Biomedical subjects

K Klaushofer

Publications and source records attributed to K Klaushofer.

At least 73 records · Page 4Linked to original sources

PubMed1991

[DEXA (dual-energy x-ray absorptiometry) and DPA (dual photon absorptiometry) in densitometry of the femoral neck: correlation of the measurements of three commercially available instruments].

The bone mineral density measurements of three different instruments at the femoral head were compared using 12 cadaver specimens. Two of these instruments were operated by x-rays (dual energy x-ray absorptiometry = DEXA), whereas one system was based on a gadolinium source (dual photon absorptiometry = DPA). Although excellent correlation between the measurements was obtained (r greater than 0,9), the measurements of one of the DEXA-instruments were significantly higher than the measurements of the two other systems. We conclude that a comparison of bone mineral density measurements obtained on different densitometry instruments may pose problems. Follow-up examinations should be done on one single densitometry unit.

Absorptiometry, Photon↗

PubMed1990

Experimental considerations on the measurement of prostaglandins during long-time incubations of neonatal mouse calvaria.

The influence of experimental conditions during long-time (72 h) incubations of neonatal mouse calvaria on the measurement of prostaglandins was investigated. Incubations of the cultured calvaria were carried out in the presence and absence of stimulating agents of bone resorption, such as thrombin and parathyroid hormone. It was found that during the first 24 h prostaglandin levels, estimated by gas chromatography negative ion chemical ionization mass spectrometry, did not correlate with calcium liberation, but were merely an artefact resulting from surgery by preparing the calvaria.

6-Ketoprostaglandin F1 alpha↗

PubMed1989

Bone-resorbing activity of thyroid hormones is related to prostaglandin production in cultured neonatal mouse calvaria.

The bone-resorbing activity of thyroid hormones was evaluated in neonatal mouse calvaria maintained in organ culture for 96 h. Thyroxine (T4) between 10(-8) and 10(-5) mol/liter and triiodothyronine (T3) between 10(-8) and 10(-7) mol/liter caused a dose-dependent release of calcium from cultured bone. The thyroid hormone effect was delayed in onset for at least 24 h, and after 96 h of culture amounted to 50-90% of the bone-resorbing activity of 10(-8) mol/liter parathyroid hormone (PTH). The bone-resorbing action of T4 as well as of T3 was completely blocked by 100 U/ml interferon-gamma (IF-gamma) or 20 mU/ml salmon calcitonin (CT). "Escape" from CT inhibition, which is a well-known phenomenon in the action of PTH, was not observed with thyroid hormone-mediated bone resorption. Thyroid hormone treatment of cultured calvaria resulted in a gradual increase between 48 and 96 h of medium concentrations of prostaglandin (PG) E2 and particularly of 6-keto-PGF1 alpha, the inactive metabolite of prostacyclin (PGI2). The release of PGF2 alpha in general was not significantly affected. Although the effect of thyroid hormones on PG release from cultured calvaria was completely abolished by 5 x 10(-7) mol/liter indomethacin, in some experiments indomethacin reduced thyroid hormone-mediated bone resorption by only 50%. This indicates that thyroid hormone action on bone is also mediated by a PG-independent mechanism.

6-Ketoprostaglandin F1 alpha↗

PubMed1989

Interferon gamma and calcitonin induce differential changes in cellular kinetics and morphology of osteoclasts in cultured neonatal mouse calvaria.

The present study compares the effects of calcitonin (CT) and interferon gamma (IFN-gamma) on the size, distribution, and ultrastructure of osteoclasts in cultured neonatal mouse calvaria. The number and cross-sectional area of osteoclasts in cultured bones was increased by the addition of parathyroid hormone (PTH) to the culture medium for 24-48 h. Prolonged treatment (up to 72 h) with PTH led to extensive rarefication and formation of holes in the mineralized matrix. PTH-activated osteoclasts exhibited an elaborate ruffled border and showed a typical zonal arrangement of intracellular organelles with the outer cytoplasmic region containing numerous membrane-bound vesicles. CT (20 mU/ml) within 90 minutes caused a complete loss of the ruffled border in PTH-activated osteoclasts. The typical zonal architecture disappeared with intracellular vesicles spread through the entire cytoplasm. Prolongation of CT treatment to 24-48 h led to the appearance of vesicles with dark granular content in inactivated osteoclasts. This morphologically distinct vesicle population allowed us to identify the latter cells as "postosteoclasts" and thereby to distinguish them from osteoclasts precursors. Small active osteoclasts that had originated very likely from these precursors appeared in calvarial bones coincidentally with escape from CT inhibition of bone resorption and resulted in increased total number of osteoclasts. In contrast, IFN-gamma (500 U/ml) acting as a proliferation inhibitor, reduced the total number of osteoclasts. In the presence of PTH it caused no immediate (90 minutes) change in the ultrastructure of PTH-induced osteoclasts apart from an increase in the number of autophagic vacuoles. After prolonged exposure (24-48 h) in the presence of PTH, osteoclasts with low resorbing activity exhibited intermediate borders at their contact zone with the mineralized matrix. In the absence of PTH, the short-term effect of the immune interferon on osteoclast morphology was almost comparable to that of CT. After prolonged treatment in the absence of PTH, postosteoclasts comparable in vesicle population and size to those after CT treatment were found.

