Search PubMed⌕ Search

Biomedical subjects

D W Kennedy

Publications and source records attributed to D W Kennedy.

At least 37 records · Page 2Linked to original sources

Identification of p53 and human papilloma virus in Schneiderian papillomas.

Schneiderian papilloma of the nose is an unusual neoplasm with the propensity for local tissue destruction, recurrence, and malignant degeneration. Human papilloma virus (HPV) is related to a subset of sinonasal papillomas and has been implicated in the pathogenesis of cancer by interaction with the host p53 protein. Detection of p53 and HPV could be clinically useful as tumor markers for lesions with oncogenic potential. Thirty specimens for p53 were studied and nine (30%) stained positive. HPV was detected in six (20%). In the presence of p53, an odds ratio for carcinoma was 1.19:1, or 19% higher than expected. In the presence of HPV the odds ratio for carcinoma was 11.5:1, or 11.5 times higher than expected. In the presence of HPV an odds ratio for finding an elevated amount of p53 was 2.2:1. The data support the hypothesis that HPV and p53 may interact in a novel manner and elevate the risk for neoplasia.

Biomarkers, Tumor↗

Histology and histomorphometry of ethmoid bone in chronic rhinosinusitis.

Mucosal changes have been well described in chronic sinusitis, yet little is known about the underlying bone, despite clinical and experimental evidence suggesting that bone may be involved in chronic sinusitis. Techniques of undecalcified bone analysis were used for detailed histologic examination of ethmoid bone in chronic sinusitis compared with controls. Bone synthesis, resorption, and inflammatory cell presence were specifically assessed. Additionally, histomorphometry techniques were used to determine ethmoid bone physiology in individuals undergoing surgery for chronic sinusitis. Overall, individuals undergoing surgery for chronic sinusitis were found to have evidence of marked acceleration in bone physiology with histologic changes including new bone formation, fibrosis, and presence of inflammatory cells. These findings are compared with osteomyelitis in long bone and the jaw. The suggestion that underlying bone may serve as a catalyst for chronic sinusitis is supported and implications for therapy are discussed.

Adult↗

Lipomas of the internal auditory canal and cerebellopontine angle.

OBJECTIVE: To evaluate lipomas of the internal auditory canal (IAC) and cerebellopontine angle (CPA). STUDY DESIGN: Retrospective review. METHODS: Review of a multi-institutional series of 17 lipomas of the IAC/CPA, combined with a Medline review of the 67 cases reported in the world literature. RESULTS: This series of 17 IAC/CPA lipomas is the largest reported series to date, bringing the total number of documented cases to 84. There appears to be a nearly 2:1 male to female predominance. Sixty percent were left-sided lesions, and three were bilateral. Hearing loss, dizziness, and tinnitus were the most common presenting symptoms. Surgical resection was performed in 52 (62%) of these lesions; however, total tumor removal was accomplished in only 17 (33%), which is most likely because of the fact that these tumors tend to have a poorly defined matrix and a dense adherence to neurovascular structures. Sixty-eight percent of patients experienced a new deficit postoperatively, 11% were unchanged, and only 19% improved with no new deficit. Only one documented case of tumor growth was identified; however, the reported follow-up was short (average, less than 3 years). CONCLUSION: With the magnetic resonance imaging techniques now available, lipomas can be reliably differentiated from other masses within the CPA and IAC, so histopathologic diagnosis is rarely necessary. Because of the potential for significant morbidity with resection of these lesions, we believe that conservative follow-up is the best treatment option for patients with these rare lesions. Surgery is indicated only when significant progressive or disabling symptoms are present.

Adolescent↗

Kinetics of central nervous system microglial and macrophage engraftment: analysis using a transgenic bone marrow transplantation model.

