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Biomedical subjects

T Kiuchi

Publications and source records attributed to T Kiuchi.

At least 19 recordsLinked to original sources

Retention and removal of a new viscous dispersive ophthalmic viscosurgical device during cataract surgery in animal eyes.

AIMS: To assess the retention and removal properties of a new viscous dispersive ophthalmic viscosurgical device (OVD), DisCoVisc, in comparison with those of cohesive (Provisc), dispersive (Viscoat), and viscoadaptive (Healon5) OVDs. METHODS: In 20 porcine eyes, cataract surgery was simulated using one of the four OVDs which were stained with fluorescein for better visualisation. Three parameters were measured. Firstly, the presence/absence of OVDs in the chamber at the completion of phacoemulsification was recorded. Secondly, the time until the OVDs were completely removed from the anterior chamber using the phaco needle was measured. Thirdly, after intraocular lens (IOL) implantation, the time needed to completely remove the OVDs from the chamber with irrigation/aspiration tip was recorded. RESULTS: At the completion of phacoemulsification, the OVDs retained in 0% (0/5) for Provisc, 80% (4/5) for Healon5, 100% (5/5) for DisCoVisc, and 100% (5/5) for Viscoat. The retention of OVDs during phacoemulsification was greatest with Viscoat followed by, in descending order, DisCoVisc, Healon5, and Provisc. The removal of OVDs after IOL implantation took longest with Viscoat followed by Healon5, DisCoVisc, and Provisc. CONCLUSION: The viscous dispersive DisCoVisc showed excellent retention during phacoemulsification, while its removal after IOL implantation was very easy. When compared with the viscoadaptive Healon5, DisCoVisc was retained better in the chamber and was easier to remove. These features of DisCoVisc should be highly advantageous when considering covering the entire cataract surgery procedure with a single OVD.

Animals↗

Initial dosage adjustment for oral administration of tacrolimus using the intestinal MDR1 level in living-donor liver transplant recipients.

The role of intestinal P-glycoprotein (encoded by the MDR1/ABCB1 gene) and/or metabolic enzyme CYP3A4 for tacrolimus therapy was examined in recipients of living-donor liver transplantation (LDLT), under the hypothesis that these proteins are factors for pharmacokinetic variability. The intestinal mRNA expression level of MDR1 and CYP3A4 was evaluated by real-time polymerase chain reaction (PCR), using the upper jejunum from a part of the Roux-en-Y limb for biliary reconstruction at LDLT. For 7 days postoperatively, good inverse correlation was found between the tacrolimus concentration/dose (C/D) ratio and the intestinal mRNA level of MDR1 (r = -0.776), but not of CYP3A4 (r = -0.096), in the 46 cases. After classifying the patients according to median of the intestinal MDR1 mRNA expression, the oral dose of tacrolimus in the high-MDR1 group was approximately twofold higher than in the low-MDR1 group (P < .001), whereas its trough level was similar between the two groups. In addition, the correlation between the intestinal MDR1 mRNA level and the tacrolimus C/D ratio was confirmed with a larger population (r = -0.645, n = 104). Using the regression line between the intestinal MDR1 mRNA level and tacrolimus C/D ratio, we could prospectively predict the individual C/D ratio of tacrolimus immediately after LDLT. Known genetic variations of the MDR1 gene had no effect on intestinal MDR1 mRNA level and tacrolimus C/D ratio in LDLT patients. This suggests that the intestinal mRNA level of MDR1 is a useful molecular marker for determination of the personalized oral dose of tacrolimus in recipients of LDLT immediately after surgery.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

S100 beta protein: the preoperative new clinical indicator of brain damage in patients with fulminant hepatic failure.

