ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Trastuzumab, a monoclonal antibody against the HER2 receptor, was recently approved for the treatment of metastatic breast cancer. However, 28% of patients receiving both an anthracycline and trastuzumab developed heart failure. Although HER2 overexpression has been associated with the development of cancer, HER2 receptors seem to be cardioprotective because they mediate the activation of important cardiac survival pathways. Because the morbidity and mortality of heart failure surpasses that of many cancers, prudent medical practice mandates that physicians learn more about the mechanisms of trastuzumab-induced cardiotoxicity and develop algorithms for assessing risk/benefit ratios before extending the use of this agent to patients with less invasive forms of breast cancer.

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundSeveral cases of unexpected death have been reported with sildenafil in patients predisposed to ischemic cardiac events. Although acute episodes of ischemia could account for some of these deaths, we hypothesized that sildenafil may have unsuspected electrophysiological effects predisposing some patients to proarrhythmia.Methods and ResultsStudies were undertaken in 10 isolated guinea pig hearts that demonstrated prolongation of cardiac repolarization in a reverse use-dependent manner by sildenafil 30 &mgr;mol/L. Action potential duration increased 15% from baseline 117±3 to 134±2 ms with sildenafil during pacing at 250 ms cycle length, whereas a 6% increase from 99±2 to 105±2 ms was seen with pacing at 150 ms cycle length. Experiments in humanether-a-go-go–related gene (HERG)–transfected HEK293 cells (n=30) demonstrated concentration-dependent block of the rapid component (IKr) of the delayed rectifier potassium current: activating current was 50% decreased at 100 &mgr;mol/L. This effect was confirmed using HERG-transfected Chinese hamster ovary (CHO) cells, which exhibit no endogenous IK-like current.ConclusionsSildenafil possesses direct cardiac electrophysiological effects similar to class III antiarrhythmic drugs. These effects are observed at concentrations that may be found in conditions of impaired drug elimination such as renal or hepatic insufficiency, during coadministration of another CYP3A substrate/inhibitor, or after drug overdose and offer a new potential explanation for sudden death during sildenafil treatment.

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundThe prevalence, clinical significance, and determinants of abnormal ECG patterns in trained athletes remain largely unresolved.Methods and ResultsWe compared ECG patterns with cardiac morphology (as assessed by echocardiography) in 1005 consecutive athletes (aged 24±6 years; 75% male) who were participating in 38 sporting disciplines. ECG patterns were distinctly abnormal in 145 athletes (14%), mildly abnormal in 257 (26%), and normal or with minor alterations in 603 (60%). Structural cardiovascular abnormalities were identified in only 53 athletes (5%). Larger cardiac dimensions were associated with abnormal ECG patterns: left ventricular end-diastolic cavity dimensions were 56.0±5.6, 55.4±5.7, and 53.7±5.7 mm (P<0.001) and maximum wall thicknesses were 10.1±1.4, 9.8±1.3, and 9.3±1.4 mm (P<0.001) in distinctly abnormal, mildly abnormal, and normal ECGs, respectively. Abnormal ECGs were also most associated with male sex, younger age (<20 years), and endurance sports (cycling, rowing/canoeing, and cross-country skiing). A subset of athletes (5% of the 1005) showed particularly abnormal or bizarre ECG patterns, but no evidence of structural cardiovascular abnormalities or an increase in cardiac dimensions.ConclusionsMost athletes (60%) in this large cohort had ECGs that were completely normal or showed only minor alterations. A variety of abnormal ECG patterns occurred in 40%; this was usually indicative of physiological cardiac remodeling. A small but important subgroup of athletes without cardiac morphological changes showed striking ECG abnormalities that suggested cardiovascular disease; however, these changes were likely an innocent consequence of long-term, intense athletic training and, therefore, another component of athlete heart syndrome. Such false-positive ECGs represent a potential limitation to routine ECG testing as part of preparticipation screening.

