New magnetic-resonance-imaging-visible poly(ε-caprolactone)-based polyester for biomedical applications

A great deal of effort has been made since the 1990s to enlarge the field of magnetic resonance imaging. Better tissue contrast, more biocompatible contrast agents and the absence of any radiation for the patient are some of the many advantages of using magnetic resonance imaging (MRI) rather than X-ray technology. But implantable medical devices cannot be visualized by conventional MRI and a tool therefore needs to be developed to rectify this. The synthesis of a new MRI-visible degradable polymer is described by grafting an MR contrast agent (DTPA-Gd) to a non-water-soluble, biocompatible and degradable poly(ε-caprolactone) (PCL). The substitution degree, calculated by (1)H nuclear magnetic resonance and inductively coupled plasma-mass spectrometry, is close to 0.5% and proves to be sufficient to provide a strong and clear T1 contrast enhancement. This new MRI-visible polymer was coated onto a commercial mesh for tissue reinforcement using an airbrush system and enabled in vitro MR visualization of the mesh for at least 1 year. A stability study of the DTPA-Gd-PCL chelate in phosphate-buffered saline showed that a very low amount of gadolinium was released into the medium over 52 weeks, guaranteeing the safety of the device. This study shows that this new MRI-visible polymer has great potential for the MR visualization of implantable medical devices and therefore the post-operative management of patients.     

Imaging Heart Failure: Current and Future Applications

A variety of cardiac imaging tests are used to help manage patients with heart failure (HF). This article reviews current and future HF applications for the major noninvasive imaging modalities: transthoracic echocardiography (TTE), single-photon emission computed tomography (SPECT), positron emission tomography (PET), cardiovascular magnetic resonance (CMR), and computed tomography (CT). TTE is the primary imaging test used in the evaluation of patients with HF, given its widespread availability and reliability in assessing cardiac structure and function. Recent developments in myocardial strain, 3-dimensional TTE, and echo contrast appear to offer superior diagnostic and prognostic information. SPECT imaging is a common method employed to detect ischemia and viability in patients with HF; however, PET offers higher diagnostic accuracy for both. Ongoing study of sympathetic and molecular imaging techniques may enable early disease detection, better risk stratification, and ultimately targeted treatment interventions. CMR provides high-quality information on cardiac structure and function and allows the characterization of myocardial tissue. Myocardial late gadolinium enhancement allows the determination of HF etiology and may predict patient outcomes and treatment response. Cardiac CT has become a reliable means for detecting coronary artery disease, and recent advances have enabled concurrent myocardial function, perfusion, and scar analyses. Overall, available imaging methods provide reliable measures of cardiac performance in HF, and recent advances will allow detection of subclinical disease. More data are needed demonstrating the specific clinical value of imaging methods and particularly subclinical disease detection in large-scale, clinical settings.     

Community‐acquired respiratory viruses and co‐infection among patients of Ontario sentinel practices,April 2009 to February 2010

Please cite this paper as: Peci et al. (2012) Community‐acquired respiratory viruses and co‐infection among patients of Ontario Sentinel practices, April 2009 to February 2010. Influenza and Other Respiratory Viruses 7(4), 559–566. Background Respiratory viruses are known to cocirculate but this has not been described in detail during an influenza pandemic. Objectives To describe respiratory viruses, including co‐infection and associated attributes such as age, sex or comorbidity, in patients presenting with influenza‐like illness to a community sentinel network, during the pandemic A(H1N1)pdm09 in Ontario, Canada. Methods Respiratory samples and epidemiologic details were collected from 1018 patients with influenza‐like illness as part of respiratory virus surveillance and a multiprovincial case–control study of influenza vaccine effectiveness. Results At least one virus was detected in 668 (65·6%) of 1018 samples; 512 (50·3%) had single infections and 156 (15·3%) co‐infections. Of single infections, the most common viruses were influenza A in 304 (59·4%) samples of which 275 (90·5%) were influenza A(H1N1)pdm09, and enterovirus/rhinovirus in 149 (29·1%) samples. The most common co‐infections were influenza A and respiratory syncytial virus B, and influenza A and enterovirus/rhinovirus. In multinomial logistic regression analyses adjusted for age, sex, comorbidity, and timeliness of sample collection, single infection was less often detected in the elderly and co‐infection more often in patients <30 years of age. Co‐infection, but not single infection, was more likely detected in patients who had a sample collected within 2 days of symptom onset as compared to 3–7 days. Conclusions Respiratory viral co‐infections are commonly detected when using molecular techniques. Early sample collection increases likelihood of detection of co‐infection. Further studies are needed to better understand the clinical significance of viral co‐infection.     

