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Improving management of type 2 diabetes mellitus: 3. Sulfonylureas

HOSPITAL PRACTICE 1999年第12期34卷 129-+页

作者： Samraj, GPN Quillen, DM Kuritzky, L Univ Florida Coll Med Dept Community Hlth & Family Practice Gainesville FL 32611 USA

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关键词：糖尿病 2型/药物疗法用药计划表药物相互作用药物疗法联合降血糖药/投药和剂量磺酰脲化合物/投药和剂量磺酰脲化合物/药代动力学治疗失败人类

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VIDARABINE THERAPY OF COMPLICATED HERPES-SIMPLEX KERATITIS

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AMERICAN JOURNAL OF OPHTHALMOLOGY 1976年第5期81卷 642-649页

作者： ODAY, DM POIRIER, RH JONES, DB ELLIOTT, JH VANDERBILT UNIV SCH MEDDEPT OPHTALMOLNASHVILLETN 37232 UNIV TEXAS SCH MEDDIV OPHTALMOLSAN ANTONIOTX 78284 BAYLOR UNIV COLL MED DEPT OPHTHALMOLHOUSTONTX

Patients with active herpetic epithelial keratitis who had toxic reactions or were resistant to idoxuridine received vidarabine. Only one of 35 cases of herpetic epithelial keratitis without stromal disease failed to heal. Of 21 patients with active epithelial keratitis complicating stromal keratitis or uveitis, 11 had complete reepithelialization by day 14. 2 Patients were removed from the trial as treatment failures. The remaining cases healed in 21 to 48 days. In most instances, the stromal keratitis was inactivated when the epithelial ulcer healed. In the authors' patients treated with vidarabine, healing of herpes simplex epithelial ulcers was biphasic: Stage 1, progression from an active to an inactive viral ulcer, and Stage 2, complete reepithelialization.

关键词：肾上腺皮质激素类/治疗应用角膜溃疡/药物疗法用药计划表抗药性微生物药物疗法联合碘苷/治疗应用角膜炎树枝状/药物疗法软膏嘌呤核苷类/治疗应用葡萄膜炎/药物疗法阿糖腺苷/治疗应用伤口愈合/药物作用人类

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Medication adherence in chronic disease: Issues in posttransplant immunosuppression

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TRANSPLANTATION PROCEEDINGS 2007年第5期39卷 1287-1300页

作者： Hansen, R. Seifeldin, R. Noe, L. Hlth Econ Ovat Res Grp San Francisco CA 94105 USA Astellas Pharma US Inc Hlth Econ & Outcomes Res Deerfield IL USA

Poor medication adherence is a widespread problem that undermines the potential benefits of medical treatment. Typical adherence rates among chronic disease patients are approximately 50%, and these low adherence rates have a substantial economic impact, estimated at $100 to $300 billion annually. Nonadherence to immunosuppressants among transplant recipients is surprisingly frequent, and the consequences are serious. Among adult renal transplant patients, the median rate of nonadherence is approximately 22% and is associated with acute rejection episodes and approximately 36% of all graft losses. In the United States, nonadherence results in an estimated 903 episodes of acute rejection and 1319 renal transplants failures annually, costing approximately $15 million and $100 million, respectively. Drug regimen complexity is known to impact adherence. Research demonstrates an inverse relationship between dosing frequency and medication adherence in various chronic diseases, with once-daily dosing resulting in the highest adherence rates. Reducing the dosing frequency may positively impact both clinical and patient-reported outcomes, as well as health care costs. However, the increased costs of less frequently administered drugs must be outweighed by the net savings achieved through improved adherence rates and better health outcomes. If trends among patients with chronic diseases apply, once-daily dosing regimens may improve adherence rates by approximately 6% to 14% among renal transplant patients and could substantially reduce the number of acute rejection episodes and graft failures, although the exact economic impact is difficult to estimate. Further research into adherence issues in transplant patients and the potential clinical and economic benefits of once-daily dosing of immunosuppressants is warranted.

