Journal of Investigative Medicine

Forty-six academic health centers have been awarded Clinical and Translational Science Awards by the National Institutes of Health to enhance health by advancing translational research.

As a recipient of a Clinical and Translational Science Award, we aimed to determine the prevalence of translational and interdisciplinary collaboration at our institution.

We surveyed all full-time faculty and postdoctoral fellows (n = 3870) in the Johns Hopkins Schools of Medicine, Public Health, Nursing and Engineering, in late 2008.

Outcomes included (1) the proportion of investigators involved in early (T1), late (T2), and reverse translational (RT) research; (2) barriers to translational research; (3) attitudes about translational research; (4) involvement in interdisciplinary collaboration; and (5) barriers to collaboration.

With 1800 respondents, the response rate was 55% for faculty and 40% for postdoctoral fellows. Of the 1314 investigators with more than 30% of their time committed to research, 69% reported conducting 1 or more types of translational research (T1 = 79%, T2 = 36%, RT = 36%). Attitudes about translational research revealed both concern and uncertainty. Fifty-four percent of respondents described translational research as having complex regulatory requirements; 42% felt that an individual's contributions suffer from underrecognition, 39% described it as high risk, and 35% consider funding less secure for translational researchers. Collaboration across school and types of research was common. Forty-seven percent of basic scientists collaborated with a clinical investigator in the last year, and 56% of clinical investigators collaborated with a basic scientist.

Overall, investigators who did translational research reported a greater number of collaborators than those who did not.

Apolipoprotein (apo) C-III gene polymorphisms have been associated with increased plasma triglycerides (TGs) and coronary artery disease, but the results have not always been concordant among diverse populations. The present study was undertaken to detect the association of the apoC-III 3238C>G polymorphism and several environmental factors with serum lipid profiles in the Guangxi Hei Yi Zhuang and Han populations.

A total of 490 subjects of Hei Yi Zhuang and 540 participants of Han Chinese aged 15 to 89 years were randomly selected from our previous stratified randomized cluster samples. Genotyping of the apoC-III 3238C>G was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis and then confirmed by direct sequencing.

There was no difference in the genotype and allele frequencies between the 2 ethnic groups (P > 0.05), but G allele and GG genotype frequencies were higher in females than in males, or in high TG than in normal TG individuals in Hei Yi Zhuang (P < 0.01); and in high total cholesterol than in normal total cholesterol subgroups, in high low-density lipoprotein cholesterol (LDL-C) than in normal LDL-C subgroups, or in high apoB than in normal apoB subgroups in Han (P < 0.05). There were also differences in the genotypic frequencies between normal apoA-I and low apoA-I subjects in Hei Yi Zhuang, and between males and females or between normal TG and high TG subgroups in Han (P < 0.05). Serum TG and apoA-I levels were correlated with genotype or allele in Hei Yi Zhuang, and TG, LDL-C, and apoB levels were associated with genotype in Han (P < 0.05). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, body weight, and body mass index.

There were no significant differences in genotypic and allelic frequencies between the Hei Yi Zhuang and Han populations. But the 3238G carriers have unfavorable serum lipid profiles. The differences in the serum lipid profiles between the 2 ethnic groups might result from different gene-environmental interactions.

We assessed the correlation between intima-media thickness (IMT) and stiffness and test whether they are independent risk factors for atherosclerotic diseases.

We enrolled 2333 participants from the general population. Among the study subjects, 197 subjects had a history of stroke or myocardial infarction (MI) and were treated as patients, and the rest were the control subjects. Intima-media thickness was measured at the common carotid artery (CCA), bifurcation, and internal carotid artery. Three parameters (arterial stiffness [β], elastic modulus, and pulse wave velocity) were measured for carotid stiffness. Correlation between IMT and stiffness was first calculated. Multivariate regression model was used to evaluate whether inclusion of both IMT and stiffness can increase the prediction of cardiovascular events.

Only CCA and bifurcation IMTs were significantly and positively correlated with stiffness. After adjusting for age and sex, the correlations were substantially attenuated. Common carotid artery IMT was most significantly associated with stroke and MI (P = 2.6 × 10⁻⁸) followed by bifurcation IMT (P = 5.5 × 10⁻⁶), and internal carotid artery IMT was least significant (P = 0.02). For stiffness, β was most significant (P = 3.6 × 10⁻⁸) for stroke and MI, followed by elastic modulus (P = 1.1 × 10⁻⁶) and pulse wave velocity (P = 6.8 × 10⁻⁶). The best model for the combined effect was from β (P < 0.03) and CCA (P = 0.056) or bifurcation IMT (P = 0.057).

