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Query: UMLS:C0039483 (giant cell arteritis)
 3,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The elderly as a whole suffer fewer headaches than the young. For the majority headache will represent a minor annoyance to be endured or treated with any available drug in the medicine chest. For some, migraine headaches or tension-type headaches become entwined with every daily activity. With the advent of modern pharmacology, headache can often be treated successfully. Trigeminal neuralgia is a source of particularly high morbidity among the elderly, but may be treated very satisfactorily with carbamazepine or baclofen. Paroxysmal hemicrania is exquisitely sensitive to indomethacin, while cluster headache patients receive relief from oxygen inhalation, corticosteroids or lithium. Headache may be the signature of the disease which leads to serious morbidity and mortality. The 'sentinel' headache of subarachnoid haemorrhage is evaluated by a physician in 15% of patients who will eventually rupture an intracranial aneurysm. Morning headache with nausea and vomiting may represent increased intracranial pressure caused by a tumour, haematoma or abscess. The elderly patient with a new headache needs emergency evaluation for temporal arteritis and rapid corticosteroid treatment if the diagnosis is confirmed, to prevent blindness. The broad spectrum of headache, at times a benign aggravation, while at others the harbinger of death, makes the careful evaluation of each headache imperative. This article attempts to make the difficult evaluation of head pain a little easier.
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PMID:Treatment of the elderly patient with headache or trigeminal neuralgia. 179 4

It is generally accepted that myocardial ischemia, and its extreme consequence, acute myocardial infarction, can result from transient or permanent disproportion between myocardial oxygen demand and coronary artery blood supply. Insufficient coronary artery blood supply may have many reasons. The aim of the study is to point to the clinical features of the coronary vasculitides as well as to the diagnostic and therapeutic possibilities. Coronary artery involvement in infectious angiitis, in Takayasu's arteritis, in granulomatous giant cell arteritis, in thromboangiitis obliterans, in polyarteritis nodosa, in Wegener's granulomatosis and in Churg--Strauss syndrome is discussed. The diagnosis of coronary vasculitis must be supposed in every patient with primary or secondary vasculitis in whom chest pain or cardiac failure appear. In young patients with clinical, electrocardiographic or laboratory signs of coronary artery disease, especially in absence of risk factors for atherosclerosis, the diagnosis of coronary vasculitis must be considered in differential diagnosis. (Fig. 4, Tab. 1, Ref. 32.).
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PMID:[Vasculitides of the coronary arteries]. 862 Mar 25

Giant cell arteritis (GCA) is a systemic vasculitis preferentially affecting large and medium-sized arteries. Inflammatory infiltrates in the arterial wall induce luminal occlusion with subsequent ischemia and degradation of the elastic membranes, allowing aneurysm formation. To identify pathways relevant to the disease process, differential display-PCR was used. The enzyme aldose reductase (AR), which is implicated in the regulation of tissue osmolarity, was found to be upregulated in the arteritic lesions. Upregulated AR expression was limited to areas of tissue destruction in inflamed arteries, where it was detected in T cells, macrophages, and smooth muscle cells. The production of AR was highly correlated with the presence of 4-hydroxynonenal (HNE), a toxic aldehyde and downstream product of lipid peroxidation. In vitro exposure of mononuclear cells to HNE was sufficient to induce AR production. The in vivo relationship of AR and HNE was explored by treating human GCA temporal artery-severe combined immunodeficiency (SCID) mouse chimeras with the AR inhibitors Sorbinil and Zopolrestat. Inhibition of AR increased HNE adducts twofold and the number of apoptotic cells in the arterial wall threefold. These data demonstrate that AR has a tissue-protective function by preventing damage from lipid peroxidation. We propose that AR is an oxidative defense mechanism able to neutralize the toxic effects of lipid peroxidation and has a role in limiting the arterial wall injury mediated by reactive oxygen species.
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PMID:Aldose reductase functions as a detoxification system for lipid peroxidation products in vasculitis. 1019 73

Giant cell arteritis (GCA) is an inflammatory vasculopathy in which T cells and macrophages infiltrate the wall of medium and large arteries. Clinical consequences such as blindness and stroke are related to arterial occlusion. Formation of aortic aneurysms may result from necrosis of smooth muscle cells and fragmentation of elastic membranes. The molecular mechanisms of arterial wall injury in GCA are not understood. To identify mechanisms of arterial damage, gene expression in inflamed and unaffected temporal artery specimens was compared by differential display polymerase chain reaction. Genes differentially expressed in arterial lesions included 3 products encoded by the mitochondrial genome. Immunohistochemistry with antibodies specific for a 65-kDa mitochondrial antigen revealed that increased expression of mitochondrial products was characteristic of multinucleated giant cells and of CD68+ macrophages that cluster in the media and at the media-intima junction. 4-Hydroxy-2-nonenal adducts, products of lipid peroxidation, were detected on smooth muscle cells and on tissue infiltrating cells, in close proximity to multinucleated giant cells and CD68+ macrophages. Also, giant cells and macrophages with overexpression of mitochondrial products were able to synthesize metalloproteinase-2. Our data suggest that in the vascular lesions characteristic for GCA, a subset of macrophages has the potential to support several pathways of arterial injury, including the release of reactive oxygen species and the production of metalloproteinase-2. This macrophage subset is topographically defined and is also identified by overexpression of mitochondrial genes. Because these macrophages have a high potential to promote several mechanisms of arterial wall damage, they should be therapeutically targeted to prevent blood vessel destruction.
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PMID:Tissue-destructive macrophages in giant cell arteritis. 1032 42

