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Sven‐Ulrik Gorr 《Periodontology 2000》2009,51(1):152-180
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The myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell diseases characterized by ineffective hematopoiesis
in one or more cell lines, resulting in insufficient bone marrow function. For most patients with MDS, supportive care by
blood transfusions is still the mainstay of treatment. Especially in low-risk patients, anemia represents the major clinical
problem, and many of these patients develop transfusional iron overload. This paper reviews the literature on transfusional
iron overload in patients with MDS, looking at pathophysiology, evaluation, and treatment of the transfusional iron burden
with desferrioxamine and oral chelators. 相似文献
76.
J?rgen Olsen Chunze Li Christian Skonberg Inga Bj?rnsdottir Ulrik Sidenius Leslie Z Benet Steen Honoré Hansen 《Drug metabolism and disposition》2007,35(5):758-764
Carboxylic acids may be metabolized to acyl glucuronides and acyl-coenzyme A thioesters (acyl-CoAs), which are reactive metabolites capable of reacting with proteins in vivo. In this study, the metabolic activation of tolmetin (Tol) to reactive metabolites and the subsequent formation of Tol-protein adducts in the liver were studied in rats. Two hours after dose administration (100 mg/kg i.p.), tolmetin acyl-CoA (Tol-CoA) was identified by liquid chromatography-tandem mass spectrometry in liver homogenates. Similarly, the acyl-CoA-dependent metabolites tolmetin-taurine conjugate (Tol-Tau) and tolmetin-acyl carnitine ester (Tol-Car) were identified in rat livers. In a rat bile study (100 mg/kg i.p.), the S-acyl glutathione thioester conjugate was identified, providing further evidence of the formation of reactive metabolites such as Tol-CoA or Tol-acyl glucuronide (Tol-O-G), capable of acylating nucleophilic functional groups. Three rats were treated with clofibric acid (150 mg/kg/day i.p. for 7 days) before dose administration of Tol. This resulted in an increase in covalent binding to liver proteins from 0.9 nmol/g liver in control rats to 4.2 nmol/g liver in clofibric acid-treated rats. Similarly, levels of Tol-CoA increased from 0.6 nmol/g to 4.4 nmol/g liver after pretreatment with clofibric acid, whereas the formation of Tol-O-G and Tol-Tau was unaffected by clofibric acid treatment. However, Tol-Car levels increased from 0.08 to 0.64 nmol/g after clofibric acid treatment. Collectively, these results confirm that Tol-CoA is formed in vivo in the rat and that this metabolite can have important consequences in terms of covalent binding to liver proteins. 相似文献
77.
Christoffer Ostri Steffen Heegaard Jan Ulrik Prause 《Acta ophthalmologica. Supplement》2008,86(8):917-920
Purpose: To report three cases of sclerosing Wegener’s granulomatosis in the orbit and to compare the histopathological morphology with those of other types of sclerosing orbital inflammation. Methods: We analysed the clinical data along with histopathological specimens from orbital biopsies and from two enucleated eyes. Results: All three patients had longstanding inflammation in the orbit and involvement of the paranasal sinuses. Proptosis, impaired ocular motility and reduced visual acuity dominated the clinical picture. All histopathological specimens featured granulomatous inflammation, tissue necrosis, vasculitis and widespread dense fibrosis. In certain areas of all specimens the fibrous tissue was arranged in characteristic concentric, onionskin‐like whorls of collagen around obliterated small blood vessels. Conclusions: Wegener’s granulomatosis may lead to orbital fibrosis and sclerosis. The stromal changes and cellular infiltrate resemble the non‐specific orbital inflammation previously termed orbital pseudotumour. We present the first ‘onionskin’ lesions in association with Wegener’s granulomatosis in the orbit. This latter morphology may represent an abnormal fibrotic reaction in inflammatory tissue. 相似文献
78.
A majority of cutaneous melanomas show activating mutations in the NRAS or BRAF proto-oncogenes, components of the Ras-Raf-Mek-Erk signal transduction pathway. Consistent data demonstrate the early appearance, in a mutually exclusive manner, of these mutations. The purpose of this paper is to summarize the literature on NRAS and BRAF activating mutations in melanoma tumors with respect to available data on histogenetic classification as well as body site and presumed UV-exposure. Common alterations of the signal transducing network seem to represent molecular hallmarks of cutaneous melanomas and therefore should continue to strongly stimulate design and testing of targeted molecular interventions. 相似文献
79.
Arne H rlyck Ulrik Henriques Anders Jakobsen 《Acta oncologica (Stockholm, Sweden)》1994,33(8):909-911
Of 668 consecutive patients with SCLC, 472 underwent bone marrow examination for staging. In 330 patients a triple examination (sternal aspiration, iliac crest aspiration and biopsy) was performed, otherwise a single procedure. Bone marrow infiltration (MI) was found in 37% of the patients with extensive disease, and the frequencies of a positive finding in single and triple examinaton were not statistically different. In the group having triple examination performed iliac crest aspiration alone disclosed MI in 32%. When all three procedures were included still more patients with MI were found (42%) but the two values were not significantly different. In 6.6% of patients who would have been classified as 'limited' did bone marrow examination change the stage to extensive disease. Based on these results we recommend iliac crest aspiration, but not triple examination with iliac crest biopsy, in the staging of SCLC. 相似文献
80.
Pedersen Ulrik Søgaard Helmer Elbrønd Ole 《European archives of oto-rhino-laryngology》1984,239(1):1-6
Summary The hypothesis that homeostatic control mechanisms control mucociliary function in ciliated mucous membrane was tested. Nasal mucociliary transport rates were recorded in chickens in vivo at successive intervals during exposure to SO2 or after inoculation with Newcastle disease virus (NDV), or both. Either agent alone caused deceleration of the turbinate clearance. However, when SO2 exposure was limited to one nasal fossa and turbinate mucociliary rates were determined in the unexposed and infected side, the two acted antagonistically and yielded approximately normal rates. Exposure of the nasal mucosae to SO2 caused decreased rates of sinus clearance, while NDV infection of nasal membranes induced increased rates of sinus clearance. Exposure of nasal mucosae to both agents acted antagonistically to effect rates of sinus clearance in normal ranges. These data support the idea of homeostasis.Research support from NIH grant no. 5 RO1 ES-00741 相似文献