Linda M. Dairiki Shortliffe

View details for DOI 10.1016/j.juro.2014.01.012

Abstract

Current clinical judgment in bladder cancer (BC) relies primarily on pathological stage and grade. We investigated whether a molecular classification of tumor cell differentiation, based on a developmental biology approach, can provide additional prognostic information. Exploiting large preexisting gene-expression databases, we developed a biologically supervised computational model to predict markers that correspond with BC differentiation. To provide mechanistic insight, we assessed relative tumorigenicity and differentiation potential via xenotransplantation. We then correlated the prognostic utility of the identified markers to outcomes within gene expression and formalin-fixed paraffin-embedded (FFPE) tissue datasets. Our data indicate that BC can be subclassified into three subtypes, on the basis of their differentiation states: basal, intermediate, and differentiated, where only the most primitive tumor cell subpopulation within each subtype is capable of generating xenograft tumors and recapitulating downstream populations. We found that keratin 14 (KRT14) marks the most primitive differentiation state that precedes KRT5 and KRT20 expression. Furthermore, KRT14 expression is consistently associated with worse prognosis in both univariate and multivariate analyses. We identify here three distinct BC subtypes on the basis of their differentiation states, each harboring a unique tumor-initiating population.

View details for DOI 10.1073/pnas.1120605109

View details for Web of Science ID 000299925000058

View details for PubMedID 22308455

Abstract

We examined trends in pediatric hospitalization for pyelonephritis from 1985 to 2006 and identified factors associated with admission.We performed a population based analysis of hospital discharges using the Office of Statewide Health Planning and Development database to evaluate trends in California regarding pediatric hospitalizations for pyelonephritis from 1985 to 2006. Multivariable logistic regression was performed to identify factors associated with admission for pyelonephritis.A total of 46,300 children were hospitalized for pyelonephritis in California from 1985 to 2006. The overall rate of hospitalization for pyelonephritis increased by greater than 80%, from 17 per 100,000 children in the California population in 1985 to 31 per 100,000 in 2005. This change was primarily due to the nearly ninefold increase in pyelonephritis hospitalizations observed in children younger than 1 year, from 28 per 100,000 in 1985 to 238 per 100,000 in 2005. Among children younger than 1 year males without private insurance and of nonwhite race had increased odds of hospitalization, while females with private insurance and of Asian race had increased odds of hospitalization, compared with nonprivate insurance and white race, respectively.A significant increase in hospital admissions for pyelonephritis, primarily in children younger than 1 year, occurred in California between 1985 and 2006. Further studies are needed to establish the cause of this striking increase and to determine why certain pediatric populations are at increased risk for hospitalization.

View details for DOI 10.1016/j.juro.2011.04.101

View details for Web of Science ID 000293688300095

View details for PubMedID 21784477

Abstract

Using statewide data, we evaluated whether the changing incidence of penile anomalies and hypospadias is reflected in the diverse California population of newborn males over the past 20 years.Discharge data from all California hospitals, prepared by the OSHPD (Sacramento, CA) was reviewed for the years 1985-2006 for male infant births with an ICD-9 code (752.6) for hypospadias, epispadias or other penile anomalies. Trends were examined by Generalized Estimation Equations for Poisson regression.From 1985 to 2006, the birth incidence of newborn penile anomalies increased in California from 47 to 57 cases per 10,000 newborn discharges, yet the trend for hypospadias alone appears stable from 1997. The rates for penile anomalies in newborns increased 1.4% annually (p < 0.001). All racial/ethnic groups analyzed showed this increase (p < 0.001 for each). During the study period there was a 2% increase per year in plural births (p < 0.001). Interestingly, the rate of change in penile anomaly incidence was greater in males of plural births compared to their singleton cohorts (2% vs 1% annually) (p < 0.001). The birth incidence of cleft palate, another congenital anomaly known to be stable over time, remained unchanged over this period.From 1985 to 2006 in California the incidence of penile anomalies increased in a statistically significant manner, but the incidence of hypospadias appears stable for the last decade. Our data support the notion that different racial/ethnic groups have distinct incidences of penile anomaly formation and that an association with plural births appears to be present.

View details for DOI 10.1016/j.jpurol.2011.03.006

View details for Web of Science ID 000292666200014

View details for PubMedID 21527236

Abstract

To create a reliable rat model with small renal cortical scars and evaluate the accuracy and sensitivity of dynamic contrast-enhanced MRI in detecting the kinds of lesions that are associated with reflux nephropathy.In 16 rats, three unilateral renal cortical lesions were created using either electrocautery or pure alcohol with the contralateral kidney serving as control. MRI on a 1.5 Tesla GE Signa was performed 10-14 days after surgery. After bolus injection of 0.2 mM/Kg Gd-DTPA, sequential MRI acquisitions were performed using a 4-inch quadrature birdcage coil. Renal and scar volumes and pathology were compared after scanning and killing.Of the 48 points of injury, 40 (83%) in the 16 rats were detected grossly. Under microscopy, 36 injuries (75%) were detected on mid-kidney cross-sections. The average lesion was 4.2 mm(3) corresponding to 0.5% of the kidney volume. Using pathological findings as the gold standard, the sensitivity and specificity of scar detection using MRI was 69% and 93%, respectively.A rat model was created to demonstrate the sensitivity of dynamic contrast-enhanced MRI for detecting renal scars. Alcohol and electrocautery created reliable renal scars that were confirmed pathologically. MRI detected these lesions that averaged 4.2 mm(3) (0.5% total renal volume) with sensitivity and specificity of 69% and 93%, respectively.

View details for DOI 10.1002/jmri.22027

View details for Web of Science ID 000277397100012

View details for PubMedID 20432348

Abstract

Antibiotic prophylaxis is commonly used for medical management of vesicoureteral reflux. Little information exists on compliance with antibiotic prophylaxis in patients with vesicoureteral reflux.We queried the i3 Innovus (Ingenix) pharmacy claims 2002 to 2007 database for patients 18 years old or younger with vesicoureteral reflux (ICD-9 code 593.7 plus claim for cystogram) and analyzed those with at least 1 year of followup data. Criteria for management with antibiotic prophylaxis were 2 or more 30-day supplies of antibiotic prescriptions, or 4 or more 14-day supplies of prescriptions if the antibiotic was a penicillin or cephalosporin. Antibiotic prophylaxis compliance was determined using a medication possession ratio, an estimate of the proportion of time that patients have a prescribed drug available for use. Compliance was established as a medication possession ratio of 80% or greater, meaning coverage with antibiotic prophylaxis for 80% of the year or more.Of 9,496 patients with vesicoureteral reflux 5,342 (56.3%) were treated with antibiotic prophylaxis. Most patients were female (81%) and 5 years old or younger (79%). Trimethoprims/sulfonamides were most commonly prescribed (62%) and antiseptics were next (24%). Of patients prescribed antibiotic prophylaxis 40% were compliant. Compliance was lower for 6 to 10-year-olds (OR 0.71, 95% CI 0.61-0.83) and 11 to 18-year-olds (OR 0.56, 95% CI 0.41-0.79) compared to younger children (5 years or less). Increased compliance was associated with 1 or more hospitalizations (OR 1.70, 95% CI 1.48-1.97) and 1 or more urologist visits (OR 1.41, 95% CI 1.25-1.58).Among patients with vesicoureteral reflux who are prescribed prophylactic antibiotics 40% are compliant with treatment. Young age, frequent hospitalization and specialist visits are associated with compliance. This knowledge may help to develop effective interventions to improve compliance and underscores the importance of reporting compliance in clinical studies evaluating the usefulness of antibiotic prophylaxis in vesicoureteral reflux management.

