Search

Testicular cancer (TC) is the most common solid tumour in white males aged 20–34 years, and its incidence has doubled over the past 40 years. Some risk factors for TC have been proposed, such as cryptorchidism, infertility and testicular dysgenesis. However, the causes of TC remain still largely unknown. Recently a genetic basis for TC has been proposed, but specific genetic alterations have not been identified. The risk of TC is markedly increased in subjects with androgen insensitivity and some authors have suggested that mutations in the androgen receptor (AR) gene or disorders of CAG and GGC repeats could be related to TC. However, definitive data have not been produced. In this study, we analysed the AR gene for mutations and CAG and GGC triplets in exon 1 in 123 patients affected by TC. In three patients (2.3%) we found a mutation in the AR gene, two of which represent a novel mutation. Evaluation of CAG and GGC repeat numbers showed no difference with respect to controls when these variables were analysed separately. However, when joint distributions of CAG and GGC were considered, we found that the combination CAG=20/GGC=17 was significantly more frequent in TC patients (8.1%) with respect to controls (1.7%, P

Objective Different etiopathological mechanisms of enuresis are today under study, and different therapies and drugs have been proposed. The Italian Multicentric Trial was undertaken in twelve pediatric and urological centers in order to assess the efficacy of two of the most popular drugs, desmopressin (DDAVP) and oxybutynin. Methods 114 enuretic patients were enrolled in the study. After a 2-week observation period, 66 patients with primary monosymptomatic enuresis were treated with DDAVP, 30 micrograms/day intranasally, for 6 weeks, 48 patients with enuresis and voiding dysfunction were randomly assigned to a protocol with oxybutynin alone or oxybutynin plus DDAVP. The efficacy of the two drugs was measured in terms of reduction of wet nights per week during the 6-week treatment period and a 2-week follow-up period. Children with 0-3 dry nights/week were considered as nonresponders. Results Patients with monosymptomatic enuresis treated with DDAVP reported a significantly lower number of wet night during treatment than during the baseline period, with 79% showing a 'good' (6-7 dry nights/week) or 'intermediate' response (4-5 dry nights/week). Of the patients with diurnal voiding disturbances and enuresis, those treated with oxybutynin alone had a 54% success rate. The patients treated with both oxybutynin and DDAVP showed a better response, with a 71% rate of success. Conclusions The efficacy of the two drugs is confirmed in patients carefully selected on the clinical basis of voiding disturbances. In patients with enuresis and voiding dysfunction, the reduced urinary output and the lower bladder filling rate due to DDAVP can reduce uninhibited bladder contractions, thus enhancing the oxybutynin action.

Many parameters are available for evaluating patients with benign prostatic hypertrophy (BPH) in order to assess the necessity for treatment and to evaluate results. At present there is no real agreement on their order of importance. This paper tries to define from a theoretical and practical point of view the role of the following parameters: symptoms; symptom scores; visual scores; time/voided volume chart; prostate size; uroflowmetry, nomograms for flow; residual urine; pressure/flow study; mathematical and computer processing of pressure/flow study. The Author underlines the critical role of invasive urodynamics (pressure/flow study) in categorizing patients as obstructed or non-obstructed, in grading the severity of outflow obstruction and in evaluating the pattern of detrusor contractility. Present studies to evaluate the results of old and recent treatments should include invasive urodynamics in order to obtain homogeneous groups of patients and to overcome the prevailing empiricism.

The authors report 2 cases of localized xanthogranulomatous pyelonephritis (XGP) in which computed tomography (CT) permitted to raise a motivated clinical suspicion of inflammatory disease: the surgical exploration documented absence of neoplasm and allowed a conservative therapy implying only the removal of the mass. A literature review confirms that some CT signs in XGP permit differentiation from carcinoma. If they are present, in unifocal cases of disease, the authors suggest a limited surgical approach and a therapeutic strategy as conservative as possible.

