Improved graft survival for flow cytometry and antihuman globulin crossmatch-negative retransplant recipients

We compared our standard NIH (extended incubation) crossmatch (XM) with antihuman globulin (AHG) and flow cytometry XMs and correlated the results with rejection episodes and graft survivals. For 89 CsA-Pred, primary renal allograft recipients, AHG and/or FCXM results did not improve on the NIH-XM-negative (NEG) graft survival results, whether testing pretransplant or historical (Hx) sera. Similarly, there was no association of a positive (POS) AHG or FCXM with increased rejection episodes in these primary recipients. However, for retransplant (Re-Tx) recipients a neg AHG or FCXM did discriminate fewer rejections and an improved graft survival compared with the NIH-XM-neg. results. The overall one-year graft survival for the 47 Re-Tx recipients studied herein was 66% (based on a neg pre-Tx NIH-XM). Pre-Tx AHG-NEG, Re-Tx recipients displayed an improved graft survival compared with NIH-XM NEG recipients (77% vs. 66%, P less than 0.05) and with AHG-POS recipients (77% vs. 47%, P less than 0.05). Similarly, pre-Tx, FCXM-NEG, Re-Tx recipients displayed improved graft survivals compared with NIH-XM-NEG recipients (83% vs. 66%, P less than 0.05) and FCXM-POS recipients (83% vs. 48%, P less than 0.05). Re-Tx recipients displaying a POS AHG and/or FCXM experienced a significantly greater number of rejections than NEG-XM recipients (P less than 0.05, respectively). The AHG and FCXM results correlated with rejections and graft survivals whether testing pre-Tx or Hx high-PRA sera. Re-Tx recipients who were AHG-XM-NEG but FCXM-POS, experienced more rejection episodes than recipients who displayed a negative XM reactivity for both AHG and FCXM (P less than 0.02), but with no resulting differences in graft survival. HLA matching, pre-Tx blood transfusions and PRA did not impact on these crossmatch and graft survival results. Use of AHG and/or FCXMs for Re-Tx, but not primary, recipients should help to improve graft survival for these high-risk recipients.     

Lyme arthritis

Evanescent arthralgias and myalgias are common early symptoms of Lyme disease. Transient, intermittent episodes of monoarticular, oligoarticular, or sometimes migratory polyarticular arthritis, lasting weeks to months, with disease-free intervals, are frequently observed in untreated patients with erythema chronicum migrans. A minority of patients develop chronic joint involvement, most commonly affecting the knee. Antibiotic therapy given during erythema chronicum migrans is often protective with regard to late joint manifestations. In chronic Lyme arthritis, however, the response to antibiotics is variable.     

The health of children of low-income families.

Childhood poverty is common in Canada: 1,114,000 children under 16 years of age live below the poverty line. The incidence is highest among children of single mothers, unemployed parents, Canadian native peoples and recent immigrants, particularly refugees. Compared with the national average, the infant mortality rate is twice as high, deaths from infectious diseases are 2.5 times more common and accidental deaths are twice as common among children of low-income families. Other problems associated with poverty are iron deficiency anemia, dental caries, chronic ear infections, mental retardation, learning disabilities, poor school performance and increased suicide rates. Health care professionals can help address the poor physical and mental health associated with poverty in children by promoting a broad range of public policies.     

A pharmacokinetic comparison of the corn oil versus microemulsion gelcap formulation of cyclosporin used de novo after renal transplantation

The initial poor absorption of the corn oil-based, gel capsule oral formulation of cyclosporin (CyA) greatly limits its use for inception of immunosuppressive therapy. Insufficient drug concentrations during the early post-transplant period predispose to renal allograft rejection. The present study served to compare the time required to achieve therapeutic CyA concentrations after de novo administration of the corn oil-based gel capsule (CyA-GC; n = 11) versus the microemulsion (CyA-ME; n = 11) formulation of CyA. During the 1st month after renal transplantation, patients underwent serial pharmacokinetic profiling from which we obtained observed and dose-corrected values of several parameters. Although patients in neither the CyA-GC nor the CyA-ME group adequately absorbed the drug during days 0–2, from day 3 to 4 patients in the CyA-ME group showed significantly greater absorption than those in the CyA-GC group (P = 0.041). Patients in the CyA-ME group reached the 1st month target average concentration (C_av) values ( ≥ 550 ng/ml) earlier than those in the CyA-GC group and required significantly lower daily CyA doses (P = 0.018). We conclude that therapeutic CyA levels can be achieved more rapidly and with lower doses of the drug after de novo administration of CyA-ME than with CyA-GC. Received: 13 September 1996 Accepted: 7 January 1997     

Nonselective measurement of cyclosporine for therapeutic drug monitoring by fluorescence polarization immunoassay with a rabbit polyclonal antibody: I. Evaluation of the serum methodology and comparison with a sheep polyclonal antibody in an 3H-tracer mediated radioimmunoassay

Among the new techniques available for CyA monitoring, the FPIA offers the advantages of rapidity and simplicity. The present communication assesses the technical performance of this test in comparison with a 3H tracer-based PC-RIA for serum CyA levels using 971 samples obtained during the first 6 posttransplant months from 14 kidney transplant recipients. The FPIA evaluation included verification of CyA concentrations in manufacturer-supplied calibrators and controls by reference methods, determination of intraassay/interassay precision and accuracy, feasibility of specimen dilution and assessed assay sensitivity, and range of linearity. Comparison of FPIA with PC-RIA indicated that trough samples, when assessed by FPIA, averaged 1.3-fold greater than the PC-RIA, whereas non-trough FPIA measurements indicated similarity between the two methods. Although the two assays showed similar trends in most renal transplant recipients, two subjects demonstrated discrepancies, presumably reflecting the differing specificities of the polyclonal antibodies used in each assay. Thus, the FPIA appears to be a useful addition to CyA monitoring technology.     

Cyclosporin-A nephrotoxicity and acute cellular rejection in renal transplant recipients: correlation between radionuclide and histologic findings

Serial radionuclide studies using both Tc-99m DTPA (perfusion) and I-131 hippuran (tubular function) were correlated with histologic findings in 25 patients with renal transplants. These cases included 15 cases of cyclosporin-A nephrotoxicity (CsA-NT) and ten cases of acute cellular rejection that were retrospectively selected on the basis of biopsy findings and favorable clinical response to therapy specific for each of these conditions. The serial radionuclide studies enabled the correct diagnosis in 12 of 15 cases of CsA-NT and eight of ten cases of acute rejection. Posttherapy radionuclide studies, furthermore, demonstrated improvement consistent with clinical response. In all cases, the radionuclide results were available at least 24 hours before biopsy findings. These results indicate that serial radionuclide studies evaluating interval changes in both perfusion and tubular function are of significant value in the diagnosis and follow-up of CsA-NT and acute cellular rejection in transplant recipients. This initial experience suggests a sensitivity of 80%.