Showing papers in "Clinical Chemistry and Laboratory Medicine in 1994"

Thyroglobulin is a More Sensitive Indicator of Iodine Deficiency than Thyrotropin: Development and Evaluation of Dry Blood Spot Assays for Thyrotropin and Thyroglobulin in Iodine-Deficient Geographical Areas

Abstract: Summary: Immunometric assays were developed for thyrotropin arid thyroglobulin using time-resolved fluorescence as the measurement signal. The assays were suitable for measurements in serum/plasma or in dry blood spots (3 mm diameter). Both assays have acceptable coefficients of Variation for dry blood spots (intra-assay median CV < 10%, interassay CV < 15%) in the concentration range of interest (thyrotropin 3—250 mU/1, thyroglobulin 10—500 g/l). The relatively high CV values are not only due to the assay design but also to the inhomogeneity of the samples used. For serum samples the median intra-assay CV was < 3% for thyrotropin in the range 0.1—50 mU/1 and for thyroglobulin between 2 and 500 g/l. The corresponding inter-assay CV were less than 5%. The assays were evaluated in field studies carried out under auspices of International Council for Control of Iodine Deficiency Disorders (ICCIDD) with the support of UNICEF in Algeria, Peru, India and Zimbabwe, and were found to be practical inasmuch as dry blood spot samples could be transported without special precautions for up to 5—6 weeks without significant loss in irnmunoreactivity. This agrees with other findings. The results showed that serum thyroglobulin levels are a more sensitive indicator of iodine deficiency than thyrotropin; elevated thyroglobulin levels were found in 182/304 children in Zimbabwe compared with elevated thyrotropin ; level in 28/304 cases. 213/304 children had enlarged thyroid glands. The cut-off levels used here were 4.5 mU/1 j thyrotropin and 20 g/l for thyroglobulk, both in whole blood. | The assays proved usefiil for assessing the e'fficacy of iodine therapy, either by oral dosage or intramuscularly (iodised ou). Single oral doses between 120 and 960 mg iodine were used, and the single intramuscular dose contained 480 mg iodine. Both serum and dry blood spots were analysed. Single oral doses of 480 and 960 mg iodine resulted in normalisation of serum thyroglobulin levels. The same was true for the 480 mg iodine given intramuscularly. Lower single doses did not reduce elevated thyroglobulin levels to normal values. The assay could also be used to determine/confirm athyroidism in newborns, results being available within 6 hours.

Glucose Intolerance in Liver Cirrhosis: Role of Hepatic and Non-Hepatic Influences

Abstract: Oral glucose tolerance was tested in a heterogeneous group of 108 patients with liver cirrhosis. Data were compared with those from 181 subjects without liver disease (44% normal, 35% impaired glucose tolerance and 21% type 2 diabetes mellitus). In cirrhosis, 27% of the patients had normal, 36% had impaired glucose tolerance, and 37% were diabetic. There was no association between glucose intolerance or diabetes and the aetiology of cirrhosis, the duration of the disease, the biochemical indicators of hepatocyte damage, cholestasis and/or liver function. Only weak associations were found between the results of quantitative liver functions tests (caffeine, xylocaine, indocyanine green) and basal and post load glucose and insulin concentrations. Cirrhotics with 1st degree relatives with type 2 diabetes mellitus (n = 16) did not show an increased prevalence of diabetes. Older and/or malnourished patients were more frequently glucose intolerant. Using the plasma glucose concentration 120 minutes after glucose load as the dependent variable, multivariate regression analysis showed that 54% of its variance is associated with the following variables: basal plasma glucose (36%) and free fatty acid concentration (5%), age (3%), basal glucose oxidation rate (3%), muscle mass (3%) and plasma free glycerol at 120 minutes after glucose load (3%). By contrast, the clinical state of the patients (i.e. the CHILD-Pugh score) accounted for only 2% of the variance. We conclude that glucose tolerance is variable in cirrhosis. After manifestation of liver disease, glucose intolerance or diabetes cannot be explained by the clinical, histological or biochemical signs of liver disease.

