early phases of treatment. Such exacerbations have been commonly mild and occur with a mean onset at 5 days, and have a mean duration of 6 days. Most patients have been able to tolerate an alternate-day schedule of prednisone therapy when maintenance levels were achieved. The effective maintenance dose has been determined as the smallest dose of prednisone which allows the patient to maintain maximal improvement. Following the establishment of maximal improvement, patients have been considered for thymectomy. In our experience, the sternum-splitting procedure has been tolerated extremely well by patients exhibiting marked imporvement or remission while on corticosteroids. In those patients where thymectomy is contraindicated, irradiation of the thymus might be considered. Patients are continued on maintenance steroid therapy following surgery for a period of time that has been arbitrary. Currently, we con

关键词：胆碱酯酶抑制剂/治疗应用用药计划表眼疾病/药物疗法眼疾病/治疗重症肌无力/药物疗法重症肌无力/治疗泼尼松/投药和剂量泼尼松/副作用泼尼松/治疗应用胸腺切除术青少年成年人老年人女(雌)性人类男(雄)性中年人

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Improvement in endothelial function by angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 1999年第6期33卷 1506-1511页

作者： O'Driscoll, G Green, D Maiorana, A Stanton, K Colreavy, F Taylor, R Univ Western Australia Dept Human Movement Nedlands WA 6907 Australia Univ Western Australia Dept Med Nedlands WA 6009 Australia Royal Perth Hosp Dept Cardiol Endocrinol Nedlands WA Australia Royal Perth Hosp Dept Diabet Nedlands WA Australia

OBJECTIVES The aim of this study was to assess the effect. of angiotensin-converting enzyme (ACE) inhibition with enalapril on forearm endothelial function in subjects with type II diabetes. BACKGROUND Endothelial function is depressed in the presence of conventional risk factors for atherosclerosis, and various therapies, such as lipid-lowering therapy in hypercholesterolemia, can improve endothelial-mediated vasodilatian. ACE inhibition has improved such function in several conditions including type I diabetes, but there is no evidence for a beneficial effect in type II diabetes. METHODS The influence of enalapril (10 mg twice daily for 4 weeks) on endothelium-dependent and -independent vasodilator function was determined in 10 type ii diabetic subjects using a. double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gage plethysmography and graded intrabrachial infusion of acetylcholine (ACh), N-G-monomethyl-L-arginine (LNMMA) and sodium nitroprusside (SNP). RESULTS Enalapril increased the response to the endothelium-dependent vasodilator, ACh (p < 0.02) and the vasoconstrictor response to the nitric oxide (NO) synthase inhibitor, LNMMA (p < 0.002). No difference was evident in the response to SNP. CONCLUSIONS In type II diabetic subjects without evidence of vascular disease, the ACE inhibitor enalapril improved stimulated and basal NO-dependent endothelial function. The study extends the Spectrum of beneficial effects demonstrated to result from ACE inhibition in diabetes. (C) 1999 by the American College of Cardiology.

关键词：乙酰胆碱血管紧张素转换酶抑制药/投药和剂量血管紧张素转换酶抑制药/副作用血流速度/药物作用血流速度/生理学糖尿病 2型/药物疗法糖尿病 2型/病理生理学糖尿病血管病变/药物疗法糖尿病血管病变/病理生理学剂量效应关系药物双盲法用药计划表依那普利/投药和剂量依那普利/副作用内皮血管/药物作用内皮血管/病理生理学前臂/血液供给硝普钠 ωN-甲基精氨酸老年人人类中年人

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Abciximab reduces mortality in diabetics following percutaneous coronary intervention

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第4期35卷 922-928页

作者： Bhatt, DL Marso, SP Lincoff, AM Wolski, KE Ellis, SG Topol, EJ Cleveland Clin Fdn Dept Cardiol Cleveland OH 44195 USA

