Novel therapies and the best new device concepts for 2013 CAS techniques: the Mo.Ma® Proximal Occlusion System.

Recently carotid artery stenting (CAS) was upgraded in the class of recommendation among other revascularization treatments for symptomatic patients with carotid artery disease. This makes CAS potentially available to a broader range of patients. Significant evolution in CAS materials and protection devices contributed towards this improvement. Particularly in the setting of symptomatic carotid stenosis the most important cerebral protection devices available today, are the proximal protection systems. Comparing to the distal, filter-type protection devices, proximal protection systems can offer complete cerebral protection by preventing embolization of debris in the brain even before lesion crossing. In the present manuscript, we are reviewing all data regarding the efficacy of the flow-blockage proximal protection system (Mo.Ma®, Medtronic, Minneapolis, MN, US) as well as its potential advantages and drawbacks.

Late cerebral embolization after emboli-protected carotid artery stenting.

Carotid artery stenting (CAS) is nowadays considered as alternative therapeutic option to carotid endarterectomy for patients suffering from carotid artery disease. Recent studies and meta-analyses have demonstrated equal performance of carotid stenting to endarterectomy as regard as the overall adverse events (death/stroke rates), especially when periprocedural myocardial infarction and nerve pulses are also included. However, carotid stenting was inferior to endarterectomy when compared in terms of acute and late embolic events. In the present review, we collect all studies available in the published literature regarding the late embolic events. We mainly attempted to gather data regarding the silent embolic events occurring after the acute post-procedural period. We analyzed the results and reported the incidence of the problem. Finally, we aimed to identify possible causes and propose effective solutions to reduce the incidence of late embolic events.

Carotid stents: which is the best option?

Nowadays, carotid artery stenting (CAS) offers a potential alternative to carotid endarterectomy (CEA). CAS main advantages over CEA are the less invasive approach and the almost equal performance to CEA in terms of stroke prevention and complications. One of the most important factors which played significant role to CAS evolution is the progress in design of modern materials, especially stents. Today, several types of dedicated carotid stents have specific mechanical properties, which provide stents with individual characteristics making each of them suitable for specific carotid lesions and anatomies. The present review analyses the specific design and construction of modern stents, trying to point out their particular mechanical properties and characteristics. Additionally, it presents all available data published on comparison between different stent designs with the intention to identify which carotid stent is the best option for particular patient and lesion characteristics.

Carotid angioplasty in asymptomatic patients undergoing CABG surgery.

AIM: Although there are studies reporting that carotid endarterectomy (CEA) is recommended before or concomitant to coronary artery bypass grafting (CABG) in patients with severe carotid stenosis, controversies still exist. Carotid artery stenting (CAS) has been recently introduced as an alternative revascularization therapy in high-risk patients. The aim of this study was to demonstrate, whether CAS is safe as an alternative treatment to carotid CEA, in asymptomatic candidates for CABG surgery. METHODS: Forty-one patients with severe carotid and coronary artery disease were studied. The mean age was 65 years; 91% were males. Within 1 week of the CAS intervention all patients underwent CABG surgery. A brain protection device was used in all CAS interventions. Balloon PTA and stenting was performed in all subjects. Adjunctive therapy with heparin was used during the procedure and clopidogrel was started immediately after cardiac surgery. Patients were assessed neurologically before and after the procedure (immediately after the CAS, at 24h, at 30 days, at 3, 6 and 12 months). The primary end point was the incidence of TIA, stroke, or death at 30 days. RESULTS: Internal carotid artery lesions of > 80%, were reduced by CAS to < 20% in all cases, achieving a procedural success of 100%. There were no neurological complications, such as TIA and stroke, or death, up to 12 months follow up. One patient developed acute coronary syndrome the day after CAS and was treated accordingly. CONCLUSION: Our results show that CAS, with brain protection in asymptomatic patients undergoing CABG surgery is feasible and safe and could be a good alternative to CEA.

Search for Lorentz and CPT violation effects in Muon spin precession.