Ethanol Induced Oxidative Stress and Membrane Injury in Rat Erythrocytes

Abstract: The aim of this study was to observe membrane injury and to investigate the mechanism of antioxidant defence systems against acute ethanol toxicity Erythrocyte superoxide dismutase and Na+, K(+)-ATPase activities were significantly decreased and catalase levels were significantly increased one hour after ethanol intoxication of male swiss albino rats These data demonstrated that superoxide dismutase and catalase are susceptible to lipid peroxidation and that these enzymes protect tissues from free radicals The possible mechanism involved in Na+, K(+)-ATPase and Ca(2+)-ATPase inhibition are discussed in relation to the development of ethanol toxicity and the role of lipid peroxidative processes

Changes in Serum, Liver and Kidneys of Cisplatin-Treated Rats; Effects of Antioxidants

Abstract: Cisplatin, a nephrotoxic chemotherapeutic agent, was injected into Sprague Dawley rats, alone or together with cysteine, vitamin E and clonidine. The effects on erythrocyte fragility, serum composition, and kidney and liver enzymes were studied. Cisplatin was administered as two i.p. injections (6 mg/kg body weight) at an interval of 120 hours. The animals were sacrificed 24 hours after the second injection. Erythrocytes were prepared from blood collection with anticoagulant. Serum was prepared from clotted blood, collected without anticoagulant. Kidneys and liver were removed and homogenized, and a supernatant prepared by high speed centrifugation. In cisplatin-treated rats, the serum activities of aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase and alkaline phosphatase were significantly decreased, whereas the activities of isocitric dehydrogenase and glutathione reductase were increased. Also, concentrations of blood urea nitrogen, creatinine, total lipids and magnesium increased while albumin and glucose decreased. Mean osmotic fragility of erythrocytes from cisplatin-treated rats was decreased, while the haematocrit was increased. In the liver, the only change seen was an increased activity of isocitric dehydrogenase. Much greater changes were found in the kidneys, with increased activity of glucose-6-phosphate dehydrogenase and decreased activities of aspartate and alanine aminotransferases, alkaline phosphatase, malic dehydrogenase, sorbitol dehydrogenase and gamma-glutamyltransferase, as well as a decreased phosphorylation to oxidation ratio in the mitochondria, indicating reduced adenosine triphosphate production. Administration of cysteine and vitamin E together with cisplatin partially reversed the uraemia and many of the biochemical changes induced by cisplatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Generation of reference values for cardiac enzymes from hospital admission laboratory data.

Abstract: An approach is described for using patient databases of a hospital information system as a source of reference values for cardiac enzymes. Of a total of 2029 emergency admission patients with serial cardiac enzyme data, 538 patients were considered "healthy" (having no damage in myocardium) because their discharge diagnoses suggested neither myocardial damage nor any other condition that could lead to elevated enzyme activities, and because their serially collected cardiac enzyme activities remained stable. Enzyme activities of creatine kinase (EC 2.7.3.2), creatine kinase isoenzyme MB, lactate dehydrogenase (EC 1.1.1.28), and lactate dehydrogenase isoenzyme 1 of these patients at admission to hospital were considered as suitable health related reference values. The upper (97.5%) reference limits of activities, measured at 37 degrees C according to Scandinavian recommendations, were as follows (age dependent limits given at 25 and at 75 years of age, U/l): creatine kinase men 268, 192; creatine kinase women 200 (no age effect); creatine kinase-MB 16, 24; lactate dehydrogenase 497, 603; lactate dehydrogenase isoenzyme 1 103, 140. For comparison, reference values were also produced conventionally from a group of 246 healthy subjects. Observed effects of age on enzyme activities were quite similar to those in the selected patient group. Calculated reference limits for isoenzymes creatine kinase-MB and lactate dehydrogenase isoenzyme 1 were also similar but reference limits for less cardiospecific total enzyme activities, creatine kinase and lactate dehydrogenase, were more variable between these two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effect of Two Regimens of Hormone Replacement Therapy on the Haemostatic Profile in Postmenopausal Women

Abstract: The effect of two different regimens of hormone replacement therapy on coagulation and fibrinolysis was measured in 30 women taking Tibolone (Livial) and 30 taking oestradiol valerate, sequentially combined with cyproterone acetate (Climen). Blood samples were taken before the beginning of the medication, then six and twelve months afterwards. The Livial group showed a rise of fibrinolytic activity as measured by the alpha 2-antiplasmin-plasmin complexes. Tissue plasminogen activator antigen and plasminogen activator inhibitor-1 decreased simultaneously. No effect was seen in the coagulation variables. In the Climen group no significant alterations were noticed, either in the coagulation or in the fibrinolysis variables. In the direct comparison of both substances only factor VII appeared to be significantly higher in the Climen group after six months and one year of treatment.

