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1.
J Craniofac Surg ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506523

RESUMO

OBJECTIVE: Crouzon syndrome with acanthosis nigricans (CAN) is caused by the specific mutation c.1172C>A (p.Ala391Glu) in the fibroblast growth factor receptor 3 gene, and has an estimated prevalence of 1:1,000,000 births. Most cases occur de novo; however, autosomal dominant inheritance may occur. The clinical presentation typically includes craniosynostosis, midface and maxillary hypoplasia, choanal atresia/stenosis, hydrocephalus, and intracranial hypertension. Patients develop acanthosis nigricans, a hyperkeratotic skin disorder. The authors present the first known study to investigate the speech, language, hearing, and feeding of patients with CAN. METHODS: A retrospective case-note review of patients with a genetically confirmed diagnosis of CAN attending the Oxford Craniofacial Unit during a 36-year period (1987-2023) was undertaken. RESULTS: Participants were 6 patients with genetically-confirmed CAN (5 females, 1 male), all cases arose de novo. All patients had craniosynostosis (n = 5/6 multisuture synostosis, n = 1/6 left unicoronal synostosis). Hydrocephalus was managed through ventriculoperitoneal shunt in 67% (n = 4/6) of patients, and 67% (n = 4/6) had a Chiari 1 malformation. Patients had a complex, multifactorial feeding history complicated by choanal atresia/stenosis (100%; n = 6/6), and significant midface hypoplasia. All patients required airway management through tracheostomy (83%; n = 5/6); and/or continuous positive airway pressure (67%; n = 4/6). All patients underwent adenotonsillectomy (100%; n = 6/6). Initial failure to thrive, low weight, and/or height were seen in 100% (n = 6/6) patients; 80% (n = 4/5) had reflux; 100% (n = 6/6) had nasogastric, or percutaneous endoscopic gastrostomy based feeding during their treatment journey. All patients had hearing loss (100%; n = 6/6). Early communication difficulties were common: receptive language disorder (50%; n = 3/6); expressive language disorder (50%; n = 3/6); and speech sound disorder in 50% (n = 3/6)-necessitating the use of Makaton in 80% of patients (n = 3/5). CONCLUSIONS: Patients with CAN experience significant respiratory, neurological, and structural obstacles to hearing, speech, language, and feeding. The authors present a recommended pathway for management to support patients in these domains.

2.
Cochrane Database Syst Rev ; 12: CD008669, 2019 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-31886897

RESUMO

BACKGROUND: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is a rare clinical syndrome of unknown cause usually identified in children. Tonsillectomy is considered a potential treatment option for this syndrome. This is an update of a Cochrane Review first published in 2010 and previously updated in 2014. OBJECTIVES: To assess the effectiveness and safety of tonsillectomy (with or without adenoidectomy) compared with non-surgical treatment in the management of children with PFAPA. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2019, Issue 4); PubMed; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 15 October 2019. SELECTION CRITERIA: Randomised controlled trials comparing tonsillectomy (with or without adenoidectomy) with non-surgical treatment in children with PFAPA. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. The primary outcomes were the proportion of children whose symptoms have completely resolved and complications of surgery (haemorrhage and number of days of postoperative pain). Secondary outcomes were: number of episodes of fever and the associated symptoms; severity of episodes; use of corticosteroids; absence or time off school; quality of life. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: Two trials were included with a total of 67 children randomised (65 analysed); we judged both to be at low risk of bias. One trial of 39 participants recruited children with PFAPA syndrome diagnosed according to rigid, standard criteria. The trial compared adenotonsillectomy to watchful waiting and followed up patients for 18 months. A smaller trial of 28 children applied less stringent criteria for diagnosing PFAPA and probably also included participants with alternative types of recurrent pharyngitis. This trial compared tonsillectomy alone to no treatment and followed up patients for six months. Combining the trial results suggests that patients with PFAPA likely experience less fever and less severe episodes after surgery compared to those receiving no surgery. The risk ratio (RR) for immediate resolution of symptoms after surgery that persisted until the end of follow-up was 4.38 (95% confidence interval (CI) 0.64 to 30.11); number needed to treat to benefit (NNTB) = 2, calculated based on an estimate that 156 in 1000 untreated children have a resolution) (moderate-certainty evidence). Both trials reported that there were no complications of surgery. However, the numbers of patients randomly allocated to surgery (19 and 14 patients respectively) were too small to detect potentially important complications such as haemorrhage. Surgery probably results in a large overall reduction in the average number of episodes over the total length of follow-up (rate ratio 0.08, 95% CI 0.05 to 0.13), reducing the average frequency of PFAPA episodes from one every two months to slightly less than one every two years (moderate-certainty evidence). Surgery also likely reduces severity, as indicated by the length of PFAPA symptoms during these episodes. One study reported that the average number of days per PFAPA episode was 1.7 days after receiving surgery, compared to 3.5 days in the control group (moderate-certainty evidence). The evidence suggests that the proportion of patients requiring corticosteroids was also lower in the surgery group compared to those receiving no surgery (RR 0.58, 95% CI 0.37 to 0.92) (low-certainty evidence). Other outcomes such as absence from school and quality of life were not measured or reported. AUTHORS' CONCLUSIONS: The evidence for the effectiveness of tonsillectomy in children with PFAPA syndrome is derived from two small randomised controlled trials. These trials reported significant beneficial effects of surgery compared to no surgery on immediate and complete symptom resolution (NNTB = 2) and a substantial reduction in the frequency and severity (length of episode) of any further symptoms experienced. However, the evidence is of moderate certainty (further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate) due to the relatively small sample sizes of the studies and some concerns about the applicability of the results. Therefore, the parents and carers of children with PFAPA syndrome must weigh the risks and consequences of surgery against the alternative of using medications. It is well established that children with PFAPA syndrome recover spontaneously and medication can be administered to try and reduce the severity of individual episodes. It is uncertain whether adenoidectomy combined with tonsillectomy adds any additional benefit to tonsillectomy alone.


