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Randomized trial of candesartan cilexetil in the treatment of patients with congestive heart failure and a history of intolerance to angiotensin-converting enzyme inhibitors

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AMERICAN HEART JOURNAL 2000年第4期139卷 609-617页

作者： Granger, CB Ertl, G Kuch, J Maggioni, AP McMurray, J Rouleau, JL Stevenson, LW Swedberg, K Young, J Yusuf, S Califf, RM Bart, BA Held, P Michelson, EL Sellers, MA Ohlin, G Sparapani, R Pfeffer, MA Duke Clin Res Inst Durham NC USA Med Univ Klin Mannheim Heidelberg Germany Warsaw Univ Sch Med Warsaw Poland Mario Negri Inst Pharmacol Res I-20157 Milan Italy Univ Glasgow Glasgow G12 8QQ Lanark Scotland Montreal Heart Inst Montreal PQ H1T 1C8 Canada Brigham & Womens Hosp Boston MA 02115 USA Univ Gothenburg Gothenburg Sweden Cleveland Clin Fdn Cleveland OH 44195 USA McMaster Univ Hamilton ON Canada Astra Hassle AB Molndal Sweden Astra Merck Pharmaceut Inc Wayne PA USA

Background Many patients with congestive heart failure do not receive the benefits of angiotensin-converting enzyme (ACE) inhibitors because of intolerance. We sought to determine the tolerability of an angiotensin II receptor blocker, candesartan cilexetil, among patients considered intolerant of ACE inhibitors. Methods patients with CHF, left ventricular ejection Fraction less than 35%, and history of discontinuing an ACE inhibitor because of intolerance underwent double-blind randomization in a 2:1 ratio to receive candesartan (n = 179) or a placebo (n = 91). The initial dosage of candesartan was 4 mg/d;the dosage was increased to 16 mg/d if the drug was tolerated. A history of intolerance of ACE inhibitor was attributed to cough (67% of patients), hypotension (15%), or renal dysfunction (11%). Results The study drug was continued for 12 weeks by 82.7% of patients who received candesartan versus 86.8% of patients who received the placebo. This 4.1% greater discontinuation rate with active therapy was not significant;the 95% confidence interval ranged from 4.8% more discontinuation with placebo to 13% more with candesartan. Titration to the 16 mg target dose was possible for 69% of patients who received candesartan versus 84% of those who received the placebo. Frequencies of death and morbidity were not significantly different between the candesartan and placebo groups (death 3.4% and 3.3%, worsening heart failure 8.4% and 13.2%, myocardial infarction 2.8% and 5.5%, all-cause hospitalization 12.8% and 18.7%, and death or hospitalization for heart failure 11.7% and 14.3%). Conclusions Candesartan was well tolerated by this population. The effect of candesartan on major clinical end points, including death, remains to be determined.

关键词：血管紧张素转换酶抑制药/治疗应用抗高血压药/治疗应用苯咪唑类/治疗应用联苯化合物/治疗应用死亡原因剂量效应关系药物双盲法用药计划表心力衰竭/诊断心力衰竭/药物疗法心力衰竭/死亡率血流动力学/药物作用试点项目存活率四唑类心室功能障碍左/诊断心室功能障碍左/药物疗法心室功能左/药物作用老年人女(雌)性人类男(雄)性中年人

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Criteria for failed labor induction: Prospective evaluation of a standardized protocol

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OBSTETRICS AND GYNECOLOGY 2000年第5期96卷 671-677页

作者： Rouse, DJ Owen, J Hauth, JC Univ Alabama Birmingham Dept Obstet & Gynecol Ctr Res Womens Hlth Birmingham AL 35294 USA

Objective: To assess the safety and efficacy of a protocol that mandated at least 12 hours of oxytocin administration after membrane rupture before cesarean delivery far failed labor induction in the latent phase. Methods: Gravidas at or beyond 36 weeks' gestation undergoing indicated induction with cervical dilatation up to 2 cm were studied prospectively. Prior cesarean was aln exclusion criterion. If the fetal heart rate pattern was reassuring, cesarean was not permitted before the active phase of labor (4-cm dilatation and at least 90% effacement or 5-cm dilatation regardless of effacement) unless the membranes had been ruptured and oxytocin administered for at least 12 hours. Results: Five hundred nine women were treated according to protocol;360 (71%) were nulliparas and 149 (29%) were parous. Twenty-five percent of nulliparas and 9% of parous women were delivered by cesarean. After 6 hours of ruptured membranes and oxytocin, 14% of nulliparas were still in the latent phase;39% of whom delivered vaginally, compared with 7% still in the latent phase after 9 hours (vaginal delivery rate 28%), and 4% after 12 hours (vaginal delivery rate 13%). In contrast, after 6 hours of ruptured membranes and oxytocin, only five (3%) parous women were still in the latent phase. Among those, none remained in the latent phase for 12 hours and all were delivered vaginally. No women had serious complications. Severe neonatal morbidities were infrequent and not related to duration of the latent phase. Conclusion: By requiring a minimum of 12 hours of oxytocin after membrane rupture before failed labor induction could be diagnosed, many nulliparas who remained in the latent phase at 6 and 9 hours had safe vaginal deliveries, and failed labor induction was eliminated as an indication for cesarean in parous women. (Obstet Gynecol 2000;916: 671-7. (C) 2000 by The American College of Obstetricians and Gynecologists).

