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Biomedical subjects

E D Vaughan

Publications and source records attributed to E D Vaughan.

At least 109 records · Page 6Linked to original sources

Inflammatory mediator profile in urine and bladder wash fluid of patients with interstitial cystitis.

Interstitial cystitis is a syndrome of urinary urgency, frequency and suprapubic pain. We investigated the role of inflammatory mediators in 96 patients with histories and symptoms consistent with interstitial cystitis, and 13 controls from The New York Hospital-Cornell Medical Center, University of Washington and University of California at San Diego. Patients were classified into either group A (meets all criteria of the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases for inclusion in research studies), group B (meets all of these criteria but without glomerulations) or an "other" group. A small number of group A patients had detectable interleukin-6 in the urine. Urinary concentrations of tumor necrosis factor, prostaglandins E2, D2 and F2 alpha, and thromboxane B2 were not different among either patient groups or controls. Urine specimens contained inhibitors of the bioactivity of interleukin-6 and tumor necrosis factors but no differences between patients or controls were found. No factors chemotactic for human neutrophils were detected in a small patient sample. Bladder wash fluid concentrations of prostaglandins E2, D2 and F2 alpha, and thromboxane were much lower than urinary levels. Bladder wash fluid interleukin-6 and tumor necrosis factor were not detectable. The results suggest that while a small subset of patients may have elevated levels of interleukin-6 the majority of patients do not appear to have elevated levels of inflammatory mediators in the urine or bladder wash fluid. Evaluation of patient bladder tissue may indicate changes not detectable in urine or bladder wash fluid. Alternatively, other etiologies must be considered in those patients.

Adult↗

An unusual cause of duodenal obstruction: ureteropelvic junction obstruction and the renoalimentary relationship.

Ureteropelvic junction obstruction may present with a variety of urologic and gastrointestinal complaints. The constellation of symptoms is most often attributed to shared visceral pathways. In cases of giant hydronephrosis, mechanical obstruction of the gastric outlet or duodenal sweep may play an additional role in presentation. We present an unusual case of duodenal obstruction caused by ureteropelvic junction stenosis. The anatomic and autonomic renoalimentary relationships are reviewed.

Adult↗

The radial forearm flap in orofacial reconstruction.

This review on the radial forearm flap deals with the multiple applications possible in orofacial reconstruction using this graft. The variations are illustrated and some salient points of the method are discussed.

Bone Transplantation↗

Identification, localization and functional analysis of imidazoline and alpha adrenergic receptors in canine prostate.

In nonsurgical management of benign prostatic hyperplasia, drugs which interfere with prostate contraction mediated through the alpha-1 adrenergic receptor are used. Clonidine acts at alpha adrenergic and I1-imidazoline receptors. In the present study, we found the Kd for [3H]clonidine binding to I1 sites in canine prostate to be 4 +/- 1 nM; the Bmax was 18 +/- 2 fmol/mg of protein. Inhibition of binding by imidazolines and by brain extracts containing putative endogenous ligand confirmed the identity of these sites as I1-imidazoline. Autoradiographic studies showed localization of both I1 and alpha-2 sites to the glandular epithelium. We sought to determine whether in vivo activation of the I1-imidazoline sites by clonidine mediates its contractile action in canine prostate. Dose-response curves were generated for para-aminoclonidine in the presence of vehicle alone, yohimbine (alpha-2 antagonist), idazoxan (alpha-2/I1/I2 antagonist) and prazosin (alpha-1 antagonist). Prazosin was the most effective antagonist. Yohimbine was less effective and did not effectively discriminate between para-aminoclonidine and phenylephrine, an alpha-1-selective agonist. Idazoxan antagonized para-aminoclonidine, but by not more than 50% at any dose. These results suggest that clonidine is active primarily at alpha-1 receptors on prostate smooth muscle in vivo. Thus the function of the I1 and alpha-2 receptors in the prostate remains to be determined; however, they may be involved in epithelial cell function.

Animals↗

Pathological findings in clinically false-negative and false-positive neck dissections for oral carcinoma.

A series of 86 patients presenting with oral cancer underwent neck dissection (114 sides of neck), after preoperative staging by palpation under general anaesthesia and CT imaging. Detailed histopathological assessment of the surgical neck dissection specimens showed the incidence of clinically false-negative and false-positive assessments was 27% and 40%, respectively. Extranodal spread of metastatic carcinoma was present in 16% of clinically negative necks. The pathological findings provided plausible explanations for the clinical misdiagnosis in all 19 of the false-positive necks and in 13 of the 18 false-negative necks, where micrometastases or metastasis to nodes measuring less than 1.7 cm accounted for five and seven misdiagnosed cases, respectively. We conclude that the most stringent clinical protocols, even when supplemented by CT scanning, cannot be expected to achieve 100% accuracy. Detailed histopathological assessment provides the most reliable, currently available method of diagnosing cervical metastatic disease.

