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1.
Front Neurol ; 13: 746640, 2022.
Article in English | MEDLINE | ID: mdl-35356457

ABSTRACT

Background: The capability in applying information communication technology (ICT) is crucial to the functional independence of older peoples of community living nowadays. The proper assessment of individuals' capability of ICT application is the corner stone for the future development of telemedicine in our aging population. Methods: With the recruitment of 300 participants of different functional and social background in home-living, hostel-living, and care-and-attention home living; and through assessing the ability of individuals in instrumental activities of daily living and cognitive assessments, this study aimed at capturing the content validity and construct validity of the Advanced Instrumental Activities of Daily Living (AIADL scale). In addition, this study assess the ability of older peoples in applying ICT and how the functional and social background affects their independence in aging-in-place. Results: The AIADL scale showed good test-retest reliability and good-to-excellent internal consistency. To determine if items of the AIADL scale measure various aspects of community living, exploratory factor analysis revealed a two-factor structure with "home living and management" and "community living". Validity analysis with the known-groups method showed a high overall accuracy of prediction of individuals' capability of independent living in the community. Conclusions: The AIADL scale is a valid and reliable instrument to assess the ability of older adults in handling ICT as part of their instrumental activities in daily living. The scale can reflect capability of older peoples in applying ICT. This instrument can serve as a reference in measuring readiness of individuals in receiving telemedicine and their ability of aging-in-place.

2.
Am J Geriatr Psychiatry ; 28(11): 1175-1184, 2020 11.
Article in English | MEDLINE | ID: mdl-32873496

ABSTRACT

OBJECTIVES: Social distancing under the COVID-19 pandemic has restricted access to community services for older adults with neurocognitive disorder (NCD) and their caregivers. Telehealth is a viable alternative to face-to-face service delivery. Telephone calls alone, however, may be insufficient. Here, we evaluated whether supplementary telehealth via video-conferencing platforms could bring additional benefits to care-recipient with NCD and their spousal caregivers at home. PARTICIPANTS: Sixty older adults NCD-and-caregiver dyads were recruited through an activity center. DESIGN, INTERVENTION: The impact of additional services delivered to both care-recipient and caregiver through video conference (n = 30) was compared with telehealth targeted at caregivers by telephone only (n = 30), over 4 weeks in a pretest-post-test design. Interviews and questionnaires were conducted at baseline and study's end. MEASUREMENTS, RESULTS: Supplementary telemedicine had averted the deterioration in the Montreal Cognitive Assessment evident in the telephone-only group (ηp2 = 0.50). It also reversed the falling trend in quality of life observed in the telephone only group (QoL-AD, ηp2 = 0.23). Varying degrees of improvements in physical and mental health (Short-Form 36 v2), perceived burden (Zarit Burden Interview Scale) and self-efficacy (Revised Caregiving Self-Efficacy Scale) were observed among caregivers in the video-conferencing group, which were absent in the telephone-only group (ηp2 = 0.23-0.51). CONCLUSION: Telemedicine by video conference was associated with improved resilience and wellbeing to both people with NCD and their caregivers at home. The benefits were visible already after 4 weeks and unmatched by telephone alone. Video conference as the modus operandi of telehmedicine beyond the context of pandemic-related social distancing should be considered.


Subject(s)
Caregivers/psychology , Coronavirus Infections , Dementia , Pandemics , Pneumonia, Viral , Quality of Life , Telemedicine/methods , Videoconferencing , Aged , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/psychology , Dementia/epidemiology , Dementia/therapy , Dementia/virology , Female , Home Care Services/trends , Hong Kong/epidemiology , Humans , Independent Living/psychology , Male , Mental Health , Patient Care Management/methods , Patient Care Management/trends , Pneumonia, Viral/epidemiology , Pneumonia, Viral/psychology , Protective Factors , SARS-CoV-2
3.
Arch Gerontol Geriatr ; 90: 104167, 2020.
Article in English | MEDLINE | ID: mdl-32663699

