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1.
Br J Clin Pharmacol ; 89(12): 3468-3490, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37452618

RESUMO

A broad-spectrum anti-vomiting effect of neurokinin1 receptor antagonists (NK1 RA), shown in pre-clinical animal studies, has been supported by a more limited range of clinical studies in different indications. However, this review suggests that compared with vomiting, the self-reported sensation of nausea is less affected or possibly unaffected (depending on the stimulus) by NK1 receptor antagonism, a common finding for anti-emetics. The stimulus-independent effects of NK1 RAs against vomiting are explicable by actions within the central pattern generator (ventral brainstem) and the nucleus tractus solitarius (NTS; dorsal brainstem), with additional effects on vagal afferent activity for certain stimuli (e.g., highly emetogenic chemotherapy). The central pattern generator and NTS neurones are multifunctional so the notable lack of obvious effects of NK1 RAs on other reflexes mediated by the same neurones suggests that their anti-vomiting action is dependent on the activation state of the pathway leading to vomiting. Nausea requires activation of cerebral pathways by projection of information from the NTS. Although NK1 receptors are present in cerebral nuclei implicated in nausea, and imaging studies show very high receptor occupancy at clinically used doses, the variable or limited ability of NK1 RAs to inhibit nausea emphasizes: (i) our inadequate understanding of the mechanisms of nausea; and (ii) that classification of a drug as an anti-emetic may give a false impression of efficacy against nausea vs. vomiting. We discuss the potential mechanisms for the differential efficacy of NK1 RA and the implications for future development of drugs that can effectively treat nausea, an area of unmet clinical need.


Assuntos
Antieméticos , Antineoplásicos , Animais , Humanos , Antagonistas dos Receptores de Neurocinina-1/farmacologia , Antagonistas dos Receptores de Neurocinina-1/uso terapêutico , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Antieméticos/farmacologia , Antieméticos/uso terapêutico , Desenvolvimento de Medicamentos , Antineoplásicos/uso terapêutico
2.
Exp Brain Res ; 241(5): 1381-1391, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37017727

RESUMO

The widespread use of visual technologies such as Virtual Reality increases the risk of visually induced motion sickness (VIMS). Previously, the 6-item short version of the Visually Induced Motion Sickness Susceptibility Questionnaire (VIMSSQ short form) has been validated for predicting individual variation in VIMS. The aim of the current study was to investigate how the susceptibility to VIMS is correlated with other relevant factors in the general population. A total of 440 participants (201 M, 239F), mean age 33.6 (SD 14.8) years, completed an anonymous online survey of various questionnaires including the VIMSSQ, Motion Sickness Susceptibility Questionnaire (MSSQ), Vertigo in City questionnaire (VIC), Migraine (scale), Social & Work Impact of Dizziness (SWID), Syncope (faintness), and Personality ('Big Five' TIPI). The VIMSSQ correlated positively with the MSSQ (r = 0.50), VIC (r = 0.45), Migraine (r = 0.44), SWID (r = 0.28), and Syncope (r = 0.15). The most efficient Multiple Linear Regression model for the VIMSSQ included the predictors MSSQ, Migraine, VIC, and Age and explained 40% of the variance. Factor analysis of strongest correlates with VIMSSQ revealed a single factor loading with VIMSSQ, MSSQ, VIC, Migraine, SWID, and Syncope, suggesting a common latent variable of sensitivity. The set of predictors for the VIMSSQ in the general population has similarity with those often observed in patients with vestibular disorders. Based on these correlational results, we suggest the existence of continuum of underlying risk factors for sensitivity, from healthy population to patients with extreme visual vertigo and perhaps Persistent Postural-Perceptual Dizziness.


Assuntos
Transtornos de Enxaqueca , Enjoo devido ao Movimento , Humanos , Adulto , Tontura/complicações , Vertigem/complicações , Enjoo devido ao Movimento/etiologia , Transtornos de Enxaqueca/complicações , Síncope/complicações , Personalidade
3.
Exp Brain Res ; 241(4): 1199-1206, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36892611

