bluuebunny/crossref_metadata_2025_split huggingface dataset:
Movement disorders: Classifications
Authors: Klein C. 
Published: April 2005

SummaryMovement disorders (ataxia, dystonic disorders, gait disorders, Huntington disease, myoclonus, parkinsonism, spasticity, tardive dyskinesia, tics and tremor) are clinically, pathologically and genetically heterogeneous and are characterized by impairment of the planning, control or execution of movement. Current classifications of these disorders have inherent shortcomings due to the complex nature of movement disorders and the lack of diagnostic tests for the majority. Undiscriminating terminology, as well as the clinical, pathological and genetic heterogeneity, further complicate the development of comprehensive categorizations. Modern classification schemes tend to focus on clinical, pathological or genetic/molecular criteria, but more recent attempts have been made to integrate across these levels. From a historical perspective, two ‘golden ages’ have shaped the current and evolving classification schemes: (1) the definition of clinical pathological entities in the early twentieth century and (2) the application of molecular neurogenetics in the past 10–15 years. However, the classification of movement disorders on clinical grounds (according to age at onset, distribution of symptoms, disease course, provoking factors and therapeutic response) remains one of the most useful modes of categorization. Postmortem criteria have been employed to distinguish between degenerative and nondegenerative disorders, and specific hallmarks may be required to establish or confirm a diagnosis. Genetic features used for classification purposes include mode of inheritance and molecular genetic data, such as linkage to a known gene locus or identification of a specific genetic defect. A final classification scheme is based on alterations in molecular mechanisms (e.g. trinucleotide expansions) or protein function (e.g. channelopathies). Despite recent advances, it may not be possible to develop the ‘ultimate’ classification of movement disorders, and different patterns of lumping and splitting may be useful for the clinician, the pathologist or the geneticist/molecular biologist. Furthermore, certain individual cases with unique features may not fit into any particular category. Continued research by both clinicians and basic scientists is necessary in order to refine and redefine classification schemes of movement disorders.
Treatment strategies in movement disorders
Authors: Speelman J. D. 
Published: April 2005

SummaryStrategies in treatment of movement disorders are discussed with the illustration of three patients with dystonia. Pharmacotherapy can be applied in two ways: (1) a precise directed therapy, or (2) a ‘shotgun’ approach. Botulinum toxin is successfully injected in focal and segmental forms of movement disorders. Stereotactic neurosurgery can be considered in pharmacotherapy‐resistant dystonias, but also in other forms of movement disorders. Intrathecal baclophen treatment by continuous infusion is only indicated in severe forms of spasticity.
Bootstrap methods for statistical inference from stereological estimates of volume fraction
Authors: MATTFELDT T. , FLEISCHER F. 
Published: April 2005

SummaryWe suggest the use of bootstrap methods for inference from stereological estimates of volume fraction. An informal introduction to stereological estimation of volume fraction and to principles of bootstrap techniques is given. The bootstrap method is a robust computer‐intensive resampling technique, based on independent random sampling from a data set with replacement. Bootstrap methods were used to estimate confidence intervals for volume fractions, and to test for a significant difference between estimated volume fractions from two samples. Two sampling designs are considered: independent replicated samples (visual fields) from a single object, and estimates of volume fraction from multiple independent objects. The methods are presented as worked examples on real data sets obtained from tumour pathology (mammary cancer, pancreatic cancer). The volume fraction of glandular lumina per total volume of the epithelial phase was chosen as target parameter. It indicates the degree of glandular differentiation in adenocarcinomas and is estimated as a ratio‐of‐means statistic with variable denominator within cases. The confidence intervals of the volume fraction estimated by the bootstrap method were slightly narrower than the parametrically calculated confidence intervals for all data sets. The outcomes of significance tests based on the bootstrap technique were unchanged as compared with classical tests based on the assumptions of normality and homoscedasticity of the data. Special attention was paid to the reproducibility of the bootstrap technique in replicated trials on the same data.
Crystallographic analysis of thin specimens
Authors: SIVEL V. G. M. , TICHELAAR F. D. , MOHDADI H. , ALKEMADE P. F. A. , ZANDBERGEN H. W. 
Published: April 2005

