Nonprogression of coronary artery atherosclerosis in homozygous familial hypercholesterolemia after 31 months of repetitive plasma exchange

The effects of plasma exchange performed every two weeks for 31 months in combination with diet and drug therapy were studied in a patient with receptor-defective homozygous familial hypercholesterolemia. Coronary angiography performed three years prior to commencing plasma exchange was compared to angiography 31 months after starting the program. Comparison of the angiograms taken six years apart showed no progression of coronary atheroma in the main left coronary artery in which a 30% narrowing was originally seen. An internal mammary artery-coronary artery bypass remained widely patent and showed no development of atherosclerosis. Plasma cholesterol levels were reduced 46% by plasma exchange, diet and drug compared to diet and drug alone. Achilles tendon xanthoma diminished significantly. It appears that plasma exchange combined with diet and drug therapy, while not producing regression of existing atheromatous lesions, does retard or prevent further progression.     

The implications of the ezetimibe and simvastatin in hypercholesterolemia enhances atherosclerosis regression trial: a return to first principles

To outward appearances, the publication of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial has led to a monolithic backlash against the use of ezetimibe by cardiologists for the treatment of hyperlipidemia. Rather than be swayed by popular opinion, we should each put the results of ENHANCE into context and ask the questions: should I put my trust in an imaging surrogate or in low‐density lipoprotein (LDL) cholesterol (LDL‐C), and how do the safety and efficacy of ezetimibe compare with other nonstatin lipid‐lowering agents? Copyright © 2008 Wiley Periodicals, Inc.     

Low-density lipoprotein apheresis in children with familial hypercholesterolemia: follow-up to 21 years

Twenty-seven patients (14 girls, 13 boys) affected by familial hypercholesterolemia who had begun low-density lipoprotein (LDL) apheresis treatment before the age of 15 were studied. The median age at diagnosis was 4 years and the blood LDL cholesterol level was 704 +/- 163 mg/dL. Screening was performed for homozygous or double heterozygous mutations of the LDL cholesterol receptor gene and mutations were found in 24 of the patients. The mean age at the beginning of treatment was 8.5 years and the mean length of follow up was 12.6 years. The two main procedures used were direct adsorption of lipoproteins and dextran sulfate cellulose adsorption. Nine patients experienced anaphylactic reactions due to bradykinin and six had to have their treatment changed. The LDL cholesterol level before the session was lowered by 45 +/- 11% of the value at diagnosis. The LDL cholesterol reduction in a session was 72 +/- 10%. Tendinous xanthomas disappeared or diminished dramatically in 62% of the children. In 22 patients no cardiovascular event occurred during LDL apheresis treatment. Three had angina pectoris; two others had surgical management of aortic stenosis, but no clinical manifestations. Seven children had normal cardiovascular pictures while on treatment. Eleven had abnormalities of the aortic root or coronary arteries, which in six cases had appeared before treatment; the other five children did not undergo prior cardiac evaluation. In five children the abnormalities appeared during treatment. Based on these data, LDL-apheresis can be recommended for the treatment of homozygous familial hypercholesterolemia, even in young children, with good efficiency on biological parameters, cutaneous lesions and cardiovascular events.     

Long-term effect of low-density lipoprotein apheresis in patients with heterozygous familial hypercholesterolemia

Clinical efficacy and safety of the therapeutic tool which directly removes LDL particles from circulation (LDL apheresis) have already been established in the treatment for refractory hypercholesterolemia in patients with familial hypercholesterolemia (FH). Two clinical studies with event-based assessment have demonstrated remarkably beneficial outcomes of long-term LDL apheresis using dextran sulfate cellulose columns plus adjunctive cholesterol-lowering drug therapy in the prevention of cardiovascular events in heterozygous FH with coronary artery disease. The results of several studies with angiographic and ultrasound-based assessment indicate a possible role for LDL apheresis in restructuring and stabilization of atherosclerotic lesions. These clinical improvements caused by LDL apheresis in heterozygous FH support the efficacy and importance of aggressive cholesterol-lowering therapy for secondary prevention of atherosclerotic cardiovascular disease in hypercholesterolemic patients.     

Relationship of backwash ileitis to ileal pouchitis after ileal pouch-anal anastomosis

To assess whether the presence of backwash ileitis predisposed to the subsequent development of ileal pouchitis after ileal pouch-anal anastomosis, 131 patients who had the operation were studied. Fifteen patients had nonspecific inflammation in the terminal ileum noted at the time of the operation, while 20 patients subsequently developed pouchitis. No correlation between the two conditions was found. Pouchitis developed in two of 15 patients (13 percent) with backwash ileitis and in 18 of 116 patients (16 percent) without the ileitis (P>0.05). Among the 20 patients (16 percent) without the ileitis (P>0.05). Among the 20 patients with pouchitis only two (10 percent) had had previous backwash ileitis. It is concluded that the presence of backwash ileitis does not predispose to later development of pouchitis, and so does not contraindicate use of the inflammed terminal ileum for construction of the ileal pouch and anastomosis. Supported by the Swedish Medical Research Council Grant 7093, Pfimmer/Meda, Virding Fortia Foundation, and the Mayo Foundation.     

