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1.
BMC Neurol ; 22(1): 442, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443737

RESUMO

BACKGROUND: People with Parkinson's disease (PD) have a high fall rate and many falls are associated with turns. Despite this, there is minimal research on effects of rehabilitation on the quality of turns. Further, quantifying turns in the home may have broader implications since rehabilitation of turns would ideally improve turning in real world mobility. METHODS: Sixty people with PD and a history of falls will be randomized to receive either a novel TURNing InTervention (TURN-IT) or no intervention (control group). The TURN-IT group will be seen for 6 weeks (18 visits) for an individualized, progressive program that is based on the specific constraints of turning in PD. Wearable sensors will be used to measure 7 days of mobility, including turns, before and after intervention or control period. In addition, blinded assessments of gait, mobility and turns will occur before and after intervention for both groups and falls will be monitored for twelve months post intervention with bimonthly email questionnaires. DISCUSSION: This study has the potential to change how we rehabilitate and assess turning in people with PD and falls. There are several novel aspects to our study including a comprehensive turning-focused intervention that is tailored to the underlying constraints that impair turning in people with PD. Further, our outcome measure of turning quality during 7 days of daily life is novel and has implications for determining real-life changes after rehabilitation. The ultimate goal of this rehabilitation intervention is to improve how patients turn in daily life and to reduce falls. TRIALS REGISTRATION: This protocol is registered at clinicaltrials.gov; #NCT04897256; https://clinicaltrials.gov/ct2/show/NCT04897256?term=Horak&cond=Parkinson+Disease&draw=2&rank=4 .


Assuntos
Doença de Parkinson , Humanos , Marcha
2.
Pneumologie ; 75(4): 259-260, 2021 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-33711848

RESUMO

Patients with asthma should be vaccinated against COVID-19. This includes patients with severe asthma. Treatment with a biological for asthma is no contra-indication for vaccination against COVID-19.


Assuntos
Asma , COVID-19 , Pneumologia , Asma/tratamento farmacológico , Áustria , Vacinas contra COVID-19 , Humanos , SARS-CoV-2 , Vacinação
3.
Pneumologie ; 75(3): 191-200, 2021 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-33728628

RESUMO

The present addendum of the guideline for the diagnosis and treatment of asthma (2017) complements new insights into the diagnosis and management of asthma as well as for the newly approved drugs for the treatment of asthma. Current, evidence-based recommendations on diagnostic and therapeutic approaches are presented for children and adolescents as well as for adults with asthma.


Assuntos
Asma , Pneumologia , Adolescente , Adulto , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/epidemiologia , Áustria , Criança , Humanos , Sociedades Médicas
4.
J Neurophysiol ; 119(1): 33-38, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28978769

RESUMO

Upright stance in humans requires an intricate exchange between the neural mechanisms that control balance and those that control posture; however, the distinction between these control systems is hard to discern in healthy subjects. By studying balance and postural control of a participant with camptocormia - an involuntary flexion of the trunk during standing that resolves when supine - a divergence between balance and postural control was revealed. A kinematic and kinetic investigation of standing and walking showed a stereotyped flexion of the upper body by almost 80° over a few minutes, and yet the participant's ability to control center of mass within the base of support and to compensate for external perturbations remained intact. This unique case also revealed the involvement of automatic, tonic control of the paraspinal muscles during standing and the effects of attention. Although strength was reduced and MRI showed a reduction in muscle mass, there was sufficient strength to maintain an upright posture under voluntary control and when using geste antagoniste maneuvers or "sensory tricks" from visual, auditory, and haptic biofeedback. Dual tasks that either increased or decreased the attention given to postural alignment would decrease or increase the postural flexion, respectively. The custom-made "twister" device that measured axial resistance to slow passive rotation revealed abnormalities in axial muscle tone distribution during standing. The results suggest that the disorder in this case was due to a disruption in the automatic, tonic drive to the postural muscles and that myogenic changes were secondary. NEW & NOTEWORTHY By studying an idiopathic camptocormia case with a detailed biomechanical and sensorimotor approach, we have demonstrated unique insights into the neural control of human bipedalism 1) balance and postural control cannot be considered the same neural process, as there is a stereotyped abnormal flexed posture, without balance deficits, associated with camptocormia, and 2) posture during standing is controlled by automatic axial tone but "sensory tricks" involving sensory biofeedback to direct voluntary attention to postural alignment can override, when required.


