bluuebunny/crossref_metadata_2025_split huggingface dataset:
Congenital IGF1 deficiency tends to confer protection against post-natal development of malignancies
Authors: Steuerman Rachel , Shevah Orit , Laron Zvi 
Published: February 2011

ObjectiveTo investigate whether congenital IGF1 deficiency confers protection against development of malignancies, by comparing the prevalence of malignancies in patients with congenital (secondary) deficiency of IGF1 with the prevalence of cancer in their family members.MethodOnly patients with an ascertained diagnosis of either Laron syndrome (LS), congenital IGHD, congenital multiple pituitary hormone deficiency (cMPHD) including GH or GHRHR defect were included in this study. In addition to our own patients, we performed a worldwide survey and collected data on a total of 538 patients, 752 of their first-degree family members, of which 274 were siblings and 131 were further family members.ResultsWe found that none of the 230 LS patients developed cancer and that only 1 out of 116 patients with congenital IGHD, also suffering from xeroderma pigmentosum, had a malignancy. Out of 79 patients with GHRHR defects and out of 113 patients with congenital MPHD, we found three patients with cancer in each group.Among the first-degree family members (most heterozygotes) of LS, IGHD and MPHD, we found 30 cases of cancer and 1 suspected. In addition, 31 malignancies were reported among 131 further relatives.ConclusionsOur findings bear heavily on the relationship between GH/IGF1 and cancer. Homozygous patients with congenital IGF1 deficiency and insensitivity to GH such as LS seem protected from future cancer development, even if treated by IGF1. Patients with congenital IGHD also seem protected.
The Relationship Between Insulin Resistance and Incidence and Progression of Coronary Artery Calcification
Authors: Blaha Michael J. , DeFilippis Andrew P. , Rivera Juan J. , Budoff Matthew J. , Blankstein Ron , Agatston Arthur , Szklo Moyses , Lakoski Susan G. , Bertoni Alain G. , Kronmal Richard A. , Blumenthal Roger S. , Nasir Khurram 
Published: February 2011

OBJECTIVE
We sought to determine whether insulin resistance predicts the incidence and progression of coronary artery calcification (CAC).

RESEARCH DESIGN AND METHODS
We studied 5,464 participants not on hypoglycemic therapy from the Multi-Ethnic Study of Atherosclerosis (MESA). Each had baseline homeostasis model assessment of insulin resistance (HOMA-IR) and baseline and follow-up CAC scores. Incident CAC was defined as newly detectable CAC; progression was defined as advancing CAC volume score at follow-up.

RESULTS
Median HOMA-IR was 1.2 (0.8–2.0). Across all ethnicities, there was a graded increase in CAC incidence and progression with increasing HOMA-IR. When compared with those in the 1st quartile, participants in the 2nd–4th quartiles had 1.2, 1.5, and 1.8 times greater risk of developing CAC. Median annualized CAC score progression was 8, 14, and 17 higher, respectively. However, HOMA-IR was not predictive after adjustment for metabolic syndrome components.

CONCLUSIONS
HOMA-IR predicts CAC incidence and progression, but not independently of metabolic syndrome.
Evaluation of a bispecific biological drug designed to simultaneously target glioblastoma and its neovasculature in the brain
Authors: Oh Seunguk , Tsai Alexander K. , Ohlfest John R. , Panoskaltsis-Mortari Angela , Vallera Daniel A. 
Published: February 2011

Object
The authors of this study aimed to genetically design a bispecific targeted toxin that would simultaneously target overexpressed markers on glioma as well as the tumor vasculature, to mutate certain amino acids to reduce the immunogenicity of this new drug, and to determine whether the drug was able to effectively reduce aggressive human brain tumors in a rat xenograft model via a novel hollow fiber (HF) catheter delivery system.

Methods
A new bispecific ligand-directed toxin (BLT) was created in which 2 human cytokines—epidermal growth factor ([EGF], targeting overexpressed EGF receptor) and amino acid terminal fragment ([ATF], targeting urokinase plasminogen activator receptor)—were cloned onto the same single-chain molecule with truncated Pseudomonas exotoxin with a terminal lysyl-aspartyl-glutamyl-leucine (KDEL) sequence. Site-specific mutagenesis was used to mutate amino acids in 7 key epitopic toxin regions that dictate the B cell generation of neutralizing antitoxin antibodies to deimmunize the drug, now called “EGFATFKDEL 7mut.” Bioassays were used to determine whether mutation reduced the drug's potency, and enzyme-linked immunosorbent assay studies were performed to determine whether antitoxin antibodies were decreased. Aggressive brain tumors were intracranially established in nude rats by using human U87 glioma genetically marked with a firefly luciferase reporter gene (U87-luc), and the rats were stereotactically treated with 2 intracranial injections of deimmunized EGFATFKDEL via convection-enhanced delivery (CED). Drug was administered through a novel HF catheter to reduce drug backflow upon delivery.