Insulin binding substances,autoimmunity and type i diabetes in kuwaiti patients and their kindred

Summary Insulin autoantibodies (IAAs) are associated with type I diabetes mellitus (DM) and have been suggested as predictive markers of the disease. Using an ELISA assay, we have studied the prevalence of binding to human insulin in sera from an Arab type I DM population and compared it with the prevalence in the family members (FMs) of the probands, in type II DM patients from the same population, and in Arab control subjects. Significant levels of binding occurred in 11/16 (69%) of type I DM patients and in 21/34 (62%) of their FMs, but in only 5/31 (16%) of type II DM patients and in 1/25 (4%) of control subjects. Within families, there was homogeneity with regard to the level of insulin binding and the mean family levels correlated with those of the proband (r=0.68, df=7, p=0.05). HLA-DR3 or -DR4 antigens occurred in 55/63 (87%) of type I DM patients and in 95/118 (81%) of their FMs. This was significantly higher (p<0.001) than in either type II DM patients (39/75, 52%) or in control subjects (34/93, 37%). ICAs were present in significantly more (25/43, 58%) of type I DM patients than their FMs (3/82, 3%) (p<0.001). They did not occur in either type II DM patients or in the control group. In conclusion, insulin binding occurred in sera from both type I diabetic patients and their kindred, and hence did not appear to be specifically associated with the development of clinical diabetes.     

Reduced platelet serotonin content and release in familial hypercholesterolaemia

Plasma and platelet serotonin (5-HT) concentrations, and resting and collagen-induced 5-HT release in platelet-rich plasma were studied in normal and familial hypercholesterolaemic (FH) subjects. Platelet 5-HT concentrations were significantly reduced (−37%, P<0.01) in FH patients whilst mean plasma concentrations, although increased, were not significantly different from those in normal subjects. Platelet 5-HT correlated negatively with plasma cholesterol when the data for normal subjects and FH patients were combined (r=−0.48, P=0.005). It also correlated negatively with low-density lipoprotein (LDL) (FH data, r=−0.59, P=0.03; normal and FH data, r=−0.49, P=0.004) but positively with high-density lipoprotein (HDL) (FH, r=0.79, P=0.001; normal and FH, r=0.37, P=0.03). Collagen (5–160 μg/ml) stimulated platelet 5-HT release occurred in a concentration-dependent manner. In FH patients stimulated 5-HT release was reduced (10 μg/ml collagen, −40%, P<0.05) and accompanied by increased collagen EC₅₀ values (P<0.02). Resting 5-HT release was increased substantially in FH patients but not significantly. Our data provide evidence for a relationship between circulating cholesterol and platelet serotonergic mechanisms. It is proposed that abnormalities relating to platelet-plasma 5-HT dynamics, perhaps due to enhanced platelet activity or decreased platelet uptake, may contribute to the cardiovascular complications in FH.     

Effect of simvastatin on high density lipoprotein subfractions and apolipoproteins in Type IIa hypercholesterolemia

Summary Changes in plasma concentrations of high density lipoproteins (HDL) and triglycerides may partly explain the ability of cholesterol-lowering drugs to decrease the incidence of coronary heart disease. We measured the response of fasting plasma lipids, lipoproteins, and apolipoproteins in 46 subjects with Type IIa hypercholesterolemia treated with simvastatin for 3 months. The initial dose of simvastatin (10 mg/day) was subsequently increased up to 40 mg/day if the plasma cholesterol concentration had not fallen below 5.2 mmol/l. Plasma concentrations of HDL cholesterol and of the apolipoproteins AI and AII were increased by simvastatin. The increase in HDL cholesterol (9%) was due to increases in both subfractions (HDL₂ 17%; HDL₃ 7%), changes that would be consistent with a beneficial effect on cardiovascular risk. Simvastatin decreased plasma triglyceride concentrations by 25%. Plasma total cholesterol concentrations fell by 35% after 3 months of treatment; this fall was proportional to the initial concentration and was due almost entirely to a 45% fall in low density lipoprotein cholesterol. In contrast, plasma concentrations of lipoprotein Lp(a) were not affected by simvastatin.     

Results of ileal J-pouch-anal anastomosis in familial adenomatous polyposis complicated by rectal carcinoma

PURPOSE: Rectal cancer frequently occurs in patients with familial adenomatous polyposis (FAP) and, in some cases, proctocolectomy and ileal pouch-anal anastomosis (IPAA) can be proposed as an alternative to end ileostomy. This study aimed to assess the results of IPAA for familial adenomatous polyposis complicated by rectal carcinoma. PATIENTS AND METHODS: Postoperative morbidity and bowel function following IPAA were assessed in six patients who had a mesorectal excision for rectal cancer. The functional results were compared with those obtained after IPAA in 134 FAP patients without bowel cancer. RESULTS: Carcinomas were located at a mean of 11 cm from the dentate line. There were no postoperative complications. One patient with synchronous hepatic metastases died 6 months after operation and the 5 others were alive without recurrence after a mean follow-up of 29 months. Mean frequency of defecation was 6.5/day (vs. 4.2/day in patients without carcinoma), 86 percent of patients had nocturnal defecation (vs. 50 percent), day and night continence were normal in 66 percent and 33 percent of patients, respectively, compared with 90 percent and 85 percent for IPAA without cancer. Pouch excision was required in one patient for unsatisfactory functional result. CONCLUSION: IPAA can be safely performed for cancer of the upper rectum complicating FAP, but a poor functional outcome related to mesorectal excision has to be expected.