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Biomedical subjects

R Ziegler

Publications and source records attributed to R Ziegler.

At least 415 records · Page 23Linked to original sources

[Paget's disease of the skeleton].

Paget's disease of bone is now regarded as a slow virus disease of the skeleton presenting with localized manifestation. The affected areas show increased turnover with irregular structure (mosaic pattern in histology). The bones are thickened but have decreased mechanical strength. The disease most frequently affects the pelvis, femora, and tibiae, followed by the calvarium, the lumbar vertebrae and others. Diagnosis is made by X-ray examination. The differential diagnosis is rarely so difficult that a bone biopsy is required. Bone scintigraphy reveals asymptomatic lesions. Alkaline serum phosphatase mirrors the activity of the disease. Indications for treatment are pains, bending, deformities, fractures, skull base involvement, nerve damage and very high alkaline phosphatase. Calcitonins and bisphosphonates are used for treatment. Single-agent therapy reduces alkaline phosphatase to 50% of the initial level. If more intensive treatment is desired, a combination of calcitonin and EHDP can be used. Paget's sarcoma develops in less than 1% of patients with Paget's disease of bone; it is uncertain whether this complication can be prevented or delayed by the therapeutic regimens currently in use.

Adult↗

[Continuous subcutaneous insulin infusion in the treatment of insulin-dependent diabetes mellitus].

Intensified insulin delivery has attained significant importance in the treatment of insulin-dependent diabetes to avoid microangiopathy involving the retina and kidney. 15 patients have been treated for periods from 2 month to 3 years, 2 years with continuous subcutaneous insulin infusion. All patients have better metabolic control than that achieved with conventional therapy. HbA1c decreased from 7.8% +/- 1.6 (SD) to 6.2% +/- 1.3 (normal value: 3.8-6.5%). Negative features of insulin-pump therapy include hyperglycemias after discontinuation of insulin infusion and cutaneous infection at the catheter site. No severe episodes of hypoglycemia were observed. Acceptability of pump treatment is good in our patients because of improved physical condition and the ability to pursue their usual activities.

Adolescent↗

[Morphologic changes in iliac crest trabecular bone in primary hyperparathyroidism and their significance for diagnosis].

Iliac crest bone biopsy specimens of 391 patients with surgically proven primary hyperparathyroidism were investigated. In 60 unselected cases quantitative analysis of trabecular bone changes was performed. The age of the patients ranged between 12 and 85 years. The observed morphological findings were divided into four stages. In a few cases no differences from normal bone tissue could be observed. In 46% occurrence of a nonspecific increase of osteoid seams, osteoblasts, and osteoclasts was observed. Of the cases 50% showed a specific, but very often mild endosteal fibrosis. Only in 4% was there a severe fibroosteoclasia with development of so-called brown tumors. The quantitative analysis showed an increase of trabecular bone mass as well as of remodeling surfaces. But there was an overlap of up to 25% with the normal controls. The results demonstrate the influence of parathyroid hormone peptides on bone morphology. However, the investigation of a bone biopsy specimen is not generally very useful for diagnostic purposes.

Adolescent↗

[Treatment of tumor hypercalcemia with clodronate. Effect on parathormone and calcitriol].

Clodronate (dichlormethylene diphosphonate) was administered to 21 patients with hypercalcemia due to malignant tumor. The drug was initially given intravenously, then orally. In 20 patients the serum calcium level had been reduced to the normal range within one week of the start of treatment (from 3.3 +/- 0.5 mmol/l to 2.4 +/- 0.3 mmol/l). With oral administration there was a renewed rise in calcium levels in some patients, which had to be treated with higher oral doses or intravenous administration. Parallel with the reduction in calcium levels there was an improvement in the originally impaired renal function. The serum level of intact parathormone(1-84) and 1.25-dihydroxy-vitamin-D3 (calcitriol) rose significantly from usually lowered initial levels. There was a non-linear inverse correlation between parathormone and calcium. No side effects were noted, even after long-term administration.

Adult↗

Procollagen-III peptide serum levels in Paget's disease of the bone.

