Toxicological study of a new maintenance fluid, Veen 3G, in rats.

A study of the different volume and infusion rates of a new maintenance fluid, Veen 3G, on the general conditions of rats was investigated during the 14 days after infusion. In Experiment I, 100 ml/kg and 200 ml/kg of Veen 3G were infused at a rate of 300 ml/kg/h in male and female rats. Results were compared with those for Gurunon Ringer solution (GRS) in male and female rats. We observed only transient polyuria in animals administered by each dose of Veen 3G and GRS for 0-15 min after infusion. Necropsy was not observed in any of the animals tested 14 days after infusion. In Experiment II, 200 ml/kg of Veen 3G was infused at rates of 200, 400, 800 and 1600 ml/kg/h in male rats. At 800 and 1600 ml/kg/h, irregular respiration and decrease in movement were observed concomitantly with polyuria. Three out of 4 rats died immediately after the infusion of Veen 3G at a rate of 1600 ml/kg/h, and one rat was still alive 14 days after the infusion. In this experiment, 200 ml/kg Veen 3G was safe when we infused at a rate of less than 400 ml/kg/h in male rats. Since this rate is about 27-80 times higher than that used clinically in maintenance treatment, Veen 3G is suggested to be safe, with the exception of polyuria, in clinical situations at the standard infusion rate (5-15 ml/kg/h).

Ipidacrine (NIK-247), a novel antidementia, rapidly enters the brain and improves scopolamine-induced amnesia in rats during the Morris water maze task.

The effects of single and repeated administrations of ipidacrine (NIK-247, 9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinoline monohydrochloride monohydrate) on scopolamine-induced spatial learning deficit were investigated in rats using the Morris water maze task. A single oral administration of ipidacrine (0.3 and 1 mg/kg) reduced the increased total latency induced by scopolamine in this task. The repeated administration of ipidacrine (1 mg/kg) of once a day for 5 successive days reduced the increased total latency induced by scopolamine to the levels of the saline-treated control rats in this task. In this pharmaco-kinetic study, ipidacrine was rapidly taken up into the brain within 5 min. Moreover, higher drug levels were observed mainly in the cortex and hippocampus, which both play important roles in learning and memory. Thus, a previous study together with this investigation indicate that ipidacrine improves amnesia which consists of the impairment of the working and reference memory in various animal models, suggesting that ipidacrine is a useful candidate for the therapy of patients with Alzheimer's disease.

[Chemoembolization therapy with lipiodol, cisplatin and etoposide for hepatocellular carcinoma].

Chemoembolization using CDDP, VP-16 and lipiodol was carried out for 7 patients with hepatocellular carcinoma (HCC). CDDP/lipiodol, CDDP/VP-16, CDDP/lipiodol (lipiodol 2-10 ml, CDDP 1-2 mg/kg, VP-16 100 mg/body) and gelatine sponge were administered in that order through the catheter located in the proper, or right or left hepatic artery. Three patients underwent hepatic resection 38-50 days after this treatment. Complete necrosis of the tumor was recognized in the one case, although the portion of necrosis did not exceed 70% in large sized HCC as the diameter of more than 10 cm. In 4 unresectable cases the decreases in tumor size were observed by ultrasonography and computed tomography. The response was: 3 partial responses and 1 no change. One out of 4 cases could undergo hepatic resection 17 months after this treatment. Two patients are alive 20 months after this treatment, although one patient died of HCC after 25 months. Serious side effect was not observed.

Treatment of hepatocellular carcinoma by transcatheter arterial embolization combined with intraarterial infusion of a mixture of cisplatin and ethiodized oil.

