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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 25-year-old man was at first dermatologically suspected as suffering from Weber-Christian syndrome because of subcutaneous panniculitis, but his skin lesions disappeared completely during the course. Hyperlipidemia, disturbances in liver function, and leukemoid reaction became remarkable and he died of subarachnoid hemorrhage eleven months after onset. Necropsy revealed subarachnoid hemorrhage at the base of the brain, lipogranulomatous and inflammatory lesions in the upper lobe of the left lung, a remarkable fatty liver, splenomegaly, pericarditis, and foam cells in the spleen, liver, and bone marrow. A comparison with 57 autopsy cases of Weber-Christian syndrome reported in the literature showed our case to be an exceptional instance of Weber-Christian syndrome, if the present case is not to be regarded as a different disease entity.
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PMID:An unusual case which began with subcutaneous panniculitis followed by fever, severe hepatic involvement and hyperlipidemia. 87 Oct 84

We describe the unique clinical and histopathologic features of a child with biochemical and immunocytochemical features of Niemann-Pick disease type C (NPC). Clinically, she was found to have multiple xanthomas of the upper aerodigestive tract with dysphagia and expressive language delay, splenomegaly, bony infarcts, and type IIb hyperlipidemia. Neurologic examination was otherwise normal. Microscopy revealed foam cells in her bone marrow, liver, tongue, tonsils, glottis, and in normal-appearing peritonsillar mucosa. Lipid analysis of a liver biopsy specimen showed a small increase in phospholipids, a twofold increase in sphingomyelin, a fivefold increase in cholesterol, and a marked (25-fold) increase in bis(monoacylglycerol) phosphate. Lysosomal acid hydrolase activities in cultured skin fibroblasts were nondiagnostic. Biochemical and immunocytochemical studies of cultured fibroblasts demonstrated lysosomal accumulation of unesterified LDL-derived cholesterol as well as delayed induction of homeostatic responses to endogenous cholesterol consistent with a diagnosis of NPC. Based upon these observations, we speculate that this patient could have a new phenotypic expression of NPC or represents a new cholesterol lipidosis biochemically resembling NPC. The chance occurrence of two separate lipid disorders seems less likely.
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PMID:Clinical, pathologic, and biochemical features of a cholesterol lipidosis accompanied by hyperlipidemia and xanthomas. 151 68

We examined 56 French Canadians, aged 1 week to 54 years, from eastern Quebec who were referred to the Laval University Lipid Research Centre and in whom coincidental finding (in 46% of the cases), abdominal pain (in 32%) or family screening (in 22%) led to the diagnosis of primary lipoprotein-lipase-activity deficiency (familial hyperchylomicronemia). Half of the patients had one or more of the following signs: lipemia retinalis, eruptive xanthomas, splenomegaly and hepatomegaly; the plasma triglyceride concentrations were significantly higher (greater than 40 mmol/L) among these patients than among those without clinical signs (mean 21.7 [standard deviation 13.5] mmol/L). The prevalence rate of this disorder was 30 times higher than the previously published rate and was highest in the counties of Charlevoix and Saguenay-Lac-St-Jean (200 and 100 cases per million respectively) because of the distinct demographic history of these areas. Because of a founder effect an autosomal recessive gene involved in lipoprotein-lipase expression or activation has probably been disseminated among this isolated French Canadian population.
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PMID:Primary lipoprotein-lipase-activity deficiency: clinical investigation of a French Canadian population. 291 62

A 35-yr-old man with moderate hypertriglyceridemia, associated with a positive family history for hyperlipidemia, developed chylomicronemia with abdominal pain, muscle pain, and splenomegaly while being treated with cimetidine for a duodenal ulcer. The chylomicronemia and the pain subsided after the drug was stopped. When the patient was rechallenged with the drug 6 mo later, the chylomicronemia reappeared after a treatment period of 6 days. Chylomicronemia and its complications should therefore be considered as a potential risk when cimetidine is prescribed to patients with known hyperlipidemia.
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PMID:Chylomicronemia induced by cimetidine. 401 6

