An Overview of Testing Procedures and Approaches for Identifying Endocrine Disrupting Substances

2001 ◽  
Vol 36 (2) ◽  
pp. 273-291 ◽  
Author(s):  
Joanne Parrott ◽  
Michael Wade ◽  
Gary Timm ◽  
Scott Brown

Abstract Concern over the potential effects of exposure to endocrine disrupting substances (EDS) has resulted in recommendations for the development of specific endocrine and reproductive tests for assessment and regulation of industrial chemicals and effluents. This document consolidates and summarizes the current approaches taken by international agencies and scientific organizations for testing and screening EDS in mammals and wildlife. The material has been gathered from the Organization for Economic Cooperation and Development meeting reports, U.S. Environmental Protection Agency's Endocrine Disruptor Screening and Testing Advisory Committee and Endocrine Disruptor Screening Program reports, and summaries of various meetings prepared by Canadian and U.S. representatives. There are commonalties between programs of individual countries and the international scientific groups in which they participate. In general, these international scientific organizations have envisioned tiered groups of tests. The first tier is composed of less complex tests and short-term assays (acute exposures) that are very responsive to EDS (and have a low 'false-negative' rate). Higher tiers contain longer tests encompassing partial and full lifecycles of organisms with assessment of functional reproductive and developmental endpoints. Compounds are less expensively screened in the first tier, and move on to more complex and expensive higher-tier tests only if necessary. We document the proposed EDS tests in mammals and wildlife (birds, fish, amphibians and invertebrates) and overview the European Union's approach to EDS research, monitoring and risk assessment. We conclude with a summary of the main recommendations from Canada's interagency workshop to develop priorities and proposed actions for EDS.

Diagnostics ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 140 ◽  
Author(s):  
Lin ◽  
Lee ◽  
Lo ◽  
Tu ◽  
Chang ◽  
...  

Background: The mucopolysaccharidoses (MPSs) are a group of rare lysosomal storage disorders characterized by the accumulation of glycosaminoglycans (GAGs) and which eventually cause progressive damage to various tissues and organs. We developed a feasible MPS screening algorithm and established a cross-specialty collaboration platform between medical geneticists and other medical specialists based on at-risk criteria to allow for an earlier confirmative diagnosis of MPS. Methods: Children (<19 years of age) with clinical signs and symptoms compatible with MPS were prospectively enrolled from pediatric clinics between July 2013 and June 2018. Urine samples were collected for a non-specific total GAG analysis using the dimethylmethylene blue (DMB) spectrophotometric method, and the quantitation of three urinary GAGs (dermatan sulfate (DS), heparan sulfate (HS), and keratan sulfate (KS)) was performed by liquid chromatography/tandem mass spectrometry (LC-MS/MS). The subjects with elevated urinary GAG levels were recalled for leukocyte enzyme activity assay and genetic testing for confirmation. Results: Among 153 subjects enrolled in this study, 13 had a confirmative diagnosis of MPS (age range, 0.6 to 10.9 years—three with MPS I, four with MPS II, five with MPS IIIB, and one with MPS IVA). The major signs and symptoms with regards to different systems recorded by pediatricians at the time of the decision to test for MPS were the musculoskeletal system (55%), followed by the neurological system (45%) and coarse facial features (39%). For these 13 patients, the median age at the diagnosis of MPS was 2.9 years. The false negative rate of urinary DMB ratio using the dye-based method for these 13 patients was 31%, including one MPS I, two MPS IIIB, and one MPS IVA. However, there were no false negative results with urinary DS, HS and KS using the MS/MS-based method. Conclusions: We established an at-risk population screening program for MPS by measuring urinary GAG fractionation biomarkers using the LC-MS/MS method. The program included medical geneticists and other medical specialists to increase awareness and enable an early diagnosis by detecting MPS at the initial onset of clinical symptoms.


2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Krisztián Sepp ◽  
Zsolt Molnár ◽  
Anna M. László ◽  
Tünde Alapi ◽  
László Tóth ◽  
...  

Homeostatic disruptor agents, and endocrine disruptor compounds (EDC) specifically, can originate from agricultural and industrial chemicals. If they modify the adaptation of living organisms as direct (e.g., by altering hormone regulation, membrane functions) and/or indirect (e.g., cell transformation mechanisms) factors, they are classified as EDC. We aimed to examine the potential endocrine-disrupting effects of phenylurea herbicides (phenuron, monuron, and diuron) on the oxytocin (OT) and arginine-vasopressin (AVP) release of neurohypophysis cell cultures (NH). In our experiments, monoamine-activated receptor functions of neurohypophyseal cells were used as a model. In vitro NH were prepared by enzymatic (trypsin, collagenase) and mechanical dissociation. In the experimental protocol, the basal levels of OT and AVP were determined as controls. Later, monoamine (epinephrine, norepinephrine, serotonin, histamine, and dopamine) activation (10−6 M, 30 min) and the effects of phenylurea (10−6 M, 60 min) alone and in combination (monoamines 10−6 M, 30 min + phenylureas 10−6 M, 60 min) with monoamine were studied. OT and AVP hormone contents in the supernatant media were measured by radioimmunoassay. The monoamine-activated receptor functions of neurohypophyseal cells were modified by the applied doses of phenuron, monuron, and diuron. It is concluded that the applied phenylurea herbicides are endocrine disruptor agents, at least in vitro for neurohypophysis function.


