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Biomedical subjects

Anthony J Schaeffer

Publications and source records attributed to Anthony J Schaeffer.

At least 19 recordsLinked to original sources

Demographic and clinical characteristics of chronic prostatitis: prospective comparison of the University of Sciences Malaysia Cohort with the United States National Institutes of Health Cohort.

PURPOSE: We compared demographic and clinical characteristics of the University of Sciences Malaysia Chronic Prostatitis Cohort to the United States National Institutes of Health Chronic Prostatitis Cohort. MATERIALS AND METHODS: Participants met the same definition of chronic prostatitis/chronic pelvic pain syndrome. Each participant had extensive demographic, medical history, previous treatment, clinical and laboratory evaluations. RESULTS: The University of Sciences Malaysia and National Institutes of Health cohorts proved similar in most respects. National Institutes of Health-Chronic Prostatitis Symptom Index total scores, pain and urinary subscores were similar for the 332 University of Sciences Malaysia Chronic Prostatitis Cohort and 488 National Institutes of Health Chronic Prostatitis Cohort participants. Differences included worse quality of life subscore for the University of Sciences Malaysia Chronic Prostatitis Cohort, differences in the location, number of sites, and types of pain/discomfort between the 2 populations, and that the University of Sciences Malaysia participants had received less previous treatment. CONCLUSIONS: The demographic characteristics and clinical presentation of chronic prostatitis/chronic pelvic pain syndrome proved remarkably similar in these diverse populations. Both cohorts experienced major reduction in their quality of life from chronic pelvic pain and urinary symptoms. Comparison of diverse populations using standard clinical, laboratory and assessment instruments is feasible, and may provide important insights into chronic prostatitis/chronic pelvic pain syndrome and the factors that determine clinical outcome.

Adult↗

Asymptomatic bacteriuria and symptomatic urinary tract infections during pregnancy.

Urinary tract infections are common complications of pregnancy; upper tract infections in particular may lead to significant morbidity for both the mother and fetus. Bacteriuria is a significant risk factor for developing pyelonephritis in pregnant women. Therefore, proper screening and treatment of bacteriuria during pregnancy is necessary to prevent complications. All women should be screened for bacteriuria in the first trimester, and women with a history of recurrent urinary tract infections or anomalies should have repeat bacteriuria screening throughout pregnancy. Treatment of bacteriuria should include 3-day therapy with appropriate antimicrobials, and women should be followed closely after treatment because recurrence may occur in up to one third of patients.

Anti-Infective Agents↗

Antigen-specific responses accelerate bacterial clearance in the bladder.

Urinary tract infections (UTIs) cause patient morbidity and have a substantial economic impact. Half of all women will suffer a UTI at least once, and 25% of these women will have recurrent infections. That 75% of previously infected women do not become reinfected strongly suggests a role for an adaptive immune response. The goal of this study was to characterize the adaptive immune responses to uropathogenic Escherichia coli (UPEC), the predominant uropathogen. A novel murine model of UTI reinfection was developed using the prototypic cystitis UPEC isolate NU14 harboring a plasmid encoding OVA as a unique antigenic marker. Bacterial colonization of the bladder was quantified following one or more infections with NU14-OVA. Animals developed anti-OVA serum IgG and IgM titers after the initial infection and marked up-regulation of activation markers on splenic T cells. We observed a 95% reduction in bacterial colonization upon reinfection, and splenic leukocytes showed Ag-specific proliferation in vitro. Adoptive transfer of splenic T cells or passive transfer of serum from previously infected mice protected naive syngeneic mice from UPEC colonization. These findings support our hypothesis that adaptive immune responses to UPEC protect the bladder from reinfection and form the basis of understanding susceptibility to recurrent UTI in women.

