1/99. Angiographic and pathological studies on regression of coronary atherosclerosis of FH patients who received LDL-apheresis treatment.We report on the most recent data confirming the angiographic and pathological efficacy of LDL-apheresis for coronary atherosclerosis of a familial hypercholesterolemia (FH) patient using collected data of a large number of cases and especially of one autopsy case. Changes in coronary artery stenosis have been assessed angiographically in 37 FH patients in the LDL-Apheresis Regression Study (LARS) group of 13 institutions in japan. Definite regression was observed in 21 segments by visual and computer analysis. Fourteen of 37 patients (37.8%) who had received LDL-apheresis treatment in combination with cholesterol-lowering drugs had at least one regressed segment without any progressed segment. We pathologically examined at autopsy the coronary arteries in one FH patient who had received long-term LDL-apheresis therapy before death. The results revealed the process of scarring of atheromatous plaque, suggesting pathological regression correlated with the angiographic regression shown in serial angiograms taken during LDL-apheresis treatment. It was further suggested that the formation of an eccentric thickened wall lesion rich in collagen fiber prevented atheromatous plaque from tearing off. Such tearing off might lead to an acute coronary event. Aggressive cholesterol-lowering therapy based on LDL-apheresis can induce both angiographic and pathological regression in coronary atherosclerosis of FH patients.- - - - - - - - - - ranking = 1keywords = coronary (Clic here for more details about this article) |
2/99. Case study: analysis of an acute anterior-lateral myocardial infarction in a 16-year-old patient with familial hypercholesterolemia.This article presents a case study of a 16-year-old male patient with a significant family history for hypercholesterolemia and coronary artery disease, who suffered an anterior lateral myocardial infarction. On admission, his electrocardiograms revealed the classic pattern of an anterior lateral acute myocardial infarction plus a left anterior hemiblock. His cholesterol level was 750 mg/dL, and his low-density lipoprotein was 650 mg/dL. He underwent a cardiac catheterization that revealed an occluded left anterior descending artery requiring a percutaneous transluminal angioplasty and three coronary stents. The 12-lead electrocardiograms on admission and before discharge are analyzed. This article discusses the electrocardiogram characteristics of anterior lateral wall myocardial infarction coupled with a left anterior hemiblock.- - - - - - - - - - ranking = 0.22222222222222keywords = coronary (Clic here for more details about this article) |
3/99. LDL-apheresis: clinical experience and indications in the treatment of severe hypercholesterolemia.LDL-cholesterol is the leading risk factor which influences the clinical outcome of patients with preexisting coronary heart disease. Clinical trials show that plasma LDL-cholesterol below 100 mg/dL decrease the rate of recurrent myocardial infarction and can induce regression in patients with coronary heart disease. However, in most cases of severe hypercholesterolemia with plasma LDL-cholesterol concentrations above 220 mg/dL LDL cannot be sufficiently decreased by maximal dietary and pharmacological therapy alone. Today this group of high risk CHD patients can be treated in addition with an extracorporeal procedure to eliminate LDL from the plasma circulation, the H.E.L.P.--LDL-apheresis. This method for selective removal of LDL, lipoprotein(a) and fibrinogen from plasma has been shown to be a clinically safe and very efficient method for the treatment of patients with homozygous familial hypercholesterolemia or CHD patients with severe hypercholesterolemia. Treatments with 1 week H.E.L.P. intervals revealed a mean reduction of minus 51% for LDL, of minus 45% for Lp(a) and of minus 46% for apo B, while HDL was increased by 12%. fibrinogen was decreased by minus 46%. Besides the marked reduction of LDL and fibrinogen plasma concentrations the H.E.L.P. treatment significantly improves hemorheological parameters and increases the oxygen tension in the tissue. We have also investigated the efficiency of a combined therapy, using HMG-CoA reductase inhibitors together with the H.E.L.P.--apheresis. Under this combined treatment, a reduction of the interval LDL-cholesterol levels of 70-80% has been achieved, while Lp(a) and fibrinogen were not further affected. We now report about our long-term clinical experience with the H.E.L.P. system in treating patients with different lipoprotein disorders: (1) Homozygous form of familial hypercholesterolemia; (2) CHD patients with familial and non-familial hypercholesterolemia; (3) CHD patients with very high concentrations of lipoprotein(a); and (4) Hypercholesterolemic patients after heart transplantation. Based on present experience guidelines for secondary prevention of coronary heart disease indications for the H.E.L.P.--LDL-apheresis treatment are discussed.- - - - - - - - - - ranking = 0.33389259042266keywords = coronary, circulation (Clic here for more details about this article) |
