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Biomedical subjects

H Majima

Publications and source records attributed to H Majima.

At least 55 records · Page 3Linked to original sources
PubMed1989

Spontaneous recovery from hypopituitarism due to postpartum hemorrhage.

A rare case is presented of a woman with spontaneous recovery from hypopituitarism following postpartum hemorrhage. One month after delivery, serum thyroid hormone, TSH, LH and FSH levels were low, and their secretion from the pituitary gland responded poorly to the TRH and LH-RH tests. Pituitary TSH response was normal 3 months after delivery. In the LH-RH test, pituitary LH and FSH response returned to normal at 2 months. Pituitary GH secretion and serum cortisol levels induced by ITT already responded normally one month postpartum. Excessive secretion of pituitary PRL was observed 3 months after delivery and improved gradually thereafter. These results indicate that the secretion of pituitary tropic hormones was sensitive to pituitary ischemia in the following order: TSH, gonadotropin, GH and ACTH. The disturbance of these hormones also persisted in the same order.

Adult↗
PubMed1989

[Present status of cisplatin (CDDP) analogues in Japan].

CDDP is an extremely active antineoplastic agent, yet has severe renal, upper GI and neurotoxicity. Therefore, extremely careful supportive care is necessary to administer this agent to patients. There are two ways to improve this agent. The first is to improve the activities of this agent, including widening the spectrum. The other is to reduce toxicity. By these two ways, the therapeutic window or efficacy of the agents will be increased. In these two factors in mind, 4 analogues, CBDCA, 254S, DWA 2114R and NK-121 are in clinical trials in Japan. These 4 agents are different from mother compound CDDP, that is the DLF is bone marrow depression with rather mild renal and upper GI toxicities with different degrees among analogues, compared with those of CDDP. Therefore, these 4 agents do not need hydration before and after the administration. The extensive studies of pharmacokinetics and dynamics are studied including plasma levels, protein bindings and urinary excretions. These above studies indicate some correlations in efficacy and toxicity, but not perfectly correlated. The experiences of the above 4 analogues are still too short to predict the possibility of neurotoxicity, however, it seems to be 4 analogues also neurotoxic. Above findings strongly suggests that the more clinical experiences are necessary to evaluate these analogues.

Antineoplastic Agents↗
PubMed1988

Cure, cell killing, growth delay and fragmentation of X-irradiated human melanoma HMV-I multicellular spheroids.

Human melanoma, HMV-I, multicellular spheroids were irradiated and cure was determined by the absence of cellular outgrowth. Their cellular radiosensitivity was measured by the colony-forming ability of cells dispersed from the spheroid. Analysis of radiocurability of spheroids in terms of their cellular radiosensitivity predicted three necessary conditions: a linearity of dose versus the double-minus logarithm of curability; constancy of a critical cell number; and constancy of cellular radiosensitivity. These conditions were found to exist in the observed data for each of three size classes of spheroids. Analysis suggests that cellular radiosensitivity in multicellular spheroids with diameters of 250 and 400 microns was different from that of monolayers, and that the increase of spheroid-control doses was found to be a function of cellular radiosensitivity, total cell number per spheroid and a critical cell number. The critical cell number increased from 0.8 in a 150 microns spheroid to 4 in a 250 microns spheroid and to 57 in 400 microns spheroid. This number is a unique characteristic of multicellular systems and is one important factor in determining their radiocurability. X-ray-induced growth delay of spheroid size was increased with increasing dose. At high doses a sharp increase in delay time was seen, sometimes accompanying fragmentation of spheroids at late postirradiation times. The clonogenic activity of these fragments may serve as a model of exfoliation, the first step of radiation-induced metastasis.

Cell Aggregation↗
PubMed1987

Phase I study of recombinant human tumor necrosis factor.

