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In March 2010, the Environmental Protection Agency (EPA) collaborated with government and nongovernmental organizations to host a groundbreaking symposium, "Strengthening Environmental Justice Research and Decision Making: A Symposium on the Science of Disproportionate Environmental Health Impacts." The symposium provided a forum for discourse on the state of scientific knowledge about factors identified by EPA that may contribute to higher burdens of environmental exposure or risk in racial/ethnic minorities and low-income populations. Also featured were discussions on how environmental justice considerations may be integrated into EPA's analytical and decision-making frameworks and on research needs for advancing the integration of environmental justice into environmental policymaking. We summarize key discussions and conclusions from the symposium and briefly introduce the articles in this issue.

Objectives: Traditional hazards such as poor sanitation currently account for most of Africa's environmentally related disease burden. However, with rapid development absent appropriate safeguards for environment and health, modern environmental health hazards (MEHHs) may emerge as critical contributors to the continent's disease burden. We review recent evidence of human exposure to and health effects from MEHHs, and their occurrence in environmental media and consumer products. Our purpose is to highlight the growing significance of these hazards as African countries experience urbanization, industrial growth, and development., Data Sources: We reviewed published epidemiologic, exposure, and environmental studies of chemical agents such as heavy metals and pesticides., Data Synthesis: The body of evidence demonstrates ongoing environmental releases of MEHHs and human exposures sometimes at toxicologically relevant levels. Several sources of MEHHs in environmental media have been identified, including natural resource mining and processing and automobile exhaust. Biomonitoring studies provided direct evidence of human exposure to metals such as mercury and lead and pesticides such as p,p'-dichlorodiphenyltrichloroethane (DDT) and organophosphates. Land and water resource pollution and industrial air toxics are areas of significant data gaps, notwithstanding the presence of several emitting sources., Conclusion: Unmitigated MEHH releases and human exposure have implications for Africa's disease burden. For Africans encumbered by conditions such as malnutrition that impair resilience to toxicologic challenges, the burden may be higher. A shift in public health policy toward accommodating the emerging diversity in Africa's environmental health issues is necessary to successfully alleviate the burden of avoidable ill health and premature death for all its communities now and in the future.

Purpose: The study aims to evaluate the efficacy and toxicity of fenretinide in preventing tumor recurrence in patients with transitional cell carcinoma (TCC) of the bladder., Experimental Design: We conducted a multicenter phase III, randomized, placebo-controlled trial of fenretinide (200 mg/day orally for 12 months) in patients with non-muscle-invasive bladder TCC (stages Ta, Tis, or T1) after transurethral resection with or without adjuvant intravesical Bacillus Calmette-Guerin (BCG). Patients received cystoscopic evaluation and bladder cytology every 3 months during the 1-year on study drug and a final evaluation at 15 months. The primary endpoint was time to recurrence., Results: A total of 149 patients were enrolled; 137 were evaluable for recurrence. The risk of recurrence was considered to be "low" in 72% (no prior BCG) and intermediate or high in 32% (prior BCG) of the evaluable patients. Of the lower-risk group, 68% had solitary tumors and 32% had multifocal, low-grade papillary (Ta, grade 1 or grade 2) tumors. The 1-year recurrence rates by Kaplan-Meier estimate were 32.3% (placebo) versus 31.5% (fenretinide; P = 0.88 log-rank test). Fenretinide was well tolerated and had no unexpected toxic effects; only elevated serum triglyceride levels were significantly more frequent on fenretinide (versus placebo). The Data Safety and Monitoring Board recommended study closure at 149 patients (before reaching the accrual goal of 160 patients) because an interim review of the data showed a low likelihood of detecting a difference between the two arms, even if the original accrual goal was met., Conclusions: Although well tolerated, fenretinide did not reduce the time-to-recurrence in patients with Ta, T1, or Tis TCC of the bladder.