The generation of reactive oxygen species (ROS) by activated Kupffer cells contributes to liver injury following liver preservation, shock, or endotoxemia. Pharmacological interventions to protect liver cells against this inflammatory response of Kupffer cells have not yet been established. Atrial natriuretic peptide (ANP) protects the liver against ischemia-reperfusion injury, suggesting a possible modulation of Kupffer cell-mediated cytotoxicity. Therefore, we investigated the mechanism of cytoprotection by ANP during Kupffer cell activation in perfused rat livers of male Sprague-Dawley rats. Activation of Kupffer cells by zymosan (150 microgram/ml) resulted in considerable cell damage, as assessed by the sinusoidal release of lactate dehydrogenase and purine nucleoside phosphorylase. Cell damage was almost completely prevented by superoxide dismutase (50 U/ml) and catalase (150 U/ml), indicating ROS-related liver injury. ANP (200 nM) reduced Kupffer cell-induced injury via the guanylyl cyclase-coupled A receptor (GCA receptor) and cGMP: mRNA expression of the GCA receptor was found in hepatocytes, endothelial cells, and Kupffer cells, and the cGMP analog 8-bromo-cGMP (8-BrcGMP; 50 microM) was as potent as ANP in protecting from zymosan-induced cell damage. ANP and 8-BrcGMP significantly attenuated the prolonged increase of hepatic vascular resistance when Kupffer cell activation occurred. Furthermore, both compounds reduced oxidative cell damage following infusion of H2O2 (500 microM). In contrast, superoxide anion formation of isolated Kupffer cells was not affected by ANP and only moderately reduced by 8-BrcGMP. In conclusion, ANP protects the liver against Kupffer cell-related oxidant stress. This hormonal protection is mediated via the GCA receptor and cGMP, suggesting that the cGMP receptor plays a critical role in controlling oxidative cell damage. Thus ANP signaling should be considered as a new pharmacological target for protecting liver cells against the inflammatory response of activated Kupffer cells without eliminating the vital host defense function of these cells.
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PMID:Prevention of Kupffer cell-induced oxidant injury in rat liver by atrial natriuretic peptide. 1033 4

T lymphocytes, encountering stimulatory signals in the adventitia of medium-size arteries, emerge as the key players in inflammation-associated injury pathways. In GCA, all injury mechanisms have been related to effector macrophages. Regulated by IFN-gamma-producing T cells, macrophages commit to distinct avenues of differentiation and acquire a spectrum of potentially harmful capabilities (Figure 1). Macrophages in the adventitia focus on production of pro-inflammatory cytokines. Macrophages in the media specialize in oxidative damage with lipid peroxidation attacking smooth muscle cells and matrix components. These macrophages also supply reactive oxygen intermediates that, in combination with nitrogen intermediates, cause protein nitration of endothelial cells. Production of oxygen radicals is complemented by the production of metalloproteinases, likely essential in the breakdown of elastic membranes. With the fragmentation of the internal elastic lamina, the intimal layer becomes accessible to migratory myofibroblasts that, driven by PDGF, form a hyperplastic intimal layer and cause occlusion of the vessel lumen. Expansion of the hyperplastic intima is accompanied by intense neoangiogenesis, supported by angiogenesis factors that again derive from specialized macrophages. Similarities in injury pathways between GCA and another arterial disease, atherosclerosis, are beginning to be recognized. Specifically, activated T cells and macrophages are increasingly appreciated as key players in the process of instability and rupture of atherosclerotic plaque. A specialized subset of CD4 T cells, CD4+ CD28- T cells, are suspected to participate in tissue injury in the plaque. These T cells are equipped with cytolytic capabilities and release large amounts of IFN-gamma. Comparative studies between patients with GCA and those with acute coronary syndromes should enhance our ability to define the principles of arterial wall inflammation, the specifics of injury in that microenvironment, and help in the identification of the eliciting signals.
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PMID:Pathogenic mechanisms in giant cell arteritis. 1208 61

