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Biomedical subjects

S Kitazawa

Publications and source records attributed to S Kitazawa.

At least 163 records · Page 9Linked to original sources
PubMed1988

Early pancreatic duct adenocarcinoma.

A 68-year-old Japanese woman presented with complaints of appetite and weight loss. Early pancreatic duct adenocarcinoma was diagnosed by endoscopic retrograde cholangiopancreatography (ERCP), which revealed partial obstruction of the main pancreatic duct. Pancreatoduodenectomy with lymph node dissection was performed. Macroscopically, no pancreatic tumor was detected. Histologically, the pancreatic lesion showed continuous changes consisting of duct epithelial cell hyperplasia, carcinoma in situ, and invasive carcinoma. Immunohistochemical stains for carcinoembryonic antigen and CA19-9 were positive in cancer cells.

Adenocarcinoma↗
PubMed1988

Modulation of N-nitrosobis(2-hydroxypropyl)amine-induced carcinogenesis by clofibrate in hamsters.

The effects of clofibrate treatment on N-nitrosobis(2-hydroxypropyl)amine (BHP) induced liver, gall bladder, pancreas, lung and kidney carcinogenesis in hamsters were studied. Animals were given BHP as an initiator at a dose of 500 mg/kg body weight subcutaneously once a week for 5 weeks followed by diet containing 0.25 or 0.5% clofibrate for 30 weeks. Both doses of clofibrate promoted hepatocarcinogenesis as judged from the associated multiplicity of liver lesions including hyperplastic nodules and hepatocellular carcinomas. gamma-Glutamyltranspeptidase (gamma-GTP) activity was not expressed in those lesions in the liver of hamsters given BHP followed by a basal diet or diets containing clofibrate. Clofibrate at a dose of 0.5% in the diet, in contrast, inhibited the development of pancreatic adenocarcinomas and lung neoplasms, including adenomas and adenocarcinomas, without affecting carcinogenesis in the gall bladder and kidney. These results clearly indicate differential modification potential of clofibrate for BHP-induced liver, pancreas and lung carcinogenesis in Syrian hamsters.

Animals↗
PubMed1988

An estimation of pharmacokinetic parameters for each dosing at unequal doses and dosing intervals.

The calculations of pharmacokinetic parameters for each dosing at unequal doses and dosing intervals were proposed. Systemic clearance of a drug following one-compartment open model can be determined by the product of the apparent first-order elimination rate constant and the apparent volume of distribution. The determination of maximum plasma concentration (Cmax) and the time required for the Cmax at each dosing were also presented here. These theoretical considerations are applicable to multicompartment open model.

Biological Availability↗
PubMed1988

Comparative evaluation of microultrafiltration devices for determination of protein binding.

The free fraction of drugs was determined comparatively with new microultrafiltration devices, Molcut II (Catalogue No. SJGC type) (MLII) and (Catalogue No. PLGC type) (NML; a device derived by changing the membrane component of MLII), which were developed by Nihon Millipore Ltd., Tokyo, Japan. The results obtained with the device are compared with those of MPS-1 (MPS), which is commercially available from Amicon Co., Danvers, MA, U.S.A. Drugs tested are phenytoin, carbamazepine, valproic acid, theophylline, phenobarbital, and gliclazide. In five of six drugs the free fraction by MLII shows lower values, although that by NML is in good agreement with MPS. The lower values of free fraction of drugs obtained with MLII may be caused by adsorption to the device. The adsorption increase is relatively correlated to increasing lipophilicity of drugs. The results suggest that physicochemical properties of each drug, especially hydrophobicity, should be taken into account, when a new device is used to examine protein binding of drugs. The NML, which is less expensive and is convenient because no special instrument is needed, is a reliable and satisfactory device for routine therapeutic free drug monitoring.

Adsorption↗
PubMed1988

Preliminary observation on pancreatic duct adenocarcinoma induced by intraductal administration of N-ethyl-N'-nitro-N-nitrosoguanidine in dogs.

Pancreatic duct adenocarcinoma was induced by intraductal administration of N-ethyl-N'-nitro N-nitrosoguanidine (ENNG) in two mongrel dogs. A dog received a total dose of 595 mg of ENNG during 12 months and was sacrificed. Duct obstruction was detected by pancreatography and duct adenocarcinoma was found. Another dog was given a total dose of 350 mg of ENNG during 8 months and was sacrificed 26 months after the first administration of the carcinogen. Duct adenocarcinoma was found. No pancreatic tumors were found in 2 dogs given intraperitoneal N-nitrosobis(2-oxopropyl)amine at a total dose of 4000 mg or in 2 dogs given Tween 60 only. These results suggest that the direct presence of a carcinogen in the pancreatic duct was able to induce duct adenocarcinoma in dogs.

Adenocarcinoma↗
PubMed1988

Comparative studies on interaction between theophylline and quinolones.