View details for DOI 10.1016/j.juro.2010.01.036

View details for Web of Science ID 000276747600134

View details for PubMedID 20303526

Abstract

Studies show that renal volume on magnetic resonance imaging correlates with differential function and is decreased in children with vesicoureteral reflux diagnosed after urinary tract infection. We examined the correlation between ultrasound renal parenchymal area and magnetic resonance imaging volume to determine whether quantitative ultrasound renal parenchymal area might be a reliable, less costly and less invasive substitute for renal magnetic resonance imaging volume.To determine the correlation of ultrasound renal parenchymal area with magnetic resonance imaging, we identified 82 children with primary vesicoureteral reflux who underwent renal magnetic resonance imaging and ultrasound. Magnetic resonance imaging volume was compared with ultrasound renal parenchymal area, renal length and calculated ellipsoid volume. To determine the correlation of ultrasound renal parenchymal area with reflux grade, ultrasound renal parenchymal area was examined in 96 children with reflux and urinary tract infection, and in 52 with reflux without urinary tract infection. Linear regression and multivariate analysis were performed to find the relationship between ultrasound renal parenchymal area and reflux grade.The correlation of ultrasound renal parenchymal area with magnetic resonance imaging volume was superior to that of renal length and calculated ellipsoid volume (r(2) = 0.90 vs 0.83 and 0.84, respectively). Hydronephrosis did not affect the correlation. On multiple regression analysis in children with reflux and urinary tract infection higher reflux grade correlated with decreased ultrasound renal parenchymal area (p = 0.0016). In children with reflux without urinary tract infection reflux grade did not correlate with decreased ultrasound renal parenchymal area (p = 0.47).Ultrasound renal parenchymal area correlates closely with magnetic resonance imaging derived 3-dimensional renal volume and is capable of detecting progressive renal area loss in patients with reflux and urinary tract infection. More studies are necessary to verify whether data from more invasive tests, such as renal magnetic resonance imaging and dimercapto-succinic acid scan, may be attained from ultrasound renal parenchymal area alone.

View details for DOI 10.1016/j.juro.2009.03.075

View details for Web of Science ID 000269764300009

View details for PubMedID 19692072

Abstract

Major clinical issues in bladder cancer include the identification of prediction markers and novel therapeutic targets for invasive bladder cancer. In the current study, we describe the isolation and characterization of a tumor-initiating cell (T-IC) subpopulation in primary human bladder cancer, based on the expression of markers similar to that of normal bladder basal cells (Lineage-CD44(+)CK5(+)CK20(-)). The bladder T-IC subpopulation was defined functionally by its enriched ability to induce xenograft tumors in vivo that recapitulated the heterogeneity of the original tumor. Further, molecular analysis of more than 300 bladder cancer specimens revealed heterogeneity among activated oncogenic pathways in T-IC (e.g., 80% Gli1, 45% Stat3, 10% Bmi-1, and 5% beta-catenin). Despite this molecular heterogeneity, we identified a unique bladder T-IC gene signature by gene chip analysis. This T-IC gene signature, which effectively distinguishes muscle-invasive bladder cancer with worse clinical prognosis from non-muscle-invasive (superficial) cancer, has significant clinical value. It also can predict the progression of a subset of recurring non-muscle-invasive cancers. Finally, we found that CD47, a protein that provides an inhibitory signal for macrophage phagocytosis, is highly expressed in bladder T-ICs compared with the rest of the tumor. Blockade of CD47 by a mAb resulted in macrophage engulfment of bladder cancer cells in vitro. In summary, we have identified a T-IC subpopulation with potential prognostic and therapeutic value for invasive bladder cancer.

View details for DOI 10.1073/pnas.0906549106

View details for Web of Science ID 000269078700071

View details for PubMedID 19666525

Abstract

Renal parenchymal damage is a well recognized sequela of urinary tract infection in the setting of vesicoureteral reflux. We investigated renal magnetic resonance imaging as a quantitative modality to detect renal parenchymal damage in children with primary vesicoureteral reflux and urinary tract infection.We retrospectively reviewed the medical records of children with primary vesicoureteral reflux and urinary tract infection who underwent renal magnetic resonance imaging evaluation. Those with other genitourinary pathology were excluded. Controls underwent magnetic resonance imaging for nongenitourinary pathologies. Kidneys were segregated among control, nonrefluxing, and low grade (I to III) and high grade (IV to V) reflux. Size plots (magnetic resonance imaging volume vs age) were drawn for comparison. Gross imaging abnormalities observed were renal scarring and small size.Magnetic resonance imaging was performed in 114 patients with vesicoureteral reflux (228 kidneys, patient age 0.5 to 17.8 years) and 21 controls (42, 0.5 to 12). Higher grades of reflux were associated with smaller volume, and smaller volume was noted in the refluxing and nonrefluxing kidneys of children with vesicoureteral reflux. Kidneys from patients with unilateral or bilateral reflux had significantly decreased renal volume compared to controls (p <0.0001). Kidneys in which vesicoureteral reflux spontaneously resolved had renal volumes similar to control kidneys (p = 0.23).Use of magnetic resonance imaging derived renal volume allows renal comparison and is helpful in evaluating patients with vesicoureteral reflux. In patients with a history of a febrile urinary tract infection and reflux the finding of measurably smaller kidneys appears to be more common than scarring. Whether these findings represent renal atrophy or hypoplasia needs further investigation.

