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M P Sullivan

Publications and source records attributed to M P Sullivan.

At least 37 records · Page 2Linked to original sources
PubMed1997

Tissue angiotensin II as a modulator of erectile function. I. Angiotensin peptide content, secretion and effects in the corpus cavernosum.

PURPOSE: Although Angiotensin II (Ang II) is a major modulator of regional blood flow in the extracavernosal segments of the vascular bed, its role in erectile function is unknown. The corpus cavernosum penis is a modified vascular tissue that contains endothelial and smooth muscle cells. In other segments of the vascular bed, these cell types produce Ang II. Therefore, we explored the presence and function of an Ang II producing paracrine system in the corpus cavernosum. METHODS: The angiotensin content of the human corpus cavernosum was measured by radioimmunoassay. The distribution pattern of Ang II containing cells within the corpus cavernosum was assessed by an immunohistochemical technique, and the rate of its secretion was determined by superfusion. The effects of Ang II and its antagonist, losartan, on intracavernosal pressure were determined under in vivo conditions, in anesthetized dogs. RESULTS: Human corpus cavernosum contained 1178 +/- 223 (SEM) fmol Ang II, 528 +/- 171 fmol Ang I, 475 +/- 67 fmol des-asp-Ang I, and 1897 +/- 371 fmol des-asp-Ang II/gm. tissue (n = 4). Ang II was found mainly in endothelial cells lining blood vessels and smooth muscle bundles within the corpus cavernosum. Superfused cavernosal tissue secreted immuno-reactive Ang II (Ang II(ir)) at a rate of 57 +/- 36.5 fmol Ang II(ir)/gm. tissue/minute (n = 10). The amount of Ang II released per gram of tissue in an hour was 3-fold greater than the Ang II content/gm. tissue, suggesting a local production of Ang II. Papaverine and prostaglandin E1 suppressed Ang II secretion significantly (p <0.001, p = 0.013). The responsiveness to inhibition was a function of the initial rate of Ang II secretion. Tissue samples with a high rate of secretion were less responsive to the inhibitors than tissue that secreted small amounts of Ang II (n = 6). In anesthetized dogs, intra-cavernosal injection of Ang II terminated spontaneous erections, while losartan increased the intracavernosal pressure in a dose dependent manner up to the mean arterial pressure (n = 4). CONCLUSIONS: The corpus cavernosum produces and secretes physiologically relevant amounts of Ang II. The rate of Ang II secretion can be modulated by pharmacologic agents that regulate cytosolic calcium levels and are used clinically to treat erectile dysfunction. Intracavernosal injection of Ang II causes contraction of cavernosal smooth muscle and terminates spontaneous erection in anesthetized dog, while administration of an Ang II receptor antagonist results in smooth muscle relaxation and thus erection.

Alprostadil↗
PubMed1996

Combinations of maximum urinary flow rate and American Urological Association symptom index that are more specific for identifying obstructive and non-obstructive prostatism.

Uroflowmetry and the American Urological Association symptom index (AUASI) are often used clinically to evaluate patients with benign prostatic hyperplasia (BPH). Since results from these tests may be used to determine a treatment course, including surgical intervention, we investigated if specific combinations of uroflowmetry and AUASI parameters could better predict urodynamically confirmed prostatic obstruction. Data from 134 men (mean age: 67.8 +/- 8.9 years) with prostatism were analyzed. The patients underwent uroflowmetry in the standing position after completing the AUASI; the post-void residual volume (PVR) was determined. The presence and severity of prostatic obstruction was assessed by video urodynamics, which included micturitional urethral pressure profilometry (MUPP). Of the 134 total patients, 66 were found to be obstructed by MUPP. Correlations of maximum urinary flow rate (Qmax), PVR, and AUASI with the degree of obstruction were poor and not substantially improved using combinations of these parameters. Threshold values of Qmax and AUASI, when used in combination, allowed accurate prediction of obstruction or non-obstruction in a small subset of the patient population. Of 14 men with both Qmax < 10 ml/s and AUASI > or = 20, 13 were obstructed (specificity = 98%). Eight of 9 men with both Qmax > or = 15 ml/s and AUASI < 10 were non-obstructed. The combined Qmax and AUASI criteria categorized only 20% of the patients as obstructed or non-obstructed. Once other causes of urinary dysfunction are ruled out, use of these criteria will enable the urologist to make an accurate diagnosis of obstruction, select a treatment more likely to benefit the patient, and make further diagnostic testing unnecessary in this small subset of patients. In a large volume clinical practice of adult male voiding dysfunctions, diagnosis of even this small proportion of patients using this simple approach can reduce patient care costs.

