Dynamic Contrast-Enhanced MRI Assessment of Hyperemic Fractional Microvascular Blood Plasma Volume in Peripheral Arterial Disease: Initial Findings

OBJECTIVES: The aim of the current study was to describe a method that assesses the hyperemic microvascular blood plasma volume of the calf musculature. The reversibly albumin binding contrast agent gadofosveset was used in dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) to assess the microvascular status in patients with peripheral arterial disease (PAD) and healthy controls. In addition, the reproducibility of this method in healthy controls was determined. MATERIALS AND METHODS: Ten PAD patients with intermittent claudication and 10 healthy control subjects were included. Patients underwent contrast-enhanced MR angiography of the peripheral arteries, followed by one DCE MRI examination of the musculature of the calf. Healthy control subjects were examined twice on different days to determine normative values and the interreader and interscan reproducibility of the technique. The MRI protocol comprised dynamic imaging of contrast agent wash-in under reactive hyperemia conditions of the calf musculature. Using pharmacokinetic modeling the hyperemic fractional microvascular blood plasma volume (V(p), unit: %) of the anterior tibial, gastrocnemius and soleus muscles was calculated. RESULTS: V(p) was significantly lower for all muscle groups in PAD patients (4.3±1.6%, 5.0±3.3% and 6.1±3.6% for anterior tibial, gastrocnemius and soleus muscles, respectively) compared to healthy control subjects (9.1±2.0%, 8.9±1.9% and 9.3±2.1%). Differences in V(p) between muscle groups were not significant. The coefficient of variation of V(p) varied from 10-14% and 11-16% at interscan and interreader level, respectively. CONCLUSIONS: Using DCE MRI after contrast-enhanced MR angiography with gadofosveset enables reproducible assessment of hyperemic fractional microvascular blood plasma volume of the calf musculature. V(p) was lower in PAD patients than in healthy controls, which reflects a promising functional (hemodynamic) biomarker for the microvascular impairment of macrovascular lesions

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Raloxifene modifies the insulin sensitivity and lipid profile of postmenopausal insulin resistant women

Objective: To investigate the effects of raloxifene on the insulin sensitivity and lipid profile in insulin-sensitive and insulin-resistant postmenopausal women. Study design: This placebo-controlled, double-blind, randomized study involved 64 postmenopausal women aged between 45 and 55 years. All subjects were screened with the insulin resistance homeostasis model assessment (IR-HOMA) and those patients in the lowest quartile (n = 16) were assigned as insulin sensitive and those in the highest quartile as insulin resistant (n = 16). Patients in both groups received either raloxifene hydrochloride (60 mg/day) or a placebo for a period of 12 weeks. Insulin sensitivity, the serum lipid profile and anthropometric measurements were established before and after therapy. Results: Women with the highest IR-HOMA scores were associated with a significantly higher weight, body mass index, waist and waist-to-hip ratio (p < 0.05). Raloxifene significantly reduced the IR-HOMA scores from 5.76 ± 2.91 to 1.93 ± 0.96 (p = 0.02) and modified the lipid profile in insulin-resistant patients when compared with the placebo group and those patients receiving raloxifene in the insulin-sensitive group. Conclusion: Raloxifene reduced insulin resistance and modified the lipid profile in insulin-resistant postmenopausal women. © 2013 Informa UK Ltd

Short- and long-term changes in extracellular glutamate and acetylcholine concentrations in the rat hippocampus following hypoxia

Sildenafil citrate has shown to display beneficial cardiovascular effects, suggesting that it may have other systemic benefits involving the endothelium. There is little data regarding the long-term use of this drug and the effects of this on different organs. Objective: The primary aim of this study was to determine whether sildenafil citrate diminishes concentrations of microalbuminuria and percentage of A1c in patients with type 2 diabetes. Design: A double-blind, randomized, controlled trial in 40 male patients, age 35-50, with type 2 diabetes. Subjects received sildenafil citrate 50 mg daily (n = 20) or placebo (n = 20) for 30 days. Levels of hs-CRP, microalbuminuria, homocysteine, A1c and erectile function were measured at baseline and to the end of the study. Results: Men that received sildenafil citrate displayed a significant decrease in the microalbuminuria concentrations (p < 0.01) versus baseline, (p = 0.02) versus placebo and A1c (p < 0.01) versus baseline, (p = 0.01) versus placebo. In addition, we observed a significant increase in the total IIEF score after 30 days of treatment (p < 0.01) versus baseline, (p < 0.01) versus placebo. Conclusions: The administration of 50 mg of sildenafil citrate for 30 consecutive days diminishes microalbuminuria and the percentage of A1c in patients with type 2 diabetes. " 2007 Elsevier Ireland Ltd. All rights reserved.",,,,,,"10.1016/j.diabres.2007.02.006",,,"http://hdl.handle.net/20.500.12104/44533","http://www.scopus.com/inward/record.url?eid=2-s2.0-34548443810&partnerID=40&md5=7d9016ac01744b76a1a70efb5d455957",,,,,,"1",,"Diabetes Research and Clinical Practice",,"13

