bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond the Individual: Toward a Nomological Network of Organizational Empowerment
Authors: Peterson N. Andrew , Zimmerman Marc A.
Published: September 2004

Empowerment research has generally been limited to the individual level of analysis. Efforts to study empowerment beyond the individual require conceptual frameworks suggesting attributes that define the construct and guide its measurement. This paper presents an initial attempt to describe the nomological network of empowerment at the organizational level of analysis—organizational empowerment (OE). Intraorganizational, interorganizational, and extraorganizational components of OE are described. Implications for empowerment theory and practice are discussed.
Abuse Experiences in a Community Sample of Young Adults: Relations with Psychiatric Disorders, Sexual Risk Behaviors, and Sexually Transmitted Diseases
Authors: Tubman Jonathan G. , Montgomery Marilyn J. , Gil Andrés G. , Wagner Eric F.
Published: September 2004

This study documents significant associations among lifetime abuse experiences, psychiatric diagnoses, and sexual risk behaviors in a multiethnic community sample of young men and women (N = 1803) in South Florida. Self‐report data were collected via structured interviews as part of a longitudinal follow‐up of a larger school‐based study. Participants were grouped according to extent of lifetime abuse experiences. Cumulative lifetime abuse experiences were associated with increased risk for a broad range of individual lifetime psychiatric disorders, as well as cumulative lifetime psychiatric disorders. Both cumulative abuse experiences and cumulative psychiatric disorders were independently associated with (a) higher levels of sexual risk behaviors and (b) higher risk for lifetime sexually transmitted diseases (STDs). Implications for selective prevention of sexual risk behaviors and STDs among young adults with histories of abuse and psychiatric disorders are discussed.
Specialized and redundant roles of TBP and a vertebrate-specific TBP paralog in embryonic gene regulation in
Xenopus
Authors: Jallow Zainab , Jacobi Ulrike G. , Weeks Daniel L. , Dawid Igor B. , Veenstra Gert Jan C.
Published: September 2004

The general transcription factor TATA-binding protein (TBP) is a key initiation factor involved in transcription by all three eukaryotic RNA polymerases. In addition, the related metazoan-specific TBP-like factor (TLF/TRF2) is essential for transcription of a distinct subset of genes. Here we characterize the vertebrate-specific TBP-like factor TBP2, using
in vitro
assays,
in vivo
antisense knockdown, and mRNA rescue experiments, as well as chromatin immunoprecipitation. We show that TBP2 is recruited to promoters in
Xenopus
oocytes in the absence of detectable TBP recruitment. Furthermore, TBP2 is essential for gastrulation and for the transcription of a subset of genes during
Xenopus
embryogenesis. In embryos, TBP2 protein is much less abundant than TBP, and moderate overexpression of TBP2 partially rescues an antisense knockdown of TBP levels and restores transcription of many TBP-dependent genes. TBP2 may be a TBP replacement factor in oocytes, whereas in embryos both TBP and TBP2 are required even though they exhibit partial redundancy and gene selectivity.
The N‐terminal copper‐binding domain of the amyloid precursor protein protects against Cu2+ neurotoxicity in vivo
Authors: Cerpa Waldo F. , Barría María I. , Chacón Marcelo A. , Suazo Miriam , González Mauricio , Opazo Carlos , Bush Ashley I. , Inestrosa Nibaldo C.
Published: September 2004

The amyloid precursor protein (APP) contains a Cu binding domain (CuBD) localized between amino acids 135 and 156 (APP135‐156), which can reduce Cu2+ to Cu1+ in vitro. The physiological function of this APP domain has not yet being established; nevertheless several studies support the notion that the CuBD of APP is involved in Cu homeostasis. We used APP synthetic peptides to evaluate their protective properties against Cu2+ neurotoxicity in a bilateral intra‐hippocampal injection model. We found that human APP135‐156 protects against Cu2+‐induced neurotoxic effects, such as, impairment of spatial memory, neuronal cell loss, and astrogliosis. APP135‐156 lacking two histidine residues showed protection against Cu2+; however, APP135‐156 mutated in cysteine 144, a key residue in the reduction of Cu2+ to Cu1+, did not protect against Cu2+ neurotoxicity. In accordance with recent reports, the CuBD of the Caenorhabditis elegans, APL‐1, protected against Cu2+ neurotoxicity in vivo. We also found that Cu2+ neurotoxicity is associated with an increase in nitrotyrosine immunofluorescence as well as with a decrease in Cu2+ uptake. The CuBD of APP therefore may play a role in the detoxification of brain Cu.
A novel bifunctionality: PAT1 and PAT2 mediate electrogenic proton/amino acid and electroneutral proton/fatty acid symport
Authors: Foltz Martin , Boll Michael , Raschka Ladislav , Kottra Gabor , Daniel Hannelore
Published: September 2004

