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Biomedical subjects

E D Vaughan

Publications and source records attributed to E D Vaughan.

At least 37 records · Page 2Linked to original sources
PubMed2003

Inducible nitric oxide synthase promotes pathophysiological consequences of experimental bladder outlet obstruction.

PURPOSE: Bladder outlet obstruction leads to histological and functional changes in the bladder over time. We investigated the role of inducible nitric oxide synthase (iNOS) in the progression of pathological changes of the bladder secondary to outlet obstruction in a rat and a mouse model. MATERIALS AND METHODS: To assess expression of iNOS in the bladder, polymerase chain reaction amplification of mRNA was done. Rats were subjected to sham operation or partial bladder outlet obstruction. They were given the iNOS inhibitor aminoguanidine in drinking water or unmodified water. After 2 weeks, awake cystometric evaluation was performed, the bladders were harvested and the degree of fibrosis was assessed. In another series of experiments mice deficient in the iNOS gene (iNOS -/-) were compared to WT mice for cystometric as well as histological changes in the bladder following partial bladder outlet obstruction or sham operation. RESULTS: Partial bladder outlet obstruction induced the expression of iNOS mRNA in the mouse bladder. iNOS -/- mice showed a significantly smaller increase in bladder volume at 3 weeks compared with WT. Pharmacological inhibition of iNOS activity significantly attenuated the increase in bladder size and the number of spontaneous bladder contractions in obstructed rats at 2 weeks. Furthermore, genetic and pharmacological decreases in iNOS led to significantly less fibrosis of the bladder after partial bladder outlet obstruction in mice and rats, respectively. CONCLUSIONS: Pharmacological or genetic decreases in iNOS resulted in amelioration of functional and fibrotic changes in the bladder after partial bladder outlet obstruction, suggesting that NO contributes to the pathophysiology of bladder outlet obstruction.

Animals↗
PubMed2002

Clinical function after primary surgery for oral and oropharyngeal cancer: an 11-item examination.

The aim of this study was to record clinical function using an 11-item clinical examination and identify the main postoperative functional deficits. Of 132 consecutive patients undergoing surgery for previously untreated disease between January 1995 and June 1997, 130 were recruited in the study. An 11-domain clinical examination was made on the day before operation, and at 6 and 12 months afterwards. This examination assessed lip competence, tongue movement, oral mucosa, dental state, mouth opening, speech, drooling, diet, appearance, oral sensation and shoulder movement. Preoperatively there were deficits in natural dentition, consistency of diet and tongue protrusion. Postoperatively functional scores fell particularly for tongue movements, mouth opening, mucosa, dentition, speech, diet, appearance, lip sensation and tongue sensation. At 1 year, dental status, sensation and oral mucosa were particularly defective. Patients with large tumours, free tissue transfer, or adjuvant radiotherapy had the worst levels of function.A simple clinical examination provides a rapid assessment of function that can be used in conjunction with validated questionnaires to provide a more comprehensive evaluation of outcome.

Activities of Daily Living↗
PubMed2002

Health-related quality of life and clinical function after primary surgery for oral cancer.

Clinical function and health-related quality of life (HRQoL) are both important outcome parameters following surgery for oral and oropharyngeal cancer. The aim of this project was to explore the relationship between an 11-point clinical examination and HRQoL. Of 132 consecutive patients undergoing surgery for previously untreated disease between January 1995 and June 1997, 130 were recruited into the study. The University of Washington Quality of Life Questionnaire (UW-QoL) was completed by each patient on the day before operation and 6 and 12 months later. On each occasion the first author made an 11-point clinical examination. The main predictors of cumulative UW-QoL scores were tumour size, clinical functional score and type of operation. The trend was for a fall from preoperative levels at 6 months and then for a slight improvement at 1 year. The differential in respect of baseline function was present at all three time points in each patient group. This suggests that functional deficits at presentation persist following treatment.

Activities of Daily Living↗
PubMed2002

Vascularized iliac crest with internal oblique muscle for immediate reconstruction after maxillectomy.

