Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment

To assess platelet function profiles in diabetic and nondiabetic patients on aspirin and clopidogrel therapy, two patient populations were included to investigate the 1) acute effects of a 300-mg clopidogrel loading dose (group 1, n = 52) and 2) long-term effects of clopidogrel (group 2, n = 120) on platelet function in diabetic compared with nondiabetic patients already on aspirin treatment. Patients were stratified according to the presence of type 2 diabetes. Platelet aggregation was assessed using light transmittance aggregometry (groups 1 and 2). Platelet activation (P-selectin expression and PAC-1 binding) was determined using whole-blood flow cytometry (group 2). Clopidogrel response was also assessed. In group 1, platelet aggregation was significantly increased in diabetic (n = 16) compared with nondiabetic (n = 36) patients at baseline and up to 24 h following a 300-mg loading dose (P = 0.005). In group 2, platelet aggregation and activation were increased in diabetic (n = 60) compared with nondiabetic (n = 60) subjects (P < 0.05 for all platelet function assays). Diabetic subjects had a higher number of clopidogrel nonresponders (P = 0.04). Diabetic patients have increased platelet reactivity compared with nondiabetic subjects on combined aspirin and clopidogrel treatment. Reduced sensitivity to antiplatelet drugs may contribute to the increased atherothombotic risk in diabetic patients.     

Increased activity of Pgp multidrug transporter in patients with Helicobacter pylori infection

AIM: To determine whether local antibiotic resistance involves P-glycoprotein (Pgp)-mediated active drug out-pumping during Helicobacter pylori (H pylori) infection treatment with classic antibiotic therapy. METHODS: Pgp activity was determined in gastric mucosa biopsy specimens obtained from 53 patients with pathohistologically verified gastritis and microbiologically confirmed H pylori infection, and compared with the Pgp activity in 12 control subjects with normal endoscopic findings. The H pylori positive patients were treated with short-term 7-d therapy consisting of two antibiotics (amoxicillin and azithromycin/metronidazole and clarithromycin) and a proton pump inhibitor. Pgp activity was determined by flow cytometry in the test of rhodamine dye efflux and quantified as mean fluorescence ratio (RMF). RESULTS: Upon the first cycle, H pylori was successfully eradicated in 20 patients, whereas therapy was continued in 33 patients. In the course of antibiotic therapy, RMF increased (P＜0.05) and gastric cells showed higher rhodamine dye efflux. The mean pre-treatment RMF values were also higher (P＜0.0001) in patients with multiple therapeutic failure than in those with successful H pylori eradication and control subjects. CONCLUSION: Pgp might be one of the causes of therapy failure in patients with H pylori and antibiotic therapy could be chosen and followed up on the basis of the Pgp transporter local activity.     

Pulmonary artery catheterization in acute coronary syndromes: insights from the GUSTO IIb and GUSTO III trials

PURPOSE: To correlate pulmonary artery catheterization (PAC) use and 30-day outcomes and to characterize the use of pulmonary artery catheters among patients with acute coronary syndromes (ACS). SUBJECTS AND METHODS: We retrospectively studied 26437 ACS patients from two large multicenter, international randomized clinical trials. Multivariable and causal inference analyses were applied to adjust for differences in baseline risk. RESULTS: PAC was performed in 735 patients (2.8%), with a median time to insertion of 24 hours. Patients undergoing PAC were older (median, 67 vs. 64 years), more often diabetic (25.7% vs.16.2%), and more likely to present with ST-segment elevation (81.6% vs. 70.2%) or Killip class III or IV (7.9% vs. 1.4%). US patients were 3.8 times more likely than non-US patients to undergo PAC. Patients managed with PAC also underwent more procedures, including percutaneous intervention (40.7% vs. 18.1%), coronary artery bypass grafting (12.5% vs. 7.7%), and endotracheal intubation (29.3% vs. 2.2%). Mortality at 30 days was substantially higher among patients with PAC for both unadjusted (odds ratio [OR] 8.7; 95% confidence interval [CI] 7.3-10.2) and adjusted analyses (OR 6.4; 95% CI 5.4-7.6) in all groups except in patients with cardiogenic shock (OR 0.99; 95% CI 0.80-1.23). CONCLUSIONS: PAC was associated with increased mortality, both before and after adjustment for baseline patient differences and subsequent events that may have led to PAC use, except in patients with cardiogenic shock. The definitive role of PAC in managing patients with ACS is still to be determined.     

