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Biomedical subjects

C E Constantinou

Publications and source records attributed to C E Constantinou.

At least 19 recordsLinked to original sources

Imaging of pelvic floor contractions using MRI.

Magnetic resonance was used to visualize the effect of voluntary pelvic floor contractions on the abdominal structures with particular emphasis in determining the dynamic relationship between the bladder and surrounding organs. The pelvic floor was imaged in 6 asymptomatic female volunteers using MRI viewed in seven coronal and seven sagittal planes. The relative displacement of the bladder resulting from voluntary pelvic floor contraction was measured and the changes from the relaxed to the contracted stage were identified. Measurements from sagittal images show superior bladder wall movement of 3.8 +/- 1.3 mm, posterior of 7.0 +/- 2.8 mm, while maximum movement in the gluteal region was 3.5 +/- 4.0 mm. The results show that voluntary contractions of the pelvic floor measured and visualized using this technique can be identified and displayed using image processing techniques. Anatomical displacement of the bladder in the superior direction is illustrated, demonstrating that pelvic floor contraction provides increased levator muscle support. There is no significant displacement of the anterior aspect of the bladder, while the posterior wall demonstrates maximum movement.

Adult

Modeling of micturition characteristics based on prostatic stiffness modulation induced using hormones and adrenergic antagonists.

We present a biosensor intended to evaluate prostatic stiffness. The stiffness of the prostate was modulated using hormonal induction and adrenergic stimulation. The results show that the sensor can be sufficiently accurate to discriminate between soft prostates used as controls and those stiffened with hormones. The modulation produced by an adrenergic agent on prostatic stiffness was detected using this system. An electrical model was constructed embodying the parameters of prostatic stiffness, micturition frequency, and volume, demonstrating that prostatic stiffness correlates with micturition frequency.

Adrenergic alpha-Antagonists

Prostate specific antigen as a predictor of an abnormal digital rectal examination.

OBJECTIVE: To assess the ability of serum prostate specific antigen (PSA) to predict and differentiate patients with normal and abnormal digital rectal findings. SUBJECTS AND METHODS: A prospective analysis of 1374 participants in a prostate cancer screening programme was performed. After completion of a questionnaire including age and voiding symptoms as well as phlebotomy for PSA analysis, digital rectal examination was performed and the findings were categorized with respect to size, consistency, symmetry and nodularity. RESULTS: In men less than 50 years of age the mean serum PSA level failed to discriminate any of the digital rectal examination categories. In men over 50 there was a statistically significant difference in mean PSA levels between symmetrical, normal sized prostates and symmetrically enlarged glands as well as between symmetrical, normal sized and abnormal prostates (P < 0.05). No statistically significant difference was found in mean serum PSA levels between symmetrically enlarged prostate glands and those with palpable nodules. PSA levels < or = 2.5 ng/ml (normal range for the Yang polyclonal assay) and < 7.4 ng/ml (corresponding to the normal range of < 4.0 ng/ml for the Hybritech monoclonal assay) demonstrated a probability of an abnormal digital rectal examination of 11% and 14% respectively. PSA levels > 18.4 ng/ml (corresponding to monoclonal levels of > 10 ng/ml) had a 67% probability of an abnormal digital rectal examination. However, moderate elevations in PSA could not be used to predict digital examination abnormalities due to the high incidence of moderate PSA elevations associated with symmetrical enlargement of the prostate. CONCLUSIONS: Serial annual PSA measurements may provide an alternative means of screening men over 50 years of age. Contamination of results with PSA elevation due to benign prostatic hyperplasia remains, however, a problem.

Adult

The effect of alpha 2 agonists and antagonists on the lower urinary tract of the rat.

