RESUMEN
BACKGROUND: Family tracing is a method recognized to find new patients with familial hypercholesterolaemia (FH). We have implemented family tracing led by FH Nurses and have determined acceptability to patients, feasibility and costs. METHODS: Nurses were located at five National Health Service (NHS) Trusts; they identified FH patients and offered them family tracing. Responses and test results were recorded on a database and summarized on a family pedigree. RESULTS: The majority ( approximately 70%) of index cases participated; the proportion was lower when patients had been discharged from the clinics and in metropolitan areas. On average, 34% (range 13-50%) of relatives lived outside the catchment area of the clinics and could not attend the nurse-led FH clinics. Of the previously untested relatives, 76% who lived in the catchment area of the clinic came forward to be tested. One-third of the relatives who came forward for testing were children Asunto(s)
Hiperlipoproteinemia Tipo II/diagnóstico
, Tamizaje Masivo/economía
, Tamizaje Masivo/métodos
, Auditoría Médica/economía
, Auditoría Médica/métodos
, Proyectos Piloto
, Adolescente
, Adulto
, Niño
, Preescolar
, Análisis Costo-Beneficio
, Femenino
, Humanos
, Hiperlipoproteinemia Tipo II/epidemiología
, Masculino
, Persona de Mediana Edad
, Linaje
, Reino Unido
, Adulto Joven
RESUMEN
BACKGROUND: Familial hypercholesterolaemia (FH) is an autosomal co-dominant disorder which is relatively common, leads to high levels of LDL-cholesterol and if untreated to early coronary heart disease. An audit of current practice at National Health Service Trusts in England was undertaken to determine whether FH patients meet the diagnostic criteria for FH; are being offered appropriate advice and treatment; and to what extent their families are contacted and offered testing for the disorder. METHODS: Medical records of known FH patients (over 18 years of age and diagnosed before 31 December 2003) were accessed to obtain information on diagnosis, treatment and family tracing. RESULTS: The records of 733 FH patients were examined, 79% met the UK 'Simon Broome' register criteria for the diagnosis of definite or possible FH. Analyses showed that patients were usually offered appropriate advice and treatment, with 89% being on a statin. However, the audit indicated a high variability in family tracing between the sites, with significant differences in the frequency of inclusion of a family pedigree in the notes (range 1-71%, mean 35%); the general practitioner (GP) being advised that first-degree relatives should be tested (range 4-52%, mean 27%); and the proportion of relatives contacted and tested (range 6-50%, mean 32%). CONCLUSION: FH patients are well cared for in lipid clinics in England, are being given appropriate lifestyle advice and medication, but an increase in recording of LDL-cholesterol levels may lead to improvements in their management. Practice in family tracing appears to vary widely between clinics.
Asunto(s)
Hiperlipoproteinemia Tipo II/diagnóstico , Auditoría Médica , Instituciones de Atención Ambulatoria , LDL-Colesterol/sangre , Inglaterra , Femenino , Humanos , Hiperlipoproteinemia Tipo II/epidemiología , Hiperlipoproteinemia Tipo II/terapia , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto , Médicos de FamiliaRESUMEN
BACKGROUND: The effect of high concentrations of protein or lipid on the measurement of plasma sodium by indirect ion selective electrode (ISE) causing pseudohyponatraemia and pseudonormonatraemia is well described. The effect of a low total protein concentration, however, has not been described. METHODS: In order to examine this, over a 2-week period the total protein concentration was measured on all samples received for urea and electrolyte measurement. All samples with a low (<50 g/L) or a high (> 80 g/L) total protein concentration had sodium measured by both direct and indirect ISE. RESULTS: There were approximately equal numbers of samples with a protein concentration less than 50 g/L (1.3%) as samples with a protein concentration greater than 80 g/L (1.3%). The frequency of erroneous sodium results owing to the use of an indirect ISE was less in hypoproteinaemic (2%) than in hyperproteinaemic (20%) samples.
Asunto(s)
Proteínas Sanguíneas/metabolismo , Hipernatremia/metabolismo , Sodio/sangre , Humanos , Electrodos de Iones SelectosRESUMEN
While it is well established that the fatty acid composition of dietary fat is important in determining plasma lipoprotein cholesterol concentrations, the effects of changing the absolute quantities of the individual fatty acids are less clear. In the present study Golden Syrian hamsters were fed on isoenergetic, low cholesterol (0.05 g/kg) diets containing 100, 150 or 200 g added fat/kg. This consisted of triolein (TO) alone, or equal proportions of TO and either trimyristin (TM), tripalmitin (TP) or tristearin (TS). Each trial also included a control group fed on a diet containing 50 g TO/kg. As the mass of TO in the diet increased, plasma VLDL-cholesterol concentrations rose. The TM-rich diets produced a concentration-dependent increase in total plasma cholesterol which was a result of significant increases in both VLDL and HDL levels. The TP-rich diets increased plasma LDL- and HDL-cholesterol levels in a concentration-dependent manner. TS-containing diets did not increase the cholesterol content of any of the major lipoprotein fractions. Hepatic LDL-receptor mRNA concentrations were significantly decreased in animals fed on TP, while apolipoprotein B mRNA concentrations were significantly increased. Thus, on a low-cholesterol diet, increasing the absolute amount of dietary palmitic acid increases LDL-cholesterol more than either myristic or stearic acid. These effects on lipoprotein metabolism may be exerted through specific modulation of the expression of the LDL receptor and apolipoprotein B genes.
Asunto(s)
Colesterol/sangre , Dieta , Ácidos Grasos/administración & dosificación , Lipoproteínas/metabolismo , Hígado/metabolismo , Animales , Apolipoproteínas B/genética , HDL-Colesterol/sangre , LDL-Colesterol/sangre , VLDL-Colesterol/sangre , Cricetinae , Ácidos Grasos/metabolismo , Masculino , Mesocricetus , ARN Mensajero/análisis , Receptores de LDL/genética , Triglicéridos/administración & dosificación , Triglicéridos/metabolismo , Trioleína/administración & dosificaciónRESUMEN
This study investigates the reliability of glycated haemoglobin, measured by electroendosmosis or by affinity chromatography, fructosamine, and albumin adjusted fructosamine, as indices of glycaemic control in Type 1 diabetes complicated by chronic renal failure. Twenty uraemic diabetic patients took part in the study, including 5 patients managed conservatively, 6 on CAPD, 3 on haemodialysis, and 6 renal transplant recipients. Results were compared with those from 15 diabetic subjects with normal renal function. In renal patients, there was significant correlation between glycated haemoglobin measured by electroendosmosis (r = 0.45; p = 0.04) or by affinity chromatography (r = 0.57; p = 0.01) and mean capillary blood glucose concentrations over the previous 6 weeks. The regression equations did not differ significantly between subjects with renal failure and those with normal renal function, suggesting that similar ranges can be used in interpreting glycated haemoglobin results from each group of patients. Patients on haemodialysis may be an exception; there was evidence that glycated haemoglobin may be misleadingly low in such subjects. Fructosamine correlated significantly with mean blood glucose concentrations measured over the previous week in patients with normal renal function (r = 0.75; p = 0.001), but not in patients with chronic renal failure (r = -0.1; p = 0.71). Calculation of an albumin adjusted fructosamine result failed to improve the correlation with blood glucose concentrations. The use of fructosamine cannot be recommended as an index of glycaemic control in uraemic patients.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 1/sangre , Nefropatías Diabéticas/sangre , Fructosamina/sangre , Hemoglobina Glucada/metabolismo , Fallo Renal Crónico/sangre , Cromatografía de Afinidad , Diabetes Mellitus Tipo 1/complicaciones , Electroforesis en Gel de Agar , Humanos , Fallo Renal Crónico/etiología , Análisis de RegresiónRESUMEN
Platelet-derived growth factor (PDGF) is implicated in the accumulation of smooth muscle cells in atherosclerotic lesions following monocyte migration through the vascular endothelium. We show here a 15- to 20-fold increase in expression of PDGF-A and -B genes (as measured by a quantitative reverse transcription-polymerase chain reaction assay of mRNA concentration) in circulating monocytes of hypercholesterolemic and hyperlipidemic patients compared with normocholesterolemic individuals. Strong positive correlations between PDGF-A and -B mRNA concentrations indicate that the two genes are coordinately regulated in mononuclear cells in both normal and hypercholesterolemic individuals. PDGF gene expression in patients correlates with concentrations of plasma total cholesterol and low-density lipoprotein cholesterol, a proven risk factor for atherosclerosis. Activation of monocyte PDGF expression may be an important component of the atherosclerotic risk associated with raised cholesterol levels and may represent an essential step in the early stages of atherogenesis. However, the marked increases in PDGF mRNA levels in patients with modest hypercholesterolemia compared with normal subjects suggest that other factors are involved. The relationship of monocyte PDGF expression to other atherosclerotic risk factors and to the different stages of atherosclerosis needs to be carefully evaluated.
