bluuebunny/crossref_metadata_2025 huggingface dataset:
A Role for Non-Antimicrobial Actions of Tetracyclines in Combating Oxidative Stress in Periodontal and Metabolic Diseases: A Literature Review
Authors: Soory M
Published: October 2008

This review addresses the role of adjunctive tetracycline therapy in the management of periodontal diseases and its efficacy in reducing inflammatory burden, oxidative stress and its sequelae in patients with coexisting features of metabolic syndrome. Removal of the dimethylamine group at C4 of the tetracycline molecule reduces its antibiotic properties, enhancing its non-antimicrobial actions; this strategy has aided the development of several chemically modified tetracyclines such as minocycline and doxycycline, by altering different regions of the molecule for focused action on biological targets. Tetracyclines are effective in reducing inflammation by inhibiting matrix metalloproteinases, preventing excessive angiogenesis, inhibiting apoptosis and stimulating bone formation. There are important applications for tetracyclines in the management of diabetic, dyslipidaemic periodontal patients who smoke. The diverse mechanisms of action of tetracyclines in overcoming oxidative stress and enhancing matrix synthesis are discussed in this review.
Identification of Salmonella enterica Serovar Typhi DNA Fragments with Transcriptional Activity Under Different Growth Conditions
Authors: Saverino Daniele , McDermott Jennifer , Ferrari McDermott , Terrile Marta , Piatti Gabriella
Published: October 2008

Salmonella enterica serovar Typhi is a human pathogenic microorganism with a very complex infective cycle,
involving the transit of bacteria across different microenvironments; to optimize the performance of attenuated Salmonella
strains suitable as live carriers of heterologous antigens, fine tuning of wild type bacteria gene expression is essential.

Several DNA fragments were obtained from a Salmonella enterica serovar Typhi (vi+, fim+) blood isolate and 18 clones
were selected according to the dimension of the insert (range <0.2-1.6 kb). These fragments showed a transcriptional activity
in a promoterless vector cloned in Escherichia coli background, according to homogeneous parameters. The results
obtained provide an insight about signals mediating gene activation in vivo, particularly in the microenvironments known
to exist during the infectious process, even if the fragments are not promoters sequences. Finally, the functional characterization
of several fragments showed that they possessed an efficient and homogeneous transcriptional activity, worth to
be further investigated.
Patho-Biotechnology – Making New Friends of Old Foes
Authors: Sleator Roy D.
Published: October 2008

Although first described over a century ago, scientists
and clinicians have only recently begun to realize the
significant medical opportunities presented by probiotic
bacteria [1, 2].

However, the most beneficial probiotics often prove to be
the most physiologically fragile; a significant limitation in
clinical applications [3, 4]. The ‘Patho-biotechnology’
concept promotes the exploitation of pathogen derived stress
survival strategies for the design of more technologically
robust probiotic cultures with improved biotechnological and
clinical applications [5, 6].

The rationale for choosing pathogens over commensal
species as a source of potential stress survival mechanisms is
based on a number of factors; not least of which is the fact
that certain pathogenic bacteria, with lifecycles bridging the
host and external milieu, have evolved sophisticated stress
management strategies enabling them to succeed in more
diverse ecological niches than those normally occupied by
most non-pathogenic species [7]. Pathogens thus represent a
rich source of genes which could potentially improve the
physiological vigor of less versatile probiotic strains, both
external to and within the host.

The advantages of such a strategy are obvious; improving
storage, delivery and clinical efficacy of probiotic cultures
[3, 4, 8]. In addition, such ‘bioengineered probiotics’ may
ultimately provide a safer alternative to attenuated pathogens
as vaccine delivery platforms or be employed as novel drug
delivery vehicles; directed against emerging antibiotic
resistant pathogens such as Clostridium difficile [9, 10].

However, while the potential of the patho-biotechnology
approach is obvious; so too are the limitations. Consumer
and regulatory acceptance of genetically modified probiotics
expressing pathogen derived genes, is one of the major
obstacles to the continued development of the field. While
the use of genetically modified organisms raises legitimate
concerns about the dissemination of antibiotic markers or
other genetic modifications to neighbouring microbes in the
environment, I feel that proper adherence to biological
containment (both active and passive [11]) will help to ease
these concerns and facilitate safe and continued innovation
in the sector: eventually promoting patho-biotechnology as a
new and exciting paradigm in probiotic research.
NcGRA2-RT-PCR to Detect Live Versus Dead Parasites in Neospora caninum-Infected Mice
Authors: Strohbusch Maria , Müller Norbert , Hemphill Andrew , Greif Gisela , Gottstein Bruno
Published: October 2008

