bluuebunny/crossref_metadata_2025 huggingface dataset:
An analytical model for Doppler frequency variations of ionospheric HF sounding caused by SSC
Authors: Pilipenko V. , Fedorov E. , Yumoto K. , Ikeda A. , Sun T. R.
Published: October 2010

A theoretical model to interpret the deviations of the Doppler sounding radio frequency during the SSC is proposed. The Doppler response is composed from long‐period deviation with time scale ∼10 min and short‐lived (∼1 min) positive spike. For the interpretation of this spike, the variations of Doppler velocity induced by compressional and Alfvén waves are theoretically estimated on the basis of the thin ionosphere approximation. The analytical model developed goes beyond the older numerical model which has been in use thus far to explain certain facets of the correlation between geomagnetic variations and HF Doppler shifts. This new model provides the possibility to easily estimate the Doppler frequency response to either Alfvén or compresssional modes for extraordinary and ordinary radio waves. A theoretical estimate indicates that, for the same amplitude of the ground magnetic disturbances, a large‐scale compressional mode produces a larger ionospheric response than an Alfvén mode. The plasma vertical displacement caused by the ULF inductive electric field is shown to be the dominating effect. The magnitudes and waveforms of the simultaneously detected ionospheric and magnetic responses on SSC at a low‐latitude site in Japan fit the considered model.
On the ionospheric application of Poynting's theorem
Authors: Richmond A. D.
Published: October 2010

It has been proposed that the geomagnetic field‐aligned component of the perturbation Poynting vector above the ionosphere, as obtained from the cross product of the electric and magnetic perturbation fields observed on a spacecraft, may be used to estimate the field line‐integrated electromagnetic energy dissipation in the ionosphere below. This paper clarifies conditions under which this approximation may be either valid or invalid. It is shown that the downward field‐aligned component of the perturbation Poynting vector can underestimate the electromagnetic energy dissipation in regions of high ionospheric Pedersen conductance, and it can significantly overestimate the dissipation in regions of low conductance. Local values of upward perturbation Poynting vector do not necessarily correspond to net ionospheric generation of electromagnetic energy along that geomagnetic field line. An Equipotential Boundary Poynting Flux (EBPF) theorem is presented for quasi‐static electromagnetic fields as follows: when a volume of the ionosphere is bounded on the sides by an equipotential surface and on the bottom by the base of the conducting ionosphere, then the area integral of the downward normal component of the perturbation Poynting vector over the top of that volume equals the energy dissipation within the volume. This equality does not apply to volumes with arbitrary side boundaries. However, the EBPF theorem can be applied separately to different components of the electric potential, such as the large‐ and small‐scale components. Since contours of the small‐scale component of potential tend to close over relatively localized regions, the associated small‐scale structures of downward perturbation Poynting vector tend to be dissipated locally.
Elevated seawater temperature causes a microbial shift on crustose coralline algae with implications for the recruitment of coral larvae
Authors: Webster Nicole S , Soo Rochelle , Cobb Rose , Negri Andrew P
Published: October 2010

Crustose coralline algae (CCA) are key reef-building primary producers that are known to induce the metamorphosis and recruitment of many species of coral larvae. Reef biofilms (particularly microorganisms associated with CCA) are also important as settlement cues for a variety of marine invertebrates, including corals. If rising sea surface temperatures (SSTs) affect CCA and/or their associated biofilms, this may in turn affect recruitment on coral reefs. Herein, we report that the CCA Neogoniolithon fosliei, and its associated microbial communities do not tolerate SSTs of 32 °C, only 2–4 °C above the mean maximum annual SST. After 7 days at 32 °C, the CCA exhibited clear signs of stress, including bleaching, a reduction in maximum quantum yield (Fv/Fm) and a large shift in microbial community structure. This shift at 32 °C involved an increase in Bacteroidetes and a reduction in Alphaproteobacteria, including the loss of the primary strain (with high-sequence similarity to a described coral symbiont). A recovery in Fv/Fm was observed in CCA exposed to 31 °C following 7 days of recovery (at 27 °C); however, CCA exposed to 32 °C did not recover during this time as evidenced by the rapid growth of endolithic green algae. A 50% reduction in the ability of N. fosliei to induce coral larval metamorphosis at 32 °C accompanied the changes in microbiology, pigmentation and photophysiology of the CCA. This is the first experimental evidence to demonstrate how thermal stress influences microbial associations on CCA with subsequent downstream impacts on coral recruitment, which is critical for reef regeneration and recovery from climate-related mortality events.
Prediction of Repeat-Dose Occupancy from Single-Dose Data: Characterisation of the Relationship between Plasma Pharmacokinetics and Brain Target Occupancy
Authors: Abanades Sergio , van der Aart Jasper , Barletta Julien AR , Marzano Carmine , Searle Graham E , Salinas Cristian A , Ahmad Javaad J , Reiley Richard R , Pampols-Maso Sabina , Zamuner Stefano , Cunningham Vincent J , Rabiner Eugenii A , Laruelle Marc A , Gunn Roger N
Published: October 2010