Assuntos
Linfadenite/cirurgia , Faringite/cirurgia , Estomatite Aftosa/cirurgia , Tonsilectomia/métodos , Adenoidectomia/métodos , Criança , Pré-Escolar , Febre/cirurgia , Humanos , Lactente , Periodicidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome
3.
Ophthalmology ; 125(3): 432-443, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29110946

RESUMO

PURPOSE: To report the initial efficacy results of the Retina Implant Alpha AMS (Retina Implant AG, Reutlingen, Germany) for partial restoration of vision in end-stage retinitis pigmentosa (RP). DESIGN: Prospective, single-arm, investigator-sponsored interventional clinical trial. Within-participant control comprising residual vision with the retinal implant switched ON versus OFF in the implanted eye. PARTICIPANTS: The Retina Implant Alpha AMS was implanted into the worse-seeing eye of 6 participants with end-stage RP and no useful perception of light vision. Eligibility criteria included previous normal vision for ≥12 years and no significant ocular or systemic comorbidity. METHODS: Vision assessments were scheduled at 1, 2, 3, 6, 9, and 12 months postimplantation. They comprised tabletop object recognition tasks, a self-assessment mobility questionnaire, and screen-based tests including Basic Light and Motion (BaLM), grating acuity, and greyscale contrast discrimination. A full-field stimulus test (FST) was also performed. MAIN OUTCOME MEASURES: Improvement in activities of daily living, recognition tasks, and assessments of light perception with the implant ON compared with OFF. RESULTS: All 6 participants underwent successful implantation. Light perception and temporal resolution with the implant ON were achieved in all participants. Light localization was achieved with the implant ON in all but 1 participant (P4) in whom the chip was not functioning optimally because of a combination of iatrogenic intraoperative implant damage and incorrect implantation. Implant ON correct grating detections (which were at chance level with implant OFF) were recorded in the other 5 participants, ranging from 0.1 to 3.33 cycles/degree on 1 occasion. The ability to locate high-contrast tabletop objects not seen with the implant OFF was partially restored with the implant ON in all but 1 participant (P4). There were 2 incidents of conjunctival erosion and 1 inferotemporal macula-on retinal detachment, which were successfully repaired, and 2 incidents of inadvertent damage to the implant during surgery (P3 and P4). CONCLUSIONS: The Alpha AMS subretinal implant improved visual performance in 5 of 6 participants and has exhibited ongoing function for up to 24 months. Although implantation surgery remains challenging, new developments such as OCT microscope guidance added refinements to the surgical technique.


Assuntos
Atividades Cotidianas , Retina/cirurgia , Retinose Pigmentar/cirurgia , Tomografia de Coerência Óptica/métodos , Acuidade Visual/fisiologia , Percepção Visual/fisiologia , Próteses Visuais , Eletrodos Implantados , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Desenho de Prótese , Retina/patologia , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/fisiopatologia , Método Simples-Cego , Resultado do Tratamento
4.
Cochrane Database Syst Rev ; (9): CD008669, 2014 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-25209127

