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Rib fracture after stereotactic radiotherapy for primary lung cancer: prevalence, degree of clinical symptoms, and risk factors.
BMC Cancer. 2013;13:68
Authors: Nambu A, Onishi H, Aoki S, Tominaga L, Kuriyama K, Araya M, Saito R, Maehata Y, Komiyama T, Marino K, Koshiishi T, Sawada E, Araki T
BACKGROUND: As stereotactic body radiotherapy (SBRT) is a highly dose-dense radiotherapy, adverse events of neighboring normal tissues are a major concern. This study thus aimed to clarify the frequency and degree of clinical symptoms in patients with rib fractures after SBRT for primary lung cancer and to reveal risk factors for rib fracture. Appropriate ?/? ratios for discriminating between fracture and non-fracture groups were also investigated.
METHODS: Between November 2001 and April 2009, 177 patients who had undergone SBRT were evaluated for clinical symptoms and underwent follow-up thin-section computed tomography (CT). The time of rib fracture appearance was also assessed. Cox proportional hazard modeling was performed to identify risk factors for rib fracture, using independent variables of age, sex, maximum tumor diameter, radiotherapeutic method and tumor-chest wall distance. Dosimetric details were analyzed for 26 patients with and 22 randomly-sampled patients without rib fracture. Biologically effective dose (BED) was calculated with a range of ?/? ratios (1-10 Gy). Receiver operating characteristics analysis was used to define the most appropriate ?/? ratio.
RESULTS: Rib fracture was found on follow-up thin-section CT in 41 patients. The frequency of chest wall pain in patients with rib fracture was 34.1% (14/41), and was classified as Grade 1 or 2. Significant risk factors for rib fracture were smaller tumor-chest wall distance and female sex. Area under the curve was maximal for BED at an ?/? ratio of 8 Gy.
CONCLUSIONS: Rib fracture is frequently seen on CT after SBRT for lung cancer. Small tumor-chest wall distance and female sex are risk factors for rib fracture. However, clinical symptoms are infrequent and generally mild. When using BED analysis, an ?/? ratio of 8 Gy appears most effective for discriminating between fracture and non-fracture patients.
PMID: 23391264 [PubMed - in process]
The association between lysosomal protein glucocerebrosidase and Parkinson's disease.
Eur Rev Med Pharmacol Sci. 2013 Jan;17(2):143-51
Authors: Kong B, Yang T, Gu JW, Kuang YQ, Cheng L, Yang WT, Yang XK, Xia X, Cheng JM, Ma Y, Zhang JH, Yu SX
BACKGROUND: In recent years, mutations in glucocerebrosidase gene (GBA), which encodes the lysosomal enzyme glucocerebrosidase (GCase) deficient in Gaucher disease (GD), were found to be the most widespread genetic for the development of Parkinson disease.
AIM: In this work, we investigated the possibility of a biological linkage between GCase and alpha-synuclein.
MATERIALS AND METHODS: siRNA was used to knockdown the GBA, then the related proteins such as alpha-synuclein were detected, additionally, the mutations of GBA were also detected. We also provide evidence that a mouse model of Gaucher disease (GBAD409H/D409H) to detect the gene types of GBA.
RESULTS: The results showed functional knockdown (KD) of GBA in neuroblastoma cells culture causes a significant accumulation of alpha-synuclein and alpha-synuclein-mediated neurotoxicity. Furthermore, KD of GBA in rat primary neurons expressing the A53T mutation of alpha-synuclein, decreases cell viability. In addition, we observed that overexpression of several GBA mutants (N370S, L444P, D409H, D409V) significantly raised human alpha-syn levels of vector control. Glucosylceramide (GlcCer), the GCase substrate, influenced formation of purified a-syn by stabilizing soluble oligomeric intermediates. We also provide evidence that a mouse model of Gaucher disease (GBAD409H/D409H) exhibited alpha-syn aggregates in substantia nigra, cortex and hippocampus regions. ELISA analysis showed a significant rise in membrane-associated ?-syn and western blot analysis showed that two forms of alpha-syn oligomers were present in brain homogenates from the hippocampus D409H mice.
CONCLUSIONS: These studies support the contention that both WT and mutant GBA can cause Parkinson disease-like alpha-synuclein pathology.
PMID: 23377801 [PubMed - in process]
Abdominal cerebrospinal fluid pseudocyst as a complication of a ventriculoperitoneal shunt.
Pediatr Emerg Care. 2013 Jan;29(1):114-6
Authors: Halverson M, Pollock AN
PMID: 23283280 [PubMed - in process]
Renal sympathetic denervation for treatment of resistant hypertension: a systematic review.