View details for Web of Science ID 000250847900082

View details for PubMedID 17937957

Abstract

Voiding cystourethrography (VCUG) is a commonly performed radiologic procedure in children that can be both painful and frightening. Given the distress that some children experience during the VCUG and the need for children to be alert and cooperative during the procedure, finding a psychological intervention that helps children to manage anxiety, distress, and pain is clearly desirable. This study was designed to examine whether relaxation and analgesia facilitated with hypnosis could reduce distress and procedure time for children who undergo this procedure.Forty-four children who were scheduled for an upcoming VCUG were randomized to receive hypnosis (n = 21) or routine care (n = 23) while undergoing the procedure. The sample consisted of 29 (66%) girls and 15 (34%) boys with a mean age of 7.6 years (SD: 2.5; range: 4-15 years). Ethnic/racial backgrounds were 72.7% white, 18.2% Asian, 4.5% Latino, 2.3% black, and 2.3% Filipino. The mean number of previous VCUGs was 2.95 (SD: 2.51; mode: 2; range: 1-15). Potential participants were identified through computerized hospital records of upcoming VCUGs. Parents were contacted by telephone and invited to participate if their child was eligible. To be eligible for the study, the child must have undergone at least 1 previous VCUG, been at least 4 years of age at that time, and experienced distress during that procedure, and both the child and the participating parent had to be English speaking. Each eligible child and parent met with the research assistant (RA) before the day of the scheduled procedure for an initial assessment. Children were queried regarding the degree of crying, fear, and pain that they had experienced during their most recent VCUG. Parents completed a series of parallel questions. Immediately after this assessment, those who were randomized to the hypnosis condition were given a 1-hour training session in self-hypnotic visual imagery by a trained therapist. Parents and children were instructed to practice using the imaginative self-hypnosis procedure several times a day in preparation for the upcoming procedure. The therapist was also present during the procedure to conduct similar exercises with the child. The majority (83%) of those who were randomized to the routine care control group chose to participate in a hospital-provided recreation therapy program (offered as part of routine care). The program includes demonstration of the procedure with dolls, relaxation and breath work training, and assistance during the procedure. On the day of the VCUG, the RA met the family at the clinic before the procedure, and both the child and the parent rated the child's present level of fearfulness. During the procedure, the RA recorded observational ratings of the child's emotional tone and behavior and timed the overall procedure and its phases. Immediately after the VCUG, the child was asked how much crying, fear, and pain he or she had experienced during the procedure; the parent rated the child's experience on the same dimensions and also how traumatic the procedure had been (both generally and compared with their previous one), and the medical staff rated the degree of procedural difficulty. Outcomes included child reports of distress during the procedure, parent reports of how traumatic the present VCUG was compared with the previous one, observer ratings of distress during the procedure, medical staff reports of the difficulty of the procedure overall, and total procedural time.Results indicate significant benefits for the hypnosis group compared with the routine care group in the following 4 areas: (1) parents of children in the hypnosis group compared with those in the routine care group reported that the procedure was significantly less traumatic for their children compared with their previous VCUG procedure; (2) observational ratings of typical distress levels during the procedure were significantly lower for children in the hypnosis condition compared with those in the routine care condition; (3) medical staff reported a significant difference between groups in the overall difficulty of conducting the procedure, with less difficulty reported for the hypnosis group; and (4) total procedural time was significantly shorter-by almost 14 minutes-for the hypnosis group compared with the routine care group. Moderate to large effect sizes were obtained on each of these 4 outcomes.Hypnotic relaxation may provide a systematic method for improving the overall medical care of children with urinary tract abnormalities and may be beneficial for children who undergo other invasive medical procedures. Because the VCUG is an essential part of the evaluation of urinary tract infections and vesicoureteral reflux in children, lower distress during the procedure may improve patient and family compliance with initial as well as follow-up evaluations. These findings augment the accumulating literature demonstrating the benefits of using hypnosis to reduce distress in the pediatric setting. The present findings are noteworthy in that this study was a controlled, randomized trial conducted in a naturalistic medical setting. In this context, we achieved a convergence of subjective and objective outcomes with moderate to large effect sizes, including those that may have an impact on patient care and procedure cost, that were consistently supportive of the beneficial effects of hypnosis-a noninvasive intervention with minimal risk. The findings, therefore, have immediate implications for pediatric care. Limitations of this study include the lack of participant and staff blindness to the child's condition assignment, which could have introduced bias into reports. However, the objective procedural time differences between groups were consistent with the other, more subjective outcome findings. The sample was also small and primarily white in ethnic/racial makeup, which may have restricted our ability to detect some differences and may limit the generalizability of findings to more representative samples. In addition, the sample comprised children who had already undergone at least 1 VCUG during which they had had difficulty. Consequently, additional research is needed to determine whether hypnosis would be helpful to those who are undergoing their first VCUG. Additional limitations, clinical observations, and directions for future research are also discussed.

View details for DOI 10.1542/peds.2004-0818

View details for Web of Science ID 000226083700012

View details for PubMedID 15629969

Abstract

To evaluate the effects of oestrogen, progesterone and pregnancy on bladder dynamics, and assess the associated histological and structural changes in the bladder wall in a rat model.Adult female Sprague-Dawley rats were divided into groups and treated as follows: nonpregnant controls (NC); pregnant (PG); oophorectomized and treated with oestrogen (ES); oophorectomized and treated with progesterone (PR); and oophorectomized controls (OO). Simultaneous and continuous renal pelvic and bladder pressures were recorded during bladder filling and emptying. Connective tissue and smooth muscle were analysed morphometrically and quantitatively, and immunohistochemistry used to evaluate the distribution and expression of collagen types I, III and IV.PG rats had significantly greater bladder compliance than NC, OO and PR rats (P < 0.05). This correlated with the morphometric analysis, with bladders of PG and PR rats having lower connective tissue to smooth muscle ratios than NC, ES and OO rats (P < 0.05). Collagen I was increased in the lamina propria of PG and ES rats, and the detrusor muscle layer showed greater localization of collagen III in the interfascicular space in the PG and PR rats than in the other groups. There was no change in the distribution of collagen IV.PG and PR rats had the highest bladder compliance and the changes paralleled structural changes in the bladders, specifically in the ratio of connective tissue to smooth muscle, and the distribution and expression of collagens I and III. These changes have age-related implications in the urinary tract.

View details for DOI 10.1111/j.1464-410X.2004.05174.x

View details for Web of Science ID 000226256100039

View details for PubMedID 15610122

Abstract

Magnetic resonance imaging (MRI) and computerized tomography (CT) are commonly used to image complex medical conditions but limited data have been reported concerning normal renal volumetric measurement with these imaging techniques. We examined whether normative renal growth curves could be constructed from data derived from these imaging modalities, and from these curves assessed normal and abnormal renal development.Patients who had undergone prior renal MRI or CT were identified. Total renal volume and renal cortical fraction (CF, cortical/total volume) were calculated, and growth curves were derived. To examine the curve utility for abnormal growth assessment, renal ultrasonography of children with reflux nephropathy was examined, and MRI and radionuclide scans were compared.A total of 60 patients 2 months to 39 years old who underwent MRI were included in the growth curve. The CF of the 120 kidneys was 75.8 +/- 4.3% and independent of sex and age. In 19 patients with vesicoureteral reflux 13 kidneys had cortical scarring, and the CF was decreased (p <0.001, 63.65 +/- 5.72%), indicating disproportionate cortical loss. No difference between CF for normal and vesicoureteral reflux unscarred kidneys was found. Differential renal function on radionuclide study correlated highly with MRI renal volume (r = 0.91). CT was performed in 70 children 1 to 15 years old (mean age 7.9) volume correlated with age and renal length, and the left kidney was larger than right kidney on MRI and CT.Normative renal growth curves can be constructed from CT and MRI derived renal volumes. Cortical fraction is consistent, and sex and age independent. In reflux nephropathy the CF is reduced and renal differential function on nuclear scan correlates with MRI derived differential volume. This concept may be useful for predicting abnormal renal growth and differential function.

