bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression and molecular changes in cerebral arteries following subarachnoid hemorrhage in the rat
Authors: Vikman Petter , Beg Saema , Khurana Tejvir , Hansen-Schwartz Jacob , Edvinsson Lars 
Published: January 2008

Object
The authors investigated early changes in the cerebral arteries of rats that occur after subarachnoid hemorrhage (SAH).

Methods
Messenger RNA was investigated by performing microarray and quantitative real-time polymerase chain reaction (PCR) analyses, and protein expression was shown by performing immunohistochemical studies. The array data indicated that the initial processes that occur after SAH involve activation of genes involved in angiogenesis, inflammation, and extracellular matrix (ECM) remodeling. The real-time PCR investigation confirmed upregulation of genes that were observed using the microarray to be regulated, including iNOS, MMP13, and cxcl2. The authors also verified the upregulation of previously implicated genes for G-protein–coupled receptors (endothelin B [ETB], angiotensin 1 [AT1], and AT2) and metalloproteinase 9. The results of an immunohistochemical study confirmed that receptor genes that were seen to be regulated produced an increase in protein expression. Double immunostaining of rat cerebral arteries with endothelial cell– or smooth-muscle cell–specific antibodies verified that an increase in ETB, 5-hydrotryptamine (5-HT1B), and 5-HT1D receptor expression occurs in smooth-muscle cells.

Conclusions
Processes occurring after SAH lead to enhanced arterial contractility and ECM remodeling either directly or through angiogenesis and inflammation. These processes are active via an increase in metalloproteinase expression, the presence of proangiogenic factors, and the expression of proinflammatory genes.
Gamma Knife surgery for metastatic brain tumors from renal cell carcinoma
Authors: Shuto Takashi , Inomori Shigeo , Fujino Hideyo , Nagano Hisato 
Published: January 2008

Object
The authors evaluated the results of Gamma Knife surgery (GKS) for the treatment of metastatic brain tumors from renal cell carcinoma (RCC).

Methods
The authors conducted a retrospective review of the clinical characteristics and treatment outcomes in 69 patients with metastatic brain tumors from RCC who underwent GKS at the authors’ institution. Fifty-one patients were men, and 18 were women. The mean patient age was 64.2 years (range 45–85 years).
The 69 patients underwent a total of 104 GKS procedures for treatment of 314 tumors. Eighteen patients received repeated GKS. Follow-up magnetic resonance (MR) imaging was used at a mean of 7.1 months after GKS to evaluate the change in 132 tumors after treatment. The mean prescription dose at the tumor margin was 21.8 Gy. The tumor growth control rate was 82.6%. Tumor volume and the delivered peripheral dose were significantly correlated with tumor growth control on univariate and multivariate analyses. Sixty (45.5%) of the 132 tumors assessed with MR imaging were associated with apparent peritumoral edema at the time of GKS. After treatment, peritumoral edema disappeared in 27 tumors, decreased in 13, was unchanged in 16, and progressed in four. Newly developed peritumoral edema after GKS was rare. The delivered peripheral dose was significantly correlated with control of peritumoral edema. The overall median survival time after GKS was 9.5 months. In this study, 34 patients died of systemic disease and 10 died of progressive brain metastases. Multivariate analysis showed that the number of lesions at the first GKS, the Karnofsky Performance Scale score at the first GKS, the recursive partitioning analysis classification, and the interval from diagnosis of RCC to brain metastasis were significantly correlated with survival time.

Conclusions
Gamma Knife surgery is effective for metastatic brain tumors from RCC. The disappearance rate of tumors is relatively low, but growth control is high. The delivered dose to the tumor margin is significantly correlated with the control of peritumoral edema. Gamma Knife surgery should be used as the initial treatment modality, if possible, even in patients with multiple metastases. Repeated GKS is recommended for newly developed brain metastases because of the low sensitivity of RCC to conventional radiation therapy.
Microhemorrhage, a possible mechanism for cyst formation in vestibular schwannomas
Authors: Park Chul-Kee , Kim Dong-Chul , Park Sung-Hye , Kim Jeong Eun , Paek Sun Ha , Kim Dong Gyu , Jung Hee-Won 
Published: January 2008

Object
Cystic vestibular schwannoma (VS) is a unique subgroup of VSs characterized by unpredictable expansion of the cyst component. Little is known, however, about the mechanism of cyst formation. In this study the authors compared neuroimaging and histological characteristics of cystic with solid VS to determine the pathogenesis of the cystic subgroup.