Assuntos
Atrofia Muscular Espinal/fisiopatologia , Equilíbrio Postural , Postura , Curvaturas da Coluna Vertebral/fisiopatologia , Idoso de 80 Anos ou mais , Retroalimentação Sensorial , Feminino , Humanos , Contração Isométrica , Força Muscular , Atrofia Muscular Espinal/diagnóstico , Músculos Paraespinais/fisiopatologia , Curvaturas da Coluna Vertebral/diagnóstico , Caminhada/fisiologia
5.
Cerebellum ; 17(5): 628-653, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29656311

RESUMO

The purpose of this consensus paper is to review electrophysiological abnormalities and to provide a guideline of neurophysiological assessments in cerebellar ataxias. All authors agree that standard electrophysiological methods should be systematically applied in all cases of ataxia to reveal accompanying peripheral neuropathy, the involvement of the dorsal columns, pyramidal tracts and the brainstem. Electroencephalography should also be considered, although findings are frequently non-specific. Electrophysiology helps define the neuronal systems affected by the disease in an individual patient and to understand the phenotypes of the different types of ataxia on a more general level. As yet, there is no established electrophysiological measure which is sensitive and specific of cerebellar dysfunction in ataxias. The authors agree that cerebellar brain inhibition (CBI), which is based on a paired-pulse transcranial magnetic stimulation (TMS) paradigm assessing cerebellar-cortical connectivity, is likely a useful measure of cerebellar function. Although its role in the investigation and diagnoses of different types of ataxias is unclear, it will be of interest to study its utility in this type of conditions. The authors agree that detailed clinical examination reveals core features of ataxia (i.e., dysarthria, truncal, gait and limb ataxia, oculomotor dysfunction) and is sufficient for formulating a differential diagnosis. Clinical assessment of oculomotor function, especially saccades and the vestibulo-ocular reflex (VOR) which are most easily examined both at the bedside and with quantitative testing techniques, is of particular help for differential diagnosis in many cases. Pure clinical measures, however, are not sensitive enough to reveal minute fluctuations or early treatment response as most relevant for pre-clinical stages of disease which might be amenable to study in future intervention trials. The authors agree that quantitative measures of ataxia are desirable as biomarkers. Methods are discussed that allow quantification of ataxia in laboratory as well as in clinical and real-life settings, for instance at the patients' home. Future studies are needed to demonstrate their usefulness as biomarkers in pharmaceutical or rehabilitation trials.


Assuntos
Ataxia Cerebelar/diagnóstico , Ataxia Cerebelar/fisiopatologia , Eletrodiagnóstico , Humanos
6.
Physiology (Bethesda) ; 31(2): 95-107, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26889015

RESUMO

People with Parkinson's disease exhibit debilitating gait impairments, including gait slowness, increased step variability, and poor postural control. A widespread supraspinal locomotor network including the cortex, cerebellum, basal ganglia, and brain stem contributes to the control of human locomotion, and altered activity of these structures underlies gait dysfunction due to Parkinson's disease.