In the present work, we optimized a recently established NcGRA2-RT-PCR based on RNA to detect live Neospora
caninum parasites in tissue, and compared the results with the conventional inoculation of diagnostic specimen onto
cell culture. C57BL/6 mice were experimentally infected with Nc-1 tachyzoites and subsequently euthanized 6 or 12 days
post infection (dpi). Selected organs were used to search for parasites by (i) PCR using genomic DNA (gDNA), (ii) PCR
using cDNA and (iii) in vitro inoculation of cell culture. At 6 dpi, Neospora-gDNA was detected in 34 out of 36 organs.
Viable parasites were detected in 11 (NcGRA2-RT-PCR) and 15 (in vitro cultivation) out of 36 organs. Comparison of
NcGRA2-RT-PCR and in vitro detection gave a fair agreement (kappa 0.29), whereas comparison of PCR using gDNA
and RT-PCR or in vitro detection resulted in a slight agreement (kappa 0.05 and 0.08, respectively) only. At 12 dpi, parasite
gDNA was found in 10 out of 36 organs. In 7 of these organs viability of parasites was confirmed with NcGRA2-RTPCR
and growth of parasites in cell culture. Comparison of NcGRA2-RT-PCR and in vitro detection gave a substantial
agreement (kappa 0.8), whereas comparison of PCR using gDNA and RT-PCR or in vitro detection resulted in a moderate
agreement (kappa 0.59 and 0.77, respectively). As NcGRA2-RT-PCR is almost as sensitive as in vitro cultivation in detecting
live parasites, it represents a fast, easy and safe method of viable parasite detection, and thus an attractive alternative
to the in vitro cultivation approach.
Measuring the Gas-Solids Distribution in Fluidized Beds -- A Review
Authors: van Ommen J. Ruud , Mudde Robert F.
Published: October 2008

In gas-solid fluidized beds, the distribution of the particles typically varies both in time and space. Since the gas-solids distribution and its variation have a strong influence on the performance of a fluidized bed for a given process, it is very important to accurately measure the gas-solids or voidage distribution. This paper reviews techniques for measuring the voidage distribution in gas-solid fluidized beds, with a focus on the developments during the last ten years. We will treat subsequently direct visualisation, tomography, optical probes, capacitance probes, and pressure measurements.Dense gas-solids flows are typically opaque to visible light. This makes optical techniques only of limited use in dense gas-solids flow. However, direct visualization can be useful for very dilute systems, pseudo 2-D beds, and the outer layer of dense, 3-D systems. Tomography is frequently used to obtain the voidage distribution in a horizontal cross-section of the bed. Electric capacitance tomography is fast, but its spatial resolution is limited and image reconstruction is still troublesome. Although some steps forward have been made, research is continuing at this point. For nuclear (X-ray and gamma-ray) tomography, the image reconstruction is much easier and the spatial resolution better, but its temporal resolution is typically much lower. Therefore, research efforts for nuclear tomography are mainly aimed at increasing the measurement frequency. Optical probes determine the voidage as a function of time in a small measurement volume, either by the degree of reflection or by the degree of transmission of a light bundle. Capacitance probes determine the voidage as a function of time in a small measurement volume by measuring the dielectric permittivity of the gas-solids suspension in the measurement volume. Both optical and capacitance probe techniques are reasonably well-developed; the current research effort spent at improving them seems limited, especially for capacitance probes. Time-averaged pressure measurements are commonly used to determine the average bed density and bed height. By sampling the local pressure at a sufficiently high frequency (typically in the order of 200 Hz), much more information can be obtained about the fluidized bed hydrodynamics. However, obtaining quantitative voidage data from pressure fluctuations measurement remains a difficult task; in-bed pressure fluctuation (and acoustic) measurements are mostly used to determine changes in the voidage dynamics and distribution.
Regulator of G-protein signalling expression and function in ovarian cancer cell lines
Authors: Hurst Jillian , Mendpara Nisha , Hooks Shelley
Published: October 2008

Regulator of G-protein signalling (RGS)2 proteins critically regulate signalling cascades initiated by G-protein coupled receptors (GPCRs) by accelerating the deactivation of heterotrimeric G-proteins. Lysophosphatidic acid (LPA) is the predominant growth factor that drives the progression of ovarian cancer by activating specific GPCRs and G-proteins expressed in ovarian cancer cells. We have recently reported that RGS proteins endogenously expressed in SKOV-3 ovarian cancer cells dramatically attenuate LPA stimulated cell signalling. The goal of this study was twofold: first, to identify candidate RGS proteins expressed in SKOV-3 cells that may account for the reported negative regulation of G-protein signalling, and second, to determine if these RGS protein transcripts are differentially expressed among commonly utilized ovarian cancer cell lines and non-cancerous ovarian cell lines. Reverse transcriptase-PCR was performed to determine transcript expression of 22 major RGS subtypes in RNA isolated from SKOV-3, OVCAR-3 and Caov-3 ovarian cancer cell lines and non-cancerous immortalized ovarian surface epithelial (IOSE) cells. Fifteen RGS transcripts were detected in SKOV-3 cell lines. To compare the relative expression levels in these cell lines, quantitative real time RT-PCR was performed on select transcripts. RGS19/GAIP was expressed at similar levels in all four cell lines, while RGS2 transcript was detected at levels slightly lower in ovarian cancer cells as compared to IOSE cells. RGS4 and RGS6 transcripts were expressed at dramatically different levels in ovarian cancer cell lines as compared to IOSE cells. RGS4 transcript was detected in IOSE at levels several thousand fold higher than its expression level in ovarian cancer cells lines, while RGS6 transcript was expressed fivefold higher in SKOV-3 cells as compared to IOSE cells, and over a thousand fold higher in OVCAR-3 and Caov-3 cells as compared to IOSE cells. Functional studies of RGS 2, 6, and 19/GAIP were performed by measuring their effects on LPA stimulated production of inositol phosphates. In COS-7 cells expressing individual exogenous LPA receptors, RGS2 and RSG19/GAIP attenuated signalling initiated by LPA1, LPA2, or LPA3, while RGS6 only inhibited signalling initiated by LPA2 receptors. In SKOV-3 ovarian cancer cells, RGS2 but not RGS6 or RGS19/GAIP, inhibited LPA stimulated inositol phosphate production. In contrast, in CAOV-3 cells RGS19/GAIP strongly attenuated LPA signalling. Thus, multiple RGS proteins are expressed at significantly different levels in cells derived from cancerous and normal ovarian cells and at least two candidate RGS transcripts have been identified to account for the reported regulation of LPA signalling pathways in ovarian cancer cells.
A three-dimensional histological atlas of the human basal ganglia. II. Atlas deformation strategy and evaluation in deep brain stimulation for Parkinson disease
Authors: Bardinet Eric , Bhattacharjee Manik , Dormont Didier , Pidoux Bernard , Malandain Grégoire , Schüpbach Michael , Ayache Nicholas , Cornu Philippe , Agid Yves , Yelnik Jérôme
Published: October 2008

