bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide analysis of the interaction between the endosymbiotic bacterium Wolbachia and its Drosophila host
Authors: Xi Zhiyong , Gavotte Laurent , Xie Yan , Dobson Stephen L
Published: January 2008

Background

Intracellular Wolbachia bacteria are obligate, maternally-inherited, endosymbionts found frequently in insects and other invertebrates. The success of Wolbachia can be attributed in part to an ability to alter host reproduction via mechanisms including cytoplasmic incompatibility (CI), parthenogenesis, feminization and male killing. Despite substantial scientific effort, the molecular mechanisms underlying the Wolbachia/host interaction are unknown.

Results

Here, an in vitro Wolbachia infection was generated in the Drosophila S2 cell line, and transcription profiles of infected and uninfected cells were compared by microarray. Differentially-expressed patterns related to reproduction, immune response and heat stress response are observed, including multiple genes that have been previously reported to be involved in the Wolbachia/host interaction. Subsequent in vivo characterization of differentially-expressed products in gonads demonstrates that Angiotensin Converting Enzyme (Ance) varies between Wolbachia infected and uninfected flies and that the variation occurs in a sex-specific manner. Consistent with expectations for the conserved CI mechanism, the observed Ance expression pattern is repeatable in different Drosophila species and with different Wolbachia types. To examine Ance involvement in the CI phenotype, compatible and incompatible crosses of Ance mutant flies were conducted. Significant differences are observed in the egg hatch rate resulting from incompatible crosses, providing support for additional experiments examining for an interaction of Ance with the CI mechanism.

Conclusion

Wolbachia infection is shown to affect the expression of multiple host genes, including Ance. Evidence for potential Ance involvement in the CI mechanism is described, including the prior report of Ance in spermatid differentiation, Wolbachia-induced sex-specific effects on Ance expression and an Ance mutation effect on CI levels. The results support the use of Wolbachia infected cell cultures as an appropriate model for predicting in vivo host/Wolbachia interactions.
A population-based study to investigate host genetic factors associated with hepatitis B infection and pathogenesis in the Chinese population
Authors: Zeng Zheng , Guan Li , An Ping , Sun Shan , O'Brien Stephen J , Winkler Cheryl A ,   the HBV study consortium
Published: January 2008

Background

Hepatitis B virus (HBV) infection is a significant public health problem that may lead to chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). Approximately 30% of the world's population has been infected with HBV and approximately 350 million (5–6%) are persistent carriers. More than 120 million Chinese are infected with HBV. The role of host genetic factors and their interactions with environmental factors leading to chronic HBV infection and its complications are not well understood. We believe that a better understanding of these factors and interactions will lead to more effective diagnostic and therapeutic options.

Methods/Design

This is a population-based, case-control study protocol to enroll 2200 Han Chinese from medical centers in northern and western China. Adult subjects in the following groups are being enrolled: healthy donors (n = 200), HBV infected persons achieving virus clearance (n = 400), asymptomatic HBV persistent carriers (n = 400), chronic hepatitis B cases (n = 400), decompensated liver cirrhosis with HBV infection cases (n = 400), and hepatocellular carcinoma with HBV infection cases (n = 400). In addition, for haplotype inference and quality control of sample handling and genotyping results, children of 1000 cases will be asked to provide a buccal sample for DNA extraction. With the exception of adult patients presenting with liver cirrhosis or HCC, all other cases and controls will be 40 years or older at enrollment. A questionnaire is being administered to capture dietary and environmental risk factors. Both candidate-gene and genome-wide association approaches will be used to assess the role of single genetic factors and higher order interactions with other genetic or environmental factors in HBV diseases.

Conclusion

This study is designed and powered to detect single gene effects as well as gene-gene and environmental-gene interactions. The identification of allelic polymorphisms in genes involved in the pathway leading to chronic viral infection, liver cirrhosis and, ultimately, hepatocellular carcinoma would provide insights to those factors leading to HBV replication, liver inflammation, fibrosis, and the carcinogenic process. An understanding of the contribution of host genetic factors and their interactions may inform public health policy, improve diagnostics and clinical management, and provide targets for drug development.
Participatory design in the development of the wheelchair convoy system
Authors: Sharma Vinod , Simpson Richard C , LoPresti Edmund F , Mostowy Casimir , Olson Joseph , Puhlman Jeremy , Hayashi Steve , Cooper Rory A , Konarski Ed , Kerley Barry
Published: January 2008

Background

In long-term care environments, residents who have severe mobility deficits are typically transported by having another person push the individual in a manual wheelchair. This practice is inefficient and encourages staff to hurry to complete the process, thereby setting the stage for unsafe practices. Furthermore, the time involved in assembling multiple individuals with disabilities often deters their participation in group activities.

Methods

The Wheelchair Convoy System (WCS) is being developed to allow a single caregiver to move multiple individuals without removing them from their wheelchairs. The WCS will consist of a processor, and a flexible cord linking each wheelchair to the wheelchair in front of it. A Participatory Design approach – in which several iterations of design, fabrication and evaluation are used to elicit feedback from users – was used.

Results

An iterative cycle of development and evaluation was followed through five prototypes of the device. The third and fourth prototypes were evaluated in unmanned field trials at J. Iverson Riddle Development Center. The prototypes were used to form a convoy of three wheelchairs that successfully completed a series of navigation tasks.