Results
In vitro, EGFATFKDEL 7mut selectively killed the human glioblastoma cell line U87-luc as well as cultured human endothelial cells in the form of the human umbilical vein endothelial cells. Deimmunization did not reduce drug activity. In vivo, when rats with brain tumors were intracranially treated with drug via CED and a novel HF catheter to reduce backflow, there were significant tumor reductions in 2 experiments (p < 0.01). Some rats survived with a tumor-free status until 130 days post–tumor inoculation. An irrelevant BLT control did not protect establishing specificity. The maximal tolerated dose of EGFATFKDEL 7mut was established at 2 μg/injection or 8.0 μg/kg, and data indicated that this dose was nontoxic. Antitoxin antibodies were reduced by at least 90%.

Conclusions
First, data indicated that the BLT framework is effective for simultaneously targeting glioma and its neovasculature. Second, in the rodent CED studies, newly developed HF catheters that limit backflow are effective for drug delivery. Third, by mutating critical amino acids, the authors reduced the threat of the interference of neutralizing antibodies that are generated against the drug. The authors' experiments addressed some of the most urgent limitations in the targeted toxin field.
Posterior fossa volume increase after surgery for Chiari malformation Type I: a quantitative assessment using magnetic resonance imaging and correlations with the treatment response
Authors: Noudel Rémy , Gomis Philippe , Sotoares Gustavo , Bazin Arnaud , Pierot Laurent , Pruvo Jean-Pierre , Bordet Régis , Roche Pierre-Hugues 
Published: February 2011

Object
The aim of this paper was to measure the posterior fossa (PF) volume increase resulting from a given-sized occipital craniectomy in Chiari malformation Type I surgery and to analyze its correlations with the PF size and the treatment response, with the perspective of tailoring the amount of bone removal to the patient-specific PF dimensions.

Methods
Between January 2005 and June 2006, 11 adult patients with symptomatic Chiari malformation Type I underwent a standardized PF decompression. A prospective evaluation with clinical examination, functional grading, and MR imaging measurement protocols was performed pre- and postoperatively. A method is reported for the measurement of PF volume (PFV) after surgery. The degree of PFV increase was compared with the preoperative size of the PF and with the clinical outcome.

Results
All 11 patients improved postoperatively, with complete and partial recovery in 4 and 7 patients, respectively. No postoperative complication occurred after a mean follow-up period of 45 months.
The mean relative increase in PFV accounted for 10% (range 1.5%–19.7%) of the initial PFV; the increase was greater in cases in which the PF was small (r = −0.52, p = 0.09) and the basiocciput was short (r = −0.37, p = 0.2). A statistically significant positive correlation was found between the degree of PFV increase and the treatment response (p = 0.014); complete recovery was observed with a PFV increase of 15% and partial recovery with an increase of 7%.

Conclusions
The treatment response is significantly influenced by the degree of PFV increase, which is dependent on the size of the PF and the extent of the craniectomy, suggesting that the optimal patient-specific PFV increase could be predicted on the basis of preoperative MR imaging and enhancing the perspective that the craniectomy size could be tailored to the individual PFV.
Posterior ring apophysis separation combined with lumbar disc herniation in adults: a 10-year experience in the surgical management of 87 cases
Authors: Akhaddar Ali , Belfquih Hatim , Oukabli Mohamed , Boucetta Mohammed 
Published: February 2011

Object
The association of posterior ring apophysis separation (PRAS) with lumbar disc herniation (LDH) is uncommon and represents a true subgroup of disc herniation mainly seen in the adolescent population. The objective of this study was to describe a decade of experience in the care of adult patients with PRAS with LDH, giving particular attention to its diagnosis, surgical treatment, and outcome.