2020 ◽  
Vol 28 (3) ◽  
pp. 203-210
Author(s):  
Sarang Younesi ◽  
Mohammad Mahdi Taheri Amin ◽  
Pourandokht Saadati ◽  
Bahareh Yazdani ◽  
Soudabeh Jamali ◽  
...  

OBJECTIVES: To evaluate the performance of the current national screening policy for Down syndrome (DS) in Iran and suggest a more efficient protocol with a wealth of a large series of first-trimester screening (FTS) data obtained from Nilou medical laboratory. To fulfill this aim, detection rate (DR), positive screening rate (PSR), false negative rate (FNR) and odds of being affected given a positive results (OAPR) were calculated at different cutoff risk. In the latest update of DS screening program in Iran, there is no place for intermediate group to be further investigated. Next, we proposed a novel parameter namely the ratio of fβ-hCG multiple of the median (MoM) value to PAPP-A MoM value to delicately categorize FTS results in a way that reduce FNR without imposing unnecessary anxious and extra money on most families. METHODS: The present investigation was conducted retrospectively on 197,210 pregnancies undergoing FTS for aneuploidies in Nilou medical laboratory, Tehran, Iran, from March 2015 to February 2016. RESULTS: Intermediate risk group is important as 23 out of 45 FN fell in the range 1:250 to 1:1100. By applying the proposed index, the ratio of fβ-hCG MoM to PAPP-A MoM and subsequent decision about NIPT, 8 out of 23 FN cases in intermediate group could be detected. CONCLUSION: Compared with the current policy, our novel proposed approach had better performance and could be applied by the Iran National Health Service to improve the screening program guideline.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Jirawut Limwattanayingyong ◽  
Variya Nganthavee ◽  
Kasem Seresirikachorn ◽  
Tassapol Singalavanija ◽  
Ngamphol Soonthornworasiri ◽  
...  

Objective. To evaluate diabetic retinopathy (DR) screening via deep learning (DL) and trained human graders (HG) in a longitudinal cohort, as case spectrum shifts based on treatment referral and new-onset DR. Methods. We randomly selected patients with diabetes screened twice, two years apart within a nationwide screening program. The reference standard was established via adjudication by retina specialists. Each patient’s color fundus photographs were graded, and a patient was considered as having sight-threatening DR (STDR) if the worse eye had severe nonproliferative DR, proliferative DR, or diabetic macular edema. We compared DR screening via two modalities: DL and HG. For each modality, we simulated treatment referral by excluding patients with detected STDR from the second screening using that modality. Results. There were 5,738 patients (12.3% STDR) in the first screening. DL and HG captured different numbers of STDR cases, and after simulated referral and excluding ungradable cases, 4,148 and 4,263 patients remained in the second screening, respectively. The STDR prevalence at the second screening was 5.1% and 6.8% for DL- and HG-based screening, respectively. Along with the prevalence decrease, the sensitivity for both modalities decreased from the first to the second screening (DL: from 95% to 90%, p = 0.008 ; HG: from 74% to 57%, p < 0.001 ). At both the first and second screenings, the rate of false negatives for the DL was a fifth that of HG (0.5-0.6% vs. 2.9-3.2%). Conclusion. On 2-year longitudinal follow-up of a DR screening cohort, STDR prevalence decreased for both DL- and HG-based screening. Follow-up screenings in longitudinal DR screening can be more difficult and induce lower sensitivity for both DL and HG, though the false negative rate was substantially lower for DL. Our data may be useful for health-economics analyses of longitudinal screening settings.


Methodology ◽  
2019 ◽  
Vol 15 (3) ◽  
pp. 97-105
Author(s):  
Rodrigo Ferrer ◽  
Antonio Pardo

Abstract. In a recent paper, Ferrer and Pardo (2014) tested several distribution-based methods designed to assess when test scores obtained before and after an intervention reflect a statistically reliable change. However, we still do not know how these methods perform from the point of view of false negatives. For this purpose, we have simulated change scenarios (different effect sizes in a pre-post-test design) with distributions of different shapes and with different sample sizes. For each simulated scenario, we generated 1,000 samples. In each sample, we recorded the false-negative rate of the five distribution-based methods with the best performance from the point of view of the false positives. Our results have revealed unacceptable rates of false negatives even with effects of very large size, starting from 31.8% in an optimistic scenario (effect size of 2.0 and a normal distribution) to 99.9% in the worst scenario (effect size of 0.2 and a highly skewed distribution). Therefore, our results suggest that the widely used distribution-based methods must be applied with caution in a clinical context, because they need huge effect sizes to detect a true change. However, we made some considerations regarding the effect size and the cut-off points commonly used which allow us to be more precise in our estimates.


Author(s):  
Brian M. Katt ◽  
Casey Imbergamo ◽  
Fortunato Padua ◽  
Joseph Leider ◽  
Daniel Fletcher ◽  
...  