Asunto(s)
Regulación de la Expresión Génica , Hipercolesterolemia/metabolismo , Leucocitos Mononucleares/metabolismo , Factor de Crecimiento Derivado de Plaquetas/genética , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factor de Crecimiento Derivado de Plaquetas/análisis , ARN Mensajero/análisis , Receptores de LDL/genéticaRESUMEN
Different dietary fatty acids exert specific effects on plasma lipids but the mechanism by which this occurs is unknown. Hamsters were fed on low-cholesterol diets containing triacylglycerols enriched in specific saturated fatty acids, and effects on plasma lipids and the expression of genes involved in hepatic lipoprotein metabolism were measured. Trimyristin and tripalmitin caused significant rises in low-density lipoprotein (LDL) cholesterol which were accompanied by significant reductions in hepatic LDL receptor mRNA levels. Tripalmitin also increased hepatic expression of the apolipoprotein B gene, implying an increased production of LDL via very-low-density lipoprotein (VLDL) and decreased removal of LDL in animals fed this fat. Hepatic levels of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA did not vary significantly between the groups. Compared with triolein, tristearin had little effect on hepatic gene expression or total plasma cholesterol. However, it caused a marked decrease in VLDL cholesterol and a rise in LDL cholesterol such that overall it appeared to be neutral. Lipid analysis suggested a rapid desaturation of much of the dietary stearate. The differential changes in plasma lipids and hepatic mRNA levels induced by specific dietary fats suggests a role for fatty acids or a metabolite thereof in the regulation of the expression of genes involved in lipoprotein metabolism.
Asunto(s)
Apolipoproteínas B/genética , Grasas de la Dieta/farmacología , Hidroximetilglutaril-CoA Reductasas/genética , Lipoproteínas/sangre , Hígado/metabolismo , Receptores de LDL/genética , Tejido Adiposo/metabolismo , Animales , Secuencia de Bases , Colesterol/sangre , Cricetinae , Grasas de la Dieta/administración & dosificación , Ácidos Grasos/administración & dosificación , Ácidos Grasos/metabolismo , Masculino , Mesocricetus , Datos de Secuencia Molecular , ARN Mensajero/metabolismo , Triglicéridos/administración & dosificación , Triglicéridos/sangre , Triglicéridos/metabolismo , Triglicéridos/farmacologíaAsunto(s)
Hidroximetilglutaril-CoA Reductasas/biosíntesis , Hipercolesterolemia/enzimología , Hiperlipidemias/enzimología , Leucocitos Mononucleares/enzimología , ARN Mensajero/sangre , Humanos , Hidroximetilglutaril-CoA Reductasas/sangre , Hipercolesterolemia/sangre , Hipercolesterolemia/genética , Hiperlipidemias/sangre , Hiperlipidemias/genética , Lipoproteínas/sangre , Reacción en Cadena de la Polimerasa/métodos , Valores de ReferenciaRESUMEN
Fifteen premenopausal women were studied before and 6 weeks after receiving subcutaneous implants of 100 mg estradiol. Serum estradiol levels doubled; increases were also seen in fasting serum total cholesterol and in high-density lipoprotein cholesterol (HDL). This increase was confined to the HDL2 subfraction, and was not reflected in the HDL apolipoproteins. Low density lipoprotein (LDL) cholesterol levels were unchanged, as were those of apolipoprotein B, the major protein component of LDL. Carbohydrate metabolism was assessed in a subgroup of 12 women. Estrogen implantation reduced fasting plasma glucose levels but did not alter the plasma glucose response to an oral glucose tolerance test. Plasma insulin levels were unchanged both in the fasted state and during the glucose tolerance test. Our findings indicate that parenteral administration of estradiol can alter lipid and carbohydrate metabolism in premenopausal women.
