Long-term follow-up of intratympanic methylprednisolone versus gentamicin in patients with unilateral Menière’s disease

Objectives: To determine whether long term (>48 months) symptomatic vertigo control is sustained in patients with Menie`re’s disease from a previous comparative trial of intratympanic methylprednisolone versus gentamicin, and if the two treatments remain nonsignificantly different at longterm follow-up. Study Design: Mail survey recording vertigo frequency in the previous one and six months, further intratympanic treatment received, and validated symptom questionnaires. Setting: Outpatient hospital clinic setting. Patients: Adult patients with definite unilateral refractory Menie`re’s disease, who previously received in tratympanic treatment in a comparative trial. Intervention: A survey of trial participants who received intratympanic gentamicin (40 mg/mL) or methylprednisolone (62.5 mg/mL). Outcome measures: Primary: number of vertigo attacks in the 6 months prior to receiving this survey compared with the 6 months before the first trial injection. Secondary: : Number of vertigo attacks over the previous 1 month; validated symptom questionnaire scores of tinnitus, dizziness, vertigo, aural fullness, and functional disability. Results: Average follow-up was 70.8 months (standard deviation 17.0) from the first treatment injection. Vertigo attacks in the 6 months prior to receiving the current survey reduced by 95% compared to baseline in both drug groups (intention-to-treat analysis, both p<0.001). No significant difference between drugs was found for the primary and secondary outcomes. Eight participants (methylprednisolone ¼ 5 and gentamicin ¼ 3) required further injections for relapse after completing the original trial. Conclusion: Intratympanic methylprednisolone treatment provides effective long-lasting relief of vertigo, without the known inner-ear toxicity associated with gentamicin. There are no significant differences between the two treatments at long term follow-up

Intratympanic methylprednisolone versus gentamicin in patients with unilateral Ménière's disease: a randomised, double-blind, comparative effectiveness trial

Background Ménière’s disease is characterised by severe vertigo attacks and hearing loss. Intratympanic gentamicin,the standard treatment for refractory Ménière’s disease, reduces vertigo, but damages vestibular function and can worsen hearing. We aimed to assess whether intratympanic administration of the corticosteroid methylprednisolone reduces vertigo compared with gentamicin. Methods In this double-blind comparative eff ectiveness trial, patients aged 18–70 years with refractory unilateral Ménière’s disease were enrolled at Charing Cross Hospital (London, UK) and Leicester Royal Infirmary (Leicester, UK). Patients were randomly assigned (1:1) by a block design to two intratympanic methylprednisolone(62·5 mg/mL) or gentamicin (40 mg/mL) injections given 2 weeks apart, and were followed up for 2 years. All investigators and patients were masked to treatment allocation. The primary outcome was vertigo frequency over the final 6 months (18–24 months after injection) compared with the 6 months before the first injection. Analyses were done in the intention-to-treat population, and then per protocol. This trial is registered with ClinicalTrials.gov, number NCT00802529. Findings Between June 19, 2009, and April 15, 2013, 256 patients with Ménière’s disease were screened, 60 of whom were enrolled and randomly assigned: 30 to gentamicin and 30 to methylprednisolone. In the intention-to-treat analysis (ie, all 60 patients), the mean number of vertigo attacks in the fi nal 6 months compared with the 6 months before the fi rst injection (primary outcome) decreased from 19·9 (SD 16·7) to 2·5 (5·8) in the gentamicin group (87% reduction) and from 16·4 (12·5) to 1·6 (3·4) in the methylprednisolone group (90% reduction; mean diff erence –0·9,95% CI –3·4 to 1·6). Patients whose vertigo did not improve after injection (ie, non-responders) after being assessed by an unmasked clinician were eligible for additional injections given by a masked clinician (eight patients in the gentamicin group vs 15 in the methylprednisolone group). Two non-responders switched from methylprednisolone to gentamicin. Both drugs were well tolerated with no safety concerns. Six patients reported one adverse event each: three in the gentamicin group and three in the methylprednisolone group. The most common adverse event was minor ear infections, which was experienced by one patient in the gentamicin group and two in the methylprednisolone group. Interpretation Methylprednisolone injections are a non-ablative, effective treatment for refractory Ménière’s disease. The choice between methylprednisolone and gentamicin should be made based on clinical knowledge and patient circumstances

