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Biomedical subjects

R A Morton

Publications and source records attributed to R A Morton.

At least 19 recordsLinked to original sources

Impact of anatomical radical prostatectomy on urinary continence.

Urinary continence following an anatomical approach to radical prostatectomy was evaluated in 593 consecutive patients, 547 (92%) of whom achieved complete urinary control. Stress incontinence was present in 46 patients (8%), of whom 34 (6%) wore 1 or fewer pads per day and 2 (0.3%) required placement of an artificial sphincter. No patient was totally incontinent. Age, weight of the prostate, prior transurethral resection of the prostate, pathological stage and preservation or wide excision of the neurovascular bundles had no significant influence on preservation of urinary control. These data suggest that anatomical factors rather than preservation of autonomic innervation may be responsible for the improved urinary control associated with an anatomical approach to radical prostatectomy.

Adenocarcinoma

Cancer control following anatomical radical prostatectomy: an interim report.

Cancer control following anatomical radical prostatectomy was evaluated in 586 men who were followed for 1 1/2 to 8 years (median followup 4 years, 166 men followed 5 years or longer). The 5-year actuarial rate was 4% for local recurrence alone, 5% for distant metastases alone, 2% for distant metastases in association with local recurrence and 3% for death of or with disease, while 10% of the men had elevated levels of prostate specific antigen without local recurrence or distant metastases. When the actuarial status at 5 years was evaluated by clinical stage there was local recurrence alone in 0% of men with a clinical stage A1 or B1 nodule, and 4% with stage B1, 7% with stage A2 and 8% with stage B2 disease. When evaluated by pathological stage at 5 years local recurrence alone was noted in 2% of men with organ-confined disease, 8% with specimen-confined disease and 8% in whom the disease involved the surgical margin, seminal vesicles or pelvic lymph nodes. Recognizing that two-thirds to three-quarters of all local recurrences occur within the first 5 years, these data suggest that the anatomical approach to radical prostatectomy is associated with local control rates that are equal to or greater than other series reported in the literature. However, without a randomized study it is impossible to compare one clinical series to another, and followup evaluations at 10 and 15 years will be necessary to confirm these findings.

Antigens, Neoplasm

Nutritional and gastrointestinal complications of the use of bowel segments in the lower urinary tract.

Almost all segments of the gastrointestinal tract have been used as urinary tract substitutes. The specific nutritional and gastrointestinal complications depend on the particular portion of bowel that is removed from the alimentary tract. The use of stomach theoretically may predispose the patient to hypergastrinemia and peptic ulcer disease, hypocalcemia, and iron deficiency or megaloblastic anemia. Resection of a large amount of jejunum causes malabsorption. Limited use of colon segments usually is well tolerated, but loss of large parts of the colon directly decreases available absorptive area, resulting in diarrhea. Resection of the ileum and ileocecal valve can lead to several disease states. One is mixed secretory-osmotic diarrhea. Decreased ileal reabsorption of bile salts results in fat malabsorption and steatorrhea. The presentation of increased amounts of bile salts and fatty acids to the colon decreases water absorption and stimulates active chloride and water secretion, producing a cholera-like high-volume secretory diarrhea. The loss of the ileocecal valve and ileum segment accelerates intestinal transit time, which does not allow for complete digestion and absorption of food. Water and electrolytes remain associated with undigested food particles and may overwhelm the absorptive capacity of the colon, resulting in an osmotic diarrhea. A second problem is vitamin B12 deficiency. Surgical reduction of sites in the terminal ileum for active and exclusive uptake of vitamin B12 might lead to hypovitaminosis. If this is unrecognized, patients may develop irreversible neurologic injury. A third problem is cholelithiasis. Derangements in bile salt metabolism can occur when as little as 10 cm of ileum is resected, and the propensity to form gallstones is increased. Pigment gallstones appear to be the predominant stone associated with ileal resections. The fourth possible problem is urolithiasis, the etiology of which is multifactorial in patients with ileal resections. With decreased availability of bile salts, fat malabsorption occurs. Fatty acids bind with calcium and magnesium to form soaps, resulting in increased levels of free oxalate available for absorption. Moreover, fatty acids directly increase colonic permeability to oxalate.(ABSTRACT TRUNCATED AT 400 WORDS)

Gastrointestinal Diseases

Differential effects of growth factor antagonists on neoplastic and normal prostatic cells.

Growth factors such as epidermal growth factor and fibroblast growth factor have been suggested to be involved as paracrine or autocrine mediators of androgen action in normal and malignant prostatic cells. Suramin and protamine are potent in vitro growth factor antagonists. To evaluate the effect of growth factor antagonists on prostatic growth, suramin and protamine were administered to castrated rats simultaneously receiving exogenous testosterone replacement in an attempt to block androgen-dependent restoration of the normal rat ventral prostate. Using this prostatic restoration model, there was no statistical difference in the prostate wet weight or total DNA content attained between rats given testosterone alone and those given testosterone in combination with either suramin or protamine. In intact rats, suramin administration caused an 80% reduction in serum testosterone; concomitantly, these rats had a 40% reduction in mean prostate weight. This decrease in size could be blocked with androgen supplementation. To examine the effects of growth factor antagonists on neoplastic prostatic cell growth, rats bearing the androgen-independent AT-2 subline of the Dunning R-3327 tumor were treated with either suramin or protamine. The same dosing regimen found to be ineffective in blocking the restoration of the involuted prostate of castrated rats resulted in a significant reduction in the growth rate of AT-2 tumors. These results suggest that the growth factor antagonists suramin and protamine given in vivo have a differential ability to slow the growth of malignant vs. normal prostatic cells.

