bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of long-term extracorporeal blood perfusion of the distal portion of isolated equine forelimbs on metabolic variables and morphology of laminar tissue
Authors: Patan Bianca , Budras Klaus-Dieter , Licka Theresia F.
Published: May 2009

Objective—To establish an ex vivo model of blood perfusion in the distal portion of isolated equine forelimbs that closely represents the in vivo situation in the laminar tissue of the hoof.

Sample Population—18 forelimbs collected from 9 healthy adult horses following slaughter at a licensed abattoir.

Procedures—The distal portion of isolated equine forelimbs from 9 horses were perfused under physiologic conditions over a period of 6, 8, and 10 hours with autologous blood. To determine cell viability in perfused tissues, indicators for metabolism (lactate generation and glucose and oxygen consumption) as well as indicators for cell damage (potassium concentration and lactate dehydrogenase activity) were examined at 1-hour intervals from samples of the perfusate. Weight gain in the forelimb was used to determine the edema index. After perfusion, light and electron microscopic examinations of laminar tissue specimens were performed.

Results—During hemoperfusion of the isolated forelimbs, mean ± SD glucose consumption was 197.4 ± 65.1 mg/h, lactate generation was 1.84 ± 0.79 mmol/h, and oxygen consumption was 6.4 × 10−6 ± 8.9 × 10−5 mL·g−1·min−1. Neither an efflux of potassium into the perfusate nor a relevant increase of the lactate dehydrogenase activity was detected, indicating low amounts of cellular damage in the perfused tissues. Weight gain of forelimbs was 1.02 ± 0.95%. Histologic and ultrastructural appearance of the laminar tissue revealed no signs of tissue damage.

Conclusions and Clinical Relevance—Isolated equine limbs were perfused under physiologic conditions over a period of ≤ 10 hours without structural damage to the laminar tissue.
Effects of adjunct electroacupuncture on severity of postoperative pain in dogs undergoing hemilaminectomy because of acute thoracolumbar intervertebral disk disease
Authors: Laim Annina , Jaggy André , Forterre Franck , Doherr Marcus G. , Aeschbacher Gina , Glardon Olivier
Published: May 2009

Objective—To compare severity of postoperative pain in dogs undergoing hemilaminectomy because of acute thoracolumbar intervertebral disk disease treated with a combination of conventional analgesics and electroacupuncture (EAP) or with conventional analgesics alone.

Design—Controlled clinical trial.

Animals—15 dogs undergoing surgery because of acute thoracolumbar disk disease.

Procedures—Dogs were alternately assigned to treatment (conventional analgesics and adjunct EAP) and control (conventional analgesics alone) groups. Analgesic treatment was adjusted as necessary by the attending clinician, who was not aware of group assignment. Pain scores were assigned 1, 3, and 12 hours after surgery and every 12 hours thereafter for 72 hours by the same individual who performed acupuncture treatments.

Results—Total dose of fentanyl administered during the first 12 hours after surgery was significantly lower in the treatment group than in the control group, but dosages of analgesics administered from 12 through 72 hours after surgery did not differ between groups. Pain score was significantly lower in the treatment group than in the control group 36 hours after surgery, but did not differ significantly between groups at any other time.

Conclusions and Clinical Relevance—Results provided equivocal evidence that adjunct EAP might provide some mild benefit in regard to severity of postoperative pain in dogs undergoing hemilaminectomy because of acute thoracolumbar intervertebral disk disease.
Looking Forward and Backward in Records for Risks among Homicidal Youth
Authors: Zagar Robert John , Busch Kenneth G. , Grove William M. , Hughes John Russell , Arbit Jack
Published: May 2009

To identify risks for commission of homicide, 26 convicted Homicidal Youth ( M age =14.9 yr., SD =1.4; n = 26; 1 girl, 25 boys) were matched with 26 Nonviolent Delinquents and 26 clinic-referred Controls. Youth were tracked backward 8 years ( M = 7.7 yr., SD =1.5) and forward 3 years ( M = 3.1 yr., SD =1.2) in records. Data analysis was Shao's bootstrapped logistic regression yielding area under the curve ( AUC) and odds ratios ( OR). Predictors of homicide were poorer executive function ( OR = 7.04e+40), violent family ( OR = 4.01e−16), and alcohol abuse ( OR = 7.33e−17; AUC=.97, 95% CI = .77−.99). From earlier studies, 101 Homicidal Youth and their Controls were reanalyzed similarly. Predictors were poorer executive function ( OR = 6.51), lower social maturity ( OR = 0.28), weapon possession ( OR = 26.10), and gang membership ( OR = 4.14; AUC= .98, 95% CI = .96−.99). Groups were combined, i.e., 26 and 101 Homicidal; 127 Homicidal Youth (7 girls, 120 boys) and their matched Controis were tracked in records. The predictor was poorer executive function ( OR= 3.34e−21; AUC = .98, 95% CI = .96−.97). When 127 Homicidal Youth were compared with 127 matched Nonviolent Delinquents, predictors were poorer executive function ( OR = 2.83e–02), weapon possession ( OR = 1.63e−10), lower social maturity ( OR= 1.15), and use of special education services ( OR = .94; AUC= .94, 95% CI= .37−.99).
Empirical Risk Factors for Delinquency and Best Treatments: Where do we go from here?
Authors: Zagar Robert John , Busch Kenneth G. , Hughes John Russell
Published: May 2009