Recently, the PAT family of proton‐dependent amino acid transporters has been identified as a novel class of mammalian amino acid symporters. PAT1 and PAT2 members mediate electrogenic uptake of small, neutral amino acids and derivatives by cotransport of protons. Analysis of the structural requirements for substrate recognition by PAT1 identified that a free amino group in a substrate is not essential for recognition. We therefore hypothesized that PAT1 and its ortholog PAT2 may also be able to recognize and transport the homologous short‐chain fatty acids (SCFAs) such as acetate, propionate, and butyrate. We examined in Xenopus laevis oocytes whether the SCFAs interact with the transporter by employing flux studies, electrophysiology and intracellular pH recordings. SCFAs did not induce positive inward currents but inhibited glycine‐induced transport currents. PAT‐mediated uptake of radiolabeled proline was also dose‐dependently reduced by SCFA and could be described by first order competition kinetics with apparent Ki‐values for butyrate of 6.0 ± 0.7 and 7.6 ± 1.3 mM for PAT1 and PAT2, respectively. Acetate as well as propionate uptake was significantly enhanced in oocytes expressing PAT1 or PAT2. An electroneutral H+/SCFA symport mode was demonstrated by recording intracellular pH changes under voltage clamp conditions with rate constants for the initial intracellular acidification in the presence of SCFAs significantly increased in PAT‐expressing oocytes. In conclusion, our data demonstrate that the PAT1 and PAT2 proteins are capable to transport selected SCFAs in an electroneutral and the homologous amino acids in an electrogenic mode and are therefore a paradigm for bifunctional solute carriers.
Amyloidogenesis recapitulated in cell culture: a peptide inhibitor provides direct evidence for the role of heparan sulfate and suggests a new treatment strategy
Authors: Elimova Elena , Kisilevsky Robert , Szarek Walter A. , Ancsin John B.
Published: September 2004

To date 22 different polypeptides, including Aβ in Alzheimer’s disease and PrPSc in prion disorders, are known to re‐fold and assemble into highly organized fibrils, which associate with heparan sulfate (HS) proteoglycans to form tissue deposits called amyloid. Mononuclear phagocytes have long been thought to be involved in this process, and we describe a monocytic cell culture system that can transform the acute‐phase protein serum amyloid A (SAA1.1) into AA‐amyloid and appears to recapitulate all the main features of amyloidogenesis observed in vivo. These features in common include nucleation‐dependent kinetics, identical proteolytic processing of SAA1.1, and co‐deposition of HS with the fibrils. Heparin and polyvinylsulfonate previously reported to block AA‐amyloidogenesis in mice are also effective inhibitors in this cell culture model. Furthermore, a synthetic peptide (27‐mer) corresponding to a HS binding site of SAA, blocks amyloid deposition at a concentration that is several‐orders‐of‐magnitude lower than any other peptide‐based inhibitor previously reported. The 27‐mer’s inhibitory activity may target the amyloidogenic pathway specifically as it does not interfere with the binding of SAA to monocytes. These data provide direct evidence that SAA1.1:HS interactions are a critical step in AA‐amyloidogenesis and suggest a novel treatment strategy for other amyloidoses.
Endothelin induces differentiation of ANP‐EGFP expressing embryonic stem cells towards a pacemaker phenotype
Authors: Gassanov Natig , Er Fikret , Zagidullin Naufal , Hoppe Uta C.
Published: September 2004

Currently, only limited insight into mechanisms promoting the differentiation and specification of the mammalian cardiac conduction system is available. Therefore, we established a murine embryonic stem (ES) cell line stably expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of the human atrial natriuretic peptide (ANP) promoter to further characterize the development of very early stages of the mammalian cardiac conduction tissue. The cardiac nature of ANP‐EGFP positive cells was confirmed by immunostaining. In ANP‐EGFP expressing ES cell‐derived cardiomyocytes, a distinct sublineage of pacemaker cells could be identified. Pacemaker cells displayed a spindle shape and exhibited a higher spontaneous beating rate, faster If current activation and larger If current densities compared with triangular atrial‐like cardiocytes. Exposure to endothelin‐1 significantly increased the percentage of pacemaker‐like cells without affecting their electrophysiological properties. These findings were corroborated by immunostaining with antibodies against connexin 40 and connexin 45, known markers for cardiac conduction tissue. Conversely, treatment of ANP‐EGFP expressing ES cells with neuregulin‐1 exhibited no effect on differentiation. These results indicate that ANP‐EGFP expression enables the identification of ES cell‐derived pacemaker cells by their fluorescence and morphology and that endothelin‐1 promotes the development of ANP‐EGFP positive cardiomyocytes to a pacemaker‐like phenotype.
Interleukin‐6: a cytokine to forget
Authors: Balschun D. , Wetzel W. , del Rey A. , Pitossi F. , Schneider H. , Zuschratter W. , Besedovsky H. O.
Published: September 2004

It is known that proinflammatory cytokines such as interleukin‐6 (IL‐6) are expressed in the central nervous system (CNS) during disease conditions and affect several brain functions including memory and learning. In contrast to these effects observed during pathological conditions, here we describe a physiological function of IL‐6 in the “healthy” brain in synaptic plasticity and memory consolidation. During long‐term potentiation (LTP) in vitro and in freely moving rats, IL‐6 gene expression in the hippocampus was substantially increased. This increase was long lasting, specific to potentiation, and was prevented by inhibition of N‐methyl‐D‐aspartate receptors with (±)‐2‐amino‐5‐phosphonopentanoic acid (AP‐5). Blockade of endogenous IL‐6 by application of a neutralizing anti‐IL6 antibody 90 min after tetanus caused a remarkable prolongation of LTP. Consistently, blockade of endogenous IL‐6, 90 min after hippocampus‐dependent spatial alternation learning resulted in a significant improvement of long‐term memory. In view of the suggested role of LTP in memory formation, these data implicate IL‐6 in the mechanisms controlling the kinetics and amount of information storage.
Life after corpse engulfment: phagocytosis of apoptotic cells leads to VEGF secretion and cell growth
Authors: Golpon Heiko A. , Fadok Valerie A. , Taraseviciene-Stewart Laima , Scerbavicius Robertas , Sauer Clemens , Welte Tobias , Henson Peter M. , Voelkel Norbert F.
Published: September 2004

