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Biomedical subjects

Y Sakata

Publications and source records attributed to Y Sakata.

At least 379 records · Page 21Linked to original sources

[Controlled study of MQF-OK therapy with FT and with UFT on various advanced gastrointestinal cancers. Hirosaki Cooperative Study Group of Cancer Chemotherapy].

Our cooperative study group carried out a controlled study of MQF-OK therapy with tegafur (FT) (group A) and with UFT (group B), a compound of FT and uracil in the molar ratio of 1:4, on various advanced gastrointestinal cancers. From January 1985 to May 1987, 91 patients were entered into this study, and 11 cases were ineligible for the protocol (11%). Fifty of 80 cases had advanced gastric cancer, 30 had pancreatic cancer or other cancers, such as colon cancer, and biliary tract cancer. They were divided into group A or B at random. There was no difference in the patient characteristics between group A and B. In gastric cancer, 23 of 50 cases were randomized into group A and 27 cases into group B. Two cases in group A (8.7%) and 7 cases in group B (25.9%) showed PR. The response rate of group B was better than that of group A, but the value of P by Kruskal-Wallis test was 0.27. Thirteen of the 30 other cancers were randomized into group A and 17 cases into group B. Three cases in group A and B, respectively, showed PR. There was no significant difference between the two groups in terms of antitumor effect, prolongation of life or side effects. In conclusion, it was suggested that the MQF-OK therapy with UFT was beneficial for the Remission Induction Therapy in advanced gastric cancer.

Adult↗

[MQF-FT and MQF-UFT in gallbladder and bile duct cancer].

Four patients with gallbladder cancer and two with bile duct cancer were treated with mitomycin C, carboquone, 5-fluorouracil and OK-432 (MQF-OK therapy) plus tegafur (FT) or UFT. MQF-OK therapy was administered according to our original method. FT and UFT were orally given in a dose of 600-800 mg/body/day and 300-400 mg/body/day, respectively. Three with gallbladder cancer and one with bile duct cancer showed PR. Myelosuppression was observed in all cases, but recovered in two weeks after MQF therapy. We recommend the further trial of MQF-OK therapy plus FT or UFT for gallbladder and bile duct cancer.

Administration, Oral↗

[Clinical studies of rokitamycin dry syrup on Chlamydia trachomatis infections in the neonate and infant].

A dry syrup preparation for infants and children of a newly developed 16-membered macrolide antibiotic, rokitamycin, was administered to 5 neonates and low birth weight infants of 6 to 25 days after births at a dose level of 10 mg/kg on an empty stomach then plasma drug levels were determined. The dry syrup preparation was also given to a total of 19 Chlamydia trachomatis infection cases of 7 days to 8 months old neonates, low birth weight infants and infants including 12 cases of pneumonia, 2 cases of conjunctivitis and 5 non-symptomatic carriers at an average daily dose level of 48.1 mg/kg in 2 to 4 doses for an average of 19 days and its clinical effects, bacteriological effectiveness, side effects and effects on laboratory test values were examined. The obtained results are summarized as follows. 1. Because the test subjects were neonates and premature infants, obtainable amounts of blood samples were limited, thus it was not possible to determine time courses of plasma drug levels to reach their peaks. Peak plasma levels, however, were speculated to be similar to those in children. Plasma half-lives of the drug were also not determinable, but they seemed to be somewhat longer than those in children. 2. Clinical efficacies were determinable in the 2 cases of conjunctivitis and 10 of the 12 cases of pneumonia, with excellent or good results in both cases of the former and with excellent or good results in 9 of the 10 determinable cases of the latter. Thus, the overall efficacy rate was high, 91.7%. 3. Bacteriological efficacies were determinable in 18 cases including non-symptomatic carriers. C. trachomatis was eradicated in 16 of the cases with an overall efficacy rate of 88.9%. 4. Diarrhea was observed in 2 cases, which were suspected as side effects of the drug. 5. No abnormalities were observed in the laboratory test results. Judging from the above results, this drug appears to be useful for the treatment of C. trachomatis infections of neonates, low birth weight infants and infants.

Chlamydia Infections↗

[Clinical studies of rokitamycin dry syrup on skin and soft tissue infections in the pediatric fields].