J Clin Hypertens (Greenwich). 2013 Jan;15(1):75-84
Authors: Gosain P, Garimella PS, Hart PD, Agarwal R
Catheter-based renal sympathetic denervation (RSD) is a novel technique that is being investigated as treatment for resistant hypertension. To systematically evaluate the existing literature on the safety and efficacy of RSD in persons with resistant hypertension, online searches of Medline and the Cochrane Library Database (up to June 2012) were performed. Randomized controlled trials, observational studies, and conference proceedings published in English language were included. Nineteen studies (N=683 persons) were included. Follow-up duration ranged from 1 to 24 months. All studies reported significant reductions in systolic and diastolic pressures. Maximal reduction of blood pressure ranged from 18 mm Hg to 36 mm Hg (systolic) and 9 mm Hg to 15 mm Hg (diastolic). Sustained benefit of blood pressure reduction at 12 months was seen in 5 studies. No worsening of renal function was reported and there were few procedure-related adverse events such as pseudoaneurysm formation, hypotension, and bradycardia. Data from short-term studies suggest that RSD is a safe and effective therapeutic option in carefully selected patients with resistant hypertension. Long-term studies with large patient populations are needed to study whether this benefit is sustained with a demonstrable difference in cardiovascular disease event rates.
PMID: 23282128 [PubMed - in process]
Neurosurgical practice and health care reform: moving toward quality-based health care delivery.
Neurosurg Focus. 2013 Jan;34(1):E1
Authors: Groman RF, Rubin KY
In an effort to rein in spending and improve patient outcomes, the US government and the private sector have adopted a number of policies over the last decade that hold health care professionals increasingly accountable for the cost and quality of the care they provide. A major driver of these efforts is the Patient Protection and Affordable Care Act of 2010 (ACA or Pub.L. 111-148), which aims to change the US health care system from one that rewards quantity to one that rewards better value through the use of performance measurement. However, for this strategy to succeed in raising the bar on quality and efficiency, it will require the development of more standardized and accurate methods of data collection and further streamlined federal regulations that encourage enhanced patient-centered care instead of creating additional burdens that interfere with the physician-patient relationship.
PMID: 23278262 [PubMed - in process]
Five 'nontraditional' techniques for use in patients with recalcitrant sinusitis.
Curr Opin Otolaryngol Head Neck Surg. 2013 Feb;21(1):39-44
Authors: Schneider JS, Archilla A, Duncavage JA
PURPOSE OF REVIEW: Although endoscopic sinus surgery remains the mainstay of surgical approaches to treating paranasal sinus disease, some disease may require alternative approaches. We review here five techniques: endoscopic middle turbinectomy, maxillary sinoscopy, the Caldwell-Luc procedure, intranasal inflammatory polyp steroid injection, and frontal sinus trephine.
RECENT FINDINGS: Recent findings suggest that endoscopic sinus surgery is limited in certain cases to access particular anatomic sites that may contain disease. The anterior, inferior maxillary wall and the frontal sinus may be accessed externally with minimal morbidity, and this access may be critical to treating the disease. The middle turbinate can contribute to preoperative and postoperative obstruction of sinus drainage, and resection of it can benefit the patient in many ways. Finally, the management of intranasal inflammatory polyps remains a challenge. In both preoperative and postoperative patients, the polyps may not respond to standard and even aggressive topical therapies. Intrapolyp steroid injection can provide a substantial anti-inflammatory effect and may avoid surgery for some patients.
SUMMARY: This article will review five ancillary procedures that add to the rhinologist's skill set to treat difficult or recalcitrant paranasal sinus disease.
PMID: 23262744 [PubMed - in process]
Robert Liston (1794-1847): surgical anatomist and resurrectionist with an interest in hydrocephalus.
Childs Nerv Syst. 2013 Jan;29(1):1-4
Authors: Mian A, Shoja MM, Watanabe K, Rozzelle CJ, Loukas M, Tubbs RS
INTRODUCTION: The Scottish surgeon Robert Liston was an accomplished anatomist of the nineteenth century. The study of anatomy during this day was often overshadowed by the so-called resurrectionists. Conclusions: The present historic paper reviews the life and contributions of Robert Liston and discusses his fascination with childhood hydrocephalus.
PMID: 23224409 [PubMed - in process]
Clinical application of interventional renal sympathetic denervation: recommendations of the Austrian Society of Hypertension 2012.
Wien Klin Wochenschr. 2012 Nov;124(21-22):789-98
Authors: Weber T, Zweiker R, Watschinger B, Grüner P, Koppelstätter C, Brandt MC, Horina J, Brussee H, Hohenstein K, Lambert T, Auer J, Hoppe UC
Increased activity of the sympathetic nervous system plays a major role in the pathophysiology of primary arterial hypertension. Interventional renal sympathetic denervation (RSD) is a novel percutaneous treatment, decreasing sympathetic activity and consecutively blood pressure by ablating sympathetic nervous fibers located in the adventitia of the renal arteries. The procedure has been tested in several clinical trials in patients with resistant hypertension (defined as systolic office blood pressure >?160 mmHg-in diabetic patients >?150 mmHg-treated with ³?3 antihypertensive drugs) and caused a meaningful blood pressure reduction, lasting for at least 3 years. So far, no major adverse events have been identified; however, data on the long-term consequences are lacking. The present position paper of the Austrian Society of Hypertension is aiming to assist in choosing possible indications for RSD in clinical routine, based on the available evidence in 2012.
