Linda M. Dairiki Shortliffe

All Publications

• Gpr124 is essential for blood-brain barrier integrity in central nervous system disease NATURE MEDICINE Chang, J., Mancuso, M. R., Maier, C., Liang, X., Yuki, K., Yang, L., Kwong, J. W., Wang, J., Rao, V., Vallon, M., Kosinski, C., Zhang, J. J., Mah, A. T., Xu, L., Li, L., Gholamin, S., Reyes, T. F., Li, R., Kuhnert, F., Han, X., Yuan, J., Chiou, S., Brettman, A. D., Daly, L., Corney, D. C., Cheshier, S. H., Shortliffe, L. D., Wu, X., Snyder, M., Chan, P., Giffard, R. G., Chang, H. Y., Andreasson, K., Kuo, C. J. 2017; 23 (4): 450-?

  Abstract

  Although blood-brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown. Here Gpr124 conditional knockout (CKO) in the endothelia of adult mice did not affect homeostatic BBB integrity, but resulted in BBB disruption and microvascular hemorrhage in mouse models of both ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt-β-catenin signaling. Constitutive activation of Wnt-β-catenin signaling fully corrected the BBB disruption and hemorrhage defects of Gpr124-CKO mice, with rescue of the endothelial gene tight junction, pericyte coverage and extracellular-matrix deficits. We thus identify Gpr124 as an endothelial GPCR specifically required for endothelial Wnt signaling and BBB integrity under pathological conditions in adult mice. This finding implicates Gpr124 as a potential therapeutic target for human CNS disorders characterized by BBB disruption.

  View details for DOI 10.1038/nm.4309

  View details for PubMedID 28288111

• New and developing diagnostic technologies for urinary tract infections. Nature reviews. Urology Davenport, M., Mach, K. E., Shortliffe, L. M., Banaei, N., Wang, T., Liao, J. C. 2017

  Abstract

  Timely and accurate identification and determination of the antimicrobial susceptibility of uropathogens is central to the management of UTIs. Urine dipsticks are fast and amenable to point-of-care testing, but do not have adequate diagnostic accuracy or provide microbiological diagnosis. Urine culture with antimicrobial susceptibility testing takes 2-3 days and requires a clinical laboratory. The common use of empirical antibiotics has contributed to the rise of multidrug-resistant organisms, reducing treatment options and increasing costs. In addition to improved antimicrobial stewardship and the development of new antimicrobials, novel diagnostics are needed for timely microbial identification and determination of antimicrobial susceptibilities. New diagnostic platforms, including nucleic acid tests and mass spectrometry, have been approved for clinical use and have improved the speed and accuracy of pathogen identification from primary cultures. Optimization for direct urine testing would reduce the time to diagnosis, yet these technologies do not provide comprehensive information on antimicrobial susceptibility. Emerging technologies including biosensors, microfluidics, and other integrated platforms could improve UTI diagnosis via direct pathogen detection from urine samples, rapid antimicrobial susceptibility testing, and point-of-care testing. Successful development and implementation of these technologies has the potential to usher in an era of precision medicine to improve patient care and public health.

  View details for DOI 10.1038/nrurol.2017.20

  View details for PubMedID 28248946

• Analysis of Kidney Ultrasound Dimensions by Body Habitus and Position JOURNAL OF UROLOGY Kouba, E., Newman, B., Shortliffe, L. M. 2016; 196 (3): 943-949

  View details for DOI 10.1016/j.juro.2016.02.044

  View details for Web of Science ID 000381272100107

• Analysis of Kidney Ultrasound Dimensions by Body Habitus and Position. journal of urology Kouba, E., Newman, B., Dairiki Shortliffe, L. M. 2016; 196 (3): 943-949

  Abstract

  Renal dimensions are an important assessment of the genitourinary tract used to evaluate critical aspects of renal growth and development. Understanding the effect of patient position is important to use and interpret these parameters. In this prospective study we determined the effect of patient position and general body habitus on renal length and parenchymal area in children undergoing renal ultrasound.Between October 2010 and January 2011 children underwent renal ultrasound while prone and supine. Bilateral renal length and renal parenchymal area were measured. Pearson and Bland-Altman statistical analyses were used to examine correlations, measurement bias and the degree of agreement between methods.Renal length measurements in both positions were complete for 201 right and 196 left kidneys. Parenchymal area measurements were complete for both kidneys in 177 children. When compared individually, supine and prone measures of renal length and parenchymal area highly correlated on Pearson analysis (greater than 0.96 and greater than 0.89, respectively). When compared by method, Bland-Altman analyses of differences vs means showed greater than 50% variance, representing wide limits of agreement with poor interrelation. Neither persistent systematic bias nor body habitus influenced results.While Pearson analysis showed high correlation for supine and prone renal measurements, Bland-Altman analysis of renal length and parenchymal area demonstrated wide limits of agreement, not allowing interchangeable use of prone and supine measurements. As such, renal ultrasound should specify standardized positions and benchmarks. These results provide guidance to standardize renal ultrasound measurements when renal size is used as an indicator of kidney health.

  View details for DOI 10.1016/j.juro.2016.02.044

  View details for PubMedID 26874315

• The transient receptor potential vanilloid 4 channel modulates uterine tone during pregnancy SCIENCE TRANSLATIONAL MEDICINE Ying, L., Becard, M., Lyell, D., Han, X., Shortliffe, L., Husted, C. I., Alvira, C. M., Cornfield, D. N. 2015; 7 (319)

  Abstract

  The importance of gaining insight into the mechanisms underlying uterine quiescence and contractility is highlighted by the absence of an effective strategy to prevent or treat preterm labor, the greatest cause of perinatal mortality and morbidity worldwide. Although current evidence suggests that in myometrial smooth muscle cells (mSMCs) calcium homeostasis is modulated near term to promote uterine contractility, the efficacy of blocking voltage-operated calcium channels is limited by dose-related cardiovascular side effects. Thus, we considered whether uterine contractility might be modulated by calcium entry via transient receptor potential vanilloid 4 (TRPV4) channels. In mSMC, TRPV4 gene and protein expression increased with gestation, and TRPV4-mediated Ca(2+) entry and contractility were increased in mSMC from pregnant compared to nonpregnant rats. Cell membrane TRPV4 expression was specifically increased, whereas the expression of β-arrestin-1 and β-arrestin-2, molecules that can sequester TRPV4 in the cytoplasm, decreased. Physical interaction of β-arrestin-2 and TRPV4 was apparent in nonpregnant, but absent in pregnant, mouse uterus. Moreover, direct pharmacologic activation of TRPV4 increased uterine contraction, but oxytocin-induced myometrial contraction was blocked by pharmacologic inhibition of TRPV4 and decreased in mice with global deletion of TRPV4. Finally, TRPV4 channel blockade prolonged pregnancy in two distinct in vivo murine models of preterm labor, whereas the absence of either β-arrestin-1 or β-arrestin-2 increased susceptibility to preterm labor. These data suggest that TRPV4 channel activity modulates uterine contractility and might represent a therapeutic target to address preterm labor.

  View details for DOI 10.1126/scitranslmed.aad0376

  View details for PubMedID 26702092

• Dietary fructose in pregnancy induces hyperglycemia, hypertension, and pathologic kidney and liver changes in a rodent model PREGNANCY HYPERTENSION-AN INTERNATIONAL JOURNAL OF WOMENS CARDIOVASCULAR HEALTH Shortliffe, L. M., Hammam, O., Han, X., Kouba, E., Tsao, P. S., Wang, B. 2015; 5 (4): 308-314

  Abstract

  The incidence of pregnancies complicated by hyperglycemia and hypertension is increasing along with associated morbidities to mother and offspring. The high fructose diet is a well-studied model that induces hyperglycemia and hypertension in male rodents, but may not affect females. We hypothesized that the physiologic stress of pregnancy may alter metabolic responses to dietary fructose.In this study female Sprague-Dawley rats were divided into two gestational dietary groups: (1) 60% carbohydrate standard rat chow (Pregnant-S-controls) and (2) 60% fructose enriched chow (Pregnant-F). Body weight, blood pressure, blood glucose, triglycerides, and insulin were measured in pregnancy and during the post-partum period. Maternal organ weight and histological changes were also assessed after delivery.By midpregnancy Pregnant-F rats had increased weight, elevated blood pressure, higher fasting glucose, and elevated triglycerides compared with Pregnant-S rats. Both groups demonstrated elevated gestational insulin levels with signs of insulin resistance (increased HOMA-IR). Pregnant-F rats showed significant histopathologic hepatic steatosis and renal tubular changes characterized by tubular dilation and glomerulosclerosis.Our study provides a model in which dietary change during pregnancy can be examined. We demonstrate, moreover, that high dietary fructose ingestion in pregnant rats may result in profound systemic and pathologic changes not appreciated during routine pregnancy.

  View details for DOI 10.1016/j.preghy.2015.08.002

  View details for Web of Science ID 000366078600010

  View details for PubMedID 26597746

• Testosterone Changes Bladder and Kidney Structure in Juvenile Male Rats JOURNAL OF UROLOGY Shortliffe, L. M., Ye, Y., Behr, B., Wang, B. 2014; 191 (6): 1913-1919

  Abstract

  Testosterone affects male development, maturation and aging but limited data exist on testosterone effects on the juvenile genitourinary system. We hypothesized that testosterone has bladder and kidney developmental effects, and investigated this in juvenile male rats.To examine the testosterone effect 21-day-old prepubertal male Wistar rats were divided into 3 groups of 12 each, including sham orchiectomy as controls, and bilateral orchiectomy with vehicle and bilateral orchiectomy with testosterone. Starting at age 28 days (week 0) testosterone enanthate (5 mg/100 gm) or vehicle was injected weekly. Testosterone was measured at study week 0 before injection, and at weeks 1, 6 and 16. Whole bladders and kidneys were evaluated for androgen receptor, bladder collagen-to-smooth muscle ratio, and renal morphometry and immunohistochemistry.Testosterone was not detectable at week 0 in all groups. It remained undetectable at weeks 1, 6 and 16 in the orchiectomy plus vehicle group. Testosterone levels were physiological in controls and rats with orchiectomy plus testosterone but levels were higher in the latter than in the former group. Rats with orchiectomy plus testosterone had increased bladder-to-body and kidney-to-body weight ratios (p<0.01 and <0.05, respectively), and decreased collagen-to-smooth muscle ratio than the orchiectomy plus vehicle and control groups. Rats with orchiectomy plus testosterone had a lower renal total glomerular count (p<0.01) but increased androgen receptor density.In juvenile male rats testosterone was associated with increased bladder and renal mass, and increased bladder smooth muscle. Testosterone associated kidneys also appeared to have fewer but larger glomeruli. These data support an important role for sex hormones in structural and functional development of the bladder and kidney.

