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Methodological aspects concerning radio-immunoassay of blood thyroxine applicable to population screening.

A research methodology concerning introduction of thyroxine radioimmunoassay applicable to screening programs is reported. The reagents necessary for T4 assay were prepared and tested and the technical parameters, the stages and technical characteristics of RIA-T4 in the laboratory were established. The RIA method for T4 was compared with the CPBA method and with the commercially available kits, both on samples taken from experimental animals and on hypo-, hyper- and normo-thyroid subjects. The range of T4 normal values could thus be established for the geographic area of Romania: 7.5-10.5 microgram dl-1, with a mean of 9.1 +/- 2 SD. The reagents were applied by extension to thyroxine assay on dry blood spots. The results are comparable with those of direct serum assay. The value of these assays in screening thyroid function in newborns and in the population with remnant thyreopathic endemic dystrophy is discussed.

Animals↗

Experience in managing a large-scale rescreening of Papanicolaou smears and the pros and cons of measuring proficiency with visual and written examinations.

Experiences in a large-scale interlaboratory rescreening of Papanicolaou smears are detailed, and the pros and cons of measuring proficiency in cytology are discussed. Despite the additional work of the rescreening project and some psychological and technical problems, it proved to be a useful measure of the laboratory's performance as a whole. One problem to be avoided in future similar studies is the creation of too many diagnostic categories. Individual testing and certification have been shown to be accurate predictors of proficiency. For cytology, such tests require a strong visual component to test interpretation and judgment skills, such as by the use of glass slides or photomicrographs. The potential of interactive videodisc technology for facilitating cytopathologic teaching and assessment is discussed.

Centers for Disease Control and Prevention, U.S.↗

Rapid tests for detection of viral markers in blood transfusion.

Since the early 1990s, rapid tests have been available for detection of HIV infection. They were intended for field diagnosis, emergency and home testing. In addition, rapid tests for anti-HIV, hepatitis B surface antigen and antihepatitis C virus have been used for blood screening in many resource-poor areas to save resources and overcome lack of funding, equipment and electrical supply. The performance of rapid tests varies widely but some have sensitivity and specificity levels that meet standards established by enzyme immunoassays for anti-HIV. Compared with genomic detection of hepatitis B virus, hepatitis B surface antigen rapid tests and enzyme immunoassays have insufficient sensitivity. The clinical consequences of this performance deficit remain to be clarified. Anti-hepatitis C virus rapid tests detect chronically infected individuals who are viremic, however, further studies are required to fully assess their performance. In settings where few blood donations are collected and equipment is unavailable, rapid tests provide a flexible, technically undemanding and relatively inexpensive approach to ensuring a safer blood supply. When utilized for predonation screening in areas of high endemicity of viral markers, rapid tests provide the means to limit blood bag wasting, store only clinically usable blood and inform and counsel deferred donors. As with any laboratory assay, adequate training and sustained quality assurance programs are critical to maintain a safe supply of blood. As a means of achieving a safe blood supply, rapid tests for viral markers and nucleic acid testing have a place next to classic enzyme immunoassays in the definition of strategies that are adapted to a setting's epidemiology, the size and type of donor base, equipment, staff training and resources.

Blood↗

[Mammographic screening. An analysis of the characteristics of interval carcinomas observed in the program in the province of Firenze (1989-1991)].

The authors evaluated 30 interval cancers consecutively observed from 1989 to 1991 and compared them to 98 screening-detected cancers observed in the same period. Interval cancers have a more advanced stage (stage I = 13 lesions, stage II + = 17 lesions) with respect to screening-detected cancers (stage 0 = 10 lesions, stage I = 61 lesions, stage II + = 27 lesions). This finding seems unrelated to an intrinsically higher aggressivity of interval cancers (length biased sampling) which do not differ significantly from screening-detected cancers as far as histopathologic characteristics of prognostic value are concerned. Diagnostic delay due to technical or reading error (9 cases), to radiologically occult cancer in clear (10 cases) or dense parenchymal areas (11 cases) is most likely. This seems to be confirmed by the low frequency observed among interval cancers of easily visible lesions such as isolated microcalcifications (3% vs. 35%) or stellate opacities (13% vs. 31%), and by the higher frequency of opacities with irregular margins (57% vs. 26%) which are more likely masked by dense parenchyma. The chances of reducing interval cancer rate by attempting to increase sensitivity or by increasing screening frequency are discussed, as well as the possible negative consequences of such protocols in terms of cost-effectiveness.

