bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of cognitive impairment to psychiatric symptoms in multiple sclerosis
Authors: Figved N , Benedict R , Klevan G , Myhr KM , Nyland HI , Landrø NI , Larsen JP , Aarsland D
Published: August 2008

Psychiatric and cognitive changes are common in patients with multiple sclerosis (MS), but their relationship has not received much attention. We studied the relationship between psychiatric symptoms and verbal memory, working memory, and mental speed in 78 patients with MS and 40 healthy control subjects using linear regression analyses. The MS group exhibited impaired performance on all cognitive tests. Apathy was associated with intrusions and depression with impaired memory and mental speed. The association between apathy and intrusions supports the hypothesis that lesions in frontal areas or frontal connections contribute to a specific neuropsychiatric syndrome in patients with MS.
Recurrent leukoencephalopathy with microhemorrhages: gradient-echo MRI study diagnostic value in CNS primary angiitis
Authors: Arias M , Osorio XR , Dapena D , Arias-Rivas S , Vázquez F
Published: August 2008

Diagnosis of primary angiitis of the central nervous system (PACNS) is difficult in relation to variability in its clinical manifestations and absence of specific signs in neuroimaging. A young patient presented with a recurrent encephalopathic clinical course. T2 and fluid-attenuated inversion recovery-magnetic resonance imaging (FLAIR-MRI) showed hyperintense lesions in the cerebral white matter suggesting demyelination. Those lesions decreased or even disappeared after treatment with steroids and immunoglobulins. In echo gradient MRI (T2*-MRI), there were permanent cortical-subcortical petechial hypointense lesions (microhemorrhages). Definite diagnosis was established after cerebral biopsy. Intravenous cyclophosphamide was administrated with no new relapses in more than 18 months of follow-up. In a compatible clinical course, the finding of petechial hemorrhages in T2*-WI could play an important role in early diagnosis of PACNS.
A pilot trial of low-dose naltrexone in primary progressive multiple sclerosis
Authors: Gironi M , Martinelli-Boneschi F , Sacerdote P , Solaro C , Zaffaroni M , Cavarretta R , Moiola L , Bucello S , Radaelli M , Pilato V , Rodegher ME , Cursi M , Franchi S , Martinelli V , Nemni R , Comi G , Martino G
Published: August 2008

A sixth month phase II multicenter-pilot trial with a low dose of the opiate antagonist Naltrexone (LDN) has been carried out in 40 patients with primary progressive multiple sclerosis (PPMS). The primary end points were safety and tolerability. Secondary outcomes were efficacy on spasticity, pain, fatigue, depression, and quality of life. Clinical and biochemical evaluations were serially performed. Protein concentration of β-endorphins (BE) and mRNA levels and allelic variants of the μ-opiod receptor gene (OPRM1) were analyzed. Five dropouts and two major adverse events occurred. The remaining adverse events did not interfere with daily living. Neurological disability progressed in only one patient. A significant reduction of spasticity was measured at the end of the trial. BE concentration increased during the trial, but no association was found between OPRM1 variants and improvement of spasticity. Our data clearly indicate that LDN is safe and well tolerated in patients with PPMS.
Catheter-Directed Thrombolysis for Acute Renal Artery Thrombosis: Report of 4 Cases
Authors: Piffaretti Gabriele , Riva Francesca , Tozzi Matteo , Lomazzi Chiara , Rivolta Nicola , Carrafiello Gianpaolo , Castelli Patrizio
Published: August 2008

Acute renal artery occlusion is a rare but threatening problem; optimal therapeutic treatment remains a challenge, and ultimate outcomes are still to be defined. In the last decades, several reports or short-case experiences have been reported describing the use of selective infusion of lytic agents into renal artery to treat acute occlusion. We report 4 cases of acute renal artery occlusion treated by catheter-directed intraarterial thrombolysis.
A Novel Alternative to Open Conversion for Type 1 Endoleak Resulting in Ruptured Aneurysm
Authors: Varcoe Ramon L. , Laird Martin P. , Frawley John E.
Published: August 2008

In this article, a novel technique for the treatment of ruptured abdominal aortic aneurysm secondary to proximal type 1 endoleak as a result of progressive neck dilatation after endovascular aneurysm repair is reported. A 74-year-old man with multiple comorbidities including severe ischemic heart disease, congestive cardiac failure, and chronic renal failure presented with a ruptured abdominal aortic aneurysm. He had an infrarenal endovascular aneurysm repair performed in 1999 and had subsequently developed a proximal type 1 endoleak. At open laparotomy, the placement of 4 nylon ties around the infrarenal aneurysm neck to refashion a seal and exclude the sac from systemic pressurization effectively treated the rupture. In the high-risk patient, ruptured proximal type 1 endoleak can be successfully treated with external banding avoiding the potential morbidity seen with the aortic clamping and blood loss of open conversion.
Low-Dose Aspirin May Prevent Growth and Later Surgical Repair of Medium-Sized Abdominal Aortic Aneurysms
Authors: Lindholt Jes S. , Sorensen Henrik T. , Michel Jean B. , Thomsen Henrik F. , Henneberg Eskild W.
Published: August 2008

