Steven S. Glazier

Angiotensin-Converting Enzyme Expression in Human Carotid Artery Atherosclerosis

Angiotensin-converting enzyme (ACE) inhibitors reduce the progression of atherosclerosis in animal models and reinfarction rates after myocardial infarction in humans. Although expression of components of the renin-angiotensin system has been reported in human coronary arteries, no data regarding their presence in carotid arteries, a frequent site for the occurrence of atherosclerosis plaques, are available. The following study sought to determine whether ACE mRNA and protein can be detected in human carotid atheromatous lesions. Twenty-four intact endarterectomy specimens were obtained from patients with severe carotid occlusive disease (17 males and 7 females, aged 68+/-1 years) and fixed within 30 minutes. Carotid artery specimens contained advanced Stary type V and VI lesions, and human ACE mRNA expression and protein were localized in cross sections by the combination of in situ hybridization and immunohistochemistry. Cell type-specific antibodies were used to colocalize ACE to smooth muscle cells, endothelial cells, macrophages, or lymphocytes. ACE protein was localized in the intima, whereas the overlying media was largely free of ACE staining. In less complicated lesions, ACE staining was modest and could be visualized in scattered clusters of macrophages and on the luminal side of carotid artery vascular endothelium. Smooth muscle cells were largely negative. ACE staining increased as lesions became more complex and was most prominent in macrophage-rich regions. The shoulder regions of plaques contained numerous ACE-positive macrophage foam cells and lymphocytes. In these areas, microvessels were positive for endothelial cell and smooth muscle cell ACE expression. However, microvessels in plaques free of inflammatory cells were stained only faintly for ACE expression. Labeling for ACE mRNA mirrored the pattern of protein expression, localizing ACE mRNA to macrophages and microvessels within the intima. In conclusion, atherosclerosis alters carotid artery ACE production, increasing transcription and translation within regions of plaque inflammation. These data provide another important mechanism by which inflammation associated with increased ACE expression may contribute to the progression of atherosclerosis.

Rheolytic catheter and thrombolysis of dural venous sinus thrombosis: a case series.

OBJECTIVEThe high morbidity and mortality rates associated with dural sinus thrombosis may be heightened by a delay in diagnosis, which necessitates prompt and effective treatment. Traditional treatment consists of the initiation of systemic anticoagulation with heparin and, more recently, regional thrombolysis with direct endovascular infusion of thrombolytic agents. We report our experience in a series of five patients in whom we accomplished mechanical clot lysis with the combination of a rheolytic device and balloon catheters. METHODSFive patients with dural sinus thrombosis were treated with a combination of pharmacological and mechanical thrombolysis with the 5-French AngioJet rheolytic catheter (Possis Medical, Minneapolis, MN) and balloon catheters. The success of the procedure was determined by resolution of or improvement in the patient’s neurological examination results and imaging features. RESULTSAll five patients demonstrated immediate improvement as observed on imaging studies or in terms of neurological status. Three patients required more than one intervention, and all but one patient continued to improve after the final intervention. Two of the five patients continued to experience mild residual neurological deficits, and two patients experienced complete recovery. The fifth patient had a delayed recurrence of thrombosis that required multiple interventions, and the patient has significant neurological deficits. Navigation of the dural sinuses was possible in all patients with the use of a microcatheter and was possible to a variable degree with the rheolytic catheter. Known complications of the procedures included two pseudoaneurysms at the femoral puncture site. CONCLUSIONMechanical clot lysis is a powerful technique for immediate restoration of antegrade venous flow in dural sinus thrombosis. In most patients, the superior sagittal sinuses and contralateral transverse sinuses could be accessed with the 5-French rheolytic catheter.

Outcome analysis of our first 75 spring-assisted surgeries for scaphocephaly.

Background: Spring-assisted surgery (SAS) has demonstrated promising results for the treatment of sagittal craniosynostosis. The purpose of this study was to assess the outcomes of the first 75 cases compared with a prospectively collected group of patients treated with cranial expansion (cranial vault remodeling [CVR]). Methods: Seventy-five children with scaphocephaly have completed this institutional review board-approved study. Patients underwent cranial surgery with removal of a 1-cm strip of sagittal suture and insertion of a mean of 2 spring distractors. Clinical outcome assessment included analysis of changes in cephalic index, shape, and volume on three-dimensional laser scans for both the SAS and the CVR treatments. Perioperative variables for both techniques were also compared. Results: All patients successfully underwent SAS without significant complications with a mean follow-up of 46 months. Perioperative variables including odds ratio, time, blood loss, transfusion requirements, intensive care unit and hospital stay lengths, and hospital costs differed significantly in favor of SAS. The mean cephalic index improved from 69 preoperatively to 75.4 after SAS, comparable with the change from 66 to 72.5 for CVR. This correction was maintained at 3- and 5-year follow-ups. Anterior frontal bossing was corrected on three-dimensional scan volume measurements. Conclusions: Spring-assisted surgery is a safe, effective, minimally invasive treatment of scaphocephaly. It combines the low morbidity and the operative time of a strip craniectomy with dynamic reshaping techniques while the implanted spring gradually distracts the skull, improving head shape. Our 7 years of experience has shown that SAS effectively corrected cranial shape including frontal bossing with maintained results over time.