The vascularized iliac crest graft with internal oblique muscle as a method of reconstruction after maxillectomy has been used routinely at the Regional Maxillofacial Unit in Liverpool since 1993. Twenty-four consecutive operations have now been done and this paper reports an audit of our experience. An analysis of case-notes was made retrospectively after checking theatre diaries and records. A detailed inspection of the case-notes was undertaken to ascertain the presenting diagnosis, the complications and the outcome in terms of recurrence and disease survival. The type of defect was recorded, as was whether it had been possible to rehabilitate the patient both dentally and facially. At the time of this study 9 patients (38%) had died of their disease leaving 15 surviving. In 13 cases full dental and facial rehabilitation had been achieved or patients were waiting for an implant-retained prosthesis. Donor site problems important enough to be recorded in the notes were minimal, one case of abdominal wall weakness was noted, which required no intervention. The vascularized iliac crest graft with internal oblique muscle offers a complete solution for reconstruction after maxillectomy, providing there has been no sacrifice of the overlying facial skin and oral sphincter. There is sufficient height and depth of bone to maintain a facial profile and the muscle epithelializes to provide an ideal oral and nasal lining. This flap provides a base to enable full dental and facial prosthetic rehabilitation with either implant-retained or conventional prostheses.

Abdominal Muscles↗
PubMed2001

Normal and malignant prostate epithelial cells differ in their response to hepatocyte growth factor/scatter factor.

Hepatocyte growth factor/scatter factor (HGF/SF) promotes the proliferation, differentiation, motility, and invasion of epithelial cells by binding to its cell surface receptor, the Met tyrosine kinase. In the prostate, Met is expressed predominantly by prostate epithelial cells (PrEC), whereas HGF/SF is synthesized by prostate stromal cells (PrSC). Met is also expressed in localized and metastatic prostate cancers. Our results show that PrECs in in vitro culture maintain expression of Met at a level comparable to DU145 cancer cell expression. HGF/SF secreted by PrSC stimulates tyrosine phosphorylation of the Met receptor. In normal PrEC, HGF/SF causes growth inhibition, sustained phosphorylation of mitogen-activated protein kinase, and increased CK18 expression consistent with cell differentiation. In contrast, HGF/SF significantly stimulates the proliferation of DU145 prostate cancer cells. HGF/SF in the conditioned medium of PrSC specifically induces migration of both normal and malignant prostate epithelial cells through MatriGel-coated Transwell filters. HGF/SF depletion reduces cell migration by approximately 50%. The response of PrEC is specific for HGF/SF since the other growth factors tested do not significantly affect growth or migration of PrECs. These results support the in vivo importance of the prostate stroma and specifically of HGF/SF as a unique stromal derived factor in the development and progression of prostate cancer.

Animals↗
PubMed2001

Role of nitric oxide in renal tubular apoptosis of unilateral ureteral obstruction.

BACKGROUND: The obstructed kidney in unilateral ureteral obstruction (UUO) is characterized by renal atrophy and tissue loss, which is mediated by renal tubular apoptosis. We sought to determine whether NO is involved in renal tubular apoptosis in vitro and in vivo. METHODS: Rat renal tubular epithelial cells (NRK-52E) were subjected to mechanical stretch, and apoptosis and cell size were analyzed by flow cytometry. Furthermore, we studied UUO in mice lacking the gene for inducible nitric oxide synthase (iNOS-/-) and their wild-type littermates. Tubular apoptosis and proliferation were detected by immunostaining. NOS activity and NOS expression were assessed by a citrulline assay and Western blot, respectively. RESULTS: Stretching-induced apoptosis in NRK-52E, which was reduced when NO was increased; conversely, stretch-induced apoptosis was increased when a NOS inhibitor was added to the cells. Stretched cells are larger and more apoptotic than unstretched cells. In UUO, the obstructed kidney of iNOS-/- mice exhibited more apoptotic renal tubules than the wild-type mice through 14 days of UUO. The obstructed kidney of iNOS-/- mice at day 3 showed more proliferative tubules compared with wild type. The obstructed kidney of wild-type mice exhibited higher total NOS activity until day 7 after UUO compared with iNOS-/- mice. However, the obstructed kidney of day 14 wild-type mice exhibited significantly lower iNOS activity and protein compared with the day 0 kidney. CONCLUSION: These results suggest that mechanical stretch is related to renal tubular apoptosis and that NO plays a protective role in this system in UUO.