The pharmacologic potential of selective alpha 2 adrenergic agents in modulating vesicourethral function was evaluated in urethane-anesthetized and conscious rats. The bladder was exposed through a midline incision and intubated via a cystostomy to measure pressure. The bladder was filled with saline at 0.05 ml./min. In six animals intravenous dexmedetomidine 0.6 micrograms./kg. followed by 2 micrograms./kg. was given. In another six rats the infusion was made with atipamezole at the same concentration. The parameters obtained were pressure/volume during cystometry, detrusor voiding pressures, and evidence of urine leakage. Conscious rats were placed in a restrainer outfitted with a voided volume sensor and a data recorder. The animals were divided in three groups. In controls, group I (n = 8), the animals were injected with a subcutaneous (SC) load of 5 ml. saline in which furosemide 10.0 mg./kg. was added. In group II (n = 6), dexmedetomidine was added in group III (n = 6), atipamezole was added. Parameters obtained were volume per micturition, latency, frequency of micturition, and patterns of micturition (such as dribbling), and total volume produced after a three hour recording. Values are expressed as mean +/- standard deviation. The results show that in an anesthetized preparation, the alpha 2 agonist dexmedetomidine produced inhibitory effects on the volume evoked micturition reflex (VEMR) at a dose level of 2.0 micrograms./kg. There was a significant decrease in peak pressure from 26.4 +/- 3.6 to 6.8 +/- 2.1 cm. H2O (p < 0.01). Urine leakage was observed at the external meatus. Atipamezole, the alpha 2 agonist, gradually increased bladder baseline pressure and inhibited VEMR. At a critical pressure there was continuous leakage from the external meatus. There was a significant elevation of baseline bladder pressure by atipamezole from 6.3 +/- 1.7 to 29.8 +/- 4.6 cm. H2O (p < 0.005). In conscious rats, the alpha 2 agonist produced urinary dribbling at approximately 20 minutes after SC injection, while the antagonists produced delayed dribbling 70 minutes after SC injection. Leakage occurred in 3 of 6 rats at a dose of 10 micrograms./kg. of atipamezole and in 5 of 6 rats at a dose of 30 micrograms./kg. The alpha 2 agonist caused a diuretic effect and a dose-dependent increase in the frequency of voiding (p < 0.05), while the antagonist decreased the frequency of voiding. Bladder capacity was decreased with the alpha 2 agonist while the antagonist increased capacity.

Adrenergic alpha-Agonists

Rapid evaluation of the efficacy of pharmacologic agents and their analogs in enhancing bladder capacity and reducing the voiding frequency.

We report here the results of a simplified screening method to rapidly compare the pharmacologic action of drugs relevant to the urinary tract. This method avoids the use of anesthesia and of external infusion into the bladder relying on the physiological stimulation of the volume-evoked micturition reflex (VEMR) by diuresis. Mature female rats weighing 240-310 g were placed in restrainer cages that afforded access to food and water but limited movement. Under the rear of the rat, a collecting funnel and weight measuring device was secured. For each VEMR, the weight of the volume voided was recorded on a polygraph which also provided a record of the time of voiding. To evaluate the relative pharmacologic efficacy of the drug under study, 1 mg/kg furosemide along with the drug to be evaluated was diluted in 5 ml of saline and injected subcutaneously. Rats received approximately equimolar concentrations of thiphenamil and 15 other analogs, Ca2+ channel blockers, and K+ channel openers. The furosemide was given to obtain a controlled level of diuresis and avoid the effects of circadian variations in urine flow. Parameters considered were 1) mean volume voided per VEMR, 2) frequency, 3) output, and 4) latency. This model allows the rapid evaluation of drugs designed to increase bladder capacity and decrease the frequency of voiding, and it is particularly useful in evaluating the relative efficacy of drugs that are chemical analogs.

Analysis of Variance

The effect of bacteriuria on bladder and renal pelvic pressures in the rat.

We investigated the effect of urinary tract infection on bladder and renal pelvic urodynamics in a rat model to examine the role of pressure during infection. Either an antibiotic solution (control group) or Escherichia coli with type 1 pili (infected group) was instilled into the bladder. After 2 to 6 days simultaneous continuous bladder and renal pelvic pressures were measured during urinary flows from less than 2 to greater than 20 ml./kg. per hour while the bladder filled and emptied. Bladder pressures from 50 to 100% of maximum capacity and maximum voiding pressures were significantly higher in the infected group than the control group (36.7 +/- 6.79 cm. water versus 25.5 +/- 5.21 cm. water, respectively, p less than 0.0001). Renal pelvic pressures were significantly higher in the infected group during bladder filling at all urinary flows examined and actually exceeded bladder pressure for the highest flows. We conclude that elevated renal pelvic pressures may contribute to renal changes observed during urinary tract infection.

Animals

Impact of radical prostatectomy on the characteristics of bladder and urethra.

