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Biomedical subjects

M Usami

Publications and source records attributed to M Usami.

At least 217 records · Page 12Linked to original sources
PubMed1988

Characteristic features of insulin secretion in the streptozotocin-induced NIDDM rat model.

Male Wistar neonatal rats at age 1.5 days (Streptozotocin [STZ] group 1) and 5 days (STZ group 2) received a subcutaneous injection of 90 mg/kg STZ. After 10 weeks, the rats were subjected to an oral glucose tolerance test (OGTT) (2 g/kg) in a conscious state. The pancreas perfusion experiments were conducted 2 weeks after the OGTT. There was no statistical difference in insulin response between the STZ group 1 and the control group. On the contrary, in the STZ group 2, the plasma glucose response to OGTT showed a typical diabetic pattern, and the plasma insulin response was markedly blunted. In the isolated perfused rat pancreas, the infusion of glucose evoked a biphasic insulin secretion, but the peak insulin levels induced by 16.7 mmol/L glucose in the STZ group 1 were significantly lower than in the controls. We further investigated characteristics of insulin secretion in response to different secretagogues in these animal models using isolated islets. The insulin content of the islets of the STZ group 1 were about one half that of the control group. Insulin secretion in the STZ group 1 was impaired in response to glucose stimulation, but remained normal in response to arginine and forskolin. These results suggest that insulin secretion of non-insulin-dependent diabetes mellitus (NIDDM) rat model is selectively impaired in response to glucose stimulation, possibly due to a disorder of signaling mechanism other than adenylate cyclase.

Animals↗
PubMed1988

LH-RH agonist, Zoladex (Goserelin), depot formulation in the treatment of prostatic cancer. Randomized dose-finding trial in Japan.

Ninety patients with advanced prostatic cancer (15 with stage B, 23 with stage C, and 52 with stage D) were randomized to receive 0.9, 1.8, or 3.6 mg, respectively, of Zoladex depot subcutaneous injection every 28 days for 12 weeks. The serum levels of LH, FSH, and testosterone were elevated after the first injection, and followed by a significant decrease. The suppression of testosterone levels in the blood to castrate levels was observed in all patients except two treated with 0.9 mg. Objective response (CR and PR) was seen in 63.6% (0.9 mg), 47.8% (1.8 mg), and 68% (3.6 mg) of patients according to the Japanese Prostatic Group Criteria. Subjective improvement (performance status, analgesic consumption) was also observed in 75-88% of patients but without a statistically significant difference between each dose group. Only minor adverse effects were found during the treatments. The drug was detected dose dependently in the blood by radioimmunoassay. These results suggest that endocrine therapy with Zoladex depot in doses of 3.6 mg subcutaneously every 4 weeks is a useful alternative to surgical castration in patients with prostatic cancer.

Aged↗
PubMed1988

Therapeutic effect of plasma exchange with the biliary drainage in the treatment of obstructive jaundice.

The effect of therapeutic plasmapheresis combined with biliary drainage was evaluated in obstructive jaundice animal models. Plasma exchange (PE) using fresh-frozen plasma was carried out with biliary drainage (BD) on a canine jaundice model created by the ligation and resection of bile duct. Routine biochemical analyses were done following PE and BD. The result was compared with that of a BD only group. Plasma bilirubin level abruptly dropped after PE and was kept at a lower level, whereas the bilirubin level of the drainage alone group decreased gradually. Decreased plasma mitochondrial GOT level in the PE group suggests improvement of liver cell damage in obstructive jaundice. Mitochondrial function of liver tissue was evaluated following partial hepatectomy, which was carried out 2 days after PE along with BD in jaundice rat. Mitochondrial respiratory control ratio and ADP/O ratio following hepatectomy were improved in the PE group. The results suggest the improvement of hepatic functional reservoir by a single PE treatment in addition to BD treatment. These results show that PE can shorten the icteric period and may improve the hepatic functions after the treatment of malignant obstructive lesion in the biliary tract.

