Search PubMed⌕ Search

Biomedical subjects

G A Broderick

Publications and source records attributed to G A Broderick.

At least 91 records · Page 5Linked to original sources
PubMed1994

Comparative studies on intracellular calcium and NADH Fluorescence of the rabbit corpus cavernosum.

Erectile function (erection and detumescence) involves the complex interaction of direct neuronal stimulation of corporal smooth muscle, neurohumoral release of specific endothelial contractile and relaxant factors, and secondary modulation by a variety of putative neuropeptides and vasoactive modulators. Using surface spectrofluorometry, we have correlated spontaneous contractile activity and the contractile response to field and pharmacological agents with intracellular calcium and NADH metabolism. The results demonstrate that the corpus cavernosal tissue has very unusual properties. Spontaneous contractile activity is correlated with a phasic increase in intracellular calcium. However, spontaneous contractile activity is most often correlated with a bi-phasic effect on the ratio of NADH/NAD. At the start of the spontaneous contraction, there is a sharp phasic increase in NADH/NAD; peak contractile force occurs simultaneous with a phasic decrease in this ratio showing that at peak force generation, there is a decrease in the level of intracellular energy. Phenylephrine stimulation results in an increase in intracellular calcium in proportion to the increase in tension; however, phenylephrine stimulation at low concentrations results in a net increase in the NADH/NAD ratio whereas high concentrations of phenylephrine result in a net decrease in the NADH/NAD ratio. In general, field stimulation results in a decrease in tension at low frequencies, a biphasic response at midfrequencies, and a contraction at high frequencies. These contractile responses are directly directly related to alterations in the intracellular concentration of calcium. That is, a decrease in tension is preceded by a decrease in intracellular calcium while an increase in tension is preceded by an increase in intracellular free calcium. Field stimulation results in a rapid and phasic alteration in the NADH/NAD ratio; however, the NADH/NAD response can be either an increase, decrease, or biphasic response. There does not appear to be a consistent relationship between the contractile/relaxant response to field stimulation and altered NADH/NAD ratio. Finally, ATP, bethanechol, and nitroprusside induce a decrease in the basal tension of the corpus cavernosal strips which corresponds with a decrease in the NADH/NAD ratio. However, whereas nitroprusside relaxation is correlated with a decreased intracellular calcium level, both ATP and bethanechol stimulate an increase in intracellular free calcium. These studies indicate that the response of the corpus cavernosal tissue to both field stimulation and pharmacological agents is complex and may involve both direct and indirect actions of a variety of cellular mediators on the corporal smooth muscle.

Animals↗
PubMed1994

A novel canine model of partial outlet obstruction secondary to prostatic hypertrophy.

Benign prostatic hyperplasia (BPH) is a major medical problem in the United States. The primary medical complication of BPH is progressive obstruction of the urethra and a subsequent in reduction the ability or the bladder to empty efficiently. The urodynamic characteristics associated with BPH include hyperreflexia, increased bladder capacity, increased frequency, decreased flow rate, and increased residual volume. Although there currently are individual animal models of prostate enlargement and animal models of partial outlet obstruction, there is no model of progressive obstruction secondary to prostate enlargement. The primary objective of the current study was to develop a canine model of BPH that would secondarily result in partial urethral obstruction and impaired urodynamics. Our model consists of encapsulating the prostate in a nylon mesh to prevent the growth of the prostate into the peritoneal cavity and then treating the dog with steroids to induce prostate growth and subsequently produce urethral constriction. The results demonstrate that encapsulation of the dog prostate and administration of steroids results in an increase in prostate mass simultaneously with an increase in urethral pressure and in changes in bladder contraction consistent with the presence of partial outlet obstruction. This preliminary study demonstrates that by preventing the outward growth of the steroid-stimulated prostate, urethral obstruction resembling BPH can be produced.

Animals↗
PubMed1994

Anoxia and corporal smooth muscle dysfunction: a model for ischemic priapism.

