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This direct method for quantifying excessive urinary glycosaminoglycan excretion exploits the specific binding of 1,9-dimethylmethylene blue (DMB). The procedure obviates cumbersome and labor-intensive procedures for separating glycosaminoglycans from other constituents of urine. Pediatric pharmaceutical formulations (except heparin), in concentrations expected in urine, do not interfere with spectrophotometry, nor does protein. Results can be expressed in terms of urinary creatinine; thus the test is applicable to very small urine specimens (0.1 mL), such as those obtainable from neonates. In a pilot study, results of the direct DMB test for 48 urine specimens agreed with the clinical diagnosis, and quantitative measurements correlated moderately (r = 0.76) with results of a commonly used procedure (carbazole-borate reactivity after precipitation with cetylpyridinium chloride). The present method was also used to assess metabolic correction in a patient with Hurler's syndrome after treatment by bone-marrow transplantation. This quantitative method surmounts the major technical problems of developing mass screening programs for infants, thus offering the potential for earlier diagnosis and treatment of mucopolysaccharidosis diseases.
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An optimal modification of the patients flow arrangement is offered for more convenient form and methods of the population screening for malignant tumours and precancerous diseases, aided by medical and computer techniques. A scheme of the mass-screening system and principal aspects of technical provision particularly for oncological screening are presented.
The presence in the serum of both cystic fibrosis (CF) homozygotes and heterozygotes of a factor inhibiting the response of lymphocyte lysosome beta-glucuronidase activity to in vitro phytohaemagglutinin (PHA) stimulation is confirmed. Studying lymphocyte beta-glucuronidase activity on PHA stimulation represents a way to confirm CF diagnosis and to screen CF heterozygotes. For technical complexity, however, the method cannot be used for mass screening, but it can be useful for confirming the diagnosis in suspected cases. Relationships between serum factor inhibiting the effect of PHA on beta-glucuronidase, ciliary dyskinesia factor and carboxypeptidase B-like activity are discussed.
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The degree to which quantitative urine cultures and the triphenyltetrazolium chloride (TTC) reduction test can be correlated can be directly related to the species of organism involved, the actual level of bacterial population in the urine and the presence of antibiotics. The influence of these various factors is discussed and it is concluded that, depending upon the group of patients involved, the TTC test will detect 70-90% of cases of significant bacteriuria. The TTC test would appear to be a useful screening procedure in the surveillance of large outpatient populations and in the detection of bacteriuria during pregnancy, considering the difficulty of applying the technique of complete quantitative culture to these groups.
The analysis of the screening stage of follow-up medical technology practice has been carried out. The study tackles the problems of selection of medical programmes of mass periodic medical check-ups, definition of diagnostic informative indices and their biometrology, programme algorithmic control with its preliminary diagnostic decisions, wide use of an individual principle of health status assessment and further organization of check-up flows, building up of technical equipment patterns for prophylactic departments. A two-stage system of technical equipment patterns of prophylactic departments in a city polyclinic is discussed. At the first stage the department should be equipped with compact, cheap, easily transported, safe and simple in operation, high-quality autonomous specialized automated diagnostic complexes. The second stage consists in the development of the data bank formation system proceeding from the examination results within the region assigned to the polyclinic.
Experience with over 6000 Guthrie tests is presented. This test is a screening procedure for phenylketonuria using small amounts of blood spotted on a filter paper which are tested by a bacterial "inhibition assay". Certain technical aspects of the test (e.g. relation between the concentration of phenylalanine in the blood and extent of the bacterial growth zones produced, type of filter paper, size of the blood spot on the paper) were investigated. It was shown that the Guthrie test clearly distinguishes between subjects with normal plasma phenylalanine levels and patients with untreated phenylketonuria.Applications of the Guthrie test in screening a mental hospital population, admissions to a penitentiary and newborn babies are described.
