BKV in Simultaneous Pancreas-Kidney Transplant Recipients: A Leading Cause of Renal Graft Loss in First 2 Years Post-Transplant

With the introduction of more potent immunosuppressive agents, rejection has decreased in simultaneous pancreas/kidney transplant (SPK) recipients. However, as a consequence, opportunistic infections have increased. The purpose of this report is to outline the course of SPK patients who developed polyomavirus-associated nephropathy (PVAN). A retrospective review of 146 consecutive SPK recipients from January 1, 1996 to December 31, 2002 was performed. Immunosuppression, rejection and development of PVAN were reviewed. Nine patients were identified. All received induction with either OKT3 or thymoglobulin. Immunosuppression included tacrolimus/cyclosporine, MMF/azathioprine and sirolimus/prednisone. Two patients were treated for kidney rejection prior to the diagnosis of PVAN. Time to diagnosis was an average of 359.3 days post-transplantation. Immunosuppression was decreased but five ultimately lost function. However, none developed pancreatic abnormalities as demonstrated by normal glucose and amylase. Two underwent renal retransplantation after PVAN diagnosis and both have normal kidney function. PVAN was the leading cause of renal loss in SPK patients in the first 2 years after transplantation and is a serious concern for SPK recipients. The pancreas, however, is spared from evidence of infection, and no pancreatic rejection occurred when immunosuppression was decreased.     

Coalition theory as a framework for understanding and implementing intersectoral health-related interventions

Although it is regarded as a central concept in the practice of health promotion, intersectoral health-related action (IHA) has, to date, failed more often than it has succeeded. In this paper we review relevant social scientific literature, offer a working definition of intersectoral action and explore the usefulness of coalition theory as a theoretical framework through which to understand IHA theoretically and practically. Coalition theory has been previously used to study political alliances but it encompasses a series of parameters pertinent to the analysis of IHA. These parameters are: the rewards people expect to gain from participation in a coalition; the political assets they have t bring to the coalition; the non-utilitarian preferences they develop; the coalition's rules for decision-making; and the organisational context in which the coalition operates. We used these five parameters to study three intersectoral endeavours in Quebec, one at the local level and two at the provincial level, including activities associated with the Healthy Cities movement. Coalition theory proved useful in unravelling the mechanisms for these endeavours and appears promising as a tool for studying and/or implementing intersectoral health-related interventions.     

A pilot study of a parent-education group for families affected by depression.

OBJECTIVE: This study assessed the feasibility and efficacy of a parent-education group for families with young children and a parent with depression. We designed the program to be readily disseminated if shown to be effective. METHOD: We recruited 44 parents with depression from clinics and family doctors in Hamilton, Ontario, and randomly assigned them to receive the parenting program or to a wait-list control group. The outcomes measured included knowledge of depression, parenting, family relationships, depression symptoms, child depressive symptoms, and functioning. We used analysis of covariance to test for posttreatment differences between experimental and control groups. RESULTS: Of the treatment group, 27% dropped out at posttreatment, and 43% by follow-up. Those who dropped out had more severe depression at baseline than did those who completed the program, and there was selective loss of parents with more severe depression in the experimental group. In intention-to-treat analyses at posttreatment, probands in the experimental group reported more improvements on family functioning, parenting sense of competence, and family and parent conflict than did control subjects. Standardized effect sizes (ES) were medium (0.4 to 0.6). When baseline depressive symptom scores were controlled in the analyses, the between-group differences were reduced, showing that selective loss of participants may have influenced the findings. CONCLUSIONS: On balance, the results are encouraging and support the further development and evaluation of the group intervention. However, the study does not provide unequivocal evidence in support of the program. Before it is transferred to other settings, the program needs further modification to improve participation by parents with more severe depression and further evaluation of its effectiveness.     