Aged↗
PubMed1996

Detrusor internal and external work in relation to passive urethral resistance in a canine model of the lower urinary tract.

This study was conducted to evaluate whether passive urethral resistance, detrusor internal work, and detrusor external work are independent measures of the voiding process. Passive urethral resistance, detrusor internal work, detrusor external work, and detrusor total work of 5 canines were determined under nonobstructive and obstructive outlet conditions. All urodynamic analyses were performed on a surgically exposed urinary tract. Solid-state pressure transducers were used to measure the intravesical and distal urethral pressures, while an ultrasonic flow meter was used to obtain a simultaneous measure of urinary flow rate. Detrusor contractions were induced using bilateral electrical stimulation of the pelvic nerves. Varying degrees of outlet obstruction were created using an inflatable sphincter cuff secured around the proximal urethra. Urethral resistance, internal work, and total work increased with increasing obstruction, while external work decreased with increasing obstruction. Internal work was linearly and negatively correlated to external work. At low degrees of obstruction, internal and external work changed more rapidly than passive urethral resistance per unit change in obstruction. As obstruction was increased, the change in work parameters per unit change in obstruction decreased, while the change in passive urethral resistance per unit change in obstruction increased. Our results indicate that at low degrees of outlet obstruction (cuff volume < 60% of isometric cuff volume), detrusor internal and external work are more sensitive to changes in obstruction than passive urethral resistance. It therefore appears prudent to use these work parameters with a passive urethral resistance relation (PURR) when evaluating early BPH and also when monitoring its progression. The data also show that a detrusor will acutely respond to a change in outlet obstruction by modulating its total work output. The mechanisms responsible for this response are presently under investigation.

Animals↗
PubMed1996

Prediction of prostatic obstruction with a combination of isometric detrusor contraction pressure and maximum urinary flow rate.

OBJECTIVES: Because isometric detrusor contraction pressure (Piso) increases with outlet obstruction and maximum urinary flow rate (Qmax) tends to decrease with obstruction, we hypothesize that specific criteria consisting of a combination of high Piso and low Qmax may be able to differentiate obstructive from nonobstructive voiding dysfunction better than either parameter alone. METHODS: Two hundred five men with lower urinary tract symptoms underwent uroflowmetry and videourodynamics, including cystometry, continuous outlet occlusion test, and micturitional urethral pressure profilometry. Combined threshold values of Qmax of less than 12 mL/s and Piso of 100 cm H2O or greater were used to predict obstruction, whereas threshold values of Qmax of at least 12 mL/s and Piso less than 100 cm H2O were used to predict nonobstruction. RESULTS: Of the 205 patients, 103 (50%) were significantly obstructed and 102 (50%) were only mildly obstructed or nonobstructed. Of the total population, 151 patients (74%) were categorized by the combined flow and contractility criteria. Of the categorized patients, 141 (93%) were correctly diagnosed with regard to infravesical obstruction (sensitivity 89%, specificity 97%, positive predictive value 97%, and negative predictive value 91%). CONCLUSIONS: A combination of Qmax and Piso criteria can predict obstructive and nonobstructive voiding dysfunctions with high positive and negative predictive values in most patients with lower urinary tract symptoms. Combining the results of uroflowmetry and isometric tests may help to guide treatment strategies that may improve the outcome of selected therapeutic options compared with strategies based on symptoms or uroflowmetry alone. Furthermore, this approach forms a basis for interpreting various noninvasive methods that have recently been introduced for the purpose of diagnosing bladder outlet obstruction.

Aged↗
PubMed1996

Micturitional urethral pressure profilometry.

The technique of micturitional urethral pressure profilometry using a trilumen catheter provides a method of assessing the dynamic behavior of the lower urinary tract during voiding. This method of evaluation is simple to perform, highly reproducible, accurate, and clinically useful not only in diagnosing the presence of outlet obstruction, but also in identifying its location and assessing its severity. The rationale for the use of this technique, the interpretation of the results, and various pressure profile configurations are discussed.