OBJECTIVES We sought to determine whether abciximab therapy at the time of percutaneous coronary intervention (PCI) would favorably affect one-year mortality in patients with diabetes. BACKGROUND Diabetics are known to have increased late mortality following PCI. METHODS Data from three placebo-controlled trials of PCI, EPIC, EPILOG, and EPISTENT, were pooled. The one-year mortality rate for patients with a clinical diagnosis of diabetes mellitus was compared with the rate for nondiabetic patients treated with either abciximab or placebo. RESULTS In the 1,462 diabetic patients, abciximab decreased the mortality from 4.5% to 2.5%, p = 0.031, and in the 5,072 nondiabetic patients, from 2.6% to 1.9%, p = 0.099. In patients with the clinical syndrome of insulin resistance-defined as diabetes, hypertension, and obesity-mortality was reduced by abciximab treatment from 5.1% to 2.3%, p = 0.044. The beneficial reduction in mortality with abciximab use in diabetics classified as insulin-requiring was from 8.1% to 4.2%, p = 0.073. Mortality in diabetics who underwent multivessel intervention was reduced from 7.7% to 0.9% with use of abciximab, p = 0.018. In a Cox proportional hazards survival model, the risk ratio for mortality with abciximab use compared with placebo was 0.642 (95% confidence interval 0.458-0.900, p = 0.010). CONCLUSIONS Abciximab decreases the mortality of diabetic patients to the level of placebo-treated nondiabetic patients. This beneficial effect is noteworthy in those diabetic patients who are also hypertensive and obese and in diabetics undergoing multivessel intervention. Besides its potential role in reducing repeat intervention for stented diabetic patients, abciximab therapy should be strongly considered in diabetic patients undergoing PCI to improve their survival. (C) 2000 by the American College of Cardiology.

关键词：心绞痛不稳定型/死亡率心绞痛不稳定型/治疗血管成形术气囊冠状动脉抗体单克隆/副作用抗体单克隆/治疗应用糖尿病血管病变/死亡率糖尿病血管病变/治疗剂量效应关系药物用药计划表随访研究免疫球蛋白Fab片段/副作用免疫球蛋白Fab片段/治疗应用心肌梗死/死亡率心肌梗死/治疗血小板聚集抑制剂/副作用血小板聚集抑制剂/治疗应用血小板糖蛋白GPⅡb-Ⅲa复合物/拮抗剂和抑制剂随机对照试验(主题) 复发危险因素支架存活率成年人老年人女(雌)性人类男(雄)性中年人

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An evaluation of intermittent therapies used to treat onychomycosis and other dermatomycoses with the oral antifungal agents

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INTERNATIONAL JOURNAL OF DERMATOLOGY 2000年第6期39卷 401-411页

作者： Gupta, AK Del Rosso, JQ Sunnybrook & Womens Coll Hlth Sci Ctr Dept Med Div Dermatol Toronto ON Canada Univ Toronto Toronto ON Canada Univ Nevada Sch Med Dept Dermatol Las Vegas NV 89154 USA

Evaluates the effectiveness of oral antifungal agents for treating onychomycosis and other dermatomycoses. Griseofulvin; Ketoconazole; Itraconazole; Fluconazole; Terbinafine.

关键词：投药口服抗真菌药/投药和剂量临床试验(主题) 皮肤真菌病/药物疗法用药计划表氟康唑/投药和剂量灰黄霉素/投药和剂量伊曲康唑/投药和剂量酮康唑/投药和剂量萘类/投药和剂量甲癣/药物疗法人类

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The management of cancer pain

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CA-A CANCER JOURNAL FOR CLINICIANS 2000年第2期50卷 70-116页

作者： Cherny, NI Shaare Zedek Med Ctr Dept Med Oncol Jerusalem Israel

Any therapeutic strategy developed for patients experiencing cancer pain depends on the goals of care, which can be broadly categorized as prolonging survival, optimizing comfort, and optimizing function. The relative priority of these goals for any individual should direct therapeutic decision-making. By combining primary treatments, systemic analgesic agents, and other techniques, most cancer patients can achieve satisfactory relief of pain. In cases where pain appears refractory to these interventions, invasive anesthetic or neurosurgical maneuvers may be necessary, and sedation may be offered to those with unrelieved pain at the end of life. The principles of analgesic therapy are presented, as well as the practical issues involved in drug administration, ranging from calculating dosage to adverse effects, and, when necessary, how to switch and/or combine therapies. Adjuvant analgesics, which are drugs indicated for purposes other than relief of pain but which may have analgesic effects, are also listed and discussed in some detail. Surgical and neurodestructive techniques, such as rhizotomy or cordotomy, although not frequently required or performed, represent yet other options for patients with unremitting pain and diminished hope of relief. Although cancer pain can be a complex medical problem arising from multiple sources, patients should be assured that suffering is not inevitable and that relief is attainable.

