Mass Screening Method Research Articles

Establishment of a Mass Screening Method of Sand Fly Vectors for Leishmania Infection by Molecular Biological Methods

Surveillance of the prevalence of Leishmania and its vector, sand fly species, in endemic and surrounding areas is important for prediction of the risk and expansion of leishmaniasis. In this study, a method for the mass screening of sand flies for Leishmania infection was established. This method was applied to 319 field-captured specimens, and 5 positive sand flies were detected. Sand fly species were identified by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) of the18S rRNA gene, and all the positive flies were Lu. hartmanni. Furthermore, cytochrome b (Cyt b) gene sequence analyses identified all the parasites as Endotrypanum species including a probable novel species. Because the method requires minimum effort and can process a large number of samples at once, it will be a powerful tool for studying the epidemiology of leishmaniasis.

Improved quantitative method for G6PD deficiency detection.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common hereditary enzyme defect that affects over 400 million people worldwide. Deficiency in G6PD can cause hemolytic anemia, which can be fatal if it is not treated properly. Mass qualitative G6PD-deficiency screening methods have been available for some time; however, in this study we developed the first high-throughput quantitative method for measuring G6PD activity. A patient's blood can be analyzed directly from the original collection tubes on a Hitachi P modular serum work area (SWA), which dramatically reduces the analysis time and the cost of the assay. The results presented here may enable the development of other improved, automated assays of whole-blood samples.

Urinary γ-glutamyltransferase (GGT) as a potential marker of bone resorption

We recently identified γ-glutamyltransferase (GGT) as a novel bone-resorbing factor. The present study was undertaken to determine whether GGT is a marker of bone resorption in two genetic models of hyper- and hypo-function of osteoclasts, as well as in postmenopausal women with accelerated bone resorption, using type I collagen N-telopeptide (NTX) and deoxypyridinoline (DPD) as established biochemical markers. Urinary excretion of GGT, corrected for creatinine, was found to be increased in osteoprotegerin (OPG)-deficient osteoporotic mice as well as in patients with postmenopausal osteoporosis (67–83 years of age); in both cases the urinary level decreased after treatment of patients or mice with alendronate, a selective inhibitor of bone resorption, concomitantly with a reduction in DPD and NTX. Conversely, in osteopetrotic op/op mice, urinary GGT increased in parallel with DPD after induction of osteoclasts with M-CSF injection. Constant infusion of parathyroid hormone (PTH) also increased urinary GGT along with DPD. In a survey of 551 postmenopausal women (50–89 years of age) at their regular health checkup, urinary GGT excretion exhibited a high correlation with DPD (ρ=0.49, p<0.0001). The calculated sensitivity and specificity for diagnosing elevated bone resorption, as determined by a DPD value higher than 7.6 nM/mM Cr, were 61% and 92%, respectively, when a cut-off value of 40 IU/g Cr was assigned for urinary GGT. Since GGT activity can be measured inexpensively in large numbers in a very short time, the measurement of urinary level may provide a convenient and useful method for mass screening to identify those with increased bone turnover and hence at increased risk for bone fracture.

Screening for Biliary Atresia by Infant Stool Color Card in Taiwan

We aimed to detect biliary atresia (BA) in early infancy to prevent additional liver damage because of the delay of referral and surgical treatment and to investigate the incidence rate of BA in Taiwan. A pilot study to screen the stool color in infants for the early diagnosis of BA was undertaken from March 2002 to December 2003. We had designed an "infant stool color card" with 7 numbers of different color pictures and attached it to the child health booklet. Parents were then asked to observe their infant's stool color by using this card. The medical staff would check the number that the parents chose according to their infant's stool color at 1 month of age during the health checkup and then send the card back to the stool color card registry center. The average return rate was approximately 65.2% (78,184 infants). A total of 29 infants were diagnosed as having BA, and 26 were screened out by stool color card before 60 days of age. The sensitivity, specificity, and positive predictive value were 89.7%, 99.9%, and 28.6%, respectively. Seventeen (58.6%) infants with BA received a Kasai operation within 60-day age period. The estimated incidence of BA in screened newborns was 3.7 of 10,000. The stool color card was a simple, efficient, and applicable mass screening method for early diagnosis and management of BA. The program can also help in estimating the incidence and creating a registry of these patients.