4/99. LDL-apheresis in treatment of two patients with heterozygous familial hypercholesterolemia and extremely elevated lipoprotein (a) levels.In hyperlipidemia and, in particular, elevated lipoprotein (a) [Lp(a)] levels there appears to be pronounced linkage between the development and progression of atherosclerosis. Our study concerned two Caucasian male patients with heterozygous forms of familial hypercholesterolemia and extremely high Lp(a) concentrations. Maximal diet regimens and the use of lipid lowering drugs achieved a serum total-, LDL-cholesterol and triglyceride reduction of up to 30%, but no reduction of the Lp(a) level was discernible. Both patients suffered three myocardial infarctions and several coronary angiographies with percutaneous transluminal angioplasties (PTCA) were necessary. In 1989, we commenced treatment with LDL-apheresis. At present, after 78 LDL-aphereses in the case of the 41-year-old patient (48 months, dextran sulfate adsorption, KANEKA, japan) and 38 aphereses in the case of the 35-year old patient (8 months, immunoadsorption, special Lp[a] columns, LIPOPAK, POCARD, russia), the Lp(a) has dropped an average of 53%, total cholesterol 31%, LDL-cholesterol 40% and triglycerides 42%. During this period neither mycardial infarctions nor cardiac complaints were observed. In the course of treatment, both patients experienced an improvement in general well-being and increased performance. These results are very encouraging: LDL-apheresis may be effective in the treatment of patients, the only risk factor for premature atherosclerosis being an extremely high Lp(a) concentration.- - - - - - - - - - ranking = 0.11111111111111keywords = coronary (Clic here for more details about this article) |
5/99. Familial hypercholesterolemia. Acceptor splice site (G-->C) mutation in intron 7 of the LDL-R gene: alternate rna editing causes exon 8 skipping or a premature stop codon in exon 8. LDL-R(honduras-1) [LDL-R1061(-1) G-->C].Familial hypercholesterolemia (FH) is an autosomal dominant lipoprotein disorder caused by defects in the low density lipoprotein (LDL) receptor (R) gene. We report a novel mutation of the LDL-R gene in a 38-year-old man with homozygous FH from the province of Trujilo in Northern honduras. The patient presented with tendinous xanthomas over the extensor tendons as well as xanthelasmas at sites of surgical scars. He was diagnosed with severe coronary artery disease requiring revascularization at age 29. After an unsuccessful course of treatment with simvastatin, the patient has been treated with plasma apheresis and macromolecular plasma filtration bi-monthly. Haplotyping of the LDL-R gene revealed homozygosity for the rare 'J' allele and a loss of the EcoRV restriction cleavage site in exon 8. Single stranded conformational polymorphism of exons 3, 6, 7, 9, 10 and 8 reveals an abnormal migration pattern in exon 8. Direct sequencing of the promoter region, exons 1, 4, 8 and 13 revealed two RFLP's and a novel mutation in intron 7. This mutation consists of G-->C transposition at the acceptor splice site of exon 8 at the last nucleotide of intron 7 [LDL-R1061(-1)G-->C]. Reverse transcriptase (RT) PCR amplification of RNA from monocytes obtained from the patient reveals a decrease in LDL-R mRNA (52% of control) and skipping of exon 8 (approximately 38%, as assessed by densitometric scanning of the amplified fragments) to form a new RNA transcript that includes exons 7 and 9 without frameshift. Alternative rna editing leads to a new cryptic acceptor splice site 17 bp downstream in exon 8 producing a frameshift mutation and a predicted premature stop codon 1138 bp from the transcriptional start site (approxiamtely 62%). Western blotting analysis using a monoclonal antibody (C7) directed at the amino terminus of the LDL-R protein reveals a marked reduction in LDL-R protein expressed in monocytes obtained from the patient. We conclude that LDL-R1061(-1)G-->C is a novel mutation of the LDL-R gene that results in marked decrease in LDL-R mRNA levels and protein expression by two alternate rna editing mechanisms, that cause skipping of exon 8 or the use of a novel cryptic acceptor splice site in exon 8 with a frameshift and premature stop codon. The patient continues to do well on selective plasma filtration but developed bilateral severe carotid artery disease requiring surgical intervention.- - - - - - - - - - ranking = 0.11111111111111keywords = coronary (Clic here for more details about this article) |
