The impact of 18F-FDG PET on the management of patients with suspected large vessel vasculitis

We aimed to assess the impact of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the management of patients with suspected large vessel vasculitis.

National institutes of health stroke scale score and vessel occlusion in 2152 patients with acute ischemic stroke

Background and Purpose—There is some controversy on the association of the National Institutes of Health Stroke Scale (NIHSS) score to predict arterial occlusion on MR arteriography and CT arteriography in acute stroke. Methods—We analyzed NIHSS scores and arteriographic findings in 2152 patients (35.4% women, mean age 66±14 years) with acute anterior or posterior circulation strokes. Results—The study included 1603 patients examined with MR arteriography and 549 with CT arteriography. Of those, 1043 patients (48.5%; median NIHSS score 5, median time to clinical assessment 179 minutes) showed an occlusion, 887 in the anterior (median NIHSS score 7/0–31), and 156 in the posterior circulation (median NIHSS score 3/0–32). Eight hundred sixty visualized occlusions (82.5%) were located centrally (ie, in the basilar, intracranial vertebral, internal carotid artery, or M1/M2 segment of the middle cerebral artery). NIHSS scores turned out to be predictive for any vessel occlusions in the anterior circulation. Best cut-off values within 3 hours after symptom onset were NIHSS scores ≥9 (positive predictive value 86.4%) and NIHSS scores ≥7 within >3 to 6 hours (positive predictive value 84.4%). Patients with central occlusions presenting within 3 hours had NIHSS scores <4 in only 5%. In the posterior circulation and in patients presenting after 6 hours, the predictive value of the NIHSS score for vessel occlusion was poor. Conclusions—There is a significant association of NIHSS scores and vessel occlusions in patients with anterior circulation strokes. This association is best within the first hours after symptom onset. Thereafter and in the posterior circulation the association is poor.

Myoelectric activity of the ileum, cecum, proximal loop of the ascending colon, and spiral colon in cows with naturally occurring cecal dilatation-dislocation

OBJECTIVE: To analyze myoelectric activity of the ileum, cecum, proximal loop of the ascending colon (PLAC), and spiral colon in cows with naturally occurring cecal dilatation-dislocation (CDD) and compare findings with those in healthy cows. ANIMALS: 8 CDD-affected and 6 healthy control cows. PROCEDURES: Immediately after diagnosis, CDD-affected cows underwent surgery; control cows underwent a similar surgical procedure. Before completion of surgery, 8 bipolar silver electrodes were implanted in the ileum (n = 2), cecum (1), PLAC (1), and spiral colon (4) of each cow. Beginning the day after surgery, intestinal myoelectric activity was recorded daily (8-hour period) for 4 days; data were analyzed by use of specialized software programs. Quantitative variables of myoelectric activity were compared between groups. RESULTS: Cows of both groups recovered without complications after surgery. In control cows, physiologic myoelectric activity was recorded in all intestinal segments on all days after surgery. Apparently normal myoelectric activity was evident in the ileum of CDD-affected cows on the first day after surgery, but myoelectric activity patterns in the cecum, PLAC, and spiral colon were variable with no organized cyclic myoelectric patterns, incomplete or normally organized migrating myoelectric complexes, and slow normalization over time. CONCLUSIONS AND CLINICAL RELEVANCE: After surgery for CDD, normal myoelectric patterns were disrupted in the large intestine of cows, especially in the spiral colon. Clinical recovery with effective transit of ingesta occurred before normalization of myoelectric activity in the large intestine. Therapeutic protocols for restoration or normalization of spiral colon motility should be developed for treatment of CDD-affected cattle.

