Biomedical subjects

Kathleen J Propert

Publications and source records attributed to Kathleen J Propert.

14 recordsLinked to original sources

PubMed2007

Discovery of morphological subgroups that correlate with severity of symptoms in interstitial cystitis: a proposed biopsy classification system.

PURPOSE: We identified morphologically distinct subgroups in interstitial cystitis using cluster analysis and investigated the associations between cluster membership and urinary symptoms. MATERIALS AND METHODS: Of 637 patients enrolled in the Interstitial Cystitis Data Base Study 203 (32%) provided bladder biopsies at baseline screening, representing the focus of this analysis. A cluster analysis algorithm implemented in SAS PROC CLUSTER using standardized distances to measure the dissimilarity of each pair of patients with respect to select histopathological features was used to construct subgroups of these patients. Multivariate regression models for baseline nighttime and 24-hour voiding frequency, urinary urgency and pain were developed, incorporating indicator variables for cluster membership as predictors. Longitudinal urinary symptom profiles during 3 years of followup were also compared among the morphology clusters. RESULTS: Three morphology clusters were identified, corresponding to unique pathological groupings. In cluster C2 7 patients showed multiple pathological features of parenchymal damage, including several inflammatory features. In cluster C1 17 patients was characterized by complete denudation of the urothelium and variable edema. In cluster C0 in 179 patients none of the pathological features were present above the specified thresholds for C2. Cluster membership was significantly associated with baseline nighttime and 24-hour frequency (p <0.001, and with urinary urgency (p = 0.03). These significant increases in baseline symptom severity among clusters from C0 to C1 to C2 persisted throughout the 3 years of followup. CONCLUSIONS: These results suggest an important role for histopathological features in the predictive modeling of interstitial cystitis symptoms.

Adult↗

PubMed2007

Pregnancy and interstitial cystitis/painful bladder syndrome.

Painful bladder syndrome (PBS) and interstitial cystitis (IC) often affect women of child-bearing age. This article includes information of interest to PBS/IC patients who are pregnant or contemplating pregnancy, and to the clinicians who care for them. One topic is how pregnancy affects PBS/IC symptoms, although little is known at this time. The article also describes the pregnancy risks associated with the most commonly used PBS/IC treatments. Finally, the current knowledge regarding genetic factors in IC is discussed.

Cystitis, Interstitial↗

PubMed2006

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↗

PubMed2006

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↗

PubMed2005

Early bacteremia in pediatric hematopoietic stem cell transplant patients on oral antibiotic prophylaxis.

BACKGROUND: Bacteremia occurs during hematopoietic stem cell transplant (HSCT) in 20%-25% of patients and the use of gut decontamination (GD) to decrease this risk is controversial. Our purpose was to determine the incidence of bacteremia and antimicrobial resistance post-HSCT in pediatric patients receiving GD, and to identify risk factors associated with infection. PROCEDURES: This was a retrospective cohort study of 182 pediatric patients undergoing first HSCT for malignant disease at The Children's Hospital of Philadelphia from January, 1999 to December, 2002. We examined the impact of age, sex, race, diagnosis, disease status, conditioning regimen, recent bacteremia, stem cell source, donor, graft versus host disease prophylaxis agents, and mucositis severity using Cox proportional hazard models. GD consisted of amoxicillin (azithromycin, if penicillin allergic) and oral gentamicin. Outcome was first episode of bacteremia prior to absolute neutrophil count (ANC) 500/mm(3). Antibiotic susceptibilities were performed on all isolates. RESULTS: Seventy-four patients (41%) developed bacteremia. The majority were Gram-positive cocci, with Staphylococcal (50%) and Streptococcal species (28%) the most common. Gram-negative organisms were identified in 22% with Pseudomonas (5.7%) and Klebsiella species (3.4%) the most common. Of the Streptococcal infections, 72% were resistant to ampicillin; only 25% of the Gram-negative bacteria were resistant to gentamicin. Race was the only factor associated with early bacteremia (hazard ratio 2.3 for non-Caucasian, non-African-American patients, CI 1.3-4.3, P = 0.007). CONCLUSIONS: Early bacteremia is common after HSCT, despite the use of GD. Resistant Gram-positive organisms predominate, consistent with recent trends in immunocompromised patients. Although used in practice, there is no clear evidence for the efficacy of GD and this study provides the basis upon which to develop a randomized clinical trial evaluating the current GD regimen with placebo.

