Search

Background: Prolonged ventilation is associated with a high risk of death. This study investigated both patient-level and hospital-level risk factors for in-hospital mortality in patients ventilated for more than 24 hours. Methods: The analyses were conducted in the framework of a German national multicenter retrospective cohort study. Patient and hospital characteristics were examined using descriptive statistics. Risk factors of in-hospital mortality were analyzed using multilevel robust Poisson regressions for binary outcomes. Potential effect modifications were examined by stratified analyses. Results: The sample includes 95 672 cases of patients ventilated >24 hours in 163 hospitals covering the period 2016 to 2017. According to the results of multilevel Poisson regressions, main patient-level risk factors for in-hospital mortality were age (per year relative risk [RR] = 1.021, 95% CI = 1.020-1.023), stroke (RR = 1.459; 95% CI = 1.361-1.563), emergency case admission (RR = 1.273, 95% CI = 1.156-1.403), and transfer from another hospital (RR = 1.169, 95% CI = 1.084-1.261). The individual risk of in-hospital death was positively associated with hospital size (RR of hospitals with 600-799 beds vs Conclusion: By providing evidence on multiple patient-level and hospital-level risk factors for in-hospital mortality in patients ventilated for more than 24 hours, this large multicenter study has main implications for quality assessment of clinical care and the adequate specification of risk adjustment models. The revealed effect modifications indicate the relevance of stratified analyses.

Dtsch med Wochenschr 1981; 106: 579-583 DOI: 10.1055/s-2008-1070359 © Georg Thieme Verlag KG Stuttgart · New York Therapie der blanden Struma: Erfahrungen mit einer Kombination von 100 µg L-Thyroxin und 10 µg L-Trijodthyronin Treatment of non-toxic goitre: results of combined treatment with 100 µg L-thyroxine and 10 µg L-triiodothyronine C. R. Pickardt, R. Gartner, J. Habermann, K. Horn, P. C. Scriba, F. A. Horster, H. Wagner, K. Hengst Medizinische Klinik Innenstadt der Universitat Munchen, Klinik fur Innere Medizin, Medizinische Hochschule Lubeck, Medizinische Klinik C und Poliklinik der Universitat Dusseldorf sowie Medizinische Klinik und Poliklinik der Universitat Munster Zusammenfassung Bei 96 Patienten mit blander Struma wurde eine offene Prufung mit einem neuen Schilddrusenhormonpraparat durchgefuhrt, das 100 µg L-Thyroxin (T4) und 10 µg L-Trijodthyronin (T3) pro Tablette enthalt. Als Parameter fur die therapeutisch wirksame Tagesdosis wurde die Suppression des TRH-stimulierten Thyreotropinspiegels im Serum gewahlt. Hierbei war eine Tagesdosis von 50 µg T4 und 5 µg T3 bei 16 Patienten unwirksam; 75 µg T4 und 7,5 µg T3waren bei nur 4 von 12 Patienten suppressiv wirksam, wahrend 100 µg T4 und 10 µg T3 bei allen Dusseldorfer und Munsteraner Patienten, aber nur bei 17 von 31 Patienten in Munchen den TRH-stimulierten TSH-Anstieg supprimierte. Wahrend der gesamten Therapiedauer blieben Thyroxin- und Trijodthyroninspiegel im Serum im Normbereich; bei einigen Patienten erhohte sich der Quotient aus Thyroxin und thyroxinbindendem Globulin uber die Norm. Zeichen einer Uberdosierung oder Unvertraglichkeit wurden nicht beobachtet. In pharmakokinetischen Untersuchungen an acht freiwilligen schilddrusengesunden Probanden erreichte der mittlere Thyroxin- und Trijodthyroninspiegel etwa 2 Stunden nach Applikation sein Maximum und naherte sich nach sechs Stunden wieder der Norm. Es zeigten sich deutliche individuelle Schwankungen in den ersten Stunden nach Applikation. Wir empfehlen deshalb, Schilddrusenhormonspiegel erst 12 oder 24 Stunden nach Applikation eines Schilddrusenhormonpraparates zu bestimmen; zu dieser Zeit sollte auch der TRH-Test durchgefuhrt werden. Die Untersuchungen bestatigen die Notwendigkeit, bei der Strumatherapie mit einem Schilddrusenhormonpraparat die suppressiv wirksame Dosis individuell zu ermitteln; diese Dosis betragt vorzugsweise 100 µg Thyroxin und 10 µg Trijodthyronin oder 150 µg Thyroxin oder 100 µg Thyroxin und 20 µg Trijodthyronin pro Tag.

