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Biomedical subjects

E D Vaughan

Publications and source records attributed to E D Vaughan.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

Altered bladder function in transgenic mice expressing rat elastin.

The elasticity of tissues subjected to repeated deformation is provided by the presence of elastic fibers in the extracellular matrix (ECM). The most abundant component of elastic fibers is elastin, whose soluble precursor is tropoelastin. To establish the role elastin plays in the bladder, this study describes the biosynthetic, histologic, and physiologic consequences of expression of an isoform of rat tropoelastin in transgenic mouse bladder. The polymerase chain reaction (PCR) was used to determine expression of a rat tropoelastin minigene in transgenic mice. Histochemical methods were used to demonstrate changes in elastic fibers in frozen sections of bladder. Cystometric analysis was carried out in transgenic and non-transgenic mice, prior to and after 3 weeks of partial outlet obstruction. The PCR assay demonstrated that bladder tissue of transgenic mice expressed rat tropoelastin mRNA, whereas non-transgenes did not. Increased deposition of elastic fibers was demonstrated with the Verhoeff-van Gieson stain. Bladders of transgenic animals were more compliant than bladders of their non-transgenic littermates. Partial outlet obstruction resulted in increased bladder volume and more compliant bladders in non-transgenic mice. In contrast, the bladder volume and compliance in transgenes was almost unchanged by obstruction. This study demonstrates that normal elastic fiber assembly is prerequisite for the compliant properties of the bladder wall. Moreover, the response of the bladder to obstruction is critically influenced by elastin synthesis.

Animals↗

Current concepts in imaging of adrenal masses.

Adrenal masses are a common entity. With the advent of improved cross-sectional imaging techniques the detection and characterization of adrenal masses has improved dramatically. We review the imaging features of benign and malignant adrenal masses and other entities that may cause mass-like enlargement of the adrenal glands.

Adrenal Gland Diseases↗

Diagnosis and treatment of primary aldosteronism.

Disorders of the adrenal cortex and medulla are often associated with hypertension, which can be cured surgically in many cases or may require specific and timely medical treatments. Therefore, knowledge of adrenal physiology, biochemistry, and molecular biology is essential such that an appropriate diagnostic evaluation can be conducted efficiently. The most common hypertensive disorder of the adrenal cortex is primary aldosteronism. Aldosterone-producing adenoma is the most common form of primary aldosteronism and is most likely to be cured by unilateral adrenalectomy when aldosterone production is highly autonomous from renin-angiotensin, lateralizes to one adrenal gland, and is associated with overproduction of 18-hydroxycortiocosterone and C18-methyloxygenated metabolites of cortisol. Variants of adrenal hyperplasia that share these characteristics can also be cured by unilateral adrenalectomy.

Diagnosis, Differential↗

Surgical options for open adrenalectomy.

We are fortunate that our ability to diagnose the specific adrenal entities that mandate a surgical approach is extremely accurate. The combination of analytical methodology to measure the appropriate adrenocortical and medullary hormone production and the radiology techniques for localization are superb. The management of these adrenal disorders with precise surgical precision following localization is highly successful, resulting in a reversal of both metabolic abnormalities and the hypertension that often accompanies these diseases. Indeed, this has become a true success story with the evolution of these different techniques over the past 50 years.

Adrenal Gland Diseases↗

Lateral transperitoneal laparoscopic adrenalectomy.

