Trastuzumab-induced cardiac dysfunction.
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Biomedical subjects
Publications and source records attributed to Diwakar Jain.
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Acute onset, transient (reversible) myocardial contraction abnormality has been described in patients with acute non-cardiac illness and after acute emotional stress. Such reversible myocardial contraction abnormalities may occur via mechanisms other than reduction in epicardial coronary blood flow. We report a case of acute transient cardiomyopathy after smoke exposure. The patient developed acute heart failure without evidence of carbon monoxide poisoning that resolved within 4 days. An association between brief smoke exposure without carbon monoxide poisoning and acute heart failure has not been previously described.
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INTRODUCTION: Current laboratory paradigms of human cocaine administration generally dictate the timing of drug access in ways that may limit assessing aspects of cocaine-taking behavior. Patient-controlled analgesia (PCA) methods, which allow individuals less restricted access to narcotic (i.e., opiate) analgesics, have proven safe and clinically effective for self-regulated treatment of pain. The current study assessed the feasibility, safety, and validity of a model of ad libitum cocaine self-administration, in which participants self-selected the timing of cocaine infusions, using PCA techniques. METHODS: Eight nontreatment seeking, otherwise medically healthy, experienced cocaine users participated in a double-blind, placebo-controlled, escalating-dose regimen of intravenous cocaine (0, 8, 16, and 32 mg per 70 kg) on 4 test days, during which time participants had 2 h of access to cocaine via manual presses of a corded PCA pump button under a fixed ratio 1: time-out 5-min schedule. RESULTS: Procedures were well-tolerated by participants, and no significant adverse events were noted. Measures of cocaine self-administration (e.g., number of responses and interinfusion intervals) indicated a significant main effect of cocaine dose, consistent with predicted dose-response relationships (i.e., decreasing responses and increasing interinfusion intervals with increasing injection dose). Participants appeared to regulate their cocaine intake in a carefully controlled manner, using considerably less cocaine (about half) that permitted by pump loading, PCA parameters, and session duration. CONCLUSIONS: Data from this study support the validity of our PCA paradigm. Moreover, results suggest the apparent feasibility and safety of allowing experienced users to self-select the timing of cocaine infusions to intervals as short as 5 min. Such procedures may enhance our ability to identify effective pharmacological treatments for cocaine addiction.
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We describe the case of a 57-year-old man with severe refractory hypoxemia, despite receiving ventilation therapy with 100% oxygen, following a gunshot wound to his left chest. A limited CT scan of the chest with contrast raised the suspicion of an arteriovenous (AV) fistula. Contrast-enhanced transthoracic echocardiography confirmed the presence of a pulmonary AV fistula. Traumatic pulmonary AV fistula is a rare, but serious and life-threatening condition that should be suspected in patients with thoracic injuries with persistent unexplained hypoxemia. Contrast echocardiography is a relatively simple, inexpensive, and readily available bedside test that can be used to confirm this diagnosis.
PURPOSE: To determine if there was any difference in the ability of physicians to predict prognosis with technetium 99m ((99m)Tc) sestamibi or (99m)Tc tetrofosmin in a large consecutive series of patients at high risk for coronary artery disease who underwent coronary angiography. MATERIALS AND METHODS: This study included 1,818 consecutive patients who underwent a rest and stress single photon emission computed tomographic (SPECT) examination with either (99m)Tc sestamibi (n = 915) or (99m)Tc tetrofosmin (n = 903) and cardiac catheterization. A clinical index was generated and consisted of clinical and demographic variables. Information concerning death, cardiovascular death, and nonfatal myocardial infarction was 93% complete during the 1.5-year study period. Cox proportional hazards models were generated to help determine the incremental contribution of SPECT sum stress score (SSS) and the imaging agent variable to the clinical index. RESULTS: Exercise was used for stress testing in 473 (52%) patients who received (99m)Tc tetrofosmin and 519 (57%) patients who received (99m)Tc sestamibi (P =.06). Cardiovascular death or myocardial infarction occurred in 130 patients. Resulting P values for chi(2) differences between models for the end points of (a) death from any cause, (b) cardiovascular death, and (c) cardiovascular death or myocardial infarction showed that SSS combined with clinical index was a significantly better model than adjusting for only baseline characteristics (P =.001, P <.001, P =.004, respectively). Incremental addition of either (99m)Tc tetrofosmin or (99m)Tc sestamibi to those models containing SSS and the clinical index did not show further significant improvement (P =.87, P =.88, and P =.26 for death from any cause, cardiovascular death, and cardiovascular death or myocardial infarction, respectively). CONCLUSION: This study shows that the type of clinically available (99m)Tc-labeled myocardial perfusion agents should not affect interpretation of results for risk stratification and prognostic assessment.
