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Biomedical subjects

K Tazawa

Publications and source records attributed to K Tazawa.

At least 73 records · Page 4Linked to original sources
PubMed1991

The clinical pharmacokinetics of two different preparations of intrarectal ketoprofen following spinal or local anesthesia for anal surgery.

Two different preparations of commercially available suppositories containing Ketoprofen (KP) were administered to 49 patients immediately following anal surgery. The KP was prepared as either fatty suppositories (FS) or gelatin capsulated suppositories (GCS) and surgery was performed under either spinal (n = 37) or local anesthesia (n = 12). Similar results were observed in the kinetics of KP after both FS and GCS administration. The extent of bioavailability of the two dosage forms in the patient groups and control subjects (n = 10) were essentially equal. When the pharmacokinetic parameters of KP were compared between patient groups under spinal and local anesthesia, significant differences were found in the values of the peak level (C max), peak time (T max), and terminal phase half-life (t 1/2). The C max decreased by one-half, while the T max and t 1/2 increased twice and four times, respectively, in patient operated on under spinal anesthesia compared to those operated on under local anesthesia. The absorption rate constant (Ka) following spinal anesthesia was significantly less than that following local anesthesia or that of the healthy subjects (p less than 0.01). A "flip-flop" phenomena could be seen in the time profiles of plasma KP concentration following spinal anesthesia.

Administration, Rectal↗
PubMed1991

[The changes in cell population and chemical mediators in BALF following local allergen challenge].

In eight subjects who showed dual asthmatic response (DAR) in bronchial provocation tests (BPT) with specific allergens, local allergen challenge (LAC) was conducted using a flexible bronchofiberscope. We examined the concentrations of histamine, leukotriene B4 and C4 (LTB4 and LTC4) and cell populations in bronchoalveolar lavage fluid (BALF) collected before LAC (control), during the immediate response phase (IR), and the late response phase (LR). Control BALF was collected from the left lingula (B4 or B5), and BALF in the IR or LR phase from the right middle lobe (B4 or B5). Each BAL was conducted with 50 ml of saline at 37 degrees C and repeated three times in succession. It was noted that histamine increased significantly (p less than 0.05) in IR-BALF from the control level. In addition, the concentrations of LTC4 and the numbers of eosinophils increased in IR-BALF. In LR-BALF, the numbers of eosinophils (p less than 0.01), and the concentrations of histamine (p less than 0.05), LTC4 (p less than 0.05) and LTB4 increased. From these results, it was suggested that infiltration of eosinophils and various chemical mediators in the bronchial mucosa play important roles in the development of late asthmatic response.

Adolescent↗
PubMed1991

[Antitumor activity of T-506, a novel synthetic FUDR derivative, on murine colon cancer and its hepatic metastasis].

T-506 is a novel synthetic FUDR derivative which releases FUDR slowly in vivo. We studied antitumor activity of T-506 by i.v. injection against mouse colon cancer, colon 26. When T-506 was administrated to mice daily, from day 1 through day 10, or every 3 days, on days 1, 4, 7, and 11, after s.c. inoculation of the tumor, the survival period was expanded significantly. The subcutaneous tumor growth was also inhibited according to the dose levels. Then, we compared the therapeutic effects on the experimental hepatic metastasis of colon 26 between T-506, 5'-DFUR and UFT at each maximal tolerable dose; that is, T-506 (0.074 m mole/kg/day; i.v. on days 1, 4, 7, and 10), 5'-DFUR (1.0 m mole/kg/day; P. O. from day 1 to 7), UFT (0.1 m mole/kg/day; P. O. from day 1 to 7). T-506 and 5'-DFUR suppressed completely the metastases of 5 of 6 (83.3%) mice and 6 of 7 (85.7%), respectively. UFT did not show a significant inhibitory effect. However, since the loss of body weight was more marked in T-506 than in the other two drugs, the side effect was thought to be a serious problem. These data suggested that if the side effect could be overcome, T-506 would be useful clinically for the treatment of gastrointestinal cancers or hepatic metastases.