View details for DOI 10.1097/01.ju.0000085676.76111.27

View details for Web of Science ID 000185401300087

View details for PubMedID 14501685

Abstract

When a partially obstructed kidney becomes infected, more rapid and extreme renal parenchymal damage appears to occur than might result from either infection or obstruction alone. Previously, we showed that either bacteriuria or partial obstruction in congenital unilateral hydronephrosis causes elevated renal pelvic pressures in a rat model. In this same model, we examined the combined effects of partial upper tract obstruction and bacteriuria on renal pelvic and bladder pressures.Female rats from an inbred colony in which more than one half are born with unilateral obstructive hydronephrosis were studied. Type 1 piliated Escherichia coli was instilled into the bladder. Two to 6 days later, the bladder and renal pelvic pressures were measured during varying urinary flows (less than 2 to more than 30 mL/kg/hr). All animals were killed and the kidneys and bladder grossly and histologically assessed. Hydronephrosis was determined at pathologic examination.Eight rats had congenital unilateral hydronephrosis; five were normal. Acute inflammation was found in all bladder and renal specimens. In hydronephrotic, infected kidneys, the renal pelvic pressures exceeded those in nonhydronephrotic, infected kidneys at all urinary flow rates. Bladder capacity and pressures did not differ between the two groups.This model demonstrates that the combination of infection and obstructive hydronephrosis in this model causes renal pelvic pressure elevation that is higher than that associated with either infection or obstructive hydronephrosis alone. These data demonstrate the compound effect that infection and obstruction may have on the kidney and offers an explanation for why this clinical situation is more likely to be associated with greater renal parenchymal injury than either alone.

View details for DOI 10.1016/S0090-4295(02)02413-5

View details for Web of Science ID 000182193500041

View details for PubMedID 12670589

Abstract

Multicystic dysplastic kidneys have negligible renal function and the contralateral kidney (solitary kidney) frequently exhibits abnormalities that may affect growth. We previously showed that nomograms related to renal size constructed from digitalized ultrasonographic measurements of renal parenchymal area are a sensitive measure of renal growth and correlate with functional mass. We assess the age-dependent characteristics of compensatory renal growth in infants and children with multicystic dysplastic kidneys by construction of a growth curve for the contralateral kidney, assess these characteristics in comparison to normal renal growth of right and left kidneys, analyze the extent of compensatory renal growth and evaluate abnormal growth in solitary kidneys in infants and children.From 1988 to 2000 we reviewed 152 serial sonograms from 48 patients with a diagnosis of multicystic dysplastic kidneys. We also reviewed 209 renal sonograms in patients whose studies, done for other purposes, showed normal bilateral kidneys. Using computer planimetry, parenchymal area and pelvicaliceal area were determined after digitalization of ultrasound images. Parenchymal area was calculated by parenchymal area minus pelvicaliceal area and expressed as a mean of 3 measurements. A parenchymal area growth curve was generated for the contralateral kidney in the multicystic dysplastic kidney group from birth to 216 months, and for right and left normal kidneys from birth to 338 months. Data were plotted as mean parenchymal area +/- 2 SD on a nomogram generated by linear regression. Differences in parenchymal area between normal right and left kidneys, between normal kidneys and the contralateral to multicystic dysplastic kidney were analyzed by unpaired Student t test.Of the 48 patients with multicystic dysplastic kidneys 36 had contralateral normal kidneys and 12 (25%) had a contralateral abnormality. Of the 12 cases 4 and an additional 5 without an identified abnormality (9 of 48) or 18.7% had solitary kidneys 2 SD below the normal growth curve for total parenchymal area, indicating a smaller than expected increase in compensatory renal growth. Conversely, 8 of 12 including 1 with grade V reflux into a solitary kidney exhibited normative compensatory renal growth. Left normal kidneys demonstrated a small but statistically significantly larger parenchymal area throughout growth. Solitary kidneys did not demonstrate growth differences associated with side. Solitary kidneys showed accelerated growth from 0 to 22 months while normal kidneys showed accelerated growth from 0 to 15 months.Nomograms constructed from ultrasonographic measurements of renal parenchymal area may be useful for assessing abnormal renal growth in solitary kidneys. Patients with solitary kidneys identified by conventional ultrasonographic measurement as normal may not exhibit expected growth. Clinical decision making may be improved by identification of solitary kidneys at risk for poor growth.

View details for DOI 10.1097/01.ju.0000027230.09175.80

View details for Web of Science ID 000178188000072

View details for PubMedID 12352368

Abstract

The authors have prospectively documented that men who undergo orthotopic bladder substitution more frequently experience bacteriuria than do normal men [19] or men with carcinoma of the prostate scheduled to have radical prostatectomy (see Table 1). Because the frequency of bacteriuria in men after prostatectomy was also lower than that after orthotopic bladder substitution (see Table 1), removal of the prostate and any of its presumed antibacterial properties probably does not account for this difference. Furthermore, the authors' data (see Table 5 ) and that of Woodside and associates [23] demonstrate that intestine incorporated into the genitourinary tract generates a local antibody response against urinary bacteria. Although others have suggested that the incorporation of bowel in the urinary tract may be associated with increased bacteriuria, this effect has never been documented prospectively. The mechanism of this increased frequency of bacteriuria is unknown. Because the anatomy of the male secretory genitourinary system may be altered after radical prostatectomy and orthotopic bladder substitution, the authors evaluated local antibody production before and after these operations. More than 20 years ago, Burdon [5] found that the initial portion of the VB1 sample in men had significantly higher levels of IgA compared with the VB2 specimen, whereas the levels of IgG were similar in the two portions. This latter finding was confirmed by Shorliffe and co-workers [22] when they examined prostatic secretion. Other investigators have found high levels of IgA in human prostatic tissue and fluid. [24,25]. On the basis of these findings, it was believed that, in men, the prostate produces most of the urinary IgA, whereas the bladder or upper urinary tracts make most of the urinary IgG. Although the authors' study confirms that most local urinary tract IgG is produced by the bladder or upper urinary tracts, this study documents that the prostate is not the only source of urethral IgA in men. Despite almost complete removal or prostate secretory epithelium by radical prostatectomy, as evidenced by a dramatic fall in postoperative VB1 and VB2 PSA compared with preoperative levels (Table 3). men who had this operation had only slightly decreased IgA levels after the operation (Table 4, Fig I). The source of this IgA must be urethral because the VB1 urinary stream contains more IgA than the VB2 urine even after radical prostatectomy. The authors have not determined whether the urinary IgA concentrations observed after radical prostatectomy are the true baseline values for a man without a prostate, or whether they actually reflect abnormal production of local IgA stimulated by radical prostatectomy. Because post-prostatectomy bacteriuris occurred frequently during urethral catheter drainage, the authors screened for postoperative IgA titers to mix 1 and mix 2 to determine whether specific production of antibody against gram-negative organisms might account for some of the postoperative IgA measured. Postradical prostatectomy mix 1 and mix 2 titers were not elevated, compared with preoperative measurements. Because urethral glandular tissue other than prostatic tissue is present in the male urethra, these glands also might be responsible for significant local antibody production. The high levels of urinary IgA and IgG after cystoprostatectomy with ileal orthotopic bladder substitution document that intestine incorporated into the urinary tract is still capable of producing local antibody. This observation corresponds with the findings of Mansson and associated [26] of elevated IgA and IgG in ileal reservoir urine compared with normal urinary tracts. It has been estimated that 1 m of intestine may secrete up to 780 mg/d of IgA [27], indicating that normal intestine production of antibody alone can account for the high IgA and IgG levels found in the patients who underwent bladder substitution. Interestingly, the ratio of IgA to IgG concentration in smal intestine fluid is 2:129, similar to the ratio of IgA to IgG in bladder substitution urine (2.92.1:52, Table 4). Because mix 1 and mix 2 IgA concentrations were elevated in VB1 and VB2 urine after ileal bladder substitution (see Table 5), some of this antibody was produced by the ileal bladder substitution in response to the inevitable bacteriuria that occurs during the prolonged postoperative catheter drainage. The findings is absent after radical prostatectomy alone. In addition, some of this increased antibody might be a result of the increased bacteriuria noted in the patients who underwent ileal bladder substitution after the initial postoperative period. The significance of the increased bacteriuria and elevated antibody levels after ileal bladder substitution is unclear. Because most of these episodes of bacteriuria were asymptomatic, whether they represent clinical infections that should be treated is not known. Bishop and associates [28] found that the bacterial flora of ileal conduits with asymptomatic bacteriuria had bacterial counts of 1000 or fewer colonies, and they noted that the healthy ileum in situ may contain more than 10,000 organisms per milliliter [29]. Because the normal urinary tract is usually sterile, it is possible that the bacteriuria found by the authors after ileal bladder substitution represents some form of bowel colonization more commonly associated with the bowel rather than clinical urinary tract infection and has limited clinial importance. Trinchieri and associated [30] found that urinary from patients with ileocystoplasty prevented attachment of E. coli to human uroepithelial cells more effectively that urine from patients with recurrent urinary infections. This observation suggests that the relatively large quantities of Iga produced by the ileal bladder substitution may, in fact, prevent clinical infection by preventing tissue invasion by the bacteria. Only long-term follow-up of patients with ileocystoplasty or ileal bladder substitution will determine the clinical significance of the bacteriuria. The authors' study had documented an increased incidence of bacteriuria in men after ileal bladder substitution and no such increase after radical prostatectomy. Analysis of the data shows that male sources other than the prostate--probably urethral glands-- must produce significant quantities of local urinary tract IgA. After ileal bladder substitution, the incorporated ileum may produce volumes of local antibody that may exceed the amounts ordinarily produce by the normal urinary tract. The clinical significance of the increased incidence of bacteriuria and elevated antibody levels in patients after illeal bladder substitution is unclear.