Unlabelled: Möbius has found numerous applications in computational biology to build and solve stochastic models of biological processes. It provides the user with a modeling workflow and several sophisticated features that are not available in the simulation tools commonly used by computational biologists., Availability: Möbius is free for academic users. It can be downloaded from www.mobius.uiuc.edu

Motivation: The stochastic kinetics of a well-mixed chemical system, governed by the chemical Master equation, can be simulated using the exact methods of Gillespie. However, these methods do not scale well as systems become more complex and larger models are built to include reactions with widely varying rates, since the computational burden of simulation increases with the number of reaction events. Continuous models may provide an approximate solution and are computationally less costly, but they fail to capture the stochastic behavior of small populations of macromolecules., Results: In this article we present a hybrid simulation algorithm that dynamically partitions the system into subsets of continuous and discrete reactions, approximates the continuous reactions deterministically as a system of ordinary differential equations (ODE) and uses a Monte Carlo method for generating discrete reaction events according to a time-dependent propensity. Our approach to partitioning is improved such that we dynamically partition the system of reactions, based on a threshold relative to the distribution of propensities in the discrete subset. We have implemented the hybrid algorithm in an extensible framework, utilizing two rigorous ODE solvers to approximate the continuous reactions, and use an example model to illustrate the accuracy and potential speedup of the algorithm when compared with exact stochastic simulation., Availability: Software and benchmark models used for this publication can be made available upon request from the authors.

A 58-year-old woman suffered pain due to a stage-IV adenocarcinoma of the right upper-lung lobe with signs of growth into the right axilla. Palliative local radiotherapy directed at the primary tumour followed by combination chemotherapy with carboplatin-gemcitabin led to partial remission. During the fourth and last cycle of her three-months course of chemotherapy, the patient again complained of pain in the right half of the thorax; later, a local swelling of the pectoralis muscles was found. She was diagnosed with myositis as a delayed reaction to irradiation (radiation-recall phenomenon) based on the clinical symptoms (redness of the skin, pain and distinct swelling) but especially on the basis of a CT-scan. This revealed a clear swelling of the pectoralis muscles, even though the tumour was in remission. The possibility of myositis as a radiation-recall phenomenon should be borne in mind whenever a patient presents with skin changes or pain within a previous irradiation field during chemotherapy with, for example, gemcitabin.

Objectives: To prospectively evaluate a clinical algorithm that predicts nodal status in patients with prostate cancer and to assess the impact on the outcome., Methods: Between September 1988 and December 1994, 192 patients with organ-confined prostate cancer and considered surgical candidates for radical perineal prostatectomy (RPP) were stratified using the algorithm: prostate-specific antigen (PSA) 20 ng/mL or less, Gleason score 7 or lower, and clinical Stage T2a or lower. Patients failing any of these criteria were placed in the high-risk group and underwent a pelvic lymphadenectomy. Patients who satisfied all the criteria were placed in the low-risk group and underwent RPP without evaluation of the pelvic lymph nodes. Another contemporaneous cohort of patients (n = 65) underwent pelvic lymphadenectomy and radical retropubic prostatectomy (RRP) without use of the algorithm and were used as a control group. Patients were monitored for at least 24 months., Results: In the RPP group, 177 patients were considered low risk according to the algorithm and were not offered staging lymphadenectomy before surgery, whereas 15 patients were categorized as high risk for metastasis and underwent staging lymphadenectomy. In the RRP and lymphadenectomy group, 41 patients were considered at low risk and 24 at high risk of disease spread according to the algorithm. In the RPP group, low-risk patients (no lymphadenectomy) had a PSA recurrence rate (27%) similar to that of low-risk patients in the RRP group with negative lymph nodes (29%), P = 0.8. Similarly, high-risk patients with negative lymph nodes in both groups had a similar recurrence rate (53% for RPP and 50% for RRP). Univariate logistic regression analysis showed that PSA was the most significant predictor for disease recurrence (P = 0.0004) followed by preoperative Gleason scores (P = 0.02) and clinical stages (P = 0.03). Multivariate stepwise analysis demonstrated that Gleason score and clinical stage did not add to the prediction of recurrence over PSA alone., Conclusions: Staging lymphadenectomy can be omitted in low-risk patients without deleterious effects on the outcome as measured by PSA recurrence.

Objectives: To determine the correlation between alkaline phosphatase levels and bone metastases in renal cell carcinoma., Methods: The records of two cohorts, including 539 and 184 patients, with metastatic renal cell carcinoma were reviewed. In both groups, metastases were shown on magnetic resonance imaging (MRI), computed tomography (CT), or bone scan. In addition, the second cohort included data concerning pain on presentation. None of the patients in either cohort had any systemic therapy (chemotherapy or immunotherapy); many patients had undergone radical nephrectomy as the primary treatment of the cancer. All radiographic and laboratory information was obtained within a 6-week enrollment period. Normal alkaline phosphatase levels were referenced according to age and sex, resulting in an upper limit of normal of 111 to 141 U/L., Results: In the first cohort bone metastases were documented by MRI, CT, and/or bone scans in 164 patients. Alkaline phosphatase levels were less than or equal to 141 U/L in 118 patients (72%) and less than or equal to 111 U/L in 87 patients (53%). There were 123 patients with bone metastases who had previously undergone a nephrectomy for presumed local disease. Alkaline phosphatase levels were less than or equal to 141 U/L in 91 patients (74%) and less than or equal to 111 U/L in 70 patients (57%). In the second cohort 22 of 37 patients (59%) had little to no pain on presentation, and 19 (86%) of that group had normal alkaline phosphatase levels., Conclusions: Alkaline phosphatase is an insensitive indicator of bone metastases.

