[Contribution to the problem of supplementing the conventional diagnosis of gonorrhea by the fluorescent antibody technic. Reply to comments of graduate biologist A. Kabátová].
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Despite having a relatively low incidence, renal cell carcinoma (RCC) is one of the most lethal urologic cancers. For successful treatment including surgery, early detection is essential. Currently there is no screening method such as biomarker assays for early diagnosis of RCC. Surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF) is a recent technical advance that can be used to identify biomarkers for cancers. In this study, we investigated whether SELDI protein profiling and artificial intelligence analysis of serum could distinguish RCC from healthy persons and other urologic diseases (nonRCC). The SELDI-TOF data was acquired from a total of 36 serum samples with weak cation exchange-2 protein chip arrays and filtered using ProteinChip software. We used a decision tree algorithm c4.5 to classify the three groups of sera. Five proteins were identified with masses of 3900, 4107, 4153, 5352, and 5987 Da. These biomarkers can correctly separate RCC from healthy and nonRCC samples.
Although most of the major discernible morphogenetic events in plants occur after germination, the overall architectural pattern of the mature plant is established during early events of embryogenesis. So far, few genes that are expressed specifically during embryogenesis have been identified. This is due primarily to technical difficulties associated with the mass ratios of the embryo and the surrounding maternal tissue and to the lack of molecular and cellular markers to direct screening efforts. We have developed a series of molecular approaches to study the early events of embryogenesis. These include 'virtual subtraction' of a cDNA library with high specific-activity cDNA probes generated from both seed and non-seed tissue, PCR amplification of gene family members from an immature seed cDNA library using primers specific to conserved domains, differential display analysis of mRNA populations and high throughput expressed sequence tag (EST) analysis. These techniques have led to the identification and isolation of several novel seed-specific cDNAs.
To determine whether systematic differences exist between hypertensive children referred for evaluation by primary care providers and children identified through community-based screening, cardiovascular risk factors and surrogate markers of hypertensive injury were compared based on subject source (referral versus screening). Children referred to a hypertension clinic for persistently elevated blood pressure were compared with children identified as hypertensive during school screening of 5102 students in Houston public schools. M-mode echocardiography of the left ventricle was performed and subsequently reviewed by 2 independent sonographers blinded to identifying subject information. Subsets of subjects also underwent carotid artery ultrasound for measurement of intimal-medial thickness, overnight urine collections for microalbuminuria, and fasting serum cholesterol, triglycerides, and glucose. Ninety-seven total subjects (54 screening and 43 referral) met inclusion criteria and had technically adequate echocardiography performed. The prevalence of left ventricular hypertrophy (LVH) was 37%. Referral subjects demonstrated significantly greater left ventricular mass index (38.8 versus 34.2 g/m(2.7); P<0.01) and a higher prevalence of LVH (49% versus 28%; P<0.05). Among subjects who underwent carotid ultrasound (n=75), carotid intimal-medial thickness was significantly higher in referral subjects (0.61 versus 0.57, P<0.05). When controlling for BMI z score, which was significantly higher in referral subjects, systematic differences by subject source did not persist. These findings suggest that hypertensive children who are predominantly overweight, independent of the manner in which patients come to medical attention, will manifest evidence of more severe cardiovascular disease assessed by surrogate markers such as left ventricular mass index or carotid artery intimal medial thickness.
Native peptides and proteins are of increasing interest in biomedical research because they hold promise to represent a large number of useful diagnostic and therapeutic biomarkers. Discovery attempts from patient samples have to deal with the complexity of biology from a disease perspective as well as with a high individual variability. High throughput screening of samples is therefore the strategy of choice to detect relevant peptidic biomarkers, and requires a high order of automation particularly in the detection process. In this contribution, a novel technical approach employing a fully automated MALDI-TOF/TOF mass spectrometer is described. This approach combines high throughput biomarker discovery with the identification of corresponding endogenous peptides in one instrument and from the same set of samples. The degree of automation allows the analysis of thousands of chromatographic fractions corresponding to up to one hundred patient samples per day. The applied relative quantification via Differential Peptide Display((R)) is performed in a label-free way and shows a dynamic range of up to four orders of magnitude in the accessible peptide concentrations. The typical limit of detection is in the mid- to low-picomolar range for body fluids such as blood plasma, urine and cerebrospinal fluid. Sequence assignment via MALDI-TOF/TOF mass spectrometry is carried out either in an overview approach, characterizing rapidly the peptide composition e.g. of a novel sample, or in a directed approach, analyzing a list of biomarker candidates deduced from statistically significant abundance differences from the biomarker discovery process.