Methods
Two cohorts, one comprising 10 patients with cystic VS and the other comprising 10 patients with solid VS, were studied. Surgery was chosen as the primary treatment in all patients, with no other modality applied. Preoperative magnetic resonance images and histological characteristics of the tumor in patients with cystic VSs were evaluated and compared with those in the group with solid VSs. Differences between the two groups were assessed using the chi-square test. Neuroimaging findings revealed that either fluid-fluid level or hemosiderin deposit was present in all cystic VSs. Histological evidence of microhemorrhage, such as hemosiderinladen macrophages (p = 0.069), hemosiderin deposits (p = 0.019), thrombotic vessels (p = 0.008), and abnormal vessel proliferation (p = 0.006) were more prominent in cystic VSs compared with solid ones. There was no difference in Antoni type dominance and Ki-67 proliferative index between the two groups.

Conclusions
Intratumoral microhemorrhage is a possible mechanism of pathogenesis in cystic VS.
Preclinical evaluation of the neuroprotective effect of soluble complement receptor Type 1 in a nonhuman primate model of reperfused stroke
Authors: Mocco J , Mack William J. , Ducruet Andrew F. , King Ryan G. , Sughrue Michael E. , Coon Alexander L. , Sosunov Sergei A. , Sciacca Robert R. , Zhang Yuan , Marsh Henry C. , Pinsky David J. , Connolly E. Sander 
Published: January 2008

Object
Postischemic cerebral inflammatory injury has been extensively investigated in an effort to develop effective neuroprotective agents. The complement cascade has emerged as an important contributor to postischemic neuronal injury. Soluble complement receptor Type 1 (sCR1), a potent inhibitor of complement activation, has been shown to reduce infarct volume and improve functional outcome after murine stroke. Given numerous high-profile failures to translate promising antiinflammatory strategies from the laboratory to the clinic and given the known species-specificity of the complement cascade, the authors sought to evaluate the neuroprotective effect of sCR1 in a nonhuman primate model of stroke.

Methods
A total of 48 adult male baboons (Papio anubis) were randomly assigned to receive 15 mg/kg of sCR1 or vehicle. The animals were subjected to 75 minutes of middle cerebral artery occlusion/reperfusion. Perioperative blood samples were analyzed for total complement activity by using a CH50 assay. Infarct volume and neurological scores were assessed at the time the animals were killed, and immunohistochemistry was used to determine cerebral drug penetration and C1q deposition. An interim futility analysis led to termination of the trial after study of 12 animals. Total serum complement activity was significantly depressed in the sCR1-treated animals compared with the controls. Immunostaining also demonstrated sCR1 deposition in the ischemic hemispheres of treated animals. Despite these findings, there were no significant differences in infarct volume or neurological score between the sCR1- and vehicle-treated cohorts.

Conclusions
A preischemic bolus infusion of sCR1, the most effective means of administration in mice, was not neuroprotective in a primate model. This study illustrates the utility of a translational primate model of stroke in the assessment of promising antiischemic agents prior to implementation of large-scale clinical trials.
Risk of cerebral vasopasm after subarachnoid hemorrhage reduced by statin therapy: a multivariate analysis of an institutional experience
Authors: McGirt Matthew J. , Blessing Robert , Alexander Michael J. , Nimjee Shahid M. , Woodworth Graeme F. , Friedman Allan H. , Graffagnino Carmelo , Laskowitz Daniel T. , Lynch John R. 
Published: January 2008

Object
Impairment of endothelial nitric oxide synthase (eNOS), endothelium-dependent relaxation, and cerebrovascular autoregulation all occur in vasospastic cerebral arteries following subarachnoid hemorrhage (SAH). The 3-hy-droxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, both improve endothelial function and increase eNOS messenger RNA, protein, and enzymatic activity threefold. Increasing experimental evidence in animal models of SAH suggests that statins may ameliorate cerebral vasospasm. The authors hypothesized that patients chronically treated with statins would have a decreased risk of symptomatic vasospasm after SAH.

Methods
The authors retrospectively reviewed the charts of 115 patients with SAH who were consecutively admitted to the Neuroscience Intensive Care Unit of Duke University between 1998 and 2001. The independent association of statin therapy to symptomatic vasospasm was assessed using multivariate logistic regression analysis. Fifteen patients (13%) admitted with SAH were receiving statin therapy for at least 1 month before admission. Forty-nine patients (43%) experienced symptomatic vasospasm a mean of 5.8 ± 3 days after onset of SAH. Current statin therapy on admission (odds ratio [OR] 0.09, 95% confidence interval [CI] 0.01–0.77) was independently associated with an 11-fold reduction in the risk of symptomatic vasospasm. Fisher Grade 3 SAH (OR 2.82, 95% CI 1.50–5.71) and rupture of anterior cerebral or internal carotid artery aneurysm (OR 3.77, 95% CI 1.29–10.91) were independently associated with an increased risk of symptomatic vasospasm.

Conclusions
In this retrospective case series, patients who received statin therapy for at least 1 month demonstrated an 11-fold decrease in the risk of developing symptomatic vasospasm after SAH.
Radiosurgical treatment for rolandic arteriovenous malformations
Authors: Andrade-Souza Yuri M. , Ramani Meera , Scora Daryl , Tsao May N. , terBrugge Karel , Schwartz Michael L. 
Published: January 2008

Object
The authors reviewed the radiosurgical outcomes in patients with arteriovenous malformations (AVMs) located in the rolandic area, including the primary motor and sensory gyri.

Methods
The study population consisted of 38 patients with rolandic-area AVMs who underwent linear accelerator radiosurgery at the University of Toronto between 1989 and 2000. Obliteration rate, risk of hemorrhage during the latency period, radiation-induced complications, seizure control, and functional status were evaluated. Patients were also divided into two subgroups according to AVM volume (< 3 cm3 and ≥ 3 cm3).
Patients were followed up for a median of 42.4 months (range 30–103 months), and the median age of the patients was 40 years (range 12–67 years). The median AVM volume was 8.1 cm3 (range 0.32–21, mean 8.32 cm3), and the median dose at the tumor margin was 15 Gy (range 15–22, mean 16.8 Gy). The risk of hemorrhage after radiosurgery was 5.3% for the 1st year, 2.6% for the 2nd, and 0% for the 3rd. Two patients (5.3%) sustained adverse effects related to radiation for more than 6 months. Complete nidus obliteration after a single radiosurgical treatment was achieved in 23 patients (60.5%). The obliteration rate for AVMs smaller than 3 cm3 was 83.3% (10 of 12) and that for AVMs larger than or equal to 3 cm3 was 50% (13 of 26). Among the patients who had seizures as the initial presentation, 51.8% were free of seizures after radiosurgery and the seizure pattern improved in 40.7% during the 3rd and last year of follow up. Overall, excellent results (obliteration and no new or worsening neurological deficit) can be achieved in approximately 60% of patients. This percentage varies according to the AVM size and can reach 83% in patients with AVMs smaller than 3 cm3.

Conclusions
Radiosurgery is a safe and effective treatment for people with rolandic AVMs. The low rate of morbidity associated with radiosurgery, compared with other treatments, indicates that this method may be the first choice for patients with AVMs located in this area.
Does dose rate affect efficacy? The outcomes of 256 Gamma Knife surgery procedures for trigeminal neuralgia and other types of facial pain as they relate to the half-life of cobalt
Authors: Balamucki Christopher J. , Stieber Volker W. , Ellis Thomas L. , Tatter Stephen B. , DeGuzman Allan F. , McMullen Kevin P. , Lovato James , Shaw Edward G. , Ekstrand Kenneth E. , Bourland J. Daniel , Munley Michael T. , Robbins Michael , Branch Charles 
Published: January 2008

Object
Gamma Knife surgery (GKS) is a treatment option for patients with refractory typical trigeminal neuralgia (TN), TN with atypical features, and atypical types of facial pain. The Gamma Knife’s 201 60Co sources decay with a half-life of 5.26 years. The authors examined whether the decrease in dose rate over 4.6 years between Co source replacements affected the control rates of facial pain in patients undergoing GKS.