View details for Web of Science ID 000176538200027

View details for PubMedID 12109353

Abstract

We studied the effectiveness of magnetic resonance imaging (MRI) for evaluating hydronephrosis, differential renal function, vesicoureteral reflux and renal scarring in children.A total of 16 patients with hydronephrosis were evaluated with MRI. Coronal T1 and axial T1 and T2-weighted images were obtained before and after the administration of intravenous contrast material. Patients with vesicoureteral reflux underwent magnetic resonance voiding cystourethrography. Differential renal function was estimated from differential parenchymal volumes determined from MRI using computer software. The results were compared to standard imaging modalities.A total of 19 MRI studies were performed in 16 patients, including 3 for ureteropelvic junction obstruction, 11 for vesicoureteral reflux and 2 for other conditions. MRI provided the best anatomic detail and clear corticomedullary differentiation. MRI identified renal scarring and cortical thinning in 8 cases, while mercaptoacetyltriglycine 3 scans did not show any renal scarring and single photon emission computerized tomography-dimercapto-succinic acid nuclear scans diagnosed only 4 of 5 cases. There was good correlation between differential function obtained from nuclear scans and differential parenchymal volumes obtained from MRI (correlation coefficient 0.86, r2 = 0.74). Magnetic resonance voiding cystourethrography diagnosed reflux in 4 of 5 patients in whom vesicoureteral reflux was previously documented by standard voiding cystourethrography.MRI provides an alternative for the evaluation of hydronephrosis in children by combining the information provided by functional and anatomic nuclear scans, voiding cystourethrography and ultrasonography in a single study without ionizing radiation. MRI appears to be as good as existing modalities in the evaluation of renal scarring and cortical thinning.

View details for Web of Science ID 000170453600083

View details for PubMedID 11490289

Abstract

We used quantitative parameters of renal sonography to differentiate children with significant obstruction requiring surgical intervention from those without significant obstruction who were followed conservatively.We retrospectively reviewed the records of children who underwent evaluation for hydronephrosis. Those with a history of vesicoureteral reflux, anatomical abnormalities or neurogenic bladder were excluded from study. Patients were divided according to hydronephrosis grade into groups 1-grades III and IV followed conservatively, 2-grades III and IV requiring surgical intervention, 3-unilateral grade II and 4-bilateral. All images were scanned into a computer. Renal parenchymal and pelvic area was determined using National Institutes of Health image software. Parenchymal-to-pelvic area ratios were calculated from all images. We evaluated the ability of these measurements to determine the likelihood of surgical intervention.The records of 81 children were available for analysis. Deterioration in parenchymal area growth was a predictor of surgical intervention. Such patients had catch-up growth of the affected kidney after pyeloplasty. A parenchymal-to-pelvic area ratio of greater than 1.6 on the initial ultrasound study after birth predicted cases that would need pyeloplasty in the future (p <0.05). No patient with grade II hydronephrosis required surgical intervention.Following serial parenchymal area on serial ultrasound is useful for evaluating children with hydronephrosis. Those with a parenchymal area below the nomogram for growth usually require pyeloplasty. A parenchymal-to-pelvic area ratio of less than 1.6 on the initial ultrasound study after birth in patients with prenatally diagnosed ureteropelvic junction obstruction or on initial ultrasound in those diagnosed postnatally indicated the need for surgical intervention in this limited series.

View details for Web of Science ID 000166366900070

View details for PubMedID 11176432

View details for PubMedID 11764723

Abstract

We investigated whether oxybutynin could lower elevated renal pelvic pressures measured in a rat with an inbred unilateral congenital hydronephrosis. Simultaneous renal pelvic and bladder pressures were measured in 8 hydronephrotic rats and compared to those of 10 hydronephrotic rats treated with intravenous injection of 1.6 mg./kg. oxybutynin. Pressures were recorded at different urinary flow rates and during bladder filling and emptying. Hydronephrotic rats not given oxybutynin showed significantly higher renal pelvic pressures (e.g. p-bladder at 50% capacity = 8.9 +/- 3.1 cm. H2O, corresponding p-pelvis = 20.8 +/- 2.1 at very high urinary flow rates) than rats treated with oxybutynin. The latter had renal pelvic pressures similar to rats with normal non-hydronephrotic kidneys (e.g. p-bladder at 50% capacity = 10.1 +/- 3.5 cm. H2O, corresponding p-pelvis = 6.3 +/- 1.1 at very high urinary flow rates). Renal pelvic pressures were, moreover, lower than corresponding bladder pressures in contrast to the untreated hydronephrotic pelvic pressure that exceeded bladder pressure. This effect of oxybutynin in lowering elevated renal pelvic pressures in the obstructed kidney has not been described before and suggests a possible role for oxybutynin in this condition.

