URODYNAMIC EFFECTS OF INTRAVESICAL RESINIFERATOXIN IN HUMANS: PRELIMINARY RESULTS IN STABLE AND UNSTABLE DETRUSOR

Purpose

Resiniferatoxin, a substance isolated from some species of euphorbia, a cactus-like plant, presents pharmacological effects similar to those of capsaicin. We studied the urodynamic effects of intravesical resiniferatoxin* in normal subjects and patients with unstable detrusor contraction to provide insight into the action mechanism of the molecule on sensory neurons and possible future pharmacological and clinical use.

Materials and Methods

A total of 15 subjects with normal (8 patients) or unstable detrusor muscle (1 with detrusor instability and 6 with detrusor hyperreflexia) underwent urodynamic assessment during and after intravesical instillation of resiniferatoxin. Volume required to elicit the first desire to void, maximum bladder capacity and maximum bladder pressure were recorded during instillation of resiniferatoxin at a flow rate of 20 ml. per minute (normal subjects) or 15 minutes after instillation of 30 cc of a saline solution containing 10 sup −8 M. of resiniferatoxin and kept for 30 minutes in patients with unstable detrusor. The experiment was examined by the analysis of variance for repeated measures and post hoc comparisons were performed by Tukey-Kramer procedure. A p value <0.05 was accepted as significant.

Results

Resiniferatoxin did not decrease the volume required to elicit the first desire to void and did not produce warm or burning sensations at the suprapubic/urethral level during infusion in subjects with normal detrusor function. In patients with bladder hyperactivity mean bladder capacity increased from 175.28 ml. plus or minus standard deviation 36.05 to 280.85 ml. plus or minus standard deviation 93.33 (p <0.01) immediately after treatment, and no significant modification of bladder pressure was recorded. Four weeks after treatment, bladder capacity remained increased in 2 patients but mean capacity did not increase significantly from 175.28 ml. plus or minus standard deviation 36.053 to 216.71 plus or minus standard deviation 86.91. The 2 patients with stable increase of bladder capacity reported significant clinical improvement of frequency, nocturia and incontinence 4 weeks later.

Conclusions

Our results suggest that in humans there may be substantial differences in urodynamic effects between resiniferatoxin and capsaicin when the drugs are instilled into the bladder. Further studies, in vitro and in vivo, are necessary to define the pharmacological and clinical effects of resiniferatoxin. Because resiniferatoxin did not produce warm or burning sensations at the suprapubic/urethral level during infusion and seems to have rapid desensitization, it could be an interesting alternative to intravesical capsaicin in the treatment of select cases of bladder hyperactivity.     

CONVENTIONAL AND AMBULATORY URODYNAMIC FINDINGS IN WOMEN WITH SYMPTOMS SUGGESTIVE OF BLADDER OVERACTIVITY

PURPOSE: We compared ambulatory urodynamics and conventional video cystometry findings in women with symptoms of bladder overactivity. MATERIALS AND METHODS: In a prospective randomized crossover study 106 women with symptoms of urinary urgency with or without incontinence were comprehensively investigated by video cystometry and ambulatory urodynamics in random order. In addition, all women completed a validated symptoms questionnaire and voiding diary. RESULTS: Involuntary detrusor activity was detected in 32 and 70 cases on video cystometry and ambulatory urodynamics, respectively (p <0.001). Video cystometry done according to International Continence Society standards diagnosed detrusor instability in 4 women with no involuntary detrusor activity on ambulatory urodynamics. Involuntary detrusor activity resulting in incontinence was observed in 39 cases on ambulatory urodynamics, including 20 (51%) with stable video cystometry results. Stress incontinence was diagnosed in 42 cases on video cystometry and in 34 on ambulatory urodynamics (p = 0.629). Increasingly severe urge and stress incontinence reported in the symptoms questionnaire correlated positively with the subsequent detection of detrusor overactivity and stress incontinence, respectively, on the 2 urodynamic tests. CONCLUSIONS: In contrast to video cystometry, ambulatory urodynamics provides objective evidence of clinically important bladder overactivity in the majority of women with symptoms suggestive of bladder overactivity. The correlation of symptoms with ambulatory urodynamic findings implies that greater reliance may be placed on symptomatic diagnosis of bladder overactivity. Improved objective assessment of detrusor function provided by ambulatory urodynamics has implications for the definition of bladder overactivity and relevance of conventional cystometry in this context. In women who complain of urgency stable conventional cystometrography findings should be interpreted with caution.     

