Mario Paranhos

Penile erection induced in vivo by a purified toxin from the Brazilian spider Phoneutria nigriventer

To verify the effect on erectile tissue of mice of two neuropeptides extracted from the poison of a spider, Phoneutria nigriventer, (Tx2‐5 and ‐6, termed ‘eretina’) after direct injection into the corpus cavernosum, to assess the minimum dosage necessary for effect, the time for initiation of action, the local duration of the erection, histological effects and the presence of local and systemic side‐effects.

Erection induced by Tx2-6 toxin of Phoneutria nigriventer spider: Expression profile of genes in the nitric oxide pathway of penile tissue of mice

The peptides Tx2-5 and Tx2-6, isolated from the whole venom of armed-spiderPhoneutria nigriventer venom, are directly linked with the induction of persistent and painful erection in the penis of mammals. The erection induced by Tx2-6 has been associated with the activation of nitric oxide synthases. There is a scarcity of studies focusing on the outcome of Tx2-6 at the molecular level, by this reason we evaluated the gene profile activity of this toxin at the nitric oxide (NO) pathway. After microarray analyses on cavernous tissue of mice inoculated with Tx2-6 we found that only 10.4% (10/96) of these genes were differentially expressed, showing a limited effect of the toxin on the NO pathway. We found the genes sparc, ednrb, junb, cdkn1a, bcl2, ccl5, abcc1 over-expressed and the genes sod1, s100a10 and fth1 under-expressed after inoculation of Tx2-6. The differential expressions of sparc and ednrb genes were further confirmed using real-time PCR. Interestingly, ednrb activates the L-arginine/NO/cGMP pathway that is involved in the relaxation of the cavernous body. Therefore the priapism induced by Tx2-6 is a consequence of a highly specific interference of this neurotoxin with the NO pathway.

The role of BPH, lower urinary tract symptoms, and PSA levels on erectile function of Brazilian men who undergo prostate cancer screening

INTRODUCTIONnLower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are common problems in middle-aged and older men. Recently, epidemiologic studies have shown significant associations between severity of LUTS and male sexual dysfunction.nnnAIMnWe analyzed the role of prostate enlargement, LUTS, and prostate specific antigen (PSA) levels in the erectile function of Brazilian men who underwent prostate cancer (PCa) screening.nnnMETHODnWe analyzed data from 1,008 consecutive patients enrolled in a PCa screening program. Benign prostatic hyperplasia (BPH) was defined as a prostate weight greater than 30 g as defined by digital rectal examination. For statistical analysis, we used the chi-squared and analysis of variance tests. The odds ratios (OR) for correlation of ED with prostate volume LUTS and PSA were estimated using logistic regression models.nnnMAIN OUTCOME MEASUREnThe American Urological Association (AUA) symptom score for LUTS and the International Index of Erectile Function.nnnRESULTSnMean patient age was 61.2 years (45-87) and median PSA value was 1.9 ng/mL. BPH was identified in 48.5% of patients. Mild, moderate, and severe LUTS were found in 52.3%, 30.9%, and 16.8% of cases, respectively. ED was classified as absent, mild, mild to moderate, moderate, and severe in 18.6%, 23.1%, 18.6%, 15.2%, and 24.5%, respectively. While only 5.4% of the patients with no ED presented severe LUTS, this finding was observed in 27.1% of patients with severe ED (P < 0.001). Univariate logistic regression analysis demonstrated that age, prostate volume, AUA symptom score, and PSA levels were significant predictors of ED. However, when controlled for patient age, only LUTS remained as an independent predictor of ED.nnnCONCLUSIONSnControlling for patient age, LUTS are independent risk factors for the development of ED among Brazilian men who undergo PCa screening. Antunes AA, Srougi M, DallOglio MF, Vicentini F, Paranhos M, and Freire GC. The role of BPH, lower urinary tract symptoms, and PSA levels on erectile function of Brazilian men who undergo prostate cancer screening.

Salvage Radical Prostatectomy: An Alternative Treatment for Local Recurrence of Radioresistant Cancer

OBJECTIVESnThe treatment of recurrent prostate cancer after radiotherapy or brachytherapy through radical prostatectomy has been little indicated due to the concern over the procedures morbidity. We present the experience of our service with postradiotherapy radical prostatectomy.nnnMATERIALS AND METHODSnBetween 1996 and 2002, 9 patients submitted to radiotherapy due to prostate cancer were treated with salvage surgery for locally recurrent disease. All patients had a biopsy of the prostate confirming the tumor recurrence, increase in the PSA levels and staging without evidence of a systemic disease. We have assessed the morbidity and the recurrence-free survival rate after salvage radical prostatectomy.nnnRESULTSnPreradiotherapy PSA varied from 6.2 to 50 ng/mL (mean 17.3) and clinical staging T1, T2 and T3 in 33.3%, 44.4% and 22.2% of the patients respectively. The interval for the biopsy after conforming external beam radiotherapy or brachytherapy varied from 8 to 108 months (median: 36). Four patients received antiandrogenic therapy neoadjuvant to the surgery with a mean of 7 months (1-48) after radiotherapy. From the six patients potent before the surgery, three have presented erectile dysfunction. Urinary incontinence as well as bladder neck sclerosis occurred in two patients (22.2%). Biochemical recurrence occurred in two individuals (22.2%) 12 months after the surgery. Biochemical recurrence-free survival rate was 77.8% with median follow-up time of 30 months (8-102).nnnCONCLUSIONnSalvage radical prostatectomy is a safe and effective alternative for the treatment of locally recurrent prostate cancer after radiotherapy and brachytherapy.