Animals↗

Prostate-specific antigen test in diagnostic evaluation of chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVES: To determine whether prostate-specific antigen (PSA), the percent free PSA, or free PSA isoforms may be used as diagnostic markers for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS; National Institutes of Health category IIIa and IIIb). METHODS: We evaluated 421 patients enrolled in the Chronic Prostatitis Cohort Study and 112 age-matched controls. Subjects were stratified by the number of white blood cells (WBCs) in their expressed prostatic secretions and pain as determined by the National Institutes of Health Chronic Prostatitis Symptom Index. RESULTS: Total PSA, free PSA, and [-2]proPSA ([-2]pPSA) were significantly elevated in those with CP/CPPS compared with controls (mean PSA 1.97 ng/mL versus 1.72 ng/mL, P = 0.03; mean free PSA 0.76 ng/mL versus 0.70 ng/mL, P = 0.01; and [-2]pPSA 2.38 ng/mL versus 1.80 ng/mL, P = 0.04). The percent free PSA was not significantly different between the patients and controls. For those with CP/CPPS, the percent free PSA was significantly lower as the WBC count rose in the expressed prostatic secretions (0 WBCs = 43.29 versus more than 25 WBCs = 26.52; P < .0001). A PSA level of 4.0 ng/mL or greater was found in 10% of patients and 7% of controls (P = 0.03). CONCLUSIONS: Men with elevated PSA values and CP/CPPS should be treated as one would any other patient screened for prostate cancer with an elevated PSA level. Although PSA, free PSA, and [-2]pPSA were slightly elevated in men with CP/CPPS, the low sensitivity and specificity do not warrant using them as biomarkers for CP/CPPS.

Biomarkers↗

Catastrophizing and pain-contingent rest predict patient adjustment in men with chronic prostatitis/chronic pelvic pain syndrome.

UNLABELLED: Cognitive/behavioral and environmental variables are significant predictors of patient adjustment in chronic pain. Using a biopsychosocial template and selecting several pain-relevant constructs from physical, cognitive/behavioral, and environmental predictors, outcomes of pain and disability in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) were explored. Men (n = 253) from a North American multi-institutional NIH-funded Chronic Prostatitis Cohort Study in 6 US and 1 Canadian centers participated in a survey examining pain and disability. Measures included demographics, urinary symptoms, depression, pain, disability, catastrophizing, control over pain, pain-contingent rest, social support, and solicitous responses from a significant other. Regressions showed that urinary symptoms (beta = .20), depression (beta = .24), and helplessness catastrophizing (beta = .29) predicted overall pain. Further, affective pain was predicted by depression (beta = .39) and helplessness catastrophizing (beta = .44), whereas sensory pain was predicted by urinary symptoms (beta = .25) and helplessness catastrophizing (beta = .37). With regard to disability, urinary symptoms (beta = .17), pain (beta = .21), and pain-contingent rest (beta = .33) were the predictors. These results suggest cognitive/behavioral variables (ie, catastrophizing, pain-contingent rest) may have significant impact on patient adjustment in CP/CPPS. Findings support the need for greater research of such pain-related variables in CP/CPPS. PERSPECTIVE: This article explores predictors of patient adjustment in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Cognitive/behavioral variables of catastrophizing and pain-contingent rest respectively predicted greater pain and disability. Catastrophic helplessness was a prominent pain predictor. These findings inform clinicians and researchers on several new variables in CP/CPPS outcomes and suggest future research.

Adaptation, Psychological↗

How does the pre-massage and post-massage 2-glass test compare to the Meares-Stamey 4-glass test in men with chronic prostatitis/chronic pelvic pain syndrome?