Assuntos
Encéfalo/fisiopatologia , Marcha/fisiologia , Locomoção/fisiologia , Doença de Parkinson/fisiopatologia , Transtornos Parkinsonianos/fisiopatologia , Caminhada/fisiologia , Animais , Humanos
7.
Allergy ; 72(3): 416-424, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27455132

RESUMO

BACKGROUND: Several hydrolyzed cow's milk (CM) formulas are available for avoidance of allergic reactions in CM-allergic children and for prevention of allergy development in high-risk infants. Our aim was to compare CM formulas regarding the presence of immunoreactive CM components, IgE reactivity, allergenic activity, ability to induce T-cell proliferation, and cytokine secretion. METHODS: A blinded analysis of eight CM formulas, one nonhydrolyzed, two partially hydrolyzed (PH), four extensively hydrolyzed (EH), and one amino acid formula, using biochemical techniques and specific antibody probes was conducted. IgE reactivity and allergenic activity of the formulas were tested with sera from CM-allergic patients (n = 26) in RAST-based assays and with rat basophils transfected with the human FcεRI, respectively. The induction of T-cell proliferation and the secretion of cytokines in Peripheral blood mononuclear cell (PBMC) culture from CM allergic patients and nonallergic individuals were assessed. RESULTS: Immune-reactive α-lactalbumin and ß-lactoglobulin were found in the two PH formulas and casein components in one of the EH formulas. One PH formula and the EH formula containing casein components showed remaining IgE reactivity, whereas the other hydrolyzed formulas lacked IgE reactivity. Only two EH formulas and the amino acid formula did not induce T-cell proliferation and proinflammatory cytokine release. The remaining formulas varied regarding the induction of Th2, Th1, and proinflammatory cytokines. CONCLUSION: Our results show that certain CM formulas without allergenic and low proinflammatory properties can be identified and they may also explain different outcomes obtained in clinical studies using CM formulas.


Assuntos
Alérgenos/imunologia , Citocinas/metabolismo , Fórmulas Infantis/efeitos adversos , Leite/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Animais , Especificidade de Anticorpos/imunologia , Biomarcadores , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Lactente , Mediadores da Inflamação/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Ativação Linfocitária , Masculino
8.
Allergy ; 72(7): 1035-1042, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28122133

RESUMO

BACKGROUND: Allergen exposure chambers (AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities. METHODS: For this task force initiative of the European Academy of Allergy and Clinical Immunology (EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation. RESULTS: The latter covered the validation process, standardization of challenges and outcomes, intra- and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues. CONCLUSION: This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future.


Assuntos
Alérgenos/imunologia , Dessensibilização Imunológica/métodos , Ambiente Controlado , Exposição por Inalação , Dessensibilização Imunológica/normas , Dessensibilização Imunológica/tendências , Política de Saúde , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/terapia , Exposição por Inalação/efeitos adversos , Reprodutibilidade dos Testes
9.
J Neurophysiol ; 114(3): 1417-23, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26108960

RESUMO

The effects of deep brain stimulation (DBS) on balance in people with Parkinson's disease (PD) are not well established. This study examined whether DBS randomized to the subthalamic nucleus (STN; n = 11) or globus pallidus interna (GPi; n = 10) improved compensatory stepping to recover balance after a perturbation. The standing surface translated backward, forcing subjects to take compensatory steps forward. Kinematic and kinetic responses were recorded. PD-DBS subjects were tested off and on their levodopa medication before bilateral DBS surgery and retested 6 mo later off and on DBS, combined with off and on levodopa medication. Responses were compared with PD-control subjects (n = 8) tested over the same timescale and 17 healthy control subjects. Neither DBS nor levodopa improved the stepping response. Compensatory stepping in the best-treated state after surgery (DBS+DOPA) was similar to the best-treated state before surgery (DOPA) for the PD-GPi group and the PD-control group. For the PD-STN group, there were more lateral weight shifts, a delayed foot-off, and a greater number of steps required to recover balance in DBS+DOPA after surgery compared with DOPA before surgery. Within the STN group five subjects who did not fall during the experiment before surgery fell at least once after surgery, whereas the number of falls in the GPi and PD-control groups were unchanged. DBS did not improve the compensatory step response needed to recover from balance perturbations in the GPi group and caused delays in the preparation phase of the step in the STN group.


