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Biomedical subjects

H Tokumo

Publications and source records attributed to H Tokumo.

14 recordsLinked to original sources

External biliary jejunal drainage through a percutaneous endoscopic gastrostomy for tube-fed patients with obstructive jaundice.

We describe a new procedure, which can help patients with obstructive jaundice improve their quality of life (QOL). Although percutaneous transhepatic biliary drainage (PTBD) can relieve jaundice, the procedure has some disadvantages. Percutaneous endoscopic gastrostomy (PEG) is a useful method for providing nutritional support to patients unable to swallow. We have combined these two techniques. We used the combination ofa 20-F catheter and a 9-F jejunal catheter for PEG. The PTBD catheter and the 9-F jejunal catheter are connected outside the patient's body. Externally drained bile from the PTBD catheter can flow back into the jejunum, and the opening between the 20-F catheter and the 9-F jejunal catheter is used for tube feeding. This procedure was adopted in a patient. Since the procedure, the patient's nutritional status and daily living activities have improved. We conclude that the procedure is useful for tube-fed patients with obstructive jaundice.

Aged↗

Effects of fluvastatin on human biliary lipids.

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have rapidly become widespread in the treatment of hypercholesterolemia and are known to be variable in efficacy. To investigate the effect on biliary lipids, a 3-month study using fluvastatin was devised. A total of 19 patients were enrolled in this study: all had hypercholesterolemia (7 men, 12 women; 13 with type IIa, 6 with type IIb). After an observation period of 4-6 weeks with placebo, fluvastatin at a daily dose of 30 mg was administered for 3 months. Fasting blood samples were taken early in the morning, before, and once a month during 3 months of fluvastatin treatment, for measurement of serum lipids. Cerulein-stimulated bile in the gallbladder was sampled using a duodenal tube, and the changes in biliary lipids were assessed. There was a marked decrease in serum total cholesterol after 12 weeks of treatment (21%; p < 0.001). However, there was no significant difference in the bile cholesterol saturation index (CSI): values before and after 3 months of drug administration were 0.93 and 0.99, respectively (Admirand-Small method). There were no significant changes in either the fatty acid composition of biliary lecithin or in the bile acid composition of bile. In conclusion, on the basis of these results, short-term (3 months) administration of fluvastatin does not appear to affect CSI.

Adult↗

A novel transcellular transport pathway for non-bile salt cholephilic organic anions.

Non-bile salt cholephilic organic anions comprise a single class of nonhomologous ligands having a range of hydrophobicity. Hydrophobicity enhances the hepatic extraction of cholephiles as well as their partitioning into secreted biliary lipid particles. When hydrophobicity is correlated with patterns of biliary excretion for studying transcellular transport, however, the more hydrophobic probes are unsuitable. Specifically, with the isolated perfused rat liver technique, the excretory times for sulfobromophthalein and rose bengal were significantly longer compared with that for the much more hydrophilic analogue phenol red (PR), which showed only a single, nearly symmetrical excretory peak at 10 min. Colchicine affected the apparently well-defined PR pathway only at a saturation dose (10,000 times the tracer dose). In contrast, the effect of a different perturbant, monensin, was striking at a tracer dose of PR, but was less evident at a saturation dose. The combined administration of colchicine and monensin had no additive inhibitory effect on PR excretion at tracer doses. At a saturation dose of PR, where monensin is less inhibiting, however, a significant additive inhibitory effect was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hepatic extraction of organic anions in the rat depends on ligand hydrophobicity.

Non-bile-salt cholephilic organic anions are efficiently taken up by the liver. Recent work from our group has suggested the possible importance of relative hydrophobicity among various organic anions in hepatic uptake. To further validate and clarify this, we studied hepatic extraction of five different cholephilic dyes using the isolated perfused rat liver in single-pass mode. Albumin binding affinities and capacities for each of the ligands were measured in vitro to permit evaluation of in vivo interactions for each of them over a spectrum of unbound ligand concentrations. As expected, a strong positive correlation was found between ligand hydrophobicity and the relative degree of albumin binding affinity and capacity. Using appropriate experimental conditions, we also found a strong positive correlation between hepatic extraction efficiency for a given ligand and both its hydrophobicity and its unbound concentration. These data indicate that where the unbound ligand concentration is significant, the greater the ligand hydrophobicity, the greater is its efficiency of hepatic extraction. We conclude that hepatic extraction efficiency for non-bile-salt cholephilic organic anions depends on a combination of ligand hydrophilic/hydrophobic balance and the availability of the unbound ligand for uptake.

Animals↗

A sensitive method for determination of cholesterol growth using model solutions of supersaturated bile.

We describe a novel, facile, and highly reproducible spectrophotometric technique to measure a cholesterol crystal growth curve. This method permits a quantitative estimate of the potency or comparative abundance of a given kinetic effector substance. In addition to several internal validation procedures, data are provided that support the usefulness of the technique in the assay of substances with either known promoting activity, i.e., human mucin glycoprotein, or those with known inhibitory activity, i.e., human apolipoprotein A-I.

Apolipoprotein A-I↗

Biliary secretion of organic anions in the dog: association with defined lipid particles.