Experimental data suggest that aspirin-induced platelet inhibition may retard growth of abdominal aortic aneurysms. In this article, whether low-dose aspirin use is associated with reduced aneurysm progression and subsequent need for surgery is examined. In this observational cohort study within a screening trial, 148 patients with small aneurysms (maximum diameter 30-48 mm) annually are followed. Patients were referred for surgery when the aneurysmal diameter exceeded 50 mm. Median follow-up time was 6.6 years. Among patients whose abdominal aortic aneurysms were initially 40 to 49 mm in size, the abdominal aortic aneurysm expansion rate for low-dose aspirin users compared with nonusers was 2.92 mm/y versus 5.18 mm/y (difference 2.27 mm/y, 95% CI, 0.42-4.11). No difference in expansion rates and risk ratios for operative repair was found for patients with abdominal aortic aneurysms <40 mm. For medium-sized abdominal aortic aneurysms, low-dose aspirin may prevent abdominal aortic aneurysm growth and need for subsequent repair, but residual confounding cannot be excluded.
Women with and without intellectual disability and psychiatric disorders
Authors: Taggart L. , McMillan R. , Lawson A.
Published: August 2008

This article examines the literature on women with and without intellectual disability and psychiatric disorders, using a gender social model of health. Relevant empirical studies, international literature reviews and policies between 1980 and 2007 were identified from electronic databases, journals and secondary sources. Three areas were examined: psychiatric disorders, their contextual background, and their clinical presentation. There are minimal levels of research into women with intellectual disability and psychiatric disorders. However, this article hypothesizes that women with intellectual disability have higher rates of psychiatric disorders than women without. This may result from greater vulnerability related both to internal factors (`intra': cognitive deficits, poorer communication skills, limited social skills) and to the external world (`inter': lack of opportunities, stigma, poor social support networks). The article argues that such women require gender-sensitive mental health services. However, more empirical evidence is required to support this claim and to inform development and delivery of services.
The views and experiences of people with intellectual disabilities concerning advocacy
Authors: Llewellyn Penny , Northway Ruth
Published: August 2008

This article discusses the first stage of a grounded theory study in which people with intellectual disabilities participated in focus groups to explore their definitions of advocacy and their advocacy support needs. Participants' ideas were influenced by their situation, the availability and type of support offered, and their relationships with supporters. Many different definitions of advocacy were revealed which were classified as reactive or proactive advocacy at micro, meso or macro level. The aim of advocacy was seen as empowerment, but this occurred only when support was readily available, concentrated on people's abilities, and facilitated opportunities for them to exert maximum possible control over their lives.
Macrosegregation in horizontal direct chill casting of aluminium slabs
Authors: Krane M. J. M. , Vušanović I.
Published: August 2008

A model for macrosegregation is applied to horizontal direct chill casting (HDC) of Al–4·5 wt-%Cu. The fluid flow in liquid is controlled by thermosolutal buoyancy, as well as shrinkage during solidification and the liquid metal inlet jet. Buoyancy acts perpendicularly to the casting direction and the top and bottom heat transfer rates are not symmetric as in vertical direct chill casting. The influences of casting speed, position of inlet jet and inlet superheat are examined. Significant asymmetry is seen in the flow patterns and macrosegregation profiles. The mixture composition profiles of Cu in the solid show strong subsurface enrichment at the bottom surface and less at the top. Casting speed influences segregation levels and the shape and depth of sump. The placement of the inlet at the top or the bottom of the ingot changed the flow pattern, except near the mushy zone, but did not have an important effect on the exit composition profiles compared to centreline entrance cases.
Structural investigation of nanohydroxyapatite doped with Y3+ and F– ions
Authors: Basar B. , Evis Z.
Published: August 2008

Pure and 2·5 mol.-%Y3+ and F– doped nanohydroxyapatites were synthesised by a precipitation method and sintered at 900 and 1100°C to investigate their densification and structure. X-ray diffraction and Fourier transform infrared spectroscopy methods were performed to identify the presence of phases and bonds after the sintering respectively. Densification of hydroxyapatite was improved by the addition of these ions. No second phases were observed by X-ray diffraction method. Structure of the materials was hexagonal. Fourier transform infrared spectroscopy investigations showed that the Y3+ and F– doped hydroxyapatites had F– bonds in addition to OH– bonds after the sintering.
Detection of genome-wide polymorphisms in the AT-rich Plasmodium falciparum genome using a high-density microarray
Authors: Jiang Hongying , Yi Ming , Mu Jianbing , Zhang Louie , Ivens Al , Klimczak Leszek J , Huyen Yentram , Stephens Robert M , Su Xin-zhuan
Published: August 2008

Background

Genetic mapping is a powerful method to identify mutations that cause drug resistance and other phenotypic changes in the human malaria parasite Plasmodium falciparum. For efficient mapping of a target gene, it is often necessary to genotype a large number of polymorphic markers. Currently, a community effort is underway to collect single nucleotide polymorphisms (SNP) from the parasite genome. Here we evaluate polymorphism detection accuracy of a high-density 'tiling' microarray with 2.56 million probes by comparing single feature polymorphisms (SFP) calls from the microarray with known SNP among parasite isolates.

Results

We found that probe GC content, SNP position in a probe, probe coverage, and signal ratio cutoff values were important factors for accurate detection of SFP in the parasite genome. We established a set of SFP calling parameters that could predict mSFP (SFP called by multiple overlapping probes) with high accuracy (≥ 94%) and identified 121,087 mSFP genome-wide from five parasite isolates including 40,354 unique mSFP (excluding those from multi-gene families) and ~18,000 new mSFP, producing a genetic map with an average of one unique mSFP per 570 bp. Genomic copy number variation (CNV) among the parasites was also cataloged and compared.