Assuntos
Estimulação Encefálica Profunda/efeitos adversos , Globo Pálido/fisiologia , Doença de Parkinson/fisiopatologia , Equilíbrio Postural , Núcleo Subtalâmico/fisiologia , Caminhada , Idoso , Fenômenos Biomecânicos , Estudos de Casos e Controles , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/terapia
10.
Clin Exp Allergy ; 45(8): 1346-55, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25900517

RESUMO

BACKGROUND: Allergic rhinitis (AR) is a common chronic disease, which has significant detrimental effect on well-being and quality of life as well as substantial socio-economic impact. Combination pharmacotherapy is utilized by 40-50% of patients to treat their symptoms. OBJECTIVE: To compare the effects of intranasal fluticasone furoate (FF)/levocabastine (LEVO) fixed-dose combination (FDC) with each component alone on allergen-induced nasal and ocular symptoms. METHODS: A randomized, double-blind, placebo-controlled, three-way, incomplete block, cross-over, proof-of-concept study in 71 patients with AR, evaluated FF 100 µg, LEVO 200 µg and FDC (FF 100/LEVO 200 µg), once daily via intranasal spray for 8 days. On days 1 and 8, total nasal symptom score (TNSS) and total ocular symptom score (TOSS) were assessed every 15 min during a 4-h allergen exposure in the Vienna Challenge Chamber. The primary endpoint was Day 8 weighted mean TNSS. RESULTS: After 8 days, FDC resulted in both statistically and clinically significant reductions in mean TNSS compared with FF and LEVO alone [adjusted mean differences (95% CI): FDC vs. FF: -2.26 (-2.90, -1.62); FDC vs. LEVO: -2.57 (-3.21, -1.93)]. All active treatments were significantly superior to placebo [adjusted mean difference (95% CI) from placebo: FDC: -4.1 (-4.86, -3.34); FF: -1.84 (-2.66, -1.03); LEVO: -1.53 (-2.34, -0.72)]. Onset of action was rapid following FDC and LEVO treatment with an approximate two unit reduction in mean TNSS from pre-dose levels by 30 min and 1 h. Mean TOSS was also reduced following all active treatments relative to placebo (range 0.6-0.8 unit reduction). All treatments were equally well tolerated. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggest that once daily FF/LEVO FDC could provide a clinical therapeutic advantage to existing standard monotherapies in the treatment of moderate-to-severe AR, and support progression to evaluation in larger phase III clinical studies.


Assuntos
Androstadienos/administração & dosagem , Piperidinas/administração & dosagem , Rinite Alérgica/tratamento farmacológico , Adolescente , Adulto , Idoso , Androstadienos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperidinas/efeitos adversos
11.
Allergy ; 70(4): 355-65, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25640808

RESUMO

The allergen challenge test has been the mainstay of diagnosis of allergic diseases for a long time since it offers a direct proof of the clinical relevance of a particular allergen for the allergic disease symptoms and severity. Standardisation and availability for daily practice (including safety issues) are still to be refined but most of the challenge tests have safely crossed the border from research tools to diagnostic tests available for daily practice for a well trained clinical staff.


Assuntos
Alérgenos/imunologia , Hipersensibilidade/diagnóstico , Hipersensibilidade/imunologia , Animais , Mordeduras e Picadas , Testes de Provocação Brônquica/efeitos adversos , Testes de Provocação Brônquica/instrumentação , Testes de Provocação Brônquica/métodos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/imunologia , Alimentos/efeitos adversos , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/imunologia , Humanos , Testes de Provocação Nasal/efeitos adversos , Testes de Provocação Nasal/instrumentação , Testes de Provocação Nasal/métodos , Testes Cutâneos , Peçonhas/imunologia
12.
BMC Neurol ; 15: 218, 2015 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-26499867

