Prolonged P wave duration is associated with right atrial dimensions, but not atrial arrhythmias, in middle-aged endurance athletes.

BACKGROUND: Atrial arrhythmias occur at a higher than expected prevalence amongst endurance athletes. Few studies have examined both atrial structure and arrhythmias in middle-aged endurance athletes. We examined the relationship between P-wave duration, atrial dimensions, and the presence of atrial ectopy in long-standing, middle-aged endurance athletes. METHODS: Middle-aged athletes with a minimum of 10 years of competitive endurance sport history and no history of structural heart disease or clinical atrial arrhythmias, had 12-lead ECGs to assess P-wave duration, signal-averaged ECGs (SAECG) to assess filtered P-wave duration, a 24 h Holter monitor to assess atrial ectopy, and echocardiography and cardiac magnetic resonance imaging to assess atrial structural characteristics. RESULTS: Amongst endurance athletes (n = 104; mean age = 54 ±â€¯5 years; 63% male), filtered P-wave duration on SAECG was correlated with P-wave duration on 12-lead ECG (r = 0.36, p, 0.0001), as well as with larger CMR-derived RA areas (r = 0.30, p = 0.01) and volumes (r = 0.24, p < 0.05). There was no correlation between filtered P-wave duration and any LA measures on imaging (p > 0.05). There was no correlation between the incidence of atrial ectopy (premature atrial contractions or atrial tachycardia) and any electrocardiographic or structural measures. CONCLUSION: Longer filtered P-wave duration was associated with larger RA areas and volumes, without an increase in atrial ectopy.

Vascular imaging in diabetes.

Diabetes is a global epidemic affecting individuals of all socioeconomic backgrounds. Despite intensive efforts, morbidity and mortality secondary to the micro- and macrovascular complications remain unacceptably high. As a result, the use of imaging modalities to determine the underlying pathophysiology, early onset of complications, and disease progression has become an integral component of the management of such individuals. Echocardiography, stress echocardiography, and nuclear imaging have been the mainstay of noninvasive cardiovascular imaging tools to detect myocardial ischemia, but newer modalities such as cardiac MRI, cardiac CT, and PET imaging provide incremental information not available with standard imaging. While vascular imaging to detect cerebrovascular and peripheral arterial disease non-invasively has traditionally used ultrasound, CT- and MRI-based techniques are increasingly being employed. In this review, we will provide an outline of recent studies utilizing non-invasive imaging techniques to assist in disease diagnosis as well as monitoring disease progression. In addition, we will review the evidence for newer modalities such as MR spectroscopy, 3D intravascular ultrasound, and optical coherence tomography that provide exquisite detail of metabolic function and coronary anatomy not available with standard imaging, but that have not yet become mainstream.

Association of Asian ethnicity with disease activity in SLE: an observational study from the Monash Lupus Clinic.

OBJECTIVE: Systemic lupus erythematosus (SLE), an autoimmune condition with diverse clinical manifestations, is reported to have different expression in populations of different ancestry. Most previous studies compared patients of different ethnic groups from geographically distinct cohorts. In our study, we aimed to characterize disease manifestations in patients of different ethnic groups from a single centre, and studied patterns of disease activity over time. METHODS: Demographics, baseline disease characteristics and autoantibody profiles, and disease activity (SLEDAI) measured at each visit, were captured from all consenting patients prospectively followed between 2007 and 2011 in an urban teaching hospital lupus clinic. Ethnicity was self-reported. RESULTS: Asian ethnicity was significantly associated with more clinically severe SLE. Time-adjusted mean SLEDAI (p = 0.01) and maximum SLEDAI (p = 0.0018) were significantly higher in Asian patients. Asians were more likely to have renal disease (OR 2.9, 95% CI 1.4-5.98; p = 0.004) and persistently active disease (PAD) (OR 2.14, 95% CI 1.05-4.38, p = 0.04). Asian lupus patients also had a significantly higher proportion of autoantibody positivity to anti-dsDNA, anti-RNP, anti-Sm, anti-Ro and anti-La, as well as increased likelihood of hypocomplementaemia and immunosuppressant use. CONCLUSION: In this single-cohort study, Asian ethnicity was found to be associated with increased SLE disease activity. This suggests significant inter-ethnic genetic contributions to the regulation of autoimmune responses and disease severity in SLE.

Asian ethnicity in systemic lupus erythematosus: an Australian perspective.

