VIpart and pointed out some mistakes and suggested some improvements.I wish to express my thanks to Professor H. Popp and Professor s.Iitaka for their constant encouragement during the preparation of the present notes. Last, but not least, I would like to express my thanks to Miss K. Motoishi for her typewriting.

Background-Ghrelin is a novel growth hormone-releasing peptide that also induces vasodilation, inhibits sympathetic nerve activity, and stimulates feeding through growth hormone-independent mechanisms. We investigated the effects of ghrelin on left ventricular (LV) function, exercise capacity, and muscle wasting in patients with chronic heart failure (CHF). Methods and Results-Human synthetic ghrelin (2 g/kg twice a day) was intravenously administered to 10 patients with CHF for 3 weeks. Echocardiography, cardiopulmonary exercise testing, dual x-ray absorptiometry, and blood sampling were performed before and after ghrelin therapy. A single administration of ghrelin elicited a marked increase in serum GH (25-fold). Three-week administration of ghrelin resulted in a significant decrease in plasma norepinephrine (1132Ϯ188 to 655Ϯ134 pg/mL; PϽ0.001). Ghrelin increased LV ejection fraction (27Ϯ2% to 31Ϯ2%; PϽ0.05) in association with an increase in LV mass and a decrease in LV end-systolic volume. Treatment with ghrelin increased peak workload and peak oxygen consumption during exercise. Ghrelin improved muscle wasting, as indicated by increases in muscle strength and lean body mass. These parameters remained unchanged in 8 patients with CHF who did not receive ghrelin therapy. Conclusions-These preliminary results suggest that repeated administration of ghrelin improves LV function, exercise capacity, and muscle wasting in patients with CHF.

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This study identified several UGT1A1 haplotypes significantly associated with the reduced AUC ratio (*28 and *6) and with the increased total bilirubin level (*28, *60, and *IB) and suggested that the novel haplotype *IB might be functionally important. These findings will be useful for further pharmacogenetic studies on adverse reactions to irinotecan.