Biomedical subjects

Timothy Meyer

Publications and source records attributed to Timothy Meyer.

6 recordsLinked to original sources

PubMed2006

Managing diabetic nephropathy: recent studies.

PURPOSE OF REVIEW: This review summarizes recent studies designed to identify improved treatments for diabetic nephropathy. RECENT FINDINGS: Recent data support the concept that angiotensin converting enzyme inhibitors and angiotensin II receptor blockers have similar renoprotective effects. Aggressive blockade of the renin-angiotensin system appears to have benefits beyond those achieved with conventional doses of single agents. Dual blockade using angiotensin converting enzyme inhibitors and angiotensin II receptor blockers is effective. Aldosterone receptor antagonists may potentiate the effect of these two classes of compounds. It remains unclear, however, whether maximum benefit can be obtained by the combination of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers or aldosterone receptor antagonists as compared to larger doses of single agents. Not enough data are available currently to recommend thiazolidinedione hypoglycemic agents for renal protection. Trials are being conducted with several new classes of agents. SUMMARY: Evidence from short-term studies favors aggressive blockade of the renin-angiotensin system. Long-term studies, however, remain to be performed. A multifactorial approach that incorporates established interventions affords our best means to retard the progression of diabetic nephropathy.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2004

Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women.

BACKGROUND: Obesity is a risk factor for impaired cardiac performance, particularly in women. Animal studies suggest that alterations in myocardial fatty acid metabolism and efficiency in obesity can cause decreased cardiac performance. In the present study, we tested the hypothesis that myocardial fatty acid metabolism and efficiency are abnormal in obese women. METHODS AND RESULTS: We studied 31 young women (body mass index [BMI] 19 to 52 kg/m2); 19 were obese (BMI >30 kg/m2). Myocardial oxygen consumption (MVO2) and fatty acid uptake (MFAUp), utilization (MFAU), and oxidation (MFAO) were quantified by positron emission tomography. Cardiac work was measured by echocardiography, and efficiency was calculated as work/MVO2. BMI correlated with MVO2 (r=0.58, P=0.0006), MFAUp (r=0.42, P<0.05), and efficiency (r=-0.40, P<0.05). Insulin resistance, quantified by the glucose area under the curve (AUC) during an oral glucose tolerance test, correlated with MFAUp (r=0.55, P<0.005), MFAU (r=0.62, P<0.001), and MFAO (r=0.58, P<0.005). A multivariate, stepwise regression analysis showed that BMI was the only independent predictor of MVO2 and efficiency (P=0.0005 and P<0.05, respectively). Glucose AUC was the only independent predictor of MFAUp, MFAU, and MFAO (P<0.05, <0.005, and <0.005, respectively). CONCLUSIONS: In young women, obesity is a significant predictor of increased MVO2 and decreased efficiency, and insulin resistance is a robust predictor of MFAUp, MFAU, and MFAO. This increase in fatty acid metabolism and decrease in efficiency is concordant with observations made in experimental models of obesity. These metabolic changes may play a role in the pathogenesis of decreased cardiac performance in obese women.

Adult↗

PubMed2004

Alterations in left ventricular structure and function in young healthy obese women: assessment by echocardiography and tissue Doppler imaging.

OBJECTIVES: This study was designed to determine the effects of obesity on left ventricular (LV) structure and function in young obese women. BACKGROUND: Severe prolonged obesity in older adults results in increased plasma volume, eccentric LV hypertrophy, and systolic and diastolic dysfunction. Obese women are at increased risk for the development of heart failure. However, the effects of the obesity on cardiac structure and function in young, otherwise-healthy women are controversial. METHODS: Fifty-one women were evaluated: 20 were obese (body mass index [BMI] > or =30 kg/m(2)) and 31 were non-obese (BMI <30 kg/m(2)). Left ventricular structure and systolic and diastolic function were assessed by two-dimensional echocardiography and tissue Doppler imaging, including the load-independent systolic myocardial velocity (Sm global) and early diastolic myocardial velocity (Em global), respectively. The effects of BMI on LV structure and function were assessed using multivariate regression analyses. RESULTS: Obese women had higher end-diastolic septal and posterior wall thickness, LV mass, and relative wall thickness than non-obese women; BMI values showed significant correlations with these variables (r = 0.58, p < 0.0001; r = 0.50, p < 0.0002; r = 0.52, p < 0.0001, and r = 0.40, p < 0.005, respectively). The Sm global and Em global were lower in obese women, suggesting systolic and diastolic function are decreased; both were negatively correlated with BMI (r = -0.43, p <. 002 and r = -0.61, p < 0.0001, respectively). Multivariate analysis showed BMI was the only independent predictor of relative wall thickness, Sm global, and Em global. CONCLUSIONS: Obesity in young otherwise-healthy women is associated with concentric LV remodeling and decreased systolic and diastolic function. These early abnormalities in LV structure and function may have important implications for explaining the myocardial dysfunction that is associated with increased cardiovascular morbidity and mortality caused by obesity.

Adult↗

PubMed2003

The effect of beta-adrenergic blockers on the prognostic value of peak exercise oxygen uptake in patients with heart failure.