The aim of this study was to clarify the role of serum S100 beta on the accurate assessment of reversibility of brain damage after fulminant hepatic failure (FHF). Among the 13 patients with FHF enrolled in this study, 12 underwent living donor liver transplantation; one patient could not the procedure because of volvulus of the sigmoid colon. Serum S100 beta was serially measured using a chemiluminescent immunoassay. Preoperative serum S100 beta in patients with diffuse brain edema was significantly higher than that in patients with localized brain edema (P < 0.05). Patients with preoperative brain death showed serum S100 beta levels over 7.0 microg/L. Serum S100 beta levels correlated with the degree of brain edema of FHF. It has the potential to be a new clinical, noninvasive indicator of brain damage due to FHF.

Adult↗

Critical progressive small-graft injury caused by intrasinusoidal pressure elevation following living donor liver transplantation.

In adult-to-adult living liver transplantation, small-for-size graft syndrome sometimes occurs. The relationship between the hemodynamic changes and histologic findings has not been studied in patients with failure of small-for-size grafts. We analyzed the relationship between the postoperative hemodynamic changes and pathologic findings in patients with small-for-size grafts that ended in graft failure. From March 1999 to December 2002, adult-to-adult living-donor liver transplantation with small-size grafts (graft volume/standard liver volume less than 40%) was performed in eight patients. Three patients died from graft failure caused by overperfusion, which was diagnosed from pathologic findings. We analyzed the relation between hepatic hemodynamic parameters, such as portal venous blood velocity or splenic arterial pulsatility index, and histologic changes in patients with graft failure. Severe portal hyperperfusion (90 cm/sec at the umbilical portion) was observed on postoperative day 1. Among patients with graft failure, critical hemodynamic changes, such as sudden onset of extremely deteriorated portal venous blood flow, occurred during the early postoperative period (postoperative day 5, 3, 6, respectively). Histologic examination revealed vacuolar changes in the cytoplasm of hepatocytes, and submassive necrosis indicated intrasinusoidal pressure elevation. These changes were not observed in the biopsy obtained soon after reperfusion. In conclusion, critically decreased vascular beds may cause intrasinusoidal pressure elevation and sinusoidal circulatory disturbances.

Adult↗

Specular microscopic study of X-ray-irradiated rabbit cornea.

PURPOSE: To investigate the influence of ionizing radiation on the corneal epithelium and endothelium of rabbit eyes. METHODS: Five healthy mature albino rabbits were unilaterally irradiated with 20 Gy of X-rays (250 kV, 12 mA). Slit-lamp biomicroscopic observation and specular microscopic examination of the corneal epithelium and endothelium were carried out before and 1, 4, 8, 12, 16, 20, 24, and 36 weeks after irradiation. We evaluated mean area of the superficial corneal epithelial cells, mean area and the percentage of hexagonal cells of the corneal endothelial cells, and corneal thickness. The statistical difference between the irradiated and control eyes was assessed using paired t-test. RESULTS: All animals developed cataract within 24 weeks. Slit-lamp biomicroscopy showed no apparent corneal abnormalities over the 36-week follow-up period. Specular microscopy revealed a significant enlargement of the superficial corneal epithelial cells from 4 to 12 weeks after irradiation (P<0.01), which disappeared at 16 weeks post-irradiation. Specular microscopy of the corneal endothelium showed enlargement and morphological alterations of the cells beginning 8 weeks after irradiation (P<0.05). These changes persisted throughout the study period. There were no statistically significant changes in corneal thickness. CONCLUSION: After X-ray radiation of 20 Gy, transient damage occurred in the corneal epithelium, while delayed and irreversible changes were seen in the endothelium.

Animals↗

Comparison of corneal thickness measurements using Orbscan II, non-contact specular microscopy, and ultrasonic pachymetry in eyes after laser in situ keratomileusis.