关键词： Chronic Disease Drug Administration Schedule Humans Immunosuppressive Agents 慢性病用药计划表免疫抑制剂病人依从移植免疫学患者拒绝治疗 Medication Adherence Kidney Transplantation acute graft rejection Chronic Disease Immunosuppressive Agents Dosing Economic impact Drug Administration Schedule

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A comparison of cilostazol and pentoxifylline for treating intermittent claudication

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AMERICAN JOURNAL OF MEDICINE 2000年第7期109卷 523-530页

作者： Dawson, DL Cutler, BS Hiatt, WR Hobson, RW Martin, JD Bortey, EB Forbes, WP Strandness, DE Wilford Hall USAF Med Ctr Lackland AFB TX 78236 USA Univ Massachusetts Worcester MA 01605 USA Univ Colorado Hlth Sci Ctr Denver CO USA Univ Med & Dent New Jersey New Jersey Med Sch Newark NJ 07103 USA Otsuka Amer Pharmaceut Inc Rockville MD USA Univ Washington Seattle WA 98195 USA

PURPOSE: We performed a randomized, double-blind, placebo-controlled, multicenter trial to evaluate the relative efficacy and safety of cilostazol and pentoxifylline. PATIENTS AND METHODS: We enrolled patients with moderate-to-severe claudication from 54 outpatient vascular clinics, including sites at Air Force, Veterans Affairs, tertiary care, and university medical centers in the United States. Of 922 consenting patients, 698 met the inclusion criteria and were randomly assigned to blinded treatment with either cilostazol (100 mg orally twice a day), pentoxifylline (400 mg orally 3 times a day), or placebo. We measured maximal walking distance with constant-speed, variable-grade treadmill testing at baseline and at 4, 8, 12, 16, 20, and 24 weeks. RESULTS: Mean maximal walking distance of cilostazol-treated patients (n = 227) was significantly greater at every postbaseline visit compared with patients who received pentoxifylline (n = 232) or placebo (n = 239). After 24 weeks of treatment, mean maximal walking distance increased by a mean of 107 m (a mean percent increase of 54% from baseline) in the cilostazol group, significantly more than the 64-m improvement (a 30% mean percent increase) with pentoxifylline (P <0.001). The improvement with pentoxifylline was similar (P = 0.82) to that in the placebo group (65 m, a 34% mean percent increase). Deaths and serious adverse event rates were similar in each group. Side effects (including headache, palpitations, and diarrhea) were more common in the cilostazol-treated patients, but withdrawal rates were similar in the cilostazol (16%) and pentoxifylline (19%) groups. CONCLUSION: Cilostazol was significantly better than pentoxifylline or placebo for increasing walking distances in patients with intermittent claudication, but was associated with a greater frequency of minor side effects. Pentoxifylline and placebo had similar effects. Am J Med. 2000;109:523-530. (C) 2000 by Excerpta Medica, Inc.

关键词：双盲法用药计划表运动试验间歇性跛行/药物疗法己酮可可碱/投药和剂量己酮可可碱/治疗应用疾病严重程度指数四唑类/投药和剂量四唑类/治疗应用时间因素治疗结果血管舒张药/投药和剂量血管舒张药/治疗应用步行老年人女(雌)性人类男(雄)性中年人

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Determinants of angiotensin-converting enzyme inhibitor prescription in severe heart failure with left ventricular systolic dysfunction:: The EPICAL study

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AMERICAN HEART JOURNAL 2000年第4期139卷 624-631页

作者： Echemann, M Zannad, F Briançon, S Juillière, Y Mertès, PM Virion, JM Villemot, JP CHU CIC INSERM F-54035 Nancy France Hop Marin Serv Epidemiol & Evaluat Clin Nancy France Univ Henri Poincare Fac Med Pharmacol Clin Lorraine France

