[Future development in clinical chemistry (author's transl)].
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Current trends in development of medicine related to advances in the technological sciences are discussed. Possibilities of cooperation of medicine and technology are reviewed, and ways of modernizing medical science and practice by utilizing achievements in this and other countries are pointed out.
alpha 1-Antitrypsin is the most abundant of several serum protease inhibitors. Its deficiency is associated with an increased incidence of emphysema in adults, jaundice in newborns, and childhood cirrhosis. We describe an automated functional assay for the Instrumentation Laboratory's Multistat III Microcentrifugal Analyzer with N-alpha-benzoyl-DL-arginine-p-nitroanilide as trypsin substrate. The assay is standardized in terms of moles of trypsin active sites inhibited per liter of serum, by use of a chromogenic titrant for trypsin active sites, p-nitrophenyl-p'-guanidinobenzoate. The method is rapid, precise, and independent of trypsin supplier, and results correlate well with those by a manual chromogenic and a nephelometric assay.
Methods for the measurement of the functional concentration of AT III, PLG, and FBG have been developed for the Du Pont aca discrete clinical analyzer. These methods are fully automated, provide excellent reproducibility, and compare favorably with existing methodologies. The availability of these and future coagulation assays on this automated analyzer will provide the hospital laboratory with a reliable means for evaluating hemostatic function. In addition, excellent method reproducibility and use of defined reference standards should significantly contribute to the standardization of coagulation methods.
The Singapore Blood Transfusion Service (BTS) collects, processes and distributes blood and blood components to all hospitals. It also provides clinical and diagnostic haematological services to the hospitals. Blood donation is based on an entirely voluntary system. Blood donor incentives include a scheme of medical benefits for regular blood donors. Major advances in the 1960s include the introduction of disposable plastic blood packs for blood collections which permitted blood components to be prepared in a closed system. The development of a mobile blood collection service has enabled many more donor sources to be tapped. Hepatitis B Surface Antigen (HBsAg) screening of blood donors was introduced in 1973 as local studies showed that HBsAg positive blood was associated with a high risk of hepatitis. HBsAg positive donors are permanently excluded from the donor panel. BTS provides reference services for Immunohaematology, Coagulation problems, a clinical and diagnostic haematology service and a haemophilia centre. A computerized system of blood donor call up and the introduction of automation in the transfusion and haematology laboratories have helped BTS cope with an increasing volume of work and at the same time restrain manpower increases.
CBC traditionally stands for complete blood count. It represents a profile of tests rather than a single test, and over the years it has been given several names, including hemogram, Coulter profile, blood cell profile, and hematology profile. The number and type of tests included in the profile has also changed over time and among laboratories, depending primarily upon capabilities of the automated analyzers used to perform the profile test.
A new PT reagent based on recombinant human tissue factor and synthetic phospholipids (phosphatidyl choline and phosphatidyl serine) with defined fatty acid side chains was calibrated against BCT/253 and CRM 149R. A small but consistent bias in the International Sensitivity Index (ISI) value was obtained using either the human or rabbit brain reference material. ISI values were around 1.0 or slightly lower depending on the respective instrument. Mixing studies with factor deficient plasmas showed a high factor sensitivity especially for factor VII as compared to commercial rabbit brain or human placenta thromboplastin. In an international field trial the reagent was tested using fully or semi automated Electra coagulometers in 4 different laboratories. Results with normal samples were in excellent agreement among the different laboratories. Mean values were 10.9, 10.9, 11.0, 11.2 s with a range of 9.5 to 12.5 s. Results of males and females were not different. In patients with liver disease very similar PT activities were found as compared to sensitive rabbit brain or human placental thromboplastins. In normals and patients with oral anticoagulation INR values correlated very well against BCT (r = 0.98, regression line y = -0.07 + 0.9 x). The distribution of samples was linear over the whole range. In the comparison against sensitive rabbit brain thromboplastin or human placental thromboplastin similar correlations were found. In a few cases higher INR values were observed for the recombinant reagent especially in patients with intensive treatment. Factor assays in those patients showed at least the strong reduction of one vitamin K-dependent coagulation factor.(ABSTRACT TRUNCATED AT 250 WORDS)
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Computer-based genetical register "GENREG" allows to carry out a prophylactic medical examination for families with children, having hereditary diseases, multifactorial pathology and congenital developmental defects of various nature, and also epidemiological examination. Automated consultative system for pre-laboratory diagnosis of genetically determined diseases after the phenotypical manifestations "DIAGEN" allows to identify up to 1200 nosologic units; diagnostic value (or weight) of the signs according to physician's evaluation is taken into consideration. The system sorts out a narrow differential-and-diagnostic row and information about specific laboratory and functional changes for every selected diagnosis. Efficiency of the system is over 94% (after the next laboratory findings). The results of computer diagnosis and final physician's diagnosis, and also questionnaire of a child are stored in archives (files) of the "DIAGEN" system. Both of the systems are realized on PC/AT IBM-compatible computer.
The primary goal of an ambulatory monitoring of motor activities (AMMA) system is to document the occurrence of random and spontaneous motor activities (e.g., sitting, lying, standing, walking, running, etc.) of the ambulatory subject in natural environmental circumstances. Much progress has been made in recording fidelity, reduction in energy requirement, fixation of the accelerometers, equipment size and weight, memory capacity and data acquisition. At present, our laboratory is interested in developing an automated off-line AMMA-signal analysis system. The system has to take care of activity (wave) detection, recognition of onsets and endpoints of the various activities (waves), and computation of a set of relevant clinical parameters (e.g., total walking time, number of times rising from a chair, etc.) from long-term recorded data. Two methods are currently being used for computerizing the off-line analysis system: using an artificial neural network and using a set of selected features extracted from the input data. The present paper is aimed at the latter method. The method was successfully applied to long-term recorded data sets of eight male amputees and three other subjects. The primary results indicate that the method is a potentially useful too to computerize the off-line analysis system.