Animals↗
PubMed1996

Detrusor contractility and compliance characteristics in adult male patients with obstructive and nonobstructive voiding dysfunction.

PURPOSE: To understand better the contractility and compliance characteristics of the detrusor in patients with varying degrees of outlet obstruction, we analyzed urodynamic studies in elderly men with obstructive and nonobstructive voiding dysfunction. MATERIALS AND METHODS: All patients were evaluated with video urodynamics, including cystometry, isometric tests, voiding profilometry and post-void residual measurement. Bladder compliance, detrusor contractility, detrusor reserve, detrusor instability and the severity of outlet obstruction were determined in each patient. Patients were stratified into 4 groups: urodynamically normal, detrusor instability, outlet obstruction and outlet obstruction with detrusor instability. RESULTS: A significant correlation was found between the maximum isometric contraction pressure and the severity of obstruction in 168 patients. Maximum isometric contraction pressure was significantly greater in patients with than without obstruction, independent of detrusor instability. Although compliance was not significantly different among the groups, the proportion of patients with poor compliance (less than 30 ml./cm. water) was lowest in the normal group. The detrusor reserve was significantly less in patients with chronic retention (post-void residual more than 200 ml.) than in those with lower post-void residuals. CONCLUSIONS: The increase in detrusor contractility with increasing outlet obstruction suggests a compensatory response to obstruction. Furthermore, a decrease in bladder compliance does not appear to be a consistent finding in patients with outlet obstruction, although the proportion of patients with poor compliance is higher in the group with obstruction and/or detrusor instability than in those with normal urodynamic findings. The decrease in detrusor reserve in patients with high post-void residual volumes suggests that the detrusor reserve reflects the degree of detrusor decompensation.

Adult↗
PubMed1995

Correlation between micturitional urethral pressure profile and pressure-flow criteria in bladder outlet obstruction.

PURPOSE: We correlate micturitional urethral pressure profilometry with pressure-flow diagnoses of outlet obstruction. MATERIALS AND METHODS: Urodynamic evaluation was done of 86 consecutive men with voiding symptoms. Obstruction criteria were a micturitional urethral pressure profile (MUPP) gradient greater than 5 cm. water, Schäfer's linear passive urethral resistance relation (PURR) greater than grade 1 and Abrams-Griffiths nomogram. RESULTS: Interpretable results were completed in 99% of the patients undergoing MUPP and 60% undergoing pressure-flow studies (p < 0.00001). MUPP diagnosis agreed with PURR (p = 0.0015) and Abrams-Griffiths nomogram results (p = 0.00004). MUPP gradients correlated well with PURR (r = 0.70, p < 0.00001). Using optimum cutoff values (11 cm. water), the sensitivity of MUPP was 83%, specificity 82% and positive predictive value 94%. CONCLUSIONS: MUPP correlates well with and yields interpretable results more often than pressure-flow studies.

Aged↗
PubMed1995

Assessment and modeling of the physical components of human corporovenous function.

To understand and quantify specific causes of venoocclusive dysfunction, an analog model of penile hemodynamics, including a mechanism of flow limitation by subtunical veins, was developed and a detailed analytic study was conducted in patients with erectile dysfunction. Computer simulations for steady-state and transient intracavernosal conditions were carried out to study graded changes in cavernosal smooth muscle tone, subtunical venular resistance, and cavernosal and tunical compliances. The model predicted a steady-state cavernosal pressure (Pca)-infusion flow relationship with two phases: an initial phase characterized by a gradual slope up to a critical flow and a second phase characterized by a much steeper slope after limitation of subtunical venular flow. Model predictions were compared with clinical data obtained during incremental saline cavernosometry (SaC) and pharmacocavernosometry (PhC) in 13 patients with erectile dysfunction with use of a computer-controlled infusion system that automatically changed from constant-flow to constant-pressure feedback control when Pca reached the threshold of 80 mmHg. Steady-state pressure-flow and pressure-circumference relationships of the penis were analyzed and interpreted in terms of specific components of the electrical analog model. These clinical studies demonstrated that patients with a functional venoocclusive mechanism (i.e., those able to achieve 100 mmHg Pca with infusion flow rates < 60 ml/min during PhC) had a steeper initial slope of the pressure-flow relationship during SaC and a greater increase in penile circumference and Pca after intracavernosal injection of papaverine-phentolamine than those with an impaired venoocclusive mechanism. From the electrical analog model, initial steepness of the pressure-flow relationship (slope) during SaC mainly represented subtunical venular resistance, whereas maintenance of flow during PhC depended on overall function of the different components, i.e., subtunical venular resistance, cavernosal and subtunical compliances, and full relaxation of cavernosal smooth muscle. We conclude that the proposed analog model can be used to interpret and characterize clinical penile hemodynamic data and may provide guidelines for more successful management of patients with erectile dysfunction.

