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Biomedical subjects

R Valdez

Publications and source records attributed to R Valdez.

At least 37 records · Page 2Linked to original sources

Longitudinal changes in cardiovascular risk from childhood to young adulthood in offspring of parents with coronary artery disease: the Bogalusa Heart Study.

CONTEXT: Although the association between parental coronary artery disease (CAD) and its risk factors in the offspring is known, the timing and the course of development of risk factors from childhood to adulthood in the offspring is not known. OBJECTIVE: To examine the association between parental CAD and longitudinal changes in risk factor profile from childhood to young adulthood in offspring. DESIGN: Cohort study. SETTING: Bogalusa, La, a semirural, biracial community. PARTICIPANTS: Individuals with clinically verified parental history of CAD (n=271) vs those without such a history (n = 1253) Mean age at first CAD event was 50 years for fathers and 52 years for mothers. MAIN OUTCOME MEASURES: Body mass index, subscapular skinfolds, blood pressure, and triglyceride, cholesterol (total, very low-density lipoprotein [VLDL-C], low-density lipoprotein [LDL-C], and high-density lipoprotein [HDL-C] cholesterols), glucose, and insulin levels. RESULTS: The offspring of parents with CAD were consistently overweight beginning in childhood. Their levels of total serum cholesterol, LDL-C, plasma glucose, and insulin became significantly higher at older ages, because of a higher rate of increase in these risk factors over time. In adulthood, the offspring with a positive parental history had a higher prevalence of obesity (body mass index >85th percentile in the National Health and Nutrition Examination Survey I, 35% vs 26%, P=.01), elevated total cholesterol (>6.2 mmol/L [240 mg/dL], 8.4% vs 4.8%, P=.05) and LDL-C levels (>4.1 mmol/L [160 mg/dL], 12.4% vs 4.7%, P=.05), and hyperglycemia (glucose, >6.6 mmol/L, 2.7% vs 0.4%, P<.001), as well as a higher coexistence of these conditions (P=.01). Further, the prevalence of dyslipidemia, either involving only LDL-C or LDL-C in combination with HDL-C or triglycerides or both, was significantly higher in the adult offspring with parental CAD. CONCLUSIONS: Offspring of parents with early CAD were overweight beginning in childhood and developed an adverse cardiovascular risk factor profile at an increased rate. These observations have important implications for prevention and intervention.

Adolescent↗

Verification of parental history of coronary artery disease and associations with adult offspring risk factors in a community sample: the Bogalusa Heart Study.

Positive parental history of coronary artery disease (CAD) (myocardial infarction, angina, angioplasty, bypass surgery) reported by 371 of 1,930 black and white adults aged 18 to 31 years in 1988 to 1991 in the Bogalusa Heart Study was verified by interviewing parents or next-of-kin. Error rates in reporting information concerning parental CAD and risk factors in offspring with a positive and negative parental history of CAD were examined. The 371 subjects who reported a positive parental history represented 304 families. Parental CAD could not be verified in 43 (14.1%) instances, and false-positive reports occurred in 45 (14.8%) cases. Among 216 families with confirmed CAD histories, the father had CAD in 175 (81.0%) cases and the mother in 70 (32.4%) cases. Both parents had CAD in 29 (13.4%) families. Of the parents with CAD, 46% of the fathers and 25% of the mothers died. The mean age at clinical onset of CAD was 51 years. Offspring with a confirmed positive parental history (n = 271) had significantly higher (P < 0.05) adjusted serum total and low-density lipoprotein cholesterol, plasma insulin and glucose, body mass index, and triceps and subscapular skinfolds than subjects with a negative parental history (n = 1,253). Those with an unconfirmed positive parental history (n = 51) had higher mean plasma insulin and serum high-density lipoprotein levels than those with a negative parental history; low-density lipoprotein levels were similar. Family history of CAD remains a useful indicator for screening adults at risk of developing CAD. An unverified family history may underestimate the importance of particular risk factors in epidemiologic studies.

Adolescent↗

Differential development of CD4 and CD8 cytotoxic T cells (CTL) in PBMC across the leprosy spectrum; IL-6 with IFN-gamma or IL-2 generate CTL in multibacillary patients.

