Systematic review of the effectiveness of community-based self-management interventions among primary care COPD patients.

COPD self-management reduces hospital admissions and improves health-related quality of life (HRQoL). However, whilst most patients are managed in primary care, the majority of self-management trials have recruited participants with more severe disease from secondary care. We report the findings of a systematic review of the effectiveness of community-based self-management interventions in primary care patients with COPD. We systematically searched eleven electronic databases and identified 12 eligible randomised controlled trials with seven included in meta-analyses for HRQoL, anxiety and depression. We report no difference in HRQoL at final follow-up (St George's Respiratory Questionnaire total score -0.29; 95%CI -2.09, 1.51; I2 0%), nor any difference in anxiety or depression. In conclusion, supported self-management interventions delivered in the community to patients from primary care do not appear to be effective. Further research is recommended to identify effective self-management interventions suitable for primary care populations, particularly those with milder disease.

Design and experimental results of the 1-T Bitter Electromagnet Testing Apparatus (BETA).

The Bitter Electromagnet Testing Apparatus (BETA) is a 1-Tesla (T) technical prototype of the 10 T Adjustable Long Pulsed High-Field Apparatus. BETA's final design specifications are highlighted in this paper which include electromagnetic, thermal, and stress analyses. We discuss here the design and fabrication of BETA's core, vessel, cooling, and electrical subsystems. The electrical system of BETA is composed of a scalable solid-state DC breaker circuit. Experimental results display the stable operation of BETA at 1 T. These results are compared to both analytical design and finite element calculations. Experimental results validate analytical magnet designing methods developed at the Dusty Plasma Laboratory. The theoretical steady state maxima and the limits of BETA's design are explored in this paper.

Sumatriptan alleviates nitroglycerin-induced mechanical and thermal allodynia in mice.

The association between the clinical use of nitroglycerin (NTG) and headache has led to the examination of NTG as a model trigger for migraine and related headache disorders, both in humans and laboratory animals. In this study in mice, we hypothesized that NTG could trigger behavioural and physiological responses that resemble a common manifestation of migraine in humans. We report that animals exhibit a dose-dependent and prolonged NTG-induced thermal and mechanical allodynia, starting 30-60 min after intraperitoneal injection of NTG at 5-10 mg/kg. NTG administration also induced Fos expression, an anatomical marker of neuronal activity in neurons of the trigeminal nucleus caudalis and cervical spinal cord dorsal horn, suggesting that enhanced nociceptive processing within the spinal cord contributes to the increased nociceptive behaviour. Moreover, sumatriptan, a drug with relative specificity for migraine, alleviated the NTG-induced allodynia. We also tested whether NTG reduces the threshold for cortical spreading depression (CSD), an event considered to be the physiological substrate of the migraine aura. We found that the threshold of CSD was unaffected by NTG, suggesting that NTG stimulates migraine mechanisms that are independent of the regulation of cortical excitability.

Medical students' attitudes towards abortion: a UK study.

BACKGROUND: There is little research into medical students' or doctors' attitudes to abortion, yet knowing this is important, as policy makers should be aware of the views held by professionals directly involved in abortion provision and changing views may have practical implications for the provision of abortion in the future. METHODS: We surveyed 300 medical students about their views on abortion, their beliefs about the status of the fetus and the rights of the mother, their attitude towards UK law and their willingness to be involved in abortion provision as qualified doctors. RESULTS: 62% of medical students were pro-choice, 33% pro-life and 7% undecided. Students' views correlated with gender, year of study and holding a religious belief. Their beliefs about abortion, the status of the fetus and the rights of women significantly correlated with their attitudes towards the UK law and their willingness to be involved in abortion provision. Students' willingness to be involved in abortion provision was related to their views on abortion, the extent of participation required, the circumstances of the pregnancy and the stage of pregnancy. CONCLUSIONS: The percentage of pro-choice students was lower than that found in research on general practitioners' attitudes to abortion. It is unclear whether this is because students become more pro-choice as they progress through their medical career or because there is genuinely a change in attitudes to abortion.

Health professionals' attitudes towards suicide prevention initiatives.

