[Clinical use of vinblastine sulfate for malignant lymphoma].
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Biomedical subjects
Publications and source records attributed to H Miyajima.
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Eight-week-old Wistar female rats were treated intramuscularly with 300, 1,000 and 3,000 mg/kg/day of cefotiam for five days. The nephrotoxicity of cefotiam was determined on the basis of the number of tubular epithelial cells excreted, the malate dehydrogenase activity in the urine and the histological examination of the kidneys. Cephalothin (3,000 mg/kg/day) was used as a reference compound. There were slight increases in the number of tubular epithelial cells excreted and in the malate dehydrogenase activity in the urine of some animals receiving 3,000 mg/kg/day of cefotiam or cephalothin. All of these changes disappeared within a few days after the dosing period. The histological examination of the kidneys at the end of both the dosing (5 days) and the recovery (7 days) periods revealed no pathological changes indicating nephrotoxicity. It was concluded that the nephrotoxicity of cefotiam was comparable to that of cephalothin; the urinary changes in animals receiving the highest dose were considered to be an early sign of nephrotoxicity. The maximum non-toxic dose of cefotiam was 1,000 mg/kg/day under the present experimental conditions.
Acute renal injury was produced in rats with K2Cr2O7 (5-40 mg/kg, sc) HgCl2 (0.5-5.0 mg/kg, sc) or cephaloridine (0.5-3.0 g/kg, sc). Histological (percentage of normal, degenerated or necrotic cells) and functional indices (relative kidney weight, renal cortical slice accumulation of organic ions, and blood urea nitrogen content) were evaluated 48 hours later. The relative sensitivity of each of these indices was determined for each nephrotoxicant. Renal cortical accumulation of organic ions appeared to be the most sensitive of the functional parameters. A quantitative histological evaluation was found to be as sensitive an indicator of nephrotoxicity as organic ion accumulation. Alterations in each of the functional indices were significantly correlated with changes in renal histology.
In this study, the authors evaluated the cerebral atrophy in 56 chronic hemodialyzed patients, who did not have clinical episodes or radiologic findings of cerebrovascular diseases, and 42 controls. Using computed tomography (CT) images, brain atrophy index (BAI), the proportion of subarachnoidal plus ventricular space in the cranial cavity, and ventricular area index (VAI), percent area of ventricle in the brain, were calculated. CT of the brain demonstrated an age-dependent increase in BAI in both hemodialyzed patients and controls. BAI and VAI were greater in hemodialyzed patients than healthy controls and the difference was significant at ages under 60 years in BAI and at ages less than 50 years in VAI. The atrophy of the frontal parts of the brain in patients on hemodialysis for 10 years or more was significantly greater than in patients dialyzed for less than 10 years. There was a significant negative correlation between BAI or VAI and hematocrit. These findings indicate that renal failure or hemodialysis itself might cause cerebral atrophy, and that the cerebral atrophy is more prominent in patients on hemodialysis for a long duration and with low hematocrit.
A 65-year-old man with progressive muscle weakness and liver dysfunction following massive small bowel resection showed myriad lipid-filled vacuoles in type I muscle fibers. Carnitine was significantly decreased in muscle, serum and urine. Carnitine supplementation was followed by clinical improvement and decreased lipid droplets in biopsied muscle. He had been receiving carnitine-deficient total parenteral nutrition. This form of carnitine deficiency may be due to a defect in carnitine biosynthesis, as well as dietary carnitine deficiency.
The development and maintenance of testicular interstitial cell (IC) tumors under the conditions of low LH levels were examined in aged Fischer 344 rats, and the enzyme activities for androgen synthesis in the tumors were estimated. Sixty-week old rats received injections of an LH-RH agonist (LH-RHa) for 28 weeks or were subjected to a procedure by which Silastic tubes containing testosterone (T) or estradiol-17 beta (E) were subcutaneously implanted. All 88-week old control animals had bilateral IC tumors, whereas 100% of the T-, E- and LH-RHa-treated rats at week 88 were tumor free. These treated rats showed significantly reduced peripheral LH levels compared to the control animals. No hyperplasia or tumors of the IC were noted in 70-week old animals receiving T for 28 weeks, while all age-matched untreated animals showed IC tumors or hyperplasia. The IC tumors in rats 69 weeks of age decreased in size in response to 4-week treatment involving the subcutaneous implantation of tubes containing T. After removal of the tubes, however, the tumors once again increased in size. Reduced and subsequently elevated serum LH levels were also observed with this treatment. These changes in tumor mass volume were mainly due to a change in the tumor cell volume which was possibly related to LH levels, i.e., large cells were predominant under relatively high peripheral LH levels and intermediate cells were predominant under low LH levels. Quantitative analyses of the in vitro products formed from [3H]progesterone and [14C]4-androstenedione in tissue-homogenates revealed a low 17 alpha-hydroxylase activity and a high 5 alpha-reductase activity in the IC tumors compared to those activities in the testicular tissues; in the tumors, low production of T and high production of 5 alpha-metabolites of progesterone were observed. From these data, it seems reasonable to conclude that sufficient levels of LH are essential for the induction of IC tumors or hyperplasia and the maintenance of tumor mass, and that the low production of T in the tumors is due, at least in part, to decreased 17 alpha-hydroxylase and increased 5 alpha-reductase activities under active steroidogenesis.