In the present study we evaluated the contribution of CD4 and CD8 T cells on the antigen-specific cytotoxic activity induced by whole Mycobacterium leprae in leprosy patients and normal controls (N) as well as the modulation of this activity by some cytokines. Peripheral blood mononuclear cells (PBMC) from N or from leprosy patients were stimulated with antigen in the presence or absence of cytokines for 7 days. M. leprae-stimulated PBMC were depleted of CD4 or CD8 antigen-bearing cells and employed as effector cells in a 4-hr [31Cr]-release assay against autologous M. leprae-pulsed macrophages. Our results demonstrate that both CD4 and CD8 T cells contribute to M. leprae-induced cytotoxic activity, with differences observed in paucibacillary (PB) and multibacillary (MB) patients. CD8-mediated cytotoxic activity is higher than that of CD4 cells in PB patients, while in MB patients CD4 cytotoxicity is predominant. Our data also demonstrate that the generation of CD4 and CD8 cytotoxic T lymphocytes (CTL) can be modulated differentially by interleukin-4 (IL-4), IL-6, gamma interferon (IFN-gamma), or IL-2. Although MB patients developed the lowest CTL response, cytokines such as IL-6 plus IL-2 or IFN-gamma were able to generate both CD4 and CD8 cytotoxic T cells from MB patients. In PB patients, IL-6 plus IFN-gamma displayed the highest stimulation on CD8 effector cells. Thus, an important role may be assigned to IL-6, together with IL-2 or IFN-gamma, in the differentiation of M. leprae-specific CTL effector cells.

Adolescent↗

[Vitamin E as protective agent against hemolysis in leprosy patients under dapsone treatment].

Dapsone (4,4'diaminodiphenyl-sulphone) commonly used in the treatment of patients who suffer from leprosy, is a strongly oxidative drug, producing damage to the red cell membrane. This study investigated whether Vitamin E would have a protective effect on the red cell membrane from oxidant damage caused by Dapsone in patients with leprosy. We have studied 16 patients for 4 months, divided into two groups. Group 1 (n = 7) dapsone (DDS): 100 mg/day; Group 2 (n = 9) dapsone: 100 mg/day in addition with Vitamin E: 800 U/day. We did not include patients with low levels of Glucose-6-Phosphate Dehydrogenase (G-6-PD) because of their sensibility to this drug. At the beginning of the treatment we determined the level of G-6-PD. All patients showed a normocytic normochromic anemia with a decrease in Haptoglobine levels (below 5 mg/dl). Statistical analyses showed that reticulocyte counts did not present significant differences between groups all through evolution. As for methemoglobin (Hi) we observed in Group 1 an increase between the first and the fourth month, which was not seen in group 2. Statistical analyses of the results suggest that oral Vitamin E confers partial protective effect and does not correct the hemolysis parameters produced by Dapsone treatment except for Hi levels which were more sensitive to the oxidant damage.

Adult↗

Efficacy of moxidectin 0.5% pour-on against naturally acquired nematode infections in cattle.

The efficacy of 0.5% moxidectin pour-on at two dosages was evaluated in 30 cattle with naturally acquired gastrointestinal nematode infections. The cattle were ranked according to pretreatment fecal egg counts and body weights, and were randomly assigned from replicates to three treatment groups. The mean number of trichostrongyle eggs in pretreatment fecal samples did not differ among the groups. Groups I and II received 0.5% moxidectin pour-on at dosages of 0.25 mg moxidectin per kg body weight and 0.5 mg moxidectin per kg body weight, respectively, and Group III cattle received moxidectin-free vehicle (control cattle). The cattle were euthanized by complete replicate 14 or 15 days posttreatment for recovery of nematodes and examination of the pour-on sites. Treatment with moxidectin was associated with a significant reduction in fecal trichostrongyle egg counts compared with the control cattle; efficacy was 99.7% and > 99.9% for cattle in Groups I and II, respectively. Eleven species of adult nematodes (Haemonchus contortus, Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, Trichostrongylus colubriformis, Bunostomum phlebotomum, Cooperia oncophora, Cooperia punctata, Nematodirus helvetianus, Oesophagostomum radiatum and Trichuris ovis) and 4th stage larvae of Ostertagia spp. and Trichostrongylus spp. were present in sufficient numbers in control cattle to evaluate the efficacy of moxidectin 0.5% pour-on. In all cases, treatment was associated with a significant reduction in the number of nematodes recovered at necropsy, with the efficacy of both dosages exceeding 99.9%. There were no significant differences in mean worm burdens or fecal egg counts between the two treated groups, and no adverse reactions were observed.

