Otto A. Sanchez

Validity and reliability of combining three methods to determine ventilatory threshold.

PURPOSE This research was undertaken to validate a combination of methodologies to determine ventilatory threshold (VT). METHODS Three methods were used individually and then combined to determine VT as follows: 1) ventilatory equivalencies, 2) excess CO2 production, and 3) a modified V-slope method. Three groups of participants-endurance athletes (N = 132), healthy, aerobically active adults (N = 31), and healthy, sedentary/low-active adults (N = 22)-were independently evaluated for VT and compared with the criterion standard lactate threshold (LT) defined as the first rise in blood lactate with increasing intensity of exercise. RESULTS VT and LT were significantly correlated using the combined VT method within each study group (r = 0.98, 0.97, and 0.95, respectively; P < 0.001). Mean VO2 values at VT and LT were not significantly different between the three groups (P > 0.20). The combined method improved the determination rate of VT and reduced the standard deviation of the LT - VT difference by 80-170% over the individual methods. During test-retest procedures VO2lt and VO2vt determined by the combined method met criteria demonstrating further reliability. CONCLUSION The combined method to determine VT is valid and reliable across a wide fitness range in healthy individuals and improves the determination rate and accuracy of VT determination over the use of single methods.

G-banding and chromosome structure

G-banding of chromosomes promises to be the most valuable technique for routine chromosome analysis due to its inherent simplicity, sensitivity, and stability of the material obtained. In the past, banding procedures have had several shortcomings in regard to efficiency and consistency of results. It is now possible to obtain good and consistent quality banding by using minor modifications of the standard technique, including the use of diluted Giemsa. This has eliminated the need of “pre-treatment” of the chromosome preparation, a point overemphasized in most of the work published so far. G-banding can also be observed using DNA (Feulgen) and histone (Alcian blue) stains. The results obtained by this simple technique suggest that banding represents a native conformational feature of chromosomes.

The G-banded prophase chromosomes of man

SummaryUsing a simple G-banding technique developed in our laboratory, analysis of late prophases enables the visualization of approximately 1000 bands in the haploid set of human chromosomes. These bands have been classified according to the recommendations of the Paris Conference. The increased resolution offered by this technique is likely to be useful in the study of the structure and molecular organization of chromosomes and in identifying minute chromosome defects in birth defects and neoplasia.

Partial trisomy 8 (8q24) and the trisomy-8 syndrome

SummaryA familial partial trisomy for the distal end of the long arm of chromosome 8 and the short arm and centromeric region of chromosome 22 is reported. Even though the segment of chromosome 8 involved is small, the findings in the affected patients fit the general description of the trisomy-8 syndrome. This suggests that the distal end of the long arm of chromosome 8 may be responsible for the bulk of the trisomy-8 phenotype.ZusammenfassungEine familiär vorkommende partielle Trisomie für das distale Ende des langen Armes von Chromosom 8 sowie für den kurzen Arm und die Zentromer-Region des Chromosomes 22 wird mitgeteilt. Obwohl das betroffene Segment des Chromosom 8 klein ist, stimmen die Befunde bei den betroffenen Patienten mit der allgemeinen Beschreibung des Trisomie 8-Syndromes überein. Dadurch wird nahegelegt, daß das distale Ende des langen Armes von Chromosom 8 für die wesentlichen Aspekte des Trisomie 8-Phänotyps verantwortlich sein könnte.

The relationship between repetitive DNA and chromosomal bands in man

The relationship between chromosomal bands and repetitious DNA has been investigated by means of the quinacrine fluorescence technique and in situ hybridization with c-RNA to different fractions of repetitive DNA. A comparison of the Q bands with the labelling patterns obtained showed a preferential distribution of repetitive DNAs at Cots ranging from 0 to 5 in those regions that are Q band positive. A distinct labelling was also observed in the pericentromeric regions and in some telomeres. It is suggested that the distribution of repetitive DNA along the chromosomes plays an important role in band formation.