Removal of apoptotic cells by neighboring viable cells or professional phagocytes is essential for the maintenance of tissue homeostastis. Here we show that the phagocytosis of apoptotic Jurkat T cells by mouse epithelial cells (HC‐11) and peritoneal macrophages leads to the secretion of growth and survival factors. We characterized VEGF as one of these factors which subsequently promote the proliferation of endothelial cells. Further we demonstrate that the phagocytosis of apoptotic bodies inhibits both spontanous and UV‐irradiation‐induced apoptosis in endothelial and epithelial cells. These effects were not observed when phagocytes had been exposed to viable or necrotic Jurkat T cells. We conclude that phagocytosis of apoptotic cells leads to secretion of growth and survival factors by phagocytes that represents a new form of life‐promoting cell‐cell interaction.
PrPc capping in T cells promotes its association with the lipid raft proteins reggie‐1 and reggie‐2 and leads to signal transduction
Authors: Stuermer Claudia A. O. , Langhorst Matthias F. , Wiechers Marianne F. , Legler Daniel F. , Hanwehr Sylvia Hannbeck von , Guse Andreas H. , Plattner Helmut
Published: September 2004

The cellular prion protein (PrPc) resides in lipid rafts, yet the type of raft and the physiological function of PrPc are unclear. We show here that cross‐linking of PrPc with specific antibodies leads to 1) PrPc capping in Jurkat and human peripheral blood T cells; 2) to cocapping with the intracellular lipid raft proteins reggie‐1 and reggie‐2; 3) to signal transduction as seen by MAP kinase phosphorylation and an elevation of the intracellular Ca2+ concentration; 4) to the recruitment of Thy‐1, TCR/CD3, fyn, lck and LAT into the cap along with local tyrosine phosphorylation and F‐actin polymerization, and later, internalization of PrPc together with the reggies into limp‐2 positive lysosomes. Thus, PrPc association with reggie rafts triggers distinct transmembrane signal transduction events in T cells that promote the focal concentration of PrPc itself by guiding activated PrPc into preformed reggie caps and then to the recruitment of important interacting signaling molecules.
Retinoid‐modulated MAT1 ubiquitination and CAK activity
Authors: He Qiaojun , Peng Hui , Collins Steven J. , Triche Timothy J. , Wu Lingtao
Published: September 2004

Human cyclin‐dependent kinase (CDK)‐activating kinase (CAK) has a dual function in cross‐regulation of cell cycle and differentiation, whereas ménage à trois 1 (MAT1) assembles CAK and determines CAK's substrate specificity. Although the dynamic state of MAT1 protein levels is found to modulate CAK activity, how intracellular regulation of MAT1 controls CAK activity is unknown. Recent studies demonstrate that retinoic acid (RA)‐induced human HL60 cell proliferation/differentiation (P/D) transition is accompanied by MAT1 degradation and decreased CAK phosphorylation of retinoic acid receptor α (RARa). Thus, we investigated the biochemical pathway of MAT1 degradation and its relationship with CAK phosphorylation of RARa. We find that RA induces ubiquitination‐proteolysis of MAT1 and that ubiquitin‐proteasome targets CAK‐free MAT1 only. RA‐induced MAT1 ubiquitination reduces CAK abundance and decreases CAK phosphorylation of RARα, whereas inhibition of MAT1 ubiquitination resists this RA‐effect. These findings reveal that RA induces MAT1 ubiquitination to decrease CAK phosphorylation of RARα, suggesting a novel mechanism of RA‐mediated P/D transition in which MAT1 ubiquitination may act as an integral part of RA‐effect to decrease CAK activity in the switch from proliferation to differentiation.
Language Hemispheric Dominance in Patients with Congenital Lesions of Eloquent Brain
Authors: Vikingstad Eric M. , Cao Yue , Thomas Ajith J. , Johnson Alex F. , Malik Ghaus M. , Welch Kenneth M. A.
Published: September 2004

OBJECTIVE

In 90% of normal subjects, the left hemisphere is dominant for language function. We investigated whether congenital lesions of the left perisylvian regions altered cortical language representation in right-handed individuals.

METHODS

Using functional magnetic resonance imaging, we studied language hemispheric dominance in five right-handed adult patients with congenitally acquired arteriovenous malformations (AVMs) originating from left hemispheric cortical language regions. The AVMs had not caused neurological symptoms during early development, but patients presented as adults with migraine, seizure, or minor hemorrhage. Results obtained from the AVM patients were contrasted to those from right-handed brain-injured stroke patients recovering from aphasia and to those from right-handed normal subjects.

RESULTS

During silent picture naming and verb generation tasks, cortical language networks lateralized primarily to the right hemisphere in the AVM group, compared with the left hemisphere in the normal group. This right hemisphere-shifted language network in the AVM group exceeded the shifts toward right hemispheric dominance found in the stroke group.

CONCLUSION

Patients with AVMs affecting the left perisylvian regions recruited the right hemisphere into language processing networks during early development, presumably in response to congenitally aberrant circulation. This early right hemisphere recruitment in the AVM patients exceeded the similar process in the brains of stroke patients whose left cortical language networks were damaged in adulthood. Our data provide evidence of effective plasticity in the developing human brain compared with the mature brain response to injury. Knowledge of cortical language representation should assist presurgical planning in patients with developmental anomalies affecting apparently language-dominant brain regions.
Microsurgery for Small Arteriovenous Malformations of the Brain: Results in 110 Consecutive Patients
Authors: Pik Justin H. T. , Morgan Michael K.
Published: September 2004

OBJECTIVE

To examine the results of surgery in 110 consecutive patients with arteriovenous malformations (AVMs) smaller than 3 cm in diameter. These results are compared with the published results of other microsurgical series as well as with results for patients treated with focused irradiation.

