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.

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.

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.

Origin of angina pectoris in patients with high-grade single-vessel coronary artery stenosis undergoing percutaneous transluminal coronary angioplasty.

This study shows that in patients with subtotal (95% to 99%) coronary artery stenosis, the presence of myocardial ischemia is dictated primarily by the presence and degree of coronary collateral flow, with anterograde flow participating little, if at all, in the origin of myocardial ischemia and angina pectoris. Conversely, in patients with severe but not subtotal coronary artery stenosis (70% to 94%), both reduced anterograde flow and coronary collateralization contribute to the evolution of myocardial ischemia and angina pectoris.

Regional blood flow and water content of the obstructed small intestine.

The effects of small-bowel obstruction on the regional distribution of blood flow and water content were studied in a new chronic dog model. Nonstrangulative obstruction was induced 40 cm proximal to the canine ileocolic valve. Blood flow was measured with 15-micron microspheres and hemodynamic and respiratory values were recorded before (experimental phase I) and five days after (experimental phase II) the induction of the obstruction. Two separate control groups of dogs were studied: baseline controls and sham-operative groups (phases I and II). Hemodynamic and respiratory values were stable in both phases in all groups. A comparison of sham phase-II data with the experimental phase-II data in the 120-cm segment of bowel proximal to the site of obstruction showed an 85% increase in blood flow (range, 49% to 106%); for the 280 cm of bowel proximal to the site of obstruction, there was a 6% increase in water content (range, 5% to 9%), and a 39% decrease in dry bowel weight (range, 34% to 46%). These findings help illustrate the pathophysiologic characteristics of microvascular changes in bowel obstruction, which are likely to have particular clinical significance for patients with cardiopulmonary diseases.

Topical hypothermia: ineffective and deleterious as adjunct to cardioplegia for myocardial protection.

BACKGROUND: Topical hypothermia, an early method developed for myocardial protection by virtue of its reduction of cardiac metabolic rate, is not without sequelae such as phrenic nerve paralysis and pulmonary complications. METHODS: The hospital records of 505 nonrandomized consecutive patients undergoing coronary artery bypass grafting between 1991 and 1995 at the University of South Alabama were reviewed to evaluate the effectiveness of topical hypothermia and its relationship to pulmonary complications. Group A included 191 patients between 1991 and 1992 who received systemic hypothermia and topical hypothermia with iced slush in addition to cold blood cardioplegia. Group B included 314 patients between 1993 and 1995 who received systemic hypothermia and intermittent cold blood cardioplegia without iced slush. RESULTS: Myocardial temperature mapping did not reveal any difference between the two groups. Postoperative cardiac morbidity, manifested as intraaortic balloon use, low cardiac output, inotrope use, and perioperative myocardial infarction, was decreased in group B, but the difference failed to achieve statistical significance. Mortality (group A, 3.14%; group B, 3.82%) and rates of significant morbidity such as sternal infection, stroke, reoperation for bleeding, renal failure, and prolonged ventilation were comparable between the two groups. However, there was a statistically significant difference in the incidence of diaphragmatic paralysis between group A and group B. Group A had a 25% incidence of diaphragmatic paralysis on the first postoperative day, 18% on the 15th postoperative day, and 8% at 6 months, as opposed to group B, which had incidences of 2% on the first postoperative day, 1% on the 15th postoperative day, and 1% at 6 months (p < 0.001). Also, there was a significant difference in incidence of pleural effusions (60% versus 25%) and rate of thoracentesis (25% versus 8%) between groups A and B (p < 0.0001). CONCLUSIONS: We conclude that topical hypothermia did not offer any additional cardioprotective benefit above systemic hypothermia and cold blood cardioplegia alone in coronary bypass patients, but significantly increased the incidence of diaphragmatic paralysis and associated pulmonary complications.

"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.

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.

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.

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.

In vivo 1H MRS choline: correlation with in vitro chemistry/histology.