A phase I clinical and pharmacokinetic study of recombinant human tumor necrosis factor (rH-TNF) was conducted in a single dose schedule in 33 patients with advanced cancer. rH-TNF was given by i.v. infusion over 30 min with a starting dose of 1 x 10(5) units/m2. The dose was escalated up to 16 x 10(5) units/m2 according to the modified Fibonacci scheme. Toxic effects were similar but not identical to those reported with interferons and interleukin-2, and included fever, rigors, nausea and vomiting and anorexia in a non-dose-dependent manner, and hypotension, leukocytosis, thrombocytopenia and transient elevation of transaminases (SGOT and SGPT) in an approximately dose-dependent manner. DIC syndrome was observed in one patient who had received 16 x 10(5) units/m2. The dose-limiting toxicities were hypotension, thrombocytopenia and hepatotoxicity, and the maximum tolerated dose in a single i.v. infusion of rH-TNF appeared to be 12 x 10(5) units/m2 when thrombocytopenia and elevation of SGOT and SGPT were taken as the dose-limiting toxicities. However, if hypotension was included, the maximum safely tolerated dose appeared to be 5 x 10(5) units/m2.

Adult↗
PubMed1987

Treatment of acute leukemia and malignant lymphoma with (2"R)-4'-O-tetrahydropyranyladriamycin.

Eighty-four previously treated adult patients with acute leukemia and malignant lymphoma were treated with (2"R)-4'-O-tetrahydropyranyladriamycin (THP). THP (10-55 mg/m2) was administered by i.v. bolus injection daily for acute leukemia, and according to three different schedules for malignant lymphoma: daily, weekly or once every 3-4 weeks. Complete and partial remission (CR and PR) were achieved by 1 (5%) and 3 of 19 patients with acute myelogenous leukemia and by 2 (13%) and 3 of 15 patients with acute lymphoblastic leukemia, respectively. All CRs were in the groups receiving 25 mg/m2 THP daily. CR and PR were achieved by 6 (14%) and 8 of 42 patients with non-Hodgkin lymphoma (NHL) and by 4 (50%) and 2 of 8 patients with Hodgkin's disease (HD), respectively. No particular sensitivity was found among the subtypes of NHL and HD. Response (CR + PR) was noted in 10 (40%) of 25 patients treated every 3-4 weeks, in 1 (17%) of 6 treated weekly, and in 9 (47%) of 19 treated daily. The major side effects were myelosuppression and gastrointestinal toxicities. Alopecia was observed in only 10 (12%) patients. ECG abnormalities were observed in 7 (10%) patients, all of whom had previously been treated with other anthracyclines. No severe cardiotoxicity was observed.

Adult↗
PubMed1987

Pharmacokinetic studies on 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077). III. Pharmacokinetics of a new nitrosourea antitumor agent TA-077 in humans (a phase I study).

A new nitrosourea antitumor agent TA-077, 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea, was intravenously administered to 15 cancer patients at doses ranging from 7 to 100 N (1 N = 30 mg/m2) in a phase I clinical trial. Time courses of blood concentrations of TA-077 and its active metabolite TA-G, 3-beta-D-glucopyranosyl analog of TA-077, were followed. The TA-G concentration reached a maximum at 7.0 +/- 2.3 min, and decreased thereafter with a half-life of 12.9 +/- 2.8 min. The time-course patterns and various pharmacokinetic parameters of TA-077 and TA-G were similar to those in the guinea pig, which, like humans, lacks plasma maltase activity. The 2 h-urinary excretion rate of TA-G in the above patients ranged from 0.15 to 7.7% of the dose. The areas under the concentration-time curve and maximal concentration values were both linearly correlated to the dose with correlation coefficients of 0.78 and 0.82, respectively. Repeated administration of TA-077 (29 to 40 N) for 5 or 6 consecutive days did not affect the pharmacokinetic parameters of TA-077 and TA-G in 7 cancer patients except for slight increases in the half-life and area under the curve of blood TA-G.

Adult↗
PubMed1987

Clinical studies of aclacinomycin A (ACM).

Aclacinomycin A (ACM) is a new anthracycline antibiotic, isolated from Streptomyces galilaeus. This agent is presenting major chemical differences from the conventional anthracycline DNR and ADM, as a class II anthracyclines which inhibit more RNA than DNA. In clinical studies, good CR responses ranging about 30% in AML patients depend upon their background. Toxicities consisted of mainly upper GI tract and bone marrow. Cardiac toxicities, especially late cumulative effects are not reported. Some responses noted in malignant lymphomas and breast carcinoma, but needed further studies, including possibility of cross resistance and differentiation effects.

Aclarubicin↗
PubMed1987

Clinical studies of (2''R)-4'-O-tetrahydropyranyl adriamycin (THP).

