Postnatal growth of intrinsic connections in mouse barrel cortex.

Surprisingly little is known about the development of connections within a functional area of the cerebral cortex. We examined the postnatal growth of connections in mouse barrel cortex during the second and third weeks after birth, coinciding with the period of rapid synaptogenesis that occurs just after the barrels first form. A barrel is a group of neurons in layer 4 of somatosensory cortex that is part of a cortical column. Each whisker/barrel column is linked anatomically and functionally to a homotopic whisker on the contralateral face. Radial groups of cortical neurons were labeled with the neuronal tracer biotinylated dextran amine in mice ranging in age from postnatal day 8 (P8; P0 is the date of birth) to adulthood. The spatial distributions of retrogradely labeled neurons in different laminae were analyzed. The barrel map in layer 4 was used as a template to compare quantitative data from different animals and to account for substantial changes in barrel and barrel field size during development. Intrinsic projections 1) innervate increasingly more distant targets within barrel cortex up to 3 weeks of age; 2) continue to form in targets after 3 weeks, effectively strengthening existing connections; 3) follow a timetable for growth that is layer-specific; 4) link more distant barrel columns in layer 4 from neurons that are found preferentially in the barrel side and the septa between barrels; and 5) form over the shortest distances between the barrel columns. These data indicate that intrinsic connections in mouse barrel cortex develop by the progressive addition of neuronal connections rather than by sculpting preliminary connections. We describe statistically significant changes in connectivity during development that may be applied to model and assess the development of connections after a variety of experimental perturbations, such as to the environment and/or the genome.     

Short tandem repeat polymorphism in exon 4 of esophageal cancer related gene 2 predicts relapse of oral squamous cell carcinoma

Short tandem repeat (STR) polymorphisms in exon 4 of esophageal cancer related gene 2 (ECRG2) are a prognostic marker for squamous cell carcinoma (SCC) of the esophagus. The aim of the present study was to correlate these STRs with clinical outcome of the similar tumor type oral squamous cell carcinoma (OSCC). DNA of 81 patients that underwent complete surgical resection of OSCC was analyzed for STRs TCA3/TCA3, TCA3/TCA4 and TCA4/TCA4 in exon 4 of ECRG2 by PCR, capillary electrophoresis and DNA sequencing. ECRG2 STR TCA3/TCA3 were found in 45 (56%), TCA3/TCA4 in 33 (41%) and TCA4/TCA4 in 3 (3%) patients. TCA3/TCA3 was significantly associated with reduced relapse-free survival of OSCC, compared with TCA3/TCA4 and TCA4/TCA4 genotypes (P<0.05; log-rank test). TCA3/TCA3 STR was independent prognostic factor determined by multivariate Cox regression analysis (p<0.05). STR polymorphism TCA3/TCA3 in exon 4 of ECRG2 is associated with poor relapse-free survival in surgically completely resected OSCC patients and might be a potential prognostic marker.     

Targeted genomic microarray analysis for identification of chromosome abnormalities in 1500 consecutive clinical cases

OBJECTIVE: To assess the yield of array-based comparative genomic hybridization. STUDY DESIGN: The results of array comparative genomic hybridization were collected on 1500 consecutive clinical cases sent to our laboratory for a variety of developmental problems. Confirmation fluorescence in situ hybridization of metaphase or interphase cells, depending on the aberration, was performed. RESULTS: Of the 1500 cases, 134 (8.9%) showed an abnormality: 36 (2.4%) showed polymorphisms or familial variants, 14 (0.9%) showed alterations of unknown clinical significance, and 84 (5.6%) showed clinically relevant genomic alterations. These included subtelomeric deletions and unbalanced rearrangements, microdeletions and reciprocal duplications, rare abnormalities, and low-level trisomy mosaicism. CONCLUSIONS: A targeted array detects a substantial proportion of abnormalities even in those patients who have already had extensive cytogenetic and/or fluorescence in situ hybridization testing. This study, although not a controlled ascertainment of subjects with specific selection criteria, accurately reflects the reality of clinical cytogenetic practice and provides an estimate of the cytogenetic abnormalities that can be identified with a targeted microarray in a diagnostic laboratory. Microarray analysis likely doubles the current yield of abnormal results detected by conventional cytogenetic analysis.     