Adult↗

Use of tissue expanders in final reconstruction of infrapubic midline scar, mons pubis, and vulva after bladder exstrophy repair.

Two patients following bladder exstrophy repair presented for final cosmetic reconstruction with the characteristic lower abdominal midline scar, bisected mons pubis, and laterally displaced labia majora. Tissue expanders were used to obtain additional skin and subcutaneous tissue. After adequate serial expansion, the expanders were removed, scar tissue excised, and primary approximation of healthy tissues performed. A tension-free closure and esthetically pleasing midline incision, mons pubis, and vulva were obtained.

Adolescent↗

Facial nerve reconstruction following ablative parotid surgery.

Sacrifice of the facial nerve during surgery for parotid malignancy is rarely necessary, but the sequelae of facial nerve paralysis necessitates some form of facial re-animation. The technique which achieves the best results is that of immediate nerve grafting. This paper records our experience with 14 cases of extra temporal reconstruction of the facial nerve, utilizing the cutaneous branch of the radial nerve as an autograft.

Adolescent↗

Parathyroid carcinoma presenting with a brown tumour of the mandible in a young man.

A 27-year-old man presented to his dentist with a swelling in his lower jaw. Histology revealed this to be a brown tumour associated with primary hyperparathyroidism and severe but asymptomatic hypercalcaemia. A large parathyroid adenoma was removed and the serum calcium fell to normal. Hypercalcaemia recurred and re-exploration of the neck revealed parathyroid metastases in cervical lymph nodes. A modified radical neck dissection was performed and he has remained normocalcaemic on Vitamin D analogues for 2 years. Bone disease of the mandible is a very rare presentation of primary hyperparathyroidism. The diagnosis of parathyroid malignancy is often difficult histologically, and the optimum treatment is uncertain.

Adenocarcinoma↗

Histological and bacteriological findings in long-term ileocystoplasty and colocystoplasty in the rat.

The long-term effects of bladder reconstruction using bowel were studied in rats. Bladder surgery consisted of cystotomy and closure, ileo- or colocystoplasty, or placement of a reverse serosal (Thal) patch of ileum. At least one-third of all groups received prophylactic cefaclor, postoperatively. Monthly urine cultures were obtained, and survivors were sacrificed at 1 year. Antimicrobial therapy markedly reduced the incidence of chronic colonization after cystoplasty. However, the majority of rats in the Thal patch group remained colonized because of acquired vesicoileal fistulae. Vesical stones were often present in this group and were also seen in 6 of 43 (14%) and 3 of 33 (9%) in the ileocystoplasty and colocystoplasty groups, respectively. Transitional cell papillomas and/or hyperplasia was seen at 20 of 42 (48%) uroileal and 20 of 31 (64%) urocolonic anastomoses (p = .15). Hyperplastic lesions could not be correlated with bacteriuria. Focal nonpapillary transitional cell carcinoma was seen once in the colocystoplasty group, and low grade papillary transitional cell tumors were noted once in each of the cystostomy and ileocystoplasty groups and twice in Thal patch rats with ileovesical fistulae. These findings suggest that the rat uroenteric anastomosis is susceptible to proliferative change which is rarely malignant in nature and occurs in the presence or absence of bacteriuria.

Animals↗

Medical management of benign prostatic hyperplasia: a canine model comparing the in vivo efficacy of alpha-1 adrenergic antagonists in the prostate.

Medical management of benign prostatic hyperplasia (BPH) is an alternative to surgical treatment of this disease. A major target for pharmacologic therapy is the alpha-1 adrenergic receptor, since activation of this receptor by endogenous catecholamines is thought to contribute to outlet obstruction. In the present study, we compared the potency of various alpha-1 adrenergic antagonists against epinephrine-induced contraction of the canine prostate. The drugs tested were dibenzyline, prazosin, terazosin and YM617. The rank order of potency, comparing inhibitory constants (Ki's), was found to be YM617 >> prazosin > terazosin > dibenzyline. This study is the first to compare all of these drugs directly in the prostate in vivo. The rank order of potency of the drugs is similar to the rank order of potency at other alpha-1 receptors. These results demonstrate that 1) our model is useful in confirming activity of drugs at the alpha-1 receptor and 2) the prostate alpha-1 receptor is similar to other alpha-1 receptors. Whether activity at the alpha-1 adrenergic receptor is a sufficient determinant of clinical efficacy of these drugs remains to be determined.

Adrenergic alpha-Antagonists↗

Studies of the hormonal control of postnatal testicular descent in the rat.

