Keratosis obturans (KO) and external auditory canal cholesteatoma (EACC) are two distinct keratinaceous lesions of the external ear. This article reviews the signs, symptoms, pathophysiology, workup, and treatment of each. Patients with either pathology can often be managed in the clinic with debridement; however, EACC is more likely to involve osteonecrosis and require more extensive operative management if disease is not confined to the canal on account of the bony erosion characteristic of cholesteatoma. If required for extensive disease, surgical approaches to both pathologies are similar.
Cholesteatoma , Ear Diseases , Keratosis , Humans , Ear Canal/diagnostic imaging , Ear Canal/surgery , Ear Diseases/diagnosis , Ear Diseases/surgery , Cholesteatoma/diagnosis , Cholesteatoma/surgery , Keratosis/diagnosis , Keratosis/pathology , Keratosis/surgery , Retrospective Studies
PURPOSE: To systematically study somatic variants arising during development in the human brain across a spectrum of neurodegenerative disorders. METHODS: In this study we developed a pipeline to identify somatic variants from exome sequencing data in 1461 diseased and control human brains. Eighty-eight percent of the DNA samples were extracted from the cerebellum. Identified somatic variants were validated by targeted amplicon sequencing and/or PyroMark® Q24. RESULTS: We observed somatic coding variants present in >10% of sampled cells in at least 1% of brains. The mutational signature of the detected variants showed a predominance of C>T variants most consistent with arising from DNA mismatch repair, occurred frequently in genes that are highly expressed within the central nervous system, and with a minimum somatic mutation rate of 4.25 × 10-10 per base pair per individual. CONCLUSION: These findings provide proof-of-principle that deleterious somatic variants can affect sizeable brain regions in at least 1% of the population, and thus have the potential to contribute to the pathogenesis of common neurodegenerative diseases.
Brain/metabolism , DNA Mismatch Repair/genetics , Exome/genetics , Genetic Diseases, Inborn/genetics , Brain/pathology , Genetic Diseases, Inborn/diagnosis , High-Throughput Nucleotide Sequencing , Humans , Mutation , Sequence Analysis, DNA , Exome Sequencing
The m.1555A>G mtDNA variant causes maternally inherited deafness, but the reasons for the highly variable clinical penetrance are not known. Exome sequencing identified a heterozygous start loss mutation in SSBP1, encoding the single stranded binding protein 1 (SSBP1), segregating with hearing loss in a multi-generational family transmitting m.1555A>G, associated with mtDNA depletion and multiple deletions in skeletal muscle. The SSBP1 mutation reduced steady state SSBP1 levels leading to a perturbation of mtDNA metabolism, likely compounding the intra-mitochondrial translation defect due to m.1555A>G in a tissue-specific manner. This family demonstrates the importance of rare trans-acting genetic nuclear modifiers in the clinical expression of mtDNA disease.
DNA-Binding Proteins/genetics , Family Health , Hearing Loss/genetics , Mitochondrial Proteins/genetics , Mutation/genetics , Adolescent , Child , Child, Preschool , DNA Mutational Analysis , Electron Transport Complex II/metabolism , Electron Transport Complex IV/metabolism , Female , Fibroblasts/metabolism , Fibroblasts/pathology , Hearing Loss/complications , Heterozygote , Humans , Infant , Male , Mitochondrial Diseases/complications , Mitochondrial Diseases/genetics , Mitochondrial Proton-Translocating ATPases/metabolism , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Muscle, Skeletal/ultrastructure , Young Adult
We present the first case of a head and neck oncological procedure accomplished in a Jehovah's Witness using the Ultracision Harmonic Scalpel (Ethicon, Cincinnati, OH). Jehovah's Witnesses present a serious challenge to the head and neck cancer surgeon due to their refusal to accept transfusion of any blood products. However, our experience reinforces the view that surgical management of head and neck cancer is possible in these patients. We show the Harmonic Scalpel, an ultrasonic tissue dissector, to be a useful surgical tool in obviating the need for blood transfusion. Preoperative optimisation, intra-operative surgical and anaesthetic techniques are also fully discussed.
Blood Loss, Surgical/prevention & control , Carcinoma, Squamous Cell/surgery , Jehovah's Witnesses , Mouth Neoplasms/surgery , Surgical Instruments , Blood Transfusion , Carcinoma, Squamous Cell/pathology , Female , Humans , Middle Aged , Mouth Neoplasms/pathology , Preoperative Care , Surgical Flaps , Treatment Outcome
Endovascular stenting has been successfully employed in the management of aortic aneurysms; however, its use in managing peripheral arterial conditions remains questionable. We review the utility of endovascular technique in the management of peripheral arterial conditions like aneurysms, pseudoaneurysms and arterio-venous fistulas in the emergency setting. Though long term data about graft patency rates is not yet available, the endovascular approach appears to be a useful minimally invasive technique in situations where open repair is either difficult or not feasible.