Incidence and characteristics of facial nerve stimulation in children with cochlear implants

OBJECTIVES: Electrical stimulation from a cochlear implant can spread beyond the auditory nerve. The aims of this study were to accurately measure facial nerve stimulation in pediatric implant users and to determine the characteristics and incidence of this unwanted activity. Part A consisted of a prospective study of a randomized sample of 44 pediatric implant users. Part B consisted of a retrospective analysis of 121 children with previously recorded electrically evoked auditory brainstem responses (EABR). STUDY DESIGN AND METHODS: Responses were evoked by 3 electrodes along the implant array in three groups of children: 1) postmeningitic, 2) abnormal cochlea, and 3) neither. Intraoperative measures were obtained under anesthesia; all other recordings were completed in awake children. RESULTS: Intraoperative recordings revealed large nonauditory responses in a number of channels, including the midline EABR. Under paralysis, these responses disappeared, and clear EABRs were recorded. Similarly, prospective postoperative electromyographic (EMG) responses from the facial nerve were found in more than 59% (26 of 44) of experienced implant users (Nucleus 24): 31% of postmeningitic children (4 of 13), 80% of those with abnormal cochlea (8 of 10), and 66% of those with neither (14 of 21). Retrospective analysis of previously recorded postoperative EABRs demonstrated facial nerve stimulation in 35% (42 of 121). In most cases, facial nerve stimulation occurred when levels were perceptually loud but comfortable. CONCLUSIONS: 1) Facial nerve potentials can be recorded using EMG in a large proportion of cochlear implant users at high levels of stimulation. 2) The EABR can be obscured in the presence of facial nerve stimulation and care should be taken to distinguish it from the EMG response, particularly when auditory brainstem activity is in question. 3) Use of surface EMG provides an additional objective measure to ensure the safe and comfortable use of cochlear implants.     

The efficacy of mitomycin-C in the treatment of laryngotracheal stenosis

OBJECTIVE: The purpose of this study is to evaluate whether the addition of topical mitomycin-C (MMC) application to the wound site after endoscopic treatment of laryngotracheal stenosis (LTS) resulted in measurable improvement in clinical outcomes. STUDY DESIGN AND SETTING: A retrospective chart review of patients with LTS treated by the senior author over a 6-year period was performed. The treatment groups were stratified into two main categories: 1) endoscopic treatment alone and 2) endoscopic treatment + topical MMC. The "symptom-free" interval was determined (in months) for each subject using a two-tailed t test for statistical analysis of the control/study groups. RESULTS: Sixty-seven procedures were performed in 36 patients with LTS with a mean of 1.86 surgical treatments per patient. The mean duration of the symptom-free interval after endoscopic treatment for LTS was 4.9 months in the endoscopic-only treatment group and 23.2 months in the endoscopic group receiving topical MMC. The symptom-free interval observed in the MMC group was significantly longer than the control subjects (P = 1 x 10). CONCLUSIONS: The results of this study suggest that MMC is an effective adjuvant in the treatment of LTS. The results of this study provide strong supporting evidence that topical MMC is an effective adjuvant in the treatment of LTS.     

Temporal bone imaging in GJB2 deafness

OBJECTIVE: To describe temporal bone findings on computed tomography (CT) imaging in GJB2-related hearing loss (HL). We asked whether evaluation of the temporal bone is required in individuals with biallelic GJB2 mutations. STUDY DESIGN: Randomized, blinded, controlled, prospective measurement. METHODS: Blood from 264 pediatric cochlear implant users was analyzed for mutations in the GJB2 gene. Thirty-six aspects of the temporal bone on CT imaging were evaluated in 53 individuals (106 ears) with biallelic disease causing GJB2 mutations. A subset of patients was age matched and compared with normally hearing individuals. Subjects with biallelic GJB2 mutations were tested for mutations in the SLC26A4 gene to rule out Pendred syndrome as a confounding cause of large vestibular aqueduct syndrome. RESULTS: Approximately 53% of ears of subjects (72% of subjects) with biallelic GJB2 mutations had at least one temporal bone anomaly. The most common findings were 1) dilated endolymphatic fossa (28%); 2) hypoplastic modiolus (25%); 3) large vestibular aqueduct (8%); 4) hypoplastic horizontal semicircular canal (8%); 5) hypoplastic cochlea (4%). Compared with normally hearing individuals, the GJB2 group had hypoplasia of the cochlear nerve canal, lateral semicircular canal vestibule, internal auditory canal (t tests, P < .001), and were 11 times more likely to have a hypoplastic modiolus. Dilated endolymphatic fossae were 1.4 times more common in the GJB2 group, and large vestibular aqueducts were 3 times more common in the GJB2 group, as compared with normally hearing controls. CONCLUSIONS: Temporal bone anomalies are common in GJB2-related HL, and imaging of the temporal bone should be included in routine evaluation of these individuals.