Animals↗

PubMed1989

Comparison between the effects of forskolin and calcitonin on bone resorption and osteoclast morphology in vitro.

The adenylate cyclase activator forskolin (1-10 mumol/L) inhibited 45Ca release from parathyroid hormone (PTH; 10 nmol/L) stimulated prelabeled neonatal mouse calvaria in short term culture (24 h). This effect of forskolin was potentiated by rolipram, Ro 20-1724, and isobutyl-methylxanthine, three structurally different inhibitors of cyclic AMP phosphodiesterase. Forskolin (10 mumol/L) and calcitonin (30 mU/mL) inhibited the mobilization of stable calcium and inorganic phosphate as well as the release of the lysomal enzymes beta-glucuronidase and beta-N-acetylglucosaminidase from PTH-stimulated unlabeled bones. Osteoclasts in PTH-stimulated calvaria showed active ruffled borders with numerous membrane infoldings. Treatment of PTH-stimulated bones with forskolin and calcitonin resulted in a rapid (2 h) loss of the active ruffled border. In addition, forskolin and calcitonin induced similar changes with respect to the number and size distribution of cytoplasmic vesicles in PTH-activated osteoclasts. After 24 h, all signs of osteoclast inactivation were still prominent, whereas after 48 h of treatment with forskolin or calcitonin, the reappearance of a ruffled border on a number of osteoclasts signaled an escape from the inhibitory action of both calcitonin or forskolin. These data indicate that forskolin inhibits bone resorption by a cyclic AMP dependent mechanism and that the effect of forskolin and calcitonin on bone resorption and osteoclast morphology are comparable. These observations lend further support to the view that cyclic AMP may be an intracellular mediator of the inhibitory action of calcitonin on multinucleated osteoclasts.

Acetylglucosaminidase↗

PubMed1989

Effect of auranofin on resorption, prostaglandin synthesis and ultrastructure of bone cells in cultured mouse calvaria.

Auranofin (AF) in concentrations between 3 x 10(-7) and 3 x 10(-6) mol/l stimulated bone resorption in cultured neonatal mouse calvariae significantly with 1 x 10(-6) mol/l being most potent. Complete inhibition by 5 x 10(-7) mol/l indomethacin and increased medium concentrations of prostaglandin (PG) E2 and 6-keto-PGF1 alpha after 72 h indicate a PG mediated mechanism. Morphology revealed active osteoclasts. Cytotoxic effects were observed with 3 x 10(-6) and 1 x 10(-5) mol/l AF with osteocytes and osteoblasts being considerably more sensitive than osteoclasts. The latter concentrations inhibited bone resorption stimulated by parathyroid hormone (PTH) 1,25-dihydroxyvitamin D3, PGE2, thrombin and interleukin 1. The stimulatory effect of AF on PG production and subsequent bone resorption could limit its therapeutic usefulness.

Animals↗

PubMed1988

Comparison of the inhibitory effect of nonsteroidal antiinflammatory drugs on bone prostaglandin synthesis and resorption.

The biopotency of various nonsteroidal antiinflammatory drugs (NSAID) in inhibiting prostaglandin (PG) mediated bone resorption was evaluated in a neonatal mouse calvaria organ culture system. Thrombin stimulated formation of the osteolytic PG, PGE2 and PGI2 (measured as 6-keto-PGF1 alpha) and the concomitant stimulation of calcium release from cultured bone were inhibited by diclofenac much greater than indomethacin much greater than flurbiprofen greater than piroxicam greater than acemetacin much greater than acetylsalicylic acid. The relative potencies of the NSAID on PG synthesis in bone differs from that observed previously in other model systems.