Mosquito densonucleosis viruses cause dramatically different infection phenotypes in the C6/36 Aedes albopictus cell line

Mosquito densoviruses generally establish persistent infections in mosquito cell lines including the C6/36 Aedes albopictus cell line. In contrast, the closely related Haemagogus equinus densovirus (HeDNV) causes dramatic cytopathic effects in the C6/36 Aedes albopictus cell line. Infection of C6/36 cells by HeDNV causes internucleosomal fragmentation of host chromosomal DNA, changes in cellular morphology (membrane budding, apoptotic bodies), caspase activation and exposure of phosphatidylserine on the cellular membrane. This is accompanied by a higher rate of infection and more vigorous production of virus in these cells. These observations are consistent with the induction of apoptosis during infection. In contrast, expression of AeDNV proteins in C6/36 cells does not cause obvious cytopathic effects although NS1 expression causes accumulation of cells in G2 phase. C6/36 cells persistently infected with AeDNV were not protected from superinfection with HeDNV. Thus, there does not seem to be an antiviral state induced by AeDNV persistent infection.     

Transition to adult health care for adolescents and young adults with congenital heart disease: Perspectives of the patient, parent and health care provider

BACKGROUND:

Pediatric institutions play a large role in preparing young adults with congenital heart disease to transition to adult care.

OBJECTIVE:

To determine the perspectives of patients, parents and providers on transition preparation.

METHODS:

Patients aged nine to 18 years with congenital heart defects and their respective parent(s) participated in semistructured interviews. Health care providers completed a self-administered survey.

RESULTS:

A total of 23 patients, 22 parents and 45 health care providers were enrolled in the study. Only 36% of patients demonstrated a clear understanding of transition and its implications for their cardiac care. Parents were extensively involved in care activities, with 95% accompanying their child to visits at the clinic, 68% staying with their child for the entire visit and 45% administering their medication. Children more knowledgeable about their diagnosis demonstrated a better understanding about their transition to adult care (100% versus 7%, respectively; P<0.01) and were more likely to communicate directly with their providers than those who were less or not knowledgeable (88% versus 33%, respectively; P=0.03). Nurses were more likely than physicians to view increased parental involvement in care activities as a barrier to transition preparation (37% versus 5%, respectively; P=0.02).

CONCLUSIONS:

A lack of clear role expectations indicates a need for the pediatric health care setting to adapt appropriately to address the shifting needs of adolescent and young adult patients and their families. A formalized approach to transition preparation for adolescents with congenital heart disease needs to emphasize comprehensive education. A delegation of explicit responsibilities and the clear definition of roles for parents, providers and patients are necessary to provide young adults with the resources and support necessary to achieve a successful transition to adult care.     

Test-retest reliability of stride time variability while dual tasking in healthy and demented adults with frontotemporal degeneration

Background

Although test-retest reliability of mean values of spatio-temporal gait parameters has been assessed for reliability while walking alone (i.e., single tasking), little is known about the test-retest reliability of stride time variability (STV) while performing an attention demanding-task (i.e., dual tasking). The objective of this study was to examine immediate test-retest reliability of STV while single and dual tasking in cognitively healthy older individuals (CHI) and in demented patients with frontotemporal degeneration (FTD).

Methods

Based on a cross-sectional design, 69 community-dwelling CHI (mean age 75.5 ± 4.3; 43.5% women) and 14 demented patients with FTD (mean age 65.7 ± 9.8 years; 6.7% women) walked alone (without performing an additional task; i.e., single tasking) and while counting backward (CB) aloud starting from 50 (i.e., dual tasking). Each subject completed two trials for all the testing conditions. The mean value and the coefficient of variation (CoV) of stride time while walking alone and while CB at self-selected walking speed were measured using GAITRite^® and SMTEC^® footswitch systems.