Glaucoma screening: current trends, economic issues, technology, and challenges

Glaucoma is one of the leading causes of irreversible blindness worldwide. Early glaucoma detection and treatment are currently the only known methods for preventing blindness and low vision resulting from this frequently asymptomatic disease. New technologies for detecting early glaucomatous damage are important in diagnosing optic nerve disease, not only in community screening settings but also in clinics. Imaging of the optic nerve head and macula and retinal nerve fiber layer analysis can provide quick, automated, and quantitative measurements in agreement with clinical estimates of optic disc structure and visual function. In the area of perimetry, frequency-doubling technology is a promising and feasible mass-screening method with reasonable sensitivity for detecting visual field loss. Central corneal thickness has emerged as a new risk factor for the development and progression of glaucoma, thereby complicating the role of tonometry and measurement of intraocular pressure as screening parameters for glaucoma. Along with technological advances, strides are also being made with public policy and legislative efforts to bring glaucoma onto the national and global health care agenda. These initiatives incorporate vision-screening goals into national disease prevention programs emphasizing the need for early glaucoma detection and treatment. Glaucoma awareness needs to be increased through better education, and compliance with follow-up care needs to be improved to decrease the economic and social costs from glaucoma. In addition, screening models need to be developed that will be effective in developing countries where the risk of blindness from glaucoma is highest.

A rapid method for mass screening for parkinsonism

Epidemiology studies of parkinsonism employ a variety of techniques for unbiased sampling of populations. No current method permits mass screening of all subjects in a population for parkinsonism by movement disorders specialists. We developed and piloted a new approach to facilitate accurate and efficient screening of large populations for diagnosis of parkinsonism and provide data on sensitivity and specificity. We evaluated 2081 welders referred for medical-legal screening. Subjects were video taped using a standardized protocol, and videos were rated on the Unified Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3). A “video rater” viewed video tapes and entered ratings through a web-based database. An “in-person” examiner performed a UPDRS3 examination in a randomly selected subgroup of 48 workers drawn from the 2081. We developed quantitative diagnostic criteria for parkinsonism that established minimum diagnostic thresholds based upon UPDRS3 scores and compared these criteria with diagnosis by an in-person examiner. Specificity of these criteria compared to in-person examination was 91–100% but sensitivity was 56%. A threshold UPDRS3 score greater than nine provided 100% sensitivity and 81% specificity. Liberal criteria identified 266 (13.1%) subjects with probable parkinsonism and 220 (10.8%) subjects with definite parkinsonism. Conservative criteria identified 260 (12.8%) with probable parkinsonism and 122 (6%) with definite parkinsonism. Our screening method permits rapid assessment of parkinsonian signs. An absolute UPDRS3 score greater than nine provided the best combination of sensitivity and specificity for the diagnosis of parkinsonism, while quantitative exam-based criteria for cardinal parkinsonian signs maximized specificity. Parkinsonism as diagnosed by our criteria was common in this group of welders.

Reliability of quantitative and qualitative tests to identify heterozygotes carrying severe or mild G6PD deficiency

Objectives: To determine if the qualitative test (cytochemical) is more reliable than the quantitative test (differential pH-metry) in identifying heterozygous G6PD − subjects. Design and methods: Identification of heterozygous G6PD − subjects was done by the measurement of G6PD activity and by a cytochemical test. Results: A cytochemical test is more sensitive than differential pH-metry to identify heterozygous G6PD − subjects. Conclusions: A cytochemical test is a reliable method for mass screening for G6PD deficiency to identify G6PD − heterozygotes.