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundWe determined whether repeated caffeine administration at different dosages and for different periods of time (400 or 600 mg/d for 1 week or 400 mg/d for 2 weeks) upregulates human platelet adenosine A2Areceptors and is accompanied by increases in cAMP accumulation and decreases in aggregation and calcium levels after stimulation of A2Areceptors by the selective agonist 2-hexynyl-5′-N-ethylcarboxamidoadenosine (HE-NECA).Methods and ResultsPlatelets were obtained from peripheral venous blood of 45 healthy human volunteers at the end of 2 weeks of caffeine abstinence and at 12, 60, and 108 hours after the last dose of caffeine. The lowest dose of caffeine, when given for only 7 days, had no effect. Increasing the total dose, either by giving 400 mg/d for 14 days or giving 600 mg/d, resulted in binding assays performed with the adenosine A2Areceptor radioligand [3H]SCH 58261 [5-amino-7(phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine], in the upregulation of A2Areceptors. Moreover, the potency of HE-NECA to produce antiaggregatory effects, a rise in cAMP accumulation, and a decrease in calcium levels was significantly increased.ConclusionsChronic caffeine intake can lead to upregulation of adenosine A2Areceptors, which is accompanied by sensitization, in a time- and dose-dependent manner, to the actions of the agonist HE-NECA.

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundProstate-specific antigen (PSA), acid phosphatase (AP), and prostatic acid phosphatase (PAP) are serum markers for adenocarcinoma of the prostate gland. Previous studies indicated that prostatic ischemia may also produce elevations of PSA. Cardiopulmonary resuscitation (CPR) is frequently associated with profound tissue hypoperfusion. The present study investigated whether PSA, AP, and PAP are influenced by prolonged CPR.Methods and ResultsPSA, AP, and PAP were assessed immediately, 12 hours, 24 hours, 2 days, 3 days, 5 days, and 7 days after prolonged CPR (>5 minutes) in 14 male and 5 female patients. No changes were noted in women. In men, serum levels increased significantly after CPR and gradually decreased to near baseline values after 7 days. PSA, AP, and PAP values above the normal range were observed in 63%, 71%, and 64% of all patients, respectively. Compared with survivors, nonsurvivors exhibited higher peak serum levels of PSA (98.6±14.3 versus 1.1±2.2 &mgr;g/L;P<0.03), AP (57.0±71 versus 8.6±8.8 U/L;P<0.05), and PAP (47.0±62 versus 5.7±8.0 U/L;P=NS). Patients with poor neurological outcome exhibited higher peak serum levels of PSA (86.4±135.5 versus 12.0±23.8 &mgr;g/L;P<0.05), AP (50.9±68.1 versus 8.7±9.6 U/L;P=NS), and PAP (41.6±59.5 versus 5.8±8.8 U/L;P=NS) than patients with good neurological outcome.ConclusionsProlonged CPR is frequently associated with increases of PSA, AP, and PAP serum levels. Therefore, PSA cannot be used for diagnosis of adenocarcinoma of the prostate during the first weeks after CPR. Further evaluation of these parameters as additional prognostic markers after CPR is warranted.

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundThis study was performed to compare implantation of a DDI pacemaker with rate hysteresis with no implant in respect to syncopal recurrences in patients with severe cardioinhibitory tilt-positive neurally mediated syncope.Methods and ResultsForty-two patients from 18 European centers were randomized to receive a DDI pacemaker programmed to 80 bpm with hysteresis of 45 bpm (19 patients) or no pacemaker (23 patients). Inclusion criteria were ≥3 syncopes over the last 2 years and a positive cardioinhibitory (Vasovagal Syncope International Study types 2A and 2B) response to tilt testing. The median number of previous syncopal episodes was 6; asystolic response to tilt testing was present in 36 patients (86%) (mean asystole, 13.9±10.2 seconds). All patients were followed up for a minimum of 1.0 years and a maximum of 6.7 years (mean, 3.7±2.2). One patient (5%) in the pacemaker arm experienced recurrence of syncope compared with 14 patients (61%) in the no-pacemaker arm (P=0.0006). In the no-pacemaker arm, the median time to first syncopal recurrence was 5 months, with a rate of 0.44 per year. On repeated tilt testing performed within 15 days after enrollment, positive responses were observed in 59% of patients with pacemakers and in 61% of patients without pacemakers (P=NS).ConclusionsIn a limited, select group of patients with tilt-positive cardioinhibitory syncope, DDI pacing with hysteresis reduced the likelihood of syncope. The benefit of the therapy was maintained over the long term. Even in untreated patients, the syncopal recurrence burden was low. A negative result of tilt testing was not a useful means to evaluate therapy efficacy.