A commercially available radioimmunoassay kit was used to determine aminoterminal procollagen-III peptide (pNcoll III) serum levels in patients with Paget's disease of the bone and control subjects. In patients with Paget's disease pNcoll III concentrations were significantly elevated. They decreased to varying degrees under chronic therapy with human and salmon calcitonin, disodium ethane 1-hydroxy 1,1-diphosphonate (EHDP), or a combination therapy of EHDP and human calcitonin. The results were compared with the effect on traditional biochemical markers of disease activity: serum alkaline phosphatase and urinary hydroxyproline excretion, both of which reacted more acutely to the various therapies than pNcoll III, although pretreatment correlations were close. The most probable source of pNcoll III is not the Pagetic bone per se, but the vascular, fibrous connective tissue replacing normal bone marrow.

Alkaline Phosphatase↗

[Katacalcin--a new tumor marker in C-cell cancer of the thyroid gland].

Katacalcin (KC) is situated on the C-terminal side of the procalcitonin molecule and is cleaved like calcitonin (CT) from this precursor peptide. Serum levels of KC were measured in 22 patients with C-cell carcinoma with a specific and sensitive radioimmunoassay (normal range, less than 0.1-0.15 ng/ml). Basal serum KC values in C-cell carcinoma patients were 0.32-290 ng/ml. There was a good correlation between KC and CT (r = 0.98, P less than 0.001). Serum KC, as well as CT, markedly increased after pentagastrin and calcium infusion. KC and CT were secreted in nearly equimolar amounts. During selective venous catheterization, KC and CT levels were increased in serum samples from veins draining tumor masses, which could be confirmed operatively. During the follow up, KC and CT measurements correlated well to the stage of disease. KC could be immunohistologically localized in C-cell carcinoma tissue. As a tumor marker, katacalcin is likely to be as useful as calcitonin in C-cell carcinoma.

Calcitonin↗

Binding of acetylated low density lipoprotein and maleylated bovine serum albumin to the rat liver: one or two receptors?

The liver is the major organ involved in clearance of acetylated low density lipoprotein (acetyl-LDL) and maleylated serum albumin (Mal-BSA). Quantitative analysis of the hepatic uptake by sequential scintigraphy in rats shows that the hepatic uptake capacity for Mal-BSA is at least 15 times larger than for acetyl-LDL particles. A membrane-associated M approximately 250,000 daltons hepatic receptor for acetyl-LDL and Mal-BSA was 1450-fold purified from total membrane by Triton X-114 solubilization, chromatography on polyethylenimine cellulose and gel filtration. This receptor incorporated into liposomes displayed a saturable binding of [131I]Mal-BSA with a dissociation constant Kd = 15 nM and to [131I]acetyl-LDL with a dissociation constant Kd = 0.9 nM. The binding of both ligands was sensitive to poly(vinyl sulfate). The purified scavenger receptor system has a binding capacity for [131I]Mal-BSA 20 times larger than for [131I]acetyl-LDL. This is similar to the maximal removal capacity of the rat liver for both ligands in vivo. Binding studies with Mal-BSA, acetyl-LDL and anti-idiotypic receptor antibodies as competitors for [131I]Mal-BSA and [131I]acetyl-LDL binding demonstrate that [131I]Mal-BSA and [131I]acetyl-LDL compete for a common binding site. However, not all of the Mal-BSA binding sites are capable of interacting with acetyl-LDL.

Albumins↗

Neuron-specific enolase in medullary thyroid carcinoma: immunohistochemical demonstration, but no significance as serum tumor marker.

Neuron-specific enolase (NSE) is an enzyme detectable in nervous and neuroendocrine tissue. Increased serum levels of NSE are found in small cell lung cancer and in patients with neuroblastoma, in whom NSE is used as a serum tumor marker. We have investigated 32 patients with histologically proven medullary thyroid carcinoma, a tumor of neuroendocrine origin, in which the classical tumor marker calcitonin (CT) was pathologically elevated. Positive immunocytochemistry for NSE and CT in C-cells was obtained in all cases. Increased serum NSE levels were found in only 5 of 32 patients, there was no correlation between NSE and CT concentrations. We also compared NSE and CT serum levels during long-term follow-up and again found no correlation between NSE and CT. After i.v. stimulation tests with pentagastrin and calcium, no correlation was found between NSE and CT serum levels. We conclude, therefore, that in medullary thyroid carcinoma NSE is useful for immunocytochemistry but not a reliable serum tumor marker.

Calcitonin↗

Inflammation-mediated osteopenia (IMO) during acute inflammation in rats is due to a transient inhibition of bone formation.

