MRI retinovascular studies in humans: research in patients with diabetes

PURPOSE: To review existing applications of MRI for detecting blood-retinal barrier (BRB) damage and retinal oxygenation response abnormalities in patients with diabetes and highlight new information available from such applications. METHODS: BRB studies were accomplished using dynamic contrast-enhanced MRI, and the retinal oxygenation response studies were accomplished by monitoring changes in the MRI signal associated with hyperoxic provocation. Participants were patients with diabetes and macular edema, with either no detectable or mild to moderate background retinopathy, as well as non-diabetic individuals of similar age (controls). Single-slice FLASH images were obtained using a Siemens Sonata, 1.5 T together with a Siemens 'Loop Small' surface coil fixed in place over the eye. Time-dependent changes in image contrast in the pre-retinal vitreous were quantified, and differences between patients and controls were assessed statistically. RESULTS: The BRB breakdown studies showed a significant difference in the temporal evolution of the MRI signal enhancement post-contrast injection between the controls and the patients with diabetic macular edema. The retinal oxygenation studies revealed a supernormal oxygenation response in the pre-retinal vitreous in patients with diabetes who had no evidence of retinopathy, as well as in patients with background diabetic retinopathy. A nasal-temporal asymmetry in the evolution of retinal oxygenation response was found in patients with diabetes that was not present in healthy subjects. CONCLUSIONS: These studies show that subtle differences in retinovascular function between patients with diabetes and non-diabetic individuals, including changes that occur in advance of the clinical appearance of diabetic retinopathy, can be detected with MRI. These results, together with previous extensive preclinical data, establish MRI as a powerful non-invasive method for measuring spatial and temporal changes in the same key retinovascular metrics in both animals and humans. Wide application of these techniques for diagnosis and evaluation of treatment efficacy in a variety of human retinopathies, including diabetic retinopathy, is expected.     

Arginine attenuates methylglyoxal- and high glucose-induced endothelial dysfunction and oxidative stress by an endothelial nitric-oxide synthase-independent mechanism

The mechanisms of ethanol addiction are not completely understood. The mesolimbic dopaminergic system is involved in many drug-related behaviors, including ethanol self-administration. The dopaminergic neurons in this system originate in the ventral tegmental area (VTA) and are under the control of GABAergic transmission. Our previous in vitro electrophysiological data indicate that glycine receptors (GlyRs) exist on the GABAergic terminals, which make synapses on VTA dopaminergic neurons, and activation of these GlyRs reduces GABAergic transmission and increases the activity of VTA dopaminergic neurons. In the current study, we tested the hypothesis that the activation of the presynaptic GlyRs in the VTA might interfere with ethanol self-administration. Glycine and strychnine, the selective antagonist of GlyRs, were injected, either alone or in combination, into the VTA of rats. Ethanol self-administration by rats was evaluated by using three different drinking models: intermittent access, continuous access, and operant self-administration. We found that the infusion of glycine into the VTA selectively reduced the intake of ethanol but not sucrose or water in rats chronically exposed to ethanol under the intermittent-access and continuous-access procedures and decreased lever-press responding for ethanol under an operant self-administration procedure. The effects of glycine probably were mediated by strychnine-sensitive GlyRs, because the coinjection of glycine and strychnine reduced neither ethanol intake in the home cages nor lever-press responding for ethanol in the operant chambers. Thus, GlyRs in the VTA may play a critical role in ethanol self-administration in animals chronically exposed to ethanol. Therefore, drugs targeting GlyRs may be beneficial for alcoholics.     