Several laparoscopic approaches to the adrenal gland have been described. The lateral transperitoneal approach has several distinct advantages when contrasted with other techniques for laparoscopic adrenalectomy (LA). We present our technique and results obtained in 50 consecutive transperitoneal LAs. We review 50 consecutive laparoscopic adrenalectomies (28 female, 19 male) performed from 1993 to 1998 S.J. Shichman or R.E. Sosa was either the primary surgeon or the first assistant for all cases. The lateral transperitoneal approach described below was used in all cases. Indications for adrenalectomy included Cushing's syndrome (13), aldosteronoma (15), pheochromocytoma (7), nonfunctioning adenoma (11), hyperplasia (2), and 1 case each of Carney's syndrome and metastasis to the adrenal gland. We performed 5 bilateral, 22 left, and 18 right laparoscopic adrenalectomies. The average time needed for bilateral adrenalectomy was 503 min (range 298-690 min); for left adrenalectomy, 227 min (range 121-337 min); and for right LA, 210 min (range 135-355 min). We demonstrated a yearly trend in lower operative times. The largest adrenal gland removed measured 13.8 x 6.7 x 3.5 cm. Intraoperative blood loss was low. Only one patient received a blood transfusion. Conversion to open adrenalectomy was not required. Postoperative analgesic requirements were low. The average length of stay was 3.8 days for bilateral LA and 3 days for unilateral LA. Complications occurred in 5 patients (2 wound infections, 2 hematomas, and 1 pleural effusion). There was no mortality. Lateral transperitoneal adrenalectomy is a safe and efficient technique for the removal of functional and nonfunctional adrenal masses. This technique is associated with low morbidity, a minimal postoperative analgesic requirement, and a short hospital stay and, in our opinion, is more versatile than the retroperitoneal approach.

Adrenal Gland Neoplasms↗

Acute and chronic interstitial cryotherapy of the adrenal as a treatment modality.

Adrenalectomy is indicated for patients with large adrenal lesions or functional tumors. Cryoablation is currently used as a surgical alternative for the treatment of prostate, lung, brain, pharynx, and liver tumors. The purpose of this study was to determine if cryosurgery could be delivered to small areas in the adrenal gland in a controllable and reproducible manner such that tissue could heal in a nonpathologic way. A total of 14 female mongrel dogs underwent acute (n = 8) or chronic (4 weeks, n = 6) cryoablation using the Cryounit. In the acute study using an open transabdominal approach a 2-mm cryoprobe was placed interstitially into the adrenal tissue, whereas 0.032-inch thermocouples were cannulated into the ipsilateral adrenal artery and vein. Adrenal parenchymal temperature changes were measured using 0.032-inch thermocouples placed at 0.4- and 0.8-cm intervals from the cryoprobe. In the chronic study, cryoablation was achieved by transperitoneal laparoscopic access using a standard laparoscopic technique. Interstitial cryoprobe temperatures decreased from 33.1 +/- 1.9 degrees C to -148 +/- 1.2 degrees C following 15 min of freezing in the acute study. Cryoablation of adrenal tissue achieved temperatures of -41.8 +/- 5.7 degrees C and -21.8 +/- 1 degrees C at distances of 0.4 and 0.8 cm from the cryoprobe, respectively. There was no significant change in adrenazl artery or vein temperatures during cryoablation. Histologically there is a clear demarcation between viable and nonviable tissue characterized by areas of multifocal hemorrhage and pyknosis. After 4 weeks of healing a well-defined line of necrotic and viable tissue is visible. Cryoablation of the adrenal can be delivered in an effective, controllable, and reproducible manner. This controllable energy form may provide a new treatment modality for tissue destruction where adrenal gland preservation is necessary and can be performed by the laparoscopic approach. Understanding the effect of adrenal cryoablation may allow us to treat selected patients with small tumors where organ preservation is necessary.

Adrenal Gland Diseases↗

Magnetic resonance imaging in the assessment of cervical nodal metastasis in oral squamous cell carcinoma.

OBJECTIVE: The accurate pre-operative assessment of cervical lymph nodes is a well recognized problem in the management of patients with oral squamous cell carcinoma. Imaging techniques have improved the accuracy of staging but cannot determine if nodal enlargement is due to reactive changes or malignant involvement. We assessed the diagnostic performance of magnetic resonance imaging (MRI) in detecting metastatic disease within the neck in oral cancer patients. MATERIALS AND METHODS: A retrospective study was performed on 58 patients treated for oral squamous cell carcinoma. All patients had pre-operative MR imaging including axial and coronal short tau inversion recovery (STIR) sequences and pre- and post-gadolinium axial T1 weighted sequences. Nineteen patients had bilateral neck dissections giving 77 sides of neck for study. MR images were reviewed for nodal involvement at each anatomical level within the neck and correlated with findings at histology. RESULTS: Twenty-seven of the 77 sides of neck contained histologically positive nodes (35.1%). MRI sensitivity was 66.7% and specificity 68%. There was a false-negative rate of 20.9% and false-positive rate of 47.1%. Some enlarged, histologically positive nodes were not detected by MRI. Furthermore, in five cases the only histological evidence of nodal malignancy was the presence of a micrometastasis (<3 mm tumour deposit). MRI detected two of these. CONCLUSION: MRI lacks sufficient sensitivity and specificity to replace elective neck dissection for both staging and prognostic purposes.

