Impaired glucose tolerance and elevated blood pressure in low birth weight, nonobese, young south african adults: early programming of cortisol axis

Low birth weight is associated with increased cardiovascular and metabolic disorders in adult life, although the mechanisms of this effect remain uncertain. There is one report of increased morning plasma cortisol levels in an elderly low birth weight cohort, but whether this is primary or secondary to other aspects of the phenotype is unclear. We investigated the association between low birth weight and glucose intolerance, blood pressure, and dyslipidemia in young, nonobese adults from a community undergoing the health transition with a high prevalence of both noncommunicable diseases and low birth weight. Additionally, we investigated whether altered basal and stimulated cortisol levels as a marker of hypothalamic-pituitary-adrenal responsiveness or cortisol metabolism were associated with low birth weight in these young adults. Twenty-year-old, historically disadvantaged, urbanized South Africans (n = 137) with birth weights either below the 10th percentile [underweight for age (UFA)] or between the 25th and 75th percentiles [appropriate for gestational age (AFA)] had anthropometry, blood pressure, lipid levels, and glucose tolerance measured. In a subset (n = 62), 0900 h plasma cortisol concentrations, cortisol responses to 1 microg ACTH, and urinary glucocorticoid metabolites were measured. The mothers of UFA infants were themselves lighter and had a lower body mass index (P: = 0. 0016). At age 20 yr, although the UFA group was still smaller and lighter, with a lower body mass index, they had higher fasting plasma glucose levels (P: = 0.047), and a greater proportion demonstrated glucose intolerance (11.9% vs. 0%; P: < 0.01). The UFA group also had higher systolic [UFA, 126.0 +/- 13.3 (+/-SD); AFA, 122.0 +/- 11.7 mm Hg; P: = 0.007] and diastolic (72.3 +/- 8.4 vs. 69. 5 +/- 8.7 mm Hg; P: = 0.02) blood pressures, after covarying for current weight and gender. Plasma cortisol levels determined at 0900 h were higher in the UFA group (484.9 +/- 166.3 vs. 418.6 +/- 160.6 nmol/L) and showed a greater plasma cortisol response to low dose ACTH stimulation (area under the curve for cortisol: UFA, 77,238 +/- 19,511; AFA, 66,597 +/- 16,064 nmol/L.min; P: = 0.04). In conclusion, the link between low birth weight and adult glucose intolerance and blood pressure elevation occurs in young adults in a high risk, disadvantaged population despite a lack of full catch-up growth. Moreover, cortisol axis activation is an early feature in the process linking low birth weight with adult cardiovascular and metabolic disease and is not dependent upon adult obesity or full catch-up growth, at least in this population undergoing the health transition.     

Accuracy of supplementary serologic testing for human T-lymphotropic virus types I and II in US blood donors. Retrovirus Epidemiology Donor Study

Blood donations in the United States have been screened for antibody to human T-lymphotropic virus type I (HTLV-I) by HTLV-I enzyme immunoassay (EIA) since November 1988. Specimens repeatedly found to be reactive by EIA undergo confirmation by supplementary serologic tests. We assessed the accuracy of blood center testing of 994 HTLV-I EIA repeat-reactive specimens in five US blood centers between November 1988 and December 1991. Of 410 confirmed HTLV-I/II donations, 407 (99.3%) were infected with HTLV-I/II, as determined by polymerase chain reaction (PCR) (403 cases) and by repeat serologic testing (4 cases). The three false- positive results occurred in the first year of testing. Of 425 HTLV- indeterminate specimens, 6 (1.4%) were found to be infected by PCR (5 with HTLV-II and 1 with HTLV-I). None of 159 confirmatory test-negative donations was PCR positive. Of HTLV-I/II-seropositive specimens, 80.2% to 95.4% could be typed as HTLV-I or HTLV-II by type-specific serologic assays. These results support recommendations that HTLV-I/II- seropositive donors should be advised that they are infected with HTLV- I, HTLV-II, or HTLV-I/II (depending on results of type-specific assays). HTLV-indeterminate donors should be advised that their results only rarely indicate HTLV infection. HTLV confirmatory test-negative donors should be reassured that they are not infected with HTLV-I or HTLV-II.     

Ten most notable family medicine research studies in Canada

Objective

To identify 10 noteworthy Canadian family medicine research studies that have affected practice in order to demonstrate the unique value that Canadian family medicine research offers.

Composition of the committee

Representatives from the Section of Researchers (SOR) and the Health Policy and Government Relations department of the College of Family Physicians of Canada developed a framework for inclusion and identified an initial list of articles. Members of the SOR Council and research directors from the 17 Canadian departments of family medicine reviewed the preliminary list and suggested additional studies.