Identification of Bordetella Pertussis in Nasopharyngeal Swabs Using the Polymerase Chain Reaction: Evaluation of Detection Methods

Abstract: A 183 base pairs or 153 base pairs DNA fragment from a repetitive region of the Bordetella pertussis genome was amplified in a polymerase chain reaction. The sensitivities of three different detection methods (Enzymun Test, silver stained polyacrylamide gel, ethidium bromide stained agarose gel) after amplification by polymerase chain reaction showed that both a one-time polymerase chain reaction (35 cycles) with Enzymun testing as well as a nested polymerase chain reaction with either of the electrophoresis methods have high levels of sensitivity for detection of the infectious organism in nasopharyngeal swabs. Smears from 53 children with whooping cough and from 50 children without infections were analysed, using these methods. 51 patients with whooping cough gave positive test results, while 2 of the sick patients and all the control children gave negative results.

Determination of oxalate excretion in spot urines of healthy children by ion chromatography.

Abstract: Summary: Evidence for the suitability of Spot urines for selective screening in children was obtained by comparing the 24-hour urinary oxalate excretion with the ratio of urinary oxalate to creatinine [mmol/mol] in spontaneously voided urine samples. Spot urines of 169 healthy children aged l day to 13 years were analysed in order to establish reference values for the urinary oxalate/creatinine ratio in relation to age and body surface area. Oxalate was measured by automated ion chroraatography. Results showed an inverse relationship between the oxalate/creatinine ratio and age. The highest ratios, 131 ± 57 mmol/mol (mean ± 2 SD), were found in infants. At age two years, the ratio was 84 ± 55, at age five years 56 ± 35, and for children older than ten years 42 ± 31. This finding can be explained by the gain of muscle mass and hence increased creatinine productiori with increasing age. Data for the urinary oxalate/creatinine ratio are presented according to body surface area for the assessment of children with abnormal growth. In 19 urine samples from nine patients with primary hyperoxaluria, the oxalate/creatinine ratio greatly exceeded (286—2022 mmol/mol) the above reference ranges. We therefore propose the determination of the oxalate/creatinine ratio in spot urines for the selective screening for hyperoxaluria in children with nephrocalcinosis or urolithiasis.

Synthesis of tissue factor pathway inhibitor in human synovial cells and chondrocytes makes joints the predilected site of bleeding in haemophiliacs.

Abstract: The synthesis of tissue factor pathway inhibitor (TFPI) was investigated in cloned human synovial cells and human chondrocytes. TFPI-specific DNA transcription products of these cells were isolated, and a full-length cDNA of about 1000 base pairs was amplified by reverse transcription and polymerase chain reaction. The amplified DNA was cloned into the vector pUC 18. The TFPI coding sequence was confirmed by double stranded sequencing and was identical with that previously published for human TFPI coding nucleotide sequence from human placental cDNA (1). The inhibitory activity of TFPI in the cell medium of cultivated human chondrocytes and cloned human synovial cells was determined by a specific chromogenic substrate assay of factor Xa activity. The inhibitory activity of TFPI in the medium of human chondrocytes and cloned human synovial cells was 630-720 mU/10(8) cells and 1080-1665 mU/10(8) cells, respectively. In addition, TFPI activity in cell culture media of human chondrocytes and cloned human synovial cell was suppressed by a polyclonal goat anti-TFPI antibody directed against the inhibitory domain I and domain II. In the chromogenic substrate assay, the anti-TFPI antibody completely suppressed the inhibitory activity of TFPI in the samples.

Plasma Glutathione Peroxidase Activity as an Index of Renal Function

Abstract: The kidney is a major source of the plasma enzyme glutathione peroxidase. We measured plasma glutathione peroxidase activity in 130 patients affected with different renal diseases at various stages, and compared it with the following indices of kidney function: serum creatinine, creatinine clearance, and urinary excretion of alpha 1-microglobulin, beta 2-microglobulin, albumin and N-acetyl-beta-D-glucosaminidase. Plasma glutathione peroxidase activity appeared significantly reduced in most of the renal diseases considered, and showed a significant correlation with most of the renal function indices. Linear discriminant analysis showed that the set of indices composed of plasma glutathione peroxidase activity, serum creatinine and creatinine clearance allowed the best classification of renal diseases. During treatment with the nephrotoxic aminoglycoside, tobramycin, plasma glutathione peroxidase activity showed an early and progressive decrease. We suggest the measurement of plasma glutathione peroxidase activity as an adjunctive index for the assessment of kidney alterations.

A comparative study of the concentrations of hypoxanthine, xanthine, uric acid and allantoin in the peripheral blood of normals and patients with acute myocardial infarction and other ischaemic diseases.

Abstract: Summary: The aim of this study was the elucidation of the role of the xanthine oxidoreductase in the purine metabolism in ischaemic diseases of man. The serum concentrations of hypoxanthine, xanthine, uric acid and allantoin were determined in peripheral blood samples from patients with angina pectoris, cerebral insult and myocardial infarction with thrombolytic therapy and were compared with the concentrations obtained for healthy males and females. No significant differences were observed for the serum hypoxanthine concentrations, xanthine concentrations, the sum (hypoxanthine + xanthine) and the ratio (xanthine/hypoxanthine) between the healthy males, healthy females, the patients suffering from angina pectoris and the patients suffering from cerebral insult. An increase of the serum xanthine concentration in patients with myocardial infarction indicates a significant metabolic involvement of xanthine oxidoreductase in this disease and therefore a possible role in the development of tissue damage in the postischaemic phase due to oxygen radicals generated by the oxidase activity of this enzyme. The serum concentrations of uric acid and allantoin showed no differences between any of the studied groups. Study of the non-enzymatic oxidation of uric acid to allantoin by oxygen radicals, a relevant radical-scavenging mechanism in other diseases, provided no indication of an increased concentration of oxygen radicals due to the xanthine oxidoreductase reaction or other radical-producing mechanisms.

Neopterin Production and Tryptophan Degradation in Acute Lyme Neuroborreliosis Versus Late Lyme Encephalopathy

Abstract: Fourteen patients with Borrelia burgdorferi infection were investigated for possible abnormalities of tryptophan and neopterin metabolism. Four patients (2 were investigated before therapy, 2 when therapy had been already started) had acute Lyme neuroborreliosis, and 10 patients were investigated months to years after an acute infection. Increased concentrations of neopterin and of the tryptophan-degradation product, L-kynurenine, were detected in the cerebrospinal fluid of patients with acute Lyme neuroborreliosis; one patient presented with subnormal tryptophan. Similar but less marked changes were seen in the treated patients and in some of the patients with Lyme encephalopathy. No such abnormalities were seen in the serum of the patients. The data indicate a role of the immune system and particularly of endogenously formed cytokines, like interferon-gamma and tumour necrosis factor-alpha, effecting tryptophan and neopterin metabolism in patients with acute Lyme neuroborreliosis.

Parallel determination of gut permeability in man with M(r) 400, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol.

Abstract: Polyethylene glycol has been in use for a number of years for the assessment of gut permeability. The methods so far employed are usually limited to polyethylene glycols in the low relative molecular mass range (up to M(r) 1300). We developed a method for the simultaneous determination of gut permeability to M(r) 400, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol, by applying a single oral dose of an appropriate mixture of these polyethylene glycols. After extraction from 24 h-urine, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol were quantified by size exclusion chromatography, while M(r) 400 polyethylene glycol was determined by reversed phase chromatography. The detection limit of polyethylene glycol in the relative molecular mass range between M(r) 1500 and M(r) 10,000 was found to be 0.2 mg/l urine, and the detection limit of M(r) 400 polyethylene glycol 5 mg/l urine. Recovery of the polyethylene glycols (N = 6) were 86.6% (CV: 4.8%) for M(r) 400, 94.1% (CV: 7.2%) for M(r) 1500, 97.1% (CV: 5.5%) for M(r) 4000 and 97.4% (CV: 5.6%) for M(r) 10,000. No significant difference was found between the excretion rates in 24 h-urine of M(r) 400 and M(r) 1500 polyethylene glycols in patients with Crohn's disease (M(r) 400: 34.4 +/- 5.5%; M(r) 1500: 5.22 +/- 2.27%; mean +/- SEM, N = 10) and healthy controls (M(r) 400: 33.6 +/- 3.2%, M(r) 1500: 1.09 +/- 0.26%; N = 21). The excretion rate of M(r) 4000 polyethylene glycol was markedly higher in patients with Crohn's disease (0.462 +/- 0.177%) than in healthy controls (0.049 +/- 0.012%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Purification of Isotransferrins by Concanavalin A Sepharose Chromatography and Preparative Isoelectric Focusing

Abstract: 1. From pooled serum containing genetically homogeneous transferrin C1, transferrin was purified and separated in three fractions (tri-tri, bi-tri- and bi-bi-antennary transferrin C1), using Concanavalin A-Sepharose. 2. Each of these fractions was separated into its sialic acid-dependent subfractions by preparative isoelectric focusing. Sixteen iso-transferrin C1 fractions were obtained, which differed in their degree of glycan branching and/or their sialic acid content. 3. Preliminary carbohydrate analyses suggest that in some iso-transferrins the N-acetylglucosamine and the galactose content is lower than expected.

