MRI of Arterial Flow Reserve in Patients with Intermittent Claudication: Feasibility and Initial Experience

Objectives: The aim of this work was to develop a MRI method to determine arterial flow reserve in patients with intermittent claudication and to investigate whether this method can discriminate between patients and healthy control subjects. Methods: Ten consecutive patients with intermittent claudication and 10 healthy control subjects were included. All subjects underwent vector cardiography triggered quantitative 2D cine MR phase-contrast imaging to obtain flow waveforms of the popliteal artery at rest and during reactive hyperemia. Resting flow, maximum hyperemic flow and absolute flow reserve were determined and compared between the two groups by two independent MRI readers. Also, interreader reproducibility of flow measures was reported. Results: Resting flow was lower in patients compared to controls (4.961.6 and 11.163.2 mL/s in patients and controls, respectively (p,0.01)). Maximum hyperemic flow was 7.362.9 and 16.463.2 mL/s (p,0.01) and the absolute flow reserve was 2.461.6 and 5.361.3 mL/s (p,0.01), respectively in patients and controls. The interreader coefficient of variation was below 10 % for all measures in both patients and controls. Conclusions: Quantitative 2D MR cine phase-contrast imaging is a promising method to determine flow reserve measures in patients with peripheral arterial disease and can be helpful to discriminate patients with intermittent claudication fro

Effectiveness of manual therapies: the UK evidence report

<p>Abstract</p> <p>Background</p> <p>The purpose of this report is to provide a succinct but comprehensive summary of the scientific evidence regarding the effectiveness of manual treatment for the management of a variety of musculoskeletal and non-musculoskeletal conditions.</p> <p>Methods</p> <p>The conclusions are based on the results of systematic reviews of randomized clinical trials (RCTs), widely accepted and primarily UK and United States evidence-based clinical guidelines, plus the results of all RCTs not yet included in the first three categories. The strength/quality of the evidence regarding effectiveness was based on an adapted version of the grading system developed by the US Preventive Services Task Force and a study risk of bias assessment tool for the recent RCTs.</p> <p>Results</p> <p>By September 2009, 26 categories of conditions were located containing RCT evidence for the use of manual therapy: 13 musculoskeletal conditions, four types of chronic headache and nine non-musculoskeletal conditions. We identified 49 recent relevant systematic reviews and 16 evidence-based clinical guidelines plus an additional 46 RCTs not yet included in systematic reviews and guidelines.</p> <p>Additionally, brief references are made to other effective non-pharmacological, non-invasive physical treatments.</p> <p>Conclusions</p> <p>Spinal manipulation/mobilization is effective in adults for: acute, subacute, and chronic low back pain; migraine and cervicogenic headache; cervicogenic dizziness; manipulation/mobilization is effective for several extremity joint conditions; and thoracic manipulation/mobilization is effective for acute/subacute neck pain. The evidence is inconclusive for cervical manipulation/mobilization alone for neck pain of any duration, and for manipulation/mobilization for mid back pain, sciatica, tension-type headache, coccydynia, temporomandibular joint disorders, fibromyalgia, premenstrual syndrome, and pneumonia in older adults. Spinal manipulation is not effective for asthma and dysmenorrhea when compared to sham manipulation, or for Stage 1 hypertension when added to an antihypertensive diet. In children, the evidence is inconclusive regarding the effectiveness for otitis media and enuresis, and it is not effective for infantile colic and asthma when compared to sham manipulation.</p> <p>Massage is effective in adults for chronic low back pain and chronic neck pain. The evidence is inconclusive for knee osteoarthritis, fibromyalgia, myofascial pain syndrome, migraine headache, and premenstrual syndrome. In children, the evidence is inconclusive for asthma and infantile colic.</p

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Metabolomics and Age-Related Macular Degeneration

Age-related macular degeneration (AMD) leads to irreversible visual loss, therefore, early intervention is desirable, but due to its multifactorial nature, diagnosis of early disease might be challenging. Identification of early markers for disease development and progression is key for disease diagnosis. Suitable biomarkers can potentially provide opportunities for clinical intervention at a stage of the disease when irreversible changes are yet to take place. One of the most metabolically active tissues in the human body is the retina, making the use of hypothesis-free techniques, like metabolomics, to measure molecular changes in AMD appealing. Indeed, there is increasing evidence that metabolic dysfunction has an important role in the development and progression of AMD. Therefore, metabolomics appears to be an appropriate platform to investigate disease-associated biomarkers. In this review, we explored what is known about metabolic changes in the retina, in conjunction with the emerging literature in AMD metabolomics research. Methods for metabolic biomarker identification in the eye have also been discussed, including the use of tears, vitreous, and aqueous humor, as well as imaging methods, like fluorescence lifetime imaging, that could be translated into a clinical diagnostic tool with molecular level resolution