  View details for DOI 10.1016/j.juro.2014.01.012

  View details for Web of Science ID 000336531100104

  View details for PubMedID 24518779

• Adult and Pediatric Intra-Institutional Trends of Ciprofloxacin Susceptibility in E. coli Positive Urinary Cultures. Antibiotics (Basel, Switzerland) Owumi, W., Banaei, N., Shortliffe, L. D. 2014; 3 (2): 163-173

  Abstract

  Antimicrobial drug resistance in treatment of urinary tract infection (UTI) continues to rise worldwide. To examine contributions of physician prescribing patterns to fluoroquinolone (ciprofloxacin, CP) resistance, we examined Escherichia coli (E. coli) resistance patterns in urinary cultures. Since CP usage is limited in children, we compared CP resistance trends in adults and children to those of more commonly used trimethoprim-sulfamethoxazole (TMP-SMX) and nitrofurantoin (NF). Our data show that although the general pediatric population has lower resistance to ciprofloxacin, resistance levels are rising with increased usage. While NF susceptibility is historically stable, TMP-SMX resistance is slightly higher in children compared to adults. In both adults and children, antimicrobial resistance patterns vary according to clinical practice site, with ambulatory urology patients showing the highest resistance. This suggests that physician's prescribing patterns contribute to antimicrobial resistance.

  View details for DOI 10.3390/antibiotics3020163

  View details for PubMedID 27025742

• Testosterone Changes Bladder and Kidney Structure in Juvenile Male Rats (Accepted Feb 07, 2014) Journal of Urology (Available ahead of publication: unedited mss) Shortliffe, L. M., Ye, Y., Behr, B., Wang, B. 2014: 1-30

  View details for DOI 10.1016/j.juro.2014.01.012

• Adult and Pediatric Intra-Institutional Trends of Ciprofloxacin Susceptibility in E. coli Positive Urinary Cultures Antibiotics Owumi, W., Banaei, N., Shortliffe, L. D. 2014; 3: 163-173
• Three differentiation states risk-stratify bladder cancer into distinct subtypes PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Volkmer, J., Sahoo, D., Chin, R. K., Ho, P. L., Tang, C., Kurtova, A. V., Willingham, S. B., Pazhanisamy, S. K., Contreras-Trujillo, H., Storm, T. A., Lotan, Y., Beck, A. H., Chung, B. I., Alizadeh, A. A., Godoy, G., Lerner, S. P., van de Rijng, M., Shortliffe, L. D., Weissman, I. L., Chan, K. S. 2012; 109 (6): 2078-2083

  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 PubMedID 22308455

• Trends in Hospitalization for Pediatric Pyelonephritis: A Population Based Study of California From 1985 to 2006 JOURNAL OF UROLOGY Copp, H. L., Halpern, M. S., Maldonado, Y., Shortliffe, L. D. 2011; 186 (3): 1028-1034

  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

• Epidemiologic trends in penile anomalies and hypospadias in the state of California, 1985-2006 JOURNAL OF PEDIATRIC UROLOGY Elliott, C. S., Halpern, M. S., Paik, J., Maldonado, Y., Shortliffe, L. D. 2011; 7 (3): 294-298

  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 PubMedID 21527236

• Clinical Decisions: Treatment of a 6-Year-Old Girl with Vesicoureteral Reflux--Repair of the Vesicoureteral Reflux New England Journal of Medicine Shortliffe LD, Hoberman A, Alon U 2011; 365 (3): 266-270
• Evaluation of Dynamic Contrast-Enhanced MRI in Detecting Renal Scarring in a Rat Injury Model JOURNAL OF MAGNETIC RESONANCE IMAGING Wang, B., Sommer, G., Spielman, D., Shortliffe, L. M. 2010; 31 (5): 1132-1136

  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

  View details for PubMedCentralID PMC2921162

• Compliance With Antibiotic Prophylaxis in Children With Vesicoureteral Reflux: Results From a National Pharmacy Claims Database JOURNAL OF UROLOGY Copp, H. L., Nelson, C. P., Shortliffe, L. D., Lai, J., Saigel, C. S., Kennedy, W. A. 2010; 183 (5): 1994-1999

  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

  View details for PubMedCentralID PMC3319712

• Quantitative Ultrasound Renal Parenchymal Area Correlates With Renal Volume and Identifies Reflux Nephropathy 60th Annual Meeting of the American-Academy-of-Pediatrics/International-Childrens-Continence-Society Wong, I. Y., Copp, H. L., Clark, C. J., Wu, H., Shortliffe, L. D. ELSEVIER SCIENCE INC. 2009: 1683–87

  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

• Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Chan, K. S., Espinosa, I., Chao, M., Wong, D., Ailles, L., Diehn, M., Gill, H., Presti, J., Chang, H. Y., van de Rijn, M., Shortliffe, L., Weissman, I. L. 2009; 106 (33): 14016-14021

  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 PubMedID 19666525

• Magnetic resonance Imaging detected renal volume reduction in refluxing and nonrefluxing kidneys JOURNAL OF UROLOGY Chang, S. L., Caruso, T. J., Shortliffe, L. D. 2007; 178 (6): 2550-2554

  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

• Hypnosis reduces distress and duration of an invasive medical procedure for children PEDIATRICS Butler, L. D., Symons, B. K., Henderson, S. L., Shortliffe, L. D., Spiegel, D. 2005; 115 (1): E77-E85

  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

• Structural changes in the bladder walls of pregnant and hormone-treated rats: correlation with bladder dynamics BJU INTERNATIONAL Rodriguez, L. V., Wang, B. Y., Shortliffe, L. M. 2004; 94 (9): 1366-1372

  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

• Evaluation of renal growth by magnetic resonance imaging and computerized tomography volumes 54th Annual Meeting of the American-Academy-of-Pediatrics Heuer, R., Sommer, G., Shortliffe, L. D. ELSEVIER SCIENCE INC. 2003: 1659–63

  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

• Effect of urinary tract infection on ureteropelvic junction obstruction in a rat model UROLOGY Hansen, M. H., Wang, B. Y., Afzal, N., BOINEAU, F. G., Lewy, J. E., Shortliffe, L. M. 2003; 61 (4): 858-863

  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

• Serial followup of the contralateral renal size in children with multicystic dysplastic kidney Annual Meeting of the Section-on-Urology American-Academy-of-Pediatrics Abidari, J. M., Park, K. H., Kennedy, W. A., Shortliffe, A. D. ELSEVIER SCIENCE INC. 2002: 1821–25

  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

• Prospective study of urinary tract infections and urinary antibodies after radical prostatectomy and cystoprostatectomy UROLOGIC CLINICS OF NORTH AMERICA Iwakiri, J., Freiha, F. S., Shortliffe, L. M. 2002; 29 (1): 251-?

  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

• Magnetic resonance imaging for the evaluation of hydronephrosis, reflux and renal scarring in children JOURNAL OF UROLOGY Rodriguez, L. V., Spielman, D., Herfkens, R. J., Shortliffe, L. D. 2001; 166 (3): 1023-1027

  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

• Evaluation of sonographic renal parenchymal area in the management of hydronephrosis JOURNAL OF UROLOGY Rodriguez, L. V., Lock, J., Kennedy, W. A., Shortliffe, L. M. 2001; 165 (2): 548-551

  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

• Revealing the spatiotemporal patterns of bacterial infectious diseases using bioluminescent pathogens and whole body imaging. Contributions to microbiology Burns, S. M., Joh, D., Francis, K. P., Shortliffe, L. D., Gruber, C. A., Contag, P. R., Contag, C. H. 2001; 9: 71-88

  View details for PubMedID 11764723

• Magnetic resonance imaging for the evaluation of hydronephrosis, reflux, and renal scarring in children. Rodriguez, L. V., Spielman, D., Herfkens, R. J., Shortliffe, L. M. AMER ACAD PEDIATRICS. 1998: 874–75

  View details for Web of Science ID 000075810500474

• Oxybutynin lowers elevated renal pelvic pressures in a rat congenital unilateral hydronephrosis JOURNAL OF UROLOGY Fichtner, J., BOINEAU, F. G., Lewy, J. E., Shortliffe, L. M. 1998; 160 (3): 887-891

  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

• Oxybutynin decreases renal pelvic pressures in normal and infected rat urinary tract JOURNAL OF UROLOGY Cowan, B. E., Shortliffe, L. M. 1998; 160 (3): 882-886

  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

• The urodynamic relationship of renal pelvic and bladder pressures, and urinary flow rate in rats with congenital vesicoureteral reflux 92nd Annual Meeting of the American-Urological-Association Angell, S. K., Pruthi, R. S., Shortliffe, L. D. ELSEVIER SCIENCE INC. 1998: 150–56

  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

• The use of renal parenchymal area in children with high grade vesicoureteral reflux Annual Meeting of the Section-on-Urology, American-Academy-of-Pediatrics Pruthi, R. S., Angell, S. K., Dubocq, F., Merguerian, P. A., Shortliffe, L. R. ELSEVIER SCIENCE INC. 1997: 1232–35

  Abstract

  We sought to apply 2-dimensional sonographic measurements of renal parenchymal area in children with high grade vesicoureteral reflux to assess reliability and accuracy in estimating differential renal function, and in predicting clinical outcome compared to traditional 1-dimensional sonographic measurements.We retrospectively evaluated 121 sonograms from 30 patients with a grade 4 or 5 primary vesicoureteral reflux, including 14 who underwent ureteral reimplantation during followup and 16 who were followed on prophylactic antibiotic therapy. One-dimensional sonographic measurements of longitudinal length and bipolar thickness were determined in refluxing and contralateral kidneys, as were 2-dimensional measurements of longitudinal parenchymal area using computer planimetry. Renal length, bipolar thickness and parenchymal area were compared to renal function data determined by nuclear renography. Renal length and area was also represented as a percent of age adjusted normal values using previously published nomograms.Differential renal function correlated well with differential parenchymal area for all patients (r = 0.924). This correlation persisted in patients with (r = 0.917) and without scarring (r = 0.890), as determined by dimercapto-succinic acid scan. Differential length did not correlate as well (r = 0.661) and bipolar parenchymal thickness did not correlate at all (r = 0.021). Sonographic age adjusted area of the refluxing kidneys was approximately two-third normal. No statistically significant difference was observed among age adjusted renal area of the observation, preoperative and postoperative groups. Contralateral kidney area was not significantly different than normal.Our data indicate that serial sonographic measurements of longitudinal renal parenchymal area provide a simple and accurate method of monitoring renal growth and function in patients with high grade vesicoureteral reflux. In contrast to 1-dimensional measurements of renal length and bipolar parenchymal thickness, renal parenchymal area correlates well with renal function. Area also appears to be a more sensitive method of monitoring renal growth in children with vesicoureteral reflux.