Improvements in creatinine methodology : a critical assessment

Abstract: A large evaluation study, analytical as well as clinical, was performed on four published improvements for the determination of creatinine in serum. Two of the methods were based on the Jaffe reaction, the other two were enzymatic methods. Analytically, all four methods showed a similar performance. In the analysis of numerous specimens from advanced care departments, however, the methods performed differently. The two enzymatic procedures scored better than the two Jaffe methods, when compared with an HPLC-based reference method. However, even the best methods produced outliers and a larger scatter than that obtained with "normal" specimens.

Dilated cardiomyopathy: computer-assisted analysis of endomyocardial biopsy protein patterns by two-dimensional gel electrophoresis.

Abstract: In order to identify disease-associated alterations in the myocardial protein patterns in dilated cardiomyopathy, we used 2-dimensional gel electrophoresis to analyse the proteins of endomyocardial biopsies from patients and controls. Proteins (150 micrograms) from biopsies (1-3 mg wet weight) were first separated by isoelectric focusing, then applied to large 2-dimensional gels. A computer-assisted system (PDQUEST) was used for spot detection, quantification and comparison of 2-dimensional protein patterns. From a single endomyocardial biopsy about 1000 different protein species were resolved. The spot pattern was influenced by the concentration of protein during sample preparation, by the amount of protein loaded onto the gels and by the development time of silver staining. Variances of spot position in the first and second dimension and in the long diagonals were less than 5%. Coefficients of variance for the spot quantities in 8 gels were 16 +/- 8%. Contaminating blood proteins could be identified in the biopsy patterns. Computer-assisted comparison between cardiomyopathy (n = 5) and controls (n = 5) over the whole gel revealed that 55 protein spots were increased 100%, 27 protein spots decreased 100%. Four proteins showed significant quantitative differences between the cardiomyopathic hearts and controls. Fourteen proteins were identified by amino acid analysis or microsequencing. An isoelectric point and molecular mass grid was laid over the whole gel based on these identified protein species, resulting in approximate isoelectric point values and molecular masses for all other protein species. Thus, myocardial 2-dimensional protein patterns obtained from endomyocardial biopsies can be used for the characterization of cardiac diseases.

Effects of Long-Term Aluminium Exposure on Certain Serum Constituents in Broiler Chickens

Abstract: The aim of this work was to study the effects of 35 days exposure to aluminium on certain serum biochemical quantities in chickens. Broiler chicks (TETRA-726 hybrid, male) were kept in a climate-controlled stall with feed and water ad libitum, from day 1 of age, for 7 weeks. From the beginning of the third week aluminium was added to the diet as aluminium chloride. Treatments included supplemental aluminium content of 0, 200, 1000 and 3000 mg/kg ration. At the end of the experiment, blood samples were taken from the v. ulnaris. The treated groups showed significantly elevated alkaline phosphatase activities, as well as increased cholesterol concentrations and decreased triacylglycerol concentrations, and these changes were dose-dependent. The concentration of uric acid was significantly higher in the group receiving 1000 mg/kg ration, but significantly lower in the group receiving 3000 mg/kg ration, compared with the controls. In the treated groups, the concentration of glucose, as well as the activities of cholinesterase, aspartate aminotransferase, gamma-glutamyl transferase and creatine kinase were similar in the controls and treated animals. High levels of alkaline phosphatase are due to increased osteoblastic activity, provoked by the disturbance of bone formation, caused in turn by aluminium. Alterations in serum uric acid may be connected with metabolic disturbances (e.g. renal function, cation--anion balance etc.). Neither hepatic nor muscle damage was found.

Glycogen Phosphorylase Isoenzyme BB Mass Release After Coronary Artery Bypass Grafting

Abstract: Glycogen phosphorylase isoenzyme BB mass release was studied in 20 patients undergoing coronary artery bypass grafting In 16 patients with uneventful coronary artery bypass grafting, glycogen phosphorylase isoenzyme BB mass concentrations showed a significant, transient increase in the post cross-clamping period and decreased to baseline values within 20 hours (peak concentrations ranged from 127 micrograms/l to 475 micrograms/l, median 40 micrograms/l) One patient did not fulfil criteria for perioperative myocardial infarction, but clinical data indicated myocardial injury after aortic unclamping In this patient only glycogen phosphorylase isoenzyme BB mass concentration and not creatine kinase isoenzyme MB catalytic concentration was increased, compared with uneventful patients In 2 patients with emergency coronary artery bypass grafting for evolving myocardial infarction, glycogen phosphorylase isoenzyme BB mass concentrations, but not creatine kinase isoenzyme MB catalytic concentrations, correlated with clinical evidence of myocardial ischaemia Our data indicate that glycogen phosphorylase isoenzyme BB mass concentration is a very sensitive laboratory marker of perioperative myocardial injury in patients undergoing coronary artery bypass grafting

Plasma pancreatic lipase activity: from analytical specificity to clinical efficiency for the diagnosis of acute pancreatitis.