PMID: 23184070 [PubMed - in process]
C2/3 instability: unusual cause of cervical myelopathy in a child with Down syndrome.
Childs Nerv Syst. 2013 Jan;29(1):163-5
Authors: Al-Habib A, AlAqeel A
We report a rare cause of cervical myelopathy (CM) in a 10-year-old Down syndrome (DS) girl. She presented with progressive CM over 1 year affecting her ability to ambulate or feed herself. The myelopathy was secondary to C2/3 instability. Surgical reduction and instrumented fusion have significantly improved her neurological status. This case emphasizes the importance of close follow-up of DS patients for early diagnosis and treatment of cervical spine abnormalities.
PMID: 23108918 [PubMed - in process]
Intracranial suppurations in the African child: a severe but preventable complication.
Childs Nerv Syst. 2013 Jan;29(1):119-23
Authors: Djientcheu VP, Mouafo TF, Esiene A, Kamga YN, Nguefack S, Bello F, Yamgoue TY, Ongolo ZC, Mbonda E
INTRODUCTION: Intracranial suppurations (ICS) are collections of pus of infectious origin in the skull. The authors present their experience.
PATIENTS AND METHOD: All children operated for ICS at the Central Hospital of Yaoundé from January 2000 to December 2008 were retrospectively included.
RESULTS: Thirty-five patients were recruited: 26 (74.29 %) males and 9 (25.71 %) females. These represent 82.9 % of all ICS operated in our institution. ICS represented 14.3 % of intracranial space-occupying lesions. The mean age was 8.34 years. They presented with headaches (80.77 %), altered consciousness (20 %), convulsions (76 %), vomiting (20 %), unilateral motor deficit (69.23 %), speech disorders (12 %), and fever (89.29 %). Bergman's triad (51.86 %) was frequent. The primary infection was: meningitis, eight cases (22.85 %); sinusitis, six cases (17.14 %); head trauma, five cases (14.28 %); otitis media, one case (2.85 %); suppurations of the face, three cases (8.56 %); cardiopathy, one case (2.85 %); and craniotomy, one case (2.85 %). In seven cases (20 %), the origin was unknown. The lesions were empyema in 23 cases (65.71 %), cerebral abscess in 8 cases (22.85 %) and pyoventriculitis in 2 cases (5.72 %). The surgical procedures were burr holes (88.89 % of empyemas) and trepano-puncture-aspiration (75 % of abscesses). The mortality (21.42 %) and morbidity (42.85 %) were recorded.
CONCLUSION: ICS are frequent but preventable (early treatment of the primary infection) pathologies of childhood in developing countries. Burr hole drainage (empyemas) and puncture-aspiration (abscesses) are simple, safe, and effective techniques.
PMID: 23053358 [PubMed - in process]
Neonatal post-hemorrhagic hydrocephalus resulting in foraminal septae-radiological technique and surgical implications.
Childs Nerv Syst. 2013 Jan;29(1):159-62
Authors: Fadzli F, Ramli NM, Rahmat K, Ganesan D
BACKGROUND: Intraventricular haemorrhage is the most common cause of hydrocephalus in a pre-term baby and may require surgical intervention depending on severity.
CLINICAL CASE: This case illustrates foraminal septae as a subtle cause of progressive quadriventricular hydrocephalus in a child born pre-term with a history of grade III intraventricular haemorrhage. The septae within the fourth ventricular exits were clearly demonstrated with 3D-FIESTA (fast imaging employing steady-state acquisition) MRI acquisitions and assisted in differentiation from communicating hydrocephalus. This finding guided the decision to a successful endoscopic third ventriculostomy.
CONCLUSION: 3D-FIESTA sequence is recommended for investigating children with hydrocephalus secondary to intraventricular haemorrhage due to its diagnostic potential and implications on surgical technique.
PMID: 22996826 [PubMed - in process]
Surgical resection of pediatric skull base meningiomas.
Childs Nerv Syst. 2013 Jan;29(1):83-7
Authors: Burkhardt JK, Neidert MC, Grotzer MA, Krayenbühl N, Bozinov O
PURPOSE: Meningiomas in children are rare, especially those located at the skull base. In this study, we report our experience of meningioma surgery in the pediatric population and compare our findings of skull base (SB) versus non-skull base (NSB) meningiomas.