AIMS: To compare central corneal thickness measurements of three pachymetry devices in eyes after laser in situ keratomileusis (LASIK). METHODS: Central corneal thickness was measured in 203 eyes after myopic LASIK. Orbscan II scanning slit topography (Bausch & Lomb), SP-2000P non-contact specular microscopy (Topcon), and ultrasonic pachymetry (Tomey) were used in this sequence. RESULTS: Three devices gave significantly different corneal thickness readings (p<0.0001, repeated measure analysis of variance). The measurements of Orbscan II (445.6 (SD 60.0) microm) were significantly smaller than those of noncontact specular microscopy (467.9 (SD 40.2) micro m; p<0.0001, Tukey multiple comparison) and ultrasonic pachymetry (478.8 (SD 41.9) microm; p<0.0001). The value obtained with SP-2000P non-contact specular microscopy was significantly smaller than that taken with ultrasonic pachymetry (p<0.001). There were significant linear correlations between scanning slit topography and non-contact specular microscopy (Pearson's correlation coefficient r = 0.912, p<0.0001), non-contact specular microscopy and ultrasonic pachymetry (r = 0.968, p<0.0001), and ultrasonic pachymetry and scanning slit topography (r = 0.933, p<0.0001). CONCLUSION: In post-LASIK eyes, Orbscan II scanning slit topography significantly underestimated corneal thickness. Non-contact specular microscopy gave smaller thickness readings than ultrasonic pachymetry, but these two units showed an excellent linear correlation.

Adult↗

Effect of tributyltin chloride on the release of calcium ion from intracellular calcium stores in rat hepatocytes.

The effects of tri-n-butyltin chloride (TBT), an environmental pollutant, on the release of Ca(2+) from intracellular stores were investigated in isolated rat hepatocytes. Isolated hepatocytes permeabilized with digitonin were suspended in solution, and the concentration of extracellular Ca(2+) was measured, using a fluorescent Ca(2+) dye, fura-2. In the solution containing permeabilized hepatocytes that had been preincubated with 4.0 microM TBT for 30 min, the extracellular Ca(2+) concentration was high, but the inositol 1,4,5-trisphosphate (InsP(3))-induced increase in Ca(2+) concentration was suppressed, suggesting that the extracellular release of Ca(2+) in response to TBT treatment was from intracellular stores. Images of the Ca(2+) concentration in the intracellular stores of primary cultured hepatocytes loaded with fura-2 were obtained after digitonin-permeabilization, using digitalized fluorescence microscopy. The permeabilized hepatocytes that had been preincubated with 4.0 microM TBT for 30 min had a very low fura-2 fluorescence ratio (340/380 nm), suggesting that stored Ca(2+) was released. When the hepatocytes were treated with 4.0 microM TBT after digitonin-permeabilization, the decrease in the fura-2 fluorescence ratio was very small. However, when the permeabilized hepatocytes were incubated with 4.0 microM TBT and 2.0 microM NADPH, the decrease was enhanced, raising the possibility that TBT might be metabolized to the active form(s), thus releasing Ca(2+) from intracellular stores. When the hepatocytes were preincubated with 0.1 microM TBT for 30 min and then were permeabilized, the fura-2 fluorescence ratio was almost the same as that in the control permeabilized hepatocytes. However, the InsP(3)-induced decrease in the fluorescence ratio was suppressed significantly in the permeabilized hepatocytes. These results suggest that TBT released Ca(2+) from the intracellular stores at high concentrations, and suppressed the InsP(3)-induced Ca(2+) release at non-toxic low concentrations. It is probable that the latter effect was responsible for the previously reported suppression of Ca(2+) response induced by hormonal stimulations (Kawanish et al., Toxicol Appl Pharmacol 1999;155:54-61).

Animals↗

Weaning of immunosuppression in living donor liver transplant recipients.

