Predictors of treatment resistant schizophrenia: a systematic review of prospective observational studies.

Treatment-resistant schizophrenia, affecting approximately 20-30% of patients with schizophrenia, has a high burden both for patients and healthcare services. There is a need to identify treatment resistance earlier in the course of the illness, in order that effective treatment, such as clozapine, can be offered promptly. We conducted a systemic literature review of prospective longitudinal studies with the aim of identifying predictors of treatment-resistant schizophrenia from the first episode. From the 545 results screened, we identified 12 published studies where data at the first episode was used to predict treatment resistance. Younger age of onset was the most consistent predictor of treatment resistance. We discuss the gaps in the literature and how future prediction models can identify predictors of treatment response more robustly.

Designing a survey to monitor multi-scale impacts of agri-environment schemes on mobile taxa.

Agri-environment schemes (AES) are key mechanisms to deliver conservation policy, and include management to provide resources for target taxa. Mobile species may move to areas where resources are increased, without this necessarily having an effect across the wider countryside or on populations over time. Most assessments of AES efficacy have been at small spatial scales, over short timescales, and shown varying results. We developed a survey design based on orthogonal gradients of AES management at local and landscape scales, which will enable the response of several taxa to be monitored. An evidence review of management effects on butterflies, birds and pollinating insects provided data to score AES options. Predicted gradients were calculated using AES uptake, weighted by the evidence scores. Predicted AES gradients for each taxon correlated strongly, and with the average gradient across taxa, supporting the co-location of surveys across different taxa. Nine 1 × 1 km survey squares were selected in each of four regional blocks with broadly homogenous background habitat characteristics. Squares in each block covered orthogonal contrasts across the range of AES gradients at local and landscape scales. This allows the effects of AES on species at each scale, and the interaction between scales, to be tested. AES options and broad habitats were mapped in field surveys, to verify predicted gradients which were based on AES option uptake data. The verified AES gradient had a strong positive relationship with the predicted gradient. AES gradients were broadly independent of background habitat within each block, likely allowing AES effects to be distinguished from potential effects of other habitat variables. Surveys of several mobile taxa are ongoing. This design will allow mobile taxa responses to AES to be tested in the surrounding countryside, as well as on land under AES management, and potentially in terms of population change over time. The design developed here provides a novel, pseudo-experimental approach for assessing the response of mobile species to gradients of management at two spatial scales. A similar design process could be applied in other regions that require a standardized approach to monitoring the impacts of management interventions on target taxa at landscape scales, if equivalent spatial data are available.

Investigating Tongue Strength and Endurance in Children Aged 6 to 11 Years.

Objective measures of tongue strength and endurance are used to assess lingual weakness and fatigue, and may have significant clinical value for dysphagia management. Recent studies investigating age and gender effects on tongue strength in children are limited by small sample sizes. The current study investigated age and gender effects on tongue strength with a larger sample size, and collected preliminary normative data for a paediatric population. This study also investigated the reliability of tongue endurance measures in children using a modified method, which has not previously been investigated. Using a cross-sectional design, this study examined tongue strength and endurance in 119 children aged 6 to 11 years, with no history of speech sound disorders, oro-motor deficits, dysphagia or cognitive impairment. Measures were collected using the Iowa Oral Performance Instrument. Children participated in two sessions, 45 min and 10 min in duration. Tongue strength was found to significantly increase with age (p < 0.001), while no gender effects were found. Modified tongue endurance measures involved using only one measure of maximal tongue strength to set parameters for tongue endurance scores. Despite this modification, data did not reach acceptable test-retest reliability, ICC = 0.68, p < 0.001; however, reliability improved from previous studies. These findings provide normative data for tongue strength, as a basis to compare individuals, and highlights the need for more reliable protocols for measuring tongue endurance. Normative data was collected from city-dwelling Australian children.

Combined investigation of bulk diffusion and surface exchange parameters of silver catalyst coated yttrium-doped BSCF membranes.

