1/5. Thrombocytopenic purpura during therapy with simvastatin.The authors describe a case of very serious thrombocytopenic purpura occurring in a diabetic and hyperlipidemic woman during therapy with simvastatin, an HMG-CoA reductase inhibitor drug. Interruption of the medical treatment produced a prompt reversal of the thrombocytic attack: one year later the patient's platelet count remains within the normal range. The authors have not found other reports in the medical literature of similar serious reactions during therapy with an HMG-CoA reductase inhibiting substance; nevertheless, a causal nexus is hypothesized but not argued in this case, since further studies will be needed before this connection can be established.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
2/5. Marked hyper-HDL2-cholesterolemia associated with premature corneal opacity. A case report.We report here a peculiar case with premature corneal opacity and extremely high levels of HDL cholesterol in serum. The patient is a 54-year-old man who was first noticed to have marked corneal opacities at age 19. His serum HDL cholesterol level was elevated to the level of 135-160 mg/dl, while total serum cholesterol and triglyceride concentrations were 254 mg/dl and 56 mg/dl, respectively. serum apoprotein A-I and E levels analyzed by single radial immunodiffusion method were elevated in the case. serum lipoprotein fractions isolated by preparative ultracentrifugation revealed that increased levels of HDL cholesterol were accounted for solely by the HDL2 fraction. HDL2 of the patient contained relatively higher amounts of apoprotein E than normal control HDL2. Elution profiles of lipoproteins in high performance liquid chromatography revealed that HDL2 particles from the patient were larger in size than those from normal controls. These characteristics of HDL are in part similar to those of HDLC which appears in experimental animals after cholesterol feeding. Such abnormalities in HDL2 fractions associated with premature corneal opacity have not been reported so far and appear to constitute a new disease entity.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
3/5. probucol-induced QT prolongation and syncope.We report a patient who experienced a reversible prolongation of the QT interval and episodes of syncope while receiving probucol. A 64-year-old woman experienced syncopal attacks 8 and 11 weeks after beginning probucol treatment (500 mg twice daily). The pre-treatment ECG showed a slight prolongation of the corrected QT interval (QTc) (0.46 sec). Her QTc increased to 0.62 sec 12 weeks after beginning probucol treatment and decreased to about the baseline value (0.48 sec) 6 weeks after treatment was discontinued. probucol is known to prolong the QT interval. A long QT interval has been linked to an increased risk of ventricular arrhythmias, syncope or sudden death. However, clinical reports which causally relate probucol treatment to syncope are very rare. Although an ECG during the episodes of syncope was not available, this patient's syncope might be due to ventricular tachyarrhythmia associated with probucol-induced QT prolongation. This case emphasizes the need for careful evaluation of the QT interval before and during probucol treatment.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
4/5. Failure of complete bile diversion and oral bile acid therapy in the treatment of homozygous familial hypercholesterolemia.Two patients with nomozygous familial hypercholesterolemia, refractory to medical therapy, underwent complete bile diversion by common-duct ligation and cholecystostomy, in an attempt to arrest the progression of their xanthomatosis and atherosclerosis by depletion of body cholesterol. clofibrate was given after operation to one patient, and cholic acid to both, in an effort to enhance further the negative sterol balance. bile diversion produced an increase of six to eight times in gastrointestinal sterol output, which was not increased further by either clofibrate or cholic acid therapy. Despite a calculated sterol loss of 560 g over 14 months in one patient and 400 g over 10 months in the other, neither plasma cholesterol nor xanthoma size decreased. Continuity of the biliary tree was therefore restored. The data suggest that patients with homozygous familial hypercholesterolemia respond to even massive gastrointestinal sterol depletion with equal increases in sterol synthesis.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
5/5. Analysis of two duplications of the LDL receptor gene affecting intracellular transport, catabolism, and surface binding of the LDL receptor.Two novel mutations of the low density lipoprotein (LDL)-receptor gene were found in two Italian familial hypercholesterolemia (FH)-heterozygotes. The first mutation was an 18 nucleotide duplication in exon 8 which is preceded by an A-->T transversion. The translation product of the mutant allele was predicted to be a receptor with an in-frame insertion of 6 amino acids in repeat B of the epidermal growth factor precursor homology domain. Analysis of LDL-receptor activity in the proband's fibroblasts showed a 50% reduction of 125I-labeled LDL binding and pulse-chase studies suggested that little, if any, of the mutant protein was processed to the mature form. The second mutation was a 7 kb duplication (from intron 2 to intron 6) of exons 3 through 6, predicted to encode an elongated receptor with the duplication of repeats 2-7 of the ligand binding domain. The elongated receptor was processed slightly more slowly than the normal receptor, but was converted to a mature form of the expected size. This mature, mutant receptor was degraded more rapidly than the normal receptor. On ligand blotting the elongated receptor bound twice as much LDL or beta-very low density lipoprotein (betaVLDL) as the normal receptor. In contrast, maximum binding of LDL to proband's cells was decreased to approximately 70% of the normal cells with a significant increase in apparent affinity. Cell association at 37 degrees C, internalization, and degradation showed a similar reduced maximum. Thus these mutations demonstrate that duplications of amino acid sequences in the low density lipoprotein LDL-receptor may disrupt the LDL-receptor pathway at different levels.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |