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  • 11
    Electronic Resource
    Electronic Resource
    Kinetik der Reaktionen von Phenylhydroxylamin mit Blutfarbstoff (1950)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 212 (1950), S. 102-102 
    Details
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00245658
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  • 12
    Electronic Resource
    Electronic Resource
    Clinical and biochemical aspects of the insulin autoimmune syndrome (IAIS) (1986)
    Springer
    Journal of molecular medicine 64 (1986), S. 929-934 
    Details
    ISSN: 1432-1440
    Keywords: Insulin-autoimmune syndrome ; Insulin autoantibodies ; Autoimmune disease ; Hypoglycemia ; HPLC ; Insulin receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 44-year old patient presented with recurrent hypoglycemic attacks after ingestion of carbohydrates. High insulin levels in the range of 350 µU/ml (normal range 〈20 µU/ml) were detected which rose to peak levels of 2,460 µU/ml (normal range 〈300 µU/ml) after oral glucose. The apparently high insulin concentrations were caused by insulin autoantibodies interfering in the radioimmunoassay (RIA) system (and thus with correct insulin quantitation).125I-insulin added to the patient's serum was not bound to dextrancoated charcoal but was precipitated with antihuman IgG serum. The antibodies bound human, porcine, and bovine insulin with similar affinity. Following Sephadex G-50 gel filtration, the patient's insulin eluted after the void volume. Free insulin was extracted from serum using Sep-Pak C18 cartridges and characterized by high pressure liquid chromatography (HPLC); it eluted similarly to synthetic human insulin. Quantitation of free insulin during a hypoglycemic attack (3.5 h after oral glucose, with a blood sugar of 20 mg/dl) showed an increased insulin level of 50 µU/ml. Insulin receptor concentration on erythrocytes was near the lower normal limit. We believe that the insulin antibodies present in this patient's serum (who supposedly never received insulin) led to the formation of a large circulating insulin pool, binding the insulin released after glucose stimulation, and causing hypoglycemias by delayed postprandial liberation of bound insulin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01728618
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  • 13
    Electronic Resource
    Electronic Resource
    Prognostic factors in medullary thyroid carcinoma: evaluation of 741 patients from the German Medullary Thyroid Carcinoma Register (1993)
    Springer
    Journal of molecular medicine 71 (1993), S. 7-12 
    Details
    ISSN: 1432-1440
    Keywords: Medullary thyroid carcinoma ; Prognostic factors ; Sporadic and familial form ; Age ; Sex ; Tumor stage at diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A retrospective study of 741 patients with medullary thyroid carcinoma diagnosed between 1967 and 1991 was carried out by members of the German Medullary Thyroid Carcinoma Study Group to evaluate prognostic factors. A total of 559 patients (75%) were considered to have sporadic disease, and 182 (25%) had the familial type. The sex ratio (male to female) was 1:1.4 in sporadic disease patients, and the mean age at diagnosis was 45.9 years (range 5-81 years). For familial disease patients the sex ratio was 1:1.1, and the mean age at diagnosis was 33.4 (range 5–77 years). The follow-up time for 630 patients ranged from 1 month to 20.8 years (mean 13.0 years). The overall adjusted survival rate was 86.7% at 5 years and 64.2% at 10 years. In a univariate analysis the stage of disease at diagnosis, age, sex, and type of disease (sporadic, familial) were relevant prognostic factors, with a better prognosis for young female patients with familial disease and diagnosed at an early stage. In a multivariate proportional hazards analysis, the difference in the survival rate of patients with familial disease versus those with the sporadic form disappeared, while prognostic information provided by age and sex was still significant. The poorer prognosis of patients with sporadic medullary thyroid carcinoma may be related to the patients' older age at detection and more advanced tumor stage at diagnosis. There seems to be no difference in biological behavior between tumors of the sporadic and those of the familial type.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00210956
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  • 14
    Electronic Resource
    Electronic Resource
