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Biomedical subjects

M C Weissler

Publications and source records attributed to M C Weissler.

At least 19 recordsLinked to original sources

Hypoxia and vascular endothelial growth factor expression in human squamous cell carcinomas using pimonidazole as a hypoxia marker.

Hypoxia in human tumors is associated with poor prognosis, but the molecular mechanisms underlying this association are poorly understood. One possibility is that hypoxia is linked to malignant progression through vascular endothelial growth factor (VEGF) induction and the associated angiogenesis and metastasis. The present clinical study measures hypoxia and VEGF expression on a cell-by-cell basis in human squamous cell carcinomas to test the hypothesis that hypoxia and VEGF protein expression are coupled in human tumors. Eighteen patients with invasive squamous cell carcinoma of the uterine cervix and head and neck have been investigated by a quantitative image analysis of immunostained sections from their tumors. The hypoxia marker pimonidazole was used to measure tumor hypoxia, and a commercially available antibody was used to measure VEGF protein expression. A quantitative immunohistochemical comparison of hypoxia and VEGF protein expression revealed no correlation between the two factors.

Biomarkers

Nasopharyngeal carcinoma: evidence for improved survival with combined chemoradiation.

Radiation therapy has been the traditional treatment for nasopharyngeal carcinoma. Patients with advanced disease have a higher rate of locoregional as well as distant metastases, which has warranted the addition of chemotherapy in an attempt to improve survival. This retrospective study was designed to determine the absolute survival of patients with nasopharyngeal cancer treated with radiation alone, compared to that of patients receiving concurrent chemoradiation. Between December 1975 and December 1993 eight patients were treated with radiotherapy alone and 14 patients were treated with concurrent chemoradiation using 5-fluorouracil and cisplatin. Analysis of Kaplan-Meier cumulative absolute survival plots revealed that patients receiving chemoradiation survived longer than those receiving radiation alone (p = 0.0321). Patients with lymphoepithelioma, as opposed to squamous cell carcinoma, and patients younger than 30 years were also found to have longer survival, although these differences were not statistically significant (p = 0.0913 and p 0.04044, respectively).

Adolescent

Alterations of the p16 gene in head and neck cancer: frequency and association with p53, PRAD-1 and HPV.

Alterations, especially homozygous deletions, of the putative tumor suppressor gene, p16 (p16INK4A, MTS1, CDKN2) have been found in tumor cell lines from a variety of neoplasms. Recent studies have reported frequent p16 gene deletions in cell lines from squamous cell carcinomas of the head and neck (SCCHN), although the prevalence of alterations was variable in primary tumors. This study determined the prevalence of point mutations and deletions of the p16 gene in 33 SCCHN. In addition, the association of p16 gene alterations and abnormalities of p53, PRAD-1 (cyclin D1), and the presence of human papillomavirus (HPV) was examined. We found an overall prevalence of p16 alterations of 36% (nine deletions, three single base substitutions, including one polymorphism). Seven tumors (of 29, 24%) had an alteration of p16 and p53; five (of 33, 15%) had alterations of p16 and PRAD-1; three (of 29, 10%) had alterations of all three genes. In addition, of the five tumors with human papillomavirus detected, only one also had a p16 gene alteration. The results indicate a potentially important role for the p16 gene in head and neck tumorigenesis. In addition, the presence of tumors with multiple somatic gene alterations suggest a possible interaction in the dysregulation of the cell cycle.

Adult

Tracheotomy and the intensive care unit patient.