Using case categories at the Center for Internal Medicine of the Medical University at Lubeck and predictions of future population trends by the German Federal Statistical Office, likely future numbers of inpatients and days of hospital stay were calculated. Assuming other conditions remaining constant, an annual rise of 0.9% of medical cases is to be expected until the year 2005. An increase above this average is expected for cases of cardiovascular and respiratory disease and of malignant neoplasms, while it will be below average for renal or gastrointestinal diseases. These data are similar to comparable projections made, on the basis of Federal statistics, of hospital cases registered with local health insurance schemes. In addition they indicate an increase of 3% for all non-paediatric admissions up to 2005.

Seit 1. 1. 1993 ist auf den Erhebungsbogen der Pflege-Personalregelung des Gesundheitsstrukturgesetzes die Angabe des ICD-Schlussels (ICD = »international classification of diseases«) der Hauptdiagnose gesetzlich vorgeschrieben. Um die Fehlerquote bei dieser Verschlusselung und deren Ursachen zu analysieren, wurden fur das 1. Halbjahr 1993 die Daten der Pflege-Personalregelung erfast und die ICD-Schlussel mit den korrespondierenden Eintragen des Diagnosenarchivs abgeglichen. Bei 671 der 2308 uberpruften Erhebungsbogen (29 %) wurden Fehler bei der Verschlusselung festgestellt. Besonders hoch war die Fehlerquote in den Bereichen Kardiologie (39 %), Angiologie (37 %), Nephrologie (36 %) und Neurologie (35 %). Allerdings stammten die falschen Diagnosen in der Kardiologie und Nephrologie zu einem hohen Prozentsatz aus demselben Diagnosenteilbereich. - Im Sinne der Qualitatssicherung mussen die an der Verschlusselung beteiligten Arzte uber die negativen Folgen fur die Personalausstattung umfassend informiert werden; die Verschlusselung mus von erfahrenen Kollegen durchgefuhrt, klinikintern uberpruft und, falls technisch moglich, mit dem Diagnosenarchiv abgeglichen werden. Die Erfassung nur einer Hauptdiagnose ist bei multimorbiden Patienten nicht sinnvoll.

Thyroid volume was determined by ultrasound in 13-year-old school-children (n = 2244) from 23 places in the Federal Republic of Germany and in 224 school-children from Stockholm (where there is adequate iodine supply). The results show that thyroid size gradually increases from north to south. There are clear endemic nests in the central region of the Federal Republic of Germany. Mean thyroid volume in Swedish children was 4.2 ml, in German children 9.3 ml. More than one third of German children have a larger thyroid volume than the largest volume measured in Swedish children. The results support the need for iodine-salt prophylaxis for the entire German Federal Republic.

Ausreichende Bewegung ist neben angemessener Ernahrung das universellste Therapeutikum, das wir kennen. An zahlreichen Organen und Gewebssystemen zeigen sich positive Auswirkungen eines regelmasigen Ausdauertrainings im Sinne einer Primarpravention. Trotzdem sind Bewegungsmangel und Ubergewicht in der deutschen Bevolkerung weit verbreitet. Neben der Eigenverantwortung des Einzelnen mussen die krankheitsorientierte Pravention und ebenso die „salutogen“ orientierte Gesundheitsforderung auf der Basis eines breiten gesellschaftlichen Konsenses verstarkt werden. Dazu ist zunachst eine verbesserte Versorgungs- und Praventionsforschung zu fordern. Diese nationale Aufgabe ist nicht allein durch die Krankenkassen zu finanzieren, stattdessen mussen Steuern und Abgaben (wie z. B. die Tabaksteuer) zur Finanzierung beitragen. Nur so ist den standig wachsenden Kosten im Gesundheitswesen entgegenzusteuern.