Primary biliary cirrhosis (PBC) is a chronic nonsuppurative, destructive cholangitis, whose etiology is unknown. Morbidity arises early from pruritus and later from hypercholesterolemia with xanthoma formation. Therapy is supportive and directed at the complications of cholestasis. Plasmapheresis has been reported to benefit patients with hyperlipidemia and PBC; thus a pilot study of plasmapheresis utilizing the Haemonetics Model 30 with replacement by albumin and saline was conducted. Five patients (four female and one male) with a mean age of 43 (range 29-58) and a mean duration of illness of 9.5 years (range 6-21) with marked jaundice, xanthomas, xanthelasma, hepatomegaly, fatigability, anorexia, and pruritus, as well as mild nausea were studied. Peripheral neuropathy was present in two patients. Two patients had splenomegaly. Two patients had an associated Sjogren syndrome. All patients had high serum bilirubin, alkaline phosphatase, and cholesterol levels and mild elevations in aspartate amino transferase and alanine amino transferase activities. Immune complexes measured in four patients were present. Antimitochondrial antibody titers were significant in all patients. Patients underwent a mean of 63 plasmapheresis procedures over a mean of 112 weeks removing a mean of 94.7 liters of plasma. No serious toxicity was seen. All patients showed a reduction in pruritus, xanthomas, xanthelasmas, and serum cholesterol values. The two patients who had evidence of Sjogren syndrome noted subjective improvement. All patients who had fatigue, anorexia and nausea also noted moderate improvement. There was no change in hepatomegaly or splenomegaly in patients demonstrating such organomegaly. Liver function did not change significantly. Overall, four patients had improvement in their condition and one patient achieved stability.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The clinical effectiveness and safety of chronic plasmapheresis in patients with primary biliary cirrhosis. 403 Jul 9

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

A 7-year-old previously healthy Czech boy was admitted due to fever, hepatosplenomegaly and pancytopenia. Aspiration of bone marrow revealed no signs of hemoblastosis (nor hemophagocytosis). He was treated with antibiotics and virostatics without effect. Progression of hepatosplenomegaly and pancytopenia induced suspicion of hemophagocytic lymphohistiocytosis (HLH). Five weeks later, bone marrow hemophagocytosis of erythrocytes, nuclear elements and platelets was detected. He was given corticoids and intravenous immunoglobulins and transferred to our haematology department. Laboratory findings of mild pancytopenia, hypofibrinogenaemia, hyperlipidaemia and elevated levels of ferritin, LDH and immunoglobulins were compatible to the diagnosis of HLH. Immunologic evaluation revealed T-lymphocyte activation. Appropriate immunosuppressive treatment with Dexamethasone, etoposide and Cyclosporine A was launched, followed by transient subside of fever and improvement of peripheral blood count, but not regression of hepatosplenomegaly. Four weeks later, relapse of fever and deterioration of blood count led to intensification of immunosuppression. However, no effect was evident. Moreover, hypertrophic cardiomyopathy with ventricular arrhythmia occurred. Treatment with antilymphocytic globulin for resistant course of HLH was planned. Before that, a fifth bone marrow aspiration was performed. Surprisingly, many Leishmania amastigotes were observed within marrow macrophages. Leishmania infection was confirmed by positive serology. Immunosuppressive treatment was withdrawn and changed for causal treatment with liposomal Amphotericin B. Positive clinical effect with subside of fever was evident in ten days, splenomegaly gradually resolved during three weeks, restoration of normal blood count lasted six weeks. No relapses of HLH nor leishmaniasis occurred. In control bone marrow aspirate performed three months later, the parasites were not detected. Ten months after the event, the patient is in complete remission of HLH with normal immunologic parameters. Most probably, he contracted visceral leishmaniasis during a visit of a Neapol area in Italy 3 months before the onset of the disease.
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PMID:[Hemophagocytic lymphohistiocytosis as a manifestation of visceral leishmaniasis]. 1242 69