METHODS

From January 1989 to November 1998, 121 patients with AVMs smaller than 3 cm were treated at our institution. One hundred ten patients underwent microsurgical removal of their AVMs. The presentation, preoperative neurological status, and postoperative outcome were recorded. Follow-up was complete for all surgical cases.

RESULTS

Of the 110 patients, 109 (99%) had angiographically confirmed obliteration of their AVMs. Two patients (1.8%) required reoperation for residual AVM. Two (4.3%) of 46 patients with AVMs in eloquent brain areas experienced worsening of their neurological status after surgery. One (1.6%) of 64 patients was worse neurologically after removal of an AVM in a noneloquent area.

CONCLUSION

Microsurgical removal is a safe and effective treatment for the majority of AVMs smaller than 3 cm in diameter. Although the treatment is accompanied by a risk of acute onset of neurological deficits, this tends to be transient in the majority of cases. Furthermore, microsurgical excision of small AVMs offers patients immediate protection from the natural history of their vascular lesions.
Aneurysms at Nonbranching Sites in the Supraclinoid Portion of the Internal Carotid Artery: Internal Carotid Artery Trunk Aneurysms
Authors: Ogawa Akira , Suzuki Michiyasu , Ogasawara Kuniaki
Published: September 2004

OBJECTIVE

Aneurysms at nonbranching sites in the supraclinoid internal carotid artery (ICA), known as blood blister-like aneurysms or ICA anterior or dorsal wall aneurysms, are not well understood. To clarify this clinical entity, 7408 patients with subarachnoid hemorrhage who were treated during a 5-year period were analyzed.

METHODS

Forty-eight patients had aneurysms that were intraoperatively confirmed to be located at a nonbranching site in the supraclinoid portion of the ICA. Neuroradiological and clinicopathological features and outcomes were studied.

RESULTS

The aneurysms were divided into the “blister type,” with a blood blister-like configuration and fragile walls, and the “saccular type,” with a saccular configuration and a relatively firm neck, like ordinary berry aneurysms. The most frequent origin was the anteromedial wall for both types. ICA dissection was associated only with the blister type, and hypertension was more frequent with the blister type (P = 0.0978). The preoperative conditions of the patients were the same, but the outcomes for patients with blister-type aneurysms were worse, because of frequent intra- and postoperative aneurysmal bleeding. Saccular-type aneurysms were safely clipped. Treatment of blister-type aneurysms by clipping on wrapping material achieved good results, but ICA trapping (P = 0.0952), clipping (P = 0.0146), and wrapping (P = 0.0110) were associated with much worse results.

CONCLUSION

Blister-type and saccular-type aneurysms have different shapes and wall characteristics. The saccular type can be treated by clipping, whereas the blister type requires clipping on wrapping material. ICA trunk aneurysms may be a better designation to express the diversity of these aneurysms, rather than ICA blood blister-like or anterior or dorsal wall aneurysms.
Adult Medulloblastoma: Prognostic Factors and Patterns of Relapse
Authors: Chan Annie W. , Tarbell Nancy J. , Black Peter McL. , Louis David N. , Frosch Matthew P. , Ancukiewicz Marek , Chapman Paul , Loeffler Jay S.
Published: September 2004

OBJECTIVE

To determine the patterns of relapse and the prognostic factors for adult medulloblastomas treated in the magnetic resonance imaging era.

METHODS

Between 1986 and 1996, 32 adult patients (age, ≥16 yr) with medulloblastomas confined to the craniospinal axis were treated in our institutions. Twenty cases involved classic histological features and 12 involved the desmoplastic variant. The Chang staging distribution was as follows: T1, 2; T2, 17; T3, 10; T4, 3; M0, 24; M1, 1; M2, 4; M3, 3. Brainstem invasion was present in nine patients. Lesions were midline in 13 cases and lateral in 19. Resection was complete in 17 cases, subtotal in 6, and partial in 5, with biopsy only in 4 cases. All patients received postoperative radiotherapy, with median doses of 36 Gy to the entire craniospinal axis and 55 Gy to the posterior fossa. Twenty-four patients received chemotherapy (20 before radiotherapy, 3 after radiotherapy, and 1 before and after radiotherapy).

RESULTS

With a median follow-up period of 5.4 years, 17 patients experienced recurrences. At 5 and 8 years, overall survival rates were 83 and 45% and disease-free survival rates were 57 and 40%, respectively. The 5- and 8-year posterior fossa control rates were 67 and 59%, respectively. Twenty-nine percent of all relapses occurred more than 5 years after treatment. The posterior fossa was the most common site of relapses. In univariate analyses, factors adversely affecting posterior fossa control were less than complete resection (P < 0.001), the presence of brainstem invasion (P = 0.02), and the use of chemotherapy (P = 0.03). The overall radiotherapy duration was marginally significant in predicting posterior fossa control, with 5-year posterior fossa control rates of 81 and 49% for durations of less than 48 days and 48 days or more, respectively (P = 0.06). In a multivariate analysis, complete resection was predictive of improved posterior fossa control (P = 0.02) and disease-free survival (P = 0.02) rates. Of the eight low-risk patients who received radiotherapy alone, three experienced recurrences in the bone as the only site of relapse.

