Jose E. Pulido

A role for excitatory amino acids in diabetic eye disease

Diabetic retinopathy is a leading cause of vision loss. The primary clinical hallmarks are vascular changes that appear to contribute to the loss of sight. In a number of neurodegenerative disorders there is an appreciation that increased levels of excitatory amino acids are excitotoxic. The primary amino acid responsible appears to be the neurotransmitter glutamate. This review examines the nature of glutamatergic signaling at the retina and the growing evidence from clinical and animal model studies that glutamate may be playing similar excitotoxic roles at the diabetic retina.

Tamsulosin and Spontaneous Passage of Ureteral Stones in Children: A Multi-Institutional Cohort Study

PURPOSE Tamsulosin is associated with increased passage of ureteral stones in adults but its effectiveness in children is uncertain. We determined the association between tamsulosin and the spontaneous passage of ureteral stones in children. MATERIALS AND METHODS We performed a multi-institutional retrospective cohort study of patients 18 years or younger who presented between 2007 and 2012 with ureteral stones up to 10 mm and who were treated with tamsulosin or oral analgesics alone. The outcome was spontaneous stone passage, defined as radiographic clearance and/or patient report of passage. Subjects prescribed tamsulosin were matched with subjects prescribed analgesics alone, using nearest neighbor propensity score matching to adjust for treatment selection. Conditional logistic regression models were used to estimate the association between tamsulosin and spontaneous passage of ureteral stones, adjusting for stone size and location. RESULTS Of 449 children with ureteral stones 334 were eligible for inclusion, and complete data were available for 274 patients from 4 institutions (99 receiving tamsulosin, 175 receiving analgesics alone). Following case matching, there were no differences in age, gender, weight, height, stone size or stone location between the 99 subjects prescribed tamsulosin and the 99 propensity score matched subjects prescribed analgesics alone. In the tamsulosin cohort 55% of ureteral stones passed, compared to 44% in the analgesics alone cohort (p=0.03). In multivariate analysis adjusting for stone size and location tamsulosin was associated with spontaneous passage of ureteral stones (OR 3.31, 95% CI 1.49-7.34). CONCLUSIONS The odds of spontaneous passage of ureteral stones were greater in children prescribed tamsulosin vs analgesics alone.

Use of and regional variation in initial CT imaging for kidney stones.

OBJECTIVE: We sought to determine the prevalence of initial computed tomography (CT) utilization and to identify regions in the United States where CT is highly used as the first imaging study for children with nephrolithiasis. METHODS: We performed a cross-sectional study in 9228 commercially insured children aged 1 to 17 years with nephrolithiasis who underwent diagnostic imaging in the United States between 2003 and 2011. Data were obtained from MarketScan, a commercial insurance claims database of 17 827 229 children in all 50 states. We determined the prevalence of initial CT use, defined as CT alone or CT performed before ultrasound in the emergency department, inpatient unit, or outpatient clinic, and identified regions of high CT utilization by using logistic regression. RESULTS: Sixty-three percent of children underwent initial CT study and 24% had ultrasound performed first. By state, the proportion of children who underwent initial CT ranged from 41% to 79%. Regional variations persisted after adjusting for age, gender, year of presentation, and insurance type. Relative to children living in West South Central states, the highest odds of initial CT utilization were observed for children living in the East South Central US Census division (odds ratio: 1.27; 95% confidence interval: 1.06–1.54). The lowest odds of initial CT were observed for children in the New England states (odds ratio: 0.48; 95% confidence interval: 0.38–0.62). CONCLUSIONS: Use of CT as the initial imaging study for children with nephrolithiasis is highly prevalent and shows extensive regional variability in the United States. Current imaging practices deviate substantially from recently published guidelines that recommend ultrasound as the initial imaging study.

Daily mean temperature and clinical kidney stone presentation in five U.S. metropolitan areas: a time-series analysis.

