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1.
G. Feussner M. Eichinger R. Ziegler 《Journal of molecular medicine (Berlin, Germany)》1992,70(11):1027-1035
Summary Nineteen adult patients with type III hyperlipoproteinemia (HLP) and homozygosity for apolipoprotein (apo) E2 were treated with the 3-hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitor simvastatin (20 or 40 mg per day) alone or in combination with the fibrate derivative gemfibrozil (450 mg per day) during a 30-week outpatient study. With the 20-mg dose (n = 19) the mean plasma cholesterol level decreased from 13.24±8.04 8.04 at baseline to 8.04±4.19 mmol/l (mean reduction 39.3%; P<0.05), and the mean plasma triglyceride level decreased from 13.47±19.22 to 7.84±7.71 mmol/l (–41.8%; NS); this was due to a decrease in very low density lipoprotein (VLDL) cholesterol from 8.95±8.64 to 4.94±4.24mmo1/l (–44.8%; NS), a decrease in low density lipoprotein (LDL) cholesterol from 3.54±0.93to 2.25 ± 0.59 mmol/l (–36.5%; P<0.01), and an increase in high density lipoprotein (HDL) cholesterol from 0.72±0.28 to 0.85±0.34 (+18.1%; NS). Thirteen patients were treated with 40 mg simvastatin per day. Under this regimen there was a further significant decrease in LDL cholesterol from 2.33±0.62 to 1.81±0.49 mmol/l (–22.3%; P<0.01). In six patients who remained hyperlipidemic on monotherapy combination drug therapy with simvastatin (40 mg per day) and gemfibrozil (450 mg per day) was given. Compared to simvastatin alone the addition of gemfibrozil further lowered plasma concentrations of total cholesterol by 14.9%, VLDL cholesterol by 23.5%, and triglycerides by 17.1%, although this was not statistically significant. No patient was discontinued from single or combination drug therapy, and no severe clinical or biochemical side effects were observed. The results of this study demonstrate the usefulness of simvastatin in the therapy of type III HLP and indicate that in individual patients who remain hyperlipidemic on monotherapy combination drug therapy with both of these drugs is effective in further reducing plasma concentrations of total cholesterol, VLDL cholesterol, and triglycerides. Although no patient in this investigation developed myopathy or rhabdomyolysis, combined fibrate-HMG CoA reductase inhibitor treatment should be considered only for severe forms of hyperlipidemia and for patients who do not respond sufficiently to mon-therapy of any of these drugs.Abbreviations Apo
Apolipoprotein
- CPK
creatine phosphokinase
- GGT
gamma-glutamyl transpeptidase
- HDL
high density lipoproteins
- HLP
hyperlipoproteinemia
- HMG CoA
3-hydroxy-3-methyl glutaryl coenzyme A
- IDL
intermediate density lipoproteins
- LDL
low density lipoproteins
- TG
triglycerides
- VLDL
very low density lipoproteins 相似文献
2.
Limited information is available concerning type III hyperlipoproteinemia (HLP) in the Asian population. Therefore, clinical and biochemical characteristics of type III HLP were examined in 16 Japanese patients. Mean plasma triglyceride (TG) and total cholesterol (chol) levels were 381 mg/dl and 253 mg/dl, respectively, and the mean very low density lipoprotein (VLDL)-chol/plasma TG ratio was 0.27, which were lower than those reported in Western countries. Eighty percent of the patients had high plasma remnant-like particles (RLP)-chol levels above 50 mg/dl and a high RLP-chol/plasma TG ratio above 0.1. Twelve patients (75.0%) were obese. Seven patients (43.8%) had type 2 diabetes mellitus and four patients (25.0%) had impaired glucose tolerance. Six patients (37.5%) had coronary heart disease (CHD), but none had peripheral vascular disease or xanthomas. TG-rich lipoproteins from type III HLP patients with diabetes mellitus stimulated cholesteryl ester synthesis by human macrophages significantly (p < 0.001) more than those from type III HLP patients without diabetes mellitus. In conclusion, the Japanese type III HLP patients had lower plasma TG and total chol levels and a lower VLDL-chol/plasma TG ratio, but CHD was more common. The patients were characterized by a high frequency of obesity and/or glucose intolerance. The TG-rich lipoproteins from type III HLP patients with diabetes mellitus were more atherogenic. 相似文献
3.
