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R Ziegler

Publications and source records attributed to R Ziegler.

At least 55 records · Page 3Linked to original sources
PubMed2000

Concentrations of insulin-like growth factor (IGF)-I, -II, and IGF binding protein-4, and -5 in human bone cell conditioned medium do not change with age.

We examined the effects of age on the secretion of insulin-like growth factor (IGF)-I, -II, and IGF binding protein-4, and -5 in long-term bone cell cultures from 71 female donors, aged 28-79 years. Our results suggest that under basal conditions, the intrinsic capacity of human bone cells to produce these IGF components is largely preserved with age.

Adult↗
PubMed2000

[Osteoporosis in the male].

BACKGROUND: Osteoporotic fractures occur frequently also in men. Epidemiologic data from Germany indicate that more than 900,000 men are affected by osteoporotic fractures. Diagnosis and therapy of male osteoporosis are hampered by a lack of clinical studies. DIAGNOSIS: Risk factor analysis, conventional spine X-rays, bone densitometry and a limited number of serum and urine analyses contribute to the diagnosis of osteoporosis and the assessment of future fracture risk. Bone densitometry at the femoral neck is superior to measurements at the lumbar spine because of the high prevalence of degenerative changes at the lumbar spine in elderly men. Major risk factors for osteoporosis are hypogonadism, glucocorticoid therapy, hypercalciuria, gastrointestinal disease, and high alcohol consumption. In individual cases, bone histology or additional biochemical studies are needed to establish the cause of osteoporosis. THERAPY: Calcium and vitamin D deficits should be substituted both in prevention and treatment of male osteoporosis. Testosterone replacement therapy is effective in hypogonadism. In primary osteoporosis and in corticosteroid-induced osteoporosis, bisphosphonates (cyclical etidronate, alendronate) and fluorides are therapeutic options. CONCLUSION: Important principles in the care of men with osteoporosis are the transfer of knowledge established for postmenopausal osteoporosis and the rigorous search for secondary osteoporosis aiming at treatment of the underlying cause. Large prospective randomized trials aiming at the reduction of fracture rate in male osteoporosis are missing. They are urgently needed.

Aged↗
PubMed2000

[Female pseudohermaphroditism in congenital adrenogenital syndrome as an incidental intraoperative finding in a 68 year old patient].

HISTORY AND CLINICAL FINDINGS: A 68-year-old man of small stature, previously always healthy and with a grown-up daughter, was suspected of having carcinoma of the colon with metastasis to the right kidney. At laparotomy internal female genitalia with cancerous changes were unexpectedly discovered in the left adnexae. The colon carcinoma, the right adrenocortical tumour and left adnexae were resected. INVESTIGATIONS: Histological examination revealed adenocarcinoma of the colon, right adrenocortical adenoma and a Brenner tumour of the left female adnexae. Postoperative tests showed increased levels of 17-OH-progesterone (3192 ng/dl), 21-desoxycortisol (1856 ng/dl) and of adrostenedione (745 ng/dl), while the concentrations of 17-OH pregnenolone, testosterone and mineralocorticoids were within normal limits. Chromosome analysis demonstrated karyotype 46 XX. DIAGNOSIS, TREATMENT AND COURSE: As far as could be ascertained, this is the first documented case in the German-speaking region of female pseudohermaphroditism diagnosed in an elderly person with uncomplicated virilizing congenital adrenogrenital syndrome due to 21-hydroxylase deficiency (deletion of CYP21 gene). To avoid a cortisone deficiency crisis the patient was regularly given hydrocortisone and he quickly recovered. But he died 6 months later of sequelae of the carcinoma of the colon. CONCLUSION: An adrenogenital syndrome should be excluded in a case of bilateral adrenocortical tumour. As this is usually benign, conservative treatment should be attempted. This case demonstrates the necessity of thorough examination which could have given an early indication of the underlying condition.

Adrenal Cortex Neoplasms↗
PubMed2000

Sex difference in the validity of vertebral deformities as an index of prevalent vertebral osteoporotic fractures: a population survey of older men and women.