RESUMO

BACKGROUND: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is a rare clinical syndrome of unknown cause usually identified in children. Tonsillectomy is considered a potential treatment option for this syndrome. This is an update of a Cochrane review first published in 2010. OBJECTIVES: To assess the effectiveness and safety of tonsillectomy (with or without adenoidectomy) in children with PFAPA. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 30 October 2013. SELECTION CRITERIA: Randomised controlled trials comparing tonsillectomy (with or without adenoidectomy) with non-surgical treatment in children with PFAPA. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: Two trials were included with a total of 67 children randomised (65 analysed); we judged both to be at low risk of bias.One trial of 39 participants recruited children with PFAPA syndrome diagnosed according to rigid, standard criteria. The trial compared adenotonsillectomy to watchful waiting and followed up patients for 18 months. A smaller trial of 28 children applied less stringent criteria for diagnosing PFAPA and probably also included participants with alternative types of recurrent pharyngitis. This trial compared tonsillectomy alone to no treatment and followed up patients for six months.Combining the trial results suggests that patients with PFAPA experience less fever and less severe episodes after surgery compared to those receiving no surgery. The risk ratio (RR) for immediate resolution of symptoms after surgery that persisted until the end of follow-up was 4.38 (95% confidence interval (CI) 0.64 to 30.11); number needed to treat to benefit (NNTB) = 2, calculated based on an estimate that 156 in 1000 untreated children have a resolution).There was a large overall reduction in the average number of episodes over the total length of follow-up in these studies (rate ratio 0.08, 95% CI 0.05 to 0.13), reducing the average frequency of PFAPA episodes from one every two months to slightly less than one every two years. The severity, as indicated by the length of PFAPA symptoms during these episodes, was also reduced. One study reported that the average number of days per PFAPA episode was 1.7 days after receiving surgery, compared to 3.5 days in the control group. The proportion of patients requiring corticosteroids was also lower in the surgery group compared to those receiving no surgery (RR 0.58, 95% CI 0.37 to 0.92).Both trials reported that there were no complications of surgery. However, the numbers of patients randomly allocated to surgery (19 and 14 patients respectively) were too small to detect potentially important complications such as haemorrhage. Other outcomes such as quality of life, number of days with pain after surgery and absence from school were not measured or reported. AUTHORS' CONCLUSIONS: The evidence for the effectiveness of tonsillectomy in children with PFAPA syndrome is derived from two small randomised controlled trials. These trials reported significant beneficial effects of surgery compared to no surgery on immediate and complete symptom resolution (NNTB = 2) and a substantial reduction in the frequency and severity (length of episode) of any further symptoms experienced. However, the evidence is of moderate quality (further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate) due to the relatively small sample sizes of the studies and some concerns about the applicability of the results. Therefore, the parents and carers of children with PFAPA syndrome must weigh the risks and consequences of surgery against the alternative of using medications. It is well established that children with PFAPA syndrome recover spontaneously and medication can be administered to try and reduce the severity of individual episodes. It is uncertain whether adenoidectomy combined with tonsillectomy adds any additional benefit to tonsillectomy alone.


Assuntos
Febre/cirurgia , Faringite/cirurgia , Estomatite Aftosa/cirurgia , Tonsilectomia , Adenoidectomia , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Linfadenite/cirurgia , Pescoço , Periodicidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Remissão Espontânea , Síndrome , Conduta Expectante
5.
Ann Otol Rhinol Laryngol ; 123(7): 485-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24690980

RESUMO

OBJECTIVE: The development of second-side Ménière's disease in the only remaining serviceable ear is difficult to treat. We describe an intervention to control disabling disease combining a labyrinthectomy and cochlear implant to restore hearing. METHODS: Following a thorough preoperative assessment and consenting process, 2 patients underwent labyrinthectomy of the affected ear with simultaneous cochlear implantation. RESULTS: Both patients achieved control of Ménière's attacks with improved hearing rehabilitation. Oscillopsia was noted by both patients. Both patients were pleased to have undergone the treatment. CONCLUSION: Severe symptomatic second-side Ménière's disease in the only hearing ear is uncommon. We report the successful treatment of 2 patients in this difficult management scenario, by simultaneous surgical labyrinthectomy and cochlear implantation. We propose this as a potential management strategy in this rare but complex group of patients in whom all less destructive measures have failed.


Assuntos
Implante Coclear , Orelha Interna/cirurgia , Perda Auditiva Bilateral/cirurgia , Doença de Meniere/cirurgia , Adulto , Perda Auditiva Bilateral/etiologia , Humanos , Masculino , Doença de Meniere/complicações , Pessoa de Meia-Idade
6.
J Craniofac Surg ; 23(4): 1020-2, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22777462

RESUMO

Children with congenital craniosynostosis syndromes have a high incidence of obstructive sleep apnea (OSA). Obstructive sleep apnea has significant consequences including impaired growth, learning and behavioral problems, and cardiovascular morbidity. Adenotonsillectomy is the treatment of choice for OSA in otherwise healthy children. In children with craniosynostosis syndromes, airway abnormalities may exist at multiple levels, but midface hypoplasia leading to a reduced nasopharyngeal airway is a common significant factor; here, even normal-sized adenoids and tonsils may contribute to obstruction. To date, few studies have evaluated adenotonsillectomy for the treatment of OSA in children with syndromic craniosynostosis. In this study, we assessed the effectiveness of adenotonsillectomy by comparing preoperative and postoperative sleep study data. We also evaluated whether adenotonsillectomy could obviate the need for tracheostomy in these patients. Five children with syndromic craniosynostosis and moderate to severe OSA underwent adenotonsillectomy at a mean age of 4.0 years (range, 1.7-5.1 y). Two patients (40%) showed improvement in OSA severity grade and 1 patient had complete resolution. Three children (60%) avoided tracheostomy and had no further airway surgery. Our results provide evidence to support the use of adenotonsillectomy in treating OSA in children with syndromic craniosynostosis. Adenotonsillectomy should be considered before tracheostomy or more major surgery in this patient group.