Arterial wall damage in giant cell arteritis (GCA) is mediated by several different macrophage effector functions, including the production of metalloproteinases and lipid peroxidation. Tissue-invading macrophages also express nitric oxide synthase (NOS)-2, but it is not known whether nitric oxide-related mechanisms contribute to the disease process. Nitric oxide can form nitrating agents, including peroxynitrite, a nitric oxide congener formed in the presence of reactive oxygen intermediates. Protein nitration selectively targets tyrosine residues and can result in a gain, as well as a loss, of protein function. Nitrated tyrosine residues in GCA arteries were detected almost exclusively on endothelial cells of newly formed microcapillaries in the media, whereas microvessels in the adventitia and the intima were spared. Nitration correlated with endothelial NOS-3 expression and not with NOS-2-producing macrophages, which preferentially homed to the hyperplastic intima. The restriction of nitration to the media coincided with the production of reactive oxygen intermediates as demonstrated by the presence of the toxic aldehyde, 4-hydroxynonenal. Depletion of tissue-infiltrating macrophages in human temporal artery-SCID mouse chimeras disrupted nitrotyrosine generation, demonstrating a critical role of macrophages in the nitration process that targeted medial microvessels. Thus, protein nitration in GCA is highly compartmentalized, reflecting the production of reactive oxygen and reactive nitrogen intermediates in the inflamed arterial wall. Heterogeneity of microvessels in NOS-3 regulation may be an additional determinant contributing to this compartmentalization and could explain the preferential targeting of newly generated capillary beds.
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PMID:Reactive nitrogen intermediates in giant cell arteritis: selective nitration of neocapillaries. 1210 96

The need of blood flow to different organs varies rapidly over time which is why there is sophisticated local regulation of blood flow. The term dysregulation simply means that blood flow is not properly adapted to this need. Dysregulative mechanisms can lead to an over- or underperfusion. A steady overperfusion may be less critical for long-term damage. A constant underperfusion, however, can lead to some tissue atrophy or in extreme situations to infarction. Unstable perfusion (underperfusion followed by reperfusion) leads to oxidative stress. There are a number of causes that lead to local or systemic vascular dysregulation. Systemic dysregulation can be primary or secondary of nature. A secondary dysregulation is due to other autoimmune diseases such as rheumatoid arthritis, giant cell arteritis, systemic lupus erythematodes, multiple sclerosis, colitis ulcerosa, or Crohns disease. Patients with a secondary vascular dysregulation normally have a high level of circulating endothelin-1 (ET-1). This increased level of ET-1 leads to a reduction of blood flow both in the choroid and the optic nerve head but has little influence on autoregulation. In contrast, primary vascular dysregulation has little influence on baseline ocular blood flow but interferes with autoregulation. This, in turn, leads to unstable oxygen supply, which seems to be a relevant component in the pathogenesis of glaucomatous optic neuropathy.
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PMID:What is the link between vascular dysregulation and glaucoma? 1799 40

Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are the two primary large-vessel arteritides. Recent advances in cellular immunology have allowed better understanding of pathogenesis of these diseases. In GCA and TA, resident adventitial dendritic cells are activated by unidentified stimuli. This activation induces chemokine synthesis which enhances recruitment of inflammatory cells. T-cells infiltrate the vascular wall and specifically recognize one or a few antigens presented by shared epitopes associated with specific HLA molecules on dendritic cells. Activated T-cells produce IFNgamma stimulating two distinct populations of macrophages. Macrophages located in the intima produce pro-inflammatory cytokines (IL-1, IL-6). Macrophages located in the media differentiate into giant cells and/or produce reactive oxygen species, nitric oxide and matrix metallo-proteinases. Macrophages of the media also produce VEGF, which leads to neovascularization and PDGF, which induces intimal hyperplasia and vascular occlusion. In TA, cytotoxic T cells infiltrate the vascular wall and induce apoptosis of the vascular cells. Better understanding of the pathogenesis of large-vessel arteritis may lead to development of immunosuppressive drugs specifically targeting the immunological mechanisms implicated in GCA and TA.
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PMID:[Pathogenesis of primary large vessel arteritis]. 1880 14

Four patients received hyperbaric oxygen therapy (HBOT): Three patients had nonarteritic central retinal artery occlusion (CRAO); a fourth patient had a CRAO in the right eye (OD) and a branch retinal artery occlusion (BRAO) with macular involvement in the left eye (OS) secondary to giant cell arteritis. The first two patients presented with a one-day history of CRAO, the third patient with a 10-day history of CRAO OD and the fourth patient with a three-week history of CRAO OD and a three-day history of BRAO OS. The initial visual acuities ranged from light perception to counting fingers at 6 feet. The visual acuity and visual field improved in the first two patients with nonarteritic CRAO. Patients 3 and 4 did not improve. There were no complications. Hyperbaric oxygen treatment may be safe and effective in selected patients with nonacute, nonarteritic CRAO.
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PMID:Hyperbaric oxygen treatment of nonacute central retinal artery occlusion. 2011 31


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