Der Vergleich von drei Methoden zum Nachweis von Schilddrusenvergroserungen bei 92 Patienten zeigt, das die Sensitivitat von sonographischer Volumetrie (93 %) und Palpation (91 %) besser als die der Rontgenaufnahmen (45 %) ist. Als Nachteil der Sonographie fiel das Fehlen des quantitativen Nachweises von retrosternalen Strumen ins Gewicht. Als Nachteil der Palpation und der Rontgen-Thoraxaufnahmen ergab sich die Haufigkeit sicher falsch-positiver Befunde von 8,7 bzw. 10,9 %.

Background The present study was performed to analyse the immunological properties of the autoantigens recognized by autoantibodies against exocrine pancreas (PAb), which have been described in Crohn's disease. Methods Autoantibodies were detected by indirect immunofluorescence. Inhibition studies were performed by preincubating tissue sections with various glycoproteins and the different fractions obtained in fractioned salt precipitation of pancreas homogenate with ammonium sulphate. Immunoblotting of human pancreas homogenate was conducted using PAb-positive sera. Results In size exclusion chromatography, the molecular weight of the pancreas autoantigen (PAg) was determined as > 800 kD. In the fractionated salt precipitation, the autoantigen could be detected in fractions I (0–25% ammonium sulphate) and III (50–90% ammonium sulphate). In immunoblotting, a number of protein bands were observed (at 16, 18, 19, 24, 27, 29, 31 and 34 kD), and the binding pattern showed little variation between individual patients. Conclusions The protein that is recognized by PAb appears to be a large protein complex consisting of several subunits which exhibit reactivity to PAb.

Earlier observations on impaired in vitro effects of aldosterone on lymphocytic sodium and potassium pointed to the involvement of a defective nongenomic rather than genomic effector in pseudohypoaldosteronism. In this study, we investigated nongenomic aldosterone action in five patients with pseudohypoaldosteronism with regard to a rapid increase of free intracellular calcium[ Ca2+]i in cultured nasal epithelial cells, assumably reflecting calcium influx through calcium channels. Patients were defined by episodes of salt loss despite high plasma aldosterone and renin levels. Four unaffected members of the families and four independent subjects served as controls. Considering an aldosterone-induced increase of [Ca2+]i by at least 10 nm as positive response, only 12% of cells from patients were responsive compared with 25% in normal subjects (P< 0.05). In terms of absolute changes, mean increase of[ Ca2+]i was 1.6 ± 1.1 nm in the patients (range - 1–4) and 9.5 ± 2.7 nm (P< 0.025) in the controls (range 1–2...

To date, it has remained unclear whether T cells infiltrating thyroid, retroorbital, and pretibial tissue of patients with Graves' ophthalmopathy and pretibial dermopathy represent a primary immune response that is directed against certain antigenic determinants shared among these involved tissues. To characterize these T cells at the molecular level, we compared the T cell antigen receptor (TcR) variable (V) region gene usage in thyroid, retroorbital, pretibial tissue, and peripheral blood mononuclear cells of two patients with Graves' disease, ophthalmopathy, and pretibial dermopathy. Ribonucleic acid was extracted, reverse transcribed, and amplified using the PCR and 22 V alpha and 23 V beta gene-specific oligonucleotide primers. The resulting TcR V alpha and V beta transcripts were verified by Southern hybridization analysis using TcR C region-specific, digoxigenin-labeled oligonucleotide probes. In addition, complementarity determining regions 3 and junctional regions of TcR V beta genes were sequenced. Marked similarities of intrathyroidal, retroorbital, and pretibial TcR V alpha and V beta gene repertoires were noted with respect to the degree of TcR V gene restriction and the patterns of individual V genes expressed. Sequence analysis of junctional domains of V beta families revealed oligoclonality of intrahyroidal, retroorbital, and pretibial T cells. In addition, certain conserved junctional motifs were shared by T cells derived the thyroid gland and the extrathyroidal sites. Our results suggest that in the two patients with Graves' disease and extrathyroidal manifestations studied, similar antigenic determinants may have contributed to the recruitment and oligoclonal expansion of T cells both within the thyroid gland and at the involved extrathyroidal sites.