1. 5-Hydroxytryptamine (5-HT) is able to potentiate the contractions induced by electrical field stimulation of pieces of human isolated urinary bladder. On the basis of available selective 5-HT agonists and antagonists, we have further investigated the receptors involved and their site of action. 2. 5-HT produced a concentration-dependent increase of the contractile response to electrical field stimulation from 0.1 nM to 1 microM. At higher concentrations (up to 100 microM) the effect decreased. These activities were mimicked by a variety of 5-HT agonists, for which the following rank order of potency was found: 5-HT greater than alpha-methyl 5-HT greater than 5-methoxytryptamine greater than 5-carboxamidotryptamine greater than 2-methyl 5-HT much greater than GR 43175. In addition the gastro-prokinetics agents metoclopramide, cisapride and the 5-HT3 antagonist ICS 205-930 behaved as 5-HT agonists, their EC50 values being 2.3, 0.3, and 0.5 (microM) respectively. 3. The 5-HT potentiating effect was resistant to antagonism by ondansetron (1 microM) and cyanopindolol (1 microM), selective 5-HT3 and 5-HT1A/1B antagonists respectively. The 5-HT2 antagonists ketanserin (1 microM), spiperone (1 microM) and methysergide (1 microM) also showed a weak inhibitory activity. Methiothepin (0.1-1 microM) antagonized only the inhibitory effect of 5-HT. Metoclopramide (0.1-1 microM), cisapride (0.01-0.1 microM) and ICS 205-930 (0.3-3 microM) all produced a rightward displacement of the 5-HT response curve with concomitant reduction of the maximum response. The pA2 values calculated were 7.4, 8.5 and 7.0 respectively. The antagonism of metoclopramide was receptor specific and was not apparently related to interactions with dopaminergic activity since domperidone showed no antagonism of 5-HT, and metoclopramide, itself, did not antagonize the potentiating effect of prostaglandin F2a.4. The receptor involved in the potentiating effect of 5-HT may be located prejunctionally because 5-HT did not potentiate responses to acetylcholine (ACh) or electrical field stimulation with the parameters of direct muscle excitation. Also, since the 5-HT potentiating effect was blocked by atropine, it may be attributed to a release of ACh.5. This study suggests that in the human urinary bladder 5-HT causes two opposite effects on the contractile response to electrical field stimulation. A potentiating effect at low concentrations due to an interaction with an atypical receptor, different from the classical 5-HT1, 5-HT2 or 5-HT3 subtypes and an inhibitory effect at greater concentrations probably due to an interaction with 5-HT1-like receptors. The possibility that this atypical receptor possesses some characteristics of those found in other isolated preparations like guinea-pig ileum, rat oesophagus and mouse embryo colliculi neurones is discussed.

Overactive bladder (OAB) affects an estimated 49 million people in Europe, but only a minority receive appropriate treatment. Others are bothered by unacceptable levels of symptoms that severely impair their quality of life and represent a significant financial burden to themselves and to their healthcare providers. Recently updated guidelines from the International Consultation on Incontinence (ICI) and the European Association of Urology (EAU) take account of important new developments in the management of bladder problems in both primary and secondary care. However, local implementation of previous guidance has been variable, with many patients with OAB and other bladder problems failing to gain full benefit from current clinical and scientific understanding of these conditions. The recent expansion of the range of treatments available for OAB and stress urinary incontinence makes it especially important that physicians become aware of the differential diagnosis of these conditions - the questions they need to ask, and the investigations which will help determine the most appropriate course of action.

The efficacy and safety of using alpha(1)-adrenergic blockers for treating primary bladder neck obstruction in young and middle-aged men was assessed as the first therapeutic step, before surgery, in a symptomatic non-neurogenic selected group of patients.From January 1995 to December 2001, primary bladder neck obstruction was diagnosed in 41 men whose average age was 43 years. All of them were evaluated by a complete clinical history, American Urological Association (AUA) symptom score index, physical examination, uroflowmetry, transabdominal ultrasound prostatic volume determination, ultrasound post-void residual determination, videourodynamics including pressure-flow analysis and upper urinary tract screening with renal ultrasound or an excretory urogram. A full daily dose of alpha(1)-adrenergic blockers (alfuzosin or tamsulosin) was administered for at least 6 months. Successful treatment was defined as improved symptoms, voiding diary, maximum flow rate and pressure-flow parameters. Patients who did not gain improvement of symptoms with pharmacological treatment were offered surgery.Overall, pharmacological treatment was successful in 29/41 patients (70.7%) whereas bladder neck endoscopic incision was mandatory in 12/41 (29.3%).alpha(1)-Blockers were effective and safe for treating young and middle-aged men with symptomatic bladder neck obstruction.