The hemodynamics of penile flaccidity, erection and detumescence requires corporal smooth muscle to function across a wide variation in pO2. The present study describes the effect of anoxia on corporal smooth muscle response to field stimulation and pharmacologic agonists and antagonists of erection. The response of isolated strips of rabbit corpus cavernosal tissue to field stimulation, phenylephrine, bethanechol, ATP and KCL was determined under oxygenated and anoxic conditions. The results can be summarized as follows: 1) Anoxia eliminated spontaneous contractile activity and reduced basal tissue tension to a minimum. 2) Neither field stimulation nor pharmacological agents (ATP, bethanechol, isoproterenol) could relax basal tension below that induced by anoxia alone. 3) Under anoxic conditions alpha-adrenergic agonists produced poorly sustained phasic contractile responses; anoxia eliminated tonic contractile responses to phenylephrine. 4) In normoxic conditions field stimulation of smooth muscle precontracted with phenylephrine produced frequency-dependent graded relaxations; under anoxic conditions field stimulation yielded contractile responses at all frequencies. Our data suggest that corporal smooth muscle tone, spontaneous contractile activity, the contractile response to alpha-agonists and field stimulated relaxation depend on the state of corporal oxygenation. The inability of alpha-stimulation to induce a tonic contraction of corporal smooth muscle under anoxia in vitro parallels the failure of penile injection of alpha-adrenergic agonists to relax ischemic priapism.

Animals↗
PubMed1994

Vesicourethral healing following radical prostatectomy: is it related to surgical approach?

OBJECTIVES: To explore how the occurrence of vesicourethral anastomotic strictures (bladder neck contractures [BNC]) following radical prostatectomy was dependent on these variables: postoperative urine extravasation, type of anastomosis, size of prostate, and surgical approach. METHODS: We retrospectively reviewed 143 cases over 36 months for the occurrence of early BNC (6 to 12 months follow-up). Voiding cystourethrograms (VCUC) were performed in all patients at 3 weeks. Radical retropubic prostatectomy (RRP) with direct anastomosis was performed in 93 cases, RRP and Vest anastomosis in 35 cases, and radical perineal prostatectomy (RPP) in 15 cases. RESULTS: The overall incidence of extravasation was 14.1%. Procedure-specific rates of incidence of extravasation were RPP 33.3%, RRP 18.1%, and radical retropubic with Vest anastomosis (Vest) 6.1%. Mean prostate weight was not significantly different between patients with or without extravasation. The anastomotic site was classified as being irregular (plicated) or smooth in appearance on the VCUG images. An irregular appearance was noted among 81% of the RRP, 42.4% of the Vest, and 40% of the RPP. Bladder neck contractures occurred in 29% of patients with Vest anastomosis, 14.1% with RRP, and none of the patients undergoing RPP. Only 1 patient in both the Vest and RRP group who experienced BNC was noted to have extravasation on VCUG at 3 weeks. CONCLUSIONS: We have noted that the type of anastomosis (Vest traction sutures) significantly increases the likelihood of early bladder neck contracture following radical prostatectomy. The presence of contrast extravasation on the postoperative VCUG study (implying urinary extravasation) did not influence the formation of an anastomotic stricture as long as patients were maintained with catheter drainage until resolution of extravasation. The appearance of the newly constructed bladder neck on the postoperative VCUG image was not predictive of a subsequent contracture.

Anastomosis, Surgical↗
PubMed1994

Three-dimensional US and volumetric assessment of the prostate.

The authors demonstrate a method for constructing three-dimensional (3D) images of the prostate based on standard two-dimensional ultrasonic (US) images. Transverse US images of the prostate in six patients (aged 61-83 years) and 10 water-filled balloon phantoms were recorded at video rates by manually withdrawing a biplane transrectal probe at a constant speed. Data acquisition time of the images was less than a minute. Typically, 50-70 scans of 0.2-0.5-mm-thick cross sections were acquired. Postprocessing of these data enabled lifelike 3D visualization of the gland and accurate measurement of its volume.

Aged↗
PubMed1994

Pharmacological effect of ethanol on the function of rabbit corporal cavernosal tissue.

Pharmacologic and behavioral effects of alcohol on male sexual activity have long been controversial. Among the varied effects of alcohol, it has been described that ethanol reduces nitric oxide production. Appreciating the importance of nitric oxide-mediated regulation of corporal smooth muscle, this study was designed to investigate the in vitro pharmacologic effect of 1-5% ethanol on rabbit corpus cavernosum function. The results are summarized as follows. In isolated organ bath experiments, basal resting tension of corporal strips was significantly reduced with 3 and 5% ethanol exposure. Relaxation induced by field stimulation over a frequency range of 2-16 Hz was significantly decreased with 3 and 5% ethanol exposure. However, field-stimulated contraction at 32 Hz was reduced by 5% ethanol only. When corporal strips were preincubated with phenylephrine, 3 and 5% ethanol significantly inhibited field stimulated relaxation at all frequencies. Both phasic and tonic contraction induced by phenylephrine was significantly suppressed by 3 and 5% ethanol. KCl-induced contraction was decreased by 5% ethanol. ATP-induced relaxation was significantly enhanced by 1, 3 and 5% ethanol. Bethanechol-induced relaxation was significantly suppressed by 1, 3 and 5% ethanol. Direct nitroprusside-induced relaxation was not affected by any concentration of ethanol administration. These results demonstrated that ethanol had significant effects on both contraction and relaxation of rabbit corpus cavernosum. In general, corporal relaxation mediated through the acetylcholine-L-arginine-nitric oxide pathway was significantly more sensitive to ethanol than either ATP- or nitroprusside-induced relaxation.

