Conversion to sirolimus of patients with chronic allograft nephropathy—a retrospective analysis of outcome and influencing factors

Purpose

The purpose of this study was to analyse the outcome and its influencing factors in patients whose therapy was converted from calcineurin inhibitors (CNI) to sirolimus (SRL) due to chronic allograft nephropathy (CAN).

Materials and methods

Therapies of 78 patients (44 men) with CAN from three European transplant centres were converted from CNI therapy to SRL and followed 24 months. Slopes for creatinine clearance before and after conversion were calculated. Influencing factors were analysed by a multivariance analysis.

Results

The slope of the creatinine clearance improved significantly (?0.90 vs. ?0.34 ml min^?1 month^?1; p?<?0.01). In patients whose therapy was converted from cyclosporine A (CyA) to SRL, the slope improved significantly, whereas conversion from Tacrolimus (Tac) to SRL did not affect the slope. The benefit was more pronounced in (1) patients with low or moderate baseline creatinine clearance, (2) patients receiving SRL after conversion without additional mycophenolate mofetil and (3) patients with low or moderate proteinuria.

Conclusion

Conversion from CyA to SRL but not from Tac to CRL is associated with a reduced loss of renal allograft function in patients with CAN.     

Validation of Prognostic Scoring Systems for Patients Undergoing Resection of Colorectal Cancer Liver Metastases

Background  

Several prognostic scoring systems have been established for patients undergoing resection of colorectal cancer (CRC) liver metastases; however, comparative analyses of their prognostic relevance is still lacking in the literature. The aim of the present study was to assess the predictive value of five published scoring systems in an independent patient cohort for the purpose of external validation.     

Radiofrequency ablation of complex fractionated atrial electrograms (CFAE): preferential sites of acute termination and regularization in paroxysmal and persistent atrial fibrillation

Introduction: Complex fractionated atrial electrograms (CFAE) have been described as a new target for ablation of atrial fibrillation (AF). This prospective study evaluates the acute effects of CFAE ablation in patients with paroxysmal or persistent AF and analyzes the preferential anatomic sites where these effects occur.
Methods and Results: Ablation of CFAE was performed in 66 symptomatic patients (mean age of 58 ± 12 years) with paroxysmal (n = 36) or persistent AF (n = 30). Termination or regularization of AF during ablation of CFAE was achieved in 56 of 66 patients (84%), with termination in 28 of 66 patients (42%) and regularization of AF in 28 of 66 patients (42%). Ablation of CFAE showed no effect in 10 of 66 patients (16%). Termination of AF occurred at 53 sites and AF regularization at 81 sites. The preferential sites of AF termination or regularization were found around the pulmonary veins (termination n = 15; regularization n = 22), at the anterior wall (termination n = 14; regularization n = 19) and at the interatrial septum (termination n = 8; regularization n = 17).
Conclusion: Termination or regularization of AF was achieved acutely in 84% of patients by ablation of CFAE. The preferential sites of AF termination or regularization were found around the pulmonary veins, at the anterior wall of the LA and at the interatrial septum. These findings may have implications for future ablation concepts.     

Organization of the torus longitudinalis in the rainbow trout (Oncorhynchus mykiss): an immunohistochemical study of the GABAergic system and a DiI tract-tracing study

The torus longitudinalis (TL) is a tectum-associated structure of actinopterygian fishes. The organization of the TL of rainbow trout was studied with Nissl staining, Golgi methods, immunocytochemistry with antibodies to gamma-aminobutyric acid (GABA), glutamic acid decarboxylase (GAD), and the GABA(A) receptor subunits delta and beta2/beta 3, and with tract tracing methods. Two types of neuron were characterized: medium-sized GABAergic neurons and small GABA-negative granule cells. GABA(A) receptor subunit delta-like immunoreactivity delineated two different TL regions, ventrolateral and central. Small GABAergic cells were also observed in marginal and periventricular strata of the optic tectum. These results indicate the presence of local GABAergic inhibitory circuits in the TL system. For tract-tracing, a lipophilic dye (DiI) was applied to the TL and to presumed toropetal nuclei or toral targets. Toropetal neurons were observed in the optic tectum, in pretectal (central, intermediate, and paracommissural) nuclei, in the subvalvular nucleus, and associated with the pretectocerebellar tract. Torofugal fibers were numerous in the stratum marginale of the optic tectum. Toropetal pretectal nuclei also project to the cerebellum, and a few TL cells project to the cerebellar corpus. The pyramidal cells of the trout tectum were also studied by Golgi methods and local DiI labeling. The connections of trout TL revealed here were more similar to those recently reported in carp and holocentrids (Ito et al. [2003] J. Comp. Neurol. 457:202-211; Xue et al. [2003] J. Comp. Neurol. 462:194-212), than to those reported in earlier studies. However, important differences in organization of toropetal nuclei were noted between salmonids and these other teleosts.     