Youth development and prevention of violence are two sides of the same public policy issue. A great deal of theoretical and empirical effort has focused on identification of risk factors for delinquency and development of interventions for general risks. Recent calls for changes in public policy are evaluated here—and challenged—in light of new comprehensive, longitudinal empirical data on urban violent delinquency. Treatments such as prenatal care, home visitation, prevention of bullying, prevention of alcohol and/or drug abuse, promotion of alternative thinking, mentoring, life skills training, rewards for graduation and employment, functional family therapy, and multidimensional foster care are effective because they prevent or ameliorate risks for delinquency occurring during development. At present, the best treatments yield 10 to 40% reductions in delinquent recidivism. Better controlled application of developmentally appropriate treatments in higher doses, with narrow targeting of the highest-risk youth based on actuarial testing—rather than less accurate clinical judgment—should result in higher effectiveness. Such a focused approach in a geographical area with high homicide rates should be cost-effective. A prediction of cost-benefit outcomes for a carefully constructed example of a large-scale program is presented.
Cost Comparisons of Raising a Child from Birth to 17 Years among Samples of Abused, Delinquent, Violent, and Homicidal Youth Using Victimization and Justice System Estimates
Authors: Zagar Agata Karolina , Bartikowski Boris , Zagar Robert John , Busch Kenneth G.
Published: May 2009

Data from youth studied by Zagar and colleagues were randomly sampled to create groups of controls and abused, delinquent, violent, and homicidal youth ( n = 30 in each). Estimated costs of raising a nondelinquent youth from birth to 17 yr. were compared with the average costs incurred by other youth in each group. Estimates of living expenses, direct and indirect costs of victimization, and criminal justice system expenditures were summed. Groups differed significantly on total expenses, victimization costs, and criminal justice expenditures. Mean total costs for a homicidal youth were estimated at $3,935,433, while those for a control youth were $150,754. Abused, delinquent, and violent youth had average total expenses roughly double the total mean costs of controls. Prevention of dropout, alcoholism, addiction, career delinquency, or homicide justifies interception and empirical treatment on a cost-benefit basis, but also based on the severe personal costs to the victims and to the youth themselves.
Equal contribution of increased intracranial pressure and subarachnoid blood to cerebral blood flow reduction and receptor upregulation after subarachnoid hemorrhage
Authors: Ansar Saema , Edvinsson Lars
Published: May 2009

Object

Cerebral ischemia remains the key cause of disability and death in the late phase after subarachnoid hemorrhage (SAH), and its pathogenesis is still poorly understood. The purpose of this study was to examine whether the change in intracranial pressure or the extravasated blood causes the late cerebral ischemia and the upregulation of receptors or the cerebral vasoconstriction observed following SAH.

Methods

Rats were allocated to 1 of 3 experimental conditions: 1) cisternal injection of 250 μl blood (SAH Group), 2) cisternal injection of 250 μl NaCl (Saline Group), or 3) the same procedure but without fluid injection (Sham Group). Two days after the procedure, the basilar and middle cerebral arteries were harvested, and contractile responses to endothelin (ET)–1 and 5-carboxamidotryptamine (5-CT) were investigated by means of myography. In addition, real-time polymerase chain reaction was used to determine the mRNA levels for ETA, ETB, and 5-HT1 receptors. Regional and global cerebral blood flow (CBF) were quantified by means of an autoradiographic technique.

Results

Compared with the sham condition, both SAH and saline injection resulted in significantly enhanced contraction of cerebral arteries in response to ET-1 and 5-CT. Regional and global CBF were reduced both in the Saline and SAH groups compared with the Sham Group. The mRNA levels for ETB and 5-HT1B receptors were upregulated after SAH and saline injection compared with the sham procedure. The effects in all parameters were more pronounced for SAH than for saline injection.

Conclusions

This study revealed that both the elevation of intracranial pressure and subarachnoid blood per se contribute approximately equally to the late CBF reductions and receptor upregulation following SAH.
The role of adenosine in hypercarbic hyperemia: in vivo and in vitro studies in adenosine 2A receptor knockout and wild-type mice
Authors: Miekisiak Grzegorz , Yoo Kristen , Sandler Adam L. , Kulik Tobias B. , Chen Jiang-Fan , Winn H. Richard
Published: May 2009

Object

The authors tested the hypothesis that adenosine, acting through the A2A receptor, is not involved in hypercarbic hyperemia by assessing the effects of increased PaCO2 on cerebral blood flow (CBF) in vivo in wild-type and A2A receptor knockout mice. In addition, they evaluated the effect of abluminal pH changes in vitro on the diameter of isolated perfused penetrating arterioles harvested from wild-type and A2A receptor knockout mice.

Methods

The authors evaluated in a blinded fashion the CBF response during transient (60-second) hypercapnic (7% CO2) hypercarbia in anesthetized, ventilated C57Bl/6 wild-type and adenosine A2A receptor knockout mice. They also evaluated the hypercarbic response in the absence and presence of the nonselective and selective adenosine antagonists.

Results

Cerebral blood flow was measured using laser Doppler flowmetry. There were no differences between the CBF responses to hypercarbia in the wild-type and the knockout mice. Moreover, the hypercarbic hyperemia response was not affected by the adenosine receptor antagonists. The authors also tested the response to alteration in abluminal pH in isolated perfused, pressurized, penetrating arterioles (average diameter 63.3 ± 3.6 μm) harvested from wild-type (6 mice) and knockout (5 mice) animals. Arteriolar dilation in response to a decrease in abluminal pH, simulating the change in vivo during hypercarbia, was similar in wild-type (15.9 ± 2.6%) and A2A receptor knockout (17.7 ± 1.3%) mice. With abluminal application of CGS 21680 (10−6 M), an A2A receptor agonist, wild-type arterioles dilated in an expected manner (9.8 ± 0.7%), whereas A2A receptor knockout vessels had minimal response.

