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Purpose To report 36-month outcomes of RIDE (NCT00473382) and RISE (NCT00473330), trials of ranibizumab in diabetic macular edema (DME). Design Phase III, randomized, multicenter, double-masked, 3-year trials, sham injection–controlled for 2 years. Participants Adults with DME (n=759), baseline best-corrected visual acuity (BCVA) 20/40 to 20/320 Snellen equivalent, and central foveal thickness (CFT) ≥275 μm on optical coherence tomography. Methods Patients were randomized equally (1 eye per patient) to monthly 0.5 mg or 0.3 mg ranibizumab or sham injection. In the third year, sham patients, while still masked, were eligible to cross over to monthly 0.5 mg ranibizumab. Macular laser was available to all patients starting at month 3; panretinal laser was available as necessary. Main Outcome Measures The proportion of patients gaining ≥15 Early Treatment Diabetic Retinopathy Study letters in BCVA from baseline at month 24. Results Visual acuity (VA) outcomes seen at month 24 in ranibizumab groups were consistent through month 36; the proportions of patients who gained ≥15 letters from baseline at month 36 in the sham/0.5 mg, 0.3 mg, and 0.5 mg ranibizumab groups were 19.2%, 36.8%, and 40.2%, respectively, in RIDE and 22.0%, 51.2%, and 41.6%, respectively, in RISE. In the ranibizumab arms, reductions in CFT seen at 24 months were, on average, sustained through month 36. After crossover to 1 year of treatment with ranibizumab, average VA gains in the sham/0.5 mg group were lower compared with gains seen in the ranibizumab patients after 1 year of treatment (2.8 vs. 10.6 and 11.1 letters). Per-injection rates of endophthalmitis remained low over time (∼0.06% per injection). The incidence of serious adverse events potentially related to systemic vascular endothelial growth factor inhibition was 19.7% in patients who received 0.5 mg ranibizumab compared with 16.8% in the 0.3 mg group. Conclusions The strong VA gains and improvement in retinal anatomy achieved with ranibizumab at month 24 were sustained through month 36. Delayed treatment in patients receiving sham treatment did not seem to result in the same extent of VA improvement observed in patients originally randomized to ranibizumab. Ocular and systemic safety was generally consistent with the results seen at month 24. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

The photochemical decolorization and mineralization of Reactive red 241 (RR241) in aqueous solution has been studied using a homogeneous photofenton process and its combination with activated charcoal and titanium dioxide. The effects of applied catalyst and adsorbent loading, dye concentrations, pH of solution, and the effect of various systems at constant UV irradiation were determined. Decolorization, COD and TOC analysis were employed to evaluate the results of the photochemical and photocatalytic degradation of RR241. The degradation of the dye was monitored by constant COD analysis and then analyzed by high performance liquid chromatography (HPLC) and IR analysis. The result shows that complete decolorization of dye with photofenton process required 240 minutes with 18.6% of maximum TOC reduction. To overcome the problem of slow decolorization and low degradation with photofenton process, it was combines with activated charcoal and Titanium dioxide. UV/Fenton/AC process gave complete decolorization ...

Experimental densities, dynamic viscosities, speeds of sound and relative permittivities for ten binary mixtures of methyl acetate +, ethyl acetate +, butyl acetate +, isoamyl acetate +, methyl propionate +, ethyl propionate +, ethyl butyrate +, methyl methacrylate +, ethyl methacrylate +, and butyl methacrylate + cyclohexane at T = 298.15 and 303.15 K have been measured. Applicability of Grunberg–Nissan, McAllister and Auslander equations was tested for correlating viscosity of mixtures. The suitability of free length and collision factor theories, and Nomoto and Junjie equations for predicting the speeds of sound in binary mixtures have been explored. Excess molar volumes, excess isentropic compressibilities, excess viscosities, relative permittivity and molar polarization deviations have been calculated and their compositional variation has been mathematically expressed by Redlich–Kister equation. The analysis of excess and deviation functions has been done to ascertain the predominant type of interactions in the bulk state of mixtures.

Glioblastoma, the most lethal brain tumor, remains incurable despite aggressive chemotherapy and surgical interventions. New chemotherapeutics for glioblastoma have been explored in preclinical models and some agents have reached the clinical setting. However, success rates are not significant. Previous investigations involving diallyl trisulfide (DATS), a garlic compound, indicated significant anti-cancer effects in glioblastoma in vitro. DATS has also been shown to inhibit histone deacetylase activity and impede glioblastoma tumor progression. We hypothesized that DATS would block ectopic U87MG tumor by multiple pro-apoptotic pathways via inhibiting histone deacetylase (HDAC). To prove this, we developed ectopic U87MG tumors in SCID mice and treated them daily with intraperitoneal injections of DATS for 7 days. Results indicated that DATS (10 μg/kg-10 mg/kg) dose-dependently reduced tumor mass and number of mitotic cells within tumors. Histological and biochemical assays demonstrated that DATS reduced mitosis in tumors, decreased HDAC activity, increased acetylation of H3 and H4, inhibited cell cycle progression, decreased pro-tumor markers (e.g., survivin, Bcl-2, c-Myc, mTOR, EGFR, VEGF), promoted apoptotic factors (e.g., bax, mcalpian, active caspase-3), and induced DNA fragmentation. Our data also demonstrated an increase in p21Waf1 expression, which correlated with increased p53 expression and MDM2 degradation following DATS treatment. Finally, histological assessment and enzyme assays showed that even the highest dose of DATS did not negatively impact hepatic function. Collectively, our results clearly demonstrated that DATS could be an effective therapeutic agent in preventing tumor progression and inducing apoptosis in human glioblastoma in vivo, without impairing hepatic function.

Glioblastoma is the most common aggressive, highly glycolytic, and lethal brain tumor. In fact, it is among the most commonly diagnosed lethal malignancies, with thousands of new cases reported in the United States each year. Glioblastoma's lethality is derived from a number of factors including highly active pro-mitotic and pro-metastatic pathways. Two factors increasingly associated with the intracellular signaling and transcriptional machinery required for such changes are anaplastic lymphoma kinase (ALK) and the hepatocyte growth factor receptor (HGFR or, more commonly MET). Both receptors are members of the receptor tyrosine kinase (RTK) family, which has itself gained much attention for its role in modulating mitosis, migration, and survival in cancer cells. ALK was first described as a vital oncogene in lymphoma studies, but it has since been connected to many carcinomas, including non-small cell lung cancer and glioblastoma. As the receptor for HGF, MET has also been highly characterized and regulates numerous developmental and wound healing events which, when upregulated in cancer, can promote tumor progression. The wealth of information gathered over the last 30 years regarding these RTKs suggests three downstream cascades that depend upon activation of STAT3, Ras, and AKT. This review outlines the significance of ALK and MET as they relate to glioblastoma, explores the significance of STAT3, Ras, and AKT downstream of ALK/MET, and touches on the potential for new chemotherapeutics targeting ALK and MET to improve glioblastoma patient prognosis.