Morphometric methods have been developed for standardized assessment of vertebral deformities in clinical and epidemiologic studies of spinal osteoporosis. However, vertebral deformity may be caused by a variety of other conditions. To examine the validity of morphometrically assessed vertebral deformities as an index of osteoporotic vertebral fractures, we developed an algorithm for radiological differential classification (RDC) based on a combination of quantitative and qualitative assessment of lateral spinal radiographs. Radiographs were obtained in a population of 50- to 80-year-old German women (n = 283) and men (n = 297) surveyed in the context of the European Vertebral Osteoporosis Study (EVOS). Morphometric methods (Eastell 3 SD and 4 SD criteria, McCloskey) were validated against RDC and against bone mineral density (BMD) at the femur and the lumbar spine. According to RDC 36 persons (6.2%) had at least one osteoporotic vertebral fracture; among 516 (88.9%) nonosteoporotics 154 had severe spondylosis, 132 had other spinal disease and 219 had normal findings; 14 persons (2.4%) could not be unequivocally classified. The prevalence of morphometrically assessed vertebral deformities ranged from 7.3% to 19.2% in women and from 3.5% to 16.6% in men, depending on the stringency of the morphometric criteria. The agreement between RDC and morphometric methods was poor. In men, 62-86% of cases with vertebral deformities were classified as nonosteoporotic (severe spondylosis or other spinal disease) by RDC, compared with 31-68% in women. Among these, most had wedge deformities of the thoracic spine. On the other hand, up to 80% of osteoporotic vertebral fractures in men and up to 48% in women were missed by morphometry, in particular endplate fractures at the lumbar spine. In the group with osteoporotic vertebral fractures by RDC the proportion of persons with osteoporosis according to the WHO criteria (T-score < -2.5 SD) was 90.0% in women and 86.6% in men, compared with 67.9-85.0% in women and 20.8-50.0% in men with vertebral deformities by various methods. Although vertebral deformities by most definitions were significantly and inversely related to BMD as a continuous variable in both sexes [OR; 95% CI ranged between (1.70; 1.07-2.70) and (3.69; 1.33-10.25)], a much stronger association existed between BMD and osteoporotic fractures defined by RDC [OR; 95% CI between (4.85; 2.30-10.24) and (15.40; 4.65-51.02)]. In the nonosteoporotic group individuals with severe spondylosis had significantly higher BMD values at the femoral neck (p < 0.01) and lumbar spine (p < 0.0004) compared with the normal group. On the basis of internal (RDC) and external (BMD) validation, we conclude that assessment of vertebral osteoporotic fracture by quantitative methods alone will result in considerable misclassification, especially in men. Criteria for differential diagnosis as used within RDC can be helpful for a standardized subclassification of vertebral deformities in studies of spinal osteoporosis.

Aged↗
PubMed2000

[Hypercalcemia].

Hypercalcemia may develop as a consequence of a disturbance of one or more links within the feedback system of calcium homeostasis. Hypercalcemic diseases may be caused by the parathyroid glands as well as by their dependent end organs, the kidneys, the intestine, the skeleton. Partial parathyroid hormone activity can be produced by many tumour factors in a paraneoplastic way. Hypercalcemia induces the symptoms of the so-called hypercalcemic syndrome which should be familiar to the physician. Hints towards the cause may be the organ manifestation in case of primary hyperparathyroidism, in case of the other causal diseases they may present with typical components of their clinical picture. Diagnostics should start with the differentiation between parathyroid-related hypercalcemia (autonomous, primary hyperparathyroidism and variants) and the broad spectrum of non-parathyroid hypercalcemia, mainly accompanying malignancies. Symptomatic treatment of hypercalcemia often has to start before the definite diagnosis is confirmed. Later on, this merely symptomatic treatment may be replaced by causal treatment, as far as possible. Symptomatic treatment of hypercalcemia may follow the 'diuretic', the 'antiresorptive', or the 'antiabsorptive' way--the 'extractive' way by hemodialysis is the treatment of choice in case of hypercalcemic crisis accompanied by renal insufficiency.

Bone Neoplasms↗
PubMed2000

No advantage of the new combined octreotide-GHRH test over established GH-stimulation tests in the diagnosis of growth hormone deficiency (GHD) in adults.