Conclusion

A Participatory Design approach to the project allowed the design of the WCS to quickly evolve towards a viable solution. The design that emerged by the end of the fifth development cycle bore little resemblance to the initial design, but successfully met the project's design criteria. Additional development and testing is planned to further refine the system.
The Munich Digitization Center at the Bayerische Staatsbibliothek
Authors: Dörr Marianne
Published: January 2008

In Summer 1997 the Munich Digitization Center (MDC) was founded at the Bayerische Staatsbibliothek (BSB; Bavarian State Library). It was the Deutsche Forschungsgemeinschaft (DFG; German Research Association) that had initiated the foundation of two so-called centers of excellence at two libraries which had already some experience in digitization. In parallel the DFG established a new grant program, named “Retrospective Digitization of library holdings” that currently sponsors about 50 projects. This program intends to encourage libraries to work up digitally library holdings with interest for researchers, holdings that exist only in print form, and to offer them freely to everybody via the WWW. The processing and presentation should realize not only universal access but also recognizable added value in search and retrieval compared to the print version. Together with the funding programs “Electronic Publishing and Virtual Subject Libraries” and “Modernisation and Rationalisation” the program “Retrospective Digitization of library holdings” aims towards a future vision of a distributed digital research library.
Medial Temporal Lobe Activity Predicts Successful Relational Memory Binding
Authors: Hannula Deborah E. , Ranganath Charan
Published: January 2008

Previous neuropsychological findings have implicated medial temporal lobe (MTL) structures in retaining object-location relations over the course of short delays, but MTL effects have not always been reported in neuroimaging investigations with similar short-term memory requirements. Here, we used event-related functional magnetic resonance imaging to test the hypothesis that the hippocampus and related MTL structures support accurate retention of relational memory representations, even across short delays. On every trial, four objects were presented, each in one of nine possible locations of a three-dimensional grid. Participants were to mentally rotate the grid and then maintain the rotated representation in anticipation of a test stimulus: a rendering of the grid, rotated 90° from the original viewpoint. The test stimulus was either a “match” display, in which object-location relations were intact, or a “mismatch” display, in which one object occupied a new, previously unfilled location (mismatch position), or two objects had swapped locations (mismatch swap). Encoding phase activation in anterior and posterior regions of the left hippocampus, and in bilateral perirhinal cortex, predicted subsequent accuracy on the short-term memory decision, as did bilateral posterior hippocampal activity after the test stimulus. Notably, activation in these posterior hippocampal regions was also sensitive to the degree to which object-location bindings were preserved in the test stimulus; activation was greatest for match displays, followed by mismatch-position displays, and finally mismatch-swap displays. These results indicate that the hippocampus and related MTL structures contribute to successful encoding and retrieval of relational information in visual short-term memory.
Pulse Inhibition of Histone Deacetylases Induces Complete Resistance to Oxidative Death in Cortical Neurons without Toxicity and Reveals a Role for Cytoplasmic p21waf1/cip1in Cell Cycle-Independent Neuroprotection
Authors: Langley Brett , D'Annibale Melissa A. , Suh Kyungsun , Ayoub Issam , Tolhurst Aaron , Bastan Birgül , Yang Lichuan , Ko Brian , Fisher Marc , Cho Sunghee , Beal M. Flint , Ratan Rajiv R.
Published: January 2008

Histone deacetylase (HDAC) inhibitors are currently in human clinical trials as antitumor drugs because of their ability to induce cell dysfunction and death in cancer cells. The toxic effects of HDAC inhibitors are also apparent in cortical neuronsin vitro, despite the ability of these agents to induce significant protection in the cells they do not kill. Here we demonstrate that pulse exposure of cortical neurons (2 h) in anin vitromodel of oxidative stress results in durable neuroprotection without toxicity. Protection was associated with transcriptional upregulation of the cell cycle inhibitor, p21waf1/cip1, both in this model and in anin vivomodel of permanent ischemia. Transgenic overexpression of p21waf1/cip1in neurons can mimic the protective effect of HDAC inhibitors against oxidative stress-induced toxicity, including death induced by glutathione depletion or peroxide addition. The protective effect of p21waf1/cip1in the context of oxidative stress appears to be unrelated to its ability to act in the nucleus to inhibit cell cycle progression. However, although p21waf1/cip1is sufficient for neuroprotection, it is not necessary for HDAC inhibitor neuroprotection, because these agents can completely protect neurons cultured from p21waf1/cip1-null mice. Together these findings demonstrate (1) that pulse inhibition of HDACs in cortical neurons can induce neuroprotection without apparent toxicity; (2) that p21waf1/cip1is sufficient but not necessary to mimic the protective effects of HDAC inhibition; and (3) that oxidative stress in this model induces neuronal cell death via cell cycle-independent pathways that can be inhibited by a cytosolic, noncanonical action of p21waf1/cip1.
Systems Neuroplasticity in the Aging Brain: Recruiting Additional Neural Resources for Successful Motor Performance in Elderly Persons
Authors: Heuninckx Sofie , Wenderoth Nicole , Swinnen Stephan P.
Published: January 2008

