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Biomedical subjects

S E Thawley

Publications and source records attributed to S E Thawley.

At least 19 recordsLinked to original sources
PubMed2001

GRbeta expression in nasal polyp inflammatory cells and its relationship to the anti-inflammatory effects of intranasal fluticasone.

BACKGROUND: Nasal polyposis disease is an inflammatory disorder with intense eosinophilic infiltration of respiratory mucosa that is often difficult to control with topical steroids. Recent evidence suggests that overexpression of the glucocorticoid receptor splice variant GRbeta in inflammatory cells might contribute to steroid insensitivity in diseases such as asthma. OBJECTIVE: The purposes of this investigation were to determine whether nasal polyp (NP) inflammatory cells overexpress GRbeta and to examine whether GRbeta overexpression is associated with insensitivity to the potent topical steroid fluticasone propionate (FP). METHODS: Biopsies were obtained from 10 subjects with NPs before and 4 weeks after treatment with intranasal FP. Middle turbinates biopsies from 6 healthy, nonallergic subjects served as normal controls. Biopsies were immunostained for inflammatory cell markers as well as GRbeta and probed for various cytokine mRNA. The anti-inflammatory response to FP was examined in relation to pretreatment levels of GRbeta expression. RESULTS: The total numbers of inflammatory cells were increased in NPs. The percentage of inflammatory cells expressing GRbeta was also increased (40.5% +/- 19.2% vs 16.1% +/- 4.0%, P =.009). GRbeta expression in NPs was almost exclusive to T lymphocytes, eosinophils, and macrophages. An inverse correlation was observed between the baseline inflammatory cell GRbeta expression and the reduction after FP treatment in EG2-positive eosinophils, CD4-positive T lymphocytes, endothelial VCAM-1 expression, and IL-4 mRNA-positive cells. NPs that were "FP-insensitive" in terms of suppression of eosinophil numbers (major basic protein-positive) had a significantly greater percentage of GRbeta-positive inflammatory cells, a higher ratio of GRbeta-positive/GRalpha-positive cells, and increased numbers of GRbeta-positive eosinophils and macrophages in comparison with those that were "FP-sensitive." "FP-insensitive" NPs also demonstrated a higher percentage of IL-5-positive inflammatory cells expressing GRbeta before and after FP treatment. CONCLUSION: GRbeta expression appears to be a marker of steroid insensitivity in NPs. Expression of GRbeta by NP inflammatory cells, particularly T cells and eosinophils, might render them resistant to suppression by topical steroids and thereby contribute to persistent NP inflammation.

Administration, Intranasal↗
PubMed1999

Effect of intranasal fluticasone on cellular infiltration, endothelial adhesion molecule expression, and proinflammatory cytokine mRNA in nasal polyp disease.

BACKGROUND: Nasal polyp (NP) disease demonstrates a gradual response to treatment with intranasal steroids. We hypothesized that various inflammatory features that promote NP eosinophilia would show a differential sensitivity to treatment with intranasal fluticasone. OBJECTIVES: We conducted a double-blind, placebo-controlled trial of 4 weeks of intranasal fluticasone propionate or matching placebo to assess their effectiveness in reducing NP inflammatory cells, expression of endothelial vascular cell adhesion molecule (VCAM)-1 and P-selectin, and expression of cytokines involved in induction of a group of adhesion molecules (ie, IL-4, IL-13, TNF-alpha, and IL-1beta). METHODS: Twenty subjects (9 women and 11 men) with severe chronic sinusitis and NP were studied. Systemic and intranasal steroids were withheld for a minimum of 1 month and 2 weeks, respectively, before the study. Biopsy specimens of NPs were obtained 1 week before and 4 weeks after treatment with intranasal fluticasone 100 microg or placebo per nostril administered twice daily. Biopsy specimens were snap frozen for immunostaining or fixed in paraformaldehyde for in situ hybridization. Pretreatment to posttreatment results were analyzed with Wilcoxon's signed-rank test. RESULTS: Fluticasone treatment significantly reduced NP eosinophilia (P =.02) and CD4(+) T lymphocytes (P =.02). Eosinophils expressing the marker EG2 were more significantly reduced (P =.007). Fluticasone also reduced the expression of P-selectin (P =.005) and the number of IL-4 and IL-13 mRNA+ cells (P =.02 and.05, respectively). In contrast, fluticasone did not significantly reduce expression of endothelial VCAM-1 or the number of TNF-alpha or IL-1beta mRNA+ cells in the polyps. CONCLUSIONS: We conclude that intranasal fluticasone reduced NP inflammation but that expression of proinflammatory cytokines and endothelial VCAM-1 were relatively unaffected by fluticasone treatment. These latter inflammatory features may contribute to the persistence of NP disease despite intranasal steroid treatment.