Radiocarbon age inversions and progression: Source and causes in Late Holocene sediments from Lake Chapala, western Mexico

Objective: To investigate the effects of raloxifene on the insulin sensitivity and lipid profile in insulin-sensitive and insulin-resistant postmenopausal women. Study design: This placebo-controlled, double-blind, randomized study involved 64 postmenopausal women aged between 45 and 55 years. All subjects were screened with the insulin resistance homeostasis model assessment (IR-HOMA) and those patients in the lowest quartile (n = 16) were assigned as insulin sensitive and those in the highest quartile as insulin resistant (n = 16). Patients in both groups received either raloxifene hydrochloride (60 mg/day) or a placebo for a period of 12 weeks. Insulin sensitivity, the serum lipid profile and anthropometric measurements were established before and after therapy. Results: Women with the highest IR-HOMA scores were associated with a significantly higher weight, body mass index, waist and waist-to-hip ratio (p < 0.05). Raloxifene significantly reduced the IR-HOMA scores from 5.76 ± 2.91 to 1.93 ± 0.96 (p = 0.02) and modified the lipid profile in insulin-resistant patients when compared with the placebo group and those patients receiving raloxifene in the insulin-sensitive group. Conclusion: Raloxifene reduced insulin resistance and modified the lipid profile in insulin-resistant postmenopausal women. " 2013 Informa UK Ltd.",,,,,,"10.3109/09513590.2013.788628",,,"http://hdl.handle.net/20.500.12104/44047","http://www.scopus.com/inward/record.url?eid=2-s2.0-84879321401&partnerID=40&md5=a681916948a479c295af6caa196b3c02",,,,,,"7",,"Gynecological Endocrinology",,"67

Changes in the costs of antihypertensive medications in a developing country: A study in Mexico comparing 1990 and 1996

In developing countries, the cost of antihypertensive medications is one of the principal limiting factors when trying to treat patients with high blood pressure. To determine the changes in cost (in US dollars) of these medications and in the percentage of the minimum wage needed to purchase them, two cost studies (1990 and 1996) done in Mexico were compared. The yearly cost of a treatment with hydrochlorothiazide was US $13.80 in 1990; in 1996 it was US$10.92. Both figures represent 1.1% of the minimum wage that was in effect at the time. Propranolol hydrochloride cost US $50.52 for a year's treatment in 1990, and US$66.12 for the same in 1996. These figures represented, respectively, 4.2% and 6.7% of the minimum wage of 1990 and 1996. The annual cost for nifedipine was US $176.76 in 1990 (14.7$242.16 in 1996 (24.8% of the minimum wage). The yearly cost of enalapril was US $233.04 in 1990 and US$433.20 in 1996; these costs represented, respectively, 19.4% and 44.2% of the minimum wage. The comparison of these two cost studies (1990 and 1996) shows why Mexico's population is finding it more difficult to purchase antihypertensive medications. Higher costs and reduced purchasing power seem to be the two principal factors causing this. This is probably affecting the population's health, as it is more difficult to control high blood pressure without proper treatment

Clinical experience of the family doctor in caring for menopausal women in Primary Care [Competencia clínica del médico de familia en la atención a la mujer en etapa de climaterio en unidades de primer contacto]

[No abstract available

Homocysteine, MTHFR C677T and A1298C polymorphisms, and clinical and biochemical variables in the mexican population [Homociste�na, polimorfismos MTHFR C677T, A1298C e vari�veis cl�nico-bioqu�micas em popula��o mexicana]

The objective of the current work was to analyze the relationship of serum homocysteine (Hcy) with MTHFR C677T and A1298C polymorphisms and clinical and biochemical variables in the Mexican population. Hcy (immunoassay) levels and polymorphism (PCR/RFLP) levels were determined in 102 individuals from the general population. The 677TT genotype showed significant association with body weight (r=0.012) and the 1298CC genotype tended to be associated with BMI (r?0.06). Serum levels of Hcy in women (51/102) were 8.33 �1.86 ?mol/L and in men (51/102) 11.64 � 4.15 ?mol/L. The Hcy was positively associated with body weight (r=0.004) and negatively with Hb and Hct (r=0.001). Higher levels of Hcy were found in smokers (r=0.009) and a tendency to hyperhomocysteinemia in alcoholics and in menopausal women. There was no association of Hcy with MTHFR C677T and A1298C polymorphisms, although the analysis with dominant inheritance model for the C677T polymorphism (TT + CT vs. CC) showed a semidominant effect (r<0.10). In this study, the presence of MTHFR C677T and A1298C polymorphisms did not represent a significant risk factor for hyperhomocysteinemia; however, those differences may point out the dependence of the relative levels of Hcy modified genotypes on various environmental factors