A large observational study was conducted to assess the frequency of urinary incontinence (UI) and overactive bladder (OAB) and to describe the diagnostic and therapeutic approach in General Medical Practice in Italy.Subjects eligible for the study were men aged50 years and women aged40 years, observed consecutively by their own General Practitioner (GP) for a check-up or medical prescription examination during the recruitment period, who agreed to participate in the study. All the subjects included in the study were interviewed by their GP using a common questionnaire that included information about their general characteristics and a specific medical history. The subject was also asked: "Have you had involuntary loss of urine during the last 3 months?"; "Do you urinate more than 8 times a day on average and/or Do you have to get up more than once a night?"; "Have you urgency problems?". If the subject answered yes to the first question or to both the second and third, a urinary problem was diagnosed, in particular UI if the anser was yes to the first and OAB if to the second and third. In these subjects the interview was continued in order to define the type of UI, using the diagnostic flow chart proposed by Wean.On the whole, 9613 men (average age 64.8, range 50-98) and 13,365 women (average age 60.3 years, range 40-98) were interviewed by 774 GPs. A diagnosis of urinary problems was made in 1084 men (11.3%) and 1507 women (11.3%). Among the men the GP was already aware of the condition in 603 cases (55.6%) and a new diagnosis was made in 481 cases (44.4%). The corresponding figures for women were 560 (37.2%) and 947 (62.8%). The proportion of new diagnosis out of all the subjects with micturition problems tended to be greater in the younger age (chi square for trend p0.05). The presence of OAB without UI was found in 3.0% [95% Confidence Interval (CI) 1.7-3.5] of the men and 1.1% (95% CI 0.9-1.3) of the women. Over all, 8.3% (95% CI 7.7-8.9) of the men and 10.2% (95% CI 9.6-10.8) of the women reported UI. The frequency of OAB and UI conditions increased with age in both men and women. On the whole, a urine test was requested in 71.9% of the subjects with a new diagnosis of UI or OAB and the frequency of haematuria was equal to 15.7% of the cases, without marked differences by type of diagnosis of micturition problem. A urine culture was done in 60.7% of the cases and was positive in 17.7%. Further diagnostic investigations were prescribed in the majority of cases, 76.6%. This was observed in particular among the men (86.2% of the cases compared to 71.7% of the women) but with no substantial differences between the different diagnoses of UI. Pharmacological treatment was suggested to 68% of the men and 44.9% of the women. The condition for which pharmacological treatment was less often prescribed was stress UI, where it was suggested in 54.5% of the men and 27.3% of the women. For men, alpha-lytics were the drugs most often prescribed for all urinary problems, regardless of the type. For women, anticholinergics were the most commonly advised type of drug, followed by anti-infectives.

— The theoretical advantages and disadvantages of the vaginal approach for the treatment of female urinary incontinence are outlined on the basis of a literature review and personal experience. The need for a better understanding of the influence of the anatomy and function of the pelvic floor on the anatomy and function of the female bladder neck and urethra is highlighted. The main advantage of vaginal surgery is the simultaneous correction of anterior, central and posterior defects, restoring or preserving vesicourethral, sexual and rectoanal anatomy and function.

Leydig Cell Tumors (LCT) are uncommon testicular neoplasms that account for 1 to 3% of all testicular tumors. Only about 10% of LCT are malignant and generally refractory to radiotherapy and conventional chemotherapy. Therefore, there is some debate about the value of Retroperitoneal Lymphadenectomy (RPLND) in Stage I disease. Indeed, although surgery is the only available therapy which is able to cure and prevent tumor spread, RPLND is a challenging invasive surgery and may be useless in 90% of the cases. The Authors observed 5 cases of patients in clinical Stage I disease with benign behaviour demonstrated after an adequate follow-up. Pathological analysis showed absence of signs of malignancy. Starting from these experiences, it is suggested that RPLND may be avoided in selected cases when definite pathological signs of malignancy are absent.