Functional imaging studies have shown that seniors exhibit more elaborate brain activation than younger controls while performing motor tasks. Here, we investigated whether this age-related overactivation reflects compensation or dedifferentiation mechanisms. “Compensation” refers to additional activation that counteracts age-related decline of brain function and supports successful performance, whereas “dedifferentiation” reflects age-related difficulties in recruiting specialized neural mechanisms and is not relevant to task performance. To test these predictions, performance on a complex interlimb coordination task was correlated with brain activation. Findings revealed that coordination resulted in activation of classical motor coordination regions, but also higher-level sensorimotor regions, and frontal regions in the elderly. Interestingly, a positive correlation between activation level in these latter regions and motor performance was observed in the elderly. This performance enhancing additional recruitment is consistent with the compensation hypothesis and characterizes neuroplasticity at the systems level in the aging brain.
Cerebellar Dysfunction Explains the Extinction-Like Abolition of Conditioned Eyeblinks After NBQX Injections in the Inferior Olive
Authors: Zbarska Svitlana , Bloedel James R. , Bracha Vlastislav
Published: January 2008

Classical conditioning of the eyeblink response is a form of motor learning that is controlled by the intermediate cerebellum and related brainstem structures. The inferior olive (IO) is commonly thought to provide the cerebellum with a “teaching” unconditioned stimulus (US) signal required for cerebellar learning. Testing this concept has been difficult because the IO, in addition to its putative learning function, also controls tonic activity in the cerebellum. Previously, it was reported that inactivation of AMPA/kainate receptors in the IO produces extinction of conditioned responses (CRs), suggesting that it blocks the transmission of US signals without perturbing the functional state of the cerebellum. However, the electrophysiological support for this critical finding was lacking, mostly because of methodological difficulties in maintaining stable recordings from the same set of single units throughout long drug injection sessions in awake rabbits. To address this critical issue, we used our microwire-based multiple single-unit recording method. The IO in trained rabbits was injected with the AMPA/kainate receptor blocker, 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), and its effects on CR expression and neuronal activity in the cerebellar interposed nuclei (IN) were examined. We found that NBQX abolished CR expression and that delayed drug effects were independent of the presentation of the conditioned stimulus and were therefore not related to extinction. In parallel to these behavioral effects, the spontaneous neuronal activity and CR-related neuronal responses in the IN were suppressed, suggesting cerebellar dysfunction. These findings indicate that testing the role of IO in learning requires methods that do not alter the functional state of the cerebellum.
Ubiquitin–Proteasome-Mediated Synaptic Reorganization: A Novel Mechanism Underlying Rapid Ischemic Tolerance
Authors: Meller Robert , Thompson Simon John , Lusardi Theresa Ann , Ordonez Andrea Nicole , Ashley Michelle Dawn , Jessick Veronica , Wang Weihzen , Torrey Daniel John , Henshall David Clifford , Gafken Philip R. , Saugstad Julie Anne , Xiong Zhi-Gang , Simon Roger Pancoast
Published: January 2008

Ischemic tolerance is an endogenous neuroprotective mechanism in brain and other organs, whereby prior exposure to brief ischemia produces resilience to subsequent normally injurious ischemia. Although many molecular mechanisms mediate delayed (gene-mediated) ischemic tolerance, the mechanisms underlying rapid (protein synthesis-independent) ischemic tolerance are relatively unknown. Here we describe a novel mechanism for the induction of rapid ischemic tolerance mediated by the ubiquitin–proteasome system. Rapid ischemic tolerance is blocked by multiple proteasome inhibitors [carbobenzoxy-l-leucyl-l-leucyl-l-leucinal (MG132), MG115 (carbobenzoxy-l-leucyl-l-leucyl-l-norvalinal), andclasto-lactacystin-β-lactone]. A proteomics strategy was used to identify ubiquitinated proteins after preconditioning ischemia. We focused our studies on two actin-binding proteins of the postsynaptic density that were ubiquitinated after rapid preconditioning: myristoylated, alanine-rich C-kinase substrate (MARCKS) and fascin. Immunoblots confirm the degradation of MARCKS and fascin after preconditioning ischemia. The loss of actin-binding proteins promoted actin reorganization in the postsynaptic density and transient retraction of dendritic spines. This rapid and reversible synaptic remodeling reduced NMDA-mediated electrophysiological responses and renders the cells refractory to NMDA receptor-mediated toxicity. The dendritic spine retraction and NMDA neuroprotection after preconditioning ischemia are blocked by actin stabilization with jasplakinolide, as well as proteasome inhibition with MG132. Together these data suggest that rapid tolerance results from changes to the postsynaptic density mediated by the ubiquitin–proteasome system, rendering neurons resistant to excitotoxicity.
Expression of a Mutant Form of the Ferritin Light Chain Gene Induces Neurodegeneration and Iron Overload in Transgenic Mice
Authors: Vidal Ruben , Miravalle Leticia , Gao Xiaoying , Barbeito Ana G. , Baraibar Martin A. , Hekmatyar Shahryar K. , Widel Mario , Bansal Navin , Delisle Marie B. , Ghetti Bernardino
Published: January 2008