Background: High ambient temperatures are a risk factor for nephrolithiasis, but the precise relationship between temperature and kidney stone presentation is unknown. Objectives: Our objective was to estimate associations between mean daily temperature and kidney stone presentation according to lag time and temperatures. Methods: Using a time-series design and distributed lag nonlinear models, we estimated the relative risk (RR) of kidney stone presentation associated with mean daily temperatures, including cumulative RR for a 20-day period, and RR for individual daily lags through 20 days. Our analysis used data from the MarketScan Commercial Claims database for 60,433 patients who sought medical evaluation or treatment of kidney stones from 2005–2011 in the U.S. cities of Atlanta, Georgia; Chicago, Illinois; Dallas, Texas; Los Angeles, California; and Philadelphia, Pennsylvania. Results: Associations between mean daily temperature and kidney stone presentation were not monotonic, and there was variation in the exposure–response curve shapes and the strength of associations at different temperatures. However, in most cases RRs increased for temperatures above the reference value of 10°C. The cumulative RR for a daily mean temperature of 30°C versus 10°C was 1.38 in Atlanta (95% CI: 1.07, 1.79), 1.37 in Chicago (95% CI: 1.07, 1.76), 1.36 in Dallas (95% CI: 1.10, 1.69), 1.11 in Los Angeles (95% CI: 0.73, 1.68), and 1.47 in Philadelphia (95% CI: 1.00, 2.17). Kidney stone presentations also were positively associated with temperatures < 2°C in Atlanta, and < 10°C in Chicago and Philadelphia. In four cities, the strongest association between kidney stone presentation and a daily mean temperature of 30°C versus 10°C was estimated for lags of ≤ 3 days. Conclusions: In general, kidney stone presentations increased with higher daily mean temperatures, with the strongest associations estimated for lags of only a few days. These findings further support an adverse effect of high temperatures on nephrolithiasis. Citation: Tasian GE, Pulido JE, Gasparrini A, Saigal CS, Horton BP, Landis JR, Madison R, Keren R, for the Urologic Diseases in America Project. 2014. Daily mean temperature and clinical kidney stone presentation in five U.S. metropolitan areas: a time-series analysis. Environ Health Perspect 122:1081–1087; http://dx.doi.org/10.1289/ehp.1307703

More Questions Than Answers: A Call for a Moratorium on the Use of Intravitreal Infliximab Outside of a Well-designed Trial

The success of intravitreal bevacizumab ( 149 kD) was unexpected because the initial studies by Ferrara, comparing ranibizumab (48 kD) with larger monoclonal antibodies, suggested that larger antibodies would not penetrate the retina.1 Interestingly, the study did not compare the penetration of ranibizumab directly to bevacizumab. The reason was apparently because the authors noted that intravitreal bevacizumab was sometimes associated with intraocular inflammation. Therefore, the authors compared exactly the same milligram amounts of ranibizumab with trastuzumab (145.5 kD), a Herceptin receptor2 antibody. The authors found greater penetration of ranibizumab than trastuzumab in the retina and believed that this showed that large antibodies did not penetrate the retina. Unfortunately, the study was flawed in that ranibizumab has a much smaller molecular weight than trastuzumab (48 versus 145.5) so that for the same amount of milligrams, they were not comparing a similar number of molecules of the 2 compounds, but rather they were comparing the penetration of 3 times as much ranibizumab than trastuzumab. More recent studies have shown that not only does intravitreal bevacizumab penetrate the retina, but it is also efficacious in treating preretinal, retinal, and choroidal neovascularization.2–4 The efficacy of intravitreal bevacizumab is such that it is taking a large multicenter trial to actually determine if there is a difference in efficacy between bevacizumab and its smaller relative, ranibizumab.5 Another large monoclonal antibody, rituximab (143.9 kD), a monoclonal antibody that binds CD20, has also shown ability to penetrate the retina.6 In addition, preliminary studies have shown some efficacy in treating primary intraocular lymphoma as well as secondary intraocular lymphoma.7 Further studies have to be performed to confirm these early findings. There are presently hundreds of monoclonal antibodies in some phase of development for clinical use and many might have ocular use as well. In light of the ability of intravitreal monoclonal antibodies to penetrate the retina and to show clinical efficacy, there is a palpable excitement in trying to find the next agent that will make a difference in the care of patients with eye disease.