The combined effect of minor yttrium doping and silver catalyst deposition on the surface kinetics (k(chem)) and bulk diffusion (D(chem)) of BSCF (Ba(0.5)Sr(0.5)Co(0.8)Fe(0.2)O(3-δ)) perovskite membranes was explored using electrical conductivity relaxation (ECR) and validated using oxygen permeation measurements. Yttrium doping of BSCF to form Ba(0.5)Sr(0.5)Co(0.8)Fe(0.175)Y(0.025)O(3-δ) (BSCFY) improved both the surface exchange kinetics and the bulk diffusion by an average of 44% and 177% respectively, supporting improved oxygen permeation measurements. The deposition of a silver catalyst on BSCFY further improved the surface kinetics by 63-450% at intermediate operating temperatures (600-750 °C), and reduced the activation energy from 163 to 90 kJ mol(-1). Interestingly, these improvements did not translate into enhanced oxygen fluxes for the silver coated thicker 0.5 and 1 mm membranes, indicating that the oxygen ion transport was limited by bulk diffusion. However, oxygen permeation measurements on catalyst-coated 0.3 mm-thick membranes yielded improvements of 20-35% in the range 600-900 °C. The silver catalyst was beneficial in overcoming surface kinetic limitations for the thinner 0.3 mm BSCFY membranes, thus suggesting that the critical thickness of BSCFY membranes lies around ∼0.4 mm and validating the ECR measurements.

Measuring stock and change in the GB countryside for policy--key findings and developments from the Countryside Survey 2007 field survey.

Countryside Survey is a unique large scale long-term monitoring programme investigating stock and change of habitats, landscape features, vegetation, soil and freshwaters of Great Britain. Repeat field surveys combine policy and scientific objectives to provide evidence on how multiple aspects of the environment are changing over time, a key goal of international science in the face of profound human impacts on ecosystems. Countryside Survey 2007 (CS2007), the fifth survey since 1978, retained consistency with previous surveys, whilst evolving in line with technological and conceptual advances in the collection and integration of data to understand landscape change. This paper outlines approaches taken in the 2007 survey and its subsequent analysis and presents some of the headline results of the survey and their relevance for national and international policy objectives. Key changes between 1998 and 2007 included: a) significant shifts in agricultural land cover from arable to grassland, accompanied by increases in the area of broadleaved woodland, b) decreases in the length of managed hedges associated with agricultural land, as a proportion deteriorated to lines of trees and c) increases in the areas and numbers of wet habitats (standing open water, ponds) and species preferring wetter conditions (1998-2007 and 1978-2007). Despite international policy directed at maintaining and enhancing biodiversity, there were widespread decreases in species richness in all linear and area habitats, except on arable land, consistent with an increase in competitive and late successional species between 1998 and 2007 and 1978 and 2007. Late successional and competitive species: Stinging nettle (Urtica dioica), Hawthorn (Cratageous monogyna) and Bramble (Rubus fruticosus), in the top ten recorded species recorded in 2007, all increased between 1998 and 2007. The most commonly recorded species in CS (1990, 1998 and 2007) was agricultural Ryegrass (Lolium perenne). Increases in both water quality and soil pH were in line with policy aimed at addressing previous deterioration of both. Headwater streams broadly showed continued improvements in biological quality from 1998 to 2007, continuing trends seen since 1990. In soils, there were significant increases in soil pH between 1998 and 2007 consistent with recovery from acidification.

Incremental modification of robotic prostatectomy technique can lead to aggregated marginal gains to significantly improve functional outcomes without compromising oncological control.

INTRODUCTION AND OBJECTIVES: Surgeons should aim for continuous quality improvement. The aim of this study was to evaluate the impact of incremental changes to Robot Assisted Radical Prostatectomy (RARP) technique on intra-operative and early post-operative outcomes. PATIENTS AND METHODS: All cases of RARP performed by a single surgeon in a tertiary institution over a 2-year period were included in this evaluation. Routine clinical data were collected. Cases were retrospectively allocated to four groups depending on key technical steps (1 = standard anterior approach; 2 = anterior approach with preservation of endopelvic fascia, puboprostatic fascia and urachus; 3 = posterior approach for nerve spare, with preservation of endopelvic fascia, puboprostatic fascia and urachus; 4 = Retzius-sparing posterior approach). RESULTS: 187 patients were allocated to groups: 1 = 22, 2 = 53, 3 = 90, 4 = 22. There were no significant differences in pre-operative characteristics, except age: 1 = 62.5, 2 = 62, 3 = 62.5, 4 = 58.5 (p = 0.02). Intra-operative differences were found in console time: 1 = 195, 2 = 167, 3 = 195 4 = 136.5 min (p < 0.001); and proportion of non-nerve sparing cases: 1 = 36%, 2 = 17%, 3 = 13%, 4 = 0% (p = 0.044). No significant differences were found in lymph node dissections, blood loss or complications. Post-operatively, no differences were found in length of stay, pathological characteristics, margin status, lymph node yield, complications or PSA levels. Significant differences were seen in pad-free continence at 6 weeks: 1 = 23%, 2 = 23%, 3 = 34%, 4 = 73% (p < 0.01); and social continence (using 1 pad) at 6-weeks: 1 = 59%, 2 = 87%, 3 = 81%, 4 = 95% (p = 0.01). Significant differences in pad-free continence persisted at 12 months: 1 = 63%, 2 = 81%, 3 = 78%, 4 = 100% (p = 0.019). CONCLUSION: Our results suggest that aggregated marginal gains from incremental modification of RARP leads to significantly improved continence outcomes without compromising patient safety or oncological control.