Preventing suicide can depend upon the ability of a range of different health professionals to make accurate suicide risk assessments and treatment plans. The attitudes that clinicians hold towards suicide prevention initiatives may influence their suicide risk assessment and management skills. This study measures a group of non-mental health professionals' attitude towards suicide prevention initiatives. Health professionals that had attended suicide prevention education showed significantly more positive attitudes towards suicide prevention initiatives. The findings in this study further support the effectiveness of educating non-mental health professionals in suicide risk awareness and management.

Emergency percutaneous coronary intervention (PCI) for the care of patients with ST-elevation myocardial infarction (STEMI).

There is general consensus that emergency percutaneous coronary intervention (PCI) is the preferred treatment for patients with ST-elevation myocardial infarction (STEMI), so long as it can be delivered in a timely fashion, by an experienced' operator and cardiac catheterization laboratory (CCL) team. STEMI is both a functional and structural issue. Although it has been recognized since the work of pioneering cardiologists and surgeons in Spokane, Washington, that approximately 88% of patients presenting within 6 hours of onset of STEMI have an occluded coronary artery, it is the pathophysiology of myocardial necrosis, and the varied consequences of necrosis that characterize STEMI. Accordingly, experience' of both primary operator and cardiac catheterization laboratory (CCL) crew, in performing an emergency PCI for STEMI, are as much a function of experience with the treatment of complex MI patients, as experience with coronary intervention. Rapidly achieving normal coronary artery flow, at both the macro and micro vascular levels, is the recognized key to aborting the otherwise progressive wavefront' of myocardial necrosis. The time urgency of decisions (Time is muscle') make emergency PCI for patients with on-going necrosis, more like emergency room (ER) care, than like most in-hospital or outpatient care. In general, most patients with acute coronary syndromes (ACS) are currently thought to have plaque rupture and/or erosion with subsequent thrombosis and embolization. Consequences of thrombo-embolism, such as slow flow' or no-reflow' are in addition to, the structural (anatomic) considerations of PCI in stable patients (such as ostial location; bifurcation involvement; heavy calcification; tortuosity of lesion or access to it; length of disease; caliber of infarct-artery; etc.). Good quality studies have provided strong support for the specific added value of glycoprotein IIb/IIIa inhibitors (especially abciximab), dual antiplatelet therapy (the addition of the thienopyridine, clopidogrel, to aspirin use), and bare-metal stents (BMS), for a broad range of STEMI patients. The added value of drug-eluting stents (DES) to bare-metal stents (BMS), primarily in terms of reducing restenosis and repeat revascularization, is supported by several randomized trials, and a number of registries, despite its being off-label' from a regulatory standpoint. The recognition of late stent thrombosis (LST) has raised additional issues, in choosing between these two options for specific STEMI patients. The added value of a number of other mechanical approaches to coronary thrombus, such as thrombus removal devices, and/or distal protection, are more controversial, and perhaps, patient specific. Whether intravascular ultrasound guidance (IVUS) for stent use should be used for the majority, or even a specific minority, of STEMI patients, is also controversial; late-stent thrombosis provides a counter-point. The advantages of developing a network approach to STEMI care, so as to optimize the number of patients receiving timely reperfusion, have been demonstrated in Prague, Denmark, and Minneapolis, among many places. The benefits of both bivalirudin (anti-thrombin drug with efficacy against clot-bound thrombin, which does not appear to stimulate platelets) and abciximab (glycoprotein IIb/IIIa inhibitor which is antibody to platelet receptors), as PCI adjuncts generally, and for STEMI patients, in particular, are supported by multiple trials. The specific choice of administering the bolus dose of either, or both, drugs via intra-coronary (IC) injection follows the precedents' of IC thrombolytics, and IC small-vessel vasodilators for no-reflow', but it has not been tested by prospective, randomized trials. Although rapid reperfusion is the first objective, one cannot ignore the other components of the oxygen delivery chain, and the importance of each of these components to on-going delivery of oxygen to all vital organs. A balance must be struck between doing those control' things which serve to stabilize other vital components of the oxygen-delivery chain, without digressing too long from the job of re-establishing brisk coronary flow. The clinical and angiographic heterogeneity of STEMI patients and the array of available therapeutic approaches make it impossible to obtain specific randomized trial direction for many of the clinical decisions in an individual emergency PCI for STEMI. There are a range of reasonable/ appropriate therapeutic choices for a given emergent PCI performed by multiple experienced and competent operators. The treatment of STEMI, and high-risk non-STEMI, patients, by means of emergent PCI, is among the most challenging and rewarding arenas in contemporary medicine.

Action and object processing in aphasia: from nouns and verbs to the effect of manipulability.

The processing of words and pictures representing actions and objects was tested in 21 aphasic patients and 20 healthy controls across three word production tasks: picture-naming (PN), single word reading (WR) and word repetition (WRP). Analysis 1 targeted task and lexical category (noun-verb), revealing worse performance on PN and verb items for both patients and control participants. For Analysis 2 we used data collected in a concurrent gesture norming study to re-categorize the noun-verb items along hand imagery parameters (i.e., objects that can/cannot be manipulated and actions which do/do not involve fine hand movements). Here, patients displayed relative difficulty with the 'manipulable' items, while controls displayed the opposite pattern. Therefore, whereas the noun-verb distinction resulted simply in lower verb accuracy across groups, the 'manipulability' distinction revealed a 'double-dissociation' between patients and control participants. These results carry implications for theories of embodiment, lexico-semantic dissociations, and the organization of meaning in the brain.

Separate neural systems for processing action- or non-action-related sounds.

The finding of a multisensory representation of actions in a premotor area of the monkey brain suggests that similar multimodal action-matching mechanisms may also be present in humans. Based on the existence of an audiovisual mirror system, we investigated whether sounds referring to actions that can be performed by the perceiver underlie different processing in the human brain. We recorded multichannel ERPs in a visuoauditory version of the repetition suppression paradigm to study the time course and the locus of the semantic processing of action-related sounds. Results show that the left posterior superior temporal and premotor areas are selectively modulated by action-related sounds; in contrast, the temporal pole is bilaterally modulated by non-action-related sounds. The present data, which support the hypothesis of distinctive action sound processing, may contribute to recent theories about the evolution of human language from a mirror system precursor.

Regulation of mesangial cell Na+/Ca2+ exchanger isoforms.

An isoform of the Na(+)/Ca(2+) exchanger (SDNCX1.10) was cloned from mesangial cells of Sprague-Dawley rat. Regulation of this isoform was compared to two other clones that were derived from the Dahl/Rapp salt sensitive (SNCX) and salt resistant rat (RNCX). All isoforms differ at the alternative splice site and at amino acid 218 for SNCX. PKC activates RNCX but not SNCX while SDNCX1.10 was also activated by PKC. Regulation of exchanger activities by intracellular calcium ([Ca(2+)](i)), pH, and kinases was assessed using Na-dependent (45)Ca(2+) uptake assays in OK-PTH cells expressing the vector, RNCX, SNCX, or SDNCX1.10. [Ca(2+)](i) was elevated from 50 to 125 nM (n = 4) with thapsigargin (40 nM) and reduced from 50 to 29 nM (n = 4) and 18 nM (n = 4) with 10 or 20 microM BAPTA, respectively. RNCX was active at all three [Ca(2+)](i) while SNCX and SDNCX1.10 were only active at lower [Ca(2+)](i). Varying extracellular pH (pH(e), without nigericin) or pH(e) and intracellular pH (pH(i), with 10 microM nigericin) from pH 7.4 to 6.2, 6.8, or 8.0 showed that SNCX activity was attenuated at both low and high pHs. SDNCX1.10 activity was attenuated only at pH 6.2 and 6.8 (with or without nigericin) while RNCX activity was attenuated at pH 6.2 (with or without nigericin) and pH 6.8 (with nigericin). Finally, only SDNCX1.10 activity was stimulated by 250 microM CPT-cAMP or 250 microM DB-cGMP treatment. Thus the differential regulation of [Ca(2+)](i) by these exchangers is dependent upon the pattern of cellular Na(+)/Ca(2+) exchanger isoform expression.

Platelet glycoprotein IIb/IIIa inhibitor therapy in non-ST segment elevation acute coronary syndromes.

