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The impact of molecular medicine upon early cardiovascular drug development

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY 2000年第1期50卷 1-8页

作者： Lunnon, MW Braddock, M Glaxo Grp Res Ltd Div Clin Pharmacol Cardiovasc Clin Pharmacol Greenford UB6 0HE Middx England Glaxo Wellcome Med Res Ctr Vasc Dis Unit Stevenage SG1 2NY Herts England

Focuses on the impact of molecular medicine on early cardiovascular drug development. Use of gene polymorphism on select patient population; Optimization of local drug delivery; Promotion of gene therapy.

关键词：心血管药物/治疗应用心血管疾病/药物疗法分子生物学寡核苷酸类反义/治疗应用人类

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From Inuit to implementation: Omega-3 fatty acids come of age

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MAYO CLINIC PROCEEDINGS 2000年第6期75卷 607-614页

作者： O'Keefe, JH Harris, WS St Lukes Hosp Mid Amer Heart Inst Kansas City MO 64111 USA Univ Missouri Dept Med Kansas City MO 64110 USA

During the past 25 years, the cardiovascular effects of marine omega-3 (omega-3) fatty acids have been the subject of increasing investigation. In the late 1970s, epidemiological studies revealed that Greenland Inuits had substantially reduced rates of acute myocardial infarction compared with Western control subjects. These observations generated more than 4500 studies to explore this and other effects of omega-3 fatty acids on human metabolism and health. From epidemiology to cell culture and animal studies to randomized controlled trials, the cardioprotective effects of omega-3 fatty acids are becoming recognized. These fatty acids, when incorporated into the diet at levels of about 1g/d, seem to be able to stabilize myocardial membranes electrically, resulting in reduced susceptibility to ventricular dysrhythmias, thereby reducing the risk of sudden death, The recent GISSI (Gruppo Italiano per lo Studio delta Sopravvivenza nell'Infarto miocardico)-Prevention study of 11,324 patients showed a 45% decrease in risk of sudden cardiac death and a 20% reduction in all-cause mortality in the group taking 850 mg/d of omega-3 fatty acids. These fatty acids have potent anti-inflammatory effects and may also be antiatherogenic, Higher doses of omega-3 fatty acids can lower elevated serum triglyceride levels;3 to 5 g/d can reduce triglyceride levels by 30% to 50%, minimizing the risk of both coronary heart disease and acute pancreatitis. This review summarizes the emerging evidence of the use of omega-3 fatty acids in the prevention of coronary heart disease.

关键词：心血管药物/副作用心血管药物/药理学心血管药物/治疗应用冠心病/并发症冠心病/流行病学冠心病/死亡率冠心病/预防和控制猝死心脏/预防和控制脂肪酸类 ω3/副作用脂肪酸类 ω3/药理学脂肪酸类 ω3/治疗应用鱼油/投药和剂量格陵兰/流行病学伊努伊特人/统计学和数值数据心肌梗死/流行病学心肌梗死/预防和控制随机对照试验(主题) α亚麻酸/治疗应用人类

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Standards in the diagnosis and treatment of sepsis

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ANASTHESIOLOGIE INTENSIVMEDIZIN NOTFALLMEDIZIN SCHMERZTHERAPIE 2003年第2期38卷 107-135页

作者： Meier-Hellmann, A HELIOS Klinikum Erfurt GmbH Klin Anasthesie Intens Med & Schmerztherapie D-99089 Erfurt Germany

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High vancomycin dosage regimens required by intensive care unit patients cotreated with drugs to improve haemodynamics following cardiac surgical procedures

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JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 2000年第3期45卷 329-335页

作者： Pea, F Porreca, L Baraldo, M Furlanut, M Univ Udine Inst Clin Pharmacol & Toxicol DPMSC I-33100 Udine Italy SM Misericordia Udine Hosp Div Cardiothorac Surg Udine Italy