Attrition in longitudinal studies among patients with schizophrenia and other psychoses; findings from the STRATA collaboration.

A major problem with longitudinal studies is the bias generated due to attrition, particularly apparent amongst patients suffering from psychotic disorders. Factors associated with study-participation were investigated as part of a larger research collaboration (STRATA). Out of 479 eligible participants, only 50 (10,4%) were successfully followed up. The present study investigated whether study participation differed depending on baseline characteristics. Results indicated that individuals who did not participate were more likely to report an alcohol use disorder while those who did respond were more likely to have been in full-time education for longer and be of white ethnicity. Participation did not differ depending on diagnosis, symptoms, GAF, age of onset or depression.

Use of dynamic soil-vegetation models to assess impacts of nitrogen deposition on plant species composition: an overview.

Field observations and experimental data of effects of nitrogen (N) deposition on plant species diversity have been used to derive empirical critical N loads for various ecosystems. The great advantage of such an approach is the inclusion of field evidence, but there are also restrictions, such as the absence of explicit criteria regarding significant effects on the vegetation, and the impossibility to predict future impacts when N deposition changes. Model approaches can account for this. In this paper, we review the possibilities of static and dynamic multispecies models in combination with dynamic soil-vegetation models to (1) predict plant species composition as a function of atmospheric N deposition and (2) calculate critical N loads in relation to a prescribed protection level of the species composition. The similarities between the models are presented, but also several important differences, including the use of different indicators for N and acidity and the prediction of individual plant species vs. plant communities. A summary of the strengths and weaknesses of the various models, including their validation status, is given. Furthermore, examples are given of critical load calculations with the model chains and their comparison with empirical critical N loads. We show that linked biogeochemistry-biodiversity models for N have potential for applications to support European policy to reduce N input, but the definition of damage thresholds for terrestrial biodiversity represents a major challenge. There is also a clear need for further testing and validation of the models against long-term monitoring or long-term experimental data sets and against large-scale survey data. This requires a focused data collection in Europe, combing vegetation descriptions with variables affecting the species diversity, such as soil acidity, nutrient status and water availability. Finally, there is a need for adaptation and upscaling of the models beyond the regions for which dose-response relationships have been parameterized, to make them generally applicable.

Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations.

BACKGROUND: Mutations in the transforming growth factor beta receptor type I and II genes (TGFBR1 and TGFBR2) cause Loeys-Dietz syndrome (LDS), characterised by thoracic aortic aneurysms and dissections (TAAD), aneurysms and dissections of other arteries, craniosynostosis, cleft palate/bifid uvula, hypertelorism, congenital heart defects, arterial tortuosity, and mental retardation. TGFBR2 mutations can also cause TAAD in the absence of features of LDS in large multigenerational families, yet only sporadic LDS cases or parent-child pairs with TGFBR1 mutations have been reported to date. METHODS: The authors identified TGFBR1 missense mutations in multigenerational families with TAAD by DNA sequencing. Clinical features of affected individuals were assessed and compared with clinical features of previously described TGFBR2 families. RESULTS: Statistical analyses of the clinical features of the TGFBR1 cohort (n = 30) were compared with clinical features of TGFBR2 cohort (n = 77). Significant differences were identified in clinical presentation and survival based on gender in TGFBR1 families but not in TGFBR2 families. In families with TGFBR1 mutations, men died younger than women based on Kaplan-Meier survival curves. In addition, men presented with TAAD and women often presented with dissections and aneurysms of arteries other than the ascending thoracic aorta. The data also suggest that individuals with TGFBR2 mutations are more likely to dissect at aortic diameters <5.0 cm than individuals with TGFBR1 mutations. CONCLUSION: This study is the first to demonstrate clinical differences between patients with TGFBR1 and TGFBR2 mutations. These differences are important for the clinical management and outcome of vascular diseases in these patients.

