We evaluated the performance of a homogeneous assay for the automated measurement of high-density... more We evaluated the performance of a homogeneous assay for the automated measurement of high-density lipoprotein cholesterol (HDL-C) and compared it with a conventional precipitation technique in the following groups of people: control subjects (group A), clinicallyhealthy elderly (group B), myocardial infarction patients (group C), nephrotic syndrome patients (group D), and liver cirrhosis patients (group E). The performance of the technique was acceptable with respect to precision, accuracy, linearity, and detection limit. Triglycerides up to 40 mmol/L and bilirubin up to 150 mol/L did not cause interferences. Hemoglobin decreased HDL-C measurements. Samples were stable at ؊20°C for up to four months. Bland-Altman plots showed a good agreement between both techniques in the control group but with a progressive divergence in the patient groups B to E. Results indicate limitations of the technique in certain clinical conditions and, coincidentally, the need for reliable calibration materials.
Enfermedad celiaca; Test psicológicos; Signos y síntomas digestivos; Psicología médica; Ansiedad;... more Enfermedad celiaca; Test psicológicos; Signos y síntomas digestivos; Psicología médica; Ansiedad; Depresión Resumen Pacientes con enfermedad celiaca del adulto de reciente diagnóstico fueron evaluados con los test GSRS y PGWBI con el objetivo de valorar las alteraciones psicológicas que presentan, su relación con la sintomatología gastrointestinal y su evolución después de la instauración de dieta sin gluten. Previo asesoramiento nutricional los pacientes iniciaron dieta sin gluten y 6 meses después fueron reevaluados. Las variables cuantitativas se expresan como medianas y percentil 25-75. Resultados: Se incluyeron 21 pacientes, 17 mujeres y 4 hombres, edad 43 años (31-47). La histología fue compatible con lesión Marsh I en 6 casos, Marsh IIIa en 6 y Marsh IIIb en 9.
Disturbances in methyl-carbon metabolism, which result in hyperhomocysteinemia, have been associa... more Disturbances in methyl-carbon metabolism, which result in hyperhomocysteinemia, have been associated with schizophrenia. Homozygosity for the T677 allele of the methylenetetrahydrofolate reductase (MTHFR) gene, which encodes for a thermolabile enzyme associated with hyperhomocysteinemia, has been found to be increased in schizophrenic patients. We have investigated whether plasma homocysteine concentration and the frequency of C677T MTHFR variant were increased in schizophrenic inpatients of a psychiatric hospital (n=210) compared with controls (n=218). There were no significant differences in plasma homocysteine concentrations between the schizophrenia and the control group. The distributions of T allele and TT genotype frequencies were similar in both groups (40% and 15%). These results show that impaired homocysteine metabolism is unlikely in schizophrenia.
Despite the obvious clinical advantages, the measurement of HDL-cholesterol (HDL-C) by reliable a... more Despite the obvious clinical advantages, the measurement of HDL-cholesterol (HDL-C) by reliable and easy-toperform methods is not yet completely free of problems. Several reports have described homogeneous (direct) assays for HDL-C that are readily adaptable to automated analyzers as online procedures (1-3 ). These methods have proved to be effective and inexpensive tools for the routine screening of HDL-C in large populations. However, in a recent article (4 ) we observed that one of these techniques significantly undervalued the concentrations of HDL-C in patients with liver cirrhosis, a condition in which alterations in lipoprotein structure and composition are commonly found (5 ). Although HDL-C is not a clinically important determination in liver cirrhosis, our finding may have consequences for research groups investigating lipoprotein metabolism and its alterations.
Although lipoprotein abnormalities of the nephrotic syndrome are assumed to be related to the pre... more Although lipoprotein abnormalities of the nephrotic syndrome are assumed to be related to the presence of proteinuria, this topic has not been investigated extensively. We measured lipoproteins from 19 nonuremic patients during and after remission of the nephrotic syndrome in an effort to determine the extent of their putative atherogenicity. As expected, disturbances involved primarily the apoprotein B-containing lipoproteins. No patient showed serum lipoprotein(a) [Lp(a)] < 300 mg/L during the acute phase. Lp(a) concentrations correlated significantly with those of apoprotein B, and both values decreased dramatically with the remission of the nephrotic syndrome. Surprisingly, despite the resolution of proteinuria, concentrations of intermediate-density lipoproteins and Lp(a) remained above normal in hypertriglyceridemic patients, suggesting a residual effect of nephrosis in the overall lipoprotein transport. Accumulation of atherogenic remnants should be considered a characteri...