关键词：剖宫产术临床方案/标准用药计划表分娩发动/药物作用引产/方法引产/标准催产素/投药和剂量妊娠结局前瞻性研究时间因素子宫收缩松解药成年人女(雌)性人类婴儿新生妊娠

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Recombinant hirudin (lepirudin) for the improvement of thrombolysis with streptokinase in patients with acute myocardial infarction -: Results of the HIT-4 trial

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 1999年第4期34卷 966-973页

作者： Neuhaus, KL Molhoek, GP Zeymer, U Tebbe, U Wegscheider, K Schröder, R Camez, A Laarman, GJ Grollier, GR Lok, DJA Kuckuck, H Lazarus, P Stadt Kliniken Kassel Med Klin 2 D-34125 Kassel Germany Med Spectrum Enschede Twente Netherlands Klinikum Lippe Detmold Detmold Germany Free Univ Berlin Klinikum Benjamin Franklin D-12200 Berlin Germany Behringwerke AG D-3550 Marburg Germany Onze Lieve Vrouw Hosp Amsterdam Netherlands CHU Caen F-14000 Caen France Deventer Ziekenhuis Deventer Netherlands Wenckebach Krankenhaus Berlin Germany Klinikum Schwerin Schwerin Germany

OBJECTIVES The purpose of this study was to compare recombinant hirudin and heparin as adjuncts to streptokinase thrombolysis in patients with acute myocardial infarction (AMI). BACKGROUND Experimental studies and previous small clinical trials suggest that specific thrombin inhibition improves early patency rates and clinical outcome in patients treated with streptokinase. METHODS In a randomized double-blind, multicenter trial, 1,208 patients with AMI less than or equal to 6 h were treated with aspirin and streptokinase and randomized to receive recombinant hirudin (lepirudin, IV bolus of 0.2 mg/kg, followed by subcutaneous (SC) injections of 0.5 mg/kg b.i.d. for 5 to 7 days) or heparin (IV placebo bolus, followed by SC injections of 12,500 IU b.i.d. for 5 to 7 days). A total of 447 patients were included in the angiographic substudy in which the primary end point, 90-min Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 of the jnfarct-related artery, was evaluated, while the other two-thirds served as "safety group" in which only clinical end points were evaluated. As an additional efficacy parameter the ST-segment resolution at 90 and 180 min was measured in may patients. RESULTS TIMI flow grade 5 was observed in 40.7% in the lepirudin and in 33.5% in the heparin group (p = 0.16), respectively. In the entire study population the proportion of patients with complete ST resolution at 90 min (28% vs. 22%, p = 0.05) and at 180 min (52% vs. 48%, p = 0.18) after start of therapy tended to be higher in the lepirtdin group. There was no significant difference in the incidence of hemorrhagic stroke (0.2% vs. 0.3%) or total stroke (1.2% vs. 1.5%), reinfarction rate (4.6% vs. 5.1%) and total mortality rate (6.8% vs. 6.4%) at 30 days, as well as the combined end point of death, nonfatal stroke, nonfatal reinfarction, rescue-percutaneous transluminal coronary angioplasty and refractory angina (22.7 vs. 24.3%) were not statistically different between the two groups. C

关键词：抗凝药/副作用抗凝药/治疗应用剂量效应关系药物双盲法用药计划表心电描记术/药物作用纤维蛋白溶解药/副作用纤维蛋白溶解药/治疗应用肝素/副作用肝素/治疗应用水蛭素疗法水蛭素类/副作用水蛭素类/类似物和衍生物输注静脉内注射皮下心肌梗死/药物疗法心肌梗死/死亡率前瞻性研究重组蛋白质类/副作用重组蛋白质类/治疗应用复发链激酶/副作用链激酶/治疗应用存活率血栓溶解疗法治疗结果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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Tissue factor pathway inhibitor dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia

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BLOOD 2000年第4期95卷 1124-1129页