CONCLUSION

Late relapse is common among adult patients with medulloblastomas, and long-term follow-up monitoring is important. Because of the high risk of systemic failure among the low-risk patients treated with radiotherapy alone, the role of chemotherapy for this group of patients needs to be further investigated. Complete resection, the absence of brainstem invasion, and an overall radiotherapy duration of less than 48 days are important prognostic factors.
Role of Cerebrospinal Fluid Shunting for Human Immunodeficiency Virus-positive Patients with Tuberculous Meningitis and Hydrocephalus
Authors: Nadvi Syed Sameer , Nathoo Narendra , Annamalai Ken , van Dellen James R. , Bhigjee Ahmed I.
Published: September 2004

OBJECTIVE

Tuberculous meningitis (TBM) and its complications continue to have devastating neurological consequences for patients. Budgetary constraints, especially in developing countries, have made it necessary to select patients for shunting who are likely to experience good recoveries. To date, the value of cerebrospinal fluid shunting for human immunodeficiency virus (HIV)-positive patients with TBM has not been clearly established.

METHODS

Thirty patients with TBM and hydrocephalus were prospectively evaluated. Coincidentally, one-half of the patients were HIV-positive. All patients underwent uniform treatment, including ventriculoperitoneal shunt placement and antituberculosis treatment. CD4 counts were measured for all patients. Outcomes were assessed at 1 month.

RESULTS

No complications related to shunt insertion were noted. The HIV-positive group fared poorly (death, 66.7%; poor outcome, 64.7%), compared with the HIV-negative group (death, 26.7%; poor outcome, 30.8%). Despite cerebrospinal fluid shunting, no patient in the HIV-positive group experienced a good recovery (Glasgow Outcome Scale score of 5). This is in contrast to the six patients (40%) in the HIV-negative group who, with the same treatment, experienced good recoveries (Glasgow Outcome Scale scores of 5) at discharge (P < 0.14). No patient (either HIV-positive or HIV-negative) who presented in TBM Grade 4 survived, whereas no HIV-positive patient who presented in TBM Grade 3 survived. A significant relationship was noted between CD4 counts and patient outcomes (P < 0.031).

CONCLUSION

In the absence of obvious clinical benefit, HIV-positive patients with TBM should undergo a trial of ventricular or lumbar cerebrospinal fluid drainage, and only those who exhibit significant neurological improvement should proceed to shunt surgery.
Cerebral Concussion in Athletes: Evaluation and Neuropsychological Testing
Authors: Maroon Joseph C. , Lovell Mark R. , Norwig John , Podell Kenneth , Powell John W. , Hartl Roger
Published: September 2004

OBJECTIVE

To conduct a topic review of studies related to cerebral concussion in athletes, as an aid to improving decision-making and outcomes.

METHODS

We review the literature to provide an historical perspective on the incidence and definition of and the management guidelines for mild traumatic brain injury in sports. In addition, metabolic changes resulting from cerebral concussion and the second-impact syndrome are reviewed, to provide additional principles for decision-making. Neuropsychological testing, as it applies to athletes, is discussed in detail, to delineate baseline assessments, the characteristics of the neuropsychological evaluation, the neuropsychological tests used, and the methods for in-season identification of cerebral concussion. Future directions in the management of concussions are presented.

RESULTS

The incidence of cerebral concussions has been reduced from approximately 19 per 100 participants in football per season to approximately 4 per 100, i.e., 40,000 to 50,000 concussions per year in football alone. The most commonly used definitions of concussion are those proposed by Cantu and the American Academy of Neurology. Each has associated management guidelines. Concussion or loss of consciousness occurs when the extracellular potassium concentration increases beyond the upper normal limit of approximately 4 to 5 mmol/L, to levels of 20 to 50 mmol/L, inhibiting the action potential and leading to loss of consciousness. This phenomenon helps to explain the delayed effects of symptoms after trauma.

CONCLUSION

Neuropsychological testing seems to be an effective way to obtain useful data on the short-term and long-term effects of mild traumatic brain injury. Moreover, knowledge of the various definitions and management strategies, as well as the utility of neuropsychological testing, is essential for those involved in decision-making with athletes with mild traumatic brain injuries.
Intracerebral Microdialysis in Clinical Practice: Baseline Values for Chemical Markers during Wakefulness, Anesthesia, and Neurosurgery
Authors: Reinstrup Peter , Ståhl Nils , Mellergård Pekka , Uski Tore , Ungerstedt Urban , Nordström Carl-Henrik
Published: September 2004

OBJECTIVE

The study was undertaken to measure baseline values for chemical markers in human subjects during wakefulness, anesthesia, and neurosurgery, using intracerebral microdialysis.

METHODS

Microdialysis catheters were inserted into normal posterior frontal cerebral cortex in nine patients who were undergoing surgery to treat benign lesions of the posterior fossa. The perfusion rate was 1.0 μl/min during anesthesia/neurosurgery and the early postoperative course and 0.3 μl/min during the later course. Bedside biochemical analyses of glucose, pyruvate, lactate, glycerol, glutamate, and urea were performed before, during, and after neurosurgery. After the bedside analyses, all samples were frozen for subsequent high-performance liquid chromatographic analyses of amino acids.

