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71.
Higashikata T Mabuchi H 《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》2003,7(4):402-407
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. 相似文献
72.
Summary Glucokinase is among the few genes which may play a key role in both insulin secretion and insulin action. Glucokinase is present in pancreatic beta cells where it may have a key role in the glucose sensing mechanism, and it is present in hepatocytes, where it may participate in glucose flux. Glucokinase defects have recently been implicated in maturity-onset diabetes of the young. To examine the hypothesis that glucokinase plays a key role in the predisposition to common familial Type 2 (non-insulin-dependent) diabetes mellitus, we typed 399 members of 18 Utah pedigrees with multiple Type 2 diabetic individuals for two markers in the 5 and 3 flanking regions of the glucokinase gene. Linkage analysis was performed under both dominant and recessive models. We also repeated these analyses with individuals with impaired glucose tolerance who were considered affected if their stimulated (2-h) glucose exceeded age-specific normal levels for 95 % of the population. Under several dominant models, linkage was significantly excluded, and under recessive models log of the odds (LOD) score was less than –1. We were also unable to demonstrate statistical support for the hypothesis that a small subgroup of pedigrees had glucokinase defects, but the most suggestive pedigree (individual pedigree LOD 1.8–1.9) ranked among the youngest and leanest in our cohort. We can exclude a major role for glucokinase in familial Type 2 diabetes, but our data cannot exclude a role for this locus in a minority of pedigrees. Further testing of the hypothesis that glucokinase defects contribute to diabetes in a small proportion of Type 2 diabetic pedigrees must await thorough sequence analysis of the glucokinase gene, including regulatory regions, particularly from pedigrees with positive LOD scores. 相似文献
73.
Relationship of backwash ileitis to ileal pouchitis after ileal pouch-anal anastomosis 总被引:6,自引:1,他引:6
Sven Gustavsson M.D. Louis H. Weiland M.D. Dr. Keith A. Kelly M.D. 《Diseases of the colon and rectum》1987,30(1):25-28
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. 相似文献
74.
Elizabeth R. Richens Azza Shaltout George M. Bahr Nabila Abdella Abdel K. Jayyab Muna Al-Saffar Kazem Behbehani 《Acta diabetologica》1989,26(2):115-122
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. 相似文献
75.
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. 相似文献
76.
Christophe Penna M.D. Emmanuel Tiret M.D. Frederic Daude M.D. Professor Rolland Parc M.D. 《Diseases of the colon and rectum》1994,37(2):157-160
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. 相似文献
77.
Serum lipid and apolipoprotein A (apo A) and B (apo B) levels were studied in a family with familial hypercholesterolemia (FH), which comprised two heterozygous parents, five heterozygous children, one homozygote and one normal child. Lipid levels were compared with those of age- and sex-matched normal controls. All subjects with FH had total serum cholesterol and low density lipoprotein-cholesterol (LDL-C) levels greater than the 90th percentile value for the reference range. High density lipoprotein-cholesterol (HDL-C) levels were less than the corresponding 13th percentile in heterozygous subjects. The homozygous child had grossly elevated levels of LDL-C and apo B, and very low levels of HDL-C and apo A. The most powerful discriminating variable between normal, heterozygous and homozygous family members was the LDL-C/HDL-C ratio. 相似文献
78.
Summary The glucokinase locus has been implicated by linkage studies in several Caucasian pedigrees with early onset, autosomal dominant
diabetes, and mutations have been identified in a large number of these pedigrees. Although mutations have been reported in
some pedigrees with late onset Type 2 (non-insulin-dependent) diabetes mellitus, linkage studies of typical familial Type
2 diabetes did not suggest a major role for this locus. Nonetheless, linkage studies were consistent with the hypothesis that
mutations of the glucokinase gene were responsible for the pathogenesis of Type 2 diabetes in a minority of pedigrees or one
gene in a polygenic disorder. To systematically address this hypothesis, we examined 60 diabetic members of 18 pedigrees ascertained
for two or more Type 2 diabetic siblings and eight unrelated diabetic spouses. Initially, the coding regions from each of
the 11 glucokinase exons were examined by the sensitive technique of single strand conformation polymorphism analysis to screen
for single nucleotide substitutions. Subsequently, we also sequenced each exon from an affected member of the single pedigree
in which a glucokinase allele was most likely to segregate with diabetes. Single strand conformation polymorphism analysis
detected only three variants, none of which altered the amino acid sequence. No coding or splice site mutations were detected.
