MR assessment of cerebral vascular response: a comparison of two methods

PURPOSE: To compare the results and reproducibility of two MR-based methods of measuring the cerebrovascular response (CVR). MATERIALS AND METHODS: In eight volunteers, CVR was assessed with two MR-based methods upon a challenge with acetazolamide. CVR was assessed by measuring changes in total cerebral blood flow (TCBF) using phase contrast (PC) MRI, and by measuring perfusion MRI. To assess reproducibility the measurements were repeated after 1 week. RESULTS: The average CVR with the PC-MRI method was 46% (SD = 16%), and for perfusion MR the measured CVR was 44% (SD = 16%). The coefficient of variation (COV) for PC-MRI was 28%, while perfusion MR had a COV of 26%. The limits of agreement between the two methods were -49% and 45%, demonstrating a lack of agreement between the two methods in terms of CVR estimation. CONCLUSION: CVR estimates based on PC-MRI and perfusion MRI showed reproducibility but a lack of agreement in healthy volunteers. This lack of agreement can be attributed to the different aspects of the CVR reflected by these methods: TCBF reflects changes in CBF, whereas our perfusion MRI method reflects cerebral blood volume (CBV).     

Optimizing blood collection,transport and storage conditions for cell free DNA increases access to prenatal testing

Objectives

Fetal mutations and fetal chromosomal abnormalities can be detected by molecular analysis of circulating cell free fetal DNA (ccffDNA) from maternal plasma. This comprehensive study was aimed to investigate and verify blood collection and blood shipping conditions that enable Noninvasive Prenatal Testing. Specifically, the impact of shipping and storage on the stability and concentration of circulating cell-free DNA (ccfDNA) in Streck® Cell-Free DNA™ Blood Collection Tubes (Streck BCTs, Streck, Omaha NE). These BCTs were designed to minimize cellular degradation, and thus effectively prevent dilution of fetal ccf DNA by maternal genomic DNA, was evaluated.

Design and methods

Peripheral venous maternal blood was collected into Streck BCTs to investigate four aspects of handling and processing conditions: (1) time from blood draw to plasma processing; (2) storage temperature; (3) mechanical stress; and (4) lot-to-lot tube variations.

Results

Maternal blood stored in Streck BCTs for up to 7 days at ambient temperature provides stable concentrations of ccffDNA. The amount of fetal DNA did not change over a broad range of storage temperatures (4 °C, 23 °C, 37 °C, 40 °C), but the amount of total (largely maternal) DNA increased in samples stored at 23 °C and above, indicating maternal cell degradation and genomic DNA release at elevated temperatures. Shipping maternal blood in Streck BCTs, did not affect sample quality.

Conclusions

Maternal plasma DNA stabilized for 0 to 7 days in Streck BCTs can be used for non-invasive prenatal molecular applications, when temperatures are maintained within the broad parameters assessed in this study.     

Cognitive performance in type 1 diabetes patients is associated with cerebral white matter volume

Aims/hypothesis Cognitive performance in type 1 diabetes may be compromised as a result of chronic hyperglycaemia. The aim of this study was to investigate the cognitive functioning of patients with type 1 diabetes (including a subgroup with a microvascular complication) and nondiabetic controls, and to assess the relationship between cognition and cerebral grey and white matter volumes. Materials and methods Twenty-five patients with type 1 diabetes (of whom ten had proliferative retinopathy) and nine nondiabetic controls (matched in terms of sex, age and education) underwent a neuropsychological examination and magnetic resonance imaging of the brain. Fractional brain tissue volumes (tissue volume relative to total intracranial volume) were obtained from each participant. Results Compared with nondiabetic controls, patients with diabetes performed worse on tests measuring speed of information processing and visuoconstruction; patients with microvascular disease performed worse on the former cognitive domain (p = 0.03), whereas patients without complications performed worse on the latter domain (p = 0.01). Patients with a microvascular complication had a significantly smaller white matter volume than nondiabetic controls (p = 0.04), and smaller white matter volume was associated with worse performance on the domains of speed of information processing and attention and executive function. Conclusions/interpretation Patients with diabetes demonstrated several subtle neuropsychological deficits, which were found to be related to white matter volume. Since patients with diabetic retinopathy had a smaller white matter volume, this suggests that cognitive decline is at least partly mediated by microvascular disease. This needs to be addressed in future studies.     

