Serum S-100 protein in stroke and cardiac surgery
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Biomedical subjects
Publications and source records attributed to U Missler.
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We investigated the level of S-100 protein in blood as an indicator of brain damage in 71 patients suffering from subarachnoid haemorrhage (SAH) due to ruptured aneurysms. Concentrations of S-100 protein were determined by micro-titre based immunofluorometic assay detecting predominantly S-100b on blood samples obtained 24 hours, 3 days and 7 days after onset of symptoms in patients with SAH and from 120 healthy control subjects. Neurological status was assessed using the Hunt and Hess (HH) scale on admission and by the Glasgow Outcome Scale (GOS) 6 months later. Mean concentrations of S-100 protein in blood were significantly (p < 0.0001) higher in patients 24 hours (0.263 +/- 0.387 microgram/l), 3 days (0.192 +/- 0.288 microgram/l) and 7 days (0.256 +/- 0.442 microgram/l) after onset of SAH symptoms compared to controls (0.050 +/- 0.081 microgram/l). More severe neurological symptoms (higher HH scale scores) on admission correlated with higher S-100 levels on admission (R = 0.70) and Day 3 (R = 0.66) (p < 0.0001). Worse outcome (lower GOS score) 6 months after SAH was also associated with higher plasma concentration of S-100 in the first week after SAH. In summary, this study showed that in patients with SAH due to ruptured aneurysm, S-100 protein levels correlate with early neurological deficit and are as sensitive as HH scores in predicting neurological outcome (GOS scores). Measurement of S-100 protein in blood is a reliable non-invasive method and may be clinically useful to screen for and monitor progression of central nervous system diseases of various origins.
OBJECTIVES: To determine whether an increase in plasma concentration of S-100 protein can serve as a marker for acute exacerbation of multiple sclerosis. MATERIAL AND METHODS: The plasma level of S-100 protein was investigated in 28 patients suffering from multiple sclerosis. Of these, 17 patients were admitted for acute exacerbation and 11 patients had a stable disease with no clinical signs for acute exacerbation. S-100 protein concentrations in plasma were determined with an immunofluorometric sandwich assay. RESULTS: Plasma concentrations were significantly elevated in patients who were examined within 7 days after the onset of acute exacerbation (n = 6). S-100 levels of patients 8 to 28 days after the onset of acute exacerbation (n = 11) did not differ from healthy controls (n = 120). Eleven patients with multiple sclerosis without acute exacerbation had moderately elevated plasma levels. CONCLUSION: The plasma concentration of S-100 protein is a sensitive although unspecific indicator of neuronal damage and may be of use as a marker of disease activity in multiple sclerosis.
BACKGROUND AND PURPOSE: Better techniques are needed to monitor infarction volume and predict neurological outcome after ischemic brain infarction. We evaluated the usefulness of serial measurements of S-100 protein versus neuron-specific enolase (NSE) in blood samples from patients with acute stroke. METHODS: Using nonisotopic sandwich immunoassays, we measured plasma concentrations of S-100 protein and NSE on admission and on days 3, 4, 7, and 14 after infarction in 44 patients (age range, 22 to 86 years; mean age, 65.1 years; 12 female, 32 male). Infarct volume was measured by volumetric CT on day 4 after ictus, and clinical outcome was assessed at discharge from hospital with the Activities of Daily Living Scale and 6 months after infarction with the Glasgow Outcome Scale. RESULTS: Peak blood levels of S-100 protein were found on day 2.5 +/- 1.3, and peak levels of NSE were found on day 1.9 +/- 0.8 after infarction. Peak plasma levels of S-100 protein correlated well with infarct volume (r = .75, P < .001) and with clinical outcome assessed with the Glasgow Outcome Scale (r = .51, P < .001). Serum levels of NSE correlated with infarct volume (r = .37, P < .05) but not with clinical outcome (r = .18, P > .05). CONCLUSIONS: The results of our study indicate that measuring blood concentrations of S-100 protein periodically in the first 10 days after cerebral infarction helps to predict infarct volume and the long-term neurological outcome more accurately than periodic measurements of blood concentrations of NSE.
