Objective To explore the causes of biliary complications related with liver donor fol- lowing liver transplantation.Methods Ninty-nine patients with improved liver donor treatment during liver transplantation from May 2005 to April 2006 were followed up and the clinical data were ana- lyzed.At the same time,the rate of biliary complications was compared with that occurring on 43 pa- tients with unimproved liver donor treatment.Results Only 4 in 99 patients with improved liver donor treatment had biliary leakage with the rate of biliary complications being 4% in comparison with 11% in those with unimproved liver donor treatment.Conclusion The improvement of liver donor treat- ment,including shortening heat-ischemia time,completely washing bile duct and remaining the whole blood supply of bile duct,can decline the occurrence of biliary complications.

OBJECTIVETo evaluate the replication and encapsidation of HBV mutants with the truncated C gene.

METHODSThe HBV mutants with the truncated C gene were constructed by molecular cloning and PCR-based deletion in vitro. The replication and encapsidation of HBV mutants were investigated by Southern blotting, PCR and real-time fluorescence PCR respectively after transfecting the HBV mutants plasmid into HepG2 cells by using liposome.

RESULTSThe C-truncated HBV mutant vectors were constructed successfully and confirmed exactly by clone sequencing and enzymes digestion. The C-truncated HBV mutants were replication defective, however, all types of HBV DNA could be detected positive in the cytoplasm and supernatant after co-transfecting the C-truncated HBV mutants plasmid and the helper constructs into HepG2 cells. The C-truncated HBV mutants were proved to produce 3-40 folds more progeny DNA than that of the wild-type HBV by DNA quantitative assay.

CONCLUSIONThe C-truncated HBV mutants are replication-deficient and could not replicate and encapsulate in the hepatocytes when transfected solely, however, the progeny HBV-variant viruses are encapsidated more effectively to secrete into supernatant when co-transfected with the helper construct which lacks part of 5 prime-proximal HBV RNA packaging signal Epsilon.

Cell Line, Tumor ; Hepatitis B Core Antigens ; genetics ; Hepatitis B virus ; genetics ; physiology ; Humans ; Mutation ; Plasmids ; genetics ; Transfection ; Virus Replication

The paper is to report the establishment of a population pharmacokinetic model for flurbiprofen (FP), an active metabolite of flurbiprofen axetil (FA). 246 FP serum concentration and clinical data were perspectively collected from 23 general anaesthesia patients receiving FA intravenously before operation in Dentofacial Surgery and Otorhinolaryngology Department of the First Affiliated Hospital of Fujian Medical University. Population pharmacokinetic data analysis was performed using NONMEM software. The measure of Bootstrap was applied for internal validation, while Visual Predictive check was adopted for external validation. The data of FP correspond with two-compartment model. The body weight (WT) had conspicuous effect on clearance and volume of central compartment, while sex, age and daily dose of administration had no marked effect on pharmacokinetic parameter of FP. The basic model was described as follows: CL (L x h(-1)) = 1.28x EXP(ETA(1)), V1 (L) = 5.03x EXP(ETA(2)), Q (L x h(-1)) = 8.5 x EXP(ETA(3)), V2 (L) = 4.39 x EXP(ETA(4)). The final model was described as follows: CL (L x h(-1)) = 1.32 x (WT/60) x EXP(ETA(1)), V1 (L) = 5.23 x (WT/60) x EXP(ETA(2)), Q (L x h(-1)) = 8.45 x EXP(ETA(3)), V2 (L) = 4.37 x EXP(ETA(4)). The population typical value of CL, V1, Q and V2 were: 1.32 L x h(-1), 5.23 L, 8.45 L x h(-1) and 4.37 L, respectively. Bootstrap and visual predictive check show that the final model of FP is stable, effective and predictable. A novel population pharmacokinetic model is developed to estimate the individual pharmacokinetic parameter for patients intravenous injecting FA in terms of patients' characteristics and dosing history, and to design a prior dosage regimen.
Adult ; Aged ; Analgesics ; blood ; pharmacokinetics ; Body Weight ; Female ; Flurbiprofen ; administration & dosage ; analogs & derivatives ; blood ; metabolism ; pharmacokinetics ; therapeutic use ; Head and Neck Neoplasms ; surgery ; Humans ; Injections, Intravenous ; Male ; Middle Aged ; Models, Biological ; Pain, Postoperative ; drug therapy ; prevention & control ; Prospective Studies ; Software ; Young Adult

