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Biomedical subjects

R Ziegler

Publications and source records attributed to R Ziegler.

At least 163 records · Page 9Linked to original sources
PubMed1996

[Bisphosphonate therapy of Paget's disease of bone with pamidronate].

BACKGROUND: Paget's disease of bone is a disease with massive focal increase of bone turnover. Bisphosphonates like etidronate inhibit of osteoclastic bone resorption and are therefore established in the treatment of Paget's disease. The aminobisphosphonate pamidronate is 100 times more potent than etidronate. To assess the therapeutic potential for Paget's disease, we have investigated the long-term efficacy of two different dosages of pamidronate. PATIENTS AND METHODS: 40 consecutive patients with Paget's disease received a total dose of either 180 mg (n = 21) or 100 mg (n = 19) of pamidronate i.v. over 9 or 5 days respectively in two independent phases of a prospective trial. Efficacy and side effects were monitored for a follow up period of up to two years. RESULTS: For both dosages a significant reduction of urinary 24-h-hydroxyprolin excretion and serum alkaline phosphatase (AP) levels as parameters of disease activity was recorded. AP levels fell to a minimum of 31 +/- 3% (180 mg) and 41 +/- 5% (100 mg) of pretreatment values, respectively. Two years after treatment, a significant reduction of disease activity could still be detected. Side effects, including transient fever, head ache or bone pain occurred in one third of the patients. CONCLUSION: Pamidronate treatment for Paget's disease of bone leads to a sustained inhibition of elevated bone turnover.

Aged↗
PubMed1996

A new type of highly polymerized yolk protein from the cochineal insect Dactylopius confusus.

A female specific protein was isolated from eggs and female hemolymph of cochineal insects, using density gradient ultracentrifugation, ammonium sulfate precipitation, and size exclusion column chromatography. The protein was found to consist of four different subunits with apparent molecular weights (Mr) 45,000, 49,000, 53,000, and 56,000, respectively. All four subunits were found to be glycosylated; no association of lipids was detected. Size exclusion column chromatography and non-denaturing polyacrylamide gel electrophoresis demonstrated that the native yolk protein exists as large polymers. Electron microscopy showed that these molecules are long, helical ribbons of variable size which are found in both hemolymph and eggs. Using cryo-electron microscopy, it was shown that the ribbons were 14.6 +/- 1.5 nm wide; the helix they form has a repeat distance of 104.9 +/- 11.3 nm and a diameter of 42.1 +/- 5 nm. A clear substructure of the ribbons was recognized. The newly identified protein is the major yolk protein of Dactylopius confusus and no other proteins resembling the more familiar vitellins of other insect species were detected. Moreover, the D. confusus yolk protein appears to be unique both in its subunit structure and in its polymerizing qualities. Thus, the cochineal yolk protein (CYP) is suggested to represent a new type of insect yolk protein.

Amino Acid Sequence↗
PubMed1996

Variations in the density of lipophorins during late larval and early pupal development of Manduca sexta.

The density of lipophorin was determined in individual Manduca sexta during development from the second day of the fifth larval instar to the second day of the pupal stage. Lipophorin formed defined bands when subjected to density gradient ultracentrifugation. All lipophorin observed was high density lipophorin; however, the densities varied from 1.100 to 1.184 g/ml, and 40% of the animals had more than one density form of lipophorin. The lipophorins were divided into five density classes: class 1 from 1.100 to 1.113 g/ml, class 2 from 1.114 to 1.132 g/ml, class 3 from 1.133 to 1.145 g/ml, class 4 from 1.146 to 1.162 g/ml, and class 5 from 1.163 to 1.184 g/ml. In feeding larvae, classes 2 and 3 were the most abundant. Larvae of the first day of wandering had either lipophorin in class 2 or in classes 2 and 5. Later during wandering the variation increased, but on the third day most of the lipophorin was in class 2. In first day pupae, only lipophorins of classes 4 and 5 were detected, while on the second day of the pupal stage, classes 2 and 3 were predominant. Class 1 lipophorin was abundant in larvae injected with Manduca adipokinetic hormone (M-AKH), and rare in young feeding larvae. In no other stage was class 1 lipophorin observed. Our results show that the density of lipophorin is much more variable than previously reported which makes it difficult to ascribe any lipophorin density to a developmental stage. These results also show that adipokinetic hormone decreases the density of lipophorin in larvae.

Animals↗
PubMed1996

Effects of androgens on subpopulations of the human osteosarcoma cell line SaOS2.