Animals↗
PubMed2001

A comparison of aesthetic, functional and patient subjective outcomes following lip-split mandibulotomy and mandibular lingual releasing access procedures.

Good access to the site of oral cancer is essential to allow for adequate three-dimensional resection of the tumour. Splitting the lower lip in conjunction with a mandibulotomy offers excellent access to all areas of the mouth and pharynx, but this inevitably produces a facial scar and there is morbidity associated with the healing of the mandibulotomy. An alternative approach is the mandibular lingual releasing technique, which provides good access to the oral cavity and avoids the morbidity associated with lip-split mandibulotomy. The aim of this study was to compare aesthetic, functional and patient subjective outcomes between the two access procedures. One hundred and fifty patients had oral access procedures between 1992-95 (ninety lip-split mandibulotomy and sixty mandibular lingual release). Thirty patients fulfilled selection criteria (primary surgery as treatment, tumour size < 5.1 cm, anterior oral cavity tumours, and reconstructed with a radial forearm free flap) and 10 patients from each group were able to attend a review appointment for objective clinical assessment of their speech, tongue mobility, lip competence and temperomandibular signs. Using items from the University of Washington quality of life questionnaire patient subjective outcomes were assessed. Using standardised photographs the clinician and lay persons assessed the overall post-operative facial appearance. The patients also assessed their own facial appearance using a similar scoring method. Resection margins were similar in both groups and it would seem that both methods provide adequate access to the anterior oral cavity. Clinical examination showed no differences in function between the two access procedures. Although there was a small number, the lip-split mandibulotomy group reported significantly better speech, swallowing and chewing. Previous concerns about a possible detrimental effect on appearance following lip-split, were not borne out in this study.

Child↗
PubMed2001

The relationship between length of stay and health-related quality of life in patients treated by primary surgery for oral and oropharyngeal cancer.

A patient's length of hospital admission is simple to measure, whilst their health related quality of life (HRQOL) is much more challenging. Similar clinical and demographic factors may exist between an increased length of stay (LOS) and a worse HRQOL outcome. The aim of this study was to assess whether LOS could serve as a proxy marker of HRQOL. One hundred and thirty consecutive patients with previously untreated oral and oropharyngeal squamous cell carcinoma were recruited. All had primary surgery. The University of Washington questionnaire (UW-QOL) and the European Organisation for Research and Treatment core cancer questionnaire (EORTC C30) were self-completed preoperatively, after 6 months and 1 year. The median LOS following laser/primary closure/split skin grafts (21 patients) was 2 days compared to 16 days following microvascular free flap reconstruction (105 patients). In the free flap group the best predictors of LOS were age, tumour size and early medical/surgery complications. Patients with a LOS greater than 16 days (median) reported significantly worse chewing (P = 0.008), swallowing (P = 0.002) and cumulative UW-QOL score (P = 0.01). No significant differences were seen in the EORTC C30. Length of stay is potentially a useful indicator of health related quality of life because it is linked by tumour size, however, the relationship is confounded by age, which tends to influence length of stay more than health related quality of life.

Adult↗
PubMed2001

Management of malignant salivary gland tumours.

Malignant tumours of both major and minor salivary glands are extremely rare: the parotid gland is most frequently affected by malignant change, followed by the submandibular gland. Malignant tumours of minor salivary glands may occur anywhere in the upper aerodigestive tract, but more common sites are the upper lip, junction of hard and soft palate and paranasal sinuses.

Adolescent↗
PubMed2001

Flap monitoring after head and neck reconstruction: evaluating an observation protocol.