Assuntos
Adenoidectomia , Craniossinostoses/complicações , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/cirurgia , Tonsilectomia , Criança , Pré-Escolar , Craniossinostoses/fisiopatologia , Feminino , Humanos , Masculino , Polissonografia , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/fisiopatologia , Resultado do Tratamento
7.
Cochrane Database Syst Rev ; (9): CD008669, 2010 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-20824883

RESUMO

BACKGROUND: PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome) is a rare clinical syndrome of unknown cause usually identified in children. OBJECTIVES: To assess the efficacy of tonsillectomy (with or without adenoidectomy) in children with PFAPA. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2010 Issue 1); MEDLINE (PubMed); EMBASE; CINAHL; mRCT (metaRegister of clinical trials, including ClinicalTrials.gov); NRR (National Research Register); LILACS; KoreaMed; IndMed; PakMediNet; China Knowledge Network; CAB Abstracts; Web of Science; BIOSIS Previews; ICTRP (International Clinical Trials Registry Platform) and Google. The date of the last search was 21 January 2010. SELECTION CRITERIA: Randomised studies comparing adeno-/tonsillectomy with non-surgical treatment. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: Two trials involving 67 children were included. One high quality study demonstrated a dramatic benefit of adenotonsillectomy in children with PFAPA diagnosed according to rigid, standard criteria with a relative 'risk' (RR) of symptom resolution after 18 months of 12.63 (95% CI 1.81 to 87.98) and a lower rate of episodes per patient-month (rate ratio 0.07; 95% CI 0.04 to 0.13). A less methodologically rigorous study enrolled some children with PFAPA, but probably included others with alternative types of recurrent pharyngitis, and performed tonsillectomy alone. This also demonstrated a significant benefit for surgery at six months: RR 1.93 (95% CI 1.11 to 3.36); rate ratio episodes per patient-month 0.10 (95% CI 0.04 to 0.28). The pooled relative risk of symptom resolution was 3.25 (95% CI 1.78 to 5.92) and the resulting number needed to treat (NNT) 2 (95% CI 1 to 3). AUTHORS' CONCLUSIONS: The trials included in this review reported follow up at 18 and six months respectively but it is well-established that children with PFAPA recover spontaneously and treatment can be administered to try and reduce the severity of individual episodes. Therefore, the parents and carers of children with PFAPA must weigh the risks and consequences of surgery (hospitalisation, a predictable period of time postoperatively away from school/nursery, the risks of surgery) against the alternative of a finite period of recurrent episodes of disease at predictable intervals, potentially requiring time off school and the regular use of medication. It is uncertain whether adenoidectomy combined with tonsillectomy adds any additional benefit to tonsillectomy alone.


Assuntos
Febre/cirurgia , Linfadenite/cirurgia , Periodicidade , Faringite/cirurgia , Estomatite Aftosa/cirurgia , Tonsilectomia , Adenoidectomia , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Pescoço , Ensaios Clínicos Controlados Aleatórios como Assunto , Remissão Espontânea , Síndrome
8.
Acta Ophthalmol ; 98(7): 736-740, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32343050

RESUMO

PURPOSE: To report the highest attained visual acuity with an electronic retinal implant for the treatment of advanced retinal degeneration following a novel intensive period of visual training. METHODS: A case study as part of the prospective, international, multi-centre, interventional clinical trial (ClinicalTrials.gov NCT02720640 and NCT01024803) of patients with the Retina Implant Alpha AMS (Retina Implant AG, Reutlingen, Germany) for advanced retinal degeneration. A patient with subretinal device implanted into worse-seeing eye with no useful perception of light vision secondary to USH2A retinal degeneration underwent intensive period of visual training. RESULTS: The device remains functional with no safety concerns at 3 years postsurgical implantation, and following visual training, the patient achieved the highest visual acuity so far with an electronic retinal device, with real, digitally unenhanced, reading vision of 0.04 decimal (equivalent to 1.39 LogMAR and 20/500 or 6/150 Snellen). In addition, perception as well as partial identification of obstacles and evaluation of distances was possible in both daylight and night-time settings. CONCLUSIONS: Retinal implants are currently the only available therapy option for advanced retinal degeneration. Visual rehabilitation postimplantation has potential to maximize visual percepts. The novel concept of intensive visual training presented herein shows what is achievable with electronic retinal implants and has implications for other therapeutic options, such as optogenetics, that aim to stimulate remaining inner retinal cells in advanced retinal degeneration.