Object

The localization of any given target in the brain has become a challenging issue because of the increased use of deep brain stimulation to treat Parkinson disease, dystonia, and nonmotor diseases (for example, Tourette syndrome, obsessive compulsive disorders, and depression). The aim of this study was to develop an automated method of adapting an atlas of the human basal ganglia to the brains of individual patients.

Methods

Magnetic resonance images of the brain specimen were obtained before extraction from the skull and histological processing. Adaptation of the atlas to individual patient anatomy was performed by reshaping the atlas MR images to the images obtained in the individual patient using a hierarchical registration applied to a region of interest centered on the basal ganglia, and then applying the reshaping matrix to the atlas surfaces.

Results

Results were evaluated by direct visual inspection of the structures visible on MR images and atlas anatomy, by comparison with electrophysiological intraoperative data, and with previous atlas studies in patients with Parkinson disease. The method was both robust and accurate, never failing to provide an anatomically reliable atlas to patient registration. The registration obtained did not exceed a 1-mm mismatch with the electrophysiological signatures in the region of the subthalamic nucleus.

Conclusions

This registration method applied to the basal ganglia atlas forms a powerful and reliable method for determining deep brain stimulation targets within the basal ganglia of individual patients.
Suprainguinal retroperitoneal approach for the successful surgical treatment of meralgia paresthetica
Authors: Alberti Olaf , Wickboldt Jürgen , Becker Ralf
Published: October 2008

Object

Neurosurgical textbooks describe an infrainguinal approach as the standard or preferred option for the surgical treatment of meralgia paresthetica (MP), the most frequent entrapment neuropathy of the lower limb. However, inhomogeneous results led the authors to adopt a suprainguinal, retroperitoneal approach for decompression of the lateral femoral cutaneous nerve. In this paper the authors' aim was to study the outcome of patients harboring MP treated via this different surgical approach.

Methods

The outcome of 55 consecutive patients who underwent surgery for MP via the suprainguinal retroperitoneal approach during a 15-year period was ascertained through postal questionnaires (in 47 patients) and follow-up visits (in 8 patients). The male to female ratio was 1:0.67, and the mean patient age was 50 ± 12.9 years. The mean follow-up was 3.2 ± 3.3 years. Seven of the patients underwent bilateral surgery.

Results

Intraoperatively the lateral femoral cutaneous nerve was consistently found in close anatomical relationship to the anterior superior iliac spine, although some variations regarding the diameter, number of branches, and underlying pathological entity were observed. Eighty-seven percent of patients showed improvement (21 patients) or complete remission (27 patients) of painful dysesthesia in the anterolateral thigh, and 13% (7 patients) remained unchanged. In addition 82% had improvement (31 patients) or complete remission (14 patients) of hypesthesia, leaving 18% with unchanged (9 patients) or worsened (1 patient) hypesthesia. In the patient-evaluated group 66% (31 of 47) were completely satisfied with the outcome, 23% (11 of 47) were partially satisfied, and 11% (5 of 47) were not satisfied with the outcome. Two cases each of recurrence, seroma, wound infection, and 1 case of hematoma requiring revision were encountered as complications.

Conclusions

The suprainguinal retroperitoneal approach is a viable first-choice option for the surgical relief of MP.
Recent trends in the treatment of spontaneous intracerebral hemorrhage: analysis of a nationwide inpatient database
Authors: Andaluz Norberto , Zuccarello Mario
Published: October 2008

Object

Recently updated guidelines failed to reflect significant progress in the treatment of intracerebral hemorrhage (ICH). Using data from a nationwide hospital database, the authors identified recent trends in therapy and outcomes for ICH, as well as the effect of associated comorbidities and procedures, including surgery.

Methods

Data from the Nationwide Inpatient Sample hospital discharge database (Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality) for the period 1993–2005 was retrospectively reviewed. Multiple variables were categorized and subjected to statistical analysis for codes related to ICH from the International Classification of Diseases, 9th revision, Clinical Modification. Data linked by the Nationwide Inpatient Sample database to associated diagnoses and procedures were also retrieved and analyzed.