Administration, Intranasal↗
PubMed1998

Indications for sinus surgery: how appropriate are the guidelines?

Sinusitis is the most commonly reported chronic disorder in America. More than 75,000 sinus surgical procedures were performed in 1993. Evaluating the appropriateness of procedures is a major focus of health care reform. The American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) collaborated with Value Health Sciences, Inc. (VHS) to develop guidelines for the use of sinus surgery. The clinical utility of these guidelines is presented. Patients undergoing sinus surgery at Barnes Hospital in St. Louis, Missouri, between November 1994 and July 1995 were eligible. Relevant patient information was used to prospectively rate surgery on the nine-point VHS appropriateness scale (1 to 3, inappropriate; 4 to 6, equivocal; 7 to 9, appropriate). Of 55 patients, 37 (67%) had chronic sinusitis, 10 (18%) recurrent sinusitis, five (9%) chronic sinusitis with nasal polyps, and three (6%) sinusitis with moderate to severe asthma; 27 (49%) had previous sinus surgery. Appropriateness ratings ranged from 1 to 9, with nine (16%) procedures rated as inappropriate, 22 (40%) uncertain, and 24 (44%) appropriate. There were no significant differences in the ratings of appropriateness between the group of patients who had undergone previous sinus surgery and the group of patients who had not. Overall, the guidelines were easily applied and clinically pertinent.

Adult↗
PubMed1991

Airway management in obesity hypoventilation syndrome.

The role of tracheostomy is limited in the obesity hypoventilation syndrome unless severe upper airway obstruction exists. If it is performed, special techniques must be applied to overcome the problems associated with tracheostomy in the morbidly obese patient. If attention is paid to these details, however, tracheostomy provides clinically important benefits in this difficult clinical situation.

Airway Obstruction↗
PubMed1990

Cervical metastases from unknown primaries: radiotherapeutic management and appearance of subsequent primaries.

Between 1964 and 1986, 72 patients who presented with squamous or undifferentiated metastatic carcinoma to neck nodes, where the primary tumor could not be found by standard clinical procedures, were treated at the Mallinckrodt Institute of Radiology. These cases were managed in the following manner: biopsy and radiotherapy in 46 out of 72 patients, radiotherapy (RT) and a planned neck dissection in 14 out of 72, and neck dissection after failure to achieve a complete response (CR) with RT in 12 out of 72. Minimum follow-up was 2 years. The initial CR rates for stages N1, N2a, N2b, N3a, and N3b were 83%, 93%, 61%, 50%, and 33%, respectively. The long-term neck tumor control for the same stages was 83%, 71%, 67%, 44%, and 50%, respectively. One patient had soft tissue necrosis and two had carotid artery ruptures, one of which left no symptomatic sequelae. Twenty-one out of 72 patients developed subsequent primary tumor. Only one of these patients survived. This incidence was not affected significantly by prophylactic treatment of the mucosal areas except in patients with bilateral neck nodes, undifferentiated or poorly differentiated histologies, and/or posterior cervical node involvement. A multivariate analysis showed that prognosticators of an improved disease-free survival were: a complete clearance of tumor by the end of radiotherapy (p less than 0.0009) and no appearance of a subsequent primary tumor (p = 0.035). The only factor that correlated with an increased loco-regional control was having a complete response by the end of radiotherapy (p less than 0.00009). The recommended management and possible ways of preventing the appearance of subsequent primaries will be discussed.

Adult↗
PubMed1990

Localization of upper airway collapse during sleep in patients with obstructive sleep apnea.

The present study was conducted to determine the effects of body position and sleep state, as well as the effect of uvulopalatopharyngoplasty (UPPP) on the regions over which the upper airway (UA) collapses during sleep. To accomplish this goal, 18 male patients with obstructive sleep apnea (OSA) underwent overnight polysomnography with simultaneous monitoring of pressures in the posterior nasopharynx, oropharynx, hypopharynx, and esophagus. From the profile of pressures recorded in the UA and esophagus, the regions over which the UA collapses during apneas could be determined. The patients were 54 +/- 14 y of age and were grossly obese with a body mass index of 37 +/- 2 kg/m2. They had moderately severe OSA with a mean apnea plus hypopnea index of 62 +/- 8 per hour. During NREM sleep, 10 of the 18 (56%) patients had collapse confined to the velopharyngeal or retropalatal segment of the upper airway. The remaining 44% of the patients demonstrated collapse of the retroglossal segment of the oropharynx located caudal to the inferior margin of the soft palate. Upper airway collapse at the level of the hyoid bone was not observed during NREM sleep. Observations made during REM sleep in nine patients demonstrated that collapse occurred in a more caudal segment of the UA in seven patients during REM than during NREM sleep. The effect of sleep position was evaluated in 10 patients and found to have little affect on the extent over which the UA collapsed during sleep independent of sleep state. The effects of UPPP on regional UA collapse were evaluated in a small group of six patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Evaluation of the upper airway by computerized tomography in patients undergoing uvulopalatopharyngoplasty for obstructive sleep apnea.