The aim of this study was to evaluate retrospectively the importance of a Bayesian pharmacokinetic approach for predicting vancomycin concentrations to individualize its dosing regimen in 18 critically ill patients admitted to intensive care units following cardiothoracic surgery. The possible influence of some coadministered drugs with important haemodynamic effects (dopamine, dobutamine, frusemide) on vancomycin pharmacokinetics was assessed. Vancomycin serum concentrations were measured by fluorescence polarization immunoassay. Vancomycin dosage regimens predicted by the Bayesian method (D-a) were compared retrospectively with Moellering's nomogram-based dosages (D-M) to assess possible major differences in vancomycin dosing. D-a values were similar to D-M in 10 patients (D-a approximate to D-M group) (20.52 +/- 8.40 mg/kg/day versus 18.81 +/- 7.24 mg/kg;P = 0.15), whereas much higher dosages were required in the other eight patients (D-a much greater than D-M group) (26.78+/- 3.01 mg/kg/day versus 18.95 +/- 3.41 mg/kg/day;P < 0.0001) despite no major difference in attained vancomycin steady-state trough concentration (C-min (ss)) (9.22 +/- 1.33 mg/L versus 8.99 +/- 1.26 mg/L;= 0.75) or estimated creatinine clearance (1.23 +/- 0.49 mL/min/kg versus 1.21 +/- 0.24 mL/min/kg;P = 0.95) being found between the two groups. The ratio between D-a and D-M was significantly higher in the D-a much greater than D-M group than in the D-a approximate to D-M group (1.44 +/- 0.18 versus 1.10 +/- 0.21;P < 0.01). In four D-a much greater than D-M patients the withdrawal of cotreatment with haemodynamically active drugs was followed by a sudden substantial increase in the vancomycin C-min ss (13.30 +/- 1.13 mg/L versus 8.79 +/- 0.87 mg/L;P < 0.01), despite no major change in bodyweight or estimated creatinine clearance being observed. We postulate that these drugs with important haemodynamic effects may enhance vancomycin clearance by inducing an improvement in cardiac output and/o

关键词：贝叶斯定理心脏外科手术强心药/治疗应用心血管药物/治疗应用肌酸酐/血液利尿药/治疗应用多巴酚丁胺/治疗应用多巴胺/治疗应用药物相互作用呋塞米/治疗应用重症监护重症监护病房手术后医护回顾性研究万古霉素/投药和剂量万古霉素/药代动力学万古霉素/治疗应用女(雌)性人类男(雄)性中年人

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Prophylactic indomethacin: Factors determining permanent ductus arteriosus closure

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JOURNAL OF PEDIATRICS 2000年第3期136卷 330-337页

作者： Narayanan, M Cooper, B Weiss, H Clyman, RI Univ Calif San Francisco Cardiovasc Res Inst Dept Pediat San Francisco CA 94143 USA Calif Sch Profess Psychol Alameda CA USA

Background: Permanent closure of the ductus arteriosus (DA) requires both effective muscular constriction to block luminal blood flow and anatomic remodeling to prevent later reopening. Objective: We examined the role of prophylactic indomethacin in producing permanent DA closure and the mechanism by which this occurs. Methods: We studied 2 separate approaches to managing a patent DA in 257 preterm infants (gestation 24 to 27 weeks): (1) prophylactic indomethacin tall infants treated during the first 15 hours after birth) or (2 symptomatic treatment (infants in this group received indomethacin only if clinical symptoms appeared;infants whose ductus closed spontaneously and never received indomethacin were included in this group). Echocardiography was performed 24 to 36 hours after the last dose of indomethacin was administered or by age 5 days if spontaneous closure occurred, Infants were monitored for the development of ductus reopening. Results: The prophylactic treatment group had a greater degree of initial ductus constriction, a higher rate of permanent anatomic closure, and a decreased need for surgical ligation than did the symptomatic treatment group. The degree of initial ductus constriction was the most important factor determining the rate of ductus reopening. Post-treatment echocardiography proved to be the best test for predicting eventual reopening. Conclusion: Prophylactic indomethacin improved the rate of permanent duct ns closure by increasing the degree of initial constriction. Prophylactic indomethacin did nor affect the remodeling process, nor did it alter the inverse relationship between infant maturity and subsequent reopening. Even when managed with prophylactic indomethacin, the race of ductus reopening remained unacceptably high in the most immature infants.