Conclusions

The results of the in vivo and in vitro studies in wild-type and A2A receptor knockout mice support the authors' hypothesis that hypercarbic vasodilation does not involve an adenosine A2A receptor–related mechanism.
Hemorrhage rates after external ventricular drain placement
Authors: Gardner Paul A. , Engh Johnathan , Atteberry Dave , Moossy John J.
Published: May 2009

Object

External ventricular drain (EVD) placement is one of the most common neurosurgical procedures performed. Rates and significance of hemorrhage associated with this procedure have not been well quantified.

Methods

All adults who underwent EVD placement at the University of Pittsburgh Medical Center between July 2002 and June 2003 were evaluated for catheter-associated hemorrhage. Patients without postprocedural imaging were excluded.

Results

Seventy-seven (41%) of 188 EVDs were associated with imaging evidence of hemorrhage after either placement or removal. Most of these were insignificant, punctate intraparenchymal, or trace subarachnoid hemorrhages (51.9%). Thirty-seven (19.7%) were associated with larger hemorrhages, which were divided into 3 groups according to volume of hemorrhage: 16 patients (8.5%) had < 15 ml of hemorrhage, 20 (10.6%) had hemorrhages of > 15 ml or associated intraventricular hemorrhage, and in 1 case there was a subdural hematoma that required surgical evacuation. No hemorrhages larger than punctate or trace were seen after EVD removal. Hemorrhage was associated with 44.3% of EVDs placed in an intensive care unit compared with 34.8% in EVDs placed in the operating room (p > 0.10).

Conclusions

External ventricular drain placement has a significant risk of associated hemorrhage. However, the hemorrhages are rarely large and almost never require surgical intervention. There is a favorable trend, but no significant risk reduction when EVDs are placed in the operating room rather than the intensive care unit.
Time-of-flight magnetic resonance angiography imaging of a residual arteriovenous malformation nidus after Onyx embolization for stereotactic radiosurgery planning
Authors: Loy David N. , Rich Keith M. , Simpson Joseph , Dorward Ian , Santanam Lakshmi , Derdeyn Colin P.
Published: May 2009

This report demonstrates that time-of-flight (TOF) MR angiography is a useful adjunct for planning stereotactic radiosurgery (SRS) of large arteriovenous malformations (AVMs) after staged embolization with Onyx.

Onyx (ethylene vinyl copolymer), a recently approved liquid embolic agent, has been increasingly used to exclude portions of large AVMs from the parent circulation prior to SRS. Limiting SRS to regions of persistent arteriovenous shunting and excluding regions eliminated by embolization may reduce unnecessary radiation doses to eloquent brain structures. However, SRS dosimetry planning presents unique challenges after Onyx embolization because it creates extensive artifacts on CT scans, and it cannot be delineated from untreated nidus on standard MR sequences.

During the radiosurgery procedure, MR images were obtained using a GE Signa 1.5-T unit. Standard axial T2 fast spin echo high-resolution images (TR 3000 msec, TE 108 msec, slice thickness 2.5 mm) were generated for optimal visualization of brain tissue and AVM flow voids. The 3D TOF MR angiography images of the circle of Willis and vertebral arteries were subsequently obtained to visualize AVM regions embolized with Onyx (TR 37 msec, TE 6.9 msec, flip angle 20°).

Adjunct TOF MR angiography images demonstrated excellent contrast between nidus embolized with Onyx and regions of persistent arteriovenous shunting within a large AVM prior to SRS. Additional information derived from these sequences resulted in substantial adjustments to the treatment plan and an overall reduction in the treated tissue volume.
Endovascular occlusion of a ruptured transitional aneurysm associated with a developmental venous anomaly
Authors: Ducruet Andrew F. , Kellner Christopher P. , Connolly E. Sander , Meyers Philip M.
Published: May 2009

Developmental venous anomalies (DVAs) represent a rare cause of intraparenchymal hemorrhage. This case demonstrates an unusual DVA associated with venous hypertension, arteriovenous shunting, and a ruptured transitional aneurysm. The authors describe the first use of embolization as a treatment method for an unstable ruptured transitional aneurysm associated with a DVA. This 33-year-old man suffered acute onset of headache, gait ataxia, and left hemiparesis. Computed tomography brain scans demonstrated a deep paramedian right frontal intraparenchymal hemorrhage. No cavernous malformation was apparent on MR imaging. Diagnostic angiography revealed arteriovenous shunting from the right anterior and middle cerebral arteries to a large DVA with an associated arteriovenous fistula, with a 3-mm aneurysm in the transition from pericallosal artery to the collecting vein. Both surgical and endovascular treatment options were considered. The patient underwent repeat angiography on hospital Day 7, at which time the aneurysm had increased to 5 mm, and endovascular treatment was selected. Acrylic occlusion of the aneurysm was performed and confirmed angiographically. The patient's neurological symptoms resolved throughout the hospital stay, and he remains symptom free in the 10 months since treatment. Developmental venous anomalies are not usually associated with arteriovenous shunting and aneurysms as a source of intraparenchymal hemorrhage. Endovascular occlusion of the aneurysm without blockage of physiologically necessary venous structures is a possible method of treatment for this complex mixed vascular lesion, and has proven safe and effective in this patient. To the authors' knowledge, this is the first presentation of this situation in the literature.
Serum and cerebrospinal fluid C-reactive protein levels as predictors of vasospasm in aneurysmal subarachnoid hemorrhage
Authors: Fountas Kostas N. , Tasiou Anastasia , Kapsalaki Eftychia Z. , Paterakis Konstantinos N. , Grigorian Arthur A. , Lee Gregory P. , Robinson Joe Sam
Published: May 2009