This study evaluated the postoperative free-flap monitoring frequency protocol used in a maxillofacial unit for patients receiving free-tissue transfer for reconstruction following orofacial cancer. All free-tissue transfers undertaken in the unit between January 1992 and October 1998 were reviewed retrospectively. Of the 370 patients evaluated, 46 returned to theatre with compromised free flaps. The compromise was purely venous in origin in 37 of these cases, arterial in three and due to a combination of arterial and venous problems in six. Thirty-five of the flaps were successfully salvaged. On average, the clinical manifestation of the problem occurred 25.5 hours postoperatively. However, there was a significant time difference between flaps that were salvaged successfully and those that were not: in the salvaged group the compromise was identified 17.5 hours postsurgery compared with 51 hours for the unsuccessful group. The timing of the return to theatre following the identification of the compromise was a significant factor in the success rate: 71 minutes for those salvaged and 103 minutes for those not salvaged. It is recommended that flaps are monitored hourly for the first 72 postoperative hours and observations recorded on a chart.

Aged↗
PubMed2000

Effect of aging on bladder function and the response to outlet obstruction in female rats.

Bladder dysfunction in the aging population is a significant problem. However the concomitant presence of other diseases in many patients can make it difficult to distinguish between changes in bladder function and other influences. The present study was designed to study, in aging rats, bladder function and the effect of partial bladder outlet obstruction (BOO) on bladder function. Cystometrics were performed in awake, female Fischer 344 rats of four age groups (6, 12, 18 and 24 months) following subcutaneous implantation of a mediport catheter. Cystometric evaluations were carried out in control rats or those subject to three weeks of BOO. Bladder compliance significantly decreased with aging, which reflected an increase in threshold pressure without changes in bladder capacity. Partial BOO caused development of severe bladder instability. Following BOO, bladder capacity and compliance were significantly increased in all age groups. Threshold pressure was lower in obstructed animals, except for 6-month rats. Younger animals were able to generate a higher contraction pressure to compensate for the BOO, whereas older animals did not. Using an awake model of cystometric measurement, we have demonstrated that aging, by itself can affect bladder function. Furthermore, aged animals respond differently to BOO than younger animals. These results demonstrate that both aging and disease can contribute to bladder dysfunction, and suggest that treatment of bladder dysfunction may require a combination of therapies targeted to multiple etiologies.

Aging↗
PubMed2000

Ureteroscopic biopsy of upper tract urothelial carcinoma: improved diagnostic accuracy and histopathological considerations using a multi-biopsy approach.

PURPOSE: We assessed the diagnostic accuracy of a ureteroscopic multi-biopsy approach to upper tract urothelial carcinoma compared with subsequently resected surgical specimens. MATERIALS AND METHODS: From 1990 to 1998, 45 upper tract lesions were ureteroscopically evaluated and biopsied with 3Fr cup forceps and/or an 11.5Fr resectoscope before nephroureterectomy or ureterectomy. A definitive diagnosis of urothelial carcinoma was made by biopsy in 40 lesions (89%). Each tumor was histopathologically graded but only staged if the lamina propria were uninvolved (Ta), and if the lamina propria were invaded by tumor (T1+). RESULTS: Of the 40 urothelial tumors 16 (40%) were in the renal pelvis, and 8 (20%) in the proximal and 16 (40%) in the distal ureter. Of the lesions 95% were papillary and 65% were grade 2. Ureteroscopic biopsy grade matched surgical pathological grade in 31 of the 40 cases (78%), and was less than surgical pathological grade in the remainder. Lamina propria was detected in 27 of the 40 biopsies, including 21 of the 34 cup (62%) and all 6 resection loop (100%) biopsies. Ureteroscopic biopsy staging in 27 cases revealed Ta and T1+ disease in 22 and 5, respectively. In the 5 cases in which ureteroscopic biopsy stage was T1+ surgical pathological stage was also pT1+ (range pT1 to pT3). Tumors were pathologically up staged to pT1+ (range pT1 to pT3) in 10 of the 22 cases (45%) in which ureteroscopic biopsy stage was Ta. Tumor location did not affect diagnostic accuracy. CONCLUSIONS: This multi-biopsy ureteroscopic approach provided the tissue diagnosis of urothelial carcinoma in 89% of cases and predicted exact histopathological grade in 78%. Although it is not accurate as a staging modality, multi-biopsy ureteroscopy may assess lamina propria invasion in two-thirds of cases.

Aged↗
PubMed2000

Interstitial fibrosis of unilateral ureteral obstruction is exacerbated in kidneys of mice lacking the gene for inducible nitric oxide synthase.