Administration, Oral↗

PubMed2005

Optimal design for dose response using beta distributed responses.

Whenever a response is naturally confined to a finite interval (such as a visual analog scale for pain severity), the beta distribution provides a simple and flexible probability distribution to model such a response. The parameters of the distribution can then be related to covariates, such as dose, in a clinical trial through the generation of a beta regression model. In this article, we explore locally optimal designs for this class of regression models, focusing mainly on minimization of the generalized variance of maximum likelihood estimators (D-optimality). Optimal designs and sensitivity to misspecification of model parameters are examined using a candidate points searching algorithm. Although formally the model assumes that the response is continuous, it provides a parsimonious approximation for ordinal data when there is a relatively large number of categories. The resulting estimators and optimal designs are simpler and may offer more ease in interpretation than those derived from models for ordered categorical outcomes. The proposed methods are applied to data from a clinical trial.

Clinical Trials as Topic↗

PubMed2005

Impact of simultaneous kidney-pancreas transplant and timing of transplant on kidney allograft survival.

Since 1988 over 10 000 simultaneous cadaveric pancreas-kidney transplants (SPK) have been performed in the United States among patients with end-stage renal disease due to Type 1 diabetes (T1DM). The two aims of this study were to assess the impact on kidney allograft survival of (i) SPK versus transplantation of a kidney alone (KA), and (ii) SPK prior to versus after initiation of chronic dialysis. This retrospective, non-concurrent cohort study examined registry data collected from 8323 patients waitlisted in the United States for an SPK and transplanted with either an SPK or a KA during January 1, 1990 - October 31, 2002. SPK recipients had an adjusted hazard ratio for kidney allograft loss of 0.63 (95% CI: 0.51-0.77, p < 0.001) compared to transplantation without pancreas allograft. SPK recipients who received their allografts prior to beginning chronic dialysis had a lower rate of kidney allograft loss than SPK recipients who received their transplant after initiation of chronic dialysis (adjusted hazard rates (HR) = 0.83, 95% CI: 0.69-0.99, p = 0.042). Simultaneous transplantation of pancreas-kidney compared to kidney transplantation alone and SPK prior to the initiation of chronic dialysis compared to SPK after initiation of dialysis were both associated with longer kidney allograft survival.

Adolescent↗

PubMed2004

Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: a randomized, double-blind trial.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men is principally defined by pain in the pelvic region lasting more than 3 months. No cause of the disease has been established, and therapies are empirical and mostly untested. Antimicrobial agents and alpha-adrenergic receptor blockers are frequently used. OBJECTIVE: To determine whether 6-week therapy with ciprofloxacin or tamsulosin is more effective than placebo at improving symptoms in men with refractory, long-standing CP/CPPS. DESIGN: Randomized, double-blind trial with a 2 x 2 factorial design comparing 6 weeks of therapy with ciprofloxacin, tamsulosin, both drugs, or placebo. SETTING: Urology outpatient clinics at 10 tertiary care medical centers in North America. PATIENTS: Patients were identified from referral-based practices of urologists. One hundred ninety-six men with a National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score of at least 15 and a mean of 6.2 years of symptoms were enrolled. Patients had received substantial previous treatment. MEASUREMENTS: The authors evaluated NIH-CPSI total score and subscores, patient-reported global response assessment, a generic measure of quality of life, and adverse events. INTERVENTIONS: Ciprofloxacin, 500 mg twice daily; tamsulosin, 0.4 mg once daily; a combination of the 2 drugs; or placebo. RESULTS: The NIH-CPSI total score decreased modestly in all treatment groups. No statistically significant difference in the primary outcome was seen for ciprofloxacin versus no ciprofloxacin (P = 0.15) or tamsulosin versus no tamsulosin (P > 0.2). Treatments also did not differ significantly for any of the secondary outcomes. LIMITATIONS: Treatment lasting longer than 6 weeks was not tested. Patients who had received less pretreatment may have responded differently. CONCLUSION: Ciprofloxacin and tamsulosin did not substantially reduce symptoms in men with long-standing CP/CPPS who had at least moderate symptoms.