METHODS: From our database of 724 surgically treated meningioma patients at the University Hospital, Zurich between 1995 and 2010, 12 patients under 18 years of age were identified. Data for those patients was retrospectively collected through chart review. A descriptive comparison between SB and NSB meningiomas was undertaken to determine statistical significance.
RESULTS: In all 12 children (seven males, five females; mean age 12.2?±?4.3 years), surgical removal of the meningioma was performed microsurgically with a mean follow-up of 53 months (range 12-137 months). Of the 12 tumors, six were located in the SB and six in the NSB. Comparing SB to NSB lesions, the mean age was 11?±?3.8 versus 14?±?4.6 years, male/female gender distribution was 5:1 compared to 1:5, mean tumor size was 7.5?±?6.2 versus 26?±?15.8 cm(2) (p?=?0.03), and mean surgery time was 347 versus 214 min. While WHO grade was similar for both groups, the Simpson grade revealed more extensive resection for NSB meningiomas. The Glasgow Outcome Scale at last follow-up was favorable for both groups.
CONCLUSIONS: Meningioma surgery was safe with favorable outcomes. SB meningiomas were significantly smaller in size, were less likely to undergo complete resection, and had a predilection for younger, male patients.
PMID: 22972400 [PubMed - in process]
Clinical outcome and predictors of survival and pneumonitis after stereotactic ablative radiotherapy for stage I non-small cell lung cancer.
Radiat Oncol. 2012;7:152
Authors: Chang JY, Liu H, Balter P, Komaki R, Liao Z, Welsh J, Mehran RJ, Roth JA, Swisher SG
BACKGROUND: Stereotactic ablative radiotherapy (SABR) can achieve excellent local control rates in early-stage non-small cell lung cancer (NSCLC) and has emerged as a standard treatment option for patients who cannot undergo surgery or those with isolated recurrences. However, factors that may predict toxicity or survival are largely unknown. We sought here to identify predictors of survival and pneumonitis after SABR for NSCLC in a relatively large single-institution series.
METHODS: Subjects were 130 patients with stage I NSCLC treated with four-dimensional computed tomography (4D CT) -planned, on-board volumetric image-guided SABR to 50?Gy in 4 fractions. Disease was staged by positron emission tomography/computed tomography (PET/CT) and scans were obtained again at the second follow-up after SABR.
RESULTS: At a median follow-up time of 26?months, the 2-year local control rate was 98.5%. The median overall survival (OS) time was 60?months, and OS rates were 93.0% at 1?year, 78.2% at 2?years, and 65.3% at 3?years. No patient experienced grade 4-5 toxicity; 15 had radiation pneumonitis (12 [9.3%] grade 2 and 3 [2.3%] grade 3). Performance status, standardized uptake value (SUV)max on staging PET/CT, tumor histology, and disease operability were associated with OS on univariate analysis, but only staging SUV(max) was independently predictive on multivariate analysis (P?=?0.034). Dosimetric factors were associated with radiation pneumonitis on univariate analysis, but only mean ipsilateral lung dose ? 9.14?Gy was significant on multivariate analysis (P?=?0.005).
CONCLUSIONS: OS and radiation pneumonitis after SABR for stage I NSCLC can be predicted by staging PET SUV(max) and ipsilateral mean lung dose, respectively.
PMID: 22963661 [PubMed - in process]
Massive cystic dilatation within a tethered filum terminale causing cauda equina compression and mimicking syringomyelia in a young adult patient.
Childs Nerv Syst. 2013 Jan;29(1):141-4
Authors: Pencovich N, Ben-Sira L, Constantini S
BACKGROUND: The ventriculus terminalis (VT) is formed during early embryonic development of the spinal cord and can only be identified histologically in both children and adults. Cystic dilatation of the VT can be seen in young children, but it rarely persists through adulthood.
CLINICAL CASE: We describe a 27-year-old female with paraparesis secondary to a massive and tethered cystic dilatation of the VT mimicking syringomyelia. Symptoms appearing in early childhood were ignored, probably leading to the much prominent presentation in early adulthood. The preoperative presentation and surgical treatment are discussed in relation to childhood history.
CONCLUSIONS: Although extremely rare, symptomatic dilatation of the VT can be seen in young adults, usually with previous manifestations in early childhood. This entity should be considered while treating tethered cord spectrum.
PMID: 22961358 [PubMed - in process]
The intracranial arachnoid mater : a comprehensive review of its history, anatomy, imaging, and pathology.
Childs Nerv Syst. 2013 Jan;29(1):17-33
Authors: Adeeb N, Deep A, Griessenauer CJ, Mortazavi MM, Watanabe K, Loukas M, Tubbs RS, Cohen-Gadol AA
INTRODUCTION: The arachnoid mater is a delicate and avascular layer that lies in direct contact with the dura and is separated from the pia mater by the cerebrospinal fluid-filled subarachnoid space. The subarachnoid space is divided into cisterns named according to surrounding brain structures.