Animals↗
PubMed1991

[Interstitial hyperthermia (MINERVE) for perineal local recurrence of rectal cancer].

Interstitial hyperthermia (MINERVE) was performed for 2 patients with perineal local recurrence of rectal cancer. The MINERVE was a 20 W generator of 550-610 kHz with 4 pairs of probes creating an electromagnetic field (Odam Co., France). The basic regimen was five irradiation treatments of 2 Gy per week, with two hyperthermia treatments (for 60 minutes at more than 43.5 degrees C) a week, 500 mg of 5-FU or 25 mg of CDDP per hyperthermia treatment, and 3 g/day of PSK. The radiation therapy was performed prior to hyperthermia, the chemotherapy at the same time. Perineal tumors and symptoms disappeared completely in 1 patient and were reduced in 1 patient. This treatment is expected to be clinically as a part of multidisciplinary treatment for superficial malignant tumors.

Adult↗
PubMed1990

[Prophylactic therapy for liver metastasis of gastrointestinal carcinomas using biological response modifiers (BRM): fundamental studies on the inhibition of experimental liver metastasis by intraportal administration of OK-432].

For prophylactic therapy to inhibit hepatic metastatic recurrence after surgical treatment of gastro-intestinal carcinomas, the effects of OK-432, a biological response modifier (BRM), were examined with inoculation of tumor cells and administration of OK-432 via portal vein. Experiments with the inhibition of liver metastasis were performed as follows. The animals were divided into five groups. Group 1: 1.0 KE of OK-432 was given intraportally 5 minutes after injection of 5.0 X 10(6) tumor cells per rat via the portal vein. Group 2: Non-medicated group, only 5.0 X 10(6) tumor cells per rat were injected into portal vein, as the control for group 1. Group 3: 0.5 KE of OK-432 and 2.5 X 10(6) tumor cells per rat were used. Group 4: 1.0 KE of OK-432 and 2.5 X 10(6) tumor cells were used. Group 5: Non-medicated group, injected with 2.5 X 10(6) tumor cells as the control group for groups 3 and 4. Colonies of metastases in the liver of each group were examined by autopsy on the 30th day after treatment. Metastases were observed in 75% of group 1, 100% of group 2, 58.8% of group 3, 64.3% of group 4 and in 90% of group 5. For the investigation of the mechanisms to inhibit these liver metastases, 51Cr labeled AH60C tumor cells were injected into the portal vein, and the remained of radioactivity in rat liver was examined. The result showed that OK-432 injected into the portal vein did not directly kill the lodging tumor cells. To prove the morphological evidence of inhibition of hepatic metastasis, the changes of tumor cells were microscopically observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Temperature sensitivity on proliferation and morphologic alteration of human esophageal carcinoma cells in culture.

As basic studies of hyperthermia and hypothermia on malignant tumor, the kinetics of proliferative activity, the morphologic changes in the two cell lines, SGF-3 and SGF-5, established in our department after the change of culture temperature were examined. The results obtained were: a) A significant difference was found in the sensitivity to temperatures between the two cell lines originated from human esophageal squamous cell carcinoma. The temperature range allowing cultured cell to proliferate were from 31 degrees to 39 degrees C in SGF-3 and from 29 degrees to 41 degrees C in SGF-5. b) Minor difference occurred in the results between the two cell lines examined during the recovery of proliferative activity, but no proliferative activity was discovered after the cells were exposed to 42 degrees C for 72 h. Two cell lines resumed their proliferation after having been exposed to 27 degrees or 28 degrees C for 72 h. c) Morphologic changes of the cell lines cultured at high temperature were cytoplasmic vacuolation and cell aggregation by phase contrast microscope and the increase of heterochromatin, the decrease of granular formation in nucleoli, and nucleolar vacuolation by transmission electron microscopy (TEM). At low temperatures the changes observed included cytoplasmic ballooning and circumnuclear halo formation by phase contrast microscope, and the increase of heterochromatin, nucleolar segregation, swelling of mitochondria, and dilatation of rough endoplasmic reticulum (rER) by TEM.

