[Show abstract][Hide abstract] ABSTRACT: Colorectal cancer is one of the most common malignancies in the world, and irinotecan (CPT-11) is useful in its treatment. However, the safety and pharmacokinetics of irinotecan in dialysis patients with metastatic colorectal cancer are unclear.
We report the case of a 74-year-old man receiving chronic hemodialysis who had metastatic colorectal cancer. Palliative chemotherapy with irinotecan (80 mg/m2 weekly) was administered after hemodialysis. Blood samples were collected before and 1.5, 3, 6, 9, and 15 hours after administration of irinotecan. The peak serum concentrations (Cmax) of irinotecan and SN-38 in this patient were 1,480 and 17.8 ng/mL, respectively, which were similar to the reported values in patients with normal renal function after a similar dose of irinotecan (75 mg/m2). The area under the serum concentration-time curve (AUC0-∞) was 8,240 ng×h/mL for irinotecan and 619 ng×h/mL for SN-38. The AUC0-∞ for SN-38 was markedly higher than that for patients with normal renal function. Sequencing analysis of the UGT1A genes found that the patient had variant alleles of UGT1A1*28, UGT1A1*60 and UGT1A9*22, which may lead to decreased glucuronidation and excretion of SN-38, and may account for increased irinotecan-related toxicity. The patient developed febrile grade 4 neutropenia on day 7 after chemotherapy and died of septic shock on day 14.
UGT1A polymorphisms and renal failure may lead to accumulation of SN-38, which may have played a role in the death of this patient. Irinotecan should be used cautiously in dialysis patients with metastatic colorectal cancer and screening for UGT1A polymorphisms may help in identifying patients with lower SN-38 glucuronidation rates and greater susceptibility to irinotecan-induced toxicity.
[Show abstract][Hide abstract] ABSTRACT: Inflammation, an important mechanism in the pathogenesis of atrial fibrillation (AF), can be regulated by CD36 in monocytes.
The purpose of this study was to test the hypothesis that CD36 in monocytes contributes to the pathogenesis of AF.
A prospective study that enrolled 87 patients with AF and 70 without AF was conducted.
Compared to patients without AF, patients with AF had monocytes with a lower level of CD36 protein, which correlated with left atrial diameter, left atrial emptying fraction, and left atrial mean voltage. In AF patients after catheter ablation, Kaplan-Meier analysis showed that the sinus rhythm maintenance rate was higher in patients with high CD36 levels. Low CD36 level was an independent predictor of recurrence. After successful ablation, the CD36 level increased by 57%, reaching that of control patients. CD36 level was not correlated with the level of high-sensitivity C-reactive protein. Analysis of mRNA levels from a buffy coat revealed that AF patients had lower CD36 and interleukin-10 levels and higher peroxisome proliferator-activated receptor-γ and tumor necrosis factor-α levels, with CD36 level positively correlated with interleukin-10 level but inversely correlated with peroxisome proliferator-activated receptor-γ and tumor necrosis factor-α levels.
Low CD36 levels in circulating monocytes were associated with AF occurrence and predicted recurrence after catheter ablation. The link between CD36 and AF identified a novel AF-related inflammatory pathway.
No preview · Article · Dec 2010 · Heart rhythm: the official journal of the Heart Rhythm Society
[Show abstract][Hide abstract] ABSTRACT: The presence of diastolic dysfunction increases the risk of atrial fibrillation (AF), and might be associated with the left atrial (LA) substrate. The aim of the present study was to investigate the relationships between the diastolic dysfunction, atrial substrate and outcome of the catheter ablation.
Eighty-three patients with paroxysmal AF were enrolled. Diastolic dysfunction was defined as a left ventricular ejection fraction (LVEF) of ≥ 50%, and one of the following criteria: (1) a mitral inflow early filling velocity to atrial filling velocity ratio (E/A) of ≤ 0.75; or (2) an E/A ratio of >0.75 and a ratio of the mitral inflow early filling velocity to the velocity of the early medial mitral annular ascent of >10. Patients with diastolic dysfunction were older than those with normal cardiac function. There were no differences in the other baseline characteristics, LA diameter, or LVEF. A decreased LA voltage, and higher recurrence rate were noted in patients with diastolic dysfunction. In the univariate analysis, the patients with recurrence had a lower LA voltage and greater diastolic dysfunction. The multivariate analysis also indicated diastolic dysfunction and LA voltage as independent predictors of recurrence.
The patients with diastolic dysfunction developed a different atrial substrate and had a worse outcome of catheter ablation for atrial fibrillation.
No preview · Article · Oct 2010 · Circulation Journal
[Show abstract][Hide abstract] ABSTRACT: Free wall rupture, the most fearful complication of myocardial infarction, mostly attacks anterior walls. Acute rupture is characterized by rapid development of mechanical arrest accompanied with bradyarrhythmia or electromechanical dissociation. The majority of patients succumb to death as the result of cardiac tamponade. Risk factors are advanced age, female gender, the first-time myocardial infarction, hypertension, and ST-segment elevation. We report a rare case of posterior wall myocardial infarction complicated with left ventricular rupture initially presenting with junctional escape rhythm.
No preview · Article · Jan 2010 · Internal Medicine