Partial trisomy 11 in a child resulting from a complex maternal rearrangement of chromosomes 11, 12 and 13

SummaryA complex structural rearrangement of chromosomes 11, 12 and 13 was found in a normal female who gave birth to an affected child with partial trisomy for the short arm of chromosome 11 and a balanced translocation 12/13. The detailed analysis of the G-banded chromosomes from early metaphases permitted the delineation of new chromosomal bands which in turn proved essential to the identification of this unusual phenomenon.ZusammenfassungBei einer normalen Frau, die ein Kind mit partieller Trisomie des kurzen Armes des Chromosoms 11 und eine balancierte Translokation 12/13 hatte, wurde ein kompliziertes strukturelles Rearrangement der Chromosomen 11, 12 und 13 gefunden. Eine detaillierte Analyse der Chromosomen nach Darstellung der G-Banden aus frühen Metaphasen erlaubte die Abgrenzung neuer Chromosomenbanden, die sich ihrerseits als notwendig für die Analyse dieses seltenen Phänomens erwiesen.

The associations between metabolic variables and NT-proBNP are blunted at pathological ranges: The Multi-Ethnic Study of Atherosclerosis

OBJECTIVE Under physiological conditions brain natriuretic peptide (BNP) is inversely associated with metabolic risk factors, but under pathological conditions these associations may tend to plateau. MATERIAL AND METHODS 5597 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA), 45-84years of age, free of overt cardiovascular disease in 2000-02 and then again in 2003-05 participated in this study. Associations between NT-proBNP and BMI, blood lipids, homeostasis model of insulin resistance (HOMA-IR) using linear regression models were adjusted for age, race, sex, BMI, % of energy from saturated fats, intentional exercise, statin use, antihypertensive medication use, diabetes and glomerular filtration rate. The inflection points (IP) at which these associations became nonlinear were determined using linear splines with knots at different levels of NT-proBNP. RESULTS Participants with NT-proBNP ≥100pg/mL (29%) tended to be older, on statins and anti-hypertensive medications vs. those with NT-proBNP <100pg/mL. The IP point varies among variables and ranged from 50-120pg/mL. NT-proBNP<IP, associated inversely with BMI, total cholesterol (TC), LDL-C, triglycerides (TG) and HOMA-IR, but positively with HDL-C. A higher proportion of participants with NT-proBNP ≥100pg/mL had subclinical CVD. All associations with NT-proBNP plateaued when NT-proBNP≥IP. Baseline level in NT-proBNP was not associated with 3-year change in BMI, TG, HDL-C or fasting glucose. CONCLUSIONS In a large cardiovascular disease-free cohort, NT-proBNP within the lower (physiological) range was inversely associated with TC, LDL-C, TG and insulin resistance with different inflection points, but at higher (pathological) levels these associations were blunted.

Comparison of the Predictive Value of GlycA and Other Biomarkers of Inflammation for Total Death, Incident Cardiovascular Events, Noncardiovascular and Noncancer Inflammatory-Related Events, and Total Cancer Events

BACKGROUND GlycA is a biomarker that reflects integrated concentrations and glycosylation states of several acute-phase proteins. We studied the association of GlycA and inflammatory biomarkers with future death and disease. METHODS A total of 6523 men and women in the Multi-Ethnic Study of Atherosclerosis who were free of overt cardiovascular disease (CVD) and in generally good health had a baseline blood sample taken. We assayed high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and d-dimer. A spectral deconvolution algorithm was used to quantify GlycA signal amplitudes from automated nuclear magnetic resonance (NMR) LipoProfile® test spectra. Median follow-up was 12.1 years. Among 4 primary outcomes, CVD events were adjudicated, death was by death certificate, and chronic inflammatory-related severe hospitalization and death (ChrIRD) and total cancer were classified using International Classification of Diseases (ICD) codes. We used Poisson regression to study baseline GlycA, hsCRP, IL-6, and d-dimer in relation to total death, CVD, ChrIRD, and total cancer. RESULTS Relative risk per SD of GlycA, IL-6, and d-dimer for total death (n = 915); for total CVD (n = 922); and for ChrIRD (n = 1324) ranged from 1.05 to 1.20, independently of covariates. In contrast, prediction from hsCRP was statistically explained by adjustment for other inflammatory variables. Only GlycA was predictive for total cancer (n = 663). Women had 7% higher values of all inflammatory biomarkers than men and had a significantly lower GlycA prediction coefficient than men in predicting total cancer. CONCLUSIONS The composite biomarker GlycA derived from NMR is associated with risk for total death, CVD, ChrIRD, and total cancer after adjustment for hsCRP, IL-6, and d-dimer. IL-6 and d-dimer contribute information independently of GlycA.

