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Background/Objectives: It is well established that combining a reduced calorie, low-fat diet with the lipase inhibitor orlistat results in significantly greater weight loss than placebo plus diet. This weight loss is accompanied by changes in adipose tissue (AT) distribution. As 60 mg orlistat is now available as an over-the-counter medication, the primary objective of this study was to determine whether 60 mg orlistat is effective as a weight loss option in a free- living community population with minimal professional input. Methods: AT and ectopic lipid content were measured using magnetic resonance imaging and ¹H MR spectroscopy, respectively, in 27 subjects following 3 months treatment with orlistat 60 mg and a reduced calorie, low-fat diet. Results: Significant reductions in intra-abdominal AT (-10.6%, P = 0.023), subcutaneous (-11.7% Po 0.0001) and pericardial fat (-9.8%, P = 0.034) volumes and intrahepatocellular lipids (-43.3%, P = 0.0003) were observed. These changes in body fat content and distribution were accompanied by improvements in plasma lipids and decreases in blood pressure and heart rate. Conclusion: These findings suggest that over-the-counter 60 mg orlistat, in combination with the type of advice a subject could expect to be given when obtaining 60 mg orlistat in a community setting, does indeed result in potentially clinically beneficial changes in body composition and risk factors for metabolic diseases. European journal of Clinical Nutrition (2011) 65, 1256-1262; doi: 10.1038/ejcn.2011.108; published online 22 June 2011 Keywords: magnetic resonance imaging; intrahepatocellular lipid; adipose tissue; weight loss; orlistat; visceral fat, Introduction There is a paucity of prescription drugs available for long-term treatment of obesity. In Europe only Xenical (orlistat 120 mg) is currently licensed. In 2007, orlistat 60 mg (alli) [...]

A fundamental issue in neuroscience is the relation between structure and function. However, gross landmarks do not correspond well to microstructural borders and cytoarchitecture cannot be visualized in a living brain used for functional studies. Here, we used diffusion-weighted and functional MRI to test structure-function relations directly. Distinct neocortical regions were defined as volumes having similar connectivity profiles and borders identified where connectivity changed. Without using prior information, we found an abrupt profile change where the border between supplementary motor area (SMA) and pre-SMA is expected. Consistent with this anatomical assignment, putative SMA and pre-SMA connected to motor and prefrontal regions, respectively. Excellent spatial correlations were found between volumes defined by using connectivity alone and volumes activated during tasks designed to involve SMA or pre-SMA selectively. This finding demonstrates a strong relationship between structure and function in medial frontal cortex and offers a strategy for testing such correspondences elsewhere in the brain.

J Neurol Neurosurg Psychiatry 2004;75:6-12 Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is a powerful approach to defining activity in the healthy and diseased human brain. BOLD [...]

Objectives: Functional reorganisation of the motor or sensory cortex has been demonstrated in animals after section of mixed peripheral nerves. Here functional changes in the motor cortex specifically after peripheral [...]

MELAS, the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, can be difficult to diagnose. The various symptoms of the syndrome are apparently all related to defects in some of the mitochondria, the tiny organelles within cells that provide critical steps in the cells' energy metabolism. The distribution of symptoms in the body is likely to be related to the distribution of defective mitochondria. Often, the disorder can be diagnosed by observing a particular pathology of muscle fibers in a small muscle biopsy specimen. However, these so-called ''ragged-red fibers'' are not always visible. Similarly, lactic acidosis, an excessive amount of lactic acid in the blood, is often but not always present. The mitochondrial abnormalities exacts their toll on brain function, but the brain abnormalities that can be visualized on computed tomography (CT) are somewhat general in appearance and cannot be used to make a specific diagnosis. On the other hand, magnetic resonance imaging (MRI) reveals alterations in the brains of patients with MELAS which may prove to be relatively specific. Three cases are presented in which MRI revealed a particular pattern. The areas on the MRI around the cerebral cortex and the cortex of the cerebellum in each case were very light, a finding referred to by MRI technicians as hyperintensity. Similar findings occur in strokes, but the areas affected by strokes are defined by the anatomical distribution of blood vessels in the brain. No obstruction of blood flow could produce the patterns of hyperintensity seen in the present patients. Some areas of affected white matter were observed, but these invariably lay immediately underneath areas of affected cortex. Although there is no cure for the MELAS syndrome, the proper diagnosis of the disorder may permit the prevention of the more serious symptoms. The avoidance of stress and exertion may help minimize the effects of this metabolic disorder. (Consumer Summary produced by Reliance Medical Information, Inc.)

In this era of impressive images constructed using magnetic resonance imaging, it might be easy to forget the original development of magnetic resonance spectroscopy as a tool for the examination of molecular structure. It is possible to use magnetic resonance imaging to detect phosphorous-containing compounds within the body, since phosphorous is a paramagnetic element. However, it is also possible to measure, albeit approximately, some of the more common phosphorous-containing compounds non-invasively within the living body using magnetic resonance spectroscopy. Using this technique, investigators recorded phosphorus magnetic resonance spectra from the muscles of 17 patients with mitochondrial myopathy and 20 patients with other muscle diseases, including myasthenia gravis, muscular dystrophy, and inflammatory and metabolic myopathies. Fourteen of the 17 patients with mitochondrial disease showed an increase in intracellular inorganic phosphate, indicating an abnormal energy state. In three of these patients, the phosphocreatine was seen to be reduced in concentration. Similar elevations of intracellular phosphate could be observed in six of 20 of the patients with other muscle diseases. In all six of these patients, there was evidence of muscle necrosis (death of muscle tissue) as determined by biopsy. The authors suggest that when used along with standard clinical and laboratory tests, phosphorus magnetic resonance spectroscopy of muscle can play a useful role in the diagnosis of mitochondrial myopathy. (Consumer Summary produced by Reliance Medical Information, Inc.)

