Approaches to a long-acting,selectiveβ 2-adrenoceptor stimulant

Selectedβ ₂-stimulants were sought that would stick more firmly than salbutamol at their sites of action on theβ ₂-adrenoceptor protein in the cell membrane. Of the substance synthesized and tested it was concluded that salmeterol represented a new class ofβ ₂-stimulants that because of their exceptionally long duration of action have potential clinical advantages over current availableβ ₂-stimulants in the treatment of asthma.     

Determinants of ventricular arrhythmias in mildly symptomatic patients with coronary artery disease and influence of inducible left ventricular dysfunction on arrhythmia frequency

To determine the relation among ventricular arrhythmias, prognostic factors and reversible ischemia in coronary artery disease, 131 drug-free, minimally symptomatic patients were studied by radionuclide angiography and 24 hour Holter electrocardiographic monitoring. High grade ventricular arrhythmias (couplets, salvos of premature ventricular complexes and R on T phenomenon) were observed in 33 patients (25%) and were related to lower rest and exercise ejection fraction, greater number of stenotic coronary arteries and higher prevalence of regional wall motion abnormalities at rest (all p less than or equal to 0.1). Among patients with subnormal rest ejection fraction, high grade arrhythmias occurred with greater prevalence in those with reversible left ventricular dysfunction (reduction in ejection fraction) during exercise compared with those with a normal ejection fraction response (59 versus 23%, p less than 0.05), a relation observed principally in patients with multivessel disease. These data indicate that in minimally symptomatic patients with coronary artery disease, arrhythmias are related to both extent of disease and severity of regional and global ventricular dysfunction and are most prevalent in patients with ventricular dysfunction and evidence of inducible ischemia, factors indicating poor long-term prognosis during medical therapy.     

Relation between exertional ischemia and prognosis in mildly symptomatic patients with single or double vessel coronary artery disease and left ventricular dysfunction at rest

The randomized multicenter trials indicate that survival in patients with coronary artery disease and left ventricular dysfunction is enhanced by surgical therapy compared with medical therapy. This beneficial effect of coronary bypass surgery was demonstrated in patients with either three vessel or left main coronary artery disease, but not in those with one or two vessel disease. To determine whether subgroups of mildly symptomatic patients with one or two vessel coronary artery disease and left ventricular dysfunction have an increased risk of death or cardiac events during medical therapy, 53 consecutive patients with angiographically defined one or two vessel disease and impaired left ventricular function (ejection fraction 20% to 40%) were studied by exercise electrocardiography (ECG) and rest and exercise radionuclide angiography. All but two patients had previous myocardial infarction, and all were asymptomatic or only mildly symptomatic during medical therapy. By univariate life table analysis, mortality during medical therapy was associated significantly with the ST segment response to exercise (p less than 0.05) and with both the exercise ejection fraction (p less than 0.05) and the magnitude of change in ejection fraction with exercise (p less than 0.005). In patients with an exercise ejection fraction greater than 30%, the probability of survival at 6 years was 97 +/- 3% (+/- SE) compared with a survival rate of 62 +/- 14% in the remaining subjects (p less than 0.005). Similarly, 6 year survival was 100% in patients whose ejection fraction increased from the value at rest but was only 74 +/- 10% in the remaining patients (p less than 0.005). Exercise capacity was not associated with survival.(ABSTRACT TRUNCATED AT 250 WORDS)     

Depression,alcohol use,and stigma in younger versus older HIV-infected pregnant women initiating antiretroviral therapy in Cape Town,South Africa