Abstract: Summary: Using five procedures (turbidimetry with the Boehringer Mannheim kit and with a home made reagent, Teflectometry with the Eastman Kodak kit, colorimetry with the Sigma kit, and UV spectrophotom etry with the Wako kit), lipase activity was assayed in the same group of 60 healthy adults and in 30 patients suffering from acute pancreatitis (n = 197 samples) as well as in a purified and stabilized preparation of human pancreatic lipase. Results indicated considerable inter-assay discrepancies for the mean values of the patients' results: catalytic activity concentrations differed by a factor of up to 16 according to the measurement procedures. For each method, mean i" patients' results were also expressed as multiples of the upper limit of normal values. This method of presentation | did not sigriificantly improve the intra-assay agreement, with maximal relative differences as high as 13-fold. When j each method was calibrated with the same material (human pancreatic lipase), the inter-assay agreement was !' considerably improved. The causes of inter-assay disagreement are discussed in detail, and the necessity for a ' validated lipase calibrator is stressed, in order to improve the efficiency of the information transmitted by clinical laboratories to clinicians. A stfategy is proposed, which includes development of a reference method and reference \ material, and a study of inter-assay commutability of secondary calibrators for a set of methods.

Plasma Myoglobin in the Early Diagnosis of Acute Myocardial Infarction

Abstract: Serum and plasma myoglobin and creatine kinase-MB catalytic activity were analysed in 157 patients admitted within 2 hours of the onset of chest pain (58 were retrospectively recognized as acute myocardial infarction). Serum and plasma values were highly correlated for both myoglobin and creatine kinase-MB. Plasma myoglobin appeared to be more sensitive than creatine kinase-MB for the early diagnosis of acute myocardial infarction; using a cut-off value of 100 micrograms/l, 90% of acute myocardial infarction cases were correctly recognized by plasma myoglobin 6 hours after the onset of chest pain, with a diagnostic specificity of 100% for non-acute myocardial infarction chest pain subjects. Plasma creatine kinase-MB showed a diagnostic sensitivity of 62% and a diagnostic specificity of 95% in the same group of patients. We suggest the inclusion of the plasma myoglobin immunonephelometric assay together with plasma creatine kinase-MB activity analysis in protocols for the early diagnosis of acute myocardial infarction.

Biological half-life of prostate-specific antigen after radical prostatectomy

Abstract: The disappearance pattern of prostate-specific antigen from serum after a standard radical prostatectomy was studied in eight patients with cancer confined to the prostate. The results were used to plot an elimination curve and calculate the best fit. A biphasic pattern was found with an average biological half-life of 1.63 hours in the alpha-phase, and 4.63 days in the beta-phase. Based on these results it is concluded that determination of prostate-specific antigen concentrations less than one month after a standard radical prostato-vesiculectomy has no value for the detection or exclusion of residual malignant processes.

The Limitations and Usefulness of C-Reactive Protein and Elastase-α1-Proteinase Inhibitor Complexes as Analytes in the Diagnosis and Follow-up of Sepsis in Newborns and Adults

Abstract: C-reactive protein and elastase-alpha 1-proteinase inhibitor complexes were compared in the diagnosis of neonatal sepsis and bacterial infections in adults on the intensive care unit. Both analytes were measured in the same sample immediately after receipt. EDTA-plasma samples (n = 115) from 28 neonates (gestational age 29-42 weeks) within the first 72 hours of life with suspected neonatal sepsis, 2 babies between 14 and 28 days old with B-streptococcus infections and 28 adults on the intensive care unit with positive bacterial cultures were analysed for both analytes. Two adults with long-term infections were followed up over a period of 28 and 65 days respectively. The results showed that in 17 cases of confirmed neonatal sepsis within the first 24 hours of life, c-reactive protein levels were undetectable in 16 cases, one level of 13 mg/l being recorded. All had elevated elastase-alpha 1-proteinase inhibitor concentrations. Of the remaining 15 samples, 13 were normal and 2 were borderline for this analyte. C-reactive protein levels were between 5 and 10 mg/l in 5 cases and undetectable in the remaining 10 samples. Those neonates with detectable c-reactive protein levels were between 20 and 72 hours old with a gestational age greater than 31 weeks. C-reactive protein was undetectable in samples taken at the same time interval after birth from full-terms babies with a gestational age of 41-42 weeks, even in confirmed cases of neonatal sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum total sialic acid and acute phase proteins in elderly subjects.