Object

Cerebral vasospasm is a common and potentially devastating complication of aneurysmal subarachnoid hemorrhage (aSAH). Inflammatory processes seem to play a major role in the pathogenesis of vasospasm. The Creactive protein (CRP) constitutes a highly sensitive inflammatory marker. The association of elevated systemic CRP and coronary vasospasm has been well established. Additionally, elevation of the serum CRP levels has been demonstrated in patients with aSAH. The purpose of the current study was to evaluate the possible relationship between elevated CRP levels in the serum and CSF and the development of vasospasm in patients with aSAH.

Methods

. A total of 41 adult patients in whom aSAH was diagnosed were included in the study. Their demographics, the admitting Glasgow Coma Scale (GCS) score, Hunt and Hess grade, Fisher grade, CT scans, digital subtraction angiography studies, and daily neurological examinations were recorded. Serial serum and CSF CRP measurements were obtained on Days 0, 1, 2, 3, 5, 7, and 9. All patients underwent either surgical or endovascular treatment within 48 hours of their admission. The outcome was evaluated using the Glasgow Outcome Scale and the modified Rankin Scale.

Results

The CRP levels in serum and CSF peaked on the 3rd postadmission day, and the CRP levels in CSF were always higher than the serum levels. Patients with lower admission GCS scores and higher Hunt and Hess and Fisher grades had statistically significantly higher levels of CRP in serum and CSF. Patients with angiographic vasospasm had higher CRP measurements in serum and CSF, in a statistically significant fashion (p < 0.0001). Additionally, patients with higher CRP levels in serum and CSF had less favorable outcome in this cohort.

Conclusions

Patients with aSAH who had high Hunt and Hess and Fisher grades and low GCS scores showed elevated CRP levels in their CSF and serum. Furthermore, patients developing angiographically proven vasospasm demonstrated significantly elevated CRP levels in serum and CSF, and increased CRP measurements were strongly associated with poor clinical outcome in this cohort.
Operative nuances of an occipital artery to posterior inferior cerebellar artery bypass
Authors: Crowley R. Webster , Medel Ricky , Dumont Aaron S.
Published: May 2009

Occipital artery to posterior inferior cerebellar artery bypasses remain an important tool for cerebrovascular neurosurgeons, particularly in the management of complex aneurysms of the posterior inferior cerebellar artery requiring proximal occlusion or trapping. The procedure requires meticulous technique and attention to detail. The authors outline their technique for accomplishing this bypass emphasizing nuances for complication avoidance.
Minimally invasive superficial temporal artery to middle cerebral artery bypass through a minicraniotomy: benefit of three-dimensional virtual reality planning using magnetic resonance angiography
Authors: Fischer Gerrit , Stadie Axel , Schwandt Eike , Gawehn Joachim , Boor Stephan , Marx Juergen , Oertel Joachim
Published: May 2009

Object

The aim of the authors in this study was to introduce a minimally invasive superficial temporal artery to middle cerebral artery (STA-MCA) bypass surgery by the preselection of appropriate donor and recipient branches in a 3D virtual reality setting based on 3-T MR angiography data.

Methods

An STA-MCA anastomosis was performed in each of 5 patients. Before surgery, 3-T MR imaging was performed with 3D magnetization-prepared rapid acquisition gradient echo sequences, and a high-resolution CT 3D dataset was obtained. Image fusion and the construction of a 3D virtual reality model of each patient were completed.

Results

In the 3D virtual reality setting, the skin surface, skull surface, and extra- and intracranial arteries as well as the cortical brain surface could be displayed in detail. The surgical approach was successfully visualized in virtual reality. The anatomical relationship of structures of interest could be evaluated based on different values of translucency in all cases. The closest point of the appropriate donor branch of the STA and the most suitable recipient M3 or M4 segment could be calculated with high accuracy preoperatively and determined as the center point of the following minicraniotomy. Localization of the craniotomy and the skin incision on top of the STA branch was calculated with the system, and these data were transferred onto the patient's skin before surgery. In all cases the preselected arteries could be found intraoperatively in exact agreement with the preoperative planning data. Successful extracranial-intracranial bypass surgery was achieved without stereotactic neuronavigation via a preselected minimally invasive approach in all cases. Subsequent enlargement of the craniotomy was not necessary. Perioperative complications were not observed. All bypasses remained patent on follow-up.

Conclusions

With the application of a 3D virtual reality planning system, the extent of skin incision and tissue trauma as well as the size of the bone flap was minimal. The closest point of the appropriate donor branch of the STA and the most suitable recipient M3 or M4 segment could be preoperatively determined with high accuracy so that the STA-MCA bypass could be safely and effectively performed through an optimally located minicraniotomy with a mean diameter of 22 mm without the need for stereotactic guidance.
Clinical course of nontraumatic, nonaneurysmal subarachnoid hemorrhage: a single-institution experience
Authors: Whiting Jobyna , Reavey-Cantwell John , Velat Gregory , Fautheree Gregory , Firment Christopher , Lewis Stephen , Hoh Brian
Published: May 2009

Object

Angiogram-negative subarachnoid hemorrhage (SAH) accounts for 15% of nontraumatic SAH and has been reported with low morbidity and mortality rates. We report on a large series of patients with angiogram-negative SAH who experienced an atypical nonbenign clinical course.