DETRUSOR INSTABILITY IN MEN: CORRELATION OF LOWER URINARY TRACT SYMPTOMS WITH URODYNAMIC FINDINGS

PURPOSE: We evaluated the correlation of lower urinary tract symptoms suggestive of detrusor instability with urodynamic findings in men. MATERIALS AND METHODS: Enrolled in our prospective study were 160 consecutive neurologically intact men referred for urodynamic evaluation of persistent lower urinary tract symptoms. All patients had storage symptoms suggestive of detrusor instability. Patients were further clinically categorized according to the chief complaint of urge incontinence, frequency and urgency, nocturia or difficult voiding. The clinical and urodynamic diagnosis in all patients as well as specific urodynamic characteristics of those with detrusor instability were analyzed according to the these 4 clinical categories. RESULTS: Mean patient age was 61 +/- 15 years. The chief complaint was urge incontinence in 28 cases (17%), frequency and urgency in 57 (36%), nocturia in 30 (19%) and difficult voiding in 45 (28%). Detrusor instability was diagnosed in 68 cases (43%). A higher incidence of detrusor instability was associated with urge incontinence than with the other clinical categories (75% versus 36%, p <0.01). Of the patients 109 (68%) had bladder outlet obstruction, including 50 (46%) with concomitant detrusor instability. The prevalence of bladder outlet obstruction was similar in all patients regardless of the chief complaint. All other urodynamic diagnoses were also similar in the 4 clinical categories. The mean bladder volume at which involuntary detrusor contractions occurred were lower in patients with urge incontinence and frequency and urgency than in those with nocturia and difficult voiding (277.1 +/- 149.4 and 267.7 +/- 221.7 versus 346.7 +/- 204.6 and 306.2 +/- 192.1 ml., respectively, not statistically significant, p = 0.07). CONCLUSIONS: Detrusor instability and bladder outlet obstruction are common in men with lower urinary tract symptoms. The symptom of urge incontinence strongly correlated with detrusor instability. Other lower urinary tract symptoms did not correlate well with any urodynamic findings. Therefore, we believe that an accurate urodynamic diagnosis may enable focused and more efficient management of lower urinary tract symptoms in men.     

EFFECTS OF NIFEDIPINE ON BLADDER OVERACTIVITY IN RATS WITH CEREBRAL INFARCTION

PURPOSE: Our objective was to evaluate the effect of the calcium (Ca2+) channel blocking agent nifedipine on bladder overactivity induced by middle cerebral artery (MCA) occlusion and determine its site of action. MATERIALS AND METHODS: Seven days after implantation of a bladder catheter, a cannula for intracerebroventricular and intrathecal administration was implanted and the left MCA was occluded with 4-0 monofilament nylon thread in male SD rats. Twenty-four hours after the induction of cerebral ischemia, saline was infused into the bladder at a constant rate (200 microL/min.) and cystometrogram was measured in conscious state. Nifedipine was administered intracerebroventricularly (5 microL) or intrathecally (20 microL) at graded doses (0.15 ng.-0.15 microg., 0.15 microg. -1.5 microg., respectively). RESULTS: Bladder capacity in conscious rats was significantly reduced after the left MCA occlusion. Intracerebroventricular administration of nifedipine significantly increased bladder capacity in cerebral infarcted rats but not in sham operated rats. Furthermore there was no significant difference in bladder capacity between before and after intrathecal administration of nifedipine in cerebral infarcted rats. CONCLUSION: These results show that Ca2+ channel blocking agents can operate especially on the supraspinal central nervous system rather than on the spinal system in rats with neurogenic bladder overactivity following cerebral infarction.     