Abomasum↗

Tumor necrosis factor-alpha stimulates aromatase gene expression in human adipose stromal cells through use of an activating protein-1 binding site upstream of promoter 1.4.

Expression of aromatase P450 (P450arom; the product of the CYP19 gene) in human adipose stromal cells in primary culture is markedly stimulated by serum in the presence of dexamethasone (DEX). Under these conditions, the majority of P450arom transcripts contain untranslated exon 1.4 at their 5'-ends. Previously, we observed that the region of the CYP19 gene upstream of exon 1.4 contains a TATA-less promoter, a glucocorticoid response element, and an interferon-gamma-activating sequence. These act to mediate the action of interleukin-6 and related cytokines to stimulate aromatase expression in the presence of DEX. In the present study, we found that tumor necrosis factor-alpha (TNF alpha) also acts synergistically with DEX to stimulate aromatase expression in adipose stromal cells in serum-free medium. We observed that the action of TNF alpha can be mimicked by ceramide. Maximal aromatase activity was obtained when cells were incubated with 5 ng/ml TNF alpha or 100 nM ceramide in the presence of 250 nM DEX. Levels of c-fos and c-jun proteins also were increased by TNF alpha or ceramide in the presence of DEX. Upstream of the interferon-gamma-activating sequence site there is an imperfect activating protein-1 (AP-1) binding site (2-bp mismatch). Gel retardation analysis using nucleotide probes containing the putative AP-1-binding sequence and nuclear extracts of human adipose stromal cells cultured in the presence of TNF alpha or ceramide plus DEX revealed that adipose stromal cells nuclear proteins bind to this site and that binding was competed by a 100-fold excess of a consensus AP-1 sequence. In addition, binding activity was competed by both anti-c-fos and anti-c-jun sera. Mutation or deletion of the putative AP-1 element resulted in the loss of TNF alpha- plus DEX-induced activity of reporter constructs comprised of 515 bp of the exon 1.4 flanking sequence linked to the luciferase gene. These results suggest that TNF alpha, probably acting through ceramide formation, stimulates the binding of both c-fos and c-jun to the AP-1 element upstream of exon 1.4. These act cooperatively with the ligand-activated glucocorticoid receptor to induce aromatase expression in adipose stromal cells in primary culture. We conclude that this TNF alpha signal transduction pathway may play an important role in the regulation of estrogen biosynthesis in adipose tissue.

Adipose Tissue↗

Use of weight-for-height indices in children to predict adult overweight: the Bogalusa Heart Study.

OBJECTIVE: To compare the body mass index (BMI) (weight/height2) and the Ponderal index (PI) (weight/height3) in childhood as predictors of adult overweight in a biracial group of children. DESIGN: Prospective, 15-y follow-up. SUBJECTS: 835 children aged 10-15 y at baseline. MEASUREMENTS: Weight in kg and height in m. OUTCOME VARIABLE: Overweight, defined as a BMI greater than 27 kg/m2 in young adults. RESULTS: Overall, the BMI and the PI at baseline were identically correlated with the BMI at follow-up (r = 0.64, p < 0.001). However, the predictions of overweight based on each index were distinctively affected by age, sex and race. The probability of adult overweight among 10-year old children was greater than 0.5 (50% overweight threshold) if their BMI exceeded 17 kg/m2 in black girls, 20 in white girls and 18 in boys of either race. Similarly, the 50% BMI overweight thresholds among 15-year-old children were 23 kg/m2 for black girls, 25 for white girls and 22 for boys of either race. The 50% PI overweight thresholds (in kg/m2) were 12 and 14 for 10-year-old black girls and white girls, respectively; and 14 and 16 for 15-year-old black girls and white girls, respectively. Among boys, the 50% PI threshold was 13 kg/m3 regardless of age or race. CONCLUSION: The BMI and the PI in childhood were both useful in assessing sex-and race-specific risks of adult overweight. However, assessments based on the Ponderal index were less affected by age and race than those based on the BMI, particularly among boys. Hence, to establish general weight goals for children, aimed at preventing adult obesity, the PI could be a much better choice than the BMI.

Adolescent↗

[Evaluation of cytokine production in leprosy patients].

