Evaluation of a single session with cooling garment for persons with multiple sclerosis – a randomized trial

Purpose. This research investigates the objective and subjective effects of wearing the Rehband® cooling garment.

Method. A multi-centre, randomized crossover study was conducted regarding 43 heat-sensitive persons with multiple sclerosis (MS), comparing active treatment with placebo. Subjects were tested immediately before and after intervention. Ten- (10TW) and 30-metre timed walk (30TW), oral temperature, spasticity, standing balance and timed up and go (TUG) and nine-hole peg test (NHPT) performance were measured. A study-specific questionnaire was used to evaluate subjective experiences.

Results. Active treatment produced statistically significant objective improvement in 10TW, 30TW, one-legged stance, tandem stance (right) and TUG; statistically significant subjective improvement was also found in fatigue, spasticity, weakness, balance, gait, transfers, ability to think clearly and time to recover. The coherence between the objective and subjective results indicates clinical relevance from the subjects' perspective. There were no statistically significant differences between treatments in terms of oral temperature, spasticity (measured by the modified Ashworth scale), tandem stance (left), step test or NHPT, or subjective signs such as difficulty in dressing, dysarthria or pain.

Conclusions. Active cooling with a Rehband® vest is likely to have a positive effect on everyday life in heat-sensitive persons with MS.     

Risk of stroke and oral anticoagulant use in atrial fibrillation: a cross-sectional survey

Background

Oral anticoagulants substantially reduce the risk of stroke in atrial fibrillation but are underutilised in current practice.

Aim

To measure the distribution of stroke risk in patients with atrial fibrillation (using the CHADS² and CHA₂DS₂-VASc scores) and changes in oral anticoagulant use during 2007–2010.

Design and setting

Longitudinal series of cross-sectional survey in 583 UK practices linked to the QResearch® database providing 99 351 anonymised electronic records from people with atrial fibrillation.

Method

The proportion of patients in each CHADS₂ and CHA₂DS₂-VASc risk band in 2010 was calculated; for each of the years 2007–2010, the proportions with risk scores ≥2 that were using anticoagulants or antiplatelet agents were estimated. The proportions identified at high risk were re-estimated using alternative definitions of hypertension based on coded data. Finally, the prevalence of comorbid conditions in treated and untreated high-risk (CHADS₂ ≥2) groups was derived.

Results

The proportion at high risk of stroke in 2010 was 56.9% according to the CHADS₂ ≥2 threshold, and 84.5% according to CHA₂DS₂-VASc ≥2 threshold. The proportions of these groups receiving anticoagulants were 53.0% and 50.7% respectively and increased during 2007–2010. The means of identifying the population of individuals with hypertension significantly influenced the estimated proportion at high risk. Comorbid conditions associated with avoidance of anticoagulants included history of falls, use of nonsteroidal anti-inflammatory drugs, and dementia.

Conclusion

Oral anticoagulant use in atrial fibrillation has increased in UK practice since 2007, but remains suboptimal. Improved coding of hypertension is required to support systematic identification of individuals at high risk of stroke and could be assisted by practice-based software.     

Aberrant forms of alpha(2)-macroglobulin purified from patients with multiple sclerosis

The biochemical properties of alpha(2)-macroglobulin were investigated in four patients with multiple sclerosis and compared to alpha(2)-macroglobulin from healthy controls. An impaired stability of alpha(2)-macroglobulin from the multiple sclerosis patients was demonstrated as a spontaneous conversion to an electrophoretic"fast" form of alpha(2)-macroglobulin upon purification and storage, with a concomitant decrease in functional capacity to inhibit proteinases. The ability to form complexes with proteinases was significantly reduced in alpha(2)-macroglobulin purified from the multiple sclerosis patients. The aberrant molecular arrangements of the protein were not due to proteinase cleavages in the bait regions of alpha(2)-macroglobulin, as demonstrated by gel electrophoresis and protein sequencing. The number of functional thiol esters, however, was reduced in alpha(2)-macroglobulin purified from the multiple sclerosis patients, an observation compatible with the impaired proteinase binding property. Furthermore, differences in isoelectric points were observed between alpha(2)-macroglobulin from the multiple sclerosis patients and alpha(2)-macroglobulin from healthy controls. The results suggest that aberrant forms of alpha(2)-macroglobulin may be present in patients with multiple sclerosis.     

Insulin absorption and subcutaneous blood flow in normal subjects during insulin-induced hypoglycemia

We studied the effects of insulin-induced hypoglycemia on the absorption of 10 U 125I-labeled soluble human insulin injected sc in the thigh in 10 normal subjects. The disappearance of 125I from the injection site was followed by external gamma-counting. Subcutaneous blood flow (ATBF) was measured concomitantly with the 133Xe washout technique. The plasma glucose nadir [mean, 2.0 +/- 0.1 (+/- SE) mmol/L] occurred at 33 +/- 3 min and resulted in maximal arterial plasma epinephrine concentrations of approximately 6 nmol/L. From 30 min before to 60 min after the glucose nadir the [125I]insulin absorption rate was depressed compared to that during normoglycemia. The first order disappearance rate constants were reduced by approximately 50% (P less than 0.01) during the first 30-min interval after the glucose nadir. During the same period ATBF increased by 100% (P less than 0.05). The results suggest that in normal subjects the absorption of soluble insulin from a sc depot is depressed in connection with hypoglycemia, despite considerably elevated ATBF.     