Animals↗

PubMed1987

Gamma interferon inhibits basal and interleukin 1-induced prostaglandin production and bone resorption in neonatal mouse calvaria.

Production of the osteolytic arachidonic acid metabolites, prostaglandin (PG) E2, PGI2 and PGF2 alpha, by neonatal mouse calvariae was quantitated by gas chromatography/mass spectrometry. Mouse recombinant interleukin 1 (rIL-1) raised medium levels of PGE2 and PGI2 (measured as 6-keto-PGF1 alpha) in the dose range tested (1.0-10.0 U/ml culture medium), while an effect on PGF2 was only observed at 10 U/ml. Bone resorption in response to rIL-1 reached a plateau at 3.0 U/ml. Mouse recombinant gamma-interferon (rIFN-gamma) between 100-500 U/ml suppressed basal PG synthesis and spontaneous resorption of cultured bone. In addition, IFN-gamma at 100 U/ml prevented stimulation of PG synthesis by 3.0 U/ml rIL-1 and thereby reduced the bone resorbing activity of the cytokine by at least 60%. 5 X 10(-7) M indomethacin was equally effective in suppression of PG synthesis and bone resorption. The present study provides evidence that IFN-gamma inhibits PG synthesis and consequently resorption of cultured bone.

Animals↗

PubMed1987

Clinical long-term results after parathyroidectomy for primary hyperparathyroidism.

The long-term clinical results of parathyroidectomy for primary hyperparathyroidism were analyzed in 176 patients. Preoperatively 152 patients (86%) showed classic symptoms, 15 (9%) were classified as minimally symptomatic (only hypertension, diffuse osteopenia or manifestations of the hypercalcemic syndrome), and nine (5%) were asymptomatic. All patients were normocalcemic at follow-up, but renal, skeletal or gastrointestinal symptoms were eliminated in only 88-91%. Preoperatively impaired renal function and hypertension were seldom improved by parathyroidectomy. Deterioration of renal function and hypertension occurred only in the symptomatic and minimally symptomatic patients, in whom the course was varied and unpredictable. During observation periods up to 22 years, 7% of the patients died of acute/chronic renal failure or consequences of hypertension. Death from uremia was more common when there was also skeletal involvement. Acute pancreatitis could occur without preoperative symptoms, but other gastrointestinal disorders responded to normalization of parathyroid metabolism. Multiple bone lesions responded functionally and lacked prognostic significance. Hypercalcemic syndrome was rapidly and lastingly relieved by parathyroidectomy.

Aged↗

PubMed1987

Cyclosporine A inhibits bone resorption in cultured neonatal mouse calvaria.

The effect of the immunosuppressive agent cyclosporine A (CsA) on the resorption of neonatal mouse calvaria was examined in vitro. CsA, at concentrations of 10(-7) to 3 X 10(-5) M, inhibited bone resorption produced by 10(-8) M parathyroid hormone, 3 U/ml of mouse recombinant interleukin-1,5 X 10(-7) M prostaglandin E2, 14 U/ml of thrombin, 5 micrograms/ml of bacterial lipopolysaccharide or 10(-9) M 1 alpha,25-dihydroxyvitamin D3. The effects of CsA on resorption were maintained over 72 h of culture with parathyroid hormone or prostaglandin E2 with no evidence of "escape". Removal of CsA from the cultures resulted in recovery of the resorptive response after a 24-h delay. CsA did not affect thymidine incorporation into DNA in the calvaria. Our results demonstrate that CsA is a nonselective antiresorptive agent in bone, with actions that differ somewhat from those of calcitonin. The results confirm and extend our previous findings on effects of CsA in fetal rat limb bones, with the exception that the inhibitory effects of CsA were more rapidly and completely reversible in the limb bone system.

Animals↗

PubMed1987

Successful parathyroidectomy in primary hyperparathyroidism: a clinical follow-up study of 212 consecutive patients.

