Evidence for the effectiveness of Alexander Technique lessons in medical and health-related conditions: a systematic review.

BACKGROUND: Complementary medicine and alternative approaches to chronic and intractable health conditions are increasingly being used, and require critical evaluation. OBJECTIVE: The aim of this review was to systematically evaluate available evidence for the effectiveness and safety of instruction in the Alexander Technique in health-related conditions. METHODS: PUBMED, EMBASE, PSYCHINFO, ISI Web-of-Knowledge, AMED, CINHAL-plus, Cochrane library and Evidence-based Medicine Reviews were searched to July 2011. Inclusion criteria were prospective studies evaluating Alexander Technique instruction (individual lessons or group delivery) as an intervention for any medical indication/health-related condition. Studies were categorised and data extracted on study population, randomisation method, nature of intervention and control, practitioner characteristics, validity and reliability of outcome measures, completeness of follow-up and statistical analyses. RESULTS: Of 271 publications identified, 18 were selected: three randomised, controlled trials (RCTs), two controlled non-randomised studies, eight non-controlled studies, four qualitative analyses and one health economic analysis. One well-designed, well-conducted RCT demonstrated that, compared with usual GP care, Alexander Technique lessons led to significant long-term reductions in back pain and incapacity caused by chronic back pain. The results were broadly supported by a smaller, earlier RCT in chronic back pain. The third RCT, a small, well-designed, well-conducted study in individuals with Parkinson's disease, showed a sustained increased ability to carry out everyday activities following Alexander lessons, compared with usual care. The 15 non-RCT studies are also reviewed. CONCLUSIONS: Strong evidence exists for the effectiveness of Alexander Technique lessons for chronic back pain and moderate evidence in Parkinson's-associated disability. Preliminary evidence suggests that Alexander Technique lessons may lead to improvements in balance skills in the elderly, in general chronic pain, posture, respiratory function and stuttering, but there is insufficient evidence to support recommendations in these areas.

The long-term results of percutaneous drainage of diverticular abscess.

INTRODUCTION: Diverticulitis is a common condition occasionally complicated by abscess formation. Small abscesses may be managed by antibiotic therapy alone but larger collections require drainage, ideally by the percutaneous route. This minimally invasive approach is appealing but there is little information regarding the long-term follow-up of patients managed in this way. To address this question, we looked at a consecutive series of patients who underwent percutaneous drainage in our institution. PATIENTS AND METHODS: A retrospective study was performed of patients undergoing percutaneous drainage of a diverticular abscess from 1999-2007. RESULTS: A total of 26 abscesses were identified in 16 patients. In 69% of cases, the abscess was located in the pelvis. The mean size of the abscesses was 8.5 +/- 0.9 cm. Drainage was performed under CT (83%) or ultrasound guidance. The mean duration of drainage was 8 days. Fistula formation following drainage occurred in 38% of cases. Eight patients (mean age, 71 years) underwent subsequent surgical resection 9 days to 22 months (mean, 7 months) following initial presentation. Eight patients with significant co-morbid conditions were managed by percutaneous drainage only. The 1-year mortality was 20% and resulted from unrelated causes. The long-term stoma rate was 13%. CONCLUSIONS: Percutaneous drainage can safely be performed in patients with a diverticular abscess. It can be used as a bridge before definitive surgery but also as a treatment option in its own right in high-risk surgical patients. We believe percutaneous drainage reduces the need for major surgery and reduces the risk of a permanent stoma.

The use of the Chandler loop to examine the interaction potential of NXY-059 on the thrombolytic properties of rtPA on human thrombi in vitro.