SummaryElectron backscattering diffraction (EBSD) is commonly used on bulk samples for crystallographic material characterization. In this work, the technique was applied on transmission electron microscopy (TEM)‐type thin specimens, prepared with a focused ion beam. Orientation maps were successfully collected on specimens made of a Cu3Au copper–gold alloy. As compared to EBSD analysis on a bulk specimen, an improved pattern quality and a high spatial resolution (well below 10 nm) were obtained. Furthermore, a clear improvement of the signal‐to‐noise ratio with decreasing sample thickness was observed.
SEM examination of human erythrocytes in uncoated bloodstains on stone: use of conventional as environmental‐like SEM in a soft biological tissue (and hard inorganic material)
Authors: HORTOLÀ P. 
Published: April 2005

SummaryAlthough nowadays the so‐called environmental scanning electron microscopes (ESEMs) allow the observation of the samples without metal or carbon coating, many conventional scanning electron microscopes (SEMs) are still in use. On the other hand, the presence of erythrocytes (red blood cells, RBCs) in a smear is considered a blood confirmation. Such a presence has been previously reported even in Lower Stone Age implements. In previous works, I have reported several studies dealing with cytomorphology of RBCs in bloodstains using scanning electron microscopy with standard specimen preparation procedures, i.e. via coating the samples before SEM analysis. In order to explore the potential of conventional SEM as environmental‐like SEM in haemotaphonomical studies, two alkaline (limestone) and two acid (flint) rock fragments were smeared with human blood from a male and a female. The bloodstains obtained in this way were then air dried indoors and stored into a non‐hermetic plastic box. Afterwards, the smears and their rock substrates were examined directly without coating, via secondary electrons, using a JEOL JSM‐6400 scanning electron microscope. Satisfactory results reveal the capability of a conventional SEM to work in secondary‐electron mode as an environmental‐like SEM on these kinds of biological and inorganic materials, and probably in many other biological and non‐biological samples.
Automated alignment and pattern recognition of single‐molecule force spectroscopy data
Authors: KUHN M. , JANOVJAK H. , HUBAIN M. , MÜLLER D. J. 
Published: April 2005

SummaryRecently, direct measurements of forces stabilizing single proteins or individual receptor–ligand bonds became possible with ultra‐sensitive force probe methods like the atomic force microscope (AFM). In force spectroscopy experiments using AFM, a single molecule or receptor–ligand pair is tethered between the tip of a micromachined cantilever and a supporting surface. While the molecule is stretched, forces are measured by the deflection of the cantilever and plotted against extension, yielding a force spectrum characteristic for each biomolecular system. In order to obtain statistically relevant results, several hundred to thousand single‐molecule experiments have to be performed, each resulting in a unique force spectrum. We developed software and algorithms to analyse large numbers of force spectra. Our algorithms include the fitting polymer extension models to force peaks as well as the automatic alignment of spectra. The aligned spectra allowed recognition of patterns of peaks across different spectra. We demonstrate the capabilities of our software by analysing force spectra that were recorded by unfolding single transmembrane proteins such as bacteriorhodopsin and NhaA. Different unfolding pathways were detected by classifying peak patterns. Deviant spectra, e.g. those with no attachment or erratic peaks, can be easily identified. The software is based on the programming language C++, the GNU Scientific Library (GSL), the software WaveMetrics IGOR Pro and available open‐source at http://bioinformatics.org/fskit/.
Variations in the evaluation of colorectal cancer risk
Authors: Hodder R. J. , Ballal M. , Selvachandran S. N. , Cade D. 
Published: April 2005