Adult↗

The significance of circumscribed malignant mammographic masses in the surveillance of BRCA 1/2 gene mutation carriers.

Breast cancers in gene mutation carriers may escape mammographic detection because of rapid growth and tumor expansion. Therefore, they may mimic benign lesions on the mammogram. Twenty-nine BRCA 1/2 mutation carriers under surveillance developed 31 breast cancers between 1994 and 2001 at a mean age of 44.2 years. Controls were 63 women with 67 breast cancers in the same period at a mean age of 53.8 years, also under surveillance because of a life time risk of at least 15%. In 26% of the carriers vs. 48% of the controls, mammography was the method that first suspected a malignancy. Seven radiologists performed a retrospective review of the original mammograms to establish technical assessment, with special attention for circumscribed lesions and estimated probability of malignancy. In the mutation carriers seven (23%) circumscribed non-calcified mammographic masses were found and three in the controls (4.5%) P=0.01. These masses were proven to be malignant. In both groups around 70% of these fast-growing circumscribed lesions were detected by the patients. The masses were situated in breasts with a good interpretable breast pattern. BRCA 1/2 mutation carriers had a significantly higher percentage of circumscribed non-calcified mammographic masses that proved to be malignant. These mammographic lesions in women at high risk should be described as at least Birads 0 and worked-up with ultrasound and needle biopsy.

Adult↗

Comparison of a bioassay and a liquid chromatography-fluorescence-mass spectrometry(n) method for the detection of incurred enrofloxacin residues in chicken tissues.

Regulatory monitoring for most antibiotic residues in edible poultry tissues is often accomplished with accurate, although expensive and technically demanding, chemical analytical techniques. The purpose of this study is to determine if a simple, inexpensive bioassay could detect fluoroquinolone (FQ) residues in chicken muscle above the FDA established tolerance (300 ppb) comparable to a liquid chromatography-fluorescencemass spectrometry(n) method. To produce incurred enrofloxacin (ENRO) tissues (where ENRO is incorporated into complex tissue matrices) for the method comparison, 40-d-old broilers (mixed sex) were orally dosed through drinking water for 3 d at the FDA-approved dose of ENRO (50 ppm). At the end of each day of the 3-d dosing period and for 3 d postdosing, birds were sacrificed and breast and thigh muscle collected and analyzed. Both methods were able to detect ENRO at and below the tolerance level in the muscle, with limits of detection of 26 ppb (bioassay), 0.1 ppb for ENRO, and 0.5 ppb for the ENRO metabolite, ciprofloxacin (liquid chromatography-fluorescence-mass spectrometry(n)). All samples that had violative levels of antibiotic were detected by the bioassay. These results support the use of this bioassay as a screening method for examining large numbers of samples for regulatory monitoring. Positive samples should then be examined by a more extensive method, such as liquid chromatography-fluorescence-mass spectrometry(n), to provide confirmation of the analyte.

Animals↗

The role of the renal specialist nurse in prevention of renal failure.

This article will investigate the care required for those with reduced renal function before renal replacement therapy (RRT) commences. Renal nurses are often involved with the technical, monitoring and evaluative aspects of RRT for those with end stage renal failure. However, many patients may experience reduced renal function many years before reaching the stage of needing RRT. Renal nurses are already involved in the preparation of patients for RRT, but are not presently exercising their specialist skills in the period before this time by contributing to the prevention of end stage renal failure (ESRF). Screening programmes carried out in various parts of the world demonstrate that many members of the population have undetected renal insufficiency, and may benefit from intervention from the nephrology team to prevent further renal dysfunction. It is for this group of patients that this article will consider the potential for the renal nurse to expand their scope of practice.

Diabetes Complications↗

Cystic fibrosis: community knowledge and attitudes towards carrier screening and prenatal diagnosis.

The rate of technical advance in genetics contrasts sharply with the slow diffusion of information on this subject to the general population. In this paper, we investigate the initial knowledge about cystic fibrosis of a group of adults with increased interest in psychosocial issues, but with no special pre-existing knowledge or training in genetics. Attitudes towards carrier screening and prenatal diagnosis for CF were also evaluated, after brief written information had been given on this disease. We found that the studied group had only a poor knowledge of the nature of CF and an even more limited awareness of its inheritance. This knowledge was mainly associated with educational level. Most respondents had no objections to population-wide carrier screening for CF, at least if the test was proposed and not systematically imposed by the government. It is striking that a smaller proportion were interested in knowing their own carrier status. The majority of the group were in favour of prenatal diagnosis for CF. Factors associated with knowledge and attitudes are described. In the discussion, special attention is paid to the psychosocial complexity of mass screening.