Results

ICC of mean value in CHI under both walking conditions were higher than ICC of demented patients with FTD and indicated perfect reliability (ICC > 0.80). Reliability of mean value was better while single tasking than dual tasking in CHI (ICC = 0.96 under single-task and ICC = 0.86 under dual-task), whereas it was the opposite in demented patients (ICC = 0.65 under single-task and ICC = 0.81 under dual-task). ICC of CoV was slight to poor whatever the group of participants and the walking condition (ICC < 0.20), except while dual tasking in demented patients where it was fair (ICC = 0.34).

Conclusions

The immediate test-retest reliability of the mean value of stride time in single and dual tasking was good in older CHI as well as in demented patients with FTD. In contrast, the variability of stride time was low in both groups of participants.     

Streptozotocin,an O-GlcNAcase inhibitor,blunts insulin and growth hormone secretion

Type 2 diabetes mellitus results from a complex interaction between nutritional excess and multiple genes. Whereas pancreatic beta-cells normally respond to glucose challenge by rapid insulin release (first phase insulin secretion), there is a loss of this acute response in virtually all of the type 2 diabetes patients with significant fasting hyperglycemia. Our previous studies demonstrated that irreversible intracellular accumulation of a glucose metabolite, protein O-linked N-acetylglucosamine modification (O-GlcNAc), is associated with pancreatic beta-cell apoptosis. In the present study, we show that streptozotocin (STZ), a non-competitive chemical blocker of O-GlcNAcase, induces an insulin secretory defect in isolated rat islet cells. In contrast, transgenic mice with down-regulated glucose to glucosamine metabolism in beta-cells exhibited an enhanced insulin secretion capacity. Interestingly, the STZ blockade of O-GlcNAcase activity is also associated with a growth hormone secretory defect and impairment of intracellular secretory vesicle trafficking. These results provide evidence for the roles of O-GlcNAc in the insulin secretion and possible involvement of O-GlcNAc in general glucose-regulated hormone secretion pathways.     

Prognosis of negative adenosine stress magnetic resonance in patients presenting to an emergency department with chest pain.

OBJECTIVES: This study was designed to determine the diagnostic value of adenosine cardiac magnetic resonance (CMR) in troponin-negative patients with chest pain. BACKGROUND: We hypothesized that adenosine CMR could determine which troponin-negative patients with chest pain in an emergency department have coronary artery disease (CAD) or future adverse cardiac events. METHODS: Adenosine stress CMR was performed on 135 patients who presented to the emergency department with chest pain and had acute myocardial infarction (MI) excluded by troponin-I. The main study outcome was detecting any evidence of significant CAD. Patients were contacted at one year to determine the incidence of significant CAD defined as coronary artery stenosis >50% on angiography, abnormal correlative stress test, new MI, or death. RESULTS: Adenosine perfusion abnormalities had 100% sensitivity and 93% specificity as the single most accurate component of the CMR examination. Both cardiac risk factors and CMR were significant in Kaplan-Meier analysis (log-rank test, p = 0.0006 and p < 0.0001, respectively). However, an abnormal CMR added significant prognostic value in predicting future diagnosis of CAD, MI, or death over clinical risk factors. In receiver operator curve analysis, adenosine CMR was a more accurate predictor than cardiac risk factors (p < 0.002). CONCLUSIONS: In patients with chest pain who had MI excluded by troponin-I and non-diagnostic electrocardiograms, an adenosine CMR examination predicted with high sensitivity and specificity which patients had significant CAD during one-year follow-up. Furthermore, no patients with a normal adenosine CMR study had a subsequent diagnosis of CAD or an adverse outcome.     

The effect of tolbutamide on cerebral blood flow during hypoxia and hypercapnia in the anaesthetized rat

The increase in blood flow in the cerebral cortex of the anaesthetized rat during hypoxia and hypercapnia was investigated. Cerebral blood flow (CBF) was measured using the hydrogen clearance method with acutely implanted platinum electrodes. Hypoxia (PaO₂ 35.3±2.4 Torr) and hypercapnia (PaCO₂ 68.1±5.1 Torr) increased basal CBF from 76.3±9.0 ml/100g/min to 168.1±20.1 ml/100g/min and 162.4±31.9 ml/100g/min respectively. The sulphonylurea tolbutamide (1mM in 1%DMSO) had no significant effect on CBF in hyperoxia or in hypercapnia. However, it attenuated the increase of CBF during hypoxia by 66 ±11% (P<0.01). This suggests that opening of tolbutamide-sensitive potassium channels may be involved in the process of hypoxic vasodilation in the rat cerebral cortex.