Methods
This retrospective study focuses on a case series of adult patients with PRAS associated with LDH who underwent surgery for lumbar disc disease in the author's neurosurgical department between 1999 and 2008. Posterior ring apophysis separation was diagnosed in 87 (5.35%) of 1625 patients surgically treated for LDH; these patients made up the PRAS group. During a 6-month period in 2005, LDH without PRAS was diagnosed in 89 consecutive patients at the same facility; these patients constituted the control group. Presenting symptoms, physical examination findings, and preoperative imaging results were obtained from medical records. Immediate operative results were assessed, as were complications, long-term outcome, and the need for repeat surgery.

Results
This study is the first to document the distinguishing features between adult patients with and those without PRAS. The difference in average age was statistically significant (p < 0.001) between the study group (36.22 years) and the control group (44.30 years), as was the incidence of male patients (86.20% vs 71.91%, p = 0.020), incidence of military patients (74.71% vs 57.30%, p = 0.015), average duration of symptoms (16.13 vs 8.4 months, p = 0.016), and incidence of reactive scoliosis (19.54% vs 4.49%, p = 0.002). The most common anatomical location of disc herniation in the PRAS group was L5–S1 (51.72%) versus L4–L5 (53.93%) in the control group (p = 0.017). In terms of previous injury, motor deficits, back and/or leg pain, lateral or central location of LDH, mean anteroposterior diameter of disc herniation, hard or soft discs, and surgical complications, there was no statistical difference between the 2 patient groups. Similarly, there was no difference in recurrence rates and clinical outcomes between the patients with or without PRAS.

Conclusions
Posterior ring apophysis separation with LDH is probably more common in adults than is generally recognized. It must be suspected when young male patients with persistent sciatic scoliosis and no history of injury show signs of calcified LDH. Computed tomography scanning with sagittal reconstructions is the procedure of choice for diagnosing. The L5–S1 intervertebral disc level is most commonly affected, especially the superior endplate of S-1. This condition needs more extensive surgical exposure and resection to relieve the nerve impingement. The occurrence of an apophyseal lesion was not associated with recurrent disc herniation or a fair outcome.
The collagenic architecture of human dura mater
Authors: Protasoni Marina , Sangiorgi Simone , Cividini Andrea , Culuvaris Gloria Tiffany , Tomei Giustino , Dell'Orbo Carlo , Raspanti Mario , Balbi Sergio , Reguzzoni Marcella 
Published: February 2011

Object
Human dura mater is the most external meningeal sheet surrounding the CNS. It provides an efficient protection to intracranial structures and represents the most important site for CSF turnover. Its intrinsic architecture is made up of fibrous tissue including collagenic and elastic fibers that guarantee the maintenance of its biophysical features. The recent technical advances in the repair of dural defects have allowed for the creation of many synthetic and biological grafts. However, no detailed studies on the 3D microscopic disposition of collagenic fibers in dura mater are available. The authors report on the collagenic 3D architecture of normal dura mater highlighting the orientation, disposition in 3 dimensions, and shape of the collagen fibers with respect to the observed layer.

Methods
Thirty-two dura mater specimens were collected during cranial decompressive surgical procedures, fixed in 2.5% Karnovsky solution, and digested in 1 N NaOH solution. After a routine procedure, the specimens were observed using a scanning electron microscope.

Results
The authors distinguished the following 5 layers in the fibrous dura mater of varying thicknesses, orientation, and structures: bone surface, external median, vascular, internal median, and arachnoid layers.

Conclusions
The description of the ultrastructural 3D organization of the different layers of dura mater will give us more information for the creation of synthetic grafts that are as similar as possible to normal dura mater. This description will be also related to the study of the neoplastic invasion.
Correlation of higher preoperative American Society of Anesthesiology grade and increased morbidity and mortality rates in patients undergoing spine surgery
Authors: Fu Kai-Ming G. , Smith Justin S. , Polly David W. , Ames Christopher P. , Berven Sigurd H. , Perra Joseph H. , McCarthy Richard E. , Knapp D. Raymond , Shaffrey Christopher I. 
Published: February 2011

Object
Patients with varied medical comorbidities often present with spinal pathology for which operative intervention is potentially indicated, but few studies have examined risk stratification in determining morbidity and mortality rates associated with the operative treatment of spinal disorders. This study provides an analysis of morbidity and mortality data associated with 22,857 cases reported in the multicenter, multisurgeon Scoliosis Research Society Morbidity and Mortality database stratified by American Society of Anesthesiologists (ASA) physical status classification, a commonly used system to describe preoperative physical status and to predict operative morbidity.