To determine the kinetics of tissue macrophage and microglial engraftment after bone marrow (BM) transplantation, we have developed a model using the ROSA 26 mouse. Transplanted ROSA 26 cells can be precisely identified in recipient animals because they constitutively express beta-galactosidase (beta-gal) and neomycin resistance. B6/129 F2 mice were irradiated and transplanted with BM from ROSA 26 donors and their tissues (spleen, marrow, brain, liver, and lung) examined at various time points to determine the kinetics of engraftment. Frozen sections from transplanted animals were stained histochemically for beta-gal to identify donor cells. At 1, 2, 6, and 12 months posttransplantation, 98% to 100% of granulocyte-macrophage colonies were of donor (ROSA 26) origin determined by beta-gal staining and by neomycin resistance. Splenic monocytes/macrophages were 89% donor origin by 1 month confirming quick and complete engraftment of hematopoietic tissues. At this time, only rare ROSA 26 tissue macrophages or microglia were observed. Alveolar macrophage engraftment was evident by 2 months and had increased to 61% of total tissue macrophages at 1 year posttransplantation. The kinetics of liver Kupffer cell engraftment were similar to those seen in the lung. However, donor microglial engraftment remained only 23% of total microglia at 6 months and increased to only 30% by 1 year. Also, donor microglia were predominantly seen at perivascular and leptomeningeal, and not parenchymal, sites. The data show that microglia derive from BM precursors but turn over at a significantly slower rate than other tissue macrophages. No clinical or histological graft-versus-host disease was observed in the recipients of ROSA 26 BM. These kinetics may impact strategies for the gene therapy of lysosomal storage diseases. Because individual donor cells can be identified in situ, the ROSA 26 model should have many applications in transplantation biology including studies of homing and differentiation.

Animals↗

Computer-assisted resection of benign sinonasal tumors with skull base and orbital extension.

OBJECTIVE: To use freehand, real-time, intraoperative, 3-dimensional computed tomography (3-D CT) localization to assist with resection of sinonasal lesions with skull-base and/or orbital extension. DESIGN: The 3-D CT is computer-assisted technology using the preoperative CT scan as a road map for resection of lesions. Previous technology, while resulting in little intraoperative error, required use of a somewhat cumbersome rigid articulated arm and attached probe, limiting mobility and requiring rigid fixation of the head to maintain system reference. A new freehand version of this technology, eliminating these limitations, has been used for resection of benign sinonasal lesions with skull-base and/or orbital extension. SETTING: Tertiary care, university-based practice. PATIENTS: Seven patients prospectively selected with benign lesions involving the sinonasal cavity and orbit and/or skull base. INTERVENTION: All patients underwent surgical resection of their tumors using endoscopic, open, or combined procedures with the assistance of freehand 3-D CT localization. MAIN OUTCOME ASSESSMENTS: Surgeon assessment of usefulness. RESULTS: In several cases, the device assisted the operator in determining the exact location of a displaced optic nerve, ensuring vision preservation, while in other cases, the location and depth of skull-base penetration was clearly determined, allowing resection via a transnasal endoscopic approach. In addition, the device was useful for determining the depth of necessary resection for optimal cosmetic result. In all cases, system accuracy was within less than 2 mm at the operative site. System limitations included need for an additional preoperative CT and time required at the beginning of the case for system setup and registration. CONCLUSIONS: Freehand 3-D CT, while still with limitations, offers the advantage of increased surgical safety, aiding anatomic understanding in distorted surgical fields for resection of benign sinonasal tumors with orbital and skull-base extension.

Adolescent↗

Computed tomography in lacrimal outflow obstruction.

BACKGROUND: Acquired nasolacrimal duct obstruction is a common ophthalmologic problem. Despite widespread understanding of treatments available for nasolacrimal duct obstruction, few authors have commented on its etiology. Because the nasolacrimal system is anatomically related to important nasal and sinus structures, the authors postulated that acquired nasolacrimal duct obstruction and its complications might occur simultaneous to, and possibly as a consequence of, rhinologic or sinus disease. MATERIALS AND METHODS: Twenty-three patients with acquired nasolacrimal duct obstruction and 100 control patients were evaluated by coronal computed tomography for evidence of sinus disease or nasal abnormalities. Specifically, five findings were noted: ostiomeatal complex disease, ethmoidal opacification, agger nasi cell opacification, concha bullosa, and nasal septal deviation. RESULTS: Overall, 20 (87%) patients with acquired nasolacrimal duct obstruction demonstrated one or more radiologic finding of sinus disease or rhinologic abnormality whereas 63 (63%) control subjects exhibited these findings. This difference was determined to be statistically significant (P < 0.05). A statistically significant higher incidence of ethmoidal opacification, agger nasi cell opacification, and nasal septal deviation was observed in patients with nasolacrimal outflow obstruction than in controls. Differences in the incidence of ostiomeatal complex disease and concha bullosa were not found to be statistically significant. CONCLUSION: These data demonstrate a correlation between computed tomography findings of sinus disease or nasal abnormality and the presence of acquired nasolacrimal outflow obstruction. This association between radiologic evidence of sinorhinologic disorders and lacrimal outflow obstruction may imply that dacryocystitis, like sinus disease, may be produced by disease of the lateral nasal wall. When evaluating a patient with acquired nasolacrimal duct obstruction, the physician should consider evaluation for concomitant nasal and sinus disease.