作者： de Jonge, E Dekkers, PEP Creasey, AA Hack, CE Paulson, SK Karim, A Kesecioglu, J Levi, M van Deventer, SJH van der Poll, T Univ Amsterdam Dept Intens Care Acad Med CtrLab Expt Internal Med Cent LabRed Cross Blood Transfus Serv NL-1100 DD Amsterdam Netherlands Univ Amsterdam Dept Vasc Med Acad Med Ctr Cent LabRed Cross Blood Transfus Serv NL-1100 DD Amsterdam Netherlands

Inhibition of the tissue factor pathway has been shown to attenuate the activation of coagulation and to prevent death In a gram-negative bacteremia primate model of sepsis, It has been suggested that tissue factor influences inflammatory cascades other than the coagulation system. The authors sought to determine the effects of 2 different doses of recombinant tissue factor pathway inhibitor (TFPI) on endotoxin-induced coagulant, fibrinolytic, and cytokine responses in healthy humans. Two groups, each consisting of 8 healthy men, were studied in a double-blind, randomized, placebo-controlled crossover study. Subjects were studied on 2 different occasions. They received a bolus intravenous injection of 4 ng/kg endotoxin, which was followed by a 6-hour continuous infusion of TFPI or placebo. Eight subjects received 0.05 mg/kg per hour TFPI after a bolus of 0.0125 mg/kg (tow-dose group), and 8 subjects received 0.2 mg/kg per hour after a bolus of 0.05 mg/kg (high-dose group). Endotoxin injection induced the activation of coagulation, the activation and subsequent inhibition of fibrinolysis, and the release of proinflammatory and antiinflammatory cytokines. TFPI infusion induced a dose-dependent attenuation of thrombin generation, as measured by plasma F1 + 2 and thrombin-antithrombin complexes, with a complete blockade of coagulation activation after high-dose TFPI. Endotoxin-induced changes in the fibrinolytic system and cytokine levels were not altered by either low-dose or high-dose TFPI, The authors concluded that TFPI effectively and dose-dependently attenuates the endotoxin-induced coagulation activation in humans without influencing the fibrinolytic and cytokine response.

关键词：抗凝药/投药和剂量抗凝药/药理学抗凝血酶Ⅲ/代谢血液凝固/药物作用血压/药物作用体温/药物作用交叉研究细胞因子类/血液双盲法用药计划表内毒素血症/血液内毒素血症/药物疗法内毒素血症/免疫学大肠杆菌感染/血液大肠杆菌感染/药物疗法大肠杆菌感染/免疫学纤维蛋白溶解/药物作用心率/药物作用输注静脉内注射静脉内脂多糖类/投药和剂量脂蛋白类/投药和剂量脂蛋白类/药理学肽水解酶类/代谢纤溶酶原激活物抑制物1/血液成年人人类男(雄)性

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AlloDerm tympanoplasty of tympanic membrane perforations

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AMERICAN JOURNAL OF OTOLARYNGOLOGY 2003年第1期24卷 6-13页

作者： Downey, TJ Champeaux, AL Silva, AB Madigan Army Med Ctr Dept Otolaryngol Head & Neck Surg Ft Lewis WA 98431 USA Madigan Army Med Ctr Dept Pathol Tacoma WA 98431 USA

Purpose: To study the effectiveness of AlloDerm (LifeCell Corporation, Branchburg, NJ) as a graft material in underlay tympanoplasty by comparison to autologous fascia in a chronic tympanic membrane perforation animal model. Materials and Methods: Seventeen chinchillas underwent creation of bilateral chronic tympanic membrane perforations over a 6-week period. Twenty-two stable perforations were divided equally between the experimental AlloDerm and control fascia graft groups. The grafts were surgically placed through a postauricular tympanomeatal flap. The tympanic membranes were examined at 4 and 10 weeks and then harvested for histopathological analysis. Tympanoplasty operative times, perforation closure rates, and gross and histological analyses were compared between the AlloDerm and fascia grafts. Results: A statistically significant difference in mean surgical time was recorded between the AlloDerm (47 minutes) and fascia (68 minutes) grafting procedures (t test, P =.001). Perforation closure was achieved in 90% of the AlloDerm and 100% of the fascia treated tympanic membranes. Gross and histopathologic inspections revealed no significant differences. Microscopically, AlloDerm and fascia grafts had similar inflammatory responses, but AlloDerm showed increased fibroblast infiltration and neovascularization. Conclusion: The avoidance of donor site morbidity, reduction of surgical time, and excellent gross and histologic outcomes in this animal model reveal that AlloDerm could be a safe, cost-effective alternative to autologous fascia. Further study would be necessary in human clinical trials.

