Multiple pilocytic astrocytomas of the cerebellum in a 17-year-old patient with neurofibromatosis type I

Objective Approximately 10% of patients with neurofibromatosis I (NFI) patients will have central nervous system (CNS) tumors. The most common of these are hypothalamic–optic gliomas, followed by brainstem and cerebellar pilocytic astrocytomas. While isolated pilocytic astrocytomas in NFI are well described, the appearance of multiple pilocytic astrocytomas in an individual patient is less common. The most frequent combination in NFI patients with more than one pilocytic astrocytoma is optic tract/hypothalamic and brainstem. Other combinations are exceedingly rare; multiple pilocytic astrocytomas have only been reported once in the cerebral hemispheres in a patient with NFI. This report presents the first documented case, to our knowledge, of multiple pilocytic astrocytomas in the cerebellum of a patient with NF1. Methods Case report. Conclusion The finding of multiple cerebellar pilocytic astrocytomas in a patient with NF1 is important because it expands the spectrum of presentations for patients with NF1 and also highlights specific diagnostic and therapeutic challenges faced by the treating physicians. The genetic and molecular basis of NF1 is reviewed. Strategies of diagnosis and treatment outlined here are relevant to both patients with NF1 and all patients with multiple posterior fossa tumors.     

Motor and non-motor sequence learning in children and adolescents with cerebellar damage.

Cerebellar involvement in motor and non-motor sequence learning was examined with serial reaction time tasks (SRT). Our sample consisted of 8 children and adolescents who had undergone surgical removal of a benign posterior fossa tumor (PFT) during childhood. None of them had undergone chemotherapy or cranial radiation therapy (CRT). Ages ranged from 1-11 years at surgery and 9-17 years at testing. The children were tested not earlier than 2.5 years after surgery (M = 5.9 years), enabling brain plasticity and recovery of functions. Their performance was compared with a matched control sample. The PFT group was not impaired in the implicit learning of sequences, as reflected in their performance in blocks with a repeated sequence, both before and after a random block. However, in the perceptual task, their performance deteriorated more than that of the control group when a random block was introduced, suggesting that it was more difficult for the patients to respond flexibly or change their response set when encountering changing task demands. These results are in line with another study by our group on task switching with the same patients.     

The politics of interprofessional working and the struggle for professional autonomy in nursing

This study of interprofessional work relations in a Canadian mental health team examines how nursing deployed different forms of power in order to alter the mental health division of labour, to gain administrative, organizational and content control over its own work, expand its jurisdictional boundaries by expropriating the work of other professionals, and exclude others from encroaching on its old and newly acquired jurisdictions. This is set against the context of nursing's long-standing professional project to consolidate and expand its professional jurisdiction. Using an ethnographic study of a single interprofessional mental health team in a psychiatric hospital in Canada, the paper attempts to understand the politics and paradoxes involved in realizing nursing's professional project and how the politics of professional autonomy and professional dominance are actually conducted through micro-political struggles. The data demonstrates the effects of the political struggles at the organizational and work process levels, particularly in the forms of collaboration that result. Nurses gained substantial autonomy from medical domination and secured practical dominion over the work of non-medical professionals. New forms of interprofessional collaboration were accomplished through both simultaneous and sequential micro-political struggles with psychiatrists and non-medical professionals, and the formation of political alliances and informal agreements. Nursing solidarity at the elite level and substantial effort by the elite nurses and their committed colleagues to mobilize their less enthused members were fundamental to their success. The nurses deployed political (power) strategies and tactics to organize and reorganize themselves and other professionals on multiple levels (politically, organizationally, ideologically, socially and culturally). This study reveals the complexity and robustness of micro-political dynamics in the constitution of professional and collaborative interprofessional work relations.     

Relaxin down-regulates renal fibroblast function and promotes matrix remodelling in vitro.

BACKGROUND: Renal fibroblasts are important effector cells in tubulointerstitial fibrosis, with experimental antifibrotic strategies focusing on the functional down-regulation of these cells. Several experimental models of fibrosis have provided evidence for the effectiveness of the polypeptide hormone relaxin as a potential antifibrotic agent. This study was conducted to further elucidate the antifibrotic mechanisms of relaxin on renal fibroblasts in vitro. METHODS: Rat cortical fibroblasts were obtained from outgrowth culture of renal tissue isolated from kidneys 3 days post-unilateral ureteric obstruction and constituted 100% of cells studied. A relaxin radio-receptor assay was used to establish binding of relaxin to renal fibroblasts in vitro. Functional studies then examined the effects of H2 relaxin (0, 1, 10 and 100 ng/ml) on fibroblast kinetics, expression of alpha-smooth muscle actin (alpha-SMA), total collagen synthesis, collagenase production and collagen-I lattice contraction. CTGF mRNA expression was also measured by northern analysis. RESULTS: H2 relaxin bound with high affinity to rat renal fibroblasts, but receptor numbers were low. Consistent with its previously reported bimodal effect, transforming growth factor (TGF-beta 1) reduced fibroblast proliferation, an effect abrogated by H2 relaxin. Fibroblasts exposed to H2 relaxin (100 ng/ml) for 24 h demonstrated decreased immunostaining for alpha-SMA and reduced alpha-SMA protein expression compared with controls. There was a trend for a relaxin-mediated reduction in total collagen synthesis and alpha 1(I) mRNA expression with large dose-related increases in collagenase protein expression being observed. TGF-beta 1-stimulated collagen-I lattice contraction was significantly inhibited following co-incubation with 100 ng/ml relaxin. Incremental doses of H2 relaxin had no significant effect on CTGF mRNA expression. CONCLUSIONS: The findings of this study suggest that the antifibrotic effects of relaxin involve down-regulation of fibroblast activity, increase in collagenase synthesis and restructuring of collagen-I lattices, which are consistent with its known physiological role of matrix remodelling. Although there appears to be an interaction between TGF-beta 1 and H2 relaxin, this does not appear to involve a reduction in CTGF mRNA expression.     

Two phases of zymogen granule lifetime in mouse pancreas: ghost granules linger after exocytosis of contents

Different cell types show widely divergent mechanisms and kinetics of exocytosis. We investigated these processes in pancreatic acinar cells by using video-rate 2-photon microscopy to image entry of extracellular dye into individual zymogen granules undergoing exocytosis. Fluorescence signals display two distinct phases; an initial peak that then decays over several seconds to a prolonged plateau. Several observations suggest that the first component reflects the binding of dye to the granule contents and their subsequent release into the acinar duct. These observations include: the peak/plateau fluorescence ratio differs between different dyes; the initial fluorescence decay mirrors the loss of granule contents as monitored by differential interference contrast microscopy; and the fall in vesicular fluorescence is accompanied by a rise in fluorescence in the adjacent duct lumen. We thus propose the use of extracellular fluorescent probes as a convenient means to monitor the kinetics of loss of proteinaceous content from secretory granules. In pancreatic acinar cells the fusion pore remains open much longer than required to ensure secretion of the granule contents, and instead the persistent empty 'ghost-granule' may act as a conduit to which secondary granules can fuse and release their contents by compound exocytosis.