Item does not contain fulltext The Ehlers-Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue disorders characterized by joint hypermobility, skin extensibility, and tissue fragility. This communication briefly reports upon the neurological manifestations that arise including the weakness of the ligaments of the craniocervical junction and spine, early disc degeneration, and the weakness of the epineurium and perineurium surrounding peripheral nerves. Entrapment, deformation, and biophysical deformative stresses exerted upon the nervous system may alter gene expression, neuronal function and phenotypic expression. This report also discusses increased prevalence of migraine, idiopathic intracranial hypertension, Tarlov cysts, tethered cord syndrome, and dystonia, where associations with EDS have been anecdotally reported, but where epidemiological evidence is not yet available. Chiari Malformation Type I (CMI) has been reported to be a comorbid condition to EDS, and may be complicated by craniocervical instability or basilar invagination. Motor delay, headache, and quadriparesis have been attributed to ligamentous laxity and instability at the atlanto-occipital and atlantoaxial joints, which may complicate all forms of EDS. Discopathy and early degenerative spondylotic disease manifest by spinal segmental instability and kyphosis, rendering EDS patients prone to mechanical pain, and myelopathy. Musculoskeletal pain starts early, is chronic and debilitating, and the neuromuscular disease of EDS manifests symptomatically with weakness, myalgia, easy fatigability, limited walking, reduction of vibration sense, and mild impairment of mobility and daily activities. Consensus criteria and clinical practice guidelines, based upon stronger epidemiological and pathophysiological evidence, are needed to refine diagnosis and treatment of the various neurological and spinal manifestations of EDS. (c) 2017 Wiley Periodicals, Inc.

Clinical trials have established surgical resection and adjuvant chemotherapy (ACT) as the standard management for stage III colon cancer; however, the extent to which these results apply to elderly patients in routine practice is unclear. This article describes the management and outcomes of elderly patients with stage III colon cancer.All cases of surgically resected colon cancer from 2002 to 2008 were identified with the population-based Ontario Cancer Registry. Pathology reports were obtained for a random sample (25% of all cases); those with stage III disease constituted the study population. The utilization of ACT, cancer-specific survival (CSS), and overall survival (OS) in elderly patients (≥70 years) and nonelderly patients (70 years) were compared.The study population included 2920 patients, and 1521 (52%) were elderly. The 30- and 90-day mortality rates increased with advanced age:70 years, 2% and 5%; 70 to 74 years, 3% and 7%; 75 to 79 years, 5% and 8%, and ≥80 years, 9% and 16% (P.001). ACT was delivered to 48% of elderly patients and to 81% of younger patients (P.001). Factors independently associated with ACT utilization among the elderly were a younger age (P.001), male sex (P = .041), and no comorbidities (P = .001). Among elderly patients, ACT was associated with improved CSS (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.60-0.88) and OS (HR, 0.71; 95% CI, 0.60-0.83); however, the magnitude of the benefit was smaller for elderly patients than younger patients (HR for CSS, 0.53; 95% CI, 0.42-0.67; HR for OS 0.56; 95% CI, 0.45-0.69).Half of elderly patients with stage III colon cancer do not receive ACT. Although the effect size is smaller than that in younger patients, ACT is associated with improved long-term survival. Cancer 2017;123:2840-49. © 2017 American Cancer Society.

Immunotherapy can be an effective treatment for pediatric medulloblastoma (MB) patients. However, major subpopulations do not respond to immunotherapy, due to the lack of antigenic mutations or the immune-evasive properties of MB cells. Clinical observations suggest that radiation therapy (RT) may expand the therapeutic reach of immunotherapy. The aim of the present investigation is to study the effect of low-dose X-ray radiation (LDXR, 1 Gy) on the functional immunological responses of MB cells (DAOY, D283, and D341). Induction of MB cell death was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Production of reactive oxygen species (ROS) was measured by fluorescent probes. Changes in the expression of human leukocyte antigen (HLA) molecules and caspase-3 activities during treatment were analyzed using Western blotting and caspase-3 assay. Western blot analysis demonstrated that LDXR upregulated the expression of HLA class I and HLA II molecules by more than 20% compared with control and high-dose (12 Gy) groups in vitro. Several of these HLA subtypes, such as MAGE C1, CD137, and ICAM-1, have demonstrated upregulation. In addition, LDXR increases ROS production in association with phosphorylation of NF-κB and cell surface expression of mAb target molecules (HER2 and VEGF). These data suggest that a combined LDXR and mAb therapy can create a synergistic effect in vitro. These results suggest that LDXR modulates HLA molecules, leading to alterations in T-cell/tumor-cell interaction and enhancement of T-cell-mediated MB cell death. Also, low-dose radiotherapy combined with monoclonal antibody therapy may one day augment the standard treatment for MB, but more investigation is needed to prove its utility as a new therapeutic combination for MB patients.

The hybrid of Particle Swarm Optimization (PSO) and Gravitational Search Algorithm (GSA) is a population-based algorithm known as PSOGSA. This technique incorporates the ability of exploitation in PSO with the ability of exploration in GSA to synthesize both strength. Synthetic MT data are used to optimized with this hybrid algorithm for obtaining the best solution. The results show that hybrid algorithm possesses a better capability to escape from local optimums with faster convergence than the PSO and GSA. Initially, the PSOGSA is demonstrated on synthetic 1-D MT data generated by the forward modelling. This algorithm is also tested on synthetic 1-D MT incorporated with 10% and 20% random noise and finally applied to field data obtained from Puga geothermal field in NW Himalaya, Ladakh district, Jammu and Kashmir, India. The analyzed results confirm the presence of a shallow conductive region in the area that is well correlated with available results.

BACKGROUND Balancing the demands of a busy medical career with personal wellness can be daunting, and there is little education on these principles available to physicians in training. OBJECTIVE To implement a voluntary wellness initiative in our neurosurgery department to promote healthy lifestyle choices. This report details the baseline data collected as part of this quality improvement initiative. METHODS The wellness initiative was implemented in July 2015 and available to all faculty and resident physicians in the Department of Neurological Surgery in collaboration with the Medical University of South Carolina Wellness Center. All participants were provided a Fitbit Surge HR wrist monitor (Fitbit, Boston, Massachusetts) and underwent baseline physical and psychological testing. RESULTS Six faculty physicians and 9 residents participated. Overall physical fitness levels varied widely between subjects. Health screening demonstrated abnormalities in 80% of participants (elevated systolic blood pressure in 60%, elevated diastolic in 47%, elevated serum low-density lipoprotein in 53%). Body composition analysis demonstrated body weight higher than ideal in 69% (47% overweight; 13% obese). Recommended average body fat mass reduction was 25.4 pounds. Seventy-nine percent reported below-average quality of life compared with the average healthy adult. All subjects reported wanting more time for personal health. CONCLUSION Baseline health and psychological screenings in our department demonstrated alarmingly prevalent, previously undiagnosed abnormalities on cardiovascular and body weight screenings. Obstacles to leading a healthier lifestyle have been identified and solutions have been incorporated into the program. This quality improvement initiative may serve as a template for other programs seeking to improve physician physical and mental well-being. ABBREVIATIONS BMI, body mass indexESS, Epworth Sleepiness ScaleHR, heart rate.

