Yoshihito Iwai

Hepatic blood flow and drug metabolism in glycerol-rechallenged rats

SummaryTo analyze the hepatic blood flow and drug metabolism during glycerol-induced acute renal failure, 24 male Wistar rats were randomly divided into three groups: Group I received an intra-muscular injection of 1 ml/100g body weight 50% glycerol, group II a second injection on day 14 and group III a second injection on day 42 after the first injection respectively. The inulin clearance, the aminopyrine N-demethylase activity, the NADPH-cytochrome P-450 activity and the cardiac output and blood flow to the organs were measured before and after glycerol injection. The total hepatic and renal blood flow decreased less significantly in group II compared to group I and III. Various P 450 activities were kept on a high level only in group II. This observation indicates that the maintenance not only of renal but also of hepatic blood flow plays an important role in preventing the development of glycerol-induced acute renal failure. The mechanism may be the induction of various P 450 activities resulting in an increased hepatic clearance of nephrotoxic substances.

Palliative Treatment of Bone Metastases in Hormone-Refractory Prostate Cancer: Effects of Pamidronate on the Carboxyterminal Telopeptide of Type-I Collagen Level in Patients with Increasing Prostate-Specific Antigen Levels

Purpose: Bisphosphonates have been reported to be effective in reducing bone pain and skeletal-related events associated with bone metastases in hormone-refractory prostate cancer (HRPC). However, whether bone resorption is reduced primarily by these particular drugs is difficult to evaluate because patients with HRPC are usually treated with secondary or tertiary hormonal manipulations including second-line antiandrogens, high-dose diethylstilbestrol, or low-dose dexamethasone therapies, some of which may also be effective. Thus, we assessed changes in the level of the carboxyterminal telopeptide of type-I collagen (ICTP), a bone resorption marker, before and after pamidronate administration in HRPC patients with increasing prostate-specific antigen (PSA) levels. Patients and Methods: Twenty-one HRPC patients with bone metastases and increasing PSA levels were intravenously treated with pamidronate at a dose of 30 mg either every 2 or every 4 weeks. Pamidronate administration was started immediately after confirmation of three consecutive increases in the PSA level. Results: In 14 patients (67%), the ICTP levels decreased after the administration of pamidronate, despite increasing PSA levels. In 7 of these cases, the ICTP levels were lower than those recorded for 6 months or longer before the start of pamidronate administration. The characteristics of the responders were compared with those of the non-responders. Conclusion: In 67% of the HRPC patients with increasing PSA levels, pamidronate reduced the accelerated turnover of bone metabolism caused by metastases of prostate cancer.

New method of retrograde urethrography. Clinical study of autourethrography

Autourethrography (A-UG), a new method of retrograde urethrography was developed, in which the patient injects the contrast medium by himself under fluoroscopical observation by urologists out side of the room. For clinical study of A-UG, comparative study between A-UG and the conventional retrograde urethrography (C-UG) was performed on 20 patients with benign prostatic hypertrophy. The mean age was 68.8 years (range 49-85 years) in A-UG and 69.4 years (range 61-86 years) in C-UG. We evaluated complications of A-UG, compared with these of C-UG. Opacification of the posterior urethra was achieved in all but one in A-UG. None of these patients in A-UG experienced pain during the examination of A-UG. On the other hand, all patient experienced pain in C-UG. Urethral bleeding occurred in only one of 19 patients in A-UG, compared with eighteen of 20 patients in C-UG. Extravasation occurred in one of 19 patients in A-UG, compared with three patients of 20 patients in C-UG. A-UG left the urologists free from the radiological exposure. It is concluded that A-UG is highly useful examination for patients and urologists.