Biomedical subjects
Publications and source records attributed to W Hubl.
Impaired wound healing is a feature of Werner's syndrome. Treatment of one such patient with painful chronic leg ulcers included topical application of PDGF-BB. Granulation increased slightly, enabling full-thickness skin grafting to take place.
The LIAISON immunoassay analyser was tested in a multicentre evaluation performed by 8 laboratories. The analytes evaluated were CA 15-3, CA 19-9, CA 125II, AFP, CEA, NSE and PSA. Excellent results were obtained for within-run and between-run precision with most assays showing within-run CVs < 5% and between-run CVs between 4 and 8%. The linearity of all assays was acceptable, however, for PSA, NSE and CA 19-9 a recovery > 110% was obtained for some of the samples tested. None of the assays revealed a high-dose hook effect. Method comparisons were performed by using the routine method of the respective study centre. Results generally showed an acceptable agreement between the LIAISON system and the different methods of comparison. The reference ranges for all assays were found to be in accordance with data known from the literature. All assays showed similar results for serum, heparinised plasma and EDTA plasma. Additionally, two experiments were performed with only one of the analytes tested: the sample-to-sample carry-over, using the CA 19-9 assay (3.3 x 10(-6)-2.3 x 10(-5)) and the functional sensitivity for the PSA assay (0.2 ng/ml).
The LIAISON thyroid hormone assays TSH, FT4, FT3, T4 and T3 were evaluated by determining the imprecision, the reference ranges, the functional sensitivity (TSH), the dilution characteristics (accuracy) (FT4, FT3), and the recovery after spiking (TSH, T4, T3). Furthermore, inter-method comparisons were performed with following methods: Elecsys (Roche Diagnostics; TSH), AxSYM (Abbott Diagnostics; TSH, FT4, FT3, T4), ACS:180 (Bayer Diagnostics; all analytes), Amerlex-M (Johnson & Johnson; T4) and LISO-Phase (Techno Genetics; FT4). The fully automated LIAISON random access analyser is based on microparticle immunoassays and chemiluminescence. The coefficients of variation (CV) of intra-assay imprecision were between 0.2-6.0%, except for the control sample with extremely low TSH concentrations and low T3 concentrations. Inter-assay imprecision was performed by measuring controls covering the measuring range over a period of 9 to 20 days, with CVs ranging from 2.3-16.0%. The suitability of the sample material was determined by analysing serum and samples treated with EDTA, citrate or heparin in parallel. The results showed good correlations of the thyroid hormone concentrations between serum and plasma samples except for LIAISON FT3, for which lower results were observed with EDTA-plasma. The regression analysis of correlation studies gave slopes from 0.849 to 0.957 for TSH, from 1.023 to 1.375 for FT4, from 0.670 to 0.911 for FT3, from 0.917 to 1.166 for T4 and 1.00 for T3 depending on the concentration range and the method of comparison. The LIAISON FT4 assay showed a trend towards higher values in the high concentration range when compared with the ACS:180. The ranges of thyroid hormone concentrations determined in serum taken from apparently healthy subjects were found to be in accordance with published data. The clinical sample study confirmed that the LIAISON thyroid hormone assays are sensitive methods for the differentiation of euthyroid subjects and patients with hyper- and hypothyroidism. In conclusion, the automated thyroid hormone immunoassays on the random-access LIAISON immunoassay analyser proved to be very satisfactory, both from the analytical and the clinical point of view.
