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Biomedical subjects

K Isurugi

Publications and source records attributed to K Isurugi.

At least 73 records · Page 4Linked to original sources

[Phase I study of bestrabucil (KM 2210)].

A phase I study was performed on a newly developed antitumor agent, Bestrabucil (KM 2210). The study was started at an initial dose of 1 n 25 mg/body, and gradually increased up to 32n 800 mg/body. With single (35 patients) and five-consecutive-day (36 patients) administration, the dose-limiting factor was found to be tarry stool, remarkable decrease in hemoglobin content, and strong nipple and breast pain. The maximum tolerated dose (MTD) was concluded to be around 700 to 800 mg/body. With long-term administration (the longest term, 20 weeks, 36 patients), the dose-limiting factor was concluded to be a decrease in the peripheral leukocyte count when the total amount administered reached about 10 g. Side effects on the alimentary system due to this agent, such as vomiting, nausea and anorexia, were observed. In addition, mastalgia and genital bleeding due to released estrogen were also seen, especially in the case of long-term administration.

Adult↗

Measurement of urinary steroid profile in patients with adrenal tumor as a screening method for carcinoma.

Results of measurement of urinary steroid metabolite profile using gas chromatographic analysis in eight patients with adrenocortical tumors, i.e. 3 adenomas with Cushing's Syndrome, one adenoma with virilization, one adenoma without clinical manifestations, one carcinoma with Cushing's syndrome and virilization, one carcinoma with Cushing's syndrome and feminization, and one carcinoma without endocrinological symptoms, are reported. A unique pattern dominated by 5 beta and 11 beta-hydroxy steroid metabolites was confirmed in five patients with Cushing's syndrome consisting of three cases with adenomas and two with carcinomas. Excessive 3 alpha, 17 alpha, 21-trihydroxy-5 beta-pregnan-20-one (tetrahydro-11-deoxycortisol, THS) and delta 5-pregnene-3 beta, 11 alpha, 20 alpha-triol (delta 5-pregnenetriol) values were found in all three carcinomas including a nonfunctional carcinoma. These findings would strongly suggest the tumor to be a carcinoma, although excessive excretion of THS and delta 5-pregnenetriol was detected in one patient with a large adenoma associated with virilization. One patient with carcinoma was responsive to ACTH stimulation while the remainder show almost no response to exogenous ACTH. Urinary steroid profiling using gas chromatographic analysis, especially the values for THS and delta 5-pregnenetriol, appears to be a useful method to use in detecting these steroid metabolic characteristics in patients with adrenocortical carcinoma.

Adenoma↗

[Effects of UFT in advanced renal cell cancer].

Clinical trials of UFT have been conducted on patients with far-advanced renal cell cancer with distant metastasis. All patients had evaluable lesions which had shown no change or progressive disease under prior therapy. Five of these cases had received Interferon as prior therapy. Thus far, the antitumor effects of the drug were evaluated in 8 cases according to the criteria proposed by the Koyama-Saito group. Partial response was obtained in 3 of 8 patients (37.5%). Two patients showed no change and three patients showed progressive disease UFT caused anemia and diarrhea in each of patients. To measure the 5-FU level in the tumor and normal kidney tissues UFT was administered at 600 mg per day on the day before radical nephrectomy in 2 patients, who had received embolization therapy of the renal artery prior to surgery. The 5-FU level was higher in tumor and normal kidney tissues than in serum, but there was no significant difference between tumor and normal kidney tissues. The embolization therapy of the renal artery may have been responsible for this result. UFT is one of the most useful drugs for the treatment of renal cell cancer.

Administration, Oral↗

Childbirth in true hermaphrodite.

14-year-old Japanese girl with a 46,XX karyotype underwent an exploratory laparotomy for signs of virilization. The left ovary and other pelvic organs were of female type. The right gonad was found to be an ovotestis which was removed. At age of 25, the patient gave birth to a normal male infant by full-term, vaginal delivery. In the literature, this is the third case of normal delivery in 7 true hermaphrodites with pregnancy and childbirth.

Adult↗

[Clinical application of KM 2210 (estradiol-chlorambucil) in patients with advanced prostatic carcinoma].

KM 2210, a combination product of 17 beta-estradiol and chlorambucil, was administered to 15 patients with advanced (stage C and D) prostatic carcinoma. We studied the clinical efficacy and the drug concentration in the blood and prostatic tissues. The administered doses were 100 mg or 150 mg p.o., in 2 or 3 divided doses/day (or every other day in a few cases) for periods ranging from 30 to 369 days; the maximum total dose was 42.5 g. Objective clinical responses, according to the criteria by Shida et al., were observed in 6 (40%) patients. Side effects included gastrointestinal symptoms, e.g. loss of appetite or nausea, anemia and leukopenia. No obvious hepatic disorder was observed.

Aged↗

[Bestrabacil: a possible target-oriented anticancer agent].

Bestrabucil, the benzoate of an estradiol-chlorambucil conjugate, was initially developed as a target-oriented anticancer agent for breast cancers with positive estrogen receptors, by conjugating a tumoricidal agent, chlorambucil, to a vehicle, estradiol. Further studies, however, revealed that regardless of the presence of estrogen receptors, bestrabucil selectively accumulates in malignant tumor cells. The unique feature of bestrabucil, selective affinity to tumor cells, was demonstrated in in vitro and in vivo studies. Significantly larger amounts of 3H-bestrabucil accumulated in malignant cells (3T3-SV40 transformed) than in normal cells (3T3). In vitro inhibition effects of bestrabucil on cell growth was observed only in malignant cells. Selective accumulation of bestrabucil in malignant tumor tissues was also demonstrated in in vivo experiments. After a single oral administration of 100 mg/kg of bestrabucil to female Wistar rats bearing Walker 256 carcinoma, bestrabucil accumulated significantly occurred in tumor tissues with little or no accumulation in normal tissues and blood. Anti-tumor effects and toxicities of bestrabucil and chlorambucil, were compared using Walker 256 carcinoma. Bestrabucil exerted its antitumor effects with little change in leucocyte counts in the peripheral blood, whereas chlorambucil showed significant side effects. Finally, selective accumulation of bestrabucil in malignant tumor tissues, was demonstrated clinically. Tumor specimens obtained during the operation of patients with various types of cancer, 24 hours after oral administration of 100 mg of bestrabucil, contained significantly larger amounts of bestrabucil compared with adjacent normal tissues. Clinical trials of bestrabucil are being carried out at present. Bestrabucil seems to be a promising target-oriented anticancer agent and deserves further investigation.

Administration, Oral↗

Responses of serum testosterone levels to human chorionic gonadotrophin stimulation in patients with Klinefelter's syndrome after long-term androgen replacement therapy.

Responses of serum testosterone levels to repeated daily injections of 5000 IU hCG for 4 days were studied in 24 patients with Klinefelter's syndrome. Eighteen patients were untreated, and 8 had been given previous treatment with depot testosterone 100 mg intramuscularly every 2-3 weeks for an average duration of 4.7 years. Among them, 4 patients were examined both before and after the therapy. The hCG test was performed at least 2 weeks (0.5-12 months) after the last injection of depot testosterone in the treated patients. Mean basal testosterone level of the treated patients, 139 +/- 98 ng/dl (Mean +/- SD), was not significantly different from that of the untreated patients, 172 +/- 110 ng/dl. Maximum stimulated testosterone level in the treated patients, 170 +/- 107 ng/dl (P less than 0.05). These results suggest that long-term androgen administration may decrease the functional reserve of Leydig cells in patients with Klinefelter's syndrome.

Adolescent↗

Carcinoma in situ of germ cells and subsequent development of an invasive seminoma in a hyperprolactinaemic man.

