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  • 1
    ISSN: 1432-1440
    Keywords: CIAA ; CF-ICA ; Beta-cell function ; IVGTT ; HLA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Out of a random population of 4208 non-diabetic pupils without a family history of Type I diabetes 44 (1.05%) individuals had islet cell antibody (ICA) levels greater or equal to 5 Juvenile Diabetes Foundation (JDF) units. 39 of these ICA-positives could be repeatedly tested for circulating insulin autoantibodies (CIAA) using a competitive radiobinding assay. The results were compared with the insulin responses in the intravenous glucose tolerance tests (IVGTT) and with HLA types. Six pupils were positive for CIAA. All of them had complement-fixing ICA, and 5 of them were HLA-DR4 positive. Three of the 6 showed a first-phase insulin response below the first percentile of normal controls. Our data indicate that in population-based studies CIAA can be considered as a high risk marker for impaired beta-cell function in non-diabetic ICA-positive individuals.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Thyrotropin-releasing hormone ; RIA-TRH ; Pharmacokinetics ; Hypothyroidism ; Hyperthyroidism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The pharmacokinetics of thyrotropin-releasing hormone (TRH) were assessed following an i.v. injection in blood of ten hyperthyroid, ten hypothyroid, and six normal subjects. A single-compartment model was employed. After methanol extraction, TRH concentrations were analyzed using a specific radioimmunoassay technique combined with fast protein liquid chromatography (FPLC). As for the basal levels of TRH, no differences were observed in either study group. Peak concentrations were always present two min after the injection of TRH. In the euthyroid subjects, TRH blood levels had a half-life (t 1/2) of 6.5±0.41 min, mean±SD, whilet 1/2 was 7.2±0.62 min in the hyperthyroid andt 1/2 was 12±1.67 min (p〈0.001) in the hypothyroid patients. The metabolic clearance rate (MCR) (82.2±15.3 liters/m2/day vs. 89.8±17.2) and the volume of distribution (Vd) (7.1±4.2 liters vs. 7.3±3.4) were approximately the same in the normal subjects and in the hyperthyroid group. MCR (66.2±15.3 Iiters/m2/day) and Vd (6.2±3.3 liters) were found to be lower in the hypothyroid patients. In FPLC, when TRH was added to plasma, it eluted in one peak. Blood samples taken 5 min after TRH i.v. injection had an elution profile of 9.94 ml. These data indicate that 1) TRH has a very short half-life, 2) hypothyroidism can prolong thet 1/2 of exogenous TRH, and 3) when TRH should be used in clinical studies, the function of the thyroid gland has to be taken into consideration.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1440
    Keywords: Coronary artery disease ; Sex hormones ; Obesity ; Body fat distribution ; Angiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relationship between circulating sex hormone levels and the occurrence of coronary artery disease (CAD) was studied in a group of 274 men undergoing coronary angiography. Hormone levels in men with CAD (n=200) were compared to those in men found to be free of coronary lesions (n=74). No significant differences were found for serum concentrations of estradiol, total testosterone, sex-hormone-binding globulin, free androgen index, dehydroepiandrosterone sulfate, or cortisol between the two groups. Serum androgens were negatively correlated to age in both groups, whereas estradiol was weakly associated with total cholesterol in the group of men without CAD. No consistent associations were detected between sex hormone levels and the degree of obesity or the distribution of body fat, the latter being assessed by the ratio of waist-to-hip circumferences. The results of this study do not support a significant role of sex steroid hormones in coronary artery disease in men.