Adult↗

Survival and patterns of recurrence in 200 oral cancer patients treated by radical surgery and neck dissection.

The outcome of 200 patients with squamous cell carcinoma of the oral/oropharyngeal mucosa managed by primary radical surgery and simultaneous neck dissection and followed for 2.2-8.5 years is reported and related to the pathological features. Ninety-nine patients (50%) had cervical lymph node metastases including 16 (8%) with bilateral metastases. Actuarial (life tables) survival analysis showed the overall 2-year survival probability was 72%, falling to 64% at 5 years. The 5-year survival probability was 81% for patients without metastasis, 64% for patients with intranodal metastases and 21% for patients with metastases showing extracapsular spread. A total of 60 patients (30%) died of/with their cancer: 36 (18%) of local recurrence; 4 (2%) of a metachronous primary tumour; 14 (7%) of regional disease, and 6 (3%) with systemic metastases. A further 15 patients (8%) had relapsed but were clinically disease-free after additional surgery. In all, 7% of the series developed metachronous primary tumours. In addition to nodal metastasis, survival was related to the site and stage of the primary tumour, the histological grade and pattern of invasion, status of the resection margins and pathological TNM stage. For patients with lymph node metastasis, extracapsular spread was an important indicator of tumour behaviour and we recommend its use as a criterion for pathological N staging.

Adult↗

Management of the radial composite donor site: an orthopaedic opinion.

Maxillofacial and plastic surgeons have reported on the management of radial composite flap donor sites, but little reference is made to orthopaedic advice. Orthopaedic surgeons manage forearm injuries more often than other specialties and we thought that an orthopaedic consensus was long overdue. The composite radial donor site subsequently fractures in up to 43% of cases. There is no agreement on the optimal management of these difficult injuries and the patient is often referred for orthopaedic advice. Options include plaster-cast immobilization, internal fixation with either a plate or intramedullary nail, and external fixation. Bone grafting may also be required. A postal questionnaire, using two case histories including radiographs, was sent to 100 consultant orthopaedic surgeons in the UK asking how they would manage the donor site primarily and how they would manage a fracture at this site. Fifty-nine adequate replies were received. Generally, six weeks of immobilization in a plaster of Paris (POP) cast was considered sufficient for the initial management of the donor site. In the event of a fracture, internal fixation with a dynamic compression plate with or without a cancellous bone graft was the most common choice.

Bone Transplantation↗

Acute and chronic interstitial cryotherapy of the adrenal gland as a treatment modality.

BACKGROUND AND OBJECTIVES: Adrenalectomy is indicated for patients with large adrenal lesions or functional tumors. Cryoablation is currently used as a surgical alternative for the treatment of prostate, lung, brain, pharynx, and liver tumors. The purpose of this study was to determine if cryosurgery could be delivered to small areas in the adrenal gland in a controllable and reproducible manner, so that tissue could heal in a nonpathological way. MATERIALS AND METHODS: Fourteen female mongrel dogs underwent acute (N = 8) or chronic (4 weeks) (N = 6) cryoablation using the Cryounit. In the acute study, using an open transabdominal approach, a 2-mm cryoprobe was placed interstitially into the adrenal tissue, while 0.032-inch thermocouples were cannulated into the ipsilateral adrenal artery and vein. Adrenal parenchymal temperature changes were measured using thermocouples placed at 0.4- and 0.8-cm intervals from the cryoprobe. In the chronic study, cryoablation was achieved by transperitoneal laparoscopic access using standard laparoscopic technique. RESULTS: Interstitial cryoprobe temperatures decreased from 33.1 +/- 1.9 degrees C to -148 +/- 1.2 degrees C following 15 minutes of freezing in the acute study. Cryoablation of adrenal tissue achieved temperatures of -41.8 +/- 5.7 degrees C and -21.8 +/- 1 degrees C at distances of 0.4 and 0.8 cm from the cryoprobe, respectively. There were no significant changes in adrenal artery or vein temperatures during cryoablation. Histologically, there was a clear demarcation between viable and nonviable tissue, the latter being characterized by areas of multifocal hemorrhage and pyknosis. After 4 weeks of healing, there was a well-defined line between necrotic and viable tissue. CONCLUSION: Cryoablation of the adrenal gland can be obtained in an effective, controllable, and reproducible manner. This controllable energy form may provide new modality for tissue destruction where adrenal gland preservation is necessary and can be delivered by the laparoscopic approach. Understanding the effect of adrenal cryoablation may allow us to treat selected patients with small tumors in whom organ preservation is necessary.

