Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 7-year-old black boy with sickle cell disease, Wolff-Parkinson-White syndrome, mild left ventricular dysfunction, and normal coronary arteries developed angina pectoris five months after cessation of hypertransfusion therapy. Exercise-induced ECG ST segment depression associated with angina disappeared following transfusion therapy.
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PMID:Angina pectoris in a child with sickle cell anemia. 67 56

Ticlopidine inhibits platelet aggregation induced by adenosine diphosphate (ADP) and most other platelet agonists in ex vivo studies of human platelets. The drug also improves other abnormalities of platelet function seen in patients with cerebrovascular disease, peripheral arterial disease, ischaemic heart disease or other conditions involving platelet hyperaggregation. Abnormal platelet activity has been implicated in a variety of clinical conditions in which patients are at high risk of thromboembolic events, and thus the effectiveness of ticlopidine has been investigated in such patients. Since the initial review of the drug appeared in the Journal, data from several large multicentre studies have shown that ticlopidine has a substantial benefit to offer patients who have experienced transient ischaemic attacks or stroke, and in those with peripheral arterial disease or ischaemic heart disease. Ticlopidine reduces the incidence of further stroke, myocardial infarction or vascular death, and is superior to placebo and aspirin in this regard in studies of patients with recent stroke or transient ischaemic attacks, or intermittent claudication. Ticlopidine is equally effective in both men and women and also improves symptoms of claudication in patients with peripheral arterial disease, and appears to reduce anginal pain. Patients with subarachnoid haemorrhage and sickle cell disease have shown some improvement with ticlopidine administration. The drug reduces thromboembolic events and re-stenosis in patients undergoing haemodialysis and cardiac surgery, and appears to prevent the progression of nonproliferative diabetic retinopathy. Ticlopidine in large clinical trials is associated with a higher incidence of adverse effects than placebo and an overall incidence similar to aspirin. Most adverse effects do not require withdrawal of treatment. Gastrointestinal symptoms (particularly diarrhoea) are most common, occurring almost twice as frequently with ticlopidine as with aspirin. Other adverse effects associated with ticlopidine include skin rash, haemorrhagic disorders, and haematological effects; these latter effects require careful monitoring of patients during the initial weeks of therapy. In conclusion, ticlopidine is a valuable addition to the prophylactic treatments available for the management of patients with cerebrovascular disease, peripheral arterial disease or ischaemic heart disease, who present a high risk of thromboembolic events. Although tolerability may be a problem for some patients, the overall benefit conferred by the drug would appear to outweigh this potential disadvantage. Because of its antiplatelet activity, ticlopidine has a promising role in other disorders mediated by platelet dysfunction. However, the precise role of the drug in these additional therapeutic indications awaits clarification with wider clinical experience.
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PMID:Ticlopidine. An updated review of its pharmacology and therapeutic use in platelet-dependent disorders. 222 15