Carotid IMT and stiffness represent different properties of atherosclerotic vessel wall. Measuring both traits provides a better characterization of atherosclerosis.

Previous studies have shown that the assessment of Doppler mitral flow velocity (DMFV) curves can be used to predict prognosis owing to left ventricular (LV) diastolic dysfunction in certain specific diseases. Our aim was to study whether the prognostic value of DMFV curves is affected by the many end-stage renal disease factors, such as chronic uremia and long-term hemodialysis (HD), which cause LV diastolic dysfunction and death.

Retrospective echo Doppler studies obtained 10 to 12 hours after HD in 90 patients (52 males; mean age, 56 years) were analyzed to determine changes in deceleration time (DT) of the early mitral filling wave (E) and the ratio of E to the atrial velocity (A). The study findings (n = 83) showed 2 groups of DT: long DT (DT > 240 milliseconds) and normal/short DT (DT ≤ 240 milliseconds). Continuous variables of LV size using internal dimensions, systolic function using ejection fraction, hypertrophy using wall thickness and mass, and pulmonary hypertension and E/A were compared between the 2 groups.

Patients with long DT versus normal/short DT had lower absolute and indexed LV mass (P = 0.03 and P = 0.02, respectively) and pulmonary hypertension (P ≤ 0.001), without a significant difference in LV systolic function or E/A. The mortality rate, adjusted for age and sex, was lower with long DT versus normal/short DT, with a hazard ratio of death, 0.44 (95% confidence interval, 0.23-0.86, P = 0.02).

Our study identified characteristics of DMFV curves in patients on long-term HD, which are clearly of value in predicting outcomes and survival in these patients.

Type 2 diabetes mellitus (DM) is a significant cause of morbidity and premature mortality especially in adults. In Turkey, there are few studies on DM incidence. This study aimed to determine the incidence of type 2 DM in women 15 years or older in Turkey.

This prospective cohort study was performed from December 2002 to May 2003. Preliminary population-based screening was performed in 1997 and 1998 on women 15 years or older living in 4 villages in the Gölbaşı, Ankara province. Five hundred sixty-three women who were considered nondiabetic in the first study comprised the population for the present study. Data collection was accomplished by using a questionnaire and randomly measuring the blood glucose levels of the women. The χ² and Fisher exact tests were used to analyze the risk factors for DM.

The 5-year incidences of type 2 DM, impaired glucose tolerance, and impaired fasting glucose were 2.3%, 0.4%, and 0.7%, respectively. The 5-year incidence of type 2 DM increased with age (P < 0.05). The DM incidence was 6.2% in those with mixed-type hypertension and 4.0% in those with a body mass index of 30 kg/m² or higher. At 5-year follow-up, age (≥35 years), hypertension, and body mass index (≥30 kg/m²) were the risk factors for incidence of abnormal glucose metabolism (P < 0.05).

The incidence of abnormal glucose metabolism in this study is in accord with that in the literature. Our results will contribute to our understanding of the incidence of DM in women in Turkey.

Inadequate vascular remodeling is contributory to increased cardiovascular events in people with type 2 diabetes mellitus (DM) and impaired fasting glucose (IFG). Vascular endothelial growth factor (VEGF) and its regulatory molecule soluble Flt-1(sFlt-1) play important roles in atherogenesis.

We measured fasting plasma concentrations of VEGF and sFlt-1 in 11 nondiabetic (ND) (aged 46.1 ± 2.1 years; body mass index [BMI], 26.1 ± 0.9 kg/m²; glucose, 5.0 ± 0.1 mM), 15 IFG (aged 52.9 ± 1.8 years; BMI, 32.7 ± 1.3 kg/m²; glucose, 6.4 ± 0.1 mM), and 8 DM (aged 55.8 ± 3.2 years; BMI, 30.0 ± 1.0 kg/m²; glucose, 9.3 ± 0.5 mM) subjects.

Plasma VEGF (42.1 ± 4.0 vs 24.2 ± 0.9 vs 29.4 ± 3.8 pg/mL, respectively) and sFlt-1 (119.4 ± 4.9 vs 58.9 ± 3.2 vs 56.7 ± 1.2 pg/mL, respectively) concentrations were higher (P < 0.04) in DM than IFG and ND subjects. Whereas VEGF concentrations were significantly lower (P < 0.05) in IFG than in ND subjects, sFlt-1 concentrations did not differ between the IFG and ND subjects.

Although plasma VEGF concentrations were higher (35%) in DM than in ND subjects, VEGF action on vascular remodeling was likely attenuated by higher sFlt-1 concentrations in DM. In contrast, IFG subjects did not have major perturbations in either VEGF or sFlt-1 levels. Further studies defining the roles of these mediators in DM and IFG are necessary to extend these observations.