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Biomedical subjects

K Chiba

Publications and source records attributed to K Chiba.

At least 397 records · Page 22Linked to original sources

Results of mobilization and drainage of the pancreas for acute pancreatitis.

The surgical treatment of acute pancreatitis remains controversial. Since 1969, we treated 60 patients with acute pancreatitis. In 34 with severe acute pancreatitis who were not responding adequately to intensive medical care, surgical intervention was made by mobilization of the pancreas from retroperitoneal tissue and drainage of the pancreatic bed (M-D procedure). Thirty-four operative cases were classified into 7 edematous, 7 hemorrhagic, and 20 necrotizing. Macroscopic findings of the pancreas did not correlate either to the severity of the acute pancreatitis or to the mortality rate. Eight of 34 who underwent M-D procedure died (23 per cent), but the rate became 14.7 per cent after excluding 3 who died of unrelated causes. These data suggest that the M-D procedure is highly effective in the treatment of early cases of severe acute pancreatitis. There was an associated marked reduction in the mortality rate with the prophylactic use of broad spectrum antibiotics. With M-D procedure, there was a low incidence of late sequelae of pancreatic or peripancreatic abscess.

Acute Disease↗

Stoichiometry and location of terbium and calcium bindings to porcine intestinal calcium-binding protein.

Quantitative analyses were carried out on Tb3+ binding to porcine intestinal calcium-binding protein (CaBP). Tb3+ (emission at 547 nm) and intrinsic tyrosine (emission at 303 nm) fluorescences upon excitation at 260 nm increase almost in parallel with increasing Tb3+ concentration up to a molar ratio of 2 against the protein in the CaBP solution. The pH dependence profile of Tb3+ fluorescence of the Tb3+-CaBP complex suggests that some free carboxylate groups are involved in the binding, as also suggested for Ca2+ binding. The results of fluorometric titration of Tb3+ and intrinsic tyrosine fluorescences of the CaBP complex with Tb3+ or Ca2+ led us to conclude that Tb3+ and Ca2+ have two common binding sites for each CaBP molecule. An equilibrium dialysis experiment showed that the dissociation constants of the two Tb3+-binding sites are 0.29 and 3.51 microM. Tb3+ strongly inhibits 45Ca binding to one of the two Ca2+-binding sites in the CaBP. All of these and previous results indicate that each Tb3+ ion can bind to either of two high-affinity Ca2+-binding sites in porcine intestinal CaBP with an affinity different from that for Ca2+ ion. We discuss the localization of the Ca2+- and Tb3+-binding sites in the CaBP.

Animals↗

Variability of serum high density lipoprotein cholesterol concentration in healthy subjects in a three year term.

The measurements of serum high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglyceride (TG) were repeated in 170 apparently healthy farming women once a year for three years (1980-2) to examine the variability of the results within the same individual. Although the mean HDL-C and TC values varied to some extent year by year, higher correlation coefficients between any pair and smaller coefficients of variation in the three annual measurements indicated that the within subject variability of HDL-C and TC is much smaller than that of TG. Variation of HDL-C appeared to be associated with lipidaemia. When the effects of age and menopause were eliminated, it was found that non-normolipidaemic people had wider individual variation both in HDL-C and TG. The importance of TG determination for HDL-C evaluation in health examination is emphasised.

Adult↗

The effects of neuroleptics (haloperidol and chlorpromazine) on the pharmacokinetics of valproic acid in schizophrenic patients.