OBJECTIVES: To assess the extent to which funding and study design are associated with high reprint orders. DESIGN: Case-control study. SETTING: Top articles by size of reprint orders in seven journals, 2002-09. PARTICIPANTS: Lancet, Lancet Neurology, Lancet Oncology (Lancet Group), BMJ, Gut, Heart, and Journal of Neurology, Neurosurgery and Psychiatry (BMJ Group) matched to contemporaneous articles not in the list of high reprint orders. MAIN OUTCOME MEASURES: Funding and design of randomised controlled trials or other study designs. RESULTS: Median reprint orders for the seven journals ranged from 3000 to 126,350. Papers with high reprint orders were more likely to be funded by the pharmaceutical industry than were control papers (industry funding versus other or none: odds ratio 8.64, 95% confidence interval 5.09 to 14.68, and mixed funding versus other or none: 3.72, 2.43 to 5.70). CONCLUSIONS: Funding by the pharmaceutical industry is associated with high numbers of reprint orders.

Achieving a pathologic complete response (pCR) after neoadjuvant therapy has been associated with better prognosis in rectal cancer patients. The objective of this study was to investigate the relationship between distance to the anal verge (DTAV) and pCR.Review of a prospectively maintained database of patients with locally advanced rectal cancer who received neoadjuvant treatment was completed. Uni- and multivariate analysis assessed the association between DTAV and pCR after neoadjuvant therapy.Of 827 included patients, 20% had a pCR. We found that pCR rates were 11% for tumors4 cm, 24% for tumors 4-6 cm, 30% for tumors at 6-8 cm, 17% for tumors 8-10 cm, and 14% for tumors10 cm from the anal verge (P = 0.002). Multivariate analysis also showed a strong association between DTAV and pCR (P = 0.008). The bimodal distribution of pCR resulted in a lower odds ratio of pCR for tumors4 and8 cm from the anal verge.Patients with low tumors (4 cm) and higher tumors (8 cm), were less likely to have a pCR. Further investigation is warranted to determine if these observations are related to tumor biology or possibly differences in radiation technique. J. Surg. Oncol. 2016;114:637-641. © 2016 Wiley Periodicals, Inc.

Object Pulsatile arterial compression (AC) of the ventrolateral medulla (VLM) is hypothesized to produce the hypertension in a subset of patients with essential hypertension. In animals, a network of subpial neuronal aggregates in the VLM has been shown to control cardiovascular functions. Although histochemically similar, neurons have been identified in the retro-olivary sulcus (ROS) of the human VLM, but their function is unclear. Methods The authors recorded cardiovascular responses to electrical stimulation at various locations along the VLM surface, including the ROS, in patients who were undergoing posterior fossa surgery for trigeminal neuralgia. This vasomotor mapping of the medullary surface was performed using a bipolar electrode, with stimulation parameters ranging from 5- to 30-second trains (20–100 Hz), constant current (1.5–5 mA), and 0.1-msec pulse durations. Heart rate (HR) and blood pressure (BP) were recorded continuously from baseline (10 seconds before the stimulus) up to 1 minute poststimulus. In 6 patients, 17 stimulation responses in BP and HR were recorded. Results The frequency threshold for any cardiovascular response was 20 Hz; the stimulation intensity threshold ranged from 1.5 to 3 mA. In the first patient, all stimulation responses were significantly different from sham recordings (which consisted of electrodes placed without stimulations). Repeated stimulations in the lower ROS produced similar responses in 3 other patients. Two additional patients had similar responses to single stimulations in the lower ROS. Olive stimulation produced no response (control). Hypotensive and/or bradycardic responses were consistently followed by a reflex hypertensive response. Slight right/left differences were noted. No patient suffered short- or long-term effects from this stimulation. Conclusions This stimulation technique for vasomotor mapping of the human VLM was safe and reproducible. Neuronal aggregates near the surface of the human ROS may be important in cardiovascular regulation. This method of vasomotor mapping with measures of responses in sympathetic tone (microneurography) should yield additional data for understanding the neuronal network that controls cardiovascular functions in the human VLM. Further studies in which a concentric bipolar electrode is used to generate this type of vasomotor map should also increase understanding of the pathophysiological mechanisms of neurogenically mediated hypertension, and assist in the design of studies to prove the hypothesis that it is caused by pulsatile AC of the VLM.

Purpose To evaluate the efficacy and safety of intravitreal ranibizumab in diabetic macular edema (DME) patients. Design Two parallel, methodologically identical, phase III, multicenter, double-masked, sham injection-controlled, randomized studies. Participants Adults with vision loss from DME (best-corrected visual acuity [BCVA], 20/40-20/320 Snellen equivalent) and central subfield thickness ≥275 μm on time-domain optical coherence tomography (OCT). Intervention Monthly intravitreal ranibizumab (0.5 or 0.3 mg) or sham injections. Macular laser was available per-protocol-specified criteria. Main outcome measures Proportion of patients gaining ≥15 letters in BCVA from baseline at 24 months. Results In RISE (NCT00473330), 377 patients were randomized (127 to sham, 125 to 0.3 mg, 125 to 0.5 mg). At 24 months, 18.1% of sham patients gained ≥15 letters versus 44.8% of 0.3-mg (P Conclusions Ranibizumab rapidly and sustainably improved vision, reduced the risk of further vision loss, and improved macular edema in patients with DME, with low rates of ocular and nonocular harm.

Glioblastoma multiforme (GBM) is recognized as the most common and lethal form of central nervous system cancer. Currently used surgical techniques, chemotherapeutic agents, and radiotherapy strategies have done very little in extending the life expectancies of patients diagnosed with GBM. The difficulty in treating this malignant disease lies both in its inherent complexity and numerous mechanisms of drug resistance. In this review, we summarize several of the primary mechanisms of drug resistance. We reviewed available published literature in the English language regarding drug resistance in glioblastoma. The reasons for drug resistance in glioblastoma include drug efflux, hypoxic areas of tumor cells, cancer stem cells, DNA damage repair, and miRNAs. Many potential therapies target these mechanisms, including a series of investigated alternative and plant-derived agents. Future research and clinical trials in glioblastoma patients should pursue combination of therapies to help combat drug resistance. The emerging new data on the potential of plant-derived therapeutics should also be closely considered and further investigated.

Meningiomas are the most common primary brain tumor reported in the United States each year and account for approximately 30% of primary neoplasms. Though in most cases the etiology of meningiomas is unclear, prior exposure to radiation is responsible for a subset of meningiomas. Some have speculated that there may be a relationship between pretreatment characteristics and radiotherapy parameters in the development of radiation-induced meningiomas (RIM). Compared with their sporadic counterparts, currently, the clinical treatment involves is similar with radiation used as a first line therapy. Novel therapeutic agents being investigated in the treatment of these tumors, rely on the direct or cell cycle-mediated induction of DNA damage to promote cellular apoptosis. Our pre-clinical data showed that disruption of p16INK4a-Cdk4-Rb (retinoblastoma) pathways plays a significant role in the development of RIM in Rb+ low-gradelow-grade meningioma cells. These observations highlight the critical role of the p16INK4a-Cdk4-Rb pathway in RIM and suggest that targeting this pathway might be a promising strategy to improve the therapeutic efficacy among RIM patients. Pretreatment characteristics and radiotherapy parameters which may influence the time interval for development of radiation-induced Rb+ meningiomas (RIM) were identified. Our results also demonstrated that CDK 4/6 Inhibitor, significantly suppresses radiation induced malignant transformation and prolonged survival in a cell-free, slice culture model and xenograft model of meningioma. Success of the proposed therapeutic strategies in both in vitro and in vivo models may form the basis for future research.