View details for Web of Science ID 000075450500082

View details for PubMedID 9720582

Abstract

Since abnormally elevated renal pelvic pressures may contribute to renal damage, we examined whether an anticholinergic agent could decrease elevated renal pelvic pressures. We have previously demonstrated in a rat model that renal pelvic pressures rise physiologically during normal bladder filling and high urinary flows; these pressures rise to abnormal levels during acute urinary tract infection (UTI). In these studies we investigated the effects of oxybutynin on the in vivo rat urinary tract. Simultaneous bladder and renal pelvic pressures were measured with and without oxybutynin at low (<2 ml./kg./hr.), moderate (2-10), high (10-20), and very high (>20) urinary flows while the rat bladder filled and emptied spontaneously. Although minimal differences were found between bladder filling pressures with and without oxybutynin, at higher urinary flows the renal pelvic pressure in oxybutynin treated rats was significantly lower than in nontreated animals. Indeed, when rats with urinary tract infection were treated with oxybutynin, their renal pelvic pressures were lower than those in uninfected rats. We conclude that oxybutynin affects rat upper urinary collecting system pressures, and is capable of decreasing abnormally elevated renal pelvic pressures due to urinary tract infection to normal or subnormal levels.

View details for Web of Science ID 000075450500081

View details for PubMedID 9720581

Abstract

We define the relationship of renal pelvic and bladder pressures with varying urinary flow rates and bladder fullness in unobstructed rats with and without vesicoureteral reflux.Sprague-Dawley rats (180 to 250 gm.) were evaluated for vesicoureteral reflux followed by simultaneous and continuous renal pelvic and bladder pressure monitoring during bladder filling cycles.The incidence of congenital right vesicoureteral reflux was 25% (14 of 57 rats, below bladder pressure of 40 cm. water). The renal pelvic pressure was significantly higher in rats with reflux compared to normal rats only at very low urine output when the bladder was 90% full or greater and when the urine output was moderate with the bladder 50% full or less. For all other urine outputs and degrees of bladder fullness, there were no significant differences in pelvic pressure between rats with and without reflux.Renal pelvic pressures in the refluxing and nonrefluxing collecting system of rats with mild to moderate reflux do not differ except under well-defined conditions. Reflux can be induced by raising the intravesical pressure when the urinary flow rate is very low. Furthermore, vesicoureteral reflux pressures decrease post mortem. Therefore, the observation of vesicoureteral reflux is a relative phenomenon defined by urinary flow rate, bladder pressure and in vivo conditions, and one must define the specific bladder pressure and urinary flow rate that are present when reflux occurs. These data help explain why the observation of reflux may be intermittent or transient during various imaging studies.

View details for Web of Science ID 000074037800068

View details for PubMedID 9628637

Abstract

We investigated whether purified prostate specific antigen (PSA), a seminal plasma serine protease of the kallikrein enzyme family, is capable of releasing kinin-like peptides from natural substrate glycoproteins in human seminal vesicle fluid.An in vivo rat bladder model was used to monitor for release of substances capable of inducing smooth muscle contractions. Purified PSA, seminal vesicle fluid (SVF) from radical prostatectomy specimens, bradykinin, saline and a bradykinin antagonist were injected intravesically into urethane-anesthetized rats, and the resulting bladder contractions were measured.Injection of either PSA or SVF alone did not induce bladder contractions. Injection of a mixture of SVF and PSA preincubated 15 minutes, however, induced strong bladder contractions (23 +/- 7 cm. H2O) that decreased with time (4 +/- 2 cm. H2O, after 90 minutes). Similar contractions were observed after injection of bradykinin (10(-4) M. = 39 +/- 14, 10(-6) M. = 27 +/- 9, 10(-8) M. = 7 +/- 4 cm. H2O). Addition of a bradykinin antagonist to the PSA-SVF mixture prior to injection blocked the observed bladder contractions (23 +/- 7 cm. H2O before, versus 0.3 +/- 1.2 cm. H2O after adding antagonist).We conclude that PSA produces a kinin-like substance by enzymatic cleavage of glycoproteins in human seminal fluid. This substance induces smooth muscle contractions which can be specifically blocked by addition of a bradykinin antagonist.

View details for Web of Science ID A1996TP49300104

View details for PubMedID 8558716

Abstract

We investigated the urodynamics of the renal pelvis and bladder during spontaneous bladder filling and emptying in 13 pregnant and 19 nonpregnant Sprague-Dawley rats to examine the characteristics of the dilated urinary tract in pregnancy. For each group renal pelvic and bladder pressures were measured continuously and simultaneously during various urinary flows, while the bladder was filled and emptied. In pregnant rats the ureter was wider and the renal pelvis was longer and wider than in nonpregnant rats. At urinary flows of 10 to 30 ml/kg. per hour pregnant rats had significantly lower renal pelvic pressures than nonpregnant rats during bladder filling. In addition, pregnant rats had higher bladder compliance and capacity than nonpregnant rats (compliance 0.09 +/- 0.12 ml./cm. water versus 0.05 +/- 0.05 ml./cm. water, p < 0.01 and bladder capacity 0.669 +/- 0.61 ml. versus 0.490 +/- 0.38 ml., p < 0.05). These findings imply that much of the hydroureteronephrosis during pregnancy may relate to increased urinary tract compliance rather than obstruction.

View details for Web of Science ID A1995RJ05100007

View details for PubMedID 7609155

Abstract

Nonbacterial prostatitis is often difficult to differentiate from other prostatic complaints and remains a vaguely characterized syndrome. Prostatic fluid inflammatory cells and elevated immunoglobulins raise the suspicion that this syndrome is caused by some undetected infection. Prostatic fluid antibodies against Chlamydia trachomatis, Ureaplasma urealyticum, staphylococcus, Staphylococcus faecalis, Bacteroides fragilis and Clostridium perfringens were measured in men with nonbacterial and bacterial prostatitis, and men without urinary symptoms by an enzyme-linked immunosorbent assay. Prostate specific antigen and prostatic acid phosphatase were measured in the prostatic fluid as indirect measures of secretory activity. Of 44 men with nonbacterial prostatitis 9 (20%) had detectable prostatic fluid antichlamydial antibody titers, compared with 3 of 25 control men (12%) and 2 of 13 (15%) with bacterial prostatitis--no evidence for a higher prevalence of prostatic fluid antichlamydial antibody in men with nonbacterial prostatitis. Prostatic antibodies to the other organisms were rarely detected. When compared with unaffected men the low levels of prostate specific antigen and prostatic acid phosphatase, and more alkaline prostatic fluid in men with bacterial and nonbacterial prostatitis suggest that secretory dysfunction accompanies the inflammation. These data show that none of the organisms studied caused the majority of the cases of nonbacterial prostatitis and that either an agent as yet unidentified or multiple agents may be involved in the etiology of nonbacterial prostatitis.