The Philadelphia chromosome-negative chronic myeloproliferative disorders (CMPD), polycythemia vera (PV), essential thrombocythemia (ET) and chronic idiopathic myelofibrosis (IMF), have overlapping clinical features but exhibit different natural histories and different therapeutic requirements. Phenotypic mimicry amongst these disorders and between them and nonclonal hematopoietic disorders, lack of clonal diagnostic markers, lack of understanding of their molecular basis and paucity of controlled, prospective therapeutic trials have made the diagnosis and management of PV, ET and IMF difficult. In Section I, Dr. Jerry Spivak introduces current clinical controversies involving the CMPD, in particular the diagnostic challenges. Two new molecular assays may prove useful in the diagnosis and classification of CMPD. In 2000, the overexpression in PV granulocytes of the mRNA for the neutrophil antigen NBI/CD177, a member of the uPAR/Ly6/CD59 family of plasma membrane proteins, was documented. Overexpression of PRV-1 mRNA appeared to be specific for PV since it was not observed in secondary erythrocytosis. At this time, it appears that overexpression of granulocyte PRV-1 in the presence of an elevated red cell mass supports a diagnosis of PV; absence of PRV-1 expression, however, should not be grounds for excluding PV as a diagnostic possibility. Impaired expression of Mpl, the receptor for thrombopoietin, in platelets and megakaryocytes has been first described in PV, but it has also been observed in some patients with ET and IMF. The biologic basis appears to be either alternative splicing of Mpl mRNA or a single nucleotide polymorphism, both of which involve Mpl exon 2 and both of which lead to impaired posttranslational glycosylation and a dominant negative effect on normal Mpl expression. To date, no Mpl DNA structural abnormality or mutation has been identified in PV, ET or IMF. In Section II, Dr. Tiziano Barbui reviews the best clinical evidence for treatment strategy design in PV and ET. Current recommendations for cytoreductive therapy in PV are still largely similar to those at the end of the PVSG era. Phlebotomy to reduce the red cell mass and keep it at a safe level (hematocrit < 45%) remains the cornerstone of treatment. Venesection is an effective and safe therapy and previous concerns about potential side effects, including severe iron deficiency and an increased tendency to thrombosis or myelofibrosis, were erroneous. Many patients require no other therapy for many years. For others, however, poor compliance to phlebotomy or progressive myeloproliferation, as indicated by increasing splenomegaly or very high leukocyte or platelet counts, may call for the introduction of cytoreductive drugs. In ET, the therapeutic trade-off between reducing thrombotic events and increasing the risk of leukemia with the use of cytoreductive drugs should be approached by patient risk stratification. Thrombotic deaths seem very rare in low-risk ET subjects and there are no data indicating that fatalities can be prevented by starting cytoreductive drugs early. Therefore, withholding chemotherapy might be justifiable in young, asymptomatic ET patients with a platelet count below 1500000/mm(3) and with no additional risk factors for thrombosis. If cardiovascular risk factors together with ET are identified (smoking, obesity, hypertension, hyperlipidemia) it is wise to consider platelet-lowering agents on an individual basis. In Section III, Dr. Gianni Tognoni discusses the role of aspirin therapy in PV based on the recently completed European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) Study, a multi-country, multicenter project aimed at describing the natural history of PV as well as the efficacy of low-dose aspirin. Aspirin treatment lowered the risk of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke (relative risk 0.41 [95% CI 0.15-1.15], P =.0912). Total and cardiovascular mortality were also reduced by 46% and 59%, respectively. Major bleedings were slightly increased nonsignificnsignificantly by aspirin (relative risk 1.62, 95% CI 0.27-9.71). In Section IV, Dr. Giovanni Barosi reviews our current understanding of the pathophysiology of IMF and, in particular, the contributions of anomalous megakaryocyte proliferation, neoangiogenesis and abnormal CD34(+) stem cell trafficking to disease pathogenesis. The role of newer therapies, such as low-conditioning stem cell transplantation and thalidomide, is discussed in the context of a general treatment strategy for IMF. The results of a Phase II trial of low-dose thalidomide as a single agent in 63 patients with myelofibrosis with meloid metaplasia (MMM) using a dose-escalation design and an overall low dose of the drug (The European Collaboration on MMM) will be presented. Considering only patients who completed 4 weeks of treatment, 31% had a response: this was mostly due to a beneficial effect of thalidomide on patients with transfusion dependent anemia, 39% of whom abolished transfusions, patients with moderate to severe thrombocytopenia, 28% of whom increased their platelet count by more than 50 x 10(9)/L, and patients with the largest splenomegalies, 42% of whom reduced spleen size of more than 2 cm.
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PMID:Chronic myeloproliferative disorders. 1463 83