Editing status at the Q/r site of the Glur2 and Glur6 glutamate receptor subunits in the surgically excised hippocampus of patients with refractory epilepsy

THE editing status of mRNA at the Q/R site of the glutamate receptor subunits GluR2 and GluR6 modulates channel conductivity and ion selectivity of ionotropic AMPA/KA receptors. Alteration of the editing process may be involved in the debilitating effects of epilepsy. The ratio of unedited/edited (Q/R) forms of GluR2 and GluR6 subunits was examined in conjunction with the expression of two double-standard RNA-specific adenosine deaminases (DRADA) in surgically excised hippocampus from patients with refractory epilepsy compared with that of control samples. In the majority of patients with long histories of epilepsy, the GluR2 transcript was detected in the completely edited form, however, in two (out of 16 tested) hippocampal samples of young subjects (2 and 10 years old) we were able to identify the unedited transcript of GluR2 subunit. The proportion of unedited fraction of GluR6(Q) subunit was decreased to 9% compared to control human hippocampus. We conclude that the editing process in epileptic specimens is selectively affected by seizure activity in the epileptic focus.

Changes in glutamate receptor subunit composition in hippocampus and cortex in patients with refractory epilepsy

An assessment of glutamate receptor subunit profiles was made in hippocampus and temporal lobe cortex of patients with refractory epilepsy. Molecular biological analyses using reverse transcription reaction (RT) followed by polymerase chain reaction (PCR) revealed changes in the distribution profile of the transcripts of AMPA/KA glutamate receptor subunits in hippocampal and cortical tissue from patients with refractory epilepsy when compared to similar tissue from six human and four non-human primate samples with no history of seizures or seizure medication. A severe mean decrease (38% of control) in mRNA for the GluR1 subunit was found in 400 mm cross-sections of hippocampus from patients with epilepsy. Less severe but significant reductions in that GluR1 subunit expression (54% of control) were exhibited in samples of excised temporal pole cortex from the same subjects. Message for the GluR4 subunit was also significantly decreased in hippocampus (68% of control), but in contrast to GluR1, GluR4 mRNA level was not decreased in temporal cortex. Levels of GluR2 mRNA were not significantly changed in epileptic hippocampal and cortical tissue relative to control samples. Protein levels of the GluR1 and GluR4 subunits quantified by Western blot analysis were also reduced in hippocampal and cortical tissue from epilepsy patients. Two other kainate subunit transcripts, GluR6 and KA1 also showed significant changes compared to non-epileptic tissue (136% and 71% of control, respectively). Results are discussed in terms of possible mechanisms by which protracted seizures could produce selective loss of certain AMPA/KA subunits.

Surgical advancement influences perioperative care: A comparison of two surgical techniques for sagittal craniosynostosis repair

Methods for surgical correction of sagittal craniosynostosis have progressed. The hypothesis is that advances in surgical interventions for craniosynostosis affect perioperative anesthetic care. We reviewed the records of eight children who underwent cranial vault reconstruction (CVR) and nine who underwent spring-mediated cranial expansion (SME) for sagittal craniosynostosis. We compared the data from the CVR procedure to data from the combined procedures for SME (insertion and removal of springs). Anesthesia times were similar between the CVR (4 h 24 min) and the combined SME (4 h 27 min) groups, whereas surgical times were different between the CVR (3 h 25 min) and combined SME groups (2 h 21 min) (P = 0.002). Length of stay was 4.1 days for the CVR group (confidence interval [CI], 3.8–4.4 days) versus 3.1 days (CI, 2.9–3.4 days) in the combined SME group (P = 0.0001). Blood loss was significantly less in the combined SME group at 48 mL (CI, 29–83 mL) compared with the CVR group at 291 mL (CI, 230–352 mL). All eight patients in the CVR group received blood with a mean of 1.4 U (range, 1–2 U). No SME patient received any blood products. The reduction in blood loss with this new surgical treatment is significant for the patient in reducing blood transfusion and for the anesthesiologist in reducing concerns of volume resuscitation.