Increased iron levels and iron-mediated oxidative stress play an important role in the pathogenesis of many neurodegenerative diseases. The finding that mutations in the ferritin light polypeptide (FTL) gene cause a neurodegenerative disease known as neuroferritinopathy or hereditary ferritinopathy (HF) provided a direct connection between abnormal brain iron storage and neurodegeneration. HF is characterized by a severe movement disorder and by the presence of nuclear and cytoplasmic ferritin inclusion bodies in glia and neurons throughout the CNS and in tissues of multiple organ systems. Here we report that the expression in transgenic mice of a humanFTLcDNA carrying a thymidine and cytidine insertion at position 498 (FTL498–499InsTC) leads to the formation of nuclear and cytoplasmic ferritin inclusion bodies. As in HF, ferritin inclusions are seen in glia and neurons throughout the CNS as well as in cells of other organ systems. Our studies show histological, immunohistochemical, and biochemical similarities between ferritin inclusion bodies found in transgenic mice and in individuals with HF. Expression of the transgene in mice leads to a significant decrease in motor performance and a shorter life span, formation of ferritin inclusion bodies, misregulation of iron metabolism, accumulation of ubiquitinated proteins, and incorporation of elements of the proteasome into inclusions. This new transgenic mouse represents a relevant model of HF in which to study the pathways that lead to neurodegeneration in HF, to evaluate the role of iron mismanagement in neurodegenerative disorders, and to evaluate potential therapies for HF and related neurodegenerative diseases.
A Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes: A New Resource for Understanding Brain Development and Function
Authors: Cahoy John D. , Emery Ben , Kaushal Amit , Foo Lynette C. , Zamanian Jennifer L. , Christopherson Karen S. , Xing Yi , Lubischer Jane L. , Krieg Paul A. , Krupenko Sergey A. , Thompson Wesley J. , Barres Ben A.
Published: January 2008

Understanding the cell–cell interactions that control CNS development and function has long been limited by the lack of methods to cleanly separate neural cell types. Here we describe methods for the prospective isolation and purification of astrocytes, neurons, and oligodendrocytes from developing and mature mouse forebrain. We used FACS (fluorescent-activated cell sorting) to isolate astrocytes from transgenic mice that express enhanced green fluorescent protein (EGFP) under the control of an S100β promoter. Using Affymetrix GeneChip Arrays, we then created a transcriptome database of the expression levels of >20,000 genes by gene profiling these three main CNS neural cell types at various postnatal ages between postnatal day 1 (P1) and P30. This database provides a detailed global characterization and comparison of the genes expressed by acutely isolated astrocytes, neurons, and oligodendrocytes. We found that Aldh1L1 is a highly specific antigenic marker for astrocytes with a substantially broader pattern of astrocyte expression than the traditional astrocyte marker GFAP. Astrocytes were enriched in specific metabolic and lipid synthetic pathways, as well as the draper/Megf10 and Mertk/integrin αvβ5phagocytic pathways suggesting that astrocytes are professional phagocytes. Our findings call into question the concept of a “glial” cell class as the gene profiles of astrocytes and oligodendrocytes are as dissimilar to each other as they are to neurons. This transcriptome database of acutely isolated purified astrocytes, neurons, and oligodendrocytes provides a resource to the neuroscience community by providing improved cell-type-specific markers and for better understanding of neural development, function, and disease.
NF-Protocadherin and TAF1 Regulate Retinal Axon Initiation and ElongationIn Vivo
Authors: Piper Michael , Dwivedy Asha , Leung Louis , Bradley Roger S. , Holt Christine E.
Published: January 2008

NF-protocadherin (NFPC)-mediated cell–cell adhesion plays a critical role in vertebrate neural tube formation. NFPC is also expressed during the period of axon tract formation, but little is known about its function in axonogenesis. Here we have tested the role of NFPC and its cytosolic cofactor template-activating factor 1 (TAF1) in the emergence of theXenopusretinotectal projection. NFPC is expressed in the developing retina and optic pathway and is abundant in growing retinal axons. Inhibition of NFPC function in developing retinal ganglion cells (RGCs) severely reduces axon initiation and elongation and suppresses dendrite genesis. Furthermore, an identical phenotype occurs when TAF1 function is blocked. These data provide evidence that NFPC regulates axon initiation and elongation and indicate a conserved role for TAF1, a transcriptional regulator, as a downstream cytosolic effector of NFPC in RGCs.
SCREENING NEWBORNS FOR SICKLE CELL DISEASE IN GHANA
Authors: Ohene-Frempong Kwaku , Oduro Joseph , Tetteh Hannah , Nkrumah Francis
Published: January 2008

INTRODUCTION: Screening of newborns for sickle cell disease (SCD) allows early initiation of prophylactic therapy, parental education, and comprehensive management, which results in reduced mortality. Since April 1993, a demonstration project to develop and implement a program of newborn screening for SCD has been conducted in Kumasi, Ghana, by the Comprehensive Sickle Cell Center at the Children's Hospital of Philadelphia in collaboration with the Ministry of Health and other institutions in Ghana.

OBJECTIVE: Our goal was to assess the program of screening and follow-up of children with SCD in Ghana.

METHODS: Infants are screened at birth or at well-infant visits within days or a few weeks after birth. Mothers are asked to come for results within 4 weeks, and failing that, an extensive tracking system is used to deliver results to the homes of families with infants with possible SCD. Tracking relies solely on information obtained from mothers at the time of screening. The goal is to enroll infants with possible SCD into the sickle cell clinic by 8 weeks of age. Pregnant women, parents with children, and the general public are educated regularly about the screening program. Children with SCD receive comprehensive care through the Sickle Cell Clinic at Komfo Anokye Teaching Hospital (Kumasi, Ghana).

