Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Beraprost sodium (BPS) is an orally stable analogue of prostacyclin that inhibits adenylate-cyclase-dependent platelet aggregation and is proposed for treatment of chronic arterial occlusion. To determine the duration and intensity of platelet antiaggregation with BPS, 12 healthy, nonsmoking, male white volunteers participated in a double-blind, dose-escalating design with randomized placebo, placebo-controlled, cross-over study. After overnight fasting, single (20, 40, 60 micrograms and placebo) and repeated [20, 40, 60 micrograms and placebo) and repeated [20, 40, 60 micrograms and placebo three times daily (t.i.d.) for 3 days] oral doses of BPS were administered. Mean percentage of inhibition of ADP-induced aggregation normalized to placebo was measured for 8 h after drug administration and related to plasma concentrations (Cp) of the active enantiomer (APS 314d). BPS 40 and 60 micrograms decreased platelet aggregation 1 h after single doses, and 0.5 h and 1 h after repeated doses. BPS 20 micrograms had no significant effect. APS 314d pharmacokinetics was linear, and its terminal half-life (t 1/2) ranged from 0.50 +/- 0.21 to 0.91 +/- 0.27 h (mean +/- SD) independently of BPS dose. Antiaggregating effects were poorly related to Cp of APS 314d (r2 < or = 0.2). Some subjects complained of moderate postdrug absorption headaches (7 of 12 after single and 8 of 12 after repeated doses) and flushes (6 of 12 and 7 of 12, respectively). These data indicate that orally active prostacyclin BPS (40 or 60 micrograms) exerts its maximal antiaggregating effects between 0.5 and 1 h.
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PMID:Pharmacokinetics and platelet antiaggregating effects of beraprost, an oral stable prostacyclin analogue, in healthy volunteers. 750 23

The antiphospholipid syndrome (APS, Hughes' syndrome), first described in 1983, is a prothrombotic disease in which neurological events feature prominently. Strokes, transient ischaemic attacks, and headaches (including migraine) are important complications. However, it is clear that other neurological symptoms, including diplopia, memory loss, ataxia, and "multiple sclerosis-like" features are common. A notable feature of Hughes' syndrome is the clinical response to anticoagulants; features such as headache and memory loss often improving dramatically with appropriate warfarin dosage. APS may well become recognised as an important (and potentially treatable) cause of neurological disease.
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PMID:Migraine, memory loss, and "multiple sclerosis ". Neurological features of the antiphospholipid (Hughes') syndrome. 1367 70

The importance of cerebral disease in patients with the Hughes syndrome is now becoming more widely recognized. The range of neuropsychiatric manifestations of APS is comprehensive, and includes focal symptoms attributable to lesions in a specific area of the brain as well as diffuse or global dysfunction. Patients with APS frequently present with strokes and TIA, but a wide spectrum of other neurologic features-also including non thrombotic neurologic syndromes-has been described in association with the presence of aPL. The recognition of APS has had a profound impact on the understanding and management of the treatment of CNS manifestations associated with connective tissue diseases, in particular, SLE. Many patients with focal neurologic manifestations and aPL, who a few years ago would have received high-dose corticosteroids or immunosuppression, are often successfully treated with anticoagulation. In our opinion, testing for aPL may have a major diagnostic and therapeutic impact not only in patients with autoimmune diseases and neuropsychiatric manifestations, but also in young individuals who develop cerebral ischemia, in those with atypical multiple sclerosis, transverse myelitis, and atypical seizures. We would also recommend testing for aPL for young individuals found with multiple hyperintensity lesions on brain MRI in the absence of other possible causes,especially when under the age of 40 years. It is our practice to anticoagulate patients with aPL suffering from cerebral ischemia with a target INR of 3.0 to prevent recurrences. Low-dose aspirin alone (with occasional exceptions)does not seem helpful to prevent recurrent thrombosis in these patients. Our recommendation, once the patient has had a proven thrombosis associated with aPL, is long-term (possibly life-long) warfarin therapy. Oral anti coagulation carries a risk of hemorrhage, but in our experience the risk of serious bleeding in patients with APS and previous thrombosis treated with oral anticoagulation to a target INR of 3.5 was similar to that in groups of patients treated with lower target ratios. Although a double-blind crossover trial comparing low molecular weight heparin with placebo in patients with aPL and chronic headaches did not show a significant difference in the beneficial effect of low molecular weight heparin versus placebo, in our experience selected patients with aPL and neuropsychiatric manifestations such as seizures, severe cognitive dys-function, and intractable headaches unresponsive to conventional treatment may respond to anticoagulant treatment. The neurologic ramifications of Hughes syndrome are extensive, and it behoves clinicians in all specialties to be aware of this syndrome because treatment with anticoagulation may profoundly change the outlook for these patients.
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PMID:Cerebral manifestations in the antiphospholipid (Hughes) syndrome. 1688 79