Conclusion

A large number of mSFP were discovered from the P. falciparum genome using a high-density microarray, most of which were in clusters of highly polymorphic genes at chromosome ends. Our method for accurate mSFP detection and the mSFP identified will greatly facilitate large-scale studies of genome variation in the P. falciparum parasite and provide useful resources for mapping important parasite traits.
Recombination and selectional forces in cyanopeptolin NRPS operons from highly similar, but geographically remote Planktothrix strains
Authors: Rounge Trine B , Rohrlack Thomas , Kristensen Tom , Jakobsen Kjetill S
Published: August 2008

Background

Cyanopeptolins are nonribosomally produced heptapetides showing a highly variable composition. The cyanopeptolin synthetase operon has previously been investigated in three strains from the genera Microcystis, Planktothrix and Anabaena. Cyanopeptolins are displaying protease inhibitor activity, but the biological function(s) is (are) unknown. Cyanopeptolin gene cluster variability and biological functions of the peptide variants are likely to be interconnected.

Results

We have investigated two cyanopeptolin gene clusters from highly similar, but geographically remote strains of the same genus. Sequencing of a nonribosomal peptide synthetase (NRPS) cyanopeptolin gene cluster from the Japanese strain Planktothrix NIES 205 (205-oci), showed the 30 kb gene cluster to be highly similar to the oci gene cluster previously described in Planktothrix NIVA CYA 116, isolated in Norway. Both operons contained seven NRPS modules, a sulfotransferase (S) and a glyceric acid loading (GA)-domain. Sequence analyses showed a high degree of conservation, except for the presence of an epimerase domain in NIES 205 and the regions around the epimerase, showing high substitution rates and Ka/Ks values above 1. The two strains produce almost identical cyanopeptolins, cyanopeptolin-1138 and oscillapeptin E respectively, but with slight differences regarding the production of minor cyanopeptolin variants. These variants may be the result of relaxed adenylation (A)-domain specificity in the nonribosomal enzyme complex. Other genetic markers (16S rRNA, ntcA and the phycocyanin cpcBA spacer) were identical, supporting that these geographically separated Planktothrix strains are closely related.

Conclusion

A horizontal gene transfer event resulting in exchange of a whole module-encoding region was observed. Nucleotide statistics indicate that both purifying selection and positive selection forces are operating on the gene cluster. The positive selection forces are acting within and around the epimerase insertion while purifying selection conserves the remaining (major) part of the gene cluster. The presence of an epimerase in the gene cluster is in line with the D-configuration of Htyr, determined experimentally in oscillapeptin E in a previous study.
Mutant polycystin-2 induces proliferation in primary rat tubular epithelial cells in a STAT-1/p21-independent fashion accompanied instead by alterations in expression of p57KIP2and Cdk2
Authors: Felekkis Kyriacos N , Koupepidou Panayiota , Kastanos Evdokia , Witzgall Ralph , Bai Chang-Xi , Li Li , Tsiokas Leonidas , Gretz Norbert , Deltas Constantinos
Published: August 2008

Background

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is characterized by the formation of multiple fluid-filled cysts that destroy the kidney architecture resulting in end-stage renal failure. Mutations in genesPKD1andPKD2account for nearly all cases of ADPKD. Increased cell proliferation is one of the key features of the disease. Several studies indicated that polycystin-1 regulates cellular proliferation through various signaling pathways, but little is known about the role played by polycystin-2, the product ofPKD2. Recently, it was reported that as with polycystin-1, polycystin-2 can act as a negative regulator of cell growth by modulating the levels of the cyclin-dependent kinase inhibitor, p21 and the activity of the cyclin-dependent kinase 2, Cdk2.

Methods

Here we utilized different kidney cell-lines expressing wild-type and mutantPKD2as well as primary tubular epithelial cells isolated from a PKD transgenic rat to further explore the contribution of the p21/Cdk2 pathway in ADPKD proliferation.

Results

Surprisingly, over-expression of wild-typePKD2in renal cell lines failed to inactivate Cdk2 and consequently had no effect on cell proliferation. On the other hand, expression of mutatedPKD2augmented proliferation only in the primary tubular epithelial cells of a rat model but this was independent of the STAT-1/p21 pathway. On the contrary, multiple approaches revealed unequivocally that expression of the cyclin-dependent kinase inhibitor, p57KIP2, is downregulated, while p21 remains unchanged. This p57 reduction is accompanied by an increase in Cdk2 levels.

Conclusion

Our results indicate the probable involvement of p57KIP2on epithelial cell proliferation in ADPKD implicating a new mechanism for mutant polycystin-2 induced proliferation. Most importantly, contrary to previous studies, abnormal proliferation in cells expressing mutant polycystin-2 appears to be independent of STAT-1/p21.
A human monoclonal autoantibody to breast cancer identifies the PDZ domain containing protein GIPC1 as a novel breast cancer-associated antigen
Authors: Rudchenko Sergei , Scanlan Matthew , Kalantarov Gavreel , Yavelsky Victoria , Levy Chen , Estabrook Alison , Old Lloyd , Chan Gerald L , Lobel Leslie , Trakht Ilya
Published: August 2008

Background

We have been studying the native autoimmune response to cancer through the isolation of human monoclonal antibodies that are cancer specific from cancer patients. To facilitate this work we previously developed a fusion partner cell line for human lymphocytes, MFP-2, that fuses efficiently with both human lymph node lymphocytes and peripheral blood lymphocytes. Using this unique trioma fusion partner cell line we isolated a panel of autologous human monoclonal antibodies, from both peripheral blood and lymph node lymphocytes, which are representative of the native repertoire of anti-cancer specific antibodies from breast cancer patients.

