Biomedical subjects
Publications and source records attributed to E D Vaughan.
This paper describes the application of endosseous titanium implants that have been inserted into the vascularized bone of the radial forearm composite flap, used for mandibular reconstruction. The technique described allows full orofacial rehabilitation to be achieved, following ablative surgery and adjuvant radiotherapy.
50 patients who underwent major surgery for head and neck cancer and reconstructed with radial forearm microvascular free flaps, were assessed with regard to social adaptation, appearance and in particular mouth function. The results were compared with a similar group of patients who underwent reconstruction with either primary repair or pedicled flaps.
Studies were performed to compare the effects of 5 alpha-reductase inhibition and antiandrogen receptor blockade on differentiation of male internal and external genital structures and prostate in the rat. Dose-response studies were performed on male rats treated in utero during the period of sexual differentiation with either the potent 5 alpha-reductase inhibitor finasteride or the antiandrogen flutamide. The treated animals were raised to adulthood and killed, and genital structures were evaluated. Treatment with the 5 alpha-reductase inhibitor finasteride at a dose of 25 mg/kg.day resulted in significant feminization of the external genitalia. There was no further feminization of the genitalia at doses up to 300 mg/kg.day. Wolffian ductal differentiation occurred at all doses evaluated. Seminal vesicle weight, however, significantly decreased at 25 mg/kg.day, but without a further decrease at higher doses of the 5 alpha-reductase inhibitor. Vas deferens and epididymal weights were unchanged at all doses evaluated. There was a significant decrease in prostate size at 25 and 50 mg/kg.day, with no further decrease at higher doses. In flutamide-treated animals, complete feminization of the genitalia occurred at 24 mg/kg.day in all animals. At 18 mg/kg.day, Wolffian ductal differentiation occurred, but seminal vesicle weight was decreased. At dosages of 100, 200, and 300 mg/kg.day flutamide, the vas deferens was absent unilaterally or bilaterally, with small remnants of epididymal head and tail present. At dosages of 24 mg/kg.day and above, the prostate was absent. Studies with the 5 alpha-reductase inhibitor finasteride demonstrate the dependency of prostate and male external genital differentiation on dihydrotestosterone (DHT). However, unlike androgen receptor blockade with flutamide, finasteride did not totally abolish prostate differentiation or completely feminize the external genitalia, despite increasingly higher doses. Since there is no evidence of multiple 5 alpha-reductase isoenzymes to date in the rat, these results suggest that testosterone (T) can compensate for DHT to some degree at the level of the androgen receptor. Wolffian differentiation, however, was not affected by inhibition of DHT, demonstrating its T dependency, but seminal vesicle growth was impaired. Thus, inhibition of 5 alpha-reductase activity limits seminal growth potential in adulthood. Studies with the antiandrogen flutamide show that at doses significantly above that required to completely block prostate differentiation and cause genital feminization, Wolffian ductal differentiation is significantly impaired. Thus, higher doses of flutamide are needed to block the paracrine effect of T on the Wolffian ducts.
Male pseudohermaphrodites with 5 alpha-reductase deficiency have ambiguous genitalia and nonpalpable prostates on rectal examination, suggesting the dihydrotestosterone dependency of these structures. To clearly delineate the status of the prostate, male pseudohermaphrodites with 5 alpha-reductase deficiency had transrectal sonography of the prostate performed, and the results were compared to that of age-matched male controls. In six male pseudohermaphrodites, magnetic resonance imaging studies of the prostate were also performed. Heterozygote fathers also had transrectal sonography of the prostate performed and the results compared to age-matched controls. The prostates of the male pseudohermaphrodites appeared as platelike soft tissue structures posterior to the urethra on both prostatic ultrasound and magnetic resonance imaging. Prostatic volume, as determined on prostatic ultrasound by two different methods, was significantly smaller (approximately one-tenth) than the volume of age-matched controls. Transurethral ultrasound guided biopsy of the prostate in two affected subjects revealed stromal tissue. These results correlate with undetectable prostate-specific antigen in affected subjects, suggesting atrophic epithelium or lack of epithelial differentiation. This study demonstrates the dihydrotestosterone dependence of the prostate for normal differentiation and growth. The presence of some prostatic tissue in the male pseudohermaphrodites may be due to the fact that there is a decrease and not an absence of 5 alpha-reductase activity, and/or that the increased level of testosterone in subjects with this condition partially compensates for the decreased level of dihydrotestosterone. There was no difference, however, in prostate size between heterozygous fathers and age-matched control males. The heterozygote fathers had dihydrotestosterone production sufficient for normal prostate growth and development.