Dual-loop circuits in postoperative atrial macro re-entrant tachycardias

Background Patients late after open-heart surgery may develop dual-loop reentrant atrial arrhythmias, and mapping and catheter ablation remain challenging despite computer-assisted mapping techniques. Objectives The purpose of the study was to demonstrate the prevalence and characteristics of dual-loop reentrant arrhythmias, and to define the optimal mapping and ablation strategy. Methods Fourty consecutive patients (mean age 52+/-12 years) with intra-atrial reentrant tachycardia (IART) after open-heart surgery (with an incision of the right atrial free wall) were studied. Dual-loop IART was defined as the presence of two simultaneous atrial circuits. Following an abrupt tachycardia change during radiofrequency (RF) ablation, electrical disconnection of the targeted reentry isthmus from the remaining circuit was demonstrated by entrainment mapping. Furthermore, the second circuit loop was localized using electroanatomic mapping and/or entrainment mapping. Results Dual-loop IART was demonstrated in 8 patients (20%, 5 patients with congenital heart disease, 3 with acquired heart disease). Dual-loop IART included an isthmus-dependant atrial flutter combined with a reentry related to the atriotomy scar. The diagnosis of dual-loop IART required the comparison of entrainment mapping before and after tachycardiamodification. Overall, 35 patients had successful RF ablation (88%). Success rates were lower in patients with dual-loop IART than in patient without dual-loop IART. Ablation failures in 3 patients with dual-loop IART were related to the inability to properly transect the second tachycardia isthmus in the right atrial free wall. Conclusions Dual-loop IART is relatively common after heart surgery involving a right atriotomy. Abrupt tachycardia change and specific entrainment mapping maneuvers demonstrate these circuits. Electroanatomic mapping appears to be important to assist catheter ablation of periatriotomy circuits.

Vascular endothelial cell-specific phosphotyrosine phosphatase (VE-PTP) activity is required for blood vessel development

VE-PTP, a receptor-type phosphotyrosine phosphatase, associates with the tyrosine kinase receptor Tie-2 and VE-cadherin and enhances the adhesive function of the latter. Here, VE-PTP was found to be restricted to endothelial cells, with a preference for arterial endothelium. Mutant mice expressing a truncated, secreted form of VE-PTP lacking the cytoplasmic and transmembrane domains and the most membrane-proximal extracellular fibronectin type III repeat, showed severe vascular malformations causing lethality at 10 days of gestation. Although blood vessels were initially formed, the intraembryonic vascular system soon deteriorated. Blood vessels in the yolk sac developed into dramatically enlarged cavities. In explant cultures of mutant allantoides, endothelial cells were found next to vessel structures growing as cell layers. No signs for enhanced endothelial apoptosis or proliferation were observed. Thus, the activity of VE-PTP is not required for the initial formation of blood vessels, yet it is essential for their maintenance and remodeling.

Closed-loop control of mean arterial blood pressure during surgery with alfentanil: clinical evaluation of a novel model-based predictive controller

BACKGROUND: In contrast to hypnosis, there is no surrogate parameter for analgesia in anesthetized patients. Opioids are titrated to suppress blood pressure response to noxious stimulation. The authors evaluated a novel model predictive controller for closed-loop administration of alfentanil using mean arterial blood pressure and predicted plasma alfentanil concentration (Cp Alf) as input parameters. METHODS: The authors studied 13 healthy patients scheduled to undergo minor lumbar and cervical spine surgery. After induction with propofol, alfentanil, and mivacurium and tracheal intubation, isoflurane was titrated to maintain the Bispectral Index at 55 (+/- 5), and the alfentanil administration was switched from manual to closed-loop control. The controller adjusted the alfentanil infusion rate to maintain the mean arterial blood pressure near the set-point (70 mmHg) while minimizing the Cp Alf toward the set-point plasma alfentanil concentration (Cp Alfref) (100 ng/ml). RESULTS: Two patients were excluded because of loss of arterial pressure signal and protocol violation. The alfentanil infusion was closed-loop controlled for a mean (SD) of 98.9 (1.5)% of presurgery time and 95.5 (4.3)% of surgery time. The mean (SD) end-tidal isoflurane concentrations were 0.78 (0.1) and 0.86 (0.1) vol%, the Cp Alf values were 122 (35) and 181 (58) ng/ml, and the Bispectral Index values were 51 (9) and 52 (4) before surgery and during surgery, respectively. The mean (SD) absolute deviations of mean arterial blood pressure were 7.6 (2.6) and 10.0 (4.2) mmHg (P = 0.262), and the median performance error, median absolute performance error, and wobble were 4.2 (6.2) and 8.8 (9.4)% (P = 0.002), 7.9 (3.8) and 11.8 (6.3)% (P = 0.129), and 14.5 (8.4) and 5.7 (1.2)% (P = 0.002) before surgery and during surgery, respectively. A post hoc simulation showed that the Cp Alfref decreased the predicted Cp Alf compared with mean arterial blood pressure alone. CONCLUSION: The authors' controller has a similar set-point precision as previous hypnotic controllers and provides adequate alfentanil dosing during surgery. It may help to standardize opioid dosing in research and may be a further step toward a multiple input-multiple output controller.

Lowered microvascular vessel wall oxygen consumption augments tissue pO2 during PgE1-induced vasodilation

Continuous infusion of intravenous prostaglandin E1 (PgE1, 2.5 mug/kg/min) was used to determine how vasodilation affects oxygen consumption of the microvascular wall and tissue pO(2) in the hamster window chamber model. While systemic measurements (mean arterial pressure and heart rate) and central blood gas measurements were not affected, PgE1 treatment caused arteriolar (64.6 +/- 25.1 microm) and venular diameter (71.9 +/- 29.5 microm) to rise to 1.15 +/- 0.21 and 1.06 +/- 0.19, respectively, relative to baseline. Arteriolar (3.2 x 10(-2) +/- 4.3 x 10(-2) nl/s) and venular flow (7.8 x 10(-3) +/- 1.1 x 10(-2)/s) increased to 1.65 +/- 0.93 and 1.32 +/- 0.72 relative to baseline. Interstitial tissue pO(2) was increased significantly from baseline (21 +/- 8 to 28 +/- 7 mmHg; P < 0.001). The arteriolar vessel wall gradient, a measure of oxygen consumption by the microvascular wall decreased from 20 +/- 6 to 16 +/- 3 mmHg (P < 0.001). The arteriolar vessel wall gradient, a measure of oxygen consumption by the vascular wall, decreased from 20 +/- 6 to 16 +/- 3 mmHg (P < 0.001). This reduction reflects a 20% decrease in oxygen consumption by the vessel wall and up to 50% when cylindrical geometry is considered. The venular vessel wall gradient decreased from 12 +/- 4 to 9 +/- 4 mmHg (P < 0.001). Thus PgE1-mediated vasodilation has a positive microvascular effect: enhancement of tissue perfusion by increasing flow and then augmentation of tissue oxygenation by reducing oxygen consumption by the microvascular wall.

Real-time closed-loop electrophysiology: towards new frontiers in in vitro investigations in the neurosciences

Reflected at any level of organization of the central nervous system, most of the processes ranging from ion channels to neuronal networks occur in a closed loop, where the input to the system depends on its output. In contrast, most in vitro preparations and experimental protocols operate autonomously, and do not depend on the output of the studied system. Thanks to the progress in digital signal processing and real-time computing, it is now possible to artificially close the loop and investigate biophysical processes and mechanisms under increased realism. In this contribution, we review some of the most relevant examples of a new trend in in vitro electrophysiology, ranging from the use of dynamic-clamp to multi-electrode distributed feedback stimulation. We are convinced these represents the beginning of new frontiers for the in vitro investigation of the brain, promising to open the still existing borders between theoretical and experimental approaches while taking advantage of cutting edge technologies.

Phylogenetic relationships of German heavy draught horse breeds inferred from mitochondrial DNA D-loop variation

We analysed a 610-bp mitochondrial (mt)DNA D-loop fragment in a sample of German draught horse breeds and compared the polymorphic sites with sequences from Arabian, Hanoverian, Exmoor, Icelandic, Sorraia and Przewalski's Horses as well as with Suffolk, Shire and Belgian horses. In a total of 65 horses, 70 polymorphic sites representing 47 haplotypes were observed. The average percentage of polymorphic sites was 11.5% for the mtDNA fragment analysed. In the nine different draught horse breeds including South German, Mecklenburg, Saxon Thuringa coldblood, Rhenisch German, Schleswig Draught Horse, Black Forest Horse, Shire, Suffolk and Belgian, 61 polymorphic sites and 24 haplotypes were found. The phylogenetic analysis failed to show monophyletic groups for the draught horses. The analysis indicated that the draught horse populations investigated consist of diverse genetic groups with respect to their maternal lineage.

Endothelial survival factors and spatial completion, but not pericyte coverage of retinal capillaries determine vessel plasticity

Pericyte loss and capillary regression are characteristic for incipient diabetic retinopathy. Pericyte recruitment is involved in vessel maturation, and ligand-receptor systems contributing to pericyte recruitment are survival factors for endothelial cells in pericyte-free in vitro systems. We studied pericyte recruitment in relation to the susceptibility toward hyperoxia-induced vascular remodeling using the pericyte reporter X-LacZ mouse and the mouse model of retinopathy of prematurity (ROP). Pericytes were found in close proximity to vessels, both during formation of the superficial and the deep capillary layers. When exposure of mice to the ROP was delayed by 24 h, i.e., after the deep retinal layer had formed [at postnatal (p) day 8], preretinal neovascularizations were substantially diminished at p18. Mice with a delayed ROP exposure had 50% reduced avascular zones. Formation of the deep capillary layers at p8 was associated with a combined up-regulation of angiopoietin-1 and PDGF-B, while VEGF was almost unchanged during the transition from a susceptible to a resistant capillary network. Inhibition of Tie-2 function either by soluble Tie-2 or by a sulindac analog, an inhibitor of Tie-2 phosphorylation, resensitized retinal vessels to neovascularizations due to a reduction of the deep capillary network. Inhibition of Tie-2 function had no effect on pericyte recruitment. Our data indicate that the final maturation of the retinal vasculature and its resistance to regressive signals such as hyperoxia depend on the completion of the multilayer structure, in particular the deep capillary layers, and are independent of the coverage by pericytes.

Angiopoietin-1 and angiopoietin-2 share the same binding domains in the Tie-2 receptor involving the first Ig-like loop and the epidermal growth factor-like repeats

Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) have been identified as ligands with different effector functions of the vascular assembly and maturation-mediating receptor tyrosine kinase Tie-2. To understand the molecular interactions of the angiopoietins with their receptor, we have studied the binding of Ang-1 and Ang-2 to the Tie-2 receptor. Enzyme-linked immunosorbent assay-based competition assays and co-immunoprecipitation experiments analyzing the binding of Ang-1 and Ang-2 to truncation mutants of the extracellular domain of Tie-2 showed that the first Ig-like loop of Tie-2 in combination with the epidermal growth factor (EGF)-like repeats (amino acids 1-360) is required for angiopoietin binding. The first Ig-like domain or the EGF-like repeats alone are not capable of binding Ang-1 and Ang-2. Concomitantly, we made the surprising finding that Tie-2 exon-2 knockout mice do express a mutated Tie-2 protein that lacks 104 amino acids of the first Ig-like domain. This mutant Tie-2 receptor is functionally inactive as shown by the lack of ligand binding and receptor phosphorylation. Collectively, the data show that the first 104 amino acids of the Tie-2 receptor are essential but not sufficient for angiopoietin binding. Conversely, the first 360 amino acids (Ig-like domain plus EGF-like repeats) of the Tie-2 receptor are necessary and sufficient to bind both Ang-1 and Ang-2, which suggests that differential receptor binding is not likely to be responsible for the different functions of Ang-1 and Ang-2.

Impact of vessel size on outcome after implantation of sirolimus-eluting and paclitaxel-eluting stents: a subgroup analysis of the SIRTAX trial

OBJECTIVES: We assessed the impact of vessel size on angiographic and long-term clinical outcome after percutaneous coronary intervention (PCI) with sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) within a randomized trial (SIRTAX [Sirolimus-Eluting Stent Compared With Paclitaxel-Eluting Stent for Coronary Revascularization]). BACKGROUND: Percutaneous coronary intervention in small-vessel disease is associated with an increased risk of major adverse cardiac events (MACE). METHODS: A total of 1,012 patients were randomly assigned to treatment with SES (n = 503) or PES (n = 509). A stratified analysis of angiographic and clinical outcome was performed up to 2 years after PCI according to size of the treated vessel (reference vessel diameter < or =2.75 vs. >2.75 mm). RESULTS: Of 1,012 patients, 370 patients (37%) with 495 lesions underwent stent implantation in small vessels only, 504 patients (50%) with 613 lesions in large vessels only, and 138 patients (14%) with 301 lesions in both small and large vessels (mixed). In patients with small-vessel stents, SES reduced MACE by 55% (10.4% vs. 21.4%; p = 0.004), mainly driven by a 69% reduction of target lesion revascularization (TLR) (6.0% vs. 17.7%; p = 0.001) compared with PES at 2 years. In patients with large- and mixed-vessel stents, rates of MACE (large: 10.4% vs. 13.1%; p = 0.33; mixed: 16.7% vs. 18.0%; p = 0.83) and TLR (large: 6.9% vs. 8.6%; p = 0.47; mixed: 16.7% vs. 15.4%; p = 0.86) were similar for SES and PES. There were no significant differences with respect to death and myocardial infarction between the 3 groups. CONCLUSIONS: Compared with PES, SES more effectively reduced MACE and TLR in small-vessel disease. Differences between SES and PES appear less pronounced in patients with large- and mixed-vessel disease. (The SIRTAX trial; http://clinicaltrials.gov/ct/show/NCT00297661?order=1; NCT00297661).