Exploring social-ecological systems in the transition from war to peace: A scenario-based approach to forecasting the post-conflict landscape in a Colombian region.

This paper describes the relationship between the landscape and the socio-economic and political characteristics of a highly biodiverse Andean region of Colombia, which is now recovering from the socio-ecological impact of protracted armed conflict. We quantify the current spatial relationship between nature and society, and we include legacy effects from the most recent period of armed conflict and its consequences of forced displacement and land use disruption. The procedure followed provides a quantitative model where a minimum number of socio-economic and political variables explain the variation in land cover. The results represent the relationship between land use intensity and the main socio-economic and political indicators, highlighting a close interaction between landscape configuration, socio-economic structure of local populations, coercive conservation and armed conflict. A simulated post-conflict landscape shows a clear transition gradient towards agrarian expansion and intensification, also in systems where naturalness is a relevant feature. The peace process in Colombia offers opportunities for new schemes of land planning and management, including natural resource governance and policy reforms to improve welfare and resilience of local communities. The results allow to define options for future planning given the possible consequences of socio-political legacy effects yet to fully play out across Colombia.

Deletion of the K(V)1.1 potassium channel causes epilepsy in mice.

Mice lacking the voltage-gated potassium channel alpha subunit, K(V)1.1, display frequent spontaneous seizures throughout adult life. In hippocampal slices from homozygous K(V)1.1 null animals, intrinsic passive properties of CA3 pyramidal cells are normal. However, antidromic action potentials are recruited at lower thresholds in K(V)1.1 null slices. Furthermore, in a subset of slices, mossy fiber stimulation triggers synaptically mediated long-latency epileptiform burst discharges. These data indicate that loss of K(V)1.1 from its normal localization in axons and terminals of the CA3 region results in increased excitability in the CA3 recurrent axon collateral system, perhaps contributing to the limbic and tonic-clonic components of the observed epileptic phenotype. Axonal action potential conduction was altered as well in the sciatic nerve--a deficit potentially related to the pathophysiology of episodic ataxia/myokymia, a disease associated with missense mutations of the human K(V)1.1 gene.

Best practice in primary care pathology: review 7.

This seventh best-practice review examines four series of common primary care questions in laboratory medicine: (1) blood count abnormalities 2; (2) cardiac troponins; (3) high-density lipoprotein cholesterol; and (4) viral diseases 2. The review is presented in a question-answer format, with authorship attributed for each question series. The recommendations are a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. The recommendations are not standards, but form a guide to be set in the clinical context. Most are consensus based rather than evidence based. They will be updated periodically to take account of new information.

The Development of Technology for Effective Respiratory-Gated Irradiation Using an Image-Guided Small Animal Irradiator.

The development of image-guided small animal irradiators represents a significant improvement over standard irradiators by enabling preclinical studies to mimic radiotherapy in humans. The ability to deliver tightly collimated targeted beams, in conjunction with gantry or animal couch rotation, has the potential to maximize tumor dose while sparing normal tissues. However, the current commercial platforms do not incorporate respiratory gating, which is required for accurate and precise targeting in organs subject to respiration related motions that may be up to the order of 5 mm in mice. Therefore, a new treatment head assembly for the Xstrahl Small Animal Radiation Research Platform (SARRP) has been designed. This includes a fast X-ray shutter subsystem, a motorized beam hardening filter assembly, an integrated transmission ionization chamber to monitor beam delivery, a kinematically positioned removable beam collimator and a targeting laser exiting the center of the beam collimator. The X-ray shutter not only minimizes timing errors but also allows beam gating during imaging and treatment, with irradiation only taking place during the breathing cycle when tissue movement is minimal. The breathing related movement is monitored by measuring, using a synchronous detector/lock-in amplifier that processes diffuse reflectance light from a modulated light source. After thresholding of the resulting signal, delays are added around the inhalation/exhalation phases, enabling the "no movement" period to be isolated and to open the X-ray shutter. Irradiation can either be performed for a predetermined time of X-ray exposure, or through integration of a current from the transmission monitor ionization chamber (corrected locally for air density variations). The ability to successfully deliver respiratory-gated X-ray irradiations has been demonstrated by comparing movies obtained using planar X-ray imaging with and without respiratory gating, in addition to comparing dose profiles observed from a collimated beam on EBT3 radiochromic film mounted on the animal's chest. Altogether, the development of respiratory-gated irradiation facilitates improved dose delivery during animal movement and constitutes an important new tool for preclinical radiation studies. This approach is particularly well suited for irradiation of orthotopic tumors or other targets within the chest and abdomen where breathing related movement is significant.

