Substituent effects on the nitrogen-15 and carbon-13 shieldings of some N-arylguanidinium chlorides

The 13C and 15N chemical shifts of five N-arylguanidinium chlorides carrying polar substituents, ranging in character from 4-methoxy to 4-nitro groups, have been determined by NMR spectroscopy at the natural-abundance level of 13C and 15N in dimethyl sulfoxide solution. Comparison of the 13C shifts of these salts with those of monosubstituted benzenes shows that the guanidinium group induces an average downfield shift of -5.8 ppm of the resonance of the aryl carbon to which it is attached (C1), an average upfield shift of +4.2 ppm for C2 and C6, and a small upfield shift of +1.9 ppm for C4. The shifts of C3 and C5 are small and erratic relative to the corresponding carbons in monosubstituted benzenes. The 15N resonances of the guanidinium nitrogens are quite sensitive to electric effects resulting from substitution of polar groups at C4. The 15N shift of the ==NAr nitrogen relative to that of the salts suggests that the predominant tautomer for N-arylguanidines is (H2N)2C==NAr. The 15N shifts of the (NH2) 2 nitrogens correlate rather well with σp- parameters, whereas the shifts of the -NHAr nitrogens seem to correlate only with R values derived from the σp- substituent constants

Acute hemodynamic effects of norepinephrine inhibition in patients with severe chronic congestive heart failure

AbstractThe pathophysiologic role of high levels of circulating catecholamines in patients with congestive heart failure remains unclear. To assess the hemodynamic contribution of circulating catecholamines, metyrosine (alpha-methylp-tyrosine), an inhibitor of catecholamine synthesis, was administered to nine patients with acutely decompensated chronic congestive heart failure. Baseline left ventricular ejection fraction averaged 23.3 ± 9.9%, whereas cardiac output averaged 3.69 ± 1.03 liters/min, with a pulmonary wedge pressure of 27.4 ± 8.5 mm Hg.After 48 h of metyrosine administration, plasma norepinephrine concentration decreased from 919.4 ± 810.6 to 335.4 ± 143.1 pg/ml (p < 0.05). Plasma epinephrine concentration averaged 176.4 ± 166.0 pg/ml at baseline, and was unchanged during metyrosine administration. Despite the significant decrease in circulating norepinephrine, no significant hemodynamic changes were observed during metyrosine administration.These results suggest that high levels of circulating norepinephrine may be more a marker of severe congestive heart failure than an important contributor to the underlying pathophysiology at this advanced stage of the disease process

Masked Hypertension and Prehypertension: Diagnostic Overlap and Interrelationships With Left Ventricular Mass: The Masked Hypertension Study

Background Masked hypertension (MHT) and prehypertension (PHT) are both associated with an increase in cardiovascular disease (CVD) risk, relative to sustained normotension. This study examined the diagnostic overlap between MHT and PHT, and their interrelationships with left ventricular (LV) mass index (LVMI), a marker of cardiovascular end-organ damage. Methods A research nurse performed three manual clinic blood pressure (CBP) measurements on three occasions over a 3-week period (total of nine readings, which were averaged) in 813 participants without treated hypertension from the Masked Hypertension Study, an ongoing worksite-based, population study. Twenty-four-hour ambulatory blood pressure (ABP) was assessed by using a SpaceLabs 90207 monitor. LVMI was determined by echocardiography in 784 (96.4%) participants. Results Of the 813 participants, 769 (94.6%) had normal CBP levels (<140/90 mm Hg). One hundred and seventeen (15.2%) participants with normal CBP had MHT (normal CBP and mean awake ABP ≥135/85 mm Hg) and 287 (37.3%) had PHT (mean CBP 120–139/80–89 mm Hg). 83.8% of MHT participants had PHT and 34.1% of PHT participants had MHT. MHT was infrequent (3.9%) when CBP was optimal (<120/80 mm Hg). After adjusting for age, gender, body mass index (BMI), race/ethnicity, history of high cholesterol, history of diabetes, current smoking, family history of hypertension, and physical activity, compared with optimal CBP with MHT participants, LVMI was significantly greater in PHT without MHT participants and in PHT with MHT participants. Conclusions In this community sample, there was substantial diagnostic overlap between MHT and PHT. The diagnosis of MHT using an ABP monitor may not be warranted for individuals with optimal CBP

Is Depression After an Acute Coronary Syndrome Simply a Marker of Known Prognostic Factors for Mortality?