RESUMO

BACKGROUND: There is emerging research detailing the relationship between balance/gait/falls and cognition. Imaging studies also suggest a link between structural and functional changes in the frontal lobe (a region commonly associated with cognitive function) and mobility. People with Parkinson's disease have important changes in cognitive function that may impact rehabilitation efficacy. Our underlying hypothesis is that cognitive function and frontal lobe connections with the basal ganglia and brainstem posture/locomotor centers are responsible for postural deficits in people with Parkinson's disease and play a role in rehabilitation efficacy. The purpose of this study is to 1) determine if people with Parkinson's disease can improve mobility and/or cognition after partaking in a cognitively challenging mobility exercise program and 2) determine if cognition and brain circuitry deficits predict responsiveness to exercise rehabilitation. METHODS/DESIGN: This study is a randomized cross-over controlled intervention to take place at a University Balance Disorders Laboratory. The study participants will be people with Parkinson's disease who meet inclusion criteria for the study. The intervention will be 6 weeks of group exercise (case) and 6 weeks of group education (control). The exercise is a cognitively challenging program based on the Agility Boot Camp for people with PD. The education program is a 6-week program to teach people how to better live with a chronic disease. The primary outcome measure is the MiniBESTest and the secondary outcomes are measures of mobility, cognition and neural imaging. DISCUSSION: The results from this study will further our understanding of the relationship between cognition and mobility with a focus on brain circuitry as it relates to rehabilitation potential. TRIAL REGISTRATION: This trial is registered at clinical trials.gov (NCT02231073).


Assuntos
Encéfalo/patologia , Transtornos Cognitivos , Terapia por Exercício/métodos , Avaliação de Resultados em Cuidados de Saúde , Doença de Parkinson , Equilíbrio Postural/fisiologia , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/reabilitação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Doença de Parkinson/reabilitação , Educação de Pacientes como Assunto , Prognóstico
13.
Laryngorhinootologie ; 99(10): 676-679, 2020 10.
Artigo em Alemão | MEDLINE | ID: mdl-32823368
14.
Front Digit Health ; 6: 1435693, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39253055

RESUMO

Introduction: Digital health technologies (DHTs) have the potential to alleviate challenges experienced in clinical trials through more objective, naturalistic, and frequent assessments of functioning. However, implementation of DHTs come with their own challenges, including acceptability and ease of use for study participants. In addition to acceptability, it is also important to understand device proficiency in the general population and within patient populations who may be asked to use DHTs for extended periods of time. We thus aimed to provide an overview of participant feedback on acceptability of DHTs, including body-worn sensors used in the clinic and a mobile application used at-home, used throughout the duration of the Wearable Assessments in the Clinic and at Home in Parkinson's Disease (WATCH-PD) study, an observational, longitudinal study looking at disease progression in early Parkinson's Disease (PD). Methods: 82 participants with PD and 50 control participants were enrolled at 17 sites throughout the United States and followed for 12 months. We assessed participants' general device proficiency at baseline, using the Mobile Device Proficiency Questionnaire (MDPQ). The mean MDPQ score at Baseline did not significantly differ between PD patients and healthy controls (20.6 [2.91] vs 21.5 [2.94], p = .10). Results: Questionnaire results demonstrated that participants had generally positive views on the comfort and use of the digital technologies throughout the duration of the study, regardless of group. Discussion: This is the first study to evaluate patient feedback and impressions of using technology in a longitudinal observational study in early Parkinson's Disease. Results demonstrate device proficiency and acceptability of various DHTs in people with Parkinson's does not differ from that of neurologically healthy older adults, and, overall, participants had a favorable view of the DHTs deployed in the WATCH-PD study.