Carcinoma, Squamous Cell↗
PubMed1990

Targeting behavior of hepatic artery injected temperature sensitive liposomal adriamycin on tumor-bearing rats.

Temperature sensitive liposomal Adriamycin (LADM) was injected into the hepatic artery of rats bearing implanted hepatic tumors. Two hours after the injection, the liver was heated at 42 degrees C and maintained for six minutes at that temperature using local hyperthermia. Blood samples were taken at regular intervals until 8 hours after injection, at which time the animals were sacrificed and the drug distribution in the tissues was examined. Results indicate that the Adriamycin was released from the liposome, with the drug concentration in circulation peaking at 30 minutes after heating. High drug levels (25.2 micrograms/g of wet tissue) in the tumor and high tumor/liver Adriamycin level ratios (TLAR; 4.1) were found. The drug levels and the TLAR of the liposomal Adriamycin injection combined with heating (LADM H) were significantly different from those of the same dose of aqueous Adriamycin with heating (ADM H) or aqueous Adriamycin (ADM) and LADM without heating. The experiment shows that the LADM is cleared from the liver slowly, and when hyperthermia treatment at phase-transition temperature of the liposome is performed, the drug level in an implanted hepatic tumor is increased, and in the parenchyma is decreased. The results imply that targeting the hepatic tumor in this way may be an effective therapeutic method, and the drug release from the liposome may be controlled externally. This method appears promising for clinical practice.

Animals↗
PubMed1990

[A giant struma histologically confirmed as a medullary carcinoma with multiple systemic bone metastasis].

Reported is the case of a 46 year old woman with no significant family medical history, who presented a neck tumor that she had had for about ten years. This large tumor was noted on her admittance to hospital due to a bone fracture. She subsequently underwent a resection of this giant neck tumor. A histologic examination of the specimen revealed a medullary carcinoma of the follicular variety. Silver impregnation by the Grimelius method caused a positive reaction, and an electron-microscopic examination revealed round, electron-dense, endocrine granules about 195 nm in diameter, Immunohistochemically, the carcinoembryonic antigen (CEA) and the presence of calcitonin proved the cells to be cancerous.

Bone Neoplasms↗
PubMed1990

[Changes in immunoparameters following cryosurgery in prostate cancer].

To determine the effect on immunoparameters of cryosurgery in cases of stage B prostatic cancer and to determine whether such changes were specifically related to the cryosurgery technique, immunoparameters were measured and compared with cases of prostatic hyperplasia treated by transurethral resection (TUR-P). A decrease in immunoparameters was recognized in the cryosurgery group at 1-3 days postoperatively (increase in IAP, decrease in NK cell activity, decrease in lymphocyte blastogenesis reaction to PHA). The protein histograms, immunoglobulin and IAP changed similarly after the two above procedures. These changes were thought to be due to the invasive nature of the procedures. However, some difference was seen between the cryosurgery group and the TUR-P group in terms of rate of lymphocyte blastogenesis reaction to PHA and Con A, IgG, complement and NK cell activity which might indicate a specific effect of cryosurgery different from TUR-P.

Aged↗
PubMed1989

[Effect of thermotherapy on human esophageal carcinoma in culture and clinical cases].

Multidisciplinary treatment for advanced esophageal carcinoma, which is not resectable in many cases, has become an important subject to study. We have reported the effectiveness of thermotherapy in treatment of esophageal carcinoma by basic experiments using three cell strains of human esophageal carcinoma designated as SGF-3,4,5. Based on the results of the basic experiments, we have performed thermotherapy combined with radiotherapy, chemotherapy and immunotherapy on cases of advanced esophageal carcinoma since October 1985. As for the basic experiment, proliferation of SGF-3 was inhibited at more than 40 degrees C, SGF-4 at more than 41 degrees C and SGF-5 at more than 42 degrees C. We did not observe the recovery of the growth of SGF-3 after heating at 41 degrees C for 72 hours and 42 degrees C for more than 24 hours. And the growth of SGF-4 after heating at 42 degrees C for more than 48 hours did not recover either. No recovery of the growth of SGF-5 after heating at 42 degrees C for 72 hours was noted. Based on the data, combined therapy was performed in 12 patients with advanced esophageal carcinoma. The evaluation of the local response to the combined thermotherapy revealed CR in five cases, PR in five and NC in two.

