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2.
Nat Microbiol ; 9(5): 1189-1206, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38548923

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with short- and long-term neurological complications. The variety of symptoms makes it difficult to unravel molecular mechanisms underlying neurological sequalae after coronavirus disease 2019 (COVID-19). Here we show that SARS-CoV-2 triggers the up-regulation of synaptic components and perturbs local electrical field potential. Using cerebral organoids, organotypic culture of human brain explants from individuals without COVID-19 and post-mortem brain samples from individuals with COVID-19, we find that neural cells are permissive to SARS-CoV-2 to a low extent. SARS-CoV-2 induces aberrant presynaptic morphology and increases expression of the synaptic components Bassoon, latrophilin-3 (LPHN3) and fibronectin leucine-rich transmembrane protein-3 (FLRT3). Furthermore, we find that LPHN3-agonist treatment with Stachel partially restored organoid electrical activity and reverted SARS-CoV-2-induced aberrant presynaptic morphology. Finally, we observe accumulation of relatively static virions at LPHN3-FLRT3 synapses, suggesting that local hindrance can contribute to synaptic perturbations. Together, our study provides molecular insights into SARS-CoV-2-brain interactions, which may contribute to COVID-19-related neurological disorders.


Assuntos
Encéfalo , COVID-19 , Homeostase , Organoides , SARS-CoV-2 , Sinapses , Humanos , SARS-CoV-2/fisiologia , COVID-19/virologia , COVID-19/metabolismo , COVID-19/patologia , Encéfalo/virologia , Sinapses/virologia , Sinapses/metabolismo , Organoides/virologia , Vírion/metabolismo , Neurônios/virologia , Neurônios/metabolismo , Receptores de Peptídeos/metabolismo , Receptores de Peptídeos/genética
3.
Eur Arch Otorhinolaryngol ; 281(5): 2383-2394, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38499694

RESUMO

PURPOSE: Necrotizing otitis externa (OEN) is an aggressive and morbid infection of the external acoustic meatus. What are the risk factors for OEN extension? METHODS: French monocentric retrospective study (2004-2021), including patients with OEN defined by the association of an inflamed EAM, a positive nuclear imaging, the presence of a bacteriological sample and the failure of a well-followed local and/or general antibiotic treatment. OEN was extensive if it was associated with vascular or neurological deficits, if nuclear imaging fixation and/or bone lysis extended beyond the tympanic bone. RESULTS: Our population (n = 39) was male (74%), type 2 diabetic (72%), aged 75.2 years and pseudomonas aeruginosa was found in 88% of cases. Complications for 43% of patients were extensive fixation on nuclear imaging, for 21% of them the presence of extensive bone lysis, for 13% the appearance of facial palsy, for 5.3% the presence hypoglossal nerve palsy and for 2.5% the presence of thrombophlebitis or other nerves palsies. 59% of our population had extensive OEN. The diagnosis of the extensive OEN was made 22 days later (p = 0.04). The clinical presentation was falsely reassuring due to easier identification of the tympanic membrane (70% vs 46%, p = 0.17) but associated with periauricular oedema (42% vs 0%), bone exposure (16% vs 0%) and a temporomandibular joint pain (41% vs 12%). CONCLUSION: Delayed treatment of OEN, identification of clinical bone lysis, especially when the tympanic membrane is easily visualized, and the presence of unbalanced diabetes are potential risk factors for extension of OEN.


Assuntos
Otite Externa , Infecções por Pseudomonas , Humanos , Masculino , Otite Externa/epidemiologia , Otite Externa/diagnóstico , Estudos Retrospectivos , Meato Acústico Externo , Infecções por Pseudomonas/epidemiologia , Antibacterianos/uso terapêutico , Fatores de Risco
4.
Eur J Cancer ; 201: 113922, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38364629