1H NMR-based metabonomics for the diagnosis of inborn errors of metabolism in urine

1H NMR-based metabonomics was used for the detection and diagnosis of inborn errors of metabolism from urine samples. 1D 1H NMR spectra from 47 normal, 9 phenylketonuric (PKU) newborns and 1 maple syrup urine disease (MSUD) child were obtained and investigated. Urine 1H NMR spectra of normal, PKU and MSUD samples exhibited differences concerning the phenylalanine (Phe) and branched-chain amino acids (leucine, valine, isoleucine) resonances, respectively. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were applied in order to establish adequate models for discrimination between pathological and normal samples. Normalization of the spectra was based to the total spectral intensity or to creatinine peak. Different data transformation procedures were used. Discrimination of PKU and MSUD samples from normal samples was achieved by the different models produced by PCA and PLS-DA. Comparing the two methods of statistical analysis, PLS-DA was found to lead to a most proper discrimination when all pathological samples were used, while PCA proved suitable to identify every single pathological sample among the physiological ones. Thus, 1H NMR in urine can be considered as an alternative to blood spots in order to develop a mass-screening method, which does not require sample pre-treatment and avoids any painful procedure for the newborns.

Virtual colonoscopy

A computer-graphics-based alternative to conventional optical colonoscopy, known as virtual colonoscopy (VC) or computed tomography colonography (CTC), is rapidly gaining popularity. During this procedure, which was concurrently developed by our group at Stony Brook University [5] and by other researchers [10], the distended colon is imaged by a helical or multislice CT scanner. The acquired abdominal CT scan commonly consists of 350--750 axial images of 512x512 sub-millimeter resolution, providing excellent contrast between the colon wall and the lumen. A 3D model of the colon is then reconstructed from the CT scan by automatically segmenting the colon out of the rest of the abdomen and employing an electronic cleansing algorithm for computer-based removal of the residual material. The PC-based visualization software employs volume rendering and allows the user, typically a physician, to interactively navigate through the virtual 3D model of the colon. An intuitive user interface with customized tools supports measurements and virtual biopsy to inspect suspicious regions. Unlike optical colonoscopy (see the sidebar "Conventional Colorectal Cancer Screening"), VC is patient friendly since the patient undergoes less rigorous preparation prior to the procedure. VC is also a fast, noninvasive, highly accurate, cost-effective method for mass screening of colon polyps.

直腸癌検出のためのX線CT画像における腹腔内脂肪分布評価

To develop a novel method of detecting rectal cancer, we assessed relationships between intra-abdominal fat distribution and rectal cancer in Japanese patients. Subjects comprised 38 patients with rectal cancer apparent on CT-colonography and 110 other cases. The intra-abdominal fat area was determined by calculating pixel distribution with attenuation values from -140 HU to -40 HU. The area of intra-abdominal fat was measured on axial images using an interslice gap of 10 mm. Profile curves of intra-abdominal fat were in the plane direction from diaphragm to anus. Of note is the fact that Ogura's peak, a secondary small peak around the rectal cancer, was apparent on the profile of intra-abdominal fat, with 73.7% of rectal cancers displaying Ogura's peak. In comparison, only 19.1% of other cases displayed Ogura's peak on this profile. The relationship between fat and rectal cancer is difficult to explain. However, making good use of these results showing intra-abdominal fat distribution, a computer-aided diagnosis (CAD) system for detecting rectal cancer according to the presence of Ogura's peak has potential as a method of mass screening. As only 148 cases were investigated in the present study, the accumulation of additional data is needed. More detailed studies with larger patient populations are warranted.