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Viral antibodies ; Beta-cell function ; population study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Viral antibodies were tested in a cohort of 44 isletcell antibody-positive individuals age 7–19 years, and 44 of their islet cell antibody-negative age and sex-matched classmates selected from a population study of 4208 pupils who had been screened for islet cell antibodies. Anti-coxsackie B1-5 IgM responses were detected in 14 of 44 (32%) of the islet cell antibody-positive subjects and in 7 of 44 (16%) control subjects. This difference did not reach the level of statistical significance. None of the islet cell antibody-positive subjects had specific IgM antibodies to mumps, rubella, or cytomegalovirus. There was also no increase in the prevalence or the mean titres of anti-mumps-IgG or IgA and anti-cytomegalovirus-IgG in islet cell antibody-positive subjects compared to control subjects. These results do not suggest any association between islet cell antibodies, and possibly insulitis, with recent mumps, rubella or cytomegalo virus infection. Further studies are required to clarify the relationship between islet cell antibodies and coxsackie B virus infections.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Continuous glucose sensing ; enzyme electrode ; glucose oxidase ; subcutaneous glucose concentration ; microdialysis ; oral glucose load
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary For the normalisation of blood glucose levels in diabetic patients by feedback controlled insulin delivery, a self-manageable and reliable method for continuous glucose estimation is still not available. By combining a commercially available needle type dialysis probe (molecular cutoff 20,000 Da) with a sensitive glucose sensor, we obtained a device for continuous glucose measurement in dialysate. This device was tested in healthy volunteers during a 75-g oral glucose tolerance test and in Type 2 (non-insulin-dependent) diabetic patients. Venous glucose and subcutaneous sensor signal were followed for 300 min (ten healthy subjects), 21 h (three healthy subjects) or 9 h (seven Type 2 diabetic patients). The recovery of the microdialysis was interindividually different, but after calibration, glucose levels in the dialysate and subcutaneous glucose sensor signal correlated well (r = 0.84–0.95). Under the assumption of a physiologic and technical delay between intravenous and subcutaneous glucose, correlation coefficient between intravenous glucose and subcutaneous sensor signal ranged from 0.60 to 0.93. We conclude that changes in blood glucose could be monitored in the subcutaneous tissue by the microdialysis technique in a continuous on line manner.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 12 (1976), S. 441-446 
    ISSN: 1432-0428
    Keywords: Sucrose ; increased body fat ; isolated perfused pancreas ; dynamics of insulin secretion ; hyperinsulinism ; insulin biosynthesis ; isolated islets of Langerhans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Long term feeding of a sucrose rich diet to rats is accompanied by a decreased glucose assimilation rate, despite high plasma insulin levels. Hyperinsulinism is at least partially based on a relative obesity, with increased amounts of abdominal- and retroperitoneal fat tissue, but unchanged total body weight compared to starch fed controls. The secretory pattern of insulin release was studied following glucose, arginine, fructose and sulfonylurea administration in the isolated perfused pancreas of sucrose and isocaloric starch fed rats. In addition, isolated islets of Langerhans were used to demonstrate the effects of glucose on insulin secretion and the incorporation of H-3 leucine into the proinsulin and insulin fraction of islet proteins. Following 11 mM glucose, the dynamics of insulin release in the isolated perfused pancreas of sucrose fed rats is characterized by a markedly elevated, late plateau-like response, usually seen only at higher glucose concentrations. Hyperinsulinism, as compared to starch fed controls, can also be demonstrated following arginine and the sulfonylurea HB-419, whereas fructose has no effect in the presence of low glucose concentrations. During incubation of the pancreatic islets, the hyperinsulinism in sucrose-, compared to starch fed rats, is more pronounced at 11 mM glucose than at 5.5 mM glucose. The incorporation of H-3 leucine into the proinsulin-insulin fraction of islet proteins in sucrose compared to starch fed rats, however, is significantly greater with glucose 5.5 mM than at high glucose level. In sucrose fed rats, secretion and biosynthesis of insulin thus appear to be elevated but closely linked only at physiological glucose concentration.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 11 (1975), S. 313-320 
