A 55-Year-Old woman with orbital inflammation.
Division of Arthritis and Rheumatic Diseases, Oregon Health and Science University, Portland Veterans Affairs Medical Center, 3181 SW Sam Jackson Park Road OP09, Portland, OR 97239. .Arthritis care & research 11/2012; 64(11). DOI: 10.1002/acr.21822
Article: Orbital and periorbital infections.[Show abstract] [Hide abstract]
ABSTRACT: Infections of the orbit and periorbital tissues are not uncommon. Trauma, skin infections, and sinusitis are frequently the underlying cause. Studies have shown changes in epidemiology and pathogens in the last decade. Although classical manifestations are usually present, atypical cases without specific signs and symptoms may confound the diagnosis. A high index of suspicion, aided by ultrasonography, computed tomography, and magnetic resonance imaging, is frequently required for an accurate diagnosis. Prompt diagnosis and treatment may lead to resolution of the infection, thus avoiding ocular sequelae. Orbital infections may spread into the globe, causing endophthalmitis. Some patients may even need an enucleation or evisceration. New materials and techniques may improve the final result of an anophthalmic socket.Current Opinion in Ophthalmology 11/2001; 12(5):335-41. DOI:10.1097/00055735-200110000-00002 · 2.64 Impact Factor
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ABSTRACT: The acute phase response is the major adverse effect of intravenously administered N-BPs. In this study we show that N-BPs cause gamma,delta-T-cell activation and proliferation in vitro by an indirect mechanism through inhibition of FPP synthase, an effect that can be overcome by inhibiting HMG-CoA reductase with a statin. These studies clarify the probable initial cause of the acute phase response to N-BP drugs and suggest a possible way of preventing this phenomenon. The acute phase response is the major adverse effect of intravenously administered nitrogen-containing bisphosphonate drugs (N-BPs), used in the treatment of metabolic bone diseases. This effect has recently been attributed to their action as non-peptide antigens and direct stimulation of gamma,delta-T-cells. However, because N-BPs are potent inhibitors of farnesyl diphosphate (FPP) synthase, they could cause indirect activation of gamma,delta-T-cells owing to the accumulation of intermediates upstream of FPP synthase in the mevalonate pathway, such as isopentenyl diphosphate/dimethylallyl diphosphate, which are known gamma,delta-T-cell agonists. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers and treated with N-BP, statin, or intermediates/inhibitors of the mevalonate pathway for 7 days in the presence of interleukin (IL)-2. Flow cytometric analysis of the T-cell-gated population was used to quantify the proportion of gamma,delta-T-cells in the CD3+ population. The ability of N-BPs to stimulate proliferation of CD3+ gamma,delta-T-cells in human PBMC cultures matched the ability to inhibit FPP synthase. Gamma,delta-T-cell proliferation and activation (interferon gamma [IFNgamma] and TNFalpha release) was prevented by mevastatin or lovastatin, which inhibit HMG-CoA reductase upstream of FPP synthase and prevent the synthesis of isopentenyl diphosphate/dimethylallyl diphosphate. Desoxolovastatin, an analog of lovastatin incapable of inhibiting HMG-CoA reductase, did not overcome the stimulatory effect of N-BP. Furthermore, statins did not prevent the activation of gamma,delta-T-cells by a synthetic gamma,delta-T-cell agonist or by anti-CD3 antibody. Together, these observations show that N-BPs indirectly stimulate the proliferation and activation of gamma,delta-T-cells caused by inhibition of FPP synthase and intracellular accumulation of isopentenyl diphosphate/ dimethylallyl diphosphate in PBMCs. Because activation of gamma,delta-T-cells could be the initiating event in the acute phase response to bisphosphonate therapy, co-administration of a statin could be an effective approach to prevent this adverse effect.Journal of Bone and Mineral Research 03/2004; 19(2):278-88. DOI:10.1359/JBMR.0301230 · 6.59 Impact Factor
New England Journal of Medicine 10/2008; 359(13):1410-1. DOI:10.1056/NEJMc0803366 · 54.42 Impact Factor
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