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Biomedical subjects

R Carmena

Publications and source records attributed to R Carmena.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Familial hypercholesterolemia: molecular identification and characterization of the first compound homozygote in Spain].

Homozygous familial hypercholestrolemia (FH) is a rare genetic disorder (one in 1 million persons) due to two different mutations in the LDL receptor gene (compound homozygous) or, rarely, to the presence of the same mutation in the two aleles. In these patients the absence of a functional LDL receptor produces extreme elevations of plasma cholesterol levels that need an aggressive and expensive treatment with LDL apheresis or hepatic transplantation. The clinical evolution is poor with early coronary heart disease. Molecular biology techniques allow a genetic diagnosis and a genetic counseling in the affected subjects. We have identified and characterized the first compound homozygous of FH in Spain using the single strand conformational polymorphism (SSCP) analysis. The patient is a 30 years old female, who carried two different mutations in the LDL receptor gene: the G528V and the D280G (a new mutation). These mutations produce significant changes in the aminoacid sequence and could be classified as class 2.

Adult↗
PubMed1998

Influence of genetic variation at the apo A-I gene locus on lipid levels and response to diet in familial hypercholesterolemia.

We have examined the apo AI - 75 (G/A) and apo AI + 83(MspI +/-) polymorphisms at the APOA1 gene locus for associations with plasma lipid levels and response to an NCEP-I diet in 69 (44 women, 25 men) heterozygotes for familial hypercholesterolemia (FH). Subjects were studied at baseline (after consuming for one month a diet with 35%, fat, 10% saturated, and 300 mg/day cholesterol) and after 3 months of an NCEP-I diet. No gender-related differences for any of the lipid variables examined were found and the data were analyzed for men and women combined. For the apo AI - 75 (G/A) polymorphism, there were 51 G/G and 18 G/A subjects. At baseline, G/A subjects showed significantly lower total cholesterol (p = 0.0036), and LDL-C (p = 0.0023), and apo B (p = 0.0209), than G/G individuals, but no differences were found for HDL-C, triglycerides and VLDL-C values. Following the NCEP-I diet these genotype-related differences remained significant for total and LDL-C. The MspI (-) allele at the apo AI + 83 polymorphism was detected in the heterozygous state in five subjects and its presence was not associated with altered baseline lipids nor with dietary response to the NCEP-I diet. Our results suggest that FH subjects carrying the A allele at the apoAI - 75 (G/A) polymorphism have significantly lower total and LDL-C and apo B baseline levels but respond to a low-fat diet with similar reductions in total and LDL-C when compared with homozygotes for the G allele at this polymorphic site.

Adult↗
PubMed1998

A study of insulin resistance using the minimal model in nondiabetic familial combined hyperlipidemic patients.

The presence of insulin resistance in 20 male nondiabetic patients with familial combined hyperlipidemia (FCH) and 20 controls of similar age and body mass index (BMI) was investigated using the minimal model method modified by the administration of insulin and an oral glucose tolerance test. The peripheral sensitivity of insulin, expressed as the insulin sensitivity index (Si), was 1.91+/-1.05 and 2.86+/-1.19 x 10(-4) x min(-1) x mU/L in FCH patients and controls, respectively (P < .01), and the corresponding value for the peripheral utilization of glucose independently of insulin (Sg) was 1.70+/-1.13 in FCH patients and 2.35+/-0.60 x 10(-2) x min(-1) in controls (P < .02). In the FCH group, the Si value correlated significantly (P < .05) with the waist to hip ratio (WHR), plasma triglycerides (TG), free fatty acids (FFA), and the area under the curve of glucose (AUCg) and insulin (AUCi). In the control group, the correlation also reached statistical significance (P < .05) with age, BMI, WHR, blood pressure, TG, AUCg, and AUCi. Subgrouping the subjects with respect to central obesity defined as a WHR of 0.95 or greater, we observed lower Si values in obese and non-obese FCH subjects relative to controls (P < .02). The mean Si value in obese subjects was significantly lower than in non-obese FCH subgroups (1.40+/-0.79 v 2.68+/-0.95 x 10(-4) x min(-1) x mU/L, respectively, P < .01). In conclusion, a higher degree of insulin resistance relative to control values appears to be an integral part of the metabolic derangements observed in FCH, and central-trunk obesity exacerbates the insulin resistance syndrome.

