Women's experiences and behaviour at onset of symptoms of ST segment elevation acute myocardial infarction

Background

Minimizing time from onset of symptoms to treatment (treatment delay) is crucial for patients with ST segment elevation acute myocardial infarction (STEMI), and one of the great challenges is to reduce the delay relating to the prehospital behaviour of the patient (patient delay). Studies indicate that women delay longer than men and insights into this area could lead to improved health education programmes aimed at reducing patient delay in women with STEMI.

Method

Open interviews with 14 women with STEMI were held during their hospital stay from June to September 2009. The interviews were aimed at exploring determinants of treatment delay, and were carried out and analysed within a phenomenological framework.

Findings

Three themes emerged important for the delay in seeking medical assistance: (1) Knowledge and ideas of AMI symptoms and risks. (2) Ambivalence whether to call for medical assistance or to cope with the situation. (3) Actions and strategies taken after onset of symptoms.

Conclusions

Three factors determined whether women showed appropriate behaviour for reduced patient delay after onset of symptoms: (1) identifying the symptoms as being of cardiac origin, (2) having a prepared action plan in case of an emergency situation, and (3) living with someone or contacting other persons.     

Effects of interferon-beta therapy on elements in the antiviral immune response towards the human herpesviruses EBV, HSV, and VZV, and to the human endogenous retroviruses HERV-H and HERV-W in multiple sclerosis

Effects of treatment of multiple sclerosis patients with IFN-β on elements of the antiviral immune response to herpesviruses were analysed in a longitudinal study. We found significantly increased seroreactivity to EBV EBNA-1, and to VZV, in patients who did not respond to IFN-β therapy. We found no significant changes in seroreactivity to EBV EA, or to HSV. For the same patient cohort, we have previously demonstrated significant decreases in seroreactivities to envelope antigens for the two human endogenous retroviruses HERV-H and HERV-W, closely linked to efficacy of therapy. We further searched for correlations between seroreactivities to EBV, HSV, and VZV, and levels of mannan-binding lectin (MBL), and MBL-associated serine protease 3. We found no such correlations. Our results are in accord with recent reports of increased seroreactivity to EBV EBNA-1, and to VZV in active MS, and they support that the herpesviruses EBV and VZV together with HERV-H/HERV-W and the antiviral immune response may play a role in MS development.     

Activin A levels are associated with abnormal glucose regulation in patients with myocardial infarction: potential counteracting effects of activin A on inflammation

OBJECTIVE

On the basis of the role of activin A in inflammation, atherogenesis, and glucose homeostasis, we investigated whether activin A could be related to glucometabolic abnormalities in patients with acute myocardial infarction (MI).

RESEARCH DESIGN AND METHODS

Activin A measurement and oral glucose tolerance tests (OGTTs) were performed in patients (n = 115) with acute MI, without previously known diabetes, and repeated after 3 months. Release of activin A and potential anti-inflammatory effects of activin A were measured in human endothelial cells. Activin A effects on insulin secretion and inflammation were tested in human pancreatic islet cells.

RESULTS

1) In patients with acute MI, serum levels of activin A were significantly higher in those with abnormal glucose regulation (AGR) compared with those with normal glucose regulation. Activin A levels were associated with the presence of AGR 3 months later (adjusted odds ratio 5.1 [95% CI 1.73–15.17], P = 0.003). 2) In endothelial cells, glucose enhanced the release of activin A, whereas activin A attenuated the release of interleukin (IL)-8 and enhanced the mRNA levels of the antioxidant metallothionein. 3) In islet cells, activin A attenuated the suppressive effect of inflammatory cytokines on insulin release, counteracted the ability of these inflammatory cytokines to induce mRNA expression of IL-8, and induced the expression of transforming growth factor-β.