(2'' R)-4'-O-Tetrahydropyranyl Adriamycin (THP) is a new antitumor agent discovered among series of similar anthracycline compound synthesized by Umezawa et al. Phase I study revealed dose limiting factor of leukopenia with upper GI toxicity. Alopecia, cardiac failure and transient hepatic failure were extremely mild. Definite responses were demonstrated in acute leukemia, lymphoma, ovarian carcinoma, head and neck carcinoma, breast carcinoma and GU carcinoma. Pharmacokinetic studies revealed rapid cell uptake and outputs in bile (20%) and urine (8%) in 24 hours. Transfer to third spaces were poor but definite. In vivo a part of THP was converted to ADM in the liver, but not in other tissues including tumors. THP would be an extremely interesting compound, because of comparable spectrum of responses to various tumors with extremely low toxicity compared with other anthracycline compounds.

Acute Disease↗
PubMed1987

[Pharmacokinetic studies on THP-ADM (tetrahydropyranyl adriamycin)].

THP-ADM is a new antitumor agent which belongs to the anthracycline family. This agent has shown a high therapeutic index compared with the mother compound, Adriamycin, in preclinical and clinical studies. This time, a pharmacokinetic study of THP-ADM was performed and the following characteristics of this agent were clarified. A short t 1/2 alpha was noted in comparison with that of Adriamycin in a 3-compartment open model. Leukocyte concentration with THP-ADM was much higher than that of plasma of red blood cells. Renal excretion over 48 hours was 9% and biliary excretion over the same period was 20%. High THP-ADM and low Adriamycin tissue concentrations were revealed in all tissues excluding the liver. In liver tissue, a high concentration of Adriamycin and a low concentration of THP-ADM was observed. A small amount of Adriamycin was noted in the plasma following THP-ADM administration. This was probably related to the small amount of existing Adriamycin in THP-ADM or conversion of THP-ADM to Adriamycin in the liver tissue, or both. Poor penetration of THP-ADM into the third space was noted.

Doxorubicin↗
PubMed1987

Variability in the kinetics of thermotolerance decay in three cell lines.

The magnitude of thermotolerance and rate of tolerance decay has been evaluated in three cell lines following isotime and isoeffect initial heat treatments at 44 degrees C. Following the development of maximal thermotolerance, all cell lines lost tolerance at an exponential rate. However, for the three cell lines examined, V-79, CHO, and A-7, differences were apparent in the time required for maximal tolerance development, magnitude of induced tolerance, and rate of tolerance decay. This variability in the thermotolerance response of cells suggests difficulties which might be encountered if in vivo fractionation protocols are to be developed to minimize damages to normal tissue and maximize damages to tumor tissue.

Adaptation, Physiological↗
PubMed1986

[Anosmia or hyposmia after long-term oral administration of tegafur--improved anosmia].

Seventeen patients who manifested anosmia or hyposmia after long-oral administration of Tegafur (FT-207) in postoperative chemotherapy for cancer were followed up. Anosmia improved in 9 of 17 patients (52.9%), and the recovery period was between 3 and 42 months after the manifestation, and between 1 and 35 months after discontinuation of FT-207. Rhinoscopy and radiography revealed no abnormal findings in the nasal septum, rima oflactoria, concha nasalis media, sinus ethmoidales, etc. As it took a long time to recover from these signs and symptoms, they were presumed to be due to reversible neurological anosmia or hyposmia.

Aged↗
PubMed1986

[Phase I clinical study of MY-1, a new biological response modifier].

MY-1 is the DNA fraction, isolated and purified from Mycobacterium bovis BCG, which is composed of water-soluble and heat-denatured nucleic acids. In preclinical study, MY-1 showed host-mediated antitumor activity against various kinds of syngeneic tumors, and revealed very low toxicity in animals. Since these results suggested that MY-1 could be used as a biological response modifier (BRM) for cancer therapy, we performed the phase I clinical study in patients with a variety of malignancies. Fifteen patients were treated using single s.c. injection of MY-1 at doses of 0.25-20 mg, and following 22 patients received 3-12.5 mg of MY-1 given s.c. 3 times a week for the period of 2 weeks. Mild and reversible side effects such as swelling, redness, and/or pain of injected site were observed in a few patients at dose level of 10 mg. There were no other toxic effects. In the latter 22 patients, immune parameters were measured weekly. After MY-1 treatment, enhanced PPD skin reaction and increased OKT4/OKT8 ratio in peripheral lymphocyte subsets were observed which were statistically significant especially at a dose level of 3 mg. The optimal dose and schedule for phase II clinical study were considered to be 3 mg s.c. 3 times a week. In addition, the methodology of the BRM phase I clinical study was discussed.