关键词：抗感染药泌尿系/治疗应用毛丝鼠属胶原用药计划表复方合剂筋膜/移植磺胺嘧啶/治疗应用时间因素甲氧苄啶/治疗应用鼓膜穿孔/药物疗法鼓膜穿孔/外科学鼓室成形术/方法动物女(雌)性

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Simplification of protease inhibitor-containing regimens with efavirenz, nevirapine or abacavir: safety and efficacy outcomes

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ANTIVIRAL THERAPY 2003年第1期8卷 27-35页

作者： Chiesa, E Bini, T Adorni, F Capetti, A Rizzardini, G Faggion, I Mussini, C Sollima, S Melzi, S Bongiovanni, M Tordato, F Cicconi, P Castelnuovo, B Rusconi, S Monforte, AD Univ Milan Inst Infect Dis & Trop Med Milan Italy CNR ITBA Milan Italy L Sacco Hosp Vialba Div Infect Dis 1 Milan Italy Univ Modena Clin Infect Dis I-41100 Modena Italy

Objective: To describe the immunological and virological outcome, and the factors associated to discontinuation in patients switching to a regimen containing efavirenz (EFV), nevirapine (NVP) or abacavir (ABC) after long-term viral suppression under protease inhibitor-including HAART. Design: Observational study at three outpatient clinics for HIV care in Italy. Methods: Patients with HIV RNA <80 copies/ml and CD4 >200 cells/ml for at least 6 months on a protease inhibitor-containing treatment who switched to NVP, EFV or ABC were included in the study. End-points were immunological failure, virological failure and discontinuation due to toxicity. Survival analyses were performed to find out any independent variables predictive of reaching the end-points. Results: 177 patients were enrolled;85 started EFV, 54 NVP and 38 ABC as part of the simplification regimen. 16/159 patients experienced immunological failure: the variables associated to CD4 count decrease were HIV RNA set point value (HR 2.32 for each log(10) copies more, P=0.040) and intolerance/toxicity as reason for simplification (HR 3.96, P=0.05). 13/151 subjects showed virological failure;an AIDS diagnosis (HR 6.04, P=0.021) and the use of NVP (HR 7.98, P=0.027) were associated to a worse virological outcome, while patients naive before HAART showed a lower risk of failure (HR 0.008, P=0.007). 16/177 patients discontinued simplification regimen due to toxicity;longer HAART duration before switch was associated to risk reduction (HR 0.92, P=0.004). Conclusions: Simplification is safe and effective, but it should be offered to patients with shorter treatment duration, and in good clinical and immunovirological conditions.

关键词：抗逆转录病毒治疗高效苯并恶嗪类 CD4淋巴细胞计数双脱氧核苷类/副作用用药计划表药物疗法联合 HIV感染/药物疗法 HIV感染/病毒学 HIV蛋白酶抑制药/副作用 HIV-1/生理学奈韦拉平/副作用恶嗪类/副作用 RNA 病毒/血液回顾性研究逆转录酶抑制剂/副作用治疗结果人类

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Therapeutic strategies in the management of patients with chronic hepatitis B virus infection

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LANCET INFECTIOUS DISEASES 2008年第3期8卷 167-178页

作者： Popotheodoridis, George V. Manolakopoulos, Spilios Dusheiko, Geoffrey Archimandritis, Athanasios J. Univ Athens Sch Med Hippokratio Gen Hosp Dept Internal Med 2 GR-11527 Athens Greece UCL Royal Free & Univ Coll Med Sch Dept Med London WC1E 6BT England

Currently available options for the treatment of chronic hepatitis B virus (HBV) infection include standard and pegylated interferon alfa and four oral antiviral agents (lamivudine, adefovir, entecavir, and telbivudine). These treatment strategies are either therapies of finite duration that aim to achieve sustained off-therapy responses, or long-term treatments that aim to maintain on-therapy remission. Pegylated interferon alfa may offer higher sustained off-therapy responses after 1 year, but most patients do not respond. Oral antivirals are the only candidates for long-term treatment of patients with chronic HBV infection. Viral suppression has favourable effects on patients' outcome and modifies the natural history of the disease. Viral resistance is the main drawback of long-term antiviral therapy. Lamivudine monotherapy is associated with higher resistance (year 1, 10-27%;year 2, 37-48%;year 4, 60-65%) than adefovir (year 1, 0%;year 2, 3%;year 5, 29%) or telbivudine (year 1, 3-4%;year 2, 9-22%). Entecavir resistance is rare in naive individuals (year 4, <1%), but increases over time in lamivudine-resistant patients (year 4, 43%). The best strategy for long-term therapy in chronic HBV infection has yet to be established.

关键词： Adjuvants Immunologic Administration Oral Algorithms Antiviral Agents 佐剂免疫投药口服算法抗病毒药用药计划表肝炎乙型慢性干扰素α entecavir Chronic Hepatitis B Patients Hepatitis B virus Antiviral Agents pegylated interferon alfa Long Term Care Lamivudine algorithms adefovir Simian B disease Mouth telbivudine

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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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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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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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