Mass cancer screening is new in France inasmuch as the country has never up to now carried out such a large-scale and wide-reaching public healthcare operation. The organisation of the screening brings up the question of where healthcare is actually heading. Should the community as a whole should have preference over the individual or, on the other hand, should the individual and his or her private life be defended against a faceless community that is becoming more and more demanding? This question is fundamental to all the difficulties that are met when organising mass screenings. There are, of course, certain technical aspects and indicators of effectiveness that are common to all screening campaigns, but there are also wider considerations that must be respected, such as social justice and liberty of both the individual and the community. Anyone who wishes to take advantage of the screening should be free to do so, but the individual must also be free to refuse. Screening must remain voluntary. It is essential to maintain full data secrecy and to provide appropriate training for the doctors involved. It is also of fundamental importance to carry out an assessment of the campaign from a neutral angle. The training issue is crucial, with the doctor's suitability to carry out the test a key factor. Doctors need to be trained to acquire the necessary skills, especially as it will soon become necessary to monitor doctors' competence in the field. An assessment will have to be made not simply of performance but also of doctors' ability to handle a given situation.
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This study was performed to investigate 1) technical modification of Guthrie method for mass screening to detect histidinemia, 2) patients with histidinemia in view of genetic and biochemical aspects, and 3) therapy of histidinemia in newborn infants. Guthrie method was the useful method for mass screening of histidinemia in newborn infants. It is possible to measure blood level of histidine using by Subutilis spore ATTCC 6633 instead of ATCC 6051. Mass screening of histidinemia was done in about 20,000 newborn infants in Hokkaido, and one case of histidinemia, which was first case in Japan found by this method, was observed. In a case of 5 year-old boy with clinical histidinemia, in whom serum histidine level was 12.1 mg/kl, histidase activity of stratum corneum was not detectable, FIGLU and urocanic acid in urine and urocanic acid in sweat were not detected, the half life of histidine at intravenous histidine loading test was too long to measure. But in other case of 13 year-old boy without clinical signs of histidinemia, elder brother of former case, serum histidine level was 4.7 mg/dl, histidase activity was 11% of normal control, excretion of FIGLU and urocanic acid in urine, and urocanic acid in sweat were observed, and the half life of histidine was 5 hours and 50 minutes (normal: 2 hours and 20 minutes). In both cases, Tryptophan absorption and metabolism were not influenced by high level of blood histidine. Therapy with low histidine milk was made in 3 cases of affected infants. When histidine was given orally in dose of 30-35 mg/kg/day, serum histidine level was down to 3-5 mg/dl in a week in all cases, but in one case low proteinemia an anemia were observed. When histidine was orally given in a dose of 40-50 mg/kg/day, serum histidine level was well controlled. In all cases with histidine limited diets, mental retardation and growth retardation were not found.
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EBV (Epstein-Barr virus) serological tests have been used for many years as accessory diagnostic predictors of NPC (nasopharyngeal carcinoma). To date, IF (indirect immunofluorescence) assays still serve as the 'gold standard' for EBV serodiagnosis. However, IF assays are time-consuming, unsuitable for automatic handling and difficult to standardize. This makes their application in mass screening of populations inconvenient. Some of the technical difficulties associated with IF have been overcome by the development of specific ELISAs, but, at present, high sensitivity and specificity cannot be achieved simultaneously by using recombinant protein-based ELISAs, as the diagnostic value of different fragments of EBV in NPC is different. In an attempt to determine a suitable recombinant EBV protein for diagnostic purposes, fragments of EBV VCA (viral capsid antigen) and EBNA1 (Epstein-Barr-virus-encoded nuclear antigen 1) genes were expressed in the methylotrophic yeast Pichia pastoris, and a novel ELISA was established using P. pastoris-expressed VCA-BALF4 [aa (amino acids) 287-623; the BALF4 gene encodes the EBV glycoprotein gp125], EBNA1 (aa 390-641) and VCA-BFRF3 (the gene BFRF3 encodes a viral structural capsid protein or tegument protein VCA p18) proteins. Serum samples were collected from patients with NPC and healthy controls and were tested using this ELISA. The sensitivity of VCA-BFRF3, VCA-BALF4 and EBNA1 tests in the NPC sera were 65.0 (195/300), 76.3 (229/300) and 81.4% (244/300) respectively, whereas the specificity of normal individuals were 92 (460/500), 96 (480/500) and 95.8% (479/500). The optimum combination is VCA-BALF4 plus EBNA1, which identified 90.3% (271/300) of the NPC patients and had a specificity of 92.8% (464/500) for normal individuals. The results obtained from the evaluation of three antibodies to EBV as markers for detecting NPC suggests that a combination of EBNA1 (aa 390-641) and VCA-BALF4 (aa 287-623) assays would give better results in screening for NPC.