Objective
Vertigo and dizziness are a frequent reason for medical consultation. However, diagnostic and therapeutic management is sometimes limited, and clinicians are faced with many unmet needs. ...The purpose of this study was to identify and prioritize these needs.
Methods
A questionnaire methodology was used to determine the need for innovation in vestibular disorder management. The questionnaire was sent to 19 teams in French-speaking ENT centers. We measured the concordance of the panel of experts on 56 questions related to the different vestibular pathologies encountered and the desired modalities of innovations.
Results
Thirteen questions were identified as priorities. The needs expressed by the experts had better knowledge of the pathophysiological mechanisms of the main diseases encountered and the development of new treatment modalities. Particular attention was paid to inner ear imaging techniques and the development of specific electrophysiology techniques.
Discussion
Some of the anticipated innovations are already under development, such as new inner ear fluid imaging techniques (hydrops visualization using MRI) or in situ treatments (transtympanic dexamethasone or gentamicin injections). Others, such as new electrophysiological techniques, are still not fully developed
Conclusion
This study provides a snapshot of the needs of the medical profession in vestibular disorder management. It highlights a real concern of the attending personnel, as well as a critical need to optimize the means of diagnosing and treating patients with vestibular disorders.
To determine the efficacy and safety of cyclosporine (CyA) in a large national registry-based population of patients with steroid-refractory (SR) acute severe ulcerative colitis (ASUC) and to ...establish predictors of efficacy and adverse events.
Multicenter study of SR-ASUC treated with CyA, based on data from the ENEIDA registry. SR-ASUC patients treated with infliximab (IFX) or sequential rescue therapy (CyA-IFX or IFX-CyA) were used as comparators.
Of 740 SR-ASUC patients, 377 received CyA, 131 IFX and 63 sequential rescue therapy. The cumulative colectomy rate was higher in the CyA (24.1%) and sequential therapy (32.7%) than in the IFX group (14.5%; P=0.01) at 3 months and 5 years. There were no differences in early and late colectomy between CyA and IFX in patients treated after 2005. 62% of patients receiving CyA remained colectomy-free in the long term (median 71 months). There were no differences in mortality between CyA (2.4%), IFX (1.5%) and sequential therapy (0%; P=0.771). The proportion of patients with serious adverse events (SAEs) was lower in CyA (15.4%) than in IFX treated patients (26.5%) or sequential therapy (33.4%; P<0.001). This difference in favor of CyA was maintained when only patients treated after 2005 were analyzed.
Treatment with CyA showed a lower rate of SAE and a similar efficacy to that of IFX thereby supporting the use of either CyA or IFX in SR-ASUC. In addition, the risk-benefit of sequential CyA-IFX for CyA non-responders is acceptable.
The total antioxidant capacity (hydrophilic plus lipophilic) of sixteen different commercial samples of pasteurized and ultra high temperature (UHT) treated milk was determined using the oxygen ...radical absorbance capacity assay using fluorescein as a fluorescent probe. A significant correlation between the percentage of fat and the value of the total antioxidant capacity was found in milk samples obtained from the same batch of raw milk. Analyses of the whole milk, whey and deproteinized milk showed that the major contributor to the total antioxidant capacity of whole milk was the casein fractions, while albumin was the major contributor to the total antioxidant capacity of whey protein. Hydrophilic antioxidant compounds, such as vitamin C and uric acid, were the main contributors to the total antioxidant capacity of the deproteinized milk. Significant differences in total antioxidant capacities were found between whey and deproteinized samples obtained from pasteurized and UHT-treated milk, the values being higher for the former.