16.
Clin Exp Allergy ; 43(5): 568-77, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23600548

RESUMO

BACKGROUND: Sustained efficacy over three pollen seasons of pre- and co-seasonal treatment with 300IR 5-grass pollen sublingual tablet has been demonstrated in adults with moderate-severe grass pollen-associated allergic rhinoconjunctivitis. OBJECTIVE: To assess the efficacy of discontinuous treatment with 300IR 5-grass pollen sublingual tablet during the post-treatment pollen season of this long-term study. METHODS: Adults aged 18-50, sensitized to grass pollen, with a history of allergic rhinoconjunctivitis for more than two pollen seasons, and a retrospective rhinoconjunctivitis total symptom score ≥ 12 (0-18 scale), were randomized to receive Placebo or a 300IR tablet daily beginning either 4 months (4M) or 2 months (2M) prior to each pollen season and continuing for its duration for three consecutive years. They were followed over the subsequent immunotherapy-free pollen season. Post-treatment efficacy was evaluated using the Average Adjusted Symptom Score (AAdSS, adjusting the Rhinoconjunctivitis Total Symptom Score for rescue medication usage) during the post-treatment pollen period. Secondary endpoints included Average Rhinoconjunctivitis Total Symptom Score (ARTSS), Average Rescue Medication Score (ARMS), overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score and safety evaluation. Efficacy variables were analysed using ancova. RESULTS: Overall, 435 patients contributed to the Year 4 efficacy analyses. The Least-Squares (LS) mean differences (95% confidence interval) in AAdSS between active treatment and Placebo over the fourth pollen period were -1.14 (-2.03; -0.26) (P = 0.0114) and -1.43 (-2.32; -0.53) (P = 0.0019) in the (4M) and (2M) groups, corresponding to -22.9% and -28.5% relative LS mean differences (vs. Placebo) respectively. The active groups also showed statistically significant differences compared to Placebo in ARTSS, ARMS and overall RQLQ score. No safety risk was identified during the post-treatment period. CONCLUSIONS AND CLINICAL RELEVANCE: Pre- and co-seasonal treatment with 300IR 5-grass pollen sublingual tablet administered discontinuously for three consecutive years is efficacious post-treatment, safe and well tolerated. Benefits of treatment were meaningful to patients.


Assuntos
Alérgenos/imunologia , Conjuntivite Alérgica/imunologia , Conjuntivite Alérgica/terapia , Dessensibilização Imunológica , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/terapia , Administração Sublingual , Adolescente , Adulto , Alérgenos/administração & dosagem , Conjuntivite Alérgica/diagnóstico , Dessensibilização Imunológica/efeitos adversos , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Rinite Alérgica Sazonal/diagnóstico , Estações do Ano , Resultado do Tratamento , Adulto Jovem
17.
Clin Exp Allergy ; 43(12): 1362-73, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24261946

RESUMO

BACKGROUND: During allergen-specific sublingual immunotherapy (SLIT), the relevance of changes in specific IgE and IgG antibody titres to treatment efficacy remains to be evaluated at an individual patient level. OBJECTIVE: To investigate whether antibody responses can be used as biomarkers for SLIT efficacy. METHODS: Comprehensive quantitative, qualitative and functional analyses of allergen-specific IgA, IgE, IgG1-4 and IgM responses were performed using purified Phl p 1 to 12 allergens in sera, saliva and nasal secretions from 82 grass pollen allergic patients. These patients were enrolled in a randomized, double-blind placebo-controlled study and assessed in an allergen challenge chamber (ClinicalTrials.gov NCT00619827). Antibody responses were monitored in parallel to clinical responses before and after daily sublingual treatment for 4 months with either a grass pollen or a placebo tablet. RESULTS: A significant mean improvement (i.e. 33-40.6%) in rhinoconjunctivitis total symptom scores was observed in SLIT recipients, irrespective of their baseline patterns of IgE sensitization (i.e. narrow, intermediate, broad) to grass pollen allergens. SLIT did not induce any de novo IgE sensitization. Clinical responders encompassed both immunoreactive patients who exhibited strong increases in titres, affinity and/or blocking activity of grass-pollen-specific IgGs (representing 17% of treated patients), as well as patients with no detectable antibody responses distinguishing them from the placebo group. No significant changes were detected in antibody titres in saliva and nasal washes, even in clinical responders. CONCLUSIONS AND CLINICAL RELEVANCE: Sublingual immunotherapy with a grass pollen tablet is efficacious irrespective of the patients' baseline sensitization to either single or multiple grass pollen allergens. Seric IgG responses may contribute to SLIT-induced clinical tolerance in a fraction (i.e. 17%) of patients, but additional immune mechanisms are involved in most patients. Consequently, antibody responses cannot be used as a marker of SLIT efficacy at an individual patient level.