URINARY CONTROL AFTER RADICAL TRANSURETHRAL RESECTION OF THE PROSTATE IN MALE PARAPLEGICS: URODYNAMIC EVALUATION OF ITS EFFECTIVENESS IN RELIEVING INCONTINENCE

We report our investigation of urinary incontinence in 51 male paraplegics with radical transurethral resection of the prostate. Pre-operatively, 28 cases (55.9%) had moderate or severe incontinence, which persisted post-operatively only in 21 cases (41.2%) and was less severe. Post-operatively, bladder compliance was improved from 22.1 22.6 ml/cmH₂O to 36.4 38.5 ml/cmH₂O, and the maximum pressure of uninhibited detrusor contraction was reduced from 40.2 21.5 cmHzO to 18.3 19.0 cmH₂O. These significant improvements are thought to contribute to the relief of urinary incontinence, regardless of the reduction in maximum urethral closure pressure.     

A SHORT-TERM, MULTICENTER, RANDOMIZED DOUBLE-BLIND DOSE TITRATION STUDY OF THE EFFICACY AND ANTICHOLINERGIC SIDE EFFECTS OF TRANSDERMAL COMPARED TO IMMEDIATE RELEASE ORAL OXYBUTYNIN TREATMENT OF PATIENTS WITH URGE URINARY INCONTINENCE

PURPOSE: We compared the short-term efficacy, safety and tolerability of transdermal versus oral oxybutynin in adults with urge urinary incontinence. MATERIALS AND METHODS: Volunteers with detrusor instability currently responding to oral immediate release oxybutynin were enrolled in our study. Those patients presenting with recurrence of incontinent symptoms after a 2-week washout underwent confirmatory cystometrogram with subsequent randomization to transdermal or oral treatment. Matching active and placebo medications included matrix patches applied twice weekly and capsules taken 2 or 3 times daily. Dose titration was based on anticholinergic symptoms. Outcome measures included comparison of baseline to 6 week changes in incontinence episodes on a 3 day urinary diary, a visual analog scale for efficacy and anticholinergic symptoms reported on a questionnaire. Safety monitoring included adverse events and skin tolerability of the transdermal system. RESULTS: A total of 76 patients were enrolled and 74 completed at least 4 weeks of treatment. Mean age in the transdermal and oral groups was 64 and 63 years, and 87% and 97% were female, respectively. Daily incontinent episodes decreased in the transdermal and oral groups (7.3 to 2.4 [66%] and 7.4 to 2.6 [72%], respectively, p = 0.39). The visual analog scale reduction in urinary leakage improved from washout in both groups (p <0.0001) with no difference between them (p = 0.9). Dry mouth occurred in significantly fewer patients in the transdermal (38%) compared with those in the oral group (94%, p <0.001). Of the patients in the transdermal group 67% noticed a reduction in dry mouth severity compared with previous oral treatment, and 90% had none or mild skin erythema. CONCLUSIONS: Transdermal delivery of oxybutynin resulted in comparable efficacy and a significantly improved anticholinergic side effect profile compared with oral administration in adults with urge urinary incontinence.     

DIFFERENTIAL EFFECTS OF SEX HORMONES AND PHYTOESTROGENS ON PEAK AND STEADY STATE CONTRACTIONS IN ISOLATED RABBIT DETRUSOR

