The photodynamic inactivation of Staphylococcus aureus in water using visible light with a new expanded porphyrin.

In this work, the results of the application of organic expanded porphyrins in the disinfection of water by the photodynamic inactivation (PDI) technique are presented. The photoinactivation properties of a novel, expanded porphyrin, namely 20-(4-carboxyphenyl)-2,13-dimethyl-3,12-diethyl-(22π) pentaphyrin (PCCox), were tested in the disinfection of water using Staphylococcus aureus as a Gram-positive bacteria model. The data showed that PCCox was effective against S. aureus bacteria at nanomolar concentrations. The variation with irradiation time and concentration was studied using both a multi-LED monochromatic light (λ = 470 nm) and an incandescent light bulb with a wide emission spectrum. A PCCox dosage of 5 µM was sufficient to achieve a 99.997% abatement of S. aureus within 1 h of 40 W/m(2) irradiation with monochromatic light (λ = 470 nm), whereas under the same conditions using irradiation with white light, the abatement was 99.9997%.

Selective bilirubin removal by plasma treatment with Plasorba BR-350 for early cholestatic graft dysfunction.

Early cholestatic graft dysfunction is a frequent cause of morbidity after orthotopic liver transplantation (OLT). We analyze the role of selective bilirubin plasma absorption (PAP) using Plasorba BR-350 in 4 OLT patients who had experienced early severe cholestatic graft dysfunction within 15 days after transplantation. Patients were treated with 3 consecutive cycles of PAP with Plasorba BR-350. The median amount of plasma treated was 7500 mL. Median treatment duration was 231 minutes. The average plasma bilirubin level was 37 +/- 1 mg/dL before PAP and decreased to 15 +/- 0.2 mg/dL at the end of the third cycle of PAP; 3 of 4 cases had progressive bilirubin normalization after PAP. The average amount of bilirubin removed from the plasma of the patients during each PAP treatment was 143 +/- 24 mg. At the beginning of each cycle of PAP, the Plasorba BR-350 was able to remove >90% of the total plasma bilirubin, a percentage that decreased to 60%, 50%, and 40% after 2 L, 4 L, and 7 L of plasma were treated, respectively. Liver biopsies performed after the third treatment showed reduced cholestasis when compared with the pretreatment biopsy specimen. The preliminary data suggested that PAP selective for bilirubin removal may not only reduce the bilirubin level, but may also improve the histological pattern of the graft in terms of reduced cholestatic signs.

Comparison of two techniques of arterial anastomosis during adult cadaveric liver transplantation.

Arterial complications are a major source of morbidity and mortality after orthotopic liver transplantation (OLT). The incidence of hepatic artery thrombosis (HAT) ranges from 1.6% to 8%, with a mortality rate that ranges from 11% to 35%. We have described herein a technique of arterial anastomosis aiming to perform the anastomosis as straight as possible to avoid any kinking, redundancy, or malposition of the artery when the liver is released in its final position. We compared this technique with the traditional technique of arterial anastomosis using an aortic Carrel patch, namely, 198 OLT (group A) with the traditional technique and 117 OLT (group B) with the modified technique. An aorto-hepatic bypass was necessary in 25% of the cases in group A and in 21% of the cases in group B (P = .33). Vascular anomalies were present in 20% of cases in group A and in 27.5% in group B (P = .14). Fourteen cases (7%) of HAT developed in group A versus 0 cases in group B (P = .003). In group B, we experienced 2 (1.7%) late arterial stenoses that were successfully treated using percutaneous transluminal angioplasty. The 14 cases of HAT occurring in group A were successfully managed using immediate surgical revascularization with graft salvage in 6 cases (43%), whereas the remaining 8 cases needed urgent retransplantation. We suggest that a technique of arterial anastomosis aimed at avoiding kinking, redundancy, or malposition of the artery may be a viable option to reduce the risk of HAT after OLT.

Long-term outcomes of orthotopic liver transplantation in human immunodeficiency virus-infected patients and comparison with human immunodeficiency virus-negative cases.

Human immunodeficiency virus (HIV) positivity is no longer a contraindication for orthotopic liver transplantation (OLT) due to the efficacy of antiretroviral therapy. The aim of this study was to compare OLT among HIV-positive and HIV-negative cohorts; the results were also stratified for hepatitis C virus (HCV) coinfection. Between 2004 and 2009, all HIV-infected patients undergoing OLT from heart-beating deceased donors (n=27) were compared with an HIV-negative cohort (n = 27). The pure HCV infection rate was similar between HIV-positive and HIV-negative subjects (63% each). HIV-positive recipients were younger (P=.013). The CD4 count for HIV-positive subjects was 376 ± 156 at transplantation. The mean model for end-stage liver disease (MELD) score at transplantation was 15 ± 7 in both groups (P=.92). No differences were observed for donor age (P=.72) or time on the waiting list (P=.56). The median follow-up was 26 (range, 1-64) and 27 months (range, 1-48) for HIV and non-HIV recipients, respectively (P=.85). The estimated 1-, 3-, and 5-year patient and graft survival rates were 88%, 83%, and 83% versus 100%, 73%, and 73% (P=.95), and 92%, 87%, and 87% versus 95%, 88%, and 88% (P=.59) for HIV and non-HIV cases, respectively. HIV/HCV-coinfected patients were younger, namely 47 (range, 40-53) versus 52 years (range, 37-68; P=.003), and displayed lower MELD scores at transplantation compared with HCV-mono-infected patients 10 (range, 7-19) versus 17 (range, 8-30) (P=.008). For HIV/HCV-coinfected and HCV-mono-infected cases the estimated 1-, 3-, and 5-year patients and graft survival rates were respectively 93%, 76%, and 76% versus 100%, 70%, and 60% (P=.99) and 93%, 84%, and 84% versus 100%, 70%, and 60% (P=.64), respectively. No difference was observed in the histological severity of HCV recurrence. In conclusion, under specific, well-determined conditions, OLT can be a safe, efficacious procedure in HIV patients.