The aim of the present study was to evaluate the cytokine production by peripheral blood mononuclear cells (PBMC) of leprosy patients when the cells were stimulated in culture by ConA, PPD or M.leprae. We measured IL-2, IL-4, IFN-gamma and IL-6 in cell-free supernatants by enzyme linked immunoassays. Our results do not suggest a clear association of a clinical form of leprosy with either Th1 or Th2 cytokine secretion profile in PBMC of leprosy patients.

Adolescent↗

Differential impact of obesity in related populations.

To search for genetic and environmental determinants of obesity, we compared the prevalences and the impact of obesity in three populations from two cities: Mexican Americans (n = 820) and non-Hispanic whites (n = 1112) from San Antonio, Texas, and Mexicans from Mexico City (n = 1878). In the age range examined, 35-64 years, only Mexican men and women showed a significant increase in the prevalence of obesity with age. On the other hand, genetic ancestry, especially in women, made significant differences in the rates of obesity. Mexican Americans showed relatively high, and non-Hispanic whites low, rates of obesity. To discriminate between genetic and environmental influences mediating the impact of obesity on a set of hemodynamic and metabolic variables, we compared this impact between Mexican Americans and both non-Hispanic whites (same macro-environment, different gene pools), and Mexicans (same gene pool, different environments). We found that obesity always worsens the hemodynamic and metabolic profiles of individuals, but the magnitude of the effects may be variable. We showed that the levels of insulin concentrations for a given level of obesity were similar in Mexicans and Mexican Americans, suggesting that genetic influences predominate in determining insulin levels; the levels of triglycerides and HDL for a given level of obesity were similar in Mexican Americans and non-Hispanic whites, suggesting predominant environmental influences on lipid levels. On the other hand, the levels of glucose and systolic blood pressure for a given level of obesity were usually different between Mexican Americans and either of the other two populations, suggesting that these levels may result from genotype-by-environment interactions.

Adult↗

A preponderance of small dense LDL is associated with specific insulin, proinsulin and the components of the insulin resistance syndrome in non-diabetic subjects.

Recently, the presence of small dense low density lipoprotein (LDL) has been postulated to be a stronger risk factor for coronary heart disease than large LDL. While small dense LDL has been associated with individual components of the insulin resistance syndrome such as hypertension, high triglyceride level, low high density (HDL) cholesterol, and diabetes mellitus, there has been little work exploring whether LDL size is decreased in subjects with multiple metabolic disorders. We examined the association of LDL size and pattern to specific insulin (which does not cross-react with proinsulin), proinsulin, increased triglyceride, decreased HDL, hypertension and impaired glucose tolerance in 488 non-diabetic subjects from the San Antonio Heart Study. LDL size was significantly related to specific insulin, proinsulin and the fasting proinsulin/insulin ratio. Small dense LDL was significantly associated with high triglyceride level, decreased HDL cholesterol, hypertension and impaired glucose tolerance. LDL size (A) decreased in a stepwise fashion with increasing number of the metabolic disorders described above (zero 262.6 +/- 9.4; one 257.0 +/- 9.3; two 256.4 +/- 9.4; three 249.0 +/- 9.1; and four 244.9 +/- 9.0). These results were similar in men and women and in non-Hispanic whites and Mexican Americans. The association between LDL size and the number of metabolic disorders remained statistically significant even after adjustment for obesity, body fat distribution, gender, ethnicity, proinsulin and insulin concentrations. Furthermore, decreases in LDL size are also significantly associated with both a selective beta-cell defect (as estimated by the fasting proinsulin/insulin ratio) and insulin resistance (as estimated by the fasting insulin concentrations) although the association was somewhat stronger for the latter. We conclude that small dense LDL may form part of the insulin resistance syndrome in non-diabetic subjects.

Diabetes Mellitus↗

Lack of cytotoxic activity against Mycobacterium leprae 65-kD heat shock protein (hsp) in multibacillary leprosy patients.

Cytotoxic T cells play an important role in host defence mechanisms, as well as in the immunopathology of leprosy. In this study, we evaluated whether Mycobacterium leprae hsp18, hsp65 and Myco. tuberculosis hsp71 could induce cytotoxic T cell activity against autologous macrophages pulsed with these hsp. Paucibacillary (PB) patients and normal controls generated more effector cells than multibacillary (MB) patients with all three hsp tested. There was no cross-reactivity between any of the hsp tested. Mycobacterium leprae hsp65 induced cytotoxic responses only in those MB patients undergoing an erythema nodosum leprosum (ENL) episode. Although hsp65 and hsp18 induced similar proliferation in MB patients, a high proportion of these patients did not generate cytotoxic effector cells in response to hsp65. Hence, those T cells reacting to hsp65 may play an important role in the control of Myco. leprae infection.