Assisting cytopathology training in medically under-resourced countries: defining the problems and establishing solutions

Cytology is able to deliver rapid accurate diagnoses with minimal equipment and laboratory infrastructure at minimal cost, and this is especially so for fine needle biopsy (FNB), which is a powerful diagnostic tool in medically resource-poor environments, where histopathology laboratories are small in number and poorly supported financially. The crucial element in the development of cytology services is to train a sufficient number of well trained cytopathologists and cytotechnologists to create a 'critical mass' of personnel who not only provide routine diagnostic services, but also can train an ever expanding number of pathologists, cytotechnologists, and health workers. A review of practical programs to train cytopathologists and cytotechnologists in their own countries will be presented, including a recent series of FNB and cytology tutorials run in sub Saharan Africa. The need for local cytopathology programs and the potential for both local and visiting cytopathologists to provide a faculty will be discussed, as well as a range of possible programs which can bring African pathologists and trainee pathologists to Western institutions for periods of their training. Ideally, the regional Societies of Cytology, including the recently formed West African Society of Cytology, will establish their own diagnostic protocols, training programs, syllabuses, examinations and accreditation and career pathways for both cytopathologists and cytotechnologists, and organize tutorials where they will invite overseas faculty to contribute. Crucially, these new societies will empower cytopathologists and cytotechnologists to approach health services and governments to state the need for cytology services as a cost-effective accurate diagnostic service that enhances patient care.     

Reduction in atherosclerotic events: a retrospective study in an outpatient cardiology practice

Introduction

Although atherosclerotic disease cannot be cured, risk of recurrent events can be reduced by application of evidence-based treatment protocols involving aspirin, beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statin medications. We studied atherosclerotic event rates in a patient population treated before and after the development of aggressive risk factor reduction treatment protocols.

Material and methods

We performed a retrospective chart review of patients presenting for follow-up treatment of coronary artery disease in a community cardiology practice, comparing atherosclerotic event rates and medication usage in a 2-year treatment period prior to 2002 and a 2-year period in 2005-2008. Care was provided in both the early and later eras by 7 board-certified cardiologists in a suburban cardiology practice. Medication usage was compared in both treatment eras. The primary outcome was a composite event rate of myocardial infarction, cerebrovascular events, and coronary interventions.

Results

Three hundred and fifty-seven patients were studied, with a follow-up duration of 12.1 (±3.5) years. There were 132 composite events in 104 patients (29.1%) in the early era compared to 40 events in 33 patients (9.2%) in the later era (p < 0.0001). From the early to the later eras, there was an increase in use of β-blockers (66% to 83%, p < 0.0001), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (34% to 80%, p < 0.0001), and statins (40% to 90%, p < 0.0001).

Conclusions

Application of aggressive evidence-based medication protocols for treatment of atherosclerosis is associated with a significant decrease in atherosclerotic events or need for coronary intervention.     

Measuring NHS performance 1990-2009 using amenable mortality: interpret with care

Objectives

The new performance framework for the NHS in England will assess how well health services are preventing people from dying prematurely, based on the concept of mortality amenable to healthcare. We ask how the different parts of the UK would be assessed had this measure been in use over the past two decades, a period that began with somewhat lower levels of health expenditure in England and Wales than in Scotland and Northern Ireland but which, after 1999, saw the gap closing.

Design

We assessed the change in age-standardized death rates in England and Wales, Northern Ireland and Scotland in two time periods: 1990–1999 and 1999–2009. Mortality data by five-year age group, sex and cause of death for the years 1990 to 2009 were analysed using age-standardized death rates from causes considered amenable to healthcare. The absolute change was assessed by fitting linear regression and the relative change was estimated as the average annual percent decline for the two periods.

Setting

United Kingdom.

Participants

Not applicable.

Main outcome measures

Mortality from causes amenable to healthcare.

Results

Between 1990 and 1999 deaths amenable to medical care had been falling more slowly in England and Wales than in Scotland and Northern Ireland. However the rate of decline in England and Wales increased after 1999 when funding of the NHS there increased. Examination of individual causes of death reveals a complex picture, with some improvements, such as in breast cancer deaths, occurring simultaneously across the UK, reflecting changes in diagnosis and treatment that took place in each nation at the same time, while others varied.

Conclusions

Amenable mortality is a useful indicator of health system performance but there are many methodological issues that must be taken into account when interpreting it once it is adopted for routine use in England.