PURPOSE: Recent evidence suggests that sex steroids may produce rapid inhibition of voltage operated Ca2+ channels (VOCCs). Detrusor smooth muscle is highly dependent upon Ca2+ influx for receptor-activated contractions. Thus, we examined the relative effectiveness of a select group of sex steroids and dietary phytoestrogens to relax detrusor contracted with the muscarinic receptor agonist, bethanechol (BE) and the purinergic P2X receptor agonist, alpha,beta-methylene ATP (alpha,beta-MeATP). MATERIALS AND METHODS: Isolated strips of rabbit detrusor were secured to isometric force transducers in a tissue bath and length-adjusted until maximum contractions were achieved. Peak (P) contractile responses were recorded for alpha,beta-MeATP (P(ATP)) and BE (P(BE)) and steady-state (SS) responses were recorded for BE (SS(BE)) in the presence and absence of selected sex steroids and phytoestrogens (10 microM, unless indicated). RESULTS: The L-type VOCC inhibitor, nifedipine (1 to 10 microM), completely inhibited P(ATP) but reduced SS(BE) by approximately 50%, whereas the VOCC and non-VOCC inhibitor, SKF 96365, inhibited SS(BE) by approximately 95%, suggesting that P(ATP) was entirely dependent on L-type VOCCs, but (BE)-induced contractions depended also on activation of non-VOCCs. 17Beta-estradiol (estradiol) and progesterone inhibited P(ATP) by approximately 60% and 20%, respectively, and 32 microM estradiol and ethinyl estradiol inhibited SS(BE) by approximately 80 and 95%, respectively. Inhibition by estradiol was potentiated, rather than blocked, by the nuclear estrogen receptor antagonist, tamoxifen. Moreover, tamoxifen alone nearly completely relaxed SS(BE). The inactive metabolite of estradiol, 17alpha-estradiol, inhibited both P(ATP) and P(BE) by approximately 40%. Testosterone had no effect on P(ATP) and P(BE). The phytoestrogen and tyrosine kinase inhibitor, genistein, inhibited SS(BE) by 44%, whereas daidzein, a phytoestrogen without tyrosine kinase inhibitory activity, produced only a 7% inhibition. None of the phytoestrogens examined inhibited P(BE), whereas all inhibited P(ATP) by approximately 20 to 35%. A comparison of inhibition of (BE) and alpha,beta-MeATP-induced contractions by selected estrogen isomers showed some distinct differences. For example, estrone did not inhibit P(BE) or SS(BE), but inhibited P(ATP) by approximately 20%, whereas DES inhibited SS(BE) by nearly 90%, but P(ATP) by a lesser degree (approximately 70%). CONCLUSIONS: Our data support the hypothesis that 17beta-estradiol, ethinyl estradiol, DES, tamoxifen and genistein may relax detrusor contractions by inhibition of both VOCCs and non-VOCCs. Moreover, our data show that genistein, a dietary phytoestrogen with tyrosine kinase inhibitory activity, selectively reduced alpha,beta-MeATP-induced peak and BE-induced steady-state contractions, sparing the maximum response to BE. Lastly, the inactive isomer, 17alpha-estradiol, inhibited both BE- and alpha,beta-MeATP-induced contractions. These data suggest that certain dietary phytoestrogens (for example, genistein) or sex steroids, especially those with weak activity at the nuclear steroid site (for example, 17alpha-estradiol), or tamoxifen may prove therapeutically useful in treating overactive bladder caused by elevated muscarinic and purinergic receptor activation.     