High‐Density Lipoprotein Subclasses and Noncardiovascular, Noncancer Chronic Inflammatory‐Related Events Versus Cardiovascular Events: The Multi‐Ethnic Study of Atherosclerosis

Background High-density lipoprotein (HDL) particles have properties beyond reverse cholesterol transport. We hypothesized that their protection extends to inflammation-related disease. The predictive value of HDL particle subclasses and inflammatory markers was studied for noncardiovascular, noncancer chronic inflammation–related death and hospitalization, and for incident cardiovascular disease (CVD). Methods and Results A multiethnic, multicenter, prospective observational study was conducted in 6475 men and women (aged 45 to 84 years) free of known CVD at baseline with median follow-up of 10.1 years. Fasting venous samples were analyzed for baseline lipid profile and lipoprotein particles. We focused on the HDL family of variables (small-, medium-, and large-diameter HDL particles and HDL cholesterol). Analyses identified the sum of small- plus medium-diameter HDL particles as important. Small- plus medium-diameter HDL particles were inversely associated with diagnostic code–based noncardiovascular, noncancer chronic inflammation–related death and hospitalization (n=1054) independent of covariates: relative risk per SD 0.85 (95% CI: 0.79 to 0.91, P<0.0001). Small- plus medium-diameter HDL particles were also associated with adjudicated fatal and nonfatal coronary heart disease events (n=423): relative risk per SD 0.88 (95% CI 0.77 to 0.98, P=0.02). Conclusions Small- plus medium-diameter HDL particles are an independent predictor for noncardiovascular, noncancer chronic inflammation–related death and hospitalization and for coronary heart disease events in subjects initially free of overt CVD. These findings support the hypothesis that smaller HDL particles of diameter <9.4 nm have anti-inflammatory properties in the general population.

Serial measurement of N-terminal pro-B-type natriuretic peptide and cardiac troponin T for cardiovascular disease risk assessment in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND N-terminal-pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (TnT) predict cardiovascular disease (CVD) risk in a variety of populations. Whether their predictive value varies by ethnicity is unknown. We sought to determine whether NT-proBNP and TnT improve prediction of incident coronary heart disease (CHD) and CVD, independent of CVD risk factors, in a multiethnic population; whether NT-proBNP improves prediction compared with the Framingham Risk Score or the Pooled Cohort Risk Equation; and whether a second NT-proBNP further improves prediction. METHODS Both NT-proBNP and TnT were measured in 5,592 MESA white, black, Hispanic, and Chinese participants (60% nonwhite; mean age 62.3 ± 10.3 years) in 2000 to 2002 and 2004 to 2005. We evaluated adjusted risk of incident CHD and CVD based on baseline and change in biomarker concentration. RESULTS Participants were followed up through 2011 and incurred 370 CVD events (232 CHD). Concentrations of NT-proBNP and TnT varied by ethnicity. Both NT-proBNP and TnT were associated with an increased risk of events (adjusted hazard ratio [HR] for CHD [95% CI] for fifth quintile vs other 4 quintiles of NT-proBNP, 2.03 [1.50-2.76]; HR for CHD for detectable vs undetectable TnT, 3.95 [2.29-6.81]). N-terminal-pro-B-type natriuretic peptide improved risk prediction and classification compared with the Framingham Risk Score and the Pooled Cohort Risk Equation. Change in NT-proBNP was independently associated with events (HR for CHD per unit increase in ΔlogNT-proBNP, 1.95 [1.16-3.26]). None of the observed associations varied by ethnicity. CONCLUSIONS Both NT-proBNP and TnT are predictors of incident CHD, independent of established risk factors and ethnicity, in a multiethnic population without known CVD. Change in NT-proBNP may add additional prognostic information.