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The CA 125 II assay on the Elecsys(R) 2010 analyzer was evaluated in an international multicenter trial. Imprecision studies yielded within-run CVs of 0.8-3.3% and between-day CVs of 2.4-10.9%; CVs for total imprecision in the manufacturer's laboratory were 2.4-7.8%. The linear range of the assay extended to at least 4500 kilounits/L (three decades). Interference from triglycerides (10.3 mmol/L), bilirubin (850 micromol/L), hemoglobin (1.1 mmol/L), anticoagulants (plasma), and several widely used drugs was undetectable. Method comparisons with five other CA 125 II assays showed good correlation but differences in standardization. A 95th percentile cutoff value of 35 kilounits/L was calculated from values measured in 593 apparently healthy (pre- and postmenopausal) women. In 95% of patients with benign gynecological diseases CA 125 was </=190 kilounits/L; 63% of patients with newly diagnosed ovarian carcinoma had values >190 kilounits/L. A comparison of CA 125 values obtained with the Elecsys test and with other common CA 125 tests in monitored patients being treated for ovarian cancer showed identical patterns. In conclusion, the Elecsys CA 125 II assay is linear over a broad range, yields precise and accurate results, is free from interferences, and compares well with other assays.
Defective aldosterone receptor binding is present in pseudohypoaldosteronism, and sporadic as well as familial cases have been reported. In familial pseudohypoaldosteronism, autosomal dominant as well as autosomal recessive inheritance has been described. The autosomal dominant form is characterized by a relative mild course of the disease and asymptomatic carriers of the defect in these families, whereas the autosomal recessive form is characterized by severe salt-losing symptoms; not uncommonly these families are consanguineous. To date no genetic mutation has been identified in the aldosterone receptor gene of affected patients. Studies to evaluate the biochemical defect and to characterize the inheritance pattern are of major interest for clinical as well as research purposes. Thus we studied the response of the renin-angiotensin-aldosterone system to sodium depletion using a single dose of furosemide. In 5 patients from five nonconsanguineous families and in all available family members the renin and aldosterone levels as well as serum sodium was measured before and after an oral dose of furosemide. The aldosterone receptor binding of peripheral mononuclear leukocytes was determined at the beginning of the study. In three families asymptomatic carriers of the defect could be identified in the baseline state by elevated levels of basal aldosterone and high renin concentration. The levels of renin and aldosterone did not differ between the symptomatic and asymptomatic individuals in these families. Interestingly the aldosterone receptor binding in the asymptomatic carriers of these families was normal. In the other two families, however, the basal hormonal data were normal in all relatives suggesting at first sporadic cases. During sodium depletion with furosemide, renin as well as aldosterone levels rose significantly in 1 parent and a sibling, respectively. In contrast to the first three families the aldosterone receptor binding in these family members was low. We propose to reclassify these family members as asymptomatic carriers and the patients as familial cases. Whether these cases are genetically identical to the 'classical autosomal dominant cases' remains to be seen. It seems that the pathogenesis of pseudohypoaldosteronism is even more heterogeneous than previously thought and factors other than aldosterone receptor binding are crucial and need further identification.
The results of measurement of 17-hydroxyprogesterone (17-OH-P) in 125 samples of amniotic fluid (AF) from early amniocenteses are presented. The fetuses from all pregnancies studied were unaffected by congenital adrenal hyperphasia caused by 21-hydroxylase deficiency. The AF 17-OH-P level increases slightly but significantly between the 11th and 15th week of gestation, with a maximum in the 14th week. There is no difference between the values measured in male and female fetuses. The AF 17-OH-P levels from the early gestation were compared with those from the 16th-22nd week of pregnancy (published previously). The overall differences of AF 17-OH-P concentrations when considered in all gestational age groups in the whole period 12-22 weeks were statistically insignificant. Thus, the biochemical prenatal diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency and control of its early fetal treatment could be carried out starting from the end of the first trimester in the same way as at the later period of gestation.
We report two patients with transient pseudohypoaldosteronism due to obstructive renal disease. Both patients presented with a salt-losing episode simulating adrenal insufficiency. In one patient, transient reduction of aldosterone receptors could be documented, while in the second patient the clinical and biochemical parameters were consistent with transient pseudohypoaldosteronism. Aldosterone receptors were normal in both patients when studied after the surgical correction of the obstruction.
