Intracoronary autologous bone marrow cell transfer after myocardial infarction: the BOOST-2 randomised placebo-controlled clinical trial.

AIMS: Intracoronary infusion of autologous nucleated bone marrow cells (BMCs) enhanced the recovery of left ventricular ejection fraction (LVEF) after ST-segment elevation myocardial infarction (STEMI) in the randomised-controlled, open-label BOOST trial. We reassessed the therapeutic potential of nucleated BMCs in the randomised placebo-controlled, double-blind BOOST-2 trial conducted in 10 centres in Germany and Norway. METHODS AND RESULTS: Using a multiple arm design, we investigated the dose-response relationship and explored whether γ-irradiation which eliminates the clonogenic potential of stem and progenitor cells has an impact on BMC efficacy. Between 9 March 2006 and 16 July 2013, 153 patients with large STEMI were randomly assigned to receive a single intracoronary infusion of placebo (control group), high-dose (hi)BMCs, low-dose (lo)BMCs, irradiated hiBMCs, or irradiated loBMCs 8.1 ± 2.6 days after percutaneous coronary intervention (PCI) in addition to guideline-recommended medical treatment. Change in LVEF from baseline (before cell infusion) to 6 months as determined by MRI was the primary endpoint. The trial is registered at Current Controlled Trials (ISRCTN17457407). Baseline LVEF was 45.0 ± 8.5% in the overall population. At 6 months, LVEF had increased by 3.3 percentage points in the control group and 4.3 percentage points in the hiBMC group. The estimated treatment effect was 1.0 percentage points (95% confidence interval, -2.6 to 4.7; P = 0.57). The treatment effect of loBMCs was 0.5 percentage points (-3.0 to 4.1; P = 0.76). Likewise, irradiated BMCs did not have significant treatment effects. BMC transfer was safe and not associated with adverse clinical events. CONCLUSION: The BOOST-2 trial does not support the use of nucleated BMCs in patients with STEMI and moderately reduced LVEF treated according to current standards of early PCI and drug therapy.

Clinical features of critically ill patients with Shiga toxin-induced hemolytic uremic syndrome.

OBJECTIVE: In Spring 2011, an unprecedented outbreak of Shiga toxin-producing Escherichia coli serotype O104:H4-associated hemolytic uremic syndrome occurred in Northern Germany. The aim of this study was to describe the clinical characteristics, treatments, and outcomes of critically ill patients with Shiga toxin-producing E. coli-associated hemolytic uremic syndrome during this outbreak. DESIGN, SETTING, AND PATIENTS: Multicenter, retrospective, observational study of critically ill adult patients with Shiga toxin-producing E. coli-associated hemolytic uremic syndrome in six hospitals in Hamburg, Germany, between May 2011 and August 2011. MEASUREMENTS AND MAIN RESULTS: During the study period, 106 patients with Shiga toxin-producing E. coli-associated hemolytic uremic syndrome were admitted to eight ICUs. The median age was 40 years (range, 18-83) with a female:male ratio of 3:1. The median time from onset of clinical symptoms to hospital admission was 3 days and from hospital to ICU admission an additional 3 days. A total of 101 patients (95.3%) had acute renal failure and 78 (73.6%) required renal replacement therapy. Intubation and mechanical ventilation were required in 38 patients (35.8%) and noninvasive ventilation was required in 17 patients (16.0%). The median duration of invasive ventilation was 7 days (range, 1-32 days) and the median ICU stay was 10 days (range, 1-45 days). Fifty-one patients (48.1%) developed sepsis; of these 51 patients, 27 (25.4%) developed septic shock. Seventy patients (66.0%) developed severe neurological symptoms. Ninety-seven patients (91.5%) were treated with plasma exchange and 50 patients (47.2%) received eculizumab (monoclonal anti-C5 antibody). The mortality rate was 4.7%. Mild residual neurological symptoms were present in 21.7% of patients at ICU discharge, and no patient required renal replacement therapy 6 months after ICU admission. CONCLUSIONS: During the 2011 Shiga toxin-producing E. coli-associated hemolytic uremic syndrome outbreak in Germany, critical illness developed rapidly after hospital admission, often in young women. The infection was associated with severe neurological and renal symptoms, requiring mechanical ventilation and renal replacement therapy in a substantial proportion of patients. Overall, recovery was much better than expected.

