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Biomedical subjects

Noam A Cohen

Publications and source records attributed to Noam A Cohen.

14 recordsLinked to original sources
PubMed2007

Mucociliary clearance--a critical upper airway host defense mechanism and methods of assessment.

PURPOSE OF REVIEW: Mucociliary clearance is a critical host defense mechanism of the airways. Effective mucociliary clearance requires appropriate mucus production and coordinated ciliary activity. The important role of these two components is best demonstrated in disorders such as primary ciliary dyskinesia and cystic fibrosis, both of which lead to lifelong recurrent respiratory tract infections. We review the methods used to analyze mucociliary clearance. RECENT FINDINGS: Utilization of microdialysis probes has improved temporal resolution of mucociliary clearance in murine airways, availing many genetic mouse models to critical mucociliary clearance analysis, while improved fixation technique for transmission electron microscopy has allowed for detailed resolution of the airway surface liquid. High-speed digital video analysis has improved quantification of ciliary beat frequency while advancements in air-liquid interface culturing techniques have generated in-vitro models to investigate mucociliary clearance. SUMMARY: Advancements in techniques for analysis of mucociliary clearance have improved our understanding of the interaction between the respiratory epithelium and the airway surface liquid, resulting in the ability to study pathologic processes involving mucociliary clearance in great detail.

Animals↗
PubMed2006

Revision endoscopic sinus surgery.

Patients with recurrent chronic sinusitis after prior surgical intervention pose a particular challenge to the otorhinolaryngologist. Establishing a correct diagnosis is the first step and requires review of the original presurgical symptoms and imaging; review of the more recent symptoms and images;and reevaluation of environmental, general, and local host factors that may contribute to persistent disease. Although primary chronic rhinosinusitis is typically a medical disease, postsurgical persistent disease may result directly from iatrogenic causes, requiring early surgical revision. Even in this setting, however, proper preoperative medical therapy is essential. Diagnostic evaluation should include meticulous endoscopic evaluation and appropriate radiologic studies. CT typically is required in the coronal and axial planes and ideally is performed using a computer-assisted surgical navigation protocol and with reconstructions in the sagittal plane, allowing for "scrolling" through the altered anatomy and conceptualizing the surgical issues at hand. When the decision to undergo revision surgery is made, the patient and the physician need to comprehend the rigorous and prolonged schedule of postoperative care and débridements that may be required for long-term success. Appropriate surgical technique emphasizing mucosal preservation and complete dissection must be adhered to. The surgeon must be aware that bony thickening is likely to be present and to make the dissection significantly more difficult than in the primary case. Medical management and endoscopic surveillance postoperatively is continued until a stable cavity is achieved.

Chronic Disease↗
PubMed2006

Familial aggregation of sinonasal polyps correlates with severity of disease.

OBJECTIVE: Investigate familial aggregation of sinonasal polyps (NP) and correlate the severity of chronic rhinosinusitis (CRS) with a family history of NP. STUDY DESIGN AND SETTING: A questionnaire documenting NP, asthma, or aspirin intolerance was completed by 174 CRS patients. Severity of sinus disease was stratified as isolated NP, NP with concomitant asthma, and Samter's triad (polyps, asthma, and aspirin intolerance). RESULTS: Compared to controls, CRS patients had a higher incidence of a family history of NP. Additionally, patients stratified with severe CRS had a higher incidence of relatives with NPs. CONCLUSIONS: Familial aggregation of NP is demonstrated in CRS patients and correlates with disease severity. EBM RATING: B-2b.

Bias↗
PubMed2006

Sinonasal mucociliary clearance in health and disease.

Although much has been elucidated in the past 170 years concerning the precise mechanism of ciliary function in the healthy or diseased human respiratory system, significant questions remain. The first description of ciliary action is credited to Sharpey in 1835. However, the importance of mucosal function was not apparent until Hilding's investigations of the postsurgical canine sinus demonstrated scar formation and disruption of mucociliary clearance. Subsequently, several techniques for mucosal coverage of exposed bone, most notably by Sewall and Boyden, were reported. The underlying physiology explaining the importance of the mucosa and the concept of mucosal preservation became apparent with the description of the sinonasal mucociliary flow patterns by Messerklinger; and thus the restoration of natural sinus physiology, ie, mucociliary clearance, became the goal of both medical and surgical treatment of sinonasal inflammatory disease. Clearance of benign and pathological substances in the mucus is governed by the propulsive force of the beating cilia and the physical characteristics of the overlying mucus. The respiratory cilia continually beat in a coordinated fashion, and in times of stress (eg, exercise, infection, or fever) ciliary beat frequency increases to accelerate mucus clearance. Thus, upper airway ciliary motility is under dynamic modulation. Multiple investigations incontrovertibly demonstrate a marked decrease in sinonasal mucociliary clearance in patients with chronic rhinosinusitis. Possible explanations for this finding are 1) a reduced basal ciliary beat frequency, 2) an alteration of the viscoelastic properties of airway secretions, and/or 3) a blunted dynamic response of sinonasal cilia to environmental stimuli. Studies of the first two explanations yield conflicting results, and to date, the third possibility remains uninvestigated. A review of the current understanding of the cellular regulation of respiratory ciliary activity and its contribution to chronic rhinosinusitis is presented.

