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ABSTRACT: Cyclooxygenase (COX) is the rate-limiting enzyme in the formation of prostaglandins from arachidonic acid. COX exists in 2 isoforms, COX-1 and COX-2. These isoforms are encoded by separate genes and demonstrate cell-specific expression and regulation. Peroxisome proliferator-activated receptor delta (PPARdelta) is a nuclear transcription factor that is activated by prostacyclin. Vascular endothelial growth factor (VEGF) is a proangiogenic factor that is up-regulated in various tumors. Vascular endothelial growth factor has been shown to interact with COX-derived prostaglandins in angiogenesis. To better understand the roles of these genes in head and neck squamous cell carcinoma (HNSCCA), we examined the differential expression of the COX1, COX2, VEGF, and PPARdelta genes in these tumors. Tissue samples from patients with HNSCCA were analyzed for COX-1, COX-2, VEGF, and PPARdelta messenger RNAs (mRNAs) by in situ hybridization. COX-1 and COX-2 mRNAs were also evaluated with Northern blot hybridization. Immunohistochemistry was used to analyze for COX-2 and PPARdelta proteins. Results showed focal areas of accumulation for COX-2, VEGF, and PPARdelta but not COX-1 in human HNSCCA. Northern blot hybridization showed higher levels of COX-2 mRNA in HNSCCA than in normal tissue. This suggests a supportive role of COX-2 in development and/or progression of HNSCCA. In addition, PPARdelta may be a receptor for COX-2-produced prostaglandins in HNSCCA. There is a potential role for selective COX-2 inhibitors in the treatment of these lesions.
Archives of Otolaryngology - Head and Neck Surgery 11/2001; 127(10):1253-9. · 1.63 Impact Factor
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ABSTRACT: While the fasciocutaneous radial forearm free flap has gained increasing popularity, the osteocutaneous radial forearm free flap has been condemned because of a high rate of pathologic donor radius fracture. On the basis of studies that demonstrated increased strength in ostectomized radii after dynamic compression plating, we believed that internal fixation at the time of graft harvest would significantly reduce the incidence of donor radius fracture. This is a retrospective review of the first 54 patients undergoing osteocutaneous radial forearm free flap reconstruction of the head and neck at our institution; 52 underwent prophylactic plating of their donor radii. No clinically significant donor radius fractures have occurred in plated patients. Five asymptomatic fractures were discovered on routine radiographs and required no treatment. Objective evaluation of forearm range of motion and strength after graft harvest demonstrated excellent function compared with unoperated arms. Serial radiographs have shown remodeling and reconstitution of donor radii without localized osteopenia.
Otolaryngology Head and Neck Surgery 01/2001; 123(6):711-7. · 1.72 Impact Factor
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ABSTRACT: The conventional subjective Allen's test (SAT) can be problematic because of its subjective nature. The objective Allen's test (OAT) was used before surgery to reliably and objectively assess forearm vascular flow in anticipation of harvesting a radial forearm free flap (RFFF) for use in head and neck reconstruction.
Retrospective analysis of 65 patients undergoing both preoperative SAT and OAT was completed at the University of Kansas Medical Center between December 1994 and March 1998.
The sensitivity and specificity of the SAT compared with the sensitivity and specificity of the OAT were only 65% and 76%, respectively. In 40 patients with at least 1 forearm with a positive SAT, only 1 (2.5%) patient was found by OAT to have vasculature that would not have allowed safe RFFF harvest in either forearm. In contrast, of the 25 patients with equivocal or negative SAT results in both arms, 18 (72%) were found by OAT to be safe candidates for RFFF harvests.
The OAT is an objective measure of forearm vascular flow and is superior to conventional SAT in RFFF donor-site selection.
Otolaryngology Head and Neck Surgery 12/2000; 123(5):553-7. · 1.72 Impact Factor
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Gastrointestinal Endoscopy 09/2000; 52(2):282-5. · 4.88 Impact Factor
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Archives of Otolaryngology - Head and Neck Surgery 05/1999; 125(4):462, 464-5. · 1.63 Impact Factor
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ABSTRACT: Pulmonary complications are a primary source of increased cost and morbidity in surgically treated head and neck cancer patients. This study investigates potential risk factors related to postoperative pulmonary complications (pneumonia, adult respiratory distress syndrome (ARDS), and prolonged mechanical ventilation) in head and neck cancer patients.
Data from 144 major head and neck procedures performed at the University of Washington between 1985 and 1991 were retrospectively reviewed. Univariate and multivariate analysis were used to evaluate preoperative and perioperative variables identified as potential risk factors for postoperative pulmonary complications.
