Tacrolimus: A Potential New Treatment for Autoimmune Chronic Active Hepatitis: Results of an Open‐Label Preliminary Trial

Autoimmune chronic active hepatitis (CAH‐A) is a chronic liver disease of unknown etiology that is believed to have an autoimmune pathogenesis. The disease is slowly progressive until hepatic failure and portal hypertension develop and either death or liver transplantation occur. Currently, the only widely recognized therapy is the administration of glucocorticoids, which have both anti‐inflammatory and immunosuppressive actions. Many patients cannot tolerate such therapy because of the psychiatric, osteoporotic, and weight‐enhancing actions of steroids. Tacrolimus (FK 506) is a new macrolide antibiotic that has an immunosuppressive activity that is estimated to be 10–200 times greater than that of cyclosporine. Because of its greater immunosuppressive activity, we have used it in the treatment of 21 patients with autoimmune chronic active hepatitis. Before each subject was treated, a liver biopsy and a panel of hematological, serological, and biochemical parameters were assessed. The Tacrolimus was administered orally at 12‐h intervals, and the dose was controlled by monitoring plasma FK trough levels. After 3 months of therapy at an oral dose of 3 mg twice a day, having achieved a median blood level of 0.5 ng/ml, the serum ALT level was reduced by 80%, and the AST level was reduced by 70%. Modest change in the white blood cell count and platelet count were noted. The median BUN level increased from a level of 12 to 18 mg/dl, and the serum creatinine increased from 0.9 to 1.3 mg/dl. These preliminary data demonstrate that: 1) Tacrolimus can be used to successfully treat CAH‐A; 2) the response of CAH‐A to Tacrolimus treatment is rapid and sustained; and 3) a minor increase in the serum BUN and creatinine levels occurs as a consequence of Tacrolimus treatment. It is anticipated that with continued treatment for periods of 1–2 yr, the natural history of CAH‐A will be changed such that hepatic failure and the requirement for liver transplantation may be averted. Copyright © 1995, Wiley Blackwell. All rights reserve

Tacrolimus (FK 506), a Treatment for Primary Sclerosing Cholangitis: Results of an Open‐Label Preliminary Trial

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the liver that is characterized by progressive cholestasis and the development of secondary biliary cirrhosis. There is no widely recognized therapy for this disease, although anti‐inflammatory agents (steroids), immunosuppressive agents (methotrexate), anti‐fihrotics (colchicine), and choleretic agents (ursodeoxycholic acid) have been used in various small series. In the present study, Tacrolimus (FK 506), a new and powerful immunosuppressive macrolide antibiotic, has been used to treat 10 patients with PSC. Each subject had a liver biopsy, ERCP with visualization of the intra‐and extrahepatic biliary tree, and a panel of hcmatological, serological, and biochemical laboratory tests before the initiation of the FK 506 therapy. The FK 506 was administered orally at 12‐h intervals and was monitored by serial plasma FK 506 trough levels. After 360 days of treatment, the median serum bilirubin level was reduced by 75%, and the serum alkaline phosphatase was reduced by 70%. Moreover, the serum ALT and AST levels were reduced by 80 and 86%, respectively. No change in the serum level of BUN and creatinine levels occurred as a consequence of the FK 506 treatment. These data demonstrate that: 1) FK 506 can be used to treat PSC; 2) the response to FK 506 by patients with PSC is rapid; and, 3) no adverse effect on the serum BUN and creatinine levels was observed. It is anticipated that FK 506 will become an important agent for the treatment of patients with PSC because of its powerful immunosuppressive activity. Copyright © 1995, Wiley Blackwell. All rights reserve

Patterns and outcomes of traumatic pancreatic injuries: A retrospective review from a large multi-institutional healthcare system

© 2017, © The Author(s) 2017. Introduction: Traumatic pancreatic injuries are rare, and morbidity and mortality information are often conflicting. To determine the frequency and outcomes of patients presenting with trauma to the pancreas, we reviewed data from a large multi-institutional healthcare system for mechanism of injury, intervention, subsequent complications, in-hospital morbidity rates, and mortality. Methods: We performed a retrospective analysis of records of all pancreatic injury cases seen at four healthcare centers from 1990 to 2014. Descriptive measures are presented for continuous and categorical data. Mortality rates were obtained using the publicly accessible Social Security Death Master File. Results: Of 69 patients with pancreatic injuries, median age was 24 years (range 1–88). Mechanisms of injury were blunt in 87% and penetrating in 11.8%. The median injury grade was 1. Most injuries involved the pancreatic head (24.6%). Median Injury Severity Score at presentation was 9. Thirty-seven (53.6%) patients required surgery. Twenty-five patients (36.2%) required total parenteral nutrition, 34 patients (49.3%) developed intra-abdominal fluid collections, 24 patients (34.8%) developed acute pancreatitis, and three (4.4%) developed endocrine insufficiency requiring insulin. Ten (14.5%) patients died. There were four (5.8%) readmissions and one re-operation (1.4%) within 30 days of discharge. Conclusion: Traumatic pancreatic injuries occur most frequently in young healthy males with little or no comorbidities, and are generally associated with other acute injuries. Contrary to past reports, our results revealed a low mortality rate but significant morbidity, with the most common complications being intra-abdominal fluid collections, acute pancreatitis, and a need for total parenteral nutrition

Transport properties and ionic association in pure imidazolium-based ionic liquids as a function of temperature.

International audienceIn this work, three transport properties (viscosity, diffusion coefficient, and electrical conductivity) were experimentally determined from 298 K to 343 K in four pure imidazolium-based ionic liquids with two anions and different alkyl chain lengths on the cation: 1-ethyl-3-methylimidazolium methylsulfate, [C1C2Im][CH3SO4], 1-butyl-3-methylimidazolium methylsulfate, [C1C4Im][CH3SO4], 1-ethyl-3-methylimidazolium triflate, [C1C2Im][CF3SO3] and 1-butyl-3-methylimidazolium triflate, [C1C4Im][CF3SO3]. Higher viscosities, lower diffusion coefficients, and electrical conductivities were measured when the alkyl chain length was increased or a sulfate anion was present. From these experimental data, the ionic association was discussed using the qualitative approach of the Walden plots and the quantitative ionicity concept. An increased ionic association was observed when the alkyl chain length on the cation was increased, while comparable ionicities were measured for both anions. Finally, the applicability of the Stokes–Einstein equation (relation between the diffusion coefficient and the viscosity) was also discussed in these systems