In this paper we describe how to more efficiently detect and treat early gastric cancer (EGC) in high-risk populations. For detection, we first assess the value of known risk factors from the viewpoint of availability for cancer screening. Serum pepsinogen appears to be the most useful and realistic of the factors examined, although its adequacy needs to be assessed in high-risk populations other than those in Japan. Helicobacter pylori infection is known to be a universal risk factor (or gastric carcinogen), and several interventional studies have recently shown positive results. However, H. pylori infection can be eradicated from at-risk populations, thereby decreasing its availability for cancer screening. Smokers are thought to be at risk epidemiologically, but the efficacy of screening in this population has yet to be elucidated, and further studies are warranted. Gender and aging can be risk factors in Japanese populations; male gender and old age are predominant in the intestinal type of carcinoma which is dominant in Japan, although this is not the case in the West. As for early diagnosis of cancer, only endoscopy can be commonly used for the detection of gastritis-like EGC, seen as a faint mucosal irregularity or discoloration. To make early diagnosis more accurate, it is indispensable to carry out detailed endoscopy together with careful scrutiny of the mucosa using dye-spraying techniques. The remarkable progress of early diagnosis in Japan prompted the endoscopic treatment for less invasive EGCs. The first success was with endoscopic mucosal resection (EMR). Although convenient, its therapeutic efficacy is inadequate, particularly for larger lesions. Endoscopic submucosal dissection (ESD) has no limitation on resection size and is expected to replace surgery, although it needs a high level of skill and there are several technical problems to be solved.
The present status of the neuroblastoma mass screening program in Japan, the first national trial in the world, is evaluated. This program, now in its fifth year, was conducted in cooperation with the infants' mothers, local health centers, screening centers, and selected hospitals. From the onset of the program in Kyoto in 1973 to the end of 1989, 337 cases were detected and analyzed. Most cases were detected at early stages and 97% are expected to be cured. Several social, technical, and clinical problems remain unresolved.
Chest X-ray is the most frequent examination in radiology and accounts for a considerable portion of total population radiation exposure, mostly in screening programs. The ideal radiographic system is the one providing the best image quality together with the lowest dose to the patient, at a low cost. In this paper the authors analyze the potentials of a new chest X-ray examination unit equipped with a large-screen image intensifier (TS 57-Siemens). Two-thousand subjects were examined with this unit. The technical aspects of everyday practice are analyzed from the radiologist's point of view, together with the dose to the patient, image quality, and costs.
BACKGROUND: Computed tomographic (CT) colography (virtual colonoscopy) is a new imaging method for detection of colon polyps and cancer. OBJECTIVE: To evaluate the sensitivity of CT colography for polyp detection in a population without symptoms that included persons without colon neoplasia and with radiologists blinded to colonoscopic findings. METHODS: Forty-six persons without symptoms underwent spiral CT followed by same-day colonoscopy with subsequent inspection of two-dimensional axial CT images, interactive multiplanar images, and surfaced and volume-rendered images of the colon (three-dimensional CT colography). RESULTS: Three-dimensional CT colography was superior to two-dimensional axial imaging for detection of colon polyps. Three-dimensional CT colography depicted 1 of 4 (25%) adenomas 2 cm in diameter or larger, 6 of 10 (60%) adenomas 1 to 1.9 cm, 6 of 14 (43%) 6 to 9 mm, and 7 of 65 (11%) 5 mm in diameter or smaller. Three-dimensional CT colography showed a polyp that might have led to colonoscopy in 3 of 4 (75%) patients whose largest adenoma was 2 cm or larger, 5 of 6 (83%) patients with largest adenoma 1 to 1.9 cm, 3 of 7 (43%) patients with largest adenoma 6 to 9 mm, and 4 of 16 patients (25%) with largest adenoma 5 mm or smaller. Large, flat adenomas of the right colon were difficult to identify with three-dimensional CT colography. The specificity of three-dimensional CT colography for patients with adenomas 1 cm in diameter or larger was 89%. Examination of patients with missed adenomas after unblinding indicated that meticulous bowel preparation and adequate distention are critical to accurate interpretation. Perceptual errors were common. CONCLUSIONS: CT colography as performed in this study is not adequate as a colorectal cancer screening test. Several technical factors that appear critical to accurate performance of CT colography are defined.