Ethnic differences in both disease susceptibility and expression have been noted in systemic lupus erythematosus (SLE). This review focuses on the evidence of disparities between SLE patients of Asian and Caucasian descent, the two predominant ethnic groups affected by SLE in the Australian context. While epidemiological studies suggest higher rates of SLE among Asian patients, multi-ethnic cohort studies have allowed direct comparison of disease characteristics between different ethnic groups. Such studies suggest that Asians are affected by more severe SLE across several disease parameters, including increased renal involvement, autoantibody positivity, disease activity and damage accumulation. As delineation of these disparities becomes clearer, uncovering the biological basis of such differences poses a significant opportunity to progress understanding of SLE pathogenesis. Understanding ethnic variation in disease provides a platform for an individualised approach to risk assessment, monitoring and management of SLE.

The accuracy of transoesophageal echocardiography in estimating pulmonary capillary wedge pressure in anaesthetised patients.

The objective of this study was to identify whether pulmonary capillary wedge pressure can be estimated in anaesthetised patients receiving mechanical ventilation, using transoesophageal echocardiography. A retrospective validation study investigated a 10-patient cohort with variable haemodynamic conditions, and a 102-patient series in which a single measurement was made during stable haemodynamic conditions. Concurrent echocardiographic Doppler and pulmonary artery catheter wedge pressure measurements were performed. In the 10-patient cohort, the systolic fraction of Doppler measurements in the pulmonary vein (r = -0.32, p = 0.035) and the E/A ratio (r = 0.56, p = 0.0009) were correlated with the wedge pressure. In all cases, the limits of agreement exceeded 10 mmHg, and sensitivity or specificity for detecting wedge pressure ≥ 15 mmHg was poor. This study demonstrates proof of concept that using transoesophageal echocardiography for estimating the pulmonary artery wedge pressure may not be sufficiently accurate for clinical use.

Ethanol photo-oxidation on a rutile TiO2(110) single crystal surface.

The reaction of ethanol has been studied on the surface of rutile TiO(2)(110) by Temperature Programmed Desorption (TPD), online mass spectrometry under UV excitation and photoelectron spectroscopy while the adsorption energies of the molecular and dissociative modes of ethanol were computed using the DFT/GGA method. The most stable configuration is the dissociative adsorption in line with experimental results at room temperature. At 0.5 ML coverage the adsorption energy was found equal to 80 kJ mol(-1) for the dissociative mode (ethoxide, CH(3)CH(2)O(a) + H(a)) followed by the molecular mode (67 kJ mol(-1)). The orientation of the ethoxides along the [001] or [110] direction had minor effect on the adsorption energy although affected differently the Ti and O surface atomic positions. TPD after ethanol adsorption at 300 K indicated two main reactions: dehydration to ethylene and dehydrogenation to acetaldehyde. Pre-dosing the surface with ethanol at 300 K followed by exposure to UV resulted in the formation of acetaldehyde and hydrogen. The amount of acetaldehyde could be directly linked to the presence of gas phase O(2) in the vacuum chamber. The order of this photo-catalytic reaction with respect to O(2) was found to be 0.5. Part of acetaldehyde further reacted with O(2) under UV excitation to give surface acetate species. Because the rate of photo-oxidation of acetates (acetic acid) was slower than that of ethoxides (ethanol), the surface ended up by being covered with large amounts of acetates. A reaction mechanism for acetaldehyde, hydrogen and acetate formation under UV excitation is proposed.

Functional, structural and molecular aspects of diastolic heart failure in the diabetic (mRen-2)27 rat.

OBJECTIVE: Diabetic cardiomyopathy is an increasingly recognized cause of cardiac failure despite preserved left ventricular systolic function. Given the over-expression of angiotensin II in human diabetic cardiomyopathy, we hypothesized that combining hyperglycaemia with an enhanced tissue renin-angiotensin system would lead to the development of diastolic dysfunction with adverse remodeling in a rodent model. METHODS: Homozygous (mRen-2)27 rats and non-transgenic Sprague Dawley (SD) rats were randomized to receive streptozotocin (diabetic) or vehicle (non-diabetic) and followed for 6 weeks. Prior to tissue collection, animals underwent pressure-volume loop acquisition. RESULTS: Diabetic Ren-2 rats developed impairment of both active and passive phases of diastole, accompanied by reductions in SERCA-2a ATPase and phospholamban along with activation of the fetal gene program. Structural features of diabetic cardiomyopathy in the Ren-2 rat included interstitial fibrosis, cardiac myocyte hypertrophy and apoptosis in conjunction with increased activity of transforming growth factor-beta (p<0.01 compared with non-diabetic Ren-2 rats for all parameters). No significant functional or structural derangements were observed in non-transgenic, SD diabetic rats. CONCLUSION: These findings indicate that the combination of enhanced tissue renin-angiotensin system and hyperglycaemia lead to the development of diabetic cardiomyopathy. Fibrosis, and myocyte hypertrophy, a prominent feature of this model, may be a consequence of activation of the pro-sclerotic cytokine, transforming growth factor-beta, by the diabetic state.

Longitudinal association of type 1 interferon-induced chemokines with disease activity in systemic lupus erythematosus.

Type I interferon (IFN) pathways are significant in SLE pathogenesis. Less is known about the utility of measuring markers of IFN activity in patients, or whether patient subsets with different profiles exist. We explored the longitudinal associations of IFN-induced chemokines with disease activity in a cohort of SLE patients. We calculated a validated composite score (IFN-CK) of three type I IFN-inducible chemokines (CCL2/CXCL10/CCL19) measured in 109 SLE patients (median 7 occasions over 3.2 years). Longitudinal associations of IFN-CK score with disease activity (SLEDAI-2K) and other variables were assessed using general estimating equation (GEE) methods. IFN-CK was detectable in all patients. SLEDAI-2K was significantly associated with IFN-CK, damage score and prednisolone dose. SLEDAI-2K remained significantly associated with IFN-CK over time after adjustment of covariates. Patients with high time-adjusted mean IFN-CK had lower complement and higher time-adjusted disease activity. Concordance between IFN-CK and SLEDAI-2K varied widely among patients, with some individuals having none, others weak, and a subset very high concordance. In summary in our cohort of SLE patients, serum IFN-CK varied over time with disease activity, but with wide variation in concordance. Differing relationships between IFN pathway activation and disease activity may be valuable in assigning patients to emerging IFN-pathway targeting treatments.

Bence Jones proteins bind to a common peptide segment of Tamm-Horsfall glycoprotein to promote heterotypic aggregation.

Bence Jones proteins (BJPs) are the major pathogenic factor causing cast nephropathy ("myeloma kidney") by coaggregation with Tamm-Horsfall glycoprotein (THP). Understanding the interaction between these proteins is therefore important in developing treatment strategies to prevent renal failure from cast formation in multiple myeloma. We developed an enzyme-linked immunoassay to examine this phenomenon. Five different human BJPs (four kappa and one lambda immunoglobulin light chains) were used in this assay that demonstrated these proteins bound THP with different affinity. BJPs competed among themselves for binding to THP. The binding site was a peptide portion of THP since these proteins also bound deglycosylated THP. Also, one monoclonal antibody directed against a peptide segment of human THP prevented binding of THP to BJPs. By altering the conformation of THP, reducing agents decreased binding between these two proteins in concentration-dependent fashion. In turbidity studies, the monoclonal antibody that prevented binding and a reducing agent, dithiothreitol, decreased coaggregation. Deglycosylated THP did not coaggregate with BJPs. We concluded that ionic interaction between BJPs and a specific peptide binding site on THP promoted heterotypic coaggregation. The carbohydrate moiety of THP was also essential for coaggregation, perhaps by facilitating homotypic aggregation of THP.

Localization of the delta opioid receptor and corticotropin-releasing factor in the amygdalar complex: role in anxiety.

