Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article has focused on the appropriate indications for lipid-lowering drugs in adult patients with different lipoprotein disorders, which we have divided into primary hypercholesterolemia, combined hyperlipidemia,and hypertriglyceridemia. The mechanism of action, efficacy, and safety profile of the major drugs have been reviewed, and based on this information, we have presented our views on the appropriate drugs of first choice and appropriate second-choice agents for treatment of adult patients with different dyslipidemias. The rationale for the use of hypolipidemic drugs is strongest in patients with hyperlipidemia who concurrently have evidence for coronary or peripheral vascular disease, in whom the goal of secondary prevention is to retard further progression of atherosclerosis and potentially induce some regression, whereas in selected high-risk patients without evidence of atherosclerosis, the goals of therapy are to prevent the premature development of CAD or, in patients with severe hypertriglyceridemia, prevent the adverse sequelae of hepatomegaly, splenomegaly, and potentially pancreatitis. We have focused on the use of hypolipidemic drugs in adult patients, and the guidelines discussed are not appropriate for use in children with hyperlipidemia, in whom drug therapy should be undertaken selectively and in consultation with a lipid specialist. Many areas of controversy in the use of lipid-lowering drugs remain to be addressed by future studies; these include the use of lipid-lowering drugs in patients with secondary causes of hyperlipidemia (e.g., the nephrotic syndrome), the use of lipid-lowering drugs in women, and recommendations for drug therapy in older patients.
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PMID:Drug treatment of dyslipoproteinemia. 828 33

Hyperlipidemia is recognized as one of the major risk factors for the development of coronary artery disease and progression of atherosclerotic lesions. Dietary therapy together with hypolipidemic drugs are central to the management of hyperlipidemia, which aims to prevent atherosclerotic plaque progression, induce regression, and so decrease the risk of acute coronary events in patients with pre-existing coronary or peripheral vascular disease. In patients at high risk of coronary artery disease but without evidence of atherosclerosis, treatment is designed to prevent the premature development of coronary artery disease, whereas in those with hypertriglyceridemia, treatment aims to prevent the development of hepatomegaly, splenomegaly, and pancreatitis. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are the most potent lipid-lowering agents currently available, and their use in the treatment of hyperlipidemia provides the focus for this review. Particular emphasis is given to cerivastatin, a new HMG-CoA reductase inhibitor that combines potent cholesterol-lowering properties with significant triglyceride-reducing effects. Recently completed primary and secondary intervention trials have shown that the significant reductions in low-density lipoprotein (LDL) cholesterol achieved with statins result in significant reductions in morbidity and mortality associated with coronary artery disease as well as reductions in the incidence of stroke and total mortality. Such benefits occur early in the course of statin therapy and have led to suggestions that these drugs may possess antiatherogenic effects over and above their capacity to lower atherogenic lipids and lipoproteins. Experimental studies have also shown statin-induced improvements in endothelial function, decreased platelet thrombus formation, improvements in fibrinolytic activity, and reductions in the frequency of transient myocardial ischemia.
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PMID:Current and future treatment of hyperlipidemia: the role of statins. 973 40

Tangier disease (TD) is an autosomal recessive disorder of lipid metabolism. It is characterized by absence of plasma high-density lipoprotein (HDL) and deposition of cholesteryl esters in the reticulo-endothelial system with splenomegaly and enlargement of tonsils and lymph nodes. Although low HDL cholesterol is associated with an increased risk for coronary artery disease, this condition is not consistently found in TD pedigrees. Metabolic studies in TD patients have revealed a rapid catabolism of HDL and its precursors. In contrast to normal mononuclear phagocytes (MNP), MNP from TD individuals degrade internalized HDL in unusual lysosomes, indicating a defect in cellular lipid metabolism. HDL-mediated cholesterol efflux and intracellular lipid trafficking and turnover are abnormal in TD fibroblasts, which have a reduced in vitro growth rate. The TD locus has been mapped to chromosome 9q31. Here we present evidence that TD is caused by mutations in ABC1, encoding a member of the ATP-binding cassette (ABC) transporter family, located on chromosome 9q22-31. We have analysed five kindreds with TD and identified seven different mutations, including three that are expected to impair the function of the gene product. The identification of ABC1 as the TD locus has implications for the understanding of cellular HDL metabolism and reverse cholesterol transport, and its association with premature cardiovascular disease.
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PMID:The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease. 1043 Dec 27

The role of preoperative stress single-photon emission computed tomographic (SPECT) imaging in patients with end-stage liver disease who underwent liver transplantation is not well established. We reviewed medical records of patients who had liver transplantation at our institution between January 1998 and November 2001. During this time, 339 patients (213 men, aged 51 +/- 11 years) underwent liver transplantation. Of these, 87 patients had preoperative stress SPECT imaging. Diabetes mellitus (30% vs 11%), hypertension (26% vs 12%), and coronary artery disease (15% vs 7%) were more prevalent in those with than without SPECT (p <0.01 each). The stress SPECT perfusion images were normal in 78 patients (91%) and the left ventricular ejection fraction was 72 +/- 10%. SPECT images revealed ascites in 66% and splenomegaly in 83% of patients. There were 35 total deaths (10%) and 5 nonfatal myocardial infarctions over a mean follow-up of 21 +/- 13 months. Most deaths (32 of 35) were noncardiac and sepsis was the most common cause of death. A normal SPECT study had a 99% negative predictive value for perioperative cardiac events. Kaplan-Meier survival curves showed an 87% 2-year cumulative survival rate in the total group. Thus, in patients undergoing liver transplantation, 2-year survival depends on early noncardiac events. A normal stress SPECT study identified patients at a very low risk for early and late cardiac events despite a higher risk profile. SPECT images also revealed unique findings, such as ascites and splenomegaly, which could produce image artifacts and may interfere with accurate image interpretation.
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PMID:Usefulness of preoperative stress perfusion imaging in predicting prognosis after liver transplantation. 1458 57