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From January 1986 through December 1995, 4,143 cases of hepatitis A virus (HAV) infection were reported in Wisconsin. The annual hepatitis A incidence remained stable from 1986 through 1988, with a mean annual rate of 4.7 cases per 100,000 (endemic HAV incidence rate). During 1989-1993, the incidence of HAV infection increased with a peak in 1992 of 19 cases per 100,000 population. A large foodborne outbreak (1992) and community wide outbreaks among African American residents (1989-1993) and Native Americans residents (1991) were associated with these high rates of HAV infection. The community wide outbreaks affected different groups: among African Americans, incidence rates were highest in young adults 15-34 years old; among Native Americans rates were highest in children 5-14 years old. Approximately 2,343 (57%) patients had no apparent risk factor (e.g., international travel, contact with person with HAV infection) for acquiring HAV infection. Factors limiting control of HAV infection in Wisconsin included poor reporting by laboratories (only 19% of all reported cases were independently reported to the Wisconsin Division of Health by a laboratory and fewer than 50% of these reports were from private laboratories), incomplete reporting by Wisconsin physicians or designees (74% of cases confirmed in Wisconsin laboratories were reported in 1995), failure to submit follow-up case report forms (14% of cases), and a prolonged interval between diagnosis and follow-up (> or = 15 days for 610 cases). Efforts should be enhanced to improve the reporting of cases of HAV infection by private laboratories, particularly through the use of automated electronic reporting.
The PAPNET-system is a current example of automated technological progress in the pathological laboratory field. As the first Department of Pathology in Denmark, we have tested the applicability of this semi-automatical screening system in screening against cervical cancer. 3000 prospectively selected cervical smears were entered into the project. 1500 of these were first prescreened by the use of PAPNET and the negative slides were then manually rescreened. The remaining 1500 slides consisted of manually screened smears diagnosed as negative or inadequate. They were subsequently rescreened by the use of PAPNET. We only found one false negative smear in each group. Compared with histological follow-up the diagnoses CIN 1-3 were histologically confirmed in both groups. The PAPNET-assisted screening of cervical smears is faster, more valid and less fatiguing than the conventional screening method. Nevertheless, our results show no diagnostic quality improvement by the use of PAPNET. This is probably due to a strict screening procedure and a limited work load of a maximum of about 40-50 slides per cytotechnologist a day in our laboratory.
A study was designed to assess the impact of the VITEK 2 automated system and the Advanced Expert System (AES) on the clinical laboratory of a typical university-based hospital. A total of 259 consecutive, nonduplicate isolates of Enterobacteriaceae members, Pseudomonas aeruginosa, and Staphylococcus aureus were collected and tested by the VITEK 2 system for identification and antimicrobial susceptibility testing, and the results were analyzed by the AES. The results were also analyzed by a human expert and compared to the AES analyses. Among the 259 isolates included in this study, 245 (94.6%) were definitively identified by VITEK 2, requiring little input from laboratory staff. For 194 (74.9%) isolates, no inconsistencies between the identification of the strain and the antimicrobial susceptibility determined by VITEK 2 were detected by the AES. Thus, no input from laboratory staff was required for these strains. The AES suggested one or more corrections to results obtained with 65 strains to remove inconsistencies. The human expert thought that most of these corrections were appropriate and that some resulted from a failure of the VITEK 2 system to detect certain forms of resistance. Antimicrobial phenotypes assigned to the strains by the AES for beta-lactams, aminoglycosides, quinolones, macrolides, tetracyclines, and glycopeptides were similar to those assigned by the human expert for 95.7 to 100% of strains. These results indicate that the VITEK 2 system and AES can provide accurate information in tests for most of the clinical isolates examined and remove the need for human analysis of results for many. Certain problems were identified in the study that should be remediable with further work on the software supporting the AES.
As part of the dramatic changes associated with the need for preparing compound libraries in pharmaceutical and agrochemical research laboratories, industry searches for new technologies that allow for the automation of synthetic processes. Since the pioneering work by Merrifield polymeric supports have been identified to play a key role in this field however, polymer-assisted solution-phase synthesis which utilizes immobilized reagents and catalysts has only recently begun to flourish. Polymer-assisted solution-phase synthesis has various advantages over conventional solution-phase chemistry, such as the ease of separation of the supported species from a reaction mixture by filtration and washing, the opportunity to use an excess of the reagent to force the reaction to completion without causing workup problems, and the adaptability to continuous-flow processes. Various strategies for employing functionalized polymers stoichiometrically have been developed. Apart from reagents that are covalently or ionically attached to the polymeric backbone and which are released into solution in the presence of a suitable substrate, scavenger reagents play an increasingly important role in purifying reaction mixtures. Employing functionalized polymers in solution-phase synthesis has been shown to be extremely useful in automated parallel synthesis and multistep sequences. So far, compound libraries containing as many as 88 members have been generated by using several polymer-bound reagents one after another. Furthermore, it has been demonstrated that complex natural products like the alkaloids (+/-)-oxomaritidine and (+/-)-epimaritidine can be prepared by a sequence of five and six consecutive polymer-assisted steps, respectively, and the potent analgesic compound (+/-)-epibatidine in twelve linear steps ten of which are based on functionalized polymers. These developments reveal the great future prospects of polymer-assisted solution-phase synthesis.
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