Adenosine Triphosphate↗
PubMed1994

Effect of chronic ethanol consumption on the pharmacological response of the rabbit corpus cavernosum.

Previous studies demonstrated that acute in vitro exposure of corpus cavernosal tissue to ethanol decreased its response to field stimulation and pharmacological stimulation. In the current study the effects of chronic ethanol consumption on the responses of the rabbit corpus cavernosum to field stimulation and various autonomic agonists were investigated. Five percent (V/V) ethanol in drinking water was given to rabbits for 6 weeks. At the end of this time the in vitro response of the corpus cavernosum to various forms of stimulation was determined. The corporal smooth muscle taken from rabbits subjected to chronic ethanol consumption demonstrated the following characteristics compared to tissue taken from control rabbits. (1) Under basal conditions, both relaxation and contraction induced by field stimulation were significantly increased. (2) Contractions to both phenylephrine and KCl increased significantly. (3) In the tissue preincubated with phenylephrine, relaxations induced by field stimulation, ATP, and bethanechol were significantly enhanced. (4) The relaxation responses to sodium nitroprusside were not changed by chronic exposure to ethanol. These findings suggest that in vivo chronic ethanol administration augmented both stimulated contracation and stimulated relaxation of the corporal smooth muscle.

Alcoholism↗
PubMed1994

In vitro determination of ruminal protein degradability using [15N]ammonia to correct for microbial nitrogen uptake.

An in vitro procedure was developed to estimate rate and extent of ruminal protein degradation using [15N]H3 to quantify uptake of protein degradation products for microbial protein synthesis. Incubations were conducted for 6 h in stirrer flasks with ruminal inoculum plus buffer, reducing solution, pectin, soluble carbohydrates, and added (15NH4)2SO4. Seven protein concentrates were tested in the system. Samples of media were analyzed for 15N enrichment of NH3, microbial N, and total solids N. Degradation rate was computed from net (i.e., protein-added minus blank) release of NH3 N plus net synthesis of microbial protein N; escape was estimated assuming ruminal passage rate = .06/h. Over the course of the incubations, pH was stable at 6.6, protozoal numbers increased slightly, and microbial protein content increased by more than 200%. Free AA had not accumulated at the end of the incubations. Microbial protein synthesis was a linear function (P < .001; r2 = .780) of extent of degradation. Mean degradation rates and ruminal escapes determined were, respectively, .569/h and 10% (casein), .148/h and 29% (solvent soybean meal), .036/h and 63% (expeller soybean meal), .026/h and 70% (low solubles fish meal), .063/h and 49% (high solubles fish meal), .034/h and 64% (corn gluten meal), and .050/h and 55% (roasted soybeans). Overall, degradation rates averaged 28% greater than those previously estimated using an inhibitor in vitro system; however, rates obtained for the fish meals using the 15N method were slower.

Ammonia↗
PubMed1994

Pharmacologic erection: time-dependent changes in the corporal environment.

Priapism is a persistent erection which fails to subside after climax and is accompanied by penile pain and tenderness. The most common form of priapism to confront contemporary urologists is persistence of erection following pharmacologic stimulation. We reviewed our experience over 18 months with initial diagnostic intracavernous challenges of prostaglandin E1. Three-hundred and sixty-six new impotence patients presented to our center and underwent PGE1/color duplex Doppler assessment; 14 patients developed persistent rigidity of two or more hours accompanied by penile discomfort. Each of these patients was successfully managed with penile aspiration and direct corporal instillation of the alpha-adrenergic agonist phenylephrine. The mean PGE1 dosage injected was 6 micrograms and mean duration of erection preceding aspiration 180 minutes. Penile blood gases were obtained from the initial aspirate in all cases. The duration of pharmacologic erections were correlated with the partial pressures of oxygen, carbon dioxide, bicarbonate and the pH using linear regression analysis. There was a clear trend towards deoxygenation, acidosis, and hypercarbia with prolonged erection (105-342 minutes). The relationship between duration of pharmacologic erection and acidosis/hypercarbia was highly significant.

Adult↗
PubMed1994

Interstitial cystitis. Current and future approaches to diagnosis and treatment.