Rokitamycin (RKM) dry syrup, a newly developed macrolide antibiotic, was administered to children with ages between 6 months and 15 years and 10 months suffering from skin and soft tissue infections including 41 cases of impetigo, one case of staphylococcal scalded skin syndrome (SSSS) and 2 cases of subcutaneous abscess totalling 44 cases. The average daily dose level used was 31.3 mg/kg divided into 3 or 4 doses, for an average of 6 days of treatment. MICs of 4 different macrolide antibiotics including RKM, erythromycin (EM), josamycin (JM) and midecamycin acetate (MDM acetate) were determined against 32 bacterial strains isolated from these cases including 30 strains of Staphylococcus aureus and 2 strains of Streptococcus pyogenes. The inoculum level used was 10(6) cells/ml. Among these strains of bacteria, 20 strains of S. aureus and 1 strain of S. pyogenes were also used, at the same inoculum size, for the determination of MICs of 4 beta-lactam antibiotics including 3 different penicillins such as ampicillin (ABPC), methicillin (DMPPC) and cloxacillin (MCIPC) and cefaclor (CCL), a cephem antibiotic. RKM was then evaluated through the above treatment for its clinical efficacy, bacteriological effects, side effects and effects on laboratory test values. Obtained results are summarized as follows. 1. Activities of drugs tested were compared to each other. MIC90 of RKM against S. aureus averaged 0.39 microgram/ml, and against no strains of S. aureus showed MIC values of higher than 25 micrograms/ml, thus, the antibacterial activity of RKM against S. aureus was the highest among the 8 drugs tested. The activity of MCIPC was next highest followed by that of DMPPC, MIC determination was done on only 2 strains, or, for some drugs, only one strain, of S. pyogenes, and RKM showed activities somewhat lower than ABPC and EM, and similar to JM and CCL within the limited testing. 2. Clinical efficacies of RKM determined by doctors in charge were 97.6% in the 41 cases of impetigo, with good or excellent efficacies were observed, 100% in the single case of SSSS and the 2 cases of subcutaneous abscess. Thus an overall efficacy on the 44 cases was rated very high, at 97.7%. 3. Clinical efficacy rating according to accumulated scores was determinable in 37 cases including all the 3 diseases on the third day of treatment with an efficacy rate of 89.2%. Ratings were determinable on the fifth and the seventh days of treatment in 24 and 21 cases, respectively, with all the cases judged good or excellent.(ABSTRACT TRUNCATED AT 400 WORDS)

Abscess↗

[Clinical and pharmacokinetic studies of gentamicin in intravenous drip infusion to children].

Eighteen children with urinary tract infection were treated with intravenous drip infusion of gentamicin (GM), and clinical efficacy and pharmacokinetics were studied. Ages of the patients ranged from 2 months to 12 years. Doses of GM ranged 1.0 to 2.5 mg/kg every 8 to 12 hours, and treatment continued for 4 to 10 days. Among 18 patients treated, clinical results were excellent in 12, and good in 6. Values of BUN and creatinine remained within normal range in all patients during and after the GM treatment. One child had an eosinophilia. There were no cases that showed signs and symptoms of oto- and nephrotoxicity. Twenty eight time-serum level curves were studied in 16 patients during and after intravenous infusion of GM over 30 minutes. Doses were 1.0 mg/kg in 4, 1.9-2.0 mg/kg in 14, and 2.2-2.5 mg/kg in 10. Peak serum levels at 30 minutes after the start of infusion were 2.66-7.38 micrograms/ml (average 5.45 micrograms/ml) in cases receiving 1.0 mg/kg, 4.67-10.8 micrograms/ml (7.26 micrograms/ml) in 1.9-2.0 mg/kg, and 6.16-16.5 micrograms/ml (8.86 micrograms/ml) in 2.2-2.5 mg/kg. Elimination half-lives were 1.75-2.48 hours (average 2.10 hours) in cases with ages less than 1 year, 1.58-2.58 hours (2.01 hours) with 1 to 6 years, and 1.20-3.07 hours (1.66 hours) with 7 to 12 years who were given doses of 1.9-2.5 mg/kg. There were no significant differences in pharmacokinetic parameters between first and last administration in these patients, suggesting that no accumulation occurred with above mentioned doses. Urinary recovery of GM ranged from 21.9 to 99.2 percent (average 62.48%) within 6.5 hours after the initiation of drip infusion.

Child↗

[Results of combination chemotherapy in advanced urothelial cancer].

Between April 1982 and March 1988, 28 patients with advanced urothelial cancer were treated with combination chemotherapy incorporating cisplatin at our hospital and the response was evaluated. Fourteen of them were managed by the CAP chemotherapy (cyclophosphamide 300-500 mg/m2 day 1, doxorubicin 30-50 mg/m2 day 1, cisplatin 40-90 mg/m2 day 2), 7 by the FAP chemotherapy (fluorouracil 300 mg/m2 day 1-5, doxorubicin 30 mg/m2 day 1, cisplatin 15 mg/m2 day 1-5) and 7 by the MEP chemotherapy (etoposide 100 mg/m2 day 1-3, cisplatin 20 mg/m2 day 1-5, methotrexate 300 mg/body day 6). Four patients (28.6%) responded to the CAP regimen; a complete response was gained in one patient who had pulmonary metastasis of excised ureteral cancer and a partial response in 3 patients with intravesical and nodal (N3, N4) cancer. A partial response was noted in 3 patients (42.9%) in the FAP group. They had intravesical lesions and two of them had regional node metastasis (N3). A higher response rate (85.7%) was obtained by the MEP regimen; a complete response in 2, who had intravesical and nodal (N2, N4) cancer, and a partial response in 4 patients, 1 had intravesical cancer, 1 had nodal (N2) and intravesical cancer and 2 had nodal or lung metastasis of excised renal pelvic cancer. Toxicity included mild to severe vomiting, alopecia, myelosuppression and mild renal or liver dysfunction. High dose metoclopramide provided a high degree of protection against cisplatin induced emesis. The results with the MEP regimen are promising for the advanced, metastatic urothelial cancer.

