Fluoridated elastomers: effect on the microbiology of plaque.

The objective of this study was to investigate the effect of fluoridated elastomeric ligatures on the microbiology of local dental plaque in vivo. This randomized, prospective, longitudinal, clinical trial had a split-mouth crossover design. The subjects were 30 patients at the beginning of their treatment with fixed orthodontic appliances in the orthodontic departments of the Liverpool and the Sheffield dental hospitals in the United Kingdom. The study consisted of 2 experimental periods of 6 weeks with a washout period between. Fluoridated elastomers were randomly allocated at the first visit to be placed around brackets on tooth numbers 12, 11, 33 or 22, 21, 43. Nonfluoridated elastomers were placed on the contralateral teeth. Standard nonantibacterial fluoridated toothpaste and mouthwash were supplied. After 6 weeks (visit 2), the elastomers were removed, placed in transport media, and plated on agar within 2 hours. Nonfluoridated elastomers were placed on all brackets for 1 visit to allow for a washout period. At visit 3, fluoridated elastomers were placed on the teeth contralateral to those that received them at visit 1. At visit 4, the procedures at visit 2 were repeated. Samples were collected on visits 2 and 4. A logistic regression was performed, with the presence or absence of streptococcal or anaerobic growth as the dependent variable. A mixed-effects analysis of variance was carried out with the percentage of streptococcal or anaerobic bacterial count as the dependent variable. The only significant independent variables were the subject variable (P =<.001) for the percentage of streptococcal and anaerobic bacterial count and the visit variable for the percentage of streptococcal count (P =<.001). The use of fluoridated or nonfluoridated elastomers was not significant for percentage of either streptococcal (P =.288) or anaerobic count (P =.230). Fluoridated elastomers are not effective at reducing local streptococcal or anaerobic bacterial growth after a clinically relevant time in the mouth.     

Thrombotic Micro‐Angiopathy with Sirolimus‐Based Immunosuppression: Potentiation of Calcineurin‐Inhibitor‐Induced Endothelial Damage?

Thrombotic microangiopathy is a rare but important finding in the context of organ transplantation. Acute renal insufficiency in the setting of hemolysis and thrombocytopenia, a triad that constitutes 'hemolytic uremic syndrome', can be associated with, or triggered by, conditions such as verocytotoxin-producing Escherichia coli, viral infections, malignant hypertension, scleroderma, allograft rejection, lupus erythematosus, pregnancy, and medications including mitomycin C, calcineurin inhibitors, and oral contraceptives. After renal transplantation, it can occur, as either a de novo episode, or recurrent disease. Calcineurin inhibitors have long been associated with post-transplantation thrombotic microangiopathy. Sirolimus has been used as a primary immunosuppressant in patients transplanted with a history of earlier hemolytic-uremic syndrome, and also as rescue therapy in patients with calcineurin-inhibitor-associated thrombotic microangiopathy. We describe four cases where there was significant thrombotic microangiopathy in the context of contemporaneous or contiguous calcineurin inhibitor and sirolimus usage. As the intrarenal cyclosporin concentration is thought to be significantly elevated when cyclosporin and sirolimus are used together, this may explain these findings, and mandates caution in their co-administration.     

Liposome-mediated transfer of vascular endothelial growth factor cDNA augments survival of random-pattern skin flaps in the rat.

Tissue engineering is an application for gene therapy that is in its infancy. We show that simple liposomal-mediated gene transfer could result in a potentially useful biological effect in the field of wound healing. cDNA encoding the 165 amino acid form of vascular endothelial growth factor complexed to commercially available liposomes was injected into rat skin 1 week before raising a random pattern 3 x 10 cm flap. The flap survival was enhanced by 14 percent, and was accomplished without accessing the arterial inflow of the territory. These results were statistically significant (p<0.002) and reproducible. No adverse effects were seen. Histological analysis of the angiogenesis localized much of the new vessel formation to the area around the hair follicles. Polymerase chain reaction amplification of extracted flap tissue confirmed the presence of the transgene.     

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.     

Dissociable roles of the ventral, medial and lateral striatum on the acquisition and performance of a complex visual stimulus-response habit.

The effects of discrete bilateral ibotenic acid lesions to 3 areas of striatum were examined on a conditional visual discrimination task involving temporal frequency (SLOW vs FAST flashes) that had previously been shown to be sensitive to the effects of dorsal striatal dopamine depletion. Two of the groups, namely, those with nucleus accumbens (ACC) and lateral caudate-putamen (LCP) lesions, were very disrupted in the acquisition of the task. The nature of the respective impairments of the 2 groups was dissociable, however. The performance of the ACC group could be improved either by manipulations of stimulus duration or inter-stimulus interval, implying an attentional deficit. In contrast, the rats with lesions of the LCP were not significantly improved by any of the behavioural challenges. Their performance was characterised by a bias to respond to the SLOW discriminandum. Under conditions of non-reward, the LCP group extinguished their responding at a similar rate to control rats whereas the ACC group were very much more persistent. Lesions of the medial caudate-putamen failed to affect any index of performance significantly. These data suggest that the LCP is necessary for the acquisition of arbitrary stimulus-response rules and that damage to an equivalent area in humans, such as in Huntington's disease, may explain deficits of procedural memory. The second part of the experiment investigated the effects of ACC lesions on established performance of the schedule. The lesioned group behaved identically to the ACC group that had been lesioned prior to acquisition, both in terms of accuracy and degree of persistence in extinction, further implying the role of attentional factors and inflexibility in the lesion-induced deficit.