Adult↗
PubMed1998

Genetic variation at the apoA-IV gene locus and response to diet in familial hypercholesterolemia.

Plasma lipid response to dietary fat and cholesterol is, in part, genetically controlled. The apolipoprotein A-IV (apoA-IV protein; APOA4, gene) has been shown to influence the response to dietary changes in normolipidemic individuals. The response to diet in subjects with familial hypercholesterolemia (FH) is also variable, and no studies are available on the influence of APOA4 mutations on dietary response in these subjects. We studied the effect of 2 common apoA-IV genetic variants (Gln360-->His and Thr347-->Ser) on the lipid response to the National Cholesterol Education Program type I (NCEP-I) diet in 67 FH heterozygotes (43 women and 24 men). Subjects were studied at baseline (after consuming for 1 month a diet with 35% fat [10% saturated] and 300 mg/d cholesterol) and after 3 months of consuming a low-fat diet. No sex-related differences were found, and results were combined for men and women. The APOA4-360 mutation was assessed in 67 subjects, 51 with genotype 1/1 and 16 with genotype 1/2. The APOA4-2 allele was associated with marginally significantly lower (P=0.049) low density lipoprotein (LDL) cholesterol levels and significantly lower (P=0.027) apoB levels independent of diet effects. After consuming an NCEP-I diet, carriers of the APOA4-2 allele showed a significantly lower reduction in apoB concentration (6.2%) than 1/1 subjects (14.1%; P=0.036); however, no significant differences in response were noted for LDL cholesterol. The APOA4-347 mutation was assessed in 63 individuals, 44 with the A/A allele and 19 with the A/T and T/T alleles. No significant differences were observed in baseline or post-NCEP-I diet values for these 2 groups in total, LDL, and high density lipoprotein cholesterol and plasma apoB levels. After dietary intervention, A/A individuals showed significant reductions in plasma triglyceride and very low density lipoprotein cholesterol levels; no changes were found in carriers of the T allele. Haplotype analysis suggested that in these FH subjects, the APOA4-360-2 allele was associated with lower plasma lipid levels during the NCEP-I diet period, whereas no significant effects were observed for the APOA4-347-T allele.

Adult↗
PubMed1998

[Psoas abscess secondary to lumbar spondylodiscitis caused by gram negative bacilli].

The association between psoas abscess and lumbar spondylodiscitis by Gram negative bacilli represents a rare clinical entity. Sometimes the absence of demonstrative symptoms complicates the diagnostic schema. We report about a 72 year-old woman, without previous known diabetes mellitus, who was admitted because of fever of one week duration and a non-ketotic hyperosmolar coma. A left psoas abscess was identified by abdominal computed tomography (CT). The abscess was in communication with the L1-L2 intervertebral space. Although Escherichia coli was identified as the causing agent and appropriate antibiotic therapy was administered, the resolution of the abscess occurred only after the implantation of a percutaneous catheter guided by CT without additional surgery. Percutaneous drainage as a diagnostic-therapeutic technique has rendered the surgery as the last resort in the treatment of psoas abscess.

Aged↗
PubMed1997

Insulin resistance in patients with familial combined hyperlipidemia and coronary artery disease.

The minimum model modified by the administration of insulin provides an objective and relatively easily measured index of peripheral sensitivity to insulin which was significantly lower (p <0.02) in familial combined hyperlipidemia (FCH) with ischemic heart disease (IHD) than in FCH without IHD and in control subjects (1.2 +/- 0.6, 1.9 +/- 1.0, 2.9 +/- 1.2 x 10(-4) mU/L/ min, respectively). In patients with FCH, insulin resistance explains, at least in part, their metabolic alterations (hypertension, abnormal glucose tolerance, hyperinsulinemia) and elevated IHD.

Blood Glucose↗
PubMed1997

[Changes in insulin secretion in familial combined hyperlipemia].