Animals↗
PubMed1988

Circulating levels and bone contents of bone gamma-carboxyglutamic acid-containing protein are decreased in streptozocin-induced diabetes. Possible marker for diabetic osteopenia.

To investigate the pathophysiology of diabetic osteopenia, circulating levels and bone contents of bone gamma-carboxyglutamic acid-containing protein (BGP) were measured in streptozocin-induced diabetic rats . Plasma calcium and total protein were significantly decreased (P less than .01) in the diabetic group, and the plasma level of BGP in diabetic rats was 19.6 +/- 2.8 (mean +/- SE) ng/ml, which is significantly lower than the value of 89.2 +/- 14.0 ng/ml in control rats (P less than .01). Bone contents of calcium and hydroxyproline per femur were significantly decreased in the diabetic group (P less than .01), and the ratios of bone calcium to hydroxyproline were not different. Bone BGP content per femur in the diabetic group was 669 +/- 58 micrograms, which was also significantly lower compared with 1241 +/- 126 micrograms in control rats (P less than .01). The decreased bone content of BGP is consistent with the hypothesis that BGP synthesis is impaired in insulin-deficient diabetes. Because a relationship between plasma levels of BGP and bone turnover has been established, the low plasma BGP value suggests there is a decrease in bone turnover in diabetic rats. Therefore, we postulate that the low bone turnover is one of the pathological features of diabetic osteopenia and is at least partly responsible for the occurrence of this complication in diabetes mellitus.

Animals↗
PubMed1988

[Instillation chemotherapy with peplomycin in superficial bladder cancer: clinical study on the effects of the direct antitumor activity and of the prophylaxis of recurrence].

Two kinds of clinical studies for intravesical instillation chemotherapy of peplomycin (PEP) were carried out, one to evaluate the direct antitumor activity in superficial bladder cancer (study I), and the other to evaluate the prophylactic effect on recurrence of bladder cancer after transurethral resection (study II). In study I, 22 patients with low stage bladder cancer were entered, and 16 of them were eligible for evaluation of efficacy. Twelve patients were treated twice a week with intravesical instillation of 20 mg of PEP/20 ml of saline for 4 weeks. Four patients were treated in the same way with 40 mg of PEP/20 ml of saline. Among the patients treated with 20 mg of PEP, two showed complete remission and one showed partial remission. Of the patients treated with 40 mg of PEP, one showed partial remission. Thus, the overall response rate was 25%. The tumors of the two complete responders were so tiny that they might have been damaged mechanically by the biopsy forceps. Therefore, we considered that the instillation chemotherapy of PEP at a dose of 20 or 40 mg/20 ml of saline had little effect on superficial bladder cancer. In study II, we performed a randomized trial designed to compare the recurrence rate after transurethral resection (TUR) alone with that after TUR followed by prophylactic instillation of PEP. Ninety-four patients newly diagnosed as having low stage bladder cancer were entered in the study. They were divided into three groups after TUR. Group A consisted of 38 patients who were treated with weekly instillation of 20 mg of PEP/20 ml of saline for 8 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗
PubMed1988

[Endocrine therapy of prostatic carcinoma with slow release (depot) formulation of the LH-RH analog ICI 118630 (Zoladex)].