Methods

Between December 2001 and November 2006, 95 patients with spontaneous nonaneurysmal SAH and negative initial angiographic evaluation were treated at the University of Florida. The authors retrospectively reviewed the patients' medical records and radiological images to determine associated morbidity and mortality.

Results

Aneurysms were found in 6 of the 95 patients on follow-up imaging after an initial negative angiogram (6.3% false negative rate); these patients were excluded leaving 89 patients as the study group. Hydrocephalus necessitating temporary CSF diversion developed in 22 of these patients (25%); 12 (13%) ultimately required permanent CSF diversion. Clinically significant vasospasm developed in 4 patients (4%), and 2 (2%) had cerebral infarctions. Three patients (3%) died.

Conclusions

The authors' experience with a large series of angiogram-negative SAH patients who had an atypical nonbenign clinical course associated with hydrocephalus, vasospasm, stroke, and mortality differs significantly from previously published case series of angiogram-negative SAH.
Cavernous carotid aneurysms: to treat or not to treat?
Authors: Eddleman Christopher S. , Hurley Michael C. , Bendok Bernard R. , Batjer H. Hunt
Published: May 2009

Most cavernous carotid aneurysms (CCAs) are considered benign lesions, most often asymptomatic, and to have a natural history with a low risk of life-threatening complications. However, several conditions may exist in which treatment of these aneurysms should be considered. Several options are currently available regarding the management of CCAs with resultant good outcomes, namely expectant management, luminal preservation strategies with or without addressing the aneurysm directly, and Hunterian strategies with or without revascularization procedures. In this article, we discuss the sometimes difficult decision regarding whether to treat CCAs. We consider the natural history of several types of CCAs, the clinical presentation, the current modalities of CCA management and their outcomes to aid in the management of this heterogeneous group of cerebral aneurysms.
Unruptured intracranial aneurysms and the assessment of rupture risk based on anatomical and morphological factors: sifting through the sands of data
Authors: Lall Rohan R. , Eddleman Christopher S. , Bendok Bernard R. , Batjer H. Hunt
Published: May 2009

Aneurysmal subarachnoid hemorrhage continues to have high rates of morbidity and mortality for patients despite optimal medical and surgical management. Due to the fact that aneurysmal rupture can be such a catastrophic event, preventive treatment is desirable for high-risk lesions. Given the variability of the literature evaluating unruptured aneurysms regarding basic patient population, clinical practice, and aneurysm characteristics studied, such as size, location, aspect ratio, relationship to the surrounding vasculature, and the aneurysm hemodynamics, a metaanalysis is nearly impossible to perform. This review will instead focus on the various anatomical and morphological characteristics of aneurysms reported in the literature with an attempt to draw broad inferences and serve to highlight pressing questions for the future in our continued effort to improve clinical management of unruptured intracranial aneurysms.
Pathogenesis and radiobiology of brain arteriovenous malformations: implications for risk stratification in natural history and posttreatment course
Authors: Achrol Achal S. , Guzman Raphael , Varga Monika , Adler John R. , Steinberg Gary K. , Chang Steven D.
Published: May 2009

Brain arteriovenous malformations (BAVMs) are an important cause of intracerebral hemorrhage (ICH) in young adults. Biological predictors of future ICH risk are lacking, and controversy exists over previous studies of natural history risk among predominantly ruptured BAVM cohorts. Recent studies have suggested that the majority of BAVMs are now diagnosed as unruptured lesions, and that the risk according to natural history among these lesions may be less than previously assumed. In the first part of this review, the authors discuss available data on the natural history of BAVMs and highlight the need for future studies that aim to develop surrogate biomarkers of disease progression that accurately predict future risk of ICH in BAVMs.

The etiology of BAVM remains unknown. Recent studies have suggested a role for genetic factors in the pathogenesis of sporadic BAVM, which is further supported by reports of familial occurrence of BAVM and association with known systemic genetic disorders (such as Osler-Weber-Rendu disease, Sturge-Weber disease, and Wyburn-Mason syndrome). Molecular characterization of BAVM tissue demonstrates a highly angiogenic milieu with evidence of increased endothelial cell turnover. Taken together with a number of reports of de novo BAVM formation, radiographic growth after initial BAVM diagnosis, and regrowth after successful treatment of BAVM, these findings challenge the long-held assumption that BAVMs are static lesions of congenital origin. In the second part of this review, the authors discuss available data on the origins of BAVM and offer insights into future investigations into genetics and endothelial progenitor cell involvement in the pathogenesis of BAVM.

Current treatment options for BAVM focus on removal or obliteration of the lesion in an attempt to protect against future ICH risk, including microsurgical resection, endovascular embolization, and stereotactic radiosurgery (SRS). In the third part of this review, the authors discuss available data on SRS in BAVMs and highlight the need for future studies on the radiobiology of BAVMs, especially in regard to biomarker detection for tracking SRS response during the latency period.