Objective: Controversy remains over whether the association between depression and mortality in patients with acute coronary syndrome (ACS) is confounded by incomplete adjustment for measures of known prognostic markers. We assessed a) whether depression was associated with the most comprehensive empirically derived index of clinical mortality predictors: the Global Registry of Acute Coronary Events (GRACE) risk score for predicting 6-month mortality after discharge for ACS; and b) whether depression remained an independent predictor of all-cause mortality after adjustment for the GRACE score and left ventricular dysfunction. Methods: We surveyed prospectively 457 patients with ACS (aged 25–92 years; 41% women, 13% black, and 11% Hispanic), hospitalized between May 2003 and June 2005. Depressive symptoms were assessed with the Beck Depression Inventory (BDI) and diagnosis of major depressive disorder (MDD) was made by a structured psychiatric interview, within 1 week of hospitalization. Results: Despite differences in individual components of the GRACE score between depressed and nondepressed participants, neither depression measure was associated with overall GRACE score. For participants with MDD, the mean ± standard deviation GRACE score was 84 ± 33, compared with 92 ± 31 for those without MDD (p = .09). Using Cox proportional hazards regression analysis, MDD and depressive symptom severity each predicted mortality after controlling for GRACE score and left ventricular dysfunction (adjusted hazard ratio for MDD = 2.51; 95% Confidence Interval = 1.45–4.37). Conclusion: Depression is not simply a marker of clinical indicators that predict all-cause mortality after ACS. This strengthens the assertion that there is something unique in the association between depression and post-ACS prognosis, independent of known prognostic markers

Usual and Unusual Care: Existing Practice Control Groups in Randomized Controlled Trials of Behavioral Interventions

Objective: To evaluate the use of existing practice control groups in randomized controlled trials of behavioral interventions and the role of extrinsic health care services in the design and conduct of behavioral trials. Method: Selective qualitative review. Results: Extrinsic health care services, also known as nonstudy care, have important but under-recognized effects on the design and conduct of behavioral trials. Usual care, treatment-as-usual, standard of care, and other existing practice control groups pose a variety of methodological and ethical challenges, but they play a vital role in behavioral intervention research. Conclusions: This review highlights the need for a scientific consensus statement on control groups in behavioral trials

Losing life and livelihood: A systematic review and meta-analysis of unemployment and all-cause mortality

Unemployment rates in the United States remain near a 25-year high and global unemployment is rising. Previous studies have shown that unemployed persons have an increased risk of death, but the magnitude of the risk and moderating factors have not been explored. The study is a random effects meta-analysis and meta-regression designed to assess the association between unemployment and all-cause mortality among working-age persons. We extracted 235 mortality risk estimates from 42 studies, providing data on more than 20 million persons. The mean hazard ratio (HR) for mortality was 1.63 among HRs adjusted for age and additional covariates. The mean effect was higher for men than for women. Unemployment was associated with an increased mortality risk for those in their early and middle careers, but less for those in their late career. The risk of death was highest during the first 10 years of follow-up, but decreased subsequently. The mean HR was 24% lower among the subset of studies controlling for health-related behaviors. Public health initiatives could target unemployed persons for more aggressive cardiovascular screening and interventions aimed at reducing risk-taking behaviors