Methods

The current study employs immunocytochemistry, immunohistochemistry, Western blot analysis as well as Northern blots, Scatchard binding studies and finally SEREX analysis for target antigen identification.

Results

By application of an expression cloning technique known as SEREX, we determined that the target antigen for two monoclonal antibodies, 27.B1 and 27.F7, derived from lymph node B-cells of a breast cancer patient, is the PDZ domain-containing protein known as GIPC1. This protein is highly expressed not only in cultured human breast cancer cells, but also in primary and metastatic tumor tissues and its overexpression appears to be cancer cell specific. Confocal microscopy revealed cell membrane and cytoplasmic localization of the target protein, which is consistent with previous studies of this protein.

Conclusion

We have determined that GIPC1 is a novel breast cancer-associated immunogenic antigen that is overexpressed in breast cancer. Its role, however, in the initiation and/or progression of breast cancer remains unclear and needs further clarification.
Effect of the ethinylestradiol/norelgestromin contraceptive patch on body composition. Results of bioelectrical impedance analysis in a population of Italian women
Authors: Piccoli Antonio , Crosignani PierGiorgio , Nappi Carmine , Ronsini Salvatore , Bruni Vincenzina , Marelli Silvia ,   the Italian EVRA Contrast Study Group
Published: August 2008

Background

As weight gain is one of the most frequently cited reasons for not using and for discontinuing hormonal contraceptives, in an open-label, single-arm, multicentre clinical study we evaluated the effect of the ethinylestradiol/norelgestromin contraceptive patch (EVRA, Janssen-Cilag International, Belgium) on body composition using bioelectrical impedance analysis (BIA).

Methods

Body weight and impedance vector components (resistance (R) and reactance (Xc), at 50 kHz frequency, Akern-RJL Systems analyzer) were recorded before entry, after 1, 3 and 6 months in 182 Italian healthy women aged 29 yr (18 to 45), and with BMI 21.8 kg/m2 (16 to 31). Total body water (TBW) was estimated with a BIA regression equation. Vector BIA was performed with the RXc mean graph method and the Hotelling's T2 test for paired and unpaired data.

Results

After 6 months body weight increased by 0.64 kg (1.1%) and TBW increased by 0.51 L (1.7%). The pattern of impedance vector displacement indicated a small increase in soft tissue hydration (interstitial gel fluid). Body composition changes did not significantly differ among groups of previous contraceptive methods. Arterial blood pressure did not significantly change over time.

Conclusion

After 6 months of treatment with the ethinylestradiol/norelgestromin contraceptive patch we found a minimal, clinically not relevant, increase in body weight less than 1 kg that could be attributed to an adaptive interstitial gel hydration. This fluctuation is physiological as confirmed by the lack of any effect on blood pressure. This could be useful in increasing women's choice, acceptability and compliance of the ethinylestradiol/norelgestromin contraceptive patch.
A novel hybrid aspirin-NO-releasing compound inhibits TNFalpha release from LPS-activated human monocytes and macrophages
Authors: Turnbull Catriona M , Marcarino Paolo , Sheldrake Tara A , Lazzarato Loretta , Cena Clara , Fruttero Roberta , Gasco Alberto , Fox Sarah , Megson Ian L , Rossi Adriano G
Published: August 2008

Background

The cytoprotective nature of nitric oxide (NO) led to development of NO-aspirins in the hope of overcoming the gastric side-effects of aspirin. However, the NO moiety gives these hybrids potential for actions further to their aspirin-mediated anti-platelet and anti-inflammatory effects. Having previously shown that novel NO-aspirin hybrids containing a furoxan NO-releasing group have potent anti-platelet effects, here we investigate their anti-inflammatory properties. Here we examine their effects upon TNFα release from lipopolysaccharide (LPS)-stimulated human monocytes and monocyte-derived macrophages and investigate a potential mechanism of action through effects on LPS-stimulated nuclear factor-kappa B (NF-κB) activation.

Methods

Peripheral venous blood was drawn from the antecubital fossa of human volunteers. Mononuclear cells were isolated and cultured. The resultant differentiated macrophages were treated with pharmacologically relevant concentrations of either a furoxan-aspirin (B8, B7; 10 μM), their respective furazan NO-free counterparts (B16, B15; 10 μM), aspirin (10 μM), existing nitroaspirin (NCX4016; 10 μM), an NO donor (DEA/NO; 10 μM) or dexamethasone (1 μM), in the presence and absence of LPS (10 ng/ml; 4 h). Parallel experiments were conducted on undifferentiated fresh monocytes. Supernatants were assessed by specific ELISA for TNFα release and by lactate dehydrogenase (LDH) assay for cell necrosis. To assess NF-κB activation, the effects of the compounds on the loss of cytoplasmic inhibitor of NF-κB, IκBα (assessed by western blotting) and nuclear localisation (assessed by immunofluorescence) of the p65 subunit of NF-κB were determined.

Results

B8 significantly reduced TNFα release from LPS-treated macrophages to 36 ± 10% of the LPS control. B8 and B16 significantly inhibited monocyte TNFα release to 28 ± 5, and 49 ± 9% of control, respectively. The B8 effect was equivalent in magnitude to that of dexamethasone, but was not shared by 10 μM DEA/NO, B7, the furazans, aspirin or NCX4016. LDH assessment revealed none of the treatments caused significant cell lysis. LPS stimulated loss of cytoplasmic IκBα and nuclear translocation of the p65 NF-κB subunit was inhibited by the active NO-furoxans.