Fifteen percent of patients had a postoperative pulmonary complication, (n = 21: 18 postoperative pneumonia; 2 ARDS; and 4 prolonged ventilation). The most common pneumonia pathogen was Staphylococcus aureus (62%). Univariate analysis identified smoking and weight loss as significant factors associated with pulmonary complications. The variables preoperative blood urea nitrogen, white blood cell count, and operative chest flap closure all approached but did not reach significance. Multivariate analysis of a subgroup of patients identified smoking history and perioperative antibiotic choice as the only independently significant variables.
Patient smoking history was the primary variable related to postoperative pulmonary problems, with evidence of increasing risk with increased exposure. Other variables added only limited additional risk association information after multivariate analysis.
Head & Neck 09/1997; 19(5):372-7. · 2.40 Impact Factor
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ABSTRACT: To compare the cost and functional results of free and pedicled soft tissue reconstruction after posterior oral cavity and oropharyngeal extirpation.
Retrospective study of 53 consecutive patients undergoing extirpation with primary soft tissue reconstruction from January 1, 1991, to December 31, 1995. Median follow-up was 298 days.
Academic tertiary care medical center.
Twenty-four patients underwent reconstruction with a pedicled pectoralis major myocutaneous flap (PMMF); 29 patients, with a fasciocutaneous free flap (FF) (27 radial forearm, 1 lateral arm, and 1 scapular).
Direct (inpatient hospital resources used and monetary costs) and intangible (post-operative complications and function) costs.
Operative time was longer for FF reconstructions (P = .003), but both patient groups had similar intensive care unit and hospital stays. Treatment cost for FF reconstructions was $41,122, compared with $37,160 for PMMF reconstructions (P = .003). This difference was due to increased professional fees for FF reconstruction (P < .001) which was offset by intangible cost differences. The PMMF group tended toward an increased rate of flap-related complications, compared with the FF group. At last follow-up, 4 patients in the FF group (15%) and 3 in the PMMF group (15%) had their tracheotomy. In contrast, 17 (85%) patients in the PMMF group and 11 (39%) patients in the FF group required enteral tube feedings (P = .002). Also, 18 (64%) patients in the FF group were eating at least a soft diet compared with 6 (30%) patients in the PMMF group (P = .02).
Comparison of direct costs reveals only a modest difference in reconstruction costs that is outweighed by the intangible costs of PMMF reconstruction. The functional benefits of FF reconstruction appear to justify its slight increased expense and its use rather than PMMF reconstruction after extirpation in the posterior oral cavity and oropharynx.
Archives of Otolaryngology - Head and Neck Surgery 07/1997; 123(7):731-7. · 1.63 Impact Factor
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ABSTRACT: Postembryonic production of inner-ear hair cells occurs both normally and after insult in lower vertebrates and avians. To determine how this proliferation is controlled, several growth factors were tested for effects on progenitor-cell division in cultured avian vestibular sensory epithelium. Mitogenic effects of bombesin, epidermal growth factor, insulin-like growth factor-I (IGF-I), insulin, and transforming growth factor-alpha were assayed in organo-typic cultures of utricles from the mature, undamaged (normal) chicken inner ear. Tritiated thymidine and autoradiographic techniques and 5-bromo-2'-deoxyuridine (BrdU) immunocytochemistry were used to identify cells synthesizing DNA. IGF-I stimulated DNA synthesis in the vestibular sensory receptor epithelium in a dose-dependent manner. DNA synthesis was also stimulated by insulin. These results suggest that stimulation of the IGF-I receptors by IGF-I or insulin binding stimulates cell proliferation in the mature avian vestibular sensory epithelium.
The Journal of Comparative Neurology 05/1997; 380(2):262-74. · 3.81 Impact Factor
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Otolaryngology Head and Neck Surgery 02/1996; 114(1):110-2. · 1.72 Impact Factor
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ABSTRACT: Previous investigations have demonstrated that the sensory epithelium of the avian vestibular system possesses the capacity to replace hair cells both on an ongoing basis and following severe damage. Supporting cells, within the sensory epithelium, are believed to be the progenitors of the regenerated hair cells. In the present study we describe the series of events leading to the formation of a regenerated vestibular hair cell in post-hatched birds. Young chickens received injections of streptomycin sulfate in order to damage the sensory epithelium of the vestibular system. These injections were followed by injections of the cell proliferation marker tritiated-thymidine. At predetermined intervals, the animals were killed, and the vestibular organs were processed for tissue autoradiography. Our results confirm that hair cells originate from supporting cells. The data also indicate that postmitotic cells migrate towards the lumen of the epithelium where they differentiate into Type II hair cells. At a later time, some of the new Type II hair cells further differentiate into Type I hair cells. These results suggest that both types of avian vestibular hair cells have a common ancestor. The data also provide evidence in support of the hypothesis that calyx enclosed Type I hair cells, only present in birds and mammals, are a more differentiated stage of Type II hair cells.
