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[Quality specifications and allowable standards for validation of methods used in clinical biochemistry].

The purpose of this work is to provide, for a large number of analysis in the field of clinical biochemistry, appropriate criteria for the evaluation of the performance of in vitro diagnostic methods. Based on a first set of data established in 1986 and the experience cumulated by organisers in charge of internal and external quality assessment surveys, an expert group has proposed acceptable limits for a large list of analysis (n = 116). Data are reported and presented in tables divided into 7 chapters including: general biochemistry, enzymes, proteins, tumour markers, hormones, drugs (and toxic), and urinary analysis. For each analysis are given: analytical and reference ranges, three concentration levels for control specimens to be used during evaluations and the range of values within which they can be chosen, reproducibility and repeatability limits expressed as CV%. Maximal tolerable systematic error and inaccuracy are given for control and biological specimens and compared to those obtained using a reference or validated method. These data are essential for evaluations using the protocol designed by the SFBC and can serve as quality criteria for the choice and validation of in vitro diagnostic systems.

Biochemistry↗

[The contribution of the Nobel laureates to biochemistry and molecular biology].

The Nobel Prize winners works are considered and analyzed. Main attention is paid to the works devoted to biochemistry or problems related to biochemistry. The most prominent biochemical investigations are considered in detail. In some cases it is given the history and chronology of important biochemical discoveries. The survey is devoted due to the 170th anniversary of birth of Alfred Bernhard Nobel--a famous scientist and businessman, the founder of the Nobel Prizes.

Biochemistry↗

[Retrospective analysis of the effect of Ukraine and USA research interrelations on the development of sport biochemistry in the XX century].

This review highlights some of the important developments in Sport Biochemistry and relates these endeavors to the current understanding of muscle biochemistry and function. Attempts have been made to establish some scientific links involved in the evolution of such research, in particular the influences shared by scientists working in some premier institutions in Ukraine and the USA in the 20th century. Research initiated in the United States by Sutherland lead to further Ukrainian investigations that aided in the understanding of the role cAMP and cAMP-dependent protein kinase in muscle metabolism during exercise. Topics covered include Palladin's pioneering research on muscle creatine in Ukraine at the beginning of the 20th century, Russian program on creatine supplements in the 1970s-1980s and its implementation at Olympic games.

Biochemistry↗

[Confirmation of pipetting performances for fully-open automatic biochemistry analyzers].

This paper introduces a kind of evaluation method in pipetting performance on new fully automated biochemistry analyzers by experiments. The performance of sample pipetting volume is confirmed by dye dilution method, the performance of reagent pipetting volume and dummy volume is done by weighing method. Meanwhile, researches and comparative researches on dummy volumes in different conditions have been made, providing valuable reference for clinical applications of automatic biochemistry analyzers.

Automation, Laboratory↗

[Biochemistry for the benefit of humanity (practical achievements of my scientific work)].

Science unites theory and practice, but theory is always in advance. Even our works (mentioned above) which are also important for practice and were awarded the State prizes could not be made without preliminary theoretical investigations. It should be said that our works with elaborated methods of therapy and drugs to treat chronic alcoholism, drug addiction, leucosis are rather of theoretical than of practical importance. Some our works which proved that carbon dioxide is the basis of life are also of especially great theoretical value. The paper deals with the investigations devoted to the problems of biochemistry in cattle breeding (the raising of fat content in milk; elaboration of the efficient method of fodder ensilage; raising of milk yield using the drug "Karboxilin"; development of the methods of isolation of crystalline glucose-oxidase and catalase used for clarifying blood) as well as to the problems of biochemistry in medicine (creation of the drug "Microcid", antileucosis drug "Corectin", drugs "Medichronal" and "Medicit" for treating alcoholism and drug addiction, drug "Namacit" for hindering the organism aging). Great attention is given to the problem of relations between the theoretical conception concerning the importance of CO2 in vital activity of human and animal organism and production of new drugs.

Agrochemicals↗

Teaching human genetics in biochemistry by computer literature searching.

We describe a new user-intense-learning experience that incorporates the teaching of clinical and research applications of human genetics in biochemistry while training first-year medical students to develop skills in computer access to the literature. Human genetics was incorporated into the biochemistry curriculum by providing each student with experience in on-line literature searching in MEDLINE, using Grateful Med, in order to write an abstract about a specific inherited biochemical disorder. We stressed the need for the students to obtain current information in order to understand and interpret the rapidly changing field of human genetics. We taught the students that the most efficient method of obtaining such information was by searching the medical literature via computer.