The spin precession frequency of muons stored in the (g-2) storage ring has been analyzed for evidence of Lorentz and CPT violation. Two Lorentz and CPT violation signatures were searched for a nonzero delta omega a(=omega a mu+ - omega a mu-) and a sidereal variation of omega a mu+/-). No significant effect is found, and the following limits on the standard-model extension parameters are obtained: bZ = -(1.0+/-1.1) x 10(-23) GeV; (m mu dZ0 + HXY)=(1.8+/-6.0) x 10(-23) GeV; and the 95% confidence level limits b perpendicular mu+ <1.4 x 10(-24) GeV and b perpendicular mu- <2.6 x 10(-24) GeV.

Measurement of the negative muon anomalous magnetic moment to 0.7 ppm.

The anomalous magnetic moment of the negative muon has been measured to a precision of 0.7 ppm (ppm) at the Brookhaven Alternating Gradient Synchrotron. This result is based on data collected in 2001, and is over an order of magnitude more precise than the previous measurement for the negative muon. The result a(mu(-))=11 659 214(8)(3) x 10(-10) (0.7 ppm), where the first uncertainty is statistical and the second is systematic, is consistent with previous measurements of the anomaly for the positive and the negative muon. The average of the measurements of the muon anomaly is a(mu)(exp)=11 659 208(6) x 10(-10) (0.5 ppm).

Measurement of the positive muon anomalous magnetic moment to 0.7 ppm.

A higher precision measurement of the anomalous g value, a(mu)=(g-2)/2, for the positive muon has been made at the Brookhaven Alternating Gradient Synchrotron, based on data collected in the year 2000. The result a(mu(+))=11 659 204(7)(5)x10(-10) (0.7 ppm) is in good agreement with previous measurements and has an error about one-half that of the combined previous data. The present world average experimental value is a(mu)(expt)=11 659 203(8)x10(-10) (0.7 ppm).

Simultaneous inhibition of glioma angiogenesis, cell proliferation, and invasion by a naturally occurring fragment of human metalloproteinase-2.

Angiogenesis, tumor cell proliferation, and migration are the hallmarks of solid tumors, such as gliomas. This study demonstrates that a fragment derived from the autocatalytic digestion of matrix metalloproteinase (MMP)-2, called PEX, acts simultaneously as an inhibitor of glioma angiogenesis, cell proliferation, and migration. PEX is detected in the cultured medium of various human glioma, endothelial, breast, and prostate carcinoma cell lines. PEX is purified from the medium of glioma cell lines by chromatography, where PEX is constitutively expressed as a free and a TIMP-2-bound form. In human glioma tissue, PEX expression correlates with histological subtype and grade and with alpha v beta 3 integrin expression to which it is bound. Systemic administration of PEX to s.c. and intracranial human glioma xenografts results in a 99% suppression of tumor growth with no signs of toxicity. Thus, PEX is a very promising candidate for the treatment of human malignant gliomas.

Clear cell pleomorphic xanthoastrocytoma: case report.

Pleomorphic xanthoastrocytoma (PXA) is a well-described astrocytic neoplasm with distinctive clinical and pathological features. Although most patients with PXAs are cured by surgical excision, other patients experience malignant progression and tumor recurrence. We describe a 47-year-old woman with a left temporal lobe PXA that had classic histopathological characteristics as well as extensive clear cell and focal papillary changes, and some anaplastic findings. The patient has now suffered two recurrences after complete resection. The case illustrates a rare, previously undescribed histological variant of PXA, with a prominent clear cell and focal papillary morphology. The study of histologically similar cases is needed to determine whether this variant is always associated with a greater likelihood of recurrence.

Alpha(v)beta3 and alpha(v)beta5 integrin expression in glioma periphery.

