PubMed Health⌕ Search

Biomedical subjects

E D Vaughan

Publications and source records attributed to E D Vaughan.

At least 19 recordsLinked to original sources
PubMed1998

Synchronous oral carcinomas: independent or common clonal origin?

Second primary tumors in patients with head and neck cancer have a detrimental impact on long-term survival; at least 15% of patients develop additional tumors. Originally, it was hypothesized that multiple tumors developed independently after widespread epithelial exposure to carcinogens (the field cancerization theory), but recent molecular studies now support the alternative theory of a common clonal origin. If multiple tumors originate from the same clone, early genetic alterations in these cells should be common to all of the tumors. We have compared the pattern of allelic imbalance in paired tumors from five male patients with two synchronous oral squamous cell carcinomas and in peripheral dysplasia using microsatellite markers on chromosomes 3p, 9p, and 17p. Discordance, usually through loss of alternate alleles at the same microsatellite loci, was detected in two patients. The remaining three patients had identical alterations in their tumors. The changes identified occurred early in tumorigenesis, because, with only one exception, these were also present in the associated dysplasia. Thus, we provide evidence that synchronous oral squamous cell carcinomas are of independent origin in some patients but may be of common clonal origin in others.

Alleles↗
PubMed1998

Transforming growth factor-beta receptor types I and II are expressed in renal tubules and are increased after chronic unilateral ureteral obstruction.

Transforming growth factor-beta (TGF-beta) is a profibrotic cytokine which has been implicated in the renal fibrosis which follows unilateral ureteral obstruction (UUO) in the rat. TGF-beta receptor type I (TGF-RI) and TGF-beta receptor type II (TGF-RII) are part of the complex which mediates the response to TGF-beta. We sought to determine if TGF-RI and TGF-RII are found in the kidney, and if their expression is changed as a result of UUO. Polymerase chain reaction (PCR) was used to determine expression of mRNA for TGF-RI and TGF-RII in the kidney. Immunoperoxidase was used to localize and quantify the expression of these receptors at 3, 7, 14, 21 and 28 days after UUO, and in sham-operated animals. Expression of mRNA for TGF-RI and TGF-RII was demonstrated in sham operated, obstructed and contralateral unobstructed kidneys using PCR. Using immunoperoxidase, a uniform distribution of TGF-RI and TGF-RII was found in cortical tubules of sham operated kidneys, whereas medullary tubules showed a patchy TGF-RI distribution and no TGF-RII staining. After UUO, an increased tubular expression of TGF-RI and TGF-RII was noted in both obstructed and contralateral kidneys compared to sham operated kidneys. No staining for either TGF-RI or TGF-RII was noted in glomeruli, vasculature or interstitial cells. TGF-beta receptors I and II were found exclusively in renal tubules and were shown to increase in both the obstructed and contralateral kidneys relative to sham operated animals. Upregulation of TGF-beta receptors in both kidneys suggests that TGF-beta may contribute to the fibrotic response in the obstructed kidney and the hypertrophic response of the contralateral kidney.

Actins↗
PubMed1998

Adult respiratory distress syndrome after microvascular free tissue reconstruction in head and neck malignancy.

Adult respiratory distress syndrome (ARDS) is an important cause of morbidity and mortality after major operations. We undertook a 10 year retrospective analysis of patients undergoing major surgery in combination with microvascular free tissue transfer for head and neck malignancy at a Regional Maxillofacial Unit to try and identify predisposing factors. In the 10 year period to 31 April 1995, roughly 418 patients underwent major head and neck reconstructions, of which 399 (95.5%) were admitted to the intensive care unit (ICU) postoperatively. Thirty patients (7.2%) spent more than 72 h in the ICU, eight developed ARDS (1.9%) of whom four died. The factors that seemed to contribute to the development of ARDS were massive blood transfusion and early postoperative complications that required a further operation under general anaesthesia.

Adult↗
PubMed1998

Oropharyngeal morbidity following transoral approaches to the upper cervical spine.

The transoral approach to the upper cervical spine is now well established. Oropharyngeal complications have not previously been critically assessed. In the present study, the overall complication rate was 31.6%. This dropped to 15.4% in those patients who did not undergo splitting of the soft palate. The complication rate of 75% in the split soft palate group means that this procedure should be discontinued where it is not absolutely necessary.

Adolescent↗
PubMed1998

The impact of surgery for oral cancer on quality of life as measured by the Medical Outcomes Short Form 36.