High-affinity progesterone-binding sites have been identified, characterized in and purified from porcine liver membranes. They were functionally solubilized by the non-denaturing zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (Chaps, 20 mM. detergent/protein mass ratio 4:1) at a yield of 75-80%. Using [3H]progesterone as radioligand, binding studies showed high-affinity and low-affinity binding sites in microsomal preparations with an apparent Kd2 of 11 nM and an apparent Kd2 of 286 nM. In solubilized fractions the high-affinity binding sites were present at an apparent Kd2 of 69 nM. In both preparations, progesterone binding was time-dependent, saturable, reversible, and showed a similar hierachy of affinities for related steroids. A purification scheme was developed based on anion-exchanger procedures. The purified fraction as identified by maximum specific progester-one-binding activity contained two major polypeptides of apparent molecular masses (SDS/PAGE) of 28 kDa and 56 kDa, respectively. Sequencing of both polypeptides showed an identical amino terminus without significant identity in the amino acid sequence to any known protein primary structure.

Thyroxine-binding globulin (TBG) is the main transport protein for thyroxine (T4) in blood. It shares considerable sequence homology with alpha 1-antitrypsin (AT) and other members of the serine proteinase inhibitor (serpin) superfamily of proteins. The crystallographic structure of AT has been determined and was found to represent the archetype of the serpins. This model has been used for structure-function correlations of TBG. Sequence analysis of the heat-resistant variant TBG-Chicago (TBG-CH) revealed a substitution of the normal tyrosine 309 with phenylalanine. For further analysis, vectors containing the coding regions of normal TBG (TBG-N) and TBG-CH were constructed, transcribed in vitro, and expressed in Xenopus oocytes. Both TBGs were secreted into the culture medium and could not be distinguished by gel electrophoresis. Scatchard analysis of T4 binding to TBG-N and -CH revealed no significant differences in binding affinity. The rate of heat denaturation of TBGs was determined by measurement of residual T4 binding capacity after incubation at 60 degrees C for various periods of time. The half-life values of denaturation of TBG-N and -CH were 7 and 132 min, respectively. The tyrosine 309 to phenylalanine substitution of TBG-CH involves a highly conserved phenylalanine residue of the serpins. The respective phenylalanine 312 of AT ties the alpha-helix hI1 to the molecule, thus stabilizing the tertiary structure. A substitution with tyrosine would disrupt this interaction. Accordingly, stabilization of the TBG molecule by replacement of tyrosine with phenylalanine in position 309 causes the increased heat stability of TBG-CH.

It is unknown whether T cells infiltrating the pretibial skin of patients with thyroid-related pretibial dermopathy represent a primary immune response or participate in a nonspecific inflammatory process. To characterize these T cells at the molecular level, we examined the T-cell antigen receptor variable region gene usage in pretibial skin biopsy specimens obtained from patients with early and late stages of pretibial dermopathy and from individuals with unrelated inflammatory conditions of the pretibial skin. RNA extracted from pretibial biopsy specimens and peripheral blood lymphocytes was reverse transcribed and amplified with the polymerase chain reaction and 22 V alpha and 23 V beta gene-specific oligonucleotide primers. The resulting T-cell receptor (TcR) V alpha and V beta transcripts were verified by Southern hybridization analysis using TcR C-region-specific, digoxigenin-labeled oligonucleotide probes. Compared with matched peripheral blood lymphocytes, the pretibial TcR V alpha and V beta gene repertoire expressed was heterogeneous but revealed marked restriction of V alpha and V beta gene usage in samples derived from patients with active inflammatory pretibial dermopathy of recent onset. In contrast, greater diversity of the TcR V alpha gene repertoire and loss of TcR V beta gene restriction were noted in patients with long-standing, clinically inactive pretibial dermopathy. TcR V gene usage in pretibial tissue and peripheral blood lymphocyte samples obtained from control subjects was unrestricted. Limited variability of TcR V gene usage in early pretibial dermopathy may reflect a primary immune response of antigen-specific T lymphocytes infiltrating the pretibial skin in thyroid-related pretibial dermopathy.