To investigate the clinical efficacy, safety and endocrinology of ICI 118630 (Zoladex) depot formulation at 3 different dose levels (0.9, 1.8 and 3.6 mg), 90 patients were randomized to receive either one of the 3 doses from April, 1985 to March, 1986 in 28 centers. The depot preparation was injected subcutaneously every 4 weeks 3 times (for up to 12 weeks). Clinical efficacy was evaluated in terms of tumor response and overall subjective response. In 70 patients eligible for tumor response evaluation, 14 out of 22 (63.6%) in the 0.9 mg group, 11 out of 23 (47.8%) in the 1.8 mg group, and 17 out of 25 (68.0%) in the 3.6 mg group showed clinical improvement, that is, either complete response or partial response. In 72 eligible patients for overall subjective response evaluation, clinical subjective improvement was observed in 75.0, 81.8 and 88.0% of the patients in the 3 groups, respectively. There was no significant difference between the groups. As for endocrinology, there were 75 eligible patients. Endocrinological effect was observed in 23 out of 25 (92.0%) in the 0.9 mg group, 100% in both 1.8 mg and 3.6 mg groups. There was no significant difference between the groups. Castration was achieved by week 3.5 +/- 1.7 of therapy on average and by week 2 in the earliest case. There was no significant difference in incidence of side effects between the 3 groups: 5 out of 26 (19.2%) in the 0.9 mg group, 8 out of 29 (27.6%) in the 1.8 mg group, and 2 out of 30 (6.7%) in the 3.6 mg group. Flares presented as an increase in bone pain in 2 and as ureteric obstruction in 2 all in the 1.8 mg group but none in the other 2 dose groups. These flares disappeared on further treatment with Zoladex. These patients showed a clinical-response. The blood level of Zoladex was dose dependent, reaching its peak at week 2 of therapy in all 3 dose groups. There was no evidence of accumulation. Since these results demonstrate that 3.6 mg produces medical castration earlier, it may well be considered as an optimal dose in men.

Buserelin↗
PubMed1988

[Clinical efficacy of long-term treatment with LH-RH analogue, ICI 118630 (Zoladex), in prostatic cancer patients. The Zoladex Multicenter Study Group].

The Zoladex (ICI 118,630) multicenter trial included 149 patients with stage B +o D prostatic cancer recruited from 1984 to date. Of them 53 clinical responders on the treatment for 40 weeks or longer were subjected to assessment of antitumour response, overall subjective response, endocrinological response, safety and usefulness. The responders consistently showed a clinical response as evidenced by antitumour response in 32 of 50 patients (64.0%) at week 12 and in 35 of 51 (68.6%) at week 40, and overall subjective response in 42 out of 47 patients (89.4%) at both week 12 and week 40. Endocrinologically, all of the 47 eligible patients maintained a 40-week or longer response. Adverse reactions were observed in 19 out of 73 patients (26.0%), subdivided by the time of occurrence as 15/73 (20.5%) up to week 12, 3/71 (4.6%) between week 12 and week 40, and 5/53 (9.4%) in and after week 40. No patient required the discontinuance of treatment. Usefulness of the drug was observed in 51 out of 52 patients (98.1%). The results indicated that Zoladex in a once monthly regimen may be of great advantage to elderly patients with prostatic cancer, and allow an improved patient compliance: Zoladex may not only produce clinical remission but also improve the quality of life.

Buserelin↗
PubMed1988

[Endocrine therapy for prostatic carcinoma--the clinical trial to compare the efficacy of LH-RH analogue, ICI 118630 (Zoladex) with castration or estrogen].

A multicenter randomized clinical trial was carried out between May, 1986 and May, 1987 involving 82 patients with stage B-D prostatic carcinoma from 29 centers. The clinical efficacy, endocrine effect, safety and usefulness of the luteinizing hormone-releasing hormone (LH-RH) analogue and other endocrine manipulations in the treatment of prostatic carcinoma. Zoladex depot containing 3.6 mg of ICI 118,630, an LH-RH analogue, was administered every four weeks 3 times in total. Patients in the control group received either 300 mg of diethylstilbestrol diphosphate orally daily for 12 weeks or orchidectomy. An antitumor effect (CR + PR) was observed in 21 of the 33 patients (63.6%) in the Zoladex group and in 22 of the 33 (66.7%) in the control group, showing no significant difference between the two groups. There was no significant difference in overall subjective response either; 21 of the 24 (87.5%) in the Zoladex group and 24 of the 30 (80.0%) in the control group. In both groups, 100% endocrine effect was obtained as shown by achievement of castration in all patients. Adverse reactions were observed in 14 of the 39 (35.9%) patients treated with Zoladex as compared with 19 of the 34 (55.9%) control patients, resulting in no significant difference in the incidence between the two groups. These adverse reactions were not so severe as to require withdrawal from the study. In both groups, the treatment was assessed as slightly or more useful in 29 of the 33 (87.9%) patients. From these results, it is concluded that Zoladex, 3.6 mg depot, is a useful drug for treatment of prostatic cancer, having clinical efficacy and endocrine effects comparable to those of the conventional endocrine manipulations, being safe, and causing less physiological and psychological pain.

