Impact of systemically active neurohumoral factors on the erectile response of the rat.

Introduction: Mean arterial pressure (MAP) and specific regulation of penile blood flow are the primary determinants of an erection. While this concept is well recognized, the differential relationship between systemically acting vasoactive factors on arterial pressure and erectile responses is not well described.

Aim: The aim of this study was to determine how the modification of systemic levels of neurohumoral factors impacts on the magnitude and efficiency of the erectile response.

A phase 1, single-dose study of fresolimumab, an anti-TGF-β antibody, in treatment-resistant primary focal segmental glomerulosclerosis.

Primary focal segmental glomerulosclerosis (FSGS) is a disease with poor prognosis and high unmet therapeutic need. Here, we evaluated the safety and pharmacokinetics of single-dose infusions of fresolimumab, a human monoclonal antibody that inactivates all forms of transforming growth factor-β (TGF-β), in a phase I open-label, dose-ranging study. Patients with biopsy-confirmed, treatment-resistant, primary FSGS with a minimum estimated glomerular filtration rate (eGFR) of 25  ml/min per 1.

Plasma organochlorine levels and prostate cancer risk.

A case-control study was conducted to determine the association between plasma organochlorine levels and prostate cancer risk. Male clinic patients scheduled for prostate core biopsy or seeing their urologist for other conditions from 1997 through 1999 in Kingston, Ontario were eligible, excluding those with an earlier cancer. Age frequency matched controls (n=329) were compared with 79 incident prostate cancer cases.

Phase II study of nitric oxide donor for men with increasing prostate-specific antigen level after surgery or radiotherapy for prostate cancer.

Objectives: To evaluate the effect of low-dose glyceryl trinitrate (GTN) on men with biochemical recurrence of prostate cancer after primary therapy. Preclinical, proof-of-principle studies have demonstrated that nitric oxide signaling plays a significant role in the hypoxia-induced progression of prostate cancer.

Methods: A prospective, open-label clinical trial of men with an increasing prostate-specific antigen (PSA) level after surgery or radiotherapy was conducted.

Restoration of female genital vasocongestive arousal responses in young and aged rats.

Introduction: Treatments of aged, male hypertensive rats that induce vascular remodeling or that normalize endothelial function are known to produce sustained improvements in erectile function. Whether the treatments targeting these processes benefit female genital vasocongestive arousal (GVA) responses is currently not known.

Aim: To determine whether the actions of nitric oxide (NO) are critical to the apomorphine (APO)-generated GVA responses in both intact and ovariectomized OVX young adult female rats (before any aging-associated decreases in the responses).

Recovery of erectile function in aging hypertensive and normotensive rats using exercise and caloric restriction.

Introduction: Using aging spontaneously hypertensive rats (SHR), we established that antihypertensive drugs can improve erections and penile vascular structure, and lower arterial pressure. Using kidney cross-transplantations, our findings revealed that the benefit of this treatment resulted from drug-induced changes specific to the penile circulation, and not to the kidney-mediated lowering of pressure.

Aim: The objective of the present study was to determine whether increased exercise and/or caloric restriction (CR) can reverse the decline in sexual responses in aging hypertensive and normotensive rats.

Pesticides and polychlorinated biphenyls as potential risk factors for erectile dysfunction.

While it is biologically plausible that environmental chemicals such as pesticides and polychlorinated biphenyls (PCBs) with suspected hormone disrupting properties may have an impact on risk of erectile dysfunction (ED), few epidemiologic studies have assessed this potential association. In a clinic-based case-control study in Kingston, Ontario, consenting subjects completed a questionnaire and donated 15 mL of blood for analysis of organochlorines and lipids by gas chromatography. Exposures were compared for 101 cases with ED and 234 comparable control subjects.

Predictive validity of five comorbidity indices in prostate carcinoma patients treated with curative intent.

Background: Comorbidity is important to consider in clinical research on curative prostate carcinoma because of the role of competing risks. Five chart-based comorbidity indices were assessed for their ability to predict survival.

Methods: This was a case-cohort study of prostate carcinoma patient cohort treated with curative intent in Toronto and Southeast Cancer Care Ontario regions between 1990 and 1996; the subcohort was drawn from these men, whereas cases were cohort members who died from causes other than prostate carcinoma.

Lower urinary tract disease: what are we trying to treat and in whom?

The diseases of the lower urinary tract are traditionally divided into abnormalities of storage and abnormalities of emptying. The targets for therapy were the organs most responsible for influencing storage and emptying. Modern understanding places the symptomatic status of the patient as the overriding criterion for treatment.

Smoking and other lifestyle factors in relation to erectile dysfunction.

Objective: To assess the association between erectile dysfunction (ED) and various lifestyle and medical factors, including smoking and cardiovascular disease (CVD) medications, among men attending urology clinics in Kingston, Canada.

Subjects And Methods: We conducted a case-control study of men aged 50-80 years in Kingston, Ontario who agreed to participate at visits to urology clinics during 1997-99. We compared 101 men with clinically diagnosed ED and 234 controls with various benign urological conditions.

Dietary patterns and risk of prostate cancer in Ontario, Canada.

Dietary patterns reflect combinations of dietary exposures, and here we examine these in relation to prostate cancer risk. In a case-control study, 80 incident primary prostate cancer cases and 334 urology clinic controls were enrolled from 1997 through 1999 in Kingston, Ontario, Canada. Food-frequency questionnaires were completed prior to diagnosis and assessed intake in the 1-year period 2-3 years prior to enrollment.

Causes of erectile dysfunction.

Erectile dysfunction (ED) arises as a result of a collision of circumstances among any of a number of factors (e.g., risk factors, causes, probable associations), each with its own primary power to affect the outcome.

Long-term penile incarceration by a metal ring resulting in urethral erosion and chronic lymphedema.

A patient presented with a metal ring around the base of his penis. The ring had been placed 3 years prior to presentation. Intra-operative findings revealed a ventral erosion with complete transection of the urethra and massive fixed lymphedema of the penile skin distal to the ring.

Nitric oxide-mediated regulation of hypoxia-induced B16F10 melanoma metastasis.

Tumour hypoxia is associated with resistance to therapy and with increased invasion and metastatic potential. Recent studies in our laboratory have shown that the hypoxic up-regulation of tumour cell invasiveness and chemoresistance is in part due to reduced nitric oxide (NO) signaling. Using B16F10 murine melanoma cells, we demonstrate here that the increased metastatic potential associated with exposure to hypoxia is mediated by a reduction in cGMP-dependent NO-signaling.

Endocrine causes of impotence (nondiabetes).

The endocrine system has a major role in erections in normal men and it can also be a cause of significant morbidity. The relationship between serum testosterone measurement and erectile function is complex. Androgen treatment should certainly be considered in patients without prostate cancer but with a clinical picture that suggests a relevant contribution of hypogonadism to the ED.

Point: urologists should take an active role in the diagnosis and treatment of hypogonadism in the aging male.

Andropause is a problem that can be identified in some men as distinct from the changes associated with aging or chronic disease. These men have mild hypogonadism and a clinical picture that is well within the scope of urologists to identify and manage. Andropause is neither life threatening nor trivial and there are clinical guidelines published that will help to refine the understanding and definition of this condition.