Asunto(s)
Metabolismo de los Hidratos de Carbono , Estradiol/farmacología , Metabolismo de los Lípidos , Adulto , Apolipoproteínas/sangre , Glucemia/metabolismo , Colesterol/sangre , Implantes de Medicamentos , Estradiol/administración & dosificación , Estradiol/uso terapéutico , Femenino , Humanos , Insulina/sangre , Lípidos/sangre , Lipoproteínas/sangre , Persona de Mediana Edad , Síndrome Premenstrual/tratamiento farmacológico , RadioinmunoensayoRESUMEN
Measurements of glycated haemoglobin by electroendosmotic and chromatographic methods, fructosamine, and fructosamine:albumin ratio were made in 91 non-diabetic subjects with chronic renal failure managed conservatively (n = 25), by continuous ambulatory peritoneal dialysis (n = 22), by haemodialysis (n = 22), or by renal transplantation (n = 22). Results were compared with those in a control group of 43 non-diabetic subjects with normal renal function. Mean glycated haemoglobin measured by electroendosmosis was significantly greater in all groups with chronic renal failure except the transplant group. Mean glycated haemoglobin measured by affinity chromatography was not significantly different from controls in any of the groups with chronic renal failure. No difference in mean fructosamine concentration was detected in the transplant or conservatively managed groups compared to controls, but values were significantly lower in the CAPD group, and greater in the haemodialysis group predialysis. Post-haemodialysis samples showed a significant reduction in mean fructosamine concentration when compared with prehaemodialysis samples. Fructosamine:albumin ratios were elevated in all groups of patients with renal failure, with the exception of the transplant group. Of the four indices of glycaemic control considered in this study, only glycated haemoglobin measured by affinity chromatography appears to be unaffected by chronic renal failure.
Asunto(s)
Hemoglobina Glucada/metabolismo , Hexosaminas/sangre , Fallo Renal Crónico/sangre , Adolescente , Adulto , Anciano , Glucemia/metabolismo , Fructosamina , Glicosilación , Humanos , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/terapia , Trasplante de Riñón , Persona de Mediana Edad , Diálisis Peritoneal Ambulatoria Continua , Diálisis RenalRESUMEN
Properties of the acid alpha-glucosidase, GAA2, the product of the GAA*2 allele have been compared with those of the common allele product GAA1, GAA2 has an altered affinity for glycogen but resembles GAA1 in its affinity for low molecular weight substrates, and also in its processing, as judged by immunoblot analysis of the denatured polypeptides. Starch gel electrophoretic analysis of fibroblasts from 15 patients with late onset glycogen storage disease type II (GSDII) failed to reveal either homozygotes or heterozygotes for the GAA*2 allele (GAA2-2 or GAA2-0) providing evidence that neither of these genotypes lead to late onset GSDII despite the impaired activity of the enzyme towards glycogen.