Adult↗

Referral criteria for growth screening.

Population height screening studies performed over the past 20 years have shown that between 17 and 21% of children with heights below the third centile have organic disease, of whom about 20% will be new diagnoses. The likelihood of organic disease increases to 50% for children with heights below -3 SDs. The age of screening will also influence the outcome as both acquired disease and disorders with progressive growth slowing, such as Turner's syndrome, are more likely to be detected by screening at an older age. Height velocity as a screening tool has evoked interest for many years as, despite technical problems, slowly growing children are thought more likely to have disease. Inclusion of height or height/weight relations may further improve screening sensitivity. It may assist in the early detection of coeliac disease or eating disorders in older children. A minimum of three measurements is required to define an individual's growth pattern and, preferably, five or six measurements spread over the preschool and primary school years. The value of extension of growth screening to the secondary school age group remains uncertain. Children should be screened for both height and weight and referred when there are major discrepancies between these two measurements (more than three centile bands). A two level system of referral with a community assessment for some children and a direct referral to a growth clinic for children with more severe growth disturbance may be the best use of resources.

Body Height↗

Cell preparation methods and criteria for sample adequacy. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Cell Preparation Methods Standardized fixation and optimal staining Sampling of cervix, sampling error, homogenization of sample, subsampling Assessment of liquid-based preparations: efficacy and economic impact Training and transitional procedures before full implementation of new technologies Criteria for Sample Adequacy Clinician responsibility for collecting and providing representative sample to laboratory Collection instruments, number of slides Cellular content of samples: evidence of transformation zone (TZ) sampling, number of squamous cells present, obscuring factors Screening issues CONSENSUS POSITION The conventional cervical smear remains the standard method of cervical cancer screening but has limitations in individual test sensitivity and specificity. Sample takers should: (1) receive appropriate training in sample collection, (2) be held responsible for providing the laboratory with appropriate samples, and (3) have their performance monitored. The instruments used for sampling should collect cells from both the ectocervix and endocervix; optimally, TZ sampling, represented by the presence of endocervical or squamous metaplastic cells, should be identifiable in samples other than atrophic specimens. The adequacy of a specimen (as judged microscopically) does not guarantee that it is representative of the cervix. Each cytology report should include a comment on cellular content/adequacy of the specimen. Liquid-based preparations may overcome many of the inherent problems with the conventional cervical smear. ONGOING ISSUES: We need further data on the cost-effectiveness of making two slides from cervical specimens and/or using two samplers rather than a single one. Do we have enough information to make recommendations as to the appropriate type of sampler to be used in particular situations, such as routine screening? What is the best method of screening for/detecting endocervical glandular neoplasia? How are such terms as unsatisfactory and inadequate defined in cervical cytology classifications other than the Bethesda System? What number and types of epithelial cells should be present (visualized) in a cervical smear or liquid-based preparation for it to be considered adequate? Do we need to have evidence of TZ sampling in specimens taken during the follow-up period after treatment of squamous intraepithelial lesion or after detection of endocervical glandular neoplasia? What criteria for obscuring factors, such as blood and inflammation, should be used in assessing adequacy? Cost-benefit analyses of utilizing liquid-based preparations are needed. Should we inform women about the technical details of the test methods available or chosen by the laboratory? Are women in a position to decide which method is the most appropriate to assess their cervical scrape sample? We need to obtain more information about the properties of proprietary liquid fixative/transport media with respect to inactivation of viral pathogens, tuberculosis and other bacterial pathogens and suitability for immunobiologic and molecular tests, etc. We need to obtain more information on the use of stoichiometric stains and the limitations of Papanicolaou stain for image analysis systems. The use of liquid-based preparations for nongynecologic cytopathology and ancillary tests must be considered, including criteria for adequacy. We need to obtain more information on the time required for and best methods of training experienced cytotechnologists to become competent at assessing liquid-based cervical preparations.

Cell Biology↗

Fibrinolytic therapy in intraventricular hemorrhage.