Antibodies to adult human endothelial cells cross-react with oxidized low-density lipoprotein and beta 2-glycoprotein I (beta 2-GPI) in systemic lupus erythematosus

Cardiovascular manifestations are common in systemic lupus erythematosus (SLE). Oxidized low-density lipoprotein (oxLDL) is implicated in cardiovascular disease, especially atherosclerosis, and cross-reacts with antibodies to cardiolipin (aCL). beta 2-GPI is a plasma protein participating in the coagulating cascade, and is also cofactor for aCL, and some aCL have been shown to be directed against beta 2-GPI and/or complexes between beta 2-GPI and phospholipids. Lysophosphatidylcholine (LPC) is a phospholipid present both in oxLDL and in damaged endothelium, and we recently showed that LPC is involved in the antigenicity of oxLDL. Antibodies to endothelial cells (aEC) correlate with diseases activity in SLE and vasculitis, and we recently showed that aEC are enhanced in cardiovascular disease such as borderline hypertension and early atherosclerosis. aEC were determined using EC from adult V. Saphena Magna. Antibody levels were determined by ELISA. aEC of IgG type were enhanced in 184 patients with SLE compared with 85 healthy controls. There was a close correlation between aoxLDL, aCL, aLPC, a beta 2-GPI and aEC. Binding of sera to EC was competitively inhibited by beta 2-GPI, LPC and oxLDL. Taken together, the data indicate that EC share antigenic epitopes with beta 2-GPI and with oxLDL, especially LPC. Phospholipids in EC membranes may thus be antigenic epitopes. beta 2-GPI may bind to these phospholipids, and become an autoantigen. LPC is formed by oxidation of phospholipids and/or proinflammatory factors leading to activation of phospholipase A2, and the findings indicate the potential role of both lipid oxidation and phospholipase A2 in SLE.     

Determination of estramustine phosphate and its metabolites estromustine, estramustine, estrone and estradiol in human plasma by liquid chromatography with fluorescence detection and gas chromatography with nitrogen-phosphorus and mass spectrometric detection

Bioanalytical methods for the determination of estramustine phosphate by liquid chromatography and its four main metabolites estromustine, estramustine, estrone and estradiol by gas chromatography are described. For the estramustine phosphate assay the plasma was purified by protein precipitation followed by a C18 solid-phase extraction. For the metabolite assay the plasma samples were purified by a C18 solid-phase and liquid-liquid extraction procedure and derivatised by silanization. Thereafter, estramustine and estromustine were quantified by gas chromatography with nitrogen-phosphorus detection and estradiol and estrone were quantified by gas chromatography with selected ion monitoring. The methods were validated with respect to linearity, selectivity, precision, accuracy, limit of quantitation, limit of detection, recovery and stability. The limit of quantitation was 2.3 micromol/l for estramustine phosphate, 30 nmol/l for estromustine and estramustine, 12 nmol/l for estrone and 8 nmol/l for estradiol. The results showed good precision and accuracy for estramustine phosphate and the four metabolites. The intermediate precision was 6.2-13.5% (C.V.) and the accuracy was 91.8-103.9%.     

Emotional perception modulated by an opioid and a cholecystokinin agonist

Rationale The cholecystokinin (CCK) and opioid neuromodulatory systems work in an antagonistic fashion and can modulate emotional states and noxious input in opposite directions. In this behavioral study, we generalize this idea and suggest that CCK and opioids can modulate the processing of other external signals, e.g., visual stimuli rather than only noxious input. Objectives The objective of this study was to determine whether CCK and an opioid agonist could modulate the emotional experience of visual stimuli. Materials and methods Thirteen healthy male volunteers viewed standardized pictures with either neutral or unpleasant content. Simultaneously, one of three treatments was administered in a randomized, double-blind crossover design: the CCK_b receptor agonist pentagastrin (0.1 μg/kg), the mu-opioid receptor agonist remifentanil (0.0625 μg/kg), or saline. Self-ratings of the emotional experience of pictures and drugs were sampled together with psychological tests and recording of heart rate. Results Pentagastrin treatment increased the rating of unpleasantness for both neutral and unpleasant pictures, while it decreased the rating of pleasantness for the neutral pictures. These effects did not correlate with the degree of general unpleasantness induced by the drug. Remifentanil treatment increased the pleasantness for the neutral pictures. While pentagastrin treatment induced a heart rate increase, unpleasant pictures induced a heart rate decrease, and the magnitude of change in heart rate correlated positively for these conditions. Conclusions This study shows that the CCK and the opioid system modulate how external stimuli are emotionally perceived, suggesting a possible involvement in affective disorders.