Adult↗
PubMed1986

[Kinetics and possible mechanism of thermotolerance: a review].

Thermotolerance examined in vitro studies was reviewed in related to their kinetics, modifying factors and also the possible mechanisms. Heat treatments which reduce the survivals at same level at different temperature 42, 43, 44, 45 degrees C induces a same degree of thermotolerance and the thermotolerance decayed in same manner. These findings showed that thermotolerance induced by acute hyperthermia and that by chronic hyperthermia are not different in the nature. Examinations of heat sensitivities and kinetics of thermotolerance among different cell lines indicated that there is a possible relationship between the cellular sensitivity to heat and the magnitude of thermotolerance. The HSP has been found to be the most likely related factor in thermotolerance. But, their functions have not yet been clearly observed. Further research on HSP and thermotolerance is necessary to elucidate the possible mechanism of thermotolerance development.

Cell Cycle↗
PubMed1986

[Pharmacokinetic studies of THP-ADM (tetrahydropyranyl adriamycin)].

THP-ADM is a new antitumor agent which belongs to the anthracycline family. This agent has shown a high therapeutic index compared with the mother compound, Adriamycin, in preclinical and clinical studies. This time, a pharmacokinetic study of THP-ADM was performed and the following characteristics of this agent were clarified. Short t1/2 was noted compared with that of Adriamycin in a 3-compartment open model. Leukocyte concentration of THP-ADM was much higher than that of plasma or red blood cells. Renal excretion over 48 hours was 9% and biliary excretion over the same period was 20%. Tissue concentration revealed high THP-ADM and low Adriamycin in all tissues excluding the liver. In liver tissue, a high concentration of Adriamycin and a low concentration of THP-ADM was observed. A small amount of Adriamycin was noted in the plasma following THP-ADM administration. The Adriamycin was most likely related to the small amount of existing Adriamycin in THP-ADM or conversion of THP-ADM to Adriamycin in the liver tissue or both. Poor penetration of THP-ADM was noted into the third space.

Doxorubicin↗
PubMed1986

[Phase II study of (2''R)-4'-O-tetrahydropyranyladriamycin (THP) in patients with solid tumors. Multi-Institutional Cooperative Study].

A Phase II Study of (2''R)-4'-O-tetrahydropyranyladriamycin (THP) in patients with various solid tumors was carried out by 44 cooperative study institutions. Seven hundred fifty-six patients administered the drug intravenously were entered into this study. Of these, 499 patients were evaluated for objective responses. THP was given mainly at a dose of 40 to 60 mg/body every 3 to 4 weeks or 20 to 30 mg/body once a week. Response rates were 18.8% for head and neck cancer, 13.1% for stomach cancer, 21.4% for breast cancer, 22.2% for bladder cancer, 30% for renal pelvic and urinary tract tumor, 26.8% for ovarian cancer and 24.2% for uterine cancer. Overall response rate was 15.4% including 10 complete responses and 67 partial responses. Adverse reactions were similar to those previously reported in the phase I study, including gastrointestinal toxicities and myelosuppression. Alopecia and stomatitis, which are major side effects of other anthracyclines, were rather mild. Incidence of ECG changes was 2.8% and no congestive heart failure was observed.

Adult↗
PubMed1985

[A study on transference of cefminox into intrapelvic tissues].

Intravenous administrations of cefminox (CMNX, MT-141) 1 g as both single shot injection and drip infusion were absorbed rapidly. CMNX showed good transference into intrapelvic organs such as uterus, oviduct and ovary, with the tissue/serum ratios of 37.6% for myometrium, 35.1% for endometrium, 41.4% for cervix uteri, 49.5% for portio vaginalis, 54.3% for ovary and 59.7% for oviduct. From these results, usefulness of CMNX in the field of obstetrics and gynecology was confirmed.

Cephamycins↗