目的:评价泽之浩(国产辛伐他汀)治疗高脂血症,尤其是高胆固醇血症和混合型高脂血症的临床疗效及安全性。方法:选择高脂血症患者,有冠心病或冠心病危险因素的高脂蛋白血症患者54例,给予泽之浩10mg/d;4周后如未达有效标准,均可加量至20mg/d,治疗8周,观察降脂疗效和不良反应。结果:(1)泽之浩治疗后,1例患者因血清谷丙转氨酶升高而中途退出研究,其余患者(n=53)的总胆固醇(TC),甘油三酯(TG),低密度脂蛋白胆固醇(LDL-C)均明显降低,高密度脂蛋白胆固醇(HDL-C)明显升高(P均<0.05),(2)高胆固醇血症(n=20)用泽之浩治疗,TC,LDL-C,(TC-HDL-C)/HDL-C显著下降(P均<0.01),(3)对于混合高脂血症患者(n=14),泽之浩可使TC,LDL-C和TG显著下降(P<0.01,P<0.05)。(4)泽之浩调脂幅度与治疗前的TC和TG水平相关。(5)泽之浩调脂的总有效率为88.7%,总显效率为83.0%,结论:泽之浩有明显的降低TC,LDL-C,TG和(TC-HDL-C)/HDL-C和升高HDL-C的作用,其不良反应较轻微,常用剂量10mg/d,少数TC,LDL-C较高者可用20mg/d。 相似文献
4.
5.
《Journal of clinical lipidology》2016,10(4):1035-1039.e2
Type I hyperlipoproteinemia (T1HLP) usually presents with extreme hypertriglyceridemia, recurrent episodes of acute pancreatitis, lipemia retinalis, and cutaneous eruptive xanthomas. We report a unique 10-year-old male of Indian origin who presented in neonatal period with transient obstructive jaundice and xanthomas in the pancreas and kidneys. Serum triglycerides stabilized with extremely low-fat diet although he subsequently developed pancreatic atrophy. Extreme hypertriglyceridemia failed to respond to treatment with fenofibrate, fish oil, and orlistat. Whole-exome sequencing of the parents and patient was performed. Copy number variation analysis revealed a large deletion in chromosome 8 containing the entire GPIHBP1, which was confirmed by Sanger sequencing to be 54,623 bp deletion. Review of the literature revealed a slightly higher maximum triglyceride levels in those with homozygous null vs missense mutations suggesting severe disease in those with nonfunctional vs dysfunctional GPIHBP1 protein. Visceral xanthomas and pancreatic atrophy can be part of the spectrum of clinical features in patients with T1HLP. We highlight the need to perform copy number variations analysis of whole-exome sequencing data for finding disease-causing variants. There is also an urgent need to develop novel targeted therapies for patients with T1HLP. 相似文献
6.
Objectives
Type 1 hyperlipoproteinemia is an autosomal recessive disorder characterized by severely elevated plasma triglyceride levels, which may lead to abdominal pain and pancreatitis, eruptive xanthomas and failure to thrive. Mutations in the genes encoding lipoprotein lipase (LPL), apolipoprotein CII (APOC2), apolipoprotein AV (APOA5), lipase maturing factor 1 (LMF1) or glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) have been found to cause Type 1 hyperlipoproteinemia.Methods
Two sibpairs belonging to two different branches of an extended pedigree were referred for molecular elucidation for their increased plasma triglyceride levels, which untreated were >27 mmol/L. The genes LPL, APOC2, APOA5, LMF1 and GPIHBP1 were analyzed by DNA sequencing.Results
No mutations were found in LPL, APOC2, APOA5 or LMF1. No PCR products were obtained for exons 3 and 4 of GPIHBP1 from DNA of the 4 affected subjects. Subsequent long-range PCR revealed that the four affected were homozygous for a deletion comprising exons 3 and 4 of GPIHBP1. No increase in LPL activity was found in post-heparin plasma from the subjects.Conclusion
Homozygosity for a deletion of exons 3 and 4 of GPIHBP1 results in Type 1 hyperlipoproteinemia. 相似文献7.