Conclusion

Here we show that furoxan-aspirin, B8, significantly reduces TNFα release from both monocytes and macrophages and suggest that inhibition of NF-κB activation is a likely mechanism for the effect. This anti-inflammatory action highlights a further therapeutic potential of drugs of this class.
Heterologous ectoine production in Escherichia coli: By-passing the metabolic bottle-neck
Authors: Bestvater Thorsten , Louis Petra , Galinski Erwin A
Published: August 2008

Transcription of the ectoine biosynthesis genes ectA, ectB and ectC from Marinococcus halophilus in recombinant Escherichia coli DH5α is probably initiated from three individual σ70/σA-dependent promoter sequences, upstream of each gene. Consequently, mRNA-fragments containing the single genes and combinations of the genes ectA and ectB or ectB and ectC, respectively, could be detected by Northern blot analysis. Under the control of its own regulatory promoter region (ectUp) a seemingly osmoregulated ectoine production was observed. In addition, aspartate kinases were identified as the main limiting factor for ectoine production in recombinant E. coli DH5α. Co-expression of the ectoine biosynthesis genes and of the gene of the feedback-resistant aspartate kinase from Corynebacterium glutamicum MH20-22B (lysC) led to markedly increased production of ectoine in E. coli DH5α, resulting in cytoplasmic ectoine concentrations comparable to those reached via ectoine accumulation from the medium.
Ectopic internal carotid artery presenting as an oropharyngeal mass
Authors: Prokopakis Emmanuel P , Bourolias Constantinos A , Bizaki Argyro J , Karampekios Spyros K , Velegrakis George A , Bizakis John G
Published: August 2008

Ectopic internal carotid artery (ICA) is a very rare variation. The major congenital abnormalities of the ICA can be classified as agenesis, aplasia and hypoplasia, and they can be unilateral or bilateral. Anomalies of the neck artery may be vascular neoplasms or ectopic position. Carotid angiograms provide absolute confirmation of an aberrant carotid artery, while EcoColorDoppler (ECD) gives also important information about the evaluation of carotid vassels. Nevertheless Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) of the neck provide spatial information about the adjacent pharyngeal anatomy and are less invasive than angiogram. Injuries to the ICA during simple pharyngeal surgical procedures can be catastrophic due to the risk of massive bleeding. We report a case of a 56 year-old male patient suffering from dysphagia associated with aberrant ICA manifesting itself as a pulsative protruding of the left lateral wall of the oropharynx.
Dorsal turning of motor corticospinal axons at the pyramidal decussation requires plexin signaling
Authors: Faulkner Regina L , Low Lawrence K , Liu Xiao-Bo , Coble Jeffrey , Jones Edward G , Cheng Hwai-Jong
Published: August 2008

Background

The development of the corticospinal tract (CST) in higher vertebrates relies on a series of axon guidance decisions along its long projection pathway. Several guidance molecules are known to be involved at various decision points to regulate the projection of CST axons. However, previous analyses of the CST guidance defects in mutant mice lacking these molecules have suggested that there are other molecules involved in CST axon guidance that are yet to be identified. In this study, we investigate the role of plexin signaling in the guidance of motor CST axons in vivo.

Results

Expression pattern studies show that plexin-A3, plexin-A4, and neuropilin-1 are expressed in the developing cerebral cortex when the motor CST axons originating from layer V cortical neurons are guided down to the spinal cord. By analyzing mutant mice, we show that motor CST axons that turn dorsally to cross the midline at the pyramidal decussation require plexin-A3 and plexin-A4 signaling. Although other CST guidance defects are found in neuropilin-1 mutants, this dorsal turning defect is not observed in either neuropilin-1 or neuropilin-2 mutants, suggesting that the local cues that activate plexin signaling at the dorsal turning point are membrane-bound semaphorins. Further expression pattern study and mutant analysis indicate that Sema6A is one of the local cues for motor CST axon turning at the pyramidal decussation.

Conclusion

Dorsal turning and midline crossing at the pyramidal decussation is a crucial step to properly direct CST axons into the dorsal spinal cord. We show that the signaling of plexin-A3, plexin-A4, and Sema6A is at least partially required for dorsal turning of the CST axons, while neuropilin-1 is required for proper fasciculation of the tract at midline crossing. Together with previous reports, these results demonstrate that several guidance cues are specifically utilized to regulate the dorsal turning and midline crossing of developing CST axons.
Preferential regulation of duplicated genes by microRNAs in mammals
Authors: Li Jingjing , Musso Gabriel , Zhang Zhaolei
Published: August 2008

Background

Although recent advances have been made in identifying and analyzing instances of microRNA-mediated gene regulation, it remains unclear by what mechanisms attenuation of transcript expression through microRNAs becomes an integral part of post-transcriptional modification, and it is even less clear to what extent this process occurs for mammalian gene duplicates (paralogs). Specifically, while mammalian paralogs are known to overcome their initial complete functional redundancy through variation in regulation and expression, the potential involvement of microRNAs in this process has not been investigated.

Results

We comprehensively investigated the impact of microRNA-mediated post-transcriptional regulation on duplicated genes in human and mouse. Using predicted targets derived from several analysis methods, we report the following observations: microRNA targets are significantly enriched for duplicate genes, implying their roles in the differential regulation of paralogs; on average, duplicate microRNA target genes have longer 3' untranslated regions than singleton targets, and are regulated by more microRNA species, suggesting a more sophisticated mode of regulation; ancient duplicates were more likely to be regulated by microRNAs and, on average, have greater expression divergence than recent duplicates; and ancient duplicate genes share fewer ancestral microRNA regulators, and recent duplicate genes share more common regulating microRNAs.

