Inactive renin in infants and children: evidence for its physiological response to orthostasis in children.

The aim of this work was to investigate the presence of inactive renin (IR) in plasma of normal infants and children and nephrectomized children and to study the plasma IR response to stimulation of the renin-angiotensin system (orthostasis) in children. The study was performed in 10 normal infants (2 days to 1 yr old), 28 normal children (1-15 yr old), 8 nephrectomized children (8-14 yr old), and 7 normal adults (20-40 yr old). IR was calculated as the difference in renin activity in trypsin-treated (1500 micrograms/ml) plasma, e.g. total renin (TR), and in untreated plasma, e.g. active renin (AR). IR was not detectable in most infants in the supine position, but their AR values were high (8.8-30 ng/ml X h). Moreover, in some of these infants, trypsin appeared to degrade renin activity, since TR values were lower than AR values. IR was detectable in 3 infants and 27 children, but their AR values were in a lower range (0.3-10 ng/ml X h). Trypsin degradation of renin activity was not found in either children or adults. With increasing age (2 days to 40 yr), AR decreased while IR and the IR to TR ratio increased significantly (P less than 0.001). A significant (P less than 0.001) inverse relationship was found between the IR and AR values of subjects 2 days to 40 yr old. IR was detectable in all nephrectomized children and represented 25% of normal values, while AR was undetectable (less than 0.1 ng/ml X h). In children in the upright position, IR decreased and AR increased significantly (P less than 0.001) in a reciprocal manner. TR did not change. These data suggest 1) that trypsin degradation of renin activity and absence of trypsin-activated IR are specific to infants with high AR levels, and 2) that IR might be activated in vivo into AR, especially after changes in position in children. IR could be a prorenin playing a physiological role in children.

Use of artificial intelligence in analytical systems for the clinical laboratory.

OBJECTIVE: To consider the role of software in system operation, control and automation, and attempts to define intelligence. METHODS AND RESULTS: Artificial intelligence (Al) is characterized by its ability to deal with incomplete and imprecise information and to accumulate knowledge. Expert systems, building on standard computing techniques, depend heavily on the domain experts and knowledge engineers that have programmed them to represent the real world. Neural networks are intended to emulate the pattern-recognition and parallel processing capabilities of the human brain and are taught rather than programmed. The future may lie in a combination of the recognition ability of the neural network and the rationalization capability of the expert system. In the second part of this paper, examples are given of applications of Al in stand-alone systems for knowledge engineering and medical diagnosis and in embedded systems for failure detection, image analysis, user interfacing, natural language processing, robotics and machine learning, as related to clinical laboratories. CONCLUSION: Al constitutes a collective form of intellectual property, and that there is a need for better documentation, evaluation and regulation of the systems already being used widely in clinical laboratories.

Evaluation of Roche fructosamine test: use for diabetic patient monitoring.

A fructosamine assay using commercially available reagents on an IL Multistat III centrifugal analyser was evaluated. Within- and between-batch precision were less than 4% (CV). Results were similar using serum or oxalated plasma, but were 5% lower than those using sodium heparinate. We compared serum fructosamine and Hb A1c results in insulin-dependent and non-insulin-dependent diabetics: serum fructosamine correlated with Hb A1c (r = 0.80) and gave at least as good a separation of patients from normal controls as did Hb A1c.

Technologies for implementation of quality assurance in the clinical laboratory.

To face the rapid evolution of the clinical laboratory activity from sample analysis towards an in-vitro diagnostic network, a Total Quality Management system must be implemented by laboratory professionals. Technological advances make it possible to introduce new tools and techniques for many issues surrounding the analytical process, as has happened for analysis automation and laboratory management. Preanalytical steps should benefit from extended traceability, using new identification devices such as electronic labels. This may promote the improvement of sample handling in this phase, such as during transportation or centrifugation. Another field is the expansion of metrology. Many factors can now easily be controlled in the clinical laboratory. New reliable automated systems are available to evaluate the performance of pipetting devices. Autonomous miniaturized recorders and probes connected to monitoring softwares allow traceable temperature monitoring. In this paper, some examples are presented to illustrate how technical solutions can support the implementation of Quality Assurance in the clinical laboratory.