Aged↗
PubMed1989

[Effects of indomethacin and prostaglandin E2 administered intrarectally on colon carcinogenesis induced by azoxymethane (AOM) in rats].

AOM was administered subcutaneously once a week for 11 consecutive weeks to the rat. On the 15th and 30th week after starting of AOM injection, PGE2 content of the colonic mucosa, tumor and blood of portal vein and NK activity of the spleen and mesenteric lymph node (MLN) were evaluated. On the 15th week, a significant high value of the PGE2 content of colonic mucosa was shown when compared with that of the AOM non-administered group (control group). However, no significant difference was observed in the PGE2 content of blood of portal vein and NK activity of the spleen and MLN. On the 30th week, significant high values of the PGE2 content of AOM-induced tumor and blood of portal vein and low values of NK activity of the spleen and MLN were shown when compared with that of the control group. When indomethacin (IND) was administered intrarectally twice a week for 19 consecutive weeks after completion of AOM injection, induced-colon tumors was significantly suppressed. For this reason, it is important to administer IND at the point when the PGE2 content of colonic mucosa begins to augment.

Administration, Rectal↗
PubMed1988

Relation of H-2 expression on murine RCT(+) sarcoma cells to lung colonization and sensitivity to NK cells.

Murine RCT(+) sarcoma cells were sorted using a fluorescence-activated cell sorter with regard to the expression of H-2 antigens and then an increased H-2-expressing subclone was established, and named RCT(+)H-2+. The experimental metastasis of RCT(+) cells was compared with that of RCT(+)H-2+ cells by counting pulmonary colonies on the 21st day after i.v. inoculation of tumor cells (5-10 x 10(4)/mouse). When mice were inoculated with RCT(+) cells, mean numbers of pulmonary colonies were 2.1(range 0-6), 2.8(range 0-7) using 5 x 10(4) and 1 x 10(5) cells, respectively. On the other hand, in the mice inoculated with RCT(+)H-2+ cells, figures obtained were 7.0(range 4-16), 31.9(range 13-79), using 5 x 10(4) and 1 x 10(5) cells, respectively. The survival rate of RCT(+)H-2+ cells was higher than that of RCT(+) cells, when this was assayed in the early stage after i.v. injection of 51Cr-labeled cells (1 x 10(5) cells/mouse). In addition, RCT(+)H-2+ cells were more resistant than RCT(+) cells to lysis mediated by natural killer cells. These data suggest that an increase in metastatic ability was paralleled by an increase in the H-2 antigen expression and a decrease in sensitivity to the natural killer cells.

Animals↗
PubMed1988

Pharmacokinetics of two rectal dosage forms of ketoprofen in patients after anal surgery.

Two kinds of dosage forms of commercially available suppositories containing ketoprofen (KP), fatty suppositories (FS) and gelatin capsulated suppositories (GCS), were administered to patients immediately after anal surgery, and results obtained were compared. No difference was found in each corresponding pharmacokinetic parameter of the two dosage forms. However, when these parameters were compared with those from healthy subjects, significant differences were found in the values of peak level (Cmax), peak time (Tmax) and terminal phase half-life (t1/2). Cmax decreased by one half, and Tmax and t1/2 increased two and four times longer, respectively, those from healthy subjects. The absorption rate constant (ka) in patients was significantly (p less than 0.01) smaller than that in healthy subjects. However, the distribution volume/bioavailability (Vd/F), elimination rate constant (kel), and area under the curve (AUC) differed only slightly. Consequently, the flip-flop phenomena could be seen in the time profiles of plasma KP concentration of patients. These results suggested that the rectal suppository of KP should be administered with care, especially in the patients operated on under spinal anesthesia.

Adult↗
PubMed1988

[Character of a human cholangiocarcinoma CHGS, serially transplanted to nude mice].