OBJECTIVE: To evaluate the sensitivity and specificity of a combined octreotide (SMS)-GHRH test we compared it with established GH stimulation tests in the diagnosis of growth hormone deficiency (GHD) in adults. DESIGN: Because there is no universally agreed gold standard for the diagnosis of GHD in adults it is difficult to define the relative merits of different tests in patients with structural pituitary disease. We have addressed this by grouping patients according to the degree of concordance between three established tests (insulin (IHT), arginine (ARG) and GHRH stimulation test (GHRH)) and serum IGF-I levels and have subsequently analysed the frequency destribution of test results across defined groups: group 1, with complete GHD in all tests, group 2, with differences between tests with regard to the diagnosis of GHD and group 3, with normal GH response in all tests. The patients also underwent a new combined SMS-GHRH test, the results of which were compared with IHT, ARG and GHRH. MEASUREMENTS: Five hours after an octreotide injection GHRH was given intravenously and GH measured. RESULTS: ARG had the highest sensitivity (Se = 100%) and specificity (Sp = 100%) of the tests used. The IHT also diagnosed GHD with precision but showed false positive as well as false negative results (Se = 90%, Sp = 100%). Se and Sp of GHRH were lower than those of IHT and ARG (Se = 100%, Sp = 89%). The SMS-GHRH worked well and was superior to GHRH but had less precision than IHT and ARG (Se = 88%, Sp = 100%). CONCLUSION: We conclude that there is discordance between the three established tests and that the octreotide-GHRH test does not have any advantages for diagnosing GHD in adults. IGF-I levels can be used as a screening test only. The arginine test was the best conventional test in our study.

Adolescent↗
PubMed2000

Circaannual rhythms and interactions of vitamin D metabolites, parathyroid hormone, and biochemical markers of skeletal homeostasis: a prospective study.

Recent studies suggest a circannual pattern of bone turnover. To further investigate the underlying mechanisms, 41 healthy subjects (25-80 years old) living in a southwestern German city were studied prospectively over a period of 18 months. Participants were examined every 4 weeks, and blood and urine samples were obtained on each visit. The following parameters were measured: serum 25-hydroxyvitamin D3 [25(OH)D3], 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and parathyroid hormone (PTH), as regulators, and serum total alkaline phosphatase (TAP), bone-specific alkaline phosphatase (BAP), urinary total pyridinoline (PYD), deoxypyridinoline (DPD), and the aminoterminal telopeptide of collagen type I (NTX), as biochemical markers of bone turnover. The presence of significant circannual rhythms for the various markers was tested using the Pharmfit method. In the total group, 25(OH)D3, 1,25(OH)2D3, and PTH as well as BAP, PYD, DPD, and NTX showed a significant seasonal variation. 25(OH)D3 revealed the highest amplitude (38.0%) with an acrophase in August. Levels of the biochemical markers and of PTH were highest in winter with amplitudes of up to 17.7% (DPD). Results were most pronounced in premenopausal women, in subjects <50 years of age, and in subjects who did show a significant individual rhythm in 25(OH)D3 levels. No differences were found regarding other anthropometric or life style factors. Correlation analyses revealed strongest associations between the amplitudes of a vitamin D metabolite and a biochemical marker in premenopausal women. We conclude that specific markers of bone turnover show significant circannual rhythms. These changes are related directly to variations in the hormonal regulation of skeletal homeostasis. In postmenopausal women and in men, other effects may superimpose the circannual variation of biomarkers of bone turnover.

Adult↗
PubMed2000

Short- and long-term effects of ibandronate treatment on bone turnover in Paget disease of bone.

BACKGROUND: In Paget disease of bone (PD), serum total alkaline phosphatase (TAP) is a valid marker of disease activity. The aim of the present longitudinal study was to compare TAP with new and potentially more specific markers of bone turnover in bisphosphonate-treated patients with PD. METHODS: Twenty patients with active PD were studied before and after treatment with 2 mg of intravenous ibandronate over a period of 12 months. TAP (by colorimetry), serum bone-specific alkaline phosphatase (BAP; by enzyme immunoassay), serum osteocalcin (OC; by ELISA), serum bone sialoprotein (BSP; by RIA), and urinary total pyridinoline (PYD; by HPLC) and deoxypyridinoline (DPD; by HPLC) were measured as markers of bone turnover. RESULTS: Before treatment, TAP, BAP, and BSP were increased in all 20 patients, whereas OC was increased in 10, PYD in 13, and DPD in 15 patients. Three months post treatment, nine patients showed normalized TAP values, and a >/=25% re-increase (i.e. , relapse) was observed in all patients after 12 months. A normalization of BAP was achieved in six patients only. No significant changes were found for OC. BSP was decreased significantly at 24 h, and DPD at 48 h post treatment. A normalization of BSP was found in 8, of PYD in 18, and of DPD in 16 cases. Both PYD and DPD increased significantly from 9 months post treatment onward. CONCLUSIONS: Most markers of bone turnover show similar long-term changes after treatment of active PD with ibandronate. With regard to cost-effectiveness and assay performance, TAP remains the marker of choice in therapeutic monitoring of PD. However, more specific markers may improve the biochemical assessment of PD in certain situations.