  View details for Web of Science ID A1997XP87000065

  View details for PubMedID 9258182

• Sonographic renal parenchymal and pelvicaliceal areas: New quantitative parameters for renal sonographic followup Annual Meeting of the Section on Urology, American-Academy-of-Pediatrics Cost, G. A., Merguerian, P. A., Cheerasarn, S. P., Shortliffe, L. M. ELSEVIER SCIENCE INC. 1996: 725–29

  Abstract

  We determined better quantitative parameters for renal sonography and applied these parameters to the evaluation and followup of prenatal hydronephrosis.We retrospectively reviewed normal renal ultrasound studies of 120 children and serial ultrasound studies of 40 with prenatal hydronephrosis. Renal length, bipolar parenchymal thickness and anteroposterior pelvic diameter were measured from serial sonograms of patients with hydronephrosis. Renal longitudinal parenchymal area and renal longitudinal pelvicaliceal area were determined from the sonograms of normal children and from serial studies of patients with hydronephrosis using computer planimetry. Data from normal children were plotted to construct a renal parenchymal area growth chart. Length and area measurements were compared using regression analysis. The ability of these parameters to predict patients who would require pyeloplasty was examined.Normal parenchymal area correlated well with normal renal length (r2 = 0.92). Differential parenchymal area correlated with differential function (r2 = 0.75), while differential length and bipolar thickness correlated poorly with function (r2 = 0.01 and 0.42, respectively). The ratio of parenchymal-to-pelvicaliceal area differentiated patients with unilateral hydronephrosis requiring pyeloplasty from those treated conservatively. The ratio was less than 1.6 in all patients requiring pyeloplasty and greater than 1.6 in those followed conservatively.Renal parenchymal area provides a more accurate estimate of renal size and function in the hydronephrotic kidney than traditional 1-dimensional measurements. In our limited series the ratio of renal parenchymal-to-pelvicaliceal area allowed the prediction of patients who required pyeloplasty.

  View details for Web of Science ID A1996UX15300045

  View details for PubMedID 8683769

• Prostate specific antigen releases a kinin-like substance on proteolysis of seminal vesicle fluid that stimulates smooth muscle contraction JOURNAL OF UROLOGY Fichtner, J., GRAVES, H. C., THATCHER, K., Yemoto, C., Shortliffe, L. M. 1996; 155 (2): 738-742

  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

• PHYSIOLOGICAL FUNCTIONS OF PROSTATE-SPECIFIC ANTIGEN 12th Symposium for Experimental Urology Fichtner, J., GRAVES, H., Shortliffe, L., Stamey, T. GEORG THIEME VERLAG. 1995: 58–60

  View details for Web of Science ID A1995RX09300021

• THE EFFECT OF PREGNANCY ON RAT URINARY-TRACT DYNAMICS JOURNAL OF UROLOGY Hsia, T. Y., Shortliffe, L. M. 1995; 154 (2): 684-689

  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

• ULTRAFAST CONTRAST-ENHANCED MAGNETIC-RESONANCE-IMAGING OF CONGENITAL HYDRONEPHROSIS IN A RAT MODEL Annual Meeting of the Section on Urology of the American-Academy-of-Pediatrics Fichtner, J., Spielman, D., Herfkens, R., BOINEAU, F. G., Lewy, J. E., Shortliffe, L. M. WILLIAMS & WILKINS. 1994: 682–87

  Abstract

  Since new ultrafast magnetic resonance imaging (MRI) might offer unique advantages for evaluating renal blood flow, anatomy and urinary excretion, we used this technique to characterize a rat model with congenital partial ureteropelvic junction obstruction. MRI of 9 rats from an inbred colony with unilateral congenital (nonsurgical) hydronephrosis was compared with the contralateral nonhydronephrotic kidney serving as control. Our new imaging technique consisted of a 1-minute ultrafast gradient recalled imaging sequence during the first minute (64 images per imaging time 960 milliseconds) after contrast bolus injection with gadolinium-diethylenetriaminepentaacetic acid for assessment of renal blood flow followed by a 30-minute period with image acquisition every 30 seconds to study contrast distribution and excretion. Signal intensities were analyzed continuously over selected, different regions of interest. Anatomic analysis of MRI noncontrast studies showed precise delineation of the hydronephrotic pelvis and corticomedullary junction. After contrast gadolinium-diethylenetriaminepentaacetic acid injection signal intensity from the region of interest from hydronephrotic kidneys differed from nonhydronephrotic kidneys by showing less cortical decrease, suggesting decreased blood flow, less medullary decrease and delayed contrast excretion. Clear contrast distribution among the cortex, medulla and collecting system allowed selective estimation of different regions of interest and excellent anatomic evaluation. Renal anatomy and renal pelvic pressures were confirmed after scans were completed. Ultrafast contrast enhanced MRI allows simultaneous assessment of renal morphology, blood flow and function. In hydronephrotic partially obstructed kidneys distinct flow and excretion patterns measured with contrast enhanced MRI allow differentiation between the obstructed and nonobstructed kidney on physiological rather than purely anatomic means. This imaging technique may provide a useful method of evaluating congenital hydronephrosis obviating the need for multiple different diagnostic procedures.

  View details for Web of Science ID A1994NW33000024

  View details for PubMedID 8021995

• CONGENITAL UNILATERAL HYDRONEPHROSIS IN A RAT MODEL - CONTINUOUS RENAL, PELVIC AND BLADDER PRESSURES Annual Meeting of the Section on Urology of the American-Academy-of-Pediatrics Fichtner, J., BOINEAU, F. G., Lewy, J. E., Sibley, R. K., Vari, R. C., Shortliffe, L. M. WILLIAMS & WILKINS. 1994: 652–57

  Abstract

  We investigated a rat model with inbred unilateral congenital hydronephrosis. Simultaneous bladder and renal pelvic pressures were measured during different urinary flows, and during bladder filling and voiding in these congenitally hydronephrotic rats (approximately 45 days old) and normal nonhydronephrotic rats from the same colony. Differential pressures between pelvis and proximal ureter were determined. Upon termination of the experiment the urinary tract was removed and processed for histological examination. Hydronephrotic rats had significantly higher renal pelvic pressures throughout bladder filling at all urinary flow rates than normal rats. These elevated renal pelvic pressures exceeded bladder pressures at high flows (for example bladder pressure at 50% capacity was 8.9 +/- 3.1 cm. water and corresponding pelvic pressure was 20.8 +/- 2.1 [hydronephrosis] versus pelvic pressure 7.4 +/- 1.1 [control]). While pressures in the proximal ureter were higher than in the pelvis in normal rats the hydronephrotic rats showed significantly higher pressures in the pelvis, suggesting that the site of obstruction is the ureteropelvic junction. Histological evaluation of the excised kidneys revealed only minimal tubular changes. This study represents a unique animal model with unilateral hydronephrosis from a partially obstructing ureteropelvic junction. Moreover, the data indicate that partial urinary obstruction and the associated renal pelvic pressures should be defined with reference to bladder fullness and urinary flow rates.

  View details for Web of Science ID A1994NW33000018

  View details for PubMedID 8021990

• THE CHARACTERIZATION OF NONBACTERIAL PROSTATITIS - SEARCH FOR AN ETIOLOGY JOURNAL OF UROLOGY Shortliffe, L. M., Sellers, R. G., SCHACHTER, J. 1992; 148 (5): 1461-1466

  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

• THE EFFECT OF BACTERIURIA ON BLADDER AND RENAL PELVIC PRESSURES IN THE RAT 1991 ANNUAL MEETING OF THE SECTION OF UROLOGY OF THE AMERICAN ACADEMY OF PEDIATRICS Issa, M. M., Shortliffe, L. M., Constantinou, C. E. ELSEVIER SCIENCE INC. 1992: 559–63

  Abstract

  We investigated the effect of urinary tract infection on bladder and renal pelvic urodynamics in a rat model to examine the role of pressure during infection. Either an antibiotic solution (control group) or Escherichia coli with type 1 pili (infected group) was instilled into the bladder. After 2 to 6 days simultaneous continuous bladder and renal pelvic pressures were measured during urinary flows from less than 2 to greater than 20 ml./kg. per hour while the bladder filled and emptied. Bladder pressures from 50 to 100% of maximum capacity and maximum voiding pressures were significantly higher in the infected group than the control group (36.7 +/- 6.79 cm. water versus 25.5 +/- 5.21 cm. water, respectively, p less than 0.0001). Renal pelvic pressures were significantly higher in the infected group during bladder filling at all urinary flows examined and actually exceeded bladder pressure for the highest flows. We conclude that elevated renal pelvic pressures may contribute to renal changes observed during urinary tract infection.

  View details for Web of Science ID A1992JF96100016

  View details for PubMedID 1640522

• EVALUATION OF NONLINEAR OPTIMIZATION FOR SCHEDULING OF FOLLOW-UP CYSTOSCOPIES TO DETECT RECURRENT BLADDER-CANCER MEDICAL DECISION MAKING Kent, D. L., NEASE, R. A., Sox, H. C., Shortliffe, L. D., Shachter, R. 1991; 11 (4): 240-248

  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

• THE EFFECT OF URINARY FLOW AND BLADDER FULLNESS ON RENAL PELVIC PRESSURE IN A RAT MODEL 1990 ANNUAL MEETING OF THE SECTION OF UROLOGY OF THE AMERICAN ACADEMY OF PEDIATRICS SMYTH, T. B., Shortliffe, L. M., Constantinou, C. E. WILLIAMS & WILKINS. 1991: 592–96

  Abstract

  We describe an in vivo animal model used to study the interactions of urinary flow, and bladder pressure and fullness on renal pelvic pressure. These parameters were examined in 17 nonrefluxing Sprague-Dawley rats. At urinary flow rates less than 14 cc/kg. per hour and bladders less than 60% full, renal pelvic pressures were below 9 cm. water but at urinary flow rates more than 30 cc/kg. per hour renal pelvic pressure increased above 10 cm. water when the bladder was only 20% full. At all urinary flow rates examined renal pelvic pressure increased to more than 20 cm. water as the bladder approached 100% fullness. To quantitate the combined effects of these changes in renal pelvic pressure and urinary flow on the renal pelvis a renal pelvic work index (renal pelvic pressure times urinary flow rate) was defined. Using this index the magnitude of the change between low urinary flows with an empty bladder and high urinary flows with a full bladder can be observed. The results of these studies in this model might be applicable to high urinary flow states or bladders that fail to empty completely.