Adult↗
PubMed1995

Correlation of American Urological Association symptom index with obstructive and nonobstructive prostatism.

The precise role of the American Urological Association (AUA) symptom index in the management of benign prostatic hyperplasia (BPH) is not well established. The AUA symptom index has been recommended only for quantifying the symptoms of BPH but not for its diagnosis. However, to our knowledge the ability to discriminate obstructive from nonobstructive BPH using the AUA symptom index has never been investigated. To establish the relationship between the AUA symptom index and prostatic obstruction 125 men (mean age 67.7 +/- 8.4 years) with voiding dysfunction presumably related to BPH were analyzed. Patients were given the AUA symptom questionnaire, following which video urodynamic studies were done, including micturitional urethral pressure profilometry for specifically diagnosing outlet obstruction. The patients were divided into 2 groups: group 1-78 with primary BPH dysfunction and group 2-47 with prostatism of ambiguous etiology. The mean AUA symptom index in group 1 (15.5 +/- 7.1) was not statistically different from that in group 2 (14.8 +/- 7.9). In both groups the mean AUA symptom index in the patients with obstruction (15.3 +/- 7.2 for group 1 and 13.9 +/- 7.9 for group 2) was not statistically different from that in the nonobstructed group (17.0 +/- 5.4 and 16.1 +/- 7.9, respectively). Of the severely symptomatic patients 22% did not have obstruction whereas all mildly symptomatic patients did. No significant correlations were found between the severity of obstruction and the AUA symptom index in either group. These observations indicate that the AUA symptom index cannot discriminate obstructed from nonobstructed BPH cases, not all severely symptomatic BPH patients will have outlet obstruction, a significant proportion of mildly symptomatic BPH patients can have outlet obstruction and voiding dysfunctions in elderly men, regardless of the etiology, produce similar symptoms.

Aged↗
PubMed1995

Continuous occlusion test to determine detrusor contractile performance.

PURPOSE: A study was conducted to determine the merits of the continuous occlusion test as a method of detrusor contractility assessment by comparing it with other stop tests and with contractility derived from pressure-flow analysis. MATERIALS AND METHODS: The continuous occlusion test was performed in elderly men by occluding the bladder outlet before the onset of a detrusor contraction and it was repeated to assess reproducibility. The magnitude of the isovolumetric contraction, maximum slope of the detrusor contraction, and duration of detrusor activation were determined. Voluntary and mechanical stop tests were performed during the mid voiding phase. Continuous occlusion test parameters were compared with the pressure-flow contractility parameters. RESULTS: The continuous occlusion test was evaluated in 159 patients. The maximum isovolumetric contraction pressure of the continuous occlusion test was significantly higher than that of the voluntary stop test (49 patients). Continuous occlusion test contractility parameters were reproducible. The maximum isovolumetric contraction pressure and the maximum slope of the detrusor contraction of the continuous occlusion test significantly correlated with the estimated maximum isovolumetric contraction pressure and estimated velocity of shortening (derived from pressure-flow), respectively (r = 0.79, p < 0.0001 and r = 0.385, p = 0.016, 39 patients). The watts factor was well correlated with maximum isovolumetric contraction pressure (r = 0.75, 39 patients). CONCLUSIONS: Our study suggests that the continuous occlusion test can be used as an effective alternative method of assessing detrusor contractility.

Adult↗
PubMed1994

Cisternal Na+ transport inhibition and the ventilatory response to CO2.