大鼠脊髓圆锥损伤后膀胱逼尿肌及其神经肌肉接头形态学变化的研究

目的初步探讨大鼠脊髓圆锥损伤后膀胱逼尿肌及其神经肌肉接头（neuromuscular junction,NMJ）组织形态学的变化规律。方法成年SD大鼠48只随机分为六组,每组8只。分别为正常对照组,脊髓圆锥损伤术后4、6、8、10及12周组,依次记作A~F组。采用L4、5平面锐性横断性脊髓圆锥损伤的动物模型。分别于术后相应时间点取材,先作膀胱逼尿肌HE染色,以观测肌纤维截面积的变化规律;同时制作电镜标本,观察膀胱逼尿肌及其NMJ超微结构的变化规律;最后将逼尿肌行Masson三色染色,计算平滑肌及结缔组织所占的百分比。结果HE染色观察,大鼠逼尿肌肌纤维截面积在E、F组与A组间差异有统计学意义（P〈0.05）;透射电镜观察,B~F组逼尿肌细胞外形、大小不一致,分布不均匀,排列走行紊乱;间质中大量排列紊乱的胶原纤维,粗面内质网明显扩张,线粒体水肿,且程度逐渐加重。逼尿肌NMJ透射电镜观察,B、C及D组可见其形态结构类似于A组,但线粒体及突触小泡的数量略少;E组可见明显退变的NMJ,突触小泡含量明显减少,伴有线粒体等细胞器减少;F组NMJ进一步退变,突触小泡含量进一步减少甚至缺如,细胞器减少或消失,并可见退变小体。Masson三色染色可见逼尿肌中结缔组织所占的比例在E、F组与A组间差异有统计学意义（P〈0.05）;且E、F组间差异亦有统计学意义（P〈0.05）。结论大鼠圆锥脊髓损伤术后10周可作为逼尿肌及其NMJ发生变化的时间节点,神经修复手术宜在此前完成。     

CONTINENCE MECHANISM OF THE ORTHOTOPIC NEOBLADDER: URODYNAMIC ANALYSIS OF ILEOCOLIC NEOBLADDER AND EXTERNAL URETHRAL SPHINCTER FUNCTIONS

Background: The main objectives of bladder substitution are the preservation of the upper urinary tract and maintenance of urinary continence. Orthotopic bladder substitution makes it possible to achieve urinary continence as well as normal passage of urine through the urethra. Creation of a low pressure reservoir and careful preservation of the distal sphincter mechanism are considered to be of utmost importance for the maintenance of urinary continence after orthotopic bladder Substitution. However, sphincter behavior after orthotopic bladder substitution has not been fully elucidated. The purpose of this study was to evaluate the vesicourethral continence mechanism after orthotopic bladder substitution in male patients. Methods: Urodynamic evaluation was performed in 14 male patients after cystoprostatectomy for bladder cancer and an ileocolic neobladder using a cecourethral anastomosis. Results: Good continence was achieved in 86% (12/14) of the patients during the day and in 79% (11/14) at night. On cystometry, maximum capacity of the neobladders was 434 ± 21 ml (mean ± SEM), and basal pressure at maximum capacity was 15.6 ± 0.9 cm water. Phasic neobladder contraction with amplitudes ranging from 14 to 40 (26.6 ± 2.7) cm water were noted in 11 of 14 patients. Sphincter electromyography demonstrated an increase in the frequency of action potentials of the external urethral sphincter during neobladder filling from empty to 80% of capacity (from 8.9 ± 1.6 to 14.6 ± 2.1 spikes per second; mean percentage increase, 64%, in patients with daytime continence). Maximum urethral closure pressure on urethral pressure profile was 49.9 ± 3.5 (range, 30 to 64) cm water in patients with daytime continence, while in two patients who were incontinent during the day and at night maximum urethral closure pressure was lower (16 and 24 cm water) and the recruitment of action potentials of the external urethral sphincter during neobladder filling was impaired (percentage increase, 15% and 20%). Conclusions: An ileocolic neobladder has characteristics of a low pressure reservoir with a satisfactory continence rate. The vesicourethral continence reflex is well preserved in patients with continence after orthotopic bladder Substitution.     

THE EFFECT OF SIMULATED BIRTH TRAUMA AND/OR OVARIECTOMY ON RODENT CONTINENCE MECHANISM. PART I: FUNCTIONAL AND STRUCTURAL CHANGE