BACKGROUND AND PURPOSE: Recombinant tissue-type plasminogen activator (rtPA) is the only globally approved treatment for acute ischaemic stroke. Other potential treatments might be administered with rtPA, making it important to discover whether compounds interfere with rtPA-induced lysis. We evaluated methods for examining the effect of the neuroprotectant NXY-059 on the lytic property of rtPA. EXPERIMENTAL APPROACH: Plasma clot formation and lysis in the presence of rtPA and NXY-059 was measured as the change in plasma turbidity. The effect of NXY-059 on rtPA-induced lysis was similarly assessed on preformed clots. Lysis of the thrombus formed in a Chandler loop measured release of fluorescent-tagged fibrinogen that had been incorporated during thrombus formation. Thrombi were exposed to both rtPA and NXY-059 throughout lysis in the presence of 80% autologous plasma and the release of label during lysis was measured. KEY RESULTS: Data interpretation is limited in the clot lysis experiments because either the rtPA was present during clot formation or the drug was added to a clot formed in static conditions. In contrast, thrombi were formed in dynamic flow conditions in the Chandler loop and the time course of lysis in plasma was examined. rtPA increased thrombolysis and the antifibrinolytic trans-4-(aminomethyl) cyclohexane carboxylic acid (AMCA) inhibited lysis. Lysis induced by rtPA was unaltered by NXY-059. CONCLUSIONS AND IMPLICATIONS: The Chandler loop method provides a reliable technique for examining the effect of compounds on rtPA-induced lysis in vitro and demonstrated that NXY-059 does not alter rtPA-induced lysis at clinically relevant concentrations of either drug.

Detection of an occult thymoma on 99Tcm-Tetrofosmin myocardial scintigraphy.

Thymoma is an uncommon tumour, which is often asymptomatic and may be detected coincidentally on cross-sectional imaging performed for other reasons. We report a case of thymoma detected on myocardial scintigraphy performed for suspected coronary artery disease. Extracardiac pathology may be suggested by abnormal non-cardiac tracer uptake on myocardial scintigraphy. An awareness of the potential causes of this is essential to allow potentially life threatening non-cardiac disorders to be recognized and treated promptly.

TAFIa, PAI-1 and alpha-antiplasmin: complementary roles in regulating lysis of thrombi and plasma clots.

PAI-1 and alpha(2)-antiplasmin (alpha(2)AP) are the principal direct inhibitors of fibrinolytic proteases. Thrombin activatable fibrinolysis inhibitor (TAFI), a plasma procarboxypeptidase activated by thrombin-thrombomodulin to form TAFIa, also regulates fibrinolysis by modulating fibrin. In this study, the relative contributions of PAI-1, alpha(2)AP and TAFIa to inhibition of lysis were assessed. In platelet-poor plasma clots, alpha(2)AP, TAFIa and PAI-1 all inhibited lysis, as shown by the addition of neutralizing antibodies to alpha(2)AP and PAI-1 +/- CPI, a potato carboxypeptidase inhibitor. alpha(2)AP played the largest role in regulating plasma clot lysis, but neutralization of inhibitors in combinations was more effective in shortening lysis times, with a maximal effect when all three inhibitors were neutralized. In platelet-rich clots, a larger contribution of PAI-1 was evident. Tissue plasminogen activator induced lysis of model thrombi, made from whole blood, was approximately doubled on incorporation of CPI, illustrating a substantial contribution of TAFIa to inhibition of thrombus lysis. Similar increases in thrombus lysis were observed on inclusion of neutralizing antibodies to PAI-1 and alpha(2)AP, with alpha(2)AP playing the dominant role. Maximal thrombus lysis occurred upon neutralization of all three inhibitors. These observations suggest that, despite the differences in concentrations and activities of inhibitors, and the different modes of action, the roles of the three are complementary in both plasma clot lysis and thrombus lysis.

The C-terminus of alpha2-antiplasmin interacts with endothelial cells.