Quality of life evaluation is an important measure of outcome following the treatment of head and neck cancer. The aim of this study was to evaluate the quality of life of patients undergoing primary surgery for oral and oropharyngeal squamous cell carcinoma. 50 consecutive patients with previously untreated oral cancer were assessed using two questionnaires, the Medical Outcomes Short Form 36 (SF-36) and University of Washington Head and Neck Questionnaire (UW-QOL) at four time intervals; pretreatment, and 3, 6, 12 months. At the time of presentation, patients with oral cancer scored lower than norms, particularly for physical role limitation, mental role limitation, and social functioning. At 3 months following surgery, there was a considerable deterioration in physical functioning, limitation of physical role, energy and general health perception. By 12 months postoperatively patients approached pretreatment scores. The SF-36 and UW-QOL provide outcome information suitable for international comparison.

Adult↗
PubMed1998

A comparison between the University of Washington Head and Neck Disease-Specific measure and the Medical Short Form 36, EORTC QOQ-C33 and EORTC Head and Neck 35.

The University of Washington Head and Neck Disease-Specific questionnaire (UW-QOL) is potentially a suitable routine measure of outcome in head and neck cancer because it is quick and simple for patients to complete and is easy to process. The aim of this study was to compare the UW-QOL with three validated instruments in a group of patients having primary surgery for oral cancer. Between May and December 1995, 34 consecutive patients with previously untreated oral and oropharyngeal squamous cell carcinoma underwent primary surgery. Patients self-completed the following questionnaires: UW-QOL, Medical Outcomes Short Form 36 (SF-36), the European Organisation for Research and Treatment of Cancer (EORTC) QOQ-C33 and the EORTC Head and Neck (H&N35). Questionnaires were distributed at four time intervals: pre-operatively, and at 3, 6 and 12 months. Patients were withdrawn if they developed recurrent disease. 29 patients agreed to participate in this prospective study and cross-sectional comparisons were made on baseline data and trends over time for longitudinal comparisons. This study emphasises the difficulties of one questionnaire to adequately evaluate quality of life. However, it would appear that the UW-QOL is a broad measure suitable for routine "low cost" assessment of disease-specific functional status.

Activities of Daily Living↗
PubMed1998

Microfocal prostate cancer: biopsy cancer volume does not predict actual tumour volume.

OBJECTIVE: To determine whether microfocal prostate cancer on needle biopsy predicts clinically insignificant disease in men undergoing radical prostatectomy. PATIENTS AND METHODS: The records of 726 men who underwent radical prostatectomy between January 1990 and September 1995 were reviewed; 83 men had pre-operative prostatic needle biopsies which revealed microfocal prostate cancer. In these men, tumour volume (length) in the biopsy was compared to the percentage of tumour in the total prostatectomy specimen, and the pathological stage and clinical outcome reviewed. RESULTS: Of the 83 men with microfocal prostate cancer on biopsy 75 (90%) had clinically significant disease. Pre-operative variables were of no use in identifying patients with clinically insignificant tumour volumes. When comparing those with microfocal tumour and those without at one institution, 69% had organ-confined (pT2) disease and 31% had capsular penetration (pT3), compared with 61% and 39%, respectively (P < 0.05). Additionally, the positive surgical margin rate for those with microfocal tumour was only 6%, compared with 26% for those without microfocal disease (P < 0.05). Biochemical failures during the median follow-up period of 24 months occurred in 6% of the men with microfocal cancer and in 15% of those undergoing total prostatectomy (P < 0.05). CONCLUSIONS: Microfocal prostate cancer determined from the needle biopsy does not predict clinically insignificant disease.

Aged↗
PubMed1998

Telomerase activity in the differentiation of benign and malignant adrenal tumors.

BACKGROUND: Telomerase is an RNA-dependent DNA polymerase that extends the ends of chromosomes by synthesizing the 6 oligonucleotide repeat TTAGGG and thus serves as a marker for cellular immortality. Although absent in most adult somatic tissues, telomerase activity is present in stem cells and is reactivated in nearly all primary human malignancies. In this study we sought to determine whether tumors of the adrenal glands contain telomerase activity and whether telomerase activity can be used to differentiate benign and malignant tumors of the adrenal glands. METHODS: Tissue was obtained from 23 specimens at adrenalectomy. Adjacent normal adrenal tissue was obtained for control. All specimens were rapidly frozen and stored at -80 degrees C until assay. Telomerase activity was determined by the telomeric repeat amplification protocol (TRAP). RESULTS: Telomerase activity was present in 5 of 23 (22%) of the adrenal tumors. All 3 malignant tumors were strongly TRAP positive. There was a single cortical adenoma that had very weak telomerase activity. The single TRAP-positive tumor of the adrenal medulla was a ganglioneuroma. CONCLUSIONS: Benign adrenal tumors infrequently contain telomerase activity, whereas telomerase reactivation appears to be common in malignant tumors of the adrenal glands. These data suggest that determination of telomerase activity may offer a novel way to facilitate the differentiation of benign and malignant adrenal tumors.