We review the development of neurosurgery at the Medical University of South Carolina (MUSC) and the emergence of MUSC as a leading academic neurosurgical center in South Carolina. Historical records from the Waring Historical Library were studied, former and current faculty members were interviewed, and the personal records of Dr Phanor J Perot were examined. Dr Frederick E Kredel was the first to perform cerebral revascularization in stroke patients using omental flaps and the first to culture glioma cells in artificial media. The MUSC Neurosurgery residency program was established in 1964 by its first formally trained neurosurgeon, Julian Youmans, MD. The first graduate of the program, Dr Russell Travis, went on to become the President of the American Association of Neurological Surgeons. In 1968, the longest serving chairman, Dr Perot, joined the department and conducted significant research in spinal cord injury, receiving a continuous, 20-year award from the National Institute of Neurological Disorders and Stroke. A major change in the neurosurgery program occurred in 2004 when Dr Sunil Patel accepted the chairmanship. He integrated neurosurgery, neurology, and basic neuroscience departments into a comprehensive Department of Neurosciences to provide integrated clinical care. This department now ranks second in the country in National Institutes of Health research funding. Recently, the Center for Global Health and Global Neurosurgery was established with a vision of caring for patients beyond national borders. Neurosurgery at MUSC has been influenced by Drs Kredel and Perot and the current leadership is moving forward with a uniquely integrated department with novel areas such as global neurosurgery.

To evaluate the safety and efficacy of Ozurdex (dexamethasone intravitreal implant) 0.7 mg in the treatment of diabetic macular edema in vitrectomized eyes.This was a prospective, multicenter, open-label, 26-week study. Fifty-five patients with treatment-resistant diabetic macular edema and a history of previous pars plana vitrectomy in the study eye received a single intravitreal injection of 0.7-mg dexamethasone intravitreal implant. The primary efficacy outcome measure was the change in central retinal thickness from baseline to Week 26 measured by optical coherence tomography.The mean age of patients was 62 years. The mean duration of diabetic macular edema was 43 months. The mean (95% confidence interval) change from baseline central retinal thickness (403 μm) was -156 μm (-190, -122 μm) at Week 8 (P0.001) and -39 μm (-65, -13 μm) at Week 26 (P = 0.004). The mean (95% CI) increase in best-corrected visual acuity from baseline (54.5 letters) was 6.0 letters (3.9, 8.1 letters) at Week 8 (P0.001) and 3.0 letters (0.1, 6.0 letters) at Week 26 (P = 0.046). At Week 8, 30.4% of patients had gained ≥10 letters in best-corrected visual acuity. Conjunctival hemorrhage, conjunctival hyperemia, eye pain, and increased intraocular pressure were the most common adverse events.Treatment with dexamethasone intravitreal implant led to statistically and clinically significant improvements in both vision and vascular leakage from diabetic macular edema in difficult-to-treat vitrectomized eyes and had an acceptable safety profile.

A 54-year-old Caucasian female presented with a 1 year history of intermittent numbness of the left leg progressing to bilateral, lower extremity sensory loss that advanced to include impaired vibration and proprioception. The subsequent thoracic spine magnetic resonance imaging (MRI) scan revealed a heterogeneous, avidly enhancing, centrally situated spinal cord mass involving T7 through T10 in association with thick linear enhancement of the anterior and posterior cord surfaces extending both superiorly and inferiorly. Both the cervical and lumbar spine MRI demonstrated diffuse leptomeningeal disease as well. A brain MRI revealed focal leptomeningeal enhancement in the left and right sylvian fissures, the suprasellar cistern, and the posterior fossa; a pattern consistent with metastatic disease. The patient underwent a T6-T10 laminectomy for tumor biopsy and debulking. Histology revealed a WHO grade III glioneuronal tumor with rosetted neuropil-like islands. Synaptophysin and neurofilament (NF) positive staining was noted within the neural appearing component, whereas, glial fibrillary acidic protein (GFAP) immunopositivity was evident in the fibrillary astrocytoma component of the tumor. The Ki-67 labeling index was 7%. This tumor pattern, now included in the 2007 World Health Organization (WHO) classification of central nervous system tumours as a pattern variation of anaplastic astrocytoma (Kleihues et al. In: Louis et al. (eds) WHO classification of tumours of the central nervous system, 2007), was first described in a four-case series by Teo et al. in 1999. The majority of subsequently reported cases described them as primary tumors of the cerebrum. Herein, we report a unique example of a spinal glioneuronal tumor with neuropil-like islands with associated leptomeningeal dissemination involving the entire craniospinal axis.

The densities and speeds of sound for ternary mixtures of methyl methacrylate (MMA) + 1-alkanols (1-butanol, 1-pentanol, 1-heptanol) + aromatic organic solvents (benzene, toluene, p-xylene, and ethylbenzene) or + cyclohexane have been measured at T/K = (298.15 and 308.15). Excess molar volumes and excess isentropic compressibilities were calculated across the mole fraction range, and the same were compared with the values calculated using similar data for the binary pairs through Redlich−Kister (RK), Tsao and Smith (TS), and Kohler (K) equations. As compared to others, the RK equation predicted the excess molar volumes and excess isentropic compressibilities adequately.

Object Convection-enhanced delivery (CED) is a novel intracerebral drug delivery technique with considerable promise for delivering therapeutic agents throughout the CNS. Despite this promise, Phase III clinical trials employing CED have failed to meet clinical end points. Although this may be due to inactive agents or a failure to rigorously validate drug targets, the authors have previously demonstrated that catheter positioning plays a major role in drug distribution using this technique. The purpose of the present work was to retrospectively analyze the expected drug distribution based on catheter positioning data available from the CED arm of the PRECISE trial. Methods Data on catheter positioning from all patients randomized to the CED arm of the PRECISE trial were available for analyses. BrainLAB iPlan Flow software was used to estimate the expected drug distribution. Results Only 49.8% of catheters met all positioning criteria. Still, catheter positioning score (hazard ratio 0.93, p = 0.043) and the number of optimally positioned catheters (hazard ratio 0.72, p = 0.038) had a significant effect on progression-free survival. Estimated coverage of relevant target volumes was low, however, with only 20.1% of the 2-cm penumbra surrounding the resection cavity covered on average. Although tumor location and resection cavity volume had no effect on coverage volume, estimations of drug delivery to relevant target volumes did correlate well with catheter score (p < 0.003), and optimally positioned catheters had larger coverage volumes (p < 0.002). Only overall survival (p = 0.006) was higher for investigators considered experienced after adjusting for patient age and Karnofsky Performance Scale score. Conclusions The potential efficacy of drugs delivered by CED may be severely constrained by ineffective delivery in many patients. Routine use of software algorithms and alternative catheter designs and infusion parameters may improve the efficacy of drugs delivered by CED.