Conclusion

Collectively, these results demonstrate that microRNAs comprise an important element in evolving the regulatory patterns of mammalian paralogs. We further present an evolutionary model in which microRNAs not only adjust imbalanced dosage effects created by gene duplication, but also help maintain long-term buffering of the phenotypic consequences of gene deletion or ablation.
Prestack wave-equation depth migration in elliptical coordinates
Authors: Shragge Jeff , Shan Guojian
Published: August 2008

We extend Riemannian wavefield extrapolation (RWE) to prestack migration using 2D elliptical-coordinate systems. The corresponding 2D elliptical extrapolation wavenumber introduces only an isotropic slowness model stretch to the single-square-root operator. This enables the use of existing Cartesian finite-difference extrapolators for propagating wavefields on elliptical meshes. A poststack migration example illustrates advantages of elliptical coordinates for imaging turning waves. A 2D imaging test using a velocity-benchmark data set demonstrates that the RWE prestack migration algorithm generates high-quality prestack migration images that are more accurate than those generated by Cartesian operators of the equivalent accuracy. Even in situations in which RWE geometries are used, a high-order implementation of the one-way extrapolator operator is required for accurate propagation and imaging. Elliptical-cylindrical and oblate-spheroidal geometries are potential extensions of the analytical approach to 3D RWE-coordinate systems.
Cerebrovascular Disease Risk in Older Head and Neck Cancer Patients After Radiotherapy
Authors: Smith Grace L. , Smith Benjamin D. , Buchholz Thomas A. , Giordano Sharon H. , Garden Adam S. , Woodward Wendy A. , Krumholz Harlan M. , Weber Randal S. , Ang K.-Kian , Rosenthal David I.
Published: August 2008

Purpose

Cerebrovascular disease is common in head and neck cancer patients, but it is unknown whether radiotherapy increases the cerebrovascular disease risk in this population.

Patients and Methods

We identified 6,862 patients (age > 65 years) from the Surveillance, Epidemiology, and End Results (SEER) –Medicare cohort diagnosed with nonmetastatic head and neck cancer between 1992 and 2002. Using proportional hazards regression, we compared risk of cerebrovascular events (stroke, carotid revascularization, or stroke death) after treatment with radiotherapy alone, surgery plus radiotherapy, or surgery alone. To further validate whether treatment groups had equivalent baseline risk of vascular disease, we compared the risks of developing a control diagnosis, cardiac events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, or cardiac death). Unlike cerebrovascular risk, no difference in cardiac risk was hypothesized.

Results

Mean age was 76 ± 7 years. Ten-year incidence of cerebrovascular events was 34% in patients treated with radiotherapy alone compared with 25% in patients treated with surgery plus radiotherapy and 26% in patients treated with surgery alone (P < .001). After adjusting for covariates, patients treated with radiotherapy alone had increased cerebrovascular risk compared with surgery plus radiotherapy (hazard ratio [HR] = 1.42; 95% CI, 1.14 to 1.77) and surgery alone (HR = 1.50; 95% CI, 1.18 to 1.90). However, no difference was found for surgery plus radiotherapy versus surgery alone (P = .60). As expected, patients treated with radiotherapy alone had no increased cardiac risk compared with the other treatment groups (P = .63 and P = .81).

Conclusion

Definitive radiotherapy for head and neck cancer, but not postoperative radiotherapy, was associated with excess cerebrovascular disease risk in older patients.
TREATMENT OF GIANT MIDDLE CEREBRAL ARTERY ANEURYSMS WITH A FLOW REPLACEMENT BYPASS USING THE EXCIMER LASER-ASSISTED NONOCCLUSIVE ANASTOMOSIS TECHNIQUE
Authors: van Doormaal Tristan P.C. , van der Zwan Albert , Verweij Bon H. , Han Kuo S. , Langer David J. , Tulleken Cornelis A.F.
Published: August 2008

OBJECTIVE

To define the clinical value of the flow replacement bypass using the excimer laser-assisted nonocclusive anastomosis (ELANA) technique in the treatment of patients with a noncoilable, nonclippable giant intracranial aneurysm of the middle cerebral artery (MCA).

METHODS

Between 1999 and 2006, 22 patients with a giant intracranial aneurysm of the MCA were treated in our hospital with an ELANA flow replacement bypass and MCA occlusion. We collected data on patient characteristics, operative aspects, complications, and functional health scores using the modified Rankin Scale. Mean follow-up was 3.6 years (range, 0.2–7.7 yr).

RESULTS

We were able to construct a patent bypass in 20 (91%) of 22 patients. All 34 ELANA attempts resulted in a patent anastomosis with a strong backflow directly after ELANA catheter retraction. The patients did not need to undergo temporary occlusion in any of the ELANA constructions. Mean ± standard deviation intracranial-to-intracranial bypass flow was 53 ± 13 ml/min. MCA aneurysm treatment was attempted in all 20 patients who had a patent bypass and was successful in 19 of them. There was a fatal hemorrhagic complication in one patient (5%), a nonfatal hemorrhagic complication in three patients (14%), and a nonfatal ischemic complication in six patients (27%). At follow-up, 17 patients (77%) had a functionally favorable outcome (modified Rankin Scale score at follow-up was the same as or less than the preoperative modified Rankin Scale score). All of these patients were independent at follow-up (modified Rankin Scale score ≤2).