Concentration-dependent metabolism of diazepam in mouse liver

Previous mouse liver studies with diazepam (DZ),N-desmethyldiazepam (NZ), and temazepam (TZ) confirmed that under first-order conditions, DZ formed NZ and TZ in parallel. Oxazepam (OZ) was generatedvia NZ and not TZ despite that preformed NZ and TZ were both capable of forming OZ. In the present studies, the concentration-dependent sequential metabolism of DZ was studied in perfused mouse livers and microsomes, with the aim of distinguishing the relative importance of NZ and TZ as precusors of OZ. In microsomal studies, theK _ms andV _maxs, corrected for binding to microsomal proteins, were 34 μM and 3.6 nmole/min per mg and 239 μM and 18 nmole/min per mg, respectively, forN-demthylation andC ₃-hydroxylation of DZ. TheK _ms andV _maxs forN-demethylation andC ₃-hydroxylation of TZ and NZ, respectively, to form OZ, were 58 μM and 2.5 nmole/min per mg and 311 μM and 2 nmole/min per mg, respectively. The constants suggest that at low DZ concentrations, NZ formation predominates and is a major source of OZ, whereas at higher DZ concentrations, TZ is the important source of OZ. In livers perfused with DZ at input concentrations of 13 to 35 μM, the extraction ratio of DZ (E{DZ}) decreased from 0.83 to 0.60. NZ was the major metabolite formed although its appearance was less than proportionate with increasing DZ input concentration. By contrast, the formation of TZ increased disporportionately with increasing DZ concentration, whereas that for OZ decreased and paralleled the behavior of NZ. Computer simulations based on a tubular flow model and thein vitro enzymatic parameters provided a poorin vitro-organ correlation. TheE{DZ}, appearance rates of the metabolites, and the extraction ratio of formed NZ (E{NZ, DZ}) were poorly predicted; TZ was incorrectly identified as the major precursor of OZ. Simulations with optimized parameters imporved the correlations and identified NZ as the major contributor of OZ. Saturation of DZN-demethylation at higher DZ concentrations increased the role of TZ in the formation of OZ. The poor aqueous solubility (limiting the concentration range of substrates usedin vitro), avid tissue binding and the coupling of enzymatic reactions in liver, favoring sequential metabolism, are possible explanations for the poorin vitro-organ correlation. This work emphasizes the complexity of the hepatic intracellular milieu for drug metabolism and the need for additional modeling efforts to adequately describe metabolite kinetics. This work was supported by the Medical Research Council of Canada (MA-9104).     

Performance of inattentive-overactive children on selected measures of prefrontal-type function

Several theorists have suggested that childhood inattention-overactivity ("attention deficit disorder," "hyperactivity") may arise from a deficit in the inhibitory mechanisms of the prefrontal cortex. Accordingly, it was hypothesized that inattentive-overactive children would exhibit prefrontal-type deficits on several relevant neuropsychological measures. Subjects were 21 elementary school pupils who had been referred for disruptive behavior problems and who had been rated as high in inattention-overactivity. Controls were 26 age-matched normal children from the same school. It was found that the Inattentive-Overactive group, relative to the Control group, performed in the direction of prefrontal-type deficit on three measures that have an empirical history of discriminating patients with prefrontal lesions from controls: Perseverative errors on the Wisconsin Card Sorting Test, errors on the sequential Matching Memory Task, and Necker Cube reversals. On three theoretical indices of prefrontal-type deficit--Trailmaking, the Stroop Color-Word Test, and a sequential memory task for children--the Inattentive-Overactive group also exhibited predicted deficits. There were no differences between groups on the WISC-R Vocabulary subtest. The results of the study are generally compatible with a prefrontal-deficit theory of inattention-overactivity. However, the presence of other deficits cannot be ruled out nor can an organic cause be inferred from these findings alone.     

Enrichment of murine splenic natural killer (NK) cells by the sequential elimination of non-NK cells

A simple and reliable three-step procedure to enrich for murine endogenous splenic NK cells is described. The method is based on the sequential elimination of non-NK cell subsets by standard and inexpensive techniques executed in a specific order. First, macrophages and other adherent cells are eliminated by incubation on plastic surface. Secondly, the T cells are excluded from the multicellular aggregates formed by agglutination of the remaining cells with wheat germ lectin. Thirdly, after dissociation of the aggregates with N-acetyl-D-glucosamine and osmotic lysis of erythrocytes, NK cells are separated from other nucleated cells by nylon wool filtration. C57BL/6 spleen cells were used to establish the enrichment procedure. Usually their NK cell activity is intermediate but occasionally either low or high NK cell activity was observed in input cell suspensions. The NK cell activity recovery and the degree of enrichment varied inversely with the initial NK cell activity level of the input cell suspension. When initial NK cell activity was intermediate, it was enriched 10-30-fold. Experiments were done to establish if suppressor cells, and nylon wool-adherent, naturally activated NK cells, putatively present in input cells, could have been responsible for the abnormal initial NK cell activity detected in some C57BL/6 spleen cell suspensions and for the variations in the degree of enrichment achieved by the method here described. Either no or negligeable suppressor cell activity was noted in the cell fractions normally discarded at each step of the procedure. On the other hand, nylon wool-adherent NK cells were eliminated during the fractionation of spleen cells with higher than average initial NK cell activity and would account for the lower NK cell enrichment obtained in these conditions.