Insights from future investigations in BAVM may not only prove important for the development of novel therapies and relevant biomarkers for BAVM, but could also potentially benefit a variety of other disorders involving new vessel formation in the CNS, including stroke, tumors, moyamoya disease, and other cerebrovascular malformations.
Cerebral arteriovenous malformations. Part 2: physiology
Authors: Moftakhar Parham , Hauptman Jason S. , Malkasian Dennis , Martin Neil A.
Published: May 2009

Object

The scientific understanding of the nature of arteriovenous malformations (AVMs) in the brain is evolving. It is clear from current work that AVMs can undergo a variety of phenomena, including growth, remodeling, and/or regression—and the responsible processes are both molecular and physiological. A review of these complex processes is critical to directing future therapeutic approaches. The authors performed a comprehensive review of the literature to evaluate current information regarding the genetics, pathophysiology, and behavior of AVMs.

Methods

A comprehensive literature review was conducted using PubMed to reveal the angioarchitecture and cerebral hemodynamics of AVMS as they relate to lesion development.

Results

Feeding artery pressures, brain AVM compartmentalization, venous drainage, flow phenomena, and vascular steal are discussed.

Conclusions

The dynamic nature of brain AVMs is at least in part attributable to hemodynamic and flow-related phenomena. These forces acting on an evolving structure are critical to understanding the challenges in endovascular and surgical therapy. As knowledge in this field continues to progress, the natural history and predicted behavior of these AVMs will become more clearly elucidated.
Intraoperative hypothermia during vascular neurosurgical procedures
Authors: Choi Raymond , Andres Robert H. , Steinberg Gary K. , Guzman Raphael
Published: May 2009

Increasing evidence in animal models and clinical trials for stroke, hypoxic encephalopathy for children, and traumatic brain injury have shown that mild hypothermia may attenuate ischemic damage and improve neurological outcome. However, it is less clear if mild intraoperative hypothermia during vascular neurosurgical procedures results in improved outcomes for patients. This review examines the scientific evidence behind hypothermia as a treatment and discusses factors that may be important for the use of this adjuvant technique, including cooling temperature, duration of hypothermia, and rate of rewarming.
Inhibition of 90-kD heat shock protein potentiates the cytotoxicity of chemotherapeutic agents in human glioma cells
Authors: Ohba Shigeo , Hirose Yuichi , Yoshida Kazunari , Yazaki Takahito , Kawase Takeshi
Published: May 2009

Object

The introduction of temozolomide (TMZ) has advanced chemotherapy for malignant gliomas. A considerable number of glioblastoma cases are refractory to TMZ, however, and the development of novel chemotherapeutic regimens is needed. The authors of previous studies have revealed that hsp90 is expressed at higher levels in human neoplastic tissues, including gliomas, than in normal tissues. Heat shock protein 90 is involved in a cytoprotective mechanism against cellular stressors such as DNA damage, and the authors hypothesized that hsp90 inhibitors might act as antitumor agents against gliomas and potentiate the cytotoxicity of DNA-damaging agents.

Methods

The authors examined the cytotoxicity of an hsp90 inhibitor, 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), both alone and in combination with 1 of 3 DNA-damaging agents (cisplatin, 1,3-bis(2-chloroethyl)-1-nitrosourea, and TMZ) in human glioma cell lines. The cytotoxicity of these agents to glioma cells was measured using a colony formation assay. The cell cycle phase distribution, protein expression, and number of apoptotic cells were measured using a fluorescence-activated cell sorting assay, immunoblot assays, and double staining with annexin V and propidium iodide. In an in vivo experiment, 17-AAG, cisplatin, or 17-AAG and cisplatin were administered intraperitoneally to mice with xenografted U87MG cells, and the resulting tumor volumes were measured.

Results

The authors found that 17-AAG reduced the clonogenicity of U87MG cells, and at a low concentration (< 100 nM) potentiated the cytotoxicity of the DNA-crosslinking agents cisplatin and 1,3-bis(2-chloroethyl)-1-nitrosourea, but not that of the DNA-methylating agent TMZ. This 17-AAG–induced potentiation of DNA crosslinking agent–induced cytotoxicity was a consequence of prolonged G2-M arrest accompanied by the suppression of cdc2 and cdc25C and of increased apoptotic cell death accompanied by the degradation of the antiapoptosis proteins Akt and survivin. Similar effects were observed when cells were treated with radicicol, another hsp90 inhibitor. The 17-AAG–induced enhancement of DNA crosslinking agent–induced cytotoxicity was also observed in other cell lines. In addition, 17-AAG sensitized xenografted U87MG cells to cisplatin in nude mice.

Conclusions

Heat shock protein 90–targeted therapy may be an effective strategy for potentiating chemotherapy using DNA-crosslinking agents for TMZ-refractory gliomas.
Seizure outcome of epilepsy surgery in focal epilepsies associated with temporomesial glioneuronal tumors: lesionectomy compared with tailored resection
Authors: Giulioni Marco , Rubboli Guido , Marucci Gianluca , Martinoni Matteo , Volpi Lilia , Michelucci Roberto , Marliani Anna Federica , Bisulli Francesca , Tinuper Paolo , Castana Laura , Sartori Ivana , Calbucci Fabio
Published: May 2009

Object

The authors retrospectively analyzed and compared seizure outcome in a series of 28 patients with temporomesial glioneuronal tumors associated with epilepsy who underwent 1 of 2 different epilepsy surgery procedures: lesionectomy or tailored resection.

Methods

The 28 patients were divided into 2 groups, with 14 cases in each group. In Group A, surgery was limited to the tumor (lesionectomy), whereas Group B patients underwent tailored resection involving removal of the tumor and the epileptogenic zone as identified by a neurophysiological noninvasive presurgical study.