Renal parenchymal area and risk of ESRD in boys with posterior urethral valves

BACKGROUND AND OBJECTIVES Approximately 20% of boys with posterior urethral valves develop ESRD; however, few factors associated with the risk of ESRD have been identified. The objective of this study was to determine if renal parenchymal area, defined as the area of the kidney minus the area of the pelvicaliceal system on first postnatal ultrasound, is associated with the risk of ESRD in infants with posterior urethral valves. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A retrospective cohort of boys who were diagnosed with posterior urethral valves at less than 6 months of age between 1988 and 2011 and followed for at least 1 year at a free-standing childrens hospital was assembled. Cox proportional hazard regression and Kaplan-Meier analysis were used to estimate the association between renal parenchymal area and time to ESRD. Cox models were adjusted for age at presentation, minimum creatinine 1 month after bladder decompression, and vesicoureteral reflux. RESULTS Sixty patients were followed for 393 person-years. Eight patients developed ESRD. Median renal parenchymal area was 15.9 cm(2) (interquartile range=13.0-21.6 cm(2)). Each 1-cm(2) increase in renal parenchymal area was associated with a lower risk of ESRD (hazard ratio, 0.64; 95% confidence interval, 0.42 to 0.98). The rate of time to ESRD was 10 times higher in boys with renal parenchymal area<12.4 cm(2) than boys with renal parenchymal area≥12.4 cm(2) (P<0.001). Renal parenchymal area could best discriminate children at risk for ESRD when the minimum creatinine in the first 1 month after bladder decompression was between 0.8 and 1.1 mg/dl. CONCLUSION In boys with posterior urethral valves presenting during the first 6 months of life, lower renal parenchymal area is associated with an increased risk of ESRD during childhood. The predictive ability of renal parenchymal area, which is available at time of diagnosis, should be validated in a larger, prospectively-enrolled cohort.

Detection of Elevated Signaling Amino Acids in Human Diabetic Vitreous by Rapid Capillary Electrophoresis

Elevated glutamate is implicated in the pathology of PDR. The ability to rapidly assess the glutamate and amino acid content of vitreous provides a more complete picture of the chemical changes occurring at the diabetic retina and may lead to a better understanding of the pathology of PDR. Vitreous humor was collected following vitrectomies of patients with PDR and control conditions of macular hole or epiretinal membrane. A capillary electrophoresis method was developed to quantify glutamate and arginine. The analysis is relatively fast (<6 minutes) and utilizes a poly(ethylene)oxide and sodium dodecylsulfate run buffer. Both amino acid levels show significant increases in PDR patients versus controls and are comparable to other reports. The levels of vitreal glutamate vary inversely with the degree of observed hemorrhage. The results demonstrate a rapid method for assessment of a number of amino acids to characterize the chemical changes at the diabetic retina to better understand tissue changes and potentially identify new treatments.

Segmentation of renal parenchymal area from ultrasoundl images using level set evolution

This paper presents a framework for segmentation of renal parenchymal area from ultrasound images based on a 2-step level set method. We used distance regularized level set evolution method to partition the kidney boundary, followed by region-scalable fitting energy minimization method to segment the kidney collecting system, and determined renal parenchymal area by subtracting the area of the collecting system from the gross kidney area. The proposed method demonstrated excellent validity and low inter-observer variability.

Labial Ecthyma Gangrenosum in an Immunocompromised Infant With Leukemia: Heightening Awareness for the Urologist

Ecthyma gangrenosum (EG) is a cutaneous infection most commonly associated with Pseudomonas aeruginosa sepsis. EG generally occurs in immunocompromised hosts, such as patients with severe neutropenia. EG presents as erythematous, hemorrhagic, or necrotic macules or plaques, most commonly in the perineal or gluteal areas, but can occur elsewhere. EG is a dermatologic emergency in immunocompromised patients and should be included in the differential diagnosis when urologists are asked to evaluate perineal lesions. We describe the case of a highly immunocompromised infant with labial EG to highlight the importance of prompt clinical diagnosis and of multidisciplinary medical and surgical management.

Early Discharge and Post-Discharge Outcomes in Patients Undergoing Radical Cystectomy for Bladder Cancer

To assess whether discharging patients early after radical cystectomy (RC) is associated with an increased risk of readmission and post‐discharge complications.