Unilateral ureteral obstruction (UUO) is characterized by decreases in renal function and increases in interstitial fibrosis. Previous studies have indicated that pharmacologic manipulations that increase nitric oxide (NO) are beneficial to the obstructed kidneys. NO is produced from arginine by nitric oxide synthase (NOS), an enzyme that exists in both constitutive and inducible (iNOS) forms. To determine the role of the inducible form of NOS in UUO, we used mice with a targeted deletion of iNOS (iNOS -/- mice) and compared them with wild-type (WT) mice. Kidneys were obstructed for 2 weeks in both WT and iNOS -/- mice, and were then removed and bisected. Half of the kidney was embedded in paraffin and tissue sections were examined for interstitial volume or the presence of macrophages. The remainder was flash-frozen and samples were used to measure tissue collagen (hydroxyproline) or transforming growth factor-beta (TGF-beta). This study demonstrates that both cortex and medulla of obstructed kidneys of iNOS -/- mice exhibit significantly increased interstitial volume and interstitial macrophages as compared with their WT counterparts. Furthermore tissue collagen was increased to 9.2+/-1.3 microg/mg tissue in WT obstructed kidneys, whereas in iNOS -/- kidneys, collagen was increased to 13.2+/-0.8 microg/mg tissue. The profibrotic cytokine TGF-beta was also significantly increased in obstructed kidneys of iNOS -/- mice, as compared with WT mice. No differences were noted between the unobstructed kidneys of iNOS -/- mice compared with WT mice in any of the parameters examined. These results demonstrate that targeted deletion of the iNOS results in exacerbation of fibrotic events in the obstructed kidney. These results confirm previous pharmacologic studies, and suggest that NO produced via the inducible NOS normally serves a protective function in UUO.

Animals↗
PubMed2000

Antibody to transforming growth factor-beta ameliorates tubular apoptosis in unilateral ureteral obstruction.

BACKGROUND: Unilateral ureteral obstruction (UUO) is characterized by progressive renal atrophy, renal interstitial fibrosis, an increase in renal transforming growth factor-beta (TGF-beta), and renal tubular apoptosis. The present study was undertaken to determine the effect of a monoclonal antibody to TGF-beta (1D11) in UUO. METHODS: Mechanical stretch was applied to tubular epithelial cells (NRK-52E) by a computer-assisted system. Three doses of 1D11 (either 0.5, 2, or 4 mg/rat) were administered to rats one day prior to UUO and every two days thereafter, and kidneys were harvested at day 13. Fibrosis was assessed by measuring tissue hydroxyproline and mRNA for collagen and fibronectin. Apoptosis was assessed with the terminal deoxy transferase uridine triphosphate nick end-labeling assay. TGF-beta levels were determined by bioassay. Western blot and immunostaining were used to identify proliferating cell nuclear antigen (PCNA), p53, bcl-2, and inducible nitric oxide synthase (iNOS). RESULTS: Stretch significantly induced apoptosis in NRK-52E cells, which was accompanied by an increased release of TGF-beta; 1D11 (10 microg/mL) totally inhibited stretch-induced apoptosis. Control obstructed kidney contained 20-fold higher TGF-beta as compared with its unobstructed kidney; 1D11 neutralized tissue TGF-beta of the obstructed kidney. Control obstructed kidney exhibited significantly more fibrosis and tubular apoptosis than its unobstructed counterpart, which was blunted by 1D11. In contrast, 1D11 significantly increased tubular proliferation. p53 immunostaining was localized to renal tubular nuclei of control obstructed kidney and was diminished by 1D11. In contrast, bcl-2 was up-regulated in the 1D11-treated obstructed kidney. Total NOS activity and iNOS activity of the obstructed kidney were increased by 1D11 treatment. CONCLUSION: The present study strongly suggests that an antibody to TGF-beta is a promising agent to prevent renal tubular fibrosis and apoptosis in UUO.

Animals↗
PubMed2000

Swallowing rehabilitation after oro-pharyngeal resection for squamous cell carcinoma.