HIV-infected pregnant women in sub-Saharan Africa are at risk for depression and alcohol abuse. Young women may be more vulnerable, but little is known about the psychosocial functioning of this population. We compared younger (18–24 years old) and older (≥25 years old) HIV-infected pregnant women initiating antiretroviral therapy (ART) in Cape Town, South Africa. Women were assessed on a range of psychosocial measures, including the Alcohol Use Disorders Identification Test and the Edinburgh Postnatal Depression Scale (EPDS). Among 625 women initiating ART, 16 % reported risky alcohol use and 21 % alcohol-related harm; these percentages were similar across age groups. When younger women were stratified by age, 37 % of 18–21 years old versus 20 % of 22–24 years old reported alcohol-related harm (p = 0.02). Overall, 11 % of women had EPDS scores suggesting probable depression, and 6 % reported self-harming thoughts. Younger women reported more depressive symptoms. Report of self-harming thoughts was 11 % in younger and 4 % in older women (p = 0.002). In multivariable analysis, age remained significantly associated with depressive symptoms and report of self-harming thoughts. Level of HIV-related stigma and report of intimate partner violence modified the association between age and depressive symptoms. Young HIV-infected pregnant women in South Africa were more likely to report depressive symptoms and self-harming thoughts compared to older women, and the youngest women reported the highest levels of alcohol-related harm. HIV-related stigma and intimate partner violence may be moderating factors. These findings have implications for maternal and infant health, underscoring the urgent need for effective targeted interventions in this vulnerable population.

     

Mice with gene alterations in the GH and IGF family

Pituitary - Much of our understanding of GH’s action stems from animal models and the generation and characterization of genetically altered or modified mice. Manipulation of genes in the...     

Applying Natural Language Processing to Evaluate News Media Coverage of Bullying and Cyberbullying

Prevention Science - Bullying events have frequently been the focus of coverage by news media, including news stories about teens whose death from suicide was attributed to cyberbullying. Previous...     

How people decide to seek health care: a qualitative study

BACKGROUND: There is considerable variation in service use, with overuse in conditions such as upper respiratory tract infections and high levels of unmet need in older patients with embarrassing conditions such as incontinence. The reasons for this situation are varied but to facilitate appropriate accessing of services the decision processes involved in help-seeking require greater understanding. OBJECTIVES: This study aimed to describe the decision making process for help-seeking in middle and older aged people with urinary storage symptoms. METHODS: In-depth qualitative interviews were carried out with 33 men and women who had sought medical care for urinary symptoms. Respondents were recruited from an epidemiological study of the prevalence of urinary symptoms in community dwelling adults aged 40 years and over. Questions were directed at help-seeking for urinary symptoms as well as help-seeking in general. Interviews were audio-taped and a thematic analysis carried out according to grounded theory methods. RESULTS: The steps in the decision process to seek medical care were drawn from the data. These consisted of appraisals of the presence and cause of symptoms, treatment options and the severity of symptoms and their impact on quality of life. Once the level of threat of the symptom was established, the costs and benefits of treatments and services were balanced against the perceived impact of symptoms on quality of life. These results were considered in relation to available models of health behaviour. CONCLUSIONS: Interventions that increase individuals' active involvement in their health care and which encourage greater knowledge of symptoms and outcomes will facilitate appropriate help-seeking and service use.     

Local field potential beta activity in the subthalamic nucleus of patients with Parkinson's disease is associated with improvements in bradykinesia after dopamine and deep brain stimulation

Parkinson's disease is treated pharmacologically with dopamine replacement medication and, more recently, by stimulating basal-ganglia nuclei such as the subthalamic nucleus (STN). Depth recordings after this procedure have revealed excessive activity at frequencies between 8 and 35 Hz ([Brown et al., 2001], [Kuhn et al., 2004] and [Priori et al., 2004]) that are reduced by dopamine therapy in tandem with improvements in bradykinesia/rigidity, but not tremor (Kuhn et al., 2006). It has also been shown that improvements in motor symptoms after dopamine correlate with single unit activity in the beta range (Weinberger et al., 2006). We recorded local field potentials (LFPs) from the subthalamic nucleus of patients with Parkinson's disease (PD) after surgery to implant deep brain stimulating electrodes while they were on and off dopaminergic medication. As well as replicating Kuhn et al., using the same patients we were able to extend Weinberger et al. to show that LFP beta oscillatory activity correlated with the degree of improvement in bradykinesia/rigidity, but not tremor, after dopamine medication. We also found that the power of beta oscillatory activity uniquely predicted improvements in bradykinesia/rigidity, but again not tremor, after stimulation of the STN in a regression analysis. However improvements after STN stimulation related inversely to beta power, possibly reflecting the accuracy of the electrode placement and/or the limits of STN stimulation in patients with the greatest levels of beta oscillatory activity.