It is well established that central nervous system norepinephrine (NE) and corticotropin-releasing factor (CRF) systems are important mediators of behavioral responses to stressors. More recent studies have defined a role for delta opioid receptors (DOPR) in maintaining emotional valence including anxiety. The amygdala plays an important role in processing emotional stimuli, and has been implicated in the development of anxiety disorders. Activation of DOPR or inhibition of CRF in the amygdala reduces baseline and stress-induced anxiety-like responses. It is not known whether CRF- and DOPR-containing amygdalar neurons interact or whether they are regulated by NE afferents. Therefore, this study sought to better define interactions between the CRF, DOPR and NE systems in the basolateral (BLA) and central nucleus of the amygdala (CeA) of the male rat using anatomical and functional approaches. Irrespective of the amygdalar subregion, dual immunofluorescence microscopy showed that DOPR was present in CRF-containing neurons. Immunoelectron microscopy confirmed that DOPR was localized to both dendritic processes and axon terminals in the BLA and CeA. Semi-quantitative dual immunoelectron microscopy analysis of gold-silver labeling for DOPR and immunoperoxidase labeling for CRF revealed that 55 % of the CRF neurons analyzed contained DOPR in the BLA while 67 % of the CRF neurons analyzed contained DOPR in the CeA. Furthermore, approximately 41 % of DOPR-labeled axon terminals targeted BLA neurons that expressed CRF while 29 % of DOPR-labeled axon terminals targeted CeA neurons that expressed CRF. Triple label immunofluorescence microscopy revealed that DOPR and CRF were co-localized in common cellular profiles that were in close proximity to NE-containing fibers in both subregions. These anatomical results indicate significant interactions between DOPR and CRF in this critical limbic region and reveal that NE is poised to regulate these peptidergic systems in the amygdala. Functional studies were performed to determine if activation of DOPR could inhibit the anxiety produced by elevation of NE in the amygdala using the pharmacological stressor yohimbine. Administration of the DOPR agonist, SNC80, significantly attenuated elevated anxiogenic behaviors produced by yohimbine as measured in the rat on the elevated zero maze. Taken together, results from this study demonstrate the convergence of three important systems, NE, CRF, and DOPR, in the amygdala and provide insight into their functional role in modulating stress and anxiety responses.

Association of MIF, but not type I interferon-induced chemokines, with increased disease activity in Asian patients with systemic lupus erythematosus.

Ethnicity is a key factor impacting on disease severity in SLE, but molecular mechanisms of these associations are unknown. Type I IFN and MIF have each been associated with SLE pathogenesis. We investigated whether increased SLE severity in Asian patients is associated with either MIF or Type I IFN. SLE patients (n = 151) had prospective recording of disease variables. Serum MIF, and a validated composite score of three Type I IFN-inducible chemokines (IFNCK:CCL2, CXCL10, CCL19) were measured. Associations of MIF and IFNCK score with disease activity were assessed, with persistent active disease (PAD) used as a marker of high disease activity over a median 2.6 years follow up. In univariable analysis, MIF, IFNCK score and Asian ethnicity were significantly associated with PAD. Asian ethnicity was associated with higher MIF but not IFNCK score. In multivariable logistic regression analysis, MIF (OR3.62 (95% CI 1.14,11.5), p = 0.03) and Asian ethnicity (OR3.00 (95% CI 1.39,6.46), p < 0.01) but not IFNCK were significantly associated with PAD. These results potentially support an effect of MIF, but not Type I IFN, in heightened SLE disease severity in Asian SLE. The associations of MIF and Asian ethnicity with PAD are at least partly independent.

XO increases neutrophil adherence to endothelial cells by a dual ICAM-1 and P-selectin-mediated mechanism.

Circulating xanthine oxidase (XO) can modify adhesive interactions between neutrophils and the vascular endothelium, although the mechanism underlying this effect are not clear. We found that treatment with XO of bovine pulmonary artery endothelial cells (EC), but not neutrophils or plasma, increased adherence, suggesting that XO had its primary effect on EC. The mechanism by which XO increased neutrophil adherence to EC involved binding of XO to EC and production of H2O2. XO also increased platelet-activating factor production by EC by a H2O2-dependent mechanism. Similarly, the platelet-activating factor-receptor antagonist WEB-2086 completely blocked XO-mediated neutrophil EC adherence. In addition, neutrophil adherence was dependent on the beta 2-integrin Mac-1 (CD11b/CD18) but not on leukocyte functional antigen-1 (CD11a/CD18). Treatment of EC with XO for 30 min did not alter intercellular adhesion molecule-1 surface expression but increased expression of P-selectin and release of von Willibrand factor. Antibodies against P-selectin (CD62) did not affect XO-mediated neutrophil adherence under static conditions but decreased both rolling and firm adhesive interactions under conditions of shear. We conclude that extracellular XO associates with the endothelium and promotes neutrophil-endothelial cell interactions through dual intercellular adhesion molecule-1 and P-selectin ligation, by a mechanism that involves platelet-activating factor and H2O2 as intermediates.

Cefotaxime ("Claforan') in routine hospital use.