RESULTS

The following baseline values were obtained during wakefulness (perfusion rate, 0.3 μl/min): glucose, 1.7 ± 0.9 mmol/L; lactate, 2.9 ± 0.9 mmol/L; pyruvate, 166 ± 47 μmol/L; lactate/pyruvate ratio, 23 ± 4; glycerol, 82 ± 44 μmol/L; glutamate, 16 ± 16 mmol/L; urea, 4.4 ± 1.7 mmol/L. Marked increases in the levels of all chemical markers were observed at the beginning and end of anesthesia/surgery.

CONCLUSION

The study provides human baseline levels for biochemical markers that can presently be measured at the bedside during neurointensive care. In addition, some changes that occurred under varying physiological conditions are described.
Oncocytoma in Melanocytoma of the Spinal Cord: Case Report
Authors: Gelman Benjamin B. , Trier Todd T. , Chaljub Greg , Borokowski Joanna , Nauta Haring J. W.
Published: September 2004

OBJECTIVE AND IMPORTANCE

Oncocytoma in the central nervous system is extremely unusual. The first reported example of oncocytoma in a melanocytoma of the spinal cord was successfully excised, and its pathological appearance is described.

CLINICAL PRESENTATION

A 71-year-old woman presented with a 25-year history of back pain and myelographic evidence of a lumbar spinal cord mass. After declining surgical treatment for two decades, she elected eventually to have the mass excised. Preoperative magnetic resonance imaging revealed a large intraspinal mass that spanned spinal levels L3 through S1.

TECHNIQUE

The mass was excised en bloc through posterior laminectomies, and histopathological analysis revealed a benign neoplasm composed predominantly of monotonous sheets of plump oncocytes. Electron microscopy confirmed that the cytoplasm of the oncocytes was packed full of mitochondria. Focal areas of the tumor contained spindle cells, with abundant intracytoplasmic granular deposits of brown melanin pigment that contained melanosomes. Positive Fontana-Masson, HMB-45, and S-100 staining confirmed the final diagnosis of melanocytoma, oncocytic variant.

CONCLUSION

The first reported case of oncocytoma arising in spinal melanocytoma is described. After surgical excision, the patient recovered completely and has remained free of symptoms for 4 years.
Subarachnoid Fat Dissemination after Resection of a Cerebellopontine Angle Dysontogenic Cyst: Case Report and Review of the Literature
Authors: Carvalho Gustavo A. , Cervio Andrés , Matthies Cordula , Samii Madjid
Published: September 2004

OBJECTIVE AND IMPORTANCE

This case report illustrates the clinical and radiological relevance of extensive intracranial subarachnoid and ventricular dissemination in dysontogenic (dermoid) tumors.

CLINICAL PRESENTATION

We describe a patient with a cerebellopontine angle dysontogenic tumor. Postoperatively, the cyst disseminated fat particles extensively into the subarachnoid space. Magnetic resonance imaging (MRI) studies revealed continuous dispersion of the fat particles into the cerebral cisterns, subarachnoid space, and ventricles.

INTERVENTION

Eight years of clinical and MRI follow-up demonstrated neither neurological deterioration in the patient nor growth of the multiple lesions.

CONCLUSION

Intracranial subarachnoid dissemination of fat material may occur during the preoperative or postoperative course of dermoid and epidermoid cysts. Aseptic meningitis or other complications such as hydrocephalus, seizures, or cranial nerve deficits also may occur owing to spillage of intracranial cyst contents into the subarachnoid space. MRI can detect the presence of fat drops that may adhere to the surrounding structures or migrate with the cerebrospinal fluid flow. Intracranial disseminated fat particles can remain silent without radiological or neurological change, justifying a wait-and-see approach. During long-term postoperative follow-up, however, regular MRI studies and clinical examinations are necessary to avoid potential complications.
Extradural Endodermal Cyst of Posterior Fossa: Case Report, Review of the Literature, and Embryogenesis
Authors: Kulkarni Vaijayantee , Daniel Roy Thomas , Haran Ramachandran Pranatharthi
Published: September 2004

OBJECTIVE AND IMPORTANCE

Posterior fossa endodermal cysts are rare. They are located in the midline, in ventral or ventrolateral locations, or intrinsic to the neural axis. Accordingly, various theories of embryogenesis have been proposed. We report the first case of an extradural, dorsolaterally situated endodermal cyst.

CLINICAL PRESENTATION

An adult male patient presented with a short history of headache and cerebellar ataxia. Neuroimaging revealed an extra-axial cystic posterior fossa mass.

INTERVENTION

An entirely extradural cyst was found and was totally excised. Immunohistochemistry confirmed the diagnosis of endodermal cyst.

CONCLUSION

The extradural, dorsal location of the endodermal cyst suggests gaps at the cranial end of the notochord causing ectodermal-endodermal adhesions during early gastrulation and the persistence of endodermal remnants in the dorsal mesenchyme of the blastemal cranium. The literature is reviewed, and proposed theories of embryogenesis are discussed.
The Insular Lobe: Physiopathological and Surgical Considerations
Authors: Duffau Hugues , Capelle Laurent , Lopes Manuel , Faillot Thierry , Sichez Jean-Pierre , Fohanno Denis
Published: September 2004

OBJECTIVE

Surgery of the insula represents a technical challenge, because of the proximity of the internal capsule to the lenticulostriate arteries and the lack of certainty concerning its functionality. Using intraoperative direct cerebral stimulation, combined with neuronavigation, the authors operated on 12 insular gliomas. On the basis of this experience, the physiopathological and surgical implications are discussed.