BACKGROUND: Some reported studies have indicated the possibility of immunosuppression withdrawal in cadaveric liver transplantation. The aim of this study was to evaluate the possibility and feasibility of weaning living donor liver transplant recipients from immunosuppression. METHODS: From June of 1990 to October of 1999, 63 patients were considered to be weaned from immunosuppression. They consisted of 26 electively weaned patients and 37 either forcibly or incidentally weaned patients (nonelective weaning) due to various causes but mainly due to infection. Regarding elective weaning, we gradually reduced the frequency of tacrolimus administration for patients who survived more than 2 years after transplantation, maintained a good graft function, and had no rejection episodes in the preceding 12 months. The frequency of administration was reduced from the conventional b.i.d. until the start of weaning to q.d., 4 times a week, 3 times a week, twice a week, once a week, twice a month, once a month, and finally, the patients were completely weaned off with each weaning period lasting from 3 to 6 months. The reduction method of nonelective weaning depended on the clinical course of each individual case. When the patients were clinically diagnosed to develop rejection during weaning, then such patients were treated by a reintroduction of tacrolimus or an additional steroid bolus when indicated. RESULTS: Twenty-four patients (38.1%) achieved a complete withdrawal of tacrolimus with a median drug-free period of 23.5 months (range, 3-69 months). Twenty-three patients (36.5%) are still being weaned at various stages. Sixteen patients (25.4%) encountered rejection while weaning at median period of 9.5 months (range, 1-63 months) from the start of weaning. All 16 were easily treated with the reintroduction of tacrolimus or additional steroid bolus therapy. CONCLUSIONS: We were able to achieve a complete withdrawal of immunosuppression in some selected patients. Although the mechanism of graft acceptance in these patients has yet to be elucidated, we believe that a majority of long-term patients undergoing living donor liver transplantation may, thus, be potential candidates to be successfully weaned from immunosuppression.

Adolescent↗

Microcirculatory changes in right lobe grafts in living-donor liver transplantation: a near-infrared spectrometry study.

BACKGROUND: A continuing shortage of cadaveric liver even for adult patients has motivated not a few centers to proceed to living-donor liver transplantation using right lobe grafts. One of controversies is potential congestion in the graft anterior segment by the deprivation of the middle hepatic vein. METHODS: Hepatic tissue oxygenation and hemoglobin concentration were investigated with a near-infrared spectroscopy in the course of harvesting and implantation in living-donor liver transplantation. Twenty adult recipients of right lobe graft were involved in the study. The aim of the analysis was to detect tissue congestion or ischemia. RESULTS: No significant change in mean hepatic tissue oxygenation and hemoglobin was noted in the right lobe during donor operation even after hepatic parenchymal transection, although some trend for relative congestion, i.e., increased tissue hemoglobin, compared with the left lobe was observed. After graft reperfusion in the recipient, both mean hepatic tissue oxygen saturation and hemoglobin decreased significantly in the anterior segment, which was accompanied by increased heterogeneity of tissue hemoglobin and oxygenation. Increased heterogeneity of oxygenation and decreased tissue hemoglobin were observed also in the posterior segment. CONCLUSIONS: The anterior segment in right lobe living-donor liver transplantation is sensitive to ischemia, rather than congestion, at least in the immediate phase after graft reperfusion. The anterior segment seems to be also more prone to circulatory disturbance than the other part of the graft.

Adult↗

Graft size assessment and analysis of donors for living donor liver transplantation using right lobe.