Stereotyped Motor Behaviors Associated with Autism in High-risk Infants: A Pilot Videotape Analysis of a Sibling Sample

This study examined motor behaviors in a longitudinal cohort of infant siblings of children with autism. Stereotypic movements and postures occurring during standardized observational assessments at 12 and 18 months were coded from videotapes. Participants included eight infant siblings later diagnosed with autism spectrum disorder (ASD), a random sample of nine non-diagnosed siblings, and 15 controls. Videos were coded blind to diagnostic group. At 12 and 18 months the ASD group “arm waved” more frequently and at 18 months, one posture (“hands to ears”) was more frequently observed in the ASD and non-diagnosed group compared to the controls. Overall, the siblings subsequently diagnosed with ASD and the comparison groups had considerable overlap in their repertoires of stereotyped behaviors.     

Emotion recognition following human pulvinar damage

Pulvinar activation has been observed while viewing fearful expressions, but the necessity of this activation to their recognition has not been previously assessed. We measured the processing of emotional facial expressions in a rare patient with complete unilateral loss of the pulvinar. With brief presentations, patient CJ was incapable of recognizing fearful expressions in his contralesional field. Three other patients, with damage limited to the anterior and to the lateral pulvinar, showed no deficits in recognition. In conjunction with anatomical studies of the monkey pulvinar, these results suggest that fear recognition is mediated by the human medial pulvinar. We outline the possible role of the pulvinar in fear recognition, considering both the pulvinar's direct and indirect cortical connections with the amygdala, and we suggest that the integrative role of the pulvinar may be primary. Our results suggest that the cortex in isolation from the entire pulvinar is incapable of recognizing fearful expressions.     

Muscle myostatin expression in children with muscle diseases

The demonstration that myostatin may negatively regulate muscle mass in adult individuals has raised the possibility of targeting the myostatin pathway to increase muscle growth in a variety of muscle-degenerative and -wasting conditions. To gain further insight into the possible role of myostatin in primary muscle diseases, the authors investigated the expression of muscle myostatin in children with congenital fiber type 1 disproportion, in others with neurogenic muscular atrophy, in others with myotonia congenita, in others with infantile glycogenosis type II, in others with Prader-Willi syndrome, and in 4 age-matched controls. No differences in the pattern of myostatin expression were found in any case, even in those patients with prominent muscular atrophy or hypertrophy. These findings suggest that muscle alterations that can be observed in primary muscle diseases do not depend on changes in myostatin expression.     

d-Amino acid oxidase and serine racemase in human brain: normal distribution and altered expression in schizophrenia

The N-methyl-D-aspartate receptor co-agonist d-serine is synthesized by serine racemase and degraded by D-amino acid oxidase. Both D-serine and its metabolizing enzymes are implicated in N-methyl-D-aspartate receptor hypofunction thought to occur in schizophrenia. We studied D-amino acid oxidase and serine racemase immunohistochemically in several brain regions and compared their immunoreactivity and their mRNA levels in the cerebellum and dorsolateral prefrontal cortex in schizophrenia. D-Amino acid oxidase immunoreactivity was abundant in glia, especially Bergmann glia, of the cerebellum, whereas in prefrontal cortex, hippocampus and substantia nigra, it was predominantly neuronal. Serine racemase was principally glial in all regions examined and demonstrated prominent white matter staining. In schizophrenia, D-amino acid oxidase mRNA was increased in the cerebellum, and as a trend for protein. Serine racemase was increased in schizophrenia in the dorsolateral prefrontal cortex but not in cerebellum, while serine racemase mRNA was unchanged in both regions. Administration of haloperidol to rats did not significantly affect serine racemase or D-amino acid oxidase levels. These findings establish the major cell types wherein serine racemase and D-amino acid oxidase are expressed in human brain and provide some support for aberrant D-serine metabolism in schizophrenia. However, they raise further questions as to the roles of D-amino acid oxidase and serine racemase in both physiological and pathophysiological processes in the brain.