RESUMO

Environmental motion can induce physiological stress and trigger motion sickness. In these situations, lower-than-normal levels of adrenocorticotropic hormone (ACTH) have been linked with increased susceptibility to motion sickness in healthy individuals. However, whether patients with primary adrenal insufficiency, who typically have altered ACTH levels compared to the normal population, exhibit alterations in sickness susceptibility remains unknown. To address this, we recruited 78 patients with primary adrenal insufficiency and compared changes in the motion sickness susceptibility scores from 10 years prior to diagnosis (i.e. retrospective sickness rating) with the current sickness measures (post-diagnosis), using the validated motion sickness susceptibility questionnaire (MSSQ). Group analysis revealed that motion sickness susceptibility pre-diagnosis did not differ between controls and patients. We observed that following treatment, current measures of motion sickness were significantly increased in patients and subsequent analysis revealed that this increase was primarily in female patients with primary adrenal insufficiency. These observations corroborate the role of stress hormones in modulating sickness susceptibility and support the notion of a sexually dimorphic adrenal cortex as we only observed selective enhancement in females. A potential mechanism to account for our novel observation remains obscure, but we speculate that it may reflect a complex sex-disease-drug interaction.


Assuntos
Doença de Addison , Enjoo devido ao Movimento , Humanos , Feminino , Caracteres Sexuais , Estudos Retrospectivos , Enjoo devido ao Movimento/etiologia , Hormônio Adrenocorticotrópico
4.
Hum Factors ; 65(1): 107-124, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-33874752

RESUMO

OBJECTIVE: Two studies were conducted to develop and validate a questionnaire to estimate individual susceptibility to visually induced motion sickness (VIMS). BACKGROUND: VIMS is a common side-effect when watching dynamic visual content from various sources, such as virtual reality, movie theaters, or smartphones. A reliable questionnaire predicting individual susceptibility to VIMS is currently missing. The aim was to fill this gap by introducing the Visually Induced Motion Sickness Susceptibility Questionnaire (VIMSSQ). METHODS: A survey and an experimental study were conducted. Survey: The VIMSSQ investigated the frequency of nausea, headache, dizziness, fatigue, and eyestrain when using different visual devices. Data were collected from a survey of 322 participants for the VIMSSQ and other related phenomena such as migraine. Experimental study: 23 participants were exposed to a VIMS-inducing visual stimulus. Participants filled out the VIMSSQ together with other questionnaires and rated their level of VIMS using the Simulator Sickness Questionnaire (SSQ). RESULTS: Survey: The most prominent symptom when using visual devices was eyestrain, and females reported more VIMS than males. A one-factor solution with good scale reliability was found for the VIMSSQ. Experimental study: Regression analyses suggested that the VIMSSQ can be useful in predicting VIMS (R2 = .34) as measured by the SSQ, particularly when combined with questions pertaining to the tendency to avoid visual displays and experience syncope (R2 = .59). CONCLUSION: We generated normative data for the VIMSSQ and demonstrated its validity. APPLICATION: The VIMSSQ can become a valuable tool to estimate one's susceptibility to VIMS based on self-reports.


Assuntos
Astenopia , Enjoo devido ao Movimento , Realidade Virtual , Masculino , Feminino , Humanos , Reprodutibilidade dos Testes , Astenopia/etiologia , Inquéritos e Questionários
5.
Int Ophthalmol ; 43(10): 3587-3594, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37402010

RESUMO

PURPOSE: To demonstrate the methodology and efficacy of using scanning laser ophthalmoscopy (SLO) and dynamic optical coherence tomography (OCT) to identify and treat symptomatic vitreous floaters using yttrium-aluminum garnet laser vitreolysis (YLV). METHODS: This is a case series highlighted from a cross sectional retrospective study conducted at the Vitreous Retina Macula Specialists of Toronto. Forty eyes from thirty-five patients were treated with YLV between November 2018 and December 2020 for symptomatic floaters and imaged with SLO and dynamic OCT. Patients were re-treated with YLV if they reported ongoing significant vision symptoms during follow-up which correlated to visible opacities on exam and or imaging. Three cases will be highlighted to present the practical applications of SLO and dynamic OCT imaging for YLV treatment. RESULTS: Forty treated eyes were enrolled in this study, with twenty-six eyes (65%) requiring at least one repeat YLV treatment following the first treatment due to ongoing symptomatic floaters. Following the first YLV, there was a significant improvement in overall mean best corrected visual acuity compared to before treatment (0.11 ± 0.20 LogMAR units vs. 0.14 ± 0.20 LogMAR units, p = 0.02 (paired t test)). Case 1 demonstrates a dense, solitary vitreous opacity that has been localized with dynamic OCT imaging to track its movements and retinal shadowing with the patient's eye movements. Case 2 shows the utility of adjusting the fixation target to monitor the movement of vitreous opacities in real-time. Case 3 exhibits an association between decreased symptom burden and vitreous opacity density after YLV. CONCLUSION: Image-guided YLV facilitates the localization and confirmation of vitreous opacities. SLO and dynamic OCT of the vitreous can provide a real-time evaluation of floater size, movement, and morphology, to help clinicians target treatment and monitoring of symptomatic floaters.