Aims/hypothesis Beta cell failure is a crucial component in the pathogenesis of type 2 diabetes. One of the proposed mechanisms of beta cell failure is local inflammation, but the presence of ...pancreatic islet inflammation in type 2 diabetes and the mechanisms involved remain under debate. Methods Chemokine and cytokine expression was studied by microarray analysis of laser-capture microdissected islets from pancreases obtained from ten non-diabetic and ten type 2 diabetic donors, and by real-time PCR of human islets exposed to oleate or palmitate at 6 or 28 mmol/l glucose. The cellular source of the chemokines was analysed by immunofluorescence of pancreatic sections from individuals without diabetes and with type 2 diabetes. Results Microarray analysis of laser-capture microdissected beta cells showed increased chemokine and cytokine expression in type 2 diabetes compared with non-diabetic controls. The inflammatory response in type 2 diabetes was mimicked by exposure of non-diabetic human islets to palmitate, but not to oleate or high glucose, leading to the induction of IL-1β, TNF-α, IL-6, IL-8, chemokine (C-X-C motif) ligand 1 (CXCL1) and chemokine (C-C motif) ligand 2 (CCL2). Interference with IL-1β signalling abolished palmitate-induced cytokine and chemokine expression but failed to prevent lipotoxic human islet cell death. Palmitate activated nuclear factor κB (NF-κB) in human pancreatic beta and non-beta cells, and chemically induced endoplasmic reticulum stress caused cytokine expression and NF-κB activation similar to that occurring with palmitate. Conclusions/interpretation Saturated-fatty-acid-induced NF-κB activation and endoplasmic reticulum stress may contribute to IL-1β production and mild islet inflammation in type 2 diabetes. This inflammatory process does not contribute to lipotoxicity ex vivo, but may lead to local chemokine release.
Liquid chromatography (LC) was the method chosen to evaluate the effects of high intensity pulsed electric fields (HIPEF), with different electric field intensities (25, 30, 35 and 40
kV/cm) and ...different treatment times (30–340
μs), on orange juice
cis/
trans carotenoid contents. In parallel, a conventional heat treatment (90
°C, 20
s) was applied to the orange juice in order to compare the effect on the carotenoid contents.
HIPEF processing of orange juice is an alternative to the thermal treatment of pasteurization, provided that it is kept refrigerated, because, when the most extreme conditions of this kind of treatment are applied, the decrease in the concentration of carotenoids with vitamin A activity is very small, and also most of the carotenoids identified have a slightly increased concentration after application of the most intense treatments, although always less than in untreated fresh juice. In any case, pasteurization treatment causes a greater decrease in the concentration of most of the carotenoids identified and the carotenoids with vitamin A activity. The total carotenoid concentration decreased by 12.6% in pasteurized orange juice with respect to untreated fresh orange juice, as opposed to decreases of 9.6%, 6.3% or 7.8% when fields of 25, 30 or 40
kV/cm were applied. Orange juice treated with HIPEF shows a greater tendency towards the colour yellow and a lesser tendency towards red with respect to untreated orange juice, while the luminance of the juice remains practically invariable. This tendency is less than in pasteurized orange juice.
The aim of the present study was to investigate the role of anxiety sensitivity (AS) as a factor relevant to pain and pain persistence. Two studies were conducted to examine the relationship between ...AS, body vigilance and the experience of pain in non-clinical samples. Study 1 investigated the relationship between AS and body vigilance that was operationalized by the detection latency for innocuous electrical stimuli; trait anxiety and neuroticism were also included as covariates. Results indicated that the high AS group (
N=69) presented shorter detection latency than the low AS group (
N=70); neuroticism and trait anxiety did not have significant effects on detection latency. Using another sample, Study 2 investigated the relationship between AS, body vigilance, pain tolerance, catastrophizing, and self-reported distress and pain during a cold pressor task. Neuroticism, trait anxiety and fear of pain were included as covariates. Results showed significant differences between high- (
N=66) and low- (
N=69) AS groups in body vigilance, catastrophizing and tolerance. The covariates neuroticism, trait anxiety and fear of pain did not have any significant effects. No significant differences were found in pain and distress ratings. Results from both studies support the importance of AS in body vigilance and the experience of pain. The theoretical, preventive and clinical implications of these findings are discussed.