RESUMO

OBJECTIVES: To analyse prognostic factors and survival outcomes of malignant tumors of the external auditory canal, to investigate the role of regional surgery, and adjuvant radiotherapy in early stages and to investigate the role of surgery in operable T4 stage. SETTING: A retrospective analysis was conducted on all patients prospectively included in the national database of the French Expertize Network for Rare ENT Cancers (REFCOR) from January 2000 to December 2016. PARTICIPANTS: 103 patients from 19 reference centers were included. A propensity score matching analysis was applied to enable comparisons between treatments. MAIN OUTCOMES AND MEASURES: Event-free survival, overall survival and factors of poor prognosis of the cohort were described. The interest of local and regional surgery and postoperative radiotherapy were evaluated. RESULTS: The factors of poor prognosis on event-free survival were immunosuppression (p = 0.002), Karnofsky status less than 90% (p = 0.02), body mass index less than 19 Kg / m2 (p = 0.0009), peripheric facial palsy (p = 0.0016), and positive margin (p = 0.0006). In early stages, locoregional surgery was associated with an increase in event-free survival (p = 0.003, HR = 0.21) versus local surgery alone, while postoperative radiotherapy was not associated with an increase in event-free survival (p = 0.86, HR = 0.91) or overall (p = 0.86, HR = 0.91). In locally advanced stages, locoregional surgery followed by radiotherapy was associated with an increase in event-free survival (p = 0.03, HR = 0.39) and overall (p = 0.02, HR = 0.34) versus chemoradiotherapy alone. CONCLUSION AND RELEVANCE: Regional surgery is recommended for early stages of cancers of the external auditory canal. In operable cases, locoregional surgery followed by radiotherapy is recommended.


Assuntos
Carcinoma de Células Escamosas , Meato Acústico Externo , Humanos , Estudos Retrospectivos , Pontuação de Propensão , Meato Acústico Externo/patologia , Carcinoma de Células Escamosas/patologia , Radioterapia Adjuvante , Prognóstico
5.
Eur Arch Otorhinolaryngol ; 281(2): 925-934, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37917163

RESUMO

PURPOSE: The objective of our study was to evaluate the ability of preoperative MRI tractography to visualize and predict the path of the facial nerve with respect to an intra-parotid mass. METHODS: We performed an observational bicentric study from June 2019 to August 2020. All patients older than 18 years old, treated for a parotid mass with surgical indication, without MRI contraindication and who agreed to participate in the study were enrolled prospectively. All patients underwent a cervico-facial MRI with tractographic analysis. Postprocessed tractography images of the intra-parotid facial nerve were analyzed by two expert radiologists in head and neck imaging. The intraoperative anatomical description of the facial nerve path and its relationship to the mass was performed by the surgeon during the operation, with no visibility on MRI examination results. A statistical study allowed for the description of the data collected as well as the measurement of inter-observer agreement and agreement between tractography and surgery using kappa coefficients. RESULTS: Fifty-two patients were included. The facial nerve trunk and its first two divisional branches were visualized via tractography in 93.5% of cases (n = 43). The upper distal branches were visualized in 51.1% of cases (n = 23), and the lower branches were visualized in 73.3% of cases (n = 33). Agreement with the location described per-operatively was on average 82.9% for the trunk, 74.15% for the temporal branch, and 75.21% for the cervico-facial branch. CONCLUSION: Fiber tractography analysis by MRI of the intra-parotid facial nerve appears to be a good test for predicting the path of the nerve over the parotid mass and could be an additional tool to guide the surgeon in the operative procedure.


Assuntos
Nervo Facial , Neoplasias Parotídeas , Adolescente , Humanos , Nervo Facial/cirurgia , Imageamento por Ressonância Magnética/métodos , Pescoço/patologia , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/cirurgia , Glândula Parótida/inervação , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/cirurgia , Neoplasias Parotídeas/patologia
6.
Eur Arch Otorhinolaryngol ; 280(4): 1661-1670, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36114332