RESULTS: From February 13, 1995 (when newborn testing was started), to December 31, 2005, a total of 202 244 infants were screened through 8 public health institutions and 14 private clinics in Kumasi and 1 private maternity center and 1 public health Center in Tikrom, a nearby, rural community. A total of 3745 (1.9%) infants were identified as having possible SCD with the following hemoglobin phenotypes according to isoelectric focusing: 2047 (1.04%) fetal sickle cell hemoglobin; 1684 (0.83%) fetal SC hemoglobin; and, 14 (0.003%) fetal SA hemoglobin (Table 1).

CONCLUSIONS: Screening and follow-up of newborns for SCD is feasible in a developing country in Africa. Extra effort in tracking is necessary to ensure that infants with disease are found early and referred for medical management.

TABLE 1.Screening and Tracking Results: February 1995 to December 2005No.%Total No. of infants screened202 244100.0Infants with possible SCD37451.9 (of infants screened)Under active tracking (newly diagnosed)(125)3.3 (of infants with possible SCD; excluded)Total possible SCD accounted for362096.7 (of infants with possible SCD; reported)Lost to follow-up/never found(494)13.6 (of infants with possible SCD; reported)Dead before contact made(34)0.9 (of infants with possible SCD; reported)No. contacted with results (eligible for enrollment)309285.4 (of infants with possible SCD; reported)    Came for results65121.0 (of those contacted)    Through home visiting244179.0 (of those contacted)Eligible but not enrolled after contact47715.4 (of those eligible)Enrolled in clinic261584.6 (of those eligible)Known deaths after enrollment1094.2 (of those enrolled)
To Pay or Not to Pay: Examining Underlying Principles in the Debate on Financial Support for Family Caregivers
Authors: Keefe Janice , Rajnovich Beth
Published: January 2008

In many countries one approach to supporting family-and-friend caregivers is direct financial or monetary support. Debates about the benefits and consequences of such policies pervade the literature. Building on the premise that values underlie public policy, the paper examines four policy paradoxes in the literature and uses selected examples from an international policy analysis to illustrate the underlying objectives and values upon which many of the policies were developed. These include the responsibility to care, economic or social objectives, gender equity, and the autonomy of care receivers. The authors conclude that policy makers need to be cautious about the unintended effects of financial support policy and develop a menu of policies and services to support caregivers. Future policy development in Canada must enable legitimate choice across the life course and ensure that neither the caregiver nor the care receiver will experience short- or long-term financial consequences of his or her choice.
Brain tissue oxygen tension response to induced hyperoxia reduced in hypoperfused brain
Authors: Hlatky Roman , Valadka Alex B. , Gopinath Shankar P. , Robertson Claudia S.
Published: January 2008

Object

Increasing PaO2 can increase brain tissue PO2 (PbtO2). Nevertheless, the small increase in arterial O2 content induced by hyperoxia does not increase O2 delivery much, especially when cerebral blood flow (CBF) is low, and the effectiveness of hyperoxia as a therapeutic intervention remains controversial. The purpose of this study was to examine the role of regional (r)CBF at the site of the PO2 probe in determining the response of PbtO2 to induced hyperoxia.

Methods

The authors measured PaO2 and PbtO2 at baseline normoxic conditions and after increasing inspired O2 concentration to 100% on 111 occasions in 83 patients with severe traumatic brain injury in whom a stable xenon–enhanced computed tomography measurement of CBF was available. The O2 reactivity was calculated as the change in PbtO2 × 100/change in PaO2.

Results

The O2 reactivity was significantly different (p < 0.001) at the 5 levels of rCBF (<10, 11–15, 16–20, 21–40, and > 40 ml/100 g/min). When rCBF was < 20 ml/100 g/min, the increase in PbtO2 induced by hyperoxia was very small compared with the increase that occurred when rCBF was > 20 ml/100 g/min.

Conclusions

Although the level of CBF is probably only one of the factors that determines the PbtO2 response to hyperoxia, it is apparent from these results that the areas of the brain that would most likely benefit from improved oxygenation are the areas that are the least likely to have increased PbtO2.
Combined internal uncusectomy and decompressive craniectomy for the treatment of severe closed head injury: experience with 80 cases
Authors: Chibbaro Salvatore , Marsella Marco , Romano Antonio , Ippolito Salvatore , Benericetti Eugenio
Published: January 2008

Object

Transtentorial brain herniation is a major cause of morbidity and death following severe closed head injury. The purpose of this study was to evaluate the efficacy of selective uncoparahippocampectomy and tentorial splitting as an adjuvant method of treating otherwise uncontrollable elevated intracranial pressure (ICP) while attempting to prevent or minimize the devastating consequences caused by transtentorial herniation.

Methods

The authors retrospectively reviewed data from a series of 80 consecutive cases of severe closed head injury (Glasgow Coma Scale [GCS] score <8) treated in their neurosurgical unit. All patients had elevated ICP and downward tentorial herniation, as documented with ICP monitoring, and clinical examination and computed tomography, respectively. Given the evidence of acute and ongoing neurological deterioration, all patients were treated with selective uncoparahippocampectomy and tentorial edge incision followed by wide decompressive craniectomy and duraplasty.