Screening for Glaucoma in a General Population with the Non-Mydriatic Fundus Camera and the Frequency Doubling Perimeter

To evaluate the usefulness of non-mydriatic fundus camera (NMFu-camera) and frequency doubling perimeter (FDP) for detecting glaucoma in a general population. This prospective observational multicenter study consisted in screening for glaucoma in the populations of three Belgian cities. Intraocular pressure (IOP) was measured with non-contact pneumo-tonometer (NCT) and applanation tonometry (AT) if NCT IOP was > or = 17 mmHg. Visual field was screened with FDP (C-20-5) and digitized optic disc photographs (ODPs) were taken with NMFu-camera. FDP was considered abnormal if at least one defective point was found. ODPs were graded as normal or glaucomatous by consensus of three glaucoma specialists. Optic disc and visual field results were matched per eye. Subjects with known ocular hypertension and/or treated primary open angle glaucoma were excluded from the analysis. A total of 1620 subjects were included in the study. Their mean age was 63.2 years. AT IOP was > 21 mmHg in 8.2%. A total of 98.1% of ODPs could be interpreted. Glaucomatous optic discs were detected in 3.5% of the subjects. In this group only 24% had an AT IOP > or = 22 mmHg. FDP was abnormal in 44.5%. The sensitivity and specificity of FDP to identify patients with an optic disc graded as glaucomatous were 58.6% and 64.3% respectively. The combined use of the NMFu-camera and the FDP is a feasible method for an initial glaucoma mass screening. NMFu-camera may be a useful and quick method to screen for glaucomatous damage in a community. FDP in screening strategy was revealed to be not sensitive enough when setting the cut-off value at one defective test location. IOP measurements were confirmed to be a poor tool to detect glaucomatous damage.

Identification of a specific marker for hepatitis C virus infection using capillary zone electrophoresis

Background: Hepatitis C virus (HCV) infection is now becoming a common health problem in both developed and developing countries. The limitation of the available diagnostic approaches enhances the efforts to have a rapid, sensitive, and specific diagnostic testing for HCV infection. Capillary zone electrophoresis (CZE) is a fully automated analytical technique whose popularity is quickly increasing in the clinical chemistry laboratory. CZE can analyze nanoliters or less of samples with detection sensitivity at the attomole level (10 −18 mol) or less. Methods: CZE was optimized for the identification of a specific marker of HCV infection. The performance characteristics of the CZE for the detection of HCV RNA peak were evaluated in comparison with standard nested PCR. Results: A characteristic peak at 2.72 min was identified only in the CZE electropherogram of urine samples from HCV-infected individuals. The nature of the characteristic peak was investigated and confirmed to be HCV RNA using PCR and other biochemical treatments including RNase, DNase, and trypsin enzymes. CZE showed high degrees of sensitivity (94%) and specificity (96%) in comparison with the nested PCR. Conclusion: CZE provides a rapid, inexpensive, sensitive, and specific analytical method for diagnosis and mass screening of a large number of HCV-infected individuals.

Application of nuclear magnetic resonance spectroscopy combined with principal component analysis in detecting inborn errors of metabolism using blood spots: a metabonomic approach

NMR spectra of extracted blood spots were used to investigate the possibility for the development of a new method for mass screening concerning the diagnosis of inborn errors of metabolism (IEM). Blood spots were collected on filter papers from normal, phenylketonuric (PKU) and maple syrup urine disease (MSUD) subjects and their Carr-Purcell-Meiboom-Gill (CPMG) 1 H NMR spectra were acquired. The spectra were reduced to a number of spectral descriptors and principal component analysis (PCA) was performed. The scores plot showed that PKU and MSUD samples were well discriminated from the main cluster of points.