Assuntos
Eletrônica , Retina/fisiopatologia , Degeneração Retiniana/fisiopatologia , Percepção Visual/fisiologia , Próteses Visuais , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Retina/cirurgia , Degeneração Retiniana/cirurgia , Acuidade Visual
9.
Cell Rep ; 30(1): 137-152.e5, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31914381

RESUMO

T follicular helper (Tfh) cells are fundamental for B cell selection and antibody maturation in germinal centers. Circulating Tfh (cTfh) cells constitute a minor proportion of the CD4+ T cells in peripheral blood, but their clonotypic relationship to Tfh populations resident in lymph nodes and the extent to which they differ from non-Tfh CD4+ cells have been unclear. Using donor-matched blood and tonsil samples, we investigate T cell receptor (TCR) sharing between tonsillar Tfh cells and peripheral Tfh and non-Tfh cell populations. TCR transcript sequencing reveals considerable clonal overlap between peripheral and tonsillar Tfh cell subsets as well as a clear distinction between Tfh and non-Tfh cells. Furthermore, influenza-specific cTfh cell clones derived from blood can be found in the repertoire of tonsillar Tfh cells. Therefore, human blood samples can be used to gain insight into the specificity of Tfh responses occurring in lymphoid tissues, provided that cTfh subsets are studied.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Células Clonais/citologia , Tonsila Palatina/imunologia , Células T Auxiliares Foliculares/imunologia , Adolescente , Adulto , Tamanho Celular , Simulação por Computador , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Subpopulações de Linfócitos/imunologia , Pessoa de Meia-Idade , Receptores CXCR3/metabolismo , Doadores de Tecidos , Adulto Jovem
11.
Laryngoscope ; 129(4): 974-980, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30456886

RESUMO

OBJECTIVES/HYPOTHESIS: This study set out to describe the progression of hearing loss in patients with neurofibromatosis type 2 (NF2), treated in a quaternary multidisciplinary clinic. It also aimed to compare hearing loss across patients grouped according to a known genetic severity score to explore its utility for prognostication. STUDY DESIGN: Retrospective cohort study. METHODS: We conducted a study of 147 patients with confirmed NF2 diagnosis for a mean observational period of 10 years. Pure-tone average (PTA), optimum discriminations scores (ODS), and genotype data were collected. Patients were classified according to hearing class (American Academy of Otolaryngology), their candidacy for auditory implantation (UK National NF2 consensus) and grouped by genetic severity as: 1 = tissue mosaic, 2A = mild classic, 2B = moderate classic, and 3 = severe. Survival analysis investigated the effect of genetic severity on the age of loss of serviceable hearing. RESULTS: Genetic severity was a significant predictor of hearing outcomes such as ODS, hearing classification, and maximum annual PTA deterioration. Although the overall median age of loss of serviceable hearing was 78 years, there was significant variation according to the genetic severity; the median for severe patients was 32 years compared to a median of 80 for tissue mosaic patients. CONCLUSIONS: This is the first description of long-term hearing outcomes in a clinical setting across a large heterogeneous cohort of patients with NF2. The results highlight the potential importance and benefit of considering the genetic severity score of patients when undertaking treatment decisions, as well as planning future natural history studies. LEVEL OF EVIDENCE: 2c Laryngoscope, 129:974-980, 2019.


Assuntos
Perda Auditiva/etiologia , Neurofibromatose 2/complicações , Neurofibromatose 2/genética , Adulto , Estudos de Coortes , Progressão da Doença , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença
12.
Front Neurosci ; 11: 445, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28878616

RESUMO

Purpose: We assessed the safety and efficacy of a technically advanced subretinal electronic implant, RETINA IMPLANT Alpha AMS, in end stage retinal degeneration in an interim analysis of two ongoing prospective clinical trials. The purpose of this article is to describe the interim functional results (efficacy). Methods: The subretinal visual prosthesis RETINA IMPLANT Alpha AMS (Retina Implant AG, Reutlingen, Germany) was implanted in 15 blind patients with hereditary retinal degenerations at four study sites with a follow-up period of 12 months (www.clinicaltrials.gov NCT01024803 and NCT02720640). Functional outcome measures included (1) screen-based standardized 2- or 4-alternative forced-choice (AFC) tests of light perception, light localization, grating detection (basic grating acuity (BaGA) test), and Landolt C-rings; (2) gray level discrimination; (3) performance during activities of daily living (ADL-table tasks). Results: Implant-mediated light perception was observed in 13/15 patients. During the observation period implant mediated localization of visual targets was possible in 13/15 patients. Correct grating detection was achieved for spatial frequencies of 0.1 cpd (cycles per degree) in 4/15; 0.33 cpd in 3/15; 0.66 cpd in 2/15; 1.0 cpd in 2/15 and 3.3 cpd in 1/15 patients. In two patients visual acuity (VA) assessed with Landolt C- rings was 20/546 and 20/1111. Of 6 possible gray levels on average 4.6 ± 0.8 (mean ± SD, n = 10) were discerned. Improvements (power ON vs. OFF) of ADL table tasks were measured in 13/15 patients. Overall, results were stable during the observation period. Serious adverse events (SAEs) were reported in 4 patients: 2 movements of the implant, readjusted in a second surgery; 4 conjunctival erosion/dehiscence, successfully treated; 1 pain event around the coil, successfully treated; 1 partial reduction of silicone oil tamponade leading to distorted vision (silicon oil successfully refilled). The majority of adverse events (AEs) were transient and mostly of mild to moderate intensity. Conclusions: Psychophysical and subjective data show that RETINA IMPLANT Alpha AMS is reliable, well tolerated and can restore limited visual functions in blind patients with degenerations of the outer retina. Compared with the previous implant Alpha IMS, longevity of the new implant Alpha AMS has been considerably improved. Alpha AMS has meanwhile been certified as a commercially available medical device, reimbursed in Germany by the public health system.