The importance of the altricial – precocial spectrum for social complexity in mammals and birds:A review

Various types of long-term stable relationships that individuals uphold, including cooperation and competition between group members, define social complexity in vertebrates. Numerous life history, physiological and cognitive traits have been shown to affect, or to be affected by, such social relationships. As such, differences in developmental modes, i.e. the ‘altricial-precocial’ spectrum, may play an important role in understanding the interspecific variation in occurrence of social interactions, but to what extent this is the case is unclear because the role of the developmental mode has not been studied directly in across-species studies of sociality. In other words, although there are studies on the effects of developmental mode on brain size, on the effects of brain size on cognition, and on the effects of cognition on social complexity, there are no studies directly investigating the link between developmental mode and social complexity. This is surprising because developmental differences play a significant role in the evolution of, for example, brain size, which is in turn considered an essential building block with respect to social complexity. Here, we compiled an overview of studies on various aspects of the complexity of social systems in altricial and precocial mammals and birds. Although systematic studies are scarce and do not allow for a quantitative comparison, we show that several forms of social relationships and cognitive abilities occur in species along the entire developmental spectrum. Based on the existing evidence it seems that differences in developmental modes play a minor role in whether or not individuals or species are able to meet the cognitive capabilities and requirements for maintaining complex social relationships. Given the scarcity of comparative studies and potential subtle differences, however, we suggest that future studies should consider developmental differences to determine whether our finding is general or whether some of the vast variation in social complexity across species can be explained by developmental mode. This would allow a more detailed assessment of the relative importance of developmental mode in the evolution of vertebrate social systems

Multiple sea-ice states and abrupt MOC transitions in a general circulation ocean model

Sea ice has been suggested, based on simple models, to play an important role in past glacial–interglacial oscillations via the so-called “sea-ice switch” mechanism. An important requirement for this mechanism is that multiple sea-ice extents exist under the same land ice configuration. This hypothesis of multiple sea-ice extents is tested with a state-of-the-art ocean general circulation model coupled to an atmospheric energy–moisture-balance model. The model includes a dynamic-thermodynamic sea-ice module, has a realistic ocean configuration and bathymetry, and is forced by annual mean forcing. Several runs with two different land ice distributions represent present-day and cold-climate conditions. In each case the ocean model is initiated with both ice-free and fully ice-covered states. We find that the present-day runs converge approximately to the same sea-ice state for the northern hemisphere while for the southern hemisphere a difference in sea-ice extent of about three degrees in latitude between the different runs is observed. The cold climate runs lead to meridional sea-ice extents that are different by up to four degrees in latitude in both hemispheres. While approaching the final states, the model exhibits abrupt transitions from extended sea-ice states and weak meridional overturning circulation, to less extended sea ice and stronger meridional overturning circulation, and vice versa. These transitions are linked to temperature changes in the North Atlantic high-latitude deep water. Such abrupt changes may be associated with Dansgaard–Oeschger events, as proposed by previous studies. Although multiple sea ice states have been observed, the difference between these states is not large enough to provide a strong support for the sea-ice-switch mechanism

Late Potentials in a Porcine Model of Anterior Wall Myocardial Infarction and Their Relation to Inducible Ventricular Tachycardia

In this study, normal values for signal averaged electrocardiographic parameters were assessed in healthy pigs (n = 100) and the development of late potentials after myocardial infarction (n = 41) in relation to inducible ventricular tachycardia was investigated. Normal values are: filtered QRS duration (QRS) less-than-or-equal-to 70 msec; root mean square voltage of the averaged QRS complex (V(tot)) greater-than-or-equal-to 51 muV, and duration of terminal activity below 30 muV (D30) less-than-or-equal-to 37 msec. The distribution of the root mean square voltage in the last 30 msec (V30) Was biphasic. Two weeks after myocardial infarction, QRS was prolonged from 55 +/- 10 to 66 +/- 19 msec (P <0.002). D30 was prolonged from 19 +/- 6 msec to 28 +/- 13 (P <0.002). V30 was decreased from 107 +/- 135 muV to 45 +/- 77 (P <0.02). The total voltage (V(tot)) was decreased from 195 +/- 78 to 123 +/- 61 muV (P <0.002). In four pigs (19%) late potentials developed. Sustained ventricular tachycardia was inducible in 11 pigs (52%), ventricular fibrillation in two pigs (10%) and eight pigs (38%) were noninducible. Three of 11 inducible pigs and one of the noninducible pigs had a late potential. The incidence of late potentials and their relation to inducible sustained ventricular tachycardia is comparable to the situation in man. Therefore, this pig model is an attractive alternative to the commonly used dog models