Aged↗
PubMed1999

Age-associated changes in the stimulatory effect of transforming growth factor beta on human osteogenic colony formation.

Previous studies have indicated that the mitogenic responsiveness of human bone cells may change with age. In the present study, we examined whether aging affects the capacity of transforming growth factor beta (TGF-beta) to stimulate the colony formation of human osteoprogenitor cells. Outgrowths of bone cells from 98 iliac crest biopsies were plated at a density of 25 cells/cm2 and cultured for 3 weeks in the presence of 10% fetal calf serum. Approximately 5% of the plated cells gave rise to clonal colonies. TGF-beta (10(-11) M) significantly increased the estimated number of cells per colony. However, the stimulatory effect of TGF-beta significantly declined with donor age (r = -0.26, P = 0.01). Whereas TGF-beta raised the average number of cells per colony in cultures from donors below the age of 50 years by 136+/-50%, the average increase was only 43+/-16% in donors older than 60 years. These data raise the possibility that aging may be associated with a declining capacity of TGF-beta to enlarge the pool of bone cells that can be generated from a single human osteoblast progenitor cell.

Adult↗
PubMed1999

[Osteo-anabolic estrogen therapy in a transsexual man].

HISTORY AND ADMISSION FINDINGS: A 31-year-old man presented at the endocrinology out-patient clinic for the initiation of sex-change treatment. His manifestly transsexual male-to-female appearance was confirmed by a psychiatric-sexological expert report. The patient had been living as a woman for one year. Physical examination showed normal male physique with typical secondary hair growth and normal male genitals. INVESTIGATIONS: The serum testosterone level was at the upper limits of normal, that for oestrogen at the lower limit. Bone densitometry showed bone density at the upper limit of normal. Other laboratory tests were unremarkable. DIAGNOSIS, TREATMENT AND COURSE: During 30 months on cyproterone, 100 mg daily, bone mass fell at the rate of 5% per year. Bone biopsy revealed high turnover osteoporosis. Bone mass rose by 4% per year after the additional oral intake of oestradiol valerate, 2 mg daily. Osteoblastic cells, isolated from part of the biopsy tissue, with the patient's consent, was found to be stimulated by oestradiol in vitro. CONCLUSION: The described bone mass changes indicate the important role played by sex hormones in the maintenance of bone mass acquired during adolescence. The findings confirm that in males not only testosterone but also oestrogens has an anabolic effect on bone.

Adult↗
PubMed1999

[Non-enzymatic glycation and oxidative stress in chronic illnesses and diabetes mellitus].

UNLABELLED: New approaches in biochemistry and molecular biology have increased the knowledge on the pathophysiology of chronic diseases as late diabetic complications, Alzheimer's disease, arteriosclerosis and vascular disease by defining the concept of "AGE-formation and oxidative stress." Nonenzymatic glycation, in which reducing sugars are covalently bound to free aminogroups of macromolecules, results in the formation of Advanced Glycation End products (AGEs) which accumulate during aging and at accelerated rate during the course of diabetes. Glycation accompanying oxidation processes support AGE-formation. AGE-formation changes the physicochemical properties of proteins, lipids and nucleic acids. In addition, binding of AGEs to specific surface receptors induces cellular signalling and cell activation. Interaction of AGEs with one of the receptors, RAGE, generates intracellular oxidative stress, which results in activation of the transcription factor NF-kappa B and subsequent gene expression, which might be relevant in late diabetic complications. CONCLUSION: Knowledge of the basis molecular mechanisms allows to understand the interplay of different inducers such as redicals, cytokines, AGE-proteins and amyloid-beta-peptids and to define oxidative stress as a "common endpoint" of cell dysfunction. With respect to therapeutic options it is now possible not only to optimize blood glycemic control, but also to design drugs such as AGE-inhibitors and AGE-"cross-link" breakers. In addition patients with chronic disease associated with increased oxidative stress ay benefit from an antioxidant rich (and AGE protein poor?) nutrition.

Alzheimer Disease↗
PubMed1999

The role of oxidative stress and NF-kappaB activation in late diabetic complications.