CONCLUSION

This study demonstrates satisfactory results in the treatment of giant MCA aneurysms with an ELANA flow replacement bypass, considering the very grave natural history and treatment complexity of these lesions. The ELANA technique is a useful tool in the treatment armamentarium of the vascular neurosurgeon.
ENDOSCOPIC ENDONASAL RESECTION OF ANTERIOR CRANIAL BASE MENINGIOMAS
Authors: Gardner Paul A. , Kassam Amin B. , Thomas Ajith , Snyderman Carl H. , Carrau Ricardo L. , Mintz Arlan H. , Prevedello Daniel M.
Published: August 2008

OBJECTIVE

The endonasal route may be feasible for the resection of anterior cranial base tumors that abut the paranasal sinuses. There are several case reports and mixed case series discussing this approach. Other than pituitary adenomas, there is a lack of literature describing the outcomes of endonasal approaches for single-tumor types such as meningiomas.

METHODS

In this study, we describe our current endoscopic endonasal technique and demonstrate the feasibility of using it to access anterior cranial base meningiomas from the back wall of the frontal sinus to the sella and laterally to the region of the midorbit. After this discussion, which includes key technical considerations and nuances, we address safety and efficacy by reporting the outcomes of our early experience with endoscopic endonasal resection of 35 anterior cranial base meningiomas.

RESULTS

A total of 35 patients underwent endoscopic endonasal resection of anterior cranial base meningiomas from October 2002 to October 2005. Degree of resection by tumor location was as follows: 10 of the 12 (83%) patients with olfactory groove meningiomas planned for complete resection underwent gross total (seven of 12) or near-total (>95%) (three of 12) resection (67% of all 15 olfactory tumors); 12 of 13 patients (92%) with tuberculum meningiomas underwent gross (11 of 13) or near (>95%) (one of 13) total resection; five patients diagnosed with petroclival meningiomas had successful resection of the parasellar portion of their tumors with relief of visual symptoms (no patients underwent complete resection of their tumors via the endoscopic, endonasal approach); two giant petroclival meningiomas were debulked with 63 and 89% resection, respectively.

All patients experienced resolution or improvement of visual symptoms. No patient experienced permanent worsening of vision after surgery. Only one (3%) patient without preoperative endocrine dysfunction experienced a new, permanent pituitary deficit, diabetes insipidus. One (3%) patient experienced a new neurological deficit after experiencing a hemorrhage 3 weeks after surgery. The postoperative cerebrospinal fluid leak rate was 40% (14 of 35) and varied by tumor location. All leaks were resolved without craniotomy. There were no cases of bacterial meningitis. One patient developed a superinfection of a sterile granuloma from a sinusitis 2 years after surgery. There were two cases of deep venous thrombosis and one pulmonary embolus. There were no operative or perioperative deaths.

CONCLUSION

Cranial base meningiomas can be successfully managed via a purely endoscopic endonasal approach with acceptable morbidity and mortality rates. The extent of resection is guided by patient factors and symptoms, not by approach. This series had a high cerebrospinal fluid leak rate. With the evolution of new reconstruction techniques, these rates have been substantially reduced.
EXTENT OF SURGICAL RESECTION OF MALIGNANT ASTROCYTOMAS OF THE SPINAL CORD
Authors: McGirt Matthew J. , Goldstein Ira M. , Chaichana Kaisorn L. , Tobias Michael E. , Kothbauer Karl F. , Jallo George I.
Published: August 2008

OBJECTIVE

The optimal management of malignant intramedullary spinal cord astrocytomas remains controversial. Although radiotherapy has become the standard of care, the relationship between extent of resection and survival remains unclear. We report the outcomes of the surgical management of 35 malignant spinal cord astrocytomas and assess the association of extent of resection with survival after aggressive resection of these tumors.

METHODS

An institutional intramedullary spinal cord tumor database (1990–2002) was reviewed to identify all patients treated for malignant astrocytomas of the spinal cord (anaplastic astrocytoma [AA] or glioblastoma multiforme [GBM]). Length of survival from surgery was charted by Kaplan-Meier plots, and association of extent of resection with survival was assessed via log rank analysis for stratified covariates and Cox proportional-hazards model for continuous covariates.

RESULTS

Twenty-seven (77%) and eight (23%) patients underwent resection of AA and GBM, respectively. Mean age was 29 ±16 years (range, 2–61 yr). Tumor involved six ± four vertebral levels. For AA cases, radical resection (no residual postoperative magnetic resonance enhancement) was achieved in 12 (44%) patients and subtotal resection (residual postoperative magnetic resonance enhancement) was achieved in 15 (56%). No GBM patients underwent radical resection (mean estimated resection, 70%). After surgery, two (6%) patients improved neurologically by modified McCormick score, 19 (54%) remained stable, and 14 (40%) declined. Median overall survival for AA patients was 72 months (85% at 1 yr; 59% at 5 yr). Median overall survival for GBM patients was 9 months (31% at 1 yr; 0% at 5 yr). Subtotal versus radical resection of AA was associated with decreased overall survival (38 versus 78% at 4 yr, P = 0.028). Postoperative tumor dissemination was associated with decreased survival (P = 0.004). When adjusting for multiple comparisons (P < 0.006 needed for significance), a trend of increased survival was observed with radical resection (P = 0.023).