OBJECTIVE: To review the literature concerning intraventricular administration of fibrinolytic agents to treat patients with intraventricular hemorrhage (IVH). DATA SOURCES: An extensive literature search (MEDLINE, EMBASE, Conference Proceedings) was conducted to identify articles in English published between 1966 and May 2000 pertaining to the pathophysiology of IVH and its treatment by intraventricular administration of recombinant tissue plasminogen activator (alteplase) or urokinase (u-PA). The bibliographies of selected identified articles were also screened for publications not found in the computerized search. STUDY SELECTION: All pertinent publications were reviewed and considered. Those describing the intraventricular administration of fibrinolytic agents to patients with IVH were included. DATA SYNTHESIS: IVH has a poor prognosis, partly due to the mass effect of blood clots on the ventricular walls. The cerebrospinal fluid has a limited fibrinolytic system. Therefore, clots may remain in the ventricles for months after a hemorrhage. The management of IVH is primarily directed at controlling intracranial pressure through an external ventricular drain, but this catheter often becomes occluded by coagulated blood. To overcome this problem, and to dissolve the residual blood clot, investigators have administered alteplase or u-PA directly into the ventricles of patients with IVH. Complications of this therapy include infection and possible rebleeding. Clinical studies of fibrinolytic therapy for IVH have found a 30-35% reduction in mortality with treatment, but to date, have not clearly documented improved neurologic outcome of the survivors. CONCLUSIONS: Fibrinolytic therapy with alteplase or u-PA may be life-saving in severe cases of IVH. Yet many technical issues remain to be resolved, such as the optimal dose, frequency, method, timing, and duration of administration of the agent. Additional randomized, double-blind, placebo-controlled studies need to be performed so that the true value of this therapy can be assessed.

Cerebral Hemorrhage↗

Image quality assurance in the prostate, lung, colorectal, and ovarian cancer screening trial network of the National Lung Screening Trial.

The National Lung Screening Trial is evaluating the effectiveness of low-dose spiral CT and conventional chest X-ray as screening tests for persons who are at high risk for developing lung cancer. This multicenter trial requires quality assurance (QA) for the image quality and technical parameters of the scans. The electronic system described here helps manage the QA process. The system includes a workstation at each screening center that de-identifies the data, a DICOM storage service at the QA Coordinating Center, and Web-based systems for presenting images and QA evaluation forms to the QA radiologists. Quality assurance data are collated and analyzed by an independent statistical organization. We describe the design and implementation of this electronic QA system, emphasizing issues relating to data security and privacy, the various obstacles encountered in the installation of a common system at different participating screening centers, and the functional success of the system deployed.

CD-ROM↗

PillCam colon capsule endoscopy compared with colonoscopy for colorectal tumor diagnosis: a prospective pilot study.

BACKGROUND AND AIMS: Colonoscopy is regarded as the gold standard for colorectal cancer (CRC) screening. PillCam capsule endoscopy could be an alternative approach for screening large populations. We report a pilot evaluation in humans of the safety, feasibility, and performance of colon capsule endoscopy compared with colonoscopy. PATIENTS AND METHODS: Patients included in this single-center comparative study had presented for screening colonoscopy or there was suspicion of polyps or CRC. The capsule was ingested in the morning. After excretion, colonoscopy was performed. Significant findings were defined either as polyps > 6 mm, or three or more polyps of any size. Colonoscopy and colon capsule endoscopy (CCE) review were performed by independent physicians. RESULTS: 41 patients (26 women), mean age 56 years (range 26 - 75) were included, and all had complete colonoscopies. Four patients were excluded due to technical problems and one could not swallow the capsule; thus, 36 patients were considered in the analysis. In six the capsule had not been expelled at 10 hours and was retrieved endoscopically. CCE identified 19 of the 25 patients (76 %) with positive findings and 10 of the 13 (77 %) with significant lesions detected by colonoscopy. CCE detected seven lesions not seen at colonoscopy and two tumors were detected by both examinations. Overall sensitivity of CCE to detect significant lesions was 77 %, specificity was 70 %, positive predictive value was 59 %, and negative predictive value was 84 %. No adverse events occurred. CONCLUSION: CCE showed promising accuracy compared with colonoscopy. This new noninvasive technique deserves further evaluation as a potential CRC screening tool.

Adult↗

Serological screening for coeliac disease: methodological standards and quality control.

To establish methodological standards for serological investigation and screening of coeliac disease, a joint venture has been launched by the European Medical Research Council and the European Society for Paediatric Gastroenterology and Nutrition. Before general screening can be recommended, robust methods and technical standards ought to be introduced. Joint test protocols were defined: an enzyme-linked immunosorbent assay for IgG and IgA gliadin antibodies and an immunofluorescent test for IgA endomysium antibodies. Protocols have now been tested prospectively by one laboratory. Eighty-eight Tuebingen patients were studied (47 coeliac disease on normal diet, 22 coeliac disease on a gluten-free, and 19 disease controls). Single tests did not produce acceptable levels, but combinations of IgA gliadin antibodies and IgA endomysium antibodies showed 98% sensitivity, 100% specificity and 98% predictive efficiency. Only standardized and refereed methods established by ring testing can serve as a reliable basis for serological coeliac screening.