Both the patient and physician must understand that there is no single cure for interstitial cystitis, nor is there a single treatment that is effective in reducing symptoms for every patient. Most patients, however, can benefit from one treatment or another, or from a combination of treatments. The author's general philosophy about the treatment of interstitial cystitis is described, and other theoretical modalities of treatment are discussed.

Clinical Trials as Topic↗
PubMed1993

Breakdown of different peptides by Prevotella (Bacteroides) ruminicola and mixed microorganisms from the sheep rumen.

Several di-, tri-, and oligopeptides were incubated individually in vitro with rumen fluid from two sheep receiving a mixed grass hay/concentrate diet and with washed cells of Prevotella (formerly Bacteroides) ruminicola M384 and P. ruminicola B(1)4. The rates of breakdown of most peptides were similar in the rumen fluid from the two sheep. Acidic and proline-containing peptides tended to be more slowly degraded than neutral or basic peptides. The dipeptide at the N-terminus of higher peptides was observed as an early product of hydrolysis, confirming that a dipeptidyl aminopeptidase type of activity was present. The relative rates of breakdown of dipeptides by P. ruminicola were different from that of rumen fluid, but the hydrolysis of higher peptides followed a similar pattern, and dipeptides from the N-terminus were detected as early products.

Amino Acid Sequence↗
PubMed1993

The syndrome of inappropriate antidiuretic hormone secretion in a patient with adenocarcinoma of the prostate.

We report the syndrome of inappropriate antidiuretic hormone secretion in a 59-year-old man with stage C adenocarcinoma of the prostate. Serum antidiuretic hormone levels returned to normal following treatment with a gonadotropin-releasing hormone analogue. To our knowledge this case represents the first in which resolution of this syndrome occurred with treatment of the carcinoma.

Adenocarcinoma↗
PubMed1993

Effects of purines on rabbit corpus cavernosum contractile activity.

At least three well documented neuropharmacologic mediators participate in physiologic erection: inhibition or cessation of alpha-adrenergic transmission, increases in both cholinergic (acetylcholine) and non-adrenergic non-cholinergic (NANC) transmission. In-vitro studies of rabbit corporal smooth muscle reveal that adenosine tri-phosphate (ATP) has a variable effect on muscle tension depending on the level of basal tone. ATP has a pronounced relaxant effect on corporal smooth muscle at either high basal tension or pre-stimulated tension. ATP stimulates a contraction in corporal smooth muscle at low tension. The current studies compare the effects of a series of purines (adenine, adenosine, AMP, ADP, ATP and beta-gamma methylene ATP) on both basal tension and on field-stimulated relaxation. The results demonstrate that all purines relax both baseline tension (2g) and phenylephrine-stimulated contraction. Following phenylephrine pre-stimulation: beta-gamma methylene ATP was significantly more potent than ATP at inhibiting tension. ADP, AMP, adenosine, and adenine produced intermediate dose-response relaxation curves. At 2 grams baseline tension, adenosine, ADP, and AMP were equally potent relaxing agents, ATP was slightly less potent. Adenine and beta-gamma-methylene ATP induced similar dose-response curves which were significantly less potent and efficacious than adenosine, AMP, ADP, and ATP. Field stimulation of phenylephrine pre-contracted tissue strips produce relaxation at both low and high frequencies. None of the purines either facilitated or inhibited the corporal response to field stimulation. We conclude that field stimulated relaxation of rabbit corporal smooth muscle is independent of purinergic relaxation.

Animals↗
PubMed1992

The hemodynamics of vacuum constriction erections: assessment by color Doppler ultrasound.

Duplex ultrasound with pulsed Doppler and color flow sonography were used to image the penis and conduct blood flow velocity studies in 5 patients. Cavernous body cross sectional area, cavernous artery diameters and peak systolic velocities were measured in the flaccid shaft, after transient exposure to negative pressure in a vacuum constriction device, and with a vacuum constriction device band applied to the tumescent shaft. We found that exposure to vacuum transiently increased central cavernous arterial blood flow velocities compared to baseline values in all patients. After a trial of a vacuum constriction device and application of the constricting band cavernous body cross sectional areas doubled. Despite increased cavernous arterial diameters in 4 of 5 patients and increased blood flow in all patients after vacuum-induced tumescence alone, we could not visualize arterial inflow in the penile shaft once the constricting band was in place. Color Doppler ultrasound can detect cavernous artery systolic flow as low as 2 to 9 cm. per second. Our data suggest that the erectile state maintained distal to the vacuum constriction device band is low flow and relatively ischemic.

