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South African Medical Journal =... Feb 2008Familial hypercholesterolaemia (FH), an autosomal dominantly inherited disorder characterised by elevated plasma low-density lipoprotein (LDL) cholesterol levels, tendon...
Familial hypercholesterolaemia (FH), an autosomal dominantly inherited disorder characterised by elevated plasma low-density lipoprotein (LDL) cholesterol levels, tendon xanthomata and premature ischaemic heart disease, is amenable to treatment with modern medication. The clinical and biochemical details of 1 031 patients with FH were analysed. FH is the most common monogenic disorder of lipoprotein metabolism presenting to the Lipid Clinic at Groote Schuur Hospital, accounting for about 20% of consultations. The hospital classified 55% of the FH patients as white, 43% as coloured, 1.5% as Asian and 0.5% as black. In the FH cohort (whose mean age at presentation was 44 years), 80% had tendon xanthomata, 36% had arcus cornealis, and 14% had xanthelasma. Tendon xanthomata was present in almost 90% of patients by the age of 50 years. Arcus cornealis was present in about 45% by the age of 40 years, further increasing in frequency with age. Cardiovascular complications included ischaemic heart disease (43%), stroke (1.5%), transient ischaemic attacks (1.3%), and peripheral vascular disease (3.7%). The mean age of death was 55 (+/-13) years; 51 ( +/-10) years in men and 61 ( +/-12) years in women. In 46% of the cohort, a defective gene was identified by testing for locally prevalent mutations.
Topics: Age Factors; Arcus Senilis; Cardiovascular Diseases; Cholesterol; Female; Genotype; Humans; Hyperlipoproteinemia Type II; Male; Middle Aged; Mutation; Prevalence; Racial Groups; Sex Factors; South Africa; Triglycerides; Xanthomatosis
PubMed: 18350202
DOI: No ID Found -
Lipids in Health and Disease Mar 2008A relationship between corneal arcus and atherosclerosis has long been suspected but is controversial. The homozygous familial hypercholesterolemia patients in this...
BACKGROUND
A relationship between corneal arcus and atherosclerosis has long been suspected but is controversial. The homozygous familial hypercholesterolemia patients in this study present a unique opportunity to assess this issue. They have both advanced atherosclerosis and corneal arcus.
METHODS
This is a cross-sectional study of 17 patients homozygous for familial hypercholesterolemia presenting to the Clinical Center of the National Institutes of Health. Plasma lipoproteins, circumferential extent of arcus, thoracic aorta and coronary calcific atherosclerosis score, and Achilles tendon width were measured at the National Institutes of Health.
RESULTS
Patients with corneal arcus had higher scores for calcific atherosclerosis (mean 2865 compared to 412), cholesterol-year score (mean 11830 mg-yr/dl compared to 5707 mg-yr/dl), and Achilles tendon width (mean 2.54 cm compared to 1.41 cm) than those without. Corneal arcus and Achilles tendon width were strongly correlated and predictive of each other. Although corneal arcus was correlated with calcific atherosclerosis (r = 0.67; p = 0.004), it was not as highly correlated as was the Achilles tendon width (r = 0.855; p < 0.001).
CONCLUSION
Corneal arcus reflects widespread tissue lipid deposition and is correlated with both calcific atherosclerosis and xanthomatosis in these patients. Patients with more severe arcus tend to have more severe calcific atherosclerosis. Corneal arcus is not as good an indicator of calcific atherosclerosis as Achilles tendon thickness, but its presence suggests increased atherosclerosis in these hypercholesterolemic patients.
Topics: Achilles Tendon; Adolescent; Adult; Arcus Senilis; Atherosclerosis; Calcinosis; Cardiomyopathies; Child; Child, Preschool; Female; Homozygote; Humans; Hypercholesterolemia; Infant; Lipoproteins; Male
PubMed: 18331643
DOI: 10.1186/1476-511X-7-7 -
Mayo Clinic Health Letter (English Ed.) Nov 2007
Topics: Arcus Senilis; Humans; Middle Aged
PubMed: 18229409
DOI: No ID Found -
Harvard Men's Health Watch Oct 2007
Topics: Aging; Arcus Senilis; Cholesterol; Humans; Male
PubMed: 18217268
DOI: No ID Found -
MMW Fortschritte Der Medizin Jun 2007
Topics: Age Factors; Aged; Arcus Senilis; Diagnosis, Differential; Humans; Hyperlipoproteinemia Type II; Male
PubMed: 18062570
DOI: 10.1007/BF03365071 -
Investigative Ophthalmology & Visual... Nov 2007Schnyder crystalline corneal dystrophy (SCCD; MIM 121800) is a rare autosomal dominant disease characterized by an abnormal increase in cholesterol and phospholipid...
PURPOSE
Schnyder crystalline corneal dystrophy (SCCD; MIM 121800) is a rare autosomal dominant disease characterized by an abnormal increase in cholesterol and phospholipid deposition in the cornea, leading to progressive corneal opacification. Although SCCD has been mapped to a genetic interval between markers D1S1160 and D1S1635, reclassification of a previously unaffected individual expanded the interval to D1S2667 and included nine additional genes. Three candidate genes that may be involved in lipid metabolism and/or are expressed in the cornea were analyzed.