PURPOSE: We examined the changes in the lower urinary tract after delivery, intravaginal ballooning and/or ovariectomy. MATERIALS AND METHODS: The study included 10 virgin and 48 primiparous pregnant rats. Cystometry and the stress/sneeze test were performed in virgin and postpartum rats shortly after delivery and at 8 weeks before sacrifice. Half of the delivered animals underwent intravaginal balloon dilation. Four weeks later half in each group underwent ovariectomy. The rats were subdivided into group 1--delivery, group 2--delivery plus balloon inflation, group 3--delivery plus ovariectomy and group 4--delivery plus balloon inflation plus ovariectomy. Tissues from the bladder, bladder neck, urethra and levator were collected, analyzed by electron microscopy, and immunostained for caveolin-1, caveolin-3 and neuronal nitric oxide synthase. RESULTS: Higher bladder capacity was detected in postpartum than in virgin rats. Urine leakage on stress/sneeze testing increased significantly in groups 2 and 4. Electron microscopy revealed a significant decrease in sarcolemma caveolae in the smooth muscle of the bladder and urethra in groups 2 to 4. In the bladder neck in group 3 caveolae were increased in smooth muscle. In groups 2 to 4 in the smooth muscle of the bladder and urethra caveolin-1 was significantly decreased. Caveolin-3 and neuronal nitric oxide synthase in striated muscle also significantly decreased in groups 2 to 4. CONCLUSIONS: These findings suggest that birth trauma simulated by ballooning and ovariectomy may contribute to stress urinary incontinence. The alteration in smooth muscle caveolae as well as the membrane protein caveolin may have a role in functional alterations caused by birth trauma and ovariectomy.     

A QUANTITATIVE STUDY OF ATROPINE-RESISTANT CONTRACTILE RESPONSES IN HUMAN DETRUSOR SMOOTH MUSCLE, FROM STABLE, UNSTABLE AND OBSTRUCTED BLADDERS

PURPOSE: The objective of the study was to quantify in vitro the magnitude of atropine-resistant contractions using human detrusor samples and to determine the cellular processes underlying these contractions. MATERIALS AND METHODS: Isometric contractile responses were measured in isolated strips of human detrusor muscle obtained from patients with i) stable, ii) unstable or iii) obstructed bladders. Preparations were electrically stimulated or exposed to carbachol and ATP in the superfusate. RESULTS: Force-frequency curves were shifted to the right in samples from unstable and obstructed bladders. These same tissue groups also showed significant atropine-resistant contractions which were abolished by the neurotoxin TTX, or the non-hydrolysable ATP analog, alpha,beta-methylene ATP, suggesting that these contractions were mediated by neurally released ATP. Sub-division of the patient group with unstable bladders demonstrated that those with neuropathic instability did not show atropine-resistance, whereas those with idiopathic instability or secondary instability after obstruction did show atropine-resistant contractions. The potency of carbachol in generating a contracture was significantly greater than ATP (mean EC50 0.65 microM and 151 microM respectively) however, for each agonist there was no difference in potency between the three patient groups. Direct muscle excitability was similar in all three patient groups. CONCLUSIONS: It is concluded that purinergic, atropine-resistant contractions are present in some types of dysfunctional bladder, and these are not caused by a differential sensitivity of the muscle to ATP and cholinergic agonists.     

SENSORY RECOVERY AFTER HAND REIMPLANTATION: A CLINICAL,MORPHOLOGICAL, AND NEUROPHYSIOLOGICAL STUDY IN HUMANS

Despite fairly good return of motor function, patients who have amputated hands reimplanted demonstrate poor sensory recovery and severe cold intolerance, two variables that are difficult to quantify reliably. In this study we wanted to find out if there is a correlation between morphological findings of sensory and sympathetic reinnervation and clinical and neurophysiological variables. Skin was biopsied from the reimplanted and corresponding area in the normal hands of eight patients who had sustained a hand amputation and subsequent reimplantation. The sections were immunostained using markers for both sensory and sympathetic nerve fibres. Comparison between the reimplanted and normal sides in each individual showed a mean loss of sensory immunoreactive nerve fibres of 30%, and for sympathetic immunoreactivity the loss was 60%. There was measurable two-point discrimination in the injured hand only in patients below the age of 40 years, corresponding to the better recovery of mechanical thresholds evaluated neurophysiologically for this age group. These results confirm the extensive loss of sensory nerve fibres after nerve injury, probably correlated to loss of sensory neurons. We have also shown that it is possible to correlate the results of clinical and neurophysiological evaluation with morphological results of skin reinnervation specific to the repaired nerve, and so improve the possibility for the quantification of sensory recovery.     