Animals ; COS Cells ; Female ; Genetic Therapy ; Interleukin-12 ; genetics ; Liver Neoplasms, Experimental ; immunology ; therapy ; Mice ; Mice, Inbred BALB C ; T-Lymphocytes, Cytotoxic ; immunology

BACKGROUNDPain has a substantial impact on patients' activities and overall quality of life, but current conventional drugs have debilitating side effects, including gastrointestinal disorders. Thus there is a pressing need for new therapies with fewer side effects to alleviate cancer pain. We recently developed a topical herbal formula Xiaotan Tongluo analgesic gel (XTTL gel) based on the principles of traditional Chinese herbalism, and we have received positive feedback from bone cancer pain patients. The aim of this study was to determine the analgesic effects and explore the mechanisms of XTTL gel in a rat model of bone cancer pain.

METHODSThe rat model of bone cancer pain was established by inoculating Walker-256 rat carcinoma cells directly into the right tibial medullary cavity of Wistar rats. The rats were randomly assigned to three groups (n = 10 per group): (1) sham bone cancer control (sham group): vehicle (PBS) inoculation without carcinoma cells plus topical administration of blank gel; (2) Sham treatment control (vehicle group): Walker-256 cell inoculation plus topical administration of blank gel; (3) XTTL gel treatment (treatment group): Walker-256 cell inoculation plus topical administration of XTTL gel. XTTL gel treatments were applied daily for 7 days starting on day 14 following inoculation. Outcomes were assessed 21 days after inoculation by mechanical allodynia, histological staining, and by measuring concentrations of type I collagen carboxy-terminal telopeptide (ICTP) and bone-specific alkaline phosphatase (BAP) in serum.

RESULTSFourteen days after cancer cell incubation, significant mechanical allodynia in the ipsilateral hind paw and tumor growth in proximal end of the tibia were observed in the vehicle and treatment groups but not in the sham group. At day 21, mechanical withdrawal thresholds in treatment group rats were significantly higher ((4.8557 +/- 0.8336) g) compared with those of the vehicle group ((1.8630 +/- 1.4369) g, P < 0.05). ICTP and BAP levels increased significantly in vehicle group rats ((101.5176+/- 11.0694) U/L and (370.7838 +/- 12.8273) U/L, respectively) compared with those of the sham group ((11.7553 +/- 1.1885) U/L and (185.7338 +/- 3.6761) U/L, respectively; P < 0.05). XTTL gel decreased the level of blood serum ICTP ((41.8998 +/- 6.4970) U/L, P < 0.05) but had little effect on blood serum BAP ((365.5338 +/- 18.5361) U/L, P > 0.05).

CONCLUSIONTopical use of XTTL gel may have an analgesic effect on bone cancer pain, an effect mediated by lowering of ICTP levels and inhibiting bone resorption.

Alkaline Phosphatase ; metabolism ; Animals ; Body Weight ; Bone Neoplasms ; complications ; Cell Line, Tumor ; Collagen Type I ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Pain ; drug therapy ; etiology ; Peptide Fragments ; blood ; Peptides ; Procollagen ; blood ; Random Allocation ; Rats ; Rats, Wistar

OBJECTIVETo evaluate the efficacy and safety of combination chemotherapy with paclitaxel and carboplatin for advanced breast cancer (ABC).

METHODSFrom January 2001 to March 2006, 45 patients with ABC were treated with combination chemotherapy of paclitaxel and carboplatin. Patients received infusion of paclitaxel 175 mg/m2 on day 1 every 3 weeks or 75 mg/m2 on day 1, 8, 15 every 4 weeks. Carboplatin was administrated on day 2 with a dose of area under the time-concentration curve (AUC) being 5.