METHODS: The medical literature on this meningeal layer was reviewed in regard to historical aspects, etymology, embryology, histology, and anatomy with special emphasis on the arachnoid cisterns. Cerebrospinal fluid dynamics are discussed along with a section devoted to arachnoid cysts.
CONCLUSION: Knowledge on the arachnoid mater and cerebrospinal fluid dynamics has evolved over time and is of great significance to the neurosurgeon in clinical practice.
PMID: 22961357 [PubMed - in process]
Improved heart rate dynamics in patients undergoing percutaneous renal denervation.
J Clin Hypertens (Greenwich). 2012 Sep;14(9):654-5
Authors: Himmel F, Weil J, Reppel M, Mortensen K, Franzen K, Ansgar L, Schunkert H, Bode F
PMID: 22947367 [PubMed - in process]
Symptomatic epileptic spasms in clusters without hypsarrhythmia: surgical management of two cases.
Childs Nerv Syst. 2013 Jan;29(1):145-8
Authors: Caraballo RH, Flesler S, Noli D, Soraru A, Cersósimo R, Bartuluchi M
PMID: 22843175 [PubMed - in process]
Craniofacial surgical strategies for the correction of pneumosinus dilatans frontalis.
J Craniomaxillofac Surg. 2013 Jan;41(1):28-33
Authors: Galiè M, Consorti G, Clauser LC, Kawamoto HK
INTRODUCTION: Pneumosinus dilatans is a rare condition and different techniques have been proposed for its management and correction. The abnormally expanded, aerated frontal sinus has been described in the literature as: frontal sinus hypertrophy, pneumosinus dilatans, pneumosinus frontalis, aerocele, pneumocele, sinus ectasia, hyperpneumatization and others. The precise aetiology and pathogenesis of the condition is unknown, although several basic hypotheses have been proposed
MATERIAL AND METHODS: The authors report two cases of frontal bossing and supraorbital ridge deformity correction using craniofacial surgical principles.
DISCUSSION: Functional and morphological results are discussed and compared with other open procedures.
CONCLUSION: A variety of surgical procedures have been proposed for the correction of the pneumosinus dilatans frontalis. The craniofacial approach is advocated to reproduce the normal anatomy of the forehead in the upper part, the supraorbital rim and glabellar area.
PMID: 22795165 [PubMed - in process]
Health-related quality of life and cost-effectiveness of treatment in subarachnoid haemorrhage.
Eur J Neurol. 2012 Nov;19(11):1455-61
Authors: Malmivaara K, Juvela S, Hernesniemi J, Lappalainen J, Siironen J
BACKGROUND: Treatment of aneurysmal subarachnoid haemorrhage (SAH) demands high healthcare resource utilization. Case fatality and disability remain as common outcomes of SAH. The purpose of this study was to perform a treatment cost-effectiveness analysis of patients with SAH.
METHODS: We performed a long-term follow-up of the SAH patients treated in our institution over a 3-year period starting February 1998. Outcome 10 years after the SAH and treatment costs were evaluated. The health-related quality of life was evaluated using the EuroQol (EQ-5D) questionnaire and visual-analogue scale (VAS). The cost of a quality-adjusted life year (QALY) was calculated.
RESULTS: Median follow-up time of the 178 patients was 10.8 years. Overall mortality rate was 24%. Of the 43 non-survivors, 42% died within 6 months. For the 135 survivors, the median EQ-5D index value was 1.00, which is similar to that for normal population. The median VAS value was 80, which is comparable to normal population's value. Of the survivors, 88% (119/135) were able to live at home and 63% (85/135) returned to work after SAH. The cost of neurosurgical treatment for one QALY was 1700?.
CONCLUSION: Long-term outcome of survivors after aneurysmal SAH was relatively good: most of them lived at home, 63% had returned to work and 36% were still working. The quality of life index of the survivors was similar to that of normal populations, and the survivors were as satisfied with their health as people in general are. Cost of neurosurgical treatment and cost of a QALY gained were acceptable.
PMID: 22591408 [PubMed - in process]
Patterns of imaging failures in glioblastoma patients treated with chemoradiation: a retrospective study.