CONCLUSIONS

We found a significant association between activin A and newly detected AGR in patients with acute MI. Our in vitro findings suggest that this association represents a counteracting mechanism to protect against inflammation, hyperglycemia, and oxidative stress.Type 2 diabetes is a chronic disease with rapidly increasing prevalence, and patients with type 2 diabetes have an increased risk of developing coronary artery disease (CAD) (1,2). The coexistence of type 2 diabetes and CAD is considerable, and type 2 diabetes has been rated as an equivalent of CAD. In contrast, many patients with established CAD have type 2 diabetes or its pre-states (3). Thus, a high prevalence of impaired glucose tolerance (IGT) and unknown type 2 diabetes has been reported in patients with CAD with no previous diagnosis of diabetes (4–6). Abnormal glucose regulation (AGR) (impaired fasting glucose [IFG], IGT, or type 2 diabetes) is approximately twice as common among patients with myocardial infarction (MI) as in population-based controls (7), and the presence of AGR is a strong risk factor for new cardiovascular events after acute MI (3,8,9).The association between cardiovascular disease and hyperglycemia may be explained by an accumulation of cardiovascular risk factors associated with the metabolic syndrome in patients with AGR (10). It may, however, also relate to mechanisms triggered by hyperglycemia and insulin resistance leading to cardiovascular damage before the onset of overt diabetes (7,11). Moreover, experimental and clinical data have illuminated a role of inflammation in atherogenesis, and it has been suggested that atherosclerosis, type 2 diabetes, and the metabolic syndrome are multifactorial diseases characterized by chronic inflammation (12). However, the reasons for the association between AGR and atherosclerotic disorders are not fully understood.Activin A, a member of the transforming growth factor (TGF)-β superfamily (13), has been recognized as a multifunctional cytokine with roles in regulation of wound repair, cell differentiation, and inflammation, and growing evidence implicates a role for activin A in inflammatory disorders potentially mediating both inflammatory and anti-inflammatory effects (14). Activin A also has been suggested to be important for glucose homeostasis, at least partly through direct stimulatory effects on pancreatic β-cells (15). However, reports on activin A levels in patients with type 2 diabetes are few and include a small number of patients (16,17). Furthermore, there are only a few reports on activin A levels during acute coronary syndrome (ACS) and no reports on patients with ST-elevation MI (STEMI) exclusively. Moreover, no data exist on the association between activin A and AGR in patients with CAD.On the basis of the role of activin A in inflammation, atherogenesis, and glucose homeostasis, we investigated whether activin A could be related to glucose abnormalities associated with STEMI, potentially representing a counteracting mechanism in response to AGR. This hypothesis was investigated by different approaches, including studies in a well-characterized population with STEMI and experimental studies in endothelial cells and pancreatic β-cells.     

Anthropometric factors and cutaneous melanoma: Prospective data from the population‐based Janus Cohort

The aim of the present study was to prospectively examine risk of cutaneous melanoma (CM) according to measured anthropometric factors, adjusted for exposure to ultraviolet radiation (UVR), in a large population‐based cohort in Norway. The Janus Cohort, including 292,851 Norwegians recruited 1972–2003, was linked to the Cancer Registry of Norway and followed for CM through 2014. Cox regression was used to estimate hazard ratios (HRs) of CM with 95% confidence intervals (CIs). Restricted cubic splines were incorporated into the Cox models to assess possible non‐linear relationships. All analyses were adjusted for attained age, indicators of UVR exposure, education, and smoking status. During a mean follow‐up of 27 years, 3,000 incident CM cases were identified. In men, CM risk was positively associated with body mass index, body surface area (BSA), height and weight (all p_trends < 0.001), and the exposure‐response curves indicated an exponential increase in risk for all anthropometric factors. Weight loss of more than 2 kg in men was associated with a 53% lower risk (HR 0.47, 95% CI: 0.39, 0.57). In women, CM risk increased with increasing BSA (p_trend = 0.002) and height (p_trend < 0.001). The shape of the height‐CM risk curve indicated an exponential increase. Our study suggests that large body size, in general, is a CM risk factor in men, and is the first to report that weight loss may reduce the risk of CM among men.     