Animals↗
PubMed2005

Mutation of critical GIRK subunit residues disrupts N- and C-termini association and channel function.

The subfamily of G-protein-linked inwardly rectifying potassium channels (GIRKs) is coupled to G-protein receptors throughout the CNS and in the heart. We used mutational analysis to address the role of a specific hydrophobic region of the GIRK1 subunit. Deletion of the GIRK1 C-terminal residues 330-384, as well as the point mutation I331R, resulted in a decrease in channel function when coexpressed with GIRK4 in oocytes and in COS-7 cells. Surface protein expression of GIRK1 I331R coexpressed with GIRK4 was comparable with wild type, indicating that subunits assemble and are correctly localized to the membrane. Subsequent mutation of homologous residues in both the GIRK4 subunit and Kir2.1 (Gbetagamma-independent inward rectifier) also resulted in a decrease in channel function. Intracellular domain associations resulted in the coimmunoprecipitation of the GIRK1 N and C termini and GIRK4 N and C termini. The point mutation I331R in the GIRK1 C terminus or L337R in the GIRK4 C terminus decreased the association between the N and C termini. Mutation of a GIRK1 N-terminal hydrophobic residue, predicted structurally to interact with the C-terminal domain, also resulted in a decrease in channel function and termini association. We hypothesize that the hydrophobic nature of this GIRK1 subunit region is critical for interaction between adjacent termini and is permissive for channel gating. In addition, the homologous mutation in cytoplasmic domains of Kir2.1 (L330R) did not disrupt association, suggesting that the overall structural integrity of this region is critical for inward rectifier function.

Amino Acid Sequence↗
PubMed2005

Endoscopic sinus surgery: where we are-and where we're going.

PURPOSE OF REVIEW: Improved understanding of sinonasal mucociliary function as well as technological advancements have led to a renaissance in the management of sinonasal disease. The current techniques, and adjunctive intraoperative technologies, have allowed for a more precise and safer surgical dissection, extending this surgical application to include the routine endoscopic management of skull base lesions and sinonasal malignancies. The anatomic boundaries of the nasal endoscope continue to be redefined. This paper will review the recent advances in the field of surgical rhinology as well as discuss directions for the future. RECENT FINDINGS: Advancements in imaging technology including image acquisition, three-dimensional reconstruction, stereotactic navigation, and CT-MRI fusion have aided in more thorough preoperative planning, enabling safer and more precise endoscopic surgical dissection. Refinement of endonasal powered instrumentation including microdebriders and high-speed suction irrigation drills have minimized trauma to normal tissues and accelerated postoperative healing. Increased experience with the endoscope has broadened the endoscopic ventral skull base exposure from the odontoid process to foramen ovale to the olfactory bulb. SUMMARY: Endoscopic sinus surgery is no longer exclusively for the management of chronic rhinosinusitis and nasal polyposis. Sinonasal malignancies, as well as anterior skull base lesions have become part of the rhinologist's responsibility. Furthermore, selective lesions managed through traditional craniotomies may now be accessed via trans-sinonasal transcranial endoscopic routes.

Debridement↗
PubMed2005

Endoscopic resection of a venous hemangioma of the optic nerve sheath.

We describe a case of a venous hemangioma that arose in the optic nerve sheath of the orbital apex in a 28-year-old man who presented with progressive vision loss. To the best of our knowledge, this is the first reported case of a venous hemangioma occurring at this location. A definitive diagnosis and partial excision was achieved via an endoscopic transsphenoethmoid approach with interactive, computer-assisted, frameless stereotactic surgical navigation. The intervention resulted in minimal morbidity, demonstrating yet again that this surgical approach is a safe and effective way to treat lesions of the orbital apex.

Adult↗
PubMed2004

Dysregulation of hypoxia inducible factor-1alpha in head and neck squamous cell carcinoma cell lines correlates with invasive potential.