    Effectiveness of prophylactic therapy on goiter recurrence in an area with low iodine intake — a sonographic follow-up study (1994)
    Springer
    Journal of molecular medicine 72 (1994), S. 967-970 
    Details
    ISSN: 1432-1440
    Keywords: Goiter ; Thyroxine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is no agreement as to whether or not drug treatment after surgery for nodular goiter is effective in preventing recurrence of goiter. Data about recurrences in areas of marginally low iodine intake (like Germany) vary widely. Therefore, we performed a retrospective study in 104 patients who had been treated surgically because of benign uninodular or multinodular goiter. The mean follow-up period was 6.4 years (minimal 1 year) with at least three examinations. Thyroid ultrasound with volumetric analysis was recorded in each patient. Thirty-two patients did not receive any prophylaxis, 50 patients were treated withl-thyroxine, 17 patients with a combination ofl-thyroxine and iodine and 5 patients with iodine alone. Recurrence of goiter was documented in 28.0% of the untreated patients and in 8.9% of the patients on prophylaxis (P 〈 0.05). The mean increase of thyroid volume was 7.3 ml versus 3.1 ml in patients without versus with prophylactic drug treatment (not significant). No significant correlation was found between the increase of thyroid volume and age of the patients, follow-up time, or intial thyroid volume, respectively. These data clearly demonstrate the effectiveness of prophylactic drug therapy to prevent recurrence of goiter after thyroid surgery in an iodine-deficient area.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00577737
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  • 15
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of antithyroid drugs (1982)
    Springer
    Journal of molecular medicine 60 (1982), S. 531-539 
    Details
    ISSN: 1432-1440
    Keywords: Antithyroid drugs ; Methimazole ; Carbimazole ; Propylthiouracil ; Pharmokinetics ; Absorption ; Metabolism ; Excretion ; Placental Transfers ; Pregnancy ; Thyreostatika ; Methimazol ; Carbimazol ; Propylthiouracil ; Pharmakokinetik ; Resorption ; Metabolismus ; Exkretion ; Plazentapassage ; Schwangerschaft
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 1. Untersuchungen der Pharmakokinetik von Thyreostatika sind durch das Fehlen einfacher und empfindlicher Bestimmungsmethoden für diese Pharmaka in biologischen Flüssigkeiten erschwert. 2. Die Resorption von Carbimazol und — besonders — Methimazol ist erheblichen interindividuellen Schwankungen unterworfen. 3. Propylthiouracil, aber nicht Methimazol wird an Plasmaproteine gebunden. 4. Nach Gabe von Carbimazol ist nur Methimazol im Serum, Urin und Schilddrüsengewebe nachweisbar. Die Konversion von Carbimazol zu Methimazol scheint enzymatisch gesteuert zu werden. Die Methimazol-Plasmaspiegel sind nach Gabe von Carbimazol niedriger als nach Gabe einer gleichen Menge von Methimazol. 10 mg Carbimazol sind äquivalent zu 6–7 mg Methimazol. 5. Verteilung und Elimination von Methimazol und Propylthiouracil können durch ein Ein-Kompartment-System mit Eliminationsweg 1. Ordnung beschrieben werden. Die Plasmahalbwertszeit von Propylthiouracil beträgt etwa 1 h, die von Methimazol 2–6 h. 6. Thyreostatika werden in der Schilddrüse angereichert. Diese Anreicherung wird bei Labortieren durch Jodmangel gehemmt. Die Hemmung der Jodidorganifikation hängt mehr von der intrathyreoidalen als der Plasmakonzentration der Thyreostatika ab. 7. In der Schilddrüse werden die Thyreostatika schrittweise oxidiert und teilweise an Thyreoglobulin gebunden. Der Hauptmetabolit von PTU ist PTU-SO2H. Ein Methimazolmetabolit, das Methylthiohydantoin, kann im Plasma und im Urin nachgewiesen werden. 8. Propylthiouracil wird rasch an Glucuronsäure gekoppelt. Ein beträchtlicher Teil der Thyreostatika und ihrer Metabolite wird mit der Galle ausgeschieden und später reabsorbiert (enterohepatischer Kreislauf). Die faekale Ausscheidung ist sehr niedrig. Im Urin erscheinen geringe Mengen der nicht metabolisierten Substanzen zusammen mit Glucuroniden, Methylderivaten (nur bei Propylthiouracil) und unidentifizierten Metaboliten. 9. In der Schwangerschaft ist die Halbwertszeit von Methimazol verkürzt (nach vorläufigen Daten). Methimazol und Propylthiouracil durchqueren die Plazentaschranke und können im fetalen Blut und in der fetalen Schilddrüse nachgewiesen werden. Die Konzentrationen in der Muttermilch sind sehr gering, besonders bei Propylthiouracil. 10. Über die Änderungen der Thyreostatika-Pharmakokinetik während der Behandlung einer Hyperthyreose gibt es bisher nur unzureichende Daten.