Background Angiotensin-converting enzyme (ACE) inhibitors have been demonstrated to reduce morbidity and mortality rates in patients with heart failure with left ventricular systolic dysfunction. Nevertheless, these drugs are underutilized in current practice and prescribed at doses below those usually recommended. The aim of this work was to identify the social, demographic, laboratory, clinical, and therapeutic factors associated with nonprescription of ACE inhibitors and/or their prescription at doses below those recommended in the treatment of severe long-term congestive heart failure (CHF). Methods and Results An epidemiologic observational study, EPICAL (EPidemiologie de l'Insuffisance Cardiaque Avancee en Lorraine), studied 417 patients with severe CHF surviving after the index hospitalization. Multivariate logistic regression determined the factors associated with ACE inhibitor nonprescription and with their prescription at lower-than-recommended doses. ACE inhibitors were taken by 75% of the patients but 38% took lower-than-recommended doses. Factors shown to be associated with nonprescription included patients >65 years of age with renal impairment (odds ratio 19.5, confidence interval [CI] 7.9-48.0), nonsinus cardiac rhythm (odds ratio 2.0, CI 1.2-3.2), and prescription of potassium-sparing diuretics (odds ratio 2.4, CI 1.2-4.7). Renal impairment was the single most important factor associated with prescription of lower-than-recommended doses, particularly in elderly patients. Conclusions Our results underline the need for optimal and better use of ACE inhibitor therapy. CHF treatment guidelines must be more uniformly applied by all physicians caring for patients with heart failure.

关键词：慢性病剂量效应关系药物用药计划表药物利用/统计学和数值数据法国肾功能试验处方药物/统计学和数值数据前瞻性研究心缩期/药物作用心室功能障碍左/诊断心室功能障碍左/药物疗法女(雌)性人类男(雄)性中年人

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Chronopharmacology of antitumor effect induced by interferon-β in tumor-bearing mice

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第2期294卷 746-752页

作者： Takane, H Ohdo, S Yamada, T Yukawa, E Higuchi, S Kyushu Univ Grad Sch Dept Clin Pharmacokinet Div Pharmaceut SciHigashi Ku Fukuoka 8128582 Japan

The mechanisms underlying the dosing time-dependent change in the antitumor effect of interferon-beta (IFN-beta) were investigated based on the sensitivity of tumor cells and the pharmacokinetics of the drug. Tumor-bearing mice were housed under standardized light-dark cycle conditions (lights on at 7:00 AM, off at 7:00 PM) with food and water available ad libitum. The antitumor effect of IFN-beta (0.5 MI.U./kg, intratumoral) was more efficient in early light phase than in early dark phase. The higher antitumor effect of IFN-beta was observed when specific binding of IFN receptor and DNA synthesis in tumor cells increased, and the lower effect was observed when these levels decreased. The dosing time-dependent effect of IFN-beta was supported by the time-dependent expression of transcription factor (signal transducers and activators of transcription 1) and cell proliferation inhibitor (p21 wild-type p53-activated fragment 1) protein induced by IFN-beta. There was a significant dosing time-dependent change in IFN-beta concentration in tumor, with a higher level in early light phase and a lower level in early dark phase. The dosing time-dependent change of IFN-beta concentration in tumor was associated with that of IFN-beta-induced antitumor effect. These results suggest that by choosing the most suitable dosing time for IFN-beta, the efficacy of the drug can be increased in certain experimental and clinical situations.

关键词：抗肿瘤药/投药和剂量抗肿瘤药/药代动力学细胞周期/药物作用细胞分裂/药物作用细胞存活/药物作用昼夜节律/生理学周期素依赖激酶抑制剂p21 细胞周期蛋白类/代谢 DNA结合蛋白质类/代谢剂量效应关系药物用药计划表干扰素α/代谢干扰素β/投药和剂量干扰素β/药代动力学黑色素瘤实验性/药物疗法黑色素瘤实验性/代谢黑色素瘤实验性/病理学小鼠近交C57BL 肿瘤移植受体干扰素αβ 受体干扰素/代谢 STAT1转录因子反式激活因子类/代谢动物人类男(雄)性小鼠

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CURRENT THERAPIES IN OSTEOSARCOMA

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CANCER TREATMENT REVIEWS 1975年第1期2卷 77-83页

作者： HANDELSMAN, H CARTER, SK NCI CANC THERAPY EVAL DIV CANC TREATMENT BETHESDA MD 20014 USA

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Protein phosphorylation cascades associated with methamphetamine-induced glial activation

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NEUROBIOLOGICAL MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES 2000年第1期914卷 238-262页