Methods

The authors developed an initial list of studies carried out by Canadian family medicine researchers from those researchers who had received awards from the College of Family Physicians of Canada since 2002. Additional studies were proposed by members of the SOR Council and the university research directors. A total of 36 published articles were reviewed by the SOR authors, and an annotated short list of 16 articles was prepared. From that list, the other authors identified 7 noteworthy studies that were used to form the basis of advocacy materials. The SOR authors, along with 3 additional members of the SOR Executive, used an informal consensus process to select the final 3 articles to arrive at the top 10.

Report

The top 10 most noteworthy family medicine research studies are presented in this article and represent the unique contribution that Canadian family medicine research brings to health care in Canada. They have helped advance health care quality and improve care delivery, beneficially influencing health care practices, health care policy, and patient experiences.

Conclusion

This project has identified 10 classic Canadian family medicine research studies that continue to influence practice today. In addition to their usefulness as tools for teaching, advocating, and championing the contribution of research to modern family practice, these studies are important examples of the value of research to patient health in Canada and around the world.     

Vascular Imaging in Diabetes

Diabetes is a global epidemic affecting individuals of all socioeconomic backgrounds. Despite intensive efforts, morbidity and mortality secondary to the micro- and macrovascular complications remain unacceptably high. As a result, the use of imaging modalities to determine the underlying pathophysiology, early onset of complications, and disease progression has become an integral component of the management of such individuals. Echocardiography, stress echocardiography, and nuclear imaging have been the mainstay of noninvasive cardiovascular imaging tools to detect myocardial ischemia, but newer modalities such as cardiac MRI, cardiac CT, and PET imaging provide incremental information not available with standard imaging. While vascular imaging to detect cerebrovascular and peripheral arterial disease non-invasively has traditionally used ultrasound, CT- and MRI-based techniques are increasingly being employed. In this review, we will provide an outline of recent studies utilizing non-invasive imaging techniques to assist in disease diagnosis as well as monitoring disease progression. In addition, we will review the evidence for newer modalities such as MR spectroscopy, 3D intravascular ultrasound, and optical coherence tomography that provide exquisite detail of metabolic function and coronary anatomy not available with standard imaging, but that have not yet become mainstream.     

Copy number variants in patients with short stature

Height is a highly heritable and classic polygenic trait. Recent genome-wide association studies (GWAS) have revealed that at least 180 genetic variants influence adult height. However, these variants explain only about 10% of the phenotypic variation in height. Genetic analysis of short individuals can lead to the discovery of novel rare gene defects with a large effect on growth. In an effort to identify novel genes associated with short stature, genome-wide analysis for copy number variants (CNVs), using single-nucleotide polymorphism arrays, in 162 patients (149 families) with short stature was performed. Segregation analysis was performed if possible, and genes in CNVs were compared with information from GWAS, gene expression in rodents'' growth plates and published information. CNVs were detected in 40 families. In six families, a known cause of short stature was found (SHOX deletion or duplication, IGF1R deletion), in two combined with a de novo potentially pathogenic CNV. Thirty-three families had one or more potentially pathogenic CNVs (n=40). In 24 of these families, segregation analysis could be performed, identifying three de novo CNVs and nine CNVs segregating with short stature. Four were located near loci associated with height in GWAS (ADAMTS17, TULP4, PRKG2/BMP3 and PAPPA). Besides six CNVs known to be causative for short stature, 40 CNVs with possible pathogenicity were identified. Segregation studies and bioinformatics analysis suggested various potential candidate genes.     

Multiscale natural moves refine macromolecules using single-particle electron microscopy projection images

The method presented here refines molecular conformations directly against projections of single particles measured by electron microscopy. By optimizing the orientation of the projection at the same time as the conformation, the method is well-suited to two-dimensional class averages from cryoelectron microscopy. Such direct use of two-dimensional images circumvents the need for a three-dimensional density map, which may be difficult to reconstruct from projections due to structural heterogeneity or preferred orientations of the sample on the grid. Our refinement protocol exploits Natural Move Monte Carlo to model a macromolecule as a small number of segments connected by flexible loops, on multiple scales. After tests on artificial data from lysozyme, we applied the method to the Methonococcus maripaludis chaperonin. We successfully refined its conformation from a closed-state initial model to an open-state final model using just one class-averaged projection. We also used Natural Moves to iteratively refine against heterogeneous projection images of Methonococcus maripaludis chaperonin in a mix of open and closed states. Our results suggest a general method for electron microscopy refinement specially suited to macromolecules with significant conformational flexibility. The algorithm is available in the program Methodologies for Optimization and Sampling In Computational Studies.