Results

In Group A (10 male and 4 female patients) the interval between onset of seizures and surgery ranged from 1 to 33 years (mean 10.6 years). Patients' ages ranged from 3 to 61 years (mean 23.1 years). The epileptogenic lesion was on the left side in 6 patients and the right in 8 patients. Mean follow-up was 9.8 years (range 6.5–15 years). The Engel classification system, used to determine postoperative seizure outcome, showed 6 patients (42.8%) were Engel Class I and 8 (57.1%) were Engel Class II. In Group B (6 male and 8 female patients) the interval between onset of seizures and surgery ranged from 0.5 to 25 years (mean 8.6 years). Patients' ages ranged from 3 to 48 years (mean 22.3 years). The tumor and associated epileptogenic area was on the right side in 8 patients and the left in 6 patients. Mean follow-up duration was 3.5 years (range 1–6.5 years). Postoperative seizure outcome was Engel Class I in 13 patients (93%) and Engel Class II in 1 (7.1%).

Conclusions

The authors' results demonstrate a better seizure outcome for temporomesial glioneuronal tumors associated with epilepsy in patients who underwent tailored resection rather than simple lesionectomy (p = 0.005). For temporomesial glioneuronal tumors associated with epilepsy, performing a presurgical noninvasive neurophysiological study intended to identify the epileptogenic zone is necessary for planning a tailored surgery. Using this surgical strategy, the presence of temporomesial glioneuronal tumors constitutes a predictive factor of excellent seizure outcome, and therefore surgical treatment can be offered early to avoid both the consequences of uncontrolled seizures as well as the side effects of pharmacological therapy.
Molecular phylogenetics of Prescottiinae s.l. and their close allies (Orchidaceae, Cranichideae) inferred from plastid and nuclear ribosomal DNA sequences
Authors: Álvarez‐Molina Aída , Cameron Kenneth M.
Published: May 2009

The Andes are a cradle of orchid evolution, but most phylogenetic studies of Orchidaceae in this biodiversity hotspot have dealt with epiphytic epidendroid lineages. Here we present a study on neotropical, terrestrial, orchidoid taxa of Prescottiinae s.l. (8 genera, ∼100 species), which are adapted to some of the highest elevation habitats on earth that support orchids. They are currently included within an expanded concept of Cranichidinae in the tribe Cranichideae, but DNA sequence data show that neither Prescottiinae s.l. nor Cranichidinae s.s. are monophyletic. Prescottiinae s.l. consist of two strongly supported lineages: the Altensteinia and Prescottia clades, which have closer affinities to Spiranthinae than to Cranichidinae. The Prescottia clade comprises two well‐supported subclades, one including most sampled species of Prescottia and a second one with Pseudocranichis thysanochila sister to Prescottia tubulosa. As a group, they are sister to Spiranthinae. Sister to this pair is the Altensteinia clade comprised of six genera, whose intergeneric relationships are well resolved. Finally, Cranichidinae s.s. is sister to all three of these clades. Morphological and ecological features distinguishing the major groups are discussed, as are potential synapomorphies to define them. The reconstructed phylogeny indicates that the classification of Cranichideae needs to be reexamined.
Crown structure and wood properties: Influence on tree sway and response to high winds
Authors: Sellier Damien , Fourcaud Thierry
Published: May 2009

Wind can alter plant growth and cause extensive, irreversible damage in forested areas. To better understand how to mitigate the effects of wind action, we investigated the sensitivity of tree aerodynamic behavior to the material and geometrical factors characterizing the aerial system. The mechanical response of a 35‐yr‐old maritime pine (Pinus pinaster, Pinaceae) submitted to static and dynamic wind loads is simulated with a finite element model. The branching structure is represented in three dimensions. Factor effects are evaluated using a fractional experimental design. Results show that material properties play only a limited role in tree dynamics. In contrast, small morphological variations can produce extreme behaviors such as either very little or nearly critical dissipation of stem oscillations. Slender trees are shown to be relatively more vulnerable to stem breakage than uprooting. Dynamic loading leads to deflections and forces up to 20% higher near the base of the tree than those calculated for a static loading of similar magnitude. Effects of branch geometry on dynamic amplification are substantial yet not linear. The flexibility of the aerial system is found to be critical to reducing the resistance to the airflow and thus to minimizing the risk of failure.
A preliminary phylogeny of the ‘didymocarpoid Gesneriaceae’ based on three molecular data sets: Incongruence with available tribal classifications
Authors: Möller Michael , Pfosser Martin , Jang Chang‐Gee , Mayer Veronika , Clark Alexandra , Hollingsworth Michelle L. , Barfuss Michael H. J. , Wang Yin‐Zheng , Kiehn Michael , Weber Anton
Published: May 2009

The ‘didymocarpoid Gesneriaceae’ (traditional subfam. Cyrtandroideae excluding Epithemateae) are the largest group of Old World Gesneriaceae, comprising 85 genera and 1800 species. We attempt to resolve their hitherto poorly understood generic relationships using three molecular markers on 145 species, of which 128 belong to didymocarpoid Gesneriaceae. Our analyses demonstrate that consistent topological relationships can be retrieved from data sets with missing data using subsamples and different combinations of gene sequences. We show that all available classifications in Old World Gesneriaceae are artificial and do not reflect natural relationships. At the base of the didymocarpoids are grades of clades comprising isolated genera and small groups from Asia and Europe. These are followed by a clade comprising the African and Madagascan genera. The remaining clades represent the advanced Asiatic and Malesian genera. They include a major group with mostly twisted capsules. The much larger group of remaining genera comprises exclusively genera with straight capsules and the huge genus Cyrtandra with indehiscent fruits. Several genera such as Briggsia, Henckelia, and Chirita are not monophyletic; Chirita is even distributed throughout five clades. This degree of incongruence between molecular phylogenies, traditional classifications, and generic delimitations indicates the problems with classifications based on, sometimes a single, morphological characters.
Sick Leave Before and After Diagnosis of Rheumatoid Arthritis —A Report from the Swedish TIRA Project
Authors: BJÖRK MATHILDA , THYBERG INGRID , RIKNER KLAS , BALOGH ISTVAN , GERDLE BJÖRN
Published: May 2009

Objective.