AbstractObjectives  To test the variability in estimating cancer risk and demonstrate the consequences that subjectivity has on patient care.Subjects and methods  Forty‐three clinicians were each asked to assess 40 symptomatic colorectal referrals. Each clinician was provided with a comprehensive history on the 40 patients. The clinicians graded the referral according to a malignancy risk score, decided on the required first line investigation and the priority of that investigation. The main outcome measures used was accuracy in cancer detection and appropriateness of investigations selected.Results  There was a wide degree of variation among all clinicians grading both benign and malignant disease with the overall correct classification of 54% (P‐value of <0.001). On average, the clinicians correctly diagnosed 71.3% of the cancer patients as compared to 44% of the benign patients. Of the cancer patients, 47% were correctly classified as an urgent referral whilst 52% of the benign patients were over classified and graded as an urgent referral. The mean number chosen by clinicians to have a flexible sigmoidoscopy as the appropriate first investigation was 13 (of 40 patients); this was despite the diagnosis being possible in all cases with a flexible sigmoidoscopy. The choice to use full colonic investigation was seen throughout all disciplines. Junior doctors demonstrated the highest tendency choosing full colonic investigation in 92.3%. Consultants and senior grades showed the least tendency to choose full colonic imaging although even here colonoscopy or barium enema represented 48.5%.Conclusion  Subjective assessment of cancer referrals is a significant problem that needs to be confronted. Improvements are needed to resolve the inherent problems of subjectivity and operator bias if uniform quality of patient care and best use of resources is to be achieved.
Unreasonable expectations in emergency colorectal cancer surgery
Authors: Metcalfe M S. , Norwood M. G. A. , Miller A. S. , Hemingway D. 
Published: April 2005

AbstractObjectives  The recently published ACPGBI colorectal cancer (ACPGBI CRC) scoring system for predicting operative mortality has been suggested as an instrument to improve patient consent procedures and to compare results between centres. This study compares the results of a surgical unit against the standards set by the ACPGBI colorectal cancer model and for emergency surgery, against the p‐POSSUM instrument.Methods  Data for the ACPGBI CRC model were collected prospectively through 2003 at the Leicester Royal Infirmary. Additional data needed for the p‐POSSUM was retrospectively collected from case records. The actual mortality was compared with that predicted by the models.Results  Seventy‐two colorectal cancer operations were performed during the study period. The observed operative mortality in elective cases was lower, and in emergency cases higher, than predicted by the ACPGBI CRC model. With emergency cases the predicted mortality using P‐POSSUM was significantly higher than that using the ACPGBI CRC model, particularly in the presence of faecal contamination.Conclusion  The ACPGBI CRC model may be accurate for elective cases, but appears to significantly underestimate predicted mortality in the emergency setting, both actual and predicted by p‐POSSUM. This may be due to a failure to incorporate adequate weighting for faecal peritonitis and the associated systemic insult into the ACPGBI model.
Progressive and extensive hypomelanosis and extensive pityriasis alba: same disease, different names?
Authors: Di Lernia Vi , Ricci C 
Published: April 2005

ABSTRACTWe report the cases of five female patients with high skin phototype affected by relapsing, hypochromic, non‐scaling macules occurring after the summer on the back and spreading over large areas of skin. Histological features disclosed decreased epidermal melanin. Psoralen plus ultraviolet A (PUVA) treatment proved to be beneficial, but new relapses were noted after stopping treatment. Clinical and histological features were consistent with the diagnosis of ‘progressive and extensive hypomelanosis’ described by Guillet in persons of mixed racial background. We discuss the differential diagnosis of the latter entity with respect to the other idiopathic acquired primitive hypomelanosis and hypothesize an overlapping with the so‐called extensive pityriasis alba (EPA).
Persistent serpentine supravenous hyperpigmented eruption associated with docetaxel
Authors: Aydogan I , Kavak A , Parlak AH , Alper M , Annakkaya AN , Erbas M 
Published: April 2005

ABSTRACTVarious mucocutaneous reactions have been reported with the use of systemic docetaxel. We describe a 47‐year‐old man who developed a persistent serpentine supravenous hyperpigmented eruption (PSSHE), beginning at the site of docetaxel injection and spreading along the superficial venous network in the anterior aspect of the right forearm and distal arm. The eruption occurred after the first infusion of docetaxel following insufficient venous washing. A second infusion was administered through a vein in the other forearm, but this time, abundant venous washing was performed and a similar eruption did not occur. To our knowledge, this is the second report of docetaxel‐induced supravenous discoloration and we discussed the terminology and mechanism of this unique reaction.
Misregulation of poly(ADP‐ribose) polymerase‐1 activity and cell type‐specific loss of poly(ADP‐ribose) synthesis in the cerebellum of aged rats
Authors: Malanga M. , Romano M. , Ferone A. , Petrella A. , Monti G. , Jones R. , Limatola E. , Farina B. 
Published: April 2005