OBJECTIVE: This study analyzed the expression of integrins alpha(v)beta3 and alpha(v)beta5 in glioma tissue and focused on the periphery of high-grade gliomas. METHODS: The analysis was performed with Western blot, immunohistochemistry, and immunofluorescence, by use of two monoclonal antibodies able to recognize the functional integrin heterodimer. The expression of integrin-related ligands and growth factors also was studied. Sections from the tumor periphery were classified as either tumor periphery (light tumor infiltrate or scant visible cells) or peritumor (heavy tumor infiltration). RESULTS: Our data on glioma tissues demonstrated that both integrins were expressed in glioma cells and vasculature and their expression correlated with the histological grade. Alpha(v)beta3 expression was prominent in astrocytic tumors. Both integrins were markers of tumor vasculature, particularly of endothelial proliferation. A high-grade glioma periphery demonstrated a prominent expression of integrin alpha(v)beta3. Cells demonstrating alpha(v)beta3 positivity were identified as tumor astrocytes and endothelial cells by double imaging. The same cells were surrounded by some alpha(v)beta3 ligands and co-localized fibroblast growth factor 2. Matrix metalloproteinase 2 also was found to be co-localized with alpha(v)beta3 in the same cells. Alpha(v)beta3 expression was more relevant in tumor astrocytes. Alpha(v)beta3 integrin and vascular endothelial growth factor expression increased from the periphery to the tumor center. CONCLUSION: Our data support the role of integrins alpha(v)beta3 and alpha(v)beta5 in glioma-associated angiogenesis. In addition, they suggest a role for integrin alpha(v)beta3 in neoangiogenesis and cell migration in high-grade glioma periphery.

Fluorescent imaging in a glioma model in vivo.

BACKGROUND AND OBJECTIVE: Nile blue dyes have been shown to have affinity for tumor tissue as compared to surrounding normal tissue and to be relatively non-toxic. We have employed EtNBA, a lipophilic, fluorescent benzophenoxazine dye, in a murine model to image subcutaneous and intracranial U-87 glioma implants. STUDY DESIGN/MATERIALS AND METHODS: The imaging system used to detect fluorescence consists of a SIT video camera fitted with a zoom microscope-magnifying lens. The tumor was illuminated with a 632.8-nm diffuse beam from a helium-neon laser. The video image was processed using a Sony image processor to give real-time pseudocolor and enhanced black and white images. RESULTS: Following subcutaneous injection of the dye at doses of 2.5-5.0 mg/kg bw, we observed a gradual increase of the fluorescent signal from the tumor which peaked 1-3 hours post-injection with variable selectivity (typically 4:1) for tumor to normal surrounding tissues permitting the clear demarcation of the tumor. CONCLUSIONS: The present in vivo study demonstrates that EtNBA is a safe and effective photodiagnostic agent, able to demarcate U87-MG solid tumors in mice on a real-time basis at a concentration of 2.5-5.0 mg/kg 1-3 hours after administration.

Precise measurement of the positive muon anomalous magnetic moment.

A precise measurement of the anomalous g value, a(mu) = (g-2)/2, for the positive muon has been made at the Brookhaven Alternating Gradient Synchrotron. The result a(mu+) = 11 659 202(14) (6) x 10(-10) (1.3 ppm) is in good agreement with previous measurements and has an error one third that of the combined previous data. The current theoretical value from the standard model is a(mu)(SM) = 11 659 159.6(6.7) x 10(-10) (0.57 ppm) and a(mu)(exp) - a(mu)(SM) = 43(16) x 10(-10) in which a(mu)(exp) is the world average experimental value.

Comparative efficacy of primary angioplasty with stent implantation and thrombolysis in restoring basal coronary artery flow in acute ST segment elevation myocardial infarction: quantitative assessment using the corrected TIMI frame count.

Following thrombolysis and primary percutaneous transluminal coronary angioplasty (PTCA) for acute ST segment elevation myocardial infarction, basal flow in the culprit artery is known to influence prognosis. The purpose of this study was to determine if differences exist in basal flow in culprit and nonculprit coronary arteries in patients with acute ST segment elevation myocardial infarction who were treated with thrombolysis or primary PTCA with stent implantation. Twenty patients were randomized to thrombolysis (with recombinant tissue plasminogen activator) and 24 to primary PTCA with stent implantation within 3 hours of onset of acute ST segment elevation myocardial infarction. Coronary angiography was performed 90-120 minutes after thrombolysis or immediately after PTCA with stent implantation and again at 18-36 hours after intervention in both groups. Patients who failed to achieve thrombolysis in myocardial infarction (TIMI) grade 2 or 3 flow were excluded. The corrected TIMI frame count was used as the index of basal coronary artery flow. Early after intervention the mean corrected TIMI frame count in the culprit coronary artery was significantly lower in the primary PTCA with stent group (27.4 +/- 7.7 frames) than in the thrombolysis group (39.8 +/- 10 frames, p < 0.001). Eight thrombolysis patients (40%) and 20 primary PTCA patients (83%, p < 0.01) achieved TIMI grade 3 flow early after intervention. By 18-36 hours after intervention there were no significant differences in the mean correct TIMI frame count between the thrombolysis and primary PTCA with stent groups. There were no significant differences in the mean corrected TIMI frame count between these two groups in the nonculprit coronary artery, either early after intervention or at 18-36 hours. In successfully reperfused coronary arteries following acute ST segment elevation myocardial infarction, primary angioplasty with stent implantation reestablished TIMI grade 2 or 3 flow faster and more effectively than thrombolysis did.