The steady state trough concentrations (Cmin) and pharmacokinetics of valproic acid were investigated in schizophrenic patients during the treatment of valproic acid, 200 mg, twice daily and after the one dose of 400 mg, respectively, with and without haloperidol (6 to 10 mg/day, N = 6) or chlorpromazine (100 to 300 mg/day, N = 6). Four to 5 Cmin were monitored just before the morning valproic acid dose for 3 to 4 days preceding the kinetic study. The overall Cmin of valproic acid with chlorpromazine (33.2 +/- 1.7 micrograms/ml, N = 25) was significantly (p less than 0.01) greater than without (27.1 +/- 1.4 micrograms/ml, N = 25). The majority of the mean valproic acid concentrations observed after the 400-mg dose were significantly (p less than 0.05 to 0.01) greater during the chlorpromazine treatment as compared to those without the phenothiazine. The mean t1/2 was shortened from 15.4 +/- 1.4 to 13.5 +/- 1.2 hours (p less than 0.05) with a comparable increase in the clearance from 7.18 +/- 0.38 to 8.32 +/- 0.34 ml/hour/kg (p less than 0.01) after the discontinuation of chlorpromazine. All the patients revealed an increase in the valproic acid clearance after the chlorpromazine therapy was discontinued. When viewed overall, such a trend as found in the chlorpromazine group was not observed in the haloperidol group. The results suggest that chlorpromazine, but not haloperidol, inhibits the metabolism of valproic acid. However, the clinical significance of the interaction awaits future study.

Adult↗

[Quality control of radioimmunoassay by bivariate analysis].

Automatic calculation of control charts for precision and accuracy of radioimmunoassay was reported by Faure, et al. Duplicate control samples independently measured was assumed to have a bivariate normal distribution. In this case they assumed that the correlation coefficient between each value of the pairs of control samples is zero. Our experience using this method revealed that a considerable number of assayed samples distributed outside the calculated control limits in case of "accuracy control". It was considered that this happened because in radioimmunoassay the between-assays precision is usually larger than the within-an-assay precision and there is a significant correlation between values of duplicates. We also found equal probability density did not make a true circle but a long circle. Therefore in the present paper we proposed for control charts of radioimmunoassay an equal probability long circle calculated by bivariate analysis of Mahalanobis' generalized distance. It was found that a Mahalanobis' long circle could explain the density distribution of radioimmunoassay with a reasonable percent of samples outside the calculated control limits. What happened here can be interpreted by a large between-assays variability shown by some commercial kits. This automatic calculation method could be applied not only for quality control but also for evaluation and comparison of radioimmunoassay system or commercial kits. Control survey could also be analyzed by such a method.

Analysis of Variance↗

Concentration-effect and time-effect relationships of carteolol.

The concentration-beta blocking effect and time-effect relationships of carteolol were examined in eight normal adults given 15 mg i.v. and 20 mg orally on separate occasions. Resting and post-exercise blood pressures and heart rates were assessed before and at various times up to 48 h after each dose. Carteolol, a beta-blocker with some partial agonist activity, produced an insignificant, transient increase in heart rate 2 to 6 h after both doses, and a fall (p less than 0.05) in diastolic blood pressure 4 and 6 h after the intravenous dose and 6 h after the oral dose in the resting supine position, as compared to the corresponding baseline values. All values of the post-exercise heart rate and the double product after each of the doses were significantly (p less than 0.001) below the baseline values for the entire period (48 h) of observation. A significant correlation between the log plasma carteolol concentration (log C) and its beta-blocking effect (E: p less than 0.001, r = 0.508 i.v.; p less than 0.001, r = 0.626, p.o.) was found. The r-values for individuals were higher (0.852 to 0.977, intravenous; 0.817 to 0.981, oral) than for the group as a whole. The slope (m) of the relationship, E = m X log C + r, showed a certain variance within and between individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Pharmacokinetics and absolute bioavailability of carteolol, a new beta-adrenergic receptor blocking agent.

The pharmacokinetics and absolute bioavailability of a new nonselective beta-adrenoreceptor blocking agent, carteolol, were investigated after administration of single intravenous and oral doses to eight normal volunteers. Plasma and urine drug concentrations were measured by an HPLC method. The pharmacokinetic parameters after intravenous dosing were obtained by a two-compartment analysis: elimination or beta-phase t1/2 4.7 +/- 0.3 h; Vc, 0.74 +/- 0.101/kg; Vd, 4.05 +/- 0.48 l/kg; Cl, 10.13 +/- 0.94 ml/min/kg; ClR, 6.56 +/- 0.58 ml/min/kg; and ClNR, 3.57 +/- 0.40 ml/min/kg. The absolute bioavailability obtained from plasma data was 83.7 +/- 8.0%, which was consistent with that derived from analysis of urine of 82.7 +/- 4.2%. The amounts excreted unchanged in urine up to 48 h after the intravenous and oral doses were 65.0 +/- 1.5% and 53.8 +/- 3.2% of the administered doses, respectively. The t1/2 for removal of the drug derived from plasma and urine findings after intravenous and oral dosing were similar, which indicates that the main route of elimination of carteolol is via the kidneys. As the ClR of carteolol exceeded the Cl of creatinine there may be renal tubular secretion of the drug.