Biochemistry↗

[Bibliography in clinical biochemistry: analysis of the literature beginning with a computerized data bank].

In which fields of medicine, and in which journals does one publish the majority of articles which concern clinical biochemistry? We are trying to reply to this question by studying the basis of the biographical data developed in our laboratory, proceeding from the perusal of 290 journals and representing 16 802 articles stored from 1978 to 1983. Clinical Chemistry is the most important journal as far as number of articles is concerned, but less articles arises from journals of clinical biochemistry than from those of general medicine and internal medicine. The theme "lipoproteins and atherosclerosis" is the most prolific. It is studied in more detail. In a general way, a theme is rarely covered in a satisfactory manner with 5 journals or less. We think that, faced with the great dispersion of the same theme across the medical literature, our results will help the biologist to make a choice both from the point of view of contract and biographical research.

Arteriosclerosis↗

The guided design strategy in the biochemistry laboratory.

This article describes a nontraditional biochemistry laboratory course for first-year dental students. The course consisted of two laboratory exercises adapted to the guided design strategy and a short research project. The major advantage of the guided design laboratories was subjectively determined to be the development of problem-solving skills, which students previously enrolled in a traditional laboratory course seemed to lack. Students exposed to the guided design approach successfully applied these skills when performing their research projects. These students also reflected a better understanding of the biochemical principles encountered. The major disadvantages were the great amount of faculty time required to prepare the guided design materials and the reduced amount of subject matter covered. Student evaluation scores of the new laboratory program showed dramatic improvement over those for the traditional laboratories. In addition, students' attitudes toward the new biochemistry laboratories were more positive than those exhibited in the traditional course.

Biochemistry↗

[Interdepartmental division of functional biochemistry].

The Department of Functional Biochemistry was organized at the Institute of Biochemistry of the National Academy of Sciences of Ukraine in 1990. Since that time the collaborators of the Department develop the aldehyde hypothesis of pathogenesis of chronic alcoholism and new high effective methods of its treatment; they have found certain adaptation mechanisms arising in the organism under stress states and pathogenetic mechanisms of formation and development of the radiation encephalopathy in victims of the accident at the Chernobyl NPP. The department researchers have published 92 works.

Academies and Institutes↗

The development and evaluation of an adaptable computer aided instruction(CAI) program for acquiring problem solving skills in biochemistry on the WWW: The "BioChem Thinker".

BioChem Thinker is a CAI program that was developed to enhance problem solving skills and ability to integrate knowledge in biochemistry for medical and dental students. The program runs on a WWW browser. BioChem Thinker is adaptable, it enables the teacher to create a new problem solving assignment, or edit existing assignments without in-depth knowledge of computer programming. This provides teachers with greater independence and flexibility so as to be able to adapt the program to their own course requirements. The program was implemented and evaluated in the 3rd year biochemistry course of The Hebrew University-Hadassah Medical School. The tool used to develop Biochem Thinker can be utilized to develop similar CAI in other biomedical areas.

Biochemistry↗

[The molecular logic of life--a half century of development in biochemistry and molecular biology].

Tremendous progress has been made in biochemistry and molecular biology during the past fifty years which substantially changed our understanding of fundamental processes of life. The progress has been especially made in the field of molecular genetics, biomembranes, cell signaling and bioenergetics. Based on the analysis of the genetic information and human genome organization and function, our understanding of health and disease is rapidly changing: the era of Molecular Medicine has emerged. The discoveries in biochemistry and molecular biology are beginning to migrate from the research laboratories into clinical practice introducing fundamentally new methods in diagnostics and therapy.

Biochemistry↗

First-trimester screening for trisomy 21 in twin pregnancy: does the addition of biochemistry make an improvement?