Adrenergic alpha-Antagonists↗

PubMed2004

Granulomatous prostatitis linked to HLA-DRB1*1501.

PURPOSE: Granulomatous prostatitis is characterized by a pattern of granulomatous inflammation in the prostate. In most cases the etiology is unknown. Based on the hypothesis that granulomatous prostatitis may be an autoimmune disease we performed intermediate and selective high resolution typing of HLA-DR in a group of patients with the disease and compared the frequency of class II HLA phenotypes to that in a control group of volunteer marrow donors in the military. MATERIALS AND METHODS: Histological records from 1 institution from 1990 to 2000 revealed 12 patients with diffuse granulomatous prostatitis. Three patients were dead and 1 refused blood drawing. Peripheral blood from the remaining 8 patients was typed along with blood from an additional 3 identified at the practice of one of us from 1999 through 2002. All slides were reviewed by 1 pathologist. Intermediate resolution typing of HLA-A, B and DR was performed by polymerase chain reaction-sequence specific oligonucleotide probe. High resolution, allele specific identification of HLA DR15 was performed if patients were DR15 positive by intermediate resolution typing. RESULTS: There were 3 black and 8 white individuals identified with diffuse nonspecific granulomatous prostatitis. Six of 8 white patients (75%) were HLA-DR15 by intermediate resolution typing. One of the 3 black American patients (33%) was HLA-DR15. In the control group 127 of 451 white (28.2%) and 23 of 89 black (25.8%) volunteer marrow donors were HLA-DR15. The case-control comparison of white patients was significantly different (Fisher's exact test p = 0.0086). There were no statistically significant differences between case-control comparisons for any other HLA-DR phenotype. High resolution DR15 typing showed that the white patients were HLA-DRB1*1501 and the black patient was HLA-DRB1*1503. CONCLUSIONS: The data suggest an association between HLA-DRB1*1501 and granulomatous prostatitis. HLA-DR15 is strongly associated with other autoimmune diseases, notably multiple sclerosis. The data are consistent with an autoimmune etiology for nonspecific granulomatous prostatitis.

Aged↗

PubMed2003

Leukocytes and bacteria in men with chronic prostatitis/chronic pelvic pain syndrome compared to asymptomatic controls.