OBJECTIVES/HYPOTHESIS: Tumor hypoxia appears to be closely associated with tumor propagation, malignant progression, and resistance to radiotherapy. Hypoxia inducible factor-1alpha (HIF-1alpha) is a transcription factor that is upregulated under hypoxic conditions and activates hypoxic adaptation pathways which include neovascularization, erythropoiesis, and glycolysis. Hypoxia inducible factor-1alpha is under tight regulation with undetectable levels of expression in normoxia and robust expression in hypoxia. Mutations that activate oncogenes or inactivate tumor suppressor genes increase the expression of HIF-1alpha. Furthermore, it has been demonstrated that HIF-1alpha is overexpressed in head and neck squamous cell carcinoma and that the degree of expression has predictive and prognostic significance for patients undergoing radiotherapy. The study investigated whether overexpression of HIF-1alpha in head and neck squamous cell carcinoma results from a physiological response to local hypoxia or from oncogenic mutational progression. STUDY DESIGN: Expression of HIF-1alpha under normoxic and hypoxic conditions was evaluated in cell lines derived from head and neck squamous cell carcinoma. Cell lines that were used displayed varying degrees of in vitro invasiveness. METHODS: Hypoxia inducible factor-1alpha expression was detected by Western blot analysis. Cells were treated for 3 hours in 1% oxygen, then re-exposed to normoxia for varying times before lysis and detection of HIF-1alpha. RESULTS: Under normoxic conditions, HIF-1alpha expression was upregulated in invasive cells compared with noninvasive cells, and the degradation of HIF-1alpha following a hypoxic stimulus was blunted in invasive cells as compared with noninvasive cells. CONCLUSION: The authors presented evidence that dysregulation of HIF-1alpha may play a role in the malignant progression of head and neck squamous cell carcinoma. It is likely that dysregulated expression of the transcription factor HIF-1alpha contributes to the invasive properties associated with hypoxia and advanced head and neck squamous cell carcinoma.

Blotting, Western↗
PubMed2004

Cellular neurothekeoma of the maxilla.

Neurothekeomas are uncommon benign soft tissue tumors of nerve sheath origin. They occur predominately in the head and neck or upper trunk of children and young adults. A 15-month-old boy presented with an enlarging mass of the right maxilla. Radiologic imaging demonstrated an expansile lesion of the nasomalar region. An incisional biopsy resulted in the diagnosis of neurothekeoma. This lesion should be considered as part of the differential diagnosis of pediatric soft tissue head and neck masses. We discuss the presentation, evaluation, and treatment of these rare benign lesions.

Humans↗
PubMedDate not supplied

Altered sinonasal ciliary dynamics in chronic rhinosinusitis.

BACKGROUND: Although multiple etiologies contribute to the development of rhinosinusitis, a common pathophysiological sequelae is ineffective sinonasal mucociliary clearance, resulting in stasis of sinonasal secretions, with subsequent infection, and persistent inflammation. The respiratory cilia beat continually at a basal rate, while during times of stress, such as exercise or infection, ciliary beat frequency (CBF) increases, accelerating mucus clearance. Previous investigations have led to conflicting results with some authors reporting decreased CBF while others have found normal values of CBF in patients with chronic rhinosinusitis (CRS). Additionally, these studies have only analyzed basal CBF. The goal of this study was to compare the basal as well as the stimulated sinonasal CBF in patients with CRS versus controls. METHODS: A dual temperature controlled perfusion chamber, differential interference contrast microscopy, and high-speed digital video were used to analyze both basal and adenosine triphosphate (100 microM)-stimulated CBF in human sinonasal mucosal explants. RESULTS: Although no difference in basal CBF was detected between control and CRS patients, a marked difference in stimulated CBF was noted. Exogenously applied adenosine triphosphate resulted in a 50-70% increase of CBF in control tissue with a minimally observed CBF increase in explants from CRS patients. CONCLUSION: Dynamic regulation of respiratory ciliary activity is critical for the respiratory epithelium to adapt to varying environmental situations. Thus, diminished or absent adaptation could predispose the sinonasal cavity to accumulation of inhaled infectious and noxious particulate matter resulting in infection/inflammation. Our findings suggest that CRS patients have decreased sinonasal ciliary adaptation to environmental stimuli.

Adenosine Triphosphate↗
PubMedDate not supplied

Surgical decisions in the management of frontal sinus osteomas.

