[Minimally invasive treatment of female urinary incontinence due to sphincter incompetence]. / Trattamento mini invasivo della incontinenza urinaria femminile da deficit sfinterico.

Urinary incontinence is one of the most frequent diseases in female urology. There are hundreds of therapeutic opportunities without sure outcomes, because of lack of the etiologic cause. Transurethral injection has good results in around of the 60% of the cases with minimal invasivity, good patients compliance, ripetitivity of the method. From 1993 to 1997 we treated 44 ladies with urinary incontinence due to low pressure of closure of the sphincter: 13 patients (29.55%) disease free, 17 (38.64%) meliorate.

Cisapride enhances detrusor contractility and improves micturition in a woman with lazy bladder.

A 32-year-old woman with lazy bladder was treated with cisapride (10 mg q.i.d.) for three weeks, obtaining a progressive improvement of the symptomatology and urodynamic parameters, and the return to pretreatment conditions after drug withdrawal. This case agrees with the evidence that cisapride potentiates the release of acetylcholine from postganglionic cholinergic nerves in the human isolated detrusor by activating 5-HT4 receptors, i.e. through the same mechanism responsible for its gastrointestinal prokinetic action. It is concluded that selective 5-HT4 agonists could be potentially useful to improve bladder emptying in micturition disorders associated with detrusor hypocontractility.

A re-appraisal of the nature of the atropine-resistant contraction to electrical field stimulation in the human isolated detrusor muscle.

We investigated whether in human isolated detrusor strips the atropine-resistant contractile response to electrical field stimulation was mediated by ATP (or a related purine), as previously shown in the urinary bladder of other mammalian species. Electrical stimulation (1-50 Hz for 5 s at 1 min intervals, 0.1 ms pulse width, 60 V) elicited reproducible, frequency-dependent twitch contractions, which were markedly reduced by atropine (10 microM). Tetrodotoxin (TTX: 1 microM) inhibited contractile responses to a similar degree. When applied together, atropine and TTX caused an inhibition which was superimposable to that caused by either drug alone. The TTX-resistant contractions were totally unaffected by omega-conotoxin GVIA (omega-CTX: 0.1 microM). The atropine-resistant contractions were unaffected by the P2-purinoceptor antagonists suramin (300 microM) and PPADS (30 microM), at concentrations which virtually suppressed the contractile response induced by applied ATP (10 microM(-1) mM). As previously described, antagonism of the ATP-induced contractions by suramin (30, 100, 300 microM) and PPADS (3, 10, 30 microM) was insurmountable, with apparent 'pA2' values (calculated at the lowest antagonist concentrations) of 4.9 and 5.2, respectively. It is concluded that, under our experimental conditions, the non-cholinergic (atropine-resistant) component of the excitatory transmission in the human detrusor is not mediated by neural release of ATP, in spite of the presence of excitatory P2-purinoceptors on the effector cells. The TTX- and omega-CTX-resistant, non-cholinergic component might be related to the release of unknown transmitter(s) through a mechanism independent of both Na+- and N-type Ca2+-channels. More likely, the atropine-resistant component may reflect direct smooth muscle excitation since the human detrusor has a very short chronaxie (Sibley 1984).

Correction of complete urogenital prolapse with infibulation.

OBJECTIVE: The clinical case presented herein is part of a study intended to demonstrate the validity of infibulation, either alone or combined with bladder neck suspension, for correction of genital prolapse associated with urinary disturbances (incontinence, urine retention) in elderly patients whose general condition does not permit the use of prolonged anesthesia or major destructive surgery. METHODS: Urodynamic and echographic tests are carried out before and after the operation to evaluate changes in mictional kinetics and postmictional residues. RESULTS: To date, four other cases have benefited from the treatment described. CONCLUSION: While no definitive conclusions can be drawn from such a limited number of cases, they do however encourage continued experimentation given the frequency of the problem and its social importance.

[Replacement bladders in Oltrepo]. / Le vesciche di sostituzione in Oltrepo.

