Assessment of myocardial perfusion by videodensitometry in the canine model

Assessment of the functional severity of coronary stenoses has become increasingly important as the intrinsic limitations of coronary angiography have been documented. Videodensitometric coronary flow reserve has been proposed as a means to assess the physiologic significance of a coronary stenosis in humans. This study compared videodensitometric assessment of coronary flow with microsphere quantitation in the closed chest canine model.In five dogs, flow rates were assessed at baseline, after vasodilation with adenosine, after vasoconstriction with vasopressin and during rapid cardiac pacing. The videodensitometric peak density, time to one-half peak density and washout time (time from peak to one-half peak density) were compared at each flow state with flow assessed by microsphere injection. Reproducibility of videodensitometric measurements from two different coronary injections during the same flow state was best with peak density (r = 0.94).Videodensitometric flow ratios (flow state under study to flow at rest) using peak density demonstrated a fair correlation with flow ratios by microsphere (r = 0.81). There was poor correlation between flow ratios when time to one-half peak or washout time was used.Videodensitometric flow measurements used in vivo to assess a wide range of drug-induced coronary flows may not accurately reflect coronary flow measured by microsphere

Evaluation of an Online Platform for Multiple Sclerosis Research: Patient Description, Validation of Severity Scale, and Exploration of BMI Effects on Disease Course

Objectives: To assess the potential of an online platform, PatientsLikeMe.com (PLM), for research in multiple sclerosis (MS). An investigation of the role of body mass index (BMI) on MS disease course was conducted to illustrate the utility of the platform. Methods: First, we compared the demographic characteristics of subjects from PLM and from a regional MS center. Second, we validated PLM’s patient-reported outcome measure (MS Rating Scale, MSRS) against standard physician-rated tools. Finally, we analyzed the relation of BMI to the MSRS measure. Results: Compared with 4,039 MS Center patients, the 10,255 PLM members were younger, more educated, and less often male and white. Disease course was more often relapsing remitting, with younger symptom onset and shorter disease duration. Differences were significant because of large sample sizes but small in absolute terms. MSRS scores for 121 MS Center patients revealed acceptable agreement between patient-derived and physician-derived composite scores (weighted kappa = 0.46). The Walking domain showed the highest weighted kappa (0.73) and correlation (rs = 0.86) between patient and physician scores. Additionally, there were good correlations between the patient-reported MSRS composite and walking scores and physician-derived measures: Expanded Disability Status Scale (composite rs = 0.61, walking rs = 0.74), Timed 25 Foot Walk (composite rs = 0.70, walking rs = 0.69), and Ambulation Index (composite rs = 0.81, walking rs = 0.84). Finally, using PLM data, we found a modest correlation between BMI and cross-sectional MSRS (rho = 0.17) and no association between BMI and disease course. Conclusions: The PLM population is comparable to a clinic population, and its patient-reported MSRS is correlated with existing clinical instruments. Thus, this online platform may provide a venue for MS investigations with unique strengths (frequent data collection, large sample sizes). To illustrate its applicability, we assessed the role of BMI in MS disease course but did not find a clinically meaningful role for BMI in this setting

In Vivo Water Dynamics in Shewanella oneidensis Bacteria at High Pressure

Abstract: Following observations of survival of microbes and other life forms in deep subsurface environments it is necessary to understand their biological functioning under high pressure conditions. Key aspects of biochemical reactions and transport processes within cells are determined by the intracellular water dynamics. We studied water diffusion and rotational relaxation in live Shewanella oneidensis bacteria at pressures up to 500 MPa using quasi-elastic neutron scattering (QENS). The intracellular diffusion exhibits a significantly greater slowdown (by −10–30%) and an increase in rotational relaxation times (+10–40%) compared with water dynamics in the aqueous solutions used to resuspend the bacterial samples. Those results indicate both a pressure-induced viscosity increase and slowdown in ionic/macromolecular transport properties within the cells affecting the rates of metabolic and other biological processes. Our new data support emerging models for intracellular organisation with nanoscale water channels threading between macromolecular regions within a dynamically organized structure rather than a homogenous gel-like cytoplasm

MLC1 is associated with the Dystrophin-Glycoprotein Complex at astrocytic endfeet