A comparative study of the pharmacokinetic and metabolic interactions between theophylline and a newly developed quinolone, T-3262, was carried out under steady-state conditions in seven healthy male volunteers, using enoxacin as the reference drug. A sustained-release theophylline formulation (200 mg twice daily) was given as monotherapy and coadministered with T-3262 (150 mg three times a day) or enoxacin (200 mg three times a day). The total and free concentrations of theophylline in the plasma and the excreted concentration of theophylline and its metabolites in the urine were measured by a high-performance liquid chromatography method. The mean steady-state plasma theophylline concentration significantly increased by approximately 1.5-fold and threefold after coadministration of T-3262 and enoxacin, respectively. In both cases, a significant decrease in the total body clearance was found for T-3262 (34%) and enoxacin (63%), but the plasma protein binding of theophylline remained unchanged. There was a significant increase in urinary theophylline and a decrease in urinary 3-methylxanthine after coadministration of T-3262 or enoxacin. The degree of change in the steady-state plasma theophylline concentration as a result of coadministration of T-3262 was small compared to that of enoxacin. A decrease in the total body clearance in the case of coadministration of a quinolone probably resulted from inhibition of the 1-demethylation metabolic pathway.

Adult↗
PubMed1988

[Chromosome abnormalities in early cancers].

The chromosome changes in early cancer had been thought to be difficult to analyse because of the technical reasons and of the complex nature of the chromosomal abnormalities as compared with hematological diseases having simple diploid karyotype. Recent advances allowed to analyse the chromosomes of solid tumors by the improved technics for cell disaggregation, short term culture, and chromosome banding. Although some advanced solid cancers kept the simple near by diploid chromosomal features, many tumors such as cervical cancers reveal complex chromosomal changes already in the pre-invasive stage. Much more data must be collected to evaluate the role of chromosomal changes in benign and early malignant tumors.

Chromosome Aberrations↗
PubMed1988

[A case of subacute thyroiditis associated with acute hepatitis].

We report one case of subacute thyroiditis associated with acute hepatitis, which is histopathologically diagnosed. A 43-year-old woman visited our hospital with chief complaints of fever, sore throat and anterior neck pain. Thyroid gland was found to be swollen and tender. Laboratory findings gave high ESR and positive test for CRP. High values of T3, T4 and RT3U indicated that the patient had hyperthyroidism. However no autoantibodies against thyroglobulin and microsome were found. High activities of serum AIP, LAP and gamma-GTP were observed. Serum GOT and GPT activities increased moderately. AIP type 2 was dominant in zymograms. Histopathological findings of liver specimen obtained by needle biopsy showed ballooning degeneration of hepatocytes with a slight focal necrosis and hyaline bodies. In addition bile plugs were observed in some biliary tubules. These findings were consistent with those of acute hepatitis. After three months all laboratory data were found to be within normal ranges and no recurrence has been observed. Subacute hepatitis associated with liver dysfunction is considered to be relatively frequent. However very few reports have been published on the case in which histopathological evidence for acute hepatitis was presented.

Acute Disease↗
PubMed1988

Is free fraction measurement of phenytoin always necessary in pediatric epileptic patients?

Sixty-two serum samples from 28 pediatric epileptic patients under treatment with phenytoin [diphenylhydantoin (DPH)] were obtained to study the correlation between total and free serum DPH concentrations. The effect of coadministered antiepileptic drugs on DPH protein binding was also studied. Binding of DPH to serum protein was assessed by ultrafiltration, and total and free DPH concentrations were determined by fluorescence polarization immunoassay. A strong correlation existed between the total and free concentrations [r = 0.958, p less than 0.001, standard error of estimate (+/- 1 SY) = 0.214]. The mean value for the DPH free fraction was 8.9% (range 5.7-16.3%). The samples obtained from patients on combination therapy with valproic acid (VPA) showed a larger DPH free fraction and greater variation. Exclusion of the 16 samples from patients concomitantly taking DPH and VPA yielded a better correlation (n = 46, r = 0.983, p less than 0.001, +/- 1 SY = 0.145). The mean free fraction in the patients not taking VPA was 7.7% (range 5.7-9.0%). The effect of VPA on the protein binding of DPH was also studied by addition of the same antiepileptic drugs to normal human plasma; the results were similar to those obtained for epileptic patients. These findings suggest that the free DPH fraction can be predicted from the total concentration, even when the drug is coadministered with other antiepileptic drugs, the sole exception being VPA.

Adolescent↗
PubMed1987

Plasma free fatty acids and protein binding of disopyramide during haemodialysis.