ABSTRACT

INTRODUCTION: Participating in meaningful activities is important for any individual's wellbeing. Activity scheduling enables older adults with dementia and their spouse caregivers to structure their activities in accordance with the things they value. METHODS: In examining the effectiveness of activity scheduling, this report details the results of a 12-week single-blinded randomized control trial using a parallel group experimental design. RESULTS: From August 2018 to August 2019, 100 community-dwelling older adults with mild to moderate dementia and their spouses completed this study. The experimental group (n = 50) practicing activity scheduling showed improvements than in control group (n = 50), with respect to alleviating the impact of the caregiving role, reducing the behavioural and psychological symptoms of dementia, decreasing the caring demand and generally improving the quality of life, with Cohen's d = .61, .45, .50 and 43 respectively. Moreover, there were significant differences between the groups indicated that over time, the experimental group showed an improvement with regard to alleviating the role of caring, with Cohen's d = .64, and alleviating disruptive and depressive behavior, with an effect size of .45 and .50 respectively. The number of caring hours needed dropped from 6.98 to 5.98 h in the experimental group. DISCUSSION & CONCLUSION: There were more activities that older adults with dementia and their spouse caregivers would like to do, and could participate in, than we had expected. Activity scheduling can facilitate their participation. This is a very important topic as non-pharmacological interventions are needed for this even-growing segment of the population.


Subject(s)
Caregivers , Dementia , Aged , Dementia/therapy , Humans , Quality of Life , Spouses
4.
Arch Gerontol Geriatr ; 87: 104012, 2020.
Article in English | MEDLINE | ID: mdl-31968279

ABSTRACT

INTRODUCTION: Executive function helps older adults maintain their activities of daily living by making plans, setting goals, and carrying them out successfully. It is important for their independence in community living. METHODS: With a carefully match-group of 80 mild cognitive impaired with 80 health control subjects. The home-based evaluation of executive function (Home-MET) was validated in subjects' own living environment. RESULTS: This Home-MET showed significant correlation in the assessment of attention control that was assessing by Test of Everyday Attention (TEA) (r = .86, p < .01), with working memory that was assessed with Trail Making Test (TMT) (r = .72, p < .01), with inhibitory control that was assessing with Stroop Test (r = .86, p < .01), with individuals' functional disability was assessed by Chinese Disability Assessment of Dementia (CDAD) (r = .77, p < .01) and cognitive assessment was assessed by Hong Kong Montreal Cognitive Assessment (HK-MoCA) (r = .88, p < .01). By benchmarking with the validated performance-based executive function assessment, the Home-MET shows significant correlation (r = .92, p < .05) with the executive function test in a standard environment in hospital, i.e. the Chinese Multiple Errands Test (the Chinese-MET). The two-stage hierarchical linear regression model with backward method showed functional disability was a marginally significant predictor (p < .059) for the Home-MET with regression model showed with R2 = .93. CONCLUSION: Results indicated the Home-MET, can provide an objective measure of executive function for subjects with mild cognitive impairment in participants' own home environment.


Subject(s)
Cognitive Dysfunction/psychology , Executive Function/physiology , Aged , Aged, 80 and over , Female , Humans , Male , Mental Status and Dementia Tests , Neuropsychological Tests , Trail Making Test
5.
J Chromatogr A ; 1575: 49-58, 2018 Nov 09.
Article in English | MEDLINE | ID: mdl-30262393