Background: Despite aggressive treatment, including surgical resection, radiation and chemotherapy, over 90% of glioblastoma (GB) patients experience tumor recurrence. This may be due to high migratory potential, abnormal angiogenesis, molecular heterogeneity and a strong immunosuppressive environment. An earlier report from our laboratory demonstrated that GB cells express high levels of carbohydrate-binding galectin protein: galectin-1 (Gal-1). However, the role of galectin-1 in GB remains elusive. The aim of this study was to evaluate whether galectin-1 promotes tumor progression through upregulation of CXCR4 via NF-κB in in vitro GB models. Methods: To investigate the molecular mechanisms of Gal-1 on tumor progression, we used RT-PCR and western blots techniques. Gal-1 was stably over-expressed in the U118 and U87MG cell line. Gal-1 (+/-) sub-clones were assayed for attachment, proliferation, migration, and tube formation. Results: Gal-1 protein expression was assessed in human GB cells. We found increased Gal-1 protein expression in human GB cells and tissue. To investigate the effects of Gal-1 silencing on angiogenesis in vitro, we collected conditioned media from Gal-1-knockdown U118 and U87MG cells then applied this to human umbilical vein endothelial cells (HUVEC) culture to analyze endothelial cell proliferation, migration, and tube formation. Proliferation rate, migrating capability, and tube formation decreased significantly when HUVECs were cultured with concentrated conditioned media from Gal-1-knockdown cells. This data suggests that Gal-1 in GB cells may promote tumor angiogenesis both in vitro and co-culture. Results showed that silencing of Gal-1 in U118 and U87MG cells significantly repressed CXCR4 expression at the mRNA level and protein levels. To further explore the role of CXCR4 in GB cells, CXCR4 knockdown resulted in significant inhibition of cell migration and clonogenic ability in vitro. Thus, Gal-1 might upregulate CXCR4 expression to promote tumor progression. A previous laboratory study indicated that NF-κB promotes cancer cell motility by upregulating CXCR4 expression. Luciferase reporter assay was used to determine the involvement of NF-κB in Gal-1-induced CXCR4 expression in U118 and U87MG cells. NF-κB luciferase activity was significantly decreased in Gal-1-knockdown cells. Moreover, decreased CXCR4 promoter activity and protein expression in Gal-1-knockdown cells were observed. This data indicates that Gal-1 might modulate CXCR4 expression via NF-κB activation. Conclusion: Our in vitro cell culture results suggest that upregulation of galectin-1 and CXCR4 might at least in part explain the aggressive infiltrative biology of GB and the Gal-1-CXCR4 axis may serve as a therapeutic target. Further studies in different animal models are warranted. Citation Format: David Cachia, Rachel Malley, William A. Vandergrift, Sunil Patel, Gabriel A. Rabinovich, Arabinda Das. Galectin-1 upregulates CXCR4 in glioblastoma through upregulation of CXCR4 via NF-κB activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3559.

Summary Congenital intralingual cysts of foregut origin are extremely rare. These cysts have the potential to compromise the fetal airway at the time of delivery. We present a case of a 37-week fetus with an intralingual cyst identified by antenatal ultrasound and subsequently further delineated by MRI. Information acquired from the imaging allowed for controlled delivery with necessary precautions to manage an impending airway obstruction. Excision of the cyst occurred at day 8 of life. We have reviewed the literature as it pertains to our case as well as the role of imaging in managing fetal oral cavity cysts.

Object The authors describe the utility of and outcomes after endoscopic transnasal craniotomy and skull reconstruction in the management of skull base pathologies. Methods The authors conducted a observational study of patients undergoing totally endoscopic, transnasal, transdural surgery. The patients included in the study underwent treatment over a 12-month period at 2 tertiary medical centers. The pathological entity, region of the ventral skull base resected, and size of the dural defect were recorded. Approach-related complications were documented, as well as CSF leaks, infections, bleeding-related complications, and any minor complications. Results Thirty consecutive patients were assessed during the study period. The patients had a mean age of 45.5 ± 20.2 years and a mean follow-up period of 182.4 ± 97.5 days. The dural defects reconstructed were as large as 5.5 cm (mean 2.49 ± 1.36 cm). One patient (3.3%) had a CSF leak that was managed endoscopically. Two patients had epistaxis that required further care, but there were no complications related to intracranial infections or bleeding. Some minor sinonasal complications occurred. Conclusions Skull base endoscopic reconstructive techniques have significantly advanced in the past decade. The use of pedicled mucosal flaps in the reconstruction of large dural defects resulting from an endoscopic transnasal craniotomy permits a robust repair. The CSF leak rate in this study is comparable to that achieved in open approaches. The ability to manage the skull base defects successfully with this approach greatly increases the utility of transnasal endoscopic surgery.

BACKGROUND: We aim to assess the long-term trend of and identify risk factors for traumatic spinal cord injury (TSCI) mortality from 1981 through 1998 in the state of South Carolina (SC). METHODS: We analyzed data from the TSCI surveillance system in SC. Poisson regression analyses were used to examine trends in TSCI mortality rates across subpopulations of interest. Multiple logistic regression was used to identify risk factors for TSCI mortality. RESULTS: The rate of TSCI mortality was 27.4 per million population between 1981 and 1998. A significant 3% annual decrease in the TSCI mortality rate was found from 1981 through 1998. Specifically, TSCI mortality rates declined the most per year in motor vehicle crashes, males, and whites. Adjusted for covariates, individuals of older ages, black race, with a cervical TSCI, and with a more severe injury, as defined by both Frankel grade and Abbreviated Injury Scale, were associated with higher odds of in-hospital mortality. Females had lower odds of in-hospital mortality than males. CONCLUSION: Although mortality rate is decreasing, TSCI remains a significant public health problem, with SC having higher rates of TSCI mortality than the United States. The association between gender and in-hospital mortality needs further exploration. Language: en

Background Endoscopic skull base reconstruction (ESBR) has been widely accepted in the management of cerebrospinal fluid (CSF) leaks. However, it is not the CSF leak itselfbut the potential for life-threatening intracranial complications (ICCs) that is of primary clinical concern. The risk of developing complications, such as meningitis, in a skull base defect is unknown. Many ESBR are multilayered soft tissue repairs, and long-term prevention of ICCs is not well described. Methods Retrospective chart review and telephone consultation was used to assess patients who had an ESBR from 2002 to 2008. The incidence of an ICCs (meningitis, cerebral abscess, and pneumocephalus) and associated risk factors were assessed before and after surgery. Results One hundred six patients underwent ESBR (mean age (∓SD), 47.7 ∓ 18.5 years; range, 2–78 years) with 95.3% long-term follow-up (mean, 19.9 ∓ 16.3 months). ICCs occurred in 21.7% of patients at presentation, in 2.8% of patients during the perioperative period (2 = 9.10; p = 0.007) and leaking encephaloceles (χ2 = 5.98; p = 0.014). Factors not associated with increased ICC were an active CSF leak at presentation (χ2 = 3.03; p = 0.082) and previous radiotherapy. Conclusion ESBR offers an excellent long-term option in preventing subsequent ICC with low perioperative complications. ESBR is robust with delayed (>2weeks) CSF leakage occurring in only 1.9% regardless of etiology. The presence of identifiable risk factors for ICC may guide the surgeon in determining the urgency of ESBR.