THE IN SITU ANTERIOR VAGINAL WALL SLING: PREDICTORS OF SUCCESS

PURPOSE: We assessed the outcome of the in situ anterior vaginal wall sling for stress urinary incontinence, identified any predictors of success and reviewed the current literature on this topic. MATERIALS AND METHODS: We identified all patients who underwent an isolated anterior vaginal wall sling procedure in a 16-month period. Charts were reviewed and telephone interviews were performed to assess the success rate of the procedure and identify parameters that may influence outcome. The pertinent literature was identified. RESULTS: Of the 42 patients identified 39 had evaluable data available. The overall success rate was 79.5% at an average 19-month followup. Abdominal Valsalva leak point pressure 50 cm. water or greater was identified as a significant predictor of success (p = 0.002). The success rate was 93% and 40% in patients with a Valsalva leak point pressure of 50 or greater and less than 50 cm. water, respectively. The pertinent literature was reviewed. CONCLUSIONS: The anterior vaginal wall sling is effective for stress urinary incontinence. In patients with a Valsalva leak point pressure of 50 cm. water or greater the success rate is 93%. We recommend the anterior vaginal wall sling procedure in these patients but different treatment in those with Valsalva leak point pressure less than 50 cm. water.     

大鼠急性胰腺炎时磷脂酶A2的变化及异搏定治疗作用的研究

目的　探讨大鼠急性胰腺炎 (AP)时胰组织磷脂酶A2 (PLA2 )的变化及异搏定治疗作用。方法　采用“十二指肠闭袢法”诱发AP大鼠模型设定AP组和异搏定组 ,对比观察AP组和异搏定治疗组PLA2 活性变化及胰组织病理学检查。结果　诱发AP 16小时和 2 4小时胰腺组织PLA2 活性 ,治疗组分别为 32 .34± 3 .87u和 35 .2 6± 4.5 2u ,AP组分别为 44.83± 5 .31u和 47.77± 5 .86u ,治疗组较AP组明显降低 ,病理改变减轻。结论　大鼠AP时存在PLA2 的活化 ,钙通道阻滞剂异搏定可抑制PLA2 的活化 ,推测对大鼠AP有一定的治疗作用。     

A COMPARISON OF THE MODE OF ACTION OF ATP AND CARBACHOL ON ISOLATED HUMAN DETRUSOR SMOOTH MUSCLE

PURPOSE: The objectives of the study were: i) to examine the ability of carbachol and ATP to raise intracellular [Ca2+] in isolated detrusor myocytes; ii) to determine the origin of the intracellular Ca2+ and iii) to address the question of whether the appearance of purinergic contractions in detrusor from unstable and obstructed human bladders is reflected in the sensitivity of the cell to the two agonists. MATERIALS AND METHODS: Intracellular Ca2+ transients generated by extracellular ATP and carbachol were recorded from isolated human detrusor myocytes. Cells were dissociated by collagenase disruption of the biopsy. Intracellular Ca2+ was measured by epifluorescence microscopy using Fura-2 and electrophysiological recordings were made with patch electrodes. RESULTS: In cells from stable bladder biopsies the half-maximal concentrations (EC50) for ATP and carbachol to generate Ca2+ transients were 0.10 and 0.25 microM respectively. With cells from unstable bladders the EC50 values for both agonists and the magnitude of the Ca2+ transients were not significantly different from those obtained in cells from normal bladders. The transient in ATP was preceded by a transient depolarisation generated by a large inward current. The carbachol-Ca2+ transient was independent of changes to membrane potential, except in a subset of cells where complex membrane potential changes followed the rise of intracellular Ca2+. The ATP-Ca2+ transient was partially abolished by nicardipine and completely abolished by zero-Ca solutions, the carbachol-Ca2+ transient was unaffected by nicardipine and less completely attenuated by zero-Ca solutions. Prior exposure to caffeine suggested that the carbachol-Ca2+ transient, but not the ATP-Ca2+ transient, originated from intracellular stores. CONCLUSIONS: It is concluded that both agonists are equipotent in increasing intracellular Ca2+, but by different routes. The generation of purinergic contractions in detrusor from unstable bladder is not due to altered sensitivities of the detrusor myocyte to ATP or cholinergic agonists.     