The binding of disopyramide (DSP) to plasma (or serum) proteins was determined using an ultrafiltration technique in three patients undergoing haemodialysis. An increase in the free fraction (FF) of DSP during dialysis occurred together with elevation of the free fatty acid (FFA) level in plasma. The effect of FFA on protein binding in vitro was examined using DSP- and FFA-spiked solutions containing human alpha 1-acid glycoprotein and serum albumin. The FF of DSP rose in proportion to increasing FFA levels, supporting the in vivo observations. The findings suggest that the free concentration of DSP should be routinely monitored, especially in haemodialysis patients.

Adult↗
PubMed1987

Variances in pharmacokinetic parameters due to assay methods for beta-methyldigoxin.

A digoxin radioimmunoassay (RIA) or fluorescence polarization immunoassay (FPIA) kit is frequently used in routine therapeutic drug monitoring (TDM) of beta-methyldigoxin (MD) by applying a calibration curve made using the corresponding digoxin calibrators. The variances in the plasma levels (61 samples) and pharmacokinetics (5 patients) due to these two different assay methods for MD were examined in our patients with congestive heart failure. Although the plasma levels of MD measured by these methods were well correlated (r = 0.956, p less than 0.001) to each other over a wide range, RIA showed significantly lower values (p less than 0.01) in the subtherapeutic range (less than 0.80 ng/ml), but significantly higher values (p less than 0.002) in the therapeutic and toxic ranges (0.80-2.00 and 2.00 less than ng/ml), respectively than FPIA. This trend occurred with increasing concentrations. When MD samples, spiked in normal human plasma, were analyzed by these methods, RIA showed almost true MD values and gave larger values than FPIA with a mean ratio of FPIA to RIA of 0.83. In contrast, normal plasma samples, each spiked with a MD metabolite such as digoxigenin-bisdigitoxide or digoxigenin-monodigitoxide, showed higher values by 10 to 22% in FPIA. These observations are in good agreement with the findings obtained in a pharmacokinetic study that RIA gave significantly higher levels than FPIA, only in the early stage after MD administration, resulting in a smaller total volume of distribution and a larger beta value in the elimination phase, as compared with FPIA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Time-dependent pharmacokinetics of theophylline: failure of application of the test-dose concept.

A comparative pharmacokinetic study of theophylline between the first and repeated oral administration and the assessment of clinical utility of theophylline test-dose concept were performed in 6 (study I) and 4 (study II) healthy male volunteers with different dosing schedules. In study I, although the average of theophylline systemic clearance (Clsys) was significantly (p less than 0.05) lower in the repeated dosing than in the first dosing, large intersubject variations were observed. Plasma free fatty acids which inhibit drug metabolizing enzyme activity were not influenced by theophylline chronic administration. In study II, the volunteers received oral multiple doses of a theophylline powder preparation to maintain 5 to 15 micrograms/ml plasma concentration on the basis of the pharmacokinetic parameters calculated from the single oral test-dose. A good prediction of the plasma concentration was observed only in one case and the maximum levels in the rest exceeded 20 micrograms/ml, a toxic concentration. Throughout the Studies, a stable Clsys was obtained in smokers, but the Clsys in non-smokers decreased by one third to a half during multiple dosing. These findings suggest that theophylline showed time-dependent pharmacokinetics and that test-dose concept for theophylline may not be applicable in all cases because of a large intersubject variation in the Clsys change between single and multiple dosing.

Administration, Oral↗
PubMed1987

Effect of valproic acid on pharmacokinetics of active metabolites of cyclophosphamide in mice.

The effects of valproic acid (VPA) on pharmacokinetics of cyclophosphamide (CPM) alkylating metabolites were investigated in male BALB/c mice. The pharmacokinetics of CPM alkylating metabolites was found to be dose-dependent representing the decrease of formation and elimination rates of the metabolites. A nonlinear increase of area under blood concentration of CPM alkylating metabolites-time curve (AUC) occurred with increasing CPM dose of 100, 200, and 300 mg/kg body weight. The effects of VPA (100 mg/kg dose) coadministered with CPM were similar to those of the increase of the CPM dose in preventing the activation of CPM and the elimination of its alkylating metabolites. The delayed disposition of CPM alkylating metabolites resulted in a 1.5-fold increase (p less than 0.02) of AUC which was considered the most important pharmacokinetic parameter in the CPM therapy. VPA which was injected i.p. at a dose of 100, 200, or 300 mg/kg increased the pentobarbital induced-sleep time by 81, 138, or 192%, respectively. In order to assess the effect of VPA on drug metabolizing enzyme(s) activity in humans, the ratio of daily urinary 6-hydroxycortisol to 17-hydroxycorticosteroids, which can reflect cytochrome P-450 activity, was determined in 5 healthy volunteers. The ratio was rapidly and significantly decreased (p less than 0.05) and this reduction continued during VPA administration. These findings and those reported in the literature concerning CPM metabolism suggest that the delay of CPM alkylating metabolites elimination resulted in part from microsomal enzyme(s) inhibition by VPA.

Animals↗