We have previously demonstrated that the Ha-ras and the Ki-ras oncogenes are overexpressed in squamous cell carcinoma of the head and neck. In this study we have used the Y13-259 monoclonal antibody to p21 ras to determine if expression of the ras oncoprotein correlates with any of the clinico-pathological parameters or with survival in 69 patients with squamous cell carcinoma of the head and neck. Forty-four specimens were from patients with previously untreated tumours and 25 from patients with previously treated disease. We have found a correlation between low levels of ras expression and the disease-free survival period in patients with previously untreated tumours. Three per cent of the patients with ras negative staining were alive 60 months after diagnosis, whereas 54 per cent of the patients with positive staining were still alive after the same time period (P less than 0.05).
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This paper describes the evolution and refinement, over a four-year period, of a simple technique for shaping and stabilising the bony component of a composite radial forearm free flap to reconstruct the mandible following segmental resection for neoplastic disease. The results of reconstruction in 30 consecutive patients are reported. The current method of adapting and stabilising the radial bony strut using a specially designed 32 hole osteosynthetic miniplate is described.
To investigate the calcium dependence of salt-induced hypertension we concurrently measured blood pressure and serum ionized calcium in conscious normotensive female dogs undergoing five infusions: 1) sodium chloride (0.9%) 2) calcium chloride (10 mg/kg), 3) combined sodium chloride and calcium chloride, 4) nicardipine (1 micrograms/kg/min), and 5) combined sodium chloride and calcium chloride in the presence of nicardipine. While saline and calcium chloride infusions individually did not affect blood pressure, saline combined with calcium chloride significantly and consistently raised mean arterial pressure (MAP) (delta MAP = 7 +/- 2 mm Hg, P less than .001 v baseline). Serum ionized calcium (Caio) levels increased within the normal range with the infusion of calcium alone (1.32 +/- 0.03 to 1.48 +/- 0.01 mmol/L, P less than .005). Extracellular Caio rose less with the combined NaCl-CaCl2 infusion (delta Caio 0.10 +/- 0.01 v 0.16 +/- 0.02 mmol/L, P less than .02). The difference in calcium elevations could not be attributed to volume expansion alone, since saline infusion itself did not affect serum ionized calcium (1.32 +/- 0.3 to 1.31 +/- 0.01 mmol/L, P = NS). Furthermore, nicardipine prevented the pressor effect of the combined saline-calcium infusion. (delta MAP = -2 +/- 3 v 7 +/- 2 mm Hg, P less than .001), and restored the rise in extracellular Caio to that seen with the nonpressor calcium infusion (delta Caio 0.15 +/- 0.01 mmol/L v 0.16 +/- 0.02 mmol/L, P = NS). Altogether, these data demonstrate that the rise in blood pressure and ionized calcium following an acute infusion of sodium and calcium chloride are interdependent.(ABSTRACT TRUNCATED AT 250 WORDS)
The endocrine control of descent of the testis in mammalian species is poorly understood. The androgen dependency of testicular descent was studied in the rat using an antiandrogen (flutamide) and an inhibitor of the enzyme 5 alpha-reductase (finasteride). Androgen receptor blockade inhibited testicular descent more effectively than inhibition of 5 alpha-reductase activity. Moreover, its inhibitory effect was limited to the outgrowth phase of the gubernaculum testis, particularly the earliest stages of outgrowth. Gubernacular size was also significantly reduced in fetuses exposed to flutamide during the outgrowth period. In contrast, androgen receptor blockade or 5 alpha-reductase inhibition applied after the initiation of gubernacular outgrowth or during the regression phase did not affect testicular descent. Successful inhibition of the development of epididymis and vas by prenatal flutamide did not correlate with ipsilateral testicular maldescent, suggesting that an intact epididymis is not required for descent of the testis. Plasma androgen assays confirmed significant inhibition of dihydrotestosterone formation in finasteride-treated rats. These data suggest that androgens, primarily testosterone, are required during the early phases of gubernacular outgrowth for subsequent successful completion of testicular descent.
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Medical management of clinical BPH is a reality. The only effective nonsurgical treatment now recommended is aimed at relieving the dynamic component of clinical BPH. Pharmacologic treatment using alpha-adrenoceptor antagonists may be used appropriately to manage patients with prostatism who are poor surgical risks but who could benefit from reduced sympathetic tone. In addition, alpha blockers are used to relieve acute retention, and to prevent retention when increased sympathetic discharge is expected. Thus far, nonsurgical therapy aimed at reducing the mechanical obstruction associated with BPH by prostatic size reduction has failed to produce consistent objective improvement. However, several drugs are now being investigated and may be effective for reducing prostatic size in patients with BPH. Clinical trials are complicated by a number of factors, especially very variable symptoms. Moreover, reduction in prostatic size induced by drugs is not permanent and regrowth occurs with drug withdrawal, necessitating chronic treatment. Ideally, future research should be aimed at the prevention of BPH at an early age. However, this presupposes a better understanding of the pathogenesis of BPH. BPH may not be a single, variable disease but a family of diseases with a number of predictable clinical courses. In the future, we should pay particular attention to histologic variability, to see if in fact different pathologic forms of BPH follow different clinical patterns. If urologists are to keep their predominant position in managing the patient with BPH, they will have to keep informed of medical treatment trials and of potential alternative treatment strategies to prostatectomy.
