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Biomedical subjects

C E Constantinou

Publications and source records attributed to C E Constantinou.

At least 55 records · Page 3Linked to original sources

Treatment of urinary incontinence by the periurethral implantation of glutaraldehyde cross-linked collagen.

Injectable materials have been used to augment the urethral sphincter and improve urinary continence with some success. However, none of these materials has received widespread use because they are difficult to inject and have been reported to migrate. We investigated the efficacy of transurethral implantation of glutaraldehyde cross-linked collagen, a highly purified bovine collagen. A total of 17 patients (16 men and 1 woman) with urinary incontinence resulting from a previous operation was selected for glutaraldehyde cross-linked collagen injection into the region of the urethral sphincter. Before and after implantation patients underwent urodynamic evaluation. Glutaraldehyde cross-linked collagen was injected into the area of the bladder neck or urinary sphincter under direct endoscopic vision. If no improvement occurred reinjection to increase the implant volume was performed at least 3 months after a previous injection. Of the 17 patients 9 were cured or improved. No complications have been reported. This investigation shows that glutaraldehyde cross-linked collagen can be injected into the urinary tract to correct urinary incontinence without observable or measurable morbidity.

Collagen↗

Frequency of spontaneous contractions in longitudinal and transverse bladder strips.

The frequency components of spontaneous contractility of rabbit bladder strips were examined with respect to their orientation and position. Spectra of longitudinal and transverse strips of bladder were studied in vitro in consecutively dissected segments from the same bladder. The frequency characteristics of these strips were characterized at rest and also with incremental extension to 125% of original length. Results show that transverse and longitudinal strips of bladder muscle undergo continuous spontaneous contractions in the frequency range of 0.01-0.25 Hz. The amplitude of the spontaneous contractions is not dependent on the amount of resting tension in either longitudinal or transverse strips. Longitudinal strips have a higher frequency of spontaneous variations of tension compared with the transverse strips. The amplitude of transverse strips is lowest at the base of the bladder, and the frequency components of activity increases in magnitude toward the bladder dome. Extension of transverse strips shows the generation of frequency peaks of tissues located at the middle of the bladder having a significantly lower rate of relaxation than the proximal or distal strips. Spontaneous contractility of the bladder indicates the presence of a potentially significant parameter that must be considered when tissue response to mechanical, electrical, or pharmacological stimulation is interpreted.

Animals↗

Renal calyceal and pelvic contraction rhythms.

An experimental study of the porcine multicalyceal pacemaker system was undertaken. In particular, the characteristic rhythmicities of in situ calyces were examined as well as rhythmicities between the calyceal system and the renal pelvis using pig kidneys perfused ex vivo via the renal artery. The temporal and spatial organization of calyceal and renal pelvic contraction rates were evaluated by simultaneously recording pressure from the renal pelvis and from three calyces. The results obtained from 15 kidneys indicate that the upper, middle, and lower calyces contract rhythmically at the essentially equal rates of 12.8 +/- 2.4, 14.0 +/- 1.6, and 13.06 +/- 2.3 min-1. The interaction between the activities of different calyces was analyzed by measuring the phase of individual calyceal contractions. Phase locking, coordination of contraction and phase oscillation, systematic fluctuations, or divergence of phase were obtained in most preparations, indicating the existance of a mechanism of coherent intercalyceal coupling. During periods in which phase locking occurred, pelvic contractions were related to all of the observed calyceal regions. When phase oscillation was present, the region of calyceal system evidencing a higher frequency was associated with pelvic contraction, whereas in the absence of calyceal coupling renal pelvic contractions could not be correlated to calyceal activity.

Animals↗

Extravesical subtrigonal injection of 50 per cent ethanol for detrusor instability.

Urinary incontinence with detrusor instability often is refractory to pharmacological therapy as well as other conservative modalities. We report the results obtained from 10 patients with detrusor incontinence who underwent extravesical subtrigonal injection of 50 per cent ethanol. Postoperatively, 9 of the 10 patients had conversion to detrusor stability and 6 had an acontractile bladder. Of the 10 patients 9 had an excellent result for at least 10 months postoperatively with 1 patient requiring 2 additional treatments to convert to detrusor stability. Complications included fistula formation in 3 patients, requiring primary closure in 2 and ileal diversion in 1. Of the 10 patients 7 remain dry or vastly improved at a mean of 24 months of followup.