View details for Web of Science ID A1992JW46000032

View details for PubMedID 1279213

Abstract

Standard recommendations for patients who have had superficial bladder cancer are inspection by cystoscopy quarterly for a year or two after tumor removal, then half-yearly and yearly. The authors assessed the potential for improvement in scheduling cystoscopies according to probabilistic optimization techniques. Eight hypothetical practices were created, based on retrospective analysis of 918 bladder-cancer-patient charts. Standard and alternative recommendations for the interval to next cystoscopy were compared. The alternatives were derived from patient-specific predictions of future tumor risks (based on the patient's prior recurrence rate and tumor stage and grade) and a nonlinear optimization approach to allocation of the same number of cystoscopies as were available for standard follow-up. The optimization proposed longer intervals between visits for low-risk patients and shorter intervals for high-risk patients. Overall, optimization reduced expected tumor detection delays by 30%, from 12.6 to 8.7 weeks. When optimization intervals were shorter than standard, cancer was found more often at subsequent cystoscopies (34% vs 27%, p less than 0.05), suggesting that the optimization was a better predictor of cancer recurrence. If reduction in tumor-detection delay is the goal of follow-up for recurrent cancers, then urologists can improve monitoring by using probabilistic optimization methods for scheduling cystoscopies. Further understanding of the accuracy of predictive models for bladder-cancer recurrence rates is desirable. Subsequently, the optimization method developed here may be tested prospectively.

View details for Web of Science ID A1991GJ22700002

View details for PubMedID 1662739

Abstract

Injectable materials have been used to augment the urethral sphincter and improve urinary continence with some success. However, none of these materials has received widespread use because they are difficult to inject and have been reported to migrate. We investigated the efficacy of transurethral implantation of glutaraldehyde cross-linked collagen, a highly purified bovine collagen. A total of 17 patients (16 men and 1 woman) with urinary incontinence resulting from a previous operation was selected for glutaraldehyde cross-linked collagen injection into the region of the urethral sphincter. Before and after implantation patients underwent urodynamic evaluation. Glutaraldehyde cross-linked collagen was injected into the area of the bladder neck or urinary sphincter under direct endoscopic vision. If no improvement occurred reinjection to increase the implant volume was performed at least 3 months after a previous injection. Of the 17 patients 9 were cured or improved. No complications have been reported. This investigation shows that glutaraldehyde cross-linked collagen can be injected into the urinary tract to correct urinary incontinence without observable or measurable morbidity.

View details for Web of Science ID A1989T519400017

View details for PubMedID 2918587

Abstract

Measurements of IgG and IgA antibodies against common gram negative organisms in pre and post prostatic massage urines were investigated. Lower tract urinary localization specimens were obtained in men with chronic bacterial prostatitis, nonbacterial prostatitis, and without evidence of infection. Quantitative cultures were performed on all specimens. A rapid and simple enzyme-linked immunosorbant assay (ELISA) was developed to measure urinary total immunoglobulins and antibodies to common gram negative organisms (mixed antigen-specific antibodies, MASA). Comparison with a previously developed radioimmunoassay yielded a correlation determinant of 0.89 per cent. Almost all patients had post prostatic massage urinary IgA and IgG levels that were higher than the premassage levels, reflecting the presence of prostatic fluid in the postmassage specimens. In only the patients with chronic bacterial prostatitis, however, were levels of IgA or IgG MASA in the postmassage urines higher than those measured in the premassage urines. This same elevation was found in the urinary specimens from men who could not be diagnosed to have bacterial prostatitis by traditional means on a specific occasion because of antibiotic treatment, inadequate specimens, or bacteriuria, but had chronic bacterial prostatitis confirmed traditionally on another occasion. No detectable MASA were measured in either the pre or postmassage urines of men without a history of previous urinary infections. From these data it appears that urinary MASA may be used to diagnose bacterial prostatitis in situations in which quantitative bacteriologic cultures cannot be performed. These measurements may, furthermore, be used to diagnose chronic bacterial prostatic infection in men who cannot be diagnosed to have bacterial prostatitis when prostatic fluid is unobtainable or culture results are uninterpretable.

View details for Web of Science ID A1989T519400049

View details for PubMedID 2918607

Abstract

Proper timing for repeated evaluations is difficult to assess. The authors analyzed scheduling of cystoscopy to monitor patients for detection of recurrent bladder cancer assuming that 1) minimizing tumor detection delay helps prevent cancer morbidities; 2) only limited numbers of cystoscopies are available; 3) prediction of recurrence or progression to invasive cancer is uncertain; 4) future tumors recur according to a Poisson process. Assumptions 3 and 4 permit estimation of each patient's recurrence rate. Thus, patients may be compared according to their relative risks of future tumors. With these assumptions, nonlinear optimization theory was used to calculate monitoring schedules for a model practice. Given 5.4 available visits per week per 100 patients, cystoscopy was recommended in 9-11 weeks for high-risk patients and in 30-40 weeks for low-risk patients, depending on stages, grades, and numbers of previous tumors. In contrast, standard cystoscopy was recommended in 13, 26, or 52 weeks, depending only on time elapsed since last recurrence. The calculated schedule implied an average detection delay for potentially invasive tumors of eight weeks, while standard practice led to detection delays of 11 weeks (38% worse). These results suggest that inclusion of each patient's tumor history in an optimization approach may improve follow-up care for patients who have superficial bladder cancers. This approach is being evaluated in a larger clinical setting.

View details for Web of Science ID A1989R671600005

View details for PubMedID 2643017

Abstract

Thirty-five patients with superficial transitional carcinoma of the bladder were treated intravesically with escalating doses of recombinant alpha-2-interferon administered weekly for 8 weeks. Of the 19 patients with high-grade intraepithelial neoplasia (17 carcinoma in situ [CIS], two severe dysplasia, all cytology positive), six (32%) had complete resolution of all histologic and cytologic evidence of disease (complete response). An additional three patients (16%) had complete resolution of CIS, but the interval appearance of a low-grade transitional cell neoplasm. Five (26%) had a partial response (complete resolution of all evidence of CIS on multiple bladder biopsies but persistently positive cytologic preparations). Sixteen patients with recurrent papillary tumors and extensive prior therapy were also treated. Four (25%) had a complete response. Twenty-three of the 35 patients had prior intravesical therapy. Seven of the 23 (30%) patients with prior intravesical chemotherapy or immunotherapy had a complete or partial response to interferon, while eight of the 12 patients (67%) without prior intravesical treatment responded. These responses were achieved with minimal local and systemic toxicity. Of the ten complete responders, five remain in continuous unmaintained remission for 18+ to 37+ months. Intracavitary alpha-2-interferon is an effective new treatment for some patients with bladder cancer.