作者： Hebert, MA O'Callaghan, JP NIOSH Ctr Dis Control & Prevent Dept Hlth & Human Serv Publ Hlth Serv Morgantown WV 26505 USA

Reactive gliosis is the most prominent response to diverse forms of central nervous system (CNS) injury. The signaling events that mediate this characteristic response to neural injury are under intense investigation. Several studies have demonstrated the activation of phosphoproteins within the mitogen-activated protein kinase (MAPK) and Janus kinase (JAK) pathways following neural insult. These signaling pathways may be involved or responsible for the glial response following injury, by virtue of their ability to phosphorylate and dynamically regulate the activity of various transcription factors. This study sought to delineate, in vivo, the relative contribution of MAPK- and JAK-signaling components to reactive gliosis as measured by induction of glial-fibrillary acidic protein (GFAP), following chemical-induced neural damage. At time points (6,24, and 48 h) following methamphetamine (METH, 10 mg/kg x 4, s.c.) administration, female C57BL/6J mice were sacrificed by focused microwave irradiation, a technique that preserves steady-state phosphorylation. Striatal (target) and nontarget (hippocampus) homogenates were assayed for METH-induced changes in markers of dopamine (DA) neuron integrity as well as differences in the levels of activated phosphoproteins. GFAP upregulation occurred as early as 6 h, reaching a threefold induction 48 li following METH exposure. Neurotoxicant-induced reductions in striatal levels of DA and tyrosine hydroxylase (TH) paralleled the temporal profile of GFAP induction. Blots of striatal homogenates, probed with phosphorylation-state specific antibodies, demonstrated significant changes in activated forms of extracellular-regulated kinase 1/2 (ERK 1/2), c-jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), MAPK/ERK kinase (MEK1/2),70-kDa ribosomal S6 kinase (p70 S6), cAMP responsive element binding protein (CRE B), and signal transducer and activator of transcription 3 (STAT3). MAPK-related phosphoproteins exhibited an acti

关键词：中枢神经系统刺激剂/投药和剂量 cAMP反应元件结合蛋白质/代谢多巴胺/代谢用药计划表基因表达调控/药物作用神经胶质原纤维酸性蛋白质/代谢 JNK丝裂原活化蛋白激酶类/代谢 MAP激酶激酶4/代谢甲基苯丙胺/投药和剂量小鼠近交C57BL 丝裂原活化蛋白激酶1/代谢模型生物学神经胶质/药物作用神经胶质/代谢磷酰化/药物作用蛋白质类/代谢核糖体蛋白质S6激酶类 70-kDa/代谢信号传导/药物作用时间因素酪氨酸单氧化酶/代谢动物女(雌)性小鼠

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Reduced postoperative atrial fibrillation using multidrug prophylaxis

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JOURNAL OF CARDIAC SURGERY 1999年第6期14卷 437-443页

作者： Ott, RA Gutfinger, DE Alimadadian, H Miller, M Selvan, A Weinberg, D Hlapcich, WL Tanner, TM Anaheim Mem Med Ctr Anaheim CA USA

Background: Atrial fibrillation (AFIB) is the most common complication following coronary artery bypass grafting (CABG). Despite three decades of recognition, efforts to reduce the high incidence reported (15%-30%) have been largely unsuccessful. Reasons for postoperative AFIB are likely multifactorial. As a result, we defined a multidrug prophylaxis based on agents known to be individually effective. This method was applied prospectively to a series of consecutive CABG patients with the goal of reducing the incidence of new-onset postoperative AFIB. Methods: Isolated CABG with cardiopulmonary bypass was performed on 517 consecutive patients. A rapid recovery protocol emphasizing AFIB multidrug prophylaxis was applied to all patients. All patients received 10 mug of triiodothyronine intraoperatively when the clamp on the aorta was released. Immediately following CABG, parenteral magnesium was administered to assure a serum magnesium > 2.2 mEq/dL. Thyroxine 200 mug was administered parenterally to all patients on postoperative days 1 and 2. Metoprolol (25 mg to 100 mg/day) was begun on all patients after extubation provided: heart rate > 85 beats/min and systolic blood pressure > 130 mmHg. Parenteral procainamide (12 mg/kg) loading dose, followed by a maintenance dose (2 mg/min), was used for patients who developed premature atrial contractions (> 1/min), nonsustained supraventricular tachycardia, or any episodes of atrial fibrillation. All patients also received postoperative digitalization, steroids, and aggressive diuresis. Results: The 30-day operative mortality was 3.7%. The overall incidence of new-onset postoperative AFIB was 10.3% (53 patients). There was no major difference in operative mortality (7.5% vs 3.2%, p = 0.23), Parsonnet risk score, or intraoperative variables between AFIB patients and the non-AFIB patients. Patients presenting with a preoperative acute myocardial infarction (p < 0.05), left main stenosis 70% (p < 0.01),