A multi-centre study was carried out in 327 patients with a wide variety of moderate to severe infections. Patients were treated with cefotaxime at the recommended dosages and, in most cases, as the sole antibiotic. The bacteriological eradication rate was 83% while 92% of clinically assessable cases were successful; 3% of cases relapsed and 5% failed to respond. There was a low incidence of side-effects.

Neurologic complications of infectious mononucleosis.

A review of the neurologic complications of Epstein-Barr viral (EBV) infections is presented. EBV has been associated with a wide range of acute neurologic diseases in children. Encephalitis, meningitis, cranial nerve palsies, mononeuropathies, and many other neurologic ailments have been described since the confirmation of EBV as the etiology of infectious mononucleosis. It is important to recognize that EBV can cause a myriad of neurologic illnesses with or without the stigmata of infectious mononucleosis.

Growth hormone safety update from the National Cooperative Growth Study.

We reviewed adverse event (AE) data in the National Cooperative Growth Study from start-up (1985) until January 1, 1999. Enrollment was 33,161. A total of 2,632 AE reports were received; 863 were serious events, with 156 deaths. The most common cause of death was recurrence of intracranial neoplasm. There were 20 reports of leukemia, and the standard morbidity ratio (SMR) was 0.73 (95% CI: 0.20-1.86) for the four cases without risk factors. There were 35 reports of extracranial nonleukemic malignancy, and the SMR was 0.44 (95% CI: 0.24-0.74) for the 14 cases without risk factors. The recurrence rate for all brain tumors present at baseline was 7.6%, and for craniopharyngiomas, 6.4%. There were 49 reports of intracranial hypertension (20 patients had papilledema), 68 reports of diabetes/hyperglycemia, 45 of slipped capital femoral epiphysis, 136 of scoliosis, and five of pancreatitis. There was no evidence of increased incidence of leukemia or extracranial nonleukemic malignancies among patients without prior risk factors. Intracranial hypertension does not necessarily occur early in growth hormone therapy. Other findings were consistent with past observations.

Infectious disease of public health significance among children and adolescents in Texas.

In the past decade, many infectious diseases in children that were perceived to have been almost eliminated have returned with a vengeance in Texas. Across the state, vaccination rates are exceptionally low, and outbreaks of measles, mumps, and pertussis have been identified. Tuberculosis cases in children increased 77%, and cases of congenital syphilis increased 578% between 1987 and 1991. The new epidemic of HIV infection has placed additional strain on an already overburdened, inadequate public health system in Texas. This article identifies some of the major infections of public health significance among the children of Texas. A common theme for most of these problems is that they are preventable diseases that are not being prevented. Many children in Texas will suffer now and in the future if these public health problems remain ignored.

Combination angiotensin converting enzyme and direct renin inhibition in heart failure following experimental myocardial infarction.

AIMS: Diminishing the activity of the renin-angiotensin system (RAS) plays a pivotal role in the treatment of heart failure. In addition to angiotensin converting enzyme (ACE) inhibitors and angiotensin-receptor blockers, direct renin inhibition has emerged as a potential adjunctive treatment to conventional RAS blockade. We sought to determine the effectiveness of this strategy after myocardial infarction (MI) in the setting of preexisting hypertension, a common premorbid condition in patients with ischemic heart disease. METHODS AND RESULTS: Ten-week-old female heterozygous hypertensive (mRen-2)27 transgenic rats (Ren-2), were randomized to one of five groups (n = 8 per group); sham, MI, MI + aliskiren, MI + lisinopril and MI + combination lisinopril and aliskiren. Cardiac function was assessed by echocardiography and in vivo cardiac catheterization. Untreated MI animals developed heart failure with hypotension, dilation, reduced ejection fraction (EF), and raised left ventricular end-diastolic pressure (LVEDP). Treatment with single agent treatment had only modest effect on cardiac function though combination therapy was associated with significant improvements in EF and LVEDP when compared to untreated MI animals (P < 0.05). Histologic analysis demonstrated increase extracellular matrix deposition and cardiomyocyte hypertrophy in the noninfarct region of all MI groups when compared with sham operated animals (P < 0.05) that was reduced by ACE inhibitor monotherapy and combination treatment but not by aliskiren alone. CONCLUSION: In a hypertensive rat model that underwent experimental MI, EF, and LVEDP, key functional indices of heart failure, were improved by treatment with combination ACE and direct renin inhibition when compared with either agent used alone.