When PCO2 rises transiently, glia or neurons may move ions across their cell membranes to restore intracellular pH, in the process changing extracellular pH. Inhibiting ion transport would result in a different extracellular fluid pH (a putative stimulus for the medullary chemoreceptors) and, therefore, in an altered ventilation in response to PCO2. We infused two ion transport inhibitors, amiloride and bumetanide, into the cisterna magna of anesthetized rabbits and compared their ventilatory response to a rebreathing maneuver with sham rabbits receiving no inhibitor. Amiloride (10(-5)-10(-3) M) had no effect; 3 h of 10(-2) M amiloride increased the frequency of breathing and decreased tidal volume but had no net effect on minute ventilation. Bumetanide (10(-3) M) had no effect after 1 h of infusion, but by 3 h it had decreased tidal volume and minute ventilation at 6 and 7% end-tidal CO2 fraction, respectively, during the rebreathe. Three hours of infusion of amiloride and bumetanide did not affect ventilation in a manner consistent with our predictions from previous studies of ionic changes in cerebrospinal fluid. During the 1st h, when neuronal and glial ion transport in the ventrolateral medulla should be inhibited, we found no effect of ion transport inhibition. We conclude that, during the transient hypercapnia of a rebreathing maneuver, Na+/H+ exchange and Na(+)-K(+)-2Cl- cotransport do not play a significant role in immediate rapid pH homeostasis by cellular ion transport in the microenvironment of the medullary chemoreceptors.

Amiloride↗
PubMed1994

Inhibition of atherosclerosis by dietary pectin in microswine with sustained hypercholesterolemia.

Sustained hypercholesterolemia is a known risk factor for development of atherosclerosis. In animal studies, grapefruit pectin fed concurrently with a high-lipid diet inhibits hypercholesterolemia and atherogenesis. The purpose of the present study was to determine if grapefruit pectin affects cholesterol levels and atherogenesis of animals with established hypercholesterolemia. Microswine were fed an atherogenic diet to establish hypercholesterolemia. Plasma cholesterol levels rose rapidly and for 360 days were sustained at levels 6- to 12-fold the normal level. Then, half the microswine, selected at random, were fed a diet in which 3% grapefruit pectin was substituted for cellulose, and the remaining animals received the original diet. Animals were killed 270 days later, and the extent of atherosclerosis was determined. In animals with established hypercholesterolemia, pectin did not lower their cholesterol levels. However, pectin reduced the extent of atherosclerosis in both the aorta and coronary arteries. The mean surface area covered by atherosclerosis in the aorta was 13.6% in the group that did not receive pectin compared with 5.3% in the group that did receive pectin. The mean coronary artery narrowing was 45% without pectin and 24% with pectin. We conclude that pectin may have a direct beneficial effect on atherosclerosis by a mechanism independent of cholesterol levels.

Animals↗
PubMed1993

Evidence for identity inhibition during selective attention in old adults.

Previous studies of negative priming have shown that, relative to young adults, old adults can effectively suppress location information associated with stimuli, but not information about the identity of stimuli. S.L. Connelly and L. Hasher (1993) attributed this dissociation to an age-related decrement in the inhibitory processes that suppress meaning-bearing information. In this study, the authors report both identity negative priming and distractor interference in a group of young and old adults. Their results force a reconsideration of an age-related decrement in the inhibitory processes underlying the suppression of meaning-bearing information. The results also suggest that whether a relationship between negative priming and interference is observed may depend on whether the 2 measures index the same level of processing.

Adolescent↗
PubMed1993

Cl- replacement alters the ventilatory response to central chemoreceptor stimulation.

To determine whether cerebrospinal fluid (CSF) Cl- has a role in determining the stimulus to the central respiratory chemoreceptors under conditions of constant CSF pH, CO2, and HCO3- concentrations, the ventral medullary surface of the anesthetized rat was perfused with mock CSF of various ion composition and pH. Four mock CSF perfusates were used: two normal pH control perfusions and two acidic solutions. One acidic perfusate was formulated in the traditional manner by substituting Cl- for HCO3-. The second acidic perfusate, and one of the normal pH control perfusates, had approximately 15% of the Cl- replaced with isethionate, an impermeant strong anion. When the two acidic solutions were perfused over the ventral medulla, consistently larger increases in both tidal volume and minute ventilation were observed with the isethionate-containing acidic solution, despite conditions of identical pH and PCO2. The unequal ventilatory effects of the two acidic perfusions suggest that Cl- transport may be a factor determining the stimulus to the central respiratory chemoreceptors.