A prospective study was done to evaluate the long-term effects of radical prostatectomy on the function of the bladder in filling and voiding. Preoperative urodynamic studies were done on 29 patients with a mean age of 62.9 +/- 5.2 years. The preoperative results show that 16 of the 29 patients demonstrated detrusor instability with maximum contractile pressures of 59 +/- 28 cm. water. Followup urodynamic assessment was done in 13 of these patients 22.9 +/- 1.1 months after surgery. Postoperatively, the maximum detrusor instability pressure did not decrease significantly (49 +/- 17 cm. water). Comparison of the operative and postoperative urodynamic characteristics of bladder filling shows that radical prostatectomy produced no significant change in the filling characteristics of the bladder in terms of bladder capacity, or volume at which sensations of fullness or urgency are reported. Voiding pressure-flow studies show a significant increase in maximum flow rate (8 +/- 1 to 13 +/- 2 ml., per second, p = 0.007), and significant decreases in maximum detrusor pressure (61 +/- 5.4 to 39 +/- 4 cm. water, p = 0.002), urethral opening pressure (45 +/- 7 to 25 +/- 4 cm. water, p = 0.004) and residual volume (150 +/- 37 to 62 +/- 43 ml., p = 0.019). Urethral profile measurements show that there was no significant change in either the maximum urethral closure pressure (94 +/- 9 to 83 +/- 9 cm. water) or external sphincter length (3.6 +/- 0.8 to 3.2 +/- 0.8 cm.). Preoperatively, the bladder neck pressures were 25 +/- 4.4 cm. water and were abolished after prostatectomy, indicating that the decrease in obstructive characteristics is due to removal of the prostate.

Aged

Relaxant effect of thiphenamil HCl on upper urinary tract frequency of contraction of healthy asymptomatic volunteers.

The pharmacologic effect of thiphenamil HCl on the upper urinary tract as a relaxant of renal pelvic contractions was studied. A total of 17 subjects with no known upper urinary tract abnormalities were scanned. A Diasonics ultrasound scanner at 3.5 MHz was used to visualize the kidney and renal pelvis with the subject in the supine position. Control recordings of renal pelvic and calyceal contractility were made on videotape for approximately 30 min. The subject was then given a single dose of 400 mg thiphenamil HCl and visualization of contractility continued for approximately 60-90 min. Criteria for the evaluation of the data were the mean frequency of pelvic contraction cross-section of the pelvis, and velocity and direction contraction. Ultrasonic images were filtered by a video filtering process and averaged using the digital conversion and summation in real time. The results show that under control conditions renal pelvic contractions are at a frequency of 2 +/- 1.8 min-1. Contractions are initiated with the intrarenal pelvis and continue towards the ureter at a rate of 1.3 +/- 0.8 cm/s. Following thiphenamil HCl, there is a significant reduction in pelvic contraction frequency, 0.6 +/- 0.6 min-1, and the opposing walls of the renal pelvis do not completely close in the formation of a bolus. The results obtained from this study demonstrate that thiphenamil suppresses upper urinary tract contractility. As a consequence of this observation, it is postulated that this agent may be of use in the acute relaxation of the upper urinary tract for renal colic and stone management.

Diphenylacetic Acids

Pharmacologic treatment of detrusor incontinence with thiphenamil HCl.

A controlled double-blind crossover study is reported in which quantitative urodynamic data and qualitative information are combined to evaluate the treatment of detrusor incontinence using thiphenamil HCl in patients with detrusor instability. Patients placed on the treatment protocol were randomized to placebo or thiphenamil 400 mg q.i.d. Two weeks of thiphenamil HCl or placebo administration were followed by 1 week of washout followed by a cross-over to an additional 2 weeks of placebo or thiphenamil HCl administration. Of the 23 patients 7 dropped out at various stages of the study. The mean age of patients studied was 44 +/- 14 years old. Throughout the study, patients were asked to complete a formalized diary card of the amount and time of voiding and the incidence of incontinence. Three urodynamics studies were done in the following sequence: pretreatment, postwashout, and posttreatment. Parameters of bladder capacity, sensations, stability and pressure/flow were obtained. In addition, resting urethral closure pressures were recorded. The results show that the frequency of incontinence, which was based on the patients' responses, decreased significantly (0.01 less than p less than 0.025). There was an insignificant decrease in the number of voidings and increase in the amount voided each time. Patients on thiphenamil reported that their pads were significantly drier from baseline (p = 0.01). In response to questions comparing problems caused by urine loss during baseline and thiphenamil treatment, analysis shows a significant decrease of problems due to loss of urine (p = 0.01) when the patient was taking the drug compared to the placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Diphenylacetic Acids

Topological localization of the frequency and amplitude characteristics of the whole and segmented renal pelvis.