Aged↗
PubMed1988

[Perfluorochemical emulsion as a perfusate in 24-hour liver preservation prior to transplantation in the rat].

Perfluorochemical (PFC) emulsion as a perfusate of liver preservation prior to transplantation was evaluated in continuous hypothermic perfusion for 24 hours followed by orthotopic transplantation in inbred male Lewis rat. Three different contents of PFC emulsion that is, 20% (original Fluosol DA), 10% and 0% PFC solution were prepared as a perfusate. Isolated liver was stored for up to 24 hours using a continuous non-pulsatile perfusion technique of closed circuit with each perfusate. Gas content, GOT, GPT, LDH, potassium and glucose of the perfusate were measured. Oxygen consumption of perfused liver was higher in PFC emulsion than non PFC perfusate. Biochemical analysis of perfusate suggested that liver was preserved best in 10% PFC emulsion. Histological findings, especially, acid phosphatase staining, showed better result in PFC groups. One week survival rates after liver graft were 4/6 (66.7%) in 10% PFC solution, 1/6 (16.7%) in 20% and 0/6 (0%) in 0% solution. In spite of the highest oxygen consumption of perfused liver in early phase, 20% PFC emulsion did not bring the good preservation of perfused liver because of impaired circulation due to higher viscosity in low temperature. Ten percent PFC solution is considered the best in hypothermic preservation of the liver.

Animals↗
PubMed1988

[Experimental study on therapeutic plasmapheresis with the biliary decompression in the treatment of obstructive jaundice].

The effectiveness of therapeutic plasmapheresis with the biliary decompression was evaluated using animal model in the treatment of obstructive jaundice. Plasma exchange (PE) using fresh frozen plasma was carried out with biliary decompression on canine jaundice model made by means of ligation and resection of bile duct. Routine biochemical analysis was performed following the PE and biliary drainage and the result was compared with the external biliary drainage group. Plasma level of total bilirubin decreased after PE and kept lower level while plasma level of bilirubin in external biliary drainage group decreased slowly. M-GOT and GOT level, those are the indicators of liver cell injury, was lower in PE group. Mitochondrial function of liver cell was evaluated following partial hepatectomy carried out two days after PE with biliary decompression on jaundiced rat. Mitochondrial respiratory control ratio and ADP/O ratio was improved in PE group. The effectiveness of PE is speculated as the combined mechanism of the removal of hepatotoxic factors in the jaundiced plasma and the addition of hepatotrophic factors within the fresh frozen plasma. These results support the effectiveness of PE to shorten the biliary drainage period and to improve the hepatic function for perioperative management.

Animals↗
PubMed1988

Removal and recovery of cholesterol in thermofiltration.

Thermofiltration, a system of membrane plasmapheresis for LDL apheresis, was applied to the treatment of hypercholesterolemic patients to assess its lipid lowering potential, clinical feasibility and post-treatment lipid recovery. Plasma separated by a membrane separator was warmed above physiologic temperature, filtered with a plasma filter and returned to the patient on-line without requiring supplemental plasma product infusion. One calculated plasma volume was treated. Treatment schedules were weekly, biweekly or monthly. Patients treated by thermofiltration in this study were diagnosed as type II hypercholesterolemia. Reductions and sievings of high density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) cholesterol were evaluated. In addition, post-treatment solute recovery was assessed. The reduction ratios of HDL cholesterol and LDL cholesterol were 0.31 +/- 0.08 and 0.58 +/- 0.08, respectively (mean +/- S.D. of 7 patients). Sieving coefficients of the plasma filter for HDL cholesterol and LDL cholesterol were 0.62 +/- 0.12 and 0.03 +/- 0.02, respectively (mean +/- S.D. of 32 treatments). Cholesterol reduction fitted well to a single pool model. HDL cholesterol recovered significantly faster than LDL cholesterol and LDL cholesterol recovery differed among individuals. For some patients total cholesterol and LDL cholesterol levels were lowered by the biweekly treatment while for others the weekly treatment was required. Significant removal of LDL cholesterol with sparing of HDL cholesterol was achieved without the requirement for plasma products.