Abstract Introduction There is a known false negative rate when using electrodiagnostic studies (EDS) to diagnose carpal tunnel syndrome (CTS). This can pose a management dilemma for patients with signs and symptoms that correlate with CTS but normal EDS. While corticosteroid injection into the carpal tunnel has been used in this setting for diagnostic purposes, there is little data in the literature supporting this practice. The purpose of this study is to evaluate the prognostic value of a carpal tunnel corticosteroid injection in patients with a normal electrodiagnostic study but exhibiting signs and symptoms suggestive of carpal tunnel, who proceed with a carpal tunnel release. Materials and Methods The group included 34 patients presenting to an academic orthopedic practice over the years 2010 to 2019 who had negative EDS, a carpal tunnel corticosteroid injection, and a carpal tunnel release. One patient (2.9%), where the response to the corticosteroid injection was not documented, was excluded from the study, yielding a study cohort of 33 patients. Three patients had bilateral disease, yielding 36 hands for evaluation. Statistical analysis was performed using Chi-square analysis for nonparametric data. Results Thirty-two hands (88.9%) demonstrated complete or partial relief of neuropathic symptoms after the corticosteroid injection, while four (11.1%) did not experience any improvement. Thirty-one hands (86.1%) had symptom improvement following surgery, compared with five (13.9%) which did not. Of the 32 hands that demonstrated relief following the injection, 29 hands (90.6%) improved after surgery. Of the four hands that did not demonstrate relief after the injection, two (50%) improved after surgery. This difference was statistically significant (p = 0.03). Conclusion Patients diagnosed with a high index of suspicion for CTS do well with operative intervention despite a normal electrodiagnostic test if they have had a positive response to a preoperative injection. The injection can provide reassurance to both the patient and surgeon before proceeding to surgery. Although patients with a normal electrodiagnostic test and no response to cortisone can still do well with surgical intervention, the surgeon should carefully review both the history and physical examination as surgical success may decrease when both diagnostic tests are negative. Performing a corticosteroid injection is an additional diagnostic tool to consider in the management of patients with CTS and normal electrodiagnostic testing.


2020 ◽  
Vol 22 (1) ◽  
pp. 25-29
Author(s):  
Zubayer Ahmad ◽  
Mohammad Ali ◽  
Kazi lsrat Jahan ◽  
ABM Khurshid Alam ◽  
G M Morshed

Background: Biliary disease is one of the most common surgical problems encountered all over the world. Ultrasound is widely accepted for the diagnosis of biliary system disease. However, it is a highly operator dependent imaging modality and its diagnostic success is also influenced by the situation, such as non-fasting, obesity, intestinal gas. Objective: To compare the ultrasonographic findings with the peroperative findings in biliary surgery. Methods: This prospective study was conducted in General Hospital, comilla between the periods of July 2006 to June 2008 among 300 patients with biliary diseases for which operative treatment is planned. Comparison between sonographic findings with operative findings was performed. Results: Right hypochondriac pain and jaundice were two significant symptoms (93% and 15%). Right hypochondriac tenderness, jaundice and palpable gallbladder were most valuable physical findings (respectively, 40%, 15% and 5%). Out of 252 ultrasonically positive gallbladder, stone were confirmed in 249 cases preoperatively. Sensitivity of USG in diagnosis of gallstone disease was 100%. There was, however, 25% false positive rate detection. Specificity was, however, 75% in this case. USG could demonstrate stone in common bile duct in only 12 out of 30 cases. Sensitivity of the test in diagnosing common bile duct stone was 40%, false negative rate 60%. In the series, ultrasonography sensitivity was 100% in diagnosing stone in cystic duct. USG could detect with relatively good but less sensitivity the presence of chronic cholecystitis (92.3%) and worm inside gallbladder (50%). Conclusion: Ultrasonography is the most important investigation in the diagnosis of biliary disease and a useful test for patients undergoing operative management for planning and anticipating technical difficulties. Journal of Surgical Sciences (2018) Vol. 22 (1): 25-29


2020 ◽  
Vol 16 ◽  
Author(s):  
Md Mahfujul Islam ◽  
Md Al Amin Molla

: The aim to examine the signs for the potency of interventions to raise cancer awareness along with promote early demonstration in most cancers to share with future and policy investigation. Several peer-reviewed journals as well as books, conference paper and authentic website (like as NCBI, PubMed, CRI, CRU, Google Scholar, MEDLINE, Web of Science, etc.) Also, we looked for bibliographic databases and reference lists Such as randomized controlled trials of interventions brought to Individuals and commanded or uncontrolled reports of interventions brought to communities. The results found the signs that interventions reach to people subconsciously increase the cancer awareness from the short term and inadequate signs they advertise premature demonstration. This analysis helps to find appropriate info about categorizing the early indicators of many kinds of cancer cells on addition to appropriate guidelines to conquer cancer in low-Mid center income areas. Whereas contained the structured screening program, which helps detect cancer early and having a heightened chance of therapeutic and treatment content, taking essential measures to elevate the consciousness of the detectable symptoms.


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