    Notes: Summary Studies of antithyroid drug pharmacokinetics suffer from the lack of simple and sensitive methods for the measurement of these drugs in biologic fluids. This is reflected by most of the data available at present. From a critical review of these studies, the following conclusions emerge: 1) Absorption of methimazole and carbimazole is subject to considerable interindividual variability, which is more pronounced for methimazole than for carbimazole. 2) Propylthiouracil, but not methimazole, is bound to plasma proteins. 3) After administration of carbimazole, only methimazole can be detected in serum and thyroid tissue. Conversion of carbimazole to methimazole appears to be an enzymatic process. Methimazole plasma levels are lower after carbimazole administration than after equal amounts (on a weight basis) of methimazole; 10 mg carbimazole are equivalent to 6–7 mg methimazole. 4) Methimazole and propylthiouracil plasma levels decrease with time according to first-order kinetics. Serum half-life of propylthiouracil is about 1 h, half-life of methimazole is 2–6 h. 5) Antithyroid drugs are concentrated by the thyroid gland. This accumulation is inhibited in iodine deficiency in animals. Inhibition of iodide organification is dependent on intrathyroidal rather than plasma concentration of antithyroid drugs. 6) Intrathyroidal metabolism of antithyroid drugs involves binding to thyroglobulin and stepwise oxidation. The main metabolite of propylthiouracil is PTU-SO2H. A metabolite of methimazole, methylthiohydantoin, can be detected in plasma and urine. 7) Propylthiouracil is rapidly coupled to glucuronic acid. A significant proportion of antithyroid drugs and their metabolites is excreted into bile and later reabsorbed (enterohepatic circulation). Fecal excretion is very low. In urine, small amounts of unchanged drugs are excreted together with glucuronides, methyl derivatives (only PTU) and unidentified metabolites. 8) In pregnancy, methimazole half-life appears to be shortened. Methimazole and propylthiouracil can cross the placenta and are detected in the fetal circulation and thyroid. Concentrations in breast milk are very low, especially for propylthiouracil.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01724208
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  • 16
    Electronic Resource
    Electronic Resource
    Pharmakokinetik von Prednisolon bei Nebenniereninsuffizienz (1982)
    Springer
    Journal of molecular medicine 60 (1982), S. 681-686 
    Details
    ISSN: 1432-1440
    Keywords: Prednisone ; Prednisolone ; Adrenal insufficiency ; Prednison ; Prednisolon ; Nebennierenrindeninsuffizienz
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 16 Patienten mit Nebennierenrindeninsuffizienz und nach bilateraler Adrenalektomie wurde Prednisolon im Serum und im Urin nach peroraler und intravenöser Gabe von Prednison und Prednisolon gemessen. Dabei sollten pharmakokinetische Daten über das Verhalten von Prednisolon gewonnen werden und die Frage geklärt werden, wie lange die Substanz nachweisbar ist. Da sich Prednisolon ähnlich wie Cortisol an Transcortin und Albumin bindet, konnte wegen des Fehlens endogener Corticosteroide eine einfache Proteinbindungsmethode zum Nachweis angewendet werden. Die Ergebnisse zeigen keinen signifikanten Unterschied in den Serumspiegeln nach oraler Gabe von Prednison oder Prednisolon. Die höchsten Konzentrationen wurden nach 2–3 h erreicht und betrugen nach 5, 7,5 und 10 mg Prednison 11,9±2,2 bzw. 15,9±3,4 und 21,5±5,9 µg/dl. Die Serumhalbwertszeit von ca 5 1/2 h läßt nach Gabe von entsprechend höheren Dosen noch auf das Vorkommen meßbarer Serumkonzentrationen nach 2 Tagen schließen. Da Prednisolon die meisten Meßmethoden für Cortisol beeinflußt, empfehlen wir, 2 Tage vor einer Cortisolbestimmung die Prednisontherapie abzusetzen. Die bei nebennierenrindeninsuffizienten Patienten ermittelte erniedrigte metabolische Clearancerate (56,0±7,2 1/24 h/m2) führen wir auf Alterationen im Corticoidstoffwechsel, möglicherweise bedingt durch eine erhöhte Transcortinproduktion, zurück.