PURPOSE: The Meares-Stamey 4-glass test is the standard method of assessing inflammation and the presence of bacteria in the lower urinary tract in men presenting with the chronic prostatitis syndrome. However, most urologists do not use it in daily practice because of the time and difficulty in performing it, as well as the additional expense. We evaluated a simpler test, the 2-glass pre-massage and post-massage test, and compared it with the Meares-Stamey 4-glass test to detect inflammation and bacteria in men with chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: The study population included 353 men enrolled in the National Institutes of Health Chronic Prostatitis Cohort study with baseline leukocyte counts and 2-day bacterial cultures on specimens obtained from a standard 4-glass test (VB1, VB2, expressed prostatic secretions, VB3). The chi-square test was performed to assess associations of white blood cell counts in expressed prostatic secretions and VB3. A receiver operating characteristic curve was constructed to determine the optimal cut point of white blood cells in VB3 in predicting white blood cells in expressed prostatic secretions. Sensitivity and specificity of VB3 cultures predicting expressed prostatic secretions and positive Meares-Stamey results were calculated from 2 x 2 contingency tables. RESULTS: Analysis of binary leukocyte outcomes (no white blood cells vs any white blood cells) suggests that white blood cells tend to be present in expressed prostatic secretions when there are any white blood cells in VB3, p <0.0001, the optimal cut point being white blood cell counts of 3 in VB3 (best predictive ability with area under ROC 0.771) to predict 5+ in expressed prostatic secretions with a sensitivity of 76% and specificity of 70%. The optimal cut point of white blood cells in VB3 to predict 10 white blood cells in expressed prostatic secretions was 4 (62% sensitivity and 75% specificity). Uropathogens localizing to expressed prostatic secretions or VB3 confirms a positive 4-glass Meares-Stamey localization test. The sensitivity and specificity of a VB3 localizing culture only in predicting a positive Meares-Stamey 4-glass test result for any uropathogen were 44% to 54% (depending on definition) and 100%, respectively. The pre-massage and post-massage test predicted a correct diagnosis in more than 96% of subjects. CONCLUSIONS: The value of localizing leukocytes and uropathogens to prostate specific specimens remains controversial in chronic heavily pretreated patients, but these data may help direct therapy (anti-inflammatory or antimicrobial) when obtained at first presentation. The pre-massage and post-massage test has strong concordance with the 4-glass test and is a reasonable alternative when expressed prostatic secretions are not obtained.

Bacteria↗

Significant clinical practice cost savings through downsizing office supply inventory and just in time ordering.

PURPOSE: Cost containment in the office is becoming more important secondary to increasing overhead costs and lower reimbursement. In an attempt to limit these particular expenditures we analyzed and restructured our methods of ordering, storing and distributing office supply inventory. MATERIALS AND METHODS: In a large academic practice with 11 urologists and approximately 20,000 annual patient visits an attempt was made to decrease overhead costs using the principle of just in time inventory popularized by large manufacturing companies. We initially issued a return of excess and/or unused supplies from our office inventory stock room. Our main supply room was then centralized to contain office supplies for up to 4 weeks. The 12 individual clinic rooms were stocked with appropriate supplies to last 1 week. Limited access to the main supply room was established and a supply manager was established to log all input and output. RESULTS: The initial credit for the return of unused/overstocked supplies was $10,107 in January 2004. Annual office supply charges in calendar year 2004 were $87,444 compared to charges in calendar year 2003 of $175,340. No stock outs occurred during year 2004 and all standing delivery orders were terminated. The total number of patient visits in calendar year 2004 was 20,170 compared to 19,455 in calendar year 2003. CONCLUSIONS: Decreasing overall inventory through accurate demand forecasting, judicious accounting, office supply centralization and just in time ordering is a potential area for significant overhead cost savings in a clinical practice.

Cost Savings↗

Uropathogenic Escherichia coli induces extrinsic and intrinsic cascades to initiate urothelial apoptosis.