Approach to automation in immunohistochemistry.

The introduction of immunochemical techniques into the routine pathology laboratory has significantly expanded the capabilities of the pathologist in diagnostic procedures. Immunostaining represents a powerful diagnostic tool in the identification and localization of cellular antigens, in paraffin sections, frozen tissues and cell preparations. The labeled-streptavidin-biotin method provides excellent sensitivity and performance. This multistep procedure includes: incubation of the slide with primary antibody, reaction with the biotinylated secondary antibody, binding with an enzyme conjugated streptavidin and revelation with chromogen substrate. Evaluation of the finished product is directly dependent on the quality of the technique. The main critical steps of this manual method are reagents application, incubation times and rinsing. These steps could be accessible to automation. Automation in immunohistochemistry could guarantee a continuous quality of labelling in improving standardisation, optimization and traceability of operations. The required qualifications are analytical flexibility, low cost, walkaway operation, user-friendly interface and biosafety.

Comparative evaluation of automated systems in immunohistochemistry.

From October 1995 to March 1997, we evaluated five instruments for immunohistochemistry automation: The Techmate 500 (Dako), the Ventana 320/ES (Ventana), the Optimax Plus (Biogenex, Menarini), the Cadenza (Shandon), and the Immunostainer (Coulter-Immunotech). The aim of the evaluation was to compare the different instruments to the manual method in our laboratory which performs about 17 500 immunohistochemistries per year. PRINCIPLE: Three instruments use flat immunohistolabelling, the others use capillarity immunohistolabelling. ANALYTICAL FLEXIBILITY: we compared the number of protocols per run, the multitask capability, and the ability to adapt manual protocols to the different instruments. To compare the management of the workcell, we used the level of selfchecking, reagent and slides preparation time, and waste management. We measured the duration of the different steps of the process, the throughput in slides/h, and the operator working time per slide. Compared to the manual method, the total cost for reagents and consumables was found to be multiplied by 3 for the Ventana which is a closed system, by 2 for the Techmate, by 1.5 for the Optimax and Cadenza, and identical for the Immunostainer. CONCLUSION: Automation of immunohistochemistry is now possible; the Optimax is still in development, small laboratories will appreciate the Cadenza, laboratories requiring a high flexibility with many protocols will use the Immunostainer open system, laboratories with few technicians will prefer the Ventana closed instrument, now available as the Nexes modular system.

International Federation of Clinical Chemistry. Use of artificial intelligence in analytical systems for the clinical laboratory. IFCC Committee on Analytical Systems.

The incorporation of information-processing technology into analytical systems in the form of standard computing software has recently been advanced by the introduction of artificial intelligence (AI) both as expert systems and as neural networks. This paper considers the role of software in system operation, control and automation and attempts to define intelligence. AI is characterized by its ability to deal with incomplete and imprecise information and to accumulate knowledge. Expert systems, building on standard computing techniques, depend heavily on the domain experts and knowledge engineers that have programmed them to represent the real world. Neural networks are intended to emulate the pattern-recognition and parallel-processing capabilities of the human brain and are taught rather than programmed. The future may lie in a combination of the recognition ability of the neural network and the rationalization capability of the expert system. In the second part of this paper, examples are given of applications of AI in stand-alone systems for knowledge engineering and medical diagnosis and in embedded systems for failure detection, image analysis, user interfacing, natural language processing, robotics and machine learning, as related to clinical laboratories. It is concluded that AI constitutes a collective form of intellectual property and that there is a need for better documentation, evaluation and regulation of the systems already being used widely in clinical laboratories.

Blood chemistry by disposable ISE with the Chempro 500 system.

Potentiometric measurements are usually done with multiple determination electrodes. Disposable electrodes were first introduced on the Ektachem systems by Kodak with the concept of differential potentiometric measurement between the specimen and a reference fluid delivered on two parts of a single slide. In the Chempro 500 system a calibrating solution and the specimen are sequentially measured by the same potentiometric system with a classic reference electrode and selective electrodes present on a disposable device in various combinations. This device is connected to a compact analyzer with a microprocessor, a display and a printer. The authors evaluated the analytical performance of the Chempro 500 on whole blood, plasma and serum specimens over a two months period. Results and practicability are discussed and compared to those of reference instruments, according to requirements of decentralized analysis.