The serpin, alpha(2)-antiplasmin (alpha(2)AP), has an extended C-terminus relative to other inhibitors. This 51-residue region contains an RGD sequence; such sequences constitute a key recognition sequence for cell adhesion, mediated through integrins. In the present study, this sequence was expressed in Escherichia coli and its binding to endothelial cells and whether binding depends on the RGD sequence was investigated. Binding to the surface of human umbilical vein endothelial cells (HUVEC-C) was observed by flow cytometry and immunohistochemistry. Binding studies on immobilised cells showed specific and RGD-dependent binding of the peptides to HUVEC-C. The binding of the wild-type peptide to the HUVEC-C was significantly higher than that of a mutant peptide, in which RGD was replaced by SAA (P < 0.05, n = 4). Similarly, ethylenediaminetetraacetic acid decreased the binding of the wild-type peptide (P < 0.05, n = 4). The binding was competed out by full-length alpha(2)AP, fibronectin and anti-alpha(5)beta(1). This is the first evidence of binding of the C-terminus of alpha(2)AP to endothelial cells via its RGD sequence, with most but not all of the binding being integrin-mediated. We speculate that this interaction with alpha(2)AP may potentially play a role in the control of cellular fibrinolysis by regulating local plasmin activity on cell surfaces.

Causes of lumbosacral plexopathy.

The lumbosacral plexus represents the nerve supply to the lower back, pelvis and legs. This review will focus on diseases and disorders affecting the pathway as demonstrated by magnetic resonance imaging (MRI) and computed tomography (CT). We stress the need to review the lumbosacral plexus in patients with non-specific symptoms such as back, hip, pelvic pain, and in those who present with sciatica unaccompanied by demonstrable intervertebral disc prolapse. We illustrate that the imaging appearances may be non-specific and re-inforce the importance of the clinical history and the use of tissue sampling to achieve an accurate diagnosis.

Radiological appearances in the pelvis following rectal cancer surgery.

Radiology has a significant role in the evaluation of surgery for rectal cancer. With recent developments in surgical techniques, the number of neorectal reservoir configurations has increased. It is important to recognize the normal and abnormal appearances, both early and late, following pelvic surgery. The aim of this pictorial review is to demonstrate the imaging techniques that are used in both the investigation and the follow-up of patients who have undergone uncomplicated or complicated rectal resection.

Fusion of contrast-enhanced breast MR and mammographic imaging data.

Increasing use is being made of Gd-DTPA contrast-enhanced MRI (CE-MRI) for breast cancer assessment since it provides three-dimensional (3D) functional information via pharmacokinetic interaction between contrast agent and tumour vascularity, and because it is applicable to women of all ages as well as patients with post-operative scarring. CE-MRI is complementary to conventional X-ray mammography, since it is a relatively low-resolution functional counterpart of a comparatively high-resolution 2D structural representation. However, despite the additional information provided by MRI, mammography is still an extremely important diagnostic imaging modality, particularly for several common conditions such as ductal carcinoma in situ (DCIS) where it has been shown that there is a strong correlation between microcalcification clusters and malignancy. Pathological indicators such as calcifications and fine spiculations are not visible in CE-MRI and therefore there is clinical and diagnostic value in fusing the high-resolution structural information available from mammography with the functional data acquired from MRI. This article is a clinical overview of the results of a technique to transform the coordinates of regions of interest (ROIs) from the 2D mammograms to the spatial reference frame of the contrast-enhanced MRI volume. An evaluation of the fusion framework is demonstrated with a series of clinical cases and a total of 14 patient examples.

MRI appearances of müllerian duct abnormalities.

Müllerian duct abnormalities are a well-documented cause of sub-fertility, and in some cases can be successfully treated in order to preserve fertility and prevent complications. In this paper we review the various types of anomaly and present their appearances as demonstrated by magnetic resonance imaging (MRI). MRI provides an excellent, non-invasive method of differentiating between the different types of anomaly and defining their suitability for surgical treatment.

Thrombus lysis by uPA, scuPA and tPA is regulated by plasma TAFI.