Aged↗
PubMed1992

Lymphocyte function in patients with interstitial cystitis.

To determine whether there is a primary immunological disorder involved in the etiology of interstitial cystitis, we compared the in vitro function of peripheral blood lymphocytes from 10 patients with interstitial cystitis to those from 10 healthy female controls. The lymphocytes were isolated and incubated in either cell culture medium alone, cell culture medium supplemented with the mitogen phytohemagglutinin or cell culture medium with autologous sterile filtered urine, the latter to detect any immunogenic potential of urine in this disease. We studied the relative proliferation of the phenotypes CD2, CD4, CD8, CD19, CD14 and CD56 by immunofluorescence and flow cytometry. To detect activation of T lymphocytes we also studied expression of HLA-Dr and interleukin-2 receptors. There was no difference in the rate of proliferation of the various lymphocyte phenotypes between the 2 groups in any of the culture media. Similarly, there was no difference between the 2 groups in the degree of lymphocytic activation after incubation. Furthermore, incubation in the presence of autologous urine caused no increase in activation above that seen in control cultures. We also assessed the production of the lymphokines interleukin-1, interleukin-2 and interferon-gamma in the supernatant fluid of the cell cultures. There was no difference in the production of these immunoregulatory cytokines between the control and patient groups, and again urine did not act as a mitogen in either group. We conclude from this study that there is no primary immunological disorder evident in patients with interstitial cystitis, and that the urine does not act as a stimulant to the immune system. This finding casts severe doubt on any theory suggesting that interstitial cystitis is an autoimmune disease or that urine contains an autoantigen causing the disease.

Adult↗
PubMed1992

Rumen protein degradation rates estimated by non-linear regression analysis of Michaelis-Menten in vitro data.

An in vitro method applying Michaelis-Menten saturation kinetics was developed as an alternative approach for estimating protein degradation rates in the rumen. Non-linear regression (NLR) analysis of the integrated Michaelis-Menten equation yielded fractional degradation rates, kd, from direct estimates of the maximum velocity: Michaelis constant ratio (kd = Vmax:Km). Degradation rates obtained using data from a series of 2 h inhibitor in vitro incubations were respectively 0.989, 0.134, and 0.037/h for casein, solvent soya-bean meal (SSBM) and expeller soya-bean meal (ESBM). Degradation rates obtained from 2 h incubations had lower standard errors than those obtained using 1 h incubations; 2 h rates were not significantly different from 1 h rates, suggesting end-product inhibition was not significant at 2 h. The NLR Michaelis-Menten method was used to determine degradation rates for twelve protein sources: casein, bovine serum albumin, two samples of lucerne (Medicago sativa) hay, and four samples each of SSBM and ESBM. Statistical analysis of NLR results revealed significant differences among the twelve protein sources. Casein was degraded most rapidly (0.827/h), and the four ESBM samples most slowly (0.050-0.098/h). Degradation rate for serum albumin was 0.135/h; rates for SSBM and lucerne hays ranged from 0.160 to 0.208/h. Degradation rates estimated using the NLR method were more rapid than those obtained with a limited substrate approach; NLR rates were more consistent with in vivo estimates of rumen protein escape. Greater concentrations of slowly degraded proteins were needed with the NLR method to define curvilinearity of the degradation curve more accurately.

Animals↗
PubMed1992

Determining optimal heat treatment of soybeans by measuring available lysine chemically and biologically with rats to maximize protein utilization by ruminants.

Soybeans were heated in a forced air oven at 120 and 130 degrees C for 60 and 180 min, and at 140, 150 and 160 degrees C for 10, 30, 60, 90 and 120 min. Two types of measurements were used to determine optimal heat treatment of soybeans to maximize protein utilization by ruminants. One was to estimate the rate and extent of protein degradation in the rumen using an in vitro ruminal system. The second was to determine the nutritional availability of lysine. Methods used to determine available lysine were an indirect fluorodinitro-benzene chemical method and a rat growth assay. The product of undegraded intake protein and available lysine content was used to estimate the amount of lysine that would escape ruminal degradation and be available for intestinal absorption. As heat input increased, ruminal undegraded intake protein increased, and protein degradation rates and total and available lysine decreased. As temperature increased, the time required to maximize post-ruminal available lysine decreased. The optimal heat treatment for soybeans heated in a forced air oven was: 140 degrees C for 120 min or greater, 150 degrees C for 60 min or 160 degrees C for 30 min. A loss of 15-22% of chemically determined available lysine was necessary to achieve the heat treatment that resulted in maximal post-ruminal available lysine.

Animals↗