A 25-year-old man was first seen complaining of impotence and found to have a pituitary tumour and hyperprolactinaemia. Both testes were small and atrophic, but a testicular tumour was not apparent. Biopsy of the right testis was performed, and the pathology report described thickening of the seminiferous tubule walls and impaired spermatogenesis. The patient refused to undergo an operation for his pituitary tumour and was lost to follow-up. 5 years later, the same patient presented with enlargement of his right testis, and this and the pituitary tumour were excised. The testicular tumour was classified as seminoma, and the pituitary tumour as an adenoma with low malignancy. Re-examination of the previous specimen of his right testis revealed foci of carcinoma-in-situ. This is an additional example of the growth of an invasive germ cell tumour from non-invasive carcinoma-in-situ of the testis.

Adenoma↗

Cytogenetic studies in a Y-to-X translocation observed in three members of one family, with evidence of infertility in male carriers.

A family is reported in which the mother and two sons are carriers of a Y-to-X translocation, der (X)t(X;Y) (p22;q11). All the the three carriers have short stature and disproportion of extremities, but otherwise normal phenotype. One of the sons, the propositus, has been affected with schizophrenia. Evidence was obtained that male carriers are probable sterile; both sons aged 26 and 30 years had azoospermia and the biopsied specimens of the testis had histologic pictures showing spermatogenetic arrest. The mother was H-Y weakly positive, and the normal X chromosome was inactivated in the majority of the cells analyzed. Dermatoglyphics of the three carriers were unusual and dissimilar to the features of Turner's syndrome. The clinical and cytogenetic findings in the present study are compared with those of the previously reported familial cases, and the genetic background causing phenotypic abnormalities in the male and female carriers is discussed.

Adult↗

Investigation of genetic markers in a true hermaphrodite with chi 46,XX/46,XY.

We documented a new case of chi 46,XX/46,XY true hermaphroditism substantiated by the evaluation of chromosomal heteromorphism in banded preparations. The patient, a 12-year-old Japanese boy with ambiguous external genitalia, was seen because of abnormal breast development. Surgical exploration showed the right gonad to be an ovotestis and the left gonad to be an ovary. Cytogenetic studies revealed cell admixtures of 46,XX and 46,XY karyotypes in peripheral lymphocytes, skin fibroblasts, and gonadal fibroblasts. From the pedigree studies, the paternal double genetic contributions were evidenced by the differences of sex chromosomes and the blood group types for the ABO and MNSs systems in the two cell lines of the patient. The maternal double genetic contributions were confirmed by the inheritance of Q-fluorescent markers on chromosomes 13 and 22 and by alleles for the Kidd blood group system.

Blood Grouping and Crossmatching↗

Responses of serum levels of testicular steroid hormones to hCG stimulation in patients with prostatic cancer and benign prostatic hypertrophy.

Serum levels of testosterone (T), dihydrotestosterone (DHT), androsterone (A), 5 alpha-androstane-3 alpha, 17 beta-diol (5 alpha-diol) and estradiol-17 beta (E2) were measured by radioimmunoassay in the sera of 9 patients with untreated prostatic cancer and in 11 with benign prostatic hypertrophy (BPH). Basal levels and responses to hCG stimulation were investigated. Although no specific changes in steroid hormone levels in either disease group were found, response patterns of serum T, DHT, and E2 were shown to be those characteristic of male senescence, suggesting a relative predominance of estrogens over androgens. Neither 5 alpha-diol nor A exhibited appreciable responses to hCG stimulation in our study.

Aged↗

Localized amyloidosis of urethra. Report of two cases.

Two cases of localized urethral amyloidosis are reported. Data pertaining to 13 cases including our two cases are reviewed. The difficulty in preoperative differentiation of an amyloid tumor from a urethral malignancy is stressed. It is advisable to perform open or transurethral biopsy of the urethral tumor before deciding on radical surgery.

Amyloidosis↗

Endocrine effects of cyproterone acetate in patients with prostatic cancer.

Cyproterone acetate was given to patients with stages C and D prostatic cancer and its effect on endocrine parameters was studied. At a daily oral dose of 100 mg. cyproterone acetate induced marked reduction in the size and consistency of tumor, while it caused moderate suppression of serum luteinizing hormone, follicle-stimulating hormone and testosterone levels. Elevation of serum prolactin levels was observed after treatment with cyproterone acetate but was to a lesser degree than that caused by estrogens.

Aged↗