Humans↗

Comparison of sinus computed tomography staging systems.

In an attempt to establish a standardized rating system for CT of the paranasal sinuses, the Committee on Rhinology and Paranasal Sinus Disease of the American Academy of Otolaryngology-Head and Neck Surgery instituted a protocol for the review of sinus CT scans at six international sites. Fifty identical scans were rated by four otolaryngologists at each site according to five established sinus CT staging systems. Twenty of 24 reviewers repeated the rating session at least 1 week later to determine intrarater variability. The number of CT scans that could not be classified by a particular rating system ranged from 1.3% to 5.5%. The range of intrarater agreement (kappa = 0.39 to 0.74) exceeded that of interrater agreement (kappa = 0.18 to 0.49). A skewed distribution of CT scans resulted in a system with high rater agreement but poor ability to differentiate among disease states. The use of a numeric rating system to assign a score to each scan produced a comprehensive and disease-sensitive system, but one with low rater agreement. A precise definition of mucosal thickening in terms of millimeters appeared to enhance the raters' ability to assign stage and improve a system's comprehensiveness and reproducibility. On the basis of these findings, recommendations are made for the use of CT rating systems to study clinical outcomes in patients with chronic sinusitis.

Humans↗

Staging for rhinosinusitis.

Interest in the surgical treatment of chronic rhinosinusitis has increased, primarily because rigid endoscopy and, more particularly, computed tomographic scanning have facilitated the visualization of disease. At the same time it has become both scientifically and financially imperative to audit therapeutic outcome. Consequently, a staging system for nonneoplastic sinus disease is needed. It is clear that any assessment of medical or surgical therapeutic response requires a method of quantifying disease severity that will be widely accepted by practitioners in the field. This acceptance will largely depend on how easy the method is to apply. With computed tomographic scanning it is possible to more accurately determine the extent of the pathologic condition in rhinosinusitis, a disease in which the severity of symptoms and the appearances on nasal endoscopy have a significantly more unpredictable correlation with the extent of disease. One goal of the Task Force on Rhinosinusitis of the American Academy of Otolaryngology-Head and Neck Surgery was to recommend a system for outcomes research that combines quantification with ease of application.

Acute Disease↗

In situ hybridization for Aspergillus and Penicillium in allergic fungal sinusitis: a rapid means of speciating fungal pathogens in tissues.

Allergic fungal sinusitis (AFS) is a serious form of sinonasal fungal disease that is commonly associated with Aspergillus or Dematiaceous fungi. This study was performed to determine the incidence of Aspergillus or Penicillium in AFS by using in situ hybridization (ISH) for Aspergillus and Penicillium ribosomal RNA (rRNA). The Fontana-Masson melanin stain (FMMS) was also used to detect pigmented fungi (A. niger and Dematiaceous fungi). ISH was performed on 26 patients: 17 AFS cases with histologic evidence of fungi, 5 AFS cases without histologic evidence of fungi, 3 cases of invasive fungal sinusitis (IFS), and 1 case of fungus ball. Nine AFS specimens with histologic evidence of fungi were ISH positive. Positivity was also noted in two of three IFS cases, while no staining was seen in the fungus ball and in six AFS specimens without fungi demonstrable by silver stains. Six ISH-positive cases were FMMS positive, suggesting A. niger. Five ISH-negative AFS specimens were FMMS positive, suggesting Dematiaceous fungi. In summary, many AFS patients in our institution demonstrate Aspergillus/Penicillium organisms. Ancillary techniques may help identify fungi responsible for AFS if cultures are negative or not performed. ISH for rRNA is a useful means for rapidly speciating fungi in human tissues.

Adult↗

Taxonomic study of aromatic-degrading bacteria from deep-terrestrial-subsurface sediments and description of Sphingomonas aromaticivorans sp. nov., Sphingomonas subterranea sp. nov., and Sphingomonas stygia sp. nov.