Hearing Research 02/1995; 82(1):125-33. · 2.70 Impact Factor
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ABSTRACT: Hearing and balance disorders caused by the loss of inner ear hair cells is a common problem encountered in otolaryngology-head and neck surgery. The postembryonic production of hair cells in cold-blooded vertebrates has been known for several decades, and recent studies in the avian inner ear after ototoxic drug and noise damage have demonstrated a remarkable capacity for both anatomic and functional recovery. The regeneration of sensory hair cells has been shown to be integral to this repair process. Current work is focusing on the cellular progenitor source of new hair cells and the trigger mechanism responsible for inducing hair cell regeneration. Preliminary studies suggest that reparative proliferation may also occur in the mammalian inner ear. Work in this field is moving at a rapid pace. The results thus far have yielded optimism that direct stimulation of hair cell production or transplantation of living hair cells may eventually become treatment modalities for the damaged human inner ear. These proposals would have been considered unrealistic less than 10 years ago, but they now have caught the full attention of both clinician and researcher.
Otolaryngology Head and Neck Surgery 10/1994; 111(3 Pt 1):281-301. · 1.72 Impact Factor
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The Laryngoscope 05/1994; 104(4):497-503. · 1.75 Impact Factor
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ABSTRACT: Damage to the avian inner ear results in up-regulation of mitotic activity resulting in regeneration of hair cells. The objective of this investigation was to determine whether the damaged inner ear epithelium releases a soluble mitogen that is responsible for the up-regulation of proliferation. The sensory epithelium from normal and drug-damaged avian inner ears was cultured alone or in the presence of other cultures. As previously shown in vivo and in vitro, damaged organs displayed increased supporting cell proliferation compared with undamaged organs, leading to eventual morphologic and functional recovery. When damaged organs were cocultured with an undamaged organ, proliferation was increased in the undamaged tissue. When undamaged organs were cultured together, proliferation was decreased. These results indicate that a soluble factor released from the damaged inner ear epithelium stimulates proliferation and suggest the release of a factor from normal tissue that suppressed mitotic activity. Thus, reparative hair cell regeneration in the inner ear appears to be regulated by a balance between proliferative and antiproliferative paracrine factors.
Proceedings of the National Academy of Sciences 03/1994; 91(4):1584-8. · 9.68 Impact Factor
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ABSTRACT: Postembryonic production of sensory hair cells occurs in both normal and aminoglycoside-damaged avian inner ears. The cellular source and mechanism that results in new differentiated hair cells were investigated in the avian vestibular epithelia using three distinct cell-cycle-specific labeling methods to identify proliferating sensory epithelial cells. First, immunocytochemical detection of the proliferating cell nuclear antigen, an auxiliary protein of DNA polymerase, allowed labeling of cells in late G1, S, and early G2 phases of the cell cycle. Second, a pulse-fix tritiated thymidine autoradiographic protocol was used to identify cells in S phase of the cell cycle. Finally, Hoechst 33342, a fluorescent DNA stain, was used to identify epithelial cells in mitosis. The distribution of cells active in the cell cycle within the normal and ototoxin-damaged vestibular epithelium suggests that supporting cells within the sensory epithelia are the cellular precursors to the regenerated hair cells. Differences between the proliferation marker densities in control and damaged end organs indicate that the upregulation of mitotic activity observed after streptomycin treatment is due primarily to an increase in the number of dividing progenitor cells. The differences between the extent of ototoxic damage and the level of reparative proliferative response suggest a generalized stimulus, such as a soluble chemical factor, plays a role in initiating regeneration. Finally, after DNA replication is initiated, progenitor cell nuclei migrate from their original location close to the basement membrane to the lumenal surface, where cell division occurs. This pattern of intermitotic nuclear migration is analogous to that observed in the developing inner ear and neural epithelium.
Journal of Neuroscience 02/1994; 14(1):140-52. · 7.11 Impact Factor
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ABSTRACT: The sensory epithelium of the avian inner ear retains into adulthood progenitor cells for inner-ear hair cells and other cell types in the epithelium. Hair cells are produced normally on an ongoing basis in the vestibular sensory epithelium, and hair-cell production is increased after insult in both auditory and vestibular sensory epithelia. The details of postnatal hair-cell production are not understood. In particular, molecular factors involved in the initiation and regulation of hair-cell genesis and differentiation are not known. Studies of this phenomena have been hampered by the lack of cell culture models. An organ culture system was developed which encourages generation and differentiation of hair cells in mature inner-ear sensory epithelia. Continuous labeling with tritiated thymidine showed genesis of both supporting cells and hair cells in normal vestibular epithelia grown in culture, and an increase in hair-cell and supporting-cell proliferation in damaged sensory epithelia grown in culture as compared to undamaged controls. This demonstrates, in vitro, both the division and differentiation of hair-cell progenitor cells in normal vestibular epithelia, and the maintenance of the hair-cell regeneration process in damaged inner-ear epithelia. This culture system should be useful for studies of hair-cell genesis and differentiation as well as studies of hair-cell and supporting-cell functioning in general.