Results

All injuries were caused by blunt trauma with signs of acute and/or progressive increased ICP causing downward transtentorial herniation. Fifty-eight patients were male and 22 were female with a mean age of 35 years and a mean preoperative GCS score of 5. Based on the current American Association of Neurological Surgeons guidelines for head trauma, an intraparenchymal ICP device (Camino, Integra) was placed in all patients who had a GCS score <8, and ICP was consistently >20 cm H2O. Whenever possible, risks and benefits were explained to family members, and then surgery was performed within 3–16 hours (median 6 hours). At a mean follow-up of 30 months, the outcome was favorable (Glasgow Outcome Scale [GOS] score of 4 or 5) in 60 patients (75%) and unfavorable (GOS score of 3) in 8 (10%), whereas the remaining 12 patients (15%) died at some point during the postoperative course. There was no survivor patient in a vegetative state. A younger age had a significant effect on positive outcome (p < 0.0005), as did an earlier operation (p < 0.04). The preoperative neurological status as assessed using the GCS as well as pupillary reactivity had no significant effect on outcome (p = 0.054 and p > 0.05, respectively).

Conclusions

A selective uncoparahippocampectomy with a tentorial edge incision and a wide decompressive craniectomy with duraplasty can be an effective adjuvant form of aggressive treatment to improve outcome in patients with severe closed head injury, especially in those who are younger if they are treated promptly.
Dose–response relationship of mannitol and intracranial pressure: a metaanalysis
Authors: Sorani Marco D. , Manley Geoffrey T.
Published: January 2008

Object

Brain edema can increase intracranial pressure (ICP), potentially leading to ischemia, herniation, and death. Edema and elevated ICP are often treated with osmotic agents to remove water from brain tissue. Mannitol is the osmotic diuretic most commonly used in the intensive care unit; however, despite its clinical importance, treatment protocols vary from center to center, and the dose–response relationship is not understood. The goal of this metaanalysis was to aggregate and analyze data from studies in which authors have described the dose–response relationship between mannitol and ICP.

Methods

The authors identified 18 studies that quantitatively characterized the dose–response relationship of mannitol and ICP. We also examined study designs and mannitol administration protocols.

Results

Meta-regression found a weak linear relationship between change in ICP (ΔICP) and dose (ΔICP = 6.6 × dose − 1.1; p = 0.27, R2 = 0.05). The lack of statistical significance could reflect the variation in protocols among studies and the variation in patients both within and among studies. However, the authors found a highly significant difference (p < 0.001) in decrease in ICP when the initial ICP was higher or lower than 30 mm Hg. Nonlinear regression suggested that ICP decrease is greatest shortly after mannitol is given (R2 = 0.63). Finally, the authors found that recent studies tend to include fewer patients and set a lower ICP threshold for mannitol administration but report more parameters of interest; the duration of mannitol's effect was the most frequently unreported parameter.

Conclusions

Despite its clinical importance, the determination of the mannitol dose–response curve continues to be challenging for many reasons. This metaanalysis highlights the need for a consensus of methods and results required to determine this important relationship.
Normoxic ventilatory resuscitation following controlled cortical impact reduces peroxynitrite-mediated protein nitration in the hippocampus
Authors: Ahn Edward S. , Robertson Courtney L. , Vereczki Viktoria , Hoffman Gloria E. , Fiskum Gary
Published: January 2008

Object

Ventilatory resuscitation with 100% O2 after severe traumatic brain injury (TBI) raises concerns about the increased production of reactive oxygen species (ROS). The product of peroxynitrite-meditated tyrosine residue nitration, 3-nitrotyrosine (3-NT), is a marker for oxidative damage to proteins. The authors hypothesized that posttraumatic resuscitation with hyperoxia (100% fraction of inspired oxygen [FiO2] concentration) results in increased ROS-induced damage to proteins compared with resuscitation using normoxia (21% FiO2 concentration).

Methods

Male Sprague–Dawley rats underwent controlled cortical impact (CCI) injury and resuscitation with either normoxic or hyperoxic ventilation for 1 hour (5 rats per group). Twenty-four hours after injury, rat hippocampi were evaluated using 3-NT immunostaining. In a second experiment, animals similarly underwent CCI injury and normoxic or hyperoxic ventilation for 1 hour (4 rats per group). One week after injury, neuronal counts were performed after neuronal nuclei immunostaining.

Results

The 3-NT staining was significantly increased in the hippocampi of the hyperoxic group. The normoxic group showed a 51.0% reduction of staining in the CA1 region compared with the hyperoxic group and a 50.8% reduction in the CA3 region (p < 0.05, both regions). There was no significant difference in staining between the injured normoxic group and sham-operated control groups. In the delayed analysis of neuronal survival (neuronal counts), there was no significant difference between the hyperoxic and normoxic groups.

Conclusions

In this clinically relevant model of TBI, normoxic resuscitation significantly reduced oxidative damage to proteins compared with hyperoxic resuscitation. Neuronal counts showed no benefit from hyperoxic resuscitation. These findings indicate that hyperoxic ventilation in the early stages after severe TBI may exacerbate oxidative damage to proteins.
Emergency decompressive craniectomy for fulminating infectious encephalitis
Authors: Adamo Matthew A. , Deshaies Eric M.
Published: January 2008

✓In patients who develop fulminant cerebral edema and elevated intracranial pressures, viral encephalitis can result in devastating neurological and cognitive sequelae despite antiviral therapy. The benefits of decompressive craniectomy, if any, in this group of patients are unclear. In this manuscript, the authors report their experience with 2 patients who presented with herpes simplex virus requiring surgical decompression resulting in excellent neurocognitive outcomes. They also review the literature on decompressive craniectomy in patients with fulminating infectious encephalitis.