Assuntos
Oftalmopatias , Vitrectomia , Humanos , Estudos Retrospectivos , Estudos Transversais , Vitrectomia/métodos , Oftalmopatias/diagnóstico , Oftalmopatias/cirurgia , Corpo Vítreo/diagnóstico por imagem , Corpo Vítreo/cirurgia , Transtornos da Visão , Tomografia de Coerência Óptica
6.
Curr Opin Neurol ; 35(1): 107-112, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34839340

RESUMO

PURPOSE OF REVIEW: Motion sickness is an ancient phenomenon that affects many people. Nausea, vomiting, disorientation, sweating, fatigue, and headache are just few of the many signs and symptoms that are commonly experienced during an episode of motion sickness. In the present review, we will provide an overview of the current research trends and topics in the domain of motion sickness, including theoretical considerations, physiological and neural mechanisms, individual risk factors, and treatment options, as well as recommendations for future research directions. RECENT FINDINGS: More recently, motion sickness has been in the focus of attention in the context of two global technological trends, namely automated vehicles and virtual reality. Both technologies bear the potential to revolutionize our daily lives in many ways; however, motion sickness is considered a serious concern that threatens their success and acceptance. The majority of recent research on motion sickness focuses on one of these two areas. SUMMARY: Aside from medication (e.g. antimuscarinics, antihistamines), habituation remains the most effective nonpharmacological method to reduce motion sickness. A variety of novel techniques has been investigated with promising results, but an efficient method to reliably prevent or minimize motion sickness has yet to emerge.


Assuntos
Enjoo devido ao Movimento , Realidade Virtual , Veículos Autônomos , Fadiga , Humanos , Enjoo devido ao Movimento/terapia , Vômito
7.
J Sci Food Agric ; 101(6): 2525-2533, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33063328

RESUMO

BACKGROUD: A common lenticel disorder which occurs in the peel of 'Xinli No. 7' pears (Pyrus bretschneideri Rehd.) had not previously been described. Symptoms of this lenticel disorder include enlarging and bulging of the lenticels which results in significant commercial losses. Understanding the physiological basis of lenticel disorder and developing practical methods to control it is crucial for the successful marketing of this pear. RESULTS: The development of this lenticel disorder was found to be closely related to the endogenous ethylene production during storage. 1-Methylcyclopropene (1-MCP) combined with an ethylene absorbent (EA) treatment was found to significantly reduce the development of the disorder by inhibiting the expression of ethylene related genes, PbACS1, PbACS2 and PbACO. It is proposed that the enlarged lenticels may result from increased lignin accumulation in the peel cells, which is inhibited by this combined postharvest treatment. It was shown that the expression of six lignin related genes decreased following the treatment. The results suggest that PbPAL, Pb4CL and PbCAD could be critical in regulating the development of this lenticel disorder. CONCLUSION: Endogenous ethylene plays a key role in the development of this lenticel disorder in 'Xinli No. 7' pear. The enlarged lenticels which is characteristic of this disorder maybe related to increased lignin accumulation in the peel cells, which were inhibited with 1-MCP combined with an EA treatment. These results provide a practical method for managing the development of lenticel disorder in 'Xinli No. 7' pear and helps clarify the developmental mechanisms of this disorder. © 2020 Society of Chemical Industry.