Abstract: Serum total sialic acid has gained recent interest as a cardiovascular risk factor. We measured serum total sialic acid and three acute phase proteins; C-reactive protein, alpha 1-antichymotrypsin and alpha 1-acid glycoprotein in 37 geriatric patients (age 80.1 +/- 7.0 years) and 50 younger subjects (age 40.3 +/- 11.4 years). Serum total sialic acid was higher in the geriatric subjects 2.41 +/- 0.39 mmol/l versus 2.04 +/- 0.35 mmol/l, P < 0.04. Serum alpha 1-acid glycoprotein, alpha 1-antichymotrypsin and C-reactive protein were also elevated in the geriatric patients; serum alpha 1-acid glycoprotein being 1.16 +/- 0.32 g/l versus 0.41 +/- 0.28 g/l, P < 0.0001, serum alpha 1-antichymotrypsin being 0.80 +/- 0.20 g/l versus 0.52 +/- 0.10 g/l, P < 0.0001 and serum C-reactive protein being 9.71 +/- 21.0 mg/l versus 4.73 +/- 1.30 mg/l, P < 0.04. There was a correlation with serum total sialic acid and serum alpha 1-acid glycoprotein and alpha 1-antichymotrypsin in the geriatric subjects and with alpha 1-acid glycoprotein, alpha 1-antichymotrypsin and C-reactive protein in the younger group.

Increased Urinary Nitrate Excretion in Inflammatory Bowel Disease

Abstract: Summary: Urinary nitrate is known to be a measure of environmental exposure. Only recently an endogenous metabolic pathway resulting in nitrate synthesis was described. We have determined the concentration of nitrate expressed as nitrate/creatinine ratio in the urine of patients in whom a significant environmental nitrate load was presumed to be absent. A significant elevation of nitrates in patients with inflammatory bowel disease compared with patients with non-inflamrnatory disorders was observed (0.173 ± 0.155 vs. 0.037 ± 0.016 mol/mol creatinine, P < 0.01). Increased nitrate excretion in the urine of patients with inflammatory bowel disease may reflect the endogenous nitrate synthesis induced by the immune activation.

Age dependent reference intervals of glucose, urea, protein, lactate and electrolytes in thermally induced sweat.

Abstract: Summary: Concentrations of electrolytes, lactafe, urea, glucose, total lipids and total protein were measured in sweat obtained by thermal Stimulation of apparently healthy volunteers. Blood and urine samples were also collected. Electrolytes, urea and total protein were also measured in serum. The concentrations of electrolytes, glucose and urea in sweat increased with age, and this increase was more apparent in males, probably due to certain agerelated changes in male sweat glands. The concentrations of lactate, total protein and total lipids in sweat, however, were not age-dependent. The concentration of total protein was higher in females than in males. The concentrations of all the other analytes were higher in males than in females of the same age group.

Posttranslational heterogeneity of bone alkaline phosphatase in metabolic bone disease.

Abstract: Summary: Bone alkaline phosphatase is a marker of osteoblast activity. In order to study the posttranscriptional modification (glycosylation) of bone alkaline phosphatase in bone disease, we investigated the relationship between mass and catalytic activity of bone alkaline phosphatase in patients with osteoporosis and hyperthyroidism. Serum bone alkaline phosphatase aetivity was measured after lectin precipitation using the Iso-ALP test kit. Mass concentration of bone alkaline phosphatase was determined with an immunoradiome tric assay (Tandem-R Ostase). In general, serum bone alkaline phosphatase mass and activity concentration correlated well. The activity : mass ratio of bone alkaline phosphatase was low in hyperthyroidi sm. Activation energy of the reaction catalysed by bone alkaline phosphatase was high in osteoporosis and in hyperthyroidism. Experiments with neuraminidase digestion further demonstrated that the thermodynamic heterogeneity of bone alkaline phosphatase can be explained by a different glycosylation of the enzyme.