International Federation of Clinical Chemistry. The expanding role of robotics in the clinical laboratory.

Increasing numbers of robots are going to be employed industrial chemical laboratories. Most of these will be used to reduce the monotonous tasks of sample preparation, to minimize human exposure to dangerous environments or to carry out huge numbers of repetitive experimental procedures. For example, looking for the most effective condition or combination in chemical synthesis or the best microorganism in a large number of cultures. In the clinical laboratory the situation is slightly different and robotics is not so widely applied in clinical laboratories, but there is a definite trend to employ robots or robotic systems both to reduce labor volume and exposure of employees to possible biohazards and to help get more precise and correct results. These needs will be hard to fulfill via the usual automated devices and especially when adequate devices are not available. Specially designed machines will have to be produced to satisfy these demands and robotics will play a part. Finally we need to evaluate the effectivity of introduction of robotics in terms of economy, strategy, biosafety and other aspects. Typical examples of implementation of robotics in the clinical laboratory are transportation of specimens, front-end automation of sample preparation, separation and aliquotting as well as selected processes in a large scale automation systems. As described previously, robots that are commercially available now, are not intelligent enough to be easily handled by personnel who are not trained for robotics. There is a need for personnel dedicated to robotics who join the project from the very beginning of the plan and who can maintain the system properly.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evaluation of enzyme modules of the Beckman Astra 8]. / Evaluation des modules enzymes de l'Astra 8 Beckman.

We evaluated the analytical performances of the Beckman Astra 8 enzyme analyser which allows the determination of the 6 enzymes (creatine kinase, Aspartate aminotransferase, Alanine aminotransferase, gamma glutamyl-transferase, lactate dehydrogenase, Alcaline Phosphatases), in a same serum sample with only two modules. We compared the results obtained in the healthy and pathological subject's sera with those given by a centrifugal analyser IL Multistat III (Delhomme) using reagents and temperature recommended by SFBC (Société Française de Biologie Clinique). Instrument utilization is greatly helped by various alarms and diagnostic programmes. Results for emergency and routine determinations accord with those announced by the manufacturer and those required for a modern enzymatic analyzer.

International Federation of Clinical Chemistry (IFCC): systematic top-down approach to clinical chemistry.

This paper introduces a systematic approach to organizing the discipline of clinical chemistry. The approach is called a top-down, systems approach because it starts at the top with the most general concepts and works down through less general concepts to the most specific details and techniques. The hypothesis is that the discipline can be organized into hierarchical levels of functional processes and operational approaches to those processes. The functional processes represent what clinical scientists do; the operational approaches represent how they do it. Because functional processes change little, if at all, with time, they are use to develop a stable infrastructure or framework for the discipline. That infrastructure is then used to organize and understand operational approaches that tend to change rapidly with time in response to technological advances. This paper begins with the most general functional processes and then uses selected examples of the more general functions to illustrate lower hierarchical levels of functional processes and operational approaches.

[Ionized calcium. An essential parameter for the study of calcium metabolism]. / Le calcium ionisé. Un paramètre essentiel pour l'étude du métabolisme calcique.

Calcium ions in plasma are either free (ionized calcium) or bound to protein and small anions. Ionized calcium is the physiologically active fraction. Several factors have recently been combined to change the measurement of ionized calcium from a specialized to a routine test. Reliable instrumentation, easy to maintain, is now available with simultaneous pH measurement. This paper focuses on both the analytical consideration required to perform reliable laboratory measurements and the clinical situations where ionized calcium has proved to provide a substantially different clinical interpretation than the measurement of total calcium.

[Determination of pH in the body: methodologic review]. / La détermination du pH dans l'organisme: rappels méthodologiques.

The maintenance of a defined free H+ concentration within narrow limits is a prerequisite and feature of living organisms. In recent years the different disciplines of biological science have made considerable progress in the elucidation of the mechanisms involved in pH homeostasis. Recent advances have occurred also in the field of pH measurement. This review focuses mainly on the modern instruments for pH and blood gas analysis. The techniques of intracellular pH currently in general use are described together with some of the techniques for determination of pH in subcellular compartments.