    Notes: Summary Prednisolone was measured in serum and urine after oral and intravenous administration of prednisone and prednisolone in 16 patients with adrenal insufficiency and after bilateral adrenalectomy. Thus, the problem of cross-reactivity with endogenous steroids, the main factor disturbing the measurement of prednisolone, was completely eliminated. Prednisolone was detected by a simple competitive protein-binding radioassay. Distribution, elimination and other bioavailability parameters were calculated from the obtained data. No significant differences between serum levels were detected after oral administration of these drugs. Peak levels were reached after 2–3 h. After 5, 7.5 and 10 mg prednisone peak serum levels averaged 11.9±2.2, 15.9±3.4 and 21.5±5.9 µg/dl, respectively. Prednisolone was still detectable 24 h after administration of 10 mg. The plasma half-time of approximately 5 1/2 h suggests that prednisolone is present in serum far about 2 days after application of higher doses. Since prednisolone interfers in most assays for cortisol, prednisone therapie has to be stopped at least 2 days before cortisol determinations. Urinary excretion was proportional to the applicated doses. The metabolic clearance rate of prednisolone was decreased (56.0±7.2 1/24 h/m2) in patients with adrenal insufficiency. This can be attributed to alterations in corticosteroid metabolism, probably due to an increased transcortin production.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01716801
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  • 17
    Electronic Resource
    Electronic Resource
    Thyroid antibodies in children of mothers with auto-immune thyroid disease (1999)
    Springer
    European journal of pediatrics 158 (1999), S. 24-28 
    Details
    ISSN: 1432-1076
    Keywords: Key words Hashimoto thyroiditis ; Graves disease ; Children ; TSH function-blocking antibody ; Cytotoxic antibody
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a cross-sectional study, 29 children aged between 1 month and 15.3 years (average age 6.8 years) born to mothers with Graves disease or Hashimoto thyroiditis were examined clinically, biochemically, and by sonography of the thyroid gland. At the time of examination all children were clinically euthyroid. Tests of thyroid peroxidase antibody, thyroglobulin antibody, TSH receptor antibody and free thyroxine (fT4) gave normal results. In 3 children subclinical hypothyroidism with elevated TSH and normal fT4 concentrations were found; one of these children had a minor decrease of total thyroxine. Three children with otherwise normal test results had marginally elevated tri-iodothyronine concentrations. Increased antibody titres were present in 8 out of 29 children. TSH function-blocking antibodies were elevated in 8 cases. In addition, cytotoxic antibodies were found in one of the children. The distribution pattern of antibodies was different in each child and unrelated to the type of maternal thyroid disease. Conclusion Children of mothers with auto-immune thyroid disease often have thyroid antibodies without signs of thyroid disease. Whether antibody-positive children have an increased risk of developing thyroid disorders later in life must be examined in a longitudinal study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310051003
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  • 18
    Electronic Resource
    Electronic Resource
    Über den Rhodangehalt im Serum bei Erkrankungen der Schilddrüse (1961)
    Springer
    Journal of molecular medicine 39 (1961), S. 130-132 
    Details
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zusammenfassung Serumrhodan wurde bei nichtrauchenden Gesunden und Schilddrüsenpatienten untersucht. Gegenüber einem mittleren CNS-Spiegel von 79,7γ-% bei 52 Normalpersonen hatten 58 blande Strumen 158,8γ-%, 28 Hyperthyreosen mit Struma 129,2 und 5 Hypothyreosen mit Struma 182,6γ-% im Serum. Athyreosen sowie Hyper- und Hypothyreosen ohne Struma unterschieden sich nicht von den Normalwerten. Der erhöhte Rhodangehalt im Serum geht der Größe der Struma parallel. Eine Abhängigkeit zwischen Serumrhodan einerseits und Jodaufnahme sowie intrathyreoidalem Umsatz andererseits besteht nicht. Nach subtotaler Strumektomie kehrt der vorher erhöhte Rhodangehalt im Serum zur Norm zurück. Der bei Strumen erhöhte Serumrhodanspiegel wird auf eine Stoffwechselstörung in der hyperplastischen Schilddrüse zurückgeführt.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01485359
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  • 19
    Electronic Resource
    Electronic Resource
    Enzymmuster der menschlichen Schilddrüse (1964)
    Springer
    Journal of molecular medicine 42 (1964), S. 731-735 
    Details
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In homogenates of 20 normal human thyroid glands the enzyme pattern was investigated. 23 enzymes of the following metabolic pathways were studied: Embden-Meyerhof pathway, pentose shunt, citric acid cycle, electron transport, fatty acid cycle, amino acid metabolism. In addition phosphatases, proteases and peptidase were also studied. Methodical errors in the preparation, errors due to blood contamination and due to variable distribution of enzymes changed the enzyme pattern very little. Only freshly operated thyroid glands were used. The enzyme pattern of thyroid glands is characterized by relatively high activities of glucose-6-phosphate dehydrogenase and acid phosphatase and by low activities of the enzymes of the Embden-Meyerhof pathway, Krebs cycle and amino acid metabolism. Enzymes of the fatty acid cycle could not be detected. The findings suggest a favored catabolism of glucose by the pentose shunt. The pecularities of the thyroid enzymes compared with the ones described in liver are discussed.