Photodynamic Therapy (PDT) for Barrett's Esophagus with High-Grade Dysplasia (BE + HGD): Cost-Effectiveness Model with Probabilistic Sensitivity Analysis

not clear whether gastric cancer screening is cost-effective, and if so, which strategy is the most cost effective. Aim: The aim of this study is to evaluate whether gastric cancer screening is cost-effective in Japan, and which strategy is the most costeffective. Methods: We conducted cost-effective analysis of the following six strategies using Markov model when 50-year-old asymptomatic Japanese men receive gastric cancer screening for 10 years: 1) no screening, 2) annual Indirect Xray (gastrography taken on predetermined 8 positions in mobile vans; the original method of mass screening in Japan), 3) annual UGI series, 4) annual pepsinogen measurement, 5) annual EGD (EGD q1y), 6) EGD every 3 years (EGD q3y). We assumed that in strategies #2 to #4, 100% of people with any abnormal finding suggesting gastric cancer proceed with EGD for further evaluation. The most assumptions were based on published literature. When data were not available from literature, we seek expert opinion. Only direct costs were considered. DATA 4.0 (TreeAge software Inc.) was used for analysis. Results: In a basecase analysis, compliance was assumed to be 50%. The most effective strategy for Japanese men was EGD q3y. When compared with no screening, this strategy resulted in 401 years of life gained per 10,000 persons, and the incremental cost-effective (CE) ratio was approximately $61,000 per year of life gained. The effectiveness of EGD q1y was comparable to that of EGD q3y. However, the cost was prohibitoly high. In this model, incremental CE ratio of annual indirect X-ray was approximately $133,000 per year of life gained when compared with no screening. Conclusions: Although annual indirectX-ray has been used for gastric cancer screening in Japan for more than 40 years, this strategy may not be cost-effective for 50-year-old asymptomatic Japanesemen. Screeningwith EGDevery 3 yearsmay bemore costeffective strategy and it should be compared with other screening strategies in prospective fashion.

Usefullness of Upper Gastrointestinal Series Using Indirect Radiography in Mass Screening Program for Gastric Cancer

Purpose: To compare the image quality of UGIS (upper gastrointestinal series) obtained by direct radiography with that of UGIS obtained by indirect radiography in a mass screening program for gastric cancer, and to assess the validity of UGIS by indirect radiography. Materials and Methods: A total of 994 persons participated in a mass screening test for gastric cancer between March 2003 and April 2003 at the Korea Association of Health Promotion (KAHP). Of these 994 persons, 494 underwent UGIS by direct radiography, while the remaining 500 underwent UGIS by indirect radiography (i.e. photofluorography using a mirror camera and a 100mm-roll film). We compared the image quality of UGIS obtained by direct and indirect radiography with, in each case, the image quality being graded as‘ excellent’‘, good’‘, fair’‘, poor’or‘ very poor’. Results: The image quality of UGIS by both direct and indirect radiography was similar: most images in both groups were rated as either‘ excellent’,‘ good’, or‘ fair’, while the incidences of poorly rated images were similar in both cases (5% versus 6%, respectively); and there were no images rated as ‘very poor’in either case. For certain sites of the stomach, the image quality of UGIS by direct radiography was superior to that of UGIS by indirect radiography, namely at the cardia (p0.05). Conclusion: There was no significant difference in the image quality between UGIS by indirect and direct radiography. Therefore, UGIS by indirect radiography may be used as a method of mass screening for gastric cancer.

Comparison of soils and sediments using major and trace element data

Abstract Analysis of geochemical data has become an important tool used in forensic comparisons of soils and sediments. The combined use of inductively coupled plasma optical emission spectrometry and mass spectrometry (ICP-OES and ICP-MS) instrumentation allows the abundance of up to 50 elements to be routinely determined in small samples (typically &gt;0.1g). However, key issues concern the extent to which analysed subsamples are representative of the parent material from which they are taken, the best means of comparing datasets for different samples, and interpretation of the significance of the results obtained. ICP measurement precision for most elements is good, but it is important to understand the degree of variation that can arise due to subsampling procedures and selective transfer mechanisms relating to forensic exhibits, as well as the extent of spatial (and sometimes temporal) variability which exists in nature. Although analysis of several different size fractions is often helpful where sufficiently large samples are available, analysis of a standardized &lt;150μm fraction separated from a bulk sample in many cases provides adequate discrimination between samples and provides the most practical method for mass-screening of samples. Where possible, duplicate or triplicate sample preparations should be made, and several analytical determinations made on each prepared subsample. However, the additional time, cost and sample size requirements involved need to be weighed against the benefits of undertaking additional types of analysis of the samples. In order to obtain maximum information from multielement geochemical data, the dataset should be evaluated using a variety of numerical, statistical and graphical procedures. This paper discusses a number of options for such data evaluation using a simple dataset example. Casework experience and experiments have shown that, even in complex situations, multi-element geochemical data can provide very sensitive environmental indicators. However, such data should normally be used in combination with the results of other analyses when making forensic comparisons of soils and sediments.