Characterization and Extracorporeal Application of a New Phosphate-Binding Agent

Abstract: A new phosphate-binding agent which does not cause any severe side effects in vivo was developed by modifying a crosslinked dextran with polynuclear iron(III)oxide-hydroxide. Its particle size ranges from 150 to 300 microns, and the iron content was about 18% by dry weight. The oxidation state of iron was characterized by ESCA and Mossbauer spectroscopy. The maximum phosphate binding capacity of the iron(III)oxide-hydroxide-modified dextran was determined with respect to aqueous phosphate solutions, human serum and whole blood. The effects on whole blood count, haemolysis, protein concentration and enzyme activities were examined. In addition, the influence of phosphate concentration, pH and temperature on the phosphate uptake of the material was determined. The results show that this new adsorbent might provide an alternative to conventional phosphate-binding agents. This paper also describes the first experiments on the therapeutic application of the material in an extracorporeal blood perfusion system for the treatment of hyperphosphataemia during haemodialysis.

The accuracy of creatinine methods based on the Jaffé reaction: a questionable matter.

Abstract: The determination of creatinine in serum based on the Jaffe reaction was evaluated with four current analysers. In particular, the comparability of results was determined also with survey specimens. Recalibration of 3 out of 4 modifications was necessary, based on the results of patient samples as verified with a HPLC-method. One of the methods proved to give an unacceptable scatter for the results in the lower range (30-150 mumol/l). A limited interference study (haemoglobin, lipids, bilirubin and acetone) and a method assessment with quality control sera supported the conclusion that the overall accuracy of creatinine methods based on the Jaffe reaction is questionable.

Accelerated bone degradation in thyroid carcinoma patients during thyroxine treatment, measured by determination of the carboxyterminal telopeptide region of type I collagen in serum

Abstract: We studied the effects of long-term suppressive thyroxine treatment on serum markers of bone collagen synthesis and degradation in thyroid carcinoma patients, and the relationship of these effects to the serum concentrations of thyrotropin, free thyroxine and free triiodothyronine were investigated. Thirty-seven thyroid carcinoma patients receiving a stable thyroxine dose, and thirty-five controls participated in a cross-sectional study. Bone collagen synthesis and degradation were measured by using specific radioimmunoassays to determine the serum concentrations of carboxyterminal propeptide of type I procollagen, and carboxyterminal telopeptide region of type I collagen, respectively. Serum thyrotropin, free T4 and free T3 were measured by time-resolved fluoroimmunoassays (Delfia). Serum carboxyterminal telopeptide region of type I collagen concentrations of thyroid carcinoma patients were significantly higher than those of the controls (p = 0.0012). Serum carboxyterminal propeptide of type I procollagen concentrations did not differ significantly between the patients and controls (p = 0.85). Significant associations between age or physical activity, and carboxyterminal propeptide of type I procollagen or carboxyterminal telopeptide region of type I collagen were found in the controls, but not in the patients. Thyrotropin, free T4 or free T3 were not significantly associated with carboxyterminal propeptide of type I procollagen or carboxyterminal telopeptide region of type I collagen in either the control or patient group. From these results it is concluded that long-term suppressive thyroxine treatment seems to accelerate bone degradation, but not bone formation, and therefore carries a risk for osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of an immunoradiometric assay for bone alkaline phosphatase mass concentration in human sera.

Abstract: The performance characteristics of an immunoradiometric assay for bone alkaline phosphatase mass concentration in human sera are reported. Within-run imprecision (n = 20) was 12.1% (mean = 7.8 micrograms/l) and 3.6% (mean = 22.8 micrograms/l), between-day imprecision (n = 8) was 10.1% (mean = 20.3 micrograms/l) and 2.8% (mean = 84.3 micrograms/l). There was a linear relationship between the concentrations of the standards employed and the counts per minute up to 120 micrograms/l. The detection limit was 0.3 micrograms/l. In 102 apparently healthy persons (51 males and 51 females; range of age: 18-56 years) the following reference intervals were established: 3.8-21.3 micrograms/l (males) and 3.4-15.0 micrograms/l (females). We compared the values obtained using the immunoassay with those obtained by precipitating of bone alkaline phosphatase with wheat-germ lectin (alkaline phosphatase activity concentration was determined at + 25 degrees C by the optimized standard method according to the Recommendations of the German Society for Clinical Chemistry). For the reference individuals the relationship between the results of the two methods is given by the following regression equation: Bone alkaline phosphatase activity concentration [U/l] = 14.81 + 3.28 x bone alkaline phosphatase mass concentration [micrograms/l] (r = + 0.783). In 89 sera from 32 patients before and after renal transplantation (range of bone alkaline phosphatase mass concentration: 2-39 micrograms/l) comparison between the two methods yielded a linear correlation coefficient of r = + 0.886.(ABSTRACT TRUNCATED AT 250 WORDS)