Methods
The Scoliosis Research Society Morbidity and Mortality database was queried for the year 2007, the year in which ASA data were collected. Inclusion criterion was a reported ASA grade. Cases were categorized by operation type and disease process. Details on the surgical approach and type of instrumentation were recorded. Major perioperative complications and deaths were evaluated. Two large subgroups—patients with adult degenerative lumbar disease and patients with major deformity—were also analyzed separately. Statistical analyses were performed with the chi-square test.

Results
The population studied comprised 22,857 patients. Spinal disease included degenerative disease (9409 cases), scoliosis (6782 cases), spondylolisthesis (2144 cases), trauma (1314 cases), kyphosis (831 cases), and other (2377 cases). The overall complication rate was 8.4%. Complication rates for ASA Grades 1 through 5 were 5.4%, 9.0%, 14.4%, 20.3%, and 50.0%, respectively (p = 0.001). In patients undergoing surgery for degenerative lumbar diseases and major adult deformity, similarly increasing rates of morbidity were found in higher-grade patients. The mortality rate was also higher in higher-grade patients. The incidence of major complications, including wound infections, hematomas, respiratory problems, and thromboembolic events, was also greater in patients with higher ASA grades.

Conclusions
Patients with higher ASA grades undergoing spinal surgery had significantly higher rates of morbidity than those with lower ASA grades. Given the common application of the ASA system to surgical patients, this grade may prove helpful for surgical decision making and preoperative counseling with regard to risks of morbidity and mortality.
Max Brödel: his art, legacy, and contributions to neurosurgery through medical illustration
Authors: Patel Smruti K. , Couldwell William T. , Liu James K. 
Published: February 2011

Max Brödel is considered the father of modern medical illustration. This report reviews his contributions to neurosurgery as a medical illustrator.
Max Brödel, a young artist from Leipzig, Germany, was hired at Johns Hopkins Hospital in 1894, where he illustrated an operative textbook of gynecology for Howard A. Kelly. Although Brödel did not have any formal medical training, he quickly acquired knowledge of anatomy, pathology, physiology, and surgery. Brödel's extraordinary illustrations were characterized by an aerial perspective that conveyed the surgeon's operative viewpoint and precise surgical anatomy. He masterfully incorporated tissue realism with cross-sectional anatomy to accentuate concepts while maintaining topographical accuracy. Brödel's reputation spread quickly and resulted in collaborations with prominent surgeons, such as Cushing, Halsted, and Dandy. Cushing, who also possessed artistic talent, became a pupil of Brödel and remained a very close friend.
In 1911, Brödel was appointed the director of the Department of Art as Applied to Medicine at Johns Hopkins, the first academic department of its kind in the world. For the next several decades, he trained generations of renowned medical illustrators. Just as Osler, Halsted, and Cushing passed their skills and knowledge to future leaders of medicine and surgery, Brödel did the same for the field of medical illustration. The advancement of neurosurgical education has been greatly facilitated by Max Brödel's artistic contributions. His unique ability to synthesize art and medicine resulted in timeless illustrations that remain indispensable to surgeons. The art produced by his legacy of illustrators continues to flourish in neurosurgical literature today.
Brain injury after intracerebral hemorrhage in spontaneously hypertensive rats
Authors: Wu Gang , Bao Xuhui , Xi Guohua , Keep Richard F. , Thompson B. Gregory , Hua Ya 
Published: February 2011

Object
Hypertension is the main cause of spontaneous intracerebral hemorrhages (ICHs), but the effects of hypertension on ICH-induced brain injury have not been well studied. In this study, the authors examined ICH-induced brain injury in spontaneously hypertensive rats (SHRs).

Methods
This 2-part study was performed in 12-week-old male SHRs and Wistar Kyoto (WKY) rats. First, the rats received an intracaudate injection of 0.3 U collagenase, and hematoma sizes were determined at 24 hours. Second, rats were injected with 100 μl autologous whole blood into the right basal ganglia. Brain edema, neuronal death, ferritin expression, microglia activation, and neurological deficits were examined.

Results
Hematoma sizes were the same in SHR and WKY rats 24 hours after collagenase injection. The SHRs had greater neuronal death and neurological deficits after blood injection. Intracerebral hemorrhage also resulted in higher brain ferritin levels and stronger activation of microglia in SHRs. However, perihematomal brain edema was the same in the SHRs and WKY rats.

