Postprandial Effect of a High-Fat Meal on Endotoxemia in Arab Women with and without Insulin-Resistance-Related Diseases

This study determined the effects of a high-fat meal on circulating endotoxin and cardiometabolic indices in adult Arab women. The cohort consisted of 92 consenting Saudi women (18 non-diabetic (ND)) control subjects; Age 24.4 ± 7.9 year; body mass index (BMI) 22.2 ± 2.2 Kg/m²), 24 overweight/obese (referred to as overweight-plus (overweight⁺)) subjects (Age 32.0 ± 7.8 year; BMI 28.5 ± 1.5 Kg/m²) and 50 type 2 diabetes mellitus (T2DM) patients (Age 41.5 ± 6.2 year; BMI 35.2 ± 7.7 Kg/m²). All were given a high-fat meal (standardized meal: 75 g fat, 5 g carbohydrate, 6 g protein) after an overnight fast of 12–14 h. Anthropometrics were obtained and fasting blood glucose, lipids, and endotoxin were serially measured for four consecutive postprandial hours. Endotoxin levels were significantly elevated prior to a high-fat meal in the overweight⁺ and T2DM than the controls (p < 0.05). Furthermore, the postprandial cardiometabolic changes led to a more detrimental risk profile in T2DM subjects than other groups, with serial changes most notable in glucose, triglycerides, high density lipoprotein-cholesterol (HDL-cholesterol), and insulin levels (p-values < 0.05). The same single meal given to subjects with different metabolic states had varying impacts on cardiometabolic health. Endotoxemia is exacerbated by a high-fat meal in Arab subjects with T2DM, accompanied by a parallel increase in cardiometabolic risk profile, suggesting disparity in disease pathogenesis of those with or without T2DM through the altered cardiometabolic risk profile rather than variance in metabolic endotoxinaemia with a high-fat meal.     

Massive pulmonary embolism in a patient with nephrotic syndrome and single lung

Journal of Thrombosis and Thrombolysis - We present a novel case of a patient with nephrotic syndrome and previous left pneumonectomy who had a massive pulmonary embolism of his remnant right...     

Budesonide once versus twice-daily administration: meta-analysis

OBJECTIVES: The aim of this study was to examine the efficacy of budesonide administered once daily compared to twice daily in asthma. METHODOLOGY: Meta-analysis of randomised controlled trials comparing budesonide administered once versus twice a day that presented data on at least one clinical outcome measure was conducted. RESULTS: A total of 10 studies, with 1922 children and adults with asthma, met the inclusion criteria. These studies were performed predominantly with mild to moderate asthmatic patients, using doses of budesonide ranging from 200 to 800 microg per day. There was no significant difference between daily dosing once or twice for all the clinical outcome variables, including withdrawals due to asthma, for which the odds ratio was 1.0 (95% confidence interval, 0.65-1.52). CONCLUSIONS: In mild to moderate asthma a once-daily budesonide regimen has a similar efficacy to a twice-daily regimen in doses up to 800 microg per day. A once-daily regimen has potential advantages in terms of patient compliance and satisfaction, when used in clinical practice.     

Role of S100A8 and S100A9 in neutrophil recruitment in response to monosodium urate monohydrate crystals in the air-pouch model of acute gouty arthritis

OBJECTIVE: To examine the role of chemokines, S100A8, and S100A9 in neutrophil accumulation induced by the causative agent of gout, monosodium urate monohydrate (MSU) crystals. METHODS: MSU crystal-induced neutrophil migration was studied in the murine air-pouch model. Release of chemokines, S100A8, S100A9, and S100A8/A9 in response to MSU crystals was quantified by enzyme-linked immunosorbent assays. Recruited cells were counted following acetic blue staining, and the subpopulations were characterized by Wright-Giemsa staining of cytospins. RESULTS: MSU crystals induced the accumulation of neutrophils following injection in the air pouch, which correlated with the release of the chemokines CXCL1, CXCL2, CCL2, and CCL3. However, none of these was found to play an important role in neutrophil migration induced by MSU crystals by passive immunization with antibodies directed against each chemokine. S100A8, S100A9, and S100A8/A9 were also found at high levels in the pouch exudates following injection of MSU crystals. In addition, injection of S100A8, S100A9, or S100A8/A9 led to the accumulation of neutrophils in the murine air pouch, demonstrating their proinflammatory activities in vivo. Passive immunization with anti-S100A8 and anti-S100A9 led to a total inhibition of the accumulation of neutrophils. Finally, S100A8/A9 was found at high concentrations in the synovial fluid of patients with gout. CONCLUSION: S100A8 and S100A8/A9 are essential to neutrophil migration induced by MSU crystals. These results suggest that they might be involved in the pathogenesis of gout.     