Adrenal Gland Neoplasms↗
PubMed1997

p53 mutations in squamous cell carcinoma of the head and neck predominate in a subgroup of former and present smokers with a low frequency of genetic instability.

We examined the p53 mutational profile of 65 squamous cell carcinomas of the head and neck (SCCHNs) from patients living in northwest England. Twenty-three p53 mutations were detected in 20 samples (31%). GC-->AT transitions were the predominant type of mutation. The p53 mutational profile of SCCHN tumors was similar to that of non-small cell lung tumors from patients within the same geographical area, supporting the idea of a common model for carcinogenesis in the upper respiratory tract. Statistical analysis showed that the incidence of p53 mutations among present and former smokers was significantly higher than that in nonsmokers (P < 0.02). In addition, p53 mutations were found to predominate in a group of SCCHN patients with low genetic damage, as indicated by the fractional allelic loss value. The above findings suggest an early initiating role for p53 and imply that at least two separate carcinogenic pathways may be involved in the development of SCCHN.

Alcohol Drinking↗
PubMed1997

p53 mutations in relation to human papillomavirus type 16 infection in squamous cell carcinomas of the head and neck.

The relationship between human papillomavirus (HPV) type 16 infection and p53 gene mutations was investigated in squamous cell carcinomas of the head and neck (SCCHN). HPV was detected by general primer-mediated and type-specific PCR. Alterations in the p53 gene were investigated using single-strand conformation polymorphism and sequence analysis in 27 SCCHN, of which 12 were HPV 16-positive and 15 were HPV-negative. Mutations were detected in 2/12 (16.7%) HPV 16-positive and 7/15 (46.7%) HPV-negative tumours; this difference was not statistically significant. The predominant mutations were deletions and C --> T transitions; G --> T transversions were found in only 2 tumours. Our results indicate that the presence of HPV 16 and p53 mutations is not mutually exclusive and detection of a p53 mutation does not exclude a potential role for HPV 16 in the pathogenesis of a subset of SCCHN.

Carcinoma, Squamous Cell↗
PubMed1997

Functional outcome in soft palate reconstruction using a radial forearm free flap in conjunction with a superiorly based pharyngeal flap.

BACKGROUND: Speech and swallowing problems due to velopharyngeal incompetence may follow soft palate resection and reconstruction. Over the past 3 years, we have developed the use of a superiorly based pharyngeal flap in conjunction with a radial forearm flap for soft palate reconstruction. METHODS: This paper describes the technique in detail and compares the functional results in a study with patients undergoing soft palate resection for squamous cell carcinoma treated with or without a pharyngeal flap as an adjunct to a radial forearm free flap for soft palate reconstruction. Seven patients had one quarter or one half soft palate defects reconstructed with a radial forearm flap alone. Of the 11 patients undergoing three quarter or total soft palate resections, all were reconstructed with a radial forearm flap, but 5 were treated with an additional superiorly based pharyngeal flap. The functional outcome for all the patients was analyzed and compared. RESULTS: Our results show that the addition of the superiorly based pharyngeal to the radical forearm flap in soft palate reconstruction results in improved speech and swallowing. We recommend the use of the additional flap in resections in which more than one quarter of the soft palate is included.

Adult↗
PubMed1997

Radial forearm flap donor-site complications and morbidity: a prospective study.

One-hundred patients undergoing radial forearm flap reconstruction in the head and neck over a 2-year period were followed prospectively to assess complications and morbidity associated with the radial flap donor site. Eighty-six patients were available follow-up at 3 months and 74 at 1 year (49 fasciocutaneous, 25 composite). Partial loss of the donor-site skin graft occurred in 14 patients (16 percent), with exposure of tendons in 11 patients (13 percent). Delay in healing of the split-thickness skin graft at the donor site occurred in 19 patients (22 percent). Fracture of the radius occurred in 6 of 35 patients with composite flaps (17 percent). Superficial radial nerve sensation was reduced in 24 patients (32 percent) at 1 year. Ten patients (14 percent) reported cold intolerance, and 21 patients (28 percent) complained of poor aesthetic result. Function of the donor arm was restricted in 8 patients (16 percent) in the fasciocutaneous group, in 7 patients (36 percent) in the composite group without fracture, and in all patients who had a fracture of the radius following harvesting of composite flaps. Detailed measurements of forearm circumference, grip strength, pinch strength, and wrist movements showed greater reduction in these parameters in patients reporting restricted function compared with those reporting normal function. It is concluded that there is a low incidence of long-term morbidity associated with fasciocutaneous flaps and a higher incidence with composite flaps. Fracture of the radius results in reduced function in all cases.

Female↗
PubMed1997

In vivo cystometric evaluation of progressive bladder outlet obstruction in rats.