    ISSN: 1432-0428
    Keywords: Insulin secretion ; perinatal period ; rat ; in vivo ; invitro ; perifusion ; isolated islets ; glucose ; glibenclamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During the perinatal period of the rat the effect of glucose and glibenclamide (HB 419) on the secretion of insulin was studied in vivo and in vitro. In the in vitro experiments isolated islets of 21 day old fetal and 5 day old newborn rats were perifused with 16.7 mM glucose or 16.7 mM glucose plus 1 μ/ml glibenclamide, while in the in vivo experiments glucose, 0.5 g/kg of body weight, or glibenclamide, 0.5 mg/kg of body weight were tested. Glucose elicited a small first phase of insulin release in 21 day old fetal islets, while glucose plus glibenclamide evoked a biphasic pattern. The injection of glibenclamide to the mother lowered the blood sugar in the fetus and increased the fetal serum insulin concentration. In one day old newborn rats glibenclamide stimulated the secretion of insulin after an i.p. injection. Glucose was without effect. Both substances increased the serum insulin concentration in five day old newborn animals. Dynamic studies at that age revealed a monophasic response to glucose and a biphasic pattern to glucose plus glibenclamide.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 54 (1976), S. 173-175 
    ISSN: 1432-1440
    Keywords: Somatostatin ; ACTH-Sekretion ; Nebennierenrindeninsuffizienz ; Somatostatin ; ACTH secretion ; Adrenal insufficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Somatostatin (250 µg as a bolus i.v. and 250 µg as a 1-hr infusion) was administered to 5 patients with adrenal insufficiency of different origin. In each patient a sustained, progressive fall in plasma ACTH was observed during the infusion period. The mean maximal reduction in plasma ACTH was 43.8±5.9%. After cessation of the somatostatin infusion there was a rise of plasma ACTH to starting levels within 1/2 hour. These findings suggest that somatostatin is a potent inhibitor of ACTH secretion, however, only in a condition in which glucocorticoids are lacking.
    Notes: Zusammenfassung Somatostatin (250 µg als Bolus i.v. und 250 µg als Dauerinfusion über eine Stunde) wurde 5 Patienten mit Nebennierenrindeninsuffizienz verschiedener Ätiologie gegeben. Bei jedem Patienten wurde ein anhaltender, kontinuierlicher Abfall des Plasma-ACTH während der Infusionsperiode beobachtet. Die durchschnittliche maximale Verminderung des Plasma-ACTH betrug 43,8±5,9%. Nach Beendigung der Somatostatininfusion stieg das Plasma-ACTH innerhalb einer halben Stunde wieder auf den Ausgangswert an. Diese Ergebnisse zeigen, daß Somatostatin ein potenter Inhibitor der ACTH-Sekretion ist, jedoch nur bei einem bestehenden Mangel an Glucokortikoiden.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 54 (1976), S. 977-982 
    ISSN: 1432-1440
    Keywords: Somatostatin ; Blutgerinnung ; Thrombozytenfunktion ; Somatostatin ; Blood coagulation ; Platelet function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The effect of short- and long-term somatostatin (GIF) administration on haemostatic function in man was investigated. The dosage programme applied in this study was 250 µg GIF as a bolus injection and 250 µg GIF/h by way of infusion. In five healthy volunteers a short-term (3 h) treatment resulted in a statistically significant drop of platelet count and impairment of platelet aggregation at the end of infusion. However, these changes were within the physiologically normal range and disappeared after two hours on all subjects. Other parameters such as bleeding time, thromboplastin and partial thromboplastin time, fibrinogen, fibrin/fibrinogen split products, plasma factor XIII, ethanol gelation test were not affected. In two patients with gastric haemorrhage and persistent amylasaemia a 67 or 120-h treatment induced no remarkable haemostatic defect. By contrast, peptic ulcer bleeding in one patient stopped 60 min after starting the GIF infusion. These studies indicated that somatostatin administration in man at the dosage programme used neither results in clinical evidence indicating bleeding tendency nor does it influence laboratory parameters in an apparent way.