Animals

Radical retropubic prostatectomy. Improved anastomosis and urinary continence.

The striated urethral sphincter is the predominant muscular structure divided posteriorly during the apical dissection in radical prostatectomy. The authors have long realized the value of this maneuver in obtaining excellent apical surgical margins and in identifying the correct plane on the anterior surface of the rectum. Recently, they also have recognized the importance of incorporating this musculature into the vesicourethral anastomosis to fix the bladder neck and thus re-establish anatomic continuity. Identification of the striated urethral sphincter ranks in importance with elucidation of the anatomy of the dorsal vein complex and the anatomic identification of the neurovascular bundle in improving the patient's quality of life postoperatively.

Anastomosis, Surgical

Genes controlling malathion resistance in a laboratory-selected population of Drosophila melanogaster.

The chromosomal locations of several genes responsible for increased malathion resistance in a laboratory-selected population of Drosophila melanogaster have been determined. These genes appear to be involved in the regulation of microsomal cytochrome P-450. A major gene on chromosome 2 (2-64) and at least two genes on chromosome 3 (near 3-58) control increased mixed function oxidase activity, and both larval and adult malathion resistance. Although the chromosome 2 locus was not associated with a significant increase in cytochrome P-450 content, SDS polyacrylamide gel electrophoresis of microsomal proteins detected increased silver staining of a polypeptide having a relative molecular mass (Mr) of about 52,000. Microsomes from strains carrying the chromosome 3 factors for resistance contained more cytochrome P-450 and increased amounts of two heme-staining protein bands (Mr = 50,000 and 54,000). The genes regulating these proteins were closely linked to striped at 3-62 and probably identical to the loci responsible for malathion resistance and increased mixed function oxidase activity. Other R genes on both chromosomes 2 and 3 as well as target resistance were required for the full expression of malathion resistance in the selected Drosophila population. Exposure of this Drosophila melanogaster population to malathion selected a polygenic system for the oxidative metabolism of insecticide.

Animals

Biochemical properties, homology, and genetic variation of Drosophila "nonspecific" esterases.

The biochemical properties and tissue distribution of two major, soluble "nonspecific" esterases have been studied in Drosophila melanogaster, D. pseudoobscura, and related species. The "alpha-like" activity is due to a monomer enzyme (MW congruent to 60 kd) having a nonspecific tissue distribution, which was inhibited by p-hydroxymercuribenzoate (5 X 10(-4)M) plus eserine (1 X 10(-5)M) and was relatively unstable during polyacrylamide gel electrophoresis. Electrophoretograms of this enzyme could be enhanced by treating gels with beta-mercaptoethanol before staining. This procedure allowed the identification of a new alpha-esterase (Est-4) in D. pseudoobscura. The "beta-like" esterase activity (EC 3.1.1.1) is due to a dimer (MW congruent to 120 kd) in most Drosophila species. D. melanogaster and its siblings (D. simulans and D. mauritiana) were exceptions in which this enzyme had an unusual tissue distribution (increased activity in the male reproductive system) and was a monomer (MW congruent to 60 kd). Differences in the genetic variability of these esterases are discussed and interpreted by a population expansion model rather than by differences in biochemical properties of enzyme forms.

Animals

Ion binding to lysine-modified derivatives of cytochrome c.

The effect of Cl- and K+ ions on the apparent equilibrium constant of the reaction between horse ferricytochrome c and potassium ferrocyanide was studied. Unmodified cytochrome was compared with two lysine-modified derivatives. One, guanidinated, had all lysyl groups converted to homoarginine (but retained the same positive charge); the other was trinitrophenylated at one lysine (measured spectrophotometrically). Both modified derivatives had a somewhat larger equilibrium constant in the reaction of the reduced protein with ferricyanide, but, unlike trifluoroacetylated cytochrome c (which has a negative charge), the redox properties were not dramatically different. The native protein and the lysine-modified cytochromes showed differential K+ binding in Tris-cacodylate buffer at constant ionic strength (0.003-0.005 M). More K+ was bound to ferrocytochrome c. This redox-linked binding, however, was unaffected by modification of lysine. All three derivatives also showed redox-linked differential Cl- ion binding (more Cl- ion was bount to ferricytochrome); however, in this case, the binding was reduced in the lysine-modified molecules. This was interpreted as loss of a single anion site. This anion site critically depends on one or a few lysines which are more reactive with trinitrobenzene sulfonate.

Binding Sites

The oxidation of ferrocytochrome c in nonbinding buffer.

The apparent equilibrium constant and rate of oxidation was investigated for the reaction of cytochrome c with iron hexacyanide. It was found that if horse heart ferricytochrome c was exposed to ferricyanide (to oxidize traces of reduced protein) the cytochrome subsequently, even after extensive dialysis, had an apparent equilibrium constant different from that of electrodialyzed protein. The effect of ferricyanide ion apparently cannot be removed by ordinary dialysis. The ionic strength dependence of the apparent equilibrium constant and bimolecular oxidation rate constant was measured in the range 1--200 mM using Tris--cacodylate or potassium phosphate buffers at pH 7.0, and electrodialyzed horse heart cytochrome c. The oxidation reaction proceeded very rapidly. Extrapolated to zero ionic strength, kox (approximately 9 X 10(9) M-1 S-1) was about 7% of that calculated for a diffusion-limited reaction. Since the exposed heme edge occupies only the order of 3% of the surface area, electron transfer apparently results at nearly every collision with the active-site region. An effective charge of + 7.8 units was estimated for the oxidation reaction. The rate of oxidation of Pseudomonas aeruginosa c551 was much slower (kox at mu = 0 was the order of 6 X 10(3)), and was not consistent with diffusion-limited kinetics.

Animals