Our study describes sick leave during 3 years before and 3 years after diagnosis of rheumatoid arthritis (RA) in relation to referents and identifies predictors for sick leave during the third year after diagnosis of RA.

Methods.

One hundred twenty patients (76% women) from the Swedish early RA study TIRA were included. Disease activity and disability were registered regularly during 3 years in TIRA. Referents were matched for sex, age, and home town. Sick leave data were obtained for patients 3 years before and 3 years after diagnosis and for the referents for the corresponding 6 years.

Results.

No differences were seen between patients and referents regarding sick leave during the first 2 years, whereas sick leave increased in patients 6 months before diagnosis, from 30% to 53%. During the 3 years after diagnosis, sick leave among patients was rather stable, varying between 50% and 60%, even though disability pension increased and sickness benefit decreased. Sick leave before diagnosis, disability 1 year after diagnosis, and type of work were identified as predictors for sick leave during the third year after diagnosis.

Conclusion.

Not surprisingly, sick leave in patients increased the year before diagnosis. Although disease activity and disability diminished after diagnosis, the patients’ sick leave remained essentially unchanged. Sick leave 3 years after diagnosis was foremost predicted by earlier sick leave, disability, and type of work.
Adult Zebrafish Model of Streptococcal Infection
Authors: Phelps Hilary A. , Runft Donna L. , Neely Melody N.
Published: May 2009

Streptococcal pathogens cause a wide array of clinical syndromes in humans, including invasive systemic infections resulting in high mortality rates. Many of these pathogens are human specific, and therefore difficult to analyze in vivo using typical animal models, as these models rarely replicate what is observed in human infections. This unit describes the use of the zebrafish (Danio rerio) as an animal model for streptococcal infection to analyze multiple disease states. This model closely mimics the necrotizing fasciitis/myositis pathology observed in humans from a Streptococcus pyogenes infection. The use of a zoonotic pathogen, Streptococcus iniae, which replicates systemic infections caused by many streptococcal pathogens, including dissemination to the brain, is also described. Protocols describing both intraperitoneal and intramuscular infections, as well as methods for histological and quantitative measurements of infection, are also described. Curr. Protoc. Microbiol. 13:9D.1.1–9D.1.27. © 2009 by John Wiley & Sons, Inc.
Dynamic folding pathway models of the villin headpiece subdomain (HP‐36) structure
Authors: Lee In‐Ho , Kim Seung‐Yeon , Lee Jooyoung
Published: May 2009

We have investigated the folding pathway of the 36‐residue villin headpiece subdomain (HP‐36) by action‐derived molecular dynamics simulations. The folding is initiated by hydrophobic collapse, after which the concurrent formation of full tertiary structure and α‐helical secondary structure is observed. The collapse is observed to be associated with a couple of specific native contacts contrary to the conventional nonspecific hydrophobic collapse model. Stable secondary structure formation after the collapse suggests that the folding of HP‐36 follows neither the framework model nor the diffusion‐collision model. The C‐terminal helix forms first, followed by the N‐terminal helix positioned in its native orientation. The short middle helix is shown to form last. Signs for multiple folding pathways are also observed. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010
Prevalence of incontinence and incontinence‐specific quality of life impairment in women with cystic fibrosis
Authors: Vella M. , Cartwright R. , Cardozo L. , Parsons M. , Madge S. , Burns Y.
Published: May 2009

Aims

Cystic fibrosis (CF) is the commonest autosomal recessive disorder in Caucasians. With advancing medical technology, the life expectancy has more than double in the last twenty years. This has led to new unforeseen health problems like urinary incontinence. The aim was to establish the prevalence, symptomatic typology, and quality of life impact of incontinence in a population of women with CF.

Methods

Women were recruited from two London tertiary referral centres for CF. They were asked to fill in a self‐ completed anonymous King's Health Questionnaire (KHQ) for assessment of symptoms and quality of life Impairment. Their age was also noted. Descriptive statistics are reported. Correlation was assessed using Pearson's Product Moment Correlation Coefficient (r).

Results

One hundred and forty six women were approached for enrolment. 98(67%) consented to take part in study. Their mean age was 28. Seventy three (74%) reported symptoms of urinary incontinence, which in all cases was perceived as stress urinary incontinence. Of these 44(60%) reported mild stress incontinence, 16(22%) moderate stress incontinence and 13(18%) severe stress incontinence. Continent and incontinent women perceived their general health to be similarly poor (mean score 40 vs 44 points). Strong positive correiations were found between age and stress urinary incontinence severity (r=0.742; P <0.001) and between age and total King's Health Questionnaire score (r=0.828; P <0.001).

Conclusions

Women with CF have a higher prevalence of stress urinary incontinence than the general population, with both the prevalence and associated quality of life impairment increasing with age. Neurourol. Urodynam. 28:986–989, 2009. © 2009 Wiley‐Liss, Inc.