ABSTRACT

Endotoxins are complex molecules and one of the most challenging impurities requiring separation in biopharmaceutical protein purification processes. Usually these contaminants are cleared during the downstream process, but if endotoxin interacts with the target protein it becomes difficult to remove. In the present study we identified a detergent, octyl-ß-D-1-thioglucopyranoside (OTG), that disrupted endotoxin-protein interactions. The integration of this detergent into washes on several chromatography media was demonstrated to provide a separation tool for decreasing endotoxin from target proteins. This study also examined the mechanism of OTG endotoxin-protein disruption through phase modification incubation and chromatographic studies. The non-ionic OTG wash was shown to break both hydrophobic and electrostatic interactions between the endotoxin and protein. This mechanism contrasts with the breaking of hydrophobic interactions by washing with known endotoxin decreasing Triton X-100 detergent. The difference in mechanisms likely results in the ability of OTG to decrease endotoxin to levels less than those resulting from a detergent wash such as Triton X-100. Finally, we show the impact of the OTG endotoxin removal tool on the biopharmaceutical industry. While maintaining monomer purity and activity levels, endotoxin removal from a fusion protein allowed for decreased background levels in a T cell functional assay. The lowered baseline of T cell responses allowed for more effective detection of molecular interaction with the cells. The detergent wash can be used to both decrease the overall level of endotoxin in a purified protein solution and to enable more effective screening of lead candidate molecules.


Subject(s)
Chemistry, Pharmaceutical/methods , Chromatography, Affinity , Endotoxins/isolation & purification , Thioglucosides/chemistry , Endotoxins/chemistry , Octoxynol/chemistry
6.
Injury ; 47(1): 192-6, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26391591

ABSTRACT

INTRODUCTION: Trampoline-related injuries in adults are uncommon. Participation in trampolining is increasing following its admission as a sport in the Olympics and the opening of local recreational trampoline centres. The aim of this study was to assess the number and outcomes of adult trampoline-related orthopaedic injuries presenting to four trauma hospitals in Victoria. METHODS: A cohort study was performed for the period 2007-2013. Adult patients registered by the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR) who had sustained a trampolining related injury were included in this study. Descriptive analyses were used to describe the patient population, the injuries sustained and their in-hospital and 6-month outcomes. RESULTS: There was an increase in trampolining injuries from 2007 (n=3) to 2012 (n=14) and 2013 (n=18). Overall, fifty patients with a median age of 25 (range 16-66) were identified. Thirty-five patients (70%) had lower limb injuries, 20 patients (40%) had spinal injuries and one patient had an upper limb injury. Thirty-nine patients (78%) required surgery. Fractures of the tibia (n=13), ankle fractures (n=12) and cervical spine injuries (n=7) were the most common injuries; all of which required surgery. Complications included death, spinal cord injuries, compartment syndrome and open fractures. At 6 months post injury, more than half (52%) of the patients had not achieved a good recovery, 32% had some form of persistent disability, 14% did not get back to work and overall physical health for the cohort was well below population norms for the SF-12. CONCLUSION: Adult trampoline-related injuries have increased in the last few years in this cohort identified through VOTOR. Lower limb and spinal injuries are most prevalent. Public awareness and education are important to reduce the risk for people participating in this activity.


Subject(s)
Accident Prevention/methods , Accidental Falls/statistics & numerical data , Accidents, Home/statistics & numerical data , Fractures, Bone/epidemiology , Hospitalization/statistics & numerical data , Neck Injuries/epidemiology , Spinal Injuries/epidemiology , Sports Equipment/adverse effects , Trauma Centers , Accidental Falls/prevention & control , Accidents, Home/prevention & control , Adult , Aged , Cohort Studies , Disability Evaluation , Female , Fractures, Bone/etiology , Fractures, Bone/prevention & control , Health Education , Humans , Incidence , Injury Severity Score , Male , Middle Aged , Neck Injuries/etiology , Neck Injuries/prevention & control , Play and Playthings , Recreation , Return to Work , Risk Factors , Spinal Injuries/etiology , Spinal Injuries/prevention & control , Trauma Centers/statistics & numerical data , Victoria/epidemiology
7.
J Chromatogr A ; 1260: 120-5, 2012 Oct 19.
Article in English | MEDLINE | ID: mdl-22980642

ABSTRACT

We describe the analytical characterization and process scale separation of a deamidated variant of an immunotoxin. The different charge variants of the immunotoxin were separated using analytical ion-exchange HPLC. These charge variants were analyzed by peptide mapping and LC-MS/MS to identify the site of modification, which was determined to reside in the toxin portion of the molecule. Using a cell-based bioassay it was also determined that deamidation led to reduced biological activity, requiring it be controlled during manufacturing. This was accomplished using process scale anion-exchange chromatography. The process was capable of reducing the deamidated form to a level low enough for the resulting product to maintain acceptable biological activity. Keys to the successful control of this impurity at process scale were a good understanding of structure-function relationship and the availability of an analytical HPLC assay to provide a surrogate for the cell-based bioassay.