THE EFFECTS OF TRANSURETHRAL NEEDLE ABLATION AND RESECTION OF THE PROSTATE ON PRESSURE FLOW URODYNAMIC PARAMETERS: ANALYSIS OF THE UNITED STATES RANDOMIZED STUDY

PURPOSE: We evaluated the effects of transurethral needle ablation and prostate resection on pressure flow urodynamic parameters in men with benign prostatic hyperplasia (BPH), compared symptomatic and objective parameters of efficacy 6 months after initial treatment, and determined whether urodynamic assessment may predict symptomatic improvement. MATERIALS AND METHODS: We enrolled 121 patients with clinical BPH, American Urological Association symptom index of 13 or greater and maximum urinary flow of 12 ml. per second or less in a randomized study comparing transurethral needle ablation to prostate resection at 7 institutions in the United States. Patients underwent baseline and followup assessments at 6 months, including pressure flow studies. RESULTS: Patients who underwent each procedure had statistically and clinically significant improvement in symptom index, BPH impact index and quality of life score. After needle ablation and prostate resection maximum flow improved from 8.8 to 13.5 (p<0.0001) and 8.8 to 20.8 ml. per second (p<0.0001), detrusor pressure at maximum flow decreased from 78.7 to 64.5 (p = 0.036) and 75.8 to 54.9 cm. water (p<0.001), and the Abrams-Griffiths number decreased from 61.2 to 37.2 (p<0.001) and 58.3 to 10.9 (p<0.001), respectively. At 6 months the differences in transurethral needle ablation and prostate resection were significant in terms of maximum flow (p<0.001) and the Abrams-Griffiths number (p<0.001) but not detrusor pressure at maximum flow or symptom assessment tools. The presence or absence of urinary obstruction at baseline did not predict the degree of symptomatic improvement in either treatment group. CONCLUSIONS: Transurethral needle ablation and prostate resection induce statistically and clinically significant improvement in various quantitative symptom assessment questionnaires at 6 months. The parameters of free flow rates and invasive pressure flow studies also significantly improve after each treatment. However, transurethral prostate resection induces a significantly greater decrease in the parameters of obstruction. Baseline urodynamic parameters do not predict the degree of symptomatic improvement and they may not be helpful in patient selection for transurethral needle ablation.     

EFFECTS OF VESICOCOLIC ANASTOMOSIS ON THE PROLIFERATION OF COLONIC MUCOSA IN A RAT MODEL

The effects of diverting the urinary stream into a defunctioned segment of the distal colon has been studied in a rat model. Distal rat colon was defunctioned using the Hartmann's procedure and a vesicocolic anastomosis was performed 14 days later. The distal colon was harvested after 10 days following the administration of a vinblastine mitotic block either 1 or 3 h before death. Both the mean crypt cell proliferation and the crypt length were increased significantly in the colonic mucosa exposed to urine when compared with the control defunctioned colon or to the functional unexposed proximal colon. An active fraction was obtained from human urine by elution from a diethylaminoethyl sepharose column using 1 mol/L NaCl. This fraction was administered intraluminally to defunctioned rat colons using Alzet miniosmotic pumps. In these animals the crypt cell production rate was significantly increased compared with the control animals. Although the crypt length did not increase significantly in these animals the atrophy normally seen in defunctioned colonic mucosa did not occur. The identity of the active molecule in this urine fraction is still being determined.