PURPOSE: Chronic prostatitis has been traditionally characterized by inflammation and/or infection of the prostate gland, objectively categorized by white blood cells and cultured bacteria in prostate specific specimens. We compared leukocyte counts and localization rates for bacterial cultures of segmented urine samples (VB1, VB2, VB3), expressed prostatic secretion (EPS) and semen in men diagnosed with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) to men without pelvic pain (controls). MATERIALS AND METHODS: A total of 463 men enrolled in the National Institutes of Health Chronic Prostatitis Cohort study and 121 age matched men without urinary symptoms had leukocyte counts performed and 5-day bacterial cultures on specimens obtained from a standard 4-glass test (VB1, VB2, EPS, VB3) and semen. All risk factor comparisons between case and control analyses were tested using generalized Mantel-Haenszel methods, and multivariable models were developed using logistic regression methods, adjusting for clustering by clinical center within both methods. RESULTS: Men with CP/CPPS had statistically higher leukocyte counts in all segmented urine samples and EPS, but not in semen compared to asymptomatic control men. However, the control population also had a high prevalence of leukocytes. Of the men with CP/CPPS 50% and 32% had 5 or more, or 10 or more white blood cells (WBCs) per high power field, respectively, in EPS compared to 40% and 20% of the control population. Similarly, 32% and 14% of the patients with CP/CPPS had 5 or more, or 10 or more WBCs per high power field in VB3 compared to 19% and 11% in the control population. Localization of uropathogenic bacteria in EPS, VB3 and/or semen was similar in men with CP/CPPS (8.0%) and asymptomatic men (8.3%). CONCLUSIONS: Men with CP/CPPS have significantly higher leukocyte counts in all segmented urine samples and EPS but not in semen as compared to controls. There is no difference in rates of localization of bacterial cultures for men with CP/CPPS compared to control men. The high prevalence of WBCs and positive bacterial cultures in the asymptomatic control population raises questions about the clinical usefulness of the standard 4-glass test as a diagnostic tool in men with CP/CPPS.

Adult↗

PubMed2002

A pilot study of in vivo liver-directed gene transfer with an adenoviral vector in partial ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency (OTCD) is an inborn error of urea synthesis that has been considered as a model for liver-directed gene therapy. Current treatment has failed to avert a high mortality or morbidity from hyperammonemic coma. Restoration of enzyme activity in the liver should suffice to normalize metabolism. An E1- and E4-deleted vector based on adenovirus type 5 and containing human OTC cDNA was infused into the right hepatic artery in adults with partial OTCD. Six cohorts of three or four subjects received 1/2 log-increasing doses of vector from 2 x 10(9) to 6 x 10(11) particles/kg. This paper describes the experience in all but the last subject, who experienced lethal complications. Adverse effects included a flu-like episode and a transient rise in temperature, hepatic transaminases, thrombocytopenia, and hypophosphatemia. Humoral responses to the vector were seen in all research subjects and a proliferative cellular response to the vector developed in apparently naive subjects. In situ hybridization studies showed transgene expression in hepatocytes of 7 of 17 subjects. Three of 11 subjects with symptoms related to OTCD showed modest increases in urea cycle metabolic activity that were not statistically significant. The low levels of gene transfer detected in this trial suggest that at the doses tested, significant metabolic correction did not occur.

Adenoviruses, Human↗

PubMed2002

Leukocyte and bacterial counts do not correlate with severity of symptoms in men with chronic prostatitis: the National Institutes of Health Chronic Prostatitis Cohort Study.

PURPOSE: We examine whether leukocytes and bacteria correlate with symptom severity in men with chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: All 488 men screened into the National Institutes of Health Chronic Prostatitis Cohort Study before close of recruitment on August 22, 2001 were selected for analysis. The National Institutes of Health Chronic Prostatitis Symptom Index, including subscores, were used to measure symptoms. Urethral inflammation was defined as white blood cell (WBC) counts of 1 or more (1+) in the first voided urine. Participants were classified as category IIIa based on WBC counts of 5 or more, or 10 or more (5+, 10+) in the expressed prostatic secretion, or 1+ or 5+ either in the post-expressed prostatic secretion urine (voided urine 3) or semen. Uropathogens were classified as localizing if the designated bacterial species were absent in voided urine 1 and voided urine 2 but present in expressed prostatic secretion, voided urine 3 or semen, or present in expressed prostatic secretion, voided urine 3 or semen at 2 log concentrations higher than at voided urine 1 or 2. Associations between symptoms, and inflammation and infection were investigated using generalized Mantel-Haenszel methods. RESULTS: Of all participants 50% had urethral leukocytes and of 397 with expressed prostatic secretion samples 194 (49%) and 122 (31%) had 5+ or 10+ WBCs in expressed prostatic secretion, respectively. The prevalence of category IIIa ranged from 90% to 54%, depending on the composite set of cut points. None of the index measures were statistically different (p >0.10) for selected leukocytosis subgroups. Based on prostate and semen cultures, 37 of 488 men (8%) had at least 1 localizing uropathogen. None of the index measures were statistically different (p >0.10) for selected bacterial culture subgroups. CONCLUSIONS: Although men with chronic prostatitis routinely receive anti-inflammatory and antimicrobial therapy, we found that leukocytes and bacterial counts as we defined them do not correlate with severity of symptoms. These findings suggest that factors other than leukocytes and bacteria also contribute to symptoms associated with chronic pelvic pain syndrome.