METHODS

A low-grade insular glioma, revealed by seizures, was diagnosed in 12 right-handed patients with a normal neurological status. Preoperative magnetic resonance imaging showed that, according to Yaşargil's classification system, three patients harbored Type 3 lesions and nine patients had Type 5 lesions (10 tumors on the right side and 2 on the left dominant side). All patients underwent surgery using direct cerebral stimulation, under general anesthesia in nine patients (motor mapping) and under local anesthesia in three patients (sensorimotor and language mapping). Ultrasonography and/or neuronavigation was used in all cases. Preoperative angio-computed tomographic scanning showed the lenticulostriate arteries in two patients.

RESULTS

The internal capsule was systematically detected, and the language areas were identified within the left insula in the awake patients. The lenticulostriate arteries were seen in two patients. Seven patients presented an immediate postoperative deficit; six of them recovered completely within 3 months. Four resections were total, six were subtotal, and two were partial (left insula).

CONCLUSION

The use of intraoperative direct cerebral stimulation and neuronavigation allows surgery of the insula with minimization of the risk of sequelae, but its use is still limited with regard to the dominant hemisphere, owing to the essential role of this structure in language.
Management Outcomes for Ruptured and Unruptured Aneurysms in the Elderly
Authors: Chung Richard Y. , Carter Bob S. , Norbash Alex , Budzik Ronald , Putnam Christopher , Ogilvy Christopher S.
Published: September 2004

OBJECTIVE

In a patient older than 70 years, the decision to treat an intracranial aneurysm remains difficult whether it is ruptured or unruptured. We sought to review our institutional risks of treatment of such lesions in the context of the risks of rupture and its associated morbidity and mortality in this age group.

METHODS

One hundred twenty-nine consecutive patients aged 70 years or older, who were treated at a single institution for an intracranial aneurysm, were retrospectively reviewed. Forty patients were treated for unruptured aneurysms, and 89 patients presented after subarachnoid hemorrhage. Seven additional patients in this age group who had solely intracavernous lesions, as well as one patient with a dolichoectatic fusiform basilar lesion, were excluded. Management outcomes were assessed using a modification of the Glasgow Outcome Scale, and additional physical and functional disability was assessed using the Barthel index and the Reintegration to Normal Living index.

RESULTS

Six-month outcomes for the unruptured group were: excellent, 70%; good, 15%; fair, 5%; poor, 7.5%; and death (2.5%). Outcomes for all patients with ruptured lesions (including those not offered aggressive therapy) were: excellent, 34%; good, 9%; fair, 5.6%; poor, 3.4%; and death, 45%. Long-term follow-up was performed by questionnaire to assess physical and functional disability. Although physical disability (Barthel index) was similar among survivors, the Reintegration to Normal Living index, a global assessment of function, was significantly higher in patients with unruptured aneurysms (84.8 versus 70.1;P = 0.05), which highlights the disabling effects of hemorrhage.

CONCLUSION

On the basis of an individual treatment center's management risks, annual aneurysmal rupture rates can be estimated that justify treatment in this difficult patient population. Despite recent controversy regarding aneurysmal hemorrhage rates, we think that symptomatic unruptured aneurysms should be treated and good results can be achieved, even in older patients.
Surgical Treatment of Clinically Nonsecreting Pituitary Adenomas in Elderly Patients
Authors: Kurosaki Masamichi , Lüdecke Dieter K. , Flitsch Jörg , Saeger Wolfgang
Published: September 2004

OBJECTIVE

The goal of this study was to evaluate the efficacy and safety of transsphenoidal pituitary surgery for elderly patients, using improved techniques of the past decade.

METHODS

We retrospectively analyzed 32 surgically treated cases of clinically nonsecreting pituitary adenomas in patients more than 70 years of age (mean, 73.9 ± 3.4 yr). These patients were identified in a review of 982 patients with pituitary adenomas who were treated at University Hospital Eppendorf, Hamburg, between January 1991 and November 1999.

RESULTS

The mean preoperative duration of symptoms was 1.9 years (2 wk to 11 yr). The chiasmatic syndrome was present for 27 patients (84.4%). All patients underwent transsphenoidal surgery. Seven patients underwent reoperations. Preoperative assessments of anterior pituitary function revealed growth hormone deficiencies for 21 of 27 patients (77.8%), thyroid insufficiencies for 10 of 30 patients (33.3%), and adrenal insufficiencies for 13 of 29 patients (44.8%). Hypogonadism and hyperprolactinemia were observed for 76.7% and 46.9% of the patients, respectively. All tumors were macroadenomas, ranging from 18 to 50 mm (average, 33.6 mm) in size, including 7 enclosed and 25 invasive adenomas. Complete microscopic tumor resection was achieved in 24 cases, and subtotal removal was performed in 8 cases. There were no severe perioperative complications. In the cases involving hyperprolactinemia, serum prolactin levels were normalized for 8 of 11 patients (72.7%). Normal thyroid function was recovered for 1 of 10 patients (10.0%) with preoperative hypothyroidism. However, growth hormone or adrenal insufficiencies persisted for all patients with preoperative insufficiencies. Visual disturbances were improved for 19 of 23 patients (82.6%). All patients recovered well after surgery, with an average hospital stay of 16.3 days. Histological and immunohistochemical studies demonstrated gonadotroph adenomas in 56.7% of cases, null-cell adenomas in 26.7%, and oncocytomas in 13.3%.