OBJECTIVE: To evaluate the effectiveness of the addition of first-trimester biochemistry to fetal nuchal translucency (NT) measurement in the Combined Test when screening for trisomy 21 in twin pregnancies. METHODS: Maternal serum free beta-hCG and PAPP-A were determined at 8 to 12 weeks and fetal NT was measured at 11 to 14 weeks. The individual risks were estimated for each of the fetuses using both NT screening alone and the Combined Test. An invasive diagnostic procedure was offered when the risk was 1:250 or over in either one of the fetuses. In the first period, only the results of NT screening were clinically applied. After previous analysis, the Combined Test was introduced into clinical practice. RESULTS: In the two-and-a-half-year study period, a complete follow-up was obtained in 100 twin pregnancies. Three fetuses (two pregnancies) with trisomy 21 were detected by both methods. The false-positive rate achieved by NT screening (14.3% of pregnancies and 8.6% of fetuses) was substantially reduced when first-trimester biochemistry was added in the Combined Test (5.1% of pregnancies and 3.6% of fetuses). CONCLUSION: The Combined Test appears to maintain the detection rate achieved by NT screening for trisomy 21 in twin pregnancies, but false-positive rates and invasive diagnostic procedures are reduced.

Adult↗

The impact of correcting for smoking status when screening for chromosomal anomalies using maternal serum biochemistry and fetal nuchal translucency thickness in the first trimester of pregnancy.

OBJECTIVES: To evaluate the influence of cigarette smoking status on maternal serum free beta-hCG, PAPP-A and fetal nuchal translucency (NT) thickness at 11 to 14 weeks of gestation in a large cohort of women screened prospectively for chromosomal anomalies. METHODS: Information on maternal cigarette smoking status, maternal age, maternal serum biochemical marker levels and fetal NT were collected from the prenatal screening computer records in two OSCAR screening centres. Data was available from 32,730 unaffected pregnancies and from 124 with Down syndrome. Statistical analysis of the marker levels in the smoking and non-smoking group were carried out. The impact on false-positive rate of correcting for smoking status was assessed from a modelling exercise. RESULTS: Prevalence of smoking was significantly affected by maternal age with an overall incidence of 11.5%, which varied from 35% in women under 20 to 7% in women over 35. In the unaffected population, the median free beta-hCG MoM was significantly lower in the smoking group (0.97 vs 1.00) as was that for PAPP-A (0.84 vs 1.02). The standard deviation of the log(10) MoM free beta-hCG was lower in the smoking group and that for PAPP-A was higher in the smoking group. The difference in median marker levels did not seem to be related to the number of cigarettes smoked per day. In the group with Down syndrome, the median MoM free beta-hCG was not significantly different in the smokers (1.69 vs 1.86) as was that for PAPP-A (0.53 vs 0.57). Fetal delta NT was not significantly different in the unaffected smokers (0.11 vs 0.0 mm) or in those with Down syndrome (1.96 vs 2.25 mm). In the smoking group, when screening using maternal serum biochemistry and age alone, the false-positive rate was 6.17%, compared to 4.67% in an age-matched group of non-smokers. Correcting for smoking status by dividing the measured MoM by the median found in the smoking group resulted in the false-positive rate falling to 4.40%. When screening using NT, maternal serum biochemistry and age, the false-positive rate in smokers was 4.48%, which reduced to 3.46% after correction-in line with the 3.76% in the non-smoking group. The impact on detection rate was too small to be accurately measured. CONCLUSIONS: The impact of smoking on first-trimester biochemical marker levels does not seem to be dose related. Whilst correcting first-trimester biochemical markers for maternal smoking status has little impact at the population level for detection rates, a considerable reduction in false-positive rate can be achieved, reducing the level to that seen in non-smokers. However, the effect on the individual patient-specific risk can be substantial and could certainly make a difference to the patient's decision on whether to have an invasive test.

Adult↗

First-trimester screening for trisomy 21 combining biochemistry and ultrasound at individually optimal gestational ages. An interventional study.

OBJECTIVE: To assess the effectiveness of the Combined Test in the prenatal detection of trisomy 21 in the general pregnant population using a new timing for the screening approach. METHODS: First-trimester maternal serum biochemical markers (pregnancy-associated plasma protein-A and free-beta hCG) were determined in maternal serum at 7 to 12 weeks. Fetal nuchal translucency and gestational age were assessed at the 10- to 14-week ultrasound scan. A combined risk was estimated and delivered to the women the same day. When the risk was 1:250 or above, chorionic villus sampling was offered. RESULTS: Mean gestational age at biochemistry was 9.4 weeks, being 12.3 at ultrasound. In the 2780 studied pregnancies with a complete follow-up, observed detection rates were 88% (7/8) for trisomy 21 and 75% (3/4) for trisomy 18, with a 3.3% (92/2765) false-positive rate. CONCLUSION: The Combined Test, assessing biochemistry and ultrasound at individually optimal ages in the first trimester, showed an 88% detection rate for trisomy 21 with a remarkably reduced false-positive rate (3.3%).