BACKGROUND: Modality of living donor liver transplantation (LDLT) has been expanded to adult cases. However, the safety of right lobectomy from living donors has not yet been proven. METHODS: A total of 62 cases of LDLT, using the right lobe, were reviewed. Study 1: Discrepancy between estimated graft volume and actual graft weight was evaluated. Study 2: Postoperative liver functions were analyzed in relation to residual liver volume (RLV) or age. Residual liver volume of donors was defined using two indices, (RLV = estimated whole liver volume - estimated graft volume and %RLV = RLV/estimated whole liver volumex100). Donors were divided into two groups on the basis of either %RLV (<40%; 40%< or =) or age (<50 years old; 50 years old < or =). Study 3: Right lobe donors were compared with left lobe donors (35 cases) in terms of their postoperative liver functions. RESULTS: Study 1: The relationship between estimated graft volume and actual graft weight was linear (y=159.136+0.735x, R2=0.571, P<0.001). Study 2: %RLV ranged from 23.5% to 55.8% (mean +/- SD: 43.2+/-6.0). Fifteen cases showed %RLV less than 40%. Postoperative bilirubin clearance was delayed in that group (%RLV<40%). Serum total bilirubin values on postoperative day 7 in the older group (age > or =50) were significantly higher than those in the younger group (age<50). Study 3: Postoperative liver functions of right lobe donors were significantly higher than those of left-lobe donors. Eleven donors (17.7%) had surgical complications, all of which were cured with proper treatment. CONCLUSIONS: Right lobectomy from living donors is a safe procedure with acceptable morbidity, but some care should be taken early after the operation for donors with small residual liver and aged donors.

Adult↗

Population pharmacokinetics of tacrolimus in adult recipients receiving living-donor liver transplantation.

OBJECTIVE: To characterize the pharmacokinetics of tacrolimus in adult recipients receiving living-donor liver transplantation (LDLT). METHODS: Thirty-five patients were given tacrolimus as 18- to 60-h intravenous infusions after surgery, followed by a 4-week course of oral dose therapy (at 0900 hours and 2100 hours). Blood samples were collected daily in the morning (0800 hours) beginning the day after surgery. Whole blood concentration data were evaluated by nonlinear mixed-effect modeling using the program NONMEM and were characterized using a one-compartment model. RESULTS: The clearance (CL, l h(-1)) was related to the grafted hepatic weight, postoperative days (POD), and hepatic and renal dysfunction. Interindividual variabilities in CL, volume of distribution (V), and bioavailability (F) were 57.4%. 39.7%, and 63.0%, respectively, and the correlation between individual CL and F was 0.776. Residual intraindividual variability was 2.9 ng ml(-1). Based on the estimated final parameters, a typical recipient of LDLT with grafted hepatic weight of 600 g and normal hepatic and renal function would have a CL of 0.737 l h(-1) on POD 0 and 1.14 l h(-1) on POD 30, V of 1.52 l kg(-1) and F of 6.8%. CONCLUSIONS: Nonlinear mixed-effect modeling was useful for analysis of pharmacokinetic characteristics of tacrolimus in LDLT patients. Immediately after surgery, patients receiving LDLT showed a smaller CL value than other transplant patients, and CL value increased with POD within 30 days after surgery. The estimated population pharmacokinetic parameters can be applied for a priori dosage calculations in adult patients with LDLT.

Adolescent↗

Biliary anastomotic complications in 400 living related liver transplantations.

The purpose of this study was to evaluate the cause and outcome of biliary anastomotic complications occurring after living related liver transplantation (LRLT). A database of 391 patients undergoing 400 LRLT from June 1990 to August 1998 was reviewed. The overall incidence of biliary anastomotic complications was 18.2% (71 patients). There were 45 bile leaks, 35 anastomotic strictures, and the bile duct was ligated inadvertently in 3 cases. Univariative analysis revealed that the manner of stent usage, intrapulmonary shunting, and gender of recipients were significant risk factors for leakage. Anastomotic leaks, cytomegalovirus infection, hepatic artery complications, and gender of recipients were significant risk factors for stricture. In pediatric patients older than 2 years old, ABO blood type compatibility was another risk factor for leakage and stricture. Choice of stent usage and earlier transplantation for patients with intrapulmonary shunting should reduce the rate of biliary leaks, and prophylaxis of leaks for patients with intrapulmonary shunting, and minimizing hepatic artery complications should reduce the rate of biliary stricture after LRLT. Avoidance of ABO-incompatible donors or innovative immunosuppression in ABO-incompatible transplantation should be considered in children.

Adolescent↗