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  • Insulin secretion  (3)
  • Osteogenesis imperfecta  (2)
  • siblings  (2)
  • Androstandiol  (1)
  • 1
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Hirsutismus ; Androstandiol ; Androstandiolglukuronid ; Gaschromatographie ; Massenspektrometrie ; Key words Hirsutism ; Androstanediol ; Androstanediol glucuronide ; Gaschromatography ; Mass spectrometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Background: It is still controversial, whether the end metabolites of peripheral androgen metabolism, 5 α-androstane-3 α, 17 β-diol and 5 α-androstane-3 α, 17 β-diol glucuronide, represent biochemical markers of hirsutism. Furthermore, discrepant plasma concentrations have been reported in the literature. Method: Using stable isotope dilution/gas chromatography-mass spectrometry, the most specific method in steroid analysis, we investigated healthy females and patients with hirsutism of various etiology. Results: Generally, both androstanediol and androstanediol-glucuronide scattered much in hirsute patients. Patients with adrenal enzyme defects (3 β-hydroxysteroid-dehydrogenasedeficiency, 21-hydroxylase-deficiency) had elevated androstanediol and androstanediol-glucuronide. Hirsute Patients with hyperandrogenaemia but without adrenal enzyme deficiencies had normal androstanediol in 33 % and normal androstanediol-glucuronide in 24 % of cases. 54 % of patients with idiopathic hirsutism had normal androstanediol and 24 % had normal androstanediol-glucuronide. Conclusion: Our results show, that neither androstanediol nor androstanediol-glucuronide are consistently elevated in hirsutism and that both do not discriminate between the various causes of hirsutism.
    Notes: Zusammenfassung Hintergrund: Ob die Endmetaboliten des peripheren Androgenstoffwechsels, 5 α-Androstan-3 α, 17 β-diol und 5 α-Androstan-3 α, 17 β-diol-glukuronid, biochemische Marker bei Hirsutismus darstellen, wird kontrovers diskutiert. Über die Plasmakonzentrationen beider Parameter gibt es ferner erhebliche Diskrepanzen bei den in der Literatur berichteten Werten. Methode: Unter Einsatz von Isotopenverdünnungs-Gaschromatographie-Massenspektrometrie, dem Verfahren mit der höchsten Spezifität in der Steroidanalytik, untersuchten wir gesunde Mädchen und Frauen sowie Patientinnen mit Hirsutismus unterschiedlicher Ätiologie. Ergebnisse: Bei hirsuten Patientinnen streuten beide Parameter stark. Bei Patientinnen mit adrenalen androgenisierenden Enzymdefekten (3 β-Hydroxysteroiddehydrogenasemangel, 21-Hydroxylasemangel) waren sowohl Androstandiol als auch Androstandiolglukuronid erhöht. Hirsute Patientinnen mit Hyperandrogenämie ohne adrenalen Enzymdefekt wiesen in 33 % normales Androstandiol und in 24 % normales Androstandiolglukuronid auf. Patientinnen mit idiopathischem Hirsutismus hatten in 54 % Androstandiol- und in 30 % Androstandiolglukuronidkonzentrationen innerhalb des Streubereichs gesunder Mädchen und Frauen. Schlußfolgerungen: Unsere Ergebnisse zeigen, daß weder Androstandiol noch Androstandiolglukuronid in allen Fällen von Hirsutismus erhöht sind und daß beide Parameter nicht zwischen unterschiedlichen Formen des Hirsutismus diskriminieren.
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  • 2
    ISSN: 1432-0428
    Keywords: Height ; weight ; obesity ; siblings ; genetic factors ; bone age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Normal growth and development, as well as the prevention of overweight, are major goals in the treatment of paediatric patients with insulin-dependent diabetes mellitus (IDDM). We therefore evaluated longitudinally the anthropometric measurements of height and weight, as well as bone age, in an unselected group of 389 patients with IDDM treated at one institution. In order to identify genetic influences on these parameters, height and weight were determined in 186 unaffected siblings and 177 pairs of parents. At diagnosis, patients were slightly taller than average (median z score: +0.37). During the subsequent course of diabetes, age-adjusted heights decreased progressively for the first 9 years, catching up again after more than 10 years of diabetes. Bone ages were progressively retarded with increasing duration of diabetes. In 76 patients of 18 years or older, median z-score for height was +0.30, not different from their unaffected siblings (median z-score: +0.22). The correlation with midparental height was identical for diabetic and nondiabetic siblings (r=0.43). In contrast, children with diabetes were significantly heavier (z-score for weight: +0.74 compared to +0.34 in unaffected siblings; p〈0.002). Obesity developed primarily during and after puberty. We conclude that: 1) during the course of diabetes, longitudinal growth is temporarily reduced and maturation is delayed in children with diabetes compared to unaffected siblings. However, this effect of diabetes is transient and small compared to genetic influences on height in an individual child. 2) As a group, children with IDDM become significantly overweight, which is likely to increase the cardiovascular risk during adulthood.
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  • 3
    ISSN: 1432-0428
    Keywords: Key words Height ; weight ; obesity ; siblings ; genetic factors ; bone age.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Normal growth and development, as well as the prevention of overweight, are major goals in the treatment of paediatric patients with insulin-dependent diabetes mellitus (IDDM). We therefore evaluated longitudinally the anthropometric measurements of height and weight, as well as bone age, in an unselected group of 389 patients with IDDM treated at one institution. In order to identify genetic influences on these parameters, height and weight were determined in 186 unaffected siblings and 177 pairs of parents. At diagnosis, patients were slightly taller than average (median z score: + 0.37). During the subsequent course of diabetes, age-adjusted heights decreased progressively for the first 9 years, catching up again after more than 10 years of diabetes. Bone ages were progressively retarded with increasing duration of diabetes. In 76 patients of 18 years or older, median z-score for height was + 0.30, not different from their unaffected siblings (median z-score: + 0.22). The correlation with mid-parental height was identical for diabetic and non-diabetic siblings (r = 0.43). In contrast, children with diabetes were significantly heavier (z-score for weight: + 0.74 compared to + 0.34 in unaffected siblings; p 〈 0.002). Obesity developed primarily during and after puberty. We conclude that: 1) during the course of diabetes, longitudinal growth is temporarily reduced and maturation is delayed in children with diabetes compared to unaffected siblings. However, this effect of diabetes is transient and small compared to genetic influences on height in an individual child. 2) As a group, children with IDDM become significantly overweight, which is likely to increase the cardiovascular risk during adulthood [Diabetologia (1994) 37: 925–929].
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  • 4
    ISSN: 1432-1076
    Keywords: Key words Cystic fibrosis ; Diabetes ; Insulin secretion ; Insulin ; resistance ; Minimal model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Traditional opinion holds that patients with cystic fibrosis (CF) develop impaired glucose tolerance or diabetes due to insulinopenia caused by fibrosis of the pancreas. However, studies on the dynamics of insulin secretion and peripheral insulin action have yielded conflicting results. We studied 18 patients with CF (9 ♂, 9 ♀, age 15–29 years) and 17 healthy control subjects (8 ♂, 9 ♀, 20–32 years). Oral glucose tolerance tests and combined i.v.-glucose-tolbutamide-tests were performed on separate days in fasting subjects. Bergman's "Minimal Model" was used to quantitate both peripheral insulin sensitivity (SI) and insulin-independent glucose disposal (glucose effectiveness; SG). Based on National Diabetes Data Group criteria, 4 patients were classified as diabetic (22%; CF-DM), 3 patients (17%) had impaired glucose tolerance (CF-IGT) while glucose metabolism was normal in 11 patients (61%; CF-NGT). Irrespective of the degree of glucose tolerance, the insulin response to oral glucose was not reduced but delayed, up to 60 min in the CF-IGT/DM group. First-phase insulin release (0–10 min) after i.v.-glucose was significantly lower in CF patients (29% of healthy controls; P 〈 0.0001), with no difference between the CF-NGT and CF-IGT/ DM groups. Insulin release following tolbutamide injection was only marginally reduced in CF patients (64% of controls). In contrast, SI was significantly reduced in the subgroup of CF patients with abnormal glucose metabolism (CF-IGT/DM: 0.97 ± 0.16 · 10–4 l/min/pmol; control group: 1.95 ± 0.25; P 〈 0.05). Conclusion The early insulin release is reduced in response to i.v.-glucose, while in the oral glucose tolerance test, insulin secretion is quantitatively preserved, but delayed. Reduced peripheral insulin sensitivity is a major factor for impaired glucose tolerance and diabetes mellitus in CF patients.