RESUMO

PURPOSE: The primary objective was to determine whether the analysis of textural heterogeneity of vestibular schwannomas on MRI at diagnosis was predictive of their radiological evolutivity. The secondary objective was to determine whether some clinical or radiological factors could also be predictive of growth. METHODS: We conducted a pilot, observational and retrospective study of patients with a vestibular schwannoma, initially monitored, between April 2001 and November 2019 within the Oto-Neurosurgical Institute of Champagne Ardenne, Texture analysis was performed on gadolinium injected T1 and CISS T2 MRI sequences and six parameters were extracted: mean greyscale intensity, standard deviation of the greyscale histogram distribution, entropy, mean positive pixels, skewness and kurtosis, which were analysed by the Lasso method, using statistically penalised Cox models. Extrameatal location, tumour necrosis, perceived hearing loss < 2 years with objectified tone audiometry asymmetry, tinnitus at diagnosis, were investigated by the Log-Rank test to obtain univariate survival analyses. RESULTS: 78 patients were included and divided into 2 groups: group A comprising 39 "stable patients", and B comprising the remaining 39 "progressive patients". Independent analysis of the texture factors did not predict the growth potential of vestibular schwannomas. Among the clinical or radiological signs of interest, hearing loss < 2 years was identified as a prognostic factor for tumour progression with a significant trend (p = 0.05). CONCLUSIONS: This study did not identify an association between texture analysis and vestibular schwannomas growth. Decreased hearing in the 2 years prior to diagnosis appears to predict potential radiological progression.


Assuntos
Neuroma Acústico , Zumbido , Humanos , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/complicações , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Audição
7.
Acta Neurol Belg ; 122(3): 615-623, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35353357

RESUMO

OBJECTIVE: Treatment of choice for trigeminal neuralgia (TN) by neurovascular conflict in case of failure of medical treatment is microvascular decompression (MVD). It is a safe and effective technique in the short and long term. But what about older patients who are considered more fragile anesthetically and surgically? Our Objective is to demonstrate the efficacy and complication rate of microvascular decompression (MVD) for older and younger patients with trigeminal neuralgia (TN) due to neurovascular conflict. METHODS: 102 patients with TN due to neurovascular conflict were included (June 2005-December 2016) in a single Regional hospital. 25 were included in the group composed of ≥ 70-year-old patients (G1), while 77 were included in the < 70-year-old group (G2). The patients were operated on by the same surgical team using a retro-sigmoid approach to access the neurovascular conflict. The epidemiologic, clinical, anesthetic, and surgical data were extracted. RESULTS: The immediate efficacy of surgical treatment (BNI pain intensity = I) was 96% in G1 and 96.10% in the G2 group (p = 0.71). At 3-year follow-up, the efficacy rate was 89% and 86%, respectively (p = 0.93). At 5 years, it was 92% and 92% (p = 0.98). Complication rates were comparable between the two groups (20% versus 27%; p = 0.47) and no deaths occurred despite the fact that G1 group had worst preoperative anesthetic score (ASA-NYHA). CONCLUSION: MVD is a durable procedure in patients over 70 years of age diagnosed with essential TN. The complication rate and immediate-, medium-, and long-term efficacy were similar to those of younger patients.


Assuntos
Cirurgia de Descompressão Microvascular , Neuralgia do Trigêmeo , Idoso , Idoso de 80 Anos ou mais , Humanos , Cirurgia de Descompressão Microvascular/efeitos adversos , Cirurgia de Descompressão Microvascular/métodos , Medição da Dor , Estudos Retrospectivos , Resultado do Tratamento , Neuralgia do Trigêmeo/etiologia , Neuralgia do Trigêmeo/cirurgia
8.
J Neurosurg ; : 1-7, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996039

