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1.
Hum Genet ; 143(5): 721-734, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38691166

RESUMO

TMPRSS3-related hearing loss presents challenges in correlating genotypic variants with clinical phenotypes due to the small sample sizes of previous studies. We conducted a cross-sectional genomics study coupled with retrospective clinical phenotype analysis on 127 individuals. These individuals were from 16 academic medical centers across 6 countries. Key findings revealed 47 unique TMPRSS3 variants with significant differences in hearing thresholds between those with missense variants versus those with loss-of-function genotypes. The hearing loss progression rate for the DFNB8 subtype was 0.3 dB/year. Post-cochlear implantation, an average word recognition score of 76% was observed. Of the 51 individuals with two missense variants, 10 had DFNB10 with profound hearing loss. These 10 all had at least one of 4 TMPRSS3 variants predicted by computational modeling to be damaging to TMPRSS3 structure and function. To our knowledge, this is the largest study of TMPRSS3 genotype-phenotype correlations. We find significant differences in hearing thresholds, hearing loss progression, and age of presentation, by TMPRSS3 genotype and protein domain affected. Most individuals with TMPRSS3 variants perform well on speech recognition tests after cochlear implant, however increased age at implant is associated with worse outcomes. These findings provide insight for genetic counseling and the on-going design of novel therapeutic approaches.


Assuntos
Estudos de Associação Genética , Perda Auditiva , Proteínas de Membrana , Serina Endopeptidases , Humanos , Feminino , Masculino , Serina Endopeptidases/genética , Adulto , Proteínas de Membrana/genética , Perda Auditiva/genética , Criança , Pessoa de Meia-Idade , Adolescente , Pré-Escolar , Genótipo , Estudos de Coortes , Fenótipo , Mutação de Sentido Incorreto , Estudos Transversais , Adulto Jovem , Estudos Retrospectivos , Idoso , Proteínas de Neoplasias
2.
Front Neurol ; 15: 1335994, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318440

RESUMO

Cochlear implants (CI) have revolutionized the treatment of patients with severe to profound sensory hearing loss by providing a method of bypassing normal hearing to directly stimulate the auditory nerve. A further advance in the field has been the introduction of "hearing preservation" surgery, whereby the CI electrode array (EA) is carefully inserted to spare damage to the delicate anatomy and function of the cochlea. Preserving residual function of the inner ear allows patients to receive maximal benefit from the CI and to combine CI electric stimulation with acoustic hearing, offering improved postoperative speech, hearing, and quality of life outcomes. However, under the current paradigm of implant surgery, where EAs are inserted by hand, the cochlea cannot be reliably spared from damage. Robotics-assisted EA insertion is an emerging technology that may overcome fundamental human kinetic limitations that prevent consistency in achieving steady and slow EA insertion. This review begins by describing the relationship between EA insertion speed and generation of intracochlear forces and pressures. The various mechanisms by which these intracochlear forces can damage the cochlea and lead to worsened postoperative outcomes are discussed. The constraints of manual insertion technique are compared to robotics-assisted methods, followed by an overview of the current and future state of robotics-assisted EA insertion.

3.
Otol Neurotol ; 45(3): 215-222, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38361289

RESUMO

OBJECTIVES: Describe the diagnosis and management of a spontaneous cerebrospinal fluid leak (sCSF-L) through the facial nerve fallopian canal and determine the role of intracranial hypertension (IH). STUDY DESIGN: Retrospective case study and systematic review of the literature. METHODS: Reviewed patient characteristics, radiographic findings, and management of the facial nerve canal CSF leak and postoperative IH. Conducted systematic literature review according to the PRISMA guidelines for surgical management and rates of IH. RESULTS: A 50-year-old female with bilateral tegmen defects and temporal encephaloceles underwent left middle cranial fossa (MCF) repair. Intraoperative CSF egressed from the temporal bone tegmen defects. Facial nerve decompression revealed CSF leak from the labyrinthine segment. A nonocclusive temporalis muscle plug was placed in the fallopian canal, and tegmen repair was completed with bone cement. A ventriculoperitoneal shunt was placed for IH. Postoperative facial nerve function and hearing were normal. A total of 20 studies met inclusion criteria with a total of 25 unique patients. Of 13 total adult cases of fallopian canal CSF leak, there is a 46% recurrence rate, and 86% of patients had documented IH when tested. CONCLUSIONS: Fallopian canal CSF leaks are rare and challenging to manage. Assessment of intracranial hypertension and CSF diversion is recommended along with MCF skull base repair to preserve facial nerve function and conductive hearing.


Assuntos
Vazamento de Líquido Cefalorraquidiano , Hipertensão Intracraniana , Humanos , Feminino , Pessoa de Meia-Idade , Hipertensão Intracraniana/cirurgia , Vazamento de Líquido Cefalorraquidiano/cirurgia , Derivação Ventriculoperitoneal , Encefalocele/cirurgia , Nervo Facial/cirurgia
4.
Otol Neurotol Open ; 2(4): e021, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38516580

RESUMO

Background: Rates of spontaneous cerebrospinal fluid leak (sCSF) repairs have increased in recent decades in line with increases in obesity rates. Objectives: To determine if the national rate of sCSF leak has continued to rise in recent years and to identify associated risk factors utilizing a comprehensive national database comprising most academic medical centers. Methods: A retrospective review from 2009 to 2018 was performed using the Vizient Clinical Database (CDB) of 105 leading academic medical centers in the United States. Patients who underwent CSF leak repair in the CDB database using ICD-9 and ICD-10 diagnostic and procedure codes. Patients with epidural hematomas over the same time frame were used as a control. National rates of craniotomy for sCSF leak repair each quarter were assessed and sCSF leak patient characteristics (age, gender, obesity, hypertension, diabetes) were calculated. Results: The rate of craniotomy for all sCSF leak repairs increased by 10.2% annually from 2009 to 2015 (P < 0.0001). There was no statistically significant change in the rate of epidural hematomas over the same period. The rate of lateral sCSF leak repair increased on average by 10.4% annually from 2009 (218 cases/year) to 2018 (457 cases/year) (P < 0.0001). A statistically significant increase was observed across all regions of the United States (P ≤ 0.005). sCSF leak patients had an average (standard deviation) age of 55.0 (13.2) years and 67.2% were female. Obesity was the only demographic factors that increased significantly over time. Likely due to comorbid factors, Black patients comprise a disproportionately large percentage of lateral sCSF leak repair patients. Conclusions: The rate of craniotomy for spontaneous CSF leaks continues to rise by approximately 10% annually.

5.
Mem. Inst. Oswaldo Cruz ; 87(supl.3): 91-4, 1992. tab, ilus
Artigo em Inglês | LILACS | ID: lil-121081

RESUMO

We identified a gametocyte-specific protein of Plasmodium falciparum called Pf11-1 and provide experimental evidence that this molecule is involved in the emergence of gametes of the infected erythrocyte (gametogenesis). A mutant parasite clone, which has deleted over 90% of the PF11-1 gene locus, was an important control to establish the gametocyte-specific expression of the Pf11-1. Molecular analysis of the Pf11-1 deletion indicates that it is presumably due a chromosome breakage with subsequent "healing" by the addition of telomeric heptanucleotides. Moreover, similar DNA rearrangements are observed in most of the laboratory isolates during asexual propagation in vitro


Assuntos
Deleção Cromossômica , Antígenos de Histocompatibilidade , Plasmodium falciparum/ultraestrutura
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