Adult↗
PubMed1987

Postoperative systemic adjuvant chemotherapy for bladder cancer.

Forty-six patients with bladder cancer without distant metastasis (M0) were treated by chemotherapy as an adjuvant after total cystectomy using three protocols (protocol I: adriamycin 50 mg/m2, cyclophosphamide 500 mg/m2, and cis-platinum 50 mg/m2 i.v., starting at least 2 weeks after surgery every 3 weeks for three cycles; protocol II: adriamycin 30 mg/m2 on the 1st postoperative day, cyclophosphamide 300 mg/m2 on the 1st and the 7th days; protocol III: FT-207 60 mg/m2, p.o. every day for 1 year). Average follow-up periods after surgery by protocol were 18 months for protocol I, 31 for protocol II, and 43 for protocol III. Analysis of the survival curves showed no statistically significant differences among the three groups or between a historical control group of 106 patients and the entire patient population examined in the present study. The histopathological grades recorded in the 46 patients were G1, G2, and G3 in 1, 22, and 23, respectively. However, from a study of 48 pT3 and pT4 cases, the survival rate of 10 patients receiving protocol I therapy was statistically significantly higher than those of 12 patients treated according to protocol II and of 26 historical controls, at 1 year and 2 years, respectively. Toxic effects, with gastrointestinal symptoms including nausea and vomiting and myelosuppression (including leukopenia and anemia) were more frequent with protocol I. Alopecia occurred in about 80%-90% of patients treated according to either protocol I or II. Almost all patients could tolerate adjuvant chemotherapy, and none of them died as a result of these regimens. The results recorded in this study justify the evaluation of combination adjuvant chemotherapy with adriamycin, cyclophosphamide and cis-platinum in a prospectively randomized trial.

Adult↗
PubMed1987

Immunosuppressive acidic protein in patients with testicular cancer.

Serum immunosuppressive acidic protein was compared to lactic dehydrogenase as a marker for testicular cancer in 54 patients with testicular cancer, 62 with benign urological diseases and 203 healthy controls. The mean value of serum immunosuppressive acidic protein in patients with testicular cancer (598 +/- 293 micrograms. per ml.) was statistically higher than that in patients with benign disease (429 +/- 163 micrograms. per ml.) and healthy controls (368 +/- 73 micrograms. per ml.). There were statistically significant differences in serum immunosuppressive acidic protein levels between controls and patients with stage 2 (p less than 0.0001) or stage 3 (p less than 0.001) testicular cancer, and between those with stage 1 and stage 2 (p less than 0.0001) or stage 3 (p less than 0.001) disease, respectively. The usefulness of immunosuppressive acidic protein as a marker for testicular cancer also was compared to that of lactic dehydrogenase. Immunosuppressive acidic protein and lactic dehydrogenase levels were elevated almost equally in patients with stage 2 or 3 disease (range 71 to 92 per cent). However, immunosuppressive acidic protein levels were elevated in only 3 of 25 patients with stage 1 cancer (12 per cent), compared to 11 of 25 (44 per cent) with elevated lactic dehydrogenase levels. Immunosuppressive acidic protein was correlated better with tumor stage. In conclusion, serum immunosuppressive acidic protein determinations may be useful in patients with testicular cancer for staging, monitoring treatment results and predicting recurrence.

Adult↗