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  • 5
    ISSN: 1432-1076
    Keywords: Insulin secretion ; Growth hormone ; Sulfonylurea ; Linear growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of glucose on insulin release and the influence of glibenclamide on linear growth were determined in five growth hormone (STH) deficient children who were treated with human growth hormone. It was found that the administration of 5 I.U. of human growth hormone twice a week improved the defective insulin secretion while prolongation of the interval between growth hormone injections to 7 days had no effect on β-cell function. The addition of treatment with 5 mg/day glibenclamide to the regular human growth hormone injections resulted in an increased growth rate in four children while one patient developed hypoglycemic symptoms. The results show that STH-deficient children may benefit from combined treatment with human growth hormone plus glibenclamide.
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  • 6
    ISSN: 1432-1076
    Keywords: Osteogenesis imperfecta ; Cardiac malformation ; Kidney stones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined 58 children aged 1–16 years with various forms of osteogenesis imperfecta (OI). Congenital cardiac malformations were diagnosed in 4 children (valvular aortic stenosis, 2 with atrial septal defect II, Fallot Tetralogy). Two additional children developed holosystolic mitral valve prolapse and regurgitation. Children suffering from a severe clinical course (type III according to the Sillence classification) showed aortic root dilatation (28%) and increased septal (40%) and posterior left ventricular wall thickening (68%) on initial evaluation. All three parameters were significantly correlated to body surface area. Kidney stones and renal papillary calcifications were detected in 4 children. Cardiovascular abnormalities and nephrolithiasis may be important extraskeletal manifestations of childhood OI.
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  • 7
    ISSN: 1432-1076
    Keywords: Cystic fibrosis ; Diabetes ; Insulin secretion ; Insulin resistance ; Minimal model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Traditional opinion holds that patients with cystic fibrosis (CF) develop impaired glucose tolerance or diabetes due to insulinopenia caused by fibrosis of the pancreas. However, studies on the dynamics of insulin secretion and peripheral insulin action have yielded confliciting results. We studied 18 patients with CF (9 ♂, 9 ♀, age 15–29 years) and 17 healthy control subjects (8 ♂, 9 ♀, 20–32 years). Oral glucose tolerance tests and combined i.v.-glucose-tolbutamide-tests were performed on separate days in fasting subjects. Bergman's “Minimal Model” was used to quantitate both peripheral insulin sensitivity (SI) and insulin-independent glucose disposal (glucose effectiveness; SG). Based on National Diabetes Data Group criteria, 4 patients were classified as diabetic 922%; CF-DM), 3 patients (17%) had impaired glucose tolerance (CF-IGT) while glucose metabolism was normal in 11 patients (61%; CF-NGT). Irrespective of the degree of glucose tolerance, the insulin response to oral glucose was not reduced but delayed, up to 60 min in the CF-IGT/DM group. First-phase insulin release (0–10 min) after i.v.-glucose was significantly lower in CF patients (29% of healthy controls;P〈0.0001), with no difference between the CF-NGT and CF-IGT/DM groups. Insulin release following tolbutamide injection was only marginally reduced in CF patients (64% of controls). In contrast, SI was significantly reduced in the subgroup of CF patients with abnormal glucose metabolism (CF-IGT/DM: 0.97±0.16·10−4 l/min/pmol; control group: 1.95±0.25;P〈0.05). Conclusion The early insulin release is reduced in response to i.v.-glucose, while in the oral glucose tolerance test, insulin secretion is quantitatively preserved, but delayed. Reduced peripheral insulin sensitivity is a major factor for impaired glucose tolerance and diabetes mellitus in CF patients.
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  • 8
    ISSN: 1432-1076
    Keywords: Osteogenesis imperfecta ; Joint contractures ; Collagen fibrils ; Mineralization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We describe a male patient with osteogenesis imperfecta (OI) who was born with contractures of the knee, elbow and ankle joints. During the first 4 years he suffered from recurrent fractures. He has white sclerae, mild dentinogenesis imperfecta, multiple wormian bones, severe scoliosis and short stature. Morphological analysis of cortical bone revealed typical characteristics of OI including varying width of the osteoid, swollen mitochondria and a dilated endoplasmic reticulum of the osteoblasts. Collagen fibrils of the osteoid had a varying diameter, a feature not found in typical OI patients. Analysis of compact bone showed that the size of apatite crystals and the extractability of collagen with pepsin were markedly elevated compared to controls and other OI type III and IV patients. Lysyl hydroxylation of collagen from the organic bone matrix and the electrophoretic mobility of collagen α1(I)- and α2(I)-chains were normal. Our results provide evidence that this patient belongs to a subtype of OI. The biochemical studies indicate that the underlying defect involves defective fibril-formation of collagen type I leading to an altered mineralization of bone.
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