Subject(s)
Bacterial Toxins/chemistry , Bacterial Toxins/isolation & purification , Chromatography, Ion Exchange/methods , Exotoxins/chemistry , Exotoxins/isolation & purification , Immunotoxins/chemistry , Immunotoxins/isolation & purification , Peptide Mapping/methods , ADP Ribose Transferases/chemistry , Amides/chemistry , Cell Line, Tumor , Chromatography, High Pressure Liquid/methods , Humans , Tandem Mass Spectrometry , Virulence Factors/chemistry , Pseudomonas aeruginosa Exotoxin A
9.
Arch Facial Plast Surg ; 12(5): 291-7, 2010.
Article in English | MEDLINE | ID: mdl-20855769

ABSTRACT

OBJECTIVES: To assess the subjective aesthetic and functional concerns of patients seeking revision rhinoplasty and to compare them with objective deformities found on evaluation by the surgeon. METHODS: This prospective study used a questionnaire to systematically target the aesthetic and functional concerns of 104 consecutive patients seeking revision rhinoplasty. Analysis of the subjective data revealed the frequency of each concern, which was then compared with objective deformities found on evaluation by the surgeon. RESULTS: The most common patient and surgeon aesthetic concerns were (1) tip asymmetry, (2) crooked middle third of the nose, and (3) upper third irregularity. A mean of 79% of patient concerns were also reported by the surgeon. Of the 64 patients describing subjective nasal obstruction, 60 (94%) had objective physical findings related to obstruction. The 3 most troublesome patient concerns were (1) tip asymmetry, (2) difficulty breathing or nasal blockage, and (3) crooked middle third of the nose. CONCLUSIONS: Tip asymmetry was the most common deformity noted. Symptomatic nasal obstruction was the second most frequent reason for seeking revision rhinoplasty. Differences in patient and surgeon findings were largely due to differences in assessment skills and should be addressed by thorough explanation of nasal aesthetics.


Subject(s)
Esthetics , Nasal Obstruction/psychology , Nasal Obstruction/surgery , Nose Deformities, Acquired/psychology , Nose Deformities, Acquired/surgery , Nose/abnormalities , Patient Satisfaction , Postoperative Complications/psychology , Postoperative Complications/surgery , Rhinoplasty/psychology , Surveys and Questionnaires , Adolescent , Adult , Aged , Attitude of Health Personnel , Female , Humans , Male , Middle Aged , Motivation , Nasal Obstruction/diagnosis , Nose Deformities, Acquired/diagnosis , Patient Participation , Physician-Patient Relations , Postoperative Complications/diagnosis , Prospective Studies , Reoperation/psychology , Young Adult
10.
Laryngoscope ; 120(8): 1576-81, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20564660