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A technique for the reproducible re-use of antibody-coated solid phases for immunoassays is described. The method based on the dissociation of the antigen-antibody complexes. Two different procedures, using glycine buffer (pH 2.3) or ethanolamine, were developed. More than ten immunoassay cycles can be realized with the same antibody-coated microtitre plates. These procedures were tested with competitive and sandwich immunoassays, monoclonal and polyclonal antibodies, and a commercial immunoassay kit.
A monoclonal antibody with a high affinity for digoxin (KA = 5.5 x 10(10) M-1) and digitoxin KA = 5.0 x 10(10) M-1) was produced by somatic cell fusion. This antibody, designated 2A3, displayed little cross reactivity with other glucosides and no cross reactivity with endogenous steroids. It was shown that 2A3 is a suitable tool in an enzyme immunoassay for digoxin and digitoxin.
The assay is based on the luminescent measurement of horseradish peroxidase. The IgG fraction of a cortisol antiserum is coated on suitable polystyrene tubes (in use for the measurement of luminescence). The enzyme activity of bound label was determined using a p-iodophenol enhanced chemiluminescent reaction. The assay was sensitive and precise for a wide cortisol concentration range and showed a good agreement with conventional ELISA-technique. There was no extraction necessary for cortisol from plasma. The diluted sample was heated to 60 degrees C or 8-aniline-1-naphthalene sulfonic acid was added in order to release cortisol from protein binding in plasma.
In a psychophysiological experiment with 18 patients with cardiovascular disorders but without infarction we proved the influence of habituallized cognitive structures on reactivity under mental load. We used the concepts of different causal attribution (Explanatory style: Peterson and Seligman) and psychic regulation of activity and action (Activity style: Günther). It can be shown that patients with pessimistic explanatory style as well as with diffuse psychic activity control show coronary-prone reaction patterns under load (indicators: cortisol and triglycerids in serum).
In 30 patients suffered from acute myocardial infarction the serum levels of zinc, copper, cortisol, aldosterone, and triiodthyronine were determined. Zinc and triiodthyronine decrease, the other parameters increase. The serum levels of the tested parameters show a characteristic course within the first days after onset of myocardial infarction. There are significant differences between patients without complications and patients with complicated course inclusive of deaths. The differences exist already on the day of admission. Therefore we conclude zinc, copper, cortisol, and aldosterone levels as well as the course of T3 level are useful for prognosis of the clinical progress fo AMI. The tested parameters are helpful in differential diagnosis of chest pains caused by myocardial ischemia with or without myocardial infarction. The strong correlations between trace elements and hormones show new aspects due to the explanation of pathological alterations of serum levels in clinical medicine.
A competitive bradykinin enzymeimmunoassay (BK-EIA) for the determination of urinary kinins was developed. The BK-EIA was based on a stable BK-peroxidase conjugate and a BK-antirabbit-antiserum. Compared with a healthy control group, a significantly lower mean kinin excretion was found in patients with essential hypertension.
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A uniform solid-phase system has been developed for enzyme (ELISA) or luminescent (LIA) immunoassays for steroids. These assays were improved by (a) irradiating microtiter plates or polystyrene tubes before coating with antibody or Protein A, (b) coating the plastic trays with nonspecific anti-gamma-globulin or Protein A instead of the steroid-specific first antibody, and (c) partial denaturation of the second antibody before coating the plates or tubes with it. Specific antibodies were raised against cortisol, aldosterone, 17-hydroxyprogesterone, and digoxin. Horseradish peroxidase was used as label for the ELISA and aminoethylisoluminol for the LIA. In comparison with the first (specific) antibody coating method we observed some advantages: From 10- to 33-fold lower concentrations of first antibodies were necessary to bind the same amount of steroids; precision was better (CV, 3.8-7.5% vs 6.9-15.5%). The high sensitivity of these assays (0.5-2.0 pg per tube for the steroids) also allows determination of the steroids and digoxin in plasma and saliva.
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