  View details for Web of Science ID A1991FZ77600022

  View details for PubMedID 1861307

• TREATMENT OF URINARY-INCONTINENCE BY THE PERIURETHRAL IMPLANTATION OF GLUTARALDEHYDE CROSS-LINKED COLLAGEN JOURNAL OF UROLOGY Shortliffe, L. M., Freiha, F. S., Kessler, R., Stamey, T. A., Constantinou, C. E. 1989; 141 (3): 538-541

  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

• MEASUREMENT OF URINARY ANTIBODIES TO CRUDE BACTERIAL-ANTIGEN IN PATIENTS WITH CHRONIC BACTERIAL PROSTATITIS JOURNAL OF UROLOGY Shortliffe, L. M., Elliott, K., Sellers, R. G. 1989; 141 (3): 632-636

  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

• EFFICIENT SCHEDULING OF CYSTOSCOPIES IN MONITORING FOR RECURRENT BLADDER-CANCER MEDICAL DECISION MAKING Kent, D. L., Shachter, R., Sox, H. C., HUI, N. S., Shortliffe, L. D., Moynihan, S., Torti, F. M. 1989; 9 (1): 26-37

  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

• ALPHA-INTERFERON IN SUPERFICIAL BLADDER-CANCER - A NORTHERN CALIFORNIA ONCOLOGY GROUP-STUDY JOURNAL OF CLINICAL ONCOLOGY Torti, F. M., Shortliffe, L. D., Williams, R. D., Pitts, W. C., Kempson, R. L., Ross, J. C., Palmer, J., Meyers, F., Ferrari, M., Hannigan, J., Spiegel, R., MCWHIRTER, K., Freiha, F. 1988; 6 (3): 476-483

  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

• MAST-CELL INVOLVEMENT IN INTERSTITIAL CYSTITIS JOURNAL OF UROLOGY LYNES, W. L., Flynn, S. D., Shortliffe, L. D., Lemmers, M., ZIPSER, R., Roberts, L. J., Stamey, T. A. 1987; 138 (4): 746-752

  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

• ADHERENCE OF ESCHERICHIA-COLI AND PROTEUS-MIRABILIS TO HUMAN TRANSITIONAL CELLS JOURNAL OF UROLOGY Szabo, R. J., Shortliffe, L. M., Stamey, T. A. 1987; 137 (4): 793-797

  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

• THE CHARACTERIZATION OF BACTERIAL AND NONBACTERIAL PROSTATITIS BY PROSTATIC IMMUNOGLOBULINS MEDICINE Shortliffe, L. M., Wehner, N. 1986; 65 (6): 399-414

  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

• PROSTATIC EVALUATION BY TRANS-RECTAL ENDOSONOGRAPHY - DETECTION OF CARCINOMA RADIOLOGY Rifkin, M. D., Friedland, G. W., Shortliffe, L. 1986; 158 (1): 85-90

  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

• TAMOXIFEN IN ADVANCED PROSTATIC-CARCINOMA - A DOSE ESCALATION STUDY CANCER Torti, F. M., Lum, B. L., Lo, R., Freiha, F., Shortliffe, L. 1984; 54 (4): 739-743

  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

• USE OF A SOLID-PHASE RADIOIMMUNOASSAY AND FORMALIN-FIXED WHOLE BACTERIAL-ANTIGEN IN THE DETECTION OF ANTIGEN-SPECIFIC IMMUNOGLOBULIN IN PROSTATIC FLUID JOURNAL OF CLINICAL INVESTIGATION Shortliffe, L. M., Wehner, N., Stamey, T. A. 1981; 67 (3): 790-799

  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

• THE DETECTION OF A LOCAL PROSTATIC IMMUNOLOGICAL RESPONSE TO BACTERIAL PROSTATITIS JOURNAL OF UROLOGY Shortliffe, L. M., Wehner, N., Stamey, T. A. 1981; 125 (4): 509-515

  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

• Urinary Tract Infection in Children: When to Worry UROLOGIC CLINICS OF NORTH AMERICA Clark, C. J., Kennedy, W. A., Shortliffe, L. D. 2010; 37 (2): 229-?

  Abstract

  Urinary tract infection (UTI) is a frequent diagnosis in children who are referred to the urologist. Although most infections will resolve without complication after appropriate treatment, a wide array of potential complicating factors exists, which can make difficult the rapid resolution of a UTI. Clinical scenarios involving these factors require a high index of suspicion and prompt initiation of appropriate therapy.

  View details for DOI 10.1016/j.ucl.2010.03.009

  View details for Web of Science ID 000279321900009

  View details for PubMedID 20569801

• Evaluation of asymptomatic, atraumatic hematuria in children and adults NATURE REVIEWS UROLOGY Tu, W. H., Shortliffe, L. D. 2010; 7 (4): 189-194

  Abstract

  Asymptomatic, atraumatic hematuria is a worrisome clinical sign for a patient that usually prompts a visit to a urologist. Hematuria is classified as microscopic versus gross; the evaluation for gross hematuria differs from that for microscopic hematuria, and the most important differentiating factor is the patient's age. The major causes of hematuria differ between children and adults, and the evaluation should reflect this. Renal disease is more common in children and malignancy more common in adults. The application and utility of laboratory tests, radiological studies, and cystoscopy are well established in adults but are more variable in children. Follow-up of hematuria after a negative evaluation is becoming more limited in adults but should be routine for children.

  View details for DOI 10.1038/nrurol.2010.27

  View details for Web of Science ID 000276540700007

  View details for PubMedID 20212514

• Top-down Approach for Evaluation of Urinary Tract Infection UROLOGY Wu, H., Shortliffe, L. D. 2010; 75 (3): 514-515

  View details for DOI 10.1016/j.urology.2009.07.1264

  View details for Web of Science ID 000275814500008

  View details for PubMedID 19879637

• The management of renal angiomyolipomas in a patient with tuberous sclerosis NATURE CLINICAL PRACTICE UROLOGY Wong, I. Y., Shortliffe, L. D. 2009; 6 (3): 168-172

  Abstract

  BACKGROUND: A 17-year-old girl, who was diagnosed with tuberous sclerosis in infancy, presented with multiple bilateral renal masses, the largest of which was 6.0 cm in diameter on the left side. INVESTIGATIONS: History and physical examination, ultrasonography, MRI, CT, magnetic resonance angiography, and measurement of serial creatinine levels. DIAGNOSIS: Bilateral angiomyolipomas.Management Observation, serial imaging, embolization and infarction.

  View details for DOI 10.1038/ncpuro1318

  View details for Web of Science ID 000263914200011

  View details for PubMedID 19265859

• Certification, Recertification and Maintenance: Continuing to Learn UROLOGIC CLINICS OF NORTH AMERICA Shortliffe, L. M. 2009; 36 (1): 79-?

  Abstract

  The process of certification, recertification, and maintenance of certification is mandated by the American Board of Urology as a member Board of the American Board of Medical Specialties. The history of maintenance of certification parallels that of private regulation of medical schools and postgraduate medical education (residency) and other nonmedical areas in which public trust is involved. Current trends in information technology that allow data gathering that measure medical practice and recognition of failure mandate that urologists practice with current knowledge. This will be documented in the maintenance of certification process.

  View details for DOI 10.1016/j.ucl.2008.08.001

  View details for Web of Science ID 000262172300011

  View details for PubMedID 19038639

• A case of ectopic dysplastic kidney and ectopic ureter diagnosed by MRI NATURE CLINICAL PRACTICE UROLOGY Duong, D. T., Shortliffe, L. M. 2008; 5 (11): 632-636

  Abstract

  A 14-year-old girl with a solitary right kidney had continuous urinary incontinence. Four months previously she had undergone surgical resection of a vaginal septum associated with uterus didelphys, which was causing obstructed menstrual flow. She was toilet trained at the age of 2 years, had a normal voiding pattern, and had no history or family history of incontinence.Pelvic examination, abdominal and pelvic ultrasonography, renal scintigraphy, voiding cystourethrography, abdominal and pelvic MRI, fluoroscopic retrograde vaginography, vaginoscopy, cystourethroscopy after administration of indigo carmine, laparoscopy, and pathologic examination of the excised specimen.Ectopic ureter draining into the vagina associated with a contralateral dysplastic kidney.Laparoscopic nephrectomy of the left renal remnant and ligation of the left distal ureter.

  View details for DOI 10.1038/ncpuro1220

  View details for Web of Science ID 000260566900011

  View details for PubMedID 18839014

• Management of Wilms tumor: current standard of care NATURE CLINICAL PRACTICE UROLOGY Sonn, G., Shortliffe, L. M. 2008; 5 (10): 551-560

  Abstract

  Wilms tumor is the most common renal malignancy in children. In the 1930s, overall survival for children with Wilms tumor was approximately 30%. Use of multidisciplinary therapy, guided by results from multi-institutional, randomized trials, has substantially improved overall survival to about 90%. Management of Wilms tumor differs substantially between Europe and the US. In Europe, the International Society of Pediatric Oncology protocols call for management of patients with presumptive Wilms tumor with neoadjuvant chemotherapy followed by nephrectomy and further chemotherapy. In the US, protocols developed by the National Wilms Tumor Study Group advise primary nephrectomy followed by a chemotherapy regimen tailored to the pathologic tumor stage. Despite these disparate strategies, overall survival is similar in patients managed according to European and US protocols. Patients with Wilms tumor now have excellent survival. Therefore, current goals aim to reduce the morbidity associated with therapy. Important complications of treatment for Wilms tumor include cardiomyopathy, renal failure, and increased risk of a secondary malignancy. Currently, the role of laparoscopic surgery in management of Wilms tumor remains extremely limited.

  View details for DOI 10.1038/ncpuro1218

  View details for Web of Science ID 000259638000010

  View details for PubMedID 18836464

• Pediatric urinary tract infections PEDIATRIC CLINICS OF NORTH AMERICA Chang, S. L., Shortliffe, L. D. 2006; 53 (3): 379-?

  Abstract

  Pediatric urinary tract infections are common. These infections have been recognized as a source of acute morbidity and long-term medical consequences in adulthood. There are various risk factors and clinical presentations in children with urinary tract infections. The main objectives in management include prompt diagnosis, appropriate antimicrobial therapy, identification of anatomic anomalies, and, in select patients, long-term follow-up.

  View details for DOI 10.1016/j.pcl.2006.02.011

  View details for Web of Science ID 000238814500005

  View details for PubMedID 16716786

• Management of delayed bladder augmentation perforation NATURE CLINICAL PRACTICE UROLOGY Adams, W., Shortliffe, L. M. 2006; 3 (6): 341-344

  Abstract

  A 17-year-old male, with a history of bladder augmentation enterocystoplasty 7 years earlier, presented with nausea, emesis and acute abdomen.Physical examination, blood and urine culture, and abdominal and pelvic CT cystography.Acute abdomen from perforation of bladder augmentation.Support and stabilization, bladder decompression, and broad-spectrum intravenous antibiotics, followed by immediate exploratory laparotomy with repair of enterocystoplasty and peritoneal lavage.

  View details for DOI 10.1038/ncpuro0509

  View details for Web of Science ID 000238210100013

  View details for PubMedID 16763646

• Laparoscopic mitrofanoff appendicovesicostomy UROLOGY Hsu, T. H., Shortliffe, L. D. 2004; 64 (4): 802-804

  Abstract

  A novel technique of performing fully laparoscopic Mitrofanoff appendicovesicostomy in the management of neurogenic bladder is described. All steps, including appendix harvesting and extravesical appendiceal-vesical anastomosis with flap-valve mechanism creation, were completed laparoscopically and provided satisfactory preliminary clinical results. Additional studies are necessary for the evaluation of this novel technique.

  View details for DOI 10.1016/j.urology.2004.04.059

  View details for Web of Science ID 000224680300043

  View details for PubMedID 15491727

• Urinary tract infection in children: etiology and epidemiology UROLOGIC CLINICS OF NORTH AMERICA Ma, J. F., Shortliffe, L. M. 2004; 31 (3): 517-?

  Abstract

  The urinary tract is a relatively common site of infection in infants and young children. Urinary tract infection (UTI) may result in significant acute morbidity, as well as longterm medical complications. Recent advances elucidating the pathogen-host interaction have broadened the understanding of the pathogenesis and clinical progression of pediatric UTI. This article focuses on the epidemiology and pathogenesis of pediatric UTI, and briefly discusses UTI-related complications.