Microtubule-Targeting Agents (MTAs) constitute a class of drugs largely used in cancer treatment. Among them, both taxanes and Vinca-alkaloids are known to inhibit cancer cell proliferation by ...inducing cell cycle arrest and subsequent apoptosis. These agents modify the cytoskeleton by affecting the tubulin/microtubule system. In cancer cells, both classes suppress microtubule dynamics through inhibition of microtubule dynamic instability and treadmilling, and commonly induce diverse signals responsible for cell death initiation and execution via the mitochondrial intrinsic pathway. However, links between microtubule network disturbance and the involvement of mitochondria in apoptosis are not obvious, and one may think that they could be independent. Nevertheless, several intracellular proteins could connect microtubules and the apoptotic machinery. The aim of the present review is to provide elements that could answer to the question: is microtubule disruption dispensable for MTA-induced apoptosis? The first section is focused on the mechanisms responsible for the MTA-mediated apoptosis. Then, links between cell cycle regulators and apoptosis are underlined since MTA induce cell cycle arrest by inhibiting microtubules. In the third part, the potential involvement of microtubule-sequestered and/or -transported proteins in apoptotic signalisation is discussed. Lastly, the possible role of the tubulin/microtubule system in direct effects of MTAs on mitochondria is summarized. Thus, it becomes clear that microtubule network and apoptosis are deeply linked in MTA effectiveness, through a cascade of cellular events. It could lead to identification of new biomarkers of MTA effectiveness, that could improve combinatorial therapy with MTAs and provide crucial arms to circumvent resistance of cancer cells.
The effects of the physicochemical and quality characteristics of various minimally pasteurized refrigerated orange Spanish juices and their changes with storage time and temperature were ...investigated. Essential oils, acidity, conductivity, diacetyl index, hydroxymethylfurfural, formol index, viscosity and ascorbic acid varied with storage time more significantly at 10
°C than at 4
°C. Density, colour and pectinmethylesterase did not vary at 4
°C. Some of the parameters could be used as indicators of quality loss or spoilage of the juices. The degradation kinetics of the concentration of remaining ascorbic acid against time follows a straight line whose slope indicates the degradation rate. A period of at least 42
days at 4
°C and 35
days at 10
°C was established as the shelf life of the juices.
The main objective was to assess the efficacy of intratympanic dexamethasone injection in controlling vertigo in unilateral Ménière's disease refractory to medical treatment.
A retrospective study ...included 25 patients with disabling unilateral Ménière's disease, defined according to the American Academy of Otorhinolaryngology-Head and Neck Surgery (AAO-HNS) criteria. Patients received intratympanic dexamethasone during the monitoring period. Control of vertigo was classified according to AAO-HNS vertigo control index, at 6 months, 1 year, and 2 years after treatment initiation. Complications and progression of hearing were also assessed.
Satisfactory control (class A or B) was obtained in 92% of patients (n=23/25) at 6 months, 68% (n=17/25) at 1 year, and 70% (n=16/23) at 2 years. There was no worsening of hearing in those patients who were well-controlled by this therapeutic strategy. No local or systemic complications were observed during follow-up.
Dexamethasone is part of the management strategy for patients with Ménière's disease refractory to conventional treatment, implemented before destructive treatment. It achieves control of vertigo in 70% of patients at 2 years.
Summary
Background
Idiopathic bile acid malabsorption (BAM) has been suggested as a cause of chronic watery diarrhoea, with a response to colestyramine in 70% of patients. However, the efficacy of ...this drug has never been investigated in placebo‐controlled trials.
Aim
To evaluate the efficacy of colestyramine as compared with hydroxypropyl cellulose in the treatment of functional chronic watery diarrhoea.
Methods
Patients with chronic watery diarrhoea were randomly assigned to groups given colestyramine sachets 4 g twice daily (n = 13) or identical hydroxypropyl cellulose sachets (n = 13) for 8 weeks. The primary end‐point was clinical remission defined as a mean of 3 or fewer stools per day during the week before the visit, with less than 1 watery stool per day. A secondary end‐point was the reduction in daily watery stool number. SeHCAT test was performed in all patients, but an abnormal test was not a prerequisite to be included.
Results
All included patients had a SeHCAT 7‐day retention ≤20%. There were no statistical differences in the percentage of patients in clinical remission at week 8 between colestyramine and hydroxypropyl cellulose with either intention‐to‐treat (53.8% vs. 38.4%; P = 0.43) or per‐protocol (63.6% vs. 38.4%; P = 0.22) analyses. However, the mean per cent decrease in watery stool number was significantly higher with colestyramine than with hydroxypropyl cellulose (−92.4 ± 3.5% vs. −75.8 ± 7.1%; P = 0.048). The rate of adverse events related to study drugs did not differ between groups.
Conclusions
Colestyramine (4 g twice daily) is effective and safe for short‐term treatment of patients with chronic watery diarrhoea presumably secondary to BAM. Clinical Trials Register number EudraCT 2009‐011149‐14.
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