Transcatheter closure of patent foramen ovale (PFO) in patients with paradoxical embolism: procedural and follow-up results after implantation of the Amplatzer®-occluder device.

BACKGROUND: Prevalence of patent foramen ovale (PFO) with detectable right-to-left shunt is higher in young adults with transient ischemic attack (TIA) and stroke compared to the general population. So far, published series included different occluder systems, various indications and regimens of postprocedural anticoagulation. In our experience, occluder systems may be associated with an increased prevalence of thrombus formation, which has also reported by other groups. The aim of the present study was to evaluate the follow-up results after implantation of the Amplatzer® occluder in patients with PFO using a consistent anticoagulation regimen. METHODS AND RESULTS: One-hundred and fourteen patients with PFO (60 men; age: 47 ± 13 years) and ≥1 thromboembolic event were included. Other causes for embolism were excluded. PFO-closure was successful in all patients. All patients were treated with aspirin (100 mg/day) and clopidogrel (75 mg/day) for 6 months. TEE was repeated at a mean of 10.3 months. Mean clinical follow-up period was 18 ± 9 months. After a mean of 10 months, no patient had either a significant residual shunt nor a suspected thrombus formation on the occluder. During follow-up, 5 patients suffered from neurological events (1 stroke, 2 TIAs, 2 epileptic seizures), though complete closure of the PFO was documented by TEE. One patient suffered from bleeding complications (upper GI-bleeding). CONCLUSION: Percutaneous closure of PFO in symptomatic patients by Amplatzer® occluder represents an effective therapy with a low incidence of peri-interventional complications and recurrent thromboembolism. Thrombus formations on the occluder system were not detected in this cohort.

Long-term effects of intracoronary bone marrow cell transfer on diastolic function in patients after acute myocardial infarction: 5-year results from the randomized-controlled BOOST trial--an echocardiographic study.

AIMS: We have recently observed that intracoronary autologous bone marrow cell (BMC)-transfer improves parameters of diastolic function in patients after acute myocardial infarction at 6 and 18 months. There is no clinical study addressing the long-term effect of BMC transfer on diastolic function. Therefore, we conducted a 5-year follow-up of the BOOST trial to evaluate a sustained benefit on echocardiographic parameters on diastolic function. METHODS AND RESULTS: After successful primary percutaneous coronary intervention (PCI) for acute ST-elevation MI, patients were randomized to a control (n = 28) or BMC transfer group (n = 28). Echocardiography was performed at 4.5 +/- 1.5 days after PCI, at 6, 18, and 60 months. Diastolic function was determined by measuring transmitral flow velocities (E/A ratio), diastolic myocardial velocities (E(a)/A(a) ratio), isovolumic relaxation time (IVRT), and deceleration time (DT). All analyses were performed in a blinded fashion. There was an overall treatment effect of BMC transfer on E/A (0.25 +/- 0.10; 95% CI 0.05-0.44; P = 0.01). E/A ratio was significantly lower at 6 (Control 0.90 +/- 0.07; BMC 1.23 +/- 0.14; P = 0.03) and 18 months (Control 0.87+/-0.04; BMC 1.13 +/- 0.09; P = 0.01) in the control group, whereas E/A ratio was not different at 60 months between both groups (Control 0.90 +/- 0.06; BMC 1.05 +/- 0.07; P = 0.12). We found no overall effect of BMC transfer on E(a)/A(a) ratio (0.21 +/- 0.14; 95% CI -0.03 to 0.46; P = 0.09), DT (-12 +/- 11 ms; 95% CI -21 to 28; P = 0.75), IVRT -6 +/- 7 ms; 95% CI -9 to 19; P = 0.43), and E/E(a) ratio (0.58 +/- 0.88; 95% CI -1.18 to 2.34; P = 0.51). CONCLUSION: Intracoronary autologous BMC transfer provides an overall treatment effect on echocardiographic parameters of diastolic function in patients after AMI. However, this effect is basically related to an early improvement of parameters of diastolic function without a sustained effect on long-term follow-up.

