Said A. Awad

Oxybutynin Versus Propantheline in Patients with Multiple Sclerosis and Detrusor Hyperreflexia

Hyperreflexia is the most common urological finding in patients with multiple sclerosis. A prospective randomized study was done to compare the effectiveness of 2 commonly used drugs, oxybutynin and propantheline. Of the 34 patients entered into the trial 19 were treated with oxybutynin and 15 with propantheline. The urological symptoms (frequency, nocturia, hesitancy, urgency and urge incontinence) were graded according to severity from 0 to 3. Patients with urinary infection were excluded. Urodynamic examination, consisting of cystometrography and electromyography, was performed in all patients before treatment. Both groups of patients had comparable neurological, urological and urodynamic status before treatment. In 4 patients (21 per cent) treated with oxybutynin and in 4 (27 per cent) treated with propantheline side effects were so severe that the treatment had to be discontinued. Symptomatic response to oxybutynin was good in 10 patients (67 per cent), fair in 2 (13 per cent) and poor in 3 (20 per cent). Propantheline produced good symptomatic results in 4 patients (36 per cent), fair in 1 (9 per cent) and poor in 6 (55 per cent). The mean increase in maximum cystometric capacity on cystometrography was significantly larger in the oxybutynin group than in the propantheline group (144 +/- 115 versus 35 +/- 101). Our results indicate that oxybutynin is more effective than propantheline in the treatment of detrusor hyperreflexia in patients with multiple sclerosis.

Relationship between neurological and urological status in patients with multiple sclerosis.

The relationship between neurological urinary symptoms and urodynamic findings in patients with multiple sclerosis was examined. The duration of multiple sclerosis was significantly longer in patients with urinary symptoms. The presence of urinary symptoms correlated with the severity of the pyramidal or sensory lesions and the total disability score. Cystometrograms revealed detrusor hyperreflexia in 67 per cent of the patients, areflexia in 21 per cent and a normal detrusor in 12 per cent. Somatic dyssynergia was found in 20 of the 39 patients whose examination revealed clear-cut results. Positive correlation was found between urge incontinence and detrusor hyperreflexia, and between hesitancy and detrusor areflexia but no relationship was found between urological symptoms and sphincter function. Analysis of the neurological lesions in relation to the cystometric findings revealed a positive correlation among pyramidal lesions, detrusor hyperreflexia and detrusor areflexia, and between cerebellar lesions and detrusor areflexia. The correlation between detrusor dysfunction and high total disability score disappeared when patients with high pyramidal scores were excluded. No correlation could be detected between somatic dyssynergia and the various neurological lesions.

Experimental evidence for a central nervous system site of action in the effect of alpha-adrenergic blockers on the external urinary sphincter

The present study was done to test the hypothesis that alpha-adrenoceptor blocking drugs (phentolamine and prazosin) could interfere with somatic control of the external sphincter through an action in the central nervous system. Stimulation of the hypogastric nerve in the chloralose-anesthetized cat caused a urethral constriction which could be antagonized by alpha-receptor blockers. However, the constriction produced by stimulation of the S1 or S2 ventral root was completely resistant to alpha blockade. The drugs therefore had the expected action against sympathetic stimulation of the urethra but had no peripheral effect on the somatic component. The central effect of these drugs was investigated by recording urethral perfusion pressure responses, or compound action potentials on the central cut end of the pudendal nerve, evoked by stimulation of the contralateral pudendal or pelvic nerve. The urethral constriction produced by stimulation of the central cut end of 1 pudendal nerve was antagonized by both prazosin and phentolamine. Action potentials evoked on the pudendal nerve by stimulation of the central cut end of the contralateral pudendal or pelvic nerve were substantially inhibited by prazosin. Phentolamine produced a more variable blockade of the pudendal-pudendal reflex. The results strongly indicate that these alpha-adrenoceptor antagonists and especially prazosin can influence pudendal nerve-dependent urethral responses through a central nervous system action and not through a peripheral mechanism.