Phylogenetic analyses of 16S rRNA gene sequences by distance matrix and parsimony methods indicated that six strains of bacteria isolated from deep saturated Atlantic coastal plain sediments were closely related to the genus Sphingomonas. Five of the strains clustered with, but were distinct from, Sphingomonas capsulata, whereas the sixth strain was most closely related to Blastobacter natatorius. The five strains that clustered with S. capsulata, all of which could degrade aromatic compounds, were gram-negative, non-spore-forming, non-motile, rod-shaped organisms that produced small, yellow colonies on complex media. Their G + C contents ranged from 60.0 to 65.4 mol%, and the predominant isoprenoid quinone was ubiquinone Q-10. All of the strains were aerobic and catalase positive. Indole, urease, and arginine dihydrolase were not produced. Gelatin was not liquified, and glucose was not fermented. Sphingolipids were present in all strains; 2OH14:0 was the major hydroxy fatty acid, and 18:1 was a major constituent of cellular lipids. Acid was produced oxidatively from pentoses, hexoses, and disaccharides, but not from polyalcohols and indole. All of these characteristics indicate that the five aromatic-degrading strains should be placed in the genus Sphingomonas as currently defined. Phylogenetic analysis of 16S rRNA gene sequences, DNA-DNA reassociation values, BOX-PCR genomic fingerprinting, differences in cellular lipid composition, and differences in physiological traits all indicated that the five strains represent three previously undescribed Sphingomonas species. Therefore, we propose the following new species: Sphingomonas aromaticivorans (type strain, SMCC F199), Sphingomonas subterranea (type strain, SMCC B0478), and Sphingomonas stygia (type strain, SMCC B0712).

Alcohols↗

Endoscopic sinus surgery. A review.

Endoscopic sinus surgery has progressed from a limited surgical intervention for chronic sinus disease to a viable approach for diffuse sinonasal polyposis, benign tumors, skull base defects, and orbital lesions. Some aspects of endoscopic diagnosis and treatment, however, remain controversial and are poorly understood. Controversies in endoscopic sinus surgery are reviewed and the primary critical issues with regard to the more recently developed instrumentation and the newer extended approaches are presented.

Endoscopy↗

Management of sinusitis in the asthmatic patient.

OBJECTIVE: To describe pathophysiologic links between sinusitis and asthma; to identify means of diagnosing sinusitis in the asthmatic; to discuss the management of asthmatic patients with sinusitis, both medical and surgical; to examine the outcome of managing the asthmatic patient with sinusitis. DATA SOURCES: Prospective and retrospective data from the author's experience was evaluated. Medline database was searched from January 1, 1984, using the keywords "asthma" and "sinusitis" without restriction to species or language; 48 articles identified. Relevant articles referenced in retrieved sources, current texts in otorhinolaryngology and sinus disease were also utilized. STUDY SELECTION: From data source abstracts, pertinent articles (33) and book chapters meeting the objectives of our paper were intensively reviewed. RESULTS: Clinical and experimental studies indicate that sinonasal inflammation can result in worsening of lower airway disease, while the exact nature of this relationship remains debated. Regardless of mechanism, identification of the asthmatic patient with chronic sinusitis using the techniques of nasal endoscopy and CT scanning can lead to treatment of sinusitis with overall sinus and asthmatic disease improvement. Proper management is first medical, while surgical approaches are reserved for persistent cases. Traditional, more radical, surgical approaches have shown good results overall, while newer techniques of functional endoscopic sinus surgery which respect anatomy and mucosal function are less studied but expected to result in similar or better long-term outcome. CONCLUSIONS: Sinusitis and asthma coexist and impact on one another at many different levels. Proper identification of the asthmatic patient with chronic sinusitis can be readily discerned by an accurate and thorough history and physical examination including nasal endoscopy and CT scanning. Proper medical and surgical management of sinusitis in the asthmatic patient can result in both improved sinonasal and asthmatic symptoms with fewer physician visits and decreased need for medication.

Asthma↗

Endoscopic repair of cerebrospinal fluid fistulae and encephaloceles.