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Platelet activating factor (PAF) and thromboxane A2 (TxA2) are two vasoactive mediators which can decrease renal blood flow. Both are synthesized by various intrarenal cell types or by macrophages which may infiltrate the kidney during unilateral ureteral obstruction (UUO). In several experimental systems, PAF receptor activation is accompanied by TxA2 release; pharmacological modification of TxA2 synthesis or receptor activation modulates the response to PAF. The involvement of PAF in UUO has not been studied previously, and the role of TxA2 has not been clearly defined by previous investigations. The hemodynamic response to acute UUO is characterized by decreases in renal blood flow (RBF) and glomerular filtration rate and an acute increase in ureteral pressure. In the present experiments, the involvement of either PAF or TxA2 in the acute response to UUO was studied by determining if blockade of either the TxA2 or PAF receptor would affect the renal hemodynamic response to UUO. In addition, the effect of blockade of the TxA2 receptor on the renal response to PAF was determined. Our results indicate that only a small portion of the renal response to PAF is mediated by TxA2, and that neither PAF nor TxA2 can be implicated in the acute hemodynamic response to UUO. TxA2 or PAF involvement in the chronic response to UUO still remains to be determined.
We studied penile blood flow changes with duplex ultrasound scanning in 8 potent young men during the flaccid state and during the erect state induced by visual sexual stimulation. Measured parameters obtained from the cavernous arteries were arterial diameter, peak blood flow velocity and blood flow acceleration. The mean arterial diameter change was 72% associated with average blood flow velocity and acceleration changes of approximately 200%. Actual values for blood flow velocity and acceleration were considerably higher when compared to papaverine-induced values measured in psychogenically impotent men. Visual sexually stimulated penile arterial changes are not analogous to papaverine-induced arterial changes and these differences raise questions about the appropriateness of using psychogenically impotent men as controls for measurement of penile arterial function with duplex scanning.
Current knowledge fails to support the notion that adaptive hyperfiltration of the remnant kidney after donor nephrectomy is deleterious. Rather than being maladaptive, hyperfiltration appropriately compensates for the loss of functional renal mass. Accordingly, most kidney donors can be expected to maintain a stable level of renal function without proteinuria or hypertension. Essential to this is proper selection of donors for nephrectomy and exclusion of high risk potential donors, bearing in mind the fact that apparently healthy, asymptomatic relatives of end stage renal disease patients are prone to the same disease processes that inflict the general population and have a higher risk of underlying renal disease.
In an effort to understand the physiologic processes which contribute to, or hinder the transport of stones through the ureter, we examined the intraluminal ureteral pressures and peristaltic activity above and below the acutely obstructed site. Because of patient differences, variability in stone size, shape and composition, an in vivo animal model was developed to study acute ureteral obstruction. Five adult mongrel dogs were anesthetized. A midline celiotomy was made and an open-ended ureteral catheter was inserted through a distal ureterotomy and advanced up the ureter. An angiographic balloon catheter was inserted through a small nephrotomy and directed down the ureter. The experiment was divided into phases: control, ureteral obstruction (balloon inflation) and release of obstruction (balloon deflation). Compared to control values, peristaltic rate above the obstruction increased significantly (p less than 0.05), as well as baseline, peak, and delta (peak minus baseline) pressures. In contrast, the peristaltic rate below the obstructed site remained approximately the same as its control, despite the significant decreases in baseline, peak, and delta (p less than 0.05) pressures. Failure of transmission of effective peristalsis across the obstructed site may hinder stone passage; however, this remains to be proven. Moreover, the failure of transmission of the increased rate of peristalsis past the balloon and persistence of peristaltic activity below the site of obstruction despite absence of urine flow suggest segmental forces influence peristaltic activity.
We assessed the value of penile blood flow acceleration as a parameter in the evaluation of the penile arteries. Duplex sonography and pulsed Doppler analysis with papaverine were performed in 50 impotent men. Measured parameters included cavernous artery diameters before and after papaverine, post-papaverine peak blood flow velocity and blood flow acceleration. Erections were graded subjectively on a scale of 1 to 4, with 4 being a full erection. Penile blood flow acceleration appeared to correlate with vessel dilatability and poor erectile response, and was subjectively more discriminating than peak blood flow velocity. This parameter provides additional measurable data about arterial function and should be obtained in addition to the other 2 parameters.