Objective. To compare the efficacy and tolerability of losartan, an antagonist of angiotensin II receptor type 1, with nifedipine for the treatment of primary and secondary Raynaud's phenomenon (RP) in a pilot study.Methods. In a randomized, parallel-group, controlled trial, patients with primary RP (n ‫؍‬ 25) or RP secondary to systemic sclerosis (SSc [scleroderma]; n ‫؍‬ 27) were allocated to receive 12 weeks' treatment with either losartan (50 mg/day) or nifedipine (40 mg/day). Primary outcome variables were the severity and frequency of RP episodes and findings on vascular measurements, including thermography and laser Doppler flowmetry. Serum levels of soluble adhesion molecules, endothelin 1, fibrinogen, von Willebrand factor, and procollagen type I N-terminal propeptide (PINP) were also measured.Results. There was a reduction in the severity of RP episodes following treatment with losartan and with nifedipine, but this effect was greater in the losartan arm of the study (P < 0.05): episode frequency was reduced only in the losartan group (P < 0.01 versus baseline). Symptomatic improvement was associated with a significant reduction in soluble vascular cell adhesion molecule 1 and PINP (P < 0.01). Subgroup analysis suggested that although these biochemical changes occurred mainly in SSc patients, the clinical benefit was greater in the primary RP group.Conclusion. This study confirms the tolerability of short-term treatment of RP with losartan, and our data suggest its clinical benefit. Further evaluation of this drug as a long-term treatment for SSc-associated RP should be considered, since it may have additional disease-modifying potential.Episodic digital ischemia provoked by cold and emotion was first described by Maurice Raynaud over 130 years ago (1). When it occurs in isolation, it is designated primary Raynaud's phenomenon (RP) to distinguish it from those cases in which there is an underlying or associated pathology. It affects ϳ10% of the adult population, with a predilection for females, and up to 5% of patients presenting with this condition later develop an autoimmune rheumatic disorder, such as systemic sclerosis (SSc; scleroderma) (2). Successful treatment is often difficult, and although clinical trials suggest that vasodilators can be effective, the responses of individual patients to a particular agent are often idiosyncratic.The pathogenesis of the vascular dysfunction underlying RP is incompletely understood, and relatively few well-controlled clinical trials with vasoactive drugs have been undertaken. Lack of distinction between primary and secondary RP in some of these studies makes their interpretation difficult. Calcium channel antagonists such as nifedipine have been shown to be effective (3-6), although striking differences in individual responses have been described (3,7). Moreover, efficacy is often particularly limited in patients with RP

An algorithm for analyzing changes in ECG morphology based on principal component analysis (PCA) is presented and applied to the derivation of surrogate respiratory signals from single-lead ECGs. The respiratory-induced variability of ECG features, P waves, QRS complexes, and T waves are described by the PCA. We assessed which ECG features and which principal components yielded the best surrogate for the respiratory signal. Twenty subjects performed controlled breathing for 180 s at 4, 6, 8, 10, 12, and 14 breaths per minute and normal breathing. ECG and breathing signals were recorded. Respiration was derived from the ECG by three algorithms: the PCA-based algorithm and two established algorithms, based on RR intervals and QRS amplitudes. ECG-derived respiration was compared to the recorded breathing signal by magnitude squared coherence and cross-correlation. The top ranking algorithm for both coherence and correlation was the PCA algorithm applied to QRS complexes. Coherence and correlation were significantly larger for this algorithm than the RR algorithm(p < 0.05 and p < 0.0001, respectively) but were not significantly different from the amplitude algorithm. PCA provides a novel algorithm for analysis of both respiratory and nonrespiratory related beat-to-beat changes in different ECG features.

Changes in the ECG IntroductionTherapeutic intervention to reduce transient myocardial ischaemic episodes could significantly improve the quality of life in affected subjects by reducing morbidity and mortality. The current methods of diagnosing these ischaemic events include cardiovascular imaging of the coronary arteries [1]. However, such specialised and resource intensive techniques are, arguably, unsuitable for studying ischaemic events brought on by activities of daily living in any one individual. Another technique, based on the analysis of the ECG waveform, has shown promise since abnormalities in the repolarization of ischaemic myocardial regions are visible in the ST segment of the ECG [2,3]. Although changes in ST elevation/depression can be quantified they can also occur because of a wide variety of other causes, including changes in heart rate, conduction pattern, hyperventilation, electrolyte abnormalities, response to medication, response to temperature changes, position of the subject, and noise in the ECG [4,5].Despite these uncertainties, ECG measurements can be highly sensitive, easy to do, and lend themselves to ambulatory (e.g. 24 hour) assessments [6][7][8] and computer-based automated analyses [9][10][11]. If it were possible to accurately distinguish between ischaemic and non-ischaemic ST changes in ambulatory ECG recordings made during subjects' normal activities, the benefits could be immediate and substantial to the patient.The aims of this study were therefore a) to produce a novel algorithm t o distinguish ischaemic and nonischaemic ST changes in the ECG waveform and b) to determine the accuracy of the algorithm using expertly annotated ambulatory ECG data sets as a reference. Methods Basic algorithmData for the changes in ST ( D ST) provided by PhysioNet were used. An example of DST is shown in figure 1. Event start times (T s ), for which the expertly classified ST changes (ischaemic or non-ischaemic) were known, were also provided and used in the development of the algorithm. DST represents the difference in ST between the current ST level and the baseline level. Principal components of ST provided by PhysioNet were also used in the optimization of the algorithm. The algorithm was based on the premise that ischaemic ST changes are large relative to non-ischaemic changes and that they are maintained for a period of time. The algorithm classified events as ischaemic if at the start of the event DST was greater than a threshold DST (V thres ), and before the end of the event DST maintained a minimum level (V min ) for a period of time (T min ).

Nine participants performed two bouts of a step exercise, during which the quadriceps muscle of one leg acted eccentrically. Before and after the exercise, isokinetic torque was measured over a range of knee angles to determine the optimum angle for torque. Immediately after the first bout of exercise, the quadriceps showed a significant (P < 0.05) shift of 15.6 +/- 1.4 degrees (mean +/-sx) of its optimum angle in the direction of longer lengths, suggesting the presence of damage. A drop in peak torque, together with delayed soreness and swelling, confirmed that damage to muscle fibres had occurred. After the second bout of exercise, 8 days later, the shift in optimum angle was 10.4 +/- 1.0 degrees, which was significantly less than after the first bout (P < 0.05). Other indicators of damage were also reduced. In addition, the muscle exhibited a sustained shift in optimum angle (3.4 +/- 0.9 degrees), suggesting that some adaptation had taken place after the first bout of exercise. We conclude that muscles like the quadriceps can show evidence of damage after a specific programme of eccentric exercise, followed by an adaptation response. This is despite the fact that the quadriceps routinely undergoes eccentric contractions in everyday activities.