The authors review their experience with endoscopic repair of skull base defects associated with cerebrospinal fluid (CSF) rhinorrhea and/or encephaloceles involving the paranasal sinuses. Between January 1991 and December 1995, 51 patients were evaluated for anterior and middle cranial fossa defects at a tertiary care facility. Of these patients, 36 underwent endoscopic repair of skull base defects. Factors related to surgical success were analyzed. These factors included etiology, defect location, number of prior attempts at repair, type of graft(s) used, fluorescein use, complications, durations of lumbar drain placement, and duration of CSF leakage prior to repair. During the first attempt, successful endoscopic repair was accomplished in 34 (94.4%) of the 36 patients. The mean duration of follow-up was 24.6 months, with a range of 2 to 57 months. The authors conclude that an endoscopic approach provides a safe and effective means for repairing many skull base defects.

Adolescent↗

Acoustic rhinometry in the study of the acute nasal allergic response.

Acoustic rhinometry is a recently developed method for the objective assessment of nasal patency. In this study, acoustic rhinometry was used to measure changes in nasal cavity dimensions in the immediate response to nasal allergen challenge in eight pollen-sensitive subjects. Acoustic rhinometric changes were compared with subjective symptoms, as well as histamine in nasal secretions, cytology of nasal mucosal scrapings, and changes in olfactory function. A significantly greater decrease in nasal airway caliber occurred following allergen challenge as compared to buffer diluent challenge in the same individuals (70% +/- 7% versus 22% +/- 5%). During an allergic response, a strong correlation was found between the minimum cross-sectional area and the volume of the nasal cavity measured by acoustic rhinometry (r = .9). However, no correlation was observed between nasal airway caliber and concomitant subjective congestion reported by the subjects. A modest decrease in olfactory function was seen following allergen challenge (3.1 +/- 1.4 fewer odors identified correctly out of 20; p = .08). However, the alterations of olfactory function did not correlate with changes in nasal patency. The results presented in this study demonstrate that acoustic rhinometry has great potential as a reproducible method for the objective assessment of nasal obstruction occurring in nasal allergen challenge studies.

Acoustics↗

Advantages and disadvantages of three-dimensional computed tomography intraoperative localization for functional endoscopic sinus surgery.

Intraoperative three-dimensional computed tomography (3-D-CT) localization has been available for use during functional endoscopic sinus surgery (FESS) for several years, although relatively few otolaryngologists operate in conjunction with this technology. Proponents of intraoperative localization believe that operating with stereotaxis enhances surgical precision and reduces complications. A 1-year review was conducted at the University of Pennsylvania from January 1994 through January 1995. During this period 5% of sinus operations were performed in conjunction with intraoperative localization. The advantages and disadvantages of using intraoperative localization were evaluated for each case. Also examined were type and indication for surgery, anesthesia used, added time, and cost. Overall, intraoperative localization was found to be helpful when anatomy was distorted or obscured. However, selecting patients who may have benefited from localization was often not possible using preoperative data. Ideally, localization should be available for all FESS. Criteria are outlined which will need to be met prior to localization becoming a significant aspect of FESS.

Adult↗

MR evaluation of frontal sinus osteoplastic flaps with autogenous fat grafts.

PURPOSE: To investigate the MR findings in patients who have had osteoplastic frontal sinus flaps placed for inflammatory sinonasal disease. METHODS: The MR images of 13 patients who had improvement of symptoms after osteoplastic frontal sinus flap placement with fat autograft were prospectively evaluated for the presence of high intensity on T2-weighted scans, contrast enhancement, and replacement of frontal sinus fat by lower-signal soft tissue. All studies were performed on a 1.5-T unit using a 5-in round surface coil placed over the nasion. Sagittal T1-weighted, axial and coronal fast spin-echo T2-weighted, and precontrast and postcontrast axial and coronal T1-weighted images were obtained through the operative bed. The T2-weighted and postgadolinium sequences were done with a fat-suppression technique. RESULTS: Hyperintensity within the frontal sinuses on T2-weighted images and enhancement (peripherally and/or centrally where fat was replaced with soft tissue) were found to some degree in all patients. The degree of replacement of frontal sinus fat with soft tissue ranged from 4% to 85% (mean, 43%). Five patients with persistent symptoms had no distinguishing MR features when compared with asymptomatic patients. CONCLUSIONS: Although increased T2-weighted intensity, fat replacement, and enhancement are findings compatible with inflammation, these changes may be seen in patients who are asymptomatic after placement of osteoplastic frontal sinus flaps; they may represent the normal granulation process. MR findings after flap placement are nonspecific and have limited utility in distinguishing symptomatic patients with recurrent inflammatory disease from asymptomatic patients whose imaging findings are related to postoperative scar tissue.

Adipose Tissue↗