Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.      

激素治疗增加绝经后健康妇女尿失禁的发病率和严重程度

问题：在绝经后健康妇女中，激素治疗（hormone therapy，HT）对尿失禁（urinary incontinence，UI）的效果如何？     

Prediction of mortality in patients with left ventricular hypertrophy by clinical,exercise stress,and echocardiographic data

OBJECTIVES: This study evaluated the clinical, exercise stress test, and echocardiographic predictors of mortality and cardiac events in patients with left ventricular hypertrophy (LVH). BACKGROUND: Left ventricular hypertrophy is associated with an increased risk of cardiovascular morbidity and mortality. METHODS: Symptom-limited treadmill exercise echocardiography was performed for evaluation of coronary artery disease in 483 patients (age, 66 +/- 11 years; 281 men) with LVH. End points during follow-up were all-cause mortality and hard cardiac events (cardiac death and nonfatal myocardial infarction [MI]). RESULTS: Forty-six patients died and 14 had nonfatal MI. The cumulative mortality rate was higher in patients with abnormal exercise echocardiography (3% vs. 0.4% at one year, 11.7% vs. 3.7% at three years, and 18.3% vs. 9.5% at five years, p < 0.001). In a sequential multivariate analysis model of clinical, exercise test, and rest and exercise echocardiographic data, incremental predictors of mortality were workload (hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3 to 0.9), rate pressure product (HR, 0.7; 95% CI, 0.5 to 0.9), left ventricular (LV) mass index (HR, 1.4; 95% CI, 1.1 to 1.8), and failure to increase ejection fraction (EF) with exercise (HR, 2.1; 95% CI, 1.1 to 3.8). Predictors of cardiac events were history of coronary artery bypass grafting (HR, 2.6; 95% CI, 1.2 to 5.4), lower exercise rate-pressure product (HR, 0.6; 95% CI, 0.5 to 0.8), resting wall motion score index (HR, 1.4; 95% CI, 1.1 to 1.8), and failure to increase EF with exercise (HR, 3.3; 95% CI, 1.6 to 6.9). CONCLUSIONS: In patients with LVH, LV mass index and EF response to exercise are independent predictors of mortality, incremental to clinical and exercise test data and resting LV function. A normal exercise echocardiogram predicts a relatively low mortality rate during the following three years.     

Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome

BACKGROUND & AIMS: Serotonin (5-HT) is a critical signaling molecule in the gut. 5-HT released from enterochromaffin cells initiates peristaltic, secretory, vasodilatory, vagal, and nociceptive reflexes. Despite being pathophysiologically divergent, ulcerative colitis (UC) and irritable bowel syndrome (IBS) are both associated with clinical symptoms that include alterations in the normal patterns of motility, secretion, and sensation. Our aim was to test whether enteric 5-HT signaling is defective in these disorders. METHODS: Rectal biopsy specimens were obtained from healthy controls and patients with UC, IBS with diarrhea (IBS-D), and IBS with constipation (IBS-C). Key elements of 5-HT signaling, including measures of 5-HT content, release, and reuptake, were analyzed with these samples. RESULTS: Mucosal 5-HT, tryptophan hydroxylase 1 messenger RNA, serotonin transporter messenger RNA, and serotonin transporter immunoreactivity were all significantly reduced in UC, IBS-C, and IBS-D. The enterochromaffin cell population was decreased in severe UC samples but was unchanged in IBS-C and IBS-D. When 5-HT release was investigated under basal and mechanical stimulation conditions, no changes were detected in any of the groups relative to controls. CONCLUSIONS: These data show that UC and IBS are associated with similar molecular changes in serotonergic signaling mechanisms. While UC and IBS have distinct pathophysiologic properties, these data suggest that shared defects in 5-HT signaling may underlie the altered motility, secretion, and sensation. These findings represent the first demonstration of significant molecular alterations specific to the gut in patients with IBS and support the assertion that disordered gastrointestinal function in IBS involves changes intrinsic to the bowel.