We correlated the in vivo 1H Magnetic Resonance Spectroscopy (MRS) concentration of the choline peak (CHO) with in vitro chemical measures of choline-containing compounds and a histological grade of cellularity in 18 patients with neoplastic and infectious brain lesions. Gas-chromatography-mass-spectrometry (GCMS) was used to measure the concentrations of free choline (Cho), glycerophosphocholine (GPCho), phosphocholine (PCho) and phosphatidylcholine (PtdCho) from biopsies in the same area where MRS was performed. Cellular density, free Cho, PCho and GPCho were the strongest determinants of 1H MRS CHO while PtdCho was not. Just as the 1H MRS 2.0 peak reflects both the concentration of n-acetyl-l-aspartate and neuronal density, the 1H MRS 3.2 peak reflects the concentration of water-soluble choline-containing compounds and cellular density.

Valve replacement for regurgitant lesions of the aortic or mitral valve in advanced left ventricular dysfunction.

Patients with aortic regurgitation and severe left ventricular dysfunction remain candidates for aortic valve replacement, as long as the risks of late left ventricular dysfunction and congestive heart failure have been fully discussed with the patient, the patient's family, and the referring physician. In contrast, patients with mitral regurgitation and severe systolic dysfunction are at considerable risk of more severe left ventricular dysfunction after operation, especially if mitral valve repair or chordal-sparing procedure cannot be performed. In patients who are candidates for such procedures that preserve the integrity of the subvalvular mitral apparatus, operation may be successful in selected patients despite moderate-to-severe depression of systolic function. Prognosis is guarded to poor in patients with regurgitant valvular lesions and advanced left ventricular dysfunction, and the emerging alternative treatments discussed in other articles in this Cardiology Clinics deserve consideration in these patients.

In vivo proton spectroscopy of intracranial infections and neoplasms.

The chemical characteristics of 10 neoplastic and 11 infectious brain masses were studied by in vivo 1H magnetic resonance spectroscopy. In tumors, peak height ratios of n-acetyl-L-aspartate to choline were decreased compared to those in normal brain tissue and infectious masses (p < 0.02), but the ratios in normal brains and those with infections did not differ. N-acetyl-L-aspartate-to-creatine/phosphocreatine ratios were significantly lower in infectious masses and tumors compared to normal brain tissue (p = 0.003). However, in progressive multifocal leukoencephalopathy, N-acetyl-L-aspartate appeared relatively unchanged. Lactate was greater than choline in 9 of 11 brains with infection, 0 of 14 control brains, and 1 of 10 tumors. Lactate-to-choline ratios were significantly elevated in infectious masses compared with tumors (p < 0.01). 1H magnetic resonance spectroscopy is promising for the noninvasive diagnosis of focal brain masses.

Analysis of brain tumors using 1H magnetic resonance spectroscopy.

BACKGROUND: Magnetic resonance imaging (MRI) is superior in delineating anatomic and pathologic information and has subsequently been married to the ability of magnetic resonance spectroscopy (MRS) to provide insight into the biochemical changes underlying pathology. Proton magnetic resonance spectroscopy (1H MRS) allows the non-invasive in vivo collection and measurement of chemical information from a selected volume of tissue (voxel). METHODS: We conducted a prospective trial in 23 patients with brain mass lesions and 16 normal subjects using proton magnetic resonance spectroscopy (1H MRS). The spectra were analyzed for N-acetyl-aspartate (NAA), choline compounds (Cho), creatine (Cr), and lactate (Lac). The ratios of the compounds in tumors were compared to normals. RESULTS: The tumors showed significant decreases in the mean peak height ratios of NAA/Cho, NAA/Cr, and significant increases in Cho/Cr when compared to tissue from normal subjects. Cho was elevated in all of the meningiomas and gliomas. In benign tumors, Cho was usually elevated while in metastases Cho was often normal or decreased. The four metastatic tumors showed NAA/Cho, NAA/Cr, and Cho/Cr that were similar to controls. Lac varied with tumor type and was elevated in many malignant primary brain tumors. CONCLUSIONS: 1H MRS is a powerful tool for safe, noninvasive analysis of tissue chemistry in vivo. Analysis of intracranial tumors reveals significant trends that might eventually be used in the classification of tumor histology and evaluation of the efficacy of tumor treatment.

