Comparative long-term evaluation of tacrolimus and cyclosporine in pediatric liver transplantation

Background. In this report, we compare the long-term outcome of pediatric liver transplantation (LTx) patients maintained with tacrolimus-based and with cyclosporine (CsA)-based immunosuppressive therapy. We examine long-term patient and graft survival, the incidence of rejection, and immunosuppression-related complications. Method. There were 233 consecutive primary LTx in children (ages <18 years) performed between October 1989 and December 1994 with tacrolimus-based immunosuppressive therapy (Group I). These were compared with 120 consecutive primary LTx performed with CsA-based immunosuppressive therapy between January 1988 and October 1989(Group II). Children in both groups were followed until July 1999. Mean follow-up was 91.41±17.7 months (range 55.6-117.8) for Group I, and 128±6.1 months (range 116.7-138.6) for Group II. Results. At 9 years of follow-up, actuarial patient and graft survival were significantly improved (patient survival 85.4% in Group I vs. 63.8% in Group II, P=0.0001; graft survival Group I 78.9% vs. 60.8% Group II, P=0.0003) and the rate of re -transplantation was significantly lower among patients in Group I (12% in Group I vs. 22.5% in Group II P=0.01). Children in Group I also experienced a significantly reduced incidence of acute rejection (0.97 per patient Group I vs. 1.5 per patient Group II P=0.002) and significantly less steroid resistant acute rejection episodes (3.1% in Group I vs. 8.6% in Group II P=0.0001). The mean steroid dose was significantly lower in Group I compared with Group II at all time points (P=0.0001) after LTx. Freedom from steroid was also significantly higher in Group I compared with Group H at all time points after LTx (ranging from 78% to 84% in Group I and 9% to 32% in Group H during a 1- to 7-year posttransplant period P=0.0001). The rate of hypertension was significantly lower in Group I than Group II (P=0.0001), and the severity of hypertension (need for more than one anti-hypertensive medication) was also significantly lower in Group I than Group II (P=0.0001). Although the rate of posttransplant lymphoproliferative disorder (PTLD) was not significantly different (13.7% Group I vs.8.3% Group II, P=0.13), the survival after PTLD was significantly better for Group I at 81.2% than for Group II at 50% after 5 years (P=0.034). Conclusion. The results suggest that tacrolimus-based therapy provides significant long-term benefit to pediatric LTx patients, evidenced by significantly improved patient and graft survival, reduced rate of rejection, and hypertension with lower steroid doses

Combined liver-kidney transplantation: Analysis of patients with preformed lymphocytotoxic antibody

In this report, we address combined liver-kidney transplantation, with particular attention to the apparent phenomenon of protection of kidney allografts to antibody mediated destruction by liver allografts. Four patients were found to have positive crossmatch before the liver phase of the combined transplant (pre-OT/KT samples). These positive crossmatches were due entirely to anti-HLA class I antibodies, as demonstrated by their removal by immunoabsorption on pololed platelets. In three of these patients, post-OT/pre-KT samples showed a conversion to a negative crossmatch (in the fourth patient this was not done). A kidney allograft, harveted from the same donor, was then placed into the recipient, and in patients no. 3, 7, and 12, good initial function was noted. In one of these patients was there evidence of hyperacute rejection. Post-OT/KT samples were collected in patients no. 3, 7, and 8, and then analyzed for the reappearance of donor specific lymphocytotoxic antibodies in the posttransplant period (data on patient no. 12 was not available at time of preparation). Lymphocytotoxic antibodies with donor specificity could not be detected in any of the samples during the first week posttransplant. The decrease in %PRA and conversion of a positive to negative crossmatch following liver transplantation was correlated to the HLA specificty of the antibody found in the pretransplant serum and the HLA type of the tranplanted organs. In the two instances where an HLA specificity could be determined by panel analysis, transplantation with donor organs bearing these HLA specificities led to a specific disppearance of these antibodies during the postransplant phase

Dynamical regimes and hydrodynamic lift of viscous vesicles under shear

The dynamics of two-dimensional viscous vesicles in shear flow, with different fluid viscosities $\eta_{\rm in}$ and $\eta_{\rm out}$ inside and outside, respectively, is studied using mesoscale simulation techniques. Besides the well-known tank-treading and tumbling motions, an oscillatory swinging motion is observed in the simulations for large shear rate. The existence of this swinging motion requires the excitation of higher-order undulation modes (beyond elliptical deformations) in two dimensions. Keller-Skalak theory is extended to deformable two-dimensional vesicles, such that a dynamical phase diagram can be predicted for the reduced shear rate and the viscosity contrast $\eta_{\rm in}/\eta_{\rm out}$. The simulation results are found to be in good agreement with the theoretical predictions, when thermal fluctuations are incorporated in the theory. Moreover, the hydrodynamic lift force, acting on vesicles under shear close to a wall, is determined from simulations for various viscosity contrasts. For comparison, the lift force is calculated numerically in the absence of thermal fluctuations using the boundary-integral method for equal inside and outside viscosities. Both methods show that the dependence of the lift force on the distance $y_{\rm {cm}}$ of the vesicle center of mass from the wall is well described by an effective power law $y_{\rm {cm}}^{-2}$ for intermediate distances $0.8 R_{\rm p} \lesssim y_{\rm {cm}} \lesssim 3 R_{\rm p}$ with vesicle radius $R_{\rm p}$. The boundary-integral calculation indicates that the lift force decays asymptotically as $1/[y_{\rm {cm}}\ln(y_{\rm {cm}})]$ far from the wall.Comment: 13 pages, 13 figure

Suicide rate in the dental profession: Fact or myth and coping strategies

This article summarizes relevant scientific data on the alleged high suicide rate among dentists as compared to other health care professions. Potential contributing risk factors for the dental profession are identified. In addition, a brief review is provided for major depressive disorder, a contributor to increased suicide, along with its symptoms, underlying theory, drug treatment and coping skills to combat this disorder.