Elevated plasma Lp(a) is an independent risk factor for cardiovascular disease. Unique to Lp(a) i... more Elevated plasma Lp(a) is an independent risk factor for cardiovascular disease. Unique to Lp(a) is the apoprotein, apo(a) which can vary from 250 to 800 kDa in molecular weight. Small isoforms are also associated with the risk of cardiovascular disease. The purpose of this study was to examine the association of Lp(a) concentration, apo(a) size, and Lp(a) lysine-binding site(s) (LBS) function in patients with early onset heart disease, and age-matched controls. Mean values of Lp(a) were significantly higher in the patients than for the age-matched group. The smallest molecular weight isoform for each subject had significantly fewer kringles for the patients than the age-matched controls. There was a significant correlation between LBS activity and kringle number in the single-banded phenotypes of the patients, but not the controls. LBS activity was significantly higher in patients with small isoforms (< or =18 kringles) compared to controls. The odds ratio for coronary artery dis...
There is considerable evidence to suggest that plasma lipoprotein(a) [Lp(a)] concentration is a c... more There is considerable evidence to suggest that plasma lipoprotein(a) [Lp(a)] concentration is a cardiovascular risk factor. Confusing results in epidemiologic studies, however, suggest that the effects of storage should be further investigated. The influence of the assay method, the initial plasma Lp(a) concentration, and the apolipoprotein(a) [apo(a)] genotype are all factors that should be considered. Blood was obtained from 65 survivors of premature myocardial infarction and 95 age-matched controls. The plasma samples were stored in sterile conditions at -70 degrees C for 5 years in the presence of antioxidant and antiproteolytic substances. Plasma Lp(a) was measured by immunoturbidimetry, and apo(a) alleles were determined by pulsed-field gel electrophoresis and Southern blotting. Plasma Lp(a) was significantly higher in patients. The mean kringle number for the smallest isoform was also lower in patients than in controls, but no differences were found in the distribution of the...
There is considerable evidence to suggest that plasma lipoprotein(a) [Lp(a)] concentration is a c... more There is considerable evidence to suggest that plasma lipoprotein(a) [Lp(a)] concentration is a cardiovascular risk factor. Confusing results in epidemiologic studies, however, suggest that the effects of storage should be further investigated. The influence of the assay method, the initial plasma Lp(a) concentration, and the apolipoprotein(a) [apo(a)] genotype are all factors that should be considered. Blood was obtained from 65 survivors of premature myocardial infarction and 95 age-matched controls. The plasma samples were stored in sterile conditions at -70 degrees C for 5 years in the presence of antioxidant and antiproteolytic substances. Plasma Lp(a) was measured by immunoturbidimetry, and apo(a) alleles were determined by pulsed-field gel electrophoresis and Southern blotting. Plasma Lp(a) was significantly higher in patients. The mean kringle number for the smallest isoform was also lower in patients than in controls, but no differences were found in the distribution of the...
Exactly how apolipoprotein a [APO(a)] isoform size affects the degree of cardiovascular risk asso... more Exactly how apolipoprotein a [APO(a)] isoform size affects the degree of cardiovascular risk associated with high lipoprotein a [LP(a)] levels is not fully understood. Using a sodium dodecyl sulfate-agarose APO(a) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; LP(a) phenotyping method, we assessed the role of APO(a) size heterogeneity according to the number of kringle 4 repeats and the differential APO(a) protein expression in 91 male Spanish patients with premature coronary heart disease (CHD) compared with 99 healthy Spanish men. CHD patients had significantly increased median plasma LP(a) levels (0.31 g/L) and a higher percentage of subjects with LP(a) levels of 0.30 g/L or greater (51%) than controls (0.15 g/L and 23%, respectively). Patients with the double-band phenotype had significantly higher plasma LP(a) levels (median 0.37 g/L) compared with those expressing a single-band phenotype (median 0.20 g/L; P =.018) and with their corresponding controls (median 0.15 g/L; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001). The double-band phenotype and LP(a) values of 0.30 g/L or greater had a significant association with CHD (odds ratio [OR] 6.47, 95% confidence interval [CI] 2.51-16.7), stronger than that observed for the entire group (OR 4.19, 95% CI 1.97-8.90). The adjusted OR for the APO(a) protein pattern that equally expressed both isoforms indicates an independent association with premature CHD (OR 3.33; 95% CI 1.08-10.3). These results suggest that APO(a) phenotyping might be used in subjects with hyperlipoproteinemia a as a powerful marker to assess the risk of premature CHD because heterozygous status, mainly when both isoforms are equally expressed, is associated with higher cardiovascular risk.