Administration, Intravesical↗

Analysis of the in vitro pharmacologic response of renal pelvis and detrusor smooth muscle to thiphenamil, oxybutynin and verapamil.

A new computerized methodology was used to acquire and analyze the relative pharmacologic sensitivity of the renal pelvis and urinary bladder of the rabbit to pharmacologic stimulation. Comparison was made of the effects of thiphenamil, verapamil and oxybutynin on the spontaneous contractions of isolated detrusor and renal pelvis. Data collected by computer were evaluated in terms of amplitude, frequency, and tension change to varying concentration of pharmacologic stimulation. Data were analyzed using a frequency/time domain algorithm developed specifically to evaluate the contribution of the oscillatory components of tension associated with smooth muscle tissues. For the renal pelvis the results show 6 X 10(-5) M thiphenamil, 10(-3) M oxybutynin, and 5 X 10(-6) M verapamil resulted in a 50% inhibition of the phasic contractions. Thiphenamil significantly increased the contractile frequency of the renal pelvis. For the bladder 10(-3) M thiphenamil resulted in a 50% inhibition of the phasic contractions, while 3 X 10(-4) M oxybutynin and 3 X 10(-6) M verapamil were needed to achieve the same level of inhibition. Thiphenamil at lower doses (10(-4) M to 5 X 10(-4) M) showed a biphasic effect--an increase of the bladder tissue activity followed by a relaxation phase--that oxybutynin and verapamil failed to produce. The results show that the calcium blocker suppresses the spontaneous activity of the upper and lower urinary tract at lower concentrations than the anticholinergic or thiphenamil.

Animals↗

Dynamics of the upper urinary tract: II. The effect of variations of peristaltic frequency and bladder pressure on pyeloureteral pressure/flow relations.

The dynamics of pyeloureteral flow is described when there is no peristalsis and for peristalsis of high and intermediate frequencies, on the assumption that the ureter is uniform except in the mid-ureter and at the outlet. The possibility of upstream transmission of bladder pressure variations to the renal pelvis is considered. The overall behaviour depends on three principal variables, the maximum tube pressure in the contraction waves, the intrinsic peristaltic carrying capacity and the peristaltic frequency f, expressed in the form fT where T is the time for a peristaltic contraction wave to sweep through the ureter. At intermediate peristaltic frequencies (fT less than but comparable with one) oscillatory flow patterns can occur, in which periods of peristaltically driven flow alternate with extraperistaltic periods of flow through the open ureter. The kidney is better isolated from bladder pressure variations when the peristaltic frequency is high, but high peristaltic frequency can by itself lead to elevated renal pelvic pressure if the flow rate is high. Experimental observations in pigs are presented to support these conclusions.

Animals↗

Internal urethrotomy in girls and its impact on the urethral intrinsic and extrinsic continence mechanisms.

The cause of incontinence in a group of 11 girls (mean age 18 +/- 3 years) who had undergone internal urethrotomy during childhood was assessed. Urodynamic methods were used to characterize the detrusor, and urethral profiles were performed to identify the impact of the operation on the extrinsic and intrinsic mechanisms of urethral closure. The results show that 4 of 11 patients demonstrated detrusor instability associated with a high voiding flow rate. The average resting urethral closure pressure in all patients showed significant reduction in maximum closure pressure (62 +/- 32 cm. water) when compared to normal age-matched controls. Transmission pressures to coughing demonstrated a high percentage of transmission to the distal and mid urethra (180 +/- 20 per cent). It was concluded that the intrinsic mechanism of urethral continence as measured by the resting urethral pressure profile was compromised by the urethrotomy. However, the extrinsic mechanisms as measured by the transmission values was not affected. On the basis of these findings it is argued that internal urethrotomy compromises the closure mechanisms intrinsic to the urethra. Continence in these patients most likely is maintained by the action of extrinsic factors transmitting high closure pressures at the distal third of the urethra. Finally, it is postulated that urethrotomy patients are at increased risk for stress incontinence at an early age.