Introduction: There are few published data regarding the ability of a clinical nurse specialist to perform upper GI endoscopy. In our unit a nurse practitioner was trained in gastroscopy in [...]

Large cohort studies have defined an increasing range of therapeutic interventions that can be applied to reduce stroke risk. However, application of these in a specialist practice is complicated by [...]

Abstract: Exposure of biological material to high levels of free radicals causes extensive cellular damage. Reactive oxygen species (ROS) generated by mitochondria have been associated with a variety of diseases and aging. We investigated the effect of low-level mitochondrial ROS production on newly synthesized mitochondrial proteins which are potentially vulnerable to mitochondrial ROS due to their location and unfolded state. We show that elevated mitochondrial ROS increases the degradation of newly synthesized mitochondrial proteins with some proteins more sensitive than others. In the long term reduced assembly of mitochondrial complexes would affect mitochondrial function and may trigger a vicious cycle of mitochondrial ROS production. [Copyright &y& Elsevier]

Previous studies have established the clinical relevance of hypointense lesions (“black holes”) on T1-weighted MRI as a surrogate marker for pathological change [36]. In contrast to measuring the volume of “black holes”, the direct measurement of T1 values allows an objective assessment of the changes contributing to hypointensity both in the focal lesions and in the normal appearing white matter (NAWM). The aims of this study were first, to determine the relationship between T1 values in the NAWM and in discrete lesions, second, to test the relationship between white matter T1 changes and measures of disability and third, to determine whether pathology leading to T1 change occurred in thalamic grey matter of patients with multiple sclerosis. 24 patients with clinically definite multiple sclerosis (13 with relapsing-remitting multiple sclerosis and 11 with secondary progressive multiple sclerosis) and 11 controls participated. White matter T1 histograms and mean T1 values for the thalamus were generated from whole brain T1 relaxation time maps measured using a novel echo-planar imaging based MRI sequence at 3Tesla. Tissue segmentation based on T2- and T1-weighted images allowed independent study of changes in lesions and NAWM. White matter T1 histograms from the patient group showed a reduced peak height and a shift towards higher T1 values (p = 0.028) relative to controls. The mean thalamic T1 was greater for secondary progressive patients than for healthy controls (p = 0.03). Mean white matter T1 values correlated significantly with disability (r = 0.48, p = 0.02). The mean T1 value in the T1-hypointense lesions correlated strongly with the mean T1 value in the NAWM (r = 0.80, p < 0.001). No significant relationship was found between mean white matter T1 value and cerebral volume (r = -0.23, p = 0.31). The T1 measurements extend previous observations suggesting that changes in the NAWM occur in parallel with pathology in lesions of MS. T1 measurements of either the total or NAWM therefore may provide a potentially observer- and scanner- independent marker of pathology relevant to disability in MS. [ABSTRACT FROM AUTHOR]

Analyzes the application of functional magnetic resonance imaging in multiple sclerosis (MS). Pathology of MS; Association between adaptive functional changes and brain injury; Localization of brain functions; Cortical functional reorganization in MS.

We wished to contrast cortical activation during hand movements in profoundly weak patients with motor neuropathy and in normal controls using a paradigm that is behaviourally matched between the two groups. Previous work has suggested that a passive movement task could be appropriate. Using functional magnetic resonance imaging (fMRI), we first characterised patterns of brain activation during active and passive index finger movements in healthy controls (n=10). Although the relative activation differences were highly variable, there was a trend for the mean number of significantly activated voxels in the primary motor cortex contralateral to the hand moved (CMC) to be lower for the passive than for the active task (40% relative decrease, P=0.09). There was a small posterior shift in the centre of mass of the CMC (mean, 8 mm, P<0.02) and of the ipsilateral sensorimotor cortex (IMC) (mean, 11 mm, P<0.05). No activation with passive movement was found in the patients with severe distal sensory neuropathy (n=2), suggesting that activation with passive movements is dependent on sensory feedback and unlikely to be due to mental imagery alone. In contrast, patients with severe pure motor neuropathies (MN, n=2) showed substantial increases in the volumes of activation compared to controls. The relative increases in numbers of voxels activated above threshold in different regions of interest for both the active (MN/controls: CMC, 2.1; IMC, 8.1; supplementary motor area [SMA], 5.2) and passive (CMC, 2.6; IMC, 8.0; SMA, 5.1) tasks were similar. These results confirm expansion of cortical representation for finger movement in patients with motor neuropathy and demonstrate central reorganisation as a consequence of the motor nerve loss. An expanded representation for finger movement in the primary motor cortex with peripheral weakness suggests the possibility that the primary motor cortex may encode motor unit activation rather directly. [ABSTRACT FROM AUTHOR]