  View details for DOI 10.1016/j.ucl.2004.04.016

  View details for Web of Science ID 000223767000014

  View details for PubMedID 15313061

• Neuroblastoma: Management, recurrence, and follow-up UROLOGIC CLINICS OF NORTH AMERICA Lee, K. L., Ma, J. F., Shortliffe, L. D. 2003; 30 (4): 881-?

  Abstract

  The clinical use of N-myc amplification in neuroblastoma management has served as a paradigm for "bench to bedside" medicine. It is hoped that the quest for molecular markers such as neurotrophin, TrkA, and TrkB will continue to advance the understanding of neuroblastoma. In addition, animal models of neuroblastoma (N-myc transgenic mice, and neuroblastoma xenografts) have been established to assess the efficacy of novel treatments. These advances are likely to improve clinical practice in the future.

  View details for DOI 10.1016/S0094-0143(03)00053-3

  View details for Web of Science ID 000187292400018

  View details for PubMedID 14680322

• Fetal renal growth as assessed through renal parenchymal area derived from prenatal and perinatal ultrasonography JOURNAL OF UROLOGY Kennedy, W. A., Chitkara, U., Abidari, J. M., Shortliffe, L. M. 2003; 169 (1): 298-302

  Abstract

  Few quantitative parameters allow for comparison of serial studies in children with prenatally detected genitourinary abnormalities. We establish the first ultrasonographically based fetal renal parenchymal growth curve that could serve as a standard for fetal renal growth assessment.Longitudinal ultrasounds of 246 normal fetal kidneys from 16 to 38 weeks of gestation were scanned with renal parenchymal area calculated and growth curves plotted. Our previously determined nomogram from birth to adolescence was then combined with this fetal nomogram to produce a composite renal growth curve. Data were plotted as mean parenchymal area +/- 2 SD using lines determined by polynomial regression.Renal growth curves were constructed independently for the right and left fetal kidneys as well as the total fetal renal parenchymal area. The polynomial regression equation for the right renal parenchymal area was y = -0.0076x(2) + 0.7141x - 8.5344 (r(2) = 0.91). The polynomial regression equation for the left renal parenchymal area was y = -0.0036x(2) + 0.5161x - 6.2337 (r(2) = 0.96). The polynomial regression equation for the total fetal renal parenchymal area was y = -0.0113x(2) + 1.234x - 14.814 (r(2) = 0.95).We propose a new quantitative standard to evaluate appropriate fetal kidney size the prenatal renal parenchymal area growth curve. Renal parenchymal growth curves for the normal fetal kidney may serve as a valuable tool to assess fetal renal pathology.

  View details for DOI 10.1097/01.ju.0000041762.66236.29

  View details for Web of Science ID 000179921200101

  View details for PubMedID 12478175

• Urinary incontinence in girls UROLOGIC CLINICS OF NORTH AMERICA Abidari, J. M., Shortliffe, L. M. 2002; 29 (3): 661-?

  Abstract

  Girls with incontinence may have minor irritative conditions or undiagnosed anatomic abnormalities that may require surgery. These abnormalities can be identified during a comprehensive history and physical examination that focuses on voiding signs and symptoms. Urinary tract infection and constipation if present should be identified. Most girls with daytime wetting will respond to conservative therapy using timed voiding, dietary changes, and anticholinergic medication. Uroflowmetry with a postvoid residual urine measurement can identify girls who may benefit from biofeedback to treat pelvic floor dysfunction. Formal urodynamics and spinal magnetic resonance imaging should be done in girls refractory to treatment. Instruments and tools to quantify dysfunctional voiding symptoms are being developed. Because most dysfunctional voiding will be treated clinically, these validated tools will be useful in documenting severity of symptoms and clinical outcomes.

  View details for Web of Science ID 000179417900016

  View details for PubMedID 12476529

• Urinary tract infection at the age extremes: Pediatrics and geriatrics AMERICAN JOURNAL OF MEDICINE Shortliffe, L. M., McCue, J. D. 2002; 113: 55S-66S

  Abstract

  Urinary tract infections (UTIs) are common and generally benign conditions among healthy, sexually active young women without long-term medical sequelae. In contrast, UTIs are more complicated among those individuals at either end of the age spectrum: infants/young children and geriatrics. UTI in children younger than 2 years has been associated with significant morbidity and long-term medical consequences, necessitating an extensive and somewhat invasive imaging evaluation to identify possible underlying functional or anatomic abnormalities. Pediatric UTI should be considered complicated until proved otherwise, and treatment should reflect the severity of signs and symptoms. Management in the acutely ill child frequently involves parenteral broad-spectrum antimicrobial agents, and less ill children can be treated with trimethoprim- sulfamethoxazole (TMP-SMX), beta-lactams, and cephalosporins.UTI among older patients (>65 years) may be complicated by comorbidities, the baseline presence of asymptomatic bacteriuria, and benign urinary symptoms that can complicate diagnosis. The etiology of UTI encompasses a broader spectrum of infecting organisms than is seen among younger patients and includes more gram-positive organisms. Symptomatic UTI is generally more difficult to treat than among younger populations. Management should be conservative, of longer treatment durations, and cover a broad spectrum of possible uropathogens. Oral or parenteral treatment with a fluoroquinolone for 7 days is the preferred empiric approach. TMP-SMX can also be considered a first-line agent in women only, but only if the pathogen is known to be TMP-SMX sensitive.

  View details for Web of Science ID 000176754300008

  View details for PubMedID 12113872

• Pediatric urinary tract infections PEDIATRIC CLINICS OF NORTH AMERICA Chon, C. H., Lai, F. C., Shortliffe, L. M. 2001; 48 (6): 1441-?

  Abstract

  Urinary tract infection in the pediatric population can lead to significant morbidity if not treated promptly and appropriately. All first infections may signify possible underlying anatomic or functional abnormality and require imaging of the lower and upper tracts. Accurate diagnosis of UTIs requires a properly collected quantitative urine culture. Treatment should be tailored to the pathogen as dictated by the urine culture sensitivities to minimize the development of multidrug-resistant organisms. Prophylactic agents should differ from the antibiotic used in the acute setting and preferably concentrated in the urinary tract, with minimal effects on the normal fecal flora. In the long term, patients with documented evidence of renal scarring should be followed up for signs of renal deterioration and hypertension.

  View details for Web of Science ID 000172285000006

  View details for PubMedID 11732124

• The effects of intravesical lidocaine on bladder dynamics of children with myelomeningocele Joint Meeting of the American-Academy-of-Pediatrics Section on Urology/European-Society-for-Paediatric-Urology Lapointe, S. P., Wang, B. Y., Kennedy, W. A., Shortliffe, L. M. ELSEVIER SCIENCE INC. 2001: 2380–82

  Abstract

  Other studies have suggested that intravesical lidocaine may temporarily improve bladder dynamics but details of these effects and their application to children have not been examined. We evaluated the effects of intravesical lidocaine on bladder urodynamics of children with myelomeningocele and tried to correlate these effects with subsequent clinical response to oral oxybutynin.Charts of children with myelomeningocele who had undergone urodynamic examinations from 1992 to 1998 were reviewed retrospectively. In children with uninhibited contractions or poor compliance 150 to 300 mg. lidocaine were instilled for 8 minutes and cystometry was repeated. Changes in bladder capacity and compliance, number of uninhibited contractions and bladder volume at which pressure of 40 cm. H2O was reached were recorded before and after the lidocaine instillation. Clinical response to subsequent treatment with oral oxybutynin was assessed from chart review.A total of 48 urodynamic studies in 22 girls and 20 boys with a mean age plus or minus standard deviation of 8.3 +/- 5.7 years and myelomeningocele were evaluable. After instillation of lidocaine, urodynamics showed increased bladder capacity in 70.8% of studies (34 of 48), with an average increase in volume of 66% (p <0.05). No change or decreased bladder capacity occurred in 29.2% of studies. Bladder compliance improved in 61.7% of the studies (29 of 47, p <0.05) and worsened in 38.3%. Bladder volume at which the pressure of 40 cm. H2O was reached increased in 77.8% of studies (14 of 18, p <0.05). After lidocaine the number of uninhibited contractions decreased by 3.2 in 56.8% of studies (21 of 37, p <0.05). Correlation of lidocaine induced changes in bladder capacity, compliance and number of uninhibited contractions with improvement on oral oxybutynin was 70.6%, 64.3% and 66.7%, respectively.Intravesical lidocaine can improve bladder capacity and compliance and decrease the number of uninhibited contractions in many children with neurogenic bladder caused by myelomeningocele. These observations suggest that intravesical lidocaine has effects on the neurogenic bladder that improve bladder dynamics. Although intravesical lidocaine testing may not reliably predict clinical response to oral oxybutynin at the prescribed dosages, a possible therapeutic role for intravesical lidocaine or similar agents should be explored further.

  View details for Web of Science ID 000168623700050

  View details for PubMedID 11371945

• Evaluation and management of pediatric urinary tract infections UROLOGIC CLINICS OF NORTH AMERICA Lindert, K. A., Shortliffe, L. M. 1999; 26 (4): 719-?

  Abstract

  Urinary tract infections (UTIs) are relatively common in children. We describe the evaluation and management of children with UTIs, as well as the risks and consequences related to the UTI. This article describes a rational approach to the evaluation and management of childhood UTIs with the relation to the natural history and risk factors.

  View details for Web of Science ID 000083292200005

  View details for PubMedID 10584613

• Progressive renal shrinkage after simple pyelonephritis UROLOGY Hansen, M. H., Shortliffe, L. M. 1998; 52 (5): 893-896

  Abstract

  Nonobstructive, nonrefluxing pyelonephritis (or "simple" pyelonephritis) is not commonly associated with progressive renal scarring and global shrinkage. Although children are believed to be particularly susceptible to renal parenchymal scarring after simple pyelonephritis, progressive and global renal shrinkage remains an elusive clinical entity. We present such a case with close radiologic documentation.

  View details for Web of Science ID 000076662300042

  View details for PubMedID 9801125

• Multicenter experience with the Mitchell technique for epispadias repair JOURNAL OF UROLOGY Zaontz, M. R., Steckler, R. E., Shortliffe, L. M., Kogan, B. A., Baskin, L., Tekgul, S. 1998; 160 (1): 172-176

  Abstract

  We present a multicenter experience using the Mitchell epispadias technique to determine if satisfactory results could be obtained by various pediatric urologists at multiple centers using the same technique to repair epispadias. This particular technique involves complete disassembly of the penis into 2 separate hemicorporeal glandular bodies and a separate urethral plate, and relies on the unique blood supply to the epispadiac phallus.A total of 17 boys 11 months to 21 years old underwent the Mitchell procedure for epispadias at 4 institutions by 6 different surgeons between 1994 and 1996. One patient in this group had undergone prior epispadias repair, which had failed.At followup (mean 13.5 months) 3 boys had pinpoint penopubic fistulas, which resolved spontaneously in 2. The 21-year-old patient had a complete wound dehiscence. All boys with intact repairs have straight erections, orthotopic meatus and satisfactory appearances. There were 15 boys with a conical glans appearance and 1 exhibiting glandular disproportion. There was 1 episode of postoperative pyelonephritis.The Mitchell technique for repair of epispadias is reproducible and successful in the hands of pediatric urologists from different centers. Chordee is reliably corrected, erectile function preserved, the urethra ventrally situated in an anatomically precise fashion and satisfactory cosmesis achieved.

