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Tsuyoshi Shimamura

Publications and source records attributed to Tsuyoshi Shimamura.

25 records · Page 2Linked to original sources
PubMed2002

Liquid chromatographic method for the determination of ganciclovir and/or acyclovir in human plasma using pulsed amperometric detection.

We have developed a simple, rapid and highly sensitive method for determining plasma concentrations of ganciclovir and/or acyclovir by using reversed-phase chromatography followed by pulsed amperometric detection. A linear relationship between the amount of ganciclovir (0.05-10 microg/ml plasma) or acyclovir (0.1-20 microg/ml plasma) and peak height ratio was obtained. The relative standard deviations of all standard curves were greater than or equal to 0.999. The limits of detection for ganciclovir and acyclovir quantitation were 10 ng/ml and 50 ng/ml (signal/noise >3), respectively. Daily fluctuations of plasma standard curves (n=5) for the ganciclovir and acyclovir samples were small, with relative standard deviations (RSD) of 3.3 and 4.5% (n=5), respectively. The intra-assay precision for the ganciclovir and acyclovir samples were 6.9 (n=5) and 5.5% (n=5), respectively. Inter-assay precision of ganciclovir (n=3) and acyclovir (n=3) ranged from 2.6 to 6.8% and 3.5 to 5.0%, respectively. Using this method, the pharmacokinetics and removal of ganciclovir during continuous hemodiafiltration (CHDF) in a liver transplant recipient being treated for severe cytomegalovirus infection was investigated. The mean (+/-SD) ratio of ganciclovir concentrations at the inlet and outlet of the dialyzer (C(outlet)/C(inlet)) was 0.56+/-0.09. The areas under the curves of ganciclovir up to 12 h postdosing (AUC(0-->12)) at the inlet and outlet of the dialyzer were 12.54 microg h/ml and 7.16 microg h/ml, respectively. The ultrafiltrate of ganciclovir was 16.6 mg. The terminal elimination half-life (T(1/2)) of ganciclovir during CHDF was 3.6 h. These results demonstrate that CHDF effectively removes ganciclovir. Until formal guidelines have been established, ganciclovir or acyclovir dosage should be adjusted according to the results of monitoring of plasma drug concentration. The method described here is suitable for clinical monitoring of plasma ganciclovir or acyclovir levels in solid organ transplant recipients and for use in studies involving pharmacokinetics.

Acyclovir↗
PubMed2002

Role of cyclic nucleotides in ischemia and reperfusion injury of canine livers.

BACKGROUND: In a series of canine liver ischemia experiments, we have shown that amelioration of hepatic injury is achievable by the inhibition of vasoconstriction, cytokine production, platelet aggregation, and neutrophil infiltration. Cyclic adenosine diphosphate (cAMP) was considered to be involved in most of these events. In our study, we tested our hypothesis that augmentation of endogenous cAMP by phosphodiesterase (PDE) 3 inhibitor, amrinone (AM), or adenylate cyclase stimulator, NKH477 (NKH), could attenuate ischemia and reperfusion injury of the liver. METHODS: Thirty-six beagle dogs were used. They were divided into group CT (untreated control), group AM, group NKH, and group CB (treated by both agents). AM or NKH were administered i.v. 1 hr before ischemia (group preAM and group preNKH) or 15 min before reperfusion (pos-AM and postNKH). Combination group animals were treated only before ischemia. Animal survival, hepatic tissue blood flow, liver enzymes, platelet counts, energy metabolism, hepatic cAMP and cyclic guanosine 3',5'-cyclic monophosphate levels, and histopathology were analyzed. RESULTS: Two-week animal survival was significantly improved by pre- or posttreatment with either agent. After reperfusion, hepatic tissue blood flow, liver enzyme release, platelet counts, energy metabolism, tissue cAMP levels, and histological architecture were also ameliorated markedly. Combination of both agents induced severe liver damage and lethal hypotension. AM treatment exhibited more protective effects than NKH, particularly when it was given before ischemia. Interestingly, not only cyclic guanosine 3',5'-cyclic monophosphate, were also restored at higher levels after reperfusion by preischemia treatment. CONCLUSIONS: Administration of amrinone or NKH477 maintained hepatic tissue concentrations of cyclic nucleotides, and attenuated ischemia and reperfusion injury of the liver. Thus, regulation of hepatic tissue cyclic nucleotides is an important alternative for prevention of hepatic damage in liver preservation and surgery.

Adenosine Triphosphate↗
PubMed2002

Control of intraoperative bleeding during liver resection: analysis of a questionnaire sent to 231 Japanese hospitals.

To determine the safest and most efficient way of performing hepatectomy, the differences in methods employed by Japanese surgeons were examined. In November 1998, a questionnaire on bleeding control during hepatectomy was sent to 270 hospitals located throughout Japan. The answers from 231 hospitals (85.6%) were analyzed. Surgical apparatus such as an ultrasonic dissector (USD) was used in 203 hospitals. Pringle's maneuver was performed routinely in 25%, for segmentectomy and subsegmentectomy in 25%, for lobectomy in 9%, depending on the situation in 34%, and never in 7%. In 135 hospitals (60%), hemostatic materials such as fibrin glue were always applied to the cut surface after hepatectomy. The USD was chosen and widely accepted by the hospitals studied. As Japanese patients with hepatoma often have liver cirrhosis, intermittent occlusion and the selective clamping of hepatic inflow were considered preferable to persistent inflow occlusion. The gentle exposure of hepatic venous branches, careful hemostasis during hepatectomy, and accurate location of the hepatic vein by intraoperative ultrasonography were all considered to be extremely important.