Methods
The authors collected complete follow-up data on 239 of 326 GKS procedures performed in patients with facial pain. Patients were classified by their type of pain. The isocenter of a 4-mm collimator helmet was targeted at the proximal trigeminal nerve root, and the dose (80–90 Gy) was prescribed at the 100% isodose line. Patients reported the amount of pain control following radiosurgery by answering a standardized questionnaire.
Eighty percent of patients experienced greater than 50% pain relief, and 56% of patients experienced complete pain relief after GKS. Neither dose rate nor treatment time was significantly associated with either the control rate or degree of pain relief. A significant association between the type of facial pain and the pain control rate after GKS was observed (p < 0.001; Pearson chi-square test).
In their statistical analysis, the authors accounted for changes in prescription dose over time to prevent the dose rate from being a confounding variable. There was no observable effect of the dose rate or of the treatment duration within the typical period to source replacement.

Conclusions
Patients with facial pain appear to receive consistent treatment with GKS at any time during the first half-life of the Co sources.
Genetic profiling of a distant second glioblastoma multiforme after radiotherapy: recurrence or second primary tumor?
Authors: van Nifterik Krista A. , Elkhuizen Paula H. M. , van Andel Rob J. , Stalpers Lukas J. A. , Leenstra Sieger , Lafleur M. Vincent M. , Vandertop W. Peter , Slotman Ben J. , Hulsebos Theo J. M. , Sminia Peter 
Published: January 2008

Object
In nearly all patients with glioblastoma multiforme (GBM) a local recurrence develops within a short period of time. In this paper the authors describe two patients in whom a second GBM developed after a relatively long time interval at a site remote from the primary tumor. The genetic profiles of the tumors were compared to discriminate between distant recurrence and a second primary tumor.

Methods
Both patients harboring a supratentorial GBM were treated with surgery and local high-dose radiotherapy. Local control of the disease at the primary tumor site was achieved. Within 2 years, a second GBM developed in both patients, not only outside the previously irradiated target areas but infratentorially in one patient and in the opposite hemisphere in the other. The tumors were examined for the presence of several genetic alterations that are frequently found in GBMs—a loss of heterozygosity at chromosome regions 1p36, 10p15, 19q13, and 22q13, and at the CDKN2A, PTEN, DMBT1, and TP53 gene regions; a TP53 mutation; and EGFR amplification.
In the first patient, genetic profiling revealed that the primary tumor had an allelic imbalance for markers in several chromosome regions for which the second tumor displayed a complete loss. In the second patient, genetic profiling demonstrated the presence of genetic changes in the second tumor that were identical with and additional to those found in the primary tumor.

Conclusions
Based on the similarities between the genetic profiles of the primary and the second tumors in these patients, the authors decided that in each case the second distant GBM was a distant recurrence rather than a second independent primary tumor.
Physiological and clinical advantages of median nerve fascicle transfer to the musculocutaneous nerve following brachial plexus root avulsion injury
Authors: Nath Rahul K. , Lyons Andrew B. , Bietz Gabriel 
Published: January 2008

Object
Loss of biceps muscle function is a significant disability after brachial plexus root avulsion injuries. Nerve grafting techniques to reestablish anatomical and functional continuity between the spinal cord and the avulsed root have not proven successful. Using nerve transfers for functional restoration of root avulsion injuries appears to be effective and has physiological advantages for reducing regeneration distances. Since the early 1990s, the Oberlin technique of transferring ulnar nerve fascicles to the motor branch of the musculocutaneous nerve has been the preferred operative technique for reinnervation and restoration of biceps muscle function. In the current study the authors examine the efficacy of an alternative technique using median nerve fascicles transferred to the musculocutaneous nerve to reinnervate the biceps muscle.

Methods
Forty consecutive patients with combined C5–6 brachial plexus root avulsions were evaluated pre- and postoperatively according to the British Medical Research Council Motor Grading Scale. Personal interviews concerning quality of life (QOL) after surgery were conducted and scored based on standards set by the World Health Organization. All patients showed some degree of improvement in biceps muscle function. Thirty-six (90%) of the 40 patients regained movement against gravity. The patients had a 77% improvement in overall QOL after the surgery; most notably, 92% of the patients reported their lack of need for medication and 75% a significant lessening of postoperative pain. Redirection of part of the healthy median nerve resulted in no measurable functional deficits, and only 28 patients reported minor sensory disturbances in the first web space for an average of 3 months after surgery.