AbstractProtein modification by ADP‐ribose polymers is a common regulatory mechanism in eukaryotic cells and is involved in several aspects of brain physiology and physiopathology, including neurotransmission, memory formation, neurotoxicity, ageing and age‐associated diseases. Here we show age‐related misregulation of poly(ADP‐ribose) synthesis in rat cerebellum as revealed by: (i) reduced poly(ADP‐ribose) polymerase‐1 (PARP‐1) activation in response to enzymatic DNA cleavage, (ii) altered protein poly(ADP‐ribosyl)ation profiles in isolated nuclei, and (iii) cell type‐specific loss of poly(ADP‐ribosyl)ation capacity in granule cell layer and Purkinje cells in vivo. In particular, although PARP‐1 could be detected in virtually all granule cells, only a fraction of them appeared to be actively engaged in poly(ADP‐ribose) synthesis and this fraction was reduced in old rat cerebellum. NAD+, quantified in tissue homogenates, was essentially the same in the cerebellum of young and old rats suggesting that in vivo factors other than PARP‐1 content and/or NAD+ levels may be responsible for the age‐associated lowering of poly(ADP‐ribose) synthesis. Moreover, PARP‐1 expression was substantially down‐regulated in Purkinje cells of senescent rats.
Ras/ERK signalling in cannabinoid tolerance: from behaviour to cellular aspects
Authors: Rubino Tiziana , Forlani Greta , Viganò Daniela , Zippel Renata , Parolaro Daniela 
Published: April 2005

AbstractWe investigated the role of the Ras/extracellular‐regulated kinase (ERK) pathway in the development of tolerance to Δ9‐tetrahydrocannabinol (THC)‐induced reduction in spontaneous locomotor activity by a genetic (Ras‐specific guanine nucleotide exchange factor (Ras‐GRF1) knock‐out mice) and pharmacological approach. Pre‐treatment of wild‐type mice with SL327 (50 mg/kg i.p.), a specific inhibitor of mitogen‐activated protein kinase kinase (MEK), the upstream kinase of ERK, fully prevented the development of tolerance to THC‐induced hypolocomotion. We investigated the impact of the inhibition of ERK activation on the biological processes involved in cannabinoid tolerance (receptor down‐regulation and desensitization), by autoradiographic cannabinoid CB1 receptor and cannabinoid‐stimulated [35S]GTPγS binding studies in subchronically treated mice (THC, 10 mg/kg s.c., twice a day for 5 days). In the caudate putamen and cerebellum of Ras‐GRF1 knock‐out mice and SL327 pre‐treated wild‐type mice, CB1 receptor down‐regulation and desensitization did not occur, suggesting that ERK activation might account for CB1 receptor plasticity involved in the development of tolerance to THC hypolocomotor effect. In contrast, the hippocampus and prefrontal cortex showed CB1 receptor adaptations regardless of the genetic or pharmacological inhibition of the ERK pathway, suggesting regional variability in the cellular events underlying the altered CB1 receptor function. These findings suggest that at least in the caudate putamen and cerebellum, the Ras/ERK pathway is essential for triggering the alteration in CB1 receptor function responsible for tolerance to THC‐induced hypomotility.
Role of glutathione in intracellular amyloid‐α precursor protein/carboxy‐terminal fragment aggregation and associated cytotoxicity
Authors: Woltjer Randall L. , Nghiem William , Maezawa Izumi , Milatovic Dejan , Vaisar Tomas , Montine Kathleen S. , Montine Thomas J. 
Published: April 2005

AbstractAlterations in glutathione (GSH) metabolism are associated with neurodegeneration in Alzheimer's disease (AD), and GSH depletion follows application of exogenous fibrillar amyloid β (Aβ) peptides in experimental systems; these results are commonly cited as evidence of oxidative damage in AD. We used MC65 human neuroblastoma cells that conditionally express carboxy‐terminal fragments of the Aβ precursor protein (Aβ/CTFs) to directly test the hypothesis that GSH is part of the cellular response to stressors associated with Aβ/CTF accumulation and not simply a marker of oxidative damage. Our data showed that Aβ/CTFs accumulated by post‐translational processes and were associated with progressive increases in oxidative damage and cytotoxicity. Ethycrinic acid (EA) or diethyl maleate (DEM), reagents that deplete GSH through non‐specific thiol adduction, gave rise to dose‐dependent cytotoxicity that was independent of Aβ/CTF expression and minimally responsive to α‐tocopherol (AT). In contrast, buthionine sulfoximine (BSO), a selective inhibitor of GSH synthase, not only augmented Aβ/CTF‐associated cell death but unexpectedly potentiated Aβ/CTF accumulation; both outcomes were completely suppressed by AT. These data suggest that antioxidants may serve as ‘Aβ targeting’ therapies that suppress toxic protein aggregation rather than simply acting as downstream radical scavengers.
INPUT/OUTPUT ANALYSIS—AN APPRAISAL IN THE CONTEXT OF AS YET AN UNFINISHED EXPERIMENT IN KENYA
Authors: Singh Parmeet 
Published: April 2005

The paper discusses the relevance of input/output tables as a tool for economic analysis and planning in developing countries. It contends that this is so only to the extent that the input out‐put tables enable consistency of production accounts to be verified while providing a suitable basis for macro projections at the same time. As a by‐product, such input out put tables, the paper adds, also provide a convenient framework for estimating the needs for extensions and improvements in basic statistics.All these requirements, it is stated, can be fulfilled by a relatively aggregated format of an input/output table—which some of the developing countries are in a position to compile. However, the paper states, it is feared that the case for input/output analysis is not based on these requirements. The main force of arguments is in fact based on the uses of input/output tables for more detailed sectoral analysis and projections. The current state of basic statistics on some key sectors, it is stated, is not sufficiently sound to yield an end‐product which is reliable. In the case of sectors where this is so the input/output analysis is not relevant either because of concentration of production in a relatively few establishments or because of limited amount of inter‐sectoral interaction. It is further felt that if such arguments were to be accepted by developing countries the result would be a distorted disposition of statistical resources. Immediate needs of the developing countries require concentration of effort in development of more reliable and relevant series on basic statistics.
Plasma Concentrations of Risperidone and Olanzapine during Coadministration with Oxcarbazepine
Authors: Rosaria Muscatello Maria , Pacetti Monica , Cacciola Massimo , La Torre Diletta , Zoccali Rocco , Arrigo Concetta D' , Migliardi Gaetana , Spina Edoardo 
Published: April 2005

Summary:  Purpose: Oxcarbazepine (OZC) is a second‐generation antiepileptic drug (AED) that also may be used as a mood stabilizer. Unlike carbamazepine (CBZ), which is an inducer of the cytochrome P‐450 isoforms and may accelerate the elimination of several therapeutic agents, OXC seems to have only a modest inducing action. The aim of this investigation was to evaluate the effect of a treatment with OXC on plasma concentrations of the new antipsychotics risperidone and olanzapine. Methods: OXC, at a dosage of 900–1,200 mg/day, was administered for 5 consecutive weeks to 25 outpatients, 10 men and 15 women, aged 25 to 64 years, with bipolar or schizoaffective disorder. Twelve patients were stabilized on risperidone therapy (2–6 mg/day) and 13 on olanzapine (5–20 mg/day). Steady‐state plasma concentrations of risperidone and its active metabolite 9‐hydroxyrisperidone (9‐OH‐risperidone) and olanzapine were measured by high‐pressure liquid chromatography (HPLC) before addition of OXC and after 5 weeks from the start of adjunctive treatment. Results: OXC caused only minimal and no significant changes in the mean plasma levels of risperidone (from 5.6 ± 3.6 ng/ml at baseline to 4.8 ± 2.6 ng/ml at week 5), 9‐OH‐risperidone (from 23.6 ± 7.5 to 24.7 ± 7.4 ng/ml), and olanzapine (from 26.5 ± 5.7 ng/ml at baseline to 27.8 ± 5.1 ng/ml). OXC coadministration with either risperidone or olanzapine was well tolerated. Conclusions: Our findings indicate that OXC does not affect the elimination of risperidone and olanzapine, thus confirming its weak inducing effect on hepatic drug‐metabolizing enzymes.