A murine model of urinary tract infection identified urothelial apoptosis as a key event in the pathogenesis mediated by uropathogenic Escherichia coli (UPEC), yet the mechanism of this important host response is not well characterized. We employed a culture model of UPEC-urothelium interactions to examine the biochemical events associated with urothelial apoptosis induced by the UPEC strain NU14. NU14 induced DNA cleavage within 5 h that was inhibited by the broad caspase inhibitor ZVAD, and urothelial caspase 3 activity was induced within 3 h of exposure to type 1 piliated NU14 and was dependent upon interactions mediated by the type 1 pilus adhesin FimH. Flow cytometry experiments using chloromethyl-X-rosamine and Indo-1 revealed FimH-dependent mitochondrial membrane depolarization and elevated [Ca(2+)](in), respectively, indicating activation of the intrinsic apoptotic pathway. Consistent with this possibility, overexpression of Bcl(XL) inhibited NU14 activation of caspase 3. Immunoblotting, caspase inhibitors, and caspase activity assays implicated both caspase 2 and caspase 8 in apoptosis, suggesting the involvement of the intrinsic and extrinsic apoptotic cascades. To reconcile the apparent activation of both extrinsic and intrinsic pathways, we examined Bid-green fluorescent protein localization and observed translocation from the cytosol to mitochondria in response to either NU14 or purified FimH. These data suggest that FimH acts as a tethered toxin of UPEC that activates caspase-dependent urothelial apoptosis via direct induction of the extrinsic pathway and that the intrinsic pathway is activated indirectly as a result of coupling by caspase 8-mediated Bid cleavage.

Adhesins, Escherichia coli↗

Prostatitis/chronic pelvic pain syndrome.

We review the diagnosis, categorization, and treatment of prostatitis/chronic pelvic pain syndrome based on the National Institutes of Health (NIH) classification. Prostatitis is an extremely common syndrome that afflicts 2%-10% of men. Formerly a purely clinical diagnosis, prostatitis is now classified within a complex series of syndromes (NIH category I-IV prostatitis) that vary widely in clinical presentation and response to treatment. Acute bacterial prostatitis (category I) and chronic bacterial prostatitis (category II) are characterized by uropathogenic infections of the prostate gland that respond well to antimicrobial treatment. In contrast, chronic prostatitis/chronic pelvic pain syndrome (category III), which accounts for 90%-95% of prostatitis cases, is of unknown etiology and is marked by a mixture of pain, urinary, and ejaculatory symptoms with no uniformly effective therapy. Asymptomatic inflammatory prostatitis (category IV) is an incidental finding of unknown clinical significance. This review describes the current status of prostatitis syndromes and explores the future prospects of new diagnostic tools and therapies.

Humans↗

Chronic prostatitis.

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5-alpha Reductase Inhibitors↗

Role of bacteria in chronic prostatitis/chronic pelvic pain syndrome.

Throughout the past century, we have refined our understanding of prostatitis, moving from using a primarily clinical definition to considering it as a complex inflammatory condition. The inconsistency in identifying uropathogens in patients with symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has led to controversy in therapeutic management. There is compelling evidence that the normal prostate has minimal inflammation and no bacteria. Clinicians using the Meares/Stamey criteria identified uropathogens localized to the prostate in only 6% to 8% of CP/CPPS patients. This suggests that bacteria may have a role in less than 10% of men with CP/CPPS. That some patients respond to antimicrobials could suggest that eradication of bacteria reduces symptoms. However, the beneficial effect of antimicrobial drugs may not be due to their antibacterial action, but to their anti-inflammatory action. The normal prostate shows minimal inflammation, but only 50% of CP/CPPS patients exhibit prostatic leukocytosis. Prudence demands that we examine the function of the white blood cells--the cytokines produced. Several basic science advances allowed new avenues of research regarding the detection of molecular evidence of causative uropathogens. New research brings new controversy and unexpected findings, but further refines our understanding of the immune system and the CP/CPPS disease process.

Animals↗

Anaphylactoid reaction after retrograde pyelography despite preoperative steroid preparation.

A 19-year-old woman with a known allergy to iodinated contrast presented with intermittent, gross hematuria of 2 years' duration. The patient was scheduled to undergo cystoscopy with bilateral retrograde pyelography, because this is considered a safe alternative to intravenous pyelography or computed tomography. Because of her contrast allergy, the patient completed a 13-hour steroid preparation before the procedure. However, within minutes of extubation, she developed an anaphylactoid reaction and, despite appropriate management, required reintubation and subsequent transfer to the intensive care unit. The patient was subsequently extubated 8 hours later and recovered completely.

Adult↗