Results

The number of discharges remained constant for ICH. The mortality rate remained unchanged at an average of 31.6%, whereas routine discharges (home) steadily declined by 25%, and discharges other than home doubled (p < 0.01). By the end of the study, length of hospital stay decreased by 30% (p < 0.01), and mean hospital charges steadily increased to more than twice the original figures. Arterial hypertension was the most frequently associated comorbidity. Seizures were associated with longer hospital stays and higher mean hospital charges. Craniotomy was associated with decreased mortality rates but also with worse outcomes and lower rates of patients discharged home (p < 0.01). No geographic differences in treatment and outcomes were noted.

Conclusions

From 1993 to 2005, no significant progress in treatment and prevention of ICH was noted. There were no regional differences in the treatment and outcome of ICH. The role of surgery for ICH remains uncertain, and large-scale controlled studies are greatly needed to clarify this role.
Stimulation-induced parkinsonism after posteroventral deep brain stimulation of the globus pallidus internus for craniocervical dystonia
Authors: Zauber S. Elizabeth , Watson Nidhi , Comella Cynthia L. , Bakay Roy A. E. , Metman Leo Verhagen
Published: October 2008

The authors report on a patient with craniocervical dystonia who was treated with bilateral GPi stimulation, with excellent improvement in dystonia but at the cost of stimulation-induced, reversible parkinsonism. Stimulation through ventral contacts resulted in maximal relief of craniocervical dystonia but induced considerable hypophonia, bradykinesia, rigidity, freezing, and impaired postural reflexes. Stimulation through dorsal contacts alleviated parkinsonism, but resulted in the return of dystonia. No stimulation parameters could alleviate the dystonia without inducing parkinsonism over the course of his 4-year follow-up.
Emergency suboccipital decompression for respiratory arrest during supratentorial surgery: the untold story of a surgeon's courage in times of despair
Authors: Shelton Beth Ann , O'Hara Edward , Tubbs R. Shane , Shoja Mohammadli M. , Barker Fred G. , Cohen-Gadol Aaron A.
Published: October 2008

The odyssey leading to the discovery of herniation syndromes was prolonged due to a lack of early understanding of the underlying pathophysiology. In 1896, Leonard Hill documented transtentorial pressure gradients as the intervening phenomenon involved in uncal herniation. In 1904, James Collier became the first to describe cerebellar tonsillar herniation as a “false localizing sign” often associated with intracranial tumors. During the infancy of neurological surgery, management of increased intracranial pressure and an improved understanding of brain herniation syndromes were of the utmost importance in achieving a safe technique. Harvey Cushing provided seminal contributions in understanding the pathophysiology of increased intracranial pressure and resulting cardiopulmonary effects.

Cushing believed that tonsillar herniation was a cause of acute cardiorespiratory compromise in patients with intracranial tumors. In this vignette, we describe the untold story of Cushing's heroic attempt to treat respiratory arrest operatively during supratentorial tumor surgery with an emergency suboccipital craniectomy to relieve the medullary dysfunction that he believed was caused by compression from tonsillar herniation. This case illustrates a surgeon's determination and courage in fighting for his patient's life in the most desperate of times.
Anterior clivectomy: surgical technique and clinical applications
Authors: Al-Mefty Ossama , Kadri Paulo A. S. , Hasan David M. , Isolan Gustavo Rassier , Pravdenkova Svetlana
Published: October 2008

Object

Midline clival lesions, whether involving the clivus or simply situated anterior to the brainstem, present a technical challenge for adequate exposure and safe resection. The authors describe, as a minimally invasive technique, an anterior clivectomy performed via an expanded transsphenoidal approach coupled with the use of a neuronavigation on mobile head and endoscopic-assisted technique. Wide and direct exposure, with the ability to resect extra- and intradural tumors, was achieved without mortality and with a low rate of complications.

Methods

Cadaveric dissections were performed to outline the landmarks and measure the window that is created by resecting the clivus anteriorly. The technique was used in 43 patients to resect tumors located at or invading the clivus. The initial exposure of the clivus was obtained via the sublabial transsphenoidal approach. The wall of the anterior maxilla, often on 1 side, was removed to allow a wide side-to-side opening of the nasal speculum. Using neuronavigation, the authors made clivectomy windows by drilling the clivus between anatomical landmarks. Bilateral intraoperative neurophysiological monitoring was used (somatosensory evoked potentials, brainstem auditory evoked responses, and cranial nerves VI–XII).

Results

Of the 43 patients, 26 were female and 17 were male, and they ranged in age from 3.5 to 76 years (mean 41.5 years). Thirty-eight patients harbored a chordoma and 5 a giant invasive pituitary adenoma.

Gross-total resection of the tumor was achieved in 34 cases (79%). Nine patients (21%) had residual tumor unreachable through the anterior clivectomy, and this required a second-stage resection. Four patients developed new transient extraocular movement deficits. One patient developed a permanent cranial nerve VI palsy. Twenty-seven patients with chordoma underwent postoperative proton-beam radiotherapy. Tumor recurred in 19% of these cases. In 3 patients a cerebrospinal fluid leak developed during hospitalization and was treated successfully. Two other patients presented with a delayed cerebrospinal fluid leak after radiotherapy. Only 1 patient, who had previously undergone Gamma Knife surgery, experienced postoperative hemiparesis.