Transportation of the intensive care unit (ICU) patient to the operating room for tracheotomy has been implicated as an unnecessary source of complications and has been cited as a relative indication for percutaneous tracheotomy. However, there is very little evidence in the literature to support this claim. We evaluated 100 consecutive patients who were transported from the ICU to the operating room for tracheotomy. There were no complications related to patient transportation. A total of five complications occurred, all unrelated to patient transportation. Two patients receiving pressure control ventilation developed a pneumothorax on postoperative days 7 and 8, respectively. There were three minor complications directly related to the tracheotomy: peristomal cellulitis, tracheitis, and hemorrhage of less than 25 cc on postoperative day 1. The minor complications were treated appropriately and resolved without any adverse sequelae. We provide a detailed review of 100 consecutive ICU patient tracheotomy cases and compare this with 109 tracheotomies in non-ICU patients. Transportation of the ICU patient does not appear to increase the risk of complications during tracheotomy and should not be cited as a cause of complications in the percutaneous tracheotomy literature. The results with standard surgical tracheotomy in the controlled setting of the operating room should serve as the standard by which other procedures are judged.

Adult

Management of complications resulting from laryngeal cancer treatment.

The most frequently encountered complications in the treatment of laryngeal cancer are discussed. Preoperative and surgical problems and complications encountered secondary to radiation and chemotherapy are included, along with airway obstruction, failure to diagnose, pharyngocutaneous fistula, stomal stenosis, and poor voice and aspiration are among the topics covered.

Airway Obstruction

p53 mutations in head and neck cancer: new data and evaluation of mutational spectra.

It has been suggested that the frequency, type, and location of p53 mutations (mutational spectra) can be linked to specific exogenous and endogenous carcinogenic agents and processes. Squamous cell carcinoma of the head and neck (SCCHN) provides an excellent tumor model to evaluate the utility of the p53 mutational spectra, given that it has well-defined and strong risk factors (tobacco and alcohol). The purpose of this analysis was to establish the pattern of p53 mutations in SCCHN and evaluate this mutational spectrum in comparison to the spectra for other cancers with similar and different risk factors, including cancers of the esophagus, lung, and colon. p53 mutational data were obtained from head and neck tumors collected at the University of North Carolina Hospitals and the published literature. A total of 14 of 33 tumors from the University of North Carolina Hospitals (42%) were found to have a p53 mutation. The alterations included three transversions, seven transitions, two deletions, and two suspected codon 47 polymorphisms. In general, SCCHN and esophageal cancer share a similar mutational pattern in contrast to colon cancer. These two aerodigestive tract cancers were statistically different from lung cancer, despite sharing tobacco as a major risk factor. For example, G-->T transversions, a mutation type considered to be characteristic of exogenous DNA-damaging agents including tobacco smoke carcinogens, varied among tobacco-related cancer sites (14% SCCHN, 11% esophageal, and 31% lung) in contrast to colon cancer (6%). The comparison of mutational spectra for SCCHN and other cancers indicates that the effects of both tobacco and alcohol exposure may yield a pattern of p53 mutations that reflects elements of both exogenous and endogenous exposures.

Adult

Immunohistochemical characterization of nitric oxide synthase activity in squamous cell carcinoma of the head and neck.

This study was designed to investigate the presence of nitric oxide in human squamous cell carcinoma of the head and neck. We localized the activity of nitric oxide synthase in these tumors through immunohistochemical analysis using antibodies to L-citrulline (a byproduct of nitric oxide synthase), to inducible nitric oxide synthase, and to constitutive nitric oxide synthase. We found presence of inducible enzyme in squamous cells throughout these tumors, with the highest intensity staining occurring directly around keratin pearls. Our findings suggest that inducible nitric oxide synthase activity is present in squamous cell carcinomas of the head and neck, leading us to conclude that inducible nitric oxide synthase may play a significant role in tumor growth.

Awards and Prizes

Effect of Lactobacillus acidophilus on antibiotic-associated gastrointestinal morbidity: a prospective randomized trial.