RESUMO

OBJECTIVE: When Ménière's disease (MD) becomes disabling due to the frequency of attacks or the appearance of drop attacks (i.e., Tumarkin otolithic crisis) despite "conservative" medical and surgical treatments, a radical treatment like vestibular neurotomy (VN) is possible. An ideal MD treatment would relieve symptoms immediately and persist after the therapy. The aim of this study was to identify if VN was effective after 10 years of follow-up regarding vertigo and drop attacks, and to collect the immediate complications. METHODS: The authors report a retrospective, single-center (i.e., in a single tertiary referral center with otoneurological surgery activity) cohort study conducted from January 2003 to April 2020. All patients with unilateral disabling MD who had received a VN with at least 10 years of follow-up were included. The therapeutic efficacy was defined by complete disappearance of vertigo and drop attacks. The postoperative complications (CSF leak, total deafness, meningitis, death) were determined immediately after the surgery, and the hearing thresholds were determined during the patient follow-up with the pure tone average (PTA). RESULTS: A total of 74 patients (of 85 who were eligible), average age 51.9 ± 11.1 years, including 38 men (51.4%), with disabling MD and/or Tumarkin drop attacks (24.3%) received VN, with at least 10 years of follow-up after surgery. After an average follow-up of 12.4 ± 1.7 years (range 10.0-16.3 years), 67 patients (90.5%) no longer presented any vertiginous attacks, and no patient experienced drop attack. The mean variation in early pre- and postoperative PTA was not statistically significant (n = 64, 2.2 ± 10.3 decibels hearing level [range -18 to 29], 95% CI [-0.4 to 4.37]; p = 0.096), and 84.4% of the patients evaluated had unchanged or improved postoperative PTA. Three significant complications were noted, including two surgical revisions for CSF leak. There was no permanent facial paralysis, meningitis, or death. CONCLUSIONS: In case of disabling MD (disabling vertigo refractory to conservative vestibular treatments-Tumarkin drop attacks), VN via the retrosigmoid approach must be the prioritized proposal in comparison to intratympanic gentamicin injections, because of the extremely low complication rate and the immediate and long-lasting effect of this treatment on vertigo and falls.

9.
Eur Arch Otorhinolaryngol ; 279(2): 1099-1104, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34476594

RESUMO

PURPOSE: Assessment of inspiratory dyspnoea associated with upper airway obstruction is based on subjective clinical and nasal fibreoptic laryngoscopy (NFL) signs. The aim of this study was to determine whether peak inspiratory flow (PIF) measurement could indicate the need for upper airway release surgery in patients with acute inspiratory dyspnoea during emergency. METHODS: A retrospective single-institution study (February 2018-March 2020) of 48 patients with acute inspiratory dyspnoea and PIF measurement (Peak Flow In-Check Dial G16®-Harlow-England) was conducted. The surgical decision was based on the clinical evaluation of the patient's respiratory tolerance and NFL. RESULTS: Forty-eight patients were included in this study. Thirty-five patients underwent surgery (PIF: 36 L/min), and 13 patients did not (PIF: 58 L/min) (p = 0.0009). Three of these 13 patients underwent an operation later (PIF value: 42 L/min versus 63 L/min for the 10 others [p = 0.25]). CONCLUSION: PIF measurement is a quantitative, objective, inexpensive, non-invasive, and quick test that is potentially useful for general practitioners, mobile medical teams, or for ear-nose-and-throat specialists. A threshold of 42 L/min can help doctors in emergency decision making to refer patients to an ear-nose-and-throat specialist to release the upper airway and perform surgery or to choose medical monitoring for patients with emergency inspiratory dyspnoea.


Assuntos
Dispneia , Nariz , Dispneia/diagnóstico , Dispneia/etiologia , Inglaterra , Humanos , Capacidade Inspiratória , Estudos Retrospectivos
10.
Otolaryngol Head Neck Surg ; 164(6): 1299-1306, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33198570

RESUMO

OBJECTIVE: To analyze the efficacy and complications of microvascular decompression for hemifacial spasm. STUDY DESIGN: Retrospective study. SETTING: Regional hospital. METHODS: Fifty-five patients with hemifacial spasm were treated by microvascular decompression. All patients with hemifacial spasm who underwent retrosigmoid microvascular decompression from May 2004 to January 2017 were included. Patients with no conflict on preoperative magnetic resonance imaging or with an alternate diagnosis were excluded. RESULTS: The overall cure rate was 83.64%, with an average follow-up of 7.4 years. A left-sided hemifacial spasm was a healing-promoting factor (P = .01). The median healing was 0.03 months, and the mean was 6 months. The efficacy remained high in the medium term (88% at 3 years), long term (90.24% at 5 years), and very long term (90.48% at 8 years). The recurrence rate was 9.8%. Favorable criteria included a right-sided spasm (P = .01) and an average age of 62 years (P = .03). The specific complications were permanent facial palsy (3.63%), unilateral deafness (5.45%), and hearing loss (3.63%). No death was reported. Regarding the quality of life of the patients, 94.7% had a modified HFS-8 postoperative score of 0 (Hemifacial Spasm 8 Quality of Life Scale). CONCLUSION: Microvascular decompression for hemifacial spasm is an effective and lasting technique. Its low rate of complications and the considerable quality-of-life improvement should lead surgeons to propose it to patients as soon as botulinum toxin injections become ineffective or poorly tolerated.