Med Oncol. 2012 Sep;29(3):2040-5
Authors: Pan H, Alksne J, Mundt AJ, Murphy KT, Cornell M, Kesari S, Lawson JD
Glioblastoma multiforme (GBM) is the most common primary brain tumor of adults and carries a poor prognosis. This study sought to investigate recurrence patterns of GBM treated with temozolomide-based chemoradiation. Records for 31 patients treated for newly diagnosed GBM between 2007 and 2009 were retrospectively analyzed. Ten patients received maximal surgical resection followed by conventionally fractionated radiation (CFR) to a median dose of 60 Gy with concurrent and planned adjuvant temozolomide. Twelve patients were treated with maximal surgical debulking, intracavitary brachytherapy (ICB), and external beam radiation therapy with concurrent and planned adjuvant temozolomide. The remaining 9 patients had unresectable disease and underwent biopsy followed by a hypofractionated course of radiation to a median dose of 60 Gy over 10 fractions. Tumor failure was classified as local, marginal, or distant according to whether the recurrence was completely inside, crossed, or completely outside the 100% isodose line. With a median follow-up of 12.6 months, 5 patients were lost to follow-up, while the remaining 26 patients (100%) developed recurrent disease. The first failures totaled 29 discrete lesions, of which 15 (52%), 6 (21%), and 8 (28%) were local, marginal, and distant failures at median times of 6.8, 10.1, and 7.9 months, respectively. Marginal or distant failure was more likely in ICB patients as compared to CFR patients. While local failure predominated, distant failures were not uncommon, particularly at later time points. As local control of GBM improves, further study is needed to identify and appropriately treat patients susceptible to distant failure.
PMID: 22108847 [PubMed - in process]
Overexpression of a disintegrin and metalloprotease 8 in human gliomas is implicated in tumor progression and prognosis.
Med Oncol. 2012 Sep;29(3):2032-7
Authors: He S, Ding L, Cao Y, Li G, Deng J, Tu Y, Wang B
A disintegrin and metalloprotease 8 (ADAM8) has been shown to be expressed in various cancer types, and its expression was associated with advanced progression of several tumors. However, little is known about ADAM8 in human gliomas. Therefore, we here evaluated the correlation of ADAM8 expression with the clinicopathological features and prognosis in the patients with gliomas. Immunohistochemistry and western blot were used to investigate the expression of ADAM8 protein, respectively, in 128 patients with gliomas. The expression levels of ADAM8 in glioma tissues were significantly higher (P = 0.002) than those in non-neoplastic brain tissues according to the immunohistochemistry analysis. In addition, a high level of ADAM8 expression was significantly more common in glioma tissues with advanced grade than those with low grade (P = 0.01), which were in line with the results of western blot analysis (P = 0.01). Moreover, the increased expression of ADAM8 was significantly correlated with low Karnofsky performance score (KPS) (P = 0.008), frequent intra-tumor necrosis (P = 0.01), and poor overall survival (P = 0.008). Furthermore, multivariate analysis identified the expression levels of ADAM8 (P = 0.01) and intra-tumor necrosis (P = 0.03) to be independent prognostic factors. These findings suggest for the first time that ADAM8 is frequently overexpressed in human gliomas and is closely associated with poor clinical outcome.
PMID: 21983884 [PubMed - in process]
Cerebral Wegener's granuloma: surgery mandatory for diagnosis and treatment.
Case Rep Neurol Med. 2013;2013:750391
Authors: Nicolosi F, Nodari G, Spena G, Roca E, Migliorati K, Esposito G, Stefini R, Fontanella M, Panciani PP
The involvement of the central nervous system in case of Wegener granulomatosis (WG) is infrequent and usually leads to cranial nerve abnormalities, cerebrovascular events, and seizures. Meningeal involvement is quite rare and usually is due to the spreading from adjacent disease in the skull base. We described the case of a remote intraparenchymal Wegener's granuloma in a 55-year-old man presenting with seizures and a history of severe generalized WG. The radiological findings were not useful for the diagnosis, and the pharmacological treatment was ineffective. The importance of a surgery in case of localized WG has been emphasized, in order to confirm the diagnosis and to avoid additional medicaments, like antiepileptic drugs, potentially harmful in immunosuppressed patients.
PMID: 23762680 [PubMed - in process]
Glioma stem cells and immunotherapy for the treatment of malignant gliomas.
ISRN Oncol. 2013;2013:673793
Authors: Toda M
Stem cell research has led to the discovery of glioma stem cells (GSCs), and because these cells are resistant to chemotherapy and radiotherapy, analysis of their properties has been rapidly pursued for targeted treatment of malignant glioma. Recent studies have also revealed complex crosstalk between GSCs and their specialized environment (niche). Therefore, targeting not only GSCs but also their niche may be a principle for novel therapies of malignant glioma. One possible novel strategy for targeting GSCs and their niches is immunotherapy with different antitumor mechanism(s) from those of conventional therapy. Recent clinical studies of immunotherapy using peptide vaccines and antibodies have shown promising results. This review describes the recent findings related to GSCs and their niches, as well as immunotherapies for glioma, followed by discussion of immunotherapies that target GSCs for the treatment of malignant glioma.
PMID: 23762610 [PubMed - in process]
NFAT1 Is Highly Expressed in, and Regulates the Invasion of, Glioblastoma Multiforme Cells.