PURPOSE: Bladder outlet obstruction in man is a common medical disorder that may result from benign prostatic hyperplasia, urethral stricture disease, or congenital anomaly. The functional changes that develop in response to obstruction include detrusor instability, elevated voiding pressures, and the presence of a residual urine. The aim of this study was to document the development of progressive bladder outlet obstruction over time in a rat model using conscious, in vivo urodynamics. MATERIALS AND METHODS: Infravesical bladder outlet obstruction was created in female rats by placing a jeweler's jump ring loosely around the proximal urethra. Gradual development of outlet obstruction was followed urodynamically in awake animals at 3, 7, 14, 21, and 28 days post obstruction using a subcutaneously implanted mediport. For each group n = 5-8 animals. RESULTS: Animals developed large capacity bladders with increased compliance, a high residual urine volume, and spontaneous activity. Bladder capacity increased from 0.20 + 0.02 ml. to 6.30 + 1.59 ml. at 28 days post obstruction (p < 0.05). Residual volume increased from 0.06 + 0.01 ml. to 5.95 + 1.54 ml. (p < 0.05). Percent void decreases from 72 + 3.7% in sham controls to 6.7 + 2.5% at 28 d (p < 0.05). Voiding pressure increased from 12 + 1.6 mm. Hg in sham animals to a maximum of 42 + 6.1 mm. Hg at 21 d (p < 0.05). Compliance was significantly higher at 28 d when compared to all other time points. 89% of obstructed animals developed bladder instability. CONCLUSIONS: This study provides clear evidence of the progressive change in bladder function which occurs following outlet obstruction. Implantation of a subcutaneous mediport allows in vivo recording of both the filling and voiding phases of micturition in awake animals that have intact neural responses. This is a precise and easily reproducible method for producing obstruction in a small animal which can provide a continuum of tissue and urodynamic data that may be used to further study the pathophysiologic changes underlying bladder outlet obstruction or other models of bladder dysfunction.

Animals↗
PubMed1996

Prevalence of mucosotropic human papillomaviruses in squamous-cell carcinoma of the head and neck.

The prevalence of mucosotropic human papillomavirus (HPV) DNA in 63 squamous-cell carcinomas (SCC) from different anatomic sites in the head and neck was determined by general primer-mediated polymerase chain reaction (GP-PCR). HPV DNA was detected in 20.6% of SCC. Additional type-specific PCR for HPV 6, 11, 16, 18, 31 and 33 demonstrated the presence of HPV 16 alone in these carcinomas. HPV 16 was also detected in normal epithelium from the resection margins of the majority of HPV-positive SCC. HPV status did not correlate with tumour site, whether primary or recurrent, TNM stage, metastases, degree of differentiation, smoking or alcohol history, fate or survival.

Alcohol Drinking↗
PubMed1996

Expression of I2-imidazoline sites in rat prostate. Effect of castration and aging.

Clonidine, idazoxan, and related imidazoline adrenergic drugs bind to non-adrenergic sites in brain and several peripheral tissues. These sites, termed imidazoline receptors, appear to exist in two major subclasses, I1 sites labeled by clonidine and I2 sites labeled by idazoxan. In this study, we investigated whether rat prostate expresses imidazoline receptors and, if so, whether their expression can be regulated by circulating testosterone. Studies in rat ventral prostate membrane revealed that [3H]idazoxan, but not [3H]p-aminoclonidine, bound to non-adrenergic sites. The binding of [3H]idazoxan was saturable (Bmax: 941 +/- 105 fmol/mg protein) and high affinity (KD: 16.4 +/- 2.3 nM). The rank order of the inhibition of binding by imidazoline ligands was cirazoline > clonidine > UK 14,304 > guanabenz, indicating an I2 subclass of imidazoline receptors. Bilateral orchiectomy increased the number of binding sites (Bmax) for [3H]idazoxan without changing the affinity (KD). Testosterone replacement, while completely restoring the plasma testosterone levels, only partially reversed the increase in Bmax. In contrast, the binding of [3H]idazoxan to prostate membranes of rats in different age groups (4, 7, and 16 months) revealed a progressive decrease in the Bmax without any change in KD. We conclude that the rat prostate expresses the I2 subclass of imidazoline receptors and that the expression is regulated by circulating testosterone.

Adrenergic Agonists↗
PubMed1996

Aesthetic lip splits.

Both upper and lower lip splits, usually with osteotomy of the underlying jaw, improve access to the deep structures of the head and neck. A simple modification to the midline lip split is to incorporate a chevron in both the peri-oral skin and vermilion margin. The advantages are: accurate wound closure, no straight line contracture and a broken line of the peri-oral scar. This improves the aesthetic result of the healed lip.

Cicatrix↗