Assuntos
Ciclopropanos/farmacologia , Etilenos/farmacologia , Frutas/crescimento & desenvolvimento , Pyrus/efeitos dos fármacos , Frutas/efeitos dos fármacos , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Lignina/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Pyrus/crescimento & desenvolvimento , Pyrus/metabolismo
8.
Int Ophthalmol ; 41(8): 2805-2815, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33830372

RESUMO

PURPOSE: To describe the feasibility of peripheral OCT imaging in retinal diseases using a novel full-field device. METHODS: A total of 134 consecutive eyes were referred and imaged on the Optos Silverstone swept-source OCT (SS-OCT) (Optos PLC; Dunfermline, UK). Scanning laser ophthalmoscope (SLO) images and the associated SS-OCT images were obtained in the posterior pole, mid-periphery or far periphery based on the nature of the referral and on new areas of interest observed in the optomap images at the time of imaging. RESULTS: A total of 134 eyes (96 patients) were enrolled in the study. One hundred and twenty-five eyes (91 patients) with 38 retinal pathologies were prospectively assessed and 9 eyes (5 patients) were excluded due to incomplete image acquisition. The average age of the subjects was 54 years (range 21-92 years). Thirty-nine out of 125 eyes (31%) had macular pathologies. Eighty-six out of 125 eyes (69%) had peripheral only pathologies, an area which cannot be visualized by standard OCT devices with a 50 degree field-of-view. CONCLUSIONS: The ability to capture peripheral pathologies using an integrated SLO-UWF imaging with full-field swept-source provided high-grade anatomical insight that confirmed the medical and surgical management in a majority of cases. Its use in the mid- and far periphery provides a holistic clinical picture, which can potentially aid in the understanding of various retinal pathologies.


Assuntos
Retina , Tomografia de Coerência Óptica , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Angiofluoresceinografia , Humanos , Pessoa de Meia-Idade , Oftalmoscópios , Retina/diagnóstico por imagem , Adulto Jovem
9.
Brain ; 142(3): 606-616, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30759189

RESUMO

Vestibular migraine is among the commonest causes of episodic vertigo. Chronically, patients with vestibular migraine develop abnormal responsiveness to both vestibular and visual stimuli characterized by heightened self-motion sensitivity and visually-induced dizziness. Yet, the neural mechanisms mediating such symptoms remain unknown. We postulate that such symptoms are attributable to impaired visuo-vestibular cortical interactions, which in turn disrupts normal vestibular function. To assess this, we investigated whether prolonged, full-field visual motion exposure, which has been previously shown to modulate visual cortical excitability in both healthy individuals and avestibular patients, could disrupt vestibular ocular reflex and vestibular-perceptual thresholds of self-motion during rotations. Our findings reveal that vestibular migraine patients exhibited abnormally elevated reflexive and perceptual vestibular thresholds at baseline. Following visual motion exposure, both reflex and perceptual thresholds were significantly further increased in vestibular migraine patients relative to healthy controls, migraineurs without vestibular symptoms and patients with episodic vertigo due to a peripheral inner-ear disorder. Our results provide support for the notion of altered visuo-vestibular cortical interactions in vestibular migraine, as evidenced by vestibular threshold elevation following visual motion exposure.


Assuntos
Transtornos de Enxaqueca/fisiopatologia , Doenças Vestibulares/fisiopatologia , Adulto , Estudos Transversais , Tontura/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Reflexo Vestíbulo-Ocular/fisiologia , Vertigem , Testes de Função Vestibular , Neuronite Vestibular/fisiopatologia , Vestíbulo do Labirinto , Percepção Visual/fisiologia
10.
J Sci Food Agric ; 100(5): 1897-1903, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31825530

RESUMO

BACKGROUND: Sapota is a popular tropical fruit characterized by a very short postharvest life. Low-temperature storage prolongs postharvest life of sapota fruit, but chilling injury symptoms can develop if the storage temperature is less than 14 °C. There have been no reports on the effects of postharvest melatonin application on the development of chilling injury in sapota fruit during cold storage. The objective of this study was to investigate the effects of different concentrations of postharvest melatonin application (0, 30, 60 and 90 µmol L-1 ) during cold storage (8 °C) for up to 30 days with an additional 1-day shelf life at ambient temperature. RESULTS: All melatonin treatments reduced chilling injury symptoms, reduced electrolyte leakage, malondialdehyde (MDA) content, H2 O2 and superoxide anion (O2 - ), and increased proline content and the activity of superoxide dismutase (SOD), catalase (CAT) and γ-aminobutyric acid (GABA), and reduced the activities of phospholipase D (PLD) and lipoxygenase (LOX) compared to the control. CONCLUSION: Postharvest melatonin treatment could be a useful strategy for reducing chilling injury during cold storage and transport of sapota fruit. The results indicate that melatonin reduces chilling injury of sapota fruit through maintaining membrane integrity, SOD and CAT activities, and reducing PLD and LOX activities. © 2019 Society of Chemical Industry.