6/99. Characterization of a novel cellular defect in patients with phenotypic homozygous familial hypercholesterolemia.Familial hypercholesterolemia (FH) is characterized by a raised concentration of LDL in plasma that results in a significantly increased risk of premature atherosclerosis. In FH, impaired removal of LDL from the circulation results from inherited mutations in the LDL receptor gene or, more rarely, in the gene for apo B, the ligand for the LDL receptor. We have identified two unrelated clinically homozygous FH patients whose cells exhibit no measurable degradation of LDL in culture. Extensive analysis of dna and mRNA revealed no defect in the LDL receptor, and alleles of the LDL receptor or apo B genes do not cosegregate with hypercholesterolemia in these families. FACS((R)) analysis of binding and uptake of fluorescent LDL or anti-LDL receptor antibodies showed that LDL receptors are on the cell surface and bind LDL normally, but fail to be internalized, suggesting that some component of endocytosis through clathrin-coated pits is defective. Internalization of the transferrin receptor occurs normally, suggesting that the defective gene product may interact specifically with the LDL receptor internalization signal. Identification of the defective gene will aid genetic diagnosis of other hypercholesterolemic patients and elucidate the mechanism by which LDL receptors are internalized.- - - - - - - - - - ranking = 0.00055925708932358keywords = circulation (Clic here for more details about this article) |
7/99. Changes in HCV viremia following LDL apheresis in a HCV positive patient with familial hypercholesterolemia.It has been suggested that hepatitis c virus (HCV) can be associated with beta-lipoprotein in human serum. According to this, the LDL receptor could promote endocytosis of such a virus. In the present study, we evaluated the changes in HCV viremia in a HCV positive patient with familial hypercholesterolemia, undergoing both selective (DALI System, Fresenius) and non-selective (plasma exchange) LDL apheresis. HCV-RNA levels did not decrease following selective LDL apheresis, on the contrary showed a random, odd variation pattern (from -35% to 72%). Conversely, plasma exchange steadily induced a drop in HCV viremia (-35/43%), to a lower extent than that of a totally intravascular plasmaprotein, i.e., alpha 2-macroglobulin (-53/54%). These data indicate that beta-lipoprotein may not function as a plasma carrier of HCV, at least in the present case. Moreover, a continuous, quantitatively unforeseeable circulation of HCV virions from the intravascular plasma compartment to other extravascular and intracellular sites, seems to occur during an apheresis session.- - - - - - - - - - ranking = 0.00055925708932358keywords = circulation (Clic here for more details about this article) |
8/99. Effects of losartan on low-density lipoprotein apheresis.The negative charges of dextran sulfate cellulose (DSC) used for low-density lipoprotein (LDL) apheresis activate the intrinsic coagulation pathway, accompanied by bradykinin production. This study was undertaken to see whether an antagonist of angiotensin receptor (AT1), losartan, could be safely used in a patient treated by DSC-LDL apheresis. losartan (50 mg/day) was given to a patient with coronary heart disease who had been treated by DSC-LDL apheresis and had experienced an anaphylactoid reaction by administration of an angiotensin converting enzyme inhibitor. The effects of losartan on blood pressures and humoral factors were examined by comparing these parameters between apheresis with and without losartan. Blood pressures and plasma levels of bradykinin, renin, and aldosterone were measured before and at 1,000, 2,000, and 3,000 ml of plasma treatment. bradykinin levels during LDL apheresis tended to be higher with losartan than without losartan (without versus with, 529 /- 121 [n = 4, mean /- SE] pg/ml vs. 1,058 /- 49 at the 2,000 ml stage, p < 0.01). The rise of plasma renin activity with losartan (221 /- 26% at the 3,000 ml stage) was significantly greater than that without losartan (144 /- 2.4%). Mean blood pressure decreased by 7% during apheresis with losartan, but blood pressure reduction was not accompanied by any complaints. These results suggest that AT1 receptor antagonists are safely used in patients treated by DSC-LDL apheresis.- - - - - - - - - - ranking = 0.11111111111111keywords = coronary (Clic here for more details about this article) |