METHODS
DNA samples were obtained from six families with clinically confirmed SCCD. Analysis of FRAP1, ANGPTL7, and UBIAD1 was performed by PCR-based DNA sequencing, to examine protein-coding regions, RNA splice junctions, and 5' untranslated region (UTR) exons.
RESULTS
No disease-causing mutations were found in the FRAP1 or ANGPTL7 gene. A mutation in UBIAD1 was identified in all six families: Five families had the same N102S mutation, and one family had a G177R mutation. Predictions of the protein structure indicated that a prenyl-transferase domain and several transmembrane helices are affected by these mutations. Each mutation cosegregated with the disease in four families with DNA samples from both affected and unaffected individuals. Mutations were not observed in 100 control DNA samples (200 chromosomes).
CONCLUSIONS
Nonsynonymous mutations in the UBIAD1 gene were detected in six SCCD families, and a potential mutation hot spot was observed at amino acid N102. The mutations are expected to interfere with the function of the UBIAD1 protein, since they are located in highly conserved and structurally important domains.
Topics: Angiopoietin-Like Protein 6; Angiopoietin-like Proteins; Angiopoietins; Arcus Senilis; Biological Factors; Carrier Proteins; Chromosomes, Human, Pair 1; Corneal Dystrophies, Hereditary; DNA Mutational Analysis; Dimethylallyltranstransferase; Female; Genes, Dominant; Humans; Male; Mutation; Pedigree; Phosphotransferases (Alcohol Group Acceptor); Polymerase Chain Reaction; Proteins; Sequence Analysis, DNA; TOR Serine-Threonine Kinases
PubMed: 17962451
DOI: 10.1167/iovs.07-0845 -
Conference Proceedings : ... Annual... 2006Eye disorders among the elderly are a major health problem. With advancing age, the normal function of eye tissues decreases and there is an increased incidence of...
Eye disorders among the elderly are a major health problem. With advancing age, the normal function of eye tissues decreases and there is an increased incidence of ocular pathology. The most common causes of age related eye disorder and visual impairment in the elderly are cataracts, iridocyclitis and corneal haze. Iridocyclitis is an inflammation of the iris (the colored part of the eye), while corneal haze is a complication of refractive surgery characterized by the cloudiness of the normally clear cornea. Computer-based intelligent system for classification of these eye diseases is very useful in diagnostics and disease management. This paper presents a comparison of three classification strategies to classify four kinds of eye data sets (three different kinds of eye diseases and a normal class). Our protocol uses three different kinds of classifiers: artificial neural network, fuzzy classifier and neuro-fuzzy classifier. Features are extracted from these raw images which are then fed to these classifiers. These classifiers are run on a database of 135 subjects using the cross-validation strategy. We demonstrate a sensitivity of more than 85% for these classifiers with the specificity of 100% and results are very promising.
Topics: Analysis of Variance; Arcus Senilis; Cataract; Databases, Factual; Decision Support Techniques; Diagnosis, Computer-Assisted; Eye Diseases; Fuzzy Logic; Glaucoma; Humans; Neural Networks, Computer; Ophthalmology; Reproducibility of Results; Signal Processing, Computer-Assisted; Software
PubMed: 17945937
DOI: 10.1109/IEMBS.2006.260211 -
Postgraduate Medical Journal Mar 2007
Topics: Antihypertensive Agents; Arcus Senilis; Bendroflumethiazide; Female; Humans; Hypercalcemia; Hypertension; Middle Aged
PubMed: 17344567
DOI: 10.1136/pgmj.2007.057141 -
Atherosclerosis Aug 2007Corneal arcus is a lipid-rich and predominantly extracellular deposit that forms at the corneoscleral limbus. It represents the most common peripheral corneal opacity... (Review)
Review
Corneal arcus is a lipid-rich and predominantly extracellular deposit that forms at the corneoscleral limbus. It represents the most common peripheral corneal opacity and is not associated with tissue breakdown but rather with the deposition of lipids. The deposition of cholesterol in the peripheral cornea and arterial wall are similar in that both are accelerated by elevated serum levels of atherogenic lipoproteins, such as low-density lipoproteins (LDL). Corneal arcus is more prevalent in men than in women and in Blacks than in Whites. Its prevalence increases with advancing age. It has been associated with hypercholesterolemia, xanthelasmas, alcohol, blood pressure, cigarette smoking, diabetes, age, and coronary heart disease. Nevertheless, it is not clear whether or not corneal arcus is an independent risk factor for coronary heart disease (CHD). The present systematic review examines the relationship of corneal arcus and CHD to determine if corneal arcus is an independent CHD risk factor. We conclude that there is no consensus that corneal arcus is an independent risk factor. The presence of corneal arcus in a young person should prompt a search for lipid abnormalities. Also, because corneal arcus represents physical evidence of early lipid deposition, its presence suggests the need for aggressive lipid therapy.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arcus Senilis; Coronary Artery Disease; Dyslipidemias; Female; Humans; Male; Middle Aged; Risk Factors
PubMed: 17049531
DOI: 10.1016/j.atherosclerosis.2006.08.060 -
Praxis Aug 2006
Topics: Abdominal Pain; Adult; Arcus Senilis; Combined Modality Therapy; Humans; Hypertriglyceridemia; Male; Prognosis; Risk Factors; Xanthomatosis
PubMed: 16909682
DOI: 10.1024/0369-8394.95.31.1155