Adult↗

[Pharmacokinetic and clinical studies of sultamicillin granule in the pediatric field].

Sultamicillin (SBTPC) is a combined drug of ampicillin (ABPC) and sulbactam (SBT) which is an inhibitor of beta-lactamase, in a clinical form of tosylate with equivalent molecules in ester linkages. A tablet form of this combined drug has been released since July, 1987 in Japan and now a granular form for pediatric patients has been developed. Hence, the granular form of SBTPC was administered to 6 boys (age: 8 years 5 months-11 years 5 months) to determine plasma and urinary concentrations of the drug and its urinary recovery-rates. The dose of 10 mg/kg or 15 mg/kg was given orally just after meal to 3 boys. To study clinical and bacteriological effects of this drug, a mean daily dose of 27.1 mg/kg divided 2-4 times a day was administered for 9 days on the average to a total of 57 cases with pharyngitis (5), tonsillitis (5), laryngitis (1), bronchitis (1), pneumonia (8), scarlet fever (1), typhoid fever (1), impetigo (16), furuncle (2), abscess (6), lymphadenitis (1) and urinary tract infection (10) except 2 cases which were unevaluable for clinical effects. MICs of 7 drugs (SBTPC, ABPC, SBT, methicillin (DMPPC), cloxacillin (MCIPC), cephalexin and cefaclor) against 12 of 22 strains isolated from patients with infections of skin and soft tissue were determined with inoculum-sizes of 10(8) and 10(8) CFU/ml to study beta-lactamase producing activities. Adverse reactions and abnormal effects on laboratory test values attributable to this drug were studied in patients including dropped-out cases. The results obtained are summarized as follows. 1. Mean plasma peak levels of ABPC and SBT were observed at 1 hour after administration in both of the 10 mg/kg and the 15 mg/kg groups with values of 2.34 and 5.57 micrograms/ml for ABPC and 1.87 and 4.66 micrograms/ml for SBT, respectively. Mean concentrations of SBT were lower than those of ABPC in both groups and individuals. Dose-responses in plasma levels and AUCs were observed in both groups. Mean half-life values of ABPC and SBT in the 2 groups were 1.93 and 1.12 hours for ABPC and 1.97 and 1.22 for SBT, respectively. Mean half-life values for ABPC and SBT were similar in each group and this tendency was also seen among individuals.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Pharmacokinetic and clinical evaluations of ceftriaxone in neonates and premature infants].

Following a one shot injection with ceftriaxone (CTRX) 10 mg/kg or 20 mg/kg into 23 neonates (1 to 24 days old) including premature infants, plasma levels of CTRX were measured up to 12 hours post-dose in some cases and up to 72 hours post-dose in others and also urinary levels and urinary recovery rates were determined up to 12 hours post-dose. Furthermore, clinical, bacteriological and infection-prophylactic effects of CTRX were evaluated by the intravenous administration with the mean dose of CTRX of 47.7 mg/kg once daily or half the dose twice daily for 9 days on the average into 46 infants (0 to 6 months old) including neonates and premature infants; i.e., 21 cases with actual or suspected bacterial infections for the evaluation of clinical and bacteriological effects and 25 without bacterial infection for the evaluation of prophylactic effects against bacterial infection. The safety of CTRX was evaluated in 53 cases including 7 which were omitted from the efficacy evaluation due to adverse reactions and also in some cases from clinical laboratory parameters. The following is a summary of the results obtained: 1. Following the administration with CTRX 10 mg/kg into each of the neonates 6, 12, 13 and 21 days old (the 21 old one was premature), plasma levels of CTRX in these subjects reached their peaks at 5 minutes post-dose at levels of 59.38, 53.13, 37.50 and 50.00 micrograms/ml, respectively. The peak levels were similar to each other with an exception of the rather low level in the 13 day-old neonate. The plasma half-life times of CTRX in these subjects were 9.762, 7.775, 7.330 and 8.149 hours, respectively: The younger the infant the longer the half-life tended to be except the premature cases. Similarly, the younger the infant the larger the AUC was except for the premature case with the AUC values of 511.169, 324.714, 236.346 and 326.825 micrograms.hr/ml, respectively. The Vds were 0.709, 1.004, 1.316 and 0.696 liters, respectively, and the value for 13 day-old neonate was the largest. Urinary levels of CTRX reached between 42.00 and 298.30 micrograms/ml at some time within 12 hours post-dose in any cases. Urinary recovery rates in 12 hours post-dose were 79.98, 52.00, 56.82 and 60.14%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗

Immunoaffinity purification of protein C by using conformation-specific monoclonal antibodies to protein C-calcium ion complex.