关键词：抗心律失常药/投药和剂量心房颤动/诊断心房颤动/死亡率心房颤动/预防和控制冠状动脉分流术剂量效应关系药物用药计划表药物疗法联合心电描记术/药物作用镁/投药和剂量美托洛尔/投药和剂量手术后并发症/诊断手术后并发症/死亡率手术后并发症/预防和控制普鲁卡因胺/投药和剂量前瞻性研究存活率甲状腺素/投药和剂量三碘甲状腺原氨酸/投药和剂量老年人女(雌)性人类男(雄)性中年人

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HIV-1-resistant strains during 8-week on 8-week off intermittent therapy and their effect on CD4⁺ T-cell counts and antiviral response

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ANTIVIRAL THERAPY 2008年第4期13卷 537-545页

作者： Izopet, Jacques Marchou, Bruno Charreau, Isabelle Saune, Karine Tangre, Philippe Molina, Jean-Michel Aboulker, Jean-Pierre Univ Toulouse INSERM U563 IFR30 Toulouse France CHU Toulouse Inst Federatif Biol Purpan Virol Lab Toulouse France CHU Toulouse Serv Malad Infect & Trop Toulouse France INSERM SC10 Villejuif France Hop St Louis Serv Malad Infect & Trop AP HP St Louis France Univ Paris 07 F-75221 Paris 05 France

Background: We aimed here to study drug-associated HIV resistance mutations in peripheral blood mononuclear cells (PBMC) and plasma during intermittent therapy. Methods: A substudy of 86 patients randomized to the intermittent treatment arm (8-week on/8-week off) of the ANRS 106 Window trial. HIV reverse transcriptase and protease genes were sequenced and resistance mutations identified according to the International AIDS Society list. Results: Resistance mutations were detected in PBMC of 27/86 (31%) patients at baseline and 25/72 (35%) patients at week 96. Resistance mutations were detected in plasma of 28/86 (33%), 24/83 (29%) and 33/80 (41%) patients at weeks 8, 40 and 88, respectively. The detection of nucleoside reverse transcriptase inhibitor and protease inhibitor associated resistance mutations in plasma remained stable over time, but there was an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI)-associated resistance mutations in patients on an NNRTI-based regimen: 1/33 (3%) versus 7/26 patients (27%) at weeks 8 and 88, respectively (P=0.02). The proportions of patients with plasma HIV RNA levels <= 400 copies/ml after 8 weeks of treatment at weeks 16, 48 and 96 in patients with drug-resistant and wild-type viruses were 93% versus 74% (P=0.04), 96% versus 88% (P=0.43) and 70% versus 84% (P=0.13), respectively. Patients with drug-resistant virus had a lower CD4(+) T-cell decrease from baseline at weeks 40 and 88 as compared to patients with wild-type virus (P=0.05 and 0.002, respectively). Conclusions: NNRTI-associated resistance mutations increased over time in plasma of patients who were given NNRTIs. Drug-associated HIV resistance mutations did not seem to impair short-term antiviral response and might be associated with reduced CD4(+) T-cell loss during interruptions.

关键词： Adult Anti-HIV Agents CD4 Lymphocyte Count Drug Administration Schedule 成年人抗HIV药 CD4淋巴细胞计数用药计划表药物疗法联合基因型 HIV感染 CD4 Lymphocyte Count CD4 Antigens Adults peripheral blood mononuclear cell Reverse Transcriptase Inhibitors Antiviral Response Mutation Anti-HIV Agents T-Lymphocytes Drug Administration Schedule Patients

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