Assuntos
Conservação de Alimentos/métodos , Conservantes de Alimentos/farmacologia , Melatonina/farmacologia , Catalase/metabolismo , Temperatura Baixa , Conservação de Alimentos/instrumentação , Armazenamento de Alimentos , Frutas/química , Frutas/efeitos dos fármacos , Frutas/metabolismo , Malondialdeído/metabolismo , Manilkara/química , Manilkara/efeitos dos fármacos , Manilkara/metabolismo , Ácido gama-Aminobutírico/metabolismo
11.
J Food Sci Technol ; 56(3): 1438-1444, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30956323

RESUMO

UV-C (180-280 nm) has been shown to extend the postharvest shelf-life of many horticulture crops. In this study, Tahitian limes (Citrus latifolia) were exposed to 0, 3.4, 7.2 and 10.5 kJ m-2 UV-C then stored for 28 days in air at 10 °C and 80% RH. Weight loss, peel colour, calyx abscission, ethylene production, respiration rate, total soluble solids (TSS), titratable acidity (TA) and acceptability index were assessed. The results showed that UV-C treatment maintained lime peel green colour and retained calyx attachment after 28 days storage. UV-C treatment also affected endogenous ethylene production and respiration rate, where the highest UV-C treatment (10.5 kJ m-2) maintained low ethylene production and low respiration rates after 28 days storage with no differences between the different UV-C intensities. In terms of fruit acceptability, limes were exposed to 10.5 kJ m-2 UV-C had a 60% acceptability index after 28 days storage, while untreated control fruit retained acceptability of 39%. In general, the pre-storage UV-C treatments did not affect fruit weight loss, TSS or TA contents during storage.

12.
Br J Clin Pharmacol ; 84(7): 1535-1543, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29522648

RESUMO

AIMS: The aim of this study was to compare the effects of the selective M3 muscarinic acetylcholine receptor antagonist darifenacin, oral hyoscine hydrobromide and placebo on motion sickness induced by cross-coupled stimulation. METHODS: The effects of darifenacin 10 mg or 20 mg, hyoscine hydrobromide 0.6 mg and placebo were assessed in a randomized, double-blind, four-way cross over trial of 16 healthy subjects. Motion sickness, skin conductance (a measure of sweating) and psychomotor cognitive function tests were investigated. RESULTS: Hyoscine hydrobromide produced significantly increased tolerance to motion versus placebo (P < 0.05 to P < 0.01). The motion protection effect of darifenacin (10 or 20 mg) was approximately one third that of hyoscine hydrobromide but was not significant versus placebo. Darifenacin and hyoscine hydrobromide both significantly reduced skin conductance versus placebo. Darifenacin produced either no effect or an enhanced effect on cognitive function in contrast to hyoscine hydrobromide, where there was significant impairment of psychomotor performance. CONCLUSION: The results suggest that selective antagonism of the M3 receptor may not be important in the prevention of motion sickness. However, selective M3 antagonism does not impair cognitive function. These observations may be important given that long-term treatment with non-selective anti-muscarinic agents such as oxybutynin may lead to an increased incidence of dementia.


Assuntos
Benzofuranos/administração & dosagem , Cognição/efeitos dos fármacos , Resposta Galvânica da Pele/efeitos dos fármacos , Enjoo devido ao Movimento/tratamento farmacológico , Antagonistas Muscarínicos/administração & dosagem , Pirrolidinas/administração & dosagem , Escopolamina/administração & dosagem , Adolescente , Adulto , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Voluntários Saudáveis , Humanos , Masculino , Placebos/administração & dosagem , Receptor Muscarínico M3/antagonistas & inibidores , Sudorese/efeitos dos fármacos , Resultado do Tratamento , Adulto Jovem
14.
J Food Sci Technol ; 55(7): 2467-2475, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30042562