View details for Web of Science ID A1988M715400011

View details for PubMedID 3280742

Abstract

A prospective study was designed to examine the relationship of mast cells, and eosinophilic leukocyte density and mediator levels to clinical and histological parameters of interstitial cystitis. Interstitial cystitis and control patients underwent bladder biopsy with histological examination, and quantification of intact and degranulated mast cell and eosinophilic leukocyte density. In addition, bladder tissue histamine content, urinary prostaglandin E2 excretion rates, and serum and urinary major basic protein levels were determined. A strong relationship among detrusor mast cell density, especially degranulated, and degree of epithelial loss, submucosal inflammation, epithelial ulceration, urinary pyuria and response to treatment was noted. Bladder tissue histamine content and urinary prostaglandin E2 excretion were increased in the interstitial cystitis patients. Eosinophil density in bladder biopsies was low uniformly, and interstitial cystitis and control patients showed no statistical difference. In addition, serum and urinary major basic protein levels were below the accepted normal lower limits for this protein. Therefore, our study demonstrates a relationship between the mast cell and the inflammatory process of interstitial cystitis. No similar relationship was noted for the eosinophil.

View details for Web of Science ID A1987K313400012

View details for PubMedID 3477649

Abstract

This study utilizes a light microscopy assay for bacterial adherence to human male transitional cells. Prior light microscopy studies have used voided squamous cells, periurethral cells or scraped vaginal cells, which are less representative of the cells lining the majority of the urinary tract. Using a modification of previous bacterial adherence assays, the mean adherence for 28 strains of E. coli in 92 bacteria-cell incubations was 10.2 +/- 11.5 (standard deviation) bacteria per cell. The mean adherence for 20 strains of P. mirabilis in 60 bacteria cell incubations was 8.1 +/- 11.4. No statistically significant difference in adherence between E. coli and P. mirabilis was found (p greater than 0.05). Studies comparing the adherence of E. coli isolated from the urine of patients with pyelonephritis (eight strains), cystitis (10 strains) and anal swabs of females without urinary tract infections (10 strains), showed no statistically significant differences in mean adherence (p greater than 0.05). However, there was a trend toward higher adherence in the more virulent groups. Experiments comparing the adherence of P. mirabilis isolated from infected renal stones to P. mirabilis isolated from anal swabs of female patients without history of P. mirabilis UTI revealed no statistically significant differences in mean adherence between the two groups (p greater than 0.05). These data do not support previous contentions that P. mirabilis adhere poorly to human transitional cells. The absence of a significant difference in adherence among strains of E. coli and P. mirabilis that differ in clinical pathogenicity suggests that factors other than adherence contribute to their virulence.

View details for Web of Science ID A1987G649900056

View details for PubMedID 3550157

Abstract

Although inflammatory diseases of most human secretory surfaces are difficult to investigate clinically, the secretory immune system of the human prostate may be studied relatively easily because prostatic fluid may be obtained from the gland by digital massage. We studied inflammatory conditions of the prostate to establish whether we could use the humoral immune response to differentiate these conditions. Using a sensitive solid-phase radioimmunoassay, we measured total IgA and IgG, and IgA and IgG antibodies to Enterobacteriaceae in the serum and prostatic fluid of men with and without prostatic inflammation. These studies show that levels of IgA and IgG in the prostatic fluid of men with bacterial prostatitis are higher than those in men without histories of urinary or prostatic infections. In men with bacterial prostatitis, prostatic antibodies to Enterobacteriaceae were elevated 12 to 18 months after curative treatment and indefinitely after ineffective treatment; anti-Enterobacteriaceal IgG levels returned to normal after infection only with cure. Total IgA and IgG in the prostatic fluid of men with nonbacterial prostatitis--men who have signs of prostatic inflammation without evidence of old or ongoing bacterial infection--are also higher than levels found in uninfected individuals. Although this finding supports an inflammatory etiology for the symptoms seen in nonbacterial prostatitis, no significant IgA or IgG Enterobacteriaceal antibody titers were detected in these patients. This excludes a remote Enterobacteriaceal infection as a cause of nonbacterial prostatitis. These observations confirm that the prostate gland is a distinct part of the male secretory immune system.

View details for Web of Science ID A1986F074700005

View details for PubMedID 3537628

Abstract

Transrectal endosonography is one of the most sensitive techniques to evaluate prostatic disease and is far more accurate than conventional sonography. A retrospective review of sonographic characteristics of the prostate was made in an attempt to define the ability of the technique to distinguish benign from malignant disease. Analysis included evaluation of the capsule (smoothness, regularity, and/or invasion), abnormal foci (echogenicity, margination, brightness, thickness, and symmetry), and presence of acoustic shadowing and/or enhancement from the abnormal foci. Evaluation of 443 pathologically proved cases (the majority being large lesions) showed that differentiation between benign and large and/or invasive malignant disease may be suggested by results of transrectal endosonography. However, there is still great overlap of the sonographic appearances.

View details for Web of Science ID A1986AWQ1300018

View details for PubMedID 3510030

Abstract

Patients with advanced prostatic carcinoma who had received minimal or no prior therapy were treated with tamoxifen citrate in escalating doses from 10 to 50 mg orally twice a day. Twenty-nine courses were evaluated in 17 patients. Entry was limited to patients with measurable sites of disease. There were no objective responses at any dose level in these measurable sites. Acid and alkaline phosphatase were reduced in 0% and 18% of courses, respectively. Serum testosterone increased by an average of 119 ng/ml. Most increases were transient; no tumor flares were observed. Transperineal prostate biopsies in selected patients after completion of treatment showed no evidence of tumor necrosis or alteration in histologic grade of the tumors. Tamoxifen citrate, over the range of doses evaluated, has no activity in metastatic prostatic carcinoma.

View details for Web of Science ID A1984TD22200024

View details for PubMedID 6430541

Abstract

The prostatic fluid of two patients with Escherichia coli bacterial prostatitis was analyzed for evidence of a local immune response to bacterial infection. A solid-phase radioimmunoassay was modified to measure the immunoglobulin (Ig)A and IgG antigen-specific antibody responses to infecting bacteria in serum and prostatic fluid from patient. Formalin-fixed whole E. coli were used as antigen. In one patient with acute E. coli prostatic infection, measurements of antigen-specific antibody confirm the presence of a systemic and local immune response. However, in another patient with a chronic E. coli prostatitis, a primarily local immune response was demonstrated. The response measured in the prostatic fluid appears to be locally stimulated and specific for the infecting bacteria. Furthermore, IgA was the predominant immunoglobulin involved in the local prostatic immune response to infection. Although elevations of serum IgA antigen-specific antibody levels were short-liver after treatment of prostatic infection, local IgA antigen-specific antibodies were detected for as long as 1 yr after the initial infection in both patients studied.

View details for Web of Science ID A1981LF08300025

View details for PubMedID 7009649

Abstract

Although local antibody responses at bronchial, pulmonary and intestinal surfaces have been studied previously a similar response from the prostatic surface has never been described. This investigation demonstrates a distinct local antibody response in the prostatic fluid of 2 patients with bacterial prostatitis. Levels of antigen-specific and total non-specific immunoglobulins A and G were measured at intervals during and following infection for at least 2 years. These studies show that local prostatic immunologic responses are independent of serum responses and specific for the infecting organism. Furthermore, local secretory immunoglobulin A is the predominant immunoglobulin involved in the response to prostatic infection. Serum antigen-specific antibody and total serum or prostatic fluid immunoglobulin measurements are in adequate reflections of the prostatic immune response.

View details for Web of Science ID A1981LN50100016

View details for PubMedID 7012386