Platelet glycoprotein (GP) IIb/IIIa inhibitors prevent fibrinogen binding and platelet aggregation. They decrease ischemic complications associated with non-ST segment elevation acute coronary syndromes and percutaneous coronary intervention. Meta-analyses of 6 randomized trials of parenteral GP IIb/IIIa inhibitors in patients with acute coronary syndromes suggest a significant reduction in death and myocardial infarction in high risk patients. These include patients undergoing early percutaneous coronary intervention or those with high TIMI risk score, elevated troponin values, or diabetes mellitus. Despite guideline recommendations supporting therapy for these indications, only a minority of appropriate candidates are being treated. The risk of major bleeding is small; thrombocytopenia can result from abciximab therapy. Optimal dosing strategies continue to evolve.

Impaired ability of the Na+/Ca2+ exchanger from the Dahl/Rapp salt-sensitive rat to regulate cytosolic calcium.

We previously cloned Na(+)/Ca(2+) exchanger (NCX1) from mesangial cells of salt-sensitive (SNCX = NCX1.7) and salt-resistant (RNCX = NCX1.3) Dahl/Rapp rats. The abilities of these isoforms to regulate cytosolic Ca(2+) concentration ([Ca(2+)](i)) were assessed in fura 2-loaded OK cells expressing the vector (VOK), RNCX (ROK), and SNCX (SOK). Baseline [Ca(2+)](i) was 98 +/- 20 nM (n = 12) in VOK and was significantly lower in ROK (44 +/- 5 nM; n = 12) and SOK (47 +/- 13 nM; n = 12) cells. ATP at 100 microM increased [Ca(2+)](i) by 189 +/- 55 nM (n = 12), 21 +/- 9 nM (n = 12), and 69 +/- 18 nM (n = 12) in VOK, ROK, and SOK cells, respectively. ATP (1 mM) or bradykinin (0.1 mM) caused large increases in [Ca(2+)](i) and ROK but not SOK cells were much more efficient in reducing [Ca(2+)](i) back to baseline levels. Parental Sprague-Dawley rat mesangial cells express both RNCX (SDRNCX) and SNCX (SDSNCX). SDRNCX and RNCX are identical at every amino acid residue, but SDSNCX and SNCX differ at amino acid 218 where it is isoleucine in SDSNCX and not phenylalanine. OK cells expressing SDSNCX (SDSOK) reduced ATP (1 mM)-induced [Ca(2+)](i) increase back to baseline at a rate equivalent to that for ROK cells. PKC downregulation significantly attenuated the rate at which ROK and SDSOK cells reduced ATP-induced [Ca(2+)](i) increase but had no effect in SOK cells. The reduced efficiency of SNCX to regulate [Ca(2+)](i) is attributed, in part, to the isoleucine-to-phenylalanine mutation at amino acid 218.

Language deficits, localization, and grammar: evidence for a distributive model of language breakdown in aphasic patients and neurologically intact individuals.

Selective deficits in aphasic patients' grammatical production and comprehension are often cited as evidence that syntactic processing is modular and localizable in discrete areas of the brain (e.g., Y. Grodzinsky, 2000). The authors review a large body of experimental evidence suggesting that morpho-syntactic deficits can be observed in a number of aphasic and neurologically intact populations. They present new data showing that receptive agrammatism is found not only over a range of aphasic groups, but is also observed in neurologically intact individuals processing under stressful conditions. The authors suggest that these data are most compatible with a domain-general account of language, one that emphasizes the interaction of linguistic distributions with the properties of an associative processor working under normal or suboptimal conditions.

Differential effects of unilateral lesions on language production in children and adults.