13.
Endocrinology ; 146(7): 2895-902, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15817662

RESUMO

In goiter, increased expression of growth factors and their receptors occurs. We have inhibited the action of some of these growth factors, alone and in combination, to determine which are important in goitrogenesis. Recombinant adenovirus vectors (RAds) expressing truncated, secreted forms of human Tie2 (RAd-sTie2) and vascular endothelial growth factor receptor 1 (RAd-sVEGFR1) or a truncated, dominant-negative fibroblast growth factor receptor 1 (RAdDN-FGFR1) were used. Goiters in mice were induced by feeding an iodide-deficient diet, containing methimazole and sodium perchlorate. RAds were administered to mice simultaneously with the goitrogenic regimen, which was continued for 14 d. RAd treatment did not significantly affect increases in TSH or reductions in thyroid hormone or thyroid hyperactivity seen in goitrogen-treated controls mice, suggesting no effect on pituitary or thyroid responses to hypothyroidism. In control goiters, a 4-fold increase in vascular volume accompanied a 2-fold increase in thyroid mass. Complete inhibition of these increases was found when animals were treated with the three RAds in combination. In thyroids from three RAd-treated animals, there was marked, significant inhibition of Tie2, FGFR1, VEGFR1, FGF-2, and VEGF expression, compared with control goiters. When used individually, RAdDN-FGFR1 partially prevented goiter and RAd-sVEGFR1 partially reduced vascular volume. Their effects were not additive. RAd-sTie2 did not reduce goiter mass or vascular volume when used alone but was essential for complete goiter inhibition. VEGF and VEGFR1 expression was reduced in these thyroids. Limitation of physiologic organ growth is complex, requiring inhibition of multiple, interdependent growth factor axes.


Assuntos
Terapia Genética , Bócio/genética , Bócio/terapia , Receptores Proteína Tirosina Quinases/genética , Receptor TIE-2/genética , Receptores de Fatores de Crescimento de Fibroblastos/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Angiopoietinas/antagonistas & inibidores , Angiopoietinas/metabolismo , Animais , Vasos Sanguíneos/patologia , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Fatores de Crescimento de Fibroblastos/metabolismo , Bócio/metabolismo , Bócio/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Receptores Proteína Tirosina Quinases/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Receptor TIE-2/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais , Glândula Tireoide/irrigação sanguínea , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
14.
J Laryngol Otol ; 119(4): 325-9, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15949093

RESUMO

A triad of retro-ocular pain, discharging ear and abducens nerve palsy, as described by Gradenigo, has been recognized for 150 years. It has traditionally been treated with surgery, but recent advances in imaging, allied with improved antibiotic treatment, allow conservative management of these cases. We present two cases of Gradenigo's syndrome: a 6-year-old child and a 70-year-old man, both without cholesteatoma, who were managed without mastoidectomy. They both had full recovery of abducens nerve function, although this took 6 and 12 weeks, respectively. In order to manage patients with Gradenigo's syndrome safely, accurate diagnostic radiology is essential, and our findings are presented and discussed. With changing medical technology, a review of the diagnostic and treatment options for this rare but serious condition, is timely.


Assuntos
Doenças do Nervo Abducente/terapia , Mastoidite/terapia , Osso Petroso , Doenças do Nervo Abducente/diagnóstico , Idoso , Criança , Humanos , Imageamento por Ressonância Magnética , Masculino , Mastoidite/diagnóstico , Otite Média Supurativa/diagnóstico , Otite Média Supurativa/terapia , Síndrome
15.
Vision Res ; 111(Pt B): 149-60, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25812924