Assuntos
Alérgenos/imunologia , Poaceae/efeitos adversos , Pólen/imunologia , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/terapia , Imunoterapia Sublingual , Alérgenos/administração & dosagem , Anticorpos/sangue , Anticorpos/imunologia , Anticorpos/metabolismo , Humanos , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Rinite Alérgica Sazonal/metabolismo , Resultado do Tratamento
18.
Contemp Clin Trials Commun ; 35: 101165, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37538197

RESUMO

Background: Methods for modulating the cerebellum with transcranial magnetic stimulation (TMS) are well established, and preliminary data from our group and others has shown evidence of transient improvements in balance after cerebellar repetitive transcranial magnetic stimulation (rTMS) in progressive suprancuclear palsy (PSP). This study examines extensive posturography measures before and after 10 sessions of cerebellar rTMS and sham TMS in PSP. Methods: Thirty subjects with PSP and postural instability will undergo cerebellar active and sham rTMS in a single-blind, crossover design with a randomized order of a 10-day intervention. Primary outcomes will be changes in sway area and medio-lateral range of sway with eyes open while standing on a stationary force-plate, and safety, tolerability, and blindedness. Secondary outcomes will include posturography and gait analysis with body-worn, triaxial inertial sensors, clinical balance scales and questionnaires, and a bedside test of vestibular function. Exploratory outcomes are changes in functional near infrared spectroscopy (fNIRS) signal over the prefrontal, supplementary motor, and primary motor cortices while standing and walking, and speech samples for future analysis. Discussion: The C-STIM crossover intervention study adds a longer duration of stimulation and extensive posturography measures to more finely measure the improvements in balance and exploratory functional near-infrared spectroscopy (fNIRS) over the prefronal, supplementary motor, and primary motor cortices during balance assessments before and after 10 sessions of cerebellar rTMS and 10 sessions of sham cerebellar TMS. This project will improve our understanding of the importance of the cerebellum for control of postural stability in PSP.

19.
Clin Exp Allergy ; 42(12): 1745-55, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23181790

RESUMO

BACKGROUND: Surrogate biomarkers of efficacy are needed in support of allergen-specific immunotherapy. OBJECTIVE: The aim of this study was to relate changes in peripheral CD4(+) T cell responses to clinical efficacy during sublingual immunotherapy (SLIT). METHODS: Allergen-specific CD4(+) T cell responses were assessed in peripheral blood mononuclear cells (PBMCs) from 89 grass pollen-allergic individuals enrolled in a double-blind placebo-controlled SLIT study conducted in an allergen exposure chamber (ClinicalTrials.gov NCT00619827). Surface phenotype, proliferative responses, cytokine production and gene expression were analysed in coded samples at baseline, and after 2 and 4 months of SLIT, in PBMCs after in vitro allergen stimulation or among MHC class II/peptide (pMHCII)-tetramer-positive CD4(+) T cells. RESULTS: SLIT induced a 29.3% improvement of the average rhinoconjunctivitis total symptom score in the active group, when compared to the placebo group. In parallel, only minor changes in proportions of CD4(+) T cells expressing Th1 (CCR5(+), CXCR3(+)), Th2 (CRTh2(+), CCR4(+)) and Treg (CD25(+), CD127(-), Foxp3(+)) markers were detected. A down-regulation of IL-4 and IL-10 gene expression and IL-10 secretion (P < 0.001) were observed, as well as a decrease in the frequency of potential "pro-allergic" CD27(-) Th2 cells from patients receiving active tablets (P < 0.001), but without any correlation with clinical benefit. pMHCII-tetramer analyses failed to document any major impact in both numbers and polarization of circulating Phl p 1- and Phl p 5-specific CD4(+) T cells, confirming that early clinical improvement during SLIT is not associated with dramatic alterations in T lymphocyte responses. CONCLUSION & CLINICAL RELEVANCE: Changes in patterns of peripheral CD4(+) T cells are not markers for the early onset of efficacy during SLIT.