Animals↗
PubMed1993

The gerbil, hamster, and guinea pig as rodent models for hyperlipidemia.

The purpose of this study was to compare the effects of a hyperlipidemic diet on three different rodent models to evaluate them on how their responses simulate human serum lipid diseases. Forty hamsters, 40 gerbils, and 20 guinea pigs were given either a chow diet or a modified high-fat, high-cholesterol diet (HF/HC) for 7 days. Food was withheld from half of the animals on each diet for 12 hours prior to collecting the blood for analysis of total cholesterol and triglyceride concentration. In all species, HF/HC feeding resulted in at least a 370% increase in total cholesterol concentration. Withholding food significantly decreased total cholesterol concentration in hamsters and gerbils fed HF/HC but had no effect on animals fed chow diet. Triglyceride concentrations were increased by the HF/HC in the hamster and the gerbil. As with total cholesterol, triglyceride concentration was decreased after food was withheld in these two animal groups. We suggest that the guinea pig is the most appropriate model for studying hypercholesterolemia because of its moderate plasma cholesterol response and normal triglyceride response to a HF/HC. We also suggest that the hamster is a good model for studying hypertriglyceridemia since increased serum triglyceride concentrations can be easily maintained on a HF/HC.

Animals↗
PubMed1992

Effect of chloride transport blockade on the MAC of halothane in the rat.

There is a growing evidence that central nervous system chloride transport via gamma-aminobutyric acid (GABAA) related Cl- conductance or Cl-/HCO3- exchange affects anesthetic requirements. To delineate the effects of GABAA-related Cl- conductance blockade versus Cl-/HCO3- exchange inhibition, we determined the change in minimum alveolar anesthetic concentration (MAC) of halothane in rats after intracisternal infusion of 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS). DIDS inhibits Cl-/HCO3- exchange transport in concentrations greater than 1 microM and in GABAA-related Cl- channels in concentrations greater than 0.1 mM. After control MAC determination, rats were given intracisternal mock cerebrospinal fluid (n = 6), 1.0 microM DIDS (n = 8), or 1 mM DIDS (n = 8) at a rate of 2 microL/min for 30 min. Mock cerebrospinal fluid did not change the MAC of halothane. The MAC of halothane increased significantly (P less than 0.001) from 0.96% +/- 0.02% to 1.11% +/- 0.03% (mean value +/- SEM) with 1 microM DIDS and from 0.94% +/- 0.02% to 1.16% +/- 0.04% with 1 mM DIDS. The increases in MAC with 1 microM and 1 mM DIDS were not statistically different. This suggests that Cl-/HCO3- exchange inhibition increases halothane requirements, whereas GABAA-related Cl- channel blockade does not.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Childhood malignant non-Hodgkin lymphomas of uncommon histology.

Uncommon histologies were identified in 36 of 1336 cases (2.7%) of newly diagnosed childhood non-Hodgkin lymphoma (NHL). Seventeen cases were classified as follicular (six cases as mixed small and large cell, nine as large cell, and two as small non-cleaved cell) and 19 cases as diffuse (18 cases as mixed small and large cell, and one as small cell lymphocytic). The follicular pattern group included a preponderance of male patients; the median age at diagnosis was 11.7 years. These children presented primarily with low-stage disease involving lymph nodes or tonsils. All patients except one achieved complete remission and remain disease-free for 11 months to 18.8 years (actuarial 5-year event-free survival, 94%). The group with diffuse histologies was similar in sex ratio, age at diagnosis (median = 12.1 years), and nodal involvement, but tended to have more advanced-stage disease. Moreover, only 14 of 19 (74%) children with diffuse intermediate-grade histologies are alive in continuous complete remission (actuarial 5-year event-free survival, 70%). These results suggest that follicular pattern childhood NHL has an excellent prognosis, whereas cases with diffuse intermediate-grade histology are prognostically similar to those with diffuse high-grade histologies.

Adolescent↗