RESUMO

A subretinal visual implant (Alpha IMS, Retina Implant AG, Reutlingen, Germany) was implanted in 29 blind participants with outer retinal degeneration in an international multicenter clinical trial. Primary efficacy endpoints of the study protocol were a significant improvement of activities of daily living and mobility to be assessed by activities of daily living tasks, recognition tasks, mobility, or a combination thereof. Secondary efficacy endpoints were a significant improvement of visual acuity/light perception and/or object recognition (clinicaltrials.gov, NCT01024803). During up to 12 months observation time twenty-one participants (72%) reached the primary endpoints, of which thirteen participants (45%) reported restoration of visual function which they use in daily life. Additionally, detection, localization, and identification of objects were significantly better with the implant power switched on in the first 3 months. Twenty-five participants (86%) reached the secondary endpoints. Measurable grating acuity was up to 3.3 cycles per degree, visual acuities using standardized Landolt C-rings were 20/2000, 20/2000, 20/606 and 20/546. Maximal correct motion perception ranged from 3 to 35 degrees per second. These results show that subretinal implants can restore very-low-vision or low vision in blind (light perception or less) patients with end-stage hereditary retinal degenerations.


Assuntos
Cegueira/reabilitação , Eletrodos Implantados , Percepção Visual/fisiologia , Atividades Cotidianas , Adulto , Idoso , Cegueira/etiologia , Cegueira/fisiopatologia , Feminino , Percepção de Forma/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Percepção de Movimento/fisiologia , Degeneração Retiniana/complicações , Degeneração Retiniana/fisiopatologia , Retinose Pigmentar/fisiopatologia , Acuidade Visual/fisiologia
16.
J Clin Endocrinol Metab ; 88(9): 4472-80, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12970326

RESUMO

Levels of fibroblast growth factor 2 (FGF-2) and its receptor, FGFR1, are elevated in goiter, but whether this is a direct effect of TSH is unknown. We have determined the regulation of FGF-2 and FGFR1 synthesis by TSH in a rat thyroid cell line (FRTL5) and have used a replication-defective adenovirus (RAd) expressing dominant negative FGFR1 (RAdDN-FGFR1) to examine the role of FGFR signaling in vitro and in goiter induced in mice. TSH induced FGF-2 and increased the expression of FGFR1 in FRTL5 cells. Infection of TSH-stimulated FRTL5 cells with RAdDN-FGFR1 inhibited growth and prevented FGF-2-mediated inhibition of (125)I uptake. Similar effects were found in primary cultures of human thyroid follicular cells. For in vivo experiments, male BALB/c mice were injected systemically with RAdDN-FGFR1 or RAd encoding green fluorescent protein, and goiter was simultaneously induced. Mouse thyroid follicles were shown to be transduced with RAd encoding green fluorescent protein. Circulating TSH was elevated comparably in the two groups. In the RAdDN-FGFR1-injected animals, goiter induced over 14 d was significantly smaller, and the vascular volume increase seen in goiter was also diminished. We conclude that the FGF axis is important in thyroid growth and that RAdDN-FGFR1 effectively blocks FGF actions, offering a means to control goitrogenesis.


Assuntos
Adenoviridae/genética , Fator 1 de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Regulação da Expressão Gênica/fisiologia , Genes Dominantes/genética , Vetores Genéticos/genética , Bócio/genética , Bócio/prevenção & controle , Glândula Tireoide/metabolismo , Animais , Vasos Sanguíneos/patologia , Western Blotting , Células Cultivadas , AMP Cíclico/farmacologia , Fator 1 de Crescimento de Fibroblastos/biossíntese , Bócio/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Radioimunoensaio , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Transdução de Sinais/genética , Testes de Função Tireóidea , Glândula Tireoide/citologia , Tireotropina/farmacologia , Tiroxina/sangue , Tri-Iodotironina/sangue , beta-Galactosidase/análise
17.
Int J Pediatr Otorhinolaryngol ; 78(3): 570-1, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24485974

RESUMO

We describe an unusual case of paradoxical vocal fold motion in a child with cerebral palsy. Clinically, the child presented with mild stridor, which worsened over months, eventually requiring emergency intubation. After an unsuccessful trial of medical management, microlaryngoscopy revealed abnormal adduction of the vocal folds during inspiration. This was successfully treated with periodic type A botulinum toxin injections to the vocal folds, sparing the child from tracheostomy.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Paralisia Cerebral/complicações , Disfunção da Prega Vocal/tratamento farmacológico , Disfunção da Prega Vocal/etiologia , Obstrução das Vias Respiratórias/diagnóstico , Obstrução das Vias Respiratórias/etiologia , Paralisia Cerebral/diagnóstico , Pré-Escolar , Esquema de Medicação , Seguimentos , Humanos , Injeções Intralesionais , Laringoscopia/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Recuperação de Função Fisiológica , Sons Respiratórios/diagnóstico , Sons Respiratórios/etiologia , Índice de Gravidade de Doença , Resultado do Tratamento , Disfunção da Prega Vocal/diagnóstico
18.
Otol Neurotol ; 34(7): 1291-8, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23921933