Autoimmune polyendocrine syndrome type II (APS-II) is the most common immunoendocrinopathy syndrome. APS-II is defined by the development of two or more of the following entities: primary adrenal insufficiency (Addison's disease), Graves' disease, type 1A diabetes mellitus, autoimmune thyroiditis, primary hypogonadism, celiac disease, and myasthenia gravis. Other frequent clinical findings are vitiligo, alopecia, pernicious anemia and/or serositis. Primary adrenal insufficiency in these patients affects the adrenal cortex, which is destroyed by autoantibodies against 21-hydroxylase. Unlike other causes of adrenal insufficiency (infectious diseases, infiltrative diseases, bleeding, tumors), the adrenal medulla is not involved. Pheochromocytomas are tumors arising from the chromaffin cells of the sympathetic nervous system in the adrenal medulla. The clinical symptoms of these tumors vary from isolated hypertension or hypertension accompanied by paroxysmal episodes -including the classical triad of headache, palpitations and diaphoresis-to potentially serious manifestations such as acute pulmonary edema, arrhythmias and sudden death. Nevertheless, up to 40% of affected patients are asymptomatic. We present the case of a patient diagnosed with APS-II who developed a pheochromocytoma. In this patient, the adrenal gland cortex was atrophied and the tumor was attached to the adrenal medulla. This coexistence of endocrinopathies, with no etiologic connection, is a surprising finding, which has not previously been described in the current literature.
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PMID:An unusual association: pheochromocytoma on an atrophied adrenal gland due to addison's disease. 2298 Apr 66

Systemic vasculitides (SVs) is a group of diseases characterised by inflammation/necrosis of the blood vessel wall in various organs. Simultaneous brain and heart involvement is a cause of increased morbidity/mortality in SV. We aimed to present evidence of concurrent brain/heart involvement in SV and the role of a combined brain/heart magnetic resonance imaging (MRI) in their risk stratification. Cerebral vasculitis (CV) can be presented as focal deficits, seizures, headache, neuropsychiatric manifestations or cognitive dysfunction and cardiovascular disease (CVD) as myocardial/vascular inflammation, perfusion/function defects and fibrosis. MRI is a non-invasive, non-radiating technique that allows the reliable identification of intraparenchymal brain lesions and the detection of myocardial/vascular inflammation and fibrosis. However, its use in SV is currently hampered by high cost, lack of availability/expertise and lack of awareness among the clinicians. Although there are no clinical data supporting the combined use of brain/heart MRI in asymptomatic SV, it would be called for in cases with clinical suspicion of brain/heart involvement, especially in those at high risk for CVD/stroke such as SLE/APS. Furthermore, it may be of value in SV with multi-organ involvement, cognitive dysfunction or other neuropsychiatric symptoms with concurrent cardiac involvement, presenting as typical or atypical symptoms with normal routine cardiac evaluation, new onset of arrhythmia and/or HF.
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PMID:Combined brain and heart magnetic resonance imaging in systemic vasculitides: fiction or real need? 2965 61