    Notes: Zusammenfassung Die Beeinflussung verschiedener Haemostaseparameter beim Menschen durch Kurzund Langzeit-Anwendung von Somatostatin (GIF) wurde untersucht. Das in der Studie eingesetzte Dosierungsschema bestand aus einer intravenösen Bolusinjektion von 250 µg GIF und einer anschließenden Dauerinfusion von 250 µg GIF/h. Bei 5 gesunden, freiwilligen Probanden war nach Beendigung einer Kurzzeittherapie über 3 h ein statistisch signifikanter Abfall der Thrombozytenzahl und eine Beeinträchtigung der Thrombozytenfunktion nachweisbar. Die Veränderungen lagen jedoch innerhalb des physiologischen Normalbereiches und waren innerhalb von 2 h nach Infusionsende voll reversibel. Andere Parameter (Blutungszeit, Thromboplastinzeit und Partialthromboplastinzeit, Fibrinogen, Fibrinogen/Fibrinspaltprodukte, Blutgerinnungsfaktor XIII, Äthanoltest) wurden nicht beeinflußt. Bei 2 Patienten mit Magenblutung bzw. persistierender Amylasämie wurde die Somatostatin-Behandlung über 67 bzw. 120 h durchgeführt. Ein klinisch relevanter Haemostasedefekt war bei Therapieende labordiagnostisch nicht erkennbar. Im Fall des Patienten mit Magenblutung kam es vielmehr 60 min nach Beginn der Therapie zum Sistieren der Haemorrhagie. Die Untersuchungen haben gezeigt, daß nach Anwendung von Somatostatin beim Menschen unter Verwendung des angegebenen Dosierungsschemas weder klinische noch labordiagnostische Hinweise bestehen, die die Annahme einer klinisch relevanten, iatrogen-induzierten haemorrhagischen Diathese rechtfertigen.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 54 (1976), S. 709-715 
    ISSN: 1432-1440
    Keywords: Pankreashormone ; Radioimmunologische Bestimmung ; Radioimmunoassay ; Pancreatic Hormones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Synthetic human C-peptide bearing a Tyrosine group at its amino end is labelled with125iodine using chloramin T or hydrogen peroxide and lactoperoxidase. The results are compared applying both methods. Antiserum to synthetic human C-peptide (without Tyrosine) which was partially coupled to rabbit albumin, is raised in guinea pigs and goats. Goats show to be superior to guinea pigs concerning antibody production. The so-called “hook effect” phenomenon is observed in setting up the standard curves for the radioimmunoassay. Monotonically decreasing standard curves are obtained on dilution of antiserum with a high antibody titer which was produced by repeated immunization in goats. Free C-peptide and C-peptide bound to antiserum are separated with the anion exchange resin Amberlite. Using this separation technique we excluded unspecific binding of labelled C-peptide to protein fractions in serum of diabetics. The sensitivity of our radioimmunoassay is approx. 0.3 ng C-peptide/ml serum. Intra- and interassay variability are below 10%. Human proinsulin is the only substance found to crossreact with the antiserum.
    Notes: Zusammenfassung Synthetisches humanes C-Peptid mit einer Tyrosin-Gruppe am Aminoende wird unter Einsatz von Chloramin T oder von Wasserstoffperoxid und Lactoperoxidase mit125Jod markiert. Die mit beiden Methoden erzielten Ergebnisse werden verglichen. Antiserum gegen synthetisches humanes C-Peptid (ohne Tyrosin), das zum Teil an Kaninchenalbumin gekoppelt wurde, wird in Meerschweinchen und Ziegen erzeugt. Ziegen eignen sich zur Antikörperbildung besser als Meerschweinchen. Bei der Herstellung von Standardkurven für den Radioimmunoassay tritt das sogenannte „hook effect“ Phänomen auf. Durch Verdünnen von Antiseren mit hohem Antikörpertiter, die nach wiederholtem Immunisieren bei Ziegen gewonnen wurden, gelingt es Standardkurven mit monotonem Abfall zu erhalten. Freies und an Antikörper gebundenes C-Peptid werden mit Hilfe des Anionaustauscher Harzes Amberlite getrennt. Durch Anwendung dieses Trennverfahrens wird eine unspezifische Bindung von markiertem C-Peptid an Eiweißfraktionen in Diabetikerseren ausgeschlossen. Die Empfindlichkeit unseres Radioimmunoassays beträgt ungefähr 0,3 ng C-Peptid/ml Serum. Intraund Interassayvariabilität liegen unter 10%. Eine Kreuzreaktion mit unserem Antiserum wird nur für humanes Proinsulin gefunden.
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