Adrenal Glands↗

Fractional allele loss indicates distinct genetic populations in the development of squamous cell carcinoma of the head and neck (SCCHN).

Loss of heterozygosity (LOH) had been widely used to assess genetic instability in tumours and a high LOH on chromosome arms 3p, 9p and 17p has been considered to be a common event in squamous cell carcinoma of the head and neck (SCCHN). We have investigated LOH in 52 SCCHN using a range of microsatellite markers. LOH was observed in 69% of individuals on 17p using seven markers, in 64% of individuals on 3p using 17 markers and in 61% of individuals on 9p using 11 markers. Fractional allele loss (FAL) has been calculated for each tumour (FAL is the number of chromosomal arms showing LOH divided by the number of informative chromosomal arms) and a median FAL value of 0.25 was obtained in the 52 SCCHN studied. The LOH data were examined on the basis of FAL scores: low FAL (LFAL), 0.00-0.19; medium FAL (MFAL), 0.20-0.32; high FAL (HFAL), 0.33-0.88. HFAL tumours demonstrated a significantly higher LOH on chromosome arms 3p, 9p and 17p, with 94% LOH on 3p, 94% on 9p and 100% on 17p compared with LFAL tumours. Six of the 16 patients in the LFAL group were found to have no LOH on 3p, 9p or 17p and of these four had LOH at other sites, on chromosomes 2p25-p24, 5q21-22, 7pter-p22, 8q13-q22.1, 11q23.3, 13q32, 17q, 18p11.21, 18q21.31 and 19q12-q13.1. These results indicate that LFAL patients form a subset of SCCHN tumours with distinct molecular initiating events which may represent a discrete genetic population.

Alleles↗

BCL-2 and p53 expression in clinically localized prostate cancer predicts response to external beam radiotherapy.

PURPOSE: Clinicians have long been hampered by the inability to distinguish patients with localized prostate cancer who will and will not respond to radiotherapy. In a significant proportion of patients therapy fails as determined by increasing posttreatment serum prostate specific antigen (PSA). We evaluated the expression of 2 key regulators of apoptosis, bcl-2 and p53, relative to treatment outcomes in patients who received external beam radiotherapy for clinically organ confined carcinoma of the prostate. MATERIALS AND METHODS: Immunohistochemical staining for bcl-2 and p53 on pretreatment needle biopsies was performed in 54 patients who were treated with radiotherapy for localized prostate cancer. Expression was scored using strict criteria. Nadir PSA less than 1 ng./ml. after therapy was considered a successful treatment response. RESULTS: There was a predominance of stage T1c cancer (74%) with a mean Gleason score of 6.9 and an average pretreatment PSA of 25.3 ng./ml. Overall 54% of the patients did not have a nadir PSA of less than 1 ng./ml. Of the bcl-2 positive cases therapy ultimately failed in 85%. Similarly 88% of the patients with p53 positive biopsies had treatment failure and in all with bcl-2 as well as p53 expression radiotherapy failed. Expression of bcl-2 and p53 was an independent prognostic variable for treatment failure with odds ratios (95% confidence interval) of 7.3 and 10.8, respectively. CONCLUSIONS: Expression of bcl-2 and p53 was associated with treatment failure after external beam radiation therapy. These findings suggest that bcl-2 and p53 expression in pretreatment biopsies may be helpful for predicting response to definitive radiotherapy.

Adenocarcinoma↗