Tacrolimus Combined with Two Different Dosages of Sirolimus in Kidney Transplantation: Results of a Multicenter Study

Tacrolimus combined with mycophenolate mofetil (MMF) is an effective regimen in kidney transplantation. This study compared the efficacy of combining tacrolimus and two different dosages of sirolimus with an established tacrolimus-MMF regimen. Each day in addition to tacrolimus, 325 patients received 2 mg sirolimus (TAC-SRL2 mg), 325 patients received 0.5 mg sirolimus (TAC-SRL0.5 mg) and 327 patients 1 g MMF (TAC-MMF). The initial tacrolimus dose was 0.2 mg/kg/day. Sirolimus patients received loading doses of 6 or 1.5 mg, and daily doses of 2 or 0.5 mg thereafter. Steroid administration was identical for all groups. The incidence of biopsy-proven acute rejection was lower in the TAC-SRL2 mg group (15.7%) compared with the TAC-SRL0.5 mg (25.2%, p = 0.003) and the TAC-MMF groups (22.3%, p = 0.036). Six-month graft survival was 91.0% (TAC-SRL2 mg), 92.6% (TAC-SRL0.5 mg) and 92.4% (TAC-MMF); the respective values for patient survival were 98.1%, 97.8% and 97.9%. Thirty-four patients (10.5%), 19 patients (5.8%) and 16 patients (4.9%) in the TAC-SRL2 mg, TAC-SRL0.5 mg and TAC-MMF groups, respectively, discontinued the study because of adverse events. Hyperlipemia was reported more often in the TAC-SRL2 mg group (24.0%) compared with 19.4% (TAC-SRL0.5 mg) and 11.0% (TAC-MMF; p < 0.05). Combining 2 mg sirolimus/day with tacrolimus results in lower rates of acute rejection, but a higher incidence of adverse events.     

Immunologic and pharmacologic concepts of monoclonal antibodies

While monoclonal antibodies have solved many of the difficulties of using immunologic reagents for radioimmunodiagnosis and therapy, in the 13 years since their introduction a number of persistent problems remain, most notably a low yield of antibody-producing cells from the fusion process, difficulty in obtaining high-affinity antibodies, and the potential immunogenicity of murine immunoglobulins (Igs). Several solutions are under development, including fusion techniques that enrich for cells producing desired antibodies, production of human-mouse chimeric antibodies by recombinant DNA technology, and the generation of human monoclonal antibodies by promising new approaches. Until these upcoming methodologies are established, and to better direct their development and application, a sound understanding of the pharmacology of presently available native and modified monoclonal antibodies is crucial. Although much has been already determined in this area, a great deal of further clarification remains necessary.     

Individualized Mycophenolate Mofetil Dosing Based on Drug Exposure Significantly Improves Patient Outcomes After Renal Transplantation

Efficacy and safety of mycophenolate mofetil (MMF) may be optimized with individualized doses based on therapeutic monitoring of its active metabolite, mycophenolic acid (MPA). In this 12-month study, 137 renal allograft recipients from 11 French centers receiving basiliximab, cyclosporine A, MMF and corticosteroids were randomized to receive either concentration-controlled doses or fixed-dose MMF. A novel Bayesian estimator of MPA AUC based on three-point sampling was used to individualize doses on posttransplant days 7 and 14 and months 1, 3 and 6. The primary endpoint was treatment failure (death, graft loss, acute rejection and MMF discontinuation). Data from 65 patients/group were analyzed. At month 12, the concentration-controlled group had fewer treatment failures (p = 0.03) and acute rejection episodes (p = 0.01) with no differences in adverse event frequency. The MMF dose was higher in the concentration-controlled group at day 14 (p < 0.0001), month 1 (p < 0.0001) and month 3 (p < 0.01), as were median AUCs on day 14 (33.7 vs. 27.1 mg*h/L; p = 0.0001) and at month 1 (45.0 vs. 30.9 mg*h/L; p < 0.0001). Therapeutic MPA monitoring using a limited sampling strategy can reduce the risk of treatment failure and acute rejection in renal allograft recipients 12 months posttransplant with no increase in adverse events.     

Review of facial muscle spasms

Facial muscle spasms, which are rare in adults, present a particularly difficult entity for the optometrist to recognise. The condition may not even manifest itself at an eye examination and the optometrist may have to rely on subjective symptoms to assist in the recognition of the condition. It is important to diagnose the condition correctly as specific and effective treatment is available.     

Evaluation of the debonding characteristics of 2 ceramic brackets: an in vitro study.

The objectives of this study were to evaluate and compare the shear bond strengths and bond failure locations of 2 currently available orthodontic ceramic brackets. Forty polycrystalline ceramic brackets (Clarity, 3M Unitek, Monrovia, Calif) and 40 monocrystalline ceramic brackets (Inspire, Ormco, Orange, Calif) were bonded to 80 extracted premolars with the same bonding system. All bonded specimens were placed in distilled water for 42 hours at 37 degrees C followed by thermal cycling for 700 complete cycles. Forty ceramic brackets, 20 of each type, were tested on a universal testing machine to determine the shear force levels required to debond them. Forty ceramic brackets were removed with the debonding pliers recommended by the manufacturers. All teeth were examined under an optical microscope, and the adhesive remnant index was used to assess the bond failure locations. The mean shear bond strength of the Clarity brackets was 21.67 +/- 5.19 MPa, and the mean shear bond strength of the Inspire brackets was 20.32 +/- 8 MPa. The mean shear bond strengths of both brackets were higher than those considered clinically optimal. Most of the brackets (85% of Clarity and 75% of Inspire) tested on the machine failed at the bracket-adhesive interface. One premolar bonded with an Inspire bracket had enamel fracture upon debonding. Most of the brackets (90% of Clarity and 95% of Inspire) debonded with pliers failed at the bracket-adhesive interface. No enamel damage was evident in any specimen when the brackets were removed with the appropriate pliers. The results indicate that the safest way to remove ceramic brackets with respect to reducing the chance of enamel damage is to use the debonding technique specifically designed for each.     

Graduate Education in the Field of Substance Abuse

Abstract: Twenty-six part-time students from a variety of professional backgrounds are enrolled in the first year of a Graduate Diploma in Social Science (Drug Dependence) at the Phillip Institute of Technology in Victoria. The course is conducted under the auspices of the School of Social Work and commenced in 1984. It is argued that the graduates from this unique course could play a key role in providing personnel to fill positions in the areas of clinical work, staff development, drug education, programme development and management and research.