Intracoronary bone marrow cell transfer after myocardial infarction: 5-year follow-up from the randomized-controlled BOOST trial.

AIMS: We assessed whether a single intracoronary infusion of autologous bone marrow cells (BMCs) can have a sustained impact on left ventricular ejection fraction (LVEF) in patients after ST-elevation myocardial infarction (STEMI). In the BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) trial, 60 patients with STEMI and successful percutaneous coronary intervention were randomized to a control and a cell therapy group. As previously reported, BMC transfer led to an improvement of LVEF by 6.0% at 6 months (P = 0.003) and 2.8% at 18 months (P = 0.27). METHODS AND RESULTS: Left ventricular ejection fraction and clinical status were re-assessed in all surviving patients after 61 +/- 11 months. Major adverse cardiac events occurred with similar frequency in both groups. When compared with baseline, LVEF assessed by magnetic resonance imaging at 61 months decreased by 3.3 +/- 9.5% in the control group and by 2.5 +/- 11.9% in the BMC group (P = 0.30). Patients with an infarct transmurality > median appeared to benefit from BMC transfer throughout the 61-month study period (P = 0.040). CONCLUSION: A single intracoronary application of BMCs does not promote a sustained improvement of LVEF in STEMI patients with relatively preserved systolic function. It is conceivable that a subgroup of patients with more transmural infarcts may derive a sustained benefit from BMC therapy. However, this needs to be tested prospectively in a randomized trial.

Adenosine stress perfusion cardiac magnetic resonance imaging in patients undergoing intracoronary bone marrow cell transfer after ST-elevation myocardial infarction: the BOOST-2 perfusion substudy.

AIMS: In the placebo-controlled, double-blind BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) 2 trial, intracoronary autologous bone marrow cell (BMC) transfer did not improve recovery of left ventricular ejection fraction (LVEF) at 6 months in patients with ST-elevation myocardial infarction (STEMI) and moderately reduced LVEF. Regional myocardial perfusion as determined by adenosine stress perfusion cardiac magnetic resonance imaging (S-CMR) may be more sensitive than global LVEF in detecting BMC treatment effects. Here, we sought to evaluate (i) the changes of myocardial perfusion in the infarct area over time (ii) the effects of BMC therapy on infarct perfusion, and (iii) the relation of infarct perfusion to LVEF recovery at 6 months. METHODS AND RESULTS: In 51 patients from BOOST-2 (placebo, n = 10; BMC, n = 41), S-CMR was performed 5.1 ± 2.9 days after PCI (before placebo/BMC treatment) and after 6 months. Infarct perfusion improved from baseline to 6 months in the overall patient cohort as reflected by the semi-quantitative parameters, perfusion defect-infarct size ratio (change from 0.54 ± 0.20 to 0.43 ± 0.22; P = 0.006) and perfusion defect-upslope ratio (0.54 ± 0.23 to 0.68 ± 0.22; P < 0.001), irrespective of randomised treatment. Perfusion defect-upslope ratio at baseline correlated with LVEF recovery (r = 0.62; P < 0.001) after 6 months, with a threshold of 0.54 providing the best sensitivity (79%) and specificity (74%) (area under the curve, 0.79; 95% confidence interval, 0.67-0.92). CONCLUSION: Infarct perfusion improves from baseline to 6 months and predicts LVEF recovery in STEMI patients undergoing early PCI. Intracoronary BMC therapy did not enhance infarct perfusion in the BOOST-2 trial.