关键词：肾上腺皮质激素类/投药和剂量抗菌药/投药和剂量消炎药非甾类/投药和剂量消炎药非甾类/副作用抗肿瘤药/投药和剂量中枢神经系统抑制药/投药和剂量剂型投药途径用药计划表肾疾病/并发症肝疾病/并发症肿瘤/并发症肿瘤/外科学肿瘤/治疗神经传导阻滞/方法疼痛/病因学疼痛管理病人遴选物质相关性障碍/预防和控制人类

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Randomization-based methods for correcting for treatment changes: Examples from the Concorde trial

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STATISTICS IN MEDICINE 1999年第19期18卷 2617-2634页

作者： White, IR Babiker, AG Walker, S Darbyshire, JH Univ London London Sch Hyg & Trop Med Med Stat Unit London WC1E 7HT England UCL Sch Med MRC HIV Clin Trials CtrMortimer Market Ctr London WC1E 6AU England

We develop analysis methods for clinical trials with time-to-event outcomes which correct for treatment changes during follow-up, yet are based on comparisons of randomized groups and not of selected groups. A causal model relating observed event times to event times that would have been observed under other treatment scenarios is fitted using the semi-parametric approach of Robins and Tsiatis (avoiding assumptions about the relationship between treatment changes and prognosis). The methods are applied to the Concorde trial of immediate versus deferred zidovudine, to investigate how the results would have differed if no participant randomized to deferred zidovudine had started treatment before reaching ARC or AIDS. We consider issues relating to model choice, non-constant treatment effects and censoring. Copyright (C) 1999 John Wiley & Sons, Ltd.

关键词：抗HIV药/投药和剂量抗HIV药/治疗应用数据说明统计疾病恶化用药计划表 HIV感染/药物疗法模型统计学随机对照试验(主题) 研究设计齐多夫定/投药和剂量齐多夫定/治疗应用人类

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Chemoradiation for carcinoma of the cervix: Advances and opportunities

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RADIATION RESEARCH 2000年第3期154卷 229-236页

作者： Eifel, PJ Univ Texas MD Anderson Canc Ctr Div Radiat Oncol Houston TX 77030 USA

Although it is possible to cure many patients with locally advanced cervical canter using radiation therapy alone, locoregional relapse continues to be a component of most recurrences. To improve control rates, clinicians have investigated ways of combining chemotherapy and radiation for more than 30 years. Despite encouraging results from phase II trials of neoadjuvant chemotherapy, randomized trials failed to improve on the results with radiation therapy alone. For a number of reasons, early trials of concurrent chemoradiation were inconclusive. However, recent reports of five large prospective randomized trials demonstrated dramatic improvements in survival and local control rates when cisplatin-containing chemotherapy was given during radiation therapy. These results also suggest a number of avenues for future research, (C) 2000 by Radiation Research Society.

关键词：抗肿瘤联合化疗方案/治疗应用博来霉素/投药和剂量癌鳞状细胞/药物疗法癌鳞状细胞/死亡率癌鳞状细胞/放射疗法癌鳞状细胞/治疗化学疗法辅助顺铂/投药和剂量综合疗法用药计划表氟尿嘧啶/投药和剂量头颈部肿瘤/药物疗法头颈部肿瘤/放射疗法羟基脲/投药和剂量子宫切除术肺肿瘤/药物疗法肺肿瘤/放射疗法丝裂霉素/投药和剂量前瞻性研究辐射耐受性辐射增敏药/投药和剂量随机对照试验(主题) 存活率治疗结果宫颈肿瘤/药物疗法宫颈肿瘤/死亡率宫颈肿瘤/放射疗法宫颈肿瘤/治疗长春新碱/投药和剂量女(雌)性人类

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