New Methods for Neonatal Drug Screening

After completing this article, readers should be able to: 1. Describe perinatal and neonatal complications of maternal use of cocaine, alcohol, opiates, and barbiturates in pregnancy. 2. List established cutoffs of conventional immunoassays of urine for common substances of abuse. 3. List the advantages of using meconium testing for substances of abuse. 4. Describe the role of fatty acid ethyl esters in detecting prenatal alcohol exposure. Maternal substance use during pregnancy can have direct consequences on both the developing fetus and the mother and is a significant public health concern. The prevalence of gestational use of drugs of abuse varies, depending on the study population and method of detection, but it generally ranges from 1% to 15%. (1) One of the largest epidemiologic studies conducted in the United States documented that although most pregnant women decrease the use of substances as the pregnancy progresses, a significant proportion of them remain regular users, even in the third trimester (eg, ethanol [13%], cannabis [9.3%], cocaine [10%], and heroin [1%]). (2) Various perinatal and neonatal complications can result from prenatal exposure to common drugs of abuse. (3) The use of cocaine during pregnancy is associated with increased risks of preterm labor, intrauterine growth retardation, and neurobehavioral abnormalities. Heavy alcohol use during pregnancy leads to fetal alcohol spectrum disorder, which is characterized by an array of congenital malformations, central nervous system abnormalities, and neurodevelopmental deficits. Neonates exposed to opiates, alcohol, and barbiturates in utero are at risk of developing neonatal abstinence syndrome, which is characterized by irritability, gastrointestinal dysfunction, respiratory distress, and other nonspecific symptoms. (1) Data in the literature conflict regarding adverse events in the immediate postnatal period that can be attributed to prenatal exposure to other illicit drugs. Thus, early identification of neonates in whom substance exposure is suspected is important for appropriate treatment intervention and …

Pilot study of mass screening for Wilson's disease in Korea

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism with copper accumulation in the liver as well as in the central nervous system. Treatment of WD includes oral chelating agents and diet and it is effective. However, once irreversible damage has occurred, the effect of treatment is diminished and the patient's quality of life is compromised. It is estimated that at least half of the patients with WD remain undiagnosed and die of untreated disease. Early detection of patients presymptomatically has been hampered by the lack of effective methods for mass screening. Recently, a sandwich ELISA method for ceruloplasmin measurement in blood spots was developed. We have used this method to analyze blood specimens collected on filter paper from 3667 children aged 3 months–15 years. The mean value of ceruloplasmin was 30.5±9.5 mg/dL. Among these children, we identified one WD case, a 32-month-old boy with markedly reduced ceruloplasmin concentration (2.3 mg/dL). Measurement of CP level in dried blood spot sample is proposed as a reliable method for population screening of WD.

Mass screening for Wilson's disease by measuring urinary holoceruloplasmin

We conducted a mass-screening method to detect presymptomatic Wilson's disease in children by measuring urinary holoceruloplasmin. Two cases of Wilson's disease were found by testing urine samples from 48,819 children. The diagnosis was confirmed by clinical laboratory tests and the detection of a mutated ATP 7B gene. (J Pediatr 2002;140:614-6)

The Present Condition and Future of Gastric Mass Screening Method for Company Employees with Endoscopy as an Option.

The Present Condition and Future of Gastric Mass Screening Method for Company Employees with Endoscopy as an Option.