The long-term clinical courses of 212 "cured" (normocalcemic) patients were analyzed for 1 to 25 years (mean, 6.8 +/- 5.4 years). Preoperatively, 181 patients (85%) were classified as having typical symptoms, 22 patients (11%) as having minimal symptoms, and nine patients (4%) as having no symptoms of primary hyperparathyroidism (PHP). Although the formation of urinary calculi was stopped in 91% of patients, deteriorated renal function and hypertension were seen in patients with symptoms (14% and 8%, respectively) and patients with minimal symptoms of PHP (6% and 15%, respectively). Renal function changes and hypertension were unpredictable despite normalization of the hyperactive parathyroid metabolism and had decisive results: 7% of the patients died of uremia or of the consequences of hypertension (stroke). Large, multiple bone lesions healed functionally and were of no prognostic significance. In the majority of patients with symptoms of PHP, gastrointestinal manifestations healed postoperatively, but two patients who had no preoperative gastrointestinal complaints died of acute pancreatitis. Almost all symptoms of the hypercalcemia syndrome disappeared immediately and permanently in patients with symptoms and patients with minimal symptoms of PHP. Neither deterioration of renal function nor elevation of blood pressure were observed postoperatively in "cured" patients who showed no symptoms of PHP preoperatively. Even in these patients, immediate surgical treatment may have avoided the complications of chronic renal failure or hypertension. As soon as organic manifestations, even in mild form, have been established, it seems impossible to predict the course and to prevent an unfavorable clinical outcome.

Adult↗

PubMed1986

[Clinical experiences following the surgical therapy of asymptomatic, oligosymptomatic and symptomatic parathyroid gland hyperfunction].

Depending on their symptomatology 152 cured (i.e., normocalcemic) patients with surgically proven primary hyperparathyroidism (pHPT) showed typical symptoms preoperatively. Besides hypercalcemia and elevated parathyroid hormone levels, 15 patients suffered only from hypertension and/or diffuse osteoporosis and/or complaints caused by the hypercalcemic syndrome (oligosymptomatic patients). Nine patients had no complaints (asymptomatic patients). The long-term clinical course of all patients was analyzed up to 22 years. Although the formation of urinary calculi was stopped in 94% of cases, a deterioration of renal function and hypertension was seen in symptomatic (12.5% and 9.2%, respectively) and oligosymptomatic patients (6.7% and 13.3%, respectively). Renal function and hypertension were unpredictable despite normalization of the hyperactive parathyroid metabolism and were of decisive prognostic significance; 6% died of acute or chronic renal failure, or of the consequences of hypertension. Multiple bone lesions, even large, healed functionally and were of no prognostic significance. In the majority of symptomatic patients gastrointestinal manifestations held postoperatively, but two patients died of acute pancreatitis without gastrointestinal complaints preoperatively. Almost all symptoms of the hypercalcemic syndrome disappeared immediately and permanently in symptomatic and oligosymptomatic patients. No deterioration of renal function and no elevation of blood pressure was observed in cured asymptomatic patients postoperatively. Immediate surgical treatment even in asymptomatic patients may have avoided complications of chronic renal failure or of hypertension. As soon as organic manifestations, even in a mild form, have been established, it seems impossible to predict the course and to prevent an unfavorable clinical outcome.

Bone Diseases, Metabolic↗

PubMed1986

Indomethacin inhibits thrombin-, but not thyroxin-stimulated resorption of fetal rat limb bones.

The bone-resorbing effects of thrombin and thyroxin, two agents that stimulate resorption in neonatal mouse calvaria by prostaglandin-dependent mechanisms, were examined in cultures of fetal rat limb bones. Thrombin produced maximal resorption in the limb bone cultures at a concentration of 100 U/ml when bones were cultured in BGJ supplemented with 1 mg/ml bovine serum albumin. The effects of thrombin were partially inhibited by 0.5 and 10 uM indomethacin. Thrombin failed to elicit resorption when the limb bones were cultured in DMEM with 15% horse serum. Thyroxin stimulated the resorption of limb bones in both BGJ-albumin and DMEM-serum media. Resorption was elicited by thyroxin concentrations of 10 nM-10 uM. 30 uM thyroxin failed to stimulate resorption. The dose-response curve to thyroxin was shallow, and the agent did not produce maximal resorption. The bone-resorbing effects of thyroxin were not affected by 0.5 or 10 uM indomethacin.

Animals↗

PubMed1985

Recombinant gamma-interferon inhibits prostaglandin-mediated and parathyroid hormone-induced bone resorption in cultured neonatal mouse calvaria.

A role of gamma-interferon in the bone remodeling process can be implicated from its interference with bone resorptive processes in cultured neonatal mouse calvaria. The immune interferon is an efficient inhibitor of endogenous prostaglandin synthesis, particularly after stimulation by thrombin or arachidonic acid, and, in addition, has a calcitonin-like inhibitory effect on PTH-induced osteoclastic bone resorption.