Chronic Disease↗

PubMed2002

Design of a multicenter randomized clinical trial for chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVES: To describe the study design and rationale for the first placebo-controlled, randomized clinical trial to be conducted by the Chronic Prostatitis Collaborative Research Network sponsored by the National Institutes of Health. METHODS: The clinical trial will use a 2 by 2 factorial design to evaluate four treatments: placebo, tamsulosin hydrochloride alone, ciprofloxacin alone, and tamsulosin hydrochloride and ciprofloxacin combined. The primary objectives are to compare the efficacy and safety endpoints in patients with chronic prostatitis/chronic pelvic pain syndrome. The study population consists of men with symptoms of discomfort or pain in the pelvic region for at least a 3-month period. One hundred eighty-four participants will be treated for 6 weeks and followed up for an additional 6 weeks. The primary endpoint is the change in the overall National Institutes of Health Chronic Prostatitis Symptom Index from baseline to 6 weeks. Secondary endpoints include a patient-reported global assessment of response and white blood cell counts and cultures in urine, expressed prostatic secretions, and semen. The evaluation of changes from 6 to 12 weeks will be used to assess the durability of the response. RESULTS: This trial was opened to enrollment in July 2001. The study is expected to require 14 months of accrual and follow-up. CONCLUSIONS: The issues considered in the design of this clinical trial may provide guidelines for future clinical trials in chronic prostatitis/chronic pelvic pain syndrome.

Adrenergic alpha-Antagonists↗

PubMed2002

Demographic and clinical characteristics of men with chronic prostatitis: the national institutes of health chronic prostatitis cohort study.

PURPOSE: We describe the study design of the National Institutes of Health Chronic Prostatitis Cohort (CPC) study characterizing men with chronic prostatitis/the chronic pelvic pain syndrome. MATERIALS AND METHODS: All 488 men screened into the CPC study before close of recruitment on August 22, 2001 were selected for analysis. The National Institutes of Health Chronic Prostatitis Symptom Index, including subscores, was used to measure symptoms. A comprehensive history, physical examination and demographic profile were obtained from each participant. Generalized Mantel-Haenszel procedures were used to investigate baseline associations between selected factors and symptoms. RESULTS: Chronic prostatitis/chronic pelvic pain syndrome is a chronic syndrome affecting men over a wide age range. The majority of CPC study participants are white, well educated and affluent. However, lower education, lower income and unemployment were associated with more severe symptoms. Patients most frequently reported pain in the perineum and tenderness in the prostate. The highest self-reported diseases were genitourinary (55%), allergies (53%), neurological (40%) and hematopoietic, lymphatic or infectious (40%). This disease has a significant negative impact on mental and physical domains of quality of life. Almost all patients (95%) reported antimicrobial drug use. Of these 488 participants 280 (57%) reported the previous or current use of 5 or more categories of prostatitis related treatments. CONCLUSIONS: Chronic prostatitis/chronic pelvic pain syndrome is a multifactorial problem affecting men of all ages and demographics. Patients with the chronic pelvic pain syndrome have dismal quality of life and many have benefited only minimally from empirical, goal directed therapy. Long-term followup of this cohort may answer important questions on the natural treated history of this syndrome.

Adult↗