We isolated protein C from a barium citrate-adsorbed fresh plasma and human factor IX concentrate by immunoaffinity chromatography on a column of Sepharose coupled with monoclonal antibodies to protein C. The antibodies used were conformation-specific monoclonal antibodies to the calcium-induced structure of protein C. Protein C was bound to antibodies coupled with Sepharose in the presence of calcium ions and was eluted with EDTA. This immunopurification resulted in a 13,000-fold purification of the fully functional zymogen from plasma. The immunoaffinity-isolated protein C was found to have higher amounts of single-chain protein C than conventionally isolated protein C when analyzed by sodium dodecyl sulfate-polyacrylamide gels under reduced conditions. The factor IX concentrate was applied to this Ca2+-dependent antibody JTC-3-immobilized Sepharose in the presence of 5 mM CaCl2, and protein C with its gamma-carboxyglutamic acid (Gla) domain intact was firstly bound to this column and then eluted by metal chelation with EDTA. When flow-through fractions were applied again in the presence of Ca2+ to this column, modified protein C which had lost its N-terminal 42-residue peptide was weakly bound to this column. It was eluted in the absence of Ca2+. However, only a low percentage of modified protein C was detectable by an enzyme-linked immunosorbent assay using Ca2+-dependent monoclonal antibody JTC-3 and peroxidase-labeled immunopurified polyclonal antibody. These results indicate that factor IX concentrate has both Gla-domain-intact and Gla-domainless protein C. Moreover, it suggests that Ca2+-dependent monoclonal antibody JTC-3 may recognize the coupled conformational change of protein C induced by the combined effect of Ca2+ binding to the Gla domain and to other parts of protein C.

Antibodies, Monoclonal↗

A sensitive colorimetric detection of virus DNA and oncogene.

Advantage of cloning probe DNA fragment in phage M13 DNA was taken to provide a larger single stranded DNA as a hybridization probe. High level of direct enzyme labels was introduced via the M13 DNA moiety as well as probe DNA. A highly sensitive colorimetric detection of virus DNA and oncogene was developed.

Coliphages↗

Suppression of antipyretic response in rabbits by intraventricular protein synthesis inhibitor, anisomycin.

Fevers induced by intravenous injection of endogenous pyrogen (EP) and intraventricular prostaglandin E2 (PGE2) were significantly prolonged when protein synthesis inhibitor, anisomycin was administrated intraventricularly 30 min before or 1 hr after injection of EP or PGE2. The present results show that protein synthesis in the central nervous system is involved in the development of antipyresis.

Animals↗

[Postoperative adjuvant chemotherapy using NCS (neocarzinostatin) and 5-FU in the treatment of gastric cancer. First report--A comparison with the 5-year survival rate of patients undergoing combined therapy with MMC and 5-FU].

As a postoperative adjuvant chemotherapy for gastric cancer, we have administered a combination of NCS (Neocarzinostatin) and 5-FU (NF treatment method) and in this paper we have compiled the results obtained in patients who were treated for 5 years in an attempt to compare the 5-year survival rate with that of patients administered a combination of MMC and 5-FU (MF treatment group) and a control group administered no anticancer agents. As the selection of either NF or MF treatment was conducted on an annual basis, this study can be considered an historical controlled study. The results obtained are summarized as follows. On comparing the survival rate of the NF treatment group and the control group, the 5-year survival rate for all patients who underwent curative resection and all patients with histological stage III cancers and the curative resection PS (+) group, as well as the survival period of the non-resected patients, showed a statistically significant difference, indicating that the survival rate was higher in the NF group. On comparing the NF group and the MF group, although no statistically significant difference was observed between then based on a stratified analysis of all resected cases, histological stage differences and n.ps factors, etc., certain values tended to indicate a higher survival rate for the NF group. Moreover, the survival rate of the non-resected patients was more favorable in the NF group. These results confirm that NCS is useful for the treatment of stomach cancer and compares favorably with MMC. The appearance of side-effects was significantly lower in the NF group in comparison with the MF group and the number of patients who had to discontinue therapy was extremely low.

Adult↗