RESUMO

OBJECTIVE: Rehabilitation of hearing is complicated in patients with profound bilateral hearing loss in the presence of sporadic vestibular schwannoma (VS) or neurofibromatosis 2 (NF2), especially if the tumor does not need to be removed. We present the outcome of patients who have had a cochlear implant in the tumor affected ear without removal of the primary tumor. DESIGN: This is a retrospective multicentre study investigating outcomes of cochlear implantation in profoundly deaf patients with vestibular schwannoma in the implanted ear. MATERIALS AND METHODS: Out of 11 implanted patients, 5 required no treatment for their tumor, whereas 6 had previously undergone radiotherapy. Nine patients experienced NF2, and 2 had unilateral VS in the only hearing ear. Postoperative hearing was assessed with open and closed set speech discrimination, including City University of New York (CUNY) in noise and Bamford, Kowal and Bench (BKB) sentence scores. RESULTS: Patients with untreated lesions experienced marked improvement in their BKB and CUNY scores in the implanted ear and were daily cochlear implant users. The improvement was less consistent in the patients who had radiotherapy where only 1 patient attained open set speech discrimination. CONCLUSION: Patients with unilateral VS (sporadic or those affected with NF2) whose tumor status was stable, benefited from cochlear implantation in their tumor-affected ear. Patients who had radiotherapy also benefited from CI, but their outcomes were variable.


Assuntos
Implantes Cocleares , Surdez/etiologia , Surdez/reabilitação , Neuroma Acústico/complicações , Adolescente , Idoso , Idoso de 80 Anos ou mais , Audiometria de Tons Puros , Interpretação Estatística de Dados , Feminino , Lateralidade Funcional/fisiologia , Audição , Humanos , Masculino , Pessoa de Meia-Idade , Neurofibromatose 2/complicações , Neuroma Acústico/patologia , Neuroma Acústico/terapia , Equipe de Assistência ao Paciente , Estudos Retrospectivos , Testes de Discriminação da Fala , Resultado do Tratamento , Adulto Jovem
19.
Otol Neurotol ; 33(4): 561-5, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22569146

RESUMO

This is a consensus statement on pediatric cochlear implantation by the European Bilateral Pediatric Cochlear Implant Forum. The consensus statement was determined by review of current scientific literature to identify areas of scientific and clinical agreement of current understanding of bilateral cochlear implantation. The statement is "Currently we feel that the infant or child with unambiguous cochlear implant candidacy should receive bilateral cochlear implants simultaneously as soon as possible after definitive diagnosis of deafness to permit optimal auditory development; an atraumatic surgical technique designed to preserve cochlear function, minimize cochlear damage, and allow easy, possibly repeated re-implantation is recommended."


Assuntos
Implantes Cocleares , Surdez/fisiopatologia , Implante Coclear , Consenso , Surdez/diagnóstico , Surdez/cirurgia , Europa (Continente) , Perda Auditiva Bilateral/congênito , Perda Auditiva Bilateral/fisiopatologia , Perda Auditiva Bilateral/cirurgia , Humanos , Desenvolvimento da Linguagem , Percepção da Fala , Fatores de Tempo , Resultado do Tratamento
20.
Laryngoscope ; 121(4): 856-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21305555

RESUMO

A perilymphatic fistula (PLF) is an abnormal communication between the inner and middle ear resulting in vestibular or cochlear symptoms. We review three pediatric traumatic temporal bone fractures with pneumolabyrinth, confirmed radiologically by the presence of air within the cochlea (pneumocochlea) or vestibule (pneumovestibule). Patients were treated conservatively with complete resolution of vestibulopathy. Hearing outcome was variable and worse in two patients with pneumocochlea. A pneumolabyrinth on radiologic imaging confirms a PLF and obviates the need for exploration to reach a diagnosis. We suggest exploration be reserved for patients with persisting cerebrospinal fluid leakage, progressive sensorineural hearing loss, or vestibular symptomatology.


Assuntos
Ar , Traumatismos em Atletas/complicações , Ciclismo/lesões , Aqueduto da Cóclea/lesões , Doenças Cocleares/diagnóstico , Orelha Média/lesões , Fístula/diagnóstico , Futebol Americano/lesões , Osso Frontal/lesões , Traumatismos Cranianos Fechados/complicações , Doenças do Labirinto/diagnóstico , Fraturas Cranianas/complicações , Osso Temporal/lesões , Ferimentos não Penetrantes/complicações , Adolescente , Traumatismos em Atletas/diagnóstico , Criança , Pré-Escolar , Doenças Cocleares/reabilitação , Surdez/diagnóstico , Surdez/etiologia , Surdez/reabilitação , Fístula/reabilitação , Seguimentos , Traumatismos Cranianos Fechados/diagnóstico , Humanos , Processamento de Imagem Assistida por Computador , Doenças do Labirinto/reabilitação , Masculino , Fraturas Cranianas/diagnóstico , Tomografia Computadorizada Espiral , Vestíbulo do Labirinto/lesões , Ferimentos não Penetrantes/reabilitação
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