    Notes: Zusammenfassung In 20 normalen menschlichen Schilddrüsen untersuchten wir die Aktivität von 23 Enzymen. Es handelt sich um Proteasen (mit Thyreoglobulin und Hämoglobin als Substrat), Peptidasen, Enzyme des Embden-Meyerhof-Cyclus (Lactat-Dehydrogenase, Aldolase, 3-Phosphoglyceratkinase, Glycerinaldehydphosphat-Dehydrogenase), Pentose-Shunts (Glucose-6-Phosphat-Dehydrogenase), Citronensäurecyclus (Isocitrico-Dehydrogenase, Malat-Dehydrogenase), der Atmungskette (Cytochrom c-Reduktase, Cytochrom c-Oxydase, Bernsteinsäure-Dehydrogenase), des Aminosäurestoffwechsels (Glutamat-Dehydrogenase, Glutamat-Oxalacetat-Transmainase, Glutamat-Pyruvat-Transaminase, TPNH- und DPNH-Glutathion-Reduktase), des Fettsäurecyclus (beta-Ketoacylthiolase, beta-Oxacyl-Dehydrogenase, Acyl-Dehydrogenase) sowie alkalische und saure Phosphatasen. In Vorversuchen wurde geklärt, wie sich bei der Aufarbeitung des Drüsengewebes verschiedene Extraktionsverfahren, Fraktionierungen, Faktoren der Alterung und Blutbeimengungen auf das Enzymmuster auswirken. Die Aktivität der Enzyme verteilt sich bis auf wenige Ausnahmen zu ca. 80% auf die 20 000 × g-Fraktion und deren Überstand. Lediglich artefiziell oder in situ gealterte Organe verzerren das Enzymspektrum. Die technischen Fehler bei der Präparation des Homogenates sind nur etwas größer als diejenigen bei der Enzymmessung selbst. Das Enzymmuster der operativ gewonnenen Schilddrüse ist durch eine relativ hohe Glucose-6-Phosphat-Dehydrogenase bei niedriger Aktivität der Enzyme der Glykolyse und des Krebs-Cyclus und Aminosäurestoffwechsels charakterisiert. Fermente des Fettsäurecyclus waren nicht nachzuweisen. Möglicherweise werden die Kohlenhydrate bevorzugt durch den Pentose-Shunt abgebaut. Ein Vergleich mit Enzymen anderer Organe ist nur mit Einschränkung möglich, weil organspezifische Eigenschaften der Enzyme nicht bekannt sind.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01487809
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  • 20
    Electronic Resource
    Electronic Resource
    T-Lymphocyten bei Schilddrüsenerkrankungen (1976)
    Springer
    Journal of molecular medicine 54 (1976), S. 987-993 
    Details
    ISSN: 1432-1440
    Keywords: Thyroid Diseases ; Immunology ; Schilddrüsenerkrankungen ; Immunologie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung T-Lymphocyten wurden bei 18 Patienten mit unbehandelter florider Hyperthyreose, 28 Patienten mit „kompensierter Hyperthyreose“ nach thyreostatischer Langzeitbehandlung mit Carbimazol oder Methimazol in Kombination mit L-Thyroxin, 14 Hyperthyreosen nach 131-Jodbehandlung, 7 Hashimoto-Thyreoiditiden und 7 blanden Strumen bestimmt und mit einem Normalkollektiv von 40 Schilddrüsengesunden verglichen. Ein Unterschied des prozentualen Anteils und der Absolutzahlen der T-Lymphocyten ließ sich weder zwischen den Gruppen mit Schilddrüsenerkrankungen noch im Vergleich zum Normalkollektiv sichern. Nach diesen Befunden sind die Absolut- und Relativwerte der T-Lymphocyten im Blut keine geeigneten Parameter für die Beurteilung der Aktivität und Prognose der verschiedenen Schilddrüsenerkrankungen und gestatten keine Aussage über die pathogenetisch vielleicht relevante Bedeutung der zellvermittelten Immunität.
    Notes: Summary Thymus-derived peripheral blood lymphocytes were studied in untreated (n=18), methimazoletreated (n=28) thyrotoxicosis, after radioiodine (n=14), in Hashimoto thyroiditis (n=7) and in euthyroid goiter (n=7). The results were compared with normal persons (n=40) without thyroid disease. There was no significant difference in the total and relative counts of T-cells either between the different groups nor compared with the controls. These findings confirm that T-cells in peripheral blood cannot give any information about activity or prognosis of the various thyroid diseases. Thus T-cells give no further suggestion concerning the possible pathogenetic role of cell-mediated-immunity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01468950
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