Exercise, diet, and personal fitness programs are essentially lacking in modern graduate medical education. In the context of long hours and alternating shift and sleep cycles, the lack of exercise and poor dietary choices may have negative consequences on physician physical and mental health. This opinion piece aims to generate important dialogue regarding the scope of the problem, the literature supporting the health benefits of exercise, potential solutions to enhancing diet and exercise among resident trainees, and possible pitfalls to the adoption of exercise programs within graduate medical education.

Glioblastoma is the most prevalent and highly malignant brain tumor that continues to defy current treatment strategies. This investigation used all-trans retinoic acid (ATRA) and taxol (TXL) as a combination therapy for controlling the growth of human glioblastoma T98G xenografted in athymic nude mice. Histopathological examination revealed that ATRA induced differentiation and combination of ATRA and TXL caused more apoptosis than either treatment alone. Combination therapy decreased expression of telomerase, nuclear factor kappa B (NFkappacapital VE, Cyrillic), and inhibitor-of-apoptosis proteins (IAPs) indicating suppression of survival factors while upregulated Smac/Diablo. Combination therapy also changed expression of Bax and Bcl-2 proteins leading to increased Bax:Bcl-2 ratio, mitochondrial release of cytochrome c and apoptosis-inducing factor (AIF), and activation of caspase-9. Increased activities of calpain and caspase-3 degraded 270 kD alpha-spectrin at the specific sites to generate 145 kD spectrin breakdown product (SBDP) and 120 kD SBDP, respectively. Further, increased activity of caspase-3 cleaved inhibitor-of-caspase-activated DNase (ICAD). In situ double immunofluorescent labelings showed overexpression of calpain, caspase-12, caspase-3, and AIF during apoptosis, suggesting involvement of both caspase-dependent and caspase-independent pathways for apoptosis. Our investigation revealed that treatment of glioblastoma T98G xenografts with the combination of ATRA and TXL induced differentiation and multiple molecular mechanisms for apoptosis.

Background The aim of this study was to compare three different techniques for transsphenoidal pituitary surgery: (1) sublabial transseptal approach with microscopic resection, (2) transnasal transseptal approach with endoscopic resection, and (3) endoscopic approach with endoscopic resection. Methods We performed a retrospective review of 50 pituitary surgeries performed by the same neurosurgeon. Demographic, radiographic, and clinical data were collected. Results Fifteen patients underwent sublabial approach with microscopic tumor resection, 21 patients underwent the transnasal approach with endoscopic resection, and 14 patients underwent the completely endoscopic technique. There were a total of 20 complications in the sublabial group, 13 transnasal complications, and 6 endoscopic complications. Cerebrospinal fluid leak incidence was 53% in the sublabial approaches, 47% transnasal, and 28% in the endoscopic patients. Diabetes insipidus was encountered in 33% of sublabial approaches, 5% of transnasal approaches, and 7% of endoscopic approaches. Lumbar drains were required in 40% of sublabial approaches, 38% of transnasal approaches, and 7% of endoscopic approaches. Nasal packing was used in 100% of sublabial and transnasal approaches and 0% of endoscopic approaches. Mean recurrence rate and follow-up was sublabial in 6.6% (50 months), transnasal in 9.5% (11 months), and endoscopic in 0% (7 months). Average hospital stay for sublabial approaches, transnasal approaches, and endoscopic approaches was 8.3, 6.2, and 3.4 days, respectively (p < 0.05). Conclusion Transsphenoidal pituitary surgery has evolved over the past several decades, because advances in technology have been the catalyst for minimally invasive surgeries. Less invasive approaches, such as the transnasal approach with endoscopic resection of tumor and the completely endoscopic technique have less morbidity and a shorter hospital stay than traditional sublabial approaches. Continued follow-up is needed to confirm long-term benefits and similar recurrence rates.

Glioblastoma is the most common astrocytic brain tumor in humans. Current therapies for this malignancy are mostly ineffective. Photodynamic therapy (PDT), an exciting treatment strategy based on activation of a photosensitizer, has not yet been extensively explored for treating glioblastoma. We used 5-aminolevulinic acid (5-ALA) as a photosensitizer for PDT to induce apoptosis in human malignant glioblastoma U87MG cells and to understand the underlying molecular mechanisms. Trypan blue dye exclusion test showed a decrease in cell viability after exposure to increasing doses of 5-ALA for 4h followed by PDT with a broad spectrum blue light (400-550 nm) at a dose of 18J/cm(2) for 1h and then incubation at 37 degrees C for 4h. Following 0.5 and 1mM 5-ALA-based PDT (5-ALA-PDT), Wright staining and ApopTag assay showed occurrence of apoptosis morphologically and biochemically, respectively. After 5-ALA-PDT, down regulation of nuclear factor kappa B (NFkappaB) and baculovirus inhibitor-of-apoptosis repeat containing-3 (BIRC-3) protein indicated inhibition of survival signals. Besides, 5-ALA-PDT caused increase in Bax:Bcl-2 ratio and mitochondrial release of cytochrome c and apoptosis-inducing factor (AIF). Activation of calpain, caspase-9, and caspase-3 occurred in course of apoptosis. Calpain and caspase-3 activities cleaved alpha-spectrin at specific sites generating 145kD spectrin breakdown product (SBDP) and 120kD SBDP, respectively. The results suggested that 5-ALA-PDT induced apoptosis in U87MG cells by suppression of survival signals and activation of proteolytic pathways. Thus, 5-ALA-PDT can be an effective strategy for inducing apoptosis in glioblastoma.

Malignant (N-type) neuroblastoma continues to defy current chemotherapeutic regimens. We tested the garlic compounds diallyl sulfide (DAS) and diallyl disulfide (DADS) for induction of apoptosis in human malignant neuroblastoma SH-SY5Y cells. Viability of human primary neurons was unaffected after 24 h treatment with 50 and 100 microM DAS and 50 microM DADS but slightly affected with 100 microM DADS. Treatment with 50 and 100 microM DAS or DADS significantly decreased viability in SH-SY5Y cells. Wright staining showed morphological features of apoptosis in SH-SY5Y cells treated with 50 and 100 microM DAS or DADS for 24 h. ApopTag assay demonstrated DNA fragmentation in apoptotic cells. Apoptosis was associated with an increase in [Ca(2+)](i), increase in Bax:Bcl-2 ratio, mitochondrial release of cytochrome c, increase in cytosolic Smac/Diablo, and down regulation of inhibitor-of-apoptosis proteins and nuclear factor kappa B (NFkappaB). Activation of caspase-9 and caspase-3 indicated involvement of intrinsic pathway of apoptosis. Calpain and caspase-3 activities produced 145 kD spectrin break down product (SBDP) and 120 kD SBDP, respectively. Also, caspase-3 activity cleaved inhibitor of caspase-activated DNase (ICAD). Results strongly suggested that the garlic compounds DAS and DADS suppressed anti-apoptotic factors and activated calpain and intrinsic caspase cascade for apoptosis in SH-SY5Y cells.

