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Gao L.,Institute of Geriatric Cardiology | He L.,Hospital and Institute of Hepatobiliary Surgery | Luo J.,General Hospital of Peoples Liberation Army | Xu B.,Institute of Geriatric Cardiology | And 10 more authors.
Chinese Medical Journal

Background Patients with the genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A are expected to require the lowest dose of warfarin, and to have a greatly increased risk of bleeding. The experience for the dosing of warfarin in such extremely rare cases has been seldom reported. Methods Demographic and clinical data from two cases with stable low dose of warfarin in China were studied by resequencing the corresponding gene segments in their whole blood DNA. The potential clinical value of the pharmacogenetic algorithm for them was evaluated by calculating the stable dose of warfarin in pharmacogenetic algorithm developed by International Warfarin Pharmacogenetics Consortium. Results Both cases (68-year-old female and 50-year-old male) were diagnosed as chronic nonvalvular atrial fibrillation needing warfarin treatment, with target international normalized ratio (INR) 2 to 3. Case 1 had stable warfarin dose of 0.625 mg/d and case 2 1.25 mg/d. They needed more than 1 month to stabilize their anticoagulation. Exceeding INR values were recorded for them when the dose of warfarin was no more than 2 mg/d. Hemorrhagic complication appeared in case 1 when the dose was titrated from 2.5 to 1.25 mg/d. No concomitant medicine to increase or decrease the INR value was recorded for them. Genotyping CYP2C9 and VKORC1 showed both patients were the carriers of the homozygous alleles-CYP2C9*3/*3 and VKORC1-1639 A/A. Their stable doses of warfarin calculated by the pharmacogenetic dose algorithm (0.672 mg/d for case 1 and 1.16 mg/d for case 2) were comparable with their actual stable therapeutic doses. Conclusions Two Chinese with the rare genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A were found to require the extremely low dose of warfarin. The pharmacogenetic algorithm incorporating the variances of VKORC1 and CYP2C9 genotypes, as well as the non-genetic factors could predict their stable dose of warfarin with high accuracy. Source

Xu H.B.,Hospital and Institute of Hepatobiliary Surgery | Wang H.D.,Dalian Medical University | Li C.H.,Hospital and Institute of Hepatobiliary Surgery | Ye S.,Hospital and Institute of Hepatobiliary Surgery | And 6 more authors.
Genetics and Molecular Research

We used a meta-analysis approach to investigate the association between proton pump inhibitor (PPI) use and risk of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. We searched Ovid Medline, Embase, and the Cochrane Library to identify eligible studies. We included studies that compared cirrhotic patients who did or did not use PPIs. The primary outcome was SBP, and the secondary outcome was overall bacterial infection. Results were pooled using random-effect models. This process led to identification of 12 journal articles and 5 conference abstracts. The pooled data showed that PPI use in patients with cirrhosis and ascites was significantly associated with an increased risk of SBP [odds ratio (OR) = 2.17; 95% confidence interval (CI) = 1.46-3.23; P < 0.05; I2 = 85.6%] and overall risk of bacterial infection (OR = 1.98; 95%CI = 1.36-2.87; P < 0.05; I2 = 0). Subgroup analysis revealed that journal articles and studies reporting adjusted effect estimates demonstrated that PPI users had a significantly increased risk of SBP (OR = 2.13; 95%CI = 1.61-2.82; P < 0.05; I2 = 29.4%; and OR = 1.98; 95%CI = 1.42-2.77; P < 0.05; I2 = 67%, respectively). In conclusion, PPI use increased the risk of SBP and overall bacterial infection in patients with cirrhosis and ascites. PPIs should be administered after careful assessment of the indications in cirrhotic patients. Future well-designed prospective studies are warranted to clarify the dose relationships and to compare infection risks associated with different classes of PPIs. © FUNPEC-RP. Source

Wang H.,Shandong University | Li C.,Hospital and Institute of Hepatobiliary Surgery | Hu J.,Hospital and Institute of Hepatobiliary Surgery | Xu H.,Hospital and Institute of Hepatobiliary Surgery | And 9 more authors.

Background:There are few studies on the hemodynamic changes after orthotopic liver transplantation in rats. In this study, we aimed to evaluate the effect of different suprahepatic vena cava (SHVC) reconstruction methods on the hemodynamics of rats after liver transplantation.Materials and Methods:Three rat liver transplantation groups were created according to the SHVC reconstruction method: Kamada's two-cuff technique, a modified veno-lined stent technique, and Harihara's three-cuff technique. Ten rats of similar weight were grouped as the control. Anatomical, ultrasonic, and hemodynamic parameters and the microcirculation of the liver were measured after transplantation. The detailed operation time, operative complications, and animal survival were recorded.Results:All the recipients showed portal hypertension one month after transplantation. The portal hypertension in the group with the modified veno-lined stent technique was the most severe. The value measured with real-time elastography was significantly higher in the recipients using the modified veno-lined stent technique than in the other two groups (P<0.01). There was no difference in the graft microcirculation after reperfusion among the three groups. The survival rate of the three groups displayed no difference, but the modified veno-lined stent technique led to more venous complications than the other two techniques.Conclusions:The hemodynamics after liver transplantation in rats is determined not only by the cuff used for portal vein reconstruction but also by the cuff or stent for the SHVC. Some SHVC reconstruction methods, such as the modified veno-lined stent technique, Miyata's or Settaf's three-cuff techniques, significantly affect the hemodynamics. © 2013 Wang et al. Source

Wang H.,Shandong University | Wang H.,Hospital and Institute of Hepatobiliary Surgery | Li C.,Hospital and Institute of Hepatobiliary Surgery | Xu H.,Hospital and Institute of Hepatobiliary Surgery | And 6 more authors.
Cell Biochemistry and Biophysics

Rat orthotopic liver transplantation (ROLT) remains a technically demanding procedure, especially regarding the reconstruction of the suprahepatic vena cava (SHVC). In this study, a new microsuture technique was developed for anastomosis of the SHVC, and a special single-groove cuff and blade-cut stent were introduced. With these modified techniques, we aimed to make a precise anastomosis of the SHVC and to provide optimal cuffs and stents for the reconstruction of the veins and bile ducts. According to different microsuture techniques for the SHVC and different types of cuffs and stents, three ROLT groups were created to compare the operation times and prognoses. Sham operations were performed as controls in the fourth group. The time expenditures with each step were compared among the transplantation groups. Biochemical parameters were tested at the end of a 1-month observation period. The short- and long-term survival rates of the transplantation groups were recorded and compared. Our new microsuture technique was faster than the conventional continuous suture technique for SHVC anastomosis (P < 0.05). The use of a single-groove cuff for reconstruction of the portal vein and the infrahepatic vena cava shortened the anastomotic time (P < 0.05). The use of blade-cut stents resulted in fewer biliary complications and better survival over the short and long terms (P < 0.05). Our new microsuture technique and the single-groove cuffs proved to be a precise method for venous reconstruction which shortened the anhepatic time and the anastomotic time significantly. The blade-cut stents apparently reduced the incidence of biliary complications. In summary, with this precise microsuture technique and delicate cuffs and stents, excellent long-term survival can be achieved easily and stably for ROLT. © 2013 Springer Science+Business Media New York. Source

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