Adolescent↗

Urinary bladder function and its control in healthy females.

Recordings in eight healthy female volunteers of bladder (detrusor) pressure and flow rate, obtained during bladder filling and during voiding, both through the urethra and through a catheter, demonstrate that a model of bladder function in which the detrusor muscle is considered as completely passive during filling and fully activated during voiding is inadequate. Assessment of the detrusor contraction strength by a new method (described in APPENDIX A) shows that in ideal normal voidings the contraction strength rises to values of 11-24 W/m2 and is sustained or rises slightly until the bladder is empty. During unstable detrusor contractions, which even in these healthy women are observed during bladder filling and also during inhibited voidings through the urethra, the contraction is weaker. During voidings through a catheter the detrusor contraction is weak, variable, and fades away before the bladder is empty. An elementary feedback analysis demonstrates that the effect of the micturition reflex governing detrusor behavior differs according to whether or not voiding is taking place. The reflex does not lead to a simple on-off mechanism but to a more complex behavior that is consistent with the observations and that appears to be important for the understanding of pathological obstructed micturition.

Adult↗

Pressure evaluation of the antireflux ability of the rat ureterovesical junction.

The bladder pressure necessary to cause vesicoureteral reflux (VUR) was measured in 16 female rats. Under general anesthesia, the ureters were exposed via an abdominal incision and a pressure catheter was placed near the ureterovesical junction. Values of bladder distension and bladder pressure increase to cause VUR were obtained by injecting isotonic saline in one ureter until VUR in the opposite ureter was detected as a sudden pressure increase. After 5 min the same procedure was done on the contralateral side. This procedure was repeated eight times in each rat with a 15-min intermission. The bladder pressure at which VUR occurred was measured through a ureteral catheter. Two groups were studied: G1, control, and G2, administration of intravenous metoclopramide (0.007 mg/100 g body weight) four times.

Animals↗

Isometric detrusor pressure during bladder filling and its dependency on bladder volume and interruption to flow in control subjects.

We characterized the isometric pressures generated by the bladder during voluntary detrusor contraction and interruption of flow. Urodynamic studies were done in 34 healthy female volunteers, with a mean age of 29.6 plus or minus 9.3 years. Control urodynamics were done first to characterize bladder and urethral parameters to filling and voiding. Subsequently, isometric detrusor pressures were elicited during bladder filling at increments of 100 ml. by asking subjects to attempt to void against a urethral obstruction produced by an inflated Foley balloon. Isometric pressures also were obtained by interruption of flow through the lumen of the 22F Foley catheter. The results showed that the maximum isometric pressure increase generated remained relatively constant during bladder filling at 39.6 plus or minus 13.1 cm. water. This pressure is not significantly different from voiding pressures developed with a 10F urethral catheter. On the other hand, isometric pressure increases during voiding showed that the increase in bladder pressure following interruption of flow was volume sensitive. The possibility that this volume dependency may result in errors in the interpretation of bladder contractility is discussed.

Adult↗

Chronic ureteric obstruction and its impact on the coordinating mechanisms of peristalsis (pyeloureteric pacemaker system).

We present the results of a study designed to characterise urine transport in the healthy and chronically obstructed upper urinary tract. Fifteen healthy and 11 hydronephrotic pigs were used; experimental hydronephrosis was produced by partially obstructing the ureter. Data consisting of the peristaltic rate, bolus volume, and the urine flow rate were collected and related to varying increments of diuresis. The transmission characteristics of renal pelvic to ureteric contractions were studied by extracellular electrodes. Similarly, in hydronephrotic preparations we studied the transmission between the proximal and middle pelvis to the ureter. In healthy preparations, the contraction frequency of the renal pelvis and the ureter is identical, while in obstructive cases, the contraction frequency of the upper pelvis is not coordinated with the lower pelvis or ureter. While diuresis increased bolus volume to a maximum of 1,200% in the healthy and 660% in the hydronephrotic kidney, the peristaltic rate changed by only 45% and 50% respectively. The results of this study show that chronic ureteric obstruction alters the coordination of ureteric peristalsis and thereby disrupts the pacemaker mechanisms of the renal pelvis.