  View details for Web of Science ID 000074037800078

  View details for PubMedID 9628644

• Laparoscopy for the evaluation and management of the nonpalpable testicle UROLOGY Merguerian, P. A., Mevorach, R. A., Shortliffe, L. D., Cendron, M. 1998; 51 (5A): 3-6

  Abstract

  To assess the usefulness of laparoscopy for the diagnosis and treatment of the nonpalpable testicle and to evaluate the results of laparoscopic orchidopexy.We retrospectively reviewed the charts of 91 laparoscopies performed over a period of 4 years. We reviewed the following parameters: findings, complications, patency of the processus vaginalis, appearance of the cord structures, and the success of the different procedures performed for the intra-abdominal testicle.Fourteen patients had bilateral and 77 unilateral nonpalpable testicles. The mean age of the patients was 39.5 +/- 50.8 months. There were three laparoscopic complications (3.2%) one of which was a major bowel laceration. Laparoscopy defined the intra-abdominal anatomy accurately in 90 of the 91 cases Of the 26 intra-abdominal testicles above the ring, a one-stage laparoscopic orchidopexy was performed in five and a single-stage standard orchidopexy in seven. All of these testicles remain viable and are in good position. Eight patients underwent a staged Fowler-Stephens orchidopexy with laparoscopic clipping of the spermatic vessels as the first stage. Of these, a second-stage open orchidopexy was performed in five and a laparoscopic orchidopexy in three. Testicular atrophy occurred in two of the patients who underwent the second-stage open orchidopexy. Three one-stage Fowler-Stephens orchidopexies were performed with testicular atrophy occurring in two of these testicles. Laparoscopic orchiectomy was performed on two patients.Laparoscopy is a valuable tool in the diagnosis and treatment of the nonpalpable testicle. Laparoscopic orchidopexy may decrease the rate of testicular atrophy since most of these can be performed laparoscopically in one stage, thus preserving the vascular supply.

  View details for Web of Science ID 000073863100003

  View details for PubMedID 9610548

• Normal pediatric testis: Comparison of power Doppler and color Doppler US in the detection of blood flow RADIOLOGY Barth, R. A., Shortliffe, L. D. 1997; 204 (2): 389-393

  Abstract

  To compare power Doppler and conventional color Doppler ultrasound (US) in the detection of blood flow in the normal pediatric testis and to assess the symmetry of blood flow and the spectral Doppler tracing waveforms in the normal pediatric testis.Testicular blood flow was assessed prospectively in 68 testes in 34 boys (age range, 6 weeks to 13 years; mean age, 4.6 years) with both conventional color and power Doppler US. Intratesticular blood flow was graded as follows: 0, no intratesticular flow; 1, single intratesticular Doppler signal identified; and 2, multiple intratesticular Doppler signals identified. The symmetry of intratesticular flow was assessed both subjectively and objectively by using the same grading system. Spectral Doppler tracings were obtained in 62 testes in 31 patients.Power Doppler US demonstrated intratesticular blood flow in 66 (97%) testes. Color Doppler US demonstrated intratesticular blood flow in 60 (88%) testes. Combined techniques depicted blood flow in all 68 (100%) testes. Testicular blood flow was judged symmetric in all 34 (100%) patients with power Doppler US and in 31 (91%) patients with color Doppler US. Spectral Doppler tracings demonstrated absence of diastolic flow in 20 (32%) of 62 testes.In children, power Doppler US is more sensitive than color Doppler US in the detection of intratesticular blood flow. With power Doppler US, testicular blood flow in healthy children is symmetric, underscoring that the asymptomatic testis can be used as a baseline for assessing flow in the symptomatic testis.

  View details for Web of Science ID A1997XL64400018

  View details for PubMedID 9240525

• Outcome analysis of the modified Mathieu hypospadias repair: Comparison of stented and unstented repairs Annual Meeting of the Section on Urology, American-Academy-of-Pediatrics Hakim, S., Merguerian, P. A., Rabinowitz, R., Shortliffe, L. D., McKenna, P. H. ELSEVIER SCIENCE INC. 1996: 836–38

  Abstract

  We compared surgical outcomes of stented and unstented Mathieu repairs in boys with primary distal hypospadias, and evaluated the efficacy and safety of caudal analgesia relative to other forms of analgesia (penile block and epidural analgesia).We retrospectively reviewed the records of 336 consecutive boys who underwent the modified Mathieu repair for primary distal hypospadias. A urethral stent was placed in 114 patients and nonstented repair was performed in 222. Adjunct caudal analgesia was given in 136 cases, a penile block in 158 and continuous epidural analgesia in 42.None of the unstented cases had urinary retention. Analysis of surgical outcomes revealed no difference in fistula formation between patients with and without stents (2.63 versus 2.70%, respectively, p > 0.999). Overall complication rates in the stented and unstented groups were not significantly different (2.63 versus 3.60%, respectively, p = 0.756). The fistula rate in patients who received adjunct caudal analgesia was no different than in those who received other forms of adjunct analgesia (2.21 versus 3.0%, respectively, p > 0.999).These data suggest that successful Mathieu hypospadias repair is independent of the use of a stent. Caudal analgesia, a penile block and epidural analgesia provided effective postoperative pain control with no difference in complication rates. To our knowledge our report represents the largest observational study reported to date comparing stented and unstented repairs. However, because of the small number of complications in each group, a much larger study is required to determine statistically significant differences among these groups.

  View details for Web of Science ID A1996UX15300081

  View details for PubMedID 8683796

• Testicular torsion with contralateral vanishing testis UROLOGY Gong, M., GEARY, E. S., Shortliffe, L. M. 1996; 48 (2): 306-307

  Abstract

  An infant with a left hydrocele and nonpalpable right testis had an antenatal ultrasonogram showing a left hydrocele and normal right testis. When left inguinal hydrocelectomy was performed, extravaginal torsion of the spermatic cord and a normal testis was discovered. The right spermatic cord ended in a testicular remnant. We propose that this was a case of bilateral antenatal torsion that would have resulted in bilateral vanishing testis syndrome had the left hydrocele not prevented vascular compromise when antenatal testicular torsion occurred. This case gives visible support to the theory that testicular remnants are the result of antenatal torsion.

  View details for Web of Science ID A1996VD09900029

  View details for PubMedID 8753748

• DISCUSSION JOURNAL OF UROLOGY Mesrobian, H. G., Puri, P., Passerini, G., Allen, T., Khoury, A., Diamond, D., Bogaert, G., Peters, C., Kogan, B., Weiss, R., Shortliffe, L., BLYTHE, B., LINN, R., Steinhardt, G., DJUHUUS 1995; 154 (2): 706-707

  View details for Web of Science ID A1995RJ05100011

• Pediatric genitourinary tumors. Current opinion in oncology JULIAN, J. C., Merguerian, P. A., SHORTLIFFE, L. M. 1995; 7 (3): 265-274

  Abstract

  Treatment of childhood genitourinary tumors continues to advance through international protocols and a multidisciplinary approach. New developments in molecular biology have provided insight into the cellular events leading to tumorigenesis in Wilms' tumor and rhabdomyosarcoma. This paper reviews the 1994 literature with an emphasis on Wilms' tumor, genitourinary rhabdomyosarcoma, and testicular intratubular germ cell neoplasia.

  View details for PubMedID 7654829

• THE MANAGEMENT OF URINARY-TRACT INFECTIONS IN CHILDREN WITHOUT URINARY-TRACT ABNORMALITIES UROLOGIC CLINICS OF NORTH AMERICA Shortliffe, L. M. 1995; 22 (1): 67-73

  Abstract

  Although most urinary tract infections in children with normal urinary tract anatomy pose little threat to renal function, pyelonephritis, particularly in infants, may cause renal scarring when not diagnosed and treated promptly. For most children, however, the problems of urinary tract infection may be related to a biologic predisposition to recurrent infections and the bothersome clinical symptoms associated with them. In these children, infections should be diagnosed carefully and then treated for 3 days with appropriate antimicrobial agents. In children with frequently recurrent infections (more than two in 6 months), a prophylactic antimicrobial agent in the proper low dosage may be useful. Children bothered by infection-associated symptoms of bladder dysfunction with persistent incontinence may improve with treatment with anticholinergic drugs and/or bladder rehabilitation. There may also be a decrease in the rate of urinary tract infections with this treatment. When covert bacteriuria is found and bothersome symptoms are associated with it, symptoms should be treated. If recurrent covert bacteriuria is truly asymptomatic, however, not treating the infection may be the best option.

  View details for Web of Science ID A1995QH23600007

  View details for PubMedID 7855961

• BOVINE BLADDER COMPLIANCE INCREASES WITH NORMAL FETAL DEVELOPMENT - DISCUSSION JOURNAL OF UROLOGY Wacksman, J., Fichtner, J., Djurhuus, J. C., Atala, A., Shortliffe, L., Khoury, A., Spencer, J., SESSIONS, R. P., Zderic, S., Cilento, B., Hutton, K. A., Snow, B., Chavez, D. R., Thomas, D. F. 1994; 152 (2): 696-697

  View details for Web of Science ID A1994NW33000027

• Biology and treatment of pediatric genitourinary tumors. Current opinion in oncology GEARY, E. S., Gong, M. C., SHORTLIFFE, L. M. 1994; 6 (3): 292-300

  Abstract

  Treatment of childhood genitourinary tumors continues to advance through the use of collaborative protocols and a multidisciplinary approach. This paper reviews the 1993 literature, with an emphasis on Wilms' tumor, rhabdomyosarcoma, and testicular intraepithelial neoplasia and its relationship to testicular maldescent.

  View details for PubMedID 8080859

• ENDOSCOPIC BLADDER NECK SUSPENSION FOR TREATMENT OF FEMALE STRESS-INCONTINENCE - THE STAMEY PROCEDURE AKTUELLE UROLOGIE Fichtner, J., VOGES, G., Shortliffe, L., Stamey, T. 1994; 25 (2): R1-R6

  View details for Web of Science ID A1994NG75000011

• PRIMARY NOCTURNAL ENURESIS - INTRODUCTION CLINICAL PEDIATRICS Shortliffe, L. M. 1993: 3-4

  View details for PubMedID 8039337

• Pediatric genitourinary tumors. Current opinion in oncology Fichtner, J., Dairiki Shortliffe, L. M. 1993; 5 (3): 530-537

  Abstract

  During the past two decades, highly effective multimodality therapy involving surgery, chemotherapy, and radiation has been developed through consecutive national and international study protocols for childhood genitourinary cancers with the model being Wilms' tumor. These studies represent a landmark achievement in the history of pediatric oncology and mark the success of multi-institutional studies. With the excellent survival rates that have been established, current interest is now directed toward examining survivors for long-term treatment complications and minimizing the side effects while preserving treatment efficacy. In addition, new developments in the molecular biology of Wilms' tumor have made this neoplasm a model for understanding the molecular and genetic aspects of tumorigenesis. This article reviews some of the publications from 1992 on pediatric genitourinary tumors.