RESUMO

The green Tahitian limes (Citrus latifolia) were exposed to 7.2 kJ m-2 UV-C and 0.5 µL L-1 1-methylcyclopropene (1-MCP) treatments both separately and in combination. After treatment, fruit were stored in ethylene free (i.e. air containing < 0.005 µL L-1) or 0.1 µL L-1 ethylene at 20 °C and 100% RH. The results showed that UV-C treatment delayed skin degreening and reduced endogenous ethylene production compared to untreated control fruit, however these effects reduced over the storage time. As expected, 1-MCP inhibited ethylene production, reduced calyx abscission and retained peel greenness during the storage. Both of the combination treatments, 1-MCP + UV-C and UV-C + 1-MCP reduced endogenous ethylene production and delayed skin yellowing. In all treatments, UV-C and 1-MCP resulted in lower fruit respiration rates than untreated control fruit, however this effect diminished during 7 and 14 days storage for fruits stored in air and 0.1 µL L-1 ethylene atmosphere, respectively. There was no difference in weight loss, SSC, TA and SSC/TA ratio between the treatments and storage conditions. The results suggest that a pre-storage UV-C treatment, followed by storage at low level of ethylene improves the quality of limes, with the additional improvement when combined with 1-MCP treatment prior or after UV-C irradiation.

15.
Lancet ; 388(10061): 2753-2762, 2016 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-27865535

RESUMO

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 effectiveness 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 final 6 months compared with the 6 months before the first 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 difference -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. FUNDING: Ménière's Society and National Institute for Health Research Imperial Biomedical Research Centre.


Assuntos
Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Gentamicinas/uso terapêutico , Doença de Meniere/complicações , Metilprednisolona/uso terapêutico , Método Duplo-Cego , Feminino , Perda Auditiva/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vertigem/prevenção & controle
17.
J Neurooncol ; 131(1): 117-124, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27796735

RESUMO

Bevacizumab is considered an established part of the treatment strategies available for schwannomas in patients with Neurofibromatosis type 2 (NF2). In the UK, it is available through NHS National Specialized Commissioning to NF2 patients with a rapidly growing target schwannoma. Regrowth of the tumour on suspension of treatment is often observed resulting in prolonged periods of exposure to bevacizumab to control the disease. Hypertension and proteinuria are common events with bevacizumab use and there are concerns with regards to the long-term risks of prolonged treatment. Dosing, demographic and adverse event (CTCAE 4.03) data from the UK NF2 bevacizumab cohort are reviewed with particular consideration of renal and cardiovascular complications. Eighty patients (48 male:32 female), median age 24.5 years (range 11-66 years), were followed for a median of 32.7 months (range 12.0-60.2 months). The most common adverse events were fatigue, hypertension and infection. A total of 19/80 patients (24 %) had either a grade 2 or grade 3 hypertension event and 14/80 patients (17.5 %) had proteinuria. Of 36 patients followed for 36 months, 78 % were free from hypertension and 86 % were free of proteinuria. Logistic regression modeling identified age and induction dosing regime to be independent predictors of development of hypertension with dose of 7.5 mg/kg 3 weekly and age >30years having higher rates of hypertension. Proteinuria persisted in one of three patients after cessation of bevacizumab. One patient developed congestive heart failure and the details of this case are described. Further work is needed to determine optimal dosing regimes to limit toxicity without impacting on efficacy.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Bevacizumab/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Hipertensão/induzido quimicamente , Neurilemoma/tratamento farmacológico , Neurofibromatose 2/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurilemoma/complicações , Neurofibromatose 2/complicações , Análise de Regressão , Reino Unido , Adulto Jovem
18.
Health Qual Life Outcomes ; 15(1): 34, 2017 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-28193237

RESUMO

BACKGROUND: Neurofibromatosis 1 (NF1) is an inherited, multi-system, tumour suppressor disorder with variable complications that cause psychological distress and social isolation. The study aim was to develop and validate a disease-specific questionnaire to measure quality of life (QOL) in NF1 that is suitable both as an assessment tool in clinical practice and in clinical trials of novel therapy. METHODS: The Impact of NF1 on Quality of Life (INF1-QOL) questionnaire was developed by a literature search for common terms, focus group (n = 6), semi-structured interviews (n = 21), initial drafts (n =50) and final 14 item questionnaire (n = 50). Bivariate correlations between items, exploratory factor analysis, correlations with severity and EuroQol were employed. RESULTS: INF1-QOL showed good internal reliability (Cronbach's alpha 0.87), mean total INF1-QOL score was 8.64 (SD 6.3), median 7.00, range 0-30 (possible range 0-42); no significant correlations with age or gender. The mean total EuroQol score was 7.38 (SD 2.87), median 6.5, mean global EuroQol score was 76.34 (SD 16.56), median 80. Total INF1-QOL score correlated with total EuroQol r = 0.82, p < 0.0001. The highest impact on QOL was moderate or severe problems with anxiety and depression (32%) and negative effects of NF1 on role and outlook on life (42%). The mean inter-relater reliability for grading of clinical severity scores was 0.71 (range 0.65-0.79), and intra-class correlation was 0.92. The mean clinical severity score was 1.95 (SD 0.65) correlating r = 0.34 with total INF1-QOL score p < 0.05 and correlated 0.37 with total EuroQol score p < 0.01. The clinical severity score was mild in 17 (34%), moderate in 16 (32%) and 17 (34%) individuals had severe disease. CONCLUSIONS: INF1-QOL is a validated, reliable disease specific questionnaire that is easy and quick to complete. Role and outlook on life and anxiety and depression have the highest impact on QOL indicating the variability, severity and unpredictability of NF1. INFI-QOL correlates moderately with clinical severity. The moderate relationship between INF1-QOL and physician rated severity emphasizes the difference between clinical and patient perception. INFI-QOL will be useful in individual patient assessment and as an outcome measure for clinical trials.