Assuntos
Espasmo Hemifacial/cirurgia , Cirurgia de Descompressão Microvascular/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
11.
Chem Senses ; 45(8): 645-654, 2020 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-32822468

RESUMO

Xenobiotic metabolizing enzymes and other proteins, including odorant-binding proteins located in the nasal epithelium and mucus, participate in a series of processes modulating the concentration of odorants in the environment of olfactory receptors (ORs) and finely impact odor perception. These enzymes and transporters are thought to participate in odorant degradation or transport. Odorant biotransformation results in 1) changes in the odorant quantity up to their clearance and the termination of signaling and 2) the formation of new odorant stimuli (metabolites). Enzymes, such as cytochrome P450 and glutathione transferases (GSTs), have been proposed to participate in odorant clearance in insects and mammals as odorant metabolizing enzymes. This study aims to explore the function of GSTs in human olfaction. Using immunohistochemical methods, GSTs were found to be localized in human tissues surrounding the olfactory epithelium. Then, the activity of 2 members of the GST family toward odorants was measured using heterologously expressed enzymes. The interactions/reactions with odorants were further characterized using a combination of enzymatic techniques. Furthermore, the structure of the complex between human GSTA1 and the glutathione conjugate of an odorant was determined by X-ray crystallography. Our results strongly suggest the role of human GSTs in the modulation of odorant availability to ORs in the peripheral olfactory process.


Assuntos
Glutationa Transferase/metabolismo , Odorantes , Mucosa Olfatória/metabolismo , Glutationa Transferase/análise , Humanos
12.
Cancers (Basel) ; 12(5)2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32422975

RESUMO

AIMS: To investigate the predictive capacity of early post-treatment diffusion-weighted magnetic resonance imaging (MRI) for recurrence or tumor progression in patients with no tumor residue after chemo-radiotherapy (CRT) for head and neck squamous cell carcinoma, and, to assess the predictive capacity of pre-treatment diffusion-weighted MRI for persistent tumor residue post-CRT. MATERIALS AND METHOD: A single center cohort study was performed in one French hospital. All patients with squamous cell carcinoma receiving CRT (no surgical indication) were included. Two diffusion-weighted MRI were performed: one within 8 days before CRT and one 3 months after completing CRT with determination of median tumor apparent diffusion coefficient (ADC). MAIN OUTCOME: The primary endpoint was progression-free survival. RESULTS: 59 patients were included prior to CRT and 46 (78.0%) completed CRT. A post-CRT tumor residue was found in 19/46 (41.3%) patients. In univariate analysis, initial ADC was significantly lower in patients with residue post CRT (0.56 ± 0.11 versus 0.79 ± 0.13; p < 0.001). When initial ADC was dichotomized at the median, initial ADC lower than 0.7 was significantly more frequent in patients with residue post CRT (73.7% versus 11.1%, p < 0.0001). In multivariate analysis, only initial ADC lower than 0.7 was significantly associated with tumor residue (OR = 22.6; IC [4.9-103.6], p < 0.0001). Among 26 patients without tumor residue after CRT and followed up until 12 months, 6 (23.1%) presented recurrence or progression. Only univariate analysis was performed due to a small number of events. The only factor significantly associated with disease progression or early recurrence was the delta ADC (p = 0.0009). When ADC variation was dichotomized at the median, patients with ADC variation greater than 0.7 had time of disease-free survival significantly longer than patients with ADC variation lower than 0.7 (377.5 [286-402] days versus 253 [198-370], p < 0.0001). Conclusion and relevance: Diffusion-weighted MRI could be a technique that enables differentiation of patients with high potential for early recurrence for whom intensive post-CRT monitoring is mandatory. Prospective studies with more inclusions would be necessary to validate our results.