Clinical and pharmacokinetic data suggest that very low doses of subcutaneous recombinant human e... more Clinical and pharmacokinetic data suggest that very low doses of subcutaneous recombinant human erythropoietin (rHuEPO) may be effective in a preoperative autologous blood deposit program. Fifty-two patients, scheduled for orthopedic surgery, were enrolled in a double-blind and placebo-controlled study. Patients were randomly assigned to the placebo group or to receive 30, 60, or 100 IU per kg of rHuEPO subcutaneously twice a week for 2 weeks before surgery. The dose of rHuEPO that was effective in facilitating the collection of 4 units of blood in the 2 weeks before surgery and that prevented a sharp decrease in hematocrit was determined. Only in patients receiving 100 IU per kg of rHuEPO did the outcome measurements differ significantly from those in the placebo group. With a higher (p &lt; 0.01) cumulative increase in red cell volume during the study period (297 +/- 127 vs. 121 +/- 44 mL), 64 percent of those receiving 100 IU per kg of rHuEPO were able to donate 4 units of blood for autologous use, as compared with 23 percent of the placebo group (p &lt; 0.05). Allogeneic transfusion was avoided, and the preoperative hematocrit and reticulocyte count were significantly higher in the patients receiving 100 IU per kg of rHuEPO (p &lt; 0.05 and p &lt; 0.01, respectively). Subcutaneously administered rHuEPO at a dose of 100 IU per kg twice a week for 2 weeks is effective in facilitating the collection of blood for autologous use and may improve the cost-benefit ratio of blood conservation interventions. Doses &lt; or = 60 IU per kg are ineffective in facilitating such collections in this surgical setting.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2005
It has been suggested that total plasma homocysteine (tHcy) concentrations and methylenetetrahydr... more It has been suggested that total plasma homocysteine (tHcy) concentrations and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms are risk factors for schizophrenia. We conducted a case-control study to investigate whether tHcy levels and MTHFR C677T and A1298C variants are associated with schizophrenia, giving special consideration to confounding factors. Logistic regression analysis showed that neither tHcy nor MTHFR polymorphisms were associated with schizophrenia. Homozygosity for MTHFR C677T was associated with higher tHcy concentrations in control and schizophrenia groups (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01), which was mainly driven by the male group. The A1298C variant did not show any association with tHcy concentrations. In conclusion, these results do not confirm an independent relationship of tHcy and MTHFR genotype with risk of schizophrenia.
Disturbances in methyl-carbon metabolism, which result in hyperhomocysteinemia, have been associa... more Disturbances in methyl-carbon metabolism, which result in hyperhomocysteinemia, have been associated with schizophrenia. Homozygosity for the T677 allele of the methylenetetrahydrofolate reductase (MTHFR) gene, which encodes for a thermolabile enzyme associated with hyperhomocysteinemia, has been found to be increased in schizophrenic patients. We have investigated whether plasma homocysteine concentration and the frequency of C677T MTHFR variant were increased in schizophrenic inpatients of a psychiatric hospital (n=210) compared with controls (n=218). There were no significant differences in plasma homocysteine concentrations between the schizophrenia and the control group. The distributions of T allele and TT genotype frequencies were similar in both groups (40% and 15%). These results show that impaired homocysteine metabolism is unlikely in schizophrenia.