Objectives: To determine the incidence of granulomatous prostatitis and acid-fast bacilli (AFB) after intravesical bacillus Calmette-Guerin (BCG) therapy for superficial bladder transitional cell carcinoma (TCC) or carcinoma in situ (CIS)., Methods: One hundred nineteen men underwent radical cystoprostatectomy for invasive bladder cancer from January 1, 1980 through December 31, 1995. Twelve patients had received intravesical BCG therapy before undergoing cystoprostatectomy. Nine men who did not receive intravesical BCG therapy before undergoing cystoprostatectomy served as controls. The surgical specimens were examined with a Ziehl-Neelsen stain for the presence of granulomatous prostatitis and for the presence of AFB., Results: Granulomatous prostatitis was identified in 9 of 12 patients (75%) who had received intravesical BCG therapy. AFB were identified in 7 of 9 patients (77%) with granulomatous prostatitis., Conclusions: Pathologic evidence of granulomatous prostatitis with AFB is a common occurrence after intravesical BCG therapy and its incidence is far greater than the reported incidence of symptomatic granulomatous prostatitis. AFB discovered during the evaluation of either an increased level of prostate-specific antigen or prostate nodule in otherwise asymptomatic men may require no specific therapy.

Background: Luteinizing hormone-releasing hormone agonists (LHRH-a) have become an established treatment for certain patients with prostate carcinoma. LHRH-a are known to decrease bone mineral density. The purpose of this study was to determine the risk of bone fracture in men receiving LHRH-a for prostate carcinoma., Methods: A retrospective chart review and phone interviews were conducted to determine the incidence of bone fractures occurring in patients receiving LHRH-a for the treatment of prostate carcinoma. Abstracted data included the number of monthly LHRH-a injections, age, clinical stage of disease, sites of metastases, and bone fracture history., Results: Twenty of the 224 patients (9%) treated with LHRH-a for prostate carcinoma between 1988 and 1995 at 3 teaching hospitals had at least 1 bone fracture during treatment with LHRH-a. The duration of treatment to the time of fracture ranged from 1 to 96 months (mean, 22.2 months). Seven fractures (32%) were osteoporotic in nature (i.e., vertebral compression fractures or hip fractures after a fall from standing), whereas 8 fractures (36%) were associated with a significant traumatic event (i.e., a motor vehicle accident, boxing, etc.) and 5 were of mixed etiology. Two of 22 fractures (9%) were pathologic., Conclusions: This study demonstrated a 9% fracture incidence in a cohort of patients receiving LHRH-a for prostate carcinoma for up to 96 months. The incidence of osteoporotic fractures was 5%.

Objectives: Prostate-specific antigen (PSA) has become the most useful serum tumor marker in the diagnosis and screening of prostate adenocarcinoma. The currently cited reference range of normal (0 to 4.0 ng/mL monoclonal) lacks both the sensitivity and specificity to be universally accepted as a screening test, and alternatives to serum PSA have been proposed, such as PSA density, PSA velocity, and age-adjusted PSA. Age-adjusted PSA takes into account the facts that as men grow older the prostate enlarges and that screening should have maximum sensitivity in younger men and maximum specificity in older men., Methods: A population of 4,710 men with no known history of prostate adenocarcinoma underwent 5,629 examinations by transrectal ultrasound of the prostate (TRUS) from 1987 to 1994. This population consists of Mobile Urology Group, Mobile, Alabama, and Emory University, Atlanta, Georgia, patient databases. We have examined our data to determine the sensitivity, specificity, and positive predictive values for normal range PSA (0 to 4 ng/mL) versus age-specific PSA values., Results: A total of 2040 patients had an abnormal digital rectal examination (DRE) and 3581 procedures were performed for an elevated PSA and a normal DRE. Biopsies were performed in 2,657 patients with 945 (35.6%) positive for cancer. Criteria for biopsy included elevated PSA (more than 4 mg/mL), PSA density more than 0.15 abnormal DRE, or suspicious TRUS. Patients were grouped according to decade: group 1 (ages 40 to 49 years, n = 183), group 2 (ages 50 to 59 years, n = 1018), group 3 (ages 60 to 69 years, n = 2358), and group 4 (ages 70 to 79 years, n = 1687)., Conclusions: Use of the age-specific range for PSA increases the sensitivity in younger men more likely to benefit from treatment, and decreases the biopsy rate in older patients who may not be candidates for aggressive treatment. Age-adjusted PSA is the most valuable for patients over the age of 70 years of whom 22% would be spared TRUS with biopsy.