Positron emission tomography (PET) is used in drug development to assist dose selection and to establish the relationship between blood and tissue pharmacokinetics (PKs). We present a new biomathematical approach that allows prediction of repeat-dose (RD) brain target occupancy (TO) using occupancy data obtained after administration of a single dose (SD). A PET study incorporating a sequential adaptive design was conducted in 10 healthy male adults who underwent 4 PET scans with [11C]DASB ([11C] N, N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine): 1 at baseline, 2 after 20 mg SD of the 5-hydroxytryptamine transporter (5-HTT) inhibitor duloxetine, and 1 after 4 days daily administration of 20 mg duloxetine. An adaptive design was used to select optimal times after SD for measurement of occupancy. Both direct and indirect PK/TO models were fitted to the SD data to characterise the model parameters and then applied to a predicted RD duloxetine plasma time course to predict the 5-HTT occupancy after RD. Repeat-dose prediction from the indirect model (OC50=2.62±0.93 ng/mL) was significantly better ( P<0.05) than that from the direct model (OC50=2.29±1.11 ng/mL). This approach increases the value of SD occupancy studies that are performed as part of first time in human drug development programmes by providing an estimate of the dose required to achieve the desired TO at RD.
Altered Expression and Function of Ryanodine Receptors and FKBP12.6 after Subarachnoid Hemorrhage: More than Meets the Eye
Authors: Jackson William F
Published: October 2010

Subarachnoid hemorrhage decreases the expression of ryanodine receptors and increases the expression of the immunophilin, FK506-binding protein (FKBP)12.6 in cerebrovascular smooth muscle cells, reducing the occurrence of Ca2+ sparks, limiting negative feedback regulation of cerebrovascular tone and promoting vasospasm. However, given the large number of binding partners with which FKBP12.6 and related proteins interact, it appears likely that the altered expression of this immunophilin will have a broader impact on cerebrovascular smooth muscle function. In addition, the mechanisms responsible for the measured changes in expression of ryanodine receptors and FKBP12.6 yet remain unknown. These topics should prove to be fertile ground for future studies.
Dynamics of Regional Distribution of Ischemic Lesions in Middle Cerebral Artery Trunk Occlusion Relates to Collateral Circulation
Authors: Cheng Bastian , Golsari Amir , Fiehler Jens , Rosenkranz Michael , Gerloff Christian , Thomalla Götz
Published: October 2010

We describe the regional distribution of acute perfusion, diffusion, and final infarct lesions in middle cerebral artery (MCA) trunk occlusion. A total of 31 patients with acute ischemic stroke and MCA trunk occlusion were studied by multiparametric magnetic resonance imaging. Probabilistic maps of lesion distribution were generated. The probability of initial and final infarcts was highest in the central MCA region with decreasing probability toward the periphery where the probability of the tissue at risk of infarction to be saved was highest. The probability of brain regions being involved in acute diffusion lesions and evolving into or escaping from the final infarct relates to the anatomy of arterial blood supply.
LipidMaps Core Update
Authors: Subramaniam Shankar , Fahy Eoin
Published: October 2010

LipidMaps (http://www.lipidmaps.org) is a multidisciplinary project involving multiple institutions. The goal of this project is to identify lipid metabolites and reconstruct pathways associated with lipids in mammalian cells using quantitative measurements of lipids in macrophage cells.
Maize gene review - A new on-line journal promotes community curation of phenotypes
Authors: Schaeffer Mary
Published: October 2010

The first formal phenotype summaries for maize can be found in early editions of theMaize Genetics Cooperation Newsletter (MNL). Prior to on-line databases, the MNLserved to systematize available mutant stocks, genetic maps, and addresses for maizegeneticists. In fact, the first phenotypic data entered into MaizeGDB, in 1991, was fromthe MNL stock center report. To support renewed, community submission of similardata, the MNL has initiated a new on-line journal, called the ‘maize gene review’ (MGR,www.maizegenereview.org). It represents an extension of the Mutants of Maize (1997),eds MG Neuffer, EH Coe, SR Wessler, where text summaries of individual mutantswere provided by experts in the field, often along with photographs. These weresubsequently incorporated into text descriptions and image files at MaizeGDB, withauthors credited. In the on-line journal MGR, each gene has a page, and an author(s),responsible for supplying a minimal set of information, and updating as new informationbecomes available. Reviewers familiar with the types of mutants described arerequested to provide criticism and updates, which are forwarded to the contributingauthor, as suggestions on updating their page(s). Reciprocal links are provided to theMaizeGDB for genome and map information and the short summary of each mutant isadded to the MaizeGDB locus record. This journal adds to the current communitycuration tools at MaizeGDB for community curation and has had an excellent response.The MNL is supported by an endowment at the University of Missouri provided by the MaizeCooperators. MaizeGDB is a USDA Agricultural Research Service funded database where thepresenting author is a curator.
Changes in Scholarly Communication and the Potential Impact on Biocuration
Authors: Bourne Philip
Published: October 2010

Open access in particular and changes in on-line scholarship have the potential to impact biocuration which often involves translating information currently read in papers to knowledge that is found in a variety of biological resources. The implication of these changes in scholarly communication to the biocuration process will be discussed with references to our work and that of others.
Respective Contributions of Maternal Insulin Resistance and Diet to Metabolic and Hypothalamic Phenotypes of Progeny
Authors: Carmody Jill S. , Wan Phyllis , Accili Domenico , Zeltser Lori M. , Leibel Rudolph L.
Published: October 2010