CONCLUSION

Surgical treatment of nonsecreting pituitary adenomas causing visual disturbances is standard, even for elderly patients. In this series, transsphenoidal surgery was a safe procedure, with minimal morbidity and excellent tolerance. Age alone is not a contraindication for active treatment, particularly with transsphenoidal surgery.
Computer-assisted Fluoroscopic Targeting System for Pedicle Screw Insertion
Authors: Choi William W. , Green Barth A. , Levi Allan D. O.
Published: September 2004

OBJECTIVE

Biplanar fluoroscopic imaging linked to a computer-driven mechanical end-effector is under development as a targeting system for spinal surgery. This technology has the potential to enhance standard intraoperative fluoroscopic information for localization of the pedicle entry point and trajectory, and it may be an effective alternative to the computed tomography-based image-guided system (IGS) in pedicle screw placement. A preclinical study to assess the accuracy and time efficiency of this system versus a conventional IGS was conducted.

METHODS

Pedicle screw placement was performed in six cadavers from T1 to S1 levels using the ViewPoint IGS (Picker International, Inc., Cleveland, OH) on one side versus the Fluorotactic guidance system (Z-Kat, Inc., Miami, FL) on the other side. Of 216 possible pedicles, 208 were instrumented; 8 pedicle diameters were too small or were not adequately imaged. Postinsertion, each pedicle was assessed for the presence and location of cortical perforation using computed tomographic scanning and direct visualization.

RESULTS

The number of successful screw placements was 89 (87.3%) of 102 for IGS and 87 (82.1%) of 106 for the Fluorotactic guidance system, respectively. The mean time to register and operate on one level using the Fluorotactic guidance system was 14:34 minutes (minutes:seconds), compared with 6:50 minutes using the IGS. The average fluoroscope time was 4.6 seconds per pedicle.

CONCLUSION

Our data indicate that this first-generation fluoroscopy-based targeting system can significantly assist the surgeon in pedicle screw placement. The overall accuracy is comparable to an IGS, especially in the region of T9–L5. A second-generation system with a faster end-effector and user-friendly interface should significantly reduce the operating and fluoroscope time.
Correlation of Neurosurgical Subspecialization with Outcomes in Children with Malignant Brain Tumors
Authors: Albright A. Leland , Sposto Richard , Holmes Emi , Zeltzer Paul M. , Finlay Jonathan L. , Wisoff Jeffrey H. , Berger Mitchel S. , Packer Roger J. , Pollack Ian F.
Published: September 2004

OBJECTIVE

This study was performed to evaluate the association between the type of neurosurgeon (general or pediatric) and either the extent of tumor removal or the frequency of complications in children undergoing malignant brain tumor resections.

METHODS

Data were analyzed from three recent Children's Cancer Group studies: two on medulloblastomas/primitive neuroectodermal tumors and one on malignant gliomas. Neurosurgeons were classified as general neurosurgeons, as designated pediatric neurosurgeons in their institutions, or as members of the American Society of Pediatric Neurosurgeons (ASPN), which requires pediatric neurosurgical experience and practice standards.

RESULTS

Data forms from 732 children were analyzed; 485 were from children with medulloblastomas/primitive neuroectodermal tumors, and 247 were from children with malignant gliomas. Operations were performed by 269 neurosurgeons, including 213 general neurosurgeons, 29 designated pediatric neurosurgeons, and 27 ASPN members. The mean number of operations per surgeon was 1.8, 4.9, and 7.6 for general neurosurgeons, designated pediatric neurosurgeons, and ASPN members, respectively. There was a significant relationship between the extent of tumor resection or the amount of residual tumor and the type of neurosurgeon. Designated pediatric neurosurgeons and ASPN members were more likely to remove more than 90% of the tumor and to leave less than 1.5 cc of residual tumor than were general neurosurgeons (P < 0.05). In these studies, the probability of extensive tumor removal correlated with the number of operations the neurosurgeon performed (P < 0.01). Neurological complications occurred in the following proportion of cases: general neurosurgeons, 23%; designated pediatric neurosurgeons, 32%; and ASPN members, 18%.

CONCLUSION

Pediatric neurosurgeons are more likely than general neurosurgeons to extensively remove malignant pediatric brain tumors. In these tumors, extent of removal has been demonstrated to influence survival.
Molecular Insight into Medulloblastoma and Central Nervous System Primitive Neuroectodermal Tumor Biology from Hereditary Syndromes: A Review
Authors: Taylor Michael D. , Mainprize Todd G. , Rutka James T.
Published: September 2004

THROUGH THE STUDY of uncommon familial syndromes, physicians and scientists have been able to illuminate the underlying mechanisms of some of the more common sporadic diseases; this is illustrated best by studies of familial retinoblastoma. A number of rare familial syndromes have been described in which affected individuals are at increased risk of developing medulloblastoma and/or supratentorial primitive neuroectodermal tumors. The descriptions of many of these syndromes are based on patients observed by clinicians in their clinical practice. Determination of the underlying genetic defects in these patients with uncommon syndromes has led to identification of a number of genes subsequently found to be mutated in sporadic medulloblastomas (tumor suppressor genes). Associated genes in the same signaling pathways have also been found to be abnormal in sporadic medulloblastoma. Identification of patients with these rare syndromes is important, as they are often at increased risk for additional neoplasms, as are family members and future children. We review the published literature describing hereditary syndromes that have been associated with an increased incidence of medulloblastoma and/or central nervous system primitive neuroectodermal tumor. Review of the underlying molecular abnormalities in comparison to changes found in sporadic neoplasms suggests pathways important for tumorigenesis.