Cognitive radio technology offers a revolutionary solution to spectral resources crisis by looking at the spectrum in an unconventional manner as a multi-dimensional space. The current wireless communication systems are governed by fixed spectrum assignment policy (licensed spectrum), which was proven by measurement to be inefficient. Cognitive radio enables maximum spectrum utilization efficiency through opportunistic access to temporarily unutilized portions of spectrum. In Cognitive Radio spectrum sensing performance is more important. By cooperative spectrum sensing probability of false alarm (Pf) is increased with given probability of detection (Pd). In this paper we formulate a cooperative spectrum sensing as noncooperative game and also formulate a optimization problem, numerical results demonstrate that limited number of SU for cooperative sensing are achieve much better performance than Nash Equilibrium. By selecting optimal strategy SU maximize their utility, maximum spectrum utilization is depend on expected utility under different SNR.

Medulloblastoma (MB) is the most common malignant brain tumor in children, and has been historically classified based on clinical markers (patient age, presence of metastases at diagnosis, extent of resection) and histopathological characteristics (classic, desmoplastic/nodular, and large cell/anaplastic). However, the recent gene expression profiling of a large number of tumors across multiple studies has provided evidence of four distinct medulloblastoma molecular subgroups (Wnt, Shh, Group 3, and Group 4), associated with remarkably different prognoses. While current therapies for medulloblastoma are often toxic, and not always effective, immunotherapy, designed to target these subgroups, may offer therapeutic improvement. Although monoclonal antibody (mAb) therapy has not yet been shown to be effective for the treatment of brain tumors, recent data indicate that radiation therapy can induce immunogenic modulation characterized by cell-surface phenotypic changes leading to augmented tumour cell/cytotoxic T-cell interaction. We examined the ability of radiation to upregulate mAb therapy targets. Our data showed that low dose radiation significantly increased cell-surface and total protein expression of mAb targets CD137 (a member of the TNF receptor superfamily), FGF, CD20, HER2, Major Histocompatability Complex (MHC) class I and intercellular adhesion molecule-1 (ICAM-I) in 3 out of 3 medulloblastoma cell lines. These findings highlight a mechanism for combining radiation with immunotherapy, to potentially expand the effect of targeted therapy in brain tumor treatment.

The therapeutic effect of curcumin (CCM), a polyphenolic compound from the rhizome of Curcuma longa, has not yet been examined in glioblastoma. We used human glioblastoma T98G cells to explore the efficacy of CCM for inducing apoptosis and identifying proteolytic mechanisms involved in this process. Trypan blue dye exclusion test showed decrease in cell viability with increasing dose of CCM. Wright staining and ApopTag assay showed, respectively, morphological and biochemical features of apoptosis in T98G cells exposed to 25 microM and 50 microM of CCM for 24 h. Treatment with CCM activated receptor-mediated pathway of apoptosis as Western blotting showed activation of caspase-8 and cleavage of Bid to tBid. Besides, CCM caused an increase in Bax:Bcl-2 ratio, and mitochondrial release of cytochrome c, Second mitochondrial activator of caspases/Direct IAP binding protein with low pI (Smac/Diablo), and apoptosis-inducing-factor (AIF) indicating involvement of mitochondria-mediated pathway as well. Down regulation of the nuclear factor kappa B (NFkappaB), increased expression of inhibitor of nuclear factor kappa B alpha (IkappaB alpha), and decreased expression of inhibitor-of-apoptosis proteins (IAPs) such as c-IAP1 and c-IAP2 in T98G cells following CCM treatment suggested suppression of survival signal. Activation of caspase-9 and caspase-3 was detected in generation of 35 kD and 20 kD active fragments, respectively. Calpain and caspase-3 activities cleaved 270 kD alpha-spectrin at specific sites to generate 145 kD spectrin break down product (SBDP) and 120 kD SBDP, respectively. Our results strongly suggest that CCM induced both receptor-mediated and mitochondria-mediated proteolytic mechanisms for induction of apoptosis in T98G cells.

We describe our experience with simultaneous bilateral laparoscopic radical nephrectomy performed in patients with acquired cystic kidney disease (ACKD) and renal tumors.Between June 2000 and September 2002, 10 patients with ACKD underwent simultaneous bilateral laparoscopic radical nephrectomy for renal lesions suspicious for carcinoma. The lesions were discovered during pretransplant evaluation in 9 patients and incidentally in 1 renal transplant recipient. A 3- or 4-port transperitoneal approach was used for each side to mobilize the kidney and secure the renal hilum. Both specimens were extracted through a midline supraumbilical incision. Operative time, blood loss, analgesic requirements, hospital stay, and convalescence and recurrence rates were determined.The mean age of the patients was 41.6 years (range, 29-47 years). Mean operative time was 6.5 hours (range, 4.5-9.7 hours) and mean estimated blood loss was 164 cc (range, 50-300 cc). There was one intraoperative complication-a clotted arteriovenous (AV) graft; and 2 postoperative complications-1 fluid overload and 1 adrenal insufficiency. The average length of hospital stay was 3.1 days (range, 2-4 days) and mean convalescence was 2.8 weeks (range, 1-6 weeks). All cancers were confined to the kidneys and there has been no recurrence during follow-up ranging from 6 to 26 months.Bilateral laparoscopic radical nephrectomy in end-stage renal disease patients is safe and feasible. The advantages of the laparoscopic approach include minimal intraoperative blood loss, shorter hospital stay, minimal postoperative pain, and a rapid return to normal activity. The laparoscopic technique offers an effective, minimally invasive therapeutic alternative to open surgery in high-risk end-stage renal disease patients.

OBJECTIVE Pulsatile arterial compression (AC) of the ventrolateral medulla (VLM) has been postulated to cause neurogenically mediated essential hypertension (EHTN). We aimed to establish whether the association between AC of specifically the retro-olivary sulcus (ROS) of the VLM and EHTN was significant, while controlling for other risks associated with EHTN. DESIGN Case-control study. METHODS Posterior fossa magnetic resonance imaging scans of 131 subjects, including 58 subjects with EHTN and 73 normotensives, were reviewed to determine the presence of AC in the ROS. The history of other risk factors for EHTN was obtained by reviewing medical records. RESULTS Multivariate logistic regression analysis of these data shows a significant association between AC in the ROS (right and/or left) and EHTN [odds ratio (OR) = 3.03, 95% confidence interval (CI) = 1.30, 7.06]. This analysis was done controlling for other known EHTN risk factors such as age, race, sex, diabetes, and obesity. A secondary analysis also controlling for these variables shows that AC of both the right and left ROS are independently associated with EHTN (right AC: OR = 5.04, 95% CI = 1.33, 19.17; left AC: OR = 3.39, 95% CI = 1.20, 9.60). CONCLUSIONS In this retrospective study of subjects with EHTN and normotensive controls that had undergone magnetic resonance imaging of the posterior fossa, AC of the ROS on either side of the medulla is a significant independent risk factor in EHTN. Further studies are required to determine whether this is true for the general population of patients with neurogenically mediated EHTN.