Hypertension is the commonest cardiovascular disorder, affecting about 20% of the adult population in many countries. It is linked with coronary heart disease, stroke, congestive heart failure and renal dysfunction and is one of the major risk factors for cardiovascular mortality, which accounts for 20-50% of all deaths. Raised awareness of the public health and economic implications of hypertension is now directing attention to the need for long-term control programmes that focus on primary prevention, early detection and adequate treatment. This report of a WHO Expert Committee reviews the epidemiology and pathophysiology of hypertension, enumerates its risk factors and predictors, and makes specific proposals for its prevention and control in populations. Current approaches to the assessment and management of patients with hypertension are discussed, with emphasis on the general usefulness of systolic blood pressure measurements and on the special features of hypertension in children and adolescents, women, elderly people and those with diabetes. The potential impact of lifestyle changes is evaluated, together with the various pharmacological treatment options. While recognizing the need to take account of resource constraints and diversity in health care systems, the Committee recommends that hypertension control programmes are set up worldwide as part of a comprehensive strategy to reduce total cardiovascular risk. Its practical recommendations for policy, hypertension management and research are intended to guide decision-makers in public health, managers of control programmes and physicians and to facilitate the selection of cost-effective means of controlling hypertension in different socioeconomic settings.
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Scoliosis is a lateral curvature of the spine, which may require treatment; this brief analysis details those factors weighed in the basic decision-making process. Additional technical details are presented in subsequent sections.
A mini-computer system for PCG interpretation has been functioning since 1971. The system can analyze as many as 100 PCG's in 3 hours. Based on our 5 years' experience, computer interpretation of PCG's has proved itself valuable for the rapid mass-screening of cardiovascular disease. It also provides more objective and quantitative information than human auscultation, though it is still at a developmental stage because of the present technical limitations. The solution of these shortcomings should achieve an automated PCG analysis of high accuracy.
The 1951 Tuberculosis Control Law of Japan is now faced with tremendous changes that have occurred during the last 50 years in tuberculosis epidemiology and in the environment in tuberculosis control implementation. The law is also challenged with the shift of the paradigm for the National Tuberculosis (TB) Programme. In order to respond properly to these changes, the Tuberculosis Panel of the Health Science Council of the Ministry of Health, Labor and Welfare submitted its report for the amendment of the law in March 2002. Based on this report, a new Tuberculosis Control Law was passed in Parliament last June, and related decrees of the Cabinet and the Ministry are now being revised in preparation for it's enactment in April 2005. In this special lecture, the main points and framework of the revisions were discussed with the perspective of the development of new technical innovations relevant to each area of the revised TB control legislation. 1. Case detection. There will be a shift from the current "indiscriminate" screening scheme to a selective one regarding periodic mass health examination. Only subjects aged 65 or older will be eligible for the screening, supplemented with selected occupational groups who are considered to be at a higher risk of TB, or may be a danger to others if they develop TB, such as health-care providers and school teachers. In addition, local autonomies are responsible for offering screening to the socio-economic high-risk populations, such as homeless people, slum residents, day laborers, and/or workers in small businesses. This means that the efforts of the autonomies are critical for the new system to be effective. The extra-ordinary examination will be limited to only the patient's contacts, and will be mandatory for those contacts so they cannot refuse to be examined by the Health Center. The public services used in the contact investigations will be greatly facilitated by such new technologies as DNA fingerprinting of TB bacilli and a new diagnostic of TB infection using whole-blood interferon-gamma determination (QuantiFERON). The quality of clinical diagnosis and monitoring of treatment should also be improved by introducing an external quality assurance system of commercial laboratory services. 