Previously, we showed that androgens stimulate murine and human osteoblast-like cell proliferation and differentiation by mechanisms involving increased responses to mitogenic growth factors (GF) and increased GF production. To explain this dual action of androgens on primary osteoblastic cell populations we advanced the hypothesis that androgens exert differential effects on osteoblastic subpopulations. We subcloned a human osteosarcoma cell line (SaOS2) into subpopulations expressing high (HAS) and low (LAS) levels of alkaline phosphatase (ALP). The obtained subclones differed significantly in their ALP production and expressed a high and low ALP phenotype, respectively, for the entire experimental period. Dihydrotestosterone (DHT) increased specific ALP activity and type-I procollagen peptide secretion in both HAS and LAS. DHT pretreatment enhanced the mitogenic action of basic fibroblast growth factor (bFGF) and insulinlike growth factor 2 (IGF2) only in HAS. The enhanced mitogenic effect of IGF2 in HAS after DHT pretreatment was associated with increased IGF2-receptor mRNA levels. Therefore, we conclude that androgens exert their osteoanabolic action (1) by stimulating differentiated functions of osteoblastic cells with a high and a low ALP phenotype, and (2) via increased growth factor receptor expression and thereby enhancing mitogenic growth factor responses only in HAS.

Alkaline Phosphatase↗
PubMed1996

Ultrasound velocity of the tibia in normal German women and hip fracture patients.

One of the latest developments in quantitative ultrasound (QUS) is the measurement of the speed of sound (SOS) of cortical bone of the midtibia. To determine the diagnostic validity of this method we measured 150 healthy women aged 22-94 years. Additionally, we report on first results of patients with hip fracture. Precision in vivo of the tibial QUS expressed as the percentage coefficient of variation (CV) was 0.39% for the first day and 0.45% after repositioning the second day (mean CV = 0.42%). No significant dependency of tibial SOS was found with weight, height, and body mass index in pre- and postmenopausal women. There was a significant decline of SOS with age in postmenopausal women (SOS = 4225 - 5.3 age, r = -0.46, P < 0. 001), whereas premenopausal women showed no decline (SOS = 3906 + 1. 3 age, r = 0.13, ns) Mean SOS values of premenopausal women were significantly higher than those of postmenopausal women (3960 +/- 78.7 m/second and 3898 +/- 120 m/second, respectively, P < 0.001). Postmenopausal women on estrogen substitution had significantly higher mean tibial SOS values than age-comparable postmenopausal women without estrogen substitution (3980 +/- 99 m/second and 3869 +/- 100 m/second, respectively, P < 0.001). Significant difference between age-matched healthy women, n = 11, and hip fracture patients, n = 13, expressed as z-score of -1.4 SD was found. In conclusion, tibial QUS declines with age and detects higher values in premenopausal women and postmenopausal women on estrogen substitution and lower values in hip fracture patients. Further prospective studies are needed to clarify its role in fracture risk assessment.

Adult↗
PubMed1996

What is a vertebral fracture?

Vertebral deformities may be caused by a variety of conditions, such as osteoporosis, severe trauma, congenital deformities, Scheuermann's disease, osteoarthritis, and multiple myeloma. For the individual patient, the correct diagnosis of an osteoporotic fracture is a prerequisite for the choice of optimal treatment and will be ensured by careful differential diagnosis based on a spinal radiograph and additional diagnostic procedures. Evaluation of radiographs by experienced radiologists is crucial for the correct diagnosis of vertebral fractures. For clinical trials and epidemiological studies of osteoporosis, qualitative radiological evaluation of radiographs has proven to be insufficient, since results lack reproducibility. Therefore, objective morphometric methods based on vertebral height measurements have been developed for fracture identification and quantification in scientific settings. Satisfactory sensitivity of these methods is usually reached at the expense of specificity, leading to a high number of false positives. With some differences in methodology, most of the morphometric approaches are of comparable validity. However, none of the morphometric methods allows any subclassification of vertebral deformities with respect to etiology. A combined approach based on morphometry as well as standardized radiological evaluation by experts appears to be the most promising solution to the problem. Further efforts are needed to standardize radiological criteria to yield comparable results between individual readers and different studies. It has to be evaluated whether the combined approach (clinical reading and morphometry) is necessary during follow-up evaluation, as morphometry may be sufficient for monitoring once the diagnosis has been established at baseline.

Clinical Trials as Topic↗
PubMed1996

Glucocorticoids decrease the production of parathyroid hormone-related protein in vitro but not in vivo in the Walker carcinosarcoma 256 rat model.