Animals↗

PubMed1985

Prostaglandin-related bone resorption in cultured neonatal mouse calvaria: evaluation of biopotency of nonsteroidal anti-inflammatory drugs.

The objective of this study was the development of an assay based on suppression of endogenous prostaglandin synthesis in cultured neonatal mouse calvaria for evaluation of the biopotency of nonsteroidal anti-inflammatory drugs in bone. In preliminary trials, osteolytic activity due to spontaneous prostaglandin production over a 72 h culture period was found highly variable, and could not be stabilized by addition of the common precursor arachidonic acid to the culture medium. Eventually, continuous exposure of mouse calvaria to moderate concentrations of thrombin (greater than or equal to 14 U/ml medium) proved to be satisfactory to achieve stable rates of bone resorption through continuous stimulation of prostaglandin synthesis from endogenous sources. Notably, the extent of net calcium release into the medium was highly reproducible in different experiments. As an example for possible applications of the bioassay, the ability of acemetacin to interfere with prostaglandin synthesis in bone, which had not been assessed before, was evaluated in a comparative assay with indomethacin and acetylsalicylic acid. While 1 X 10(-8) M acemetacin appeared to augment thrombin-induced bone resorption, as did 5 X 10(-6) M acetylsalicylic acid, a dose-dependent inhibition of calcium release was observed between 10(-7)-10(-5) M acemetacin. In this respect, the biopotency of indomethacin was 50 times higher than that of acemetacin and exceeded that of acetylsalicylic acid by a factor of more than 2000. These data could be useful for the appraisal of multiple effects of the investigated drugs on prostaglandin-related bone turnover.

Animals↗

PubMed1984

Primary hyperparathyroidism is associated with decreased insulin receptor binding and glucose intolerance.

We studied insulin receptor-binding and carbohydrate and metabolism in 15 patients with symptomatic primary hyperparathyroidism in comparison with 20 healthy controls. Insulin binding to monocytes and erythrocytes was measured by radioreceptor-ligand-assay. Furthermore, patients and controls were characterized by testing oral (100 g glucose load) glucose tolerance as well as insulin tolerance (0.1U insulin/kg body weight). Compared with controls, patients with primary hyperparathyroidism exhibited marked hyperinsulinemia (P less than 0.01) and significantly higher glucose levels (P less than 0.01) after an oral glucose load. The glucose lowering effect of intravenous insulin was significantly diminished in primary hyperparathyroidism compared with controls (P less than 0.01). Receptor studies revealed a significantly lower (P less than 0.01) insulin binding to monocytes and to erythrocytes in patients with primary hyperparathyroidism compared with controls. The present data indicate an insulin-resistant state in primary hyperparathyroidism, which is caused at least in part, by a downregulation of insulin receptors.

Adult↗

PubMed1981

[Hyperparathyreoidism and chronic lymphocytic leukemia (author's transl)].

A 55 year old patient with chronic lymphocytic leukemia is reported in whom hypercalcemia occurred associated with hypophosphatemia and elevated parathyroid hormone levels (C-terminal assay). Bone histology gave further evidence for hyperparathyroidism. During neck and mediastinal exploration numerous lymph nodes were exstirpated. Although pathologic parathyroid tissue could not be identified it is concluded from postoperative normalisation of calcium levels that hyperparathyroidism had been cured by surgery. The patient died the seventh postoperative day on bronchopulmonary infection. Early differential diagnostic evaluation of the rare symptom hypercalcemia in chronic lymphocytic leukemia is postulated.

Diagnosis, Differential↗

PubMed1980

[New aspects on diagnosis and therapy of primary hyperparathyroidism (author's transl)].

26, out of them 20 surgically proven cases of primary hyperparathyroidism are presented. The value of different laboratory, radiographic and scintigraphic analysis is examined. The estimation of calcium and phosphate in serum, the iPTH-determination and fine detail hands radiographs were found to be sufficient to establish diagnosis and indication for surgery. The chloride/phosphate-ratio proved valuable in comparative statistical analysis between pHPT and two control groups. Venous sampling at present seems to be the superior method for preoperative localization of parathyroid disease. It should be performed before second surgical intervention in the cervical region, in elderly (more than 60 years old) and risk patients. Early diagnosis and therapy of pHPT is important as pHPT is a chronic disease with many organ complications. The value of calcium-screening in an age group between 40 and 60 years is discussed.

Aged↗