Self-Esteem and the Acute Effect of Anxiety on Ambulatory Blood Pressure

Objectives: Recent research suggests that self-esteem may be associated with improved parasympathetic nervous system functioning. This study tested whether high self-esteem is associated with decreased ambulatory systolic blood pressure (ASBP) reactivity to anxiety in healthy adults during the waking hours of a normal day. Methods: Each of 858 participants completed a short version of the Rosenberg Self-Esteem Scale and then wore an ABP monitor that took two blood pressure readings per hour for 24 hours. Immediately after each blood pressure reading, participants completed an electronic diary report that included an anxiety rating on a 100-point visual analog scale. Using multilevel models, we assessed the association of momentary anxiety, high trait self-esteem, and their interaction on momentary ASBP, with adjustment for age, sex, race, ethnicity, and body mass index. Sensitivity analyses were conducted examining psychological factors associated with self-esteem: sense of mastery, optimism, social support, and depressive symptoms. Results: On average, a 1-point increase in cube root–transformed anxiety was associated with a 0.80-mm Hg (standard error = 0.09, p < .001) increase in ASBP, and the interaction of high self-esteem and momentary anxiety was significant, such that this effect was 0.48 (standard error = 0.20, p = .015) less in individuals with high self-esteem compared with all others. Results for self-esteem remained significant when adjusting for sex and psychological factors. Conclusions: Momentary increases in anxiety are associated with acute increases in ASBP, and high self-esteem buffers the effect of momentary anxiety on blood pressure. Thus, high self-esteem may confer cardiovascular benefit by reducing the acute effects of anxiety on systolic blood pressure

Misery loves company? A meta-regression examining aggregate unemployment rates and the unemployment-mortality association

Purpose: Individual-level unemployment has been consistently linked to poor health and higher mortality, but some scholars have suggested that the negative effect of job loss may be lower during times and in places where aggregate unemployment rates are high. We review three logics associated with this moderation hypothesis: health selection, social isolation, and unemployment stigma. We then test whether aggregate unemployment rates moderate the individual-level association between unemployment and all-cause mortality. Methods: We use six meta-regression models (each using a different measure of the aggregate unemployment rate) based on 62 relative all-cause mortality risk estimates from 36 studies (from 15 nations). Results: We find that the magnitude of the individual-level unemployment-mortality association is approximately the same during periods of high and low aggregate-level unemployment. Model coefficients (exponentiated) were 1.01 for the crude unemployment rate (P = .27), 0.94 for the change in unemployment rate from the previous year (P = .46), 1.01 for the deviation of the unemployment rate from the 5-year running average (P = .87), 1.01 for the deviation of the unemployment rate from the 10-year running average (P = .73), 1.01 for the deviation of the unemployment rate from the overall average (measured as a continuous variable; P = .61), and showed no variation across unemployment levels when the deviation of the unemployment rate from the overall average was measured categorically. Heterogeneity between studies was significant (P < .001), supporting the use of the random effects model. Conclusions: We found no strong evidence to suggest that unemployment experiences change when macroeconomic conditions change. Efforts to ameliorate the negative social and economic consequences of unemployment should continue to focus on the individual and should be maintained regardless of periodic changes in macroeconomic conditions

Meta-analysis of marital dissolution and mortality: Reevaluating the intersection of gender and age

The study of marital dissolution (i.e. divorce and separation) and mortality has long been a major topic of interest for social scientists. We conducted meta-analyses and meta-regressions on 625 mortality risk estimates from 104 studies, published between 1955 and 2011, covering 24 countries, and providing data on more than 600 million persons. The mean hazard ratio (HR) for mortality in our meta-analysis was 1.30 (95% confidence interval [CI], 1.23–1.37) among HRs adjusted for age and additional covariates. The mean HR was higher for men (HR, 1.37; 95% CI, 1.27–1.49) than for women (HR, 1.22; 95% CI: 1.13–1.32), but the difference between men and women decreases as the mean age increases. Other significant moderators of HR magnitude included sample size; being from Western Europe, Israel, the United Kingdom and former Commonwealth nations; and statistical adjustment for general health status