Polymorphisms in human apolipoprotein(a) kringle IV-10 and coronary artery disease: relationship ... more Polymorphisms in human apolipoprotein(a) kringle IV-10 and coronary artery disease: relationship to allele size, plasma lipoprotein(a) concentration, and lysine binding site activity Abstract Elevated plasma levels of lipoprotein(a) [Lp(a)] represent a major independent risk factor for the development of atherosclerosis. The kringle IV type 10 of apolipoprotein(a) [apo(a)] is the primary lysine binding site (LBS) of Lp(a) and is associated with lesion formation in transgenic mice. The purpose of this study was to search for mutations in the apo(a) kringle IV type 10 which could alter the LBS activity of Lp(a) from patients with coronary artery disease. We found the DNA region of kringle IV type 10 of apo(a) to be mutable but relatively well preserved in the Spanish population. We identified a novel mutation which probably leads to a truncated form of apo(a) in a patient heterozygous for the mutation and with low lysine binding activity and low plasma Lp(a) concentration. Two other mutations have been previously identified in humans, the substitutions W81R and M75T. The W81R was not found in our sample, but the M75T mutation was present in 43% of patients with coronary artery disease and 23% of agematched controls. The genotype TT conferred a significant risk for myocardial infarction (odds ratio 2.53). This association was not due to linkage disequilibrium with kringle IV repeats. The M75T polymorphism was not associated with the LBS function of apo(a), but it influenced plasma Lp(a) concentration.
The aim of the present study was to analyze, on a double-blind basis, the relationships between t... more The aim of the present study was to analyze, on a double-blind basis, the relationships between the apolipoprotein(a) (apo(a)) gene and protein size polymorphisms in healthy volunteers (n = 99) and patients with premature myocardial infarction (n = 91). Apo(a) genotypes were determined by pulse-field electrophoresis and phenotypes were separated by sodium dodecyl sulfate-agarose gel electrophoresis. Results showed that phenotyping overestimated apo(a) size with respect to genotyping (mean (SD) = 3.7 (3.4) kringle units; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) in subjects with a double-band genotype, although both measurements were highly correlated (r = 0.83; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). We also observed that the protein band in subjects with a single-band phenotype was related more closely to the smallest allele than to the largest allele band. The correlation of plasma lipoprotein(a) (Lp(a)) concentration was stronger with the phenotype than with the genotype. We hypothesize that post-translational modifications in the apo(a) molecule may be the most plausible explanation for the discrepancies observed. In conclusion, the present study highlights the dissimilarities between phenotyping and genotyping methods for the measurement of apo(a) size and suggests that laboratories should carefully consider these relationships and the transfer of results between such methodologies.
We evaluated the performance of a homogeneous assay for the automated measurement of high-density... more We evaluated the performance of a homogeneous assay for the automated measurement of high-density lipoprotein cholesterol (HDL-C) and compared it with a conventional precipitation technique in the following groups of people: control subjects (group A), clinicallyhealthy elderly (group B), myocardial infarction patients (group C), nephrotic syndrome patients (group D), and liver cirrhosis patients (group E). The performance of the technique was acceptable with respect to precision, accuracy, linearity, and detection limit. Triglycerides up to 40 mmol/L and bilirubin up to 150 mol/L did not cause interferences. Hemoglobin decreased HDL-C measurements. Samples were stable at ؊20°C for up to four months. Bland-Altman plots showed a good agreement between both techniques in the control group but with a progressive divergence in the patient groups B to E. Results indicate limitations of the technique in certain clinical conditions and, coincidentally, the need for reliable calibration materials.
Enfermedad celiaca; Test psicológicos; Signos y síntomas digestivos; Psicología médica; Ansiedad;... more Enfermedad celiaca; Test psicológicos; Signos y síntomas digestivos; Psicología médica; Ansiedad; Depresión Resumen Pacientes con enfermedad celiaca del adulto de reciente diagnóstico fueron evaluados con los test GSRS y PGWBI con el objetivo de valorar las alteraciones psicológicas que presentan, su relación con la sintomatología gastrointestinal y su evolución después de la instauración de dieta sin gluten. Previo asesoramiento nutricional los pacientes iniciaron dieta sin gluten y 6 meses después fueron reevaluados. Las variables cuantitativas se expresan como medianas y percentil 25-75. Resultados: Se incluyeron 21 pacientes, 17 mujeres y 4 hombres, edad 43 años (31-47). La histología fue compatible con lesión Marsh I en 6 casos, Marsh IIIa en 6 y Marsh IIIb en 9.