Best practice in primary care pathology: review 3.

This best practice review examines four series of common primary care questions in laboratory medicine: (i) "minor" blood platelet count and haemoglobin abnormalities; (ii) diagnosis and monitoring of anaemia caused by iron deficiency; (iii) secondary hyperlipidaemia and hypertriglyceridaemia; and (iv) glycated haemoglobin and microalbumin use in diabetes. The review is presented in question-answer format, referenced for each question series. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards, but form a guide to be set in the clinical context. Most of the recommendations are based on consensus rather than evidence. They will be updated periodically to take account of new information.

Dobutamine-atropine stress echocardiography for the detection of coronary artery disease in patients with left ventricular hypertrophy. Importance of chamber size and systolic wall stress.

BACKGROUND: Left ventricular hypertrophy is a heterogeneous disorder with distinct morphologies. Changes in wall thickness, left ventricular chamber diameter, and mass alter systolic wall stress of the left ventricle and may influence ischemic threshold. Thus, the goal of this study was to investigate the effect of the different patterns of left ventricular hypertrophy on the accuracy of dobutamine-atropine stress echocardiography. METHODS AND RESULTS: Three-hundred eighty-six patients underwent multistage dobutamine-atropine stress echocardiography and diagnostic angiography. Echocardiograms were measured for mean and relative wall thicknesses, chamber size, left ventricular mass, and end-systolic wall stress. The patterns of ventricular hypertrophy were concentric hypertrophy (increased wall thickness and mass), eccentric hypertrophy (normal wall thickness and increased mass), and concentric remodeling (increased wall thickness and normal mass). The overall sensitivity, specificity, and accuracy of dobutamine-atropine stress echocardiography for the detection of coronary artery disease were 85%, 87%, and 86%, respectively. Increased left ventricular mass index alone did not affect accuracy. Sensitivity was markedly reduced (36%) only in those with concentric remodeling. The univariate predictors of false-negative studies were single-vessel left circumflex disease, increased wall thickness, small chamber size, hyperdynamic ejection fraction, and left ventricular concentric remodeling. Multivariate predictors were concentric remodeling (P<0.0001; odds ratio, 13.5), left ventricular ejection fraction >2 SD above normal (P<0.0001), and single-vessel left circumflex disease (P<0.0007; odds ratio, 7.6). Sensitivity was excellent in patients with small ventricles and normal wall thickness and in those with normal or large chambers regardless of wall thickness. CONCLUSIONS: Dobutamine-atropine stress echocardiography is an accurate test in most patients with left ventricular hypertrophy, but it is insensitive in the small subset with concentric remodeling.

Reduced cytosolic Ca(2+) loading and improved cardiac function after cardioplegic cold storage of guinea pig isolated hearts.