OBJECTIVE: The complication of severe hyperlipoproteinemia with anorexia nervosa is very rare. We investigated the mechanisms of severe hyperlipoproteinemia in a patient with anorexia nervosa. METHODS: The measurement of plasma levels of lipids, apolipoproteins (Apo), lipoprotein subfractions, free T3, and estrogen, apo (lipoprotein) E phenotyping, and the assay of lymphocyte low-density lipoprotein (LDL)-receptor activity were accomplished in a 40-year-old female patient with anorexia nervosa. RESULTS: Her body mass index was 10.3 kg/m2. Her plasma levels of total cholesterol (C), triglyceride (TG), apoB, apoE, very-low-density lipoprotein (VLDL)-C, and intermediate-density lipoprotein (IDL)-C were 757 mg/dl, 526 mg/dl, 288 mg/dl, 13.6 mg/dl, 133 mg/dl, and 99 mg/dl, respectively. VLDL was cholesterol rich (C/TG ratio = 0.68; normal value = 0.2). The plasma LDL was high and skewed to less dense fractions. Her apoE phenotype was E 3/2. Her lymphocyte LDL-receptor activity was 79% of normal subjects. The plasma level of estradiol was low and that of free T3 was subnormal. DISCUSSION: We concluded that the plasma lipoprotein abnormality of this anorexia nervosa patient was induced by the impaired removal of TG-rich lipoprotein remnants and less dense LDL due to apoE phenotype E 3/2, subnormal LDL-receptor activity, subnormal plasma level of free T3, and diminished secretion of estrogen. 相似文献
8.
de Beer F Smelt AH van Vark LC Hoogerbrugge N Havekes LM Gevers Leuven JA 《Journal of internal medicine》2002,251(2):148-155
OBJECTIVE: To investigate the short-term effect of treatment with tibolone on plasma lipid and lipoprotein levels in postmenopausal women with type III hyperlipoproteinemia (HLP). DESIGN AND INTERVENTION: Patients were randomized to receive, in a double-blind cross-over fashion, a fixed dose of tibolone, 2.5 mg once daily or placebo for 8 weeks. The two treatment periods were separated by a wash-out period of 6 weeks. At each visit body weight and blood pressure were determined. Before and after each treatment period, fasting venous blood samples were obtained from the patients for biochemical measurements. SETTING: The Leiden University Medical Center. SUBJECTS: Postmenopausal women with type III HLP (aged < or = 65 years) were recruited from the Lipid Clinics of the Leiden University Medical Center, the Amsterdam Medical Center, the Utrecht Medical Center and the University Hospital Rotterdam. Five out of 25 women with type III HLP were eligible to be included in the study. Four of the five included patients completed the study according to the protocol. One patient was excluded from blinded therapy because total cholesterol levels increased above 20 mmol L(-1). MAIN OUTCOME MEASURES: A significant reduction of plasma triglyceride, total cholesterol, VLDL cholesterol and VLDL triglyceride levels. RESULTS: Plasma triglyceride and total cholesterol levels decreased from 6.82 +/- 3.58 to 2.45 +/- 1.36 mmol L(-1) and from 13.53 +/- 3.64 to 6.61 +/- 2.03 mmol L(-1), respectively (both P < 0.05). The body mass index remained unchanged. The glycated haemoglobin percentage decreased significantly from 5.8 to 5.3%. Treatment with tibolone resulted in a profound reduction in plasma apolipoprotein E, VLDL cholesterol and VLDL triglyceride levels (mean reductions of 66, 77 and 70%, respectively, P < 0.05). CONCLUSIONS: Tibolone is a valuable adjuvant to current therapy in postmenopausal women with type III HLP. 相似文献
9.
The discovery of the first human lipoprotein polymorphism by Allison and Blumberg [Lancet i:634-637, 1961] and the availability of alloimmune sera stimulated us to begin immunogenetic studies on swine in search of lipoprotein diversity and its relationship to biological functions. We found considerable lipoprotein polymorphism, complexity, and heterogeneity in this species. These results and the correlation between immunogenetically defined lipoprotein type and arterial lipidosis in swine, fed a high fat diet, are discussed. Immunogenetic studies of lipoproteins, initiated more recently in rhesus monkeys, will be reviewed also. Preliminary data show similarities between these two species with regard to polymorphism, complexity, phenotypic expression of lipoprotein genes and, most importantly, their serological relationship to human lipoproteins. We also note immunogenetic studies on lipoproteins done by other investigators, or in other species. Brief remarks on implications of the lipoproteins in atherosclerosis, their general classification, immunological properties, and immunological methods used in their study precede the immunogenetic presentation. 相似文献
10.
Richard Straube Helmut Kingreen 《Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy》1998,2(3):243-245
Abstract: This paper reports 2 years' experience with lipoprotein (a) (Lp[a]) immunapheresis which was successfully handled on a now 40-year-old patient with familial Lp(a) hyperlipoproteinemia inducing severe coronary heart disease with 2 myocardial infarctions and diffuse coronary sclerosis. Continued treatment by Lp(a) immun-absorption with specific sheep antibodies reduced stenosis in coronary vessels more than 50% and stopped the progression of coronary heart disease. A special apheresis technique and the results of continued absorption effects are described. 相似文献