CYFRA 21-1--clinical applications and analytical requirements.

CYFRA 21-1 has proved to be a useful marker for non-small-cell lung cancer (NSCLC), which is the major form of lung cancer. Its most effective application is in monitoring. CYFRA 21-1 provides diagnostic information about the success of primary surgery, the response to chemotherapy and the detection of relapse. It is also an independent prognostic factor. The diagnostic potential may not be fully used because decision-making is currently based on group reference ranges. It seems useful to carry out systematic studies to investigate if the application can be improved and extended by using individual reference ranges for decision-making. In contrast to most of the other tumour markers the comparability of the commercial CYFRA 21-1- assays currently available on the market is good. The high degree of comparability should be maintained by international standardization. The analytical performance of the currently available commercial CYFRA 21-1 tests meets requirements derived from its current clinical applications. However, there are no data available about the analytical performance under field conditions. CYFRA 21-1, an established tumour marker for lung cancer, should be included in external quality assurance schemes.

Individual reference ranges of CA 15-3, MCA and CEA in recurrence of breast cancer.

The long-term intra-individual variation of the title tumour markers was studied in the group of 33 patients which developed no relapse. The average biological intra-individual CV was 11.2% for CA 15-3 and 14.9% for MCA whereas those of CEA strongly depended on the concentration. The intra-individual standard deviation of CEA was independent of concentration and amounted to 0.23 g/L. Individual reference ranges the analytes were much smaller than the group reference ranges. Individual reference limits were calculated on the basis of the average intra-individual variation. In 21 of the 22 patients who developed recurrence during the follow-up period, individual reference limits of CA 15-3 and/or CEA were exceeded 1 to 31 months (median 10 months) before clinical evidence (diagnostic sensitivity 95%). Group reference limits were exceeded only in 13 patients (diagnostic sensitivity 60%) and occurring later. The diagnostic specificity was 97%. MCA did not provide additional information. The combination of CA 15-3 and CEA is an excellent for detection and exclusion of recurrence in the follow-up of breast cancer patients if decision-making is based on individual reference limits. Improvement of the long-term analytical quality of the tumour marker assays, particularly in the low concentration range is necessary.

Analytical variation in immunoassays and its importance for medical decision making.

The analytical variation of immunoassays is at present significantly larger than that of other methods in clinical chemistry. The main sources of this large variation are variation between methods, lot to lot variation, and the large imprecision between-runs and within-runs when the methods are not performed on automated instruments. The variation can be substantially reduced by standardization, by ensuring the comparability between lots, and by automation of the analytical procedure. The extent to which the variation should be reduced is determined by the needs of medical decision making. It is demonstrated using the analytes TSH and CA 15-3 as examples that quality requirements have to be individually specified for each analyte. Such guidelines should be established by teams of international experts. They should include suggestions for reference methods, guidelines on the extent of comparability between routine methods, the maximum allowable deviations from lot to lot, and the minimum requirements for between-run precision. Such guidelines could form the basis for improvements which are directed towards the medical requirements.

[The effect of oral contraceptives on the intraindividual variation of clinico-biochemical parameters]. / Einfluss oraler Kontrazeptiva auf die intraindividuelle Variation klinisch-biochemischer Parameter.

The effects of oral contraceptives on the average biological intra-individual variation of 22 clinical-biochemical analytes were investigated. There was no effect for sodium, chloride, potassium, calcium, urea, creatinine, uric acid, HDL-cholesterol, triglycerides, thyroxin, triiodothyronine, ASAT, ALAT, gamma-GT, AAP, ChE in serum. Whereas the average biological intra-individual variation of total protein, albumin, cholesterol, hemoglobin and amylase were significantly higher in the group of women taking oral contraceptives. For these analytes the use of oral contraceptives must be considered in establishing decision making criteria for longitudinal monitoring.

Diagnostic validity of multivariate combinations of biochemical analytes as markers for rejection and infection in the follow-up of patients with heart transplants.

The diagnostic validity of multivariate combinations of alpha 1-antitrypsin, alpha 2-macroglobulin, C-reactive protein, complement C3, complement C4, neopterin in serum, and neopterin in urine as markers for acute cardiac allograft rejection and for differential diagnosis of rejection and infections was investigated in the follow-up of 37 patients with heart transplants. Rejection was diagnosed by endomyocardial biopsy. Infections were classified as 'no infection', 'viral infection', and 'bacterial, fungal or mixed infections'. Although there are significant differences between the mean levels of analytes, multivariate discriminant analysis does not provide an adequate discrimination of rejection and infection states. In separate rejection diagnosis, multivariate combinations of analytes cannot replace endomyocardial biopsy. However, a multivariate combination of alpha 1-antitrypsin, alpha 2-macroglobulin, C-reactive protein, C3, C4 in serum, and neopterin in urine can be used as a screening procedure to reduce the number of endomyocardial biopsies.

Intra-individual variation of serum thyroxin and triiodothyronine in pregnancy.

The mean concentrations of triiodothyronine (T3) and thyroxin (T4) in serum were increased in pregnancy, the increases for individuals remaining stable for week 16 to week 40 of gestation. For this period biological intra-individual variations of T3 and T4 in serum were estimated and compared with those of non-pregnant women. The average biological intra-individual CVs for T3 and T4 were of the same order for pregnant and non-pregnant women (6.9-8.4%). The ratios of the biological intra-individual CVs to the biological group CVs were 0.5 to 0.6. Individual values were normally distributed. There was no increase of the intra-individual variation with the lapse of time between two consecutively observed values. The estimated average biological intra-individual CVs were used to derive decision-making criteria in monitoring thyroid function during the 2nd and 3rd trimester of gestation.

Influence of hypertension and antihypertensive drugs on the biological intra-individual variation of electrolytes and lipids in serum.

Biological intra-individual CVs for Na+, Cl-, K+, calcium, cholesterol, high-density lipoprotein cholesterol, triglycerides in serum, and hemoglobin in blood were estimated in men with essential hypertension (EH) treated with beta-blockers and diuretics, and compared with those of normotensive men. Although in EH the mean concentrations of Na+, Cl-, K+, hemoglobin, and triglycerides were increased and that of HDL cholesterol was decreased, the average intra-individual CVs did not significantly differ between the two groups. The mean concentration of cholesterol, as well as the average intra-individual CV for it, was significantly higher in EH. There was no correlation between the intra-individual CVs for the analytes and the mean blood pressure of the individuals. Individual values were normally distributed for all analytes. There was no increase of the intra-individual CV with the lapse of time between consecutively measured values. The estimated average biological intra-individual CV was used to derive decision-making criteria for interpretation of test results observed in monitoring EH.

Intra-individual variation of analytes in serum from patients with chronic liver diseases.

The average biological intra-individual CV in 20 patients with chronic liver diseases (CLD), estimated for 14 analytes during a stationary phase, significantly exceeded that for a normal group in the cases of Na+, K+, Cl-, total protein, albumin, cholinesterase, hemoglobin, and alpha-amylase; it did not differ significantly from the normal group for cholesterol, alkaline phosphatase, aspartate aminotransferase, and alanine aminopeptidase; and it was significantly lower than in the normal group for alanine aminotransferase and gamma-glutamyltransferase. There were no significant sex-related differences in mean intra-individual variation in CLD patients. Individual values were gaussian-distributed for all analytes, including enzymes. The estimated biological component of intra-individual variation and the analytical variation as determined for each laboratory can be used to derive decision-making criteria in monitoring CLD.

Intra-individual variation of some analytes in serum of patients with chronic renal failure.

Biological intra-individual variation in the concentration of 15 biochemical analytes in serum was estimated for 17 patients with chronic renal failure (CRF) and compared with results for apparently healthy individuals. The ratio of the average intra-individual variation in CRF patients to that in normal subjects was 1.5 to 2.0 for sodium, chloride, calcium, and creatinine; 1.2 to 1.5 for hemoglobin, total protein, albumin, globulin, uric acid, cholesterol, and alpha-amylase. The intra-individual CVs for urea, high-density-lipoprotein cholesterol, triglycerides, and alkaline phosphatase did not differ significantly between groups. The intra-individual variation of calcium and the concentration of creatinine in serum correlate significantly (r = 0.661, p less than 0.01). Individual values showed a gaussian distribution for all analytes. There was no time dependence of the intra-individual variation during a three-week interval, except for calcium and cholesterol. The estimated biological component of intra-individual variation and the analytical variation can be used to derive decision-making criteria in monitoring CRF.

Intra-individual variation of some analytes in serum of patients with insulin-dependent diabetes mellitus.

Biological intra-individual variation in concentrations of 16 clinical biochemical analytes in serum was estimated for 27 patients with insulin-dependent diabetes mellitus (IDDM), and results were compared with those for apparently healthy individuals. In general, the variation was significantly higher in the patients. The ratio of the average intra-individual variation in IDDM patients to that in normal subjects exceeded 2.0 for Na+, K+, creatinine, and alpha-amylase; 1.50 to 2.0 for Cl-, total protein, albumin, cholesterol, and hemoglobin; and 1.2 to 1.5 for urea, uric acid, high-density-lipoprotein cholesterol, and aspartate aminotransferase. This increased variability in IDDM patients may be caused by variations in osmotic diuresis. Average intra-individual variations were greater for women than for men for Na+, total protein, albumin, and hemoglobin. Individual values showed a gaussian distribution for all analytes, including enzymes and triglycerides. No intra-individual variation was time dependent. For practical purposes, decision-making criteria in monitoring IDDM can be derived from the estimated biological component of intra-individual variation and the analytical variation established for each laboratory.