CONCLUSION

Neurological function can be preserved with aggressive resection of malignant intramedullary spinal astrocytomas; however, motor decline may be observed in many cases. Radical resection of AA was associated with a trend of increased overall survival in nondisseminated AA cases. Radical surgery and radiotherapy of GBM was associated with poor survival, similar to historical controls of diagnostic biopsy and radiotherapy. A markedly shorter survival may be expected in cases in which AA disseminates along the neuraxis. Biopsy alone may not provide the best outcomes for patients with malignant spinal cord tumors.
PROSPECTIVE RANDOMIZED COMPARISON OF SAFETY AND EFFICACY OF NICARDIPINE AND NITROPRUSSIDE DRIP FOR CONTROL OF HYPERTENSION IN THE NEUROSURGICAL INTENSIVE CARE UNIT
Authors: Roitberg Ben Z. , Hardman Julian , Urbaniak Klaudia , Merchant Amina , Mangubat Erwin Z. , Alaraj Ali , Mlinarevich Nada , Watson Karriem S. , Ruland Sean
Published: August 2008

OBJECTIVE

The calcium channel blocker nicardipine (NC) is effective for acute control of hypertension. However, efficacy and safety in neurosurgical patients have not been evaluated. We sought to compare NC with the most commonly used agent, sodium nitroprusside (SNP), in patients with subarachnoid or intracerebral hemorrhage.

METHODS

We performed a prospective randomized comparison of the safety and efficacy of NC and SNP in patients with subarachnoid or intracerebral hemorrhage. We assessed the number of dose adjustments per patient day, proportion of time within set blood pressure parameters, use of additional medications for blood pressure control, clinical outcome, and drug-related complications.

RESULTS

Two hundred patients were screened and 163 patients were randomized, including 89 in the SNP group and 74 in the NC group. In 107 patients, intravenous blood pressure control was started; 60 of these patients received SNP and 47 received NC. When analyzed by intent to treat, patients randomized to NC had fewer dose adjustments per day: 5.7 versus 8.8 in the nitroprusside group (P = 0.0012, Wilcoxon rank-sum test). There were fewer additional medications per day to maintain blood pressure control in the NC group: 1.4 versus 1.9 for SNP (P = 0.043, Wilcoxon rank-sum test). Blood pressure control was similar (NC, 66% of the time within parameters; SNP, 69%). “As-treated” analysis maintained the apparent advantage of NC.

CONCLUSION

When used for control of hypertension in patients with subarachnoid or intracerebral hemorrhage, NC and SNP were both safe and effective, but patients on an NC drip required fewer dose adjustments and fewer additional medications.
PITUICYTOMA
Authors: Wolfe Stacey Quintero , Bruce Jocelyn , Morcos Jacques J.
Published: August 2008

OBJECTIVE

Pituicytoma is a rare but distinct low-grade glioma of the neurohypophysis. To date, we have found only 28 cases reported in the literature and have reviewed these in addition to our own case to delineate the clinical implications of this relatively recently defined tumor.

CLINICAL PRESENTATION

A 71-year-old woman presented with bitemporal hemianopsia and was found to have a large sellar tumor, resembling a pituitary adenoma. Transsphenoidal resection was attempted but was complicated by significant tumor vascularity. Pathology at that time was interpreted as a “granular cell tumor.” The patient was then referred to our institution for management of the residual tumor.

INTERVENTION

The patient underwent preoperative embolization to decrease tumor vascularity, and subtotal tumor resection was performed via a craniofacial approach. Postoperatively, the patient has enjoyed significantly improved visual fields despite residual tumor. No adjuvant treatment was given. There has been no regrowth of the residual tumor, as shown on magnetic resonance imaging, over a follow-up period of 1.5 years. The final pathological diagnosis was pituicytoma.

CONCLUSION

Pituicytomas are benign, slow-growing tumors that seem to be cured by gross total resection. The role of radiation therapy is controversial. We advocate an aggressive surgical approach with possible preoperative embolization to reduce the vascularity of the tumor.
TRANSIENT INHIBITION OF MOTOR FUNCTION INDUCED BY THE CAVITRON ULTRASONIC SURGICAL ASPIRATOR DURING BRAIN MAPPING
Authors: Carrabba Giorgio , Mandonnet Emmanuel , Fava Enrica , Capelle Laurent , Gaini Sergio M. , Duffau Hugues , Bello Lorenzo
Published: August 2008

OBJECTIVE

We report, for the first time, the occurrence of interference between a Cavitron ultrasonic surgical aspirator (CUSA) and intraoperative brain mapping performed by direct electrical stimulation (DES).

METHODS

Intraoperative polygraphic recordings (electrocorticogram and electromyogram) were gathered from a 44-year-old patient harboring a recurrent Grade II oligoastrocytoma operated on with the aid of a CUSA and DES.

RESULTS

Simultaneous use of CUSA and DES at the subcortical level in proximity to the corticospinal tract brought about the abolition of previously evident motor responses. This abolition was fully reversible after the CUSA was turned off. An analogous pattern of motor response inhibition was evident when the DES was applied cortically and the CUSA was used subcortically close to motor pathways. Interestingly, the authors had already observed a similar phenomenon in many patients when the CUSA was used for resection of lesions located within or in proximity to subcortical language pathways. In this setting, the CUSA induced transient speech disturbances that were confirmed afterwards by the DES. This interference with language and motor mapping might be interpreted as a transitory inhibition of axonal conduction.

CONCLUSION

The clinical significance of this interference is relevant when the CUSA and DES are used simultaneously for motor mapping because the CUSA can decrease the sensitivity of the brain mapping technique. Further studies will be required to determine the neurophysiological mechanism underlying this interference.