A common endpoint of hyperglycemia dependent cellular changes is the generation of reactive oxygen intermediates (ROIs) and the presence of elevated oxidative stress. Therefore, oxidative stress is supposed to play an important role in the development of late diabetic complications. Formation of advanced glycation end products (AGE's) due to elevated nonenzymatic glycation of proteins, lipids and nucleic acids is accompanied by oxidative, radical-generating reactions and thus represents a major source for oxygen free radicals under hyperglycemic conditions. Once formed, AGE's can influence cellular function by binding to several binding sites including the receptor for AGE's, RAGE. Binding of AGE's (and other ligands) to RAGE results in generation of intracellular oxidative stress and subsequent activation of the redox-sensitive transcription factor NF-kappaB in vitro and in vivo. Consistently, activation of NF-kappaB in diabetic patients correlates with the quality of glycemic control and can be reduced by treatment with the antioxidant alpha-lipoic acid. The development of techniques allowing for a tissue culture independent measurement of NF-kappaB activation in patients with diabetes mellitus gives insights into the molecular mechanisms linking diabetes mellitus and hyperglycemia with formation of advanced glycated endproducts and generation of oxidative stress finally resulting in oxidative stress mediated cellular activation.

Animals↗
PubMed1999

[Definition of hyperparathyroidism and indication for surgical therapy].

Parathyroid excess may happen as a result of autonomous overactivity of the parathyroid glands (primary hyperparathyroidism). Secondary hyperparathyroidism is the consequence of chronic hypocalcemia, leading to parathyroid hyperplasia. Long-lasting secondary hyperparathyroidism may turn to autonomy in the sense of tertiary hyperparathyroidism. In primary hyperparathyroidism indications for surgical intervention are renal, intestinal or osseous organ manifestations, as well as relevant clinical symptoms of the so-called hypercalcemic syndrome. In truly asymptomatic primary hyperparathyroidism, observation is justified. However, the patients need regular supervision. If there is progression indicating health risk, the strategy must switch from observation to operation. Secondary hyperparathyroidism has must be treated by surgery if renal osteodystrophy progresses or tertiary hyperparathyroidism develops.

Chronic Kidney Disease-Mineral and Bone Disorder↗
PubMed1999

[Endocrinology].

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Endocrinology↗
PubMed1999

Peripheral blood mononuclear cells isolated from patients with diabetic nephropathy show increased activation of the oxidative-stress sensitive transcription factor NF-kappaB.

Increased oxidative stress and subsequent activation of the transcription factor NF-kappaB has been linked to the development of late diabetic complications. To determine whether oxidative stress dependent NF-kappaB activation is evident in patients with diabetic nephropathy we used an Electrophoretic Mobility Shift Assay based semiquantitative detection system which enabled us to determine NF-kappaB activation in ex vivo isolated peripheral blood mononuclear cells. We examined 33 patients with diabetes mellitus (Type I and Type II). Patients with diabetic nephropathy showed higher NF-kappaB binding activity in Electrophoretic Mobility Shift Assays and stronger immunohistological staining for activated NF-kappaBp65 than patients without renal complications. NF-kappaB binding activity correlated with the degree of albuminuria (r = 0.316) and with thrombomodulin plasma concentrations (r = 0.33), indicative for albuminuria associated endothelial dysfunction. In a 3 day intervention study in which 600 mg of the antioxidant thioctic acid (alpha-lipoic acid) per day were given to nine patients with diabetic nephropathy oxidative stress in plasma samples was decreased by 48% and NF-kappaB binding activity in ex vivo isolated peripheral blood mononuclear cells by 38%. In conclusion, activation of the transcription factor NF-kappaB in ex vivo isolated peripheral blood mononuclear cells of patients with diabetes mellitus correlates with the degree of diabetic nephropathy. NF-kappaB activation is at least in part dependent on oxidative stress since thioctic acid (alpha-lipoic acid) reduced NF-kappaB binding activity.

Adult↗
PubMed1999

Changes in the concentration of insulin-like growth factor I and transforming growth factor beta1 in rat femoral bone during growth.

Our knowledge of the concentration of growth factors in growing bone is limited. In the present study, we examined the developmental changes in the concentrations of insulin-like growth factor I (IGF-I) and transforming growth factor beta (TGF-beta) in the rat femur between weanling and maturity. We show that during the rapid growth phase there is a continuous rise in bone matrix IGF-I and TGF-beta in all compartments of the femoral bone. The association between IGF-I and TGF-beta is not only temporal, but with few exceptions is also observed within the animals of each age class. These data support the hypothesis that IGF-I and TGF-beta play an important role in the growth-associated accumulation of bone mass.

Aging↗