Conclusions

A complete anterior clivectomy via a simple extension of the transsphenoidal approach allows the surgeon access to different lesions involving the clivus or situated anterior to the brainstem. The exposure is similar to that provided by more extensive transfacial approaches. Instrument manipulation is easy. Neuronavigation, endoscopy, and intraoperative monitoring are easily incorporated and enhance the capability and safety of this approach.
Microsurgical management of 53 jugular foramen schwannomas: lessons learned incorporated into a modified grading system
Authors: Bulsara Ketan R. , Sameshima Tetsuro , Friedman Allan H. , Fukushima Takanori
Published: October 2008

Object

Due to the proximity and involvement of critical neurovascular structures, the resection of jugular foramen schwannomas can pose a formidable challenge. The authors review their experience in the microsurgical management of jugular foramen schwannomas and propose a modified grading scale to guide surgical management.

Methods

All jugular foramen schwannoma cases treated by the senior author (T.F.) between 1980 and 2004 were retrospectively reviewed. The average age at presentation, surgical approach, tumor characteristics, cranial nerve (CN) deficits, and tumor recurrence rates were assessed. The authors present the following modified grading scale: Type A, intradural tumors; Type B, dumbbell-shaped tumors; and Type C, triple dumbbell tumors with a high cervical extension.

Results

The authors treated jugular foramen tumors in 129 patients during the study period. Of these, 53 patients (41%) had jugular foramen schwannomas. The mean patient age was 52 years (range 14–74 years); there were 12 male and 41 female patients. The mean follow-up period was 8.4 years. Patients presented most commonly with deficits of the vagus nerve, followed by vestibular/cochlear nerve and glossopharyngeal nerve deficits. Gross-total resection of the tumor was achieved in 48 patients (90.5%). New postoperative paresis in a previously normal CN was not seen; however, worsening of preoperative CN deficits was frequently noted. The highest incidence occurred with the glossopharyngeal and vagus nerves (30%), with 26% of the deficits being permanent. There were no deaths related to surgery in this series. Three patients (5.7%) experienced tumor recurrence.

Conclusions

The microsurgical resection of jugular foramen schwannomas carries a risk of worsening preoperative CN deficits; however, these are often transient. Based on their experience, the authors have formulated a grading scale that predicts the optimal surgical approach to these lesions. Considerable technical training and microneuroanatomical knowledge of the region is required. The modified grading scale presented facilitates preoperative planning.
Transient expansion of vestibular schwannoma following stereotactic radiosurgery
Authors: Nagano Osamu , Higuchi Yoshinori , Serizawa Toru , Ono Junichi , Matsuda Shinji , Yamakami Iwao , Saeki Naokatsu
Published: October 2008

Object

The authors prospectively analyzed volume changes in vestibular schwannomas (VSs) after stereotactic radiosurgery.

Methods

One hundred consecutive patients with unilateral VS treated with Gamma Knife surgery (GKS) at Chiba Cardiovascular Center between 1998 and 2006 were analyzed in this study. For each lesion the Gd-enhanced volume was measured serially every 3 months in the 1st year, then every 6 months thereafter, using volumetric software. The frequency and degree of transient tumor expansion were documented and possible prognostic factors were analyzed. Concurrently, neurological deterioration involving trigeminal, facial, and cochlear nerve functions were also assessed.

Results

The mean observation period was 65 months (range 25–100 months). There were 32 men and 68 women, whose mean age was 59.1 years (range 29–80 years). Tumor volumes at GKS averaged 2.7 cm3 (range 0.1–13.2 cm3), and the lesions were irradiated at the mean 52.2% isodose line for the tumor margin (range 50–67%), with a mean dose of 12.2 Gy (range 10.5–13 Gy) at the periphery. The tumor volume was increased by 23% at 3 months and 27% at 6 months. Tumors shrank to their initial size over a mean period of 12 months. The maximum volume increase was < 10% (no significant increase) in 26 patients, 10–30% in 23, 30–50% in 22, 50–100% in 16, and > 100% in 13. The peak tumor expansion averaged 47% (range 0–613%). A high-dose (≥ 3.5 Gy/min) treatment appears to be the greatest risk factor for transient tumor expansion, although the difference did not reach statistical significance. Transient facial palsy and facial dysesthesia correlated strongly with tumor expansion, but only half of the hearing loss was coincident with this phenomenon.

Conclusions

Transient expansion of VSs after GKS was found to be much more frequent than previously reported, strongly suggesting a correlation with deterioration of facial and trigeminal nerve functions.
Preoperative prognostic classification system for hemispheric low-grade gliomas in adults
Authors: Chang Edward F. , Smith Justin S. , Chang Susan M. , Lamborn Kathleen R. , Prados Michael D. , Butowski Nicholas , Barbaro Nicholas M. , Parsa Andrew T. , Berger Mitchel S. , Mcdermott Michael M.
Published: October 2008

Object

Hemispheric low-grade gliomas (LGGs) have an unpredictable progression and overall survival (OS) profile. As a result, the objective in the present study was to design a preoperative scoring system to prognosticate long-term outcomes in patients with LGGs.

Methods

The authors conducted a retrospective review with long-term follow-up of 281 adults harboring hemispheric LGGs (World Health Organization Grade II lesions). Clinical and radiographic data were collected and analyzed to identify preoperative predictors of OS, progression-free survival (PFS), and extent of resection (EOR). These variables were used to devise a prognostic scoring system.