  View details for PubMedID 8388257

• RENAL DAMAGE, INFECTION AND REFLUX - DISCUSSION JOURNAL OF UROLOGY Belman, A. B., Smellie, J., Bailey, R., KINCAIDSMITH, P., Braren, V., King, L., Roberts, J., Shortliffe, L., Rushton, H. G., Ransley, P., Bernstein, J., BERG, U., Allen, T., Weiss, R., Lebowitz, R., VANGOOL, J., MAJD, M., Hellstrom, M., Parrot, T., Jodal, U., Snyder, H. 1992; 148 (5): 1735-1738

  View details for Web of Science ID A1992JW46200027

• OPERATIVE TECHNIQUE - DISCUSSION JOURNAL OF UROLOGY Parrott, T., Bassiouny, I., Kramer, S., Ransley, P., Belman, A. B., Ehrlich, R., Ritchey, M., Baumann, L., Husmann, D., Kass, E., Broecker, B., Bartone, F., Bartholomew, T., Gill, B., Duckett, J., Shortliffe, L., Bauer, S. B., Rink, R., Scherz, H., Koyle, M., Rushton, G., Mitchell, M., Kaplan, G., Houle, A. M., Dean, W., Nguyen, D., Khoury, A., Hanna, M., McLorie, G., Scherz, H. 1992; 148 (2): 711-713

  View details for Web of Science ID A1992JF96100065

• NEUROPATHIC BLADDER INCONTINENCE - DISCUSSION JOURNAL OF UROLOGY Bartholomew, T., Wan, J., Steinhardt, G., Schwartz, R., Shortliffe, L., Walker, R. D., PARKHOUSE, H., Franco, I., Snyder, H., Decter, R. 1992; 148 (2): 654-654

  View details for Web of Science ID A1992JF96100047

• VESICOURETERAL REFLUX URINARY-INFECTION - DISCUSSION JOURNAL OF UROLOGY Braren, V., Elder, J., Starr, N., Frey, P., Zaontz, M., Ewalt, D., Leonard, M., Canning, D., Puri, P., Atala, A., Reinberg, Y., Ritchey, M., Shortliffe, L., STCLAIR, S., Koff, S., Franco, I., Greenfield, S., Rushton, G., Zaontz, M. 1992; 148 (2): 737-738

  View details for Web of Science ID A1992JF96100071

• RESEARCH - DISCUSSION JOURNAL OF UROLOGY Diamond, D., Kambic, H., Khoury, A., Kay, R., Tanagho, E., Shortliffe, L., Ewalt, D., Mitchell, M., Cartwright, P., Kaplan, W., Boone, T., Reinberg, Y., Issa, M., Spencer, J. 1992; 148 (2): 564-565

  View details for Web of Science ID A1992JF96100017

• Pediatric genitourinary tumors. Current opinion in oncology Cowan, B. E., SHORTLIFFE, L. M. 1992; 4 (3): 455-462

  Abstract

  Although genitourinary tumors make up only 10% of childhood cancers, with Wilms' tumor accounting for most, the study of these tumors has yielded a model of cancer development. Tremendous interinstitutional and international cooperation has improved the survival and lowered the morbidity of treatment. Advances in molecular biology and improvement in experimental techniques make this a tremendously exciting field, with discoveries being made almost routinely. Most importantly, however, the study of this group of tumors and the ensuing application of multi-modality therapy has saved the lives of thousands of children.

  View details for PubMedID 1323333

• Pediatric genitourinary tumors. Current opinion in oncology Issa, M. M., SHORTLIFFE, L. M. 1991; 3 (3): 545-552

  Abstract

  Childhood genitourinary tumors are rare and continue to demand collaborative protocols to accumulate adequate numbers of patients for studies, and a multidisciplinary approach for treatment. This paper reviews all the 1990 literature on the most common of these tumors--Wilms' and testicular tumors and rhabdomyosarcoma. The molecular and cellular biology and pathology of Wilms' tumor, as well as treatment advances, are discussed, emphasizing attempts to minimize treatment morbidity and mortality while maintaining optimal quality and quantity of life.

  View details for PubMedID 1654129

• THE HISTOLOGY OF INTERSTITIAL CYSTITIS AMERICAN JOURNAL OF SURGICAL PATHOLOGY LYNES, W. L., Flynn, S. D., Shortliffe, L. D., Stamey, T. A. 1990; 14 (10): 969-976

  Abstract

  Several studies have reported histologic findings in interstitial cystitis (IC) bladder biopsy specimens. However, these studies used a variety of criteria to define IC, which may explain the variation noted in the histologic changes. Clinical experience shows that these biopsy specimens are often not helpful in confirming the diagnosis. Our study was designed to examine the histologic features identified in bladder biopsy specimens from patients with IC and compare them with biopsy specimens from a control population. Although IC patients as a group had a higher incidence and degree of denuded epithelium, ulceration, and submucosal inflammation, none of these findings was pathognomonic. In addition, these findings occurred only in interstitial cystitis patients with pyuria or small bladder capacity. The inflammatory infiltrate seen in IC was composed predominantly of lymphocytes, with increasing numbers of plasma cells as the degree of inflammation increased. There was no specific predilection for the inflammatory infiltrate to be perineural. Submucosal inflammation was associated with denuded epithelium, ulceration, pyuria, and a clinical response to therapy suggesting a pathophysiologic relationship. Epithelial and basement membrane thickness, submucosal edema, vascular ectasia, fibrosis, and detrusor muscle inflammation and fibrosis were not significantly different in the IC and control patients. These findings suggest that IC is a chronic submucosal inflammatory disease, at least in those patients with small bladder capacities or pyuria. IC is best diagnosed from its clinical features; the histologic changes identified in the bladder biopsy play a supportive role in this diagnosis. Mast cells play a limited role in the diagnosis of IC.

  View details for Web of Science ID A1990EA36800011

  View details for PubMedID 2403198

• Pediatric genitourinary tumors. Current opinion in oncology SMYTH, T. B., SHORTLIFFE, L. M. 1990; 2 (3): 507-513

  View details for PubMedID 1965488

• BUYING TIME FOR THE GOOD THINGS IN LIFE WESTERN JOURNAL OF MEDICINE Shortliffe, L. M. 1988; 149 (6): 773-774

  View details for Web of Science ID A1988R670700032

  View details for PubMedID 18750512

• SUPERFICIAL BLADDER-CANCER - THE PRIMACY OF GRADE IN THE DEVELOPMENT OF INVASIVE DISEASE JOURNAL OF CLINICAL ONCOLOGY Torti, F. M., Lum, B. L., Aston, D., Mackenzie, N., FAYSEL, M., Shortliffe, L. D., Freiha, F. 1987; 5 (1): 125-130

  Abstract

  Tumor characteristics thought to predict for development of deep muscle invasion after resection of superficial bladder cancer were retrospectively analyzed in 252 patients with transitional cell carcinoma of the bladder at Stanford University Medical Center. Stage 0 patients accounted for 190 of the patient population (75.5%), while stage A and B1 comprised 51 (20%) and 11 (4.5%), respectively. The median follow-up time was 62 months. Forty-three patients subsequently developed deep muscle invasion; these included 24 (12.6%), 14 (27.5%), and 5 (45.5%) of stage 0, A, and B1 patients (P = .002), or 15 (10%), 15 (9%), and 13 (33%) of grade 1, 2, and 3 tumors (P = .001), respectively. When analyzed by univariate logistic regression, grade (P = .0001) and stage (P = .0118) were significant predictors for invasive disease. Site of tumor and number of tumors at presentation were not significant factors for invasion deep into the bladder wall. When multiple logistic regression was performed, only grade remained as a significant tumor variable to predict for invasive disease (P less than .0091). Risk of invasive disease did not appear to increase with increasing number of recurrences, remaining at approximately an 11% invasion rate through 12 recurrences. In this analysis, grade was the most significant tumor variable in superficial bladder cancer predicting for the development of invasive carcinoma. Future clinical trials for definitive or adjuvant therapy of this disease must stratify for this variable.

  View details for Web of Science ID A1987F677800020

  View details for PubMedID 3806155

• INFECTION STONES - EVALUATION AND MANAGEMENT UROLOGIC CLINICS OF NORTH AMERICA Shortliffe, L. M., SPIGELMAN, S. S. 1986; 13 (4): 717-726

  Abstract

  Infection stones may be the cause of persistent or recurrent bacterial urinary infection. Evaluation of the infection and the character of the stones often aids in the selection of management and treatment options. The ultimate success of the treatment of infection stones should be measured, however, by control or removal of both the stone and the urinary infection.

  View details for Web of Science ID A1986E835700014

  View details for PubMedID 3535212

• ASYMPTOMATIC BACTERIURIA - SHOULD IT BE TREATED UROLOGY Shortliffe, L. M. 1986; 27 (2): 19-25

  View details for Web of Science ID A1986A014700004

  View details for PubMedID 3946048

• PROSTATITIS PRIMARY CARE Shortliffe, L. M. 1985; 12 (4): 787-794

  Abstract

  Classification of patients with prostatic complaints into one of the categories of bacterial or nonbacterial prostatitis or prostatodynia (see Table 3) enables a physician to give rational advice to men with confusing symptoms. By examining the prostatic fluid of patients with prostatic symptoms, a physician may easily identify those men with prostatodynia who will never respond to antimicrobial or anti-inflammatory agents. Carefully obtained fractionated cultures of the urine will usually distinguish patients with bacterial and nonbacterial prostatitis, so that only those men who have bacterial prostatitis are treated with long courses of antimicrobial agents. Although recent measurements documenting elevated IgA and IgG in the EPS of men with nonbacterial prostatitis support theories of an antigenic cause for the prostatic inflammation and symptoms, the causes for this inflammation must still be identified. In addition, the etiology of prostatodynia is also unclear. As a result, the optimal treatment for most patients with nonbacterial prostatitis and prostatodynia remains unknown.