Pulsatile arterial compression in the retro-olivary sulcus along the surface of the ventrolateral medulla has been postulated as a mechanism in both essential hypertension and diabetes. The objective of this study was to test the independent effect of arterial compression in the retro-olivary sulcus on each of these diseases, using separate logistic regression models to control for other known risk factors. Study design was case–control. The study population consisted of 147 consecutive patients treated for neurological conditions requiring MRI of the posterior cranial fossa. Information on essential hypertension, diabetes, and risk factors for each disease was abstracted from medical records. Presence of arterial compression was determined by blinded review of magnetic resonance images. In the essential hypertension analysis, odds of arterial compression among hypertensive patients were 2.99-times the odds among normotensive subjects ( P =0.04), controlling for hypertension risk factors such as age, body mass index, race, diabetes, and family history of hypertension. Of compressed hypertensive subjects, 56% were compressed on the left and 44% were compressed on the right. In the diabetes analysis, odds of arterial compression among diabetic subjects were 1.14-times the odds among nondiabetic subjects ( P =0.83). Of compressed diabetic subjects, 60% were compressed on the left, and 40% were compressed on the right. Results suggest that arterial compression of the retro-olivary sulcus may be an independent risk factor for essential hypertension in this population, supporting the postulate for a treatable (with microvascular decompression) neural mechanism for essential hypertension. However, in the diabetic population, the slight increase in the odds of arterial compression was not significant.

OBJECTIVE: We report the safety and feasibility of using convection-enhanced delivery to administer Cotara (Peregrine Pharmaceuticals, Inc., Tustin, CA), a novel radioimmunotherapeutic agent, to patients with malignant glioma. METHODS: Between April 1998 and November 2002, 51 patients with histologically confirmed malignant glioma received Cotara by convection-enhanced delivery. Most patients (88%) were treated with Cotara targeting tumor volume-dependent, single or multiple administrations of activity ranging from 0.5 to 3.0 mCi/cm3 of baseline clinical target volume. Two weeks after infusion, single-photon emission computed tomographic imaging determined the spatial distribution of Cotara. Patients were followed for as long as 41 months (average follow-up, 5 mo). Safety was evaluated on the basis of incidence of procedure-related, neurological, and systemic adverse events. Feasibility was evaluated in a subset of patients on the basis of the correlation between the prescribed activity and the actual activity administered to the targeted region. RESULTS: Fifty-one patients, 37 with recurrent glioblastoma multiforme, 8 with newly diagnosed glioblastoma multiforme, and 6 with recurrent anaplastic astrocytomas, were treated. Average tumor volume was 36 ± 27.6 cm3 (range, 5–168 cm3). Of the 67 infusions, 13 (19%), 52 (78%), and 2 (3%) delivered less than 90%, 100 ± 10%, and more than 110%, respectively, of the prescribed administered activity to the targeted region. Treatment-emergent, drug-related central nervous system adverse events included brain edema (16%), hemiparesis (14%), and headache (14%). Systemic adverse events were mild. Several patients had objective responses to Cotara. CONCLUSION: The majority of Cotara infusions delivered between 90 and 110% of the prescribed administered activity to the targeted region. This method of administration has an acceptable safety profile compared with literature reports of other therapeutics delivered by convection-enhanced delivery.

Human glioblastoma is a deadly brain tumor that is often treated with a combination of drugs. A new alkylating agent, temozolomide (TMZ), has recently been found efficacious in the clinical trials for glioblastoma. Steroids, such as dexamethasone (DXM), are often used concomitantly as a supportive therapy to treat cerebral edema. However, any possible modulatory effect of the steroids on the efficacy of TMZ has not yet been evaluated experimentally. In this study, we have examined whether DXM provides synergistic or antagonistic effect on TMZ-induced apoptosis in human glioblastoma T98G cells. T98G cells were pretreated with various doses of DXM followed by TMZ. The cell viability was assessed by the trypan blue dye exclusion test. Wright staining and the TdT-mediated dUTP nick-end labeling (TUNEL) assay were used to evaluate apoptotic cell death based on the morphological and biochemical (DNA fragmentation) features, respectively. More biochemical features of apoptotic death, such as upregulation of Bax:Bcl-2 ratio, calpain activity, and caspase-3 activity, were assessed by Western blot analysis. A significant number of T98G cells committed apoptosis after treatment with 200 microM TMZ. However, a pretreatment with 100 microM or 200 microM DXM protected T98G cells against TMZ-induced apoptosis, concomitantly decreasing Bax:Bcl-2 ratio, calpain activity, and caspase-3 activity. These experimental results indicate that DXM works as an antagonistic agent in combination with TMZ. Therefore, our investigation strongly implies that the combination of DXM and TMZ may be counteractive in treating human glioblastoma.

Synchrotron-based photoelectron spectroscopy (PES) has been used to investigate the interaction of atomic gold and silver with a covalently bound C60-monolayer adsorbed on Si(111)7×7. In contrast to the relatively benign interaction of silver with the C60/Si(111)7×7 surface, core-level photoemission data reveal a strong interaction of gold with the underlying silicon despite the presence of a chemisorbed fullerene monolayer. The Si 2p PES data exhibit dramatic changes consistent with the formation of a gold silicide, which is also evident from the corresponding Au 4f spectra. Valence band photoemission also reveals the absence of any density of states at the Fermi level following the adsorption of either metal, indicating a negligible transfer of electrons from the adsorbed metal to the C60 cage.

Ischemic cerebrovascular disease (stroke) is one of the leading causes of death and long-time disability. Ischemia/reperfusion to any organ triggers a complex series of biochemical events, which affect the structure and function of every organelle and subcellular system of the affected cells. The purpose of this study was to investigate the therapeutic efficacy of N-acetyl cysteine (NAC), a precursor of glutathione and a potent antioxidant, to attenuate ischemia/reperfusion injury to brain tissue caused by a focal cerebral ischemia model in rats. A total of 27 male Sprague-Dawley rats weighing 250-300 g were used in this study. Focal cerebral ischemia (45 min) was induced in anesthetized rats by occluding the middle cerebral artery (MCA) with an intra-luminal suture through the internal carotid artery. The rats were scored post-reperfusion for neurological deficits. They were then sacrificed after 24 h of reperfusion and infarct volume in the brain was assessed by 2,3,5-triphenyl tetrazolium chloride (TTC). Brain sections were immunostained for tumor necrosis factor (TNF-alpha) and inducible nitric oxide synthase (iNOS). Animals treated with NAC showed a 49.7% (S.E.M.=1.25) reduction in brain infarct volume and 50% (S.E.M.=0.48) reduction in the neurological evaluation score as compared to the untreated animals. NAC treatment also blocked the ischemia/reperfusion-induced expression of tumor necrosis factor and inducible nitric oxide synthase. The data suggest that pre-administration of NAC attenuates cerebral ischemia and reperfusion injury in this brain ischemia model. This protective effect may be as a result of suppression of TNF-alpha and iNOS.

A 33-year-old male presented with a rare intracranial oculomotor schwannoma not associated with neurofibromatosis manifesting as an 8-month history of right oculomotor nerve paresis. Neuroimaging examinations revealed a 4-cm mass in the right crural cistern. The tumor was totally removed. The right oculomotor nerve paresis resolved 7 months after surgery. Removal of the oculomotor or trochlear schwannoma usually results in parent nerve paresis, but subcapsular tumor resection in our case probably allowed complete recovery of the nerve function.