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E D Vaughan

Publications and source records attributed to E D Vaughan.

At least 55 records · Page 3Linked to original sources

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↗

Preperitoneal prosthetic mesh hernioplasty during radical retropubic prostatectomy.

PURPOSE: The number of radical retropubic prostatectomies performed in the United States has increased during the last decade. There are 5 to 10% of candidates for radical retropubic prostatectomy who have a detectable inguinal hernia on physical examination. Furthermore, recent data suggest that there is an increased incidence of inguinal hernia after radical retropubic prostatectomy. We evaluated the role of simultaneous inguinal hernioplasty during radical prostatectomy. MATERIALS AND METHODS: During 575 radical prostatectomy procedures from June 1991 to June 1997, 70 hernioplasties were performed in 48 patients. Retrospective chart review was performed for all men who underwent simultaneous hernia repair. Mean patient age was 60.9 years (range 43 to 73). Polypropylene or polyester fiber prostheses were used for mesh hernioplasty. All repairs were performed using a preperitoneal approach during radical retropubic prostatectomy. RESULTS: There were 35 hernioplasties performed without and 35 with mesh. Mean postoperative followup was 24 months (range 6 to 66). Of the hernias 71% were indirect and 29% were direct. No recurrence was detected after mesh hernioplasty, whereas 5 hernias (14%) recurred in the nonmesh group. In this group 2 men (4%) also had de novo hernias on the contralateral side during followup. All recurrent hernias were diagnosed within 1 year of the initial operation. No patient had wound infection, persistent neuralgia or ischemic orchitis. CONCLUSIONS: Simultaneous repair of inguinal hernias during radical retropubic prostatectomy is effective and technically feasible. There is convenient access to the preperitoneal space during radical retropubic prostatectomy and hernia repair adds only 5 to 10 minutes of operative time. Mesh repair appears to offer optimized results compared to the nonmesh technique. Despite the use of prosthetic material, no complications were attributable to its application during these genitourinary procedures.

Adult↗

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↗

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↗

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↗