Analysis of imaging modalities, staging systems, and prognostic indicators for renal cell carcinoma

A retrospective analysis of 314 patients with renal cell carcinoma was done focusing mainly on imaging modalities and prognostic significance of tumor stage using both the Robson and TNM systems. Computerized tomography (CT) scan proved to be the most effective modality for staging. Overall staging accuracy was 62 and 68 percent for TNM and Robson staging, respectively, and understaging was more frequent than overstaging. The actuarial five-year survival using the Robson system was 73 percent for Stage A, 68 percent Stage B, 51 percent Stage C, and 20 percent Stage D. The main limitation of the Robson system is the heterogeneity of the Stage C group which includes patients with renal vein and those with nodal involvement with a significant difference in survival. The survival by the TNM system showed no difference in those with T1, T2, T3a and T3b disease but a significant difference in those with T3c or T4a. One hundred sixteen patients (37%) presented with metastatic disease with a median survival of seventeen months (range 2-204) for those with solitary metastasis and six months (range 1-132) for those with multiple metastases (the difference was not statistically significant). Except for anecdotal cases, nephrectomy with or without treatment of the metastases did not seem to affect survival significantly. The presence of spindle cell, alone or in association with clear or granular cell, affected the prognosis adversely. Thirty-one patients had their tumors identified incidentally. Their stage at diagnosis was earlier than the symptomatic group (Stage T1-T2: 77% vs 34%), and there was a significant difference in the disease-free survival at fifty-four months between the two groups (79% vs 57%, respectively).

Factors that Influence the Incidence of Detrusor Instability in Women

Detrusor instability was examined in 108 women with urinary incontinence. The presence of instability correlated with the symptoms of urge incontinence in 81 of 99 patients. The technique of the cystometrogram also proved important and minor variations significantly altered the incidence. Finally, there seems to be a significant correlation between reduced urethral closure as measured by the urethral pressure profile and instability, suggestive of a causal relationship. An understanding of the factors that affect the incidence of detrusor instability will help to place it in the right perspective in terms of its diagnostic value and pathogenesis.

External sphincter dyssynergia: an abnormal continence reflex.

Some of the characteristics of detrusor-external sphincter dyssynergia were examined in 14 patients with traumatic upper motor neuron lesions within 44 weeks of injury. The sacral evoked response latencies of the male patients were shortened at any time after injury. A continence reflex could be demonstrated in most patients at any time after injury. Comparing averaged values for the group at 4-week intervals, resting pressure at the external urethral sphincter and post-void residual volumes reached nadirs at 12 weeks while voiding efficiency peaked at this time. Thus, voiding function appears to be optimal 12 weeks after injury. During reflex detrusor activity, increases in external urethral sphincter electromyographic activity and external urethral sphincter pressure were associated clearly with a positive slope of the intravesical pressure trace, whereas decreases in both parameters were associated with a negative slope. Voiding occurred only during a negative slope. Although propantheline induced detrusor areflexia, episodic peaks in external urethral sphincter pressure and electromyographic activity continued to occur. We propose that external sphincter dyssynergia, which is independent of detrusor contraction, is the continence reflex exaggerated owing to the loss of supraspinal influences. We believe that the multiple patterns of dyssynergia described previously by others are variations, largely owing to technique, of the single pattern we have observed. The observation of synergic-like urethral responses in some patients during a negative slope of the intravesical pressure, even with complete suprasacral spinal lesions, implies existence of a pathway for synergic-like voiding in the spinal cord.

Idiopathic Reduced Bladder Storage versus Interstitial Cystitis

Idiopathic reduced bladder storage is a term we used to describe a group of patients who have subjective and objective evidence (by cystometrogram) of diminished bladder capacity without a demonstrable cause. We performed a prospective study comparing this condition with interstitial cystitis. We studied the clinical, urodynamic and histological features, and response to therapy in these 2 groups of patients. No statistical difference was found between the incidence of irritative bladder symptoms and/or suprapubic pain. Only minor differences were noted in the maximum cystometric capacity and incidence of bladder instability. Histological and immunofluorescent features were analogous. Also, the reduced bladder storage and interstitial cystitis patients responded similarly to bladder dilation and pharmacological therapy. Augmentation ileocystoplasty used in patients refractory to medical treatment produced comparable results in the short term. Based upon similar findings, it is likely that these 2 conditions represent the same disease entity with the only difference being the cystoscopic findings.