We have studied the relationship between insulin activation of insulin-receptor kinase and insulin stimulation of glucose uptake in isolated rat adipocytes. Glucose uptake was half-maximally or maximally stimulated, respectively, when only 4% or 14% of the maximal kinase activity had been reached. To investigate this relationship also under conditions where the insulin effect on activation of receptor kinase was decreased, the adipocytes were exposed to 10 microM-isoprenaline alone or with 5 micrograms of adenosine deaminase/ml. An approx. 30% (isoprenaline) or approx. 50% (isoprenaline + adenosine deaminase) decrease in the insulin effect on receptor kinase activity was found at insulin concentrations between 0.4 and 20 ng/ml, and this could not be explained by decreased insulin binding. The decreased insulin-effect on kinase activity was closely correlated with a loss of insulin-sensitivity of glucose uptake. Moreover, our data indicate that the relation between receptor kinase activity and glucose uptake (expressed as percentage of maximal uptake) remained unchanged. The following conclusions were drawn. (1) If activation of receptor kinase stimulates glucose uptake, only 14% of the maximal kinase activity is sufficient for maximal stimulation. (2) Isoprenaline decreases the coupling efficiency between insulin binding and receptor-kinase activation, this being accompanied by a corresponding decrease in sensitivity of glucose uptake. (3) Our data indicate that the signalling for glucose uptake is closely related to receptor-kinase activity, even when the coupling efficiency between insulin binding and kinase activation is altered. They thus support the hypothesis that receptor-kinase activity reflects the signal which originates from the receptor and which is transduced to the glucose-transport system.

We report a rare case of sarcoidosis of the hypothalamic and suprasellar region, with clinical course and the magnetic resonance imaging follow-up.

A full-length cDNA clone for a progesterone membrane binding protein from porcine vascular smooth muscle cells was isolated and the complete nucleotide sequence determined. The cDNA encodes a protein of 194 amino acids with a transmembrane segment. This protein is likely to represent the first steroid membrane receptor or a part of it for which sequence information is available.

Heufelder AE, Scriba PC. Characterization of adhesion receptors on cultured microvascular endothelial cells derived from the retroorbital connective tissue of patients with Graves' ophthalmopathy. Eur J Endocrinol 1996:134:51–60 T lymphocytes have been demonstrated recently to play an important role in the pathogenesis and propagation of Graves' ophthalmopathy (GO). Recruitment of T cells to the retroorbital tissue in GO involves the activation of certain adhesion molecules both in the vascular endothelium and in the extravascular connective tissue within the retroorbital space. To characterize the interactions between orbital endothelial cells (OECs) and circulating T cells in vitro, we designed a two-step immunopurification procedure with bead-immobilized Ulex europaeus I lectin and anti-human endothelial cell antigen (CD3I) monoclonal antibody for rapid and reproducible isolation of highly pure microvascular endothelial cell populations from small quantities of retroorbital connective tissue. Endothelial origin of the resulting cell populations was confirmed by positive immunoreactivity for von Willebrand factor. CD 3 I and thrombomodulin. Under baseline conditions, GO-OECs, but not normal OECs, expressed intercellular adhesion molecule 1 (ICAM-1) and CD44 immunoreactivity but no immunoreactivity for endothelial leukocyte adhesion molecule I (ELAM-1) and vascular cell adhesion molecule I (VCAM-1) was detected. Exposure of GO-OEC and normal OEC monolayers to interferon γ, interleukin 1 α and tumor necrosis factor α resulted in marked up-regulation of immunoreactivity for ICAM-1 and in induction of ELAM-1 and VCAM-1. Blocking experiments using monoclonal antibodies directed against various adhesion molecules demonstrated that interactions between matched activated T lymphocytes and OECs were mediated by integrin-dependent ICAM-1/leukocyte function-associated antigen 1 (LFA-1): VCAM-1/very late antigen 4 (VLA-4)) and integrin-independent (CD44) pathways, and revealed marked differences when comparing GO-OECs and normal OECs. In conclusion, the availability of OECs from affected retroorbital tissue of patients with GO provides a valuable tool for studying further the mechanisms responsible for orbit-specific lymphocyte recruitment in GO. Armin E Heufelder, Molecular Thyroid Research Unit, Medizinische Klinik, Klinikum Innenstadt, Ziemssenstrasse 1, 80336 München, Germany