We present the first direct comparison of language production in brain-injured children and adults, using age-corrected z scores for multiple lexical and grammatical measures. Spontaneous speech samples were elicited in a structured biographical interview from 38 children (5-8 years of age), 24 with congenital left-hemisphere damage (LHD) and 14 with congenital right-hemisphere damage (RHD), compared with 38 age- and gender-matched controls, 21 adults with unilateral injuries (14 LHD and 7 RHD), and 12 adult controls. Adults with LHD showed severe and contrasting profiles of impairment across all measures (including classic differences between fluent and nonfluent aphasia). Adults with RHD (and three nonaphasic adults with LHD) showed fluent but disinhibited and sometimes empty speech. None of these qualitative or quantitative deviations were observed in children with unilateral brain injury, who were in the normal range for their age on all measures. There were no significant differences between children with LHD and RHD on any measure. When LHD children were compared directly with LHD adults using age-corrected z scores, the children scored far better than their adult counterparts on structural measures. These results provide the first systematic confirmation of differential free-speech outcomes in children and adults and offer strong evidence for neural and behavioral plasticity following early brain damage.

Predictors of length of stay after coronary stenting.

BACKGROUND: Postprocedure length of stay (LOS) remains an important determinant of medical costs after coronary stenting. Variables that predict LOS in this setting have not been well characterized. METHODS: We evaluated 359 consecutive patients who underwent coronary stenting with antiplatelet therapy. Sequential multiple linear regression (MLR) models were constructed with use of 4 types of variables to predict log-transformed LOS: preprocedure, intraprocedure, and postprocedure factors and adverse outcomes. RESULTS: Preprocedure factors alone explained more than one third of the variability in postprocedure LOS (adjusted R(2) = 0.37). The addition of procedural variables added little to the model (adjusted R(2) = 0.39). Entering nonoutcome postprocedure variables significantly enhanced the predictive capacity of the model, explaining more than half the variability in postprocedure LOS (adjusted R(2) = 0.54). In the final model, addition of outcome variables increased its predictive capacity only slightly (adjusted R(2) = 0.61). In this model, significant preprocedure factors included: myocardial infarction (MI) within 24 hours, MI within 1 to 30 days, women with peripheral vascular disease, intravenous heparin, and chronic atrial fibrillation. High-risk intervention was the only significant intraprocedure variable. Significant postprocedure factors included periprocedure ischemia; cerebrovascular accident or transient ischemic attack; treatment with intravenous heparin or nitroglycerin or intra-aortic balloon pump; and need for blood transfusion. Significant adverse outcomes included contrast nephropathy, gastrointestinal bleeding, arrhythmia, vascular complication, and repeat angiography. CONCLUSION: This prediction model identifies a number of potentially reversible factors responsible for prolonging LOS and may enable the development of more accurate risk-adjusted methods with which to improve or compare care.

Bivalirudin for percutaneous coronary intervention and in acute coronary syndromes.

This review focuses on the use of bivalirudin as a replacement anticoagulant for heparin in patients undergoing percutaneous coronary intervention, or who are being treated for unstable angina pectoris, ST-elevation, or non-ST-elevation myocardial infarction. Potential advantages of bivalirudin include a lack of dependence on antithrombin III for anticoagulant activity, the ability to inactivate both fibrin-bound and soluble thrombin, a lack of aggregatory effects on platelets, a predictable anticoagulant response without monitoring, and a wider therapeutic window. Clinical trial results to date suggest that bivlirudin is at least as effective as heparin with superior safety due to lower bleeding rates.

Processing of grammatical gender in normal and aphasic speakers of Russian.

Sensitivity to grammatical gender was investigated in 22 Russian-speaking aphasic patients, compared with young controls. Experiment 1 used a cued shadowing paradigm to assess gender priming (facilitation and/or inhibition of lexical access by a prenominal modifier with congruent, incongruent or neutral gender). Experiment 2 used a grammaticality judgment paradigm with similar stimuli. Normals showed significant interactions between gender and priming in Experiment 1 (facilitation for feminine and neuter nouns but not for masculines) and Experiment 2 (larger effects of context on feminine and neuter nouns) that we interpret as a Markedness Effect. Patients showed significant priming in Experiment 1 and above-chance accuracy in Experiment 2, but failed to show reduced effects for the least-marked masculine gender (the Markedness Effect) in either experiment. Context effects were not related to specific aphasic symptoms or subtypes in either experiment. However, canonical correlation revealed differential effects of specific aphasic symptoms on judgment accuracy (false alarms vs. misses). We conclude that knowledge of grammatical gender is spared in Russian aphasics, but gender processing is deviant. A possible model to account for these differences is discussed.