This study utilized computerized tomography (CT) to evaluate the effects of uvulopalatopharyngoplasty (UPPP) on upper airway (UA) dimensions. The objectives were to determine whether CT scan results would be useful in identifying UA characteristics predictive of a good surgical result as well as elucidating reasons for failure of this operative procedure. Twenty-three male patients with obstructive sleep apnea (OSA) had CT scans and polysomnography performed before and after UPPP. Preoperatively, the apnea plus hypopnea index (AHI) was 64 +/- 6 per hour and the minimal UA cross-sectional area (Amin) was located at 10 and 20 mm below the level of the hard palate in 87% (20 of 23) of the patients. Uvulopalatopharyngoplasty more than doubled UA cross-sectional areas at these two proximal levels. In contrast, the hypopharyngeal segment located 50 to 70 mm below the hard palate decreased in cross-sectional area by 23 to 25% after surgery. Eight patients (35%) had a good response to UPPP based on a greater than 50% decrease in AHI. Preoperatively, seven of these eight patients had Amin located 20 mm below the hard palate. Uvulopalatopharyngoplasty increased Amin and oropharyngeal cross-sectional areas to a greater extent in the good than in the poor responders. A poor response to UPPP was associated with preoperative Amin greater than 1 cm2, location at site other than 20 mm below the hard palate, and postoperative narrowing at the level of the hard palate. Patients with Amin less than 1.0 cm2 located 20 mm below the hard palate (lower velopharynx) were most likely to obtain a favorable result with surgery.

Carbon Dioxide↗
PubMed1988

Adenocarcinomas of major and minor salivary gland origin: a histopathologic review of treatment failure patterns.

Fifty-four cases of adenocarcinoma of major and minor salivary gland origin were seen between 1960 and 1980. Fifty of these were treated definitively. Planned surgery combined with radiation was the initial treatment for 22 patients (44%), surgery alone for 15 (30%), and radiation alone for 13 (26%). Of the patients receiving surgery with curative intent, 82% underwent complete resections (i.e., negative margins). Cervical lymph node involvement was present in 23% of cases, and 73% of these patients died of their disease within 3 years. Distant metastases developed in 37% of patients, with a median time of 1 year; 93% of these patients died within 3 years. Histologic grading was performed using objective criteria. Thirty-four percent of tumors were well-differentiated, 27% moderately differentiated, and 39% poorly differentiated. Patients with well-differentiated adenocarcinomas tended to survive disease-free longer and developed fewer distant metastases than those patients with moderately or poorly differentiated tumors.

Actuarial Analysis↗
PubMed1986

Adenoid cystic salivary gland carcinoma. A histopathologic review of treatment failure patterns.

Seventy-one cases of adenoid cystic salivary gland carcinoma were reviewed according to treatment modality and clinical course. Thirty-six patients (51%) were treated by combined surgery and radiation therapy. The tumors were classified by their histologic patterns into tubular, cribriform, and solid forms. Distant metastases, in 52%, were the most frequent and ominous sources of failure. In 35% of cases, distant metastases developed despite local control at the primary site. In this group, the disease had a more fulminant course with shorter survival. Histopathologically, the cribriform subtype was associated with multiple local recurrences, greater local aggressiveness, and a poorer salvage rate as compared with the tubular subtype. Late onset of local recurrences and distant metastases was especially associated with the cribriform subtype. Overall prognosis in terms of distant metastases and survival was worst for the solid subtype. Control of local disease is best achieved with combined surgery and radiation therapy. The high incidence of distant metastases may not be affected by this regimen. The ultimate outcome of therapy is poorly predicted. Survival appears to be based on the pattern in which distant metastases develop. Overly aggressive and mutilating surgical approaches for these tumors are not recommended in many instances. The need for the development of new, more effective forms of therapy is emphasized.

Aged↗
PubMed1986

Improved treatment of salivary adenocarcinomas: planned combined surgery and irradiation.

The treatment outcome of 47 patients with adenocarcinoma of major and minor salivary gland origin treated at the Washington University Medical Center between 1960 and 1980 was retrospectively reviewed by site, histologic grade, and treatment modality. Planned irradiation with surgery was the initial treatment for 21 patients, irradiation alone for 14 patients, surgery alone for 11 patients, and chemotherapy for 1. Four patients presented with distant metastases at diagnosis and were not treated definitively. Twenty-seven patients had tumors histologically graded at the time of original treatment; one-third of these were low-grade, and two-thirds were high grade. Treatment results were analyzed in terms of local control as well as overall survival. Median survival for the entire group was 4.1 years. Local-regional disease control was significantly improved in the combination therapy group (81%) compared with the groups treated with irradiation alone (29%) and surgery alone (8%). Disease free survival was also significantly improved with combination therapy. Patients with low-grade adenocarcinoma had better local control and survived longer than those with high-grade. However, one-third of the patients with high-grade tumors survived 5 years. We conclude that both local disease control and survival of patients with adenocarcinoma of salivary gland origin were improved with the planned combination of irradiation and surgery.