Ticlopidine is an inhibitor of platelet action that has been used in the treatment of a variety of disease states in which platelets play a prominent role. Studies in animals and man have demonstrated that ticlopidine is a potent inhibitor of platelet aggregation induced by adenosine diphosphate (ADP), and variably inhibits aggregation due to collagen, adrenaline (epinephrine), arachidonic acid, thrombin, and platelet activating factor. Inhibition of platelet aggregation is both dose- and time-related, with its onset of activity being 24 to 48 hours, its maximal activity occurring after 3 to 5 days, and its activity still being present 72 hours after a final dose. Ticlopidine also inhibits the release reaction of platelets, prolongs bleeding time, reduces plasma levels of platelet factor 4 and beta-thromboglobulin in patients in whom these proteins are elevated, and may also inhibit platelet adhesion, increase red cell filtrability and decrease whole blood viscosity. In a large number of animal models, ticlopidine markedly inhibits thrombus formation or graft occlusion. Ticlopidine is well absorbed after oral administration. It is extensively metabolised and at least one of its metabolites is pharmacologically active. Therapeutic trials in patients with chronic arterial occlusion due to thrombangitis obliterans or arteriosclerosis obliterans, post-myocardial infarction, cerebrovascular thromboembolic disease, subarachnoid haemorrhage, vascular shunts or fistulas for haemodialysis, and sickle cell disease have shown promise for the use of ticlopidine. However, trials of patients with intermittent claudication, angina pectoris, diabetes mellitus with microvascular disease, aortocoronary bypass grafts, and vascular prostheses have had conflicting results or have shown an unfavourable side effect profile. Further studies are clearly required to establish the role of ticlopidine in many of these areas, some of which are already in progress. Overall, side effects occur in 10 to 15% of patients receiving ticlopidine. The most common side effects are gastrointestinal disturbances and skin rashes. Neither of these necessarily require discontinuation of therapy in most patients. Agranulocytosis, thrombocytopenia, and cholestatic jaundice have also been reported. Bleeding is infrequent except possibly in patients receiving ticlopidine prior to some surgical procedures.
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PMID:Ticlopidine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in platelet-dependent disease states. 330 67

Advanced renal failure occurred in nine adult sickle cell disease patients. There were six men and three women with a mean age of 38.6 years. Eight patients had homozygous SS disease, one had sickle cell thalassemia. Three patients had acute renal failure from which they partially recovered. Six developed endstage kidney disease requiring dialysis. Two of these received a kidney transplant, and there was one death in the immediate postoperative period. Angina pectoris, hyperkalemia, and severe anemia complicated chronic dialysis, suggesting that early transplantation should be considered for sickle cell anemia patients with renal failure.
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PMID:Advanced renal failure in patients with sickle cell anemia: clinical course and prognosis. 675 51

Angina, the prototypic vasoocclusive pain, is a radiating chest pain that occurs when heart muscle gets insufficient blood because of coronary artery disease. Other examples of vasoocclusive pain include the acute pain of heart attack and the intermittent pains that accompany sickle cell anemia and peripheral artery disease. All these conditions cause ischemia - insufficient oxygen delivery for local metabolic demand - and this releases lactic acid as cells switch to anaerobic metabolism. Recent discoveries demonstrate that sensory neurons innervating the heart are richly endowed with an ion channel that is opened by, and perfectly tuned for, the lactic acid released by muscle ischemia.
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PMID:ASIC3: a lactic acid sensor for cardiac pain. 1280 43

Ischaemic complications are common in SS homozygotic sickle cell disease in children, but the heart does not appear to be the target organ. The early detection of myocardial ischaemic in these children could prevent cardiac complications. The authors undertook a study of myocardial perfusion by myocardial scintigraphy in children with sickle cell disease. Twenty-three patients (average age 12 +/- 5 years) underwent Thallium 201 myocardial scintigraphy. Exercise on a bicycle ergometer and/or intravenous injection of dipyridamole were carried out depending on the age. The images (on exercise and late recovery period) were analysed in the 3 standard projections of the left ventricle: short axis, long axis and 4-chamber view. The left ventricular ejection fraction was measured by gamma angiography. Myocardial perfusion was abnormal in 14 patients (61%). The perfusion defects were reversible in the late recovery period in 9 patients and irreversible in 5 patients. The average left ventricular ejection fraction was 63 +/- 9%. Its value was not related to symptoms, haemoglobin level or the results of myocardial scintigraphy. Four patients with perfusion defects were symptomatic (cardiac failure, angina or ventricular tachycardia); 1 patient died and 3 were treated with hydroxyurea. Myocardial scintigraphy was carried out 6 months later and showed improved perfusion in 3 patients. Abnormalities of myocardial perfusion are therefore common in sickle cell disease. Often asymptomatic in childhood, there is a real risk of ischaemic cardiomyopathy and its complications in adulthood. Specific treatment of sickle cell disease with hydroxyurea should be considered in cases with significant abnormalities of myocardial perfusion.
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PMID:[Abnormalities of myocardial perfusion in sickle cell disease in childhood: a study of myocardial scintigraphy]. 1283 42

