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Biomedical subjects

T Inaba

Publications and source records attributed to T Inaba.

At least 415 records · Page 23Linked to original sources
PubMed1984

[Treatment of advanced neuroblastoma with regimens containing cis-dichlorodiammineplatinum--effect and toxicity].

Ten children with advanced neuroblastoma were treated with regimens containing cis-dichlorodiammineplatinum (CDDP-regimens). Six cases had been refractory or had evidenced inadequate response to previous chemotherapy consisting of cyclophosphamide and adriamycin or vincristine, and radiotherapy. Clinical response was evaluable for 9 cases. Complete response was obtained in 2 cases, partial response in 2 cases, minor response in 2 cases, no change in 1 case and progressive disease in 2 cases. Six of these 9 cases had 2nd look surgery after several CDDP-regimens. Complete resection of tumor was possible in 1 case, subtotal resection in 4 cases and partial resection in 1 case. In an additional case whose clinical response was impossible because of absence of palpable tumor, the tumor had completely disappeared by the time of surgery. Three cases have survived for 5 months, 5 months and 28 months respectively without clinical evidence of tumor, 2 cases for 9 months and 12 months, respectively, with tumor. Four cases died of progressive tumor growth at 9 months, 10 months, 10 months, and 59 months, respectively. One case died of pneumonia at 10 months without clinical evidence of tumor. These results are far better than in our previous experience. Nephrotoxicity was observed in all cases, but it was tolerable in all cases including 3 heminephrectomized children. Hypomagnesemic, hypocalemic tetany was observed in 1 case. This complication was ameliorated by administration of magnesium gluconate. Mean +/- standard deviation of the lowest serum concentration of calcium and magnesium during this medication was 9.75 +/- 0.76 mg/dl and 1.39 +/- 0.44 mg/dl, respectively, against 7.56 +/- 1.64 mg/dl and 0.90 +/- 0.29 mg/dl without the medication, respectively. CDDP is concluded to be against neuroblastoma and its toxicity is tolerable. Magnesium gluconate administration is essential for prevention of tetany.

Abdominal Neoplasms↗
PubMed1983

Inhibition of sparteine oxidation in human liver by tricyclic antidepressants and other drugs.

Testing for competitive inhibition of sparteine oxidation in the 9000 x g supernatant fraction from human liver provides an in vitro means to identify drugs which can bind to the same form of cytochrome P450 which oxidizes sparteine. There has so far been only two outcomes of this test: either the drug examined competed with sparteine for a common binding site, or it did not inhibit the reaction. The results of such in vitro testing implicated the involvement of guanoxan, nortriptyline, desipramine, imipramine, amitriptyline and chlorpromazine with this enzyme. Amobarbital, tolbutamide and guanethidine in therapeutic concentrations did not interfere with sparteine oxidation by this preparation.

Antidepressive Agents, Tricyclic↗
PubMed1983

Early pregnancy diagnosis in sows by ultrasonic linear electronic scanning.

A rapid and accurate technique for pregnancy diagnosis in sows has been developed. A portable ultrasonic linear electronic scanner was used in conjunction with 3.5 MHz multitransducers. The scanner employed ultrasonic waves to generate a two-dimensional image of an interior cross-section of an animal and the image was displayed on a TV monitor. The tip of the transducer was placed in contact with the lower flank of the standing sow about 5 cm posterior to the navel and just lateral to the nipple line directing toward the uterus. Results of tests conducted under controlled conditions on a farm, using 145 sows, proved that accuracy of the technique approaches 100% for diagnosing pregnancy from day 22 of gestation through term. The time of feeding before scanning did not affect the accuracy of pregnancy diagnosis.

Journal Article↗
PubMed1983

Variation in amobarbital metabolism: evaluation of a simplified population study.

Kinetic constants of amobarbital metabolism were established for 52 subjects on the basis of urinary analysis extending over several days, usually 96 hr. There was no evidence of effect of age or sex on any of the constants. C-Hydroxylation was induced by cigarette smoking as much as 100%, but glucosidation was not affected. A factor influencing the constants was ethnicity of subjects (Caucasian or Oriental). This study confirms ethnic differences in amobarbital metabolism that were reported after measuring the concentration of metabolites in single samples of urine, that is, urine specimens voided during the postdistributive phase after oral drug intake. It appears that extreme simplification of sampling methods may be contemplated in the design of metabolic investigations of populations.

Adult↗
PubMed1983

Comparative pharmacogenetics of sparteine and debrisoquine.

Capacities to oxidize sparteine and debrisoquine in healthy Canadian Caucasians were compared. The Spearman rank correlation between the conventional urinary metabolic ratios (drug/metabolite) was rs = 0.79 (P less than 0.001), but the sparteine metabolic ratio appears to be the more discriminating probe to distinguish metabolizers and nonmetabolizers. The urinary amount of oxidized sparteine alone may allow reliable detection of nonmetabolizers. From a total of 17 poor metabolizers observed in this study and in studies in Germany and Sweden, all were deficient in metabolizing capacity for both sparteine and debrisoquine.

Chromatography, Gas↗
PubMed1983

Human metabolism of antipyrine labelled with 14C in the pyrazolone ring or in the N-methyl group.