ABSTRACT

OBJECTIVES/HYPOTHESIS: Although the diagnostic accuracy of paradoxical vocal fold movement disorder and chronic cough has improved, the underlying pathophysiology remains relatively unknown. We hypothesize that one potential etiological factor in these patients is an aberrant laryngeal sensory response and sought to determine if respiratory retraining in addition to antireflux therapy alters this aberrant response. STUDY DESIGN: Retrospective, outcomes. METHODS: Sixteen patients who had been on at least 3 months of twice-daily proton pump inhibitors with no subjective improvement in their primary complaint of cough, self-reported symptoms of gastroesophageal and laryngopharyngeal reflux, and concurrent paradoxical vocal fold movement (PVFM) were included in the current study. In addition to continuing twice daily pharmacological therapy, subjects underwent a course of respiratory retraining. Outcome measures including the Reflux Symptom Index (RSI), transnasal flexible laryngoscopy, and laryngopharyngeal sensory discrimination thresholds were obtained prior to and following a course of respiratory retraining. RESULTS: Mean bilateral laryngeal sensory response improved significantly after combined respiratory retraining and aggressive proton pump inhibitor therapy (P = .01). In addition, mean RSI score decreased significantly following treatment (P = .02). Specifically, 13 of 16 patients experienced improved sensory response, corresponding with patient reports of improved PVFM symptoms following treatment. CONCLUSIONS: Aberrant laryngeal sensation was identified in patients with PVFM and chronic cough. This response, however, normalized following a limited course of respiratory retraining, corresponding with improved patient symptoms.


Subject(s)
Breathing Exercises , Laryngeal Diseases/physiopathology , Laryngeal Diseases/therapy , Vocal Cords/physiopathology , Adult , Aged , Cough/physiopathology , Humans , Laryngopharyngeal Reflux/physiopathology , Middle Aged , Movement Disorders/physiopathology , Retrospective Studies
11.
Arch Facial Plast Surg ; 12(3): 159-65, 2010.
Article in English | MEDLINE | ID: mdl-20479431

ABSTRACT

OBJECTIVE: To evaluate the efficacy of the Mitek minianchor suture system as an adjunctive procedure for static facial suspension and assess its ability to improve functional and aesthetic outcomes in patients with complete facial paralyses. METHODS: A retrospective review of 5 patients who underwent adjunctive static facial suspension with the Mitek GII minianchor suture system at a tertiary care academic center. A bone anchor in the maxilla connected to 2 suture arms was used. One suture arm elevated the oral commissure on the paralyzed side. The second suture arm adjusted for upper lip segment asymmetry and Cupid's bow deviation, or lateralized the external nasal valve. Outcome was evaluated by photodocumentation and clinical examination. RESULTS: There was an average of 76.9% improvement in vertical symmetry of the oral commissure (range, 43%-100%), an average of 65.0% improvement in horizontal deviation of the Cupid's bow (range, 50%-100%), and an average of 85.3% improvement in symmetry of upper lip segments (range, 67%-100%). All patients experienced improvement in oral-nasal competency. CONCLUSIONS: The Mitek minianchor suture system is a safe and effective adjunctive method to improve facial symmetry and oral-nasal competency in patients with facial paralyses. Its multivector design approximates the ideal positions of key anatomical points of the midface during static facial suspension surgery.


Subject(s)
Facial Paralysis/surgery , Plastic Surgery Procedures/methods , Suture Anchors , Adult , Aged , Esthetics , Facial Paralysis/etiology , Female , Humans , Retrospective Studies , Treatment Outcome
12.
Diagn Cytopathol ; 38(3): 184-7, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19774616

ABSTRACT

Pleomorphic lipoma is a rare lipocytic neoplasm that most commonly occurs in the head and neck region in middle-aged to elderly men. Clinically, it presents as a slow-growing, well-circumscribed subcutaneous mass. Histopathologically and cytogenetically, it has some features overlapping with other benign and malignant tumors, such as benign spindle cell lipoma, atypical lipomatous tumor, liposarcoma, and malignant fibrous histiocytoma. However, cure rates are high when pleomorphic lipoma is treated with complete surgical excision with clear margins. Therefore, an accurate preoperative diagnosis is very important for proper treatment. Due to the rarity of this tumor, few cases diagnosed by cytology have been reported in the English literature. Here, we report two cases of pleomorphic lipoma, the diagnoses of which were suggested on fine needle aspiration biopsies and subsequently confirmed by surgical excisions.