  View details for Web of Science ID A1985AWK0400013

  View details for PubMedID 3853240

• A RANDOMIZED STUDY OF DOXORUBICIN VERSUS DOXORUBICIN PLUS CISPLATIN IN ENDOCRINE-UNRESPONSIVE METASTATIC PROSTATIC-CARCINOMA CANCER Torti, F. M., Shortliffe, L. D., Carter, S. K., Hannigan, J. F., Aston, D., Lum, B. L., Williams, R. D., SPAULDING, J. T., Freiha, F. S. 1985; 56 (11): 2580-2586

  Abstract

  Thirty-seven patients with hormonally refractory prostatic carcinoma entered a randomized trial comparing doxorubicin and doxorubicin plus cisplatin. All patients had failed prior hormonal treatment. Mean Karnofsky performance status (76% doxorubicin versus 75% combination), percent of patients with prior palliative irradiation (40% doxorubicin versus 35% combination), and hemoglobin levels of less than or equal to 12 g/dl (30% doxorubicin versus 24% combination) were roughly equivalent in the two treatment groups. More patients treated with doxorubicin than the combination treatment had an elevated acid phosphatase level at study entry (90% versus 65%). Measurable bidimensional tumors were present in 13 patients in 16 sites in the doxorubicin arm and in 10 patients in 11 sites in the combination arm. Partial responses were seen in 1 of 13 patients in the doxorubicin arm and 2 (20%) of 10 patients in the combination arm. Improvement in Karnofsky performance status of 20% or greater was rarely observed with either treatment (7% doxorubicin versus 8% combination). Acid phosphatase levels normalized or improved by 50% in 39% of patients who received doxorubicin and 27% of patients who received the combination. The overall response rate by National Prostatic Cancer Project Criteria was 53% for doxorubicin and 59% for doxorubicin plus cisplatin. Myelotoxicity and gastrointestinal toxicity were severe, particularly in the combination arm, and required discontinuation of treatment in some patients who responded to treatment. Moderate renal dysfunction (creatinine value 2.0-3.0 mg/dl) occurred only in the combination arm at an incidence of 23%. Time to progression and survival were similar for the two treatment groups. In this small group of 37 patients, the combination of cisplatin and doxorubicin showed no improvement over doxorubicin alone in response, response duration, or survival, and was difficult to administer in this patient population.

  View details for Web of Science ID A1985ATY0900007

  View details for PubMedID 4052935

• THE ROLE OF AN INDIUM LEUKOCYTE SCAN IN THE DIAGNOSIS OF A PYELODUODENAL FISTULA ASSOCIATED WITH SPONTANEOUS DISAPPEARANCE OF A STAGHORN CALCULUS JOURNAL OF UROLOGY Shortliffe, L. M. 1985; 133 (6): 1020-1021

  Abstract

  The use of a 111indium oxine-leukocyte scan (white cell scan) to establish the diagnosis of a pyeloduodenal fistula is described. The patient had a fistula that was associated with spontaneous disappearance of a large staghorn calculus in the involved kidney. The disappearance of the calculus and the presence of a pyeloduodenal fistula were confirmed at surgical exploration. Although neither an excretory urogram nor a retrograde pyelogram was useful to diagnose the fistula preoperatively a 111indium oxine-leukocyte scan revealed the renal abscess and pyeloduodenal fistula.

  View details for Web of Science ID A1985AJN3700023

  View details for PubMedID 3923210

• CISPLATIN, METHOTREXATE, AND VINBLASTINE (CMV) - AN EFFECTIVE CHEMOTHERAPY REGIMEN FOR METASTATIC TRANSITIONAL CELL-CARCINOMA OF THE URINARY-TRACT - A NORTHERN-CALIFORNIA-ONCOLOGY-GROUP STUDY JOURNAL OF CLINICAL ONCOLOGY Harker, W. G., Meyers, F. J., Freiha, F. S., Palmer, J. M., Shortliffe, L. D., Hannigan, J. F., MCWHIRTER, K. M., Torti, F. M. 1985; 3 (11): 1463-1470

  Abstract

  Fifty-eight patients with metastatic transitional cell carcinoma of the urinary tract received cisplatin, methotrexate, and vinblastine (CMV) combination chemotherapy. Complete responses (CRs) were noted in 14 of the 50 (28%) evaluable patients and partial responses (PRs) in 14 patients for an overall response rate of 56% (95% confidence limits of 42% to 70%). The median duration of the 14 CRs was 9 months. Six of the 14 CRs (43%) remain in unmaintained remission from 6 + to 35 + months from onset of treatment. The median survival of evaluable patients receiving CMV was 8 months. Median survival for CRs was 11 months v 7 months for PRs (P less than .05) and 6 months for nonresponders. Renal and hematologic toxicities with this regimen were moderate. CMV is an effective regimen for patients with metastatic transitional cell carcinoma of the bladder. Prolonged disease-free survival may result from a CR to this regimen.

  View details for Web of Science ID A1985ATE4000005

  View details for PubMedID 4056840

• THE FATE OF THE BLADDER IN PATIENTS WITH METASTATIC BLADDER-CANCER TREATED WITH CISPLATIN, METHOTREXATE AND VINBLASTINE - A NORTHERN-CALIFORNIA-ONCOLOGY-GROUP STUDY JOURNAL OF UROLOGY Meyers, F. J., Palmer, J. M., Freiha, F. S., HARKER, E. G., Shortliffe, L. D., Hannigan, J., MCWHIRTER, K., Torti, F. M. 1985; 134 (6): 1118-1121

  Abstract

  We report the efficacy and toxicity of combined cisplatin, methotrexate and vinblastine for the treatment of metastatic transitional cell carcinoma of the bladder in 50 evaluable patients. Of these 50 patients 17 had not undergone cystectomy and had residual invasive bladder cancer. Of these 17 patients 11 had complete response of the bladder lesions following cisplatin, methotrexate and vinblastine for metastatic disease, including 6 of 12 treated by cisplatin, methotrexate and vinblastine alone, and 5 of 5 treated with cisplatin, methotrexate and vinblastine plus palliative or preoperative pelvic irradiation. Complete response was confirmed in 10 of the 11 patients by endoscopy and biopsy, and in 1 by cystectomy. One patient whose liver metastasis responded to cisplatin, methotrexate and vinblastine had conversion to complete response by cystectomy for persistent bladder cancer. Of these 17 patients 7 are alive, including 5 without disease, 4 to 41 months after treatment. The bladder appears to be responsive to this combination chemotherapy for invasive transitional cell carcinoma. This experience underscores the need for regular pathological re-staging of the bladder cancer in patients receiving chemotherapy.

  View details for Web of Science ID A1985AVJ8800013

  View details for PubMedID 3903223

• PERSISTENT URINARY INFECTIONS IN A YOUNG WOMAN WITH BILATERAL RENAL STONES JOURNAL OF UROLOGY Shortliffe, L. M., McNeal, J. E., Wehner, N., Stamey, T. A. 1984; 131 (6): 1147-1151

  View details for Web of Science ID A1984SU31400033

  View details for PubMedID 6726918

• THE EXTENT OF SURGERY AFTER CHEMOTHERAPY FOR ADVANCED GERM-CELL TUMORS JOURNAL OF UROLOGY Freiha, F. S., Shortliffe, L. D., Rouse, R. V., Mark, J. B., Hannigan, J. F., Aston, D., SPAULDING, J. T., Williams, R. D., Torti, F. M. 1984; 132 (5): 915-917

  Abstract

  The histopathological findings of tissue removed from 40 patients with a residual mass after completion of induction chemotherapy with cis-platinum, vinblastine and bleomycin are reviewed. These patients with advanced testicular cancer were treated with chemotherapy until normalization of tumor markers and until there was no further decrease in the size of palpable or radiologically evident masses for 2 successive cycles of chemotherapy. The mean number of chemotherapy cycles preoperatively was 5.2. Residual carcinoma was found in only 1 patient (3 per cent), teratoma in 18 (45 per cent), and fibrotic and/or necrotic masses in 21 (52 per cent). With this tailored treatment regimen in which an operation is performed after maximal chemotherapeutic response, the number of patients with viable residual tumor at operation can be minimized. Complete retroperitoneal lymph node dissection concomitant with resection of the residual mass was performed in 22 of 32 patients with residual masses in the retroperitoneum. The 1 patient with carcinoma in the mass also had carcinoma in several of the lymph nodes, and 4 of the 11 with teratoma in the mass had teratoma in the lymph nodes. Since the histopathological findings of the mass often parallel those of the lymph nodes, and since masses containing only fibrosis and/or necrosis cannot be ascertained with accuracy at operation, a complete retroperitoneal lymph node dissection is recommended in patients with a residual retroperitoneal mass.

  View details for Web of Science ID A1984TQ18300015

  View details for PubMedID 6208386

• PROSTATITIS - STILL A DIAGNOSTIC AND THERAPEUTIC DILEMMA WESTERN JOURNAL OF MEDICINE Shortliffe, L. M. 1983; 139 (4): 542-544

  View details for Web of Science ID A1983RP63200035

  View details for PubMedID 6649609

• WEEKLY DOXORUBICIN IN ENDOCRINE REFRACTORY CARCINOMA OF THE PROSTATE JOURNAL OF CLINICAL ONCOLOGY Torti, F. M., Aston, D., Lum, B. L., Kohler, M., WILLIAMS, R., SPAULDING, J. T., Shortliffe, L., Freiha, F. S. 1983; 1 (8): 477-482

  Abstract

  Twenty-five patients with endocrine-refractory prostatic carcinoma were treated with doxorubicin, 20 mg/m2 given weekly. All patients had prior hormonal therapy (68% had two or more prior hormonal maneuvers), and 21 (84%) had prior therapeutic or palliative irradiation. Median Karnofsky performance status at the time of entry was 70. Hemoglobin was less than 12.0 g/dL in 15 patients. Bidimensional tumors were present in 12 patients in 19 disease sites; four of the 12 patients (33%) responded in eight of the 19 sites (42%); and three of eight patients had a 75% decrease in prostatic nodule size. Ten of 20 evaluable patients had an improvement of 20% or greater in Karnofsky performance status and 67% (14 of 21) had marked improvement in pain. A greater than 50% reduction or normalization of acid phosphatase occurred in 19% and of alkaline phosphatase in 53%. The overall response rate by National Prostatic Cancer Project criteria was 84%. Gastrointestinal toxicity and alopecia were minimal and myelosuppression was not life threatening in any patient.

  View details for Web of Science ID A1983RJ76300004

  View details for PubMedID 6668511

• NEWER APPROACHES TO THE CORRECTION OF URINARY STRESS-INCONTINENCE IN FEMALE PATIENTS SURGICAL CLINICS OF NORTH AMERICA Shortliffe, L. M., Stamey, T. A. 1982; 62 (6): 1035-1045

  View details for Web of Science ID A1982PW76000010

  View details for PubMedID 6217566

• RESOLUTION OF BONY METASTASES AFTER BILATERAL ORCHIECTOMY FOR CARCINOMA OF PROSTATE UROLOGY Shortliffe, L. D., Freiha, F. S. 1981; 17 (4): 353-355

  Abstract

  Resolution of multiple bony metastases after bilateral orchiectomy for carcinoma of prostate was documented by roentgenogram and scintigraphy. This marked improvement was correlated with a decline in serum acid phosphatase, disappearance of soft tissue tumor, and clinical improvement in the patient.

  View details for Web of Science ID A1981LL84700013

  View details for PubMedID 7222327

• Prospects for research on schizophrenia. IV. Genetic and environmental factors. Schizophrenia X normal matings: predictions of the polygenic model. Neurosciences Research Program bulletin Matthysse, S., Shortliffe, L. 1972; 10 (4): 419-421

  View details for PubMedID 4663821