Ontogeny of behavioral sensitization to cocaine

The ontogeny of the behavioral effects of acute cocaine administration and behavioral sensitization to cocaine in rat pups was investigated. Acute behavior stimulating effects of cocaine were observed in pups as young as 7 postnatal days (PND) old, although they needed a higher dose of cocaine than adult rats to evoke the same motor effects. An adult dose-response curve pattern of stereotypy and locomotion to acute cocaine treatment was observed at PND 21, and of rearing at PND 28. Rats aged PND 7, 14, 21, 28, and 56 received repeated injections of saline or cocaine (15 mg/kg) twice a day for 5 consecutive days. After a 3-week period of abstinence, sensitization to a challenge dose of cocaine was assessed. Cocaine-induced stereotyped behavior was enhanced significantly only in rats in which cocaine pretreatment was initiated on PND 21, 28, and 56, but not earlier on PND 7 and 14. Adult female rats given repeated cocaine injections on PND 56–60 showed significantly greater sensitization than males, but no such sex difference was observed in pups given cocaine repeatedly on PND 21–25 or 28–32. These results show clearly that cocaine-induced behavioral sensitization in rats occurred only when subchronic cocaine administration was commenced on PND 21 or later.     

Clinical and pathological evaluations of methotrexate, vinblastine, Adriamycin and cisplatin chemotherapy for advanced urothelial cancers

We have treated advanced transitional-cell carcinoma of the urothelial tract with methotrexate, vinblastine, Adriamycin, and cisplatin (M-VAC) chemotherapy since July of 1985. We analyzed the effect of that chemotherapy in 26 patients with advanced urothelial cancer who were treated in our hospital and followed up. They were divided into two groups. Group 1 consisted of 15 patients with distant metastases. In all, 11 of them received M-VAC as adjuvant chemotherapy for metastatic lesions after surgical removal of the primary lesion, and the remaining 4 patients were not operable since they had very advanced-stage tumors; they received only M-VAC chemotherapy. Group 2 contained 11 patients who received M-VAC neo-adjuvant chemotherapy. In group 1, the overall response rate was 57.1% and the mean duration of response was 12.6 months. In the 11 patients who had received M-VAC as adjuvant therapy after surgical removal of the primary tumor, the mean duration of response was 14.1 months. After M-VAC chemotherapy, six patients underwent surgical resection of metastatic lesions and restaging was done pathologically in these cases. The clinical response coincided with the pathological response in all six cases. In group 2,5 of 11 patients experienced histological downstaging of the resected bladder. M-VAC chemotherapy combined with surgical resection of residual tumors has proved to be an effective option against advanced urothelial cancer.Presented at the 4th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 16–17 November 1990, Osaka, Japan     

A case of renal pelvic carcinoma in situ]

A 72-year-old female visited our hospital with the complaint of macroscopic hematuria on Jan. 29, 1990. Cystoscopic examination revealed hematuria flowing out from the left ureteral orifice. A 1 cm mass was found in the left upper calyx by retrograde pyelography (RP). Urine cytology obtained by RP was class IIIb. Later, the mass was found in the left middle calyx by CT. Repeated RP revealed no mass and the wall of the left upper calyx was irregular. Washing cytology from the left renal pelvis was class V. Left total nephroureterectomy was performed on Feb. 2, 1990. Macroscopically, no tumor mass was apparent. Microscopically, transitional cell carcinoma in situ was widely spread from the left renal pelvis to the middle ureter. The preoperative upper calyceal mass was thought to have been a blood clot. At twelve months after the operation, there has been no evidence of tumor recurrence.     

Clinical studies on morphological changes in the prostate in patients with benign prostatic hypertrophy after antiandrogen therapy--by means of transrectal ultrasonotomography]

Transrectal ultrasonotomography is useful in following patients with benign prostatic hypertrophy, because prostatic shape and weight are precisely assumed. We studied the effect of chlormadinone acetate (CMA) on benign prostatic hypertrophy. CMA (50 mg/day) was administered to 30 patients with benign prostatic hypertrophy. Weight reduction over 10% of the gland was noticed in 24 cases (80%). Mictional conditions were improved in 70% subjectively and in 71.4% objectively. However, the number of nocturia decreased in only 18.9%. Reduction rate of the weight was unrelated with the weight of prostate before administration of CMA. Duration of administration of CMA and the reduction rate were estimated. There was no definite difference in reduction rate for the first 15 months, but there was a slightly high reduction rate after administration of CMA for more than 24 months. In 3 cases, the shape and weight of prostate were studied after discontinuation of CMA. The size of prostate showed a tendency to increase gradually.     