Organic anions have recently been found to partition in vitro into various biliary lipid particulate species according to their relative hydrophobicities. To establish the physiological relevance of these observations, we intravenously injected various radiolabeled organic anions and assessed the distributions of parent compounds and their metabolites to lipid particles in canine bile. Partitioning into various biliary lipid particles was determined by gel permeation chromatography. Relative hydrophobicities of the various organic anions and their radiolabeled conjugates were determined by reverse-phase high-pressure liquid chromatography. A strong positive correlation (P less than 0.001) was found between percent vesicular association and degree of hydrophobicity for a given organic anion and/or its more polar conjugate. We conclude that 1) the hydrophobic-hydrophilic balance of organic anions is a key factor governing their partitioning to lipid particles secreted in bile; 2) the present study agrees well with our previously published in vitro observations; and 3) other chemical constituents, e.g., proteins, mucin, etc., appear to have little or no effect on organic anion transport in bile.

Aminolevulinic Acid↗

[Therapeutic effect of ceftizoxime on infections in aged patients].

Ceftizoxime (CZX) were administered and tested for the efficacy and safety in 80 elderly patients who were older than 65 years of age with infections. The sensitivity of bacteria found in these infections to CZX was examined before the administration of the drug. Serum concentrations and the rate of urinary output of the drug were examined in 3 cases. The clinical effect of CZX was as follows: 29 cases (36.3%) of excellent effectiveness and 31 cases (38.8%) showed moderate effectiveness. The patients were divided into 2 groups depending on the presence or the absence of other diseases in their backgrounds. Effectiveness of CZX for patients with and without other diseases were 74.0% and 85.7%, respectively. The effectiveness of CZX in patients with other diseases in their background was lower than the group without other diseases. Other antibiotics were used in 16 cases before the use of CZX. The effectiveness of CZX for these patients was 62.5%. Infecting bacteria were detected in a total of 46 cases (19 cases of respiratory infections and 27 cases of urinary tract infections). Among the respiratory cases, 8 were due to Gram-positive bacteria and 11 were due to Gram-negative bacteria. No Gram-positive organisms were detected from urinary tract infections, which were all due to Gram-negative bacteria. Sensitivities of isolates of these infecting bacteria to CZX were very sensitive 3 isolates, sensitive (++) 8 and slightly sensitive (+) 1 isolate. It was found that CZX was effective against 39 of 46 cases from which causative organisms were identified. The effectiveness ratio was 84.8%. Serum concentration of CZX was determined after a drip injection of 1 g CZX for 1 hour. The half-lives of CZX in plasma in healthy subjects and aged patients were 1.33 hours and 2.15 hours, respectively. The rate of urinary output of CZX during 6 hours after the injection was 76.4% in healthy subjects. Delayed urinary output which was 58.2% during 7 hours after injection was observed in aged patients. Fever in 1 patient and eosinophilia in 3 cases were observed after administration of CZX.

Age Factors↗

Reversibility of organic anion-induced cholestasis: association with compensatory hypersecretion of biliary phospholipid and protein in the dog.

The effect of a concomitant infusion of organic anions, structurally related phthaleins, on bile flow was studied in anaesthetized dogs. A combination of rose bengal and sulfobromophthalein was found to uniquely and synergistically produce an acute, reversible form of intrahepatic cholestasis (< 10% of control level). This phenomenon was not observed with the administration of those individual organic anions at concentrations previously associated with the induction of intrahepatic cholestasis. The infusion of either a micelle forming bile salt, sodium taurocholate, or a non-micelle forming bile salt, sodium dehydrocholate, rapidly reversed the intrahepatic cholestasis (within 20 min after bile salt infusion). During the choleretic phase immediately following the bile salt infusion, a transient but marked hypersecretion, a disproportionately increased output in relation to that of bile acids, of biliary phospholipid (176% of control level by taurocholate and 138% of control level by dehydrocholate), and an even more striking amount of biliary protein hypersecretion were observed (392% of control level by taurocholate and 357% of control level by dehydrocholate). Although the significance of these new post-cholestatic observations requires clarification, it is suggested that the intrahepatic cholestasis induced by organic anions reflects a reversible defect in the mechanism(s) involved in transcellular transport.

Animals↗

A new case of familial lecithin: cholesterol acyltransferase (LCAT) deficiency--paradoxical findings regarding LCAT mass and activity in 23 members of a family.

LCAT activity and mass were assayed simultaneously in 23 members of a new family case, revealing two homozygotes with a markedly low HDL--cholesterol level and ester cholesterol ratio. The LCAT mass in these patients was only 0.8 and 0.9 micrograms/ml, respectively (normal range 4.4-8.1) and their LCAT activity was 4 and 6 nM/ml/h 37 degrees C (normal range 60-120). Apolipoprotein (Apo) A-I and II levels were significantly low; however, apolipoprotein E tended to be high. In two-dimensional electrophoresis, apo A-I isoform visualized the increase of immature apo A-I; that is, A-I2. One subject showed the clinical characteristics of classic LCAT deficiency; however, the other, who was a vegetarian, showed corneal opacities and red cell deformity, but not proteinuria. This suggests that a low fat diet which decreases the level of atherogenic large LDL, may lead to a more favourable prognosis with a reduced risk for renal insufficiency. There were two different types of LCAT abnormality in this family series. Among the 10 examined paternal kindred of the proband who was one of two homozygotes, seven had a low LCAT mass but normal LCAT activity with the exception of one kindred who had a low mass and low activity. In contrast, among his seven maternal kindred examined, two had a low LCAT activity but normal mass.

Adult↗