13.
Ann Anat ; 225: 57-64, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31284072

RESUMO

Pancreatic cancer is associated with a poor prognosis, mainly due to lymph node invasion and lymph node recurrence after surgical resection, even after extended lymphadenectomy. The peripancreatic lymphatic system is highly complex and the specific lymphatic drainage of each part of the pancreas has not been established. The aim of this study was to determine the lymphatic drainage pathways specific to each part of the pancreas on live pigs using Patent Blue. The pancreases of 14 live pigs were injected in different parts of the gland. The technique was efficient and reproducible. The diffusion patterns were similar for each location and were reported. Our results in pigs allowed us to define specific nodal relay stations and lymphatic drainage for each part of the pancreas and confirm that independent anatomical-surgical pancreatic segments can be described. It is interesting to note that lymphatic drainage for the upper part of the proximal part of pancreas (duodenal lobe) occurred on the left side of the portal vein. This suggests that lymph node resection during cephalic duodenopancreatectomy in humans should be extended to the left side of the mesenteric vein, and probably to the right side of the superior mesenteric artery, as recently suggested. These results could help surgeons perform safe anatomical-segmental pancreatic resections with accurate lymphadenectomies and improve survival in patients with pancreatic cancer. Based on these results we will perform an innovative prospective study. Patent Blue will be injected into different parts of the gland in patients operated for pancreatic resection, and lymphatic diffusion of the dye will be recorded in relation to their origin from the theoretical pancreatic segments (ClinicalTrials.gov Identifier: NCT03597230).


Assuntos
Vasos Linfáticos/anatomia & histologia , Pâncreas/anatomia & histologia , Suínos/anatomia & histologia , Animais , Corantes , Modelos Animais , Corantes de Rosanilina
14.
J Shoulder Elbow Surg ; 28(9): 1788-1794, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31036420

RESUMO

BACKGROUND: Sensory innervation to the shoulder provided by the distal suprascapular nerve (dSSN) remains the subject of debate. The purpose of this study was to establish consensus with respect to the anatomic features of the sensory branches of the dSSN. The relevant hypothesis was that the dSSN would give off 3 sensory branches providing innervation to the posterior glenohumeral (PGH) capsule, the subacromial bursa, in addition to the coracoclavicular and acromioclavicular ligaments. METHODS: The division, course, and distribution of the sensory branches that originated from the dSSN and innervated structures around the shoulder joint were examined macroscopically by dissecting 37 shoulders of 19 fresh-frozen cadavers aged of 83.0 years (range, 74-98 years). RESULTS: The 37 dSSN provided 1 medial subacromial branch (MSAb), 1 lateral subacromial branch (LSAb), and 1 PGH branch (PGHb) to the shoulder joint. This arrangement allowed for bipolar-MSAb and LSAb-innervation of the subacromial bursa, acromioclavicular (MSAb and LSAb) and coracoclavicular (MSAb) ligaments, as well as the PGH capsule (PGHb). CONCLUSIONS: The dSSN provided 2 subacromial branches and 1 PGHb to the shoulder joint. This arrangement allowed for bipolar-MSAb and LSAb-innervation of the subacromial bursa, acromioclavicular and coracoclavicular ligaments, as well as the PGH capsule.


Assuntos
Articulação Acromioclavicular/inervação , Bolsa Sinovial/inervação , Ligamentos Articulares/inervação , Nervos Periféricos/anatomia & histologia , Articulação do Ombro/inervação , Idoso , Idoso de 80 Anos ou mais , Cadáver , Feminino , Humanos , Masculino , Células Receptoras Sensoriais , Ombro
15.
Otol Neurotol ; 40(1): 121-129, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30531642

