De novo Prograf versus de novo Advagraf: are trough level profile curves similar?

BACKGROUND: According to the clinical trials, Advagraf (ADV) has efficacy and safety profile similar to Prograf (PROG). The aim of this study was to compare the graft functions, dosages, and tacrolimus (TAC) trough level profile curves of patients on de novo PROG and ADV therapy. METHODS: The ADV group included 39 de novo renal cases who had received initial immunosuppression (IS) with once-daily TAC (1 × 0.2 mg/kg from day1 after transplantation). We compared them with a PROG group of 38 transplant patients who received equivalent IS with twice-daily TAC (2 × 0.1 mg/kg from day1). In both groups, the IS was combined with antimetabolites and steroids. The mean follow-up time was similar (13.5 ± 7 days) in both groups after renal transplantation until the emission of the patients from our clinic. RESULTS: TAC mean total daily dose was reduced and whole-blood trough levels decreased over the time in early postoperative days. Only on day 3 and day 4 after transplant, a significant higher adjustment in the ADV dosage was necessary to achieve sufficient TAC trough levels. The average TAC trough level profile curves were similar in PROG and ADV groups, but the individual curves were very different. Mainly in patients on ADV therapy, the initial concentrations were often >30 ng/mL, and in some cases on the 9th posttransplant day decreased to <5 ng/mL, then slowly increased into the required therapeutic range. CONCLUSIONS: The results demonstrate that patients after renal transplantation can be safely treated de novo with ADV. Setting the required therapeutic TAC blood levels may require more attention to avoid the "fluctuations" of trough level profile curve during the early postoperative period. Our data suggest that dose adjustment of ADV can be carried out more carefully compared with PROG on the basis of clinical symptoms and the value of TAC blood levels to avoid acute rejection and toxicity.

Endogenous thrombin potential and examination of a further 31 analytes in liver transplant candidates.

BACKGROUND: To predict the change in patient status and differentation of the basic diseases, endogenous thrombin potential (ETP), clinical chemistry, and coagulation variables were measured in liver transplant-listed patients with different etiologies. METHODS: Differences in values of ETP and analytes of 30 control persons and 164 cirrhotic patients were examined by means of binary logistic regression. The relationship between the analytes and ETP parameters were analyzed by means of Spearman correlation. The different etiologies of cirrhosises were studied by factor and discriminant analyses. Binary logistic regression was applied to forecast changes in clinical status. Survival analysis was carried out with the appropriate variable. RESULTS: International Normalized Ratio and activated partial thromboplastin time values were higher, whereas the area-under-the-curve values were lower in cirrhosis than in healthy subjects. A strong relationship was found only between the peak height and the anti-thrombin III (ATIII) values. In the factor analysis, 3 factors were found, which explained 81.6% of the total variance. Combination of aspartate aminotransferase and ATIII mostly separated the basic disease groups from each other in the discriminant analysis. From 35 variables, the lactate dehydrogenase (LDH) and ATIII have been suited for predicting the change in patient status. Eighty percent of patients with low ATIII and high LDH levels had deterioration of their clinical status. CONCLUSIONS: Our study demonstrated that the ETP parameters did not provide additional information compared with "conventional" coagulation tests in cirrhosis. On the basis of our study, LDH and ATIII appear to be promising analytes to assess the clinical status of patients with cirrhosis. In our opinion, the classification system of liver transplant-listed patients can be improved with their use.

Significance of mycophenolate monitoring in liver transplant recipients: toward the cut-off level.

Mycophenolate mofetil blocks the "de novo" -purine synthesis to reduce the incidence and severity of acute rejection episodes. There has been an increased interest in utility of monitoring mycophenolic acid (MPA) levels, however currently the MPA monitoring is not part of the protocol following liver transplantation. We assessed whether trough MPA monitoring could be advisable in liver transplant patients or not. For this reason MPA levels of 56 liver transplants were measured on 3, 5, 10, 14, 21, 30, 60, and 180 posttransplant days. The optimal cut-off of MPA level (≥1.73 mg/L) for all (56) and ≥1.34 mg/L for ciclosporin-treated- and ≥1.98 mg/L for the tacrolimus-treated transplants were calculated by statistical analysis to reduce the incidence of acute rejection. MPA concentrations of 3 days period before the day of clinical diagnosis acute rejection were well below the cut-off value. Only 3 (16%) out 19 patients with acute rejection had higher MPA levels than the cut-off value on the day of diagnosis of acute rejection. In conclusion, our data suggests that MPA predose level monitoring, especially in the early "filling phase" after transplantation, is applicable in liver allograft recipients given adjunctive MMF, protecting them from the ineffective immunosuppression.

Small difference in international normalized ratio may yield a significant impact on prioritizing patients listed for liver transplantation.

Priority for liver transplantation is currently based on the Model for End-stage Liver Disease (MELD) score. The aim of our study was to assess in detail the contribution of international normalized ratio (INR) differences for MELD scores because of interlaboratory variability. The samples from 92 cirrhotic patients were measured on different systems combining three coagulometers and three thromboplastin products to determine variations in INR and MELD score. The INR differences among the first four systems varied between 0 and 0.2, resulting in MELD differences of 0 to 2. The MELD scores of 92 patients changed only among 10 possible integers so that normally 2 to 10 patients shared the same MELD value. In some cases, one MELD score difference resulted in a 10 superpositioning on the waiting list. Including one more system (mechanical vs optical) into our investigations achieved a five MELD difference. Supposing an extreme situation where one patient competes with his or her lowest, all the other with their highest possible score (and visa versa), the difference may be even 20 positions, overturning the complete waiting list. In conclusion substantial interlaboratory differences in MELD score have profound clinical consequences.

Teleoncology in the Department of Defense: a tale of two systems.

Two telemedicine networks were developed for the purpose of conducting multidisciplinary oncology ("teleoncology") conferences. The infrastructure of each system differed: one system was Internet-based; the other was delivered via Integrated Services Digital Network (ISDN) lines. The purpose of this study was to describe the infrastructure and cost, consultative process, technical aspects, and conference format of the two teleoncology programs. The two systems' technical aspects, participant satisfaction with the systems, and conference participation were compared qualitatively. Assessment of the technical aspects of the systems suggested that each had distinct advantages. Survey results indicated that provider satisfaction with the technical and logistical aspects of each type of teleoncology conference was high. The present study may prove helpful for individuals who are considering implementing their own teleoncology programs.

Effect of metal ions on the aspartate transaminase (E.C.2.6.1.1.) activity in tobacco tissue culture.

Aspartate transaminase enzyme was prepared from tobacco tissue cultures. Effect of 13 different metal ions on the enzyme activity was preliminarily studied. The enzyme activity was inhibited by five ions, namely Cd2+, Hg2+, Zn2+, Cu2+, and Ag+. None of the ions investigated enhanced the activity. Fe2+ caused an apparent activity increase in the reaction mixture. Pyridoxal-phosphate enhanced this effect of the Fe2+.

Some further data on the effects of two organophosphate pesticides on the oxidative metabolism in the liver.

Sumithion is the most active cholinesterase inhibitor. The cholinesterase inhibiting action of the organophosphates (OPs) is better compensated by vitamin E in normal animals, but by vitamin A in vitamin A-deficient animals. The lipid peroxidation (LP) is enhanced by the antioxidant vitamins in the liver of normal rats; although they decrease it in the liver of vitamin A-deficient animals, in no case do they prevent the LP-enhancing effect of the OPs examined. The OPs examined inhibit protein synthesis in the liver of vitamin A-deficient animals.