Low-molecular-weight heparins in ischemic heart disease

PURPOSE OF REVIEW: The objective of this review was to summarize the recent developments regarding the use of low-molecular-weight heparins in the management of acute coronary syndromes. RECENT FINDINGS: In the setting of unstable angina and non-ST-elevation myocardial infarction, enoxaparin is superior to unfractionated heparin in reducing death, myocardial infarction, and recurrent ischemia both in the short-term and to 1 year. However, this does not necessarily imply a class effect of low-molecular-weight heparins in general. When combined with glycoprotein IIb/IIIa inhibitors, enoxaparin appears to be effective and safe even for patients treated according to an early invasive strategy. In patients receiving fibrinolytics for ST-elevation myocardial infarction, low-molecular-weight heparins are as effective as unfractionated heparin in maintaining patency of the infarct-related artery and in reducing the composite endpoint of death and reinfarction. However, serious bleeding is more common, especially among the elderly, and the optimal dosing regimen in ST-elevation myocardial infarction remains to be defined. SUMMARY: Low-molecular-weight heparins are safe and effective in the management of unstable angina and non-ST-elevation myocardial infarction, with or without concurrent administration of glycoprotein IIb/IIIa inhibitors. Ongoing studies will clarify the role of low-molecular-weight heparins as adjunctive therapy for fibrinolysis.     

Prognostic value of exercise tests in male veterans with chronic coronary artery disease

PURPOSE: The authors evaluate the prognostic value of treadmill testing in a large consecutive series of patients with chronic coronary artery disease. Exercise testing is widely performed, but analyses of the prognostic value of test results have largely concentrated on patients referred for the diagnosis of coronary artery disease, patients after an acute coronary event or procedure, or patients with congestive heart failure. METHODS: All patients referred for evaluation at two university-affiliated Veterans Affairs Medical Centers who underwent exercise treadmill tests for clinical indications between 1987 and 2000 were determined to be dead or alive using the Social Security Death Index after a mean 5.8-year follow-up. Patients without established heart disease and those with congestive heart failure were excluded, leaving the target population of those with a history myocardial infarction or coronary intervention. Clinical and exercise test variables were collected prospectively according to standard definitions; testing and data management were performed in a standardized fashion using a computer-assisted protocol. All-cause mortality was used as the endpoint for follow-up. Standard survival analysis was performed including Kaplan Meier curves and the Cox Hazard Model. RESULTS: Of the 1,473 patients with coronary artery disease who had exercise testing, 273 (19%) patients had a revascularization procedure (Revascularization group); 813 (55%) had a history of myocardial infarction, diagnostic Q waves (MI group), or both; and 387 (26%) had a history of myocardial infarction or Q wave and revascularization (Combined group). Mean age of the patients was 61.8 +/- 9 years. A total of 401 deaths occurred during a mean follow-up of 5.8 years with an annual mortality rate of 4.5%. Only two variables, age and maximal exercise capacity, were independently and statistically associated with time to death in all three groups and were the strongest predictors of all cause mortality. CONCLUSION: A simple score based on METs, age, and history of myocardial infarction or diagnostic Q waves can stratify prognosis in patients with chronic coronary artery disease. The score enabled the identification of a group at low risk (32% of the cohort) with an annual mortality rate of 2%, a group at intermediate risk (42% of the cohort) with an annual mortality rate of about 4%, and a group at high risk (26% of the cohort) with an average annual mortality rate of approximately 7%.