Maternal obesity can influence susceptibility to obesity and type 2 diabetes in progeny. We examined the relationship of maternal insulin resistance (IR), a metabolically important consequence of increased adiposity, to adverse consequences of obesity for fetal development. We used mice heterozygous for a null allele of the insulin receptor (Insr) to study the contributions of maternal IR to offspring phenotype without the potential confound of obesity per se, and how maternal consumption of high‐fat diet (HFD) may, independently and interactively, affect progeny. In progeny fed a 60% HFD, body weight and adiposity were transiently (5–7 weeks) increased in wild‐type (+/+) offspring of Insr+/− HFD‐fed dams compared to offspring of wild‐type HFD‐fed dams. Offspring of HFD‐fed wild‐type dams had increased body weight, blood glucose, and plasma insulin concentrations compared to offspring of chow‐fed wild‐type dams. Quantification of proopiomelanocortin (POMC) and neuropeptide‐Y (NPY) populations in the arcuate nucleus of the hypothalamus (ARH) of offspring of wild‐type vs. Insr+/− dams was performed to determine whether maternal IR affects the formation of central feeding circuits. We found a 20% increase in the number of Pomc‐expressing cells at postnatal day 9 in offspring of Insr+/− dams. In conclusion, maternal HFD consumption—distinct from overt obesity per se—was a major contributor to increased body weight, adiposity, IR, and liver triglyceride (TG) phenotypes in progeny. Maternal IR played a minor role in predisposing progeny to obesity and IR, though it acted synergistically with maternal HFD to exacerbate early obesity in progeny.
Pericardial Fat Amount Is an Independent Risk Factor of Coronary Artery Stenosis Assessed by Multidetector‐Row Computed Tomography: The Korean Atherosclerosis Study 2
Authors: Kim Tae Hyuk , Yu Sung Hoon , Choi Sung Hee , Yoon Ji Won , Kang Seon Mee , Chun Eun Ju , Choi Sang Il , Shin Hayley , Lee Hong Kyu , Park Kyong Soo , Jang Hak Chul , Lim Soo
Published: October 2010

Pericardial fat surrounding the heart and coronary arteries might aggravate vessel wall inflammation and stimulate the progression of coronary atherosclerosis. However, there has been little comprehensive evaluation of the effects of pericardial fat on coronary artery disease (CAD). We investigated the relationship between pericardial fat volume and the severity of coronary artery stenosis assessed by computed tomography and angiography among patients with suspected CAD. Participants from the cohort of the Korean Atherosclerosis Study 2 (n = 402, mean age of 54 years, 57.0% men) underwent 64‐slice multidetector‐row computed tomography (MDCT) to assess pericardial fat amount, coronary artery calcium score (CACS), severity of coronary artery stenosis, and plaque characteristics. Patients with atherosclerotic lesion had significantly larger volume of pericardial fat than patients without atherosclerosis (308 ± 96 cm3 vs. 251 ± 93 cm3; P < 0.01). In a multivariate regression analysis adjusting for age, gender and BMI, subjects with more pericardial fat had a higher risk for significant (>50%) stenosed coronary vessels (odds ratio (OR) = 1.012; 95% confidence interval (CI) 1.001–1.030; P = 0.017). This association remained after adjusting for hypertension, diabetes, smoking status, and lipid profiles (OR = 1.007; 95% CI 1.001–1.014; P = 0.042). In conclusion, an increased pericardial fat volume was an independent risk factor for stenotic CAD and could be helpful in assessing subclinical CADs.
Global assessment of scaffold hopping potential for current pharmaceutical targets
Authors: Hu Ye , Bajorath Jürgen
Published: October 2010

A scaffold-based target network is shown together with scaffold pairs having different scaffold hopping potential for a given target.
Inactivation of eukaryotic initiation factor 5A (eIF5A) by specific acetylation of its hypusine residue by spermidine/spermine acetyltransferase 1 (SSAT1)
Authors: Lee Seung Bum , Park Jong Hwan , Folk John E. , Deck Jason A. , Pegg Anthony E. , Sokabe Masaaki , Fraser Christopher S. , Park Myung Hee
Published: October 2010

eIF5A (eukaryotic translation initiation factor 5A) is the only cellular protein containing hypusine [Nϵ-(4-amino-2-hydroxybutyl)lysine]. eIF5A is activated by the post-translational synthesis of hypusine and the hypusine modification is essential for cell proliferation. In the present study, we report selective acetylation of the hypusine and/or deoxyhypusine residue of eIF5A by a key polyamine catabolic enzyme SSAT1 (spermidine/spermine-N1-acetyltransferase 1). This enzyme normally catalyses the N1-acetylation of spermine and spermidine to form acetyl-derivatives, which in turn are degraded to lower polyamines. Although SSAT1 has been reported to exert other effects in cells by its interaction with other cellular proteins, eIF5A is the first target protein specifically acetylated by SSAT1. Hypusine or deoxyhypusine, as the free amino acid, does not act as a substrate for SSAT1, suggesting a macromolecular interaction between eIF5A and SSAT1. Indeed, the binding of eIF5A and SSAT1 was confirmed by pull-down assays. The effect of the acetylation of hypusine on eIF5A activity was assessed by comparison of acetylated with non-acetylated bovine testis eIF5A in the methionyl-puromycin synthesis assay. The loss of eIF5A activity by this SSAT1-mediated acetylation confirms the strict structural requirement for the hypusine side chain and suggests a possible regulation of eIF5A by hypusine acetylation/deacetylation.
HEBSWeb: creating a World Wide Web health information service
Authors: DONALDSON KERR , MACKAY DONALD
Published: October 2010

The strategic issues and practical challenges involved in creating a World Wide Web health information service are discussed with particular reference to HEBSWeb, the World Wide Web site of the Health Education Board for Scotland(HEBS). The outcomes of the project and possible future developments are presented.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 1
Authors: Santoro L , Briani C , Giannini F , Girlanda P , Vitelli E , Schenone A , Benedetti A , Bogliun G , Manganelli F , Mazzeo A , Beghi E
Published: October 2010

Peripheral neuropathy (PN) has been found to be among the complications of hepatitis C virus (HCV) infection. Although the mechanisms of PN in patients with HCV infection are still unknown, cryoglobulinemia has been implicated as a possible cause of ischemic peripheral nerve impairment mediated by vasoconstriction, altered blood viscosity, and thrombosis of small vessels. However, available information is mostly based on referral patients with chronic HCV infection. In this study, an unselected sample of cases with newly diagnosed HCV infection has been examined to assess the prevalence and type of PN and to correlate the disease with the presence of cryoglobulinemia. The study population included 41 patients with HCV infection and no documented risk factors for PN (18 women and 23 men, aged 17 to 72 years) referred to the neurophysiology units of 7 Italian centers (Genova, Lodi, Messina, Monza, Napoli, Padova, and Siena) for a clinical and electrophysiological screening of peripheral nerve disease. The mean latency between diagnosis of HCV infection (interpreted as a surrogate of the duration of infection) and study entry was 6.8 months (range 1–12). PN was documented in 13 cases (31.7%). Of these, 7 had mononeuropathy and 6 had polyneuropathy. Cryoglobulinemia was present in 4 patients (9.8%) and 3 of them had PN (polyneuropathy 2, mononeuropathy 1). The odds ratio of PN in patients with cryoglobulinemia, adjusted for age, sex, and duration of infection, was 4.4 (95% confidence interval, CI: 0.3–68.2) and was fairly similar (4.1; 95% CI 0.3–56.3) when the analysis was limited to the presence of polyneuropathy. The lack of statistical significance may by explained by the small sample size. Based on these findings, cryoglobulinemia can be interpreted as an independent risk factor for PN at the presence of HCV infection. However, given the fairly high prevalence of PN in patients with newly diagnosed HCV infection and the high proportion of cases not attributable to cryoglobulinemia (9 out of 13), other factors should be investigated to clarify the mechanisms of HCV neuropathy.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 9
Authors: Vinci P , Perelli SL , Martini D
Published: October 2010

Charcot‐Marie‐Tooth disease (CMT) is a genetic neuropathy characterized by a length‐dependent degeneration of motor and sensory nerve fibers. Whereas all authors agree that weakening starts from the intrinsic foot muscles, there is still controversy whether the tibialis anterior muscle (TA) is weak or not in the early stages of the disease. To know this could be important either to understand how the cavus deformity develops or, consequently, to adopt surgical (tendon transfers) and conservative (orthotics, physiotherapy) strategies for prevention or early correction. We measured the power of TA in 110 feet of 62 patients (41 CMT1A, 1 CMT1B, 9 CMT1 without genetic evaluation, 5 CMTX, and 6 CMT2) fitting in the first two stages of the functional classification proposed by Vinci and Perelli. Thirty‐one feet were at stage 1 (forefootdrop or mild footdrop: leg‐sole angle >90< = 100) and 79 at stage 2 (same as stage 1 plus foot rotation on the longitudinal axis: heel angle <0 or >10). Muscle strength was measured by the manual muscle testing and scores according to the Medical Research Council scale. TA power graded 5/5 in 87 (79.1%) feet, 4/5 in 17 (15.5%) and 2/5 in 6 (5.4%). TA was strong (MRC 4/5 and 5/5) in the large majority (94.6%) of the feet in the two earlier stages of the disease. Interestingly, the 6 patients with weaker TA had CMT2. These results support our hypothesis that, in the earliest phase of CMT, foot rotation is due to a stronger and hyperactivated TA, which compensates the footdrop caused by the deficit of the metatarsophalangeal joint stabilization and, in many cases, is not balanced by the weak peroneal muscles.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 32
Authors: Aprile I , Padua L , Caliandro P , Pazzaglia C , Conti V , Tonali P ,   for the “Italian CTS study group.”
Published: October 2010

Carpal Tunnel Syndrome (CTS) is a well‐known entrapment disease. Recently, many study allowed us to improve our knowledge on CTS. Nevertheless many other topics on this common entrapment are not thoroughly assessed. The Italian CTS Study Group performed a multicenter (11 centers) survey study on more than 500 CTS hands with a large, multi‐perspective and multi‐measurement assessment. We used validated clinical, neurophysiological, and patient‐oriented measurements of CTS. In this study we assessed the following issues: 1) It is well known that menopause is related with CTS but no studies evaluated the clinical relationship between the entrapment and the clinical condition. 2) It is still matter of debate if alcohol may be related with CTS. 3) Someone hypothesized that computer pointing devices (mouse and keyboards) may cause CTS. 4) It is well known that patients with CTS complain of partial disability of the hand with frequent falling objects, but no study evaluated this important aspect in daily activity and related with the severity of the disease. Further issues, acquired through the database were assessed. Multi‐perspective and multi‐measurement assessment, even by using validated patient‐oriented tool, provided interesting information confirming and clarifying some poorly studied aspects often observed in CTS patients.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 37
Authors: Logullo F , Manicone M , Candela M , Agostinelli RM , Svegliati G , Di Bella P
Published: October 2010

In chronic hepatitis C virus (HCV) infection there is high prevalence of numerous extrahepatic manifestations. Peripheral neuropathy (PN), in the form of symmetric polyneuropathy, asymmetric polyneuropathy, and multineuropathy, may be associated also with HCV infection and is usually related to mixed cryoglobulinemia (CG). However, some HCV+ patients with PN without CG were recently reported, suggesting a possible direct role of HCV in the pathogenesis of PN. From January 2000 to December 2002 we studied 50 HCV+ patients: 21 with symptomatic CG and 29 with chronic HCV without symptomatic CG (23 without CG, 5 with asymptomatic CG). Particular care was taken to exclude other possible causes of PN. Patients without symptomatic CG were examined before starting combined therapy with interferon‐alpha and ribavirin, if needed. Fifteen patients with symptomatic CG had axonal sensorimotor polyneuropathy, 6 axonal sensorimotor multineuropathy or asymmetric polyneuropathy. Six HCV+ patients had other causes of PN (1 CIDP, 2 diabetes, 1 CIDP and diabetes, 1 alcoholism, 1 paraneoplastic with anti‐Hu antibodies). No HCV+ patients without (symptomatic) CG or other possible causes of PN showed clinical and electrophysiological evidence of PN. Our study casts doubts on the existence of a PN directly caused by HCV and suggests that finding a PN in a HCV+ patient without CG should prompt to search for a different cause of PN.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 50
Authors: Angiari C , Fabrizi GM , Cavallaro T , Ferrarini M , Cabrini I , Simonati A , Rizzuto N
Published: October 2010

The axonal form of Charcot‐Marie‐Tooth neuropathy (CMT type 2) has autosomal dominant inheritance and is genetically heterogeneous. Only 2 genes are known so far. Two unrelated Caucasian pedigrees (from Russia and Belgium) had 2 distinct mutations in the neurofilament‐light gene (NF‐L)(CMT2E, chromosome 8p21); a single Japanese pedigree had a mutation in the kinesin 1B gene (KIF1B)(CMT2A, chromosome 1p35‐p36). We aimed at investigating the epidemiological relevance of NF‐L in an Italian series with CMT2. The series included 30 index cases with CMT2 diagnosed according to clinical, electrophysiological and pathological criteria, in whom we have ruled out mutations of MPZ/P0 and CX32. In the selected series, the entire coding region of NF‐L was investigated by automated direct nucleotide sequencing. Direct molecular test of the novel identified mutation was performed by analyzing a restriction fragment length polymorphism (RFLP) for AatII. In a single five‐generation pedigree, with 3 affected member examined, we identified a novel heterozygous c.64C > T transition which substitutes a proline with a serine at amino acid residue 22 (Pro22Ser). The mutation appeared to be pathogenic because it co‐segregated with the disease in the pedigree and it was absent in more than 100 healthy controls. The amino acid change occurs in the N‐terminal head domain which regulates the assembly of neurofilaments. The report emphasizes the etiological role of NF‐L in CMT2.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 55
Authors: Cocito D , Isoardo G , Ciaramitaro P , Migliaretti G , Cavallo F , Rota E , Poglio F , Durelli L , Bergamasco B
Published: October 2010

BACKGROUND: Chronic demyelinating polyneuropathy associated with both IgM paraproteinemia and anti‐MAG antibody (MAG‐PN) is regarded as a clinical entity distinct from chronic inflammatory demyelinating PN (CIDP) even in association with paraproteinemia. MAG‐PN satisfy current electrophysiological criteria for CIDP and 18 to 37 % of patients fulfilling these criteria have high titers of IgM anti‐MAG antibody (Ab). Anti‐MAG Ab assay is rather expensive and time consuming, thus resulting sometimes in delaying the appropriate treatment in patients without these Ab. On the contrary, patients with MAG‐PN may be treated inappropriately before anti‐MAG Ab detection. OBJECTIVE: Determining the predictive value of clinical and electrophysiological features of patients with chronic dysimmune demyelinating PN for the presence of anti‐MAG Ab. MATERIALS AND METHODS: 49 patients fulfilling the diagnostic criteria for CIDP established by Rotta et al. (2001) were prospectively included. All of them were submitted to anti‐MAG Ab assay and research of paraproteinemia. The following features at the initial evaluation were considered for the analysis: presence of distal or proximal weakness at limbs, asymmetry of motor deficit, presence of sensory ataxia, presence of vibration or pinprick sense deficit, presence of conduction blocks, low terminal latency index (TLI) in at least two nerves at upper limbs, absence of M‐response (CMAP) at lower limbs. A discriminative analysis method was used to determine which features were significantly associated with the presence of anti‐MAG Ab, then sensitivity, specificity and likelihood ratio of these features were calculated. RESULTS: Low TLI, absence of CMAP at lower limbs, absence of proximal and distal weakness at lower limbs, were the features significantly associated with the presence of anti‐;MAG Ab. The combination of low TLI in two nerves and absence of CMAP at lower limbs or low TLI and absence of proximal and distal weakness at lower limbs had the greatest sensitivity, specificity and likelihood ratio, resulting in a very high increase in probability that a patient had MAG‐PN. DISCUSSION: Low TLI value in at least two upper limb nerves, absence of CMAP and of proximal weakness at lower limbs are the most informative features indicating the presence of anti‐MAG Ab in patients with chronic dysimmune demyelinating PN.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 59
Authors: Suozzi R , Galassi G , Ariatti A
Published: October 2010

A wide range of axonal peripheral neuropathies, especially subacute sensory and motor neuronopathies have been reported as remote effect of cancer. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) most often occurs isolated but it may accompany several autoimmune diseases. The association of CIDP and carcinoma is rare and its relevance is still debated. Few cases have been associated with gastrointestinal cancers. This 53‐year old man was admitted in December 1989 because of severe extremity weakness after EBV infection. Neurologic examination showed facial paresis, proximal and distal limb weakness, areflexia, distal loss for touch and deep sensibilities. Patient recovered with PE but mild symptoms and signs persisted in the limbs. In June 1997, patient developed acute relapse of his neuropathy after an episode of pneumonia. Electrophysiology, CSF and nerve biopsy were consistent with CIDP. Search for anti‐nerve antibodies was negative except for anti‐neurofilament IgM. IVIG had partial benefit. During the following four years, patient received IVIG 1 g/Kg monthly; however he continued to experience relapses of the neuropathy often occurring after trivial infections. Laboratory tests (monoclonal IgG; elevated SR and WB count, serum electrophoresis, carcinoembryonic antigen titer) suggested a systemic disease. In September 2001 a rectosigmoidal adenocarcinoma with bladder and liver metastases was discovered on abdominal CT scan and surgically treated. Patient's general and neurologic conditions rapidly deteriorated despite of chemotherapy with fluorouracil and leucovorin. He died on late summer 2002. We outline the unusual association of CIDP and intestinal cancer and the long interval elapsed between neuropathy onset and cancer detection.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 66
Authors: Giannini F , Marsili T , Bibbò G , Mondelli M , Padua L ,   and Italian CTS Study Group.
Published: October 2010

To better assess historical, physical and neurophysiological features of UNE, 20 centers widely distributed in the national country have joined a collaborative study in November 2001. Case recognition was based on clinical ground: symptoms or signs suggestive of ulnar nerve impairment at elbow, as numbness/ paresthesia in the part of ulnar innervated hand with or without sensory loss, elbow pain and weakness of ulnar hand muscles with or without hypotrophy. Electrophysiological examination was performed by a proper protocol according to AAEM/AAN recommendations (1999). Two validated (DASH and BCTQ) and one newly proposed self‐administered questionnaires were used for patient‐oriented evaluation. Clinical severity was assessed with a 3‐stage scale (Antoniadis, 1997) and a 4‐stage scale (Giannini, 2001). Electrophysiological severity was quantified using a 5‐step neurophysiological classification (Padua, 2001) and a 13‐point neurophysiological score (Mondelli, 2000). Two hundred‐seven patients (218 limbs affected) were collected until October 2002. The females/males ratio was 1:1.9 and females were younger than males (mean age 44.5 and 52.5 yrs. respectively). Repetitive stress injury was reported as possible pathogenetic factor in 50.5% of cases and Carpal Tunnel Syndrome ‐ comorbidity was diagnosed in 22.5% of limbs without gender difference. Reduction of ulnar nerve motor conduction across the elbow was found in 86.2% of limbs. EMG neurogenic pattern in ulnar supplied hand muscles and digit‐wrist ulnar SAP abnormalities were respectively observed in 61.5% and 49.1% of cases. Pain (61%), associated with positive provocative test (p < 0.01), was equally distributed in each clinical classes and was related with higher BCTQ score (p < 0.001). DASH questionnaire showed the highest relation to clinical scale and electrophysiological score (p < 0.001). High relations were found among clinical scales, neurophysiological classification and electrophysiological score (p < 0.001). These preliminary results show a very good reliability of most measurements used for multiperspective assessment of UNE syndrome.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 72
Authors: Pisano C , Pratesi G , Laccabue D , Zunino F , Lo Giudice P , Bellucci A , Pacifici L , Camerini B , Vesci L , Castorina M , Cicuzza S , Tredici G , Marmiroli P , Nicolini G , Galbiati S , Calvani M , Carminati P , Cavaletti G
Published: October 2010

Peripheral neurotoxicity is a severe side effect of several effective antineoplastic drugs. Different attempts have been previously performed in order to reduce the neurotoxicity of antineoplastic compounds, but so far an effective neuroprotective treatment is not available. Acetyl‐l‐carnitine (ALC) is a natural occurring compound with a neuroprotective activity in several experimental paradigms and in clinical use for the treatment of painful neuropathies. In this study we have tested in two rat models the hypothesis that ALC may have a protective role on cisplatin‐ and paclitaxel‐induced neuropathy. Preliminary in vitro and in vivo experiments in different tumor systems indicated the lack of interference of ALC in the antitumor effects of cisplatin and paclitaxel. ALC co‐treatment was able to significantly reduce the neurotoxicity of both cisplatin and paclitaxel in well‐established rat models and this effect was correlated with a modulation of the plasma levels of nerve growth factor (NGF) in the cisplatin model. The protective effect of ALC was confirmed also in in vitro studies on differentiated rat pheochromocytoma PC12 cells, where ALC treatment counteracted the paclitaxel and cisplatin‐induced cell damage, as measured by reduction of neurite elongation. In a search for the mechanism(s) of ALC neuroprotection, the transcriptional profile of gene expression in PC12 cells determined by microarray analysis indicated that ALC, in the presence of NGF, was able to modulate various genes relevant in the tissue‐specific toxicity, such as NGFI‐A. Moreover, we observed that labeled acetyl groups derived from ALC were transferred into histones and that cells co‐treatment with NGF and ALC increased the level of histones H4 acetylation. These findings suggest that up‐regulation of genes implicated in the protection against specific damage induced by neurotoxic agent may be the result of modulation of histone acetylation mediated by transfer of ALC acetyl groups. Overall, these results provide the first evidence that ALC is a neuroprotective agent acting through a novel mechanism that appears to be important for counteracting the chemotherapy‐induced neurotoxicity secondary to cisplatin and paclitaxel treatment.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 73
Authors: Inglese C , Allegri I , Alfieri S , Melli G , Giuberti T , Marbini A , Gemignani F
Published: October 2010

Cryoglobulinemic neuropathy is probably the commonest form of vasculitic neuropathy in Mediterranean countries, as usually related to the widespread hepatitis C virus (HCV) infection. We describe the spectrum of manifestations in a large series of patients with cryoglobulinemic neuropathy, also analyzing the impact of comorbid factors, which are quite frequent in HCV‐related mixed cryoglobulinemia. The cohort included 60 patients (10 men, 50 women) with peripheral neuropathy associated with mixed cryoglobulinemia as main or sole cause (type 2 in 36 cases, type 3 in 4, not typized in 20), HCV‐related in all patients but 8 (3 men and 5 women). Median age of patients was 65 years (range 41–85), and median age at onset of neuropathy was 59 (range 40–84). Peripheral neuropathy represented an onset manifestation of mixed cryoglobulinemia in about half patients. The most frequent clinical pattern was pure sensory neuropathy in 40 patients, including 4 patients with prominent ataxia; sensory neuropathy was asymmetrical in distribution in 9 patients, and in 14 patients sensory action potentials (SAPs) of the sural nerve were normal, suggesting selective involvement of the small sensory fibers. The remaining patients had sensorimotor neuropathy (15 cases) and mononeuropathy multiplex (5 cases). Positive sensory symptoms and restless legs syndrome were the most common manifestations. Neurophysiological study showed axonal degeneration of varying severity in all patients. In 20 patients, additional causes of neuropathy were present, including type 2 diabetes (5 patients), glucose intolerance (6 patients), non‐Hodgkin lymphoma (3 patients), and alcohol (2 patients). With respect with this subset of patients, in “pure” cryoglobulinemic neuropathy there was more often a pattern of sensory neuropathy (31/40 vs. 6/20; p = 0.001), with more frequent asymmetrical distribution (9 vs 0; p = 0.05) and small fiber involvement (11 vs 3). Severity of neuropathy, as judged on the basis of the Rankin scale and of neurophysiological changes, was similar in the two subgroups. Our study confirms that sensory neuropathy, often asymmetrical, is the most common clinical pattern in cryoglobulinemic neuropathy, and is consistently present in pure cryoglobulinemic neuropathy rather than in patients with other associated causes of neuropathy; in these latter, paradoxically, clinical and neurophysiological impairment seems not greater than in pure cryoglobulinemic neuropathy.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 76
Authors: Pareyson D , Scaioli V , Milani M , Ciano C , Moroni I , Morbin M , Erbetta A , Chiapparini L , Lauria G , Sghirlanzoni A , Taroni F
Published: October 2010

The X‐linked form of Charcot‐Marie‐Tooth disease (CMTX) is associated with mutations in the Connexin 32 gene (Cx32) and is the second most common CMT subtype after CMT1A, in which the 17p11.2 duplication is the underlying molecular defect. CMTX is characterized by no male‐to‐male transmission, intermediate motor conduction velocities (MCV), and more severe disease in males. In our series of CMT patients, we found 9 different Cx32 mutations in 11 families. Overall there were 26 patients, 13 males and 13 females, aged 11–76 yrs. Age at onset ranged considerably (1–60 yrs), but symptoms began earlier in males (mean 15.4 yrs, 77% within age 20) than in females (mean 25 yrs). All patients were autonomous, but disease severity was greater in males, while 4 female carriers were asymptomatic. Pain and tremor were frequent complaints. Two patients had Babinski sign and one had rest tremor. Nerve conduction studies were performed in 23 patients (13 males, 10 females). Upper limb motor conduction velocities (MCV) ranged between 25 and 57 m/s, and were slower in males (25–48 m/s) than in females (34–57 m/s). MCV were in the upper range of CMT1 (25–38 m/s) in 10/13 males but only in 3/10 females. In some cases, nerve conduction slowing was non‐uniform within single nerves, and one female patient had a previous diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy. There was considerable asymmetry of involvement between different nerves. The median nerve was often more severely affected than the ulnar nerve, and not only in females, as previously reported, but also in males. Therefore, it appears unlikely that this asymmetry is accounted for by a Lyonization phenomenon. Subclinical abnormalities of central nervous system as revealed by multimodal evoked potential studies were found in 8/10 patients. Expression of Cx32 in the brain is the likely explanation of this finding that confirms previous non‐systematic observations. We found seven missense and two nonsense mutations (one novel mutation). Two families presented distinct mutations at the same codon (Arg164), while the Arg22Stop and Arg220Stop mutations were each found in two unrelated cases.

Partially supported by a grant from the Italian Ministry of Health to F.T and D.P. (Progetto Ricerca Finalizzata ICS 030.3/RF00.174).
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 77
Authors: Lauria G , Morbin M , Borgna M , Lombardi R , Pareyson D , Manconi M , Geppetti P
Published: October 2010

The vanilloid receptor VR‐1 is a non‐selective ligand‐gated channel, structurally related to the transient receptor potential (TRP) family of ion channels. It responds to noxious stimuli including capsaicin, heating in the noxious range, and extracellular acidification. It is able to integrate simultaneous exposure to these stimuli and is involved in different forms of tissue hypersensitivity. VR‐1 is predominantly expressed in small‐diameter neurons of rat dorsal root ganglia (DRG), which give rise to unmyelinated sensory nerve fibers, but its immunoreactivity in human nerve fibers is not known. We assessed the expression of VR‐1 in human intra‐epidermal nerve fibers (IENF) of hairy and glabrous skin and in sural nerve biopsy. Skin biopsies were taken from proximal thigh, distal leg, trunk, arm, and fingertip in 10 healthy subjects. Immunohistochemical and confocal immunofluorescence studies using polyclonal anti‐PGP 9.5 (PGP), monoclonal anti‐unique b‐tubulin (TuJ1), and polyclonal anti‐human VR‐1 antibodies were performed. Double staining studies were carried out in the following combinations: PGP‐TuJ1 and TuJ1‐VR‐1. In each site, PGP‐positive IENF showed TuJ1 labeling and, most interestingly, VR‐1 diffusely co‐localized with all TuJ1‐positive IENF. These findings indirectly demonstrated the co‐localization between VR‐1 and the panaxonal marker PGP in IENF. VR‐1 immunoreactivity was assessed in formalin fixed, paraffin‐embedded sural nerve sections from a patient without morphological signs of sensory involvement. Almost 2/3 of unmyelinated fibers showed an intense VR‐1 immunoreactivity, which was present also in smooth muscle cells of perineurial and epineurial arterioles. VR‐1 immunolabeling was absent in myelinated fibers and in part of unmyelinated fibers, which possibly represented autonomic fibers. In conclusion, we demonstrated that VR‐1 is widely expressed in somatic human unmyelinated nerve fibers. Particularly, the diffuse immunoreactivity of IENF, which are naked terminals of small‐diameter DRG sensory neurons, suggests that they are essential for selective modalities of nociception and primarily involved in neuropathic hyperalgesia.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 83
Authors: Lauria G , Canafoglia L , Franceschetti S , Tripaldi F , Scaioli V , Villani F , Micco A , Pareyson D , Roccamo B , Besana C , Avanzini G
Published: October 2010

We describe a 64‐year‐old patient complaining of progressive gait disturbance, referred to the compressive effect of multiple discal protrusions, for about 3 years. At the age of 62 he presented epileptic seizures during a febrile episode. Cerebral MRI showed bilateral frontobasal T2‐weighted hyperintensity involving cortex and white matter. Partial seizures reappeared one year later and a MRI revealed a mild frontobasal atrophy. At the moment of our observation, neurological examination showed waddling gait with bilateral foot drop, muscular atrophy and weakness limited to the gluteal muscles and widespread deep tendon areflexia. Nerve conduction studies showed absent F‐waves at both upper and lower limb examination, with normal distal sensorimotor nerve conduction. Needle EMG examination detected mild chronic partial denervation, predominant in proximal muscles of lower limbs. Somatosensory evoked potentials recorded from upper extremities showed bilateral increase in early latencies (N9). Overall, neurophysiological findings indicated a widespread radiculopathy. Serum exams revealed positive anti‐nucleus (1:640, granular). CSF examination detected increased IgG level and several oligoclonal bands. Chest radiogram was normal. Soon after our first observation, the patient showed symptoms of respiratory insufficiency. A CT scans revealed a thoracic mass compatible with microcytoma, whereas anti‐Hu (3 +) antibodies and increased NSE (neuronal specific enolase) titer were found. In the following two weeks, the patient showed a progressive worsening of the general clinical conditions and died. We interpreted this complex neurological picture, which included an atypical limbic encephalitis and a slowly progressive polyradiculopathy, as a paraneoplastic syndrome. The almost complete resolution of the encephalitic process and the subtle chronic involvement of the peripheral nervous system, characterized by a limited, though widespread, radicular impairment, are rather peculiar features.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 84
Authors: Donadio V , Liguori R , Cortelli P , Pierangeli G , Magnifico F , Barducci R , Di Stasi V , Baruzzi A , Montagna P
Published: October 2010

The aim of the study is to determine the site of autonomic lesion in a patient with Holmes‐Adie Syndrome (HAS) who subsequently developed generalized anhydrosis. We describe a 38‐year‐old woman who from age 33 showed a right pupil larger than the left and from age 34 complained of focal and, a year later, generalized anhydrosis. Neurological examination showed absent tendon reflexes and right mydriatic pupil. Brain MRI, EEG, motor and sensory conduction studies were normal. Serologic screening for autoimmune disease was negative. To determine the site of the autonomic lesion the patient underwent the following investigations: pupillary tests with a diluted solution of pilocarpine (0.062%) and adrenaline (0.1%); cardiovascular reflexes; thermoregulatory sweat test (TST); circadian rhythm of body core temperature (CRT°); sympathetic skin response (SSR); microneurography recording of skin sympathetic activity (SSA) from median and peroneal nerves, and muscle sympathetic activity (MSA) from peroneal nerve; skin biopsy to evaluated the eccrine glands. Pupillary tests showed postganglionic parasympathetic and sympathetic denervation only of the right pupil. TST showed complete anhydrosis, SSR and SSA were absent and skin biopsy revealed normal morphology of the eccrine glands with hypotrophy of their structures. These results indicated a lesion of the postganglionic skin sympathetic fibers. Mechanisms for heat loss and conservation, cardiovascular reflexes and MSA were normal excluding a hypothalamic dysfunction or a more diffuse involvement of the autonomic nervous system. In conclusion, our patient showed a HAS associated with generalized anhydrosis and the autonomic investigations suggested underlying postganglionic parasympathetic and sympathetic autonomic lesions.