Type III hyperlipoproteinemia (type III HLP) rarely manifests in childhood. Long-term follow-up (37 years) of the first patient revealed hypothyroidism at diagnosis requiring thyroxine replacement, palmar xanthomas requiring surgical removal, splenomegaly requiring splenectomy, 18 episodes of pancreatitis and premature coronary artery disease. Investigation revealed an apolipoprotein E phenotype of E2/E2 and partial lipoprotein lipase deficiency. Investigation of the second patient revealed a combination of apoE2/E2 phenotype and heterozygous familial hypercholesterolaemia. The third patient had a complete deficiency of lipoprotein lipase activity, an abnormal thyroid stimulating hormone on diagnosis (with subsequent normalisation without treatment), and apoE2/E2 phenotype. Type III HLP is a serious disorder with lifelong consequences of premature vascular disease and recurrent pancreatitis. Early presentation of disease in our patients was associated with additional precipitating factors. Drug treatment of paediatric type III HLP is indicated if dietary modifications alone are insufficient in managing the dyslipidaemia.
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PMID:Case series of type III hyperlipoproteinemia in children. 2269 86

A 50-year-old man was admitted to the hospital with left shoulder and arm discomfort. He had no recent history of change in his energy level, limitations to activity, exertional chest pain, or shortness of breath. He had cardiac risk factors, including a strong family history of pre-mature coronary artery disease and dyslipidemia. He had a syncopal episode in 2003 with a positive troponin I, but had a negative cardiac workup, including cardiac catheterization that showed luminal irregularities and no significant coronary artery disease. An echocardiogram was performed to rule out potential cardiac causes for shoulder pain and showed regional wall motion abnormalities. Follow-up cardiac catheterization revealed left anterior descending artery proximal and mid dissection and a long area of dissection in the first diagonal branch. Laboratory evaluation showed significant platelet elevation and positive JAK2 study. Ultrasound of the abdomen revealed moderate splenomegaly. The enlarged spleen, positive JAK2 study, and persistently elevated platelet count confirmed the diagnosis of essential thrombocythemia. Essential thrombocythemia can predispose individuals to vascular dysfunction and damage, which may contribute to coronary artery dissection. With this case, we propose that essential thrombocythemia should be excluded in the presence of coronary dissection and thrombocytosis.
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PMID:Coronary dissection in a patient with essential thrombocytosis. 2584 33

Sneddon syndrome (SS) is a rare condition and the diagnosis is made only when other more common disease entities have been excluded. Common manifestations in SS patients include hypertension, coronary artery disease, venous thrombosis, miscarriages, psychiatric disturbances, and arterial and venous thrombotic events. Most patients present in their early 30s with classic neurovascular and dermatologic signs. Currently, the main criteria for the diagnosis of SS include livedo racemosa, focal neurological deficits or evidence of stroke on magnetic resonance imaging, or characteristic vascular alterations seen on biopsy. We present the case of a 37-year-old woman with extensive livedo racemosa, chronic migraine headaches, splenomegaly, and lymphadenopathy. Cutaneous biopsies demonstrated a superficial perivascular lymphocytic infiltrate without the subendothelial proliferative changes or fibrosis seen in some patients with SS. The patient's medical history suggested idiopathic livedo racemosa with possible full progression to SS. This case highlights the variability in the clinical presentation of SS and that the disease often can be diagnosed before neurovascular events. Earlier diagnosis can lead to prevention of chronic occlusive neurovascular manifestations and irreversible damage such as myocardial infarction and stroke. Familiarity with the highly variable early course of SS can aid in diagnosis and reduction of morbidity and mortality that is associated with this disease.
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PMID:Idiopathic livedo racemosa presenting with splenomegaly and diffuse lymphadenopathy. 2787 92

Clinical and biochemical manifestations of lecithin-cholesterol acyltransferase (LCAT) deficiency include an abnormal lipid profile (characterized by hypercholesterolemia with markedly decreased high-density lipoprotein cholesterol [HDL-C] and hypertriglyceridemia), corneal opacities, hematologic abnormalities (normochromic anemia of varying intensity), splenomegaly, variable early coronary artery disease and nephropathy (initially proteinuria followed by progressive deterioration of renal function). We presented a patient with nephrotic syndrome, which renal biopsy revealed classic features of LCAT deficiency. To our knowledge, the present case is the first reported case of LCAT deficiency presenting with symptoms related to nephrotic syndrome in a patient with no obvious family history without any corneal deposits and normal HDL-C levels.
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PMID:An unusual presentation of LCAT deficiency as nephrotic syndrome with normal serum HDL-C level. 2850 23