Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial erythrophagocytic lymphohistiocytosis, a rare disorder affecting infants, is characterized by a visceral infiltration of histiocytes and lymphocytes resulting in rapid death. It has recently been reported that use of epipodophyllotoxin, VP 16-213, could induce a complete remission of the disease. Such treatment does not, however, prevent fatal CNS relapse. Four patients with the characteristic features of the disease--fever, hepatosplenomegaly, pancytopenia, low plasmatic fibrinogen level, hyperlipidemia, and histiocytic meningitis--are described. These patients were treated with a combination therapy including systemic administration of VP 16-213, steroids, and intrathecal methotrexate followed by cranial irradiation after the age of 12 months. The four patients achieved complete remission of the disease after clearing of the CNS localization. Two patients had secondary relapses, but all four patients have had a disease-free survival exceeding 12 months. All patients have been in remission of the disease for 27, 20, 16, and 13 months, respectively, after disease onset without major setbacks from the treatment. This combination therapy appears to be a promising approach toward long-term remission of the disease.
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PMID:Treatment of four patients with erythrophagocytic lymphohistiocytosis by a combination of epipodophyllotoxin, steroids, intrathecal methotrexate, and cranial irradiation. 383 78

Clinical course and histopathologic features of a typical case of familial hemophagocytic lymphohistiocytosis (FHLH) are presented. FHLH, initially known as familial hemophagocytic reticulosis (FHR), is rare and without proper treatment is invariably rapidly fatal, usually accompanied by fever, anorexia, vomiting, irritability and pallor. Sporadic examples with prolonged survival have been reported. Other significant findings include hepatosplenomegaly, progressive anemia, leukopenia, thrombocytopenia, hyperlipidemia and hypofibrinogenemia. Varying degrees of hemophagocytosis by widely disseminated histiocytes in different organs and structures is one hallmark of the disease. Hemophagocytosis may also occur in viral and bacterial infections and in certain malignant processes. Very high parental consanguinity in FHLH was mentioned in two relatively recent reports. A probable immunologic defect has been the focus of recent investigations. The genetic defect is believed to be transmitted as an autosomal recessive trait.
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PMID:Familial hemophagocytic lymphohistiocytosis (FHLH). 909 88

Two substrains of the fawn-hooded (FH) rat have been developed, one of which develops progressive hypertension and proteinuria, the FHH, and one which shows little increase in blood pressure and no renal damage, the FHL. Other hypertensive rodent models show primary metabolic disturbances before the development of renal damage, notably hypertriglyceridemia, which may also contribute to progression of renal disease. In this study we evaluated whether hyperlipidemia is a primary disturbance in FHH, or only occurs secondary to proteinuria. Lipid levels were determined before and after development of proteinuria, and compared to those found in age-matched FHL. We also determined whether reducing proteinuria with lisinopril would normalize lipid levels in aging FHH. At 4 weeks of age, proteinuria was very low (2-3 mg/day) in both FHH and FHL. While proteinuria increased steadily in aging FHH, reaching 350 +/- 62 mg/day at 40 weeks, much less increase was observed in FHL over the same period (32 +/- 5 mg/day at 40 weeks). Blood pressure was markedly higher in adult FHH than in FHL (158 +/- 2 vs. 129 +/- 2 mm Hg, p < 0.01). In 4-week-old FHL and FHH, plasma cholesterol levels were similar. Subsequently, cholesterol increased in FHH, reaching 3.4 +/- 0.9 mmol/l at 40 weeks, whereas cholesterol was barely affected by aging in FHL (2.1 +/- 0.2 mmol/l at 40 weeks). At 4 weeks, triglyceride levels were lowest in FHH. Subsequently, triglycerides increased in FHH, reaching 3.5 +/- 1.5 mmol/l at 40 weeks, as compared to 1.3 +/- 0.2 mmol/l in FHL. Besides a transient increase in triglyerides in lisinopril-treated FHH at 11 weeks, increments in blood pressure, proteinuria, cholesterol, triglycerides and apolipoproteins A-I, B and E aging FHH were effectively prevented by lisinopril. These data strongly suggest that there is no primary difference in lipid metabolism between FHH and FHL and that changes in plasma lipids in FHH as compared to FHL are all secondary to proteinuria.
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PMID:Hyperlipidemia is secondary to proteinuria and is completely normalized by angiotensin-converting enzyme inhibition in hypertensive fawn-hooded rats. 937 31

To investigate the relationship among lipids, coagulation and thrombosis in the absence of atherosclerosis, spontaneous or dietary-induced hyperlipidemic (FHL) rats were studied. FHL showed higher levels of coagulation factors VII, IX, X, VIII and XII and a shortening of the occlusion time (OT) of an artificial arterial prosthesis as compared with normolipidemic (FNL) animals. Damage of abdominal aorta of FHL was followed by increased fibrin deposition in the vascular intima as compared to FNL. After 5 months of cholesterol-rich diet FNL showed increased cholesterol, triglycerides and factor II, VII, IX, X, XII levels. A significant shortening of the OT and increased fibrin deposition was also observed. Two-month diet withdrawal restored the initial condition. Warfarin treatment, at a dose decreasing vitamin K-dependent factor to levels found in FNL, prolonged the OT and reduced fibrin deposition, without modifying F XII or changing lipid profile. An increase in the activated form of F VII was observed. In contrast, no difference was found in F VII clearance. High lipid levels favour the process of thrombus formation by increasing the activation of vitamin K-dependent coagulation factors. Low-dose warfarin treatment reverts the prothrombotic effect of hyperlipidemia.
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PMID:Experimental arterial thrombosis in genetically or diet induced hyperlipidemia in rats--role of vitamin K-dependent clotting factors and prevention by low-intensity oral anticoagulation. 1177 12

We describe four classical cases of familial hemophagocytic lymphohistiocytosis (FHL), a macrophage-related, autosomal recessive fatal disorder. Parental consanguinity was present in three cases. All patients presented with fever, neurological involvement of varying degrees, hepatosplenomegaly, cytopenias, deranged liver function tests, and coagulogram, hypofibrinogenemia (three cases), and hyperlipidemia (one case). An antemortem diagnosis could not be made, although it was suspected in one case. Necropsy (done in three cases and postmortem liver biopsy in one case) revealed classical features of FHL. Florid lymphohistiocytic infiltrate exhibiting hemophagocytosis was seen in the bone marrow, liver, spleen, lymph nodes and brain (examined in two case). In addition to this, focal infiltrates were seen in the kidneys, lung, pancreas, testes, adrenals, and skin. Marked lymphoid depletion was seen in one case in the lymph nodes and spleen.
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PMID:Familial hemophagocytic lymphohistiocytosis: an autopsy study. 1274 74