Poorly understood, lower genitourinary tract syndromes in men cause major morbidity and expenditure of health care resources. For example, half of all adult men suffer from """"""""prostatitis"""""""" at some time, but the etiology is uncertain for over 90% of patients. Because we have limited understanding of the causes, therapy is empirical and often ineffective. The long-term objective of this project is to determine the causes, consequences and optimal therapy for these idiopathic lower genitourinary tract syndromes. This limited proposal addresses discrete aspects of the larger problem and will establish promising approaches for more wide- ranging investigations. Uncontrolled studies suggest that a number of conditions, especially prostatitis, nongonococcal urethritis, other inflammations of the genitalia and urethral stricture disease, are highly prevalent in men with trichomoniasis. Specific clinical aims are to define: the prevalence of disease among men with prostatitis and other longstanding genitourinary tract syndromes, the optimal methods for diagnosis, and the results of specific therapy on symptoms and objective signs of inflammation. Particular attention will be given to evaluation of anatomical or functional abnormalities of the lower urinary tract, and host defense factors, such as the zinc content and activity of prostatic secretions. Control groups will be selected from high- risk populations. Risk factors, clinical findings, objective evidence of inflammation and the relationship of signs and symptoms to urological abnormalities and simultaneous presence of multiple pathogens will be compared among cases, their partners and control men from the same populations. A double- blind, placebo-controlled study will evaluate therapy. Specific experimental aims are to determine properties which may be associated with active disease including: patterns of reactivity with monoclonal antibodies, virulence in an animal model and in tissue culture systems, hemolytic activity, and sensitivity studies. Biological and immunological characteristics will be compared to the clinical presentation, results of therapy and the natural history of disease. These studies will elucidate fundamental aspects of pathogenesis and facilitate recommendations for urological evaluation and treatment of millions of men annually in the United States.
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