PLoS One. 2013;8(6):e66008
Authors: Tie X, Han S, Meng L, Wang Y, Wu A
Members of the nuclear factor of activated T cells (NFAT) family have been identified as regulators of oncogenic transformation in several human malignancies. A prominent member of this family, NFAT1, is associated with tumor cell survival, apoptosis, migration and invasion. Here, we investigated the role of NFAT1 in glioma cells. In 111 clinical samples, microarray analysis demonstrated that NFAT1 was over-expressed in glioblastoma multiforme (GBM), compared with low-grade gliomas, a result confirmed by RT-PCR in 24 clinical samples and in the U87 and U251 cell lines. Immunohistochemistry and immunofluorescence stain indicated that over-expressed NFAT1 was mainly located in the nucleus, where it acted as a transcription factor. After treatment with the NFAT antagonist cyclosporin A (CsA) and FK506, levels of NFAT1 in the nuclei of U87 GBM cells were dramatically reduced. The invasive potential of U87 cells was reduced by the same treatment, as well as by inhibition of NFAT1 expression using small hairpin RNA. Proliferation of U87 cells was unaffected by CsA, FK506 and NFAT1 shRNA transfection. Clustering analysis and Pearson correlation analysis of microarray data showed that the expression of NFAT1 correlated with the expression of the invasion-related genes cyclooxygenase-2 (COX-2), matrix metalloproteinase-7 (MMP-7) and MMP-9, a result confirmed by in vitro analysis. These findings demonstrate that NFAT1 contributes to the invasive potential but not the proliferation of GBM cells, and suggest that CsA may find application as an adjuvant in combined treatment strategies for GBM.
PMID: 23762456 [PubMed - in process]
Sensorimotor cortical changes assessed with resting-state fMRI following total brachial plexus root avulsion.
J Neurol Neurosurg Psychiatry. 2013 Jun 12;
Authors: Qiu TM, Chen L, Mao Y, Wu JS, Tang WJ, Hu SN, Zhou LF, Gu YD
OBJECTIVE: Peripheral nerve injury can induce immediate and long-standing remodelling of the brain cortex, which may affect outcomes of nerve repair. This study examined changes of corresponding cortical representations in patients with brachial plexus injuries. METHODS: Resting-state fMRI was acquired for 13 adult patients with total brachial plexus root avulsion, three of whom underwent second scans 7 or 8 months later. The time of examination ranged from 1 to 16 months after injuries. Nine healthy adults were enrolled as control. Seed-based functional connectivity was performed for all subjects. RESULTS: For nine patients whose first fMRI was performed from 1 to 4 months after brachial plexus injuries, images showed that their cortical maps of sensorimotor areas corresponding to the hand and arm in the hemisphere contralateral to the injured side had much weaker correlation with the supplementary motor area (SMA) than those ipsilateral to the injured side. Symmetrical maps of bilateral cortical sensorimotor areas corresponding to the hand and arm were observed in other four cases with fMRI tested from 7 to 16 months after injuries. For three of the nine patients with asymmetrical cortical representations, second scans indicated symmetric results or even stronger correlation with SMA in the cerebral cortex contralateral to the injured side. CONCLUSIONS: Total brachial plexus root avulsion causes cortical representations of the brachial plexus to undergo a change from an inactive to an active state. This implies that peripheral deafferentation after brachial plexus injuries will induce corresponding cortical representations to be occupied by adjacent non-deafferented cortical territories.
PMID: 23761913 [PubMed - as supplied by publisher]
Activation of NF-?B in Schwann Cells Is Dispensable for Myelination In Vivo.
J Neurosci. 2013 Jun 12;33(24):9932-6
Authors: Morton PD, Dellarole A, Theus MH, Walters WM, Berge SS, Bethea JR
Peripheral myelination is a dynamic process orchestrated by axons and Schwann cells. Although the signaling mechanisms governing myelination are not fully understood, NF-?B activation in Schwann cells has been implicated as a key regulator in vitro. Using a mouse model, we show that nuclear factor ?B activation in Schwann cells is not required for myelination in vivo.
PMID: 23761888 [PubMed - in process]
Expression of brain-specific angiogenesis inhibitor 1 is inversely correlated with pathological grade, angiogenesis and peritumoral brain edema in human astrocytomas.