Subject(s)
Head and Neck Neoplasms/pathology , Lipoma/pathology , Soft Tissue Neoplasms/pathology , Aged, 80 and over , Biomarkers, Tumor/metabolism , Biopsy, Fine-Needle , Chromosome Aberrations , Chromosomes, Human, 16-18 , Chromosomes, Human, Pair 13 , Diagnosis, Differential , Fat Necrosis/diagnosis , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/surgery , Humans , Incidental Findings , Lipoma/genetics , Lipoma/metabolism , Lipoma/surgery , Magnetic Resonance Imaging , Male , Middle Aged , Soft Tissue Neoplasms/genetics , Soft Tissue Neoplasms/metabolism , Soft Tissue Neoplasms/surgery , Spinal Neoplasms/pathology , Treatment Outcome
14.
Laryngoscope ; 114(2): 309-16, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14755210

ABSTRACT

OBJECTIVE/HYPOTHESIS: To assess the audiologic and surgical outcomes for pediatric cochlear implant patients with inner ear malformations. STUDY DESIGN: Retrospective review of 315 pediatric cochlear implant cases from 1994 to 2002. METHODS: Twenty-eight pediatric cochlear implant patients with known inner ear malformations determined on high-resolution computed tomography (HRCT) of the temporal bone were the subjects of review. Results of HRCT findings, intraoperative findings, postoperative complications, and objective measures of both closed- and open-set testing of speech perception were analyzed. RESULTS: Patients with the constellation of an incompletely partitioned (IP) cochlea, enlarged vestibular aqueduct (EVA), and a dilated vestibule (i.e., Mondini's malformation) as well as those with an isolated EVA or partial semicircular canal aplasia have relatively good levels of speech perception. Patients with total semicircular canal aplasia, isolated IP, cochlear hypoplasia, or common cavity demonstrated lower levels of performance. Poor performance may be related to associated developmental delays rather than labyrinthine anatomy alone. Complications of surgery were relatively limited. CONCLUSIONS: Cochlear implantation can be successfully performed in children with inner ear malformations. These children and their parents can expect significant auditory benefits from this intervention. The various types of inner ear malformations may have quite different prognoses for good auditory performance.


Subject(s)
Cochlear Implantation , Ear, Inner/abnormalities , Adolescent , Child , Child, Preschool , Cochlea/abnormalities , Ear, Inner/surgery , Humans , Infant , Postoperative Complications , Retrospective Studies , Speech Perception/physiology , Temporal Bone/diagnostic imaging , Tomography, X-Ray Computed , Treatment Outcome , Vestibular Aqueduct/abnormalities , Vestibule, Labyrinth/abnormalities
15.
Arch Otolaryngol Head Neck Surg ; 130(1): 21-7, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14732763

ABSTRACT

BACKGROUND: The presence or absence of metastatic disease in cervical lymph nodes is the single most important determinant of therapy and prognosis for patients with head and neck squamous cell carcinoma (HNSCC). However, histologic examination fails to detect metastatic disease in a subset of neck dissection specimens. The accuracy of neck staging may be improved by the use of molecular techniques. Cytokeratins 5, 14, and 20 may be appropriate markers for HNSCC because they are expressed in HNSCC but not in lymphatic tissue. DESIGN: To test the sensitivity of detection of cytokeratin 5, 14, and 20 messenger RNA by quantitative reverse transcription polymerase chain reaction (RT-PCR), full-length coding DNA sequences were cloned and transcribed. The expression of cytokeratin 5, 14, and 20 messenger RNA was quantified in 4 HNSCC cell lines and 11 tumors. A cell culture lymph node model was created. RESULTS: As few as 32 molecules of cytokeratin 14 could be detected using quantitative RT-PCR. Cytokeratins 5 and 14 were easily detected in all 4 HNSCC cell lines and almost all tumors. Cytokeratin 20 was not a useful marker, as expression was absent or significantly reduced in cell lines and tumors. In the lymph node model, cytokeratin 14 quantitative RT-PCR was able to detect 1 cancer cell in a background of 10 million lymphatic cells. CONCLUSIONS: Quantitative RT-PCR detection of cytokeratin 5 or 14 is a sensitive new molecular technique that may be used for detection of cervical micrometastases in head and neck cancer.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/secondary , Head and Neck Neoplasms/pathology , Keratins/analysis , Lymphatic Metastasis/diagnosis , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Head and Neck Neoplasms/genetics , Humans , Keratins/genetics , Molecular Probes , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Tumor Cells, Cultured
16.
Otolaryngol Head Neck Surg ; 129(6): 637-46, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14663429