After ingestion of [N-14CH3]antipyrine by two healthy male subjects, the urinary recoveries of radioactivity plus norantipyrine (non-radioactive) were 63 and 73%. After ingestion of [3-14C]antipyrine in the same two subjects, the urinary recoveries of radioactivity were 84 and 99%. Therefore, N-demethylated metabolites which have not been identified before, besides norantipyrine, must account for 21--26% of the dose. Serum half-lives of total 14C were about 50% greater than those of unchanged antipyrine. The difference was less in the saliva. Three major metabolites of antipyrine, norantipyrine, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine, in urine were determined by radio-t.l.c. and g.l.c. These three metabolites and antipyrine accounted for 50--69% of the administered dose. The urinary excretion half-lives of these three metabolites were similar to each other and to the serum half-life of antipyrine. 3-Hydroxymethylantipyrine in one subject was excreted more slowly than the other metabolites. The radioactive metabolite not extracted from urine by organic solvents was very polar, as judged by t.l.c.

Adult↗
PubMed1983

Comparison of in-vivo thermochemotherapy of isolated rat liver through portal vein and hepatic artery.

A model for the in-vivo perfusion of the isolated rat liver with either cytotoxic agents or hyperthermic saline, administered through either the hepatic artery or the portal vein, is described. Rats were able to survive following perfusion with a dose of up to 0.25 g/kg of 5-fluorouracil and 2.0 to 2.5 mg/kg of mitomycin-C by both routes. Regional hyperthermic perfusion of the liver produced temperature and time-dependent hepatotoxic effects. A marked elevation of serum glutamic oxaloacetic and glutamic pyruvic transaminase levels was noted 24 hours after perfusion, but was reversible. Aminopyrine N-demethylase activity in both normal intact and regenerating rat liver was not affected; however, the activity in normal intact liver was markedly suppressed with hyperthermic perfusion at 43 degrees C only. Incorporation of tritiated thymidine into hepatic deoxyribonucleic acid 24 hours after partial hepatectomy was severely inhibited by prior hepatic perfusion with either cytotoxic drugs or hyperthermic saline. This in-vivo isolated perfusion technique could be used to assess the effect of thermochemotherapy on tumour growth in the liver.

Aminopyrine N-Demethylase↗
PubMed1982

Simultaneous determination of antipyrine, 4-hydroxyantipyrine, 3-hydroxymethylantipyrine and norantipyrine in urine by gas chromatography chemical ionization mass spectrometry.

A simple, accurate and precise procedure was developed to quantify, in a single run, antipyrine, 4-hydroxyantipyrine, 3-hydroxymethylantipyrine and norantipyrine in urine. The stable isotope-labelled internal standards for the assay were obtained from a subject who ingested deuterium labelled antipyrine and produced urine containing the labelled drug and metabolites.

Antipyrine↗
PubMed1982

Sparteine metabolism in Canadian Caucasians.

The capacity for sparteine (SP) metabolism was determined in 48 Caucasian subjects by measuring amounts of drug and dehydrogenated metabolites in urine after an oral dose of SP sulfate. Three phenotypes were recognized and were assumed to represent individuals homozygous for poor SP oxidation (group III) and those heterozygous (group II) and homozygous (group I) for extensive SP oxidation. Separation of groups I and II, although incomplete, was improved by alterations in the published analytic procedure. The pattern of deviations from the normal distribution was similar for both dehydrosparteine metabolites. This supports the hypothesis of a common intermediate, the formation of which is monogenically controlled. Correlation analysis of the two metabolites indicates the possibility of further metabolism of 5-dehydrosparteine.

Canada↗
PubMed1982

In vitro metabolism of sparteine by human liver: competitive inhibition by debrisoquine.

Population data indicate that the genetic control is the same for the oxidation of sparteine and debrisoquine, although whether the level of control is regulatory or enzymatic is not clear. Therefore, the influence of debrisoquine on the rates of in vitro formation of the two dehydrogenated metabolites of sparteine in the 9000 x g supernatant fractions of human liver was examined. The interaction of these two drugs was competitive, indicating that the same form of cytochrome P450 is responsible for their biotransformation. Antipyrine at concentrations as high as 4 mM had no effect on sparteine oxidation.

Antipyrine↗
PubMed1981

Debrisoquine hydroxylation capacity: problems of assessment in two populations.

Following the investigation of debrisoquine (D) metabolism to 4-hydroxydebrisoquine (4OHD) in two populations, problems with the current practice of assessing this capacity by urinary D:4OHD ratios presented themselves. The distributions of both components of this ratio, when examined separately, clearly displayed interethnic differences. The mean 0- to 8-hr recovery of 4OHD in the Caucasian group was 15.5 +/- 1.1% (SE) of a 20-mg dose and 8.0 +/- 1.5% in the Oriental group. The corresponding values for unchanged D excretion were 33.0 +/- 4.1% in Orientals and 18.2 +/- 2.3% in Caucasians, a difference that is overlooked when D:4OHD ratios alone are examined. Although D and 4OHD excretion rates were equally variable, they correlated poorly; that is, they tended to vary independently of each other. This finding, in conjunction with the two separate ethnic differences, indicates that the ratio D:4OHD does not solely reflect an individual's capacity towards D 4-hydroxylation, and that equating these is unwarranted. This limitation does not necessarily invalidate judicious use of the ratio at the edges of the distribution curve, but it does call for additional investigations into the means to assess D metabolizing capacity in most subjects.

Asian People↗