Administration, Oral↗

Bioavailability and pharmacokinetics of theophylline in plain uncoated and sustained-release dosage forms in relation to smoking habit. I. Single dose study.

The bioavailability and pharmacokinetics of theophylline from a plain uncoated and 2 newly designed, sustained-release tablet formulations, as compared to intravenous aminophylline, were studied in 12 healthy adult male volunteers. The subjects were divided into two groups (n = 6) with respect to smoking habit and on 4 separate occasions each received, on a randomized cross-over basis, a single dose of 400 mg equivalent of theophylline from every dosage form. The intravenous aminophylline study showed that habitual smoking had a significant (p less than 0.05) effect on plasma theophylline clearance (0.051 +/- 0.006 vs 0.035 +/- 0.004 l/kg/h). Smoking significantly reduced the raw AUC from the 4 dosage forms (p less than 0.05), but did not change the characteristics of absorption of each formulation. There was a non-significant trend towards reduced absolute bioavailability of theophylline from sustained-release formulations in smokers (percentage mean difference - 16% for one formulation and 13% for another). The trend was not observed for the plain uncoated tablet, which was rapidly absorbed (p less than 0.01 to 0.05 in Ka, tmax and Cmax compared to sustained-release tablets). Similarity of the in vitro dissolution profiles of the two sustained-release formulations did not imply similarity of the in vivo absorption characteristics. Plasma clearances of theophylline and antipyrine were significantly correlated (p less than 0.05, r = 0.693, n = 10). Thus, smoking enhanced the elimination of theophylline regardless of the dosage form administered. However, the extent to which habitual smoking may affect the hepatic first-pass effect on theophylline from sustained-release formulations requires further study. The results also suggest that theophylline and antipyrine may share a similar or common and presumably polycyclic hydrocarbon-inducible form(s) of microsomal drug-metabolizing enzyme.

Administration, Oral↗

Nationwide survey of high-density lipoprotein cholesterol among farmers in Japan.

A total of 2,134 blood samples (788 from men and 1,346 from women), were collected nationwide from adult farmers in Japan (44 regions in 21 prefectures) during the winters of 1978 through 1981. They were analyzed in a single laboratory for high-density lipoprotein cholesterol (HDL) by means of a precipitation method. The serum HDL level was 47.3 +/- 14.2 mg/100 ml (mean +/- SD; n = 788) in men and 47.4 +/- 12.8 mg/100 ml (n = 1,346) in women. Sex and age differences in HDL were not statistically significant (P greater than 0.10). Alcohol consumption was associated with elevated HDL levels in both sexes; the association was statistically significant only in men (P less than 0.05) and was positively correlated with daily alcohol consumption (P less than 0.05). Conversely, smoking habits were negatively (P less than 0.05) associated with HDL in men. The comparison of HDL in the nondrinking and nonsmoking population revealed that HDL in women (47.0 +/- 12.8 mg/100 ml; n = 900) did not differ significantly (P greater than 0.10) from the male values (45.3 +/- 12.5 mg/100 ml; n = 60). When 23 nondrinking and nonsmoking married couples were selected from 348 couples, for whom information on drinking and smoking habits was available, the HDL (+/- SD) was essentially the same in husbands (44.2 +/- 12.8 mg/100 ml) and in wives (43.7 +/- 9.5 mg/100 ml). In the blood samples collected from 535 subjects once in winter and once in summer, HDL concentration was significantly higher in summer than in winter (P less than 0.01 in both men and women); the HDL means (+/- SD) in winter and in summer were 48.1 +/- 14.3 and 50.9 +/- 11.3 mg/100 ml, respectively, for men, and 47.0 +/- 12.0 and 50.3 +/- 11.0 mg/100 ml, respectively, for women. The mean HDL distributed across a fairly wide range depending on the 44 regions studied. Maximum-minimum mean values were 58.3-33.1 mg/100 ml in men and 59.7-37.4 mg/100 ml in women, and the regional difference was statistically significant (P less than 0.01) both in men and women. Furthermore, a significant inverse relation (P less than 0.05) was observed in men between the mean regional HDL values and standardized regional ratios of mortality from coronary heart diseases.