Safety of conversion from twice-daily tacrolimus (Prograf) to once-daily prolonged-release tacrolimus (Advagraf) in stable liver transplant recipients.

Nonadherence to immunosuppressive regimens among solid organ transplantation to range has been estimated from 15% to 55%. This problem has been identified as a leading cause of preventable graft loss. Tacrolimus once daily Advagraf has been developed to provide a more convenient dosing regimen to improve adherence. The aim of this study was to analyze the safety of a 1:1 dose conversion from twice-daily tacrolimus (Prograf) to Advagraf in 36 stable liver transplant recipients. The tacrolimus whole blood trough level at T0 was 6.7 +/- 2.9 ng/mL with a daily dose of 3.7 +/- 1.8 mg. The mean tacrolimus blood trough levels at T1 (7 days) and T2 (14 days) were 5.8 +/- 2.5 and 5.8 +/- 1.8 ng/mL with mean daily doses of 3.9 +/- 1.9 and 4.1 +/- 1.8 mg, respectively. There was no significant difference between T0, T1, and T2, either for tacrolimus blood trough levels or for tacrolimus daily dosages. Liver and renal function tests remained stable; no episodes of acute rejection were encountered after the conversion. A switching policy using a dose ratio of 1:1 from twice-daily tacrolimus to once-daily prolonged-release tacrolimus was safely applied to stable liver transplant recipients.

Steatosis of the graft is a risk factor for posttransplantation biliary complications.

BACKGROUND: Despite recent advances in organ preservation, immunosuppression, and surgical techniques, the biliary tree is still considered the Achilles' heel of liver transplantation. The aim of this study was to retrospectively analyze the incidence of biliary complications and identify predisposing risk factors. METHODS: From January 2004 to December 2007, 117 consecutive deceased donor liver transplantations were retrospectively analyzed for the development of biliary complications by review of medical records. Patients were divided into group 1 with biliary complications (n = 43) and group 2 without biliary complications (n = 74). RESULTS: The overall biliary complication rate was 36.8%; leakage 6% and stricture 30.8%. Univariate analysis indicated that significant predictors of biliary complications were the time interval between portal and arterial reperfusion (P = .037) and macrovacuolar steatosis of the graft >25% (P = .004). A stepwise logistic regression model demonstrated that >25% macrosteatosis of the graft was the only independent risk factor predicting biliary complications after liver transplantation (odds ratio [OR] = 5.21; CI 95% [1.79-15.15]; P = .002). No differences were noted in patient or graft survival between the 2 groups. CONCLUSION: Transplantation of a liver with >25% steatosis was a risk factor for the development of a biliary complication.

Thermodynamic stability and kinetic inertness of MS-325, a new blood pool agent for magnetic resonance imaging.

Stability constants were measured for complexes formed between a modified DTPA ligand and the metal ions Gd(III), Eu(III), Fe(III), Ca(II), Cu(II), and Zn(II) at 25 degrees C in 0.1 M NaClO4. The gadolinium complex of this ligand is MS-325, a novel blood pool contrast agent for magnetic resonance imaging currently undergoing clinical trials. Stability constants were determined by 4 different methods: direct pH titration, pH titration with competition by EDTA, competition with DTPA using an HPLC-MS detection system, and competition with Eu(III) by monitoring equilibrium by luminescence spectroscopy. The 1:1 stability constants, log beta101, are the following: Gd, 22.06 (23.2 in 0.1 M Me4NCl); Eu, 22.21; Fe, 26.66; Ca, 10.45; Cu, 21.3; Zn, 17.82. The exchange kinetics of the Gd complex, MS-325, with the radioactive tracer (152,154)Eu were studied at 25 degrees C in 0.1 M NaClO4. The exchange reaction has acid-dependent and acid-independent terms. The rate expression is given by the following: R = k(a)[GdL][H]2 + kb[GdL][Gd][H] + kc[GdL][Gd]. The rate constants were determined to be the following: k(a) = 1.84 x 10(6) M(-2) x min(-1), kb = 2.87 x 10(3) M(-2) x min(-1), kc = 3.72 x 10(-3) M(-1) x min(-1). MS-325 is 2-3 times more stable than GdDTPA at pH 7.4 and is 10-100 times more kinetically inert.