RESULTSThe median number of cycles was 3 (range, 2-6). The overall response rate was 62.2%. Median time to progression was 7.0 months (95% CI: 5.1-8.9). Median overall survival was 29.0 months (95% CI: 20.1-37.9). One year survival rate was 73.3%. Response rate for first line and second line treatment were 62.1% and 62.5% , respectively. No significant difference in response existed between visceral metastasis and soft tissue metastasis. The main side effects included nausea/vomiting, neurotoxicity, and hematologic toxicities. Grade III to IV adverse events included nausea/vomiting in 2 cases (4.4%), leukopenia in 17 cases (37.8%) , and alopecia in 6 cases (13.3%).

CONCLUSIONCombination of paclitaxel and carboplatin is active in treatment of ABC with an acceptable toxicity profile.

Alopecia ; chemically induced ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; mortality ; pathology ; Carboplatin ; administration & dosage ; Drug Administration Schedule ; Female ; Humans ; Leukopenia ; chemically induced ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Metastasis ; Paclitaxel ; administration & dosage ; Postmenopause ; Premenopause ; Soft Tissue Neoplasms ; drug therapy ; secondary ; Survival Rate ; Vomiting ; chemically induced

OBJECTIVETo summarize the clinical data in preventing HBV recurrence after liver transplantation and explore a optimal individual protocol in prophylaxis of HBV recurrence.

METHODSWe retrospected outcomes in 195 recipients who underwent a liver transplantation for HBV-related liver disease between June 2004 and July 2008. According to the anti-virus protocol these recipients are divided into two groups as following: group A received a protocol of combination treatment of lamivudine with HBIG, and group B with combination treatment of adefovir with HBIG. With mean follow-up of 23.7 months, HBV recurrent rate was observed in overall and each group separately.

RESULTSA total of 195 liver transplant recipients were identified that met the study criteria. At the sixth and eleventh month after operation, HBV recurrence appeared in 2 recipients, each in two groups, which were due to LAM cessation and HBV mutation respectively. Recurrent rate was 0.6% in group A, 3.7% in group B and 1% in total. There was no significant difference in HBV recurrent rate between group A and B.

CONCLUSIONLamivudine combined with HBIg should be considered as a reliable method in preventing HBV recurrence after liver transplantation. Better outcomes can be achieved by individual anti-virus protocol and HBIg administration according to HBV status in recipient.

Adolescent ; Adult ; Aged ; Antibiotic Prophylaxis ; Antiviral Agents ; therapeutic use ; Female ; Hepatitis B ; prevention & control ; surgery ; Hepatitis B virus ; drug effects ; physiology ; Humans ; Lamivudine ; therapeutic use ; Liver Transplantation ; Male ; Middle Aged ; Recurrence ; Young Adult

OBJECTIVE: We wanted to report our experience of metallic stent placement after insufficient balloon dilation in graft hemodialysis patients. MATERIALS AND METHODS: Twenty-three patients (13 loop grafts in the forearm and 10 straight grafts in the upper arm) underwent metallic stent placement due to insufficient flow after urokinase thrombolysis and balloon dilation. The indications for metallic stent deployment included 1) recoil and/or kinked venous stenosis in 21 patients (venous anastomosis: 17 patients, peripheral outflow vein: four patients); and 2) major vascular rupture in two patients. Metallic stents 8-10mm in diameter and 40-80 mm in length were used. Of them, eight stents were deployed across the elbow crease. Access patency was determined by clinical follow-up and the overall rates were calculated by Kaplan-Meier survival analysis. RESULTS: No procedure-related complications (stent fracture or central migration) were encountered except for a delayed Wallstent shortening/migration at the venous anastomosis, which resulted in early access failure. The overall primary and secondary patency rates (+/- standard error) of all the vascular accesses in our 23 patients at 3, 6, 12 and 24 months were 69% +/- 9 and 88% +/- 6, 41% +/- 10 and 88% +/- 6, 30% +/- 10 and 77% +/- 10, and 12% +/- 8 and 61% +/- 13, respectively. For the forearm and upper-arm grafts, the primary and secondary patency rates were 51% +/- 16 and 86% +/- 13 vs 45% +/- 15 and 73%+/-13 at 6 months, and 25% +/- 15 and 71% +/- 17 vs 23% +/- 17 and 73% +/- 13 at 12 months (p = .346 and .224), respectively. CONCLUSION: Metallic stent placement is a safe and effective means for treating peripheral venous lesions in dialysis graft patients after insufficient balloon dilation. No statistically difference in the patency rates between the forearm and upper-arm patient groups was seen.
Vascular Patency ; Treatment Failure ; Stents ; Renal Dialysis ; Polytetrafluoroethylene ; Middle Aged ; Metals ; Male ; Humans ; Graft Occlusion, Vascular/*therapy ; Forearm ; Female ; *Arteriovenous Shunt, Surgical ; *Angioplasty, Balloon ; Aged, 80 and over ; Aged