Adult↗

Serum folic acid levels and antipyrine clearance rates in smokers and non-smokers.

Serum folic acid (FA) levels and antipyrine clearance rates were determined in 15 healthy male subjects who had not been administered any drug and alcohol for a month preceding the study. Eight of the 15 subjects smoked cigarettes daily while the remaining seven did not. The serum FA levels were measured by Lactobacillus casei bioassay. The antipyrine clearance rates were estimated in plasma or saliva obtained after oral administration of antipyrine for evaluating the activity of hepatic microsomal oxidase. The serum FA levels in the smokers were significantly lower than those in the non-smokers and the antipyrine clearance rates were significantly higher in the smokers compared with the non-smokers. The increase of the antipyrine clearance rates in the smokers was supposed to be caused by an increase in the activity of hepatic microsomal oxidase since it has been established that polycyclic aromatic hydrocarbons contained in cigarette smoke induce these enzymes. The association of the decrease in the serum FA levels and the increase of the antipyrine clearance rates was investigated.

Adult↗

Quantitative analysis of calcium binding to porcine intestinal calcium-binding protein.

An equilibrium dialysis study has revealed that porcine intestinal calcium-binding protein (CaBP) has two binding sites for Ca2+ whose dissociation constants (Kd) are the same, 0.56 microM. The intrinsic fluorescence spectrum of the CaBP shows a peak (at 303 nm) in tyrosine band. Ca2+ binding to the CaBP induces a monophasic increase in the intensity of intrinsic fluorescence without any shift to either excitation or emission maximum. The change in the fluorescence intensity induced by Ca2+ binding is complete at a bound Ca2+/CaBP molar ratio of about 2, and the apparent Kd value is 0.51 microM. The same bound Ca2+/CaBP molar ratio has been obtained from the maximal changes in UV absorption and CD spectrum of the CaBP upon addition of Ca2+. A CD study has shown an about 5% increase in alpha-helix content in the CaBP at the maximal binding of Ca2+. All these results indicate that the porcine intestinal CaBP has two high-affinity binding sites with equal affinity for Ca2+ and suggest that it undergoes a quantitative conformation change accompanying Ca2+ binding in the vicinity of single tyrosine and phenylalanine residues of the protein molecule.

Animals↗

Simultaneous liquid chromatographic determination of chloramphenicol and antiepileptic drugs (phenobarbital, phenytoin, carbamazepine, and primidone) in plasma.

A method for the simultaneous analysis of chloramphenicol and four antiepileptic drugs (phenobarbital, phenytoin, carbamazepine, and primidone) in plasma by high-performance liquid chromatography (HPLC) is described. The method involves a preliminary extraction of 0.1 ml of plasma with diethyl ether containing phenacetin as an internal standard, chromatography with a reversed-phase column with a methanol-water mobile phase, and detection by measuring ultraviolet absorbance at 210 nm. The method demonstrated sufficient precision, sensitivity, and specificity: the recoveries of the drugs were greater than 95% with the exclusion of primidone (80.3%); the maximum within-day and day-to-day coefficients of variation for all drugs were less than 5%; the lower detection limits were 0.5 microgram/ml or less for all drugs analyzed; and six other antibiotics, phenylethylmalondiamide, carbamazepine-10,11-epoxide, and chloramphenicol esters did not interfere with the analysis. The HPLC method was tested for clinical applicability by analyzing plasma samples from a volunteer who received concurrent single doses of chloramphenicol, phenobarbital, and phenytoin. This method can be used for studying drug interactions between chloramphenicol and antiepileptic drugs and for monitoring the concentrations of these drugs in plasma when administered concurrently, to prevent concentration-related side effect(s) of each drug.

Adult↗