Bone marrow cells are a rich source of growth factors and cytokines: implications for cell therapy trials after myocardial infarction.

AIMS: Results from clinical trials suggest that cardiac function after acute myocardial infarction (AMI) can be enhanced by an intracoronary infusion of autologous unselected nucleated bone marrow cells (BMCs). Release of paracrine factors has been proposed as a mechanism for these therapeutic effects; however, this hypothesis has not been tested in humans. METHODS AND RESULTS: BMCs and peripheral blood leucocytes (PBLs) were obtained from 15 patients with AMI and cultured in serum-free medium to obtain conditioned supernatants (SN). BMC-SN stimulated human coronary artery endothelial cell proliferation, migration, and tube formation, and induced cell sprouting in a mouse aortic ring assay. Moreover, BMC-SN protected rat cardiomyocytes from cell death induced by simulated ischaemia or ischaemia followed by reperfusion. While PBL-SN promoted similar effects on endothelial cells and cardiomyocytes, BMC-SN and PBL-SN in combination promoted synergistic effects. As shown by ProteinChip and GeneChip array analyses (each performed in triplicate), BMCs and PBLs expressed distinct patterns of pro-angiogenic and cytoprotective secreted factors. CONCLUSION: Our data support the paracrine hypothesis and suggest that characterization of the BMC secretome may lead to an identification of factors with therapeutic potential after AMI.

Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months' follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial.

BACKGROUND: Intracoronary transfer of autologous bone marrow cells (BMCs) may enhance recovery of left ventricular (LV) function in patients after acute myocardial infarction (AMI). However, clinical studies addressing the effects of BMCs after AMI have covered only limited time frames ranging from 3 to 6 months. The critical question of whether BMC transfer can have a sustained impact on LV function remains unanswered. METHODS AND RESULTS: After percutaneous coronary intervention with stent implantation (PCI) of the infarct-related artery, 60 patients were randomized 1:1 to a control group with optimal postinfarction therapy and a BMC transfer group that also received an intracoronary BMC infusion 4.8+/-1.3 days after PCI. Cardiac MRI was performed 3.5+/-1.5 days, 6+/-1 months, and 18+/-6 months after PCI. BMC transfer was not associated with adverse clinical events. In the control group, mean global LV ejection fraction increased by 0.7 and 3.1 percentage points after 6 and 18 months, respectively. LV ejection fraction in the BMC transfer group increased by 6.7 and 5.9 percentage points. The difference in LVEF improvement between groups was significant after 6 months but not after 18 months (P=0.27). The speed of LV ejection fraction recovery over the course of 18 months was significantly higher in the BMC transfer group (P=0.001). CONCLUSIONS: In this study, a single dose of intracoronary BMCs did not provide long-term benefit on LV systolic function after AMI compared with a randomized control group; however, the study suggests an acceleration of LV ejection fraction recovery after AMI by BMC therapy.

Monitoring of bone marrow cell homing into the infarcted human myocardium.

BACKGROUND: Intracoronary transfer of autologous bone marrow cells (BMCs) promotes recovery of left ventricular systolic function in patients with acute myocardial infarction. Although the mechanisms of this effect remain to be established, homing of BMCs into the infarcted myocardium is probably a critical early event. METHODS AND RESULTS: We determined BMC biodistribution after therapeutic application in patients with a first ST-segment-elevation myocardial infarction who had undergone stenting of the infarct-related artery. Unselected BMCs were radiolabeled with 100 MBq 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) and infused into the infarct-related coronary artery (intracoronary; n=3 patients) or injected via an antecubital vein (intravenous; n=3 patients). In 3 additional patients, CD34-positive (CD34+) cells were immunomagnetically enriched from unselected BMCs, labeled with 18F-FDG, and infused intracoronarily. Cell transfer was performed 5 to 10 days after stenting. More than 99% of the infused total radioactivity was cell bound. Nucleated cell viability, comparable in all preparations, ranged from 92% to 96%. Fifty to 75 minutes after cell transfer, all patients underwent 3D PET imaging. After intracoronary transfer, 1.3% to 2.6% of 18F-FDG-labeled unselected BMCs were detected in the infarcted myocardium; the remaining activity was found primarily in liver and spleen. After intravenous transfer, only background activity was detected in the infarcted myocardium. After intracoronary transfer of 18F-FDG-labeled CD34-enriched cells, 14% to 39% of the total activity was detected in the infarcted myocardium. Unselected BMCs engrafted in the infarct center and border zone; homing of CD34-enriched cells was more pronounced in the border zone. CONCLUSIONS: 18F-FDG labeling and 3D PET imaging can be used to monitor myocardial homing and biodistribution of BMCs after therapeutic application in patients.