In our Department we performed 269 radical cystectomies from January 1985 to April 1996. As regard the urinary diversion 64 patients were undergone to a cutaneous ureterostomy; in 137 we performed a Wallace uretero-intestinal anastomosis; in 6 a Mauclaire rectal diversion; in 12 patients a Mainz Pouch II and 50 selected patients (44 man and 6 ladies) we performed a Vesica Ileale Padovana (VIP). In these cases the stage was lowly, good renal function, no are hydronephrosis. The patients were motivated for a long follow-up and preoperatively undergone to urethral biopsies. We have had the following complications: an early bowel obstruction, 4 wound infections and for the long term follow-up 2 inguinal hernias, 1 laparocele, 5 patients with bilateral hydronephrosis. At the moment we cannot state a correct oncological report for the short follow-up: only 1 patient died after 18 months for a pelvic relapse. We can suggest that VIP is a good solution for the ladies: its mandatory to take care of the urethra and the pelvic floor for a good continence limiting the lymphadenectomy. We haven't any suggestions about the deep of the colpectomy and the opportunity of the vaginal suspension.

Neural 5-HT4 receptors in the human isolated detrusor muscle: effects of indole, benzimidazolone and substituted benzamide agonists and antagonists.

1. In strips of human isolated detrusor muscle, the 5-hydroxytryptamine (5-HT) receptor (5-HT4) that mediates facilitation of neuromuscular cholinergic transmission was further characterized by using 5-HT and a series of ligands known for their 5-HT4 agonist (5-methoxytryptamine: 5-MeOT, cisapride, (R,S)-zacopride, BIMU 8) or antagonist (RS 23597, GR 125487, DAU 6285) properties. 2. In the presence of methysergide (1 microM) and ondansetron (3 microM) to isolate pharmacologically the 5-HT4 receptors, 5-HT (0.3 nM-1 microM), 5-MeOT (10 nM -30 microM), BIMU 8 (10 nM-3 microM), cisapride (0.1-10 microM) and (R,S)-zacopride (0.1-30 microM) potentiated cholinergic contractions to electrical field stimulation in a concentration-dependent manner. RS 23597 (10 nM-10 microM), a competitive 5-HT4 receptor antagonist in other systems, also showed agonist properties. The following rank order of potency as an agonist was obtained: 5-HT (pEC50 = 8.0) > RS 23597 (7.0) = BIMU 8 (6.9) > or = cisapride (6.6) > 5-MeOT (6.0) > or = (R,S)-zacopride (5.7). Relative to 5-HT (intrinsic activity = 1), 5-MeOT acted as a full agonist (1.03), while BIMU 8 (0.76), (R,S)-zacopride (0.61), RS 23597 (0.60) and cisapride (0.41) behaved as partial agonists. 3. The potentiation by 5-HT was competitively antagonized by the selective 5-HT4 receptor antagonist GR 125487 (0.3-3 nM) with a pA2 estimate of 9.75 (Schild slope of 1.09), and by DAU 6285 (1 microM; pK3 = 6.45). Additionally, GR 125487 (3 nM) antagonized the responses to 5-MeOT (pKB = 9.72) and reversed the potentiation induced by RS 23597. As an antagonist, RS 23597 (10, 30 and 100 nM) inhibited the response to 5-HT. In addition, 30 and 100 nM RS 23597 reduced the 5-HT response maximum by 30 and 50%, respectively. The pKB value calculated at 10 nM was 8.0. 4. Thus, in the human isolated detrusor muscle, the 5-HT4 receptors mediating facilitation of cholinergic neuromuscular transmission are activated by indoleamines (5-HT, 5-MeOT), substituted benzamide (cisapride, (R,S)-zacopride), benzoate (RS 23597) and benzimidazolone (BIMU 8) derivatives. The activities (in terms of both potency and efficacy) of most agonists, as well as the affinity estimates of the antagonists GR 125487 and DAU 6285, are comparable to those found in other peripheral tissues. Exceptions are RS 23597, which acted either as a partial agonist or as an antagonist of the response to 5-HT1 and 5-MeOT that showed an unusually low potency. The latter findings may be ascribed to differences in the efficiency of receptor coupling mechanisms and/or in the molecular structure (i.e. splice variants) of the 5-HT4 receptor.