BACKGROUND: We have studied the abnormalities in glucose and insulin metabolism in a group of nondiabetic subjects with familial combined hyperlipidemia (FCH) in order to ascertain the contribution of metabolic risk factors to the elevated coronary heart disease incidence observed in FCH. PATIENTS AND METHODS: The study includes 42 non-diabetic subjects (25 male and 17 women, mean age 49.1 +/- 9.3 years), diagnosed with FCH by clinical and analytical studies of the probands and first degree relatives. Forty two control subjects of similar age, sex and body weight were also studied. In both groups plasma lipids and lipoproteins, plasma glucose and insulin basal and after oral glucose tolerance test (OGTT) were studied. RESULTS: The mean age, BMI and the separation by gender was similar in the two groups. The mean systolic and diastolic blood pressures were higher (p < 0.01) in the FCH group compared with controls (145.4/90.1 and 131.5/76.3 mmHg, respectively). The levels of lipids and apo B were also higher in the FCH group. The plasma glucose values were significantly higher at 30, 60, 90 and 120 minutes during OGTT and the plasma insulin at 0, 60, 90 and 120 minutes of OGTT in FCH respect to controls. The area under the curve of the secretion of insulin was 11652.0 +/- 2281.1 and 7205.4 +/- 2289.1 pmol/l/min in FCH and controls (p < 0.01), respectively. The percentage of subjects with basal hyperinsulinemia was 66.6% in the FCH group and 9.5% in the controls (p < 0.01); at 2 hours OGTT, 78.5% and 9.5% in FCH and controls, respectively (p <0.01). The insulin secretion was significantly related with the plasma triglycerides levels, cholesterol bourded to very low density lipoproteins and systolic and diastolic blood pressure. CONCLUSIONS: Hyperinsulinism is a frequent finding in non-diabetic subjects with FCH, both with normal and abnormal glucose tolerance and could contribute to the high incidence of cardiovascular risk in these patients.

Adult↗
PubMed1997

Influence of obesity on plasma lipoproteins, glycaemia and insulinaemia in patients with familial combined hyperlipidaemia.

The influence of obesity on blood pressure and plasma lipoproteins, glucose and insulin levels was investigated in patients with familial combined hyperlipidaemia (FCH). Sixty seven FCH patients mean age 49.0 +/- 8.9 y (45 male, 22 female) defined as obese (BMI > or = 27 kg/m2, n = 39) or non-obese (BMI < 27 kg/m2, n = 28) were compared with control subjects matched for age, gender and body weight. Blood pressure, plasma lipoproteins, glucose and insulin were measured at baseline and following standard oral glucose load. The analysis indicate that FCH subjects with BMI > or = 27 kg/m2 had significantly higher systolic and diastolic blood pressure, blood glucose and insulin levels following oral glucose tolerance test than those with BMI < 27 kg/m2. Fasting plasma insulin values were also significantly higher in the BMI > or = 27kg/m2 subjects (138.5 +/- 66.6 vs 111.0 +/- 29.9 pmol/l, respectively, P < 0.05). Quantification of the area under the curve of the insulin secretion showed hyperinsulinaemia in 64.1% of patients with BMI > or = 27kg/m2 compared to 28.5% in the group with BMI < 27 kg/m2 (P < 0.01). Plasma insulin values were positively related to triglyceridaemia. There were no differences in the plasma lipid values between the two FCH groups. We conclude that fasting and post-glucose stimulated plasma insulin levels are frequent findings in patients with FCH when compared with control subjects of similar age, gender and BMI. Moreover, obesity (BMI > or = 27kg/m2) exacerbates the hyperglycaemia, hyperinsulinaemia and blood pressure values in these FCH subjects. These factors, together with lipid abnormalities, can predispose to the elevated risk of cardiovascular disease observed in FCH subjects.

Adult↗
PubMed1997

Hyperinsulinemia as a determinant of microalbuminuria in essential hypertension.