The carboxypeptidase, TAFIa or CPU, is known to prolong plasma clot lysis by tissue plasminogen activator (tPA) and to have a role in thrombus stability in vivo. This current study examined lysis by urokinase (uPA) and single chain urokinase (scuPA) in addition to tPA. Further, we investigated the role of TAFIa in a model thrombus system, in which thrombi are formed under conditions of flow. We show that human thrombi, formed in vivo, and model thrombi both contain TAFI. No effect of thrombus TAFIa was observed in thrombus lysis assays, except when thrombi were bathed in plasma, in which case addition of potato tuber carboxypeptidase inhibitor (CPI) resulted in doubling of the rate of lysis. TAFIa inhibited lysis of model thrombi and plasma clots by uPA, scuPA in addition to lysis by tPA. The effect of TAFIa was more evident at high concentrations of plasminogen activator such as those used in thrombolytic therapy. Addition of plasminogen increased lysis and, in its presence, the enhancement by CPI was smaller. Thus the action of TAFIa could be partially overcome by plasminogen, whether lysis was by tPA, uPA or scuPA. This is consistent with TAFIa exerting its effect primarily through modifying the binding of plasminogen to fibrin and to a lesser extent through modification of the binding of tPA to fibrin.

Substituting dietary saturated fat with polyunsaturated fat changes abdominal fat distribution and improves insulin sensitivity.

AIMS/HYPOTHESIS: British dietary recommendations are to decrease total fat intake to less than 30 % of daily energy intake and saturated fat to less than 10 %. In practice, it is difficult for people to make these changes. It may be easier to encourage people to switch from a diet rich in saturated fatty acids to one rich in polyunsaturated fatty acids. METHODS: A total of 17 subjects - six people with Type II (non-insulin-dependent) diabetes mellitus, six non-obese and five obese people without diabetes - were randomised to spend two 5-week periods on a diet rich in saturated or in polyunsaturated fatty acids, in a crossover design. At the start of the study and after each dietary period, we assessed abdominal fat distribution using magnetic resonance imaging, insulin sensitivity using hyperinsulinaemic-euglycaemic clamps and fasting lipid parameters. RESULTS: Dietary compliance, assessed by weekly 3-day dietary records and measurement of biochemical markers, was good. Energy and fat intake appeared to be reduced on the diet rich in polyunsaturated fatty acids although body weights did not change. Insulin sensitivity and plasma low density lipoprotein cholesterol concentrations improved with the diet rich in polyunsaturated fatty acids compared with the diet rich in saturated fatty acids. There was also a decrease in abdominal subcutaneous fat area. CONCLUSION/INTERPRETATION: If this result is confirmed in longer-term studies, this dietary manipulation would be more readily achieved by the general population than the current recommendations and could result in considerable improvement in insulin sensitivity, reducing the risk of developing Type II diabetes.

Creatine kinase: a role for arginine-95 in creatine binding and active site organization.

Sequence homology analysis reveals that arginine-95 is fully conserved in 29 creatine kinases sequenced to date, but fully conserved as a tyrosine residue in 16 arginine kinases. Site-directed mutants of rabbit muscle creatine kinase (rmCK) were prepared in which R95 was replaced by a tyrosine (R95Y), alanine (R95A), or lysine (R95K). Kinetic analysis of phosphocreatine formation for each purified mutant showed that recombinant native rmCK and all R95 mutants follow a random-order, rapid-equilibrium mechanism. However, we observed no evidence for synergism of substrate binding by the recombinant native enzyme, as reported previously [Maggio et al., (1977) J. Biol. Chem. 252, 1202-1207] for creatine kinase isolated directly from rabbit muscle. The catalytic efficiencies of R95Y and R95A are reduced approximately 3000- and 2000-fold, respectively, compared to native enzyme, but that of R95K is reduced only 30-fold. The major contribution to the reduction of the catalytic efficiency of R95K is a 5-fold reduction in the affinity for creatine. This suggests that while a basic residue is required at position 95 for optimal activity, R95 is not absolutely essential for binding or catalysis in CK. R95Y has a significantly lower affinity for creatine than the native enzyme, but it also displays a somewhat lower affinity for MgATP and 100-fold reduction in k(cat). Interestingly, R95A appears to bind either creatine or MgATP first with affinities similar to those for the native enzyme, but it has a 10-fold lower affinity for the second substrate, suggesting that replacement of R95 by an alanine disrupts the active site organization and reduces the efficiency of formation of the catalytically competent ternary complex.

A comparison of MRI and echocardiography in hypertrophic cardiomyopathy.

This study compares MRI and echocardiography as imaging modalities in hypertrophic cardiomyopathy, with particular reference to measurement of left ventricular wall thickness and mass. 10 subjects underwent echocardiography and MRI. Contiguous 10 mm short axis 35 degrees flip angle cine gradient recalled echo MR images were acquired from the apex to the base of the left ventricle at 1.5 tesla. Standard M-mode and cross-sectional echocardiographic views of the left ventricle were obtained. Excellent agreement between measurements occurred with MRI and M-mode echocardiographic assessment of the thickness of the anterior interventricular septum (95% limits of agreement -1.5 to +1.5 mm). Other comparisons of MRI vs M-mode echocardiographic measurements had the following limits of agreement: posterior free wall -3.3 to +2.9 mm; end-diastolic dimension -5 to +8 mm, left ventricular mass -291 to +55.5 g. Comparing MRI with cross-sectional echocardiographic measurements, the limits of agreement were: anterior interventricular septum -2.4 to +1.7 mm, posterior interventricular septum -2.4 to +2.9 mm, posterior free wall -3.4 to +2.5 mm, anterior free wall -2.4 to +1.7 mm, end-diastolic dimension -4.1 to +8 mm. MRI estimates of LVM in systole vs diastole showed good agreement with 95% limits of agreement of -20 to +17 g, with excellent interobserver variability in diastole (-9 to +5 g) and in systole (-7 to +12 g). In conclusion, MRI is superior to echocardiography for the quantification of ventricular mass in the abnormal left ventricle because it does not make invalid geometrical assumptions. Comparisons of wall thickness show greater discrepancy with increasing distance from the echocardiographic transducer. This study suggests that sequential echocardiography could rationalize the need for MRI in left ventricular hypertrophy. A change in anterior septal thickness of > or = 3 mm on echocardiography merits a further MRI study.

Circulating tissue-type plasminogen activator and plasminogen activator inhibitor type 1 in proliferative diabetic retinopathy: a pilot study.

Several haemostatic abnormalities are associated with proliferative diabetic retinopathy. While abnormalities in plasma fibrinolytic activity have been described in diabetic retinopathy, platelets (a rich source of plasminogen activator inhibitor type 1, PAI-1) have received little attention. As a result, little is known about the fibrinolytic potential of circulating whole blood in diabetic retinopathy. The concentrations of tissue-type plasminogen activator (t-PA) and of its fast-acting inhibitor. PAI-1 were measured in plasma from eight patients with type 1 diabetes complicated by proliferative retinopathy, and from eight patients with type 1 diabetes and background or no retinopathy, matched for age, sex and duration of diabetes. The concentration of PAI-1 in platelets was also measured. The ratio of t-PTA to PAI-1 in plasma was significantly higher in patients with proliferative retinopathy than in those without (0.66 vs. 0.37, p < 0.02). The average quantity of PAI-1 per platelet was significantly lower in the group with proliferative retinopathy (0.33 vs. 0.50 ng/10(6) platelets, p < 0.02). These data suggest that among patients with type 1 diabetes, total circulating fibrinolytic potential is higher in those with proliferative retinopathy.

Does chronic smoking influence fibrinolytic potential in type 1 diabetes mellitus?

Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) were studied in 18 smokers and 18 closely matched non-smokers, all of whom had Type 1 diabetes mellitus (DM). None of the patients had advanced complications of diabetes. The t-PA and PAI-1 antigen levels were measured in plasma before and after venous occlusion, and were normal in Type 1 diabetes regardless of smoking status. Platelet PAI-1 levels were also measured and were found to be normal both in smokers and non-smokers. In smokers with Type 1 DM, plasma PAI-1 was significantly correlated with triglycerides. The normal fibrinolytic potential found in smokers with diabetes contrasts starkly with the significantly elevated plasma PAI-1 reported in smokers without diabetes. In smokers, triglycerides may effect low levels of PAI-1 release into plasma; this process may be significantly augmented in the presence of smoking-induced insulin resistance. The lack of endogenous insulin release in Type 1 diabetes may obviate the characteristic rise in plasma PAI-1 found in smokers who do not have diabetes.