Disturbances in methyl-carbon metabolism, which result in hyperhomocysteinemia, have been associa... more Disturbances in methyl-carbon metabolism, which result in hyperhomocysteinemia, have been associated with schizophrenia. Homozygosity for the T677 allele of the methylenetetrahydrofolate reductase (MTHFR) gene, which encodes for a thermolabile enzyme associated with hyperhomocysteinemia, has been found to be increased in schizophrenic patients. We have investigated whether plasma homocysteine concentration and the frequency of C677T MTHFR variant were increased in schizophrenic inpatients of a psychiatric hospital (n=210) compared with controls (n=218). There were no significant differences in plasma homocysteine concentrations between the schizophrenia and the control group. The distributions of T allele and TT genotype frequencies were similar in both groups (40% and 15%). These results show that impaired homocysteine metabolism is unlikely in schizophrenia.
Despite the obvious clinical advantages, the measurement of HDL-cholesterol (HDL-C) by reliable a... more Despite the obvious clinical advantages, the measurement of HDL-cholesterol (HDL-C) by reliable and easy-toperform methods is not yet completely free of problems. Several reports have described homogeneous (direct) assays for HDL-C that are readily adaptable to automated analyzers as online procedures (1-3 ). These methods have proved to be effective and inexpensive tools for the routine screening of HDL-C in large populations. However, in a recent article (4 ) we observed that one of these techniques significantly undervalued the concentrations of HDL-C in patients with liver cirrhosis, a condition in which alterations in lipoprotein structure and composition are commonly found (5 ). Although HDL-C is not a clinically important determination in liver cirrhosis, our finding may have consequences for research groups investigating lipoprotein metabolism and its alterations.
Although lipoprotein abnormalities of the nephrotic syndrome are assumed to be related to the pre... more Although lipoprotein abnormalities of the nephrotic syndrome are assumed to be related to the presence of proteinuria, this topic has not been investigated extensively. We measured lipoproteins from 19 nonuremic patients during and after remission of the nephrotic syndrome in an effort to determine the extent of their putative atherogenicity. As expected, disturbances involved primarily the apoprotein B-containing lipoproteins. No patient showed serum lipoprotein(a) [Lp(a)] < 300 mg/L during the acute phase. Lp(a) concentrations correlated significantly with those of apoprotein B, and both values decreased dramatically with the remission of the nephrotic syndrome. Surprisingly, despite the resolution of proteinuria, concentrations of intermediate-density lipoproteins and Lp(a) remained above normal in hypertriglyceridemic patients, suggesting a residual effect of nephrosis in the overall lipoprotein transport. Accumulation of atherogenic remnants should be considered a characteri...
Elevated plasma Lp(a) is an independent risk factor for cardiovascular disease. Unique to Lp(a) i... more Elevated plasma Lp(a) is an independent risk factor for cardiovascular disease. Unique to Lp(a) is the apoprotein, apo(a) which can vary from 250 to 800 kDa in molecular weight. Small isoforms are also associated with the risk of cardiovascular disease. The purpose of this study was to examine the association of Lp(a) concentration, apo(a) size, and Lp(a) lysine-binding site(s) (LBS) function in patients with early onset heart disease, and age-matched controls. Mean values of Lp(a) were significantly higher in the patients than for the age-matched group. The smallest molecular weight isoform for each subject had significantly fewer kringles for the patients than the age-matched controls. There was a significant correlation between LBS activity and kringle number in the single-banded phenotypes of the patients, but not the controls. LBS activity was significantly higher in patients with small isoforms (< or =18 kringles) compared to controls. The odds ratio for coronary artery dis...
There is considerable evidence to suggest that plasma lipoprotein(a) [Lp(a)] concentration is a c... more There is considerable evidence to suggest that plasma lipoprotein(a) [Lp(a)] concentration is a cardiovascular risk factor. Confusing results in epidemiologic studies, however, suggest that the effects of storage should be further investigated. The influence of the assay method, the initial plasma Lp(a) concentration, and the apolipoprotein(a) [apo(a)] genotype are all factors that should be considered. Blood was obtained from 65 survivors of premature myocardial infarction and 95 age-matched controls. The plasma samples were stored in sterile conditions at -70 degrees C for 5 years in the presence of antioxidant and antiproteolytic substances. Plasma Lp(a) was measured by immunoturbidimetry, and apo(a) alleles were determined by pulsed-field gel electrophoresis and Southern blotting. Plasma Lp(a) was significantly higher in patients. The mean kringle number for the smallest isoform was also lower in patients than in controls, but no differences were found in the distribution of the...