RESUMO

OBJECTIVE: To describe the genetic and phenotypic spectrum of Usher syndrome after 6 years of studies by next-generation sequencing, and propose an up-to-date classification of Usher genes in patients with both visual and hearing impairments suggesting Usher syndrome, and in patients with seemingly isolated deafness. STUDY DESIGN: The systematic review and meta-analysis protocol was based on Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed 1) a meta-analysis of data from 11 next-generation sequencing studies in 684 patients with Usher syndrome; 2) a meta-analysis of data from 21 next-generation studies in 2,476 patients with seemingly isolated deafness, to assess the involvement of Usher genes in seemingly nonsyndromic hearing loss, and thus the proportion of patients at high risk of subsequent retinitis pigmentosa (RP); 3) a statistical analysis of differences between parts 1) and 2). RESULTS: In patients with both visual and hearing impairments, the biallelic disease-causing mutation rate was assessed for each Usher gene to propose a classification by frequency: USH2A: 50% (341/684) of patients, MYO7A: 21% (144/684), CDH23: 6% (39/684), ADGRV1: 5% (35/684), PCDH15: 3% (21/684), USH1C: 2% (17/684), CLRN1: 2% (14/684), USH1G: 1% (9/684), WHRN: 0.4% (3/684), PDZD7 0.1% (1/684), CIB2 (0/684). In patients with seemingly isolated sensorineural deafness, 7.5% had disease-causing mutations in Usher genes, and are therefore at high risk of developing RP. These new findings provide evidence that usherome dysfunction is the second cause of genetic sensorineural hearing loss after connexin dysfunction. CONCLUSION: These results promote generalization of early molecular screening for Usher syndrome in deaf children.


Assuntos
Mutação , Síndromes de Usher/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Linhagem
16.
J Anat ; 233(5): 679-684, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30101484

RESUMO

Surgical laparoscopic procedures in the retroperitoneal and supramesocolic spaces are increasingly frequent. There is a high risk of iatrogenic intraoperative injury of the retroperitoneal lymphatic structures during these procedures. A precise understanding of the anatomy of the thoracic duct (TD) and the cisterna chyli (CC) is essential for safe surgical procedures in this area. However, routine imaging procedures rarely and often incorrectly visualize the CC. The objective of this study was to evaluate the feasibility of a retrograde injection of the TD to fill the CC with a contrast agent in 16 human cadavers. Both magnetic resonance lymphography (MRI) and computed tomography (CT) studies could be performed on the same anatomical specimen, using a contrast medium which hardened, allowing gross dissection. MRI and CT detectability were evaluated, and imaging results were compared with the anatomical dissection. The CC of 12/16 cadavers were successfully injected, and four were unsuccessful due to technical difficulties, showing the effectiveness of the method. This technique can improve understanding of the anatomy of the TD and CC and provides an original option to study the complex anatomy of these structures by correlating precise cadaveric dissections with cross-sectional imaging.


Assuntos
Imageamento por Ressonância Magnética/métodos , Ducto Torácico/anatomia & histologia , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Cadáver , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Invest Ophthalmol Vis Sci ; 59(7): 2679-2686, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29860454

RESUMO

Purpose: Anti-angiogenic agents stand first in the treatment of neovascular diseases of the retina. CD160 appeared in several experimental studies as a marker of activated endothelial cells, suggesting it could represent a promising target for novel anti-angiogenic therapies. The aim of the present study was to assess the distribution of CD160 in the human eye, and to search for a possible correlation with retinal neovascular diseases. Methods: The physiological distribution of CD160 in the normal eye was assessed with immunolabeling in 10 human donor eyes. Then, in a retrospective cohort of 75 surgical retinal specimens, the density of CD160+ microvessels was evaluated, along with immunolabeling on serial sections against ERG (pan-endothelial cell marker), CD105 (activated endothelial cell marker), and α-SMA (pericyte cell marker). The cohort was divided into two groups: 29 patients with neovascular disease (NV+) and 46 control patients (NV-). Results: CD160 was physiologically expressed by several cell types: endothelial cells of retinal blood vessels, ganglion cells, macrophages, epithelial cells of the conjunctiva, ciliary body, and retinal pigment epithelium. In the patient cohort, the percentage of CD160+ vessels in the retina was significantly and independently higher in patients suffering from neovascular diseases (P = 0.04). On the contrary, the expression of CD105 was correlated neither with retinal neovascular diseases, nor with CD160 expression. Conclusions: CD160 was expressed in some retinal vessels in both normal and pathologic eyes. CD160 expression by endothelial cells of retinal vessels was correlated with ocular neovascular diseases. CD160 could therefore represent an interesting target for novel anti-angiogenic therapies.