Four published articles consisting of 13 patients were identified in which the authors had reported their experience with decompressive craniectomy for fulminant infectious encephalitis. Herpes simplex virus was confirmed in 6 cases, Mycoplasma pneumoniae in 2, and an unidentified viral infection in 5 others. All patients developed clinical signs of brainstem dysfunction and underwent surgical decompression resulting in good (Glasgow Outcome Scale [GOS] Score 4) or excellent (GOS Score 5) functional recoveries.

The authors conclude that infectious encephalitis is a neurosurgical disease in cases in which there is clinical and imaging evidence of brainstem compression. Surgical decompression results in excellent recovery of functional independence in both children and adults despite early clinical signs of brainstem dysfunction.
Craniopagus twins
Authors: Browd Samuel R. , Goodrich James T. , Walker Marion L.
Published: January 2008

✓Craniopagus twins represent a rare phenomenon of congenital misfortune. Modern neurosurgical techniques have created opportunities for successful separation and the promise of a normal existence for these children, who in the past were often left as historical footnotes or put on display as oddities of nature. The authors document a brief history of conjoined twinning and discuss the modern science of craniopagus epidemiology, classification, and separation. In particular, the strategies used and the rationale for staged surgical separation are highlighted.
Antibiotic prophylaxis for surgical introduction of intracranial ventricular shunts: a systematic review
Authors: Ratilal Bernardo , Costa João , Sampaio Cristina
Published: January 2008

Object

Systemic antibiotics and antibiotic-impregnated shunt (AIS) systems are often used to prevent shunt infection. The authors conducted a systematic review to evaluate its effectiveness of antibiotics in patients who underwent placement of intracranial ventricular shunts.

Methods

The authors searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, LILACS, and the meeting proceedings from the American Association of Neurological Surgeons and from the European Association of Neurosurgical Societies until June 2005. Randomized and quasi-randomized trials comparing the use of prophylactic antibiotics (either systemic or AIS systems) in intracranial ventricular shunt procedures with placebo or no antibiotics were included in the review.

Results

Seventeen trials involving 2134 patients were included. Results from the metaanalysis showed that the use of systemic antibiotic prophylaxis for internal shunts was associated with a decrease in shunt infection (odds ratio 0.51; 95% confidence interval 0.36–0.73). The authors found no significant differences between the subgroups evaluated in type of internal shunt (ventriculoperitoneal/ventriculoatrial), age, or duration of the administration of antibiotics.

Conclusions

The authors found a benefit of systemic prophylactic antibiotics in preventing shunt infection, regardless of the patient's age and the type of internal shunt used. The benefit of its use after the first 24 hours postoperatively remains uncertain. Future trials should be conducted to evaluate the effectiveness of different regimens of systemic antibiotics rather than placebo, namely single preoperative dose versus multiple doses. It should also be mandatory to evaluate the effectiveness of systemic prophylactic antibiotics for external ventricular drains. Evidence suggests that antibiotic-impregnated catheters reduce the incidence of shunt infection, although more well-designed clinical trials are needed.
Treatment of a complex posterior fossa aneurysm in a child using side-to-side posterior inferior cerebellar artery–posterior inferior cerebellar artery bypass
Authors: Chandela Sid , Alzate Juan , Sen Chandranath , Song Joon , Nimi Yasunari , Berenstein Alejandro , Langer David
Published: January 2008

✓Endovascular and cerebral bypass therapies are rarely used in children. The authors describe the treatment of a partially coiled giant distal vertebral artery (VA)–posterior inferior cerebellar artery (PICA) aneurysm in a child. They performed a side-to-side PICA–PICA anastomosis followed by endovascular VA aneurysm deconstruction with PICA preservation.

A healthy 11-year-old boy developed progressive holocephalic headaches over the course of 2 months. Magnetic resonance imaging and magnetic resonance angiography revealed a large right PICA aneurysm causing brainstem compression. In November 2005, 2 Neuroform stents and Guglielmi detachable coils and Matrix were placed in the aneurysm at an outside institution. In 2006, angiography demonstrated aneurysm enlargement from which the PICA originated, coil compaction, and increased mass effect. The patient underwent a PICA–PICA bypass with intraoperative flow measurements followed by endovascular embolization of the aneurysm and parent VA. An angiogram obtained after the procedure demonstrated filling of the right PICA medullary branch through the bypass and obliteration of the aneurysm. The patient remained neurologically intact.