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a progressive cerebral white matter disease with onset in childhood, caused by mutations in the MLC1 gene. MLC1 is a protein with unknown function that is mainly expressed in the brain in astrocytic endfeet at the blood–brain and cerebrospinal fluid–brain barriers. It shares its localization at astrocytic endfeet with the dystrophin-associated glycoprotein complex (DGC). The objective of the present study was to investigate the possible association of MLC1 with the DGC. To test this hypothesis, (co)-localization of DGC-proteins and MLC1 was analyzed by immunohistochemical stainings in gliotic brain tissue from a patient with multiple sclerosis, in glioblastoma tissue and in brain tissue from an MLC patient. In control tissue, a direct protein interaction was tested by immunoprecipitation. Results revealed that MLC1 is co-localized with DGC-proteins in gliotic brain tissue. We demonstrated that both MLC1 and aquaporin-4, a member of the DGC, were redistributed in glioblastoma cells. In MLC brain tissue, we showed absence of MLC1 and altered expression of several DGC-proteins. We demonstrated a direct protein interaction between MLC1 and Kir4.1. From these results we conclude that MLC1 is associated with the DGC at astrocytic endfeet

Suprarenal fixation of endovascular aortic stent grafts: assessment of medium-term to long-term renal function by analysis of juxtarenal stent morphology.

Objective: The effect of supra-renal stent fixation during endovascular aortic aneurysm repair (EVAR) on renal function remains unclear. Using a unique validated 3D intraluminal imaging technique, we analysed the effect of suprarenal stent position relative to renal artery orifices and its medium to long term effects on renal function.Methods: Thirty-four consecutive patients from a single institution were studied following EVAR using the Zenith endograft system from September 1999 to March 2002. The precise locations of the uncovered supra-renal stent struts were assessed by a virtual endoscopic imaging technique. Anatomical and quantitative categorisation of patients was made according to the configuration of uncovered stent struts across the renal artery ostia (RAO). The anatomical subgroups were defined as struts located centrally or peripherally across both RAO. The quantitative subgroups were defined as RAO crossed by multiple struts, a solitary strut or no struts. The subgroups were compared for their renal function as assessed by temporal measurements of serum creatinine concentration and creatinine clearance, and renal parenchymal perfusion defects as assessed using contrast-enhanced computerised tomography (CT).Results: Mean follow-up was 52.7 months. Separate subgroup analysis for both anatomical and quantitative configurations did not demonstrate any significant difference in renal function between the different strut permutations (p>0.05). Follow-up imaging confirmed one case of renal infarction secondary to an occluded accessory renal artery, although, this patient had normal creatinine levels.Conclusion: RAO coverage by supra-renal uncovered stents does not appear to have a significant effect on renal function as evaluated by creatinine measurements in patients with normal pre-operative renal function

Blocking the tropomyosin receptor kinase A (TrkA) receptor inhibits pain behaviour in two rat models of osteoarthritis

Objectives: Tropomyosin receptor kinase A (TrkA) mediates nociceptor sensitisation by nerve growth factor (NGF), but it is unknown whether selective TrkA inhibition will be an effective strategy for treating osteoarthritis (OA) pain. We determined the effects of a TrkA inhibitor (AR786) on pain behaviour, synovitis and joint pathology in two rat OA models. Methods: Knee OA was induced in rats by intraarticular monosodium-iodoacetate (MIA) injection or meniscal transection (MNX) and compared with saline injected or sham-operated controls. Pain behaviour was assessed as weight-bearing asymmetry and paw withdrawal threshold to punctate stimulation. Oral doses (30 mg/kg) of AR786 or vehicle were administered twice daily in either preventive (day −1 to –27) or treatment (day 14–28) protocols. Effect maintenance was evaluated for 2 weeks after treatment discontinuation. Alterations in knee structure (cartilage, subchondral bone and synovium) were examined by macroscopic visualisation of articular surfaces and histopathology. Results: Preventive AR786 treatment inhibited pain behaviour development and therapeutic treatment attenuated established pain behaviour. Weight-bearing asymmetry increased 1 week after treatment discontinuation, but remained less than in vehicle- treated arthritic rats, whereas paw withdrawal thresholds returned to levels of untreated rats within 5 days of treatment discontinuation. AR786 treatment reduced MIA-induced synovitis and did not significantly affect osteochondral pathology in either model. Conclusions: Blocking NGF activity by inhibiting TrkA reduced pain behaviour in two rat models of OA. Analgesia was observed both using preventive and treatment protocols, and was sustained after treatment discontinuation. Selective inhibitors of TrkA therefore hold potential for OA pain relief

Cardiovascular magnetic resonance of pulmonary artery growth and ventricular function after Norwood procedure with Sano modification

For hypoplastic left heart syndrome (HLHS), there have been concerns regarding pulmonary artery growth and ventricular dysfunction after first stage surgery consisting of the Norwood procedure modified with a right ventricle-to-pulmonary artery conduit. We report our experience using cardiovascular magnetic resonance (CMR) to determine and follow pulmonary arterial growth and ventricular function in this cohort

Results of the ANCHOR prospective, multicenter registry of EndoAnchors for type Ia endoleaks and endograft migration in patients with challenging anatomy

ObjectiveProximal attachment site complications continue to occur after endovascular repair of abdominal aortic aneurysms (EVAR), specifically type Ia endoleak and endograft migration. EndoAnchors (Aptus Endosystems, Sunnyvale, Calif) were designed to enhance endograft proximal fixation and sealing, and the current study was undertaken to evaluate the potential benefit of this treatment.MethodsDuring the 23-month period ending in December 2013, 319 subjects were enrolled at 43 sites in the United States and Europe. EndoAnchors were implanted in 242 patients (75.9%) at the time of an initial EVAR procedure (primary arm) and in 77 patients with an existing endograft and proximal aortic neck complications (revision arm). Technical success was defined as deployment of the desired number of EndoAnchors, adequate penetration of the vessel wall, and absence of EndoAnchor fracture. Procedural success was defined as technical success without a type Ia endoleak at completion angiography. Values are expressed as mean ± standard deviation and interquartile range.ResultsThe 238 male (74.6%) and 81 female (25.4%) subjects had a mean age of 74.1 ± 8.2 years. Aneurysms averaged 58 ± 13 (51-63) mm in diameter at the time of EndoAnchor implantation (core laboratory measurements). The proximal aortic neck averaged 16 ± 13 (7-23) mm in length (42.7% <10 mm and 42.7% conical) and 27 ± 4 mm (25-30 mm) in diameter; infrarenal neck angulation was 24 ± 15 (13-34) degrees. The number of EndoAnchors deployed was 5.8 ± 2.1 (4-7). Technical success was achieved in 303 patients (95.0%) and procedural success in 279 patients (87.5%), 217 of 240 (89.7%) and 62 of 77 (80.5%) in the primary and revision arms, respectively. There were 29 residual type Ia endoleaks (9.1%) at the end of the procedure. During mean follow-up of 9.3 ± 4.7 months, 301 patients (94.4%) were free from secondary procedures. Among the 18 secondary procedures, eight were performed for residual type Ia endoleaks and the others were unrelated to EndoAnchors. There were no open surgical conversions, there were no aneurysm-related deaths, and no aneurysm ruptured during follow-up.ConclusionsUse of EndoAnchors to treat existing and acute type Ia endoleaks and endograft migration was successful in most cases. Prophylactic use of EndoAnchors in patients with hostile aortic neck anatomy appears promising, but definitive conclusions must await longer term follow-up data

Altered sensory-weighting mechanisms is observed in adolescents with idiopathic scoliosis

BACKGROUND: Scoliosis is the most common type of spinal deformity. In North American children, adolescent idiopathic scoliosis (AIS) makes up about 90% of all cases of scoliosis. While its prevalence is about 2% to 3% in children aged between 10 to 16 years, girls are more at risk than boys for severe progression with a ratio of 3.6 to 1. The aim of the present study was to test the hypothesis that idiopathic scoliosis interferes with the mechanisms responsible for sensory-reweighting during balance control. METHODS: Eight scoliosis patients (seven female and one male; mean age: 16.4 years) and nine healthy adolescents (average age 16.5 years) participated in the experiment. Visual and ankle proprioceptive information was perturbed (eyes closed and/or tendon vibration) suddenly and then returned to normal (eyes open and/or no tendon vibration). An AMTI force platform was used to compute centre of pressure root mean squared velocity and sway density curve. RESULTS: For the control condition (eyes open and no tendon vibration), adolescent idiopathic scoliosis patients had a greater centre of pressure root mean squared velocity (variability) than control participants. Reintegration of ankle proprioception, when vision was either available or removed, led to an increased centre of pressure velocity variability for the adolescent idiopathic scoliosis patients whereas the control participants reduced their centre of pressure velocity variability. Moreover, in the absence of vision, adolescent idiopathic scoliosis exhibited an increased centre of pressure velocity variability when ankle proprioception was returned to normal (i.e. tendon vibration stopped). The analysis of the sway density plot suggests that adolescent idiopathic scoliosis patients, during sensory reintegration, do not scale appropriately their balance control commands. CONCLUSION: Altogether, the present results demonstrate that idiopathic scoliosis adolescents have difficulty in reweighting sensory inputs following a brief period of sensory deprivation