Conclusions
Median nerve fascicle transfer resulted in a significant improvement in biceps muscle function with an acceptable level of morbidity and should be considered an effective, and in many cases preferable, alternative to ulnar nerve fascicle transfer.
Resection of benign sciatic notch dumbbell-shaped tumors
Authors: Spinner Robert J. , Endo Toshiki , Amrami Kimberly K. , Dozois Eric J. , Babovic-Vuksanovic Dusica , Sim Franklin H. 
Published: January 2008

Object
The operative management of combined intrapelvic and extrapelvic sciatic notch dumbbell-shaped tumors is challenging. The relatively rare occurrence of these tumors and the varied extent of disease have made it difficult for surgeons to establish definitive surgical indications or predict favorable neurological outcomes based on preoperative imaging data.

Methods
In the past 3 years, the authors treated five patients presenting with radiating leg pain as a result of benign sciatic notch dumbbell-shaped tumors. These tumors in three patients with unilateral leg symptoms were considered unresectable by other neurosurgeons because of presumed direct intrinsic neural involvement. After high-resolution magnetic resonance (MR) imaging demonstrated that the extensive tumors were separate from the sciatic nerve and the lumbosacral plexus, however, these patients underwent a combined one-stage transabdominal and posterior transgluteal complete resection. Normal neurological status was maintained postoperatively in these three patients, and after more than 1 year of postoperative follow up, there were no tumor recurrences.
In two patients with bilateral symptoms and extensive tumor burden, serial MR images showed that innumerable tumors directly involved the entire cross-sectional area of the sciatic nerves and extended longitudinally to the lumbosacral plexuses. Tumor debulking or resection in these patients would have resulted in neurological deficits and would not have addressed their neuropathic pain, and therefore no surgery was performed. These two patients were treated pharmacologically and advised to monitor their tumor status over the course of their lifetimes in case of malignant transformation of the tumor.

Conclusions
A combined one-stage transabdominal and transgluteal approach allows safe resection of selected benign but extensive sciatic notch tumors. High-resolution MR imaging is a useful tool in the management of these tumors because it allows the surgeon to visualize the anatomical relationships of the tumor to the sciatic nerve. The authors believe that as this imaging technology advances, it will provide surgeons with a method to predict definitively which sciatic notch tumors displace rather than directly involve the sciatic nerve, and therefore indicate which tumors can be resected safely and completely.
Effects of ethanol on limited resuscitation in a model of traumatic brain injury and hemorrhagic shock
Authors: Zink Brian J. , Stern Susan A. , McBeth Brian D. , Wang Xu , Mertz Michelle 
Published: January 2008

Object
Limited resuscitation following uncontrolled hemorrhagic shock (HS) has been associated with improved outcomes in various animal models, although it has not been previously studied in the setting of traumatic brain injury (TBI) and ethanol intoxication. The aim of the present study was to determine the effects of ethanol intoxication in a model of experimental TBI and HS treated with limited resuscitation.

Methods
After induction of anesthesia and the placement of instruments, swine were subjected to a fluid-percussion injury of 3 atm. Simultaneously, hemorrhage was induced from an arterial catheter via a computerized roller pump to a mean arterial blood pressure (MABP) of 50 mm Hg, at which time uncontrolled hemorrhage was induced by the creation of an aortic tear. When the MABP decreased to 30 mm Hg, limited resuscitation to a MABP of 60 mm Hg was begun. After 60 minutes, animals were aggressively resuscitated to baseline MABP levels. Two groups of animals were studied: those receiving tap water by gastrostomy tube and those receiving ethanol (4 g/kg) by gastrostomy tube. Animals were monitored for 180 minutes after TBI. Hemorrhage volumes were significantly greater in ethanol-infused animals (mean ± standard deviation, 41 ± 34 mm Hg) compared with tap water–infused animals (17 ± 18 mm Hg; p = 0.048). Resuscitation requirements were significantly higher and metabolic parameters significantly worse in the ethanol group. Survival time was also significantly decreased in the animals infused with ethanol (81 ± 60 minutes) compared with those infused with tap water (130 ± 51 minutes; p = 0.035).

Conclusions
Ethanol intoxication led to increased hemorrhage volume and worsened hemodynamic and metabolic profiles in this model of limited resuscitation after TBI and HS. Ethanol-exposed animals had increased resuscitation requirements and decreased survival times.