Non-alcoholic steatohepatitis (NASH) is one of the most common liver disorders. This is highly prevalent in obese and diabetic subjects. Persons with central obesity are at particular risk. Other clinical predictors are age more than 40-50 years and hyperlipidemias, but none of these factors is invariable for causation of NASH. Other reported associations are, celiac disease, Wilson's Disease and few other metabolic diseases. Drugs, particularly amiodarone, tamoxifen, nucleoside analogues and methotrxate have also been linked to NASH. The disease is evenly distributed in both sexes but advanced disease is more common in women. Ethnic variation exists and African Americans are less affected than Hispanic Americans. Specific clinical features of NASH are infrequent. Patients usually come to clinical attention by elevated liver enzymes found on routine evaluation but on history, about two third of patients will admit to have mild fatigue and about half will report right upper quadrant pain. Rarely, patient may present with a complication of cirrhosis. Physical examination may reveal hepatomegaly and splenomegaly. Research in last few years has stressed that development of steatosis, stetohepatitis, fibrosis with subsequent cirrhosis are most probably the result of insulin resistance. Therefore, clinical features may reflect existence of insulin resistance. Obesity, particularly central obesity is most important of these. Patients may have sleep apnea syndrome. Hypertension and manifestations of diabetes mellitus like polyuria, polydypsia, and neurological deficits may occur. Patients may have varying combination of obesity, diabetes, hyperlipidemia, hypertension and impaired fibrinolysis (syndrome X). Children with insulin resistance may show acanthosis nigricance. Patients with polycystic ovary syndrome, which consists of insulin resistance, diabetes, obesity, hirsutism, oligo or polymenorrha and hyperlipidemia may have NASH. Other rare manifestations of insulin resistance, which can be seen in patients of NASH are lipomatosis, lipoatrophy/lipodystrophy and panniculitis. Most other rare conditions known to cause NASH like peroxisomal diseases, mitochondialpathies, Weber-Christian disease, Mauriac syndrome, Madelung's lipomatosis and abetaliopprotenemia also have insulin resistance. This is believed that primary defect underlying insulin resistance is impairment in postreceptor pathways (through tyrosine kinase activity) of insulin action. Primary defect in insulin receptors appear uncommon. This results in down regulation of insulin receptor substance 1 (IRS-1) signaling by excess free fatty acids. In muscle, activated IRS-1 promotes translocation of glucose transporter protein 4 (GLUT4) to cell membrane. As a result, monocyte glucose uptake by GLUT4 increases glucose disposal from blood and reduced need for insulin. PKC-0 is a likely candidate as serine kinase in muscle regulated by fatty acids that can impair the activation of IRS-1. Insulin resistance is usually evaluated by fasting insulin levels, Quantitative Insulin Check Index (QUICKI) and Homeostasis Model Assessment of Insulin Resistance (HOMA), C-peptid/insulin ratio oral glucose tolerance test and hyper insulinemic euglycemic clamp. The clamp technique is considered the gold standard.
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PMID:Insulin resistance and clinical aspects of non-alcoholic steatohepatitis (NASH). 1619 20


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