Oral antibiotic therapy can alter the gastrointestinal microflora and result in troublesome gastrointestinal complaints. Patients who have experience with broad-spectrum antibiotics may be reluctant to start or to comply with antibiotic therapy due to the associated discomfort. In the field of otolaryngology, oral antibiotic therapy is commonplace, and patient intolerance of a particular antibiotic may result in compromise to a less effective choice. Yogurt, which contains Lactobacillus acidophilus, is often recommended by practitioners to help reduce the side effects of oral antibiotic therapy. We wanted to objectively evaluate the effect of orally administered L. acidophilus on the gastrointestinal side effects of oral broad-spectrum antibiotic therapy. Twenty-seven outpatients, 10 years of age or older, with ear, sinus, or throat infections, in whom amoxicillin/clavulanate was felt to be the antibiotic of choice, were randomly assigned to amoxicillin/clavulanate only, or amoxicillin/clavulanate and Lactobacillus treatment groups. Each patient was advised by the nursing staff to consume a well-balanced diet, and a detailed explanation of the medication schedule was given. A questionnaire was given to each patient at the conclusion of therapy. The data were analyzed using Spearman's rank-order correlations. Concomitant therapy of L. acidophilus with amoxicillin/clavulanate was associated with a significant decrease in patient complaints of gastrointestinal side effects and yeast superinfection. Almost all patients (89%) reported resolution of infection during the course of therapy. We believe that use of L. acidophilus is warranted in patients on broad-spectrum antibiotic therapy with gastrointestinal complaints.

Adolescent

Measurement of laryngeal resistance in the evaluation of botulinum toxin injection for treatment of focal laryngeal dystonia.

In the past, there has been no consistent, objective method of following patients undergoing botulinum toxin injections for treatment of laryngeal dystonia. Herein, the application of translaryngeal resistance measurements to 15 dysphonic patients is described. Laryngeal resistance is calculated from analysis of translaryngeal pressure and airflow during the utterance /pi/, and found to fall predictably after successful toxin injection. In our series of patients, laryngeal resistance dropped by 69.1% after initial toxin injection. The changes in resistance over time correlate with subjective impressions of voice quality. Translaryngeal resistance measurements can be used objectively to follow patients longitudinally after injection and to collect objective data for analysis. No previously described measurements have met all these criteria. Laryngeal resistance measurement is an ideal method of documenting the results of botulinum toxin injection for the treatment of focal laryngeal dystonia.

Airway Resistance

ras mutations and expression in head and neck squamous cell carcinomas.

Mutational activation and overexpression of the family of ras proto-oncogenes have been associated with many human tumors. The role of mutations of H-ras, K-ras, and N-ras, as well as expression of the respective protein products (p21s) in normal mucosa, dysplastic mucosa, and squamous cell carcinomas (SCCs) of the head and neck has not been fully described. In our study, 51 tumors (40 paraffin embedded and 11 fresh frozen) were examined to determine if mutational activation of ras is an important molecular event in head and neck SCC. Analyses of codons 12, 13, and 61 of H-ras, K-ras, and N-ras revealed no mutations, suggesting that mutational activation of ras is not important in the majority of head and neck SCCs. Immunocytochemistry (ICC) was used to define the expression of H-ras, K-ras, and N-ras in normal mucosa, dysplastic mucosa, and SCC of the head and neck and to determine if expression of ras family members correlated with early or late events in the development of SCC. Expression of p21N-ras in nine samples of histologically normal head and neck mucosa revealed moderate staining in the basal proliferative layers with progressively less staining as cells matured. The most superficial layers of normal mucosa failed to express p21N-ras. A low level of p21H-ras was expressed in all layers of normal mucosa while K-ras was not expressed. ICC of SCC tumor sections revealed cytoplasmic expression of N-ras in nine of nine tumors, H-ras in five of nine tumors, and K-ras in one of nine tumors. Expression of H-ras, K-ras, and N-ras in head and neck SCC was not related to histologic differentiation or TNM staging; however, p21N-ras was overexpressed in seven of nine tumors. Furthermore, the pattern of N-ras expression in dysplastic lesions revealed expression in all layers of the mucosa in contrast to normal mucosa, which expresses p21N-ras primarily in the basal proliferative layer. The change in p21N-ras expression pattern in dysplastic mucosa and its overexpression in the majority of tumors suggest that loss of control of N-ras expression may be an early step in carcinogenesis of head and neck SCC.