Bone-marrow-derived cell transfer after ST-elevation myocardial infarction: lessons from the BOOST trial.

Emerging evidence suggests that bone-marrow-derived stem and progenitor cells can be used to improve cardiac function after acute myocardial infarction. We tested this concept in the randomized, controlled, BOOST (bone marrow transfer to enhance ST-elevation infarct regeneration) clinical trial. Following successful percutaneous coronary intervention for acute ST-elevation myocardial infarction, patients received an intracoronary transfer of autologous bone marrow cells (BMCs). After 6 months, global left ventricular ejection fraction, as determined by magnetic resonance imaging, was significantly improved in the BMC-treated group compared with the control group. BMC transfer enhanced left ventricular systolic function, primarily in myocardial segments adjacent to the infarcted area, and also had a positive effect on diastolic function. BMC transfer did not increase the risk of adverse clinical events and did not promote in-stent re-stenosis or proarrhythmic effects. In principle, the effects of BMC transfer on ejection fraction were sustained at 18-month follow-up. Notably, radioactive labeling of BMCs and positron emission tomography showed that these beneficial effects are achieved with limited cardiac homing of BMCs after intracoronary application. Taken together, our studies indicate that intracoronary transfer of autologous BMCs is a safe, promising, and novel approach to further improving systolic function in patients with successful reperfusion after acute myocardial infarction.

Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial.

BACKGROUND: Emerging evidence suggests that stem cells and progenitor cells derived from bone marrow can be used to improve cardiac function in patients after acute myocardial infarction. In this randomised trial, we aimed to assess whether intracoronary transfer of autologous bone-marrow cells could improve global left-ventricular ejection fraction (LVEF) at 6 months' follow-up. METHODS: After successful percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction, 60 patients were randomly assigned to either a control group (n=30) that received optimum postinfarction medical treatment, or a bone-marrow-cell group (n=30) that received optimum medical treatment and intracoronary transfer of autologous bone-marrow cells 4.8 days (SD 1.3) after PCI. Primary endpoint was global left-ventricular ejection fraction (LVEF) change from baseline to 6 months' follow-up, as determined by cardiac MRI. Image analyses were done by two investigators blinded for treatment assignment. Analysis was per protocol. FINDINGS: Global LVEF at baseline (determined 3.5 days [SD 1.5] after PCI) was 51.3 (9.3%) in controls and 50.0 (10.0%) in the bone-marrow cell group (p=0.59). After 6 months, mean global LVEF had increased by 0.7 percentage points in the control group and 6.7 percentage points in the bone-marrow-cell group (p=0.0026). Transfer of bone-marrow cells enhanced left-ventricular systolic function primarily in myocardial segments adjacent to the infarcted area. Cell transfer did not increase the risk of adverse clinical events, in-stent restenosis, or proarrhythmic effects. INTERPRETATION: Intracoronary transfer of autologous bone-marrow-cells promotes improvement of left-ventricular systolic function in patients after acute myocardial infarction.

[Allopurinol-induced hypersensitivity syndrome resulting in death]. / Allopurinolinduziertes Hypersensitivitätssyndrom mit Todesfolge.