Assuntos
Neurofibromatose 1/psicologia , Qualidade de Vida/psicologia , Índice de Gravidade de Doença , Inquéritos e Questionários/normas , Adulto , Idoso , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Psicometria , Reprodutibilidade dos Testes , Adulto Jovem
19.
Psychol Res ; 81(2): 480-489, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26902293

RESUMO

Spatial perspective-taking that involves imagined changes in one's spatial orientation is facilitated by vestibular stimulation inducing a congruent sensation of self-motion. We examined further the role of vestibular resources in perspective-taking by evaluating whether aberrant and conflicting vestibular stimulation impaired perspective-taking performance. Participants (N = 39) undertook either an "own body transformation" (OBT) task, requiring speeded spatial judgments made from the perspective of a schematic figure, or a control task requiring reconfiguration of spatial mappings from one's own visuo-spatial perspective. These tasks were performed both without and with vestibular stimulation by whole-body Coriolis motion, according to a repeated measures design, balanced for order. Vestibular stimulation was found to impair performance during the first minute post stimulus relative to the stationary condition. This disruption was task-specific, affecting only the OBT task and not the control task, and dissipated by the second minute post-stimulus. Our experiment thus demonstrates selective temporary impairment of perspective-taking from aberrant vestibular stimulation, implying that uncompromised vestibular resources are necessary for efficient perspective-taking. This finding provides evidence for an embodied mechanism for perspective-taking whereby vestibular input contributes to multisensory processing underlying bodily and social cognition. Ultimately, this knowledge may contribute to the design of interventions that help patients suffering sudden vertigo adapt to the cognitive difficulties caused by aberrant vestibular stimulation.


Assuntos
Julgamento , Orientação/fisiologia , Desempenho Psicomotor/fisiologia , Percepção Espacial/fisiologia , Adulto , Humanos , Imaginação/fisiologia , Masculino , Percepção de Movimento/fisiologia , Vestíbulo do Labirinto/fisiologia
20.
J Sci Food Agric ; 97(11): 3706-3711, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28111769

RESUMO

BACKGROUND: The marketability of fresh-cut banana slices is limited by the rapid rate of fruit softening and browning. However, there is no scientific literature available about the role of postharvest calcium propionate and chitosan treatment on the quality attributes of fresh-cut banana. Therefore, the aim of the present study was to investigate these effects. RESULTS: The application of calcium propionate plus chitosan (CaP+Chit) retained higher firmness, higher ascorbic acid content, higher total antioxidant activity and higher total phenolic compounds, along with lower browning, lower polyphenol oxidase, lower peroxidase, lower polygalacturonase and lower pectin methyl esterase activities and microbial growth, compared to control banana slices after 5 days of cold storage. CONCLUSION: The results of the present study show that CaP+Chit could be used to slow the loss of quality at the same time as maintaining quality and inhibiting microbial loads. © 2017 Society of Chemical Industry.


Assuntos
Quitosana/farmacologia , Conservação de Alimentos/métodos , Conservantes de Alimentos/farmacologia , Frutas/química , Frutas/efeitos dos fármacos , Musa/química , Propionatos/farmacologia , Antioxidantes/análise , Antioxidantes/metabolismo , Ácido Ascórbico/análise , Ácido Ascórbico/metabolismo , Armazenamento de Alimentos , Frutas/metabolismo , Musa/efeitos dos fármacos , Musa/metabolismo , Fenóis/análise , Fenóis/metabolismo
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