Oncol Lett. 2013 May;5(5):1513-1518
Authors: Wang W, DA R, Wang M, Wang T, Qi L, Jiang H, Chen W, Li Q
As the most common intracranial malignant neoplasms, astrocytomas are characterized by high neovascularization and severe peritumoral brain edema (PTBE). Angiogenesis is a prerequisite for the growth of solid tumors, including astrocytoma, and brain-specific angiogenesis inhibitor 1 (BAI1) is a novel angiogenesis inhibitor. In the present study, the expression levels of BAI1, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were investigated using immunohistochemical methods in 90 human brain astrocytoma specimens of various pathological grades and in 11 normal human brain tissues. Vascular endothelial cells were stained for CD105 and the microvessel density (MVD) was assessed. The volume of astrocytoma and PTBE in each case was evaluated by magnetic resonance imaging (MRI). The results showed that BAI1 was highly expressed in the normal brain tissues, but that the expression decreased with the rising pathological grades of astrocytoma, MVD number and PTBE, indicating that BAI1 expression was inversely correlated with these factors. Furthermore, it was observed that the expression of VEGF and bFGF were inversely correlated with BAI1 expression in the human brain astrocytomas. These results indicate that the BAI1 gene may be used as a marker of decreased tumor progression and tumoral neovascularization, as well as PTBE.
PMID: 23761815 [PubMed - as supplied by publisher]
Chemotherapy for gliomas in mainland China: An overview.
Oncol Lett. 2013 May;5(5):1448-1452
Authors: Sai K, Yang QY, Shen D, Chen ZP
Chemotherapy is currently the standard treatment modality for malignant gliomas. Many patients with gliomas are treated in mainland China every year. The history and development of chemotherapy for glioma, however, are not well documented. In this study, an extensive literature search of Pubmed and major Chinese electronic databases was performed to identify clinical studies. A total of 210 publications were identified, with a total of 10,105 patients. Among these studies, 76.2% were retrospective and 23.8% were prospective. Chemotherapy was found to have been administered by the Department of Neurosurgery in 143 studies (68.1%). Oral or intravenous administration was found in 55.7% of studies, followed by intra-arterial (26.7%) and interstitial (15.7%) chemotherapy. Nitrosoureas were the most frequently used chemotherapeutic agents, as found in 133 studies (63.3%). Since 2003, 56 studies on temozolomide (TMZ) have been published. Studies on chemotherapy for gliomas began in the 1970s in mainland China but well-designed randomized controlled trials (RCTs) are rare. Much effort and collaboration should be made to carry out high-quality multicenter RCTs on chemotherapy for gliomas.
PMID: 23761809 [PubMed - as supplied by publisher]
Can S100B Predict Cerebral Vasospasms in Patients Suffering from Subarachnoid Hemorrhage?
Front Neurol. 2013;4:65
Authors: Amiri M, Astrand R, Romner B
Background: Protein S100B has proven to be a useful biomarker for cerebral damages. Increased levels of serum and cerebrospinal fluid (CSF) S100B have been shown in patients suffering subarachnoid hemorrhage (SAH), severe head injury and stroke. In patients with SAH, the course of S100B levels has been correlated with neurological deficits and outcome. Cerebral vasospasm is a major contributor to morbidity and mortality. The primary aim of this study was to investigate the potential of S100B protein as a predictor of cerebral vasospasm in patients with severe SAH. Materials and Methods: Patients with SAH, Fisher grade 3 and 4, were included in the study. Five samples of CSF and serum S100B were collected from each patient. The first sample (baseline sample) was drawn within the first 3?days following ictus and the following four samples, once a day on days 5-8, with day of ictus defined as day 1. Clinical suspicion of cerebral vasospasm confirmed by computed tomography angiography was used to diagnose cerebral vasospasm. Results: A total of 18 patients were included. Five patients (28%) developed cerebral vasospasm, two (11%) developed ventriculitis. There were no significant differences between S100B for those with and without vasospasm. Serum S100B levels in patients with vasospasm were slightly lower within the first 5?days following ictus, compared to patients without vasospasm. Two out of five patients had elevated and increasing serum S100B prior to vasospasm. Only one showed a peak level of S100B 1?day before vasospasm could be diagnosed. Due to the low number of patients in the study, statistical significance could not be reached. Conclusion: Neither serum nor CSF S100B can be used as predictor of cerebral vasospasm in patients suffering from SAH.
PMID: 23761779 [PubMed - in process]
Blind endovascular catheterization and direct access of an occluded superior ophthalmic vein for treatment of carotid cavernous fistula.
BMJ Case Rep. 2013;2013
Authors: Alaraj A, Kim B, Oh G, Aletich V
We describe a case of an elderly patient who presented with right-sided ophthalmoplegia, proptosis, chemosis, and increased intraocular pressure. An angiogram showed feeding vessels from the bilateral internal and external carotid arteries. Our initial attempt to blindly probe the inferior petrosal sinus was unsuccessful. This was followed by a right anterior orbitotomy exposing the superior ophthalmic vein which was directly cannulated with an 18 gauge angiocatheter. However, a proximal third of the superior ophthalmic vein within the orbit which was thrombosed was probed blindly. The thrombosed vein was cannulated with a microcatheter to obtain coil embolization of the carotid cavernous fistula. The implications of the procedure are discussed, given that, to our knowledge, such an endeavor has never been performed.
PMID: 23761619 [PubMed - in process]