OBJECTIVE: To analyze the relationship between insulinemia and urinary albumin excretion in a group of nonobese, young adult hypertensive patients, who had never been treated with antihypertensive drugs. PATIENTS AND METHODS: Forty-nine patients who fulfilled the inclusion criteria were included. Twenty-four-hour ambulatory blood pressure monitorings, urinary albumin excretion (UAE) measurements, and an oral glucose-tolerance test measuring glucose and insulin, were performed, and left ventricular mass was measured by echocardiography. Hypertensive patients were classified as normoalbuminuric when their UAE was < 30 mg/24 h (40 patients; mean UAE 13.4 +/- 7.0 mg/24 h), and as microalbuminuric when their UAE was 30-300 mg/24 h (nine patients; mean UAE 90.5 +/- 86.6 mg/24 h). RESULTS: In comparison with that of the normoalbuminuric group, the fasting plasma glucose concentration for the microalbuminuric group was only slightly higher (100 +/- 9 versus 95 +/- 8 mg/dl, NS). In contrast, the fasting insulin concentration in the microalbuminuric group was significantly higher than that observed in the normoalbuminuric group (25.2 +/- 6.7 versus 16.6 +/- 5.2 microU/ml, P<0.0001). During the oral glucose-tolerance test, the area under the curve (AUC) for glucose (317 +/- 41 versus 253 +/- 53 mg/dl x 2/h, P<0.001) and the AUC for insulin (253 +/- 171 versus 124 +/- 43 microU/ml x 2/h, P<0.001) were significantly higher in the microalbuminuric group than were those AUC observed in the normoalbuminuric group. After adjustments for age, sex, body mass index and average 24 h ambulatory mean blood pressure were made, the fasting insulin level was associated independently with an increase in UAE in a multiple regression model with base 10 logarithm of the UAE as the dependent variable. Variations in fasting insulin level alone accounted for 33% of the UAE variance. In contrast, the 24 h ambulatory mean blood pressure, rather than the insulin level, was the strongest predictor of the left ventricular mass index. CONCLUSIONS: Mild hypertensive patients with microalbuminuria were hyperinsulinemic in the absence of obesity, and their insulin level was the main determinant of microalbuminuria in these patients. Microalbuminuria in essential hypertension seems to identify patients with a cluster of cardiovascular risk factors and a bad risk profile. Thus, assessment of microalbuminuria may be useful in the stratification of risk in essential hypertension.

Adult↗
PubMed1997

Modulatory effect of erythrocytes on the platelet reactivity to collagen in IDDM patients.

Platelets participate in the atherothrombotic complications of diabetes. Recent data demonstrate that platelet reactivity can be modulated via cell-cell interactions with erythrocytes and neutrophils. In this study, platelet reactivity was evaluated in 30 IDDM patients. We used an analytical procedure that permits an independent evaluation of platelet activation (granule release, eicosanoid formation) and platelet recruitment (pro-aggregatory activity of cell-free releasates) after platelet stimulation with collagen in the presence or absence of other blood cells. The interaction between platelets and erythrocytes (hematocrit 40%) resulted in a marked enhancement of platelet activation (5HT, betaTG, TXA2 release) and recruitment in both patients and control subjects. The erythrocyte enhancement of platelet TXA2 synthesis and recruitment was significantly higher in the patients, while no differences were detected in platelet granule release. The elevated platelet recruitment in the IDDM patients was found to be due to 1) increased susceptibility of diabetic platelets to the prothrombotic effect of erythrocytes and 2) the greater response of diabetic platelets to their own cell-free releasate. Patients with poor metabolic control (elevated HbA1c) or longer evolution time had an even greater platelet recruitment. The presence of microalbuminuria is not related to the platelet recruitment. Since platelet recruitment is an essential step in thrombus growth, its enhancement may favor thrombotic complications in IDDM.

Adolescent↗
PubMed1997

[Hypertriglyceridemia and plasma insulin in combined familial hyperlipidemia].

UNLABELLED: Changes in insulin secretion were investigated in a group of non obese subjects with combined familial hyperlipidemia (CFH), with normal glucose tolerance, relating the observed changes with plasma triglycerides and lipoprotein phenotype. MATERIALS AND METHODS: The study was conducted with 21 subjects (16 males and 5 females; mean age: 45.9 +/- 9.1 years), diagnosed of CFH after the clinical and analytical study of patients and their first degree relatives (9 with phenotype IIa, 8 IIb, and 4 IV) and 21 healthy control subjects, of similar age, sex and body weight. In both groups, lipids, plasma lipoproteins, glucose, basal plasma insulin, and insulin after and oral glucose overload (OGO) were quantitated. RESULTS: Diastolic blood pressure was higher (p < 0.01) in CFH group compared with controls (means: 132/80 vs 123/71 mmHg, respectively). TC, TG and Apo B were also higher in the CFH group. With OGO significantly higher serum insulin levels were observed at 0, 30, 60, 90 and 120 minutes in CFH subjects compared with control group. Basal serum insulin and the area under the curve of insulin secretion after OGO was higher in subjects with triglycerides (45,579 +/- 13,056 in controls, 61,385 +/- 22,254 in CFH IIa, 70,645 +/- 17,271 IIb and 124,884 +/- 36,944 in CFH IV. Insulin secretion correlated significantly (p < 0.01) with plasma triglycerides. As conclusion, hyperinsulinism is a finding in CFH non obese subjects and with normal glucose tolerance, and has an increasing frequency in subjects with high triglycerides levels.

