246 research outputs found

    Risk of cancer in patients with dermatomyositis or polymyositis, and follow-up implications: a Scottish population-based cohort study

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    We conducted a national, retrospective population-based cohort study of 705 patients hospitalized with a first diagnosis of dermatomyositis (DM) or polymyositis (PM) during 1982–1996 based on linkage of hospital discharge, cancer registration, and death records in Scotland. Risks of cancer were assessed by calculating standardized incidence ratios (SIR). A first malignancy was diagnosed concurrently or subsequently in 50 patients with DM (SIR 7.7, 95% CI 5.7–10.1), and 40 patients with PM (2.1, 1.5–2.9). Significantly elevated risks were observed for lung, cervix uteri, and ovarian cancer in patients with DM, and for Hodgkin’s disease in patients with PM. The excess risk of cancer was highest around the time of diagnosis, and for patients with DM remained high for at least 2 years. Risks were elevated for both sexes but only significantly so for females, and were highest in patients aged 45–74 years at the time of diagnosis for DM and 15–44 for PM. © 2001 Cancer Research Campaign http://www.bjcancer.co

    Drug-mediated inhibition of Fli-1 for the treatment of leukemia

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    The Ets transcription factor, Fli-1 is activated in murine erythroleukemia and overexpressed in various human malignancies including Ewing's sarcoma, induced by the oncogenic fusion protein EWS/Fli-1. Recent studies by our group and others have demonstrated that Fli-1 plays a key role in tumorigenesis, and disrupting its oncogenic function may serve as a potential treatment option for malignancies associated with its overexpression. Herein, we describe the discovery of 30 anti-Fli-1 compounds, characterized into six functional groups. Treatment of murine and human leukemic cell lines with select compounds inhibits Fli-1 protein or mRNA expression, resulting in proliferation arrest and apoptosis. This anti-cancer effect was mediated, at least in part through direct inhibition of Fli-1 function, as anti-Fli-1 drug treatment inhibited Fli-1 DNA binding to target genes, such as SHIP-1 and gata-1, governing hematopoietic differentiation and proliferation. Furthermore, treatment with select Fli-1 inhibitors revealed a positive relationship between the loss of DNA-binding activity and Fli-1 phosphorylation. Accordingly, anti-Fli-1 drug treatment significantly inhibited leukemogenesis in a murine erythroleukemia model overexpressing Fli-1. This study demonstrates the ability of this drug-screening strategy to isolate effective anti-Fli-1 inhibitors and highlights their potential use for the treatment of malignancies overexpressing this oncogene

    Branch Retinal Vein Occlusion: Pathogenesis, Visual Prognosis, and Treatment Modalities

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    In branch retinal vein occlusion (BRVO), abnormal arteriovenous crossing with vein compression, degenerative changes of the vessel wall and abnormal hematological factors constitute the primary mechanism of vessel occlusion. In general, BRVO has a good prognosis: 50–60% of eyes are reported to have a final visual acuity (VA) of 20/40 or better even without treatment. One important prognostic factor for final VA appears to be the initial VA. Grid laser photocoagulation is an established treatment for macular edema in a particular group of patients with BRVO, while promising results for this condition are shown by intravitreal application of steroids or new vascular endothelial growth factor inhibitors. Vitrectomy with or without arteriovenous sheathotomy combined with removal of the internal limiting membrane may improve vision in eyes with macular edema which are unresponsive to or ineligible for laser treatment

    Genetic polymorphism of the iron-regulatory protein-1 and -2 genes in age-related macular degeneration

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    Iron can be involved in the pathogenesis of AMD through the oxidative stress because it may catalyze the Haber–Weiss and Fenton reactions converting hydrogen peroxide to free radicals, which can induce cellular damage. We hypothesized that genetic polymorphism in genes related to iron metabolism may predispose individuals to the development of AMD and therefore we checked for an association between the g.32373708 G>A polymorphism (rs867469) of the IRP1 gene and the g.49520870 G>A (rs17483548) polymorphism of the IRP2 gene and AMD risk as well as the modulation of this association by some environmental and life-style factors. Genotypes were determined in DNA from blood of 269 AMD patients and 116 controls by the allele-specific oligonucleotide-restriction fragment length polymorphism and the polymerase chain reaction-restriction fragment length polymorphism. An association between AMD, dry and wet forms of AMD and the G/G genotype of the g.32373708 G>A-IRP1 polymorphism was found (OR 3.40, 4.15, and 2.75). On the other hand, the G/A genotype reduced the risk of AMD as well as its dry or wet form (OR 0.23, 0.21, 0.26). Moreover, the G allele of the g.49520870 G>A-IRP2 polymorphism increased the risk of the dry form of the disease (OR 1.51) and the A/A genotype and the A allele decreased such risk (OR 0.43 and 0.66). Our data suggest that the g.32373708 G>A-IRP1 and g.49520870 G>A-IRP2 polymorphisms may be associated with increased risk for AMD

    Bilateral transient osteoporosis of the knee during pregnancy

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    Transient osteoporosis is a rare disease, which can affect pregnant women in the third trimester. Bone marrow edema syndrome, transient bone demineralization, hip algodystrophy, regional migratory osteoporosis, and even reflex sympathetic dystrophy all are terms that have been used to describe the condition. Babinsky and Fromen first documented the symptoms of transient osteoporosis in 1916, and in 1959 Curtiss and Kincaid discussed two cases affecting women in the third trimester of pregnancy. The hip joints are most commonly affected in pregnant women, being reported in 76 % of cases
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