Actuarial Analysis↗
PubMed1986

Nasal septal abscess: unusual causes, complications, treatment, and sequelae.

Abscesses of the nasal septum are most likely to occur after trauma. Proper management of a nasal septal abscess requires prompt diagnosis, adequate surgical drainage, and parenteral antibiotics to prevent the potentially dangerous spread of infection and the development of severe functional and cosmetic sequelae. Without a history of prior trauma, physicians should be alert to other, less obvious causes for nasal septal abscesses. A rare case of an isolated sphenoid sinus infection leading to a nasal septal abscess illustrates the surgical treatment of these entities.

Abscess↗
PubMed1986

Tension pneumocephalus: a case following otologic surgery.

Asymptomatic pneumocephalus associated with cerebrospinal fluid drainage through a dural defect following extensive skull base surgery is not uncommon. Its occurrence following otologic surgery, however, is rare. Tension pneumocephalus, if not recognized, can rapidly lead to death due to increased intracranial pressure. A case of tension pneumocephalus is presented to demonstrate its clinical features and surgical management. The pathophysiology, diagnosis, and management of tension pneumocephalus are reviewed.

Cholesteatoma↗
PubMed1985

Surgical treatment of obstructive sleep apnea.

In selected patients with obstructive sleep apnea, the uvulopalatopharyngoplasty procedure may be performed to remove excessive tissue in the oropharyngeal airway. This may improve the symptoms of sleep apnea as well as snoring. Tracheostomy may be indicated in patients with obstructive sleep apnea with associated severe medical problems.

Female↗
PubMed1985

Laryngeal epidermoid carcinoma associated with juvenile laryngeal papillomatosis.

The speculation whether juvenile laryngeal papillomatosis may transform into or be associated with epidermoid carcinoma is explored. We document a case of invasive laryngeal carcinoma arising in preexisting juvenile laryngeal papillomatosis. After multiple childhood laryngoscopies and a tracheotomy, a 54-year-old, 30-pack per year smoker, who had never received radiation therapy, developed a florid exophytic transglottic squamous cell carcinoma. Histologically, the invasive epidermoid carcinoma was surrounded by a field of papillomata with varying degrees of atypical changes. After total laryngectomy, isolated papillomata were found in the lower trachea. There were no cervical lymph node metastases. No postoperative radiation therapy was given. Persistent squamous papillomata in the tracheostomy site, the lower trachea, and the posterior pharynx were treated with the CO2 laser. We emphasize the need to maintain a high index of suspicion for malignancy. In addition, we review the problem of benign papillomata in the aerodigestive tract following laryngectomy.

Carcinoma, Squamous Cell↗
PubMed1985

High-grade malignancies of the parotid gland: effective use of planned combined surgery and irradiation.

The trend toward treatment of parotid gland malignancies with planned combined surgery and postoperative radiation therapy is currently being followed by many centers, although prospective studies confirming the efficacy of this treatment regimen have only recently begun. We have reviewed only our "high-grade" histologic types: adenocarcinomas, malignant mixed tumors, high-grade mucoepidermoid carcinomas, squamous cell carcinomas, and undifferentiated carcinomas. Acinic cell carcinomas, adenoid cystic carcinomas, and low-grade mucoepidermoid carcinomas were excluded from study because of their different biologic behavior. Since 1974, we have employed the approach of surgical extirpation with preservation of the facial nerve when possible for all parotid tumors, combined with planned postoperative radiation therapy (50-70 Gy). We reviewed the 37 cases of "high-grade" parotid gland malignancies and compared the patients treated with the combined modality approach with our historical patients treated initially with surgery alone. Despite an apparent higher stage at presentation, our combined treatment group ultimately had significantly better local control (70% vs. 20%), and an equivalent survival rate at five years. Tumor was present at the margin of resection in 14 (74%) cases treated with combined surgery and irradiation. The facial nerve was preserved in six of these patients with positive margins, and only one of these patients developed a local or regional treatment failure. In conclusion, our data confirms the efficacy of surgical exploration to determine the extent of disease and surgical resection, preserving facial nerve function if possible, followed by postoperative radiation therapy at adequate doses. Control of local-regional disease was much improved by combined modality therapy as opposed to surgical resection alone, despite the prevalence of residual microscopic disease in the resection margins. Facial nerve function is optimally preserved by this approach of conservative surgery combined with postoperative radiation therapy.

Adenocarcinoma↗