There is considerable evidence to suggest that plasma lipoprotein(a) [Lp(a)] concentration is a c... more There is considerable evidence to suggest that plasma lipoprotein(a) [Lp(a)] concentration is a cardiovascular risk factor. Confusing results in epidemiologic studies, however, suggest that the effects of storage should be further investigated. The influence of the assay method, the initial plasma Lp(a) concentration, and the apolipoprotein(a) [apo(a)] genotype are all factors that should be considered. Blood was obtained from 65 survivors of premature myocardial infarction and 95 age-matched controls. The plasma samples were stored in sterile conditions at -70 degrees C for 5 years in the presence of antioxidant and antiproteolytic substances. Plasma Lp(a) was measured by immunoturbidimetry, and apo(a) alleles were determined by pulsed-field gel electrophoresis and Southern blotting. Plasma Lp(a) was significantly higher in patients. The mean kringle number for the smallest isoform was also lower in patients than in controls, but no differences were found in the distribution of the...
Exactly how apolipoprotein a [APO(a)] isoform size affects the degree of cardiovascular risk asso... more Exactly how apolipoprotein a [APO(a)] isoform size affects the degree of cardiovascular risk associated with high lipoprotein a [LP(a)] levels is not fully understood. Using a sodium dodecyl sulfate-agarose APO(a) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; LP(a) phenotyping method, we assessed the role of APO(a) size heterogeneity according to the number of kringle 4 repeats and the differential APO(a) protein expression in 91 male Spanish patients with premature coronary heart disease (CHD) compared with 99 healthy Spanish men. CHD patients had significantly increased median plasma LP(a) levels (0.31 g/L) and a higher percentage of subjects with LP(a) levels of 0.30 g/L or greater (51%) than controls (0.15 g/L and 23%, respectively). Patients with the double-band phenotype had significantly higher plasma LP(a) levels (median 0.37 g/L) compared with those expressing a single-band phenotype (median 0.20 g/L; P =.018) and with their corresponding controls (median 0.15 g/L; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001). The double-band phenotype and LP(a) values of 0.30 g/L or greater had a significant association with CHD (odds ratio [OR] 6.47, 95% confidence interval [CI] 2.51-16.7), stronger than that observed for the entire group (OR 4.19, 95% CI 1.97-8.90). The adjusted OR for the APO(a) protein pattern that equally expressed both isoforms indicates an independent association with premature CHD (OR 3.33; 95% CI 1.08-10.3). These results suggest that APO(a) phenotyping might be used in subjects with hyperlipoproteinemia a as a powerful marker to assess the risk of premature CHD because heterozygous status, mainly when both isoforms are equally expressed, is associated with higher cardiovascular risk.
Clinical and pharmacokinetic data suggest that very low doses of subcutaneous recombinant human e... more Clinical and pharmacokinetic data suggest that very low doses of subcutaneous recombinant human erythropoietin (rHuEPO) may be effective in a preoperative autologous blood deposit program. Fifty-two patients, scheduled for orthopedic surgery, were enrolled in a double-blind and placebo-controlled study. Patients were randomly assigned to the placebo group or to receive 30, 60, or 100 IU per kg of rHuEPO subcutaneously twice a week for 2 weeks before surgery. The dose of rHuEPO that was effective in facilitating the collection of 4 units of blood in the 2 weeks before surgery and that prevented a sharp decrease in hematocrit was determined. Only in patients receiving 100 IU per kg of rHuEPO did the outcome measurements differ significantly from those in the placebo group. With a higher (p &lt; 0.01) cumulative increase in red cell volume during the study period (297 +/- 127 vs. 121 +/- 44 mL), 64 percent of those receiving 100 IU per kg of rHuEPO were able to donate 4 units of blood for autologous use, as compared with 23 percent of the placebo group (p &lt; 0.05). Allogeneic transfusion was avoided, and the preoperative hematocrit and reticulocyte count were significantly higher in the patients receiving 100 IU per kg of rHuEPO (p &lt; 0.05 and p &lt; 0.01, respectively). Subcutaneously administered rHuEPO at a dose of 100 IU per kg twice a week for 2 weeks is effective in facilitating the collection of blood for autologous use and may improve the cost-benefit ratio of blood conservation interventions. Doses &lt; or = 60 IU per kg are ineffective in facilitating such collections in this surgical setting.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2005
It has been suggested that total plasma homocysteine (tHcy) concentrations and methylenetetrahydr... more It has been suggested that total plasma homocysteine (tHcy) concentrations and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms are risk factors for schizophrenia. We conducted a case-control study to investigate whether tHcy levels and MTHFR C677T and A1298C variants are associated with schizophrenia, giving special consideration to confounding factors. Logistic regression analysis showed that neither tHcy nor MTHFR polymorphisms were associated with schizophrenia. Homozygosity for MTHFR C677T was associated with higher tHcy concentrations in control and schizophrenia groups (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01), which was mainly driven by the male group. The A1298C variant did not show any association with tHcy concentrations. In conclusion, these results do not confirm an independent relationship of tHcy and MTHFR genotype with risk of schizophrenia.