1. Cumulative concentration-response curves (CRC) to prostaglandin E1 (PGE1), PGE2, PGD2 and PGF2alpha (0.01-30 microM) and to the thromboxane A2 (TXA2) receptor agonist U-46619 (0.01-30 microM) were constructed in human isolated detrusor muscle strips both in basal conditions and during electrical field stimulation. 2. All the agonists tested contracted the detrusor muscle. The rank order of agonist potency was: PGF2alphaU-46619PGE2 whereas weak contractile responses were obtained with PGD2 and PGE1. Any of the agonists tested was able to induce a clear plateau of response even at 30 microM. 3. The selective TXA2 antagonist, GR 32191B (vapiprost), antagonized U-46619-induced contractions with an apparent pK(B) value of 8.27+/-0.12 (n = 4 for each antagonist concentration). GR 32191B (0.3 microM) did not antagonize the contractile responses to PGF2alpha and it was a non-surmountable antagonist of PGE2 (apparent pK(B) of 7.09+/-0.04; n = 5). The EP receptor antagonist AH 6809 at 10 microM shifted to the right the CRC to U-46619 (apparent pK(B) value of 5.88+/-0.04; n = 4). 4. Electrical field stimulation (20 Hz, 70 V, pulse width 0.1 ms, trains of 5 s every 60 s) elicited contractions fully sensitive to TTX (0.3 microM) and atropine (1 microM). U-46619 (0.01-3 microM) potentiated the twitch contraction in a dose-dependent manner and this effect was competitively antagonized by GR 32191B with an estimated pK(B) of 8.54+/-0.14 (n = 4 for each antagonist concentration). PGF2alpha in the range 0.01-10 microM (n = 7), but not PGE2 and PGE1 (n = 3 for each), also potentiated the twitch contraction of detrusor muscle strips (23.5+/-0.3% of KCl 100 mM-induced contraction) but this potentiation was unaffected by 0.3 microM GR 32191B (n = 5). 5. Cumulative additions of U-46619 (0.01-30 microM) were without effect on contractions induced by direct smooth muscle excitation (20 Hz, 40 V, 6 ms pulse width, trains of 2 s every 60 s, in the presence of TTX 1 microM; n = 3). Moreover, pretreatment of the tissue with 0.3 microM U-46619 did not potentiate the smooth muscle response to 7 microM bethanecol (n = 2). 6. We concluded that TXA2 can induce direct contraction of human isolated urinary bladder through the classical TXA2 receptor. Prostanoid receptors, fully activated by PGE2 and PGF2alpha are also present. All these receptors are probably located post-junctionally. The rank order of agonist potency and the fact that GR 32191B, but not AH6809, antagonized responses to PGE2 seem to indicate the presence of a new EP receptor subtype. Moreover, we suggest the presence of prejunctional TXA2 and FP receptors, potentiating acetylcholine release from cholinergic nerve terminals.

An original technique for complete bladder replacement using an ileal segment--the VIP pouch--is described. The long-term functional results and early and late complications are presented.The records of 209 VIPs performed following radical cystectomy for invasive bladder cancer from 1987 through 1995 were reviewed. Follow-up ranged from 6 to 87 months (mean: 24 mo.); the age of the patients ranged from 35 to 76 years (mean: 59.6 yrs.).188 patients with a follow-up of at least 6 months have been evaluated. There was 1 postoperative death from massive pulmonary embolism, 23 pts. died from tumor progression and 4 are still alive with metastases. Early complications were observed in 10.5% of the pts., comprising 9 cases of prolonged ileus (5 functional and 4 obstructive), 3 pelvic hematomas, 2 deep venous thrombosis and 2 fistulas between the enteric anastomosis and the VIP pouch. Late complications were observed in 39.5%, in particular, 28 uretero-ileal stenosis (15%), 21 urethro-ileal stenosis (11%) and 15 laparoceles (8%). Clinically relevant metabolic disturbance has not been observed. Complete daytime continence was achieved in more than 90% of the cases and night-time continence was observed in 75% of the patients. The mean VIP manometric capacity was around 400 ml with low pressure during reservoir emptying; 39 patients (20%), showed voiding problems with a mean postmicturition residual of 150 ml (3 pts. require clean intermittent self-catheterization).VIP offers a simple and easy-to-perform surgical technique to provide a good capacity, low pressure, non refluxing reservoir employing only a 40 cm. ileal segment. The clinical and urodynamic results are good and offer high quality of life to patients undergoing cystectomy. The overall rate of late complications is fairly high, although conservative management is effective in most cases.