Risk factors for male lower urinary tract symptoms: the role of metabolic syndrome and androgenetic alopecia in a Latin American population.

OBJECTIVEnTo evaluate the association of male lower urinary tract symptoms (LUTS) with metabolic syndrome (MetS) and androgenetic alopecia in a Latin American population.nnnMETHODSnWe enrolled 907 patients for prospective evaluation at a single institution. LUTS were evaluated with the International Prostate Symptom Score (IPSS). Subjects were evaluated with respect to hypertension, diabetes, dyslipidemia, previous cardiovascular events, body mass index (BMI), waist and hip circumference, and a laboratorial investigation including prostate-specific antigen (PSA), C-reactive protein (CRP), and gonadal steroids. Alopecia was classified according to the Norwood-Hamilton scale.nnnRESULTSnMean patient age was 61.0 years; 57.5% of subjects had moderate/severe LUTS; MetS was present in 17.2% of subjects and 53.9% were classified as bald. Age, hypertension, diabetes, dyslipidemia, alopecia, previous cardiovascular event, and elevated waist-to-hip ratio (WHR) were associated with moderate/severe LUTS and with storage symptoms (Pxa0<.05). On multivariable analysis, age (odds ratio [OR] 2.30, 95% confidence interval [CI] 1.63-3.25), cardiovascular events (OR 1.73, 95% CI 1.07-2.78), and WHR (OR 1.65, 95% CI 1.13-2.40) were independent predictors for LUTS. For storage symptoms, age (OR 1.80, 95% CI 1.28-2.54), cardiovascular event (OR 2.07, 95% CI 1.27-3.39), WHR (OR 1.54, 95% CI 1.06-2.25), and MetS (OR 1.70, 95% CI 1.01-2.86) were independent risk factors. Age and cardiovascular event were the only independent predictors for voiding symptoms.nnnCONCLUSIONnComponents of the MetS were strongly associated with moderate and severe LUTS. WHR and cardiovascular events were independent predictors of voiding and storage symptoms, and MetS was an independent predictor of storage symptoms. Alopecia was not an independent predictor of LUTS.

Interactions between Lower Urinary Tract Symptoms and Cardiovascular Risk Factors Determine Distinct Patterns of Erectile Dysfunction: A Latent Class Analysis

PURPOSEnAn epidemiological association between lower urinary tract symptoms and erectile dysfunction is well established. However, interactions among multiple risk factors and the role of each in pathological mechanisms are not fully elucidatednnnMATERIALS AND METHODSnWe enrolled 898 men undergoing prostate cancer screening for evaluation with the International Prostate Symptom Score (I-PSS) and simplified International Index of Erectile Function-5 (IIEF-5) questionnaires. Age, race, hypertension, diabetes, dyslipidemia, metabolic syndrome, cardiovascular disease, serum hormones and anthropometric parameters were also evaluated. Risk factors for erectile dysfunction were identified by logistic regression. The 333 men with at least mild to moderate erectile dysfunction (IIEF 16 or less) were included in a latent class model to identify relationships across erectile dysfunction risk factors.nnnRESULTSnAge, hypertension, diabetes, lower urinary tract symptoms and cardiovascular event were independent predictors of erectile dysfunction (p<0.05). We identified 3 latent classes of patients with erectile dysfunction (R2 entropy=0.82). Latent class 1 had younger men at low cardiovascular risk and a moderate/high prevalence of lower urinary tract symptoms. Latent class 2 had the oldest patients at moderate cardiovascular risk with an increased prevalence of lower urinary tract symptoms. Latent class 3 had men of intermediate age with the highest prevalence of cardiovascular risk factors and lower urinary tract symptoms. Erectile dysfunction severity and lower urinary tract symptoms increased from latent class 1 to 3.nnnCONCLUSIONSnRisk factor interactions determined different severities of lower urinary tract symptoms and erectile dysfunction. The effect of lower urinary tract symptoms and cardiovascular risk outweighed that of age. While in the youngest patients lower urinary tract symptoms acted as a single risk factor for erectile dysfunction, the contribution of vascular disease resulted in significantly more severe dysfunction. Applying a risk factor interaction model to prospective trials could reveal distinct classes of drug responses and help define optimal treatment strategies for specific groups.