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Transcranial color-coded duplex sonography is a recently introduced method for visualizing (1) the blood flow velocity of the basal cerebral arteries and (2) the brain parenchyma as an acoustic impedance image. Dislocation of the third ventricle due to space-occupying stroke is an important clinical marker. This study evaluated the dislocation of the third ventricle from the brain midline by transcranial duplex sonography in 10 healthy volunteers. The mean dislocation was 0.2 +/- 0.3 mm. Eighteen stroke patients were investigated within 12 hours by both duplex sonography and computed tomography (CT) and the dislocation of the third ventricle was measured. Correlation between the two methods was high (r = 0.87, N = 27). Twelve stroke patients divided into three subgroups according to the extent of the space-occupying effects of the lesion were followed for 3 weeks. The increase and decrease of the dislocation of the third ventricle over the time were monitored. In conclusion, transcranial duplex sonography is a reliable tool to monitor dislocation of the third ventricle due to space-occupying stroke.
Previous studies have suggested that human and porcine insulin exert identical effects on blood glucose and counter-regulatory hormones but elicit different neurophysiological reactions. A major goal of the present study was to investigate whether this could be caused by different relative affinities of the insulins from different species to insulin receptors from the brain compared to other tissues. Insulin receptors isolated from human brain, muscle or adipocytes as well as from cultured cells over-expressing either of the human insulin receptor isoforms (exon 11- or exon 11 +) were immobilized to microwells coated with monoclonal anti-insulin receptor antibody. Subsequently the binding of human, porcine and bovine insulin was measured. While the receptors derived from the different tissues had different affinities for insulin, there were no tissue-specific differences in the relative binding of the insulins of the three species. The insulins of the three species were also not different with regard to their binding to the receptor isoforms. Finally, in human brain homogenates no differences in the degradation rates for human, porcine and bovine insulin were detected. Thus, our data do not support the hypothesis that different neurophysiological reactions during hypoglycaemia due to human or porcine insulin are caused by differences of the binding of the insulins to human brain insulin receptors or their degradation in the human brain.
An immunofluorometric sandwich assay for determination of S-100 protein in cerebrospinal fluid (CSF) and blood is described. The lower detection limit was 0.015 micrograms/l of S-100 protein. Intra-assay and inter-assay imprecision (coefficients of variation, CVs) were 2.1 to 3.2% and 7.8 to 11.6%, respectively. S-100 protein recovery in cerebrospinal fluid was 94 to 103%. In blood the recovery varied from 67 to 96%, depending on blood samples used and the concentration of S-100 protein. The best recovery in blood was found using heparinized plasma. In healthy subjects 0.098 +/- 0.11 micrograms/l (mean +/- SD) of S-100 protein was detected (n = 30). In the CSF of otherwise healthy patients undergoing a myelography for lumbar pain 1.43 +/- 0.49 micrograms/l (mean +/- SD) of S-100 protein was found. Preliminary results from longitudinal studies on S-100 protein in neurosurgical patients indicate a positive correlation between S-100 protein blood levels and clinical course. Thus, the determination of S-100 protein in blood appears to be helpful in the monitoring of patients with neuronal damage.
Although two recent studies have failed to reveal lipoprotein(a) (LP(a)) serum concentrations > 300 mg/l to be an independent risk factor for early onset of atherosclerosis, Lp(a) serum concentrations are frequently measured to evaluate the additional risk of coronary heart disease. We describe a time-resolved immunofluorometric assay (TRIFMA) for quantifying Lp(a) levels in humans serum using commercially available reagents, which is rapid, robust and simple to perform. The two-site immunometric assay was based on microtitre plates as solid phase coated with a polycloncal anti Lp(a) antibody. The liquid-phase antibody was labelled with biotin and detected by europium labelled streptavidin in the DELFIA 1232 fluorometer. The measuring range was 2-1600 mg/l. The intra-assay imprecision was < 7% (CV), the inter-assay imprecision < 12% (CV). No interference was detected with plasminogen concentration up to 2.2 g/l. There was an acceptable correlation with a commercially available enzyme immunoassay (r = 0.95) and with electroimmunodiffusion (r = 0.85) on 100 routine serum samples measured. The assay appeared to detect different Lp(a) isoforms as dilution curves were parallel for B/F, S2 and S4 isoforms.