Case-Control Studies↗

Use of limited color-flow duplex for a carotid screening project.

BACKGROUND: Although the efficacy of carotid endarterectomy for asymptomatic carotid stenosis has been established, no cost-effective approach for identification of these patients has yet been devised. The purpose of this study was to develop a limited carotid duplex screening examination to be utilized for the detection of asymptomatic carotid stenoses. METHODS: Carotid screening examinations employed rapid identification of the carotid bifurcation using color-flow duplex imaging and an immediate Doppler-derived velocity of the segment of the internal carotid artery with the most turbulent flow. Complete examinations were then finished using well-established protocols in our accredited vascular laboratory. A total of 512 patients were referred for complete studies based upon standard indications. Criteria for at least a 50% internal carotid artery stenosis on the complete examination was defined as a peak systolic velocity (PSV) of at least 125 cm/sec. Receiver operator characteristic (ROC) curves were then constructed to identify the optimal screening velocity criteria as compared with the final results on the complete examination. RESULTS: Five screening examinations were technically limited yielding a total of 507 patients with 1,014 carotid arteries available for analysis. Comparison of screening examinations versus complete examinations for a PSV of 125 cm/sec yielded sensitivity 86%, specificity 98%, positive predictive value (PPV) 95%, and a negative predictive value (NPV) 93%. ROC analysis identified a "cut point" of 115 cm/sec on the screening examinations to achieve sensitivity 91%, specificity 95%, PPV 89%, and NPV 96%. Time to perform screening examinations averaged 3.2 minutes per patient. Three patients had common carotid lesions not identified on the limited internal carotid screening examinations. CONCLUSIONS: Screening carotid examinations are a rapid, reliable, and relatively inexpensive method for detection of patients with asymptomatic internal carotid artery stenosis. Limited screening examinations should be developed in each vascular laboratory and utilized in high-risk patients.

Blood Flow Velocity↗

Proteomics meets microbiology: technical advances in the global mapping of protein expression and function.

The availability of complete genome sequences for a large number of pathogenic organisms has opened the door for large-scale proteomic studies to dissect both protein expression/regulation and function. This review highlights key proteomic methods including two-dimensional gel electrophoresis, reference mapping, protein expression profiling and recent advances in gel-free separation techniques that have made a significant impact on the resolution of complex proteomes. In addition, we highlight recent developments in the field of chemical proteomics, a branch of proteomics aimed at functionally profiling a proteome. These techniques include the development of activity-based probes and activity-based protein profiling methods as well as the use of synthetic small molecule libraries to screen for pharmacological tools to perturb basic biological processes. This review will focus on the applications of these technologies to the field of microbiology.

Bacterial Proteins↗

Solid phase red cell adherence immunoassay for anti-HIV 1: a simple, rapid, and accurate method for donor screening.

In technically developed countries in which acquired immunodeficiency syndrome is a risk to the recipients of blood or tissue, it is mandatory to screen the donor for evidence of HIV (human immunodeficiency virus) infection. Current tests, based on enzyme-linked immunoassay, are time-consuming and expensive and as such are unsuitable for developing countries. We describe a second generation test using anti-human IgG coupled to red cells as the indicator of antibody having reacted with test antigen (1). The test is complete within ten minutes, simple to perform and to read and has 100% sensitivity and 99% specificity compared with Western blot. It is ideal for the rapid screening of organ donors and for the screening of blood donors where cost is a major consideration.

Antibodies, Viral↗

Mammographic screening: international perspective.

The twentieth century saw the introduction of mammography as a diagnostic tool and its refinement as a screening method. It appears guaranteed that women who are well informed will seek mammography screening with high expectations of technical quality and accurate interpretation. More refined knowledge of breast anatomy and pathology will assist radiologists to interpret with high specificity. We will learn how to recognized more accurately normal structures and doubtful findings. We will gain experience in interpretation through faithful review of interval cancers and subtle screen-detected cancers, and will use educational tools that have the potential to improve the efficiency of education by directing attention to specific deficiencies. Mammographic screening has been advanced through the efforts of dedicated teams of physicians, scientists, and other professionals throughout the world. The international communication of ideas and discoveries will continue to challenge the boundaries of what can be accomplished in early detection as well as noninvasive therapy, and this body of knowledge will continue to be enriched by these diverse contributions.

Breast Neoplasms↗