Modeling can be used to predict the performance of picture archiving and communication system (PACS) configurations under various load conditions at an early design stage. This is important because choices made early in the design of a system can have a significant impact on the performance of the resulting implementation. Because PACS consist of many types of components, it is important to do such evaluations in a modular manner, so that alternative configurations and designs can be easily investigated. Stochastic activity networks (SANs) and reduced base model construction methods can aid in doing this. SANs are a model type particularly suited to the evaluation of systems in which several activities may be in progress concurrently, and each activity may affect the others through the results of its completion. Together with SANs, reduced base model construction methods provide a means to build highly modular models, in which models of particular components can be easily reused. In this article, we investigate the use of SANs and reduced base model construction techniques in evaluating PACS. Construction and solution of the models is done using UltraSAN, a graphic-oriented software tool for model specification, analysis, and simulation. The method is illustrated via the evaluation of a realistically sized PACS for a typical United States hospital of 300 to 400 beds, and the derivation of system response times and component utilizations.

A fiber-optic star-based picture archiving and communication system (PACS) network that is based on a multiplexed passive star local area network with wavelength-division multiplexing (WDM) to provide separate logical channels for transfer of control and image data is discussed. The system consists of an image network (INET), for image transfer at a rate of 140 Mb/s, and a control network (CNET), operating at 10 Mb/s, for mediating the flow of image transfers. INET is a circuit switched network devoted solely to image transfer, while CNET employs the CSMA/CD protocol for bus arbitration. Stochastic activity networks were used to develop a detailed model of the command and image channels. The performance of the system was then evaluated under realistic workload conditions. In particular, a number of important performance variables, including the image response time, command channel delay, and queue length at each type of node and the network supervisor, are estimated. The results (1) show that stochastic activity networks are an appropriate model type for evaluating picture archiving and communication systems, (2) delineate the workload conditions under which PACS may effectively operate, and (3) show that even when these conditions are exceeded, the command channel load remains extremely light.

The use of a Rotex screw biopsy needle is advocated for percutaneous ultrasound-guided management of pericardial fluid. This procedure is performed under sonographic guidance while the needle tip is clearly visualized during introduction, thereby improving optimal placement and limiting the possibility of complications.

An IgG lambda and two IgE kappa proteins were isolated from the serum of a patient (DB) with anaemia associated with myelofibrosis. Idiotype-specific antisera produced against the three proteins were studied by precipitation in double immunodiffusion and by enzyme-linked immunosorbent assay (ELISA) and indicated that the two IgE kappa components shared idiotypic determinants while the IgG lambda protein did not show any cross-idiotypic reaction. The idiotypic determinants of the three proteins were not present in pooled normal serum, normal IgG, normal IgE or IgE from a patient with multiple myeloma.

A human pancreatic tumor cell line has been established from the ascites of a patient with histopathologically confirmed adenocarcinoma of the head of the pancreas and maintained for more than 12 months in the laboratory. Epithelioid tumor cell colonies, which resulted from primary tissue cultures of the ascitic cell component, were mechanically isolated by needle micromanipulation. Tumorigenicity was proven in athymic nude mice. Morphologically the pancreatic tumor epithelial cells grew to confluency with moderately tight adhesion to the culture plastic surface and with free-floating cells in the medium. Upon re-establishment of the tumoral xenograft in tissue culture, the epithelial cells retained their original morphology. Histologically the tumor grown in nude mice exhibited prototypic characteristics of the primary adenocarcinoma in the patient, producing abundant mucin and displaying a broad spectrum of glandular differentiation, which ranged from well to poorly differentiated adenocarcinomas with occasionally localized lymphocytic infiltrations. Furthermore, the tumor expressed carcinoembryonic antigen and human pancreas cancer associated antigen. This tumor line, designated AsPC-1, has been cultured for at least 10 passages in vitro and 3 in vivo. It represents a new model for human pancreatic cancer.