Likewise, no additional mutations were detected upon direct sequence analysis. However, additional screening of promoter and
3′ untranslated regions detected a variant pattern in the untranslated region of exon 10 which appeared to segregate with
diabetes and impaired glucose tolerance in one pedigree. Sequence analysis demonstrated the deletion of a cytosine in exon
10 at position 906, but this deletion was not associated with Type 2 diabetes among unrelated spouses, was not linked to diabetes,
and was not associated with significant elevations of fasting glucose or insulin among non-diabetic pedigree members. Similarly,
two common variants in the islet promoter did not segregate with diabetes. We conclude that among typical familial Type 2
diabetes in a population representative of Northern European Caucasians, glucokinase mutations are an unlikely cause of diabetes.
[Diabetologia (1994) 37: 182–187]
Received: 10 June 1993 and in revised form: 20 August 1993 相似文献
79.
R. Scicali A. Di Pino R. Platania G. Purrazzo V. Ferrara A. Giannone F. Urbano A. Filippello V. Rapisarda E. Farruggia S. Piro A.M. Rabuazzo F. Purrello 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2018,28(1):35-43
Background and aims
Familial hypercholesterolemia (FH) is underdiagnosed and public cholesterol screening may be useful to find new subjects. In this study, we aim to investigate the prevalence of FH patients in a hospital screening program and evaluate their atherosclerotic burden using intima-media thickness (IMT).Methods and results
We screened 1575 lipid profiles and included for genetic analysis adults with a low-density lipoprotein (LDL) cholesterol >190 mg/dL and triglycerides <200 mg/dL and first-degree child relatives with LDL cholesterol >160 mg/dL and triglycerides <200 mg/dL. The diagnosis of FH was presumed by Dutch Lipid Clinic Network (DLCN) criteria and confirmed by the presence of the genetic variant. Mean common carotid intima-media thickness (IMT) was assessed using consensus criteria. After confirming LDL cholesterol value and excluding secondary hypercholesterolemia, 56 subjects with a DLCN ≥4 performed genetic analysis. Of these, 26 had an FH genetic variant. The proportion of patients with a mutation having a DLCN score of 6–8 was 75%; in individuals with a DLCN score >8 it was 100%. Mean IMT was higher in FH patients compared to non FH (0.73 [0.61–0.83] vs 0.71 [0.60–0.75] mm, p < 0.01). Moreover, we detected two mutations not previously described. Finally, simple regression analysis showed a correlation of IMT with LDL cholesterol >190 mg/dL and corneal arcus (p < 0.01 and p < 0.001, respectively).Conclusions
A hospital screening was useful to detect FH subjects with increased atherosclerosis. Also, next-generation sequencing was able to detect new FH mutations. 相似文献80.
Nicole Schupf Sandra Barral Thomas Perls Anne Newman Kaare Christensen Bharat Thyagarajan Michael Province Winifred K. Rossi Richard Mayeux 《Neurobiology of aging》2013
Exceptional longevity is associated with substantial heritability. The ?4 allele in apolipoprotein E and the linked G allele in rs2075650 of TOMM40 have been associated with increased mortality and the ?2 allele with decreased mortality, although inconsistently. Offspring from long-lived families and spouse controls were recruited at 3 sites in the United States and Denmark. We used generalized estimating equations to compare the likelihood of carrying risk alleles in offspring (n = 2307) and spouse controls (n = 764), adjusting for age, sex, level of education, and family membership. The likelihood of carrying an APOE ?4 allele or a G allele in rs2075650 was lower (odds ratio [OR], 0.75; p = 0.005 and OR, 0.70; p = 0.002) and the likelihood of carrying an APOE ?2 allele was higher (OR, 1.5; p = 0.007) among family members in the offspring generation than among their spouse controls. Our findings support the hypothesis that both reduction in the frequency of the ?4 allele and increase in the frequency of the ?2 allele contribute to longevity. 相似文献