ABSTRACT

OBJECTIVES: The study goals were (1) to determine if the degree and pattern of semicircular canal dysmorphology and the presence or absence of a cochlea in patients with congenital sensorineural hearing loss predict audiologic outcome, severity, or the frequencies involved and (2) to review the recent advances in molecular genetics of the semicircular canals and correlate this information with audiologic and anatomic patterns seen in our series of patients. DESIGN AND SETTING: We conducted a retrospective study at a tertiary care center with a large otologic and cochlear implant service. PATIENTS AND METHODS: The study population consisted of 16 patients with congenital sensorineural hearing loss in 28 congenitally malformed inner ears consisting of semicircular canal dysplasia or aplasia, with or without cochlear malformation. History, physical examination, computed tomography scans, and serial audiograms were reviewed. Factors analyzed included other phenotypic dysmorphology characteristic of syndromes, audiometric configuration, severity and type of hearing loss, and the presence of associated inner ear anomalies other than the vestibular system. An extensive review of the literature regarding molecular genetic factors in semicircular canal anomalies, with or without cochlear abnormalities, was performed. RESULTS: Sixteen patients (31 ears) were identified with profound sensorineural hearing loss and semicircular canal abnormalities. Only 3 patients had known syndromes, although 4 patients had other congenital anomalies. Most radiographic detectable abnormalities were bilateral. Audiograms of the patients demonstrated pure tone averages between 90 and 100 dB in the affected ears with few exceptions. No correlation was found between type and severity of malformation of either the cochlea or semicircular canals with the severity of hearing loss. There was no stepwise progression of hearing loss increasing malformation severity. Seven of the 16 patients received cochlear implants. Of these 7, 3 patients had cochlear hypoplasia and 1 patient had a common cavity deformity. Audiologic follow-up on all 7 patients revealed improvement in both speech assessment threshold and pure tone average. Presence or absence of the cochlea was not a factor in outcome after cochlear implantation. CONCLUSION: We have assembled the largest series of patients with semicircular canal dysmorphology, with or without various cochlear abnormalities. Our study failed to correlate the type and severity of semicircular canal malformation with any specific audiologic outcome. The variation in hearing loss severity and pattern even in patients with similar bony radiographic findings must be explained by other non-radiologically detectable defects, likely abnormalities in membranous labyrinthine development. New molecular genetic discoveries have linked specific genes to the development of certain inner ear structures in mice studies. The independent development of the individual semicircular canals in relation to the cochlea and vestibule and the variability in hearing loss suggest a more complex embryologic process than merely an arrest in development as previously thought. As genetic studies are extended into humans, we will likely be able to stratify these patients by molecular defect and severity of hearing loss.


Subject(s)
Hearing Loss, Sensorineural/congenital , Hearing Loss, Sensorineural/genetics , Molecular Biology , Semicircular Canals/abnormalities , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Predictive Value of Tests , Severity of Illness Index
17.
Laryngoscope ; 113(6): 1047-9, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12782820