Dihydrotestosterone is believed to control the transinguinal phase of testicular descent based on hormonal manipulation studies performed in postnatal rats. In the present study, these hormonal manipulation experiments were repeated, and the results were compared with those obtained using the antiandrogens flutamide and cyproterone acetate. 17 beta-estradiol completely blocked testicular descent, but testosterone and dihydrotestosterone were equally effective in reversing this inhibition. Neither flutamide nor cyproterone acetate prevented testicular descent in postnatal rats despite marked peripheral antiandrogenic action. Further analysis of the data revealed a correlation between testicular size and descent. Androgen receptor blockade did not produce a marked reduction in testicular size and consequently did not prevent testicular descent, whereas estradiol alone caused marked testicular atrophy and testicular maldescent. Reduction of the estradiol dosage or concomitant administration of androgens or human chorionic gonadotropin resulted in both increased testicular size and degree of descent. These data suggest that growth of the neonatal rat testis may contribute to its passage into the scrotum.

Androgen Antagonists↗

Toradol, an NSAID used for renal colic, decreases renal perfusion and ureteral pressure in a canine model of unilateral ureteral obstruction.

Toradol is a new parenteral, nonsteroidal anti-inflammatory drug which is efficacious in treating renal coli. In the present experiments, Toradol was administered to both control dogs and dogs with unilateral ureteral obstruction. In control dogs, Toradol had no effect on RBF or GFR, despite inhibition of renal prostaglandin synthesis (measured as urinary prostaglandin release). In contrast, RBF fell acutely by 35% (p < 0.001) within 15 minutes of Toradol administration in the setting of ureteral obstruction; contralateral RBF was unaffected. Ipsilateral ureteral pressure also fell. Changes in RBF and ureteral pressure, together with the known effects of NSAIDs on pain pathways, may contribute to the pain relief observed clinically with Toradol. However, the abrupt changes in renal hemodynamics brought on by Toradol to the obstructed kidney may compromise renal reserve, and Toradol should be used cautiously in treating renal colic.

Animals↗

The unique steroidogenesis of the aldosteronoma in the differential diagnosis of primary aldosteronism.

18-Hydroxycortisol and 18-oxocortisol have been isolated from the urine of patients with aldosterone producing adrenocortical adenomas, but not from those with idiopathic hyperaldosteronism associated with bilateral adrenal hyperplasia. These C-18 oxygenated cortisols are biosynthesized by the substitution of cortisol for the normal substrate, corticosterone, in the terminal oxidase system required for the biosynthesis of 18-hydroxycorticosterone and aldosterone. To make use of this biochemical difference between the two groups in the preoperative diagnosis of primary aldosteronism, we have developed and utilized a specific primary standard analytical method, stable isotope dilution mass fragmentography, for quantifying 18-hydroxycortisol and the tetrahydro metabolite of 18-oxocortisol in 24-h urine samples. The normal range by this technique of 4.6 +/- 1.8 micrograms/day tetrahydro 18-oxocortisol and 43 +/- 23 micrograms/day 18-hydroxycortisol in urine was lower and narrower than previous estimates using other methods. Excretion of the 18-oxocortisol metabolite ranged from 2-12 micrograms/day in bilateral hyperplasia and 17-1203 micrograms/day in typical adenomas. 18-Hydroxycortisol excretion similarly separated bilateral hyperplasia (23-59 micrograms/day) from typical adenomas (60-2750 micrograms/day). The cortisol C-18 oxidation pathway describes a unique steroidogenic mechanism in the aldosteronoma not present in idiopathic aldosteronism due to bilateral adrenal hyperplasia and as such provides a basis for the biochemical classification of primary aldosteronism and the differentiation of these two groups. This unique biochemistry was also observed in unilateral hyperplasia but not in the renin-dependent aldosteronoma.

Adenoma↗

Accuracy of computed tomography in predicting adrenal tumor size.

We undertook a multi-institutional, retrospective study of 51 patients with adrenal tumors (pheochromocytomas, functioning and nonfunctioning cortical adenomas, cysts and carcinomas). All patients had computed tomography (CT) with a maximum of 5 millimeter cuts the week before undergoing complete adrenalectomy. Pathologists were asked to measure the tumor to the nearest 0.1 centimeter. Tumor size obtained from pathologic reports (actual size) and CT reports (estimated size) were compared. Adrenal tumors were divided into two groups on the basis of size--tumors with actual size of 6 centimeters or greater and tumors with actual size of less than 6 centimeters. Statistical analysis was performed with Newman-Keuls analysis of variance. After controlling for tumor type and for the institution at which the measurement was made, we found that CT consistently underestimated adrenal tumor size in both tumor groups. Moreover, the average, underestimated difference for tumors 6 centimeters or greater was 32 percent, but 47 percent for tumors less than 6 centimeters (p = 0.060). CT seemed to underestimate the size of small adrenal tumors more than large tumors. Because the decision to operate on solid, nonfunctioning adrenal tumors is based on tumor size and because CT is currently the standard technique used to estimate size, our findings need to be considered before undertaking surgical treatment.

Adenoma↗