Adult↗
PubMed1996

Effect of olive and sunflower oils on low density lipoprotein level, composition, size, oxidation and interaction with arterial proteoglycans.

The atherogenicity of low density lipoproteins (LDL) may be modulated by its serum levels, structure and affinity for components of the intima, all properties that can be altered by diet. Linoleic acid-rich diets (n-G, 18:2) reduce the levels of LDL whereas those rich in oleic (n-9,18:1) are considered 'neutral'. However, LDL enriched in linoleic acid have been reported to be more vulnerable to free radical-mediated oxidation than those enriched in oleic, a potentially atherogenic property. The effect of dietary fats on other properties of LDL that may also modulate atherogenesis, such as size and capacity to interact with intima components, are not well established. We explored here how a change from an olive oil-rich diet (OO) to a sunflower oil-rich one (SFO) affects these parameters in a community with a traditional Mediterranean diet. Eighteen free-living volunteers were placed for 3 weeks on a diet with 31% of caloric intake as sunflower oil and then shifted for an additional 3 weeks to a diet in which OO provided 30.5% of the calories. The LDL after SFO had a fatty acids ratio of (18:2 + 18:3 + 20:4) to (16:0 + 16:1 + 18:0 + 18:1) of 1.06 +/- 0.11 compared to 0.73 +/- 0.06 after the OO period. Serum LDL was significantly lower after SFO than after OO. Unexpectedly, copper-catalyzed oxidation of LDL from the SFO period was significantly less than that of the particles from the OO period. The resistance to oxidation of LDL of the SFO and OO period related to alterations in content of the antioxidants alpha-tocopherol, beta-carotene and retinol, in addition to changes in size and fatty acids composition. In vitro binding of LDL to human arterial proteoglycans was also significantly lower for the SFO-LDL than the OO-LDL, a result that can also be attributed to the larger size of the SFO-LDL. Therefore, three properties of LDL: circulating levels, oxidizability, and affinity with intima proteoglycans, that may modulate its atherogenicity, were shifted in a favorable direction by diets rich in linoleic acid and natural antioxidants.

Adult↗
PubMed1996

Erythrocyte membrane cholesterol/phospholipid changes and hemorheological modifications in familial hypercholesterolemia treated with lovastatin.

Fourteen patients with familial hypercholesterolemia treated with lovastatin (40 mg/day) for three months were studied to find out whether the expected changes in plasma lipids are accompanied by modifications in the lipid composition of the erythrocyte membrane and whether these in turn induce changes in the rheological behavior of the red blood cell. Our results demonstrate the efficacy of lovastatin in reducing the plasma concentration of cholesterol and LDL cholesterol. The changes observed in the plasma lipids correlate with a significant decrease in the cholesterol/phospholipid ratio of the red blood cell membrane, from 1.19 +/- 0.19 in a basal situation to 0.92 +/- 0.23 (p < 0.01) at the end of treatment. These changes in the lipid composition of the cell are statistically related to a decrease in erythrocyte aggregability and an improvement in blood filterability, which means beneficial change in the patients' hemorheological situation.

Adult↗
PubMed1996

Seven DNA polymorphisms in the LDL receptor gene: application to the study of familial hypercholesterolemia in Spain.