Assuntos
Alérgenos/imunologia , Linfócitos T CD4-Positivos/imunologia , Conjuntivite Alérgica/terapia , Dessensibilização Imunológica/métodos , Proteínas de Plantas/imunologia , Poaceae/imunologia , Rinite Alérgica Sazonal/terapia , Administração Sublingual , Alérgenos/administração & dosagem , Antígenos de Plantas/administração & dosagem , Antígenos de Plantas/imunologia , Conjuntivite Alérgica/imunologia , Citocinas/metabolismo , Método Duplo-Cego , Feminino , Humanos , Ativação Linfocitária , Masculino , Proteínas de Plantas/administração & dosagem , Pólen/imunologia , Valor Preditivo dos Testes , Rinite Alérgica Sazonal/imunologia , Resultado do Tratamento
20.
Allergy ; 67(12): 1572-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23025511

RESUMO

BACKGROUND: CRTH2 mediates activation of Th2 cells, eosinophils and basophils in response to prostaglandin D(2). The CRTH2 antagonist OC000459 has previously been demonstrated to reduce airway inflammation and improve lung function in moderate persistent asthma. The objective of the present study was to determine the involvement of CRTH2 in promoting nasal and ocular symptoms in allergic subjects exposed to grass pollen. METHODS: A single centre, randomised, double-blind, placebo-controlled, two-way crossover study was conducted in 35 male subjects allergic to grass pollen comparing OC000459 200 mg bid with placebo for 8 days. Subjects were exposed to grass pollen (≥ 1400 grains/m(3)) for 6 h on the 2nd and 8th days of treatment and assessed for nasal symptoms, ocular symptoms, other symptoms, nasal secretion weight and rhinomanometry over the 6-h period. After a washout period of 3 weeks, subjects were switched to the alternative treatment for a further 8 days. The trial was registered on the clinical trials.gov database (Identifier NCT01448902). RESULTS: During the first treatment period, treatment with OC000459 significantly reduced both nasal and ocular symptoms in allergic subjects compared with placebo after challenge with grass pollen. A significant effect was observed on the 2nd day of dosing which was increased on the 8th day of dosing. The therapeutic effects of OC000459 persisted into the second treatment period despite a 3-week washout phase. The safety profile of OC000459 was similar to that of placebo. CONCLUSION: Treatment with OC000459 was well tolerated and led to a significant and persistent reduction in the symptoms of rhinoconjunctivitis.


Assuntos
Alérgenos/imunologia , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/imunologia , Ácidos Indolacéticos/uso terapêutico , Poaceae/imunologia , Pólen/imunologia , Quinolinas/uso terapêutico , Receptores Imunológicos/antagonistas & inibidores , Receptores de Prostaglandina/antagonistas & inibidores , Adulto , Conjuntivite Alérgica/tratamento farmacológico , Conjuntivite Alérgica/imunologia , Humanos , Ácidos Indolacéticos/efeitos adversos , Ácidos Indolacéticos/farmacologia , Masculino , Quinolinas/efeitos adversos , Quinolinas/farmacologia , Rinite Alérgica Sazonal/tratamento farmacológico , Rinite Alérgica Sazonal/imunologia , Resultado do Tratamento , Adulto Jovem
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