OBJECTIVES: Our aim was to determine the effect of beta-adrenergic blockade on the prognostic value of peak oxygen consumption testing in patients with heart failure. BACKGROUND: Peak oxygen consumption has been shown to be a useful prognostic tool in patients with heart failure. However, studies demonstrating the utility of peak oxygen consumption were conducted before beta-blocker therapy became widespread. Thus, our objective was to determine the effect of beta-blockers on the prognostic value of peak oxygen consumption in patients with heart failure. METHODS: Actuarial, anthropomorphic, hemodynamic and exercise ventilatory data were collected from 369 patients with heart failure. Death and orthotopic heart transplants were the events tracked. Patients were divided into those taking beta-blockers and those not taking them. Event-free survival days were calculated. RESULTS: One hundred ninety-nine patients on beta-blockers and 170 not on beta-blockers were studied. There were 40 orthotopic heart transplants and 82 deaths during follow-up. Peak oxygen consumption (milliliters per kilogram per minute) trended toward being an independent predictor of event-free survival (p = 0.055). In patients on and not on beta-blockers, a peak oxygen consumption of >14 ml/kg.min was associated with a 1-year event rate of approximately half of that associated with a peak oxygen consumption </=14 ml/kg x min. However, for every level of peak oxygen consumption, the event rate was lower in the group taking beta-blockers. CONCLUSIONS: Beta-blocker status does not change the predictive power of peak oxygen consumption in patients with heart failure, but beta-blocker status is important to consider when using peak oxygen consumption to predict event-free survival in patients with heart failure.

Adrenergic beta-Antagonists↗

PubMed2003

Timing of cardiac transplantation in patients with heart failure receiving beta-adrenergic blockers.

BACKGROUND: Previous work shows that patients with heart failure patients who have peak oxygen consumption (VO2 peak) >14 ml/kg/min do not derive a survival benefit from cardiac transplantation. However, this was shown before beta-blocker therapy for patients with systolic heart failure became common, and beta-blockers improve survival in patients with heart failure without changing VO(2) peak. Our purpose was to re-evaluate the utility of VO(2) peak >14 ml/kg/min as an indicator of the need for cardiac transplantation in patients with heart failure who are taking beta-blockers. METHODS: Actuarial, hemodynamic, and exercise ventilatory data were collected from 540 patients with heart failure, 256 of whom were taking beta-blockers. We tracked death and cardiac transplantation. We stratified the percentage of patients event-free 1 and 3 years after VO(2) peak study by their VO(2) peak and beta-blocker status, and compared 1- and 3-year post-transplant survival (United Network of Organ Sharing [UNOS] data). We also compared total mortality for the patients with heart failure as stratified by beta-blocker stats and VO(2) peak (excluding the 42 who underwent transplantation) with UNOS post-transplant survival. RESULTS: Patients with heart failure who were receiving beta-blockers and whose VO(2) peak was > or =12 ml/kg/min had greater 1- and 3-year event-free survival rates (95% confidence intervals, 92.6%-96.6% and 85.8%-96.0%) than did post-transplant patients (83.9%-86.3% and 75.4%-76.6%). However, in patients with heart failure not taking beta-blockers, VO(2) peak <14 ml/kg/min was associated with worse 3-year survival (38.9 - 62.1%) than that for post-transplant patients. Excluding the 42 patients with heart failure in our study who underwent transplantation and then evaluating survival of the remaining patients with heart failure (not event-free survival) did not substantially change these results. CONCLUSIONS: Patients with heart failure who are receiving beta-blockers do not derive a survival advantage at 1 and 3 years after cardiac transplantation if VO(2) peak is > or =12 ml/kg/min. Patients not taking beta-blockers whose VO(2) peak is <14 ml/kg/min have superior survival with cardiac transplantation.

Adrenergic beta-Antagonists↗

PubMed2002

Phenotype and regulation of persistent intracerebral T cells in murine Toxoplasma encephalitis.

Toxoplasma gondii is a parasite causing asymptomatic, persistent encephalitis. Protective CD4 and CD8 T cells are recruited to and accumulate in the brain in acute Toxoplasma encephalitis (TE), with slowly decreasing numbers in chronic TE. It is unclear how the size of the intracerebral T cell pool is regulated. Conceivably, permanent recruitment, proliferation, and apoptosis may be involved. We observed that in murine TE recruitment of T cells to the brain was terminated in chronic TE. In vivo 5-bromo-2'-deoxyuridine incorporation and in vitro T cell proliferation experiments revealed that intracerebral T cells did not proliferate, which was explained by the expression of the cell cycle inhibitors p21(Waf/cip1) and p27(Kip1) and the inhibitory activity of intracerebral F4/80(+) cells. TUNEL staining detected apoptotic T cells at low frequency corresponding to an increased expression of the anti-apoptotic molecules Bcl-2 and Bcl-x(L) and a reduced expression of the pro-apoptotic molecules Bad, Bax, and Fas ligand in CD4 and CD8 T cells. During progression from acute to chronic TE, both CD4 and CD8 T cells down-regulated CD45RB expression and expressed a differential pattern of cytokines. From these experiments it is concluded that the number of intracerebral T cells increases by recruitment of T cells during acute infection, whereas proliferation of intracerebral T cells does not play a role. In chronic TE, T cell recruitment is terminated, the phenotype of intracerebral T cells changes, and their number is gradually downsized by low level apoptosis, which, however, does not completely resolve the T cell infiltrates.

Animals↗