We have performed restriction fragment length polymorphism (RFLP) analysis at the low density lipoprotein receptor (LDLR) locus in order to investigate the molecular genetics of familial hypercholesterolemia (FH) in Spain. Firstly, a sample of 50 unrelated patients with a clinical diagnosis of FH was screened for the presence of major rearrangements at this locus by Southern blot analysis of BglII digested genomic DNA. Four different mutations were detected, accounting for 8% of the mutant alleles in the Spanish FH sample. Then, we determined the relative allele frequency and estimated linkage disequilibrium between seven RFLPs of the LDLR gene in the remaining 46 FH patients and in 61 normolipidemic controls. HincII, AvaII, PvuII, MspI, and NcoI are the most polymorphic sites with individual PIC values higher than 0.28, whereas the TaqI and StuI sites display low levels of polymorphism. The usefulness of the seven RFLPs to confirm a clinical diagnosis of FH was investigated in 15 FH-families, consisting of 118 individuals, in whom the presence of Familial Defective Apolipoprotein B-100 (FDB) due to the apoB3500 mutation was excluded. Independent haplotypes were constructed for 71 chromosomes: 15 FH and 56 control haplotypes. A total of 14 different haplotypes was found. In 12 families, clinical diagnosis of FH was confirmed by cosegregation analysis, which makes these RFLPs useful for studying the inheritance of the LDLR gene in 80% of Spanish families with FH. Comparison of haplotypes found in the Spanish sample with those found in Swiss and Norwegians suggests heterogeneity of haplotypes among European populations.

Bacterial Proteins↗
PubMed1996

Effect of HMG-CoA reductase inhibitors on red blood cell membrane lipids and haemorheological parameters, in patients affected by familial hypercholesterolemia.

Eighteen patients with familial hypercholesterolemia treated with lovastatin (40 mg/day) for three months were studied to find out whether the drug induces modifications in the lipid composition of the erythrocyte membrane and whether these induce changes in the rheological behaviour of the red blood cell. Our results show that the changes observed in plasma lipids correlate with a significant decrease in the cholesterol/phospholipid ratio of the red blood cell membrane. These changes in the lipid composition of the cell are statistically related to a decrease in the erythrocyte aggregability and an improvement in blood filterability probably due to an increase in the red blood cell deformability.

Adult↗
PubMed1996

Lp(a) levels and atherosclerotic vascular disease in a sample of patients with familial hypercholesterolemia sharing the same gene defect.

There is considerable variation in the severity of cardiovascular disease among patients with familial hypercholesterolemia (FH). Some reports have suggested that plasma lipoprotein(a) [Lp(a)] levels may explain such variation and that FH subjects deficient in LDL receptors, especially those with coronary heart disease, tend to have elevated Lp(a) levels. We have investigated the possible role of the LDL receptor in determining plasma Lp(a) levels in genetically homogeneous FH population and the contribution of Lp(a) to cardiovascular risk. A total of 98 FH subjects and 66 healthy first- and second-degree relatives from 30 families with FH due to the French-Canadian > 10-kilobase deletion of the LDL receptor gene were studied. A reference group of 392 normolipidemic French-Canadian participants in a Heart Health Survey was used for comparison. FH subjects were subdivided into subsets of 63 individuals free from atherosclerotic vascular disease (AVD) and 35 individuals with AVD. A complete cardiovascular evaluation was performed, and plasma lipid, lipoprotein, and Lp(a) levels were measured in all subjects in the absence of medication. Apolipoprotein (a) [apo(a)] phenotype was determined in 112 of FH and non-FH subjects. The log-transformed values for plasma Lp(a) were not significantly different among the three groups: 0.98 +/- 0.54 (mean +/- SD) in FH subjects with AVD, 0.89 +/- 0.51 in FH subjects without AVD, and 0.82 +/- 0.64 in their relatives. The distribution of the apo(a) phenotypes did not differ between the FH and non-FH groups. Comparison of two age- and sex-matched subgroups of FH subjects, with and without AVD, failed to show any differences in Lp(a) level. However, mean Lp(a) log values in the reference group (n = 392) were significantly lower than values obtained for the total FH group (0.79 +/- 0.57 versus 0.92 +/- 0.52, respectively; P < .05) but were not different from those of the unaffected family members. Thus, in our sample, the LDL receptor appears not to influence plasma Lp(a) levels; rather, these levels reflect shared apo(a) genes. The cardiovascular risk in this group of subjects with FH was related to age, male sex, total and LDL cholesterol, and higher apoB but not Lp(a) levels.

Adolescent↗