Disturbances in methyl-carbon metabolism, which result in hyperhomocysteinemia, have been associa... more Disturbances in methyl-carbon metabolism, which result in hyperhomocysteinemia, have been associated with schizophrenia. Homozygosity for the T677 allele of the methylenetetrahydrofolate reductase (MTHFR) gene, which encodes for a thermolabile enzyme associated with hyperhomocysteinemia, has been found to be increased in schizophrenic patients. We have investigated whether plasma homocysteine concentration and the frequency of C677T MTHFR variant were increased in schizophrenic inpatients of a psychiatric hospital (n=210) compared with controls (n=218). There were no significant differences in plasma homocysteine concentrations between the schizophrenia and the control group. The distributions of T allele and TT genotype frequencies were similar in both groups (40% and 15%). These results show that impaired homocysteine metabolism is unlikely in schizophrenia.
Polymorphisms in human apolipoprotein(a) kringle IV-10 and coronary artery disease: relationship ... more Polymorphisms in human apolipoprotein(a) kringle IV-10 and coronary artery disease: relationship to allele size, plasma lipoprotein(a) concentration, and lysine binding site activity Abstract Elevated plasma levels of lipoprotein(a) [Lp(a)] represent a major independent risk factor for the development of atherosclerosis. The kringle IV type 10 of apolipoprotein(a) [apo(a)] is the primary lysine binding site (LBS) of Lp(a) and is associated with lesion formation in transgenic mice. The purpose of this study was to search for mutations in the apo(a) kringle IV type 10 which could alter the LBS activity of Lp(a) from patients with coronary artery disease. We found the DNA region of kringle IV type 10 of apo(a) to be mutable but relatively well preserved in the Spanish population. We identified a novel mutation which probably leads to a truncated form of apo(a) in a patient heterozygous for the mutation and with low lysine binding activity and low plasma Lp(a) concentration. Two other mutations have been previously identified in humans, the substitutions W81R and M75T. The W81R was not found in our sample, but the M75T mutation was present in 43% of patients with coronary artery disease and 23% of agematched controls. The genotype TT conferred a significant risk for myocardial infarction (odds ratio 2.53). This association was not due to linkage disequilibrium with kringle IV repeats. The M75T polymorphism was not associated with the LBS function of apo(a), but it influenced plasma Lp(a) concentration.
The aim of the present study was to analyze, on a double-blind basis, the relationships between t... more The aim of the present study was to analyze, on a double-blind basis, the relationships between the apolipoprotein(a) (apo(a)) gene and protein size polymorphisms in healthy volunteers (n = 99) and patients with premature myocardial infarction (n = 91). Apo(a) genotypes were determined by pulse-field electrophoresis and phenotypes were separated by sodium dodecyl sulfate-agarose gel electrophoresis. Results showed that phenotyping overestimated apo(a) size with respect to genotyping (mean (SD) = 3.7 (3.4) kringle units; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) in subjects with a double-band genotype, although both measurements were highly correlated (r = 0.83; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). We also observed that the protein band in subjects with a single-band phenotype was related more closely to the smallest allele than to the largest allele band. The correlation of plasma lipoprotein(a) (Lp(a)) concentration was stronger with the phenotype than with the genotype. We hypothesize that post-translational modifications in the apo(a) molecule may be the most plausible explanation for the discrepancies observed. In conclusion, the present study highlights the dissimilarities between phenotyping and genotyping methods for the measurement of apo(a) size and suggests that laboratories should carefully consider these relationships and the transfer of results between such methodologies.
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