In 50-90% of cases, humoral hypercalcemia of malignancy (HHM) is due to tumor secretion of parathyroid hormone-related protein (PTHrP). Glucocorticoids are sometimes used as calcium lowering agents and there are in vitro results showing that glucocorticoids diminish PTHrP production. In this study we tested whether the serum-calcium-lowering effect of glucocorticoids is due to decreased PTHrP production by the tumor. As an animal and cell culture model we used the Walker carcinosarcoma (WCS) 256, a rat mammary carcinoma cell line producing PTHrP. In vitro, dexamethasone caused a dose-dependent inhibition of PTHrP production, whereby already 1-5 nmol/L revealed a significant decrease by WCS 256 cells. In contrast to these in vitro results, in WCS 256 tumor-bearing rats, dexamethasone (4 mg/kg body weight on day 4, and 1 mg/kg body weight from day 5 until day 7 after WCS transplantation; circulating dexamethasone levels > 20 nmol/L) did not decrease PTHrP production, PTHrP secretion, serum calcium, or tumor weight in vivo. We conclude that, in this PTHrP-mediated model of humoral hypercalcemia of malignancy, glucocorticoids do not decrease PTHrP production and secretion in vivo and do not show a calcium-lowering effect.

Analysis of Variance↗
PubMed1996

Smoking and endocrine ophthalmopathy: impact of smoking severity and current vs lifetime cigarette consumption.

OBJECTIVE: Smoking has been associated with an increased incidence of endocrine ophthalmopathy (EO). In this study we examined the relation between smoking severity and the incidence of EO symptoms in patients with Graves' hyperthyroidism. DESIGN: Patients were prospectively followed for at least one year after the onset of hyperthyroidism. Smoking and EO status were evaluated at 3-6- months intervals. PATIENTS: Two hundred and fifty-three ambulatory patients with recent onset of Graves' hyperthyroidism were studied. MEASUREMENTS: The incidence of total EO symptoms, proptosis, and diplopia at any time point before and after the occurrence of Graves' hyperthyroidism was assessed by interview and physical examination. RESULTS: Smoking was associated with a 1.3-fold increase in the overall incidence of symptomatic EO, and a 2.6 and 3.1-fold increase in the incidence of proptosis and diplopia, respectively. The relative risk increased in parallel with the current number of cigarettes smoked per day. In contrast, lifetime tobacco use was not an independent risk factor for the development of EO symptoms. Former smokers had a significantly lower risk for the occurrence of proptosis and diplopia than active smokers with a comparable lifetime cigarette consumption. CONCLUSIONS: Our data suggest that current, but not lifetime, tobacco consumption constitutes a risk for the incidence of proptosis and diplopia in patients with Graves' hyperthyroidism, and that this risk increases with smoking severity.

Adult↗
PubMed1996

Lower serum 25-hydroxyvitamin D is associated with increased bone resorption markers and lower bone density at the proximal femur in normal females: a population-based study.

Subclinical vitamin D deficiency is considered to be a risk factor for osteoporosis. Therefore, we studied vitamin D status and bone mineral density (BMD) in an age- and sex-stratified population based sample (209 males and 206 females aged between 50 and 80 years). In addition, urinary excretion of pyridinium crosslinks of collagen was determined in order to monitor bone resorption. We found a seasonal variation of serum 25-hydroxyvitamin D (25(OH)D) levels with higher values detected in the summer (27 +/ - 10 ng/ml) and lower values measured in the winter (17 +/- 9 ng/ml). Further analyses were performed separately for winter and summer, respectively. We also excluded subjects taking osteotropic medication. In men, we found no significant relationship between vitamin D status and bone density or pyridinium crosslinks. In women, we found significant positive correlations between 25(OH)D and proximal femur BMD in winter (r = 0.21, p < 0.05) and in summer (r = 0.36, p < 0.01). The association between 25(OH)D and proximal femur BMD persisted after correction for age and body mass index. Serum 25(OH)D and urinary pyridinium crosslinks were inversely correlated in females in winter (r = -0.24, p < 0.02) and in summer (r = -0.32, p < 0.02). Our data support the hypothesis that already moderately low serum levels of 25(OH)D within the "normal" range lead to osteopenia via increased bone resorption.

Age Factors↗
PubMed1996

Application of genetic screening in families with hereditary medullary thyroid carcinoma.