The contractile characteristics of pacemaker regions in the unicalyceal renal pelvis of the rabbit were examined in vitro. The amplitude and frequency spectra of spontaneous contractions of whole and separated circular and longitudinal renal pelvic strips were identified. The effect of stretch on these parameters were examined in order to establish whether the pacemaker region that generates contractions in the renal pelvis was sensitive to distention. The results show that the frequency of spontaneous contractions in the whole pelvis (65 +/- 18 mHz) was significantly higher than any part of the circularly (41 x 8 mHz) or longitudinally cut (43 +/- 8 mHz) pelvis. The amplitude of longitudinal strips, 52 +/- 11 mg, was significantly smaller than that of the circular strips, 267 +/- 52 mg. In the circularly separated pelvis the frequency of spontaneous contractions was highest in the proximal part (41 +/- 8 mHz) and lowest in the pelviureteral junction (8 +/- 1 mHz). No significant increase in frequency was seen upon stretch in the whole or separated pelvis although there was a decrease in the amplitude of both the whole and separated pelvis. These results show that the frequency of contraction of the whole or the segmented renal pelvis is not sensitive to stretch.

Animals

Renal pelvic pressure isolation from active and passive bladder pressures in the rat: the facilitating effect of urine flow rate.

The circumstances facilitating hydrostatic pressure communication between the bladder and renal pelvis were evaluated. In particular, we compared active detrusor contractions occurring spontaneously during voiding and evoked contractions produced during electrical pelvic nerve stimulation with passive abdominal compression. These variables were evaluated with respect to urine flow rate and bladder capacity. Waveform analysis of the pacemaker characteristics of the renal pelvis shows that the rat pelvis has a narrow frequency band of spontaneous contraction at 0.5 +/- 0.06 Hz. The baseline waveform and pressure of the pelvis is effected by urine flow and bladder capacity. Significant elevations in pelvic pressure of 25.8 +/- 7.9 and 28.7 +/- 5.8 cm H2O were observed for bladder pressures of 30 cm H2O (n = 8) at flow rates in the range of 2.5-5.0 and over 5.0 ml/kg/h respectively (p less than 0.05). At flow rates between 2.5 and 5.0 ml/kg/h, spontaneous contractions produced an increase in pelvic pressure in all rats, while electrical stimulation produced an increase in pelvic pressure in 63%. At flow rates above 5 ml/kg/h, abdominal compression produced sharp elevations in pelvic pressure in 75%. At the same flow rate, electrical stimulation produced a slow increase in 75% and spontaneous contraction produced a slow increase in 86%. These results suggest that the exposure of the upper urinary tract to vesical pressures occurring during active and passive contractions is facilitated by flow.

Animals

Pharmacologic effect of thiphenamil HCl on lower urinary tract function of healthy asymptomatic volunteers.

The effect of thiphenamil HCl on the urodynamic parameters of bladder filling, voiding and isometric contraction was examined in controls. Data were obtained from 25 control female subjects with a mean age of 27.6 +/- 6.6 years. Three urodynamic studies were done on each subject on 3 different days. These studies were: (1) control study, (2) drug study with a single oral dose of 400 mg thiphenamil HCl and (3) another with 800 mg. Each urodynamic study involved filling and voiding cystometrograms to characterize stability, sensations of fullness and urgency, bladder capacity, urethral opening pressure, maximum flow rate, maximum detrusor pressure and residual urine. In addition, isometric detrusor pressure measurements were made at bladder volume increments of 100 ml. Each urodynamic study was done in the sitting position using medium fill water cystometry at 20 ml/min. Isometric pressures were made by catheterizing the subject with an 18-french three-way Foley catheter with a 30-ml balloon. One lumen was used to fill the bladder and the second to measure pressure. The results show that bladder capacity and the volume at which sensations of fullness and urgency are expressed are not significantly changed under the influence of thiphenamil HCl. Significant differences were seen in the maximum pressure generated by the detrusor during voiding and in the maximum urine flow rate. These differences were most pronounced at the 800-mg thiphenamil HCl dose. The isometric data show a highly significant increase in the maximum isometric pressure developed at the low bladder volumes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Regional effects of indomethacin, acetylsalicylic acid and SC-19220 on the contractility of rabbit renal pelvis (pacemaker regions and pelviureteric junction).