Results

The 5-year estimated survival probability was 0.86. Multivariate Cox proportional hazards modeling demonstrated that 4 factors were associated with lower OS: presumed eloquent location (hazard ratio [HR] 4.12, 95% confidence interval [CI] 1.71–10.42), Karnofsky Performance Scale score ≤ 80 (HR 3.53, 95% CI 1.56–8.00), patient age > 50 years (HR 1.96, 95% CI 1.47–3.77), and tumor diameter > 4 cm (HR 3.43, 95% CI 1.43–8.06). A scoring system calculated from the sum of these factors (range 0–4) demonstrated risk stratification across study groups, with the following 5-year cumulative survival estimates: Scores 0–1, OS = 0.97, PFS = 0.76; Score 2, OS = 0.81, PFS = 0.49; and Scores 3–4, OS = 0.56, PFS = 0.18 (p < 0.001 for both OS and PFS, log-rank test). This proposed scoring system demonstrated a high degree of interscorer reliability (kappa = 0.86). Four illustrative cases are described.

Conclusions

The authors propose a simple and reliable scoring system that can be used to preoperatively prognosticate the degree of lesion resectability, PFS, and OS in patients with LGGs. The application of a standardized scoring system for LGGs should improve clinical decision-making and allow physicians to reliably predict patient outcome at the time of the original imaging-based diagnosis.
Characterization of a side population of astrocytoma cells in response to temozolomide
Authors: Chua Constance , Zaiden Norazean , Chong Kooi-Hoong , See Siew-Ju , Wong Meng-Cheong , Ang Beng-Ti , Tang Carol
Published: October 2008

Object

Cancer progenitor–like cells isolated by Hoechst 33342 dye efflux (termed the “side population” [SP]) have been studied in a variety of cancers, including malignant brain tumors. In this study, the authors investigate the nature of the SP phenotype in 2 glioma cell lines, U87MG and T98G, and their response to temozolomide. The roles of several adenosine triphosphate–binding cassette (ABC) multidrug transporters expressed by SP cells, in particular ABCG2, are also examined.

Methods

Using fluorescence-activated cell sorting, the cells were separated into SP and non-SP fractions and analyzed for progenitor cell–like properties with immunofluorescence staining, quantitative real-time polymerase chain reaction, and their ability to reform glioma mass in an immune-compromised mouse. The response of the SP cells to temozolomide was investigated at the cellular and molecular levels. Small interfering RNA knockdown was used to examine the specific role of the ABCG2 transporter, and the cells' tumorigenic potential was measured using the soft agar clonogenic assay.

Results

Side population cells are characterized by the presence of progenitor cell–like properties: increased expression of nestin, musashi-1, and ABCG2 were observed. In addition, only SP cells were able to reconstitute cellular heterogeneity; these cells were also more invasive than the non-SP cells, and possessed tumorigenic capacity. Temozolomide treatment increased the number of SP cells, and this corresponded to more progenitor-like cells, concurrent with elevated expression of several ABC transporters.

Conclusions

Knockdown of ABCG2 transporters did not abrogate the SP cell response to temozolomide. Upregulation of several other ABC drug transporter genes is proposed to account for this chemoresistance.
Changes in myelin basic protein and demyelination in the rat brain within 3 months of single 2-, 10-, or 30-Gy whole-brain radiation treatments
Authors: Tian Ye , Shi Zhige , Yang Shu , Chen Yingzhu , Bao Shiyao
Published: October 2008

Object

The aim of this study was to determine the relation between changes in myelin basic protein (MBP) levels during the acute and subacute phases of central nervous system injury following whole-brain radiation and delayed demyelination in the radiation-injured brain tissue.

Methods

Adult Sprague–Dawley rats were treated with single fractions of 2, 10, or 30 Gy of whole-brain radiation. The authors measured MBP gene expression and protein levels in the brain tissue by using reverse transcription–polymerase chain reaction and enzyme-linked immunosorbent assay at 1 week and 1–3 months following irradiation to monitor myelin changes in the brain. Demyelination was determined with Luxol fast blue myelin staining and routine histopathological and electron microscopy examination of injured brain tissue. The changes in MBP levels in the different animal groups at specific time points were correlated with demyelination in corresponding dose groups.

Results

At 1 month after applying the 10 and 30 Gy of radiation, MBP mRNA expression showed a transient but significant decrease, followed by recovery to baseline levels at 3 months after treatment. The MBP levels were decreased by only 70–75% at 1 month after 10 and 30 Gy of radiation. At 2–3 months after applying the higher dose of 30 Gy, however, the MBP levels continued to decline, and typical demyelination changes were observed with myelin staining and ultrastructural examination.

Conclusions

The authors' results suggest that the early radiation-induced MBP changes between 1 and 3 months after single treatments of 10 and 30 Gy of radiation to the whole brain are indicative of permanent injury shown as demyelination of irradiated brain tissue.
Use of high-dose oral bisphosphonate therapy for symptomatic fibrous dysplasia of the skull
Authors: Chao Kevin , Katznelson Laurence
Published: October 2008

Fibrous dysplasia of the bone in adults is a rare anomaly of skeletal development caused by a defect in differentiation of osteoblasts. This condition is associated with bone pain, bone deformity, and an increased incidence of fracture. Involvement of the skull is associated with headache along with dysmorphic features. Until recently, the principal treatment has been resection or fracture repair, although the latter is often palliative at best. However, new insight into the molecular mechanism of fibrous dysplasia has led to the use of bisphosphonates to treat this disease.