With the progress in surgical technique, remarkable improvement has been noted in the treatment of bile duct carcinoma. However, in the cholangiocarcinoma at porta hepatis or in the progressive carcinoma, many cases have been reported, for which radical surgery is not achievable. In recent years, discussion has been concentrated on the necessity of multidisciplinary treatment for the bile duct carcinoma, but fundamental research has not been done enough. In the present paper, the process for obtaining CHGS strain implantable to the nude mouse derived from a human cholangiocarcinoma as achieved in our department was discussed, and its biological characteristics-above all, the sensitivity to carcinostatic agents and to radiation-were evaluated. The doubling time of CHGS strain is 6.2 days, and nude mice showed stable proliferation with 100% viability. Histologically, it was tubular adenocarcinoma similar to the primary tumor. It has high mucin producing ability, and necrosis hardly occurs. The search for DNA ploidy by flow cytometry revealed the presence of two types of cells: The cells of diploid pattern and aneuploid pattern. In the tests to determine the sensitivity of CHGS strains to carcinostatic in MMC, ADR, 5-FU and CDDP groups, and to radiation according to the Battele Columbus Laboratories Protocol, the regression of tumor was observed in MMC, ADR, CDDP groups. Particularly, in MMC group, some of the tumors had disappeared. Recurrence was also noted in this case, but the survival, was still recognized nearly four years after the operation through the postoperative auxiliary therapy. This was regarded as the case, where the sensitivity test using the nude mouse implantable tumor strain was reflected well in clinical application.

Adenoma, Bile Duct↗
PubMed1988

[A case report of carcinoid of the rectum coexisting with adenocarcinoma in a single lesion].

A 69-year-old female, chiefly complaining of diarrhea, was admitted to the Toyama Medical & Pharmaceutical University Hospital. A barium enema and an endoscopic examination revealed a villous adenocarcinoma of the rectum. Computerized tomography disclosed multiple metastatic lesions in the liver. She underwent an amptatio recti and an intra-arterial cannulation of the common hepatic artery in order to administer anticancer agents. Gross findings of the resected specimen showed villous adenocarcinoma containing a small ulcerated lesion. Histologic findings of this lesion revealed a collision neoplasm containing both an adenocarcinoma and a carcinoid with no obvious transitional region between the two lesions. The type D carcinoid, determined according to Soga's histologic classification, showed positive argyrophil granules but no argentaffin granules in the cytoplasm. The electron-microscopic findings of the carcinoid revealed small electron-dense endocrine granules measuring about 150 approximately 300 nm in diameter. The woman died 4 months after this operation.

Adenocarcinoma↗
PubMed1988

[Inhibition of pulmonary metastases in mice by beta-cyclodextrin-benzaldehyde].

The effect of beta-cyclodextrin-benzaldehyde (CDBA) on the pulmonary metastasis in C3H/He mice was examined. When mice were treated daily with CDBA, 3 weeks later the number of lung nodules developed after i.v. inoculation of 1 X 10(6) RCT (+) cells was significantly decreased. The mean numbers of the lung nodules were 69.9 and 73.4 in the water-and cyclodextrin (CD)-treated mice, respectively. However, these were 17.8, 9.8 and 2.9 in 0.5, 5 and 25 mg/mouse per day CDBA-treated mice, respectively. And also, daily treatment of CDBA prolonged the survival time of the tumor bearing mice in both experimental and spontaneous metastasis studies. Two or three weeks after subcutaneous inoculation of RCT (+) cells (1 X 10(6) cells) to the foot pad, left hindlimbs were amputated and then mice were daily treated or untreated with CDBA. Five weeks after tumor inoculation, the number of lung nodules was counted. Twenty eight point six and 100% of untreated mice had lung metastases when amputation was carried out 2 (earlier operation group) and 3 (latero peration group) weeks after tumor inoculation. However, in CDBA-treated mice, these values were noticeably decreased, that is, 6.7% and 60% in earlier and later operation groups, respectively. Furthermore, in the later operation group, mean number of the lung nodules in CDBA-treated mice was only 2.7 while this was 12.9 in untreated mice. These data suggest that CDBA improve the survival time of tumor bearing mice through the inhibition of the lung metastasis.

Administration, Oral↗