Heufelder AE, Herterich S, Ernst G, Bahn RS, Scriba PC. Analysis of retroorbital T cell antigen receptor variable region gene usage in patients with Graves' ophthalmopathy. Eur J Endocrinol 1995; 132: 266–77. ISSN 0804–4643 To date, it has remained unclear whether orbit-infiltrating T cells in patients with Graves' ophthalmopathy (GO) represent a primary immune response in which a limited number of T cell clones driving the disease are activated against specific antigens, or whether they participate in a non-specific inflammatory process. To characterize these T cells at the molecular level, we examined the T cell antigen receptor (TcR) V gene repertoire in situ in retroorbital tissue specimens obtained from patients with early and late stages of clinically severe GO and from patients with non-GO orbital conditions. Ribonucleic acid extracted from orbital tissue and peripheral blood lymphocytes (PBL) was reverse transcribed and amplified using the polymerase chain reaction and 22 Vα and 24 Vβ genespecific oligonucleotide primers. The resulting TcR Vα and Vβ transcripts were verified by Southern hybridization analysis using TcR C region-specific, digoxigenin-labeled oligonucleotide probes. Compared with matched PBL, the retroorbital TcR Vα and Vβ gene repertoire expressed was heterogeneous, but revealed marked restriction of V gene usage in samples derived from retroorbital connective tissue and extraocular muscle of all eight patients with severe GO of short duration studied. In contrast, greater diversity of the TcR Vβ gene repertoire and loss of TcR Vα gene restriction was noted in four patients with late GO undergoing reconstructive eye muscle surgery. Unrestricted TcR V gene usage was demonstrated in orbital tissue and PBL samples obtained from control subjects. These results suggest that retroorbital TcR V gene usage is variable but markedly restricted during the earlier stages of GO. With increasing disease duration, greater diversity of the TcR V gene repertoire appears to develop, and oligoclonality of the T cell response may be lost. Selection of patients with early stages of GO will be important when further dissecting TcR usage and antigen specificity of orbit-infiltrating T lymphocytes in GO. Armin E Heufelder, Molecular Thyroid Research Unit, Lab 280, Medizinische Klinik, Klinikum Innenstadt, Ludwig-Maximilians-Universität, Ziemssenstraße 1, 80336 München, Germany

Objective We developed a wallet-sized learning memory decision support system that helps patients with insulin-dependent diabetes mellitus adjust their insulin dosages. Research Design and Methods To determine the efficacy of the support system, we designed a randomized clinical trial with patients participating in a program in a diabetes education center. Patients were assigned to two groups of 21 patients each. All patients performed self-monitoring of blood glucose (SMBG) and were treated with multiple daily injections of insulin. Each of the patients was examined over a 32-day period. The basic educational program, i.e., practical advice in SMBG, diet, and exercise under homelike conditions, was identical in both groups. The only difference was that the first group used the computer for adjusting the insulin dose, whereas the second group received recommendations from the education team. Results The baseline HbA1 levels (9.8 ± 1.6 vs. 9.9 ± 1.6%) of both groups did not differ significantly. Mean blood glucose over the last 2 wk of the study was higher (P < 0.01) in the second group (8.4 ± 1.4 vs. 9.2 ± 2.0 mM); the frequencies of hypoglycemic episodes were not different (1.7 vs. 2.3%). Conclusions Metabolic control and safety were comparable in both groups. Thus, patients may benefit from such a system at home where no support by diabetes educators is available.