Giant aneurysms of the posterior circulation are rare but do occur in children. With the aid of combined surgical and endovascular strategies the authors were able to safely eliminate the aneurysm from circulation with good outcome. Cerebral bypass and endovascular deconstructive therapies can be used safely in children but should be reserved for cases in which direct treatment carries significant risk. Careful surgical and endovascular planning with intraoperative flow assessment is essential for good outcome.
Patients with autosomal-recessive osteopetrosis presenting with hydrocephalus and hindbrain posterior fossa crowding
Authors: Al-Tamimi Yahia Z. , Tyagi Atul K. , Chumas Paul D. , Crimmins Darach W.
Published: January 2008

✓ Osteopetrosis is a heterogeneous group of disorders characterized by abnormal bone sclerosis. As a result, patients often require input regarding various neurological complications. Although autosomal-recessive osteopetrosis has been associated with hydrocephalus, it has not been linked to hindbrain abnormalities. The authors present 3 cases of auto-somal-recessive osteopetrosis in patients who presented with hydrocephalus. In each of these patients, cerebrospinal fluid diversion procedures were required and hindbrain compression developed. To date, only 1 patient has needed craniocervical decompression due to symptomatic brainstem compression.
Patient selection for lumbar arthroplasty and arthrodesis: the effect of revision surgery in a controlled, multicenter, randomized study
Authors: Geisler Fred H. , Guyer Richard D. , Blumenthal Scott L. , McAfee Paul C. , Cappuccino Andrew , Bitan Fabien , Regan John J.
Published: January 2008

Object

Patient selection is perhaps the most important factor in successful lumbar surgery. In this study, the authors analyzed the clinical outcomes of patients enrolled in the CHARITÉ investigational device exemption (IDE) trial who underwent revision surgery after primary total disc replacement with CHARITÉ or an anterior lumbar interbody fusion (ALIF) with placement of a BAK cage and iliac crest autograft. This revision surgery was either a supplemental posterior lumbar fixation or a 360° fusion. Statistical analysis was conducted to compare clinical success in patients who underwent revision surgery with those who did not.

Methods

The patients enrolled in the CHARITÉ IDE study were divided into 6 groups according to treatment and repeated operation status, and their Oswestry Disability Index (ODI) and visual analog scale (VAS) scores at the 2-year follow-up and at baseline were compared. The patients had received the following treatments by group: A) ALIF without reoperation; B) ALIF with conversion to 360° fusion; C) arthroplasty (randomized) without repeated operation; D) arthroplasty with supplemental posterior lumbar fixation; E) arthroplasty (nonrandomized) without repeated operation; and F) arthroplasty (nonrandomized) with supplemental posterior lumbar fixation. Outcome scores in the groups of patients who required revision surgeries (Groups B, D, and F; 23 patients) were compared with the groups that did not require revision surgery (Groups A, C, and E; 299 patients).

Results

Patients who required revision surgery had a significantly lower level of clinical improvement than those who did not. The mean change in ODI score was −53.0% in Groups A, C, and E, but just −12.7% in Groups B, D, and F (p < 0.0001). The mean change in VAS score was −59.1% in Groups A, C, and E, compared to −23.4% in Groups B, D, and F (p < 0.0001). No significant differences were identified in analyzing absolute change in scores and the percentage change. A comparison of outcomes in patients who had undergone arthroplasty without reoperation (Groups C and E) with all patients who had undergone revision surgery (Groups B, D, and F) demonstrated similar results (p < 0.0001).

Conclusions

The 7.1% of patients who underwent a secondary stabilization procedure had poor clinical improvement. This finding may indicate that if the alternative treatment had been the initial treatment, these patients would not have benefited, and further implies a 7.1% rate of imprecision in preoperative evaluation.
A long-term follow-up study of anterior tibial allografting and instrumentation in the management of thoracolumbar tuberculous spondylitis
Authors: Çavuşoğlu Halit , Kaya Ramazan Alper , Türkmenoğlu Osman Nuri , Tuncer Cengiz , Çolak İbrahim , Aydandinodot;n Yunus
Published: January 2008

Object

The purpose of this study was to determine the efficacy of anterior instrumentation following radical debridement and tibial allografting and its long-term progression in patients with multilevel spinal tuberculosis.

Methods

This prospective observational study was undertaken to analyze 22 patients with multilevel spinal tuberculosis (Pott disease) who underwent anterior radical debridement, decompression, and fusion using anterior spinal instrumentation and tibial allograft replacement between 1999 and 2001. Clinical outcomes were assessed using the American Spinal Injury Association (ASIA) Impairment Scale and a visual analog scale (VAS). Preoperative and postoperative plain radiographs were obtained, and the focal kyphotic angle of the surgically treated spinal segments and the overall sagittal and coronal contours of the thoracic and lumbar spine were evaluated in all patients.

Results

The mean follow-up time was 84 months (range 36–96 months). All patients demonstrated clinical healing of the tuberculosis infection. All patients showed evidence of successful bone fusion. The mean late postoperative kyphosis correction was 74% (range 63–91%). On average, 2° (range 0–5°) of loss of correction was noted in the local kyphotic angle postoperatively in late follow-up findings. Evaluation of the surgical effect on sagittal global contours showed a significant correction rate in thoracic, thoracolumbar, and lumbar regions. The mean late postoperative coronal plane alignment correction was 99%. The ASIA Impairment Scale scores demonstrated significant improvement in late follow-up results in our series. Surgical decompression also resulted in a dramatic reduction of overall pain in all patients (late postoperative VAS score 1.61 ± 0.81).

Conclusions

Anterior tibial allografting and instrumentation provide correction of the curvature, prevention of further deformation, improvement of sagittal and coronal balance, and restoration of neurological function in patients with spinal tuberculosis.