The present report describes the case of a 67-year-old patient who developed an allopurinol-induced hypersensitivity syndrome (AHS) with toxic epidermal necrolysis and subsequently died of septic multiorgan failure. Considering the increasing prescription rate of allopurinol, the present case report intends to demonstrate the underestimated threat of AHS.

Transcatheter closure of patent foramen ovale in patients with paradoxical embolism. Procedural and follow-up results after implantation of the Starflex occluder device with conjunctive intensified anticoagulation regimen.

BACKGROUND: Prevalence of patent foramen ovale (PFO) is higher in patients with paradoxical embolism and associated with increased risk for recurrent thromboembolic events. By percutaneous closure of PFO, surgical closure or permanent oral anticoagulation can be avoided. So far, published series included different occluder systems and various indications and regimens of postprocedural anticoagulation. The aim of the present study was to evaluate the short- and long-term results after implantation of the Starflex occluder in patients with PFO using an intensified anticoagulation regimen. METHODS AND RESULTS: 154 patients with PFO (94 men; age: 44 +/- 13 years) and >or=1 thromboembolic event were included. Other causes for embolism were excluded. PFO closure was successful in 147 patients (95.5%). All patients were treated with phenprocoumon (INR 2.5) and aspirin (100 mg/die) for 6 months. Transesophageal echocardiography (TEE) was repeated at 6 months. Mean clinical follow-up period was 26 +/- 18 months. After 6 months, five patients had a significant residual shunt, and five patients had suspected thrombus formation on the occluder. In three of these five patients, the occluder was surgically removed and foreign body reaction was noted. During follow-up, nine patients suffered from neurological events (two strokes, seven transient ischemic attacks [TIA]), though complete closure of the PFO was documented by TEE. Two patients died during follow-up; three patients had bleeding complications. CONCLUSION: Percutaneous closure of PFO in symptomatic patients by Starflex occluder represents an effective therapy with a low incidence of periinterventional complications and recurrent thromboembolism. However, thrombus formation at the occluder system may occur in some patients despite an aggressive anticoagulation regimen.

The role of stem cells in the post-MI patient.

Studies suggest that cardiac transfer of stem and progenitor cells can have a favorable impact on tissue perfusion and contractile performance after acute myocardial infarction (AMI). Although the mechanistic background of stem cell therapy is still intensely debated, stem cell therapy has been introduced into the clinical setting, where the first randomized, controlled trials indicate that it is feasible and safe in patients. Preliminary efficacy data indicate that stem cells have the potential to enhance myocardial perfusion and/or contractile performance in patients with AMI. The field now is rapidly moving toward intermediate-size, double-blind trials to gather more safety and efficacy data and the first insights into clinical end points. Ultimately, large outcome trials will be needed. At the same time, continued basic research is needed to elucidate the underlying mechanism of stem cell therapy.

Impact of intracoronary bone marrow cell transfer on diastolic function in patients after acute myocardial infarction: results from the BOOST trial.

AIMS: We have recently shown in the randomized-controlled BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) trial that intracoronary autologous bone marrow cell (BMC) transfer improves left ventricular (LV) ejection fraction recovery in patients after acute myocardial infarction (AMI). However, the impact of BMC therapy on LV diastolic function in patients after AMI has remained uncertain. METHODS AND RESULTS: Using (tissue) Doppler echocardiography, we evaluated the effects of BMC transfer on LV diastolic function in patients enrolled in the BOOST trial. After successful primary percutaneous coronary intervention (PCI) for acute ST-elevation myocardial infarction (MI), patients were randomized to a control (n = 29) or BMC transfer group (n = 30). Diastolic function was determined 4.5+/-1.5 days after PCI, at 6 months, and at 18 months by measuring transmitral flow velocities (E/A ratio), diastolic myocardial velocities (Ea/Aa ratio), isovolumic relaxation time (IVRT), and deceleration time (DT). All analyses were performed in a blinded fashion. There was an overall effect of BMC transfer on E/A [0.33+/-0.12; 95% confidence interval (CI): 0.09-0.57; P = 0.008] and Ea/Aa ratios (0.29+/-0.14; 95% CI: 0.01-0.57; P = 0.04). In contrast, we found no effect of BMC transfer on DT (-5+/-14 ms; 95% CI: -33 to 22; P = 0.70), IVRT (-7+/-7 ms; 95% CI: -20 to 6; P = 0.29), and E/Ea ratio (0.35+/-0.14; 95% CI: -0.92 to 1.62; P = 0.57). CONCLUSION: Intracoronary autologous BMC transfer improves echocardiographic parameters of diastolic function in patients after AMI.

Double-chambered right ventricle or sub-infundibular stenosis assessed by cardiovascular magnetic resonance.

This paper presents magnetic resonance findings in four adults with double-chambered right ventricle or sub-infundibular stenosis, a condition that is treatable by surgery, but which can be difficult to assess echocardiographically. Four patients referred for cardiovascular magnetic resonance in the last 2 years were identified from CMR findings, although not necessarily from previous echocardiography, as having sub-infundibular stenosis. We used multislice spin echo imaging, cine imaging in oblique sagittal planes, and phase velocity mapping. We performed spin echo imaging of a post-mortem heart without known structural abnormality to illustrate right ventricular myocardial morphology. Results in patients showed evidence of sub-infundibular muscular obstruction separating the hypertrophied inlet and apical portions of the right ventricle from a thin-walled, unobstructed infundibular region in each case, with a systolic jet originating at least 15 mm beneath the unstenosed pulmonary valve. In addition to previously described structural components contributing to stenosis--enlargement and/or displacement of the septomarginal trabeculation, septoparietal trabeculations or the moderator band--CMR suggested additional components: a right ventricular papillary muscle in one, an anteriorly bulging aortic sinus in one, and hypertrophied muscular ridges of the parietal wall of the right ventricle. Even in this small group of patients, the causes of sub-infundibular stenosis appeared to be varied and multi-factorial. The abilities of magnetic resonance to give unrestricted, multi-planar views of right ventricular anatomy, movement and flow make it well suited for diagnosis and characterization of sub-infundibular stenosis, especially in adults.

Ethanol's effects on gait dynamics in mice investigated by ventral plane videography.

BACKGROUND: Performance of mice in motor function tests for ethanol sensitivity is often task dependent, not reflective of coordinated movement, and reported qualitatively. Therefore, we applied a new imaging technique to record and quantify coordinated gait dynamics in mice in response to ethanol. METHODS: We applied ventral plane videography to record and report gait indices in mice walking on a transparent treadmill belt. We examined the effects of ethanol on gait in C57BL/6J (B6) and DBA/2J (D2) mice walking at a speed of 25 cm/sec. B6 and D2 are two inbred strains that are widely used to study the genetic influences of ethanol on motor function. RESULTS: Gait posture in D2 mice was less stable than in B6 mice. B6 mice always showed an alternate step sequence, whereas D2 mice sometimes showed cruciate and rotary step sequences. Ethanol in increasing doses increased stride frequency, decreased stride length, and increased stride length variability in D2 mice but not in B6 mice. The forelimb braking duration was significantly shortened and the hind limb propulsion duration was significantly prolonged with a high dose of ethanol in D2 mice but not in B6 mice. Differences in gait indices between the two strains of mice were more pronounced of the forelimbs with the highest dose of ethanol (2.75 g/kg). CONCLUSION: Our data suggest that the higher susceptibility of D2 compared with B6 mice to the effects of ethanol on motor function may be attributed to less stable basal gait characteristics that are perturbed by ethanol. The ability of this method to quantify step sequence patterns and gait indices of forelimb and hind limbs could provide new data regarding ethanol-induced motor incoordination.