The authors examined the effects of high-dose oral alendronate (40 mg daily) for 6 months on 3 adult patients with intractable headache due to fibrous dysplasia of the skull. Each patient had disease processes not amenable to surgery. The patients underwent clinical follow-up at 1, 3, and 6 months. Their pain levels were documented at each visit by using a visual analog scale. All 3 patients demonstrated a significant decrease in pain levels and became independent of scheduled analgesics. Tumor bulk did not progress during this interval in any patient. Overall, alendronate was tolerated well, although in 1 patient it was discontinued early due to esophagitis. High-dose oral bisphosphonate therapy is an alternative therapeutic option for the palliative treatment of patients with fibrous dysplasia of the skull.
Ultrasonic aspiration in neuroendoscopy: first results with a new tool
Authors: Oertel Joachim , Krauss Joachim Kurt , Gaab Michael Robert
Published: October 2008

Neuroendoscopic techniques are often considered inapplicable to lesion resection because most lesions are too large for effective endoscopic resection in an appropriate time frame. To evaluate the potential of ultrasonic aspiration in neuroendoscopic procedures, the authors developed a new handpiece for endoscopic application. The instrument was subsequently tested in 10 cadaveric pig brains and applied in 5 clinical cases. In the pig brain, a precise and accurate aspiration of ventricular ependyma and brain parenchyma was obtained. Clinically, the device was applied in 3 patients with obstructive hydrocephalus, and via an endonasal transsphenoidal approach in 2 patients with pituitary macroadenomas. In all cases, the lesion was effectively aspirated without complications. Ultrasonic aspiration can be applied safely and successfully in selected endoscopic procedures. The use of this technique could expand the indications for endoscopic approaches to include intraventricular lesions and in minimally invasive transsphenoidal endonasal approaches.
Dependency of cerebrospinal fluid outflow resistance on intracranial pressure
Authors: Andersson Nina , Malm Jan , Eklund Anders
Published: October 2008

Object

The outflow resistance (Rout) of the cerebrospinal fluid (CSF) system has generally been accepted by most investigators as independent of intracranial pressure (ICP), but there are also those claiming that it is not. The general belief is that this question has been investigated numerous times in the past, but few studies have actually been specifically aimed at looking at this relationship, and no study has been able to provide scientific evidence to elucidate fully this fundamental and important issue. The objective of this study was to investigate the relationship between ICP and CSF outflow in 30 patients investigated for idiopathic normal-pressure hydrocephalus.

Methods

Lumbar infusion tests with constant pressure levels were performed, and ICP and corresponding flow were measured on 6 pressure levels for each patient. All data were standardized for comparison.

Results

In the range of moderate increases from baseline pressure (~ 5–12 mm Hg, mean baseline pressure 11.7 mm Hg), the assumption of a pressure-independent Rout was confirmed (p = 0.5). However, when the pressure increment from baseline pressure was larger (~ 15–22 mm Hg), the relationship had a nonlinear tendency (p < 0.05).

Conclusions

The results of this study support the classic textbook theory of a pressure-independent Rout in the normal ICP range, where the CSF system is commonly operating. However, the theory might have to be questioned in regions where ICP exceeds baseline pressure by too much.
Sylvian aqueduct syndrome with slit ventricles in shunted hydrocephalus due to adult aqueduct stenosis
Authors: Maroulis Helen , Halmagyi G. Michael , Heard Robert , Cook Raymond J.
Published: October 2008

The authors report on 3 patients who developed sylvian aqueduct syndrome (SAS) in the context of shunt dysfunction and slit ventricles. All 3 patients had received shunts for adult onset hydrocephalus due to aqueduct stenosis and were stable for years before presenting with loss of upward gaze, convergence-retraction nystagmus, and slit ventricles, all due to shunt overdrainage. All 3 improved after either shunt revision or a third ventriculostomy procedure. Although it is well known that SAS can be caused by shunt blockage producing a transtentorial pressure gradient, these cases emphasize that an identical clinical pattern can occur with a reverse transtentorial pressure gradient and slit ventricles due to shunt overdrainage. The authors propose a simple management plan for patients with shunted hydrocephalus who develop SAS.
Suprascapular nerve release for treatment of shoulder and periscapular pain following intracranial spinal accessory nerve injury
Authors: Flores Leandro Pretto
Published: October 2008

Iatrogenic injury to the spinal accessory nerve is one of the most common causes of trapezius muscle palsy. Dysfunction of this muscle can be a painful and disabling condition because scapular winging may impose traction on the soft tissues of the shoulder region, including the suprascapular nerve. There are few reports regarding therapeutic options for an intracranial injury of the accessory nerve. However, the surgical release of the suprascapular nerve at the level of the scapular notch is a promising alternative approach for treatment of shoulder pain in these cases. The author reports on 3 patients presenting with signs and symptoms of unilateral accessory nerve injury following resection of posterior fossa tumors. A posterior approach was used to release the suprascapular nerve at the level of the scapular notch, transecting the superior transverse scapular ligament. All patients experienced relief of their shoulder and scapular pain following the decompressive surgery. In 1 patient the primary dorsal branch of the C-2 nerve root was transferred to the extracranial segment of the accessory nerve, and in the other 2 patients a tendon transfer (the Eden–Lange procedure) was used. Results from this report show that surgical release of the suprascapular nerve is an effective treatment for shoulder and periscapular pain in patients who have sustained an unrepairable injury to the accessory nerve.
Significant reduction in neural adhesions after administration of the regenerating agent OTR4120, a synthetic glycosaminoglycan mimetic, after peripheral nerve injury in rats
Authors: Zuijdendorp H. Mischa , Smit Xander , Blok Joleen H. , Caruelle Jean Pierre , Barritault Denis , Hovius Steven E. R. , van Neck Johan W.
Published: October 2008