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Immunometric assays were developed for thyrotropin and 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/l, thyroglobulin 10-500 micrograms/l). The relatively high CV values are not only due to the assay design but also 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/l and for thyroglobulin between 2 and 500 micrograms/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 immunoreactivity. 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/l thyrotropin and 20 micrograms/l for thyroglobulin, both in whole blood. The assays proved useful for assessing the efficacy of iodine therapy, either by oral dosage or intramuscularly (iodised oil).(ABSTRACT TRUNCATED AT 250 WORDS)
In the past, chronic spondylogenic cervical myelopathy has been thought of being a disease often resistant to neurosurgical therapy. 56 out of 70 patient treated by laminectomy or different ventral fusion procedures improved immediately following operation. Only 36, however, continued to be improved at follow-up 5 to 8 years later, whereas additional 8 had worsened again, and another 5 mean-while had died due to myelopathy. Laminectomy turned out to be the least successful procedure of treatment. Nevertheless, early diagnosis, early operation, appropriate and individual surgical procedures, careful re-evaluation at follow-up, and -- if needed -- an early decision for a second-step operation can impressively improve the prognosis.
The assay described in this article is based on microtitre plate technology; it employs an europium label. The streptavidin-biotin system has been used and all components are commercially available. The lower detection limit of the assay is below 0.003 mU/l; the standards are made up in newborn calf serum. Correlation with a commercially available immunoluminometric assay (Berilux--Behringwerke) was excellent (r = 0.92, n = 201 data pairs, range covered 0-10 mU/l). The regression line using a double logarithmic transformation was: (log y) = 0.91 (log x)-0.08. The assay precision at the clinical limits of decision--i.e. between hyper- and euthyroidism (0.2 mU/l) and eu- and hypothyroidism (4 mU/l)--was acceptable. The median coefficient of variation was 1.93% in the range 0.02-1 mU/l and 2.11% in the range 1.0-3.5 mU/l, with both values being determined from precision profiles using 214 and 188 data pairs respectively. Inter-assay coefficients of variation determined in over 30 consecutive assays were under 6% in the range 1.3-20 mU/l. From 201 sera measured in both assays, 194 sera gave clinically identical values; 8 sera gave clinically discrepant values. The assay has a large dynamic range covering a concentration range of above 5 decades, with the count ratio between the 100 mU/l standard and the zero standard being in excess of 4150:1. A high dose hook effect was first seen in excess of 500 mU/l. The maximum signal was achieved around 150 mU/l, which registered around 8 x 10(6) counts per second, a figure more than 8000 times higher than that in the zero standard.
A 66-year-old woman presenting with pituitary insufficiency was operated on for an intrasellar tumor. Surprisingly, this tumor, at first suspected to be a hormone-inactive pituitary adenoma, consisted in fact of sarcoid granulomatous tissue in the pituitary gland as found histologically. The morphological picture as seen in the cranial computed tomography was identical with that of an adenoma. This possibility had not previously been considered, although there had been an extracerebral manifestation of the sarcoidosis in the left ovary.
A solid phase quantitative immunoluminometric assay for antibodies to hepatitis B surface antigen (Anti-HBsAg) is described. This solid phase assay uses polystyrene balls of 6.4 mm diameter, coated with pure hepatitis B surface antigen (HBsAg) obtained from the plasma of chronic HBsAg carriers. After incubation with patient serum (90 min), HBsAg labelled with 7-(4-aminobutyl-N-ethyl)naphthalene 1,2-dicarboxylic acid hydrazide hemisuccinamide (ABEN-H) was used as the signal carrier. Dilutions of samples and standards were made with sera previously shown to be negative for anti HBsAg. The lower detection limit was about 1.3 U/l the upper limit for undiluted serum about 1000 U/l. The mean coefficient of variation was 5%. The dynamic range (expressed as the signal ratio of the highest standard: zero standard) was 182:1 and covered the range 23-4200 relative light units. The assay was tested for specificity and gave no false-positive reactions in the presence of other hepatitis B antigens and antibodies.
One hundred and forty-one patients for general and urological surgery were anaesthetized by epidural anesthesia (PDA) using bupivacaine-CO2 0.5% solutions. A frequency peak for the initial dose between 21-23 ml was noted. The response time and latency period were found to be 2.99 +/- 1.40 min and 11.02 +/- 3.66 min (smallest time unit 0.5 min). The effective duration was 5.02 +/- 0.93 h. The sensory spread reached on average to T 6.06 +/- 1.41 segments for the patients with typical injection locations at L2/3-L4/5. A mean dose of 6.25 +/- 0.18 mg per spinal segment was used. Side effects were not seen apart from occasional hypotension. The failures were not related to the anesthetic drug. The degree of muscle relaxation was for the majority of cases evaluated at 2 +, which was sufficient for the abdominal operations. The results are compared with the data obtained using bupivacaine-HC1; the advantages of bupivacaine-CO2 are described.
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