BACKGROUND: The development of chronic rhinosinusitis, a mucocele, or persistent headaches is a common indication for the removal of a frontal sinus osteoma. The best surgical approach to ensure complete and safe removal of the lesion is less clearcut. The advent of specialized frontal sinus instruments, angled endoscopes, and surgical navigational systems has made removal of frontal sinus osteomas possible through an endoscopic approach. The aim of this study is to review our recent experience with the surgical management of frontal sinus osteomas, and the anatomic features that make specific lesions more or less amenable to endoscopic resection. METHODS: A retrospective review of all frontal sinus osteomas surgically resected from the years 1999 to 2003 was used. This period was selected to reflect the invention and popularization of surgical navigation systems and specialty instruments designed specifically for the frontal sinus. CT scans, operative reports and postoperative course were reviewed. RESULTS: Nine patients were identified. A grading system was devised to reflect the three variables involved in the limitations for endoscopic removal. These are the location of the base of attachment, relative size to the frontal recess, and location in relation to a virtual sagittal plane through the lamina papyracea. Three osteomas were removed through an endoscopic approach. Four were removed by a combined osteoplastic flap and endoscopic dissection of the frontal recess. Two were removed through an osteoplastic flap with obliteration of the sinus. CONCLUSION: The ability to remove a frontal sinus osteoma endoscopically can be determined preoperatively, taking into account the location and size of the lesion. There is still a role for external procedures in the surgical management of these lesions, and such procedures may be combined with endoscopic techniques for optimal results.

Adult↗
PubMedDate not supplied

Quantification of ciliary beat frequency in sinonasal epithelial cells using differential interference contrast microscopy and high-speed digital video imaging.

BACKGROUND: Mucociliary clearance is a critical upper airway host defense mechanism. Ciliated epithelium in the mammalian airway continually beat at a baseline frequency. Importantly, during times of stress such as exercise or infection, the cilia beat faster to increase clearance. Nasal epithelial ciliary beat frequency (CBF) has been analyzed previously in ex vivo specimens using a variety of methods including photodiode detectors and conventional video recording. Recent studies performed using lower airway ciliated mucosa have shown poor correlation between CBF quantified by photodiode/conventional video and those using high-speed digital video capture at temperatures close to physiological temperatures. Thus, to more rigorously interrogate sinonasal CBF at physiological conditions, we have incorporated a high-speed digital video camera to our CBF analysis system. This is the first report of sinonasal epithelial CBF analysis performed using high-speed video digital analysis. METHODS: Ex vivo samples of sinonasal epithelium were placed in lactated Ringer's in a temperature-controlled microscope stage chamber. An edge of tissue containing beating cilia was observed at a magnification of 630x using differential interference contrast microscopy. The images were captured using a high-speed digital camera with a sampling rate of 250 frames per second. CBF was determined using computerized data analysis. RESULTS: The mean nasal CBF was calculated from a minimum of five regions for each sample. Temperature curves were generated from tissue obtained from chronically infected subjects. CONCLUSION: Analysis of high-speed digital video capture of sinonasal CBF observed under differential interference contrast microscopy is a powerful method to investigate environmental as well as host influences on mucociliary clearance within the upper airways.

Cilia↗
PubMedDate not supplied

Regional analysis of sinonasal ciliary beat frequency.

BACKGROUND: Mucociliary clearance, a primary host defense mechanism, depends on mucus production and its clearance by the coordinated beating of cilia lining the airways. Numerous investigations have analyzed ciliary activity in brushings from the inferior turbinate. To date, only one study has investigated whether there exists variation in ciliary beat frequency (CBF) within the sinonasal cavity. We analyzed CBF from the inferior turbinate, uncinate process, and sphenoethmoid recess in nonsinusitis patients to determine regional variability of ciliary activity within the sinonasal cavity. METHODS: Explants of sinonasal epithelium were analyzed at 37 degrees C. Beating cilia were visualized with differential interference contrast microscopy. Images were captured using a high-speed digital camera with a sampling rate of 250 frames per second. A one-dimensional tracking algorithm analyzed individual pixel grayscale values within each frame of the video. The differences in grayscale were plotted as a time-dependent waveform, and frequency was calculated as the inverse of the peak-to-peak distance. A minimum of three areas of beating cilia were analyzed per regional sample. Statistical analysis was performed with repeated-measures analysis of variance. RESULTS: Complete sampling of all three sites was accomplished in 10 patients. No difference in CBF within the sinonasal cavity was identified (p < 0.05). The mean CBF for all sites in all patients was 12.6 +/- 2.9 Hz, in agreement with published values. CONCLUSION: This study shows no regional differences in CBF within the sinonasal cavity, supporting previous work and validating analysis of inferior turbinate cilia.

Adult↗