Assuntos
Antígenos CD/metabolismo , Receptores Imunológicos/metabolismo , Neovascularização Retiniana/metabolismo , Vasos Retinianos/metabolismo , Actinas/metabolismo , Idoso , Biomarcadores/metabolismo , Corpo Ciliar/metabolismo , Túnica Conjuntiva/metabolismo , Endoglina/metabolismo , Endotélio Vascular/metabolismo , Células Epiteliais/metabolismo , Feminino , Proteínas Ligadas por GPI/metabolismo , Humanos , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Células Ganglionares da Retina/metabolismo , Estudos Retrospectivos , Doadores de Tecidos , Regulador Transcricional ERG/metabolismo
19.
Rev Prat ; 68(8): 855-856, 2018 Oct.
Artigo em Francês | MEDLINE | ID: mdl-30869448

RESUMO

Épidémiologie et dépistage de la surdité de l'enfant. L'intérêt d'un dépistage systématique de la surdité à la naissance n'est plus discuté ; 1 enfant sur 1 000 naît malentendant. La France, en retard dans ce domaine, a rendu ce dépistage obligatoire en avril 2012, confiant aux agences régionales de santé le soin de l'organiser dans un délai de deux ans. Théoriquement donc, dans toutes les maternités françaises, des signes de l'audition sont recherchés chez tous les nouveaunés à l'aide de la détection des otoémissions acoustiques ou de l'enregistrement des potentiels évoqués auditifs. Les enfants suspects sont alors adressés rapidement au centre référent de la maternité, centre chargé de confirmer l'éventuelle surdité, puis de la qualifier et de la quantifier. L'article fait le point quant à l'organisation de ce dépistage et ses résultats sur le territoire national en 2018, et rappelle le rôle primordial du médecin traitant prenant en charge les nourrissons et en mesure de vérifier si ce dépistage a bien été effectué.


Assuntos
Surdez , Criança , Surdez/diagnóstico , Humanos , Lactente
20.
Rev Prat ; 68(8): 857-861, 2018 Oct.
Artigo em Francês | MEDLINE | ID: mdl-30869449

RESUMO

Epidemiology and newborns universal hearing screening, The value and benefits of newborns' systematic hearing screening is no longer debated; one in a thousand children is born deaf. France, being behind in this field, made this screening mandatory in April 2012, giving to the Regional Health Agencies the duty and care to organise this screening within a period of two years. Therefore, theoretically, in all French maternities, hearing signs are sought in all newborns using the detection of otoacoustic emissions or the recording of auditory evoked potentials. Suspected children are then sent promptly to the referring center of the maternity, which will be responsible for confirming the possible deafness and, subsequently, qualifying and quantifying it. The article takes stock of the organisation of this screening process and its results in France in 2018. It is, especially, a reminder of the key role of the general practitioner who is taking care of infants and who is also able to verify if this screening has been performed.


Épidémiologie et dépistage de la surdité de l'enfant. L'intérêt d'un dépistage systématique de la surdité à la naissance n'est plus discuté ; 1 enfant sur 1 000 naît malentendant. La France, en retard dans ce domaine, a rendu ce dépistage obligatoire en avril 2012, confiant aux agences régionales de santé le soin de l'organiser dans un délai de deux ans. Théoriquement donc, dans toutes les maternités françaises, des signes de l'audition sont recherchés chez tous les nouveaunés à l'aide de la détection des otoémissions acoustiques ou de l'enregistrement des potentiels évoqués auditifs. Les enfants suspects sont alors adressés rapidement au centre référent de la maternité, centre chargé de confirmer l'éventuelle surdité, puis de la qualifier et de la quantifier. L'article fait le point quant à l'organisation de ce dépistage et ses résultats sur le territoire national en 2018, et rappelle le rôle primordial du médecin traitant prenant en charge les nourrissons et en mesure de vérifier si ce dépistage a bien été effectué.


Assuntos
Potenciais Evocados Auditivos do Tronco Encefálico , Transtornos da Audição , Triagem Neonatal , Criança , França , Transtornos da Audição/diagnóstico , Testes Auditivos , Humanos , Lactente , Recém-Nascido , Emissões Otoacústicas Espontâneas
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