Object

Extradural and intraneural scar formation after peripheral nerve injury frequently causes tethering and compression of the nerve as well as inhibition of axonal regeneration. Regenerating agents (RGTAs) mimic stabilizing and protective properties of sulphated glycosaminoglycan toward heparin-binding growth factors. The aim of this study was to assess the effect of an RGTA known as OTR4120 on extraneural fibrosis and axonal regeneration after crush injury in a rat sciatic nerve model.

Methods

Thirty-two female Wistar rats underwent a standardized crush injury of the sciatic nerve. The animals were randomly allocated to RGTA treatment or sham treatment in a blinded design. To score neural adhesions, the force required to break the adhesions between the nerve and its surrounding tissue was measured 6 weeks after nerve crush injury. To assess axonal regeneration, magnetoneurographic measurements were performed after 5 weeks. Static footprint analysis was performed preoperatively and at Days 1, 7, 14, 17, 21, 24, 28, 35, and 42 postoperatively.

Results

The magnetoneurographic data show no significant difference in conduction capacity between the RGTA and the control group. In addition, results of the static footprint analysis demonstrate no improved or accelerated recovery pattern. However, the mean pullout force of the RGTA group (67 ± 9 g [mean ± standard error of the mean]) was significantly (p < 0.001) lower than that of the control group (207 ± 14 g [mean ± standard error of the mean]).

Conclusions

The RGTAs strongly reduce nerve adherence to surrounding tissue after nerve crush injury.
Intraoperative assessment of endoscopic third ventriculostomy success
Authors: Greenfield Jeffrey P. , Hoffman Caitlin , Kuo Eugenia , Christos Paul J. , Souweidane Mark M.
Published: October 2008

Object

The authors' aim in this study was to determine if standardizing the evaluation of intraoperative findings during endoscopic third ventriculostomy (ETV) could predict patients with hydrocephalus in whom endoscopic treatment will fail and require ventriculoperitoneal shunt treatment. The creation of a uniform scale with predictive outcomes may reduce returns to the operating room for shunt treatment and reliance on postoperative externalized ventricular monitoring and MR imaging.

Methods

The authors evaluated the preoperative history, intraoperative findings, and postoperative monitoring and imaging findings in 109 consecutive patients undergoing 112 consecutive attempted ETVs for obstructive hydrocephalus. A 5-grade scale was developed to assess preoperative risk factors and intraoperative evaluation to unify criteria that have been suspected to influence outcome independently. A grade of 0 was assigned to patients with no negative predictors, whereas increasing scores were assigned to patients who had multiple preoperative and intraoperative risks identified. Patients' grades were compared with outcome of the procedure, utility of externalized ventricular monitoring, and results of postoperative MR imaging.

Results

Of 112 ETVs, 77 were successful and 35 were unsuccessful. Fifty-nine patients received a grade of 0, 27 received a grade of 1, 11 received a grade of 2, and 15 received a grade of ≥ 3. In all 15 patients receiving a grade ≥ 3 attempted ETV procedures failed, and the patients required a ventriculoperitoneal shunt. Postoperative monitoring with externalized ventricular drains and MR images demonstrating radiographic evidence of flow was independently less reliable than intraoperative grading in predicting success. Patients with a grade of 0 almost uniformly had successful surgery, independent of MR imaging findings. Patients with a grade of 1 or 2 who had successful surgery almost always lacked negative intraoperative predictive findings.

Conclusions

Despite reliance in recent years on post-ETV MR images and externalized ventricular monitoring, these modalities, although often useful adjuncts, appear less reliable as predictive tests than a simple assessment at the time of endoscopic fenestration. By using a uniform grading scale, the authors have introduced a novel means through which intraoperative and postoperative decision making can be aided, with the goal of reducing unnecessary procedures and tests and preventing unnecessary returns to the operating room.
Spontaneous resolution of Chiari malformation Type I in monozygotic twins
Authors: Miller Jeffrey H. , Limbrick David D. , Callen Matthew , Smyth Matthew D.
Published: October 2008

The spontaneous resolution of isolated tonsillar ectopia in Chiari malformation Type I (CM-I) is a known and reported entity in 2 previous single study case reports. However, it has not been previously described in monozygotic twins. Two children, ~ 1 year of age with CM-I and presumed episodes of pallid syncope or breath-holding spells presented for neurosurgical evaluation. Although Chiari decompression was considered, the authors decided to proceed with conservative management with close follow-up due to the uncertain nature of these episodes. Approximately 4 years later, both children's symptoms had resolved. Repeated MR imaging examinations also showed spontaneous resolution of the malformation in both girls. These cases emphasize that when patients with CM-I present with atypical symptoms, spontaneous resolution or improvement is possible, which may influence the decision to pursue a trial of nonsurgical management. The possible pathophysiological mechanisms and genetic influences of CM-I are also briefly discussed.