Attitude of Health Personnel↗
PubMed2002

A novel leflunomide derivative, FK778, for immunosuppression after kidney transplantation in dogs.

BACKGROUND: Leflunomide and its metabolite, A77 1726, interfere with pyrimidine metabolism and exert potent immunosuppression in experimental organ transplantation. However, clinical use of the agents has been restrained because of an extended half-life. FK778, one synthetic malononitrilamide derived from A77 1726, is synthesized to overcome this problem while maintaining similar therapeutic efficacy. METHODS: Immunosuppressive effect, pharmacokinetics, and adverse events of FK778, as a single drug treatment or combination with tacrolimus or cyclosporine, were determined in a canine kidney transplantation model. The agents were daily administered orally to the animals for 90 days after surgery. Animal survival, pharmacokinetics, biochemistry, hematology, and histopathology were evaluated. RESULTS: FK778 at 4 mg/kg prolonged median survival of the control animals from 10 days to 30.5 days. Administration of 4 mg/kg FK778 with 0.3 mg/kg tacrolimus or 10 mg/kg cyclosporine increased median survival to 75.5 days and 50.5 days, respectively. In combined treatments, trough levels of FK778 at 4 mg/kg ranged between 40 microg/mL and 100 microg/mL after 1 month. Vomiting and diarrhea were common in animals given FK778. Bone marrow suppression was seen at higher doses. CONCLUSIONS: FK778 is a promising new immunosuppressant that may be used in combination with current standard drugs in organ transplantation.

Alkynes↗
PubMed2002

[Liver transplantation for patients with hepatitis B/C virus cirrhosis or hepato cellular carcinoma].

The outcome of liver transplantation for patients with hepatitis B/C virus (HBV/HBC) cirrhosis or with hepatocellular carcinoma(HCC) was deemed pessimistic until the early 1990s due to the high rate of recurrence and mortality. However, with the advent of new antiviral agents and strict adherence transplant indications, the results of liver transplantation in patients with these disease have improved progressively. Coadministration of lamivudine and anti-HBV immunoglobulin, and of interferon and ribavirin inhibits the recurrence of hepatitis B and hepatitis C, respectively. Excluding HCC patients with extrahepatic or lymph node metastasis, vascular invasion, a single lesion more than 5 cm in diameter, or multiple lesions more than 3 cm in diameter, the 5-year patient survival rate has improved from 30% to 85%, with a disease-free survival rate of more than 90%. However, the development of lamivudineresistant mutants after prolonged use of the agent needs to be overcome, possibly by new antiviral agents such as adefovir. In addition, to expand the current limited transplant indications for HCC, the efficacy of perioperative anticancer treatment and the importance of molecular diagnosis of circulating hepatoma cells must be determined in future.

Adult↗
PubMedDate not supplied

A nomogram for predicting the optimal oral dosage of tacrolimus in liver transplant recipients with small-for-size grafts.

No optimal tacrolimus dosage regimen suitable for clinical use in liver transplant recipients has yet been established. The purpose of this study was to determine the factors affecting the optimal dosage and pharmacokinetics of tacrolimus in living donor liver transplantation, and a nomogram for optimal tacrolimus dosage in the immediate postoperative period for recipients with small-for-size grafts was constructed. Twenty-four liver transplant patients (nine males and 15 females) and 24 donors (10 males and 14 females) were enrolled in this study. Two studies were performed. In study 1, the effect of the actual ratio of graft volume to standard liver volume (GV/SV ratio) on the elimination half-life (T1/2) of tacrolimus in the immediate postoperative period was analysed, and a nomogram for estimating the optimal oral dose of tacrolimus required to reach a target concentration was established. In study 2, the effect of donor age on the recovery of hepatic function with ability of the graft to eliminate tacrolimus was analysed. In the immediate postoperative period, T1/2 of tacrolimus showed great variability between patients, with values ranging from 16.3 to 110.9 h. Graft size (GV/SV ratio) is important and could influence intraindividual variations in the optimal dosage and T1/2 of tacrolimus. The recovered T1/2 ratio (T1/2 ratio=T1/2 1-10 d/T1/2 30-40 d), this ratio being related to the recovery of hepatic function with ability of the graft to eliminate tacrolimus, showed great variability between patients, with values ranging from 1.08 to 4.21 (mean+/-SD, 1.95+/-0.81). Age of the donor is a major factor affecting the recovered ratio of the graft to metabolize tacrolimus. The nomogram that we have constructed, based on graft size (GV/SV ratio), will easily provide optimal dose for each patient with small-for-size graft in the early postoperative period.

Adolescent↗