A case of double cancer: renal cell carcinoma and transitional cell carcinoma of urinary bladder

This is a case report on a patient with double cancer of kidney and urinary bladder. The patient was a 65-year-old female, and she was admitted with the chief complaint of gross hematuria and right flank pain. After careful examinations, she was diagnosed with right nonfunctioning kidney caused by invasive bladder cancer. Computerized tomography incidentally revealed a mass in the upper pole of the left kidney. Selective left renal arteriography showed stretched arteries and irregularity and tortuosity of the smaller vessels. She was diagnosed with double cancer of bladder and left kidney. Owing to the damage of the right renal function, left partial nephrectomy, total cystectomy, right nephroureterectomy and left ureterocutaneostomy were performed. According to DMSA scintigraphy measured 15 days later, the uptake value of the left kidney was 13.25%, compared to the preoperative value of 25.62%. To date, this case is 36th reported case in Japan.     

A simple method for screening assessment of acute toxicity of chemicals

We proposed a simple method for screening assessment of acute oral and dermal toxicity using only three rats and mice of each sex at each dose level. Animals were first treated with chemicals at a dose of 2000 mg/kg and were carefully observed for compound-related morbidity and mortality. If none of the animals died, the following toxicity tests were suspended. If some of the animals died, toxicity tests at doses of 200 and 20 mg/kg were performed. The approximate LD₅₀ values calculated by this method showed little difference between two separate laboratories and were in good agreement with LD₅₀ values reported in the literature. Our toxicological data also showed that LD₅₀ values were about 2–2.5 times the MNLD (maximum non lethal dose) in acute oral and dermal toxicity. This meant that a chemical could be regarded as having an LD₅₀ of about 4000 mg/kg or higher when there was no mortality at the dose of 2000 mg/kg. A chemical with such low toxicity would not require further testing for lethal effects. Therefore, this simple method combining the fixed-dose procedure with the limit test is suitable for determination of approximate LD₅₀ values of chemicals and for screening for necessity for classical full LD₅₀ test using many animals.This work was supported by a grant from Ministry of Health and Welfare in Japan (No. 467 and 511)     

Biocompatibility of zirconia dispersed hydroxyapatite ceramics

Because of the lack of adequate strength and toughness, hydroxyapatite (HA) ceramic can not be used for a substitute for a bone and joint despite its excellent affinity for the bone. The present authors have succeeded in producing a new type of HA ceramic containing zirconia. This new ceramic material is superior to ordinary HA ceramic in quality and exceeds compact bone in bending strength and fracture toughness. The Young's modulus was about 3-4 times greater than that of compact bone. The new ceramic material contained either 1.6 or 50% of zirconia by volume and was produced using a special technique to disperse the metal dioxide. In order to assess their affinity for the bone, the new ceramic materials were implanted into rabbit femurs. Sections of the bones removed at different times after operation were prepared without decalcification and subjected to optical microscopy, scanning electronmicroscopy (SEM), and electron-probe X-ray microanalyser (EPMA). The formation of direct chemical bonds with the bone was seen without intervening membrane. Thus, the new ceramic material was shown to have an excellent affinity for the bone, comparable to that of ordinary HA ceramic.     

Two cases of subcortical hemorrhage with asymptomatic occlusion of the main trunk of cerebral artery

We report two cases of asymptomatic occlusion of the main trunk of the cerebral artery associated with subcortical hemorrhage in the area fed by collateral circulation. The first patient, a 51-year-old female who had suffered from untreated hypertension for 20 years, was hospitalized in a state of coma. Computed tomography (CT) revealed a subcortical hemorrhage in the right parietal lobe as well as subdural and subarachnoid hemorrhages. Cerebral angiography disclosed occlusion of the right internal carotid artery at its origin. The region normally supplied by the right anterior (ACA) and middle cerebral (MCA) arteries was supplied instead by the posterior cerebral artery via leptomeningeal anastomosis. The hematoma was removed and the patient was discharged 1 month later. The second patient was a 54-year-old female who had suffered from uncontrollable hypertension for 27 years and was hospitalized after sudden development of stupor, right hemiparesis and motor aphasia. CT demonstrated a subcortical hemorrhage in the left parietal lobe. Cerebral angiography disclosed occlusion of the left MCA at its origin. The area normally fed by the left MCA was supplied instead by the ACA by way of leptomeningeal anastomosis. One month after operation the patient was transferred to another hospital for rehabilitation of right hemiparesis. Both of these middle-aged women had long-standing hypertension. The hemorrhages were thought to result from rupture of the leptomeningeal anastomosis, which had developed as collateral vessels. It is probable that the relatively weak leptomeningeal anastomosis could no longer withstand the increased blood flow brought on by the hypertension.