Thyroid volume of 1397 German and 303 Swedish adults were estimated by sonography. Thyroid size of 6–16 year old Germans (n = 619) was determined and compared with findings on palpation. Thyroid volume was more than twice as great in German (21.4 ± 15.6 ml, mean ± sd) than in Swedish adults (10.1 ± 4.9 ml). The echopattern was abnormal in 16% of the Germans and in 3.6% of the Swedes. German children have a thyroid volume ranging from 1.8 ± 0.4 ml at 6 years to 10.8 ± 6.0 ml at 16 years of age. Palpation is by comparison an unreliable method for determining thyroid size. In Germany, the iodine excretion was less in children (n = 619, 39.5 ± 30.5, 34.1 μg I/g creatinine, mean ± sd, median) than in adults (n = 1193, 83.7 ± 94.4, 62.6), (P P < 0.0001). Serum thyrotropin concentration was significantly higher (P P

Summary: This article describes the synthesis of a pure cortisol-3-(0-carboxymethyl) oxime with its subsequent usein producing highly specific antibodies and a 125 I-tracer with a shelf life in excess of several weeks.An assay was developed using a pH of 4, thus allowing a direct measurement of cortisol in serum without extractionor heat denaturation.The quality-control parameters were checked — the intra-assay C. V. in the working range (area of clinical interest)was under 5%, and the interassay C.V. under 11%. Correlation studies with results using other antisera and with 3 H-tracer are highly significant with the slope of the regression curve deviating less than 2% from the ideal volume.Finally the assay is fully automatable and is suitable for most automatic pipetting and analysis systems. Die Entwicklung eines direkten homologen Radioimmunoassay s fur Serum-Cortisol Zusammenfassung: Diese Arbeit beschreibt die Herstellung eines reinen Cortisol-3-(O-carboxymethyl) oxims undseine weitere Verwendung zur Gewinnung hochspezifischer Antiseren und eines

Urinary iodine excretion of 1945 schoolchildren aged 13 to 15-years from 24 cities throughout the Federal Republic of Germany (FRG) was measured. For comparison, urinary excretion of 5678 adults from 20 cities was calculated from the 24-hour radio-iodine uptake (RIU) by the method of Oddie. On the average the schoolchildren excreted 25.1 mug iodine per g creatinine: by WHO criteria this can be classified as a grade II iodine deficiency. There was a significant decline of urinary iodine excretion from North to South of the FRG. Urinary iodine excretion of children with thyroid enlargement (21.9 mug/g) was significantly less than that of normal children (26.1 mug/g creatinine; P less th that 0.0005). Urinary iodine excretion of adults averaged 25 to 35 mug/g creatinine, values calculated from RIU agreeing well with those determined chemically. Alimentary iodine intake was found to vary between 30 and 70 mug/d throughout the FRG, which is less than 30% of WHO recommended figures for optimal goitre prevention (150-200 mug iodine per day). Alimentary iodine deficiency has been demonstrated throughout the FRG, increasing from North to South in parallel with an increase in goitre rate. Goitre prevention through compulsory iodinization of salt is recommended.

The results of a thyrotropin external quality assessment survey (EQAS) carried out in 1980 using the "Munich Model" and including a "matched reagent" experiment are presented and are compared with the results from similar surveys carried out in 1974 and 1977. Despite the fact that in 1974 only 4 different kits were used, compared with 12 in 1977 and 17 in 1980, the inter-laboratory precision has continually improved. This was reflected by the inter-laboratory coefficient of variation (CV) for all laboratories, which, for a sample with ca. 15 microU/l thyrotropin were: 65% (1974), 22% (1977) and 12% (1980), and for a sample containing ca. 5 microU/l thyrotropin: 75% (1974), 45% (1977) and 20% (1980). During the same period, the fraction of participants using commercial kits increased from 0.65 to 0.95. There was a definite trend towards shorter assays, even though with such assays there is a danger that the measured values for low thyrotropin concentrations will be too high. In spite of the fact that the "high-blank" effects have to a large extent disappeared, many kits showed an unacceptably high cross-reactivity with human chorionic gonadotropin. A fraction of 0.30 of all participants in 1974 used computer-assisted data-processing, compared with 0.78 in 1980. In 1980, the most commonly used algorithm was a spline function (0.46 of participants using a computer for data-processing). Although the number of kits has increased, the precision has improved, showing that more robust methods are now employed. This has partly come about because of the introduction of human thyrotropin-free serum as matrix for the standards (1974 - 0.16, 1980 - 0.83 of all participants). Further external quality assessment programmes are discussed for the continual monitoring of hormone assay performance.