Clinical Experience With Radiation Therapy in the Management of Neurofibromatosis-Associated Central Nervous System Tumors

PURPOSE Patients with neurofibromatosis (NF) develop tumors of the central nervous system (CNS). Radiation therapy (RT) is used to treat these lesions. To better define the efficacy of RT in these patients, we reviewed our 20-year experience. METHODS AND MATERIALS Eighteen patients with NF with CNS tumors were treated from 1986 to 2007. Median follow-up was 48 months. Progression was defined as growth or recurrence of an irradiated tumor on serial imaging. Progression-free survival (PFS) was measured from the date of RT completion to the date of last follow-up imaging study. Actuarial rates of overall survival (OS) and PFS were calculated according to the Kaplan-Meier method. RESULTS Eighty-two tumors in 18 patients were irradiated, with an average of five tumors/patient. Median age at treatment was 25 years (range, 4.3-64 years). Tumor types included acoustic neuroma (16%), ependymoma (6%), low-grade glioma (11%), meningioma (60%), and schwanomma/neurofibroma (7%). The most common indication for treatment was growth on serial imaging. Most patients (67%) received stereotactic radiosurgery (median dose, 1,200 cGy; range, 1,000-2,400 cGy). The OS rate at 5 years was 94%. Five-year PFS rates were 75% (acoustic neuroma), 100% (ependymoma), 75% (low-grade glioma), 86% (meningioma), and 100% (schwanomma/neurofibroma). Thirteen acoustic neuromas had a local control rate of 94% with a 50% hearing preservation rate. CONCLUSIONS RT provided local control, OS, and PFS rates similar to or better than published data for tumors in non-NF patients. Radiation therapy should be considered in NF patients with imaging progression of CNS tumors.

Successful treatment of ventriculostomy-related meningitis caused by vancomycin-resistant Enterococcus with intravenous and intraventricular quinupristin/dalfopristin.

We report a case of ventriculostomy-related meningitis caused by vancomycin-resistant Enterococcus faecium (VRE). The patient was successfully treated with administration of quinupristin/dalfopristin by both intravenous and intraventricular routes. A brief review of the literature is provided, which indicates that optimal management with quinupristin/dalfopristin should include daily intraventricular doses of at least 2 mg.

Transfusion-related acute lung injury in an infant during craniofacial surgery.

UNLABELLED Transfusion-related acute lung injury (TRALI) is a potentially life-threatening, systemic, immune-mediated reaction to transfused blood product. The symptoms may be masked under general anesthesia. In this case report, we describe an infant who developed TRALI under general anesthesia for craniofacial surgery. The difficulty with diagnosis, the pathophysiology, and the need for understanding and recognition to reduce morbidity and mortality are discussed. IMPLICATIONS Transfusion-related acute lung injury (TRALI) is a life-threatening problem that can occur during blood product transfusion in patients of any age. Understanding the pathophysiology may help make an earlier diagnosis to reduce more serious adverse outcomes.

Surgical management of foramina parietalia permagna.

Enlarged parietal foramina are rare congenital skull defects identified on physical examination and confirmed radiographically. They are round or oval defects situated on each parietal bone approximately 1 cm from the midline and 2 to 3 cm superior to the lambdoid suture. Although small parietal foramina are common variants in up to 60% to 70% of normal skulls, large parietal foramina ranging from 5 mm to multiple centimeters are less common, with a prevalence of 1:15,000 to 1:25,000. We present a case series of four patients with large persistent parietal foramina managed surgically for the correction of this deformity. Two infants were treated with autologous calvarial bone grafts, and two were treated with a mesh plating system and hydroxyapatite. No patient developed any perioperative complications. No perioperative or delayed infections occurred in our patient population. The mean postoperative follow-up was 36 months. One patient required a second procedure with methylmethacrylate because of late bone graft failure, whereas the others were successfully treated by the initial procedure. Foramina parietalia permagna, otherwise known as fenestrae parietals symmetricae, enlarged parietal foramina, giant parietal foramina, or Catlin marks, are a rare clinical entity. A spontaneous decrease in the size of these defects with growth of the infant has been reported, but this closure is usually incomplete. Surgical intervention of persistent large foramina protects the child against potential injury to the underlying brain. We advocate cranioplasty for active young children and those at risk for injury (i.e., seizure disorder) to decrease the risk for potential intracranial injury.