Local inflammation was induced in rats through the subcutaneous injection of magnesium silicate. Trabecular bone volume of the tibia decreased progressively during a 3 week observation period following the inflammatory stimulus. The trabecular bone surface covered with osteoblasts was strikingly reduced during the first week but had normalized by the end of the third week. Calcification rate in the cortical bone of the tibia was reduced with a parallel reduction in endosteal osteoid seam width. Both calcification rate and tetracycline double-labeled surface of vertebral trabecular bone were reduced during the first 2 weeks. Neither total bone resorption surface nor active bone resorption surface were increased. There was a decrease in osteoclast numbers/mm2 bone tissue associated with decreasing bone volume. Our data demonstrate a transient inhibition of bone formation during acute inflammation in the rat and indicate that changes in osteoblast function are part of the acute phase response following local inflammation.

Acute-Phase Reaction↗

Action of calcitonin gene-related peptide at the calcitonin receptor of the T47D cell line.

Some effects of calcitonin (CT) can also be produced by calcitonin gene-related peptide (CGRP), an alternative product of the calcitonin gene. This might be mediated by interaction of CGRP at the CT-receptor site. The human breast cancer cell line T47D possesses well characterized CT-receptors (KD = 2.3 x 10(-10) M for 125I salmon CT). 50% inhibition of 125I-sCT binding was achieved with 10(-9) M sCT, 5 x 10(-6) M rat CGRP and 10(-5) M human CGRP. Half maximal cAMP production in T47D cells was seen with 6 x 10(-10) M sCT, 5 x 10(-6) M rCGRP and 10(-5) M hCGRP. Binding and displacement capacity as well as the biological activity of CT and CGRP seems to correlate well. These findings suggest that CGRP in pharmacological doses acts via the CT-receptor. This could be explained by the homology and conformational similarities between CT and CGRP.

Breast Neoplasms↗

sn-1,2-Diacylglycerols and phorbol diesters stimulate thromboxane synthesis by de novo synthesis of prostaglandin H synthase in human promyelocytic leukemia cells.

We studied the regulation of thromboxane (TX) synthesis in promyelocytic leukemia cells during macrophage differentiation. Cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) showed rates of TXB2 synthesis from exogenous arachidonic acid that exceeded that of control cells by a factor of up to 81. Cells treated with sn-1,2-dioctanoylglycerol (diC8) showed similarly high TXB2 synthesis rates when diC8 was added concomitantly with a subthreshold concentration of TPA or when given in multiple doses. These activities depended on de novo synthesis of prostaglandin H (PGH) synthase because: microsomal PGH synthase activity showed large increases in Vmax values, and mass measurements of PGH synthase revealed the presence of PGH synthase in differentiating cells whereas the enzyme was undetectable in control cells. These results indicate that macrophage differentiation is associated with stimulation of TXB2 synthesis that requires both activation of protein kinase C and de novo synthesis of PGH synthase.

Arachidonic Acid↗

[Microabscesses of the spleen in patients with acute leukemia].

Eight patients with acute myelogenous leukemia in complete remission after induction chemotherapy developed septic fever. Fever was unresponsive to broad-spectrum antibiotic therapy. Ultrasonography showed multiple 0.5-2 cm in diameter, anechoic densities and some 1-3 cm "target" appearances in spleen and liver. Computed tomography demonstrated multiple, round, 0.5-2 cm areas of diminished attenuation in spleen and liver, which did not enhance like the surrounding parenchyma. These microabscesses increased in size and number without equivalent antifungal therapy and decreased or disappeared after specific treatment. Candida-infection was confirmed by histologically from liver specimens in four patients, fungal organisms were seen microscopically an liver-biopsy in one patient and at autopsy one patient was found to have candida disseminated to the spleen, liver, kidneys, lung and CNS.

Abscess↗

[Adrenomyeloneuropathy, a rare cause of primary adrenal cortex insufficiency].

Inherited via the X chromosome, adrenomyeloneuropathy is a rare cause of primary adrenocortical insufficiency. Neurological signs are of central and peripheral demyelinization, while endocrinologically it is characterized by Addison's disease and primary testicular insufficiency. In two patients with this condition the metabolic defect in the breakdown of long-chain fatty acids was confirmed by an increased hexakosan (C 26) blood level. One patient had an isolated failure of the zona fasciculata; in the other there was clinically manifest complete adrenocortical insufficiency. Both patients had incipient hypogonadism. In the second case, neurological symptoms preceded the endocrinological ones, while in the first both the family history and the adrenocortical insufficiency led to the diagnosis. In peripheral neuropathy in a young male, attention should always be given to signs of incipient adrenocortical insufficiency.

Addison Disease↗