Adult

Unique chromosomal rearrangement and mucin production in a novel salivary myoepithelial cell strain.

Pleomorphic adenoma is the most frequently occurring benign neoplasm of the salivary glands. We describe the culture characteristics, biochemical properties, immunohistochemical staining, and genetic rearrangements found in a novel cell strain (UNC4) established from a human benign pleomorphic adenoma. Serum and/or butyrate stimulation of UNC4 cultures results in upregulation of mucin production. This is confirmed by periodic acid-Schiff, periodic acid-Schiff digest, alcian blue, and mucicarmine staining as well as by gel electrophoresis. Fluorescent immunohistochemical studies detect cellular cytokeratin, desmin, and epithelial membrane antigen. Immunofluorescent staining for S100 protein is negative. Examination of the karyotype of UNC4 reveals a unique rearrangement between one chromosome 8 and the two chromosome 9s involving the 8q12 locus. UNC4 represents an in vitro model of a benign salivary gland neoplasm that can provide the basis for further molecular and biochemical studies on genetic rearrangement and salivary mucin production.

Adenoma, Pleomorphic

Simultaneous chemoradiation in the treatment of advanced head and neck cancer.

Fifty-eight patients with either advanced or unresectable squamous cell carcinoma of the head and neck were randomly selected to receive either twice daily radiation alone or twice daily radiation plus concomitant chemotherapy with cisplatin and fluorouracil (5-fluorouracil). There was no advantage in survival or time to progression with the addition of chemotherapy to twice daily radiation for patients with advanced resectable cancers. In the group of patients with unresectable cancers, however, there was a statistically significant advantage to the addition of chemotherapy, both in terms of disease-free survival and date to progression.

Adult

Immediate mandibular replacement using reconstruction plates.

Mandibular reconstruction at the time of tumor resection remains a surgical dilemma. Primary reconstruction allows for immediate reconstitution of mandibular form and function. Various methods have been attempted, but none enjoys uniform success. With advances in the field of microvascular surgery have come numerous options in replacing these defects. These procedures, however, require special surgical teams and are associated with an increase in operative time as well as morbidity at the donor site. An alternative method involves the use of mandibular reconstruction plates to bridge the defect between segments. This review focuses on 19 patients whose jaws were reconstructed in this fashion. Although not free of complications, mandibular plate reconstruction offers the advantages of (1) lack of donor site morbidity, (2) expediency, (3) excellent mandibular contour, and (4) the ability to reconstruct the condyle when necessary. The technique, results, and complications associated with this procedure are discussed.

Adult

The prevention of postoperative stridor and laryngospasm with topical lidocaine.

Tonsillectomy and adenoidectomy can predispose to stridor and laryngospasm in the immediate postextubation period. A prospectively randomized study of 133 patients undergoing tonsillectomy and adenoidectomy was undertaken to determine if the topical application of 4 mg/kg of 4% lidocaine at the time of intubation would decrease the incidence of postoperative stridor and laryngospasm. Taken together, eight (12%) of 67 control patients suffered stridor or laryngospasm vs two (3%) of 66 patients receiving lidocaine. It is concluded that lidocaine administered topically at the time of intubation for adenotonsillectomy helps prevent postoperative stridor and laryngospasm. Surgery of the upper aerodigestive tract often involves not only the technical aspects of the surgical procedure but also concomitant management of the airway. This can present a challenge to even the most adept otolaryngologist and anesthesiologist. Accidental extubation is always possible, and reintubation can be difficult in the presence of blood and saliva. The difficulty is often compounded with a patient who is not completely paralyzed.

Adenoidectomy