Penile prosthesis implantation in an academic institution in Latin America

PURPOSEnWe performed a retrospective study to analyze the effectiveness of implantable penile prostheses in the treatment of erectile dysfunction.nnnMATERIALS AND METHODSnThis study included 249 patients who received implants between 2001 and 2008. A total of 139 patients who underwent penile prosthesis implantation were interviewed.nnnRESULTSnApproximately half of patients had previously used oral drugs before implantation of the prosthesis. About 45% had diabetes, 25.9% had previously undergone radical prostatectomy (RP), and 64% had hypertension. Exchange was performed in 5.7% for fracture, inadequate size, or extrusion. A total of 24.5% of men had immediate postoperative pain, 7.9% had local infection, and 8.6% had other complications. Patients who had previously undergone RP were 3.2 times more likely to experience a postoperative complication than patients who had not (p = 0.061). Eighty-nine (64%) patients returned to having sex as they had before being diagnosed with ED. Ninety-two of the men (66.2%) had sexual intercourse one to two times per week. One hundred twenty patients (86.3%) rated their level of satisfaction as good, excellent or very good, which was similar to the percentage of partners. The mean follow-up was 40 months.nnnCONCLUSIONnHigher rates of postoperative infections and mechanical problems with the implant were found in this study as compared to other studies, which was probably associated with the relative lack of experience of the trainees who were performing the surgeries. Patients with a history of RP or diabetes mellitus prior to implantation were at higher risk of postoperative complications.

The prevalence of erectile dysfunction among Brazilian men screened for prostate cancer

To determine the prevalence of erectile dysfunction (ED) in a large cohort of Brazilian men who were screened for prostate cancer, and to determine risk factors in this population, as there are large cultural differences among countries in reporting the frequency of ED, and it is likely that the prevalence of ED among men screened for prostate cancer cannot be generally applied across countries.

Microvascular invasion is an independent prognostic factor in patients with prostate cancer treated with radical prostatectomy

OBJECTIVEnCurrent published data regarding the prognostic value of microvascular invasion (MVI) in patients with prostate cancer (PCa) have yielded mixed results. Furthermore, most important series had surgical procedures performed by multiple surgeons and surgical specimens analyzed by multiple pathologists. We determined the relation of MVI with other pathologic features and whether this finding can be used as an independent prognostic factor in patients with PCa.nnnMATERIALS AND METHODSnWe selected 428 patients with clinically localized PCa treated with radical prostatectomy (RP). MVI was correlated to other pathologic features. The Kaplan-Meier method was used to evaluate survival curves and statistical significance was determined by the log-rank test. Multivariate analysis was performed through a Cox proportional hazards regression model.nnnRESULTSnEleven percent out of the 428 patients presented MVI. Except for the lack of association with biopsy Gleason score, MVI was related to all clinical and pathologic features of RP specimens. Mean follow up after surgery was 53.9 +/- 20.1 months. Patients with MVI presented a recurrence rate of 44.6% compared to only 20.2% for patients without MVI (Log-rank test - p < 0.001). After Cox regression analysis, MVI was an independent prognostic feature related to biochemical recurrence.nnnCONCLUSIONSnMVI is associated to advanced pathologic features of PCa and is an important prognostic factor regarding disease recurrence in patients treated with RP. These findings support the recommendations to the routine evaluation of this variable in pathologic reports of RP specimens.

Perineural invasion by transitional cell carcinoma of the bladder in patients submitted to radical cystectomy: what is the prognostic value?

OBJECTIVEnDetermine the prognostic value of perineural invasion (PNI) in patients with transitional cell carcinoma (TCC) of the bladder treated with radical cystectomy.nnnMATERIALS AND METHODSnFrom January 1993 to January 2005, 113 people were selected from 153 patients with TCC of the bladder treated with radical cystectomy. The association between the presence of PNI and other pathologic characteristics were analyzed through Fisher exact test. The Kaplan-Meier method was utilized to assess the survival curve and the statistical significance was determined by the Breslow test. The multivariate analysis was performed through the Cox regression model.nnnRESULTSnThe PNI was identified in 10 (8.8%) of the 113 patients. This variable significantly related to the microvascular invasion and to tumor staging. The mean segment after surgery was 31.7 +/- 28.5 months. Recurrence occurred in 5 (50%) and in 41 (39.8%) patients (p=0.363) and mortality occurred in 2 (20%) and 22 (21.9%) patients (p=0.606) with or without PNI respectively. In Cox regression analysis, patients with PNI presented with 1.53 times (IC 95% 0.60 to 3.91; p=0.371) and 1.60 times (IC 95% 0.37 to 6.95; p=0.532) the risk of recurrence and mortality when compared to patients without PNI.nnnCONCLUSIONSnThe PNI does not constitute an independent variable of disease-free and cancer specific survival in patients with TCC of the bladder treated with radical cystectomy.