Soluble CD14 from urine copurifies with a potent inducer of cytokines

Here we report that soluble CD14 isolated from the urine of nephrotic patients (uCD14) contains a potent cytokine inducing activity. CD14 derived from urine appeared to consist of two major polypeptides of about 54 and 48 kDa. In uCD14 isolated from three different nephrotic patients the cytokine-inducing activity appeared to co-migrate with the 48-kDa polypeptide which upon sequencing had the same N-terminal sequence as native CD14. Treatment of human monocytes and the human astrocytoma cell line U373 with uCD14 resulted in a strong secretion of tumor necrosis factor (TNF) and interleukin-6, respectively. The cytokine-inducing activity of the uCD14 preparations was unaffected by the absence of serum. This is in contrast to the activation of human monocytes and U373 cells by lipopolysaccharide (LPS) which is highly dependent on the presence of serum. The cytokine-inducing activity was not affected by LPS-binding protein (LBP) or polyclonal rabbit antibodies against LBP The TNF-inducing activity of uCD14 was also heat labile in contrast to the cytokine-inducing activity of LPS, which was relatively heat resistant. The results suggest that CD14 may exist in at least two forms of which one is involved in cytokine induction.     

Effect of the NSAID flurbiprofen on remodelling after periodontal surgery

The aim of the present experiment was to assess the effect of the administration of the NSAID flurbiprofen (Froben®) on tissue healing after periodontal surgery. Sites from patients with the same treatment modality (modified Widman flap) but receiving a placebo drug and sites within each patient not exposed to surgery served as controls. Nineteen patients suffering from moderate to severe periodontal disease were recruited and they signed informed consent forms. These patients required periodontal surgery as assessed at the periodontal re-evaluation. The sites chosen for the study were all diagnosed with PPD ≥ 5 mm and were bleeding on probing. During the healing phase 10 patients received 50 mg Froben® 3 times per day for 30 d whereas 9 patients received a placebo drug. Two sites with PPD ≥ 5 mm after initial therapy and bleeding on probing served as surgical sites, whereas 2 similar sites were not exposed to surgery. The study design was set up double-blind. The radiographic examination consisted of 2–4 standardized vertical bitewings obtained at the periodontal re-evaluation (BL) at 1, 3 and 6 months post-surgically for digital subtraction and computer assisted densitometric image analysis (CADIA). The regions of interest analysed were mesial or distal crestal sites. Minimal remodelling activity was observed radiographically after periodontal surgery in both patient groups. There were no statistically significant differences between the four groups of sites regarding the mean changes in density when analysing the pairs of radiographs 0–1, 0–3, 0–6 months. A frequency analysis was performed to list the number of sites with different ranges of density change. No differences in the distributions of the numbers of sites were observed when comparing the 4 site groups (Kolmogorov-Smirnov, p > 0.05). A significant reduction of the probing pocket depth and a significant amount of clinical attachment gain was noted at the surgically treated sites irrespective of whether the patients had used flurbiprofen or placebo. Whereas the pathways leading to bone resorption in periodontally diseased sites have been shown, in other studies, to be influenced by NSAID, the results of the present study could not justify general administration of Froben® for the purpose of reduction of bone resorption after periodontal surgical procedures in patients with adult periodontitis.     

Emotional perception modulated by an opioid and a cholecystokinin agonist

Rationale The cholecystokinin (CCK) and opioid neuromodulatory systems work in an antagonistic fashion and can modulate emotional states and noxious input in opposite directions. In this behavioral study, we generalize this idea and suggest that CCK and opioids can modulate the processing of other external signals, e.g., visual stimuli rather than only noxious input. Objectives The objective of this study was to determine whether CCK and an opioid agonist could modulate the emotional experience of visual stimuli. Materials and methods Thirteen healthy male volunteers viewed standardized pictures with either neutral or unpleasant content. Simultaneously, one of three treatments was administered in a randomized, double-blind crossover design: the CCK_b receptor agonist pentagastrin (0.1 μg/kg), the mu-opioid receptor agonist remifentanil (0.0625 μg/kg), or saline. Self-ratings of the emotional experience of pictures and drugs were sampled together with psychological tests and recording of heart rate. Results Pentagastrin treatment increased the rating of unpleasantness for both neutral and unpleasant pictures, while it decreased the rating of pleasantness for the neutral pictures. These effects did not correlate with the degree of general unpleasantness induced by the drug. Remifentanil treatment increased the pleasantness for the neutral pictures. While pentagastrin treatment induced a heart rate increase, unpleasant pictures induced a heart rate decrease, and the magnitude of change in heart rate correlated positively for these conditions. Conclusions This study shows that the CCK and the opioid system modulate how external stimuli are emotionally perceived, suggesting a possible involvement in affective disorders.