BACKGROUND: Hypothermia is cardioprotective, but it causes Ca(2+) loading and reduced function on rewarming. The aim was to associate changes in cytosolic Ca(2+) with function in intact hearts before, during, and after cold storage with or without cardioplegia (CP). METHODS AND RESULTS: Guinea pig hearts were initially perfused at 37 degrees C with Krebs-Ringer's (KR) solution (in mmol/L: Ca(2+) 2.5, K(+) 5, Mg(2+) 2.4). One group was perfused with CP solution (Ca(2+) 2.5, K(+) 18, Mg(2+) 7.2) during cooling and storage at 3 degrees C for 4 hours; another was perfused with KR. LV pressure (LVP), dP/dt, O(2) consumption, and cardiac efficiency were monitored. Cytosolic phasic [Ca(2+)] was calculated from indo 1 fluorescence signals obtained at the LV free wall. Cooling with KR increased diastolic and phasic [Ca(2+)], whereas cooling with CP suppressed phasic [Ca(2+)] and reduced the rise in diastolic [Ca(2+)]. Reperfusion with warm KR increased phasic [Ca(2+)] 86% more after CP at 20 minutes and did not increase diastolic [Ca(2+)] at 60 minutes, compared with a 20% increase in phasic [Ca(2+)] after KR. During early and later reperfusion after CP, there was a 126% and 50% better return of LVP than after KR; during later reperfusion, O(2) consumption was 23% higher and cardiac efficiency was 38% higher after CP than after KR. CONCLUSIONS: CP decreases the rise in cardiac diastolic [Ca(2+)] observed during cold storage in KR. Decreased diastolic [Ca(2+)] and increased systolic [Ca(2+)] after CP improves function on reperfusion because of reduced Ca(2+) loading during and immediately after cold CP storage.

Dobutamine-atropine stress echocardiography for reversible dysfunction during the first week after acute myocardial infarction: limitations and determinants of accuracy.

OBJECTIVES: We sought to compare the accuracy of biphasic and ischemic responses and sustained improvement for reversible dysfunction and to identify causes of false negative and false positive findings. BACKGROUND: Previous studies have shown that low dose dobutamine echocardiography was accurate for detecting reversible dysfunction after acute myocardial infarction (MI) but did not determine whether accuracy was improved by peak dose findings or influenced by the test interval or clinical or angiographic factors. METHODS: Dobutamine-atropine stress echocardiography (DASE) (baseline, low dose [5 and 10 microg/kg body weight per min] and peak dose) and coronary angiography were performed in 115 patients 2 to 7 days after MI (test interval). Segmental wall thickening was analyzed according to the 16-segment model. Sustained improvement and biphasic and ischemic responses included improved wall thickening at low and peak doses, improved wall thickening at the low dose with worsening at peak dose and no change in wall thickening at the low dose with worsening at peak dose, respectively. Follow-up echocardiography was performed at 4 to 8 weeks, and reversible dysfunction was defined as improved wall thickening. RESULTS: Wall thickening improved at follow-up in 305 (44%) of 688 dysfunctional segments. The test interval was 2 days in 16 patients, 3 days in 24, 4 days in 24, 5 days in 12, 6 days in 16 and 7 days in 23. No change at low and peak doses accurately predicted fixed dysfunction (318 [88%] of 360 segments), especially in akinetic and dyskinetic segments (276 [91%] of 303), irrespective of the test interval or clinical and angiographic factors. Ischemic segmental responses also predicted fixed dysfunction (63% [12 of 19 patients]), especially in medically treated compared with revascularized patients (100% [8 of 8] vs. 36% [4 of 11], p = 0.013). Both biphasic responses and sustained improvement (77% [179 of 231 segments] vs. 87% [84 of 97], p = 0.082) were highly predictive of reversible dysfunction, especially in akinetic segments, irrespective of the test interval or clinical and angiographic factors. The only limitation was reduced accuracy (77% [177 of 222 segments], p < 0.001) due to false positive results (16%) in hypokinetic segments. CONCLUSIONS: No change and ischemic responses during DASE were specific for fixed dysfunction. Improved wall thickening at the low dose, irrespective of changes at peak dose, was highly predictive of reversible dysfunction. Accuracy was only limited by false positive results in hypokinetic segments and not by the test interval or clinical or angiographic factors.

Dobutamine-atropine stress echocardiography and dipyridamole sestamibi scintigraphy for the detection of coronary artery disease: limitations and concordance.