The definition of myocardial ischemia as a clinical entity of thrombotic etiology was established in 1912 by James Herrick. His proposal was based on the work of William Heberden, who in 1772 defined the clinical profile of angina pectoris, and the observations of Edward Jenner about a century later on intracoronary thrombosis in patients who had died with such symptoms. On the basis of these results, Jenner and Caleb Parry proposed that the main cause of angina were alterations in the coronary arteries, while Marshall Hall, in 1842, attributed sudden death in these patients to interruption of the coronary circulation. The discovery of a common cause for angina pectoris and myocardial infarction, inducing a reduction or interruption of oxygen supply to myocardial tissue, the atherosclerotic etiology of intracoronary lesions, and the importance of plaque fissuring in the sudden formation of intracoronary thrombi, were successive milestones in our understanding in the 20th century, the culmination of the process of meticulous observation begun many years before.
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PMID:Ischemic myocardial disease as an example of a thrombotic event. A historical note. 1691 Jan 61

In this PhD thesis, we report that VF is still a common complication of STEMI, with an incidence of 11.6% in the population of Danish STEMI patients who survive to reach the hospital. In this STEMI population, we identified several risk factors associated with VF independent of MI. We identified and confirmed findings from several previous studies and found several risk factors, such as younger age, a family history of sudden death, a TIMI flow grade of 0, the absence of angina, anterior infarction (i.e., VF before PPCI), and inferior infarction (i.e., VF during PPCI) that were associated with VF in a Danish cohort. Furthermore, a history of atrial fibrillation and alcohol intake were identified as novel risk factors for VF. To the best of our knowledge, this study contains data on the largest VF cohort with the longest reported follow-up published; we found that VF mortality is significantly higher within the first 30 days for patients who experience VF before and during PPCI compared with STEMI patients without VF. However, the long-term mortality rates of the three groups are the same. Importantly, our results contradict the previous understanding that VF during PPCI is "benign"; the mortality rate within the first 30 days was as high for patients with VF during PPCI as the mortality rate of patients with VF before PPCI. Finally, although it is difficult to draw clinical implications from a descriptive study, due to the comprehensiveness of Danish death certificates, we reported a high incidence of cardiac symptoms and contact with healthcare professionals based on cardiac symptoms in young SCD patients who died due to CAD, although death was not avoided.
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PMID:Ventricular fibrillation and sudden cardiac death during myocardial infarction. 2712 21

Adenosine receptors (ARs) function in the body's response to conditions of pathology and stress associated with a functional imbalance, such as in the supply and demand of energy/oxygen/nutrients. Extracellular adenosine concentrations vary widely to raise or lower the basal activation of four subtypes of ARs. Endogenous adenosine can correct an energy imbalance during hypoxia and other stress, for example, by slowing the heart rate by A1AR activation or increasing the blood supply to heart muscle by the A2AAR. Moreover, exogenous AR agonists, antagonists, or allosteric modulators can be applied for therapeutic benefit, and medicinal chemists working toward that goal have reported thousands of such agents. Thus, numerous clinical trials have ensued, using promising agents to modulate adenosinergic signaling, most of which have not succeeded. Currently, short-acting, parenteral agonists, adenosine and Regadenoson, are the only AR agonists approved for human use. However, new concepts and compounds are currently being developed and applied toward preclinical and clinical evaluation, and initial results are encouraging. This review focuses on key compounds as AR agonists and positive allosteric modulators (PAMs) for disease treatment or diagnosis. AR agonists for treating inflammation, pain, cancer, non-alcoholic steatohepatitis, angina, sickle cell disease, ischemic conditions and diabetes have been under development. Multiple clinical trials with two A3AR agonists are ongoing.
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PMID:Historical and Current Adenosine Receptor Agonists in Preclinical and Clinical Development. 3098 76