Hearing Research 11/1993; 70(1):85-108. · 2.70 Impact Factor
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American Journal of Otolaryngology 22(2):132-7. · 0.87 Impact Factor
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ABSTRACT: The objective of this article is to evaluate our experience with sestamibi scanning in patients with primary and secondary hyperparathyroidism.
A retrospective review of patients referred to the radiology department at the University of Kansas Medical Center for parathyroid studies between January 1, 1993, and August 1, 1998, was done. Patients included in the study were those who underwent both dual-phase technetium (Tc-99m) sestamibi scanning and subsequent parathyroidectomy at our institution (n = 34). Twenty-six patients had primary hyperparathyroidism and 8 patients had secondary hyperparathyroidism. Fifteen had previous history of neck exploration.
Sensitivity of sestamibi scans in detection of all abnormal pathology in cases of primary hyperparathyroidism was 60% overall. Among the subset of adenoma cases, sensitivity was 82% (14/17). Among cases of primary parathyroid hyperplasia, no scan correctly localized all abnormal glands; however 60% (3/5) showed localization of at least one hyperplastic gland. Of the 2 patients with parathyroid carcinoma, in only one case was there evidence of sestamibi retention in the correct thyroid lobe. In patients with secondary hyperparathyroidism, sestamibi scanning was successful in identifying all hyperplastic tissue in only one case (sensitivity 13%). In 7 of the 8 cases of secondary hyperparathyroidism, the scan localized at least one hyperplastic gland.
Sestamibi scanning is useful in the localization of abnormal pathology in cases of primary hyperparathyroidism, especially adenomas. In cases of hyperplasia, whether attributable to primary or secondary hyperparathyroidism, sestamibi imaging is less successful.
American Journal of Otolaryngology 21(6):355-9. · 0.87 Impact Factor
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American Journal of Otolaryngology 18(4):263-8. · 0.87 Impact Factor
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ABSTRACT: Contamination of a head and neck surgical wound with oropharyngeal secretions has been shown to dramatically increase the incidence of wound complications. Appropriate perioperative antibiotic prophylaxis has significantly reduced contaminated wound infection rates in several previous reports. The current study examined multiple patient parameters to determine risk factors for all perioperative complications following clean-contaminated head and neck surgical procedures.
Retrospective review of medical records from 159 patients who underwent clean-contaminated major head and neck surgical procedures at the University of Washington between 1985 and 1991. More than 30 preoperative and operative parameters were evaluated, and all complications were recorded. The data were examined using a multivariate statistical analysis.
An overall complication rate of 63% included 22% with wound infections (oro/pharyngocutaneous fistula or purulent drainage), 22% with other types of infections, and 51% with noninfectious complications. The overall perioperative mortality rate was 1.2% (two patients). Prior radiotherapy, operative time, perioperative transfusion, and flap reconstruction were all associated with a significantly higher overall complication rate (p < or = 0.05). Only prior radiotherapy therapy correlated with an increase in wound infection rate (p = 0.05).
Prior radiotherapy significantly increases the risk of perioperative complications and wound infections following clean-contaminated head and neck surgical procedures. Other factors reflecting the complexity of the procedure also influence the overall complication rate.
Head & Neck 17(1):7-13. · 2.40 Impact Factor
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ABSTRACT: The preoperative assessment of mandibular invasion by oral or oropharyngeal squamous cell carcinoma poses a challenge for the head and neck surgeon. A study of 64 composite resection patients was performed to determine which variables in the patient's history, physical exam, and diagnostic workup had a predictive association with carcinomatous mandibular invasion. Four postoperative variables were included in this analysis. Thirty-nine percent of the mandibular specimens demonstrated cancerous involvement. A multivariate recursive partitioning statistical analysis was performed to create a decision tree. Branching was based on the two statistically predictive variables: computed tomographic (CT) scan results and primary tumor location. The guide provides improved predictive accuracy with a 100% negative predictive value (NPV) and a 46% positive predictive value (PPV). This decision guide should help the surgeon provide accurate patient counseling, anticipate reconstructive needs, and maximize surgical oncologic effectiveness.
Head & Neck 16(2):116-26. · 2.40 Impact Factor