BACKGROUND: Scintigraphic myocardial perfusion imaging is the most widely used noninvasive modality for the detection of coronary artery disease (CAD). A technique for direct imaging of exercise-induced myocardial ischemia is highly desirable and preferable over perfusion imaging but is presently unavailable. We evaluated the feasibility and diagnostic accuracy of direct imaging of exercise-induced myocardial ischemia with fluorine-18-2-deoxyglucose (18FDG). METHODS AND RESULTS: Twenty-six patients with known or suspected CAD and no prior myocardial infarction underwent simultaneous myocardial perfusion and ischemia imaging after the intravenous injection of Tc-99m-sestamibi (99mTc-sestamibi) and 18FDG at peak exercise. Rest perfusion imaging was carried out separately. All patients underwent coronary angiography. Exercise 18FDG myocardial images were compared with exercise-rest 99mTc-sestamibi images and coronary angiography. Of 22 patients with > or =50% narrowing of > or =1 coronary arteries, 18 had perfusion abnormalities (sensitivity 82%) whereas 20 had abnormal myocardial 18FDG uptake (sensitivity 91%, P=NS). Perfusion abnormalities were seen in myocardial segments corresponding to 25 vascular territories of a total of 51 vessels with > or =50% luminal narrowing in 22 patients (sensitivity 49%), whereas increased 18FDG uptake was seen in 34 vascular territories (sensitivity 67%, P=0.008). 18FDG images were of high quality and easy to interpret but required simultaneous perfusion images for localizing abnormal myocardial 18FDG uptake. CONCLUSIONS: Exercise-induced myocardial ischemia can be imaged directly with 18FDG. Combined exercise 18FDG-99mTc-sestamibi imaging provides a better assessment of exercise-induced myocardial ischemia compared with exercise-rest perfusion imaging. Direct ischemia imaging eliminates some of the limitations of presently used myocardial perfusion imaging. Large-scale clinical studies are warranted.
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Technetium-99m sestamibi has attracted interest for assessment of the function of P-glycoproteins, which are well expressed in the liver and have roles in biliary transport and the removal of chemotherapeutic drugs. To further examine the cross-reactivity of (99m)Tc-sestamibi for P-glycoprotein family members, we conducted studies in animals. Hepatobiliary secretion of (99m)Tc-sestamibi was determined in normal FVB/N mice, mutant mice with specific P-glycoprotein deficiencies in the FVB/N background, normal Long-Evans Agouti (LEA) rats, and Long-Evans Cinnamon (LEC) rats with abnormal copper transport and liver disease but intact P-glycoprotein expression. After intrasplenic injection, (99m)Tc-sestamibi was rapidly incorporated in the mouse and rat liver, with maximal accumulation after 102+/-31 and 109+/-16 s, respectively ( P=NS). In normal mice and rats, 55%+/-11% and 55%+/-6%, respectively, of the maximal sestamibi activity was retained in the liver after 1 h ( P=NS). In double knockout mice lacking both mdr1a and mdr1b homologs of the human MDR1 ( ABCB1) gene, 88%+/-11% of maximal sestamibi activity was retained in the liver after 1 h ( P<0.001). In knockout mice deficient in either mdr1a gene or mdr2 ( ABCB4) gene, biliary sestamibi excretion was also impaired, although this impairment was relatively less pronounced in ABCB4-deficient mice than in double knockout mice lacking both ABCB1 gene homologs ( P<0.03). Hepatobiliary sestamibi excretion in LEC rats was not different from that in control normal rats, despite the presence of significant liver disease in the former. Hepatobiliary sestamibi excretion requires P-glycoproteins and is unperturbed in chronic liver disease. Sestamibi appears to be a substrate for both ABCB1 and ABCB4 genes, although the former utilizes it far more efficiently. Assessment of P-glycoprotein activity with sestamibi should consider how regulation of ABCB1 and related family members might modulate sestamibi incorporation.