Left ventricular internal resistance and unloaded ejection flow assessed from pressure-flow relations: a flow-clamp study on isolated rabbit hearts

Left ventricular pressure-flow relations were studied, using excised working rabbit hearts and imposing constant flow ejections (flow-clamps) to separate the effects of flow on pressure from those of time, flow duration, starting volume, ejected volume, and volume at specified time. Pressure-flow data at given volume and time were independent of flow duration, starting volume, and ejected volume for flow-clamp durations exceeding 30 msec. Flow history independent of pressure-flow relations was linear for flow values larger than +/- 5 ml/sec. The time-varying elastance model, E(t), of the ventricle was extended with a resistive component. Transient effects of flow can be explained by including a second elastance. The resulting verified 3-component model is consistent with recent reported experimental findings. The properties of internal resistance correspond to a constant unloaded ejection flow Qmax, which was tested by extrapolating the linear pressure-flow relations to zero pressure. Qmax reached a plateau value of approximately 25 ml/sec within 50 msec after the start of contraction. In relaxation, Qmax is only slightly smaller. Qmax did not depend on volume; therefore, the following equation was adequate for the relation between pressure, p(t); volume, V(t); and flow Q(t), during the flow-clamped ejections from 30 minutes after the start of the flow: (t) = E(t).(V(t)-Vd).(1-Q(t)/Qmax)     

Quality of Diabetes and Hyperlipidemia Screening Before a First Myocardial Infarction

Background

There has been significant attention to the quality of care for acute myocardial infarction (MI). However, little is known about the quality of preventive care before a patient's first MI.

Methods

We conducted a retrospective, cohort analysis of 5688 patients admitted with their first MI to 96 acute care hospitals in Ontario, Canada, from April 2004 to March 2005 using the Enhanced Feedback For Effective Cardiac Treatment clinical study database. We calculated rates of screening for diabetes and hyperlipidemia according to guidelines using linkages to the Ontario Health Insurance Plan database. Screening rates were stratified by age, sex, socioeconomic status, and number of primary care visits in the past 5 years.

Results

Among the 5688 eligible patients, 27.1% did not receive serum cholesterol screening in the 5 years preceding their MI and 27.5% of patients did not receive a fasting blood glucose or glucose tolerance test in the 3 years before their MI. Women were more likely to be screened than men. Screening rates generally increased with age and were similar across socioeconomic categories. There was a positive association between the number of primary care visits and the likelihood of being screened.

Conclusions

A significant number of patients admitted with their first MI were not screened for important modifiable risk factors. Opportunities for the prevention of coronary disease are being missed. More emphasis is needed on identifying risk factors before the development of acute coronary disease.     

Genetic and Shared Environmental Influences on Interferon-γ Production in Response to Mycobacterium tuberculosis Antigens in a Ugandan Population

Interferon-γ (IFN-γ) is a key cytokine in the immune response to Mycobacterium tuberculosis (Mtb). Many studies established IFN-γ responses are influenced by host genetics, however differed widely by the study design and heritability estimation method. We estimated heritability of IFN-γ responses to Mtb culture filtrate (CF), ESAT-6, and Antigen 85B (Ag85B) in 1,104 Ugandans from a household contact study. Our method separately evaluates shared environmental and genetic variance, therefore heritability estimates were not upwardly biased, ranging from 11.6% for Ag85B to 22.9% for CF. Subset analyses of individuals with latent Mtb infection or without human immunodeficiency virus infection yielded higher heritability estimates, suggesting 10–30% of variation in IFN-γ is caused by a shared environment. Immunosuppression does not negate the role of genetics on IFN-γ response. These estimates are remarkably close to those reported for components of the innate immune response. These findings have implications for the interpretation of IFN-γ response assays and vaccine studies.     

Investigation of Obstacles to Accessing Information Regarding Private Medical Insurance Coverage and Physician Reimbursement for Adolescent Vaccination

PurposeTo investigate accessing insurance company vaccine reimbursement and coverage information.MethodA telephone survey was conducted from June 2006 to August 2006. Participating organizations were insurance companies in the states of New York, Oregon, and Texas. The main outcome measure was the obstacles encountered while trying to obtain information on vaccine costs and reimbursement.ResultsObstacles identified included the predominance of automated answering systems and the necessity of leaving voicemail messages, company nonresponse, and refusal to participate.ConclusionsObstacles result in difficulty obtaining vaccine reimbursement and coverage information by phone. Greater transparency is necessary to enable stakeholders to make informed decisions about immunizations.     

Safe use of a once‐a‐week glucagon‐like peptide‐1 receptor agonist in a 16‐year‐old girl with type 2 diabetes when approved therapy options fail

This case report demonstrates that using a non‐approved long‐acting GLP‐1‐RA (dulaglutide) in adolescents with T2D is possible and feasible under special circumstances when approved therapeutic options for the pediatric population fail to achieve adequate glycemic control.