Lubricating Bacteria Model for Branching growth of Bacterial Colonies

Various bacterial strains (e.g. strains belonging to the genera Bacillus, Paenibacillus, Serratia and Salmonella) exhibit colonial branching patterns during growth on poor semi-solid substrates. These patterns reflect the bacterial cooperative self-organization. Central part of the cooperation is the collective formation of lubricant on top of the agar which enables the bacteria to swim. Hence it provides the colony means to advance towards the food. One method of modeling the colonial development is via coupled reaction-diffusion equations which describe the time evolution of the bacterial density and the concentrations of the relevant chemical fields. This idea has been pursued by a number of groups. Here we present an additional model which specifically includes an evolution equation for the lubricant excreted by the bacteria. We show that when the diffusion of the fluid is governed by nonlinear diffusion coefficient branching patterns evolves. We study the effect of the rates of emission and decomposition of the lubricant fluid on the observed patterns. The results are compared with experimental observations. We also include fields of chemotactic agents and food chemotaxis and conclude that these features are needed in order to explain the observations.Comment: 1 latex file, 16 jpeg files, submitted to Phys. Rev.

Weakly non-ergodic Statistical Physics

We find a general formula for the distribution of time averaged observables for weakly non-ergodic systems. Such type of ergodicity breaking is known to describe certain systems which exhibit anomalous fluctuations, e.g. blinking quantum dots and the sub-diffusive continuous time random walk model. When the fluctuations become normal we recover usual ergodic statistical mechanics. Examples of a particle undergoing fractional dynamics in a binding force field are worked out in detail. We briefly discuss possible physical applications in single particle experiments

Modelling of the injured spinal cord using 3-dimensional cell cultures; strategies for improving tissue engineered repair

Traumatic injuries to the spinal cord and dorsal root entry zone (DREZ) are debilitating and often lead to paralysis and loss of sensation for the patient. At the cellular and molecular level, the repair site microenvironment is inhibitory for axon growth due to formation of a glial scar. A common finding of current strategies aimed at bridging CNS lesions, in particular recent tissue engineering approaches using fibronectin (Phillips et al., Biomaterials 2004), is that whilst axons readily enter and traverse the bridging graft, they are less likely to exit the graft and reconnect with their targets. The aim of this work was to develop a cell culture model to investigate reactive gliosis following damage to the spinal cord. Astrocytes in the CNS under physiological conditions express low levels of GFAP, but following trauma exhibit a reactive phenotype characterised by GFAP up-regulation. Primary glial cell cultures were analysed in 2D monolayers and 3D collagen gels for GFAP expression. In 2D cultures approximately twice the number of cells were positive for GFAP compared to those cultured in 3D collagen gels. As 3D astrocyte cultures more closely modelled the in vivo situation, we used this model to investigate the response of astrocytes to cells found at the inhibitory interface following damage. The preliminary model involved placing dorsal root ganglia (DRG) explants into the centre of astrocyte gels. Classification of astrocyte morphology revealed significantly more ramified cells in DRG-adjacent regions (6 fold higher), than in control areas away from the DRG. A more advanced model was then developed in which dissociated DRGs were labelled with CellTrackerTM, seeded onto astrocyte-populated collagen gels and maintained in culture for 5 days. Astrocytes near the DRG interface showed marked GFAP up-regulation and adopted a reactive morphology which was observed up to 1mm away. Intensity of GFAP fluorescence at this interface was 3 fold higher than that seen away from the interface or in controls (astrocyte only gels). Astrocytes in 3D culture exhibit a lower basal level of reactivity than cells grown in monolayer. This model provides a useful tool for investigating triggers of reactive gliosis, as demonstrated by the response observed to cells found at the inhibitory interfaces formed following damage to the spinal cord and could be used as a way to improve existing therapies and develop new strategies aimed at CNS repair

Not all activated satellite cell progeny commit to differentiation

Satellite cells provide skeletal muscle with a remarkable capacity for repeated repair and regeneration. Quiescent satellite cells are MyoD-ve, with MyoD being induced in >98% of satellite cells within 24hrs of activation (Zammit, Exp. Cell Res. 281, 39, 2002). Here, we explore the subsequent fate of these satellite cells, as they proliferate and begin to differentiate. Satellite cells associated with myofibres, cultured without exposure to serum/CEE, still activated MyoD but the majority failed to divide, demonstrating an uncoupling of the two events. In contrast, myofibres cultured with serum/CEE had clones of satellite cells. MyoD-ve cells were detected in these clones, in which the rest of the cells were MyoD+ve, implying they had arisen after division but were not adopting the same fate. Three possible explanations for MyoD-ve cells were explored: phosphorylated histone markers and BrdU labelling showed that the lack of MyoD was not cell cycle dependent; myogenin immunostaining demonstrated that satellite cells committing to differentiation initially contained MyoD; Pax7 expression was generally down-regulated in the majority of satellite cells by 72hrs, but some remained strongly Pax7+ve. Together, these data suggest that MyoD-ve cells are returning to a quiescent state