Several self-injection devices have been recently proposed as an aid to home intracavernosal self-injection treatment for erectile dysfunction, with the purpose of allowing an easier drug administration, decreasing the artificiality of intracavernosal pharmacotheraphy, with the overall goal of increasing the acceptability of this treatment. We propose a classification of these devices according to the type of mechanical impact on the cavernosal tissue: self-injection pens, allowing for manual needle insertion and manual drug delivery; autoinsertors, with automatic needle insertion and manual drug delivery, and autoinjectors, that provide both automatic needle insertion and automatic drug delivery. The use of autoinjectors bears two theoretical risks: extra-corporal drug delivery in cases of wrong injection site, and trabecular damage due to high delivery pressure. In one device pressures 15 times higher the values reached by manual injection, and statistically higher than pressures obtained by maximal strength manual injection, were observed in an in-vitro investigation. Specific studies are needed to define a threshold pressure value for trabecular damage in the flaccid state; accordingly, information on autoinjector developed pressures should be provided by manufacturers. Clinical studies with adequate follow-up are needed as well, to verify the risk of autoinjector-induced extracorporal drug delivery, and the occurrence of intracavernosal nodules or penile curvature, compared to manual self-injection.

The contractile effect of two highly potent, selective and peptidase-resistant neurokinin (NK) 1 and NK2 receptor agonists, namely delta-Aminovaleryl-[L-Pro9, N-MeLeu10]substance P-(7-11) (GR 73632) and [Lys3, Gly8-R-gamma-lactam-Leu9]NKA-(3-10) (GR 64349), respectively, was investigated on smooth muscle strips dissected from specimens of human detrusor, prostatic urethra and prostate. Furthermore, the potencies of two peptidic NK2 receptor antagonists, GR 87389 L 659,837, in antagonizing GR 64349-induced contractions were compared in these three tissues. In human detrusor muscle the rank order of agonist potency was: [beta Ala8 (NKA-(4-10)]GR 64349NKA-(4-10)SP = GR 73632SP-methylester. The NK2 receptor antagonist, GR 87389, antagonized GR 64349-induced contractions in a competitive manner, whereas L 659,837 was a noncompetitive antagonist. In the prostatic urethra the rank order of agonist potency was GR 64349NKA-(4-10)SPGR 73632, whereas in the prostate it was: GR 64349[beta Ala8 (NKA-(4-10)]NKA-(4-10)SP; GR 73632 was ineffective up to 30 microM. In the prostatic urethra and in the prostate GR 87389 was a noncompetitive antagonist with a potency similar to that exhibited in the detrusor. On the contrary, L 659,837 appeared to be a competitive antagonist in the prostate and in the prostatic urethra, having approximately the similar potency in these two tissues. The selective NK3 agonist senktide was ineffective up to 30 microM in all three tissues. These results are discussed in the view of the proposed NK2 receptor subtypes and considering possible therapeutic implications in the treatment of urinary bladder disorders.

The classification of purinergic receptors is seriously hampered by the lack of specific antagonists. Furthermore, there is increasing evidence that other purinoceptor subtypes may exist that are different than the relatively well characterized P2X, P2Y, P2Z and P2T. Human isolated urinary bladder was reported to contract in response to challenge with alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-MeATP) and adenosine 5'-triphosphate (ATP), probably through activation of P2X purinoceptors. In this work, we tried to classify the purinoceptors subtypes present in human detrusor muscle by using adenosine 5'-[beta-thio]diphosphate (ADP beta S), alpha,beta-MeATP, 2-methylthio adenosine 5'-triphosphate (2-MeSATP), ATP and uridine 5'-triphosphate (UTP). We also examined the activity of two putative P2 antagonists (p-chloromercuribenzensulfonic acid [PCMBS] and Reactive Blue 2 [RB-2]). The agonist rank order of potency was alpha,beta-MeATP = ADP beta S2-MeSATPATPUTP. Cumulative responses to alpha,beta-MeATP induced a very rapid desensitization, but responses to alpha,beta-MeATP and ADP beta S, both at 100 microM, were additive. PCMBS antagonized ADP beta S-induced contractions with a pKB of 6.49, but it was inactive against alpha,beta-MeATP. The putative P2Y antagonist RB-2 had no effect against ADP beta S-induced contraction. We conclude that human detrusor muscle contains two contractile purinoceptor subtypes. One is activated by alpha,beta-MeATP and is probably the P2X subtype; the other is activated by ADP beta S and appears to be different from those accepted by the current classification. The similarity between our results and those obtained by other investigators is discussed.