[pT1G3 tumor of the bladder]. / Il tumore della vescica pT1 G3.

The management of the superficial bladder tumor is commonly performed by transurethral resection (TUR) and a following chemotherapy or immunotherapy with exception of Tis. A lot of doubts and questions raise in the management of pT1G3 bladder tumor (BT) for the high grade of recurrencies and progressions. Our experience from 1984 to 1994 about 109 patients (pts) with pT1G3 BT undergone to radical cystectomy (47 pts) and TUR (62 pts) allows us to state that when Tis is present a radical cystectomy is mandatory, but the TUR option must be followed to frequent and accurate random biopsies in order to discovery foci of Tis. In the case of pT1G3 monofocal there is always a therapeutic disconcerting.

[Incision of the bladder neck]. / L'incisione del collo vescicale.

Transurethral incision of the bladder neck (TUIBN) is a simple method of relieving bladder outflow obstruction producing similar results to transurethral resection of the prostate (TURP) when obstruction is caused by small prostate (< 40 gr). The complication rate is low and retrograde ejaculation has a far less degree than after TURP, so less bleeding. The major advantage of TUIBN are: short hospitalization, less bladder neck contractures. The drawback of the absence of prostate tissue for an earlier diagnosis of cancer can be balanced performing a biopsy before treatment.

[Intraurethral devices in the treatment of prostatic obstruction]. / I dispositivi intrauretrali nella terapia dell'ostruzione prostatica.

We describe our experience (started in 1988) about the use of urethral stents implanted into patients with prostatic outflow obstruction, unit for prostatic surgery. This technique has been applied successfully with few complications. The use of different stents (Fabian's spiral, mesh stent) allowed us to get the right choices in the different shapes of prostatic urethra and in the different expectancies of the patients. Lastly we can offer an useful recommendation about the patients evaluation and the stents selection.

Characterization of the 5-HT receptor potentiating neuromuscular cholinergic transmission in strips of human isolated detrusor muscle.

In human isolated detrusor strips, submaximal contractile responses evoked by electrical stimulation were resistant to hexamethonium (30 microM) and abolished by tetrodotoxin (0.6 microM) and hyoscine (1 microM), indicating the activation of postganglionic cholinergic nerves. In methysergide (1 microM) and ondansetron (3 microM) pretreated tissues, 5-hydroxytryptamine (5-HT) (0.3 nM-1 microM) caused a concentration-dependent increase in the amplitude of contractions (pEC50 = 8.1), which was antagonized by the selective 5-HT4 receptor antagonist GR 113808 (3, 10 and 30 nM) in a competitive manner. Schild analysis yielded a pA2 estimate of 8.9, a value comparable to that reported for GR 113808 in other animal and human peripheral tissues (8.8-9.7). Our findings indicate that neuromuscular cholinergic transmission in human isolated detrusor muscle is facilitated by neural 5-HT receptors belonging to the 5-HT4 subtype. The human urinary bladder can thus be regarded as an additional site in which 5-HT4 receptors are distributed.

[Experience with rIL2 in the treatment of metastatic renal carcinoma]. / Esperienze con rIL2 nel trattamento del carcinoma renale metastatizzato.

Eight patients with metastatic renal cell carcinoma, all nephrectomized, were treated with rIL2 continuous i.v. infusion or subcutaneous administering (+/- INF). Six patients alive. Continuous infusion is possible event out of Intensive Care Unity. Adverse effects, sometimes serious, rapidly decrease with suspension. Subcutaneous infusion is more easy and with lower adverse effects. We don't know methodic of which can give more security.

[Interferon and vinblastine in advanced renal carcinoma]. / Interferone e vinblastina nel carcinoma renale avanzato.

19 patients with renal adenocarcinoma and mets were treated with INF alfa 2b (10 x 10(6) U/m square s.c. three times weekly) plus VBL (0.1 mg/kg every 3 weeks). We followed up the patients for 12 weeks with monitoring of major parameters. The outcomes have been positive in 16.6% of the cases with mean survival of 20.7 months. We point out the efficacy in lung mets. The outcomes of therapy with INF alfa 2b plus VBL are unsuccessful and we state that an alternative solution could be interleukin 2.