In 34 families out of 35 with hereditary medullary thyroid cancer a mutation in the RET proto-ongene could be identified. In 84 family members gene carrier state could be proven, in 75 family members gene carrier state could be excluded. The majority of gene carriers (67 out of 84) were symptomatic while 17 gene carriers were diagnosed in a presymptomatic state. 9 of the 17 presymptomatic gene carriers had prophylactic thyroidectomy. On histological examination C-cell hyperplasia or multifocal microcarcinomas could be proven. In one of our families with familial MTC no germline mutation in the RET gene could be detected. In this family pentagastrintests and indirect genotyping are necessary. Four family members of MEN 2A families have had thyroidectomy on the basis of pentagastrin testing and now proved not to be gene carriers. The application of genetic testing in families with hereditary thyroid carcinoma has further improved management in these families - it is the first step in the evaluation of family members at risk.

Adolescent↗
PubMed1996

[APC (activated protein C) resistance and oral contraceptives].

Resistance to activated protein C [1,2,3,4,5,6] is the most frequent hereditary cause of thromboses and is widespread through-out the population. Women with APC resistance have an enhanced risk of thrombosis compared to the total population. The risk increase, with the intake of oral contraceptives.

Blood Coagulation Tests↗
PubMed1996

Relationship between circulating insulin-like growth factor components and sex hormones in a population-based sample of 50- to 80-year-old men and women.

There is a large body of evidence that points to a systemic link between the somatotropic axis and sex hormones, but epidemiologic data on the interactions between the two hormonal systems are still missing. We examined here the associations between the plasma levels of insulin-like growth factor (IGF) I, IGF-II, IGF-binding protein 3 (IGFBP-3), and sex hormones in a population-based sample of 486 men and women, aged 50-80 yr. The strongest association was an age-independent inverse correlation between all three circulating IGF components and sex hormone-binding globulin (SHBG), the major testosterone-binding protein in plasma. Consistent with this, bio-available (non-SHBG-bound) but not total testosterone levels were positively associated with the IGF system in men, and 3 alpha-androstanediol glucuronide was positively correlated with circulating IGFs in women. Moreover, part of the correlation between the circulating IGF system and bone mineral density at the femur and the calcaneus could be accounted for by SHBG. Our data suggest that sex hormones and the GH/IGF system are significantly interrelated in the elderly population. These hormonal interactions may play an important role in human aging and the pathogenesis of age-related diseases.

Aged↗
PubMed1996

Serum immunoreactive bone sialoprotein as a new marker of bone turnover in metabolic and malignant bone disease.

Bone sialoprotein (BSP) is a phosphorylated glycoprotein with a M(r) of 70-80 kDa that accounts for approximately 5-10% of the noncollagenous proteins of bone. Due to its relatively restricted distribution to mineralized tissues, BSP may serve as a potential marker of bone metabolism. Employing a recently developed RIA, serum BSP was measured in 133 healthy subjects, aged 20-80 yr, and in patients with primary hyperparathyroidism (pHPT; n = 26), Paget's disease of bone (PD; n = 14), untreated multiple myeloma (MM; n = 32), and breast cancer with bone metastases (BC; n = 19). Results were compared to clinical and laboratory data, including serum total alkaline phosphatase as a marker of bone formation, and the urinary cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) as markers of bone resorption. In healthy adults, serum BSP values ranged between 5.0-21.6 ng/mL (5-95% interval), with a median of 10.5 ng/mL (total group). In healthy females, a linear correlation was found between serum BSP and age (r = 0.51; P < 0.001), with significantly higher values in postmenopausal than in premenopausal women (13.3 +/- 4.8 vs. 9.0 +/- 3.8; P < 0.01). In the healthy group, BSP values did not change with body mass index, lumbar bone mineral density, serum calcium, serum creatinine, or serum total alkaline phosphatase levels. In contrast, a weak, but significant, correlation was observed between serum BSP and the urinary excretion of PYD and DPD. Compared to those in healthy controls, serum BSP levels were significantly higher in patients with pHPT, PD, MM, or BC (P < 0.01 for all groups). These differences remained after analyses were adjusted for age and sex. In pHPT, serum BSP levels were closely correlated to urinary PYD and DPD (r = 0.87 and 0.83, respectively; P < 0.01), whereas in PD, no correlation was observed between any of the bone markers. Serum BSP levels were highest in patients with MM, and there was a significant difference between early and advanced stages of the disease (30.2 +/- 8.0 vs. 64.3 +/- 6.8; P < 0.01). In a subgroup of 15 patients with metastatic BC, iv bisphosphonate treatment resulted in a rapid reduction of serum BSP levels to 40% of the baseline values within 4 days of treatment. In conclusion, BSP appears to be a sensitive marker of bone turnover, and the present data suggest that its serum levels predominantly reflect processes related to bone resorption.

Adult↗