[Principles of cooperation between the specialties of internal medicine, pathology and clinical biochemistry]. / Grundlagen für die Zusammenarbeit zwischen den Fachgebieten Innere Medizin sowie Pathologische und Klinische Biochemie.

The optimal utilization of the knowledge and possibilities of pathological and clinical biochemistry presumes a close cooperation between it and the clinical specialties. The common working team of the GDR Society of Internal Medicine and the GDR Society for Clinical Chemistry and Laboratory Diagnostics makes theses of the central points of the cooperation in care, education, further education and postgraduate study and in research a subject for discussion. As essential tasks in the process of medical care are regarded the balance of the examination programme standing at the disposal, the establishment of diagnostic programmes, the establishment of organisational measures, the ascertainment of a use according to indication, the guarantee of the representance of examination material, the control of plausibility and the interpretation of test results. Since the realization of the tasks to a large extent depends on the cooperation of the specialities in education, further education and postgraduate study during the further education the clinician should become acquainted with the possibilities, the limits and the prerequisites for the performance of laboratory diagnostic investigations, the clinical biochemist with the problems of medical care and the value of the laboratory diagnosis in the total process of the treatment. In the field of research the result is a necessary cooperation in the clarification of patho-biochemical mechanisms, in the search for suitable laboratory diagnostic parameters for diagnostics and control of the course as well as in the statement of the validity of laboratory diagnostic parameters and parameter combinations taking into consideration the factors expenses, benefit and risk as well as further diagnostic possibilities.

[Antimalarial 6-aminoquinolines. XIV. 6-(4-Diethylamino-1-methylbutylamino)-4-methoxy-2-methyl- and -2,4-dimethylquinolines with variations of substituents in positions 5 and 8]. / Gegen Malaria wirksame 6-Aminochinoline. XIV. 6-(4-Diethylamino-1-methylbutylamino)-4-methoxy-2-methyl- und -2,4-dimethylchinoline mit Variationen der Substituenten in 5- und 8-Stellung.

3 derivatives 2g--i of 6-(4-diethylamino-1-methylbutylamino)-4-methoxy-2-methylquinoline and 6 derivatives 2k--p of 6-(4-diethylamino-1-methylbutylamino)-2,4-dimethylquinoline were synthesized with variations of substituents in positions 5 and 8 (--H, --OH, --OCH3, --CH3, --Cl) with the aim of studying the influence of these substituents, which facilitate, complicate or prevent oxidation to o- and (or) p-quinones, on antimalarial activity and toxicity. One methoxy group is necessary for activity against Plasmodium vinckei in position 5 or 8, no substituent that prevents oxidation is allowed in para position to this methoxy group.

[Information value of 2 color tests in the determination of alanine and aspartate-aminotransferases in liver and biliary tract diseases]. / Informationswert zweier Farbteste zur Bestimmung der Alanin- und Aspartrat-Aminotransferase bei Leber-Gallenwegs-Erkrankungen

On the basis of examinations of altogether 197 patients the results of the changes of GOT and GPT were compared with the old and new colour tests of the AWD Dresden in normal histology, virus hepatitis, fatty liver, liver cirrhosis and posthepatic occlusion. Though the new colour test reveals a higher sensitivity, the differential diagnosis between selected liver diseases, especially virus hepatitis and posthepatic occlusion syndrome have become more difficult. The cause for this is the less significant separability between the individual regions of reference.

[Old and new standardized color test for the determination of aspartate aminotransferase in the differential diagnosis of heart infarct and angina pectoris]. / Alter und neuer standardisierter Farbtest zur Bestimmung der Aspartataminotransferase in der Differentialdiagnose zwischen Herzinfarkt und Angina pectoris

The usability of the new and old standardized colour test for the determination of the aspartate aminotransferase (GOT) (set of test instruments VEB Arzneimittelwerk Dresden) in the differential diagnosis between acute myocardial infarction and angina pectoris are compared. Concerning this problematics the new colour test does not evoke a better separation effect than the old one. Since with the change-over there were connected considerable uncertainties in the clinic it is recommended in case of a future standardisation to publish the regions of reference and first clinical experiences before the change-over.