Asunto(s)
Alelos , Enfermedad del Almacenamiento de Glucógeno Tipo II/genética , Lisosomas/enzimología , alfa-Glucosidasas/genética , Línea Celular , Femenino , Fibroblastos , Genotipo , Glucógeno/metabolismo , Enfermedad del Almacenamiento de Glucógeno Tipo II/enzimología , Humanos , Immunoblotting , Masculino , Fenotipo , Especificidad por Sustrato , alfa-Glucosidasas/metabolismoRESUMEN
An inherited metabolic disorder in a strain of New Zealand White rabbits, characterized by marked hypercholesterolemia (394 +/- 100 mg/dl), with moderately elevated or normal triglyceride levels is described. Low density lipoprotein (LDL), intermediate density lipoprotein (IDL) and very low density lipoprotein (VLDL) cholesterol levels were increased. VLDL and IDL, and to a lesser extent LDL, had increased free cholesterol and esterified cholesterol content, and triglyceride content was reduced. Kinetic studies with 131I and 125I-labelled rabbit lipoproteins showed a marked increase in production rates of VLDL apo B and LDL apo B. LDL cholesterol levels were directly related to LDL apo B production rate (r = 0.938, p less than 0.001). Both in hypercholesterolemic and normal rabbits injected with labelled VLDL, the specific activity-time curves of VLDL apo B and LDL apo B did not intersect, indicating that LDL apo B was in part derived from sources other than VLDL. No defect was demonstrated in receptor-mediated catabolism of LDL by cultured skin fibroblasts from hyperlipidemic animals. The fractional catabolic rate of LDL apo B was subnormal, but increased when the expanded LDL apo B pool size was reduced by exchange transfusion; the low fractional catabolism may therefore be attributable, at least in part, to saturation of LDL receptors consequent upon the increased pool size of LDL. The hyperlipidemia in this strain of rabbits may be unique in that the underlying mechanism appears to be overproduction of VLDL and LDL.
Asunto(s)
Hiperlipidemias/veterinaria , Lipoproteínas/biosíntesis , Animales , Aorta/patología , Apolipoproteínas B/metabolismo , Hipercolesterolemia/genética , Hipercolesterolemia/veterinaria , Hiperlipidemias/genética , Lipoproteínas/metabolismo , Tasa de Depuración Metabólica , Conejos , Triglicéridos/sangreRESUMEN
In the rare familial disorder fish-eye disease, hypertriglyceridaemia is associated with elevated levels of very-low-density lipoprotein (VLDL) and enrichment of low-density lipoprotein (LDL) with triglyceride. The kinetic basis of the dyslipoproteinaemia was investigated by studying the metabolism of the apolipoprotein-B moeity of VLDL, intermediate-density lipoprotein (IDL) and LDL in a 68-year-old woman with this condition. The major kinetic abnormality was a pronounced reduction in the rate of fractional conversion of VLDL-B to IDL-B and of IDL-B to LDL-B, suggesting that the dyslipoproteinaemia represents accumulation in plasma of partly degraded products of VLDL metabolism. This kinetic disorder has features in common with type-III hyperlipoproteinaemia. In studies in vitro no defect in the enzyme, activator or substrate components of the lipoprotein lipase or hepatic lipase systems was observed.
Asunto(s)
Oftalmopatías/sangre , Hiperlipoproteinemia Tipo IV/sangre , Lipoproteínas/sangre , Anciano , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Oftalmopatías/complicaciones , Femenino , Humanos , Cinética , Lipoproteínas IDL , Lipoproteínas VLDL/sangre , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
To augment the effectiveness of conventional lipid-lowering treatment, a diet has been evolved combining modified fat content with an increase in vegetable-derived fibre and protein. This was evaluated in 37 hyperlipidaemic and normal ambulant subjects in whom plasma lipid and lipoprotein responses were measured for 4.7-11 months. Mean reductions in plasma cholesterol, triglyceride and low density lipoprotein cholesterol levels were 22, 24 and 25% respectively; there was no significant change in the cholesterol concentrations in high density lipoprotein or in its HDL2 subclass. The effectiveness of the diet in reducing hyperlipidaemia, its influence in optimizing the distribution of cholesterol between plasma lipoprotein classes, and its nutrient composition suggest that it is an advance on existing lipid-lowering dietary patterns.
