This Month in Investigative Urology

Article Outline

• α1-Adrenoceptor Antagonist Exposure May Decrease the Incidence of Prostate Cancer
• Viral Infections and Lower Urinary Tract Symptoms
• Diabetic Urethropathy Compounds the Effects of Cystopathy
• Real-Time Intraoperative Ureteral Guidance Using Invisible Near-Infrared Fluorescence
• Dietary Oxalate and Calcium Oxalate Stones
• Copyright

Back to Article Outline

α1-Adrenoceptor Antagonist Exposure May Decrease the Incidence of Prostate Cancer 

The quinazoline based α1-adrenoceptor antagonists doxazosin and terazosin suppress prostate tumor growth via induction of apoptosis and reduction of tissue vascularity. To assess the effect of α1-blocker exposure on the incidence of prostate cancer, an exploratory, observational cohort study was performed by Harris et al (page 2176) from Lexington, Kentucky. The medical records of male patients were searched to identify men treated with quinazoline based α1-adrenoreceptor antagonists for hypertension and/or benign prostate enlargement. Medical records were subsequently linked to a statewide population based central cancer registry that is part of the National Cancer Institute Surveillance, Epidemiology and End Results Program to identify all incident prostate cancer cases diagnosed. Measures of disease incidence, relative risk and attributable risk were calculated to compare the risk of prostate cancer in α1-blocker exposed vs unexposed men. Men exposed to quinazoline α1-adrenoceptor antagonists had a 1.46 times lower relative risk and 31.7% lower attributable risk of prostate cancer than unexposed men. There was no association between α1-adrenoceptor antagonist exposure and overall survival. This evidence suggests that the apoptotic and anti-angiogenic effects of quinazoline based α1-adrenoceptor antagonists may prevent the development of prostate cancer.

Back to Article Outline

Viral Infections and Lower Urinary Tract Symptoms 

Previous epidemiological studies have described suggestive positive associations between sexually transmitted infections, particularly gonorrhea and human immunodeficiency virus infection, and lower urinary tract symptoms (LUTS). To my knowledge no studies have investigated other infections, such as human papillomavirus type 16, herpes simplex virus type 2, cytomegalovirus, human herpesvirus type 8, herpes simplex virus type 1, and hepatitis B and C virus infection in relation to LUTS. Sutcliffe et al (page 2181) from Baltimore, Maryland examined each of these associations in the Third National Health and Nutrition Examination Study, a representative, cross-sectional survey of the United States population conducted between 1988 and 1994. Each participant provided a blood sample and completed a computer assisted interview including questions on LUTS (nocturia, incomplete emptying, hesitancy and weak stream). Blood samples were tested for IgG antibodies against each virus. In this cross-sectional study of American men suggestive positive associations were observed between several viral infections and LUTS, primarily in men 30 to 59 years old. These findings provide interesting hypotheses and preliminary evidence for future etiological studies of infections and LUTS.

Back to Article Outline

Diabetic Urethropathy Compounds the Effects of Cystopathy 

Diabetic cystopathy has been attributed primarily to peripheral polyneuropathy, involving autonomic and somatic sensory and motor nerves. However, diabetes mellitus also damages the innervation of the urethra, and directly impairs urethral striated and smooth muscle. The resulting diabetic urethropathy could degrade voiding function by impairing outlet function and urethra-to-bladder reflexes. Because this urethropathy may be time dependent, Yang et al (page 2213) from Durham, North Carolina investigated the effects of short and long-term streptozotocin induced diabetes mellitus on external urethral sphincter (EUS) and urethral smooth muscle (USM) using a preparation that functionally separates the urethra from the bladder. Isovolumetric bladder pressure, urethral perfusion pressure and EUS electromyography were measured in female rats 5 or 10 weeks after streptozotocin induced diabetes mellitus. Urethral responses to serial administration of various agents were determined in diabetes mellitus and age matched controls. Diabetes mellitus induced urethropathy was characterized by EUS dysfunction, decreased USM relaxation and nitric oxide responsiveness, and increased USM responsiveness to α₁-adrenergic agonists. These changes increased outlet resistance, and thereby, decreased voiding efficiency. This exacerbated voiding dysfunction, creating a vicious cycle of progressive lower urinary tract damage and dysfunction. These results suggest that early intervention targeting outlet resistance may be indicated.

Back to Article Outline

Real-Time Intraoperative Ureteral Guidance Using Invisible Near-Infrared Fluorescence 

Invisible near-infrared light is safe, and penetrates relatively deeply through tissue and blood without altering the surgical field. Tanaka et al (page 2197) from Boston, Massachusetts hypothesized that near-infrared fluorescence imaging would enable visualization of the ureteral anatomy. The carboxylic acid form of near-infrared fluorophore IRDye^TM 800CW (CW800-CA) was injected intravenously, and its renal clearance kinetics and imaging performance were quantified in rats and pigs. The clinically available near-infrared fluorophore indocyanine green was also used via retrograde injection into the ureter. Using both near-infrared fluorophores the ureters were imaged under conditions of steady state, intraluminal foreign bodies and injury. Retrograde injection of indocyanine green also permitted the detection of normal ureter and pinpointed urine leakage caused by injury. Electrospray time-of-flight mass spectrometry, and absorbance and fluorescence spectral analysis confirmed that the fluorescent material in urine was chemically identical to CW800-CA. A convenient intravenous injection of CW800-CA or direct injection of indocyanine green permits high sensitivity visualization of ureters under steady state and abnormal conditions using invisible light.

Back to Article Outline

Dietary Oxalate and Calcium Oxalate Stones 

Urinary oxalate (Ox) is derived in approximately equal parts from dietary and endogenous sources. Increased urinary excretion of oxalate or hyperoxaluria is considered a major risk factor for calcium oxalate (CaOx) nephrolithiasis. Patients with CaOx kidney stones are advised to reduce the consumption of foods that contain oxalate. It is hypothesized that a decrease in dietary Ox will lead to a reduction in urinary excretion of Ox and decreased stone recurrence. Khan et al (page 2191) from Gainesville, Florida tested the hypothesis in an animal model of CaOx nephrolithiasis. Hydroxy-L-proline (HLP) (5%), a precursor of Ox found in collagenous foods, was given with rat chow to male rats. After 42 days rats in group 1 continued on HLP while those in group 2 were given chow without the added HLP for the next 21 days. Hyperoxaluria, CaOx crystalluria and nephrolithiasis developed in rats receiving HLP, and by day 42 all rats contained renal CaOx crystal deposits. Urinary excretion of lactate dehydrogenase, 8-isoprostane and hydrogen peroxide increased significantly. After HLP was discontinued in group 2 there was a significant reduction in urinary Ox, 8-isoprostane and hydrogen peroxide. Half of the group 2 rats appeared to be crystal-free. Dietary sources of oxalate can induce hyperoxaluria and crystal deposition in the kidneys with associated degradation in renal biology. Elimination of Ox from the diet reduces not only urinary oxalate, but also CaOx crystal deposits in the kidneys and improves their function.