Adolescent↗

Myocardial infarction and cardiovascular risk factors in Mexico City and San Antonio, Texas.

Because the epidemiology of cardiovascular disease in Mexico is largely unknown, we examined the prevalence of cardiovascular risk factors and myocardial infarction (MI) in adults from low-income colonias in Mexico City. Data were collected as part of the Mexico City Diabetes Study, a population-based survey of diabetes and cardiovascular disease conducted between 1987 and 1992. Results were compared with those obtained from a comparable survey conducted previously among low-income Mexican Americans in San Antonio, Tex. A total of 2271 individuals between the ages of 35 and 64 years from Mexico City and 1143 adults of the same age range from San Antonio were studied. Despite being leaner and having lower levels of total cholesterol, Mexicans in Mexico City had markedly higher levels of triglycerides (P < .001) and lower levels of HDL cholesterol (P < .001) than Mexican Americans in San Antonio. MI was assessed by Minnesota-coded electrocardiograms and by a self-reported history of physician-diagnosed heart attack. In men, the prevalence of self-reported heart attack was significantly higher in San Antonio than in Mexico City (odds ratio, 5.85; P < .001), and in women, the prevalence of electrocardiogram-documented MI was significantly higher in San Antonio than Mexico City (odds ratio, 2.51; P < .001). The apparent excess of MI in San Antonio relative to Mexico City could be due to higher case-fatality in Mexico City or to a higher incidence in San Antonio.

Adult↗

Apolipoprotein E polymorphism and insulin levels in a biethnic population.

OBJECTIVE: To study the association of apolipoprotein E (apoE) polymorphism with important cardiovascular risk factors other than cholesterol levels, such as insulinemia and insulin resistance. RESEARCH DESIGN AND METHODS: In this report, we study the association of three major apoE phenotypes (apoE 3/2, apoE 3/3, and apoE 4/3) with indicators of insulin resistance such as fasting insulin, glucose, and lipid levels in 320 nondiabetic Mexican-Americans and non-Hispanic whites from San Antonio, TX. RESULTS: The two ethnic groups differed in the frequencies of the three major apoE phenotypes. However, the associations of these phenotypes with lipid and insulin levels were similar in both ethnic groups and in both sexes. Compared with the other two major apoE phenotypes, the apoE 3/2 phenotype was associated with lower levels of total and low-density lipoprotein cholesterol and lower levels of fasting and 2-h postload insulin. CONCLUSIONS: In addition to the association with cholesterol levels, the variability at the apoE locus may be associated with a much broader set of metabolic factors that relate to insulin resistance.

Alleles↗

Birthweight and adult health outcomes in a biethnic population in the USA.

Recent data indicate that low-birthweight adults are at a higher risk than their high-birthweight peers of developing ischemic heart disease or a cluster of conditions known as the IRS, which includes dyslipidaemias, hypertension, unfavorable body fat distribution and NIDDM. Thus far these observations have been limited to Caucasians from the United Kingdom. we extended these observations to a broader segment of the general population by studying the association of birthweight and adult health outcomes in a biethnic population of the United States. We divided a group of 564 young adult Mexican-American and non-Hispanic white men and women participants of the San Antonio Heart Study into tertiles of birthweight and compared metabolic, anthropometric, haemodynamic, and demographic characteristics across these tertile categories. Additionally, we studied birthweight as a predictor of the clustering of diseases associated with the IRS, defined as any two or more of the following conditions: hypertension, NIDDM or impaired glucose tolerance, dyslipidaemia. Normotensive, non-diabetic individuals whose birthweight was in the lowest tertile had significantly higher levels of fasting serum insulin and a more truncal fat deposition pattern than individuals whose birthweight was in the highest tertile, independently of sex, ethnicity, and current socioeconomic status. Also, the odds of expressing the IRS increased 1.72 times (95% confidence interval: 1.16-2.55) for each tertile decrease in birthweight. These findings were independent of sex, ethnicity, and current levels of socioeconomic status or obesity. In conclusion, low birthweight could be a major independent risk factor for the development of adult chronic conditions commonly associated with insulin resistance in the general population.

Adult↗