The effects of the cyclooxygenase inhibitors indomethacin and acetylsalicylic acid (ASA) and the prostaglandin (PG) antagonist 1-acetyl-2-[8-chloro-10,11-dihydrodibenz (b,f)(1,4) oxazepine-10-carbonyl]hydrazine (SC-19220) on smooth muscle strips from the rabbit renal pelvis were examined. Circularly oriented tissues were taken from within the renal pelvis and subdivided into the four adjoining regions, from fornix to pelviureteric junction (PUJ). They were set in a tissue bath and isometric tension changes were recorded. Spontaneous contractions were observed and electrical field stimulations evoked twitch-like contractions. The frequency of spontaneous contractions was dependent on the region within the renal pelvis from which they were dissected, gradually decreasing from fornix (3.92/min.) to PUJ (0.43/min.). Indomethacin (10(-5)M) or ASA (10(-4)M) significantly increased the frequencies of spontaneous contractions in all four regions. In the upper three regions (pacemaker regions), both agents significantly decreased the amplitudes of spontaneous and stimulation-induced contractions. In the PUJ region, both agents significantly increased the amplitudes of spontaneous and stimulation-induced contractions. SC-19220 (3 x 10(-5)M) significantly increased the frequencies and decreased amplitudes of spontaneous contractions in all four regions. These results suggest that the PUJ has different contractile characteristics from those of pacemaker regions and that decrease of amplitude by indomethacin or ASA is based on their cyclooxygenase inhibitor property.

Animals

The effect of urinary flow and bladder fullness on renal pelvic pressure in a rat model.

We describe an in vivo animal model used to study the interactions of urinary flow, and bladder pressure and fullness on renal pelvic pressure. These parameters were examined in 17 nonrefluxing Sprague-Dawley rats. At urinary flow rates less than 14 cc/kg. per hour and bladders less than 60% full, renal pelvic pressures were below 9 cm. water but at urinary flow rates more than 30 cc/kg. per hour renal pelvic pressure increased above 10 cm. water when the bladder was only 20% full. At all urinary flow rates examined renal pelvic pressure increased to more than 20 cm. water as the bladder approached 100% fullness. To quantitate the combined effects of these changes in renal pelvic pressure and urinary flow on the renal pelvis a renal pelvic work index (renal pelvic pressure times urinary flow rate) was defined. Using this index the magnitude of the change between low urinary flows with an empty bladder and high urinary flows with a full bladder can be observed. The results of these studies in this model might be applicable to high urinary flow states or bladders that fail to empty completely.

Animals

Urethral pressure and pressure variations in healthy fertile and postmenopausal women with reference to the female sex hormones.

The impact of female sex hormones on the rhythmic urethral pressure variations (UPV) was analysed based on data from one hour urethral pressure recordings from 10 healthy fertile female volunteers measured three times during the menstrual cycle and from 12 healthy postmenopausal women measured twice within two months. The mean maximum urethral pressure (mMUP) and the mean maximum urethral closure pressure (mMUCP) had a median value of 66.5 (Interquartile 58.0-86.0) and 60.0 (49.0-80.0) cm.H2O respectively in the healthy fertile females. The postmenopausal women had a significantly lower mMUP and mMUCP of 55.5 (48.5-58.5) and 43.5 (35.5-47.0) cm.H2O) respectively. Rhythmic UPV was recorded inhealthy fertile and postmenopausal women. Frequency analysis of the UPV revealed a frequency spectrum from 0.0015 to 0.035 Hz on top of which were respiration fluctuations and vascular pulsations. The UPV amplitude was related to the mMUP and increased with increasing mMUP. The parameters analysed were stable during the menstrual cycle and during menopause. Thus no difference in the UPV frequencies or amplitudes was observed between the healthy fertile and the postmenopausal women. The investigation shows that the pressure variation in urethra apparently is not modulated by female sex hormones.

Adult

Effects of [1-desamino-8-D-arginine]vasopressin and papaverine on rabbit renal pelvis.

The effects of [1-desamino-8-D-arginine]vasopressin (DDAVP) (V2 receptor agonist) and papaverine on four continuous circular smooth muscle strips in rabbit renal pelvis were studied by an isometric tension recording methods. DDAVP suppressed spontaneous contractions in a dose-dependent and region-dependent way. Papaverine suppressed these contractions in a dose-dependent way simultaneously in all four portions. These results suggest that there may be distribution differences of V2 receptors in the renal pelvis. Together with its anti-diuretic action, DDAVP may merit consideration for the treatment of renal colic.

Animals