OBJECTIVES: We sought to compare dobutamine-atropine stress echocardiography (DASE) and dipyridamole Technetium 99-m (Tc-99m) sestamibi single photon emission computed tomography (SPECT) scintigraphy (DMIBI) for detecting coronary artery disease (CAD). BACKGROUND: Both DASE and DMIBI are effective for evaluating patients for CAD, but their concordance and limitations have not been directly compared. METHODS: To investigate these aims, patients underwent multistage DASE, DMIBI and coronary angiography within three months. Dobutamine-atropine stress echocardiography and stress-rest DMIBI were performed according to standard techniques and analyzed for their accuracy in predicting the extent of CAD. Segments were assigned to vascular territories according to standard models. Angiography was performed using the Judkin's technique. RESULTS: The 183 patients (mean age: 60 +/- 11 years, including 50 women) consisted of 64 patients with no coronary disease and 61 with single-, 40 with two- and 18 with three-vessel coronary disease. Dobutamine-atropine stress echocardiography and DMIBI were similarly sensitive (87%, 104/119 and 80%, 95/119, respectively) for the detection of CAD, but DASE was more specific (91%, 58/64 vs. 73%, 47/64, p < 0.01). Sensitivity was similar for the detection of CAD in patients with single-vessel disease (84%, 51/61 vs. 74%, 45/61, respectively) and multivessel disease (91%, 53/58 vs. 86%, 50/58, respectively). Multiple wall motion abnormalities and perfusion defects were similarly sensitive for multivessel disease (72%, 42/58 vs. 66%, 38/53, respectively), but, again, DASE was more specific than DMIBI (95%, 119/125 vs. 76%, 95/125, respectively, p < 0.01). Dobutamine-atropine stress echocardiography and DMIBI were moderately concordant for the detection and extent of CAD (Kappa 0.47, p < 0.0001) but were only fairly (Kappa 0.35, p < 0.001) concordant for the type of abnormalities (normal, fixed, ischemia or mixed). CONCLUSIONS: Dobutamine-atropine stress echocardiography and DMIBI were comparable tests for the detection of CAD. Both were very sensitive for the detection of CAD and moderately sensitive for the extent of disease. The only advantage of DASE was greater specificity, especially for multivessel disease. Dobutamine-atropine stress echocardiography may be advantageous in patients with lower probabilities of CAD.

Intracoronary amiloride prevents contractile dysfunction of postischemic "stunned" myocardium: role of hemodynamic alterations and inhibition of Na+/H+ exchange and L-type Ca2+ channels.

OBJECTIVES: This study sought to establish the effect of amiloride on stunned myocardium and to determine the role of hemodynamic alterations and inhibition of sodium/proton (Na+/H+) exchange and L-type cytosolic calcium (Ca2+) channels. BACKGROUND: Amiloride is a nonspecific agent that may reduce reperfusion injury, but its effect on reversible dysfunction or stunned myocardium is unclear. METHODS: Ninety-seven open chest dogs undergoing 15 min of left anterior descending coronary artery occlusion and 3 h of reperfusion with monitoring of hemodynamic variables, systolic shortening and myocardial blood flow were randomized to seven intracoronary infusions: control dogs (5% dextrose, n = 16); low dose amiloride (1 mg/min, n = 14); high dose amiloride (5 mg/min) with (n = 12) and without (n = 16) atrial pacing; sodium nitroprusside (20 micrograms/min, n = 16); hexamethylene amiloride (a specific inhibitor of Na+/H+ exchange, 60 micrograms/min, n = 14); and nifedipine (a specific inhibitor of L-type Ca2+ channels, 5 micrograms/min, n = 9). Drug infusions were started 40 min before occlusion and stopped at 30 min after reperfusion. RESULTS: Forty-three dogs were excluded because of ventricular fibrillation or high collateral flow. The incidence of ventricular fibrillation was similar in all groups to that in control dogs. Systolic shortening completely recovered (p = NS vs. baseline; p < 0.01 vs. control group) by 2 h after reperfusion in the low dose amiloride group and 30 min in the high dose group (p < 0.01 vs. low dose). High dose amiloride increased myocardial blood flow and had positive inotropic and negative chronotropic effects (p < 0.05 vs. control group). Atrial pacing did not attenuate recovery. The only effect of low dose amiloride was increased myocardial blood flow after reperfusion. Systolic shortening did not deteriorate after washout of drug effects. Sodium nitroprusside and nifedipine similarly increased myocardial blood flow, but systolic shortening never recovered. Hexamethylene amiloride had no hemodynamic effects, and systolic shortening never recovered. CONCLUSIONS: Amiloride prevented the contractile dysfunction of myocardial stunning but did not prevent arrhythmias. Hemodynamic alterations, increased myocardial blood flow and inhibition of Na+/H+ exchange or L-type Ca2+ channels alone did not account for the improved function. Inhibition of Na+/Ca2+ exchange may be the mechanism of improved postischemic function.