BACKGROUND: Observational studies have suggested that psychological stress increases the incidence of sudden cardiac death. Whether emotional or physical stressors can trigger spontaneous ventricular arrhythmias in patients at risk has not been systematically evaluated. METHODS AND RESULTS: Patients with implantable cardioverter-defibrillators (ICDs) were given diaries to record levels of defined mood states and physical activity, using a 5-point intensity scale, during 2 periods preceding spontaneously occurring ICD shocks (0 to 15 minutes and 15 minutes to 2 hours) and during control periods 1 week later. ICD-stored electrograms confirmed the rhythm at the time of shock. A total of 107 confirmed ventricular arrhythmias requiring shock were reported by 42 patients (33 men; mean age, 65 years; 78% had coronary artery disease) between August 1996 and September 1999. In the 15 minutes preceding shock, an anger level > or =3 preceded 15% of events compared with 3% of control periods (P<0.04; odds ratio, 1.83; 95% confidence intervals, 1.04 to 3.16) Other mood states (anxiety, worry, sadness, happiness, challenge, feeling in control, or interest) did not differ. Patients were more physically active preceding shock than in control periods. Anger and physical activity were independently associated with the preshock period. CONCLUSIONS: Anger and physical activity can trigger ventricular arrhythmias in patients with ICDs. Future investigations of therapies aimed at blocking a response to these stressors may decrease ventricular arrhythmias and shocks in these patients.
BACKGROUND: The Multicenter Study of Enhanced External Counterpulsation (MUST-EECP) was the first prospective, randomized, blinded, sham-controlled study of enhanced external counterpulsation (EECP) in the treatment of chronic stable angina. We previously reported that EECP therapy lengthens the time to exercise-induced myocardial ischemia and reduces angina. We now describe the effects of EECP therapy versus a sham-treated control group in terms of patients' functioning, their senses of well-being and other Health-Related Quality Of Life (HQOL) parameters from baseline to end of treatment and from baseline to 12 months after treatment. OBJECTIVE: To determine whether a 35-hour course of EECP affects the HQOL of patients with symptomatic coronary artery disease, 12 months following treatment. METHODS: Seventy-one of the 139 patients enrolled in MUST-EECP provided evaluable patient-completed questionnaires at baseline, at the end of treatment, and 12 months post-treatment. The Medical Outcomes Study 36-Item Short-Form Health Survey and the Quality of Life Index-Cardiac Version III were used to assess effects on HQOL. RESULTS: Both groups had similar HQOL scores at baseline. At end of treatment and at 12-month follow up, patients who had active-CP reported greater improvement than those who had inactive-CP in all nine quality of life scales, including ability to perform activities of daily living, ability to work, bodily pain, confidence in health, energy, ability to engage in social activities with family and friends, anxiety and depression, and quality of life issues from the effects of angina on health and functioning. Despite small sample sizes, active-CP patients demonstrated significantly greater improvement at 12 months following treatment in bodily pain, social functioning, and quality of life specific to cardiac patients compared with inactive-CP patients. CONCLUSION: Significant health-related quality of life improvements were measurable up to 12 months after the completion of treatment with EECP. Improvements in this controlled study are consistent with HQOL changes reported in case series and patient registries. Larger studies are warranted.
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