Animals↗

Spatial distribution and timing of transmitted and reflexly generated urethral pressures in healthy women.

We localized the temporal and spatial distribution of pressures in the urethra to identify their contribution to continence. With the data obtained we resolved the timing between the passively transmitted and actively generated urethral pressures. Data were obtained from 11 healthy female volunteers, with a mean age of 22 years. Simultaneous measurements of bladder and urethral pressures were taken from subjects during the Valsalva maneuver and coughing, and then holding with the subject in the supine, standing and sitting positions. The ratio of urethral to bladder pressure increase and the latency between these pressure increases were analyzed. A biphasic pressure distribution results from coughing with subjects in all positions. The first phase occurs at the normalized distance of 10 to 15 per cent from the bladder neck, where the ratio of urethral to bladder pressure increase is 0.8. The second phase occurs at 60 to 70 per cent of the urethral length and has a 1.5 to 1.7 ratio of urethral to bladder pressure increase, indicating the presence of pressure magnification. Simultaneous latency measurements indicate that the pressure increase in the urethra precedes that of the bladder by 240 plus or minus 30 msec. in the region that exhibits maximum pressure magnification. These results indicate that a fast-acting contraction occurs in the distal third of the urethra, which contributes reflexly to the compressive forces of the proximal urethra, thereby preventing urine loss during stress.

Adolescent↗

The effects of drugs on pacemaker regions of isolated rabbit renal pelvis.

Acetylcholine failed to change the frequency of spontaneous contractions in the proximal region of isolated rabbit renal pelvis, but significantly increased the contractile frequency in the middle and distal regions, which then reached similar levels to those of the proximal region. Pretreatment with reserpine caused a decrease in the frequency of spontaneous contractions in the proximal, but not in the middle or distal regions. Reserpine-pretreated tissues developed hypersensitivity to catecholamines, while acetylcholine produced effects similar to those observed in control preparations. Atropine and N-methyl-scopolamine antagonized the action of acetylcholine in both the middle and the distal regions, suggesting that the action was exerted through muscarinic receptors. Adrenaline and alpha-stimulating drugs, but not isoprenaline, significantly increased the contractile frequency of all three tissues: the increase in the proximal region reached levels in excess of its fundamental maximal frequency. Phentolamine caused a significant decrease in the frequency of the proximal region and fully inhibited the stimulating action of catecholamines, indicating that this stimulation was mediated by alpha-adrenoceptors. The myogenic nature of pacemaking cells was confirmed by the effect of tetrodotoxin, ouabain and verapamil. The decrease in frequency in the pacemaker region of the proximal pelvis whether caused by reserpine or phentolamine indicates a significant role of catecholamines in modulating pacemaker activity.

Acetylcholine↗

Pyeloureteral dynamics in the intact and chronically obstructed multicalyceal kidney.

The transport of urine in the upper urinary tract of the multicalyceal kidney was studied in healthy and chronically obstructed pigs in terms of renal pelvic pressure, rate of and coordination of ureteral contractions, and bolus volume. The variations of these parameters to diuresis was examined by incremental elevation of urine output effected by intravenous infusion of mannitol. In 16 healthy animals the mean variation in urine flow was 0.01-3.20 ml/min, the change in peristaltic rate ranged from 0.763 to 5.125 min-1, and bolus volume from 0.003 to 2.083 ml.. In 14 chronically obstructed kidneys, for a mean variation in urine flow of 0.006-5.4 ml/min, peristaltic rate ranged from 0.237 to 6.095 min-1 and bolus volume from 0.00 to 1.80 ml. Discoordinated contractions, bursts of peristalsis, and incompletely transmitted pelvic contractions were characteristic of a chronically obstructed system. These observations are compared with the unobstructed unicalyceal and multicalyceal kidney. The disrupting impact of chronic ureteral obstruction on the hierarchical organization of the pyeloureteral pacemaker system is discussed.

Animals↗