Adolescent↗

The potential of fluorinated surfactants in membrane biochemistry.

Detergents are important reagents in membrane biochemistry. Since each membrane system studied places different demands on the detergent in terms of desirous physicochemical properties, detergents new to biochemistry must continuously be sought. Ammonium perfluorooctanoate (APFO) was investigated, as representative of fluorinated surfactants, in terms of its suitability as a "biological detergent." It did not interfere with the Markwell modification of the Lowry procedure at detergent concentrations of up to 2% (w/v). Critical micellization concentration (cmc) values (0.013-0.0275 M) for this detergent were determined in a number of buffers of biological interest. It was demonstrated that the detergent can be removed by dialysis, albeit slowly. This slow removal may be particularly useful for reconstitution/crystallization studies. Solubilization studies on several membrane systems containing the proteins listed (the major protein of the membrane sector of the vacuolar H(+)-ATPase (16 kDa protein); photosystem II; equine herpes virus (EHV) envelope proteins) indicate that it is a potent solubilizing agent, likely to enhance the yield in cases where solubilization has already been demonstrated, and, in other cases, to solubilize proteins formerly recalcitrant to solubilization. The removal of APFO from solubilized 16-kDa protein by means of Extracti-Gel D resin as a means of exchanging detergents quickly and with a minimum requirement for second detergent was investigated.

Caprylates↗

Biochemistry of chitin synthase.

This article compiles the papers dealing with the biochemistry of chitin synthase (CS) published during the last decade, provides up-to-date information on the state of knowledge and understanding of chitin synthesis in vitro, and points out some firmly entrenched ideas and tenets of CS biochemistry that have become of age without hardly ever having been critically re-evaluated. The subject is dealt with under the headings "Components of the CS reaction" (educt, cation requirement and intermediates; product), "Regulation of CS" (cooperativity and allostery; non-allosteric activation or priming of CS; latency), "Concerted action of CS and enzymes of chitinolysis", "Inhibition of CS", "Multiplicity of CSs", and "Structure of CS" (the putative UDPGlcNAc-binding domain of CS; identification of CS polypeptides; glycoconjugation). The prospects are outlined of obtaining a refined three-dimensional (3D) model of the catalytic site of CS for biotechnological applications.

Animals↗

Biochemistry of parasites.

Parasite biochemistry is a field growing in parallel with the new surge of interest in tropical diseases. Whereas previously parasitologists have been required to adopt biochemical methodology in order to stay abreast of developments, today we find a new phenomenon: biochemists abandoning their classical systems (E. coli, red blood cells, etc.) to work on parasites. The 13th annual meeting of the Federation of European Biochemical Societies (FEBS) held in Jerusalem in August 1980 presented the perfect opportunity to summarize work done by parasite biochemists and to introduce this field to workers in classical biochemistry.

Animals↗

Gender affects doxorubicin pharmacokinetics in patients with normal liver biochemistry.

We studied the variability in doxorubicin pharmacokinetics in 27 patients, all of whom had normal liver biochemistry tests. Blood samples were collected after the first cycle of single-agent doxorubicin given as an i.v. bolus and plasma levels were measured by high-performance liquid chromatography (HPLC). The relationship of doxorubicin clearance (dose/AUC) with biochemical tests (AST, bilirubin, alkaline phosphatase, albumin, creatinine) and physical characteristics (age, gender, height, weight, tumour type) was investigated. The 6 men had a significantly higher doxorubicin clearance than did the 21 women (median values, 59 and 27 lh-1 m-2, respectively; P = 0.002). Doxorubicin clearance was significantly lower in patients with breast cancer than in those with other tumours (median values, 26 and 53 lh-1 m-2, respectively; P = 0.0008). The other biochemical and physical parameters did not correlate with doxorubicin clearance. However, in multivariate analysis, gender was the only factor predicting doxorubicin clearance (r2 = 40%). The ratio of the AUCs for doxorubicinol and doxorubicin (R) was higher in the men than in the women (median values, 0.62 and 0.36, respectively; P = 0.03). We conclude that gender may be an important determinant of doxorubicin clearance in patients with normal liver biochemistry.

Adult↗