The resection of even relatively small tumours that involve the base of tongue can lead to problems with swallowing. Free tissue transfer has improved the functional results and reduced the complications of head and neck surgery. The outcome after ablative operations depends on the site and extent of the resection, and in cases where the tongue base is involved, swallowing can be severely impaired. Aspiration in a patient with swallowing difficulties is of particular concern, however, there is a range of techniques that can be introduced during videofluoroscopy to reduce or eliminate aspiration. It is during the rehabilitation phase that procedures and techniques to improve swallowing and prevent aspiration should be incorporated. The efficacy of adaptive manoeuvres needs further evaluation, and in this study we aim to assess the effectiveness of compensatory procedures and therapy techniques (chin tuck and supraglottic swallow) in eliminating aspiration. We report on a study of the swallow function of 13 patients following surgical resection of the oropharynx including the base of tongue. Postoperative assessment by videofluoroscopy was carried out at 2 weeks, 1 month, 3 months, and 6 months according to a standard protocol. Subjects were analysed in two groups depending on the degree of resection of the tongue base resection (less than 1/4,1/4 or more).Patients' swallowing disorders were related to the extent of the resection and the consistency of the bolus. Those with involvement of a quarter of the tongue base or more generally had greater impairment, and radiotherapy tended to exacerbate these problems. Compensatory procedures and therapy techniques were effective in 50% of patients who aspirated, and tended to be more effective between the one month and 6 month follow-up in patients with smaller resections.

Aged↗
PubMed2000

Repair of the radial free flap donor site with full or partial thickness skin grafts. A prospective randomised controlled trial.

The radial forearm free flap has become the mainstay in the reconstruction of soft tissue defects following ablative resection in the oral cavity. The method of repair of the associated forearm tissue defect has been the subject of considerable debate. The options range from direct closure, to local soft tissue flaps or skin graft repair. Larger defects usually require a skin graft and we have routinely used partial thickness skin. An audit of our complication rate led to the consideration of whether a full thickness repair would reduce the morbidity. We randomly allocated successive patients to receive full or partial thickness skin graft repair of the radial donor site in a consecutive series of 68 patients over an 18-month period. Sixty-four patients completed the initial assessment period of wound healing. Thirty seven patients completed a questionnaire at one year to subjectively assess the aesthetic appearance of the forearm wound and the skin graft donor site. They were also assessed for pain at both sites. The partial thickness donor site required significantly more re-dressings. There was no significant difference between the two groups in graft take or number of re-dressings at the recipient site. There was no significant difference in patient assessment of aesthetic appearance or pain in either the forearm recipient site or the skin graft donor site. Provided that an adequate graft is taken, full thickness and partial thickness skin grafts have the same short-term and long-term outcomes in the repair of the radial free flap donor site.

Forearm↗
PubMed1999

The University of Washington head and neck cancer measure as a predictor of outcome following primary surgery for oral cancer.

BACKGROUND: The purpose of this study was to investigate the disease specific functional status of patients with oral cancer treated by primary surgery. The University of Washington head and neck cancer questionnaire (UW-QOL) was used, and outcome was compared against patient's age, sex, T category, site, surgical procedure, and adjuvant radiotherapy. METHODS: In the year 1995, consecutive patients with previously untreated squamous cell carcinoma of the oral region were recruited. Questionnaires were given at four time intervals: preoperatively and at 3, 6, and 12 months. RESULTS: Fifty patients underwent primary surgery for oral cancer between 4 January and 12 December 1995. Of 48 patients recruited, 41 (85%) had microvascular free tissue reconstruction. Patients with T category 3 or 4 tumors tended to report more severe problems than did patients with T category 1 or 2 tumors; this was especially true for increased pain (p <.001). There was a marked fall in cumulative UW-QOL scores by 3 months, with some recovery to 12 months. Of the initial 48 patients, 29 (60%) were alive and disease free at 1 year, and there were 25 completed questionnaires. The trend at 1 year was for better scores in women, T category 1 and 2, anterior oral cavity, primary closure/laser treatments, and patients not requiring adjuvant radiotherapy. CONCLUSIONS: Patients undergoing surgery for oral cancer have a profound fall in quality of life scores by 3 months, and their scores approach pretreatment levels by 12 months. Clinical parameters are useful in predicting trends in UW-QOL outcome at 1 year and are also associated with differences in individual domain scores.

Aged↗