Asunto(s)
Grasas de la Dieta/administración & dosificación , Hiperlipidemias/dietoterapia , Adulto , Colesterol/sangre , Femenino , Humanos , Lipoproteínas/sangre , Masculino , Persona de Mediana EdadRESUMEN
1. Measurements were made of the maximal low-density lipoprotein (LDL) receptor activities of blood lymphocytes from 81 healthy men with a wide range of plasma LDL cholesterol concentrations (1.45-7.55 mmol/l). 2. Receptor activity was quantified by measuring the degradation of 125I-labelled LDL (10 micrograms of protein/ml) to trichloroacetic acid-soluble material during a 6 h incubation, after derepression of the lymphocytes for 72 h in lipoprotein-deficient medium. 3. No significant correlation existed between LDL receptor activity in vitro and plasma LDL cholesterol concentration in vivo (r = -0.08).
Asunto(s)
Lipoproteínas LDL/sangre , Linfocitos/metabolismo , Receptores de Superficie Celular/metabolismo , Adulto , Colesterol/sangre , LDL-Colesterol , Humanos , Lipoproteínas HDL/sangre , Lipoproteínas VLDL/sangre , Masculino , Persona de Mediana Edad , Receptores de LDLRESUMEN
Aggregation tests were performed on platelet-rich plasma from healthy male volunteers to determine the minimum concentration of adenosine diphosphate (ADP), epinephrine, collagen, or thrombin required to induce secondary aggregation. Platelets were also analyzed for cholesterol and phospholipid, and in some cases their membrane fluidity was determined by fluorescence depolarization of the probe, diphenylhexatriene. Concentrations of the major lipoprotein fractions in the plasma were measured and related to the sensitivity of platelets to the four agonists. Low density lipoprotein (LDL) and total cholesterol concentrations, but not high density lipoproteins (HDL) or very low density lipoproteins (VLDL), were positively correlated with sensitivity to aggregation by epinephrine, but not by other agonists. By arrangement of the lipoprotein concentration into quintiles, the effect of LDL was most striking in the lower two quintiles, where the sensitivity to adrenaline and ADP were much diminished. The middle and upper two quintiles showed a similar sensitivity. Lower platelet cholesterol/phospholipid ratios were also associated with a reduced sensitivity to epinephrine or ADP, but only at the lower end of the range. Membrane microviscosity was correlated negatively with collagen sensitivity and with VLDL cholesterol concentrations, but positively with HDL cholesterol concentrations. Platelet behavior appears, therefore, to be influenced by lipoprotein concentrations within the range found in a healthy population.
Asunto(s)
Lipoproteínas/sangre , Agregación Plaquetaria , Adenosina Difosfato/farmacología , Adulto , Plaquetas/efectos de los fármacos , Colesterol/sangre , Colágeno/farmacología , Epinefrina/farmacología , Humanos , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Lipoproteínas VLDL/sangre , Masculino , Persona de Mediana Edad , Fosfolípidos/sangre , Trombina/farmacologíaRESUMEN
Some epidemiological studies have suggested an inverse relation between serum cholesterol concentration and mortality from cancer. Two hypotheses that might explain such a relation were investigated. To assay potentially deleterious effects of hypocholesterolaemia on cell membranes the lipid content and fluidity of blood mononuclear cells were measured in healthy male volunteers with a wide range of serum cholesterol concentration (3.2-10.0 mmol/l (124-387 mg/100 ml)). Fluidity, unesterified cholesterol content, and the ratio of cholesterol to phospholipid were unrelated to serum cholesterol and to low density lipoprotein cholesterol concentrations. Similar measurements were made on fibroblasts and mononuclear cells incubated with a range of concentrations of low density lipoprotein; fluidity was altered only at extremely low concentrations, suggesting that changes in cell membranes are unlikely to occur at serum cholesterol concentrations attainable by dietary or drug treatment of hyperlipidaemia. In the same population direct relations were confirmed between low density lipoprotein concentration and plasma concentrations of retinol and beta carotene. This is compatible with the suggestion that an association between low cholesterol concentration and cancer may be secondary to a relation between low retinoid concentrations and cancer.