ABSTRACT

OBJECTIVE: At the conclusion of the report, the readers should be able to recognize the rare complication of adenotonsillectomy of Grisel syndrome, discuss its pathogenesis, and provide early, effective treatment. STUDY DESIGN: Analysis of the clinical presentation, plain radiographs, computed tomography scans, and magnetic resonance imaging scans of a child with Grisel syndrome after adenotonsillectomy. METHODS: Retrospective study of the case record and a review of the literature regarding the pathogenesis, treatment modalities, outcome, and prognosis after early and delayed treatment of Grisel syndrome. RESULTS: Pathophysiology of atlantoaxial subluxation revolves around the periodontoid vascular plexus that drains the posterosuperior pharyngeal region. Infectious and inflammatory emboli cause synovial engorgement, weakening paraspinal ligaments. Radiological studies play an important role in diagnosis. Treatment consists of cervical immobilization, muscle relaxants, analgesics, and antibiotics. Full resolution is expected with early conservative management. Failure to recognize the syndrome can lead to catastrophic results. CONCLUSIONS: Recognition of Grisel syndrome in addition to other rare complications of adenotonsillectomy requires a high index of suspicion. Early intervention is the critical factor for a positive outcome. However, delayed diagnosis is common and can result in catastrophic consequences, including neurological deficits, cosmetic deformity and, in rare instances, paralysis and death in the short term.


Subject(s)
Adenoidectomy , Atlanto-Axial Joint/injuries , Joint Dislocations/etiology , Postoperative Complications/etiology , Sleep Apnea, Obstructive/surgery , Tonsillectomy , Child , Diagnostic Imaging , Follow-Up Studies , Humans , Immobilization , Joint Dislocations/therapy , Male , Orthotic Devices , Physical Therapy Modalities , Postoperative Complications/diagnosis , Postoperative Complications/therapy , Retrospective Studies , Sleep Apnea, Obstructive/etiology , Syndrome
18.
Laryngoscope ; 112(9): 1587-93, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12352668

ABSTRACT

OBJECTIVE: The tumor suppressor gene p16 encodes a cyclin-dependent kinase inhibitor that normally inhibits cell proliferation by causing a G1 cell cycle arrest. The p16 gene is frequently mutated in a variety of somatic tumors, as well as in familial melanoma and familial pancreatic carcinoma. We identified a family with a high incidence of head and neck squamous cell carcinoma (HNSCC) and melanoma. Molecular analyses of the p16 gene locus in blood and tumor DNA from this family was performed to determine whether an association between germline p16 gene mutation and HNSCC exists. STUDY DESIGN: Molecular pedigree analyses. METHODS: Exon 2 of p16 was polymerase chain reaction amplified from blood, tumor, or nontumor DNA isolated from affected and unaffected members, then directly sequenced and compared with consensus p16 sequence. Cell cycle position of cells expressing wild-type or mutant p16 was determined by flow cytometry. RESULTS: Molecular analyses revealed a nonfunctional germline point mutation within exon 2 of the p16 gene that encodes a mutant p16 protein substituting proline at amino acid position 87 for the wild-type arginine (p16R87P). Relative to wild-type p16, p16R87P lost ability to cause a growth arrest following ectopic expression. The mutant (p16R87P) allele segregated with cancer predisposition in tested family members, and analyses of HNSCC tumor tissues demonstrated universal loss of wild-type allele. CONCLUSIONS: Significance of the mutant p16 (p16R87P) in HNSCC tumorigenesis is strongly suggested by its loss of cell cycle arrest activity and its retention in tumor tissue with simultaneous loss of the wild-type allele. Further, the germline p16 mutation segregated with cancer predisposition within the family. In aggregate, these data suggest that there is a direct causal relationship between the germline p16 mutation in this family and HNSCC tumorigenesis. Based on our observations, the spectrum of familial cancers associated with p16 mutations should include a new clinical entity, familial HNSCC.


Subject(s)
Carcinoma, Squamous Cell/genetics , Cyclin-Dependent Kinase Inhibitor p16 , Genes, Tumor Suppressor , Germ-Line Mutation , Head and Neck Neoplasms/genetics , Melanoma/genetics , Alleles , Amino Acid Substitution , Exons , Family Health , Flow Cytometry , Gene Expression , Genetic Predisposition to Disease , Humans , Pedigree , Polymerase Chain Reaction
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