The significance of prior anti-incontinence surgery in women who present with urinary incontinence

In a series of 148 consecutive female patients with urinary incontinence 62 (group 1) had undergone 1 or more prior anti-incontinence operations and 86 (group 2) had none. After clinical and urodynamic assessment the incidence of detrusor instability in the 2 groups (44 and 51 per cent) was not significantly different but the incidence of stress incontinence in group 1 was significantly greater than in group 2 (58 and 38 per cent, p less than 0.05). Of the 69 patients with a final diagnosis of stress urinary incontinence 45 (24 in group 1) had surgery and were followed for a mean of 17 months postoperatively. Of the patients 43 (95 per cent) were cured or improved. A total of 17 patients (71 per cent) in group 1 and 3 (17 per cent) in group 2 had a fascial sling. Eight patients had symptomatic postoperative detrusor instability and all had a fascial sling. There also was a significant decrease in postoperative peak flow rate (p less than 0.01) in these patients. Neither the number of previous operations nor the presence of preoperative detrusor instability had a significant effect on the incidence of postoperative detrusor instability.

Bladder and Urethral Function and Supersensitivity to Subcutaneously Administered Bethanechol in Cats with Chronic Cauda Equina Lesions

The failure of bethanechol chloride to induce voiding in patients with neurogenic bladder, despite a positive bethanechol test, is being reported more frequently. An experimental model was designed in the cat to study the response of the bladder and urethra to subcutaneous and intraarterial bethanechol after complete and partial sacral decentralization. Complete sacral rhizotomy abolished the micturition reflex. Basal urethral perfusion pressure was not affected by complete sacral rhizotomy and a significant part of this basal urethral pressure remained sympathetically mediated. However, the urethral constriction response to bladder filling was lost in half the cats with complete lesions. Bladder and urethral supersensitivity to bethanechol chloride in cats with complete lesions was characterized by a shift to the left of the i.a. dose-response curve, and by the presence of responses to doses of s.c. bethanechol chloride which are subthreshold in normal cats. The urethra also showed exaggerated constriction responses to i.a. and s.c. bethanechol. After complete lesions a part of the bladder and urethral responses to s.c. bethanechol was adrenergically mediated and exerted through the vesicourethral short neuron system. The rest of the response was due to stimulation of urethral muscarinic receptors. Partial sacral lesions were compatible with a micturition reflex and the urethra retained its reflex response to bladder distension. After partial decentralization the bladder and urethra also showed responses to subthreshold doses of s.c. bethanechol. While the bladder response to s.c. bethanechol did not show a significant adrenergic component in cats with partial lesions, most of the urethral response was sympathetically mediated. In conclusion, complete cauda equina lesions result in an areflexic detrusor with frequent loss of the urethral responsiveness to bladder filling. Urethral supersensitivity to s.c. bethanechol might be responsible for a non-voiding outcome after bethanechol injection in patients with complete cauda equina lesions, despite a positive bethanechol test. Because the detrusor reflex is preserved and the urethra is less supersensitive to bethanechol after partial cauda equina lesions, these may represent a better indication for bethanechol therapy than do complete ones.

The Pathophysiology of Contractile Activity in the Chronic Decentralized Feline Bladder

Autonomous wave activity occurs in the decentralized bladder and may contribute to upper tract damage and incontinence. In order to clarify the poorly understood pathophysiology and neuropharmacology of autonomous waves, cats were prepared with L7-S3 ventrodorsal rhizotomy alone or with L7-S3 ventral rhizotomy with and without total sympathectomy. The incidence of autonomous waves was < 15% 12 weeks after ventral or ventrodorsal rhizotomy, but acute sympathectomy at 13 weeks increased the incidence to 58% in these groups. With chronic sympathectomy the incidence was 100%. This suggests that the waves arise locally via a mechanism which is independent of L7-S3 dorsal roots, due to lack of a suppressive sympathetic pathway. Autonomous waves were inhibited by atropine after acute sympathectomy and by prazosin after chronic sympathectomy, but increased inhibition occurred after both drugs in either case. Adrenergic neuron depletion with 6-hydroxydopamine enhanced wave activity, which was incompletely inhibited by subsequent atropine. This implies that the peripheral reflex pathway has facilitatory alpha 1-adrenergic, muscarinic and also noncholinergic nonadrenergic elements. Clinically, sensory or sympathetic damage caused incontinence, but sympathectomy also caused high pressure waves, which may cause upper tract damage and treatment resistant incontinence in patients.