Additional effect of low iron diet on iron reduction therapy by phlebotomy for chronic hepatitis C.

BACKGROUND/AIMS: Iron-induced oxidative stress plays an important role in the pathogenesis of chronic hepatitis C. Both phlebotomy for removing body iron stores and low iron diet for minimizing portal iron supply to the liver have been shown to improve serum transaminase levels in patients with the disease. However, the cooperative effects of phlebotomy and low iron diet have not yet been elucidated in detail. METHODOLOGY: A pilot study was undertaken to investigate whether a low iron diet could improve the efficacy of phlebotomy in iron reduction therapy. Of 21 patients diagnosed with chronic hepatitis C, 10 patients were treated with phlebotomy alone (group A) while 11 patients were treated with a low iron plus phlebotomy (group B). Phlebotomy was repeated biweekly until serum ferritin levels reached 10 ng/mL in both A and B groups. In addition, a low iron diet (iron intake of 8 mg/day or less) was recommended for group B, followed by estimation of iron intake from daily diet records. RESULTS: Serum alanine aminotransferase levels were significantly improved from 106+/-30 to 68+/-22 IU/L (p<0.005, paired t-test) in group A and from 100+/-33 to 46+/-10 IU/L (p<0.002, paired t-test) in group B. The enzyme levels after treatment were significantly higher in group A (p<0.02, non-paired t-test), which showed a higher upward distribution of the enzyme activity. The estimated dietary iron intake in group B was reduced from 17.6+/-6.1 to 8.2+/-3.7 mg/day. CONCLUSIONS: These findings suggest that phlebotomy alone does not completely remove iron-induced oxidative stress and a low iron diet induces an additional effect in iron reduction therapy for chronic hepatitis C.

[The efficacy of phlebotomy with a low iron diet in the management of pulmonary iron overload].

Numerous studies have shown that workers in ferriferous industries have an elevated risk of respiratory tract neoplasia and other airway diseases. Evidence is presented that iron is a carcinogenic and tissue toxic hazard as regarding the inhalation of ferriferous substances. Elimination of the inhaled iron and prevention from accumulation of iron in the lung seems to be very important. A 26-year-old man was admitted to our hospital complaining of right chest pain. He had worked as an arc welder for two years without a mask. A chest CT showed diffuse ground glass opacity in the bilateral lung fields. A transbronchial lung biopsy specimen showed numerous alveolar and interstitial iron-laden macrophages. A 200 ml phlebotomy was carried out biweekly in combination with a low iron diet (8 mg/day). When serum ferritin reached 20 ng/ml, phlebotomy was stopped. After that, serum ferritin level was kept at around 20 ng/ml with the low iron diet alone. A transbronchial lung biopsy was carried out again 7 months later and the specimen showed remarkable reduction in the number of iron-laden alveolar and interstitial macrophages. Phlebotomy in combination with a low iron diet might become a useful strategy in the management of pulmonary conditions associated with iron loading.

Phase I studies of nogitecan hydrochloride for Japanese.

BACKGROUND: SmithKline Beecham synthesized camptothecin analogs and identified nogitecan hydrochloride (topotecan) with a broad spectrum of antitumor activity and less toxicity than camptothecin. Because preclinical and overseas clinical data indicated the antitumor effect of nogitecan hydrochloride with a 5-day repeat-dose schedule, we carried out phase I studies in Japan to determine the maximum tolerated dose (MTD), pharmacokinetics, and antitumor effect of nogitecan hydrochloride. METHODS: Phase I studies of nogitecan hydrochloride given by single and 5-day repeat dosing were carried out in patients with various solid tumors at 15 medical institutions in Japan. Pharmacokinetic evaluations were performed for both single and 5-day repeated dosing. RESULTS: The dose-limiting factor (DLF) was reversible leucopenia, and the maximum tolerated dose (MTD) was higher than 22.5 mg/m2 in the single-dose study. In the 5-day repeat-dose study, the DLF was also reversible leucopenia, and the MTD was estimated to be 1.5 mg/m2 per day. The plasma concentration of nogitecan hydrochloride increased with increasing dose, and the half-life after single dosing ranged from 3 to 5h. There was no evidence of accumulation or delayed excretion during 5-day repeat dosing. CONCLUSION: Based on these results and the finding that there were responders among patients treated at 1.5 mg/m2 per day by 5-day repeat dosing in overseas studies, 5-day repeat dosing of 1.2mg/m2 per day, one dose level lower than the MTD, was selected for phase II studies in Japan.