Alpha(v)beta3 and alpha(v)beta5 integrin expression in meningiomas.

OBJECTIVE: Integrins are emerging as alternative receptors capable of mediating several biological functions, such as cell-matrix and cell-cell adhesion, cell migration, signal transduction, and angiogenesis. Two alpha(v) integrins, i.e., alpha(v)beta3 and alpha(v)beta5, play critical roles in mediating these activities, particularly in tumors. No data are available on the expression of these integrins in meningiomas. METHODS: Using Western blot and immunohistochemical analyses with LM609 and PG32, two monoclonal antibodies capable of recognizing the functional integrin heterodimer, we evaluated the expression of alpha(v)beta3 and alpha(v)beta5 integrins in a series of 34 meningiomas of different histological subtypes and grades. We studied their expression in tumor cells and vasculature, as well as the expression of their related angiogenic factors (fibroblast growth factor 2 and vascular endothelial growth factor) and the alpha(v)beta3 ligand vitronectin. RESULTS: Alpha(v)beta3 and alpha(v)beta5 integrins were expressed by neoplastic vasculature and cells. Alpha(v)beta3 and alpha(v)beta5 expression was associated and correlated with that of their respective growth factors (fibroblast growth factor 2 and vascular endothelial growth factor) and microvessel counts and densities. Alpha(v)beta3 was more strongly expressed than alpha(v)beta5 in two cases of histologically benign meningiomas with aggressive clinical behavior. Alpha(v)beta3 expression was associated with that of its related ligand vitronectin and was also evident in small vessels of brain tissue closely surrounding meningiomas. CONCLUSION: Our data demonstrate the expression of alpha(v)beta3 and alpha(v)beta5 integrins in meningioma cells and vasculature. Our findings suggest a role for both of these integrins, and particularly alpha(v)beta3, in meningioma angiogenesis.

Expression of cyclooxygenase 2 (COX-2) in human glioma and in vitro inhibition by a specific COX-2 inhibitor, NS-398.

The up-regulation of cyclooxygenase 2 (COX-2) expression is a frequent occurrence in a variety of different tumors. In this study, COX-2 protein expression was investigated in 50 glioma and 3 normal brain specimens by immunohistochemistry. Expression of COX-2 protein was observed in all normal brain and glioma specimens by immunohistochemistry, regardless of histological grade. The immunoreactive score was significantly higher in high-grade glioma than low-grade glioma and normal brain specimens. For a subset of these tumors (nine gliomas and three normal brain), Western blot analysis was also performed. COX-2 protein was detected in all specimens by Western blot analysis. The effect of the specific COX-2 inhibitor NS-398 on monolayer cell cultures and three-dimensional glioma spheroids was investigated using U-87MG and U-251MG human glioblastoma cell lines. The proliferation rate was assessed in monolayer cultures. In addition, a growth assay, a migration assay, an apoptosis assay, and a tumor invasion assay were performed in a three-dimensional spheroid culture system. NS-398 was able to reduce the proliferation of monolayer cell cultures, as well as the growth of spheroids and tumor cell migration, in a dose-dependent manner. There was also a moderate increase in the number of apoptotic cells in the treated spheroids. NS-398 did not have an inhibitory effect on tumor invasion in the coculture spheroid system. Our study provides evidence that COX-2 is up-regulated in the majority of high-grade gliomas and that a potential role of COX-2 inhibitors as an adjuvant therapy for brain tumors may exist.

"Cobrahead" graft for intercostal artery implantation during descending aortic replacement.