关键词：心血管药物/治疗应用动脉导管未闭/并发症动脉导管未闭/预防和控制吲哚美辛/治疗应用婴儿早产疾病/预防和控制女(雌)性人类婴儿新生男(雄)性

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Prognostic implications of Tc-99m Sestamibi viability imaging and subsequent therapeutic strategy in patients with chronic coronary artery disease and left ventricular dysfunction

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第3期36卷 739-745页

作者： Sciagrà, R Pellegri, M Pupi, A Bolognese, L Bisi, G Carnovale, V Santoro, GM Univ Florence Dept Clin Physiopathol Nucl Med Unit I-50134 Florence Italy Careggi Hosp Div Cardiol Florence Italy Univ Turin Turin Italy

OBJECTIVES The aim of the study was to verify the prognostic implications of viability detection using baseline-nitrate sestamibi imaging in patients with left ventricular (LV) dysfunction due to chronic coronary artery disease (CAD) submitted to different therapeutic strategies. BACKGROUND The prognostic meaning of preserved viability in these patients is still debated. Sestamibi is increasingly used for myocardial perfusion scintigraphy and is being accepted also as viability tracer, but no data are available about the relationship between viability in sestamibi imaging, subsequent treatment, and patient's outcome. METHODS Follow-up data were collected in 105 CAD patients with LV dysfunction who had undergone baseline-nitrate sestamibi perfusion imaging for viability assessment and had been later treated medically (group 1), or submitted to revascularization, which was either complete (group 2A) or incomplete (group 2B). RESULTS Eighteen hard events (cardiac death or nonfatal myocardial infarction) were registered during the follow-up. A significantly worse event-free survival curve was observed in the patients of group 1 (p < 0.0002) and group 2B (p < 0.03) compared to those of group 2A. Using a Cox proportional hazard model, the most powerful prognostic predictors of events were the number of nonrevascularized asynergic segments with viability in sestamibi imaging (p < 0.003, risk ratio [RR] = 1.4), and the severity of CAD (p < 0.02, RR = 1.28). CONCLUSIONS Viability detection in sestamibi imaging has important prognostic implications in CAD patients with LV dysfunction. Patients with preserved viability kept on medical therapy or submitted to incomplete revascularization represent high-risk groups.

关键词：血管成形术气囊冠状动脉心血管药物/治疗应用慢性病冠心病/并发症冠心病/诊断显像冠心病/治疗随访研究心肌血管重建术硝酸盐类预后放射性药物 99m锝甲氧基异丁基异腈组织存活体层摄影术发射型计算机单光子心室功能障碍左/诊断显像心室功能障碍左/病因学老年人女(雌)性人类男(雄)性中年人

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Hypertrophic cardiomyopathy - Tools for identifying risk and alleviating symptoms

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POSTGRADUATE MEDICINE 2000年第7期107卷 127-+页

作者： DeLuca, M Tak, T Scott & White Mem Hosp & Clin Dept Med Div Cardiol Temple TX 76508 USA Texas A&M Univ Coll Med Hlth Sci Ctr Scott Sherwood & Brindley Fdn Temple TX 76508 USA

Hypertrophic cardiomyopathy is characterized by left or right ventricular hypertrophy that is usually asymmetric and involves the interventricular septum. The condition has numerous genetic, anatomic, and clinical variations and continues to stimulate interest and investigation into causes and treatment options. New genetic forms of the disorder are being identified because of the rapid growth of molecular genetics. However, even with technological advances and a large database of information, risk stratification and treatment of hypertrophic cardiomyopathy remain difficult and controversial. Because of the high risk of sudden death, it is imperative that patients be advised against participation in competitive sports.

关键词：心血管药物/治疗应用猝死/病因学心电描记术体格检查危险因素人类

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The acute myocardial infarction

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PRIMARY CARE 2000年第3期27卷 631-+页

作者： Pollard, TJ Cent Maine Med Ctr Family Practice Residency Lewiston ME 04240 USA

Cardiovascular death is the number one cause of death in the United States, with a rate that is more than double that for cancer. Over half of these cardiovascular deaths are due to acute myocardial infarction. Management of the patient with acute myocardial infarction during and after hospitalization is discussed with an emphasis on primary and secondary prevention, patient autonomy and decision making. There is also a review of the directions that treatment of acute myocardial infarction will take in the future.