OBJECTIVETo evaluate the anti-apoptotic effect of aldehyde dehydrogenase 2 (ALDH2) on myocardial ischemia/reperfusion (I/R) injury in diabetic rats.

METHODSNormal male SD rats were divided into normal, diabetes and ethanol (the agonist of ALDH2) + diabetes groups. In the latter two groups, diabetes was induced by an intraperitoneal injection of 55 mg/kg STZ. Four weeks after the modeling, myocardial I/R was mimicked ex vivo, and lactate dehydrogenase (LDH) content in the coronary flow was determined. The activities of caspase-3 and ALDH2 were evaluated, and the expressions of Bcl-2 and Bax mRNA in the left anterior myocardium were detected using RT-PCR.

RESULTSIn diabetic group, LDH release and caspase-3 activity were increased, while ALDH2 activity and Bcl-2/Bax mRNA expression were decreased as compared to those in normal control group. Compared with the diabetic group, ALDH2 agonist ethanol significantly reduced LDH release and caspase-3 activity, increased ALDH2 activity and Bcl-2/Bax mRNA expression.

CONCLUSIONIn diabetic rats, enhanced ALDH2 expression can offer mycardial protection possibly in relation to suppress cell apoptosis.

Aldehyde Dehydrogenase ; metabolism ; Aldehyde Dehydrogenase, Mitochondrial ; Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Diabetes Mellitus, Experimental ; complications ; enzymology ; Ethanol ; pharmacology ; Male ; Mitochondrial Proteins ; agonists ; metabolism ; Myocardial Ischemia ; enzymology ; etiology ; Myocardial Reperfusion Injury ; enzymology ; pathology ; prevention & control ; Myocardium ; enzymology ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo investigate the relationship between plasma cytochrome P450 3A4 (CYP3A4) 894C>T gene polymorphism and the risk of recurrence of adverse cardiac events after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS).

METHODSA total of 275 patients with ACS received standard dual antiplatelet therapy and PCI. Platelet aggregation rate (PAR) was detected in each patient before and 7 days after administration of the anti-platelet drugs. Single nucleotide polymorphism of CYP3A4 gene 894C>T was detected with PCR and microarray technique. The number of coronary artery lesions was determined by PCI and the Gensini score was calculated. The patients were followed up for 3-12 months after discharge.

RESULTSNo significant difference was found in CYP3A4 gene polymorphism between patients with clopidogrel resistance (CR group) and those without CR (NCR group) (P>0.05). Multivariate logistic regression analysis showed that CYP3A4 gene 894C>T polymorphism was not correlated with CR in patients with ACS (OR 1.359, P>0.05). During the follow-up, the incidence of cardiovascular events was significantly higher in CR group than in NCR group (P<0.05), but this difference was not related to the mutation type of 894C>T locus of CYP3A4 gene.

CONCLUSIONThe CYP3A4 gene 894C>T polymorphism is not associated with the effect of anti-platelet therapy and the risk of cardiovascular event in patients with ACS following PCI.

Acute Coronary Syndrome ; therapy ; Alleles ; Blood Platelets ; Cytochrome P-450 CYP3A ; genetics ; Humans ; Percutaneous Coronary Intervention ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; therapeutic use ; Platelet Function Tests ; Polymorphism, Single Nucleotide ; Ticlopidine ; analogs & derivatives ; therapeutic use