A technique for a separate sidearm graft ("cobrahead") to facilitate reattachment of intercostal arteries in descending aortic replacement is described. The technique allows for very prompt restoration of spinal cord blood flow (via a Y attachment from the arterial perfusion circuit). The technique permits a simple, quick, and fully accessible anastomosis, technically more facile than the traditional side-to-side anastomosis. None of 7 patients treated with this technique had early or late paraplegia. Preliminary computed tomographic follow-up scans confirm patency of the cobrahead graft.

Molecular analysis of alterations of the p18INK4c gene in human meningiomas.

Meningiomas are common primary brain tumours frequently presenting with deleted and/or mutated NF2 gene located on 22q.1p has been reported as the second most commonly deleted chromosomal region in these neoplasms. A new member of the INK4 family of CDK inhibitors, the p18INK4c gene, has recently been mapped to this chromosomal arm. By virtue of its structural and functional similarities with the p16 gene, p18 has been implicated as a tumour suppressor gene in a variety of cancers. In this paper 40 human meningiomas were analysed for loss of heterozygosity (LOH) at the p18 locus, mutations and inactivating methylation of the p18 gene. LOH at D1S193, D1S463 and D1S211 microsatellite marker loci mapped to 1p32 was detected in 13 of 35 (37%), four of 20 (20%), and six of 24 (25%) tumour samples, respectively. One sample presented with homozygous deletion at D1S193. Mutational analysis using single stranded conformational polymorphism (SSCP) and direct sequencing did not detect any missense mutation but revealed a novel silent mutation, G to T, at coding nucleotide 435. Analysis of HgaI, BsaHI, ScrFI and Eco0109I restriction sites of p18 exon 1 revealed absence of inactivating methylation. Immunohistochemistry with p18 monoclonal antibody detected presence of cytoplasmic p18 staining in 21 of 22 examined samples. One sample did not stain and was shown to carry homozygous deletion at D1S193. Despite the high frequency of LOH at 1p32 microsatellite markers, the lack of genetic and epigenetic aberrations in the p18 gene together with the presence of p18 protein in all but one meningioma samples argues against the role of p18 as a tumour suppressor gene important for meningioma development.

Spontaneous thrombosis of vein of Galen aneurysmal malformation.

Two cases of aneurysmal malformations of the vein of Galen (AVG) with spontaneous thrombosis are reported. Angiogram and MRI before thrombosis demonstrated AVGs with slow arteriovenous shunts and associated stagnation of contrast in the venous sac secondary to severe outflow restriction. Based on these findings, one patient was managed conservatively, and the other underwent placement of a ventriculoperitoneal shunt. Surveillance of the lesions with subsequent MRIs revealed spontaneous thrombosis of the AVGs with excellent clinical outcomes. Proposed mechanisms of spontaneous thrombosis include slow flow shunts, obstruction of the venous outflow or obstruction of the feeding artery. Similar cases in the literature are reviewed with special emphasis on diagnostic tests, symptomatology, mechanisms of thrombosis and therapeutic options.

Idiopathic pinealitis. Case report.

This 63-year-old man presented with complaints of "having a feeling of falling backward" over a 3-month period. Results of his general physical examination, laboratory studies, and neurological examination were unremarkable. A magnetic resonance image revealed a 1.8 x 1.4 x 1.2-cm enhancing mass in the posterior third ventricle just above the corpora quadrigemina. The pineal gland was found to be diffusely enlarged at operation and separable from the posterior thalamus and was totally resected. The patient had an uneventful postoperative course but continues to be somewhat confused. The lesion consisted of a remarkable chronic inflammatory cell infiltrate permeating the pineal lobules and was composed of T and B lymphocytes, macrophages, eosinophils, and mast cells. Immunoperoxidase studies did not demonstrate Langerhans cells, and a search for microorganisms was unrevealing. There was no evidence of neoplasia; results of immunostaining for germ cell markers and other tumor-associated antigens were negative.

Apical hypokinesis in a patient with hypertrophic cardiomyopathy and myocardial bridging: reversal with beta-blockade--a case report.

A 42-year-old man presented with effort angina pectoris of 20 minutes' duration. Hypertrophic obstructive cardiomyopathy, severe myocardial bridging involving the midleft anterior descending coronary artery, and apical hypokinesis were identified. Regional wall motion normalized following the initiation of beta blockade.