关键词：心血管药物/治疗应用重症监护/方法心肌梗死/并发症心肌梗死/诊断心肌梗死/康复心肌梗死/治疗心肌血管重建术门诊部医院老年人女(雌)性人类男(雄)性

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The results of a randomized trial of a quality improvement intervention in the care of patients with heart failure

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AMERICAN JOURNAL OF MEDICINE 2000年第6期109卷 443-449页

作者： Philbin, EF Rocco, TA Lindenmuth, NW Ulrich, K McCall, M Jenkins, PL Henry Ford Hosp Sect Heart Failure & Cardiac Transplantat Detroit MI 48202 USA Unity Hlth Syst Div Cardiol Rochester NY USA Finger lakes Reg Hlth Syst Dept Med Geneva NY USA Faxton Hosp Utica NY USA St Lukes Mem Hosp Utica NY USA Bassett Healthcare Bassett Res Inst Cooperstown NY USA

PURPOSE: Quality improvement and disease management programs for heart failure have improved quality of care and patient outcomes at large tertiary care hospitals. The purpose of this study was to measure the effects of a regional, multihospital, collaborative quality improvement intervention on care and outcomes in heart failure in community hospitals. PATIENTS AND METHODS: This randomized controlled study included 10 acute care community hospitals in upstate New York. After a baseline period, 5 hospitals were randomly assigned to receive a multifaceted quality improvement intervention (n = 762 patients during the baseline period;n = 840 patients postintervention), while 5 were assigned to a "usual care" control (n = 640 patients during the baseline period;n = 664 patients postintervention). Quality of care was determined using explicit criteria by reviewing the charts of consecutive patients hospitalized with the primary diagnosis of heart failure during the baseline period and again in the postintervention period. Clinical outcomes included hospital length of stay and charges, in-hospital and 6-month mortality, hospital readmission, and quality of life measured after discharge. RESULTS: Patients had similar characteristics in the baseline and postintervention phases in the intervention and control groups. Using hospital-level analyses, the intervention had mixed effects on 5 quality-of-care markers that were not statistically significant. The mean of the average length of stay among hospitals decreased from 8.0 to 6.2 days in the intervention group, with a smaller decline in mean length of stay in the control group (7.7 to 7.0 days). The net effects of the intervention were nonsignificant changes in length of stay of - 1.1 days (95% confidence interval [CI]: -2.9 to 0.7 days, P = 0.18) and in hospital charges of -$817 (95% CI: -$2560 to $926, P = 0.31). There were small and nonsignificant effects on mortality, hospital readmission, and quality of life. CONCLUSION

关键词：心血管药物/治疗应用临床路径/利用卫生服务研究心力衰竭/血液心力衰竭/诊断心力衰竭/药物疗法心力衰竭/经济学心力衰竭/病理生理学医院收费医院社区/标准保险健康住院时间纽约结果与过程评价(卫生保健) 病人再入院质量保证卫生保健生活质量疾病严重程度指数钠/血液每搏输出量全面质量管理老年人女(雌)性人类男(雄)性

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Subgroups, treatment effects, and baseline risks: Some lessons from major cardiovascular trials

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AMERICAN HEART JOURNAL 2000年第6期139卷 952-961页

作者： Parker, AB Naylor, CD Univ Toronto Fac Med Inst Med Sci Toronto ON M5S 1A8 Canada SOCAR Cardiac Res Ltd Toronto ON Canada Univ Toronto Dept Med Toronto ON M5S 1A8 Canada Univ Toronto Clin Epidemiol & Hlth Serv Res Program Sunnybrook & Womens Coll Unit Toronto ON M5S 1A8 Canada Inst Clin Evaluat Sci Toronto ON Canada

Background The objective of this study was to determine how subgroup analyses are performed in large randomized trials of cardiovascular pharmacotherapy. Methods and Results We reviewed 67 randomized, double-blind, controlled trials involving pharmacotherapy in at least 1000 patients with unstable angina, myocardial infarction, left ventricular dysfunction, or heart failure with clinical outcomes as primary end points, published between 1980 and 1997. Nine had no subgroup analyses but 43 reported on 5 or more subgroups and 31 reported subgroups without formal statistical tests for treatment-subgroup interactions. In most trials, a rationale for subgroup selection was missing. All but 6 focused on single-factor subgroups. Conclusions Trial subgroups should ideally be defined a priori on 2 bases: single-factor subgroups with a strong rationale for biological response modification and multifactorial prognostic subgroups defined from baseline risks. However, single-factor subgroup analyses are often reported without a supporting rationale or formal statistical tests for interactions. We suggest that clinicians should interpret published subgroup-specific variations in treatment effects skeptically unless there is a prespecified rationale and a significant treatment-subgroup interaction.

关键词：心绞痛不稳定型/药物疗法心血管药物/治疗应用数据说明统计双盲法心肌梗死/药物疗法回顾性研究危险性评估治疗结果心室功能障碍左/药物疗法人类

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