The therapeutic effectiveness of transcatheter arterial embolization (TAE) with intraarterial infusion of cisplatin/ethiodized oil mixture in treatment of resectable and unresectable hepatocellular carcinoma was compared with TAE with intraarterial infusion of doxorubicin mixed with and without ethiodized oil. The series included 97 patients with unresectable hepatocellular carcinoma and 40 patients with resectable hepatocellular carcinoma. With TAE using doxorubicin infusion, a partial response of the tumor was seen in only 11%, and the 2-yr survival was calculated to be only 5%. Histologic examination of the specimens obtained by hepatectomy also showed that this treatment was relatively ineffective in daughter tumor and portal tumor thrombi. In contrast, TAE with infusion of cisplatin/ethiodized oil mixture significantly increased the rate of partial response (38%), and significantly prolonged the 2-yr survival (45%). Histologically this treatment gave severe necrosis in daughter tumors (69%) and tumor thrombi (78%) as well as main tumor (75%). This treatment was significantly better than TAE with doxorubicin and ethiodized oil infusion in terms of the tumor regression and histologic responses of main tumor and portal vein tumor thrombi, but not in terms of the 2-yr survival. However, 2 patients (8%) died within 4 wk of the latter treatment, whereas no deaths were reported after the former treatment. Therefore, TAE combined with intraarterial infusion of cisplatin/ethiodized oil mixture may be a safe and useful treatment modality for hepatocellular carcinoma.

A pre-operative chemoembolization therapy using lipiodol, cisplatin and gelatin sponge for hepatocellular carcinoma.

The significance of pre-operative transcatheter arterial chemoembolization therapy using lipiodol, cisplatin and gelatin sponge (Gelfoam) for the prevention of the recurrence of hepatocellular carcinoma (HCC) was evaluated. On the 103 patients who underwent radical operations for HCC with a tumor size less than 10 cm, 52 patients received no pre-operative therapy (group C), and 51 patients received pre-operative chemoembolization using lipiodol, a chemotherapeutic agent and Gelfoam. Of these 51 patients, 37 patients received a combination of lipiodol, cisplatin and Gelfoam (group A), while the remaining 14 patients received lipiodol, adriamycin and Gelfoam (group B). The disease-free survival rates after surgery were compared between group A, group B and group C. The 2-year disease-free survival rates in group A, group B and group C were 72%, 46% and 54%, respectively. These rates therefore suggest that pre-operative chemoembolization using lipiodol, cisplatin and Gelfoam is a useful method to prevent the recurrence of HCC after surgery.

A new approach to chemoembolization therapy for hepatoma using ethiodized oil, cisplatin, and gelatin sponge.

This article reports on a new approach to hepatic arterial chemoembolization therapy using ethiodized oil (Lipiodol, Ultra Fluide), cisplatin, and gelatin sponge (Gelfoam, Upjohn, Kalamazoo, MI) for hepatocellular carcinoma (HCC). The anticancer effects of this therapy on 20 patients who underwent subsequent hepatic resection were evaluated mainly by histologic examination. All main tumors were reduced in size following this therapy. It is notable that in 65% of the patients the tumor size was reduced to less than 50% of that before therapy. All the values of serum alpha-fetoprotein (AFP) in the patients who exhibited pretreatment levels exceeding 100 ng/ml dropped by more than 50%, and in 55% of them it fell below 20 ng/ml. The concentration of platinum in the tumor tissue was significantly higher than that in the nontumorous tissue. In 15 of 20 patients (75%), the main nodules were completely necrotic. Thirteen of the patients had daughter nodules and/or small intrahepatic metastases (Group A); nine had tumor emboli in the portal (hepatic) vein (Group B); 17 had intracapsular invasions (Group C); and ten had extracapsular invasions (Group D). The ratios of patients with completely necrotic cancer cells in Group A were nine of 13 (69%); in Group B, seven of nine (78%), in Group C, 11/17 (65%); and in Group D, four of 10 (40%). In eight of the 20 patients (40%) no viable cancer cells were recognized at any foci. Lesions other than those with extracapsular invasion could be considerably eliminated with this form of therapy. It is expected that this method will become the therapy of choice not only for palliative treatment but also for preoperative treatment.