Preferred pedal rate: an index of cycling performance

The purpose of this study was to determine whether preferred pedal rate (PPR) could be used as an index of cycling performance. Thirteen competitive cyclists cycled at PPR during a graded test and a supra-threshold constant power test (CPT). The results showed that PPR values reported in CPT were correlated to both peak power determined from the graded test and exhaustion time assessed in CPT. Furthermore, multiple regression revealed that PPR values and P (peak) were two predictors of exhaustion time in CPT. Hence, this study suggests that coaches and sports scientists have to take into account PPR values complementary to P (peak) in order to evaluate the capacity of cycling performance.     

Critical swimming speed does not represent the speed at maximal lactate steady state

Critical power and critical swimming speed (CSS) are mathematically defined as intensities that could theoretically be maintained indefinitely without exhaustion. Several investigations have been conducted to attribute a physiological meaning to these variables, but results in swimming remain equivocal. Thus, the purpose of this study was to compare CSS with direct determination of the speed at maximal lactate steady state (S (MLSS)). Eight well-trained swimmers (aged 18.6 +/- 1.9 years) performed four tests to exhaustion (95, 100, 105, and 110 % of maximal aerobic speed [MAS]) in order to determine CSS from the distance-time relationship. S (MLSS) was determined from four sub-maximal 30-min constant intensity tests (ranging from 75 % to 90 % MAS). CSS (92.7 +/- 2.6 % MAS) was significantly higher than S (MLSS) (88.3 +/- 2.9 % of MAS) and the bias +/- 95 % limits of agreement for comparisons between CSS and S (MLSS) (0.07 +/- 0.13 m x s(-1)) indicated that the extent of disagreement was too great to use these two variables interchangeably. However, CSS and S (MLSS) were strongly correlated (r = 0.87; SEE = 0.033 m x s(-1); p < 0.01). Results from the present study demonstrate that in swimming, CSS does not represent the maximal speed that can be maintained without a continuous rise of blood lactate concentration and direct determination of S (MLSS) is necessary if precision is required in experimental studies.     

Feeding induced by increasing doses of neuropeptide Y: dual effect on hypothalamic serotonin release in normal rats

Endogenous neuropeptide Y (NPY) levels increase during fasting and before dark onset in rats. The feeding that follows these states elicits the release of serotonin in the lateral hypothalamus (LH), as part of the physiological mechanisms controlling satiety. With the hypothesis that exogenous NPY-induced feeding should also stimulate serotonin, we measured its release in the LH of non-fasted rats, which received a single intracerebroventricular injection of either 1.0, 2.0, or 5.0 microg of NPY. After 1.0 microg, the cumulative 2-h intake was of 13 g and serotonin release significantly increased (54% peak). These feeding and serotonergic responses were highly similar to the ones we observed in a previous study, in which feeding followed an overnight fast. Thus, the 1.0 microg NPY dose stimulated intake while preserving the normal serotonergic activation. Contrarily, as the NPY dose was increased to either 2.0 or 5.0 microg, the cumulative 2-h intakes were of 18 g, but the serotonergic stimulation was absent. It is suggested that this dual NPY effect relies on a finely tuned control mechanism, reflecting the existence of a narrow range of NPY levels within which the serotonergic stimulation resembles those seen in physiological states.     

Testing a methodology to evaluate organization, access, and technical quality of care for childhood diarrhea

In order to evaluate the issues of access and technical quality in actions to control diarrhea in a selected municipality in the State of Bahia, Brazil, a study of multiple cases was conducted with two levels of analysis: practices themselves and the coordination between them. Cases were defined as hospitalization (8) or death (3) due to diarrhea. All deaths were investigated, and hospitalizations were submitted to intentional selection. Aspects and approaches vis-a-vis technical quality evaluation and estimation of the degree of implementation in diarrhea control measures were derived from the theoretical model. Health care trajectories for diarrhea were reconstituted from interviews and patient chart data. The results identified: organizational barriers related to long waiting time at primary care units; geographic barriers, or the distance from users' place of residence to health services; and financial barriers due to shortage of financial resources for transportation. Quality of care was considered inadequate, and diarrhea control measures were classified as insufficient in practically all of the dimensions analyzed.