2. Chemoprophylaxis. Although not explicitly defined in the new legislation, the expansion and improvement of chemoprophylaxis to cover anyone with any risk of clinical development of TB would have a tremendous effect in Japan, especially since 90% of patients who developed TB were infected tens of years ago. These technical innovations in diagnosis of TB infection will be very helpful. Development of new drug regimens for the preventive treatment is also badly needed. 3. Immunization. Prior to the amendment of the Law, the BCG vaccination of students entering primary and junior high schools has been already abandoned. In order to encourage the early primary vaccination for infants, the new Law will adopt the direct vaccination scheme in which babies will be given the BCG vaccine without tuberculin testing. This program will be implemented safely, only if it is given to young babies, e.g., less than one year old, as defined by the decree. It is essential to maintain the high level of vaccination coverage under the new program. The autonomy may encounter difficulty mobilizing client babies shortly after their birth (only one year, as compared with the current four years). To avoid the possible, though very rare, adverse health effects due to the vaccination of infected babies, careful questioning should be conducted regarding the risk of exposure to infection prior to vaccination. A ready course of treatment and examinations for abnormal reactions after vaccination (Koch's phenomenon) is also warranted. 4. Treatment and patient care: The revised Law clearly states the governmental responsibility for treating TB patients in close cooperation with a doctor. This is an important legal basis for the expansion of the DOTS Japan version. While the development of new anti-tuberculosis drugs will be realized in the near future, Japan still has to overcome the issue of improper practice of treatment, as well as the government's slow process for approving new drugs to be used for multi-drug resistant TB and non-tuberculous mycobacterioses. 5. Prefectural TB Control Plan: In order to resolve the problems specific to the respective prefectures in terms of epidemiological parameters or available resources, the new Law requests every prefecture to develop its own TB control plan. In order for the new TB Control Law to be effective, strong government commitment supported by technological innovation is mandatory. It is for that reason that the Japanese Society of Tuberculosis should aggressively join the global movement to stop TB along with the general public of Japan.
As screening tests in a currently asymptomatic population, all of the available methods for predicting low back pain and disability have serious technical, ethical and legal limitations. From a technical point of view, none of the predictive tests appear to have sufficient sensitivity or specificity to justify routine usage. The most sensitive indicator (a past history of low back pain) lacks reliability and specificity. Muscle strength-testing may be predictive of future musculoskeletal injury as part of a well-designed program that considers specific job demands in relation to specific worker capabilities. Unfortunately, the conditions necessary for a well designed program--a large number of predictable high-risk jobs that have measurable specific demands that can be reproduced reliably in a testing situation--are rarely met. In the future, the use of computer-assisted multivariate models analogous to those used in the prediction of cardiovascular risk may be capable of integrating information about an individual's medical history, physical exam, physical capacity and other tests with specific job requirements to give us a more accurate prediction of the future risk of back pain and disability. If such predictive models are ever developed and verified, it would then be appropriate to examine various interventions and their effectiveness in modifying risks for the population and the individual worker. From a legal point of view, all of the techniques described hold potential for significant discrimination against legally protected groups. Making employment decisions with regard to a past history of low back pain or on the basis of an x-ray will lead to systematic age discrimination and discrimination against the handicapped. The use of muscle strength-testing will systematically discriminate against women and certain ethnic groups. The ethical implications of predictive screening for low back pain clearly depends on what is done with the information that is garnered from such tests. If the information is used only to make a safe job placement for an individual, and this placement does not affect the individual's salary or future job possibilities, then the testing program may have a net social value to the extent that it leads to true prevention of low back pain and disability. If the tests are used merely to reduce employer liability by refusing employment to those who are thought to be at "high risk," the technical, legal and ethical limitations will far outweigh any perceived benefits.