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundVariations in the ventricular response interval (VRI) during atrial fibrillation (AF) may be reduced in patients with adverse clinical outcomes. The properties of VRI dynamics associated with prognosis remain undetermined.Methods and ResultsIn 107 patients with chronic AF (age, 64±9 years), we analyzed a 24-hour ambulatory ECG for VRI variability (SD, SD of successive differences, and SD of 5-minute averages) and VRI irregularity (Shannon entropy of histogram, symbolic dynamics, and approximate entropy of beat-to-beat and minute-to-minute fluctuations [ApEnb-band ApEnm-m]). During a follow-up period of 33±16 months, 18 patients died (17%), 9 from cardiac causes, 7 from fatal strokes, and 2 from malignancies. Reductions in all VRI variability and irregularity measures were associated with an increased risk for cardiac death but not for fatal stroke. A significant association with cardiac death was also found for ejection fraction (relative risk, 1.10; 95% confidence interval [CI], 1.04 to 1.17, per 1% decrement) and ischemic AF (relative risk, 6.52; 95% CI, 1.62 to 26.3). After adjustment for these clinical variables, all irregularity measures except symbolic dynamics had predictive value (relative risks [95% CIs] per 1SD decrement: Shannon entropy of histogram, 2.03 [1.14 to 3.61]; ApEnb-b, 1.72 [1.14 to 2.60]; and ApEnm-m, 1.90 [1.03 to 3.52]); however, the predictive power of variability measures was no longer significant. When the patients were stratified with the 33rd and 67th percentile values of ApEnb-b(1.83 and 1.94, respectively), the 5-year cardiac mortality rates for the upper, middle, and lower tertiles were 0%, 13%, and 43%, respectively (log-rank test,P=0.04).ConclusionsReduced VRI irregularity in a 24-hour ambulatory ECG has an independent prognostic value for cardiac mortality during long-term follow-up in patients with chronic AF.

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundIt is unclear whether, given a current blood pressure level, the previous 2-year change in blood pressure adds important predictive information for cardiovascular disease (CVD).Methods and ResultsWe conducted a prospective cohort study of 11 150 middle-aged and older men reporting blood pressure in the Physicians’ Health Study. These men had no history of CVD or antihypertensive medication use through the time of the 2-year follow-up questionnaire; after this time, follow-up for the current study began. A total of 905 incident cases of CVD (705 cases of coronary heart disease and 200 cases of stroke) occurred during a median follow-up of 10.8 years. After controlling for current blood pressure and other coronary risk factors, we found that previous 2-year changes in systolic blood pressure were not associated with the risk of CVD. A similar lack of association was found for individual end points of coronary heart disease and stroke. However, previous 2-year changes in diastolic blood pressure (DBP) may be inversely associated with the risk of CVD (linear trend,P=0.049) independent of coronary risk factors and current DBP. In subgroup analyses, previous 2-year blood pressure changes only added information in leaner men (body mass index <24.39 kg/m2).ConclusionsIn this normotensive population of men, the prior 2-year change in DBP, but not systolic blood pressure, may add information to current levels in relation to the risk of CVD. Clinicians may need to consider the previous pattern of DBP change when considering the risk associated with the current DBP level. These data require confirmation in other studies in which blood pressure is measured.

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID