Clinical impact of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer’s disease: a multicenter study

Annals of Nuclear Medicine - Amyloid positron emission tomography (PET) can reliably detect senile plaques and fluorinated ligands are approved for clinical use. However, the clinical impact of...     

Receptor activator of NF-κB ligand-dependent expression of caveolin-1 in osteoclast precursors, and high dependency of osteoclastogenesis on exogenous lipoprotein

Although extensive studies have done much to clarify the molecular mechanisms of osteoclastogenesis during the last ten years, there may still be unknown molecules associated with osteoclast differentiation. Thus, we used fluorescent differential display to screen for genes whose expression is induced by receptor activator of NF-κB ligand (RANKL), a crucial molecule for osteoclast formation. We identified caveolin-1 (Cav-1) as a RANKL-induced gene. Cav-1 is a major structural protein of caveolae and lipid rafts, cholesterol-enriched microdomains in the plasma membrane (PM). The RANKL-induced Cav-1 was immediately conveyed to lipid rafts. Conversely, expression of flotillin-1 (Flot-1), another scaffolding protein of lipid rafts, was reduced during osteoclastogenesis, indicating conversion of Flot-1-predominant rafts into Cav-1-enriched rafts. However, in vitro osteoclastogenesis of precursor cells from Cav-1-null mice was comparable to that of wild-type mice, while Cav-2 expression in the knockout osteoclasts was maintained. Conversely, Cav-2 gene silencing in Cav-1-null osteoclast precursors using siRNA for Cav-2 increased osteoclast formation, suggesting that the Cav-1/Cav-2 complex may act as a negative regulator for osteoclastogenesis. On the other hand, destruction of lipid rafts by removal of cholesterol from the PM by methyl-ß-cyclodextrin (MCD) treatment caused disordered signal transductions for osteoclastogenesis, such as hyperactivation of Erk1/2 and insensitivity of Akt to RANKL stimulus. The abnormal signaling was reproduced by deleting exogenous lipoproteins from the culture medium, which also resulted in reduced osteoclast formation. In addition, the deletion caused delayed expression of nuclear factor of activated T cells c1 (NFATc1), and depressed its activation in the cytosol and inhibited its translocation into nuclei. Simultaneously, the deletion reduced the level of FcRγ, a trigger protein for initiating the calcium signaling needed to activate NFATc1, and decreased Cav-1 in lipid rafts. These findings indicate that the molecular mechanisms of osteoclastogenesis are highly dependent on extracellular lipoprotein and the integrity of lipid rafts, and suggest possible involvement of cholesterol.     

Neutrophil elastase activity in pulmonary venous blood during lung resection

OBJECTIVES Neutrophil elastase has been reported to play an important role in acute lung injury, which is a major cause of postoperative mortality after pulmonary resection. Neutrophil elastase released in the lungs reaches the peripheral circulation via the pulmonary veins. This study was performed to compare neutrophil elastase activity in pulmonary venous blood (collected during lobectomy) with that in the peripheral blood, and to determine the perioperative changes of neutrophil elastase activity. METHODS In 34 patients undergoing lobectomy with mediastinal lymph node dissection, the leucocyte count, neutrophil count, neutrophil elastase activity and levels of tumour necrosis factor-α, interleukin-6 and interleukin-8 were measured in the pulmonary venous blood and peripheral arterial blood before and after surgery. Then, these parameters were compared between before and after surgery with peripheral and pulmonary blood. RESULTS Neutrophil elastase activity was found to be significantly higher in pulmonary venous blood at the completion of surgery than at the start (during thoracotomy), while the neutrophil elastase activity of peripheral arterial blood showed no significant change between the start and completion of surgery. CONCLUSIONS In conclusion, measurement of neutrophil elastase activity in pulmonary venous blood revealed changes associated with lobectomy.     

Platelet-rich plasma combined with hydroxyapatite for lumbar interbody fusion promoted bone formation and decreased an inflammatory pain neuropeptide in rats

STUDY DESIGN.: A prospective interventional trial, using a rat model of lumbar interbody fusion. OBJECTIVE.: To examine the potential efficacy of platelet-rich plasma (PRP) for lumbar interbody fusion, using hydroxyapatite (HA). SUMMARY OF BACKGROUND DATA.: PRP is an autologous product containing a high concentration of platelets in a small volume of plasma and has osteoinductive effects. HA has osteoconductive ability and has been used in combination with autogenous bone for spine fusion. However, reports using PRP with HA for spine fusion are very few. The purpose of this study was to examine the efficacy of PRP with HA for spinal interbody fusion and at the same time to estimate the change in immunoreactivity of the inflammatory neuropeptide, calcitonin gene-related peptide (CGRP), in dorsal root ganglion (DRG) neurons innervating spinal discs. METHODS.: A total of 35 Sprague-Dawley rats were used in this study. Twenty-one rats were used for conducting interbody fusion experiments, 7 rats were used as immunostaining controls, and 7 other rats were used as blood donors for making PRP. L5-L6 interbody fusion was performed on 21 rats using HA + PRP (n = 7), HA + platelet-poor plasma (n = 7), or HA + saline (n = 7). Simultaneously, Fluoro-Gold neurotracer was applied to the intervertebral space to detect DRG neurons innervating the discs. L5-L6 lumbar radiographs were obtained and lumbar DRGs were immunostained for CGRP. The rate of bone union and the change in CGRP immunoreactive DRG neurons innervating the discs were evaluated and compared among groups. RESULTS.: All L5-L6 lumbar discs were fused in the PRP + HA group (fused 7/total 7), whereas only 1 case was fused in the platelet-poor plasma group (1 of 7) and no cases in the HA-only group (0 of 7), which was a significant difference. Upon immunohistochemical analysis, CGRP-positive neurons innervated L5-L6 intervertebral discs in nonunion cases, and these were significantly increased compared with those in union cases. CONCLUSION.: Our study suggests that using PRP with HA was beneficial for spine fusion. This combination may promote bone union and also decrease inflammatory neuropeptide in sensory neurons innervating the discs.     

Early and late outcomes of coronary artery bypass surgery versus percutaneous coronary intervention with drug-eluting stents for dialysis patients

Abstract Background: Advances in percutaneous coronary intervention (PCI) using drug‐eluting stents (DES) have impacted clinical practice. However, the efficacy of DES for dialysis patients still remains controversial. This study compares the early and long‐term clinical outcomes of coronary artery bypass grafting (CABG) and PCI with DES in dialysis patients. Methods: A retrospective review was performed in 125 dialysis patients treated between 2004 and 2007. Fifty‐eight patients underwent CABG and 67 underwent PCI with DES. The overall death, cardiac death, and cardiac‐related event rates were analyzed using the Kaplan‐Meier method. For the risk‐adjusted comparisons, multivariable logistic and Cox regression analyses were used. Results: The preoperative characteristics of the patients were similar except for the ejection fraction (p = 0.002) and the number of diseased vessels (p < 0.001). The 30‐day mortality was 0 in both groups. The overall survival rates at one, three, and five years were 84.2%, 64.7%, and 56.2% in CABG group and 88.2%, 75.5%, and 61.7% in DES group, respectively (p = 0.202). The rates of freedom from cardiac‐related events at one, three, and five years were 76.6%, 68.1%, and 48.6%, and 63.0%, 31.4%, and 0% in CABG and DES groups (p < 0.001), respectively, including seven (10%) late thromboses in the DES group. Although the risk‐adjusted analysis showed no significant difference for overall and cardiac death rates, the rates of cardiac‐related events and graft/stent failure were significantly higher in the DES group. Conclusions: CABG is superior for revascularization in dialysis patients compared with PCI using DES in terms of freedom from cardiac‐related events. (J Card Surg 2012;27:281‐287)     

Clinical, histological, and genetic features of fourth ventricle ependymoma in the elderly

A 71-year-old woman presented with a rare case of geriatric ependymoma originating from the fourth ventricle manifesting as progressive gait and memory disturbance. Imaging studies revealed an extraaxial mass in the fourth ventricle protruding into the right cerebellomedullary cistern, with concomitant obstructive hydrocephalus. Surgery achieved subtotal removal since the tumor tightly adhered to the right vestibular area of the fourth ventricular floor. The histological diagnosis was ependymoma, which was also confirmed by comparative genetic hybridization. Although she developed severe laryngeal edema and worsening of the hydrocephalus postoperatively which required additional treatment, she recovered with residual mild gait disturbance, and was transferred to a rehabilitation facility. Fourth ventricle ependymoma in the elderly is rare. Comparative genetic hybridization may be important in the diagnosis of geriatric ependymoma and in the choice for adjuvant therapy as well as in estimating the prognosis for patients with rare types of ependymoma.     

Median nerve deformation in differential finger motions: ultrasonographic comparison of carpal tunnel syndrome patients and healthy controls

We investigated the median nerve deformation in the carpal tunnel in patients with carpal tunnel syndrome and controls during thumb, index finger, middle finger, and a four finger motion, using ultrasound. Both wrists of 29 asymptomatic volunteers and 29 patients with idiopathic carpal tunnel syndrome were evaluated by ultrasound. Cross‐sectional images during motion from full extension to flexion were recorded. Median nerve cross‐sectional area, perimeter, aspect ratio of the minimal enclosing rectangle, and circularity in extension and flexion positions were calculated. Additionally, a deformation index was calculated. We also calculated the intra‐rater reliability. In both controls and patients, the median nerve cross‐sectional area became significantly smaller from extension to flexion in all finger motions (p < 0.05). In flexion and extension, regardless of the specific finger motion, the median nerve deformation, circularity and the change in perimeter were all significantly greater in CTS patients than in controls (p < 0.05). We found excellent intra‐rater reliability for all measurements (ICC > 0.84). With this study we have shown that it is possible to assess the deformation of the median nerve in carpal tunnel syndrome with ultrasonography and that there is more deformation of the median nerve in carpal tunnel syndrome patients during active finger motion. These parameters might be useful in the evaluation of kinematics within the carpal tunnel, and in furthering our understanding of the biomechanics of carpal tunnel syndrome in the future. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:643–648, 2012     

A silicone-based wire-reinforced tracheal tube with a hemispherical bevel reduces nasal morbidity for nasotracheal intubation

We tested the hypothesis that a silicone-based wire-reinforced tracheal tube with a hemispherical bevel is superior to a polyvinyl chloride (PVC)-based precurved tube with a conventional diagonal bevel for nasotracheal intubation. Eighty anesthetized paralyzed adults (ASA physical status I-II) requiring nasotracheal intubation for tonsillectomy were randomly allocated into two equal-sized groups for airway management with the silicone tracheal tube or PVC tracheal tube. Intubation was subdivided into three phases: 1). passage through the nose into the pharynx, 2). laryngoscope-guided passage into the glottic inlet, and 3). laryngoscope-guided passage into the trachea. A specific sequence of airway maneuvers was followed at each stage if it was unsuccessful. The number of attempts and intubation time were documented by an unblinded observer. The frequency of epistaxis and postoperative nasal complications was documented by blinded observers. There were no intubation failures. The number of attempts at pharyngeal (47 versus 56; P = 0.04) and tracheal (43 versus 55; P = 0.005) placement was smaller for the silicone tracheal tube, but the number of attempts at glottic placement was more (72 versus 49; P < 0.0001). Intubation time was similar. The frequency (32% versus 80%; P < 0.0001) and severity of epistaxis were less for the silicone tracheal tube. The total number of postoperative nasal symptoms was smaller for the silicone tracheal tube (10 versus 21; P < 0.05). We conclude that the pharyngeal and tracheal placement phases of nasotracheal intubation require fewer attempts with the silicone tracheal tube than the PVC tracheal tube but that the glottic placement phase requires more attempts. Nasal morbidity is less common with the silicone tracheal tube. IMPLICATIONS: The pharyngeal and tracheal placement phases of nasotracheal intubation require fewer attempts with a silicone-based wire-reinforced tracheal tube with a hemispherical bevel than with a polyvinyl chloride-based precurved tracheal tube with a conventional diagonal bevel, but the glottic placement phase requires more attempts. Nasal morbidity is less common with the silicone tracheal tube.     

Three-dimensional blood flow analysis in a wide-necked internal carotid artery-ophthalmic artery aneurysm

OBJECT: The aim of this study was to evaluate axial and secondary flow structures in a wide-necked internal carotid artery-ophthalmic artery aneurysm, one of the most common locations for endovascular coil placement. METHODS: A clear acrylic aneurysm model was manufactured from a three-dimensional computerized tomography angiogram. Intraaneurysm blood flow analysis was conducted using an acrylic aneurysm model together with laser Doppler velocimetry and particle imaging velocimetry. The maximal axial blood flow velocities in the inflow and outflow zones at the aneurysm orifice were noted at the peak systolic phase, measuring 46.8 and 24.9% of that in the parent artery, respectively. The mean size of the inflow zone during one cardiac cycle was 44.3 +/- 9.8% (range 35.6-58.7%) the size of the axial section at the aneurysm orifice. In the lower and upper planes of the aneurysm dome, the mean size of inward and outward flow areas were 43.3 +/- 6.7% and 43.8 +/- 6.8% the size of the axial cross-sectional plane, respectively. The axial flow velocity structures were dynamically altered throughout the cardiac cycle, particularly at the aneurysm orifice. The fastest secondary flow at the opening was also noted at the peak systolic and early diastolic phases. Axial blood flow velocity was slower in the upper axial plane of the aneurysm dome than in the lower one. Conversely, the secondary flow component was faster in the upper plane. CONCLUSIONS: The side-wall aneurysm in this study did not demonstrate a simple flow pattern as was previously seen in ideally shaped experimental aneurysms in vitro and in vivo. The flow patterns of inflow and outflow zones were very difficult to predict based on the limited flow information provided on standard digital subtraction angiography, even in an aneurysm with a relatively simple dome shape.     

Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes

Diabetic nephropathy is a leading cause of end-stage renal failure. Several mechanisms, including activation of protein kinase C, advanced glycation end products, and overexpression of transforming growth factor (TGF)-beta, are believed to be involved in the pathogenesis of diabetic nephropathy. However, the significance of inflammatory processes in the pathogenesis of diabetic microvascular complications is poorly understood. Accumulation of macrophages and overexpression of leukocyte adhesion molecules and chemokines are prominent in diabetic human kidney tissues. We previously demonstrated that intercellular adhesion molecule (ICAM)-1 mediates macrophage infiltration into the diabetic kidney. In the present study, to investigate the role of ICAM-1 in diabetic nephropathy, we induced diabetes in ICAM-1-deficient (ICAM-1(-/-)) mice and ICAM-1(+/+) mice with streptozotocin and examined the renal pathology over a period of 6 months. The infiltration of macrophages was markedly suppressed in diabetic ICAM-1(-/-) mice compared with that of ICAM-1(+/+) mice. Urinary albumin excretion, glomerular hypertrophy, and mesangial matrix expansion were significantly lower in diabetic ICAM-1(-/-) mice than in diabetic ICAM-1(+/+) mice. Moreover, expressions of TGF-beta and type IV collagen in glomeruli were also suppressed in diabetic ICAM-1(-/-) mice. These results suggest that ICAM-1 is critically involved in the pathogenesis of diabetic nephropathy.