Conclusions
Moderate chronic hypertension resulted in more severe ICH-induced neuronal death and neurological deficits, but did not exaggerate hematoma enlargement and perihematomal brain edema in the rat ICH models.
Selective ophthalmic artery infusion of chemotherapy for advanced intraocular retinoblastoma: initial experience with 17 tumors
Authors: Peterson Eric C. , Elhammady Mohamed Samy , Quintero-Wolfe Stacey , Murray Timothy G. , Aziz-Sultan Mohammad Ali 
Published: February 2011

Object
Retinoblastoma is the most common ocular neoplasm in children. Left untreated it spreads to the brain via the optic nerve. Traditional therapy is enucleation, and while this procedure is still the most common treatment worldwide, modern eye-preserving therapies can often spare the globe. However, patients with retinoblastoma often present in advanced stages of the disease when these globe-preserving strategies are often insufficient to prevent enucleation. In these challenging cases, direct infusion of chemotherapy into the ophthalmic artery has been attempted to achieve tumor control. The authors' aim in this study was to report on their initial experience with and clinical results for this approach.

Methods
The authors prospectively collected data on all cases of retinoblastoma treated with selective intraophthalmic melphalan at Bascom Palmer Eye Institute. All cases were classified as International Intraocular Retinoblastoma Classification (IIRC) Group D or Reese-Ellsworth Group Vb, had not responded to aggressive multimodal therapy consisting of chemotherapy and focal consolidating laser therapy, and were pending enucleation. Using digital subtraction angiography, a microcatheter was navigated under roadmap guidance into the ophthalmic artery, and melphalan was infused over 40 minutes. Early in the series, patients were treated with 3 or 5 mg of melphalan, but after low response rates occurred all eyes were treated with 7.5 mg of melphalan. All patients were examined with funduscopy while under anesthesia 3 weeks after treatment and every 3 months thereafter. Patients with persistent disease were retreated with repeat infusions of melphalan.

Results
Twenty-six procedures were performed to treat 17 tumors in 15 patients. Successful cannulation of the ophthalmic artery was achieved in all cases. The follow-up ranged from 3 to 12 months, with a mean of 8.6 months. Overall, 76% of the tumors responded to therapy and these cases were spared enucleation. The average number of treatments was 1.5 per tumor. Of the responders, 54% responded to a single dose of melphalan. Treatment with the higher dose of 7.5 mg up front was associated with a lower enucleation rate (0% vs 36%) as compared with the lower starting dose. Delayed vitreous hemorrhage occurred after 4 (15%) of 26 treatments, and these cases were treated with enucleation.

Conclusions
In this challenging group of advanced retinoblastomas refractory to aggressive multimodal therapy, virtually 100% of eyes are generally enucleated. In contrast, the authors' protocol of infusing melphalan directly into the ophthalmic artery led to a dramatic decrease in the enucleation rate to 23.5%. While it is now the treatment of choice for refractory retinoblastoma at their center, its role in less advanced disease remains to be elucidated.
Perspectives énergétiques entre 1980 et 2000
Authors: Boudy Michel 
Published: February 2011

L'augmentation du prix du pétrole a engagé un processus évolutif vers un nouveau système énergétique. Si ce processus apparaît irréversible, le rythme auquel se développeront les énergies de substitution apparaît largement indéterminé.
L'auteur remarque qu'en l'an 2000 la consommation mondiale d'énergie aura progressé de 4 milliards de t.e.p. et cela malgré des économies qui, à cette époque, seront de l'ordre de 2 milliards de t.e.p.
La comparaison avec les prévisions d'avant 1973 est frappante : les besoins escomptés aujourd'hui pour l'an 2000 sont inférieurs de près de moitié à ceux prévus avant 1973.
20 % des besoins nouveaux seront couverts par les énergies nouvelles. C'est-à-dire que les énergies traditionnelles resteront largement prépondérantes, les hydrocarbures assurant à eux seuls la satisfaction de la moitié des besoins mondiaux en énergie.
Ce redéploiement est un défi de grande ampleur lancé aux pays industrialisés. En mobilisant leur potentiel scientifique et financier pour mettre en valeur leurs ressources naturelles, ces pays retrouveront à terme la maîtrise de leur approvisionnement en énergie.