A 22-year-old woman with recurrent goiter, hyperthyroidism, galactorrhea, and amenorrhea due to a pituitary tumor is described. She had been treated surgically twice for recurrent goiter with tracheal compression. Despite clinical signs of hyperthyroidism and slightly elevated plasma thyroid hormone levels (T4: 11 mug/dl; T3: 189 ng/dl), without thyroid hormone replacement therapy the basal TSH level was elevated up to 23 muU/ml and could not be suppressed by exogenous thyroid hormones: even when the serum thyroid hormone levels were raised into the thyrotoxic range (T4: 16.2 mug/dl T3: 392 ng/dl), the basal TSH fluctuated between 12 and 29 muU/ml. The basal PRL level was elevated up to 6000 muU/ml. The administration of TRH (200 mug iv) led only to small increments of TSH and PRL levels. Bromocriptin (5 mg p.o.) or l-dopa (0.5 g p.o.) suppressed TSH and PRL values significantly. After transsphenoidal hypophysectomy, TSH and PRL were below normal and the patient development panhypopituitarism. The adenoma showed two cell types which could be identified as lactotrophs and thyrotrophs by electronmicroscopy and immunofluorescence. From these data we conclude that the patient had a pituitary tumor with an overproduction of thyrotropin and prolactin.

Isolation of the corticosteroid-binding globulin CBG was achieved by 5 chromatographical steps on cortisol Sepharose, QAE-Sephadex A-50, Con A-Sepharose and hydroxylapatite. The purity of the isolated CBG was demonstrated in polyacrylamide gel electrophoresis, SDS electrophoresis, immunodiffusion and ultracentrifugation. Microheterogeneity was shown in isoelectric focusing by 5 bands in the pH range of 3.7–4.2, which could be reduced to one major band after neuraminidase treatment. The equimolar binding of cortisol to CBG was demonstrated by binding studies. The association constant for cortisol was 2.8 × 108 m−1, for progesterone 1.7 × 106 m−1. From analytical ultracentrifugation, the molecular weight was calculated on 50 700; the sedimentation coefficient was 3.6 S, the partial specific volume 0.690 ml/g, the Stokes radius 38 Å and the frictional coefficient ratio 1.5. A specific radioimmunoassay for CBG was established using the purified CBG for immunization, radioiodination and for calibration standards. The normal range of CBG levels in human serum was 2.4–4.4 mg/100 ml (mean ± 2 sd). Studies were performed to compare the levels of CBG and thyroxine-binding globulin (TBG). No sex differences but a significant biphasic age dependence were observed for both proteins. In pregnancy and under oestrogen treatment of women and men, CBG was demonstrated to be the more distinct indicator of oestrogenic activity as compared with TBG, whereas the sensitivity of TBG was more pronounced to supposedly antioestrogenic substances like Danazol, and in severe disease. No coincidence of genetic CBG and TBG deficiencies have been found so far.

Continuous plasmapheresis with the IBM blood cell separator showed to be a successful therapy in a 26 year old patient with thyroid storm. The patient regained consciousness already during plasmapheresis whereby 5 liters of plasma were exchanged within 3.5 h. Although 633 mug thyroxine (T4) and 13.6 mug triiodothyronine (T3) were removed with the 51 plasma, no fall occurred in total serum T4 and T3 levels, probably due to the rapid reflux of thyroid hormones from the tissue into the intravascular space. Though total T4 and T3 did not change, there was a significant fall in free thyroid hormone levels documented by reduction of T3-uptake test and particularily of urine T4 and T3 excretion. These findings show that the elevation of thyroid hormone binding sites with donor plasma is even more important than the removal of thyroid hormones.