Neurosurgical considerations in supratentorial low-grade gliomas: experience with 175 patients.

The authors reviewed 175 low-grade hemispheric gliomas surgically treated by one surgeon (P.B.) between 1987 and 1996: 74 astrocytomas (42%), 35 oligodendrogliomas (20%), 52 mixed gliomas (30%), 12 gangliogliomas (7%), and two ependymomas (1%). Patient age ranged from 7.5 to 81.9 years (mean 39.2 years); 84 patients (48%) were males and 91 (52%) females. Postsurgical follow-up review ranged from 0.1 to 225.2 months (mean 36.2 months, median 24.9 months). Either T(2)-weighted or contrast-enhanced T(1)-weighted magnetic resonance (MR) images were used to evaluate the percentage of resection achieved and volume of residual disease postoperatively. The majority of patients (55%) had seizures as the presenting symptom, and 45% experienced preoperative symptoms for more than 12 months. Tumor enhancement was present in 21% of cases. In 66% of surgical procedures at least one of the following technical adjuncts was used: monitored local anesthesia, real-time MR imaging, stereotactic guidance with computerized tomography, three dimensional reconstruction, cortical mapping with cortical stimulation, somatosensory or visual evoked potential recording, corticography, or intraoperative ultrasound. Intraoperative MR imaging was used for 40 (22.9%) of the craniotomies and nine (5.14%) biopsies. There were no surgery-related deaths. Complications appeared in 6% of the patients. Progression to a higher-grade tumor occurred in 9.2% of patients within the 3-year follow-up period.

Effects of conversation on intracranial pressure in comatose patients.

In this time series design study we investigated the effects of conversation on intracranial pressure (ICP). Two conversation types were used, and continuous measurements of ICP were recorded. Type 1 conversation was an emotionally referenced conversation that reflected an actual nursing report on the patient's current condition. Type 2 conversation was a predetermined dialogue unrelated to the patient. Two hypotheses were tested to determine the existence of differences between the ICP measurements at baseline and the ICP measurements during any conversation, and differences between the ICP measurements recorded during type 1 conversation and during type 2 conversation. Eight subjects served as their own control. T tests were performed between the mean scores of the minimum, maximum, and average ICP measurements before, during, and after both conversations. The hypotheses were not supported by the findings. There was, however, a statistically significant decrease in ICP when minimum ICP measurements before type 2 conversations were compared with measurements recorded during type 2 conversation. The data also demonstrated a wide variation of individual patient responses. The results of the current study suggest that the direction of influence from conversation on the ICP is individual and may be influenced greatly by the patient's level of consciousness.

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.

Symptomatic reinfarctation of a previously silent myocardial region four months after successful reperfusion--a case report.

Coronary collateral circulation helps to preserve myocardial perfusion distal to severely stenotic or totally obstructed coronary arteries. The presence or absence of angina pectoris and the state of myocardial function depend on the extent of collateralization and its functional contribution to myocardial blood flow. Clinical and experimental observations have suggested that newly developed collaterals usually remain even after successful revascularizaton. The authors present a case of a patient with extensive intercoronary collaterals and hibernating myocardium after an acute inferior wall myocardial infarction who underwent successful percutaneous transluminal coronary angioplasty of a totally obstructed, dominant right coronary artery and then experienced extensive reinfarction following reocclusion 4 months later. This case demonstrates failure of extensive collaterals to prevent acute myocardial infarction.

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.

Resuscitation of patients with central nervous system trauma.

The care patients with spinal cord or head injury receive in the acute phase of their injury is critical to outcome. The basics of trauma care are of primary importance to the patient with central nervous system trauma. In the SCI patient, extreme care must be used in establishing an airway. The focus in the head-injured patient is to provide adequate oxygenation and ventilation sufficient to cause hypocarbia. Proper immobilization of the neck is a priority concomitant to establishing an airway in the SCI patient, while control of ICP is a challenge in the head-injured patient. Paramedics, nurses, and physicians who are aware of these important factors in caring for the neurotrauma patient will ensure the patient every chance of functional recovery.