9/99. Coronary ectasia in familial hypercholesterolemia: histopathologic study regarding matrix metalloproteinases.A 39-year-old male heterozygous familial hypercholesterolemia patient with marked ectasia over the entire coronary artery tree had been treated with several kinds of lipid-lowering single or combined drug therapies using clofibrate, compactin, cholestyramine, probucol, and pravastatin, and LDL-apheresis. During the 19-year follow-up, he suffered myocardial infarction three times and some of the ectatic coronary segments became enlarged, others narrowed, and one of them occluded in spite of the treatment. At the age of 58, he died after a fourth cardiac attack and subsequent cardiogenic shock. The autopsy indicated that his three coronary arteries showed diffuse ectatic changes and the largest lumen diameter of the left anterior descending artery was 25 mm, of the circumflex artery 12 mm, and of the right coronary artery 13 mm. The ectatic artery wall was not thick and the major part of the lumen was occupied by organized thrombi. Microscopic examinations showed that the larger the diameter of the lumen, the more severe the structural damage of the intima and tunica media and the larger the number of infiltrated cells, including lymphocytes, macrophages, and plasma cells. Immunoreactivity against matrix metalloproteinase (MMP)-1, and MMP-2 was observed in smooth muscle cells, macrophages, lymphocytes, and endothelial cells of the vasa vasorum or neovasculature. MMP-9 immunoreactivity was also localized in intimal foamy macrophages and round cells (macrophages and lymphocytes) of the media and adventitia. MMP-1 increased with the lumen diameter of the ectatic arteries. The ratio of immunoreactivity against both MMP-2 and MMP-9 to that against tissue inhibitor of metalloproteinase (TIMP)-2 also increased with the lumen diameter, but it no longer increased when the diameter was over 10 mm. These observations suggest that the MMP-TIMP system appears to play a significant role in the development of coronary ectasia- - - - - - - - - - ranking = 0.55555555555556keywords = coronary (Clic here for more details about this article) |
10/99. liver transplantation in patients with homozygotic familial hypercholesterolemia previously treated by end-to-side portocaval shunt and ileal bypass.Familial hypercholesterolemia is the result of mutations in the gene that encodes the synthesis of the cellular receptor for low density lipoprotein (LDL). In the homozygous form of the disease (HFHC), cellular LDL receptors either do not form, or, when present, cannot bond LDL and mediate its cellular uptake LDL, and the cholesterol that it transports accumulate in plasma, producing severe premature atherosclerosis and death from coronary artery disease usually before the age of 20. Currently, the only effective treatment is liver transplantation, which, alone or in association with medications, normalizes plasma cholesterol levels. The authors report the cases of 2 siblings with HFHC who underwent portocaval shunt at the ages of 2.5 and 1.5 years, respectively. Portocaval shunt produced an immediate, but insufficient decrease in cholesterol (by 40% and 35%, respectively), leaving them with cholesterol concentrations of about 500 mg/dL. One year later they each underwent ileal bypass without obtaining any significant response. liver transplantation at the ages of 18 and 16 years, respectively, reduced plasma cholesterol concentrations to 129 and 225 mg/dL, respectively. The earlier operations seriously increased the technical difficulty of liver transplantation and did not produce a favorable effect on the natural course of the disease, so portocaval shunt and ileal bypass are not indicated in HFHC, not even for the purpose of delaying liver transplantation.- - - - - - - - - - ranking = 0.11111111111111keywords = coronary (Clic here for more details about this article) |
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