bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Posterior Cruciate Ligament Injury and Reconstruction on Meniscal Strain
Authors: Pearsall Albert W. , Hollis J. Marcus
Published: August 2004

Background

The relationship between posterior cruciate ligament insufficiency and meniscal injury is unclear.

Hypothesis

Posterior cruciate ligament insufficiency results in increased medial and lateral meniscal strain.

Study Design

Descriptive anatomic study.

Methods

Eight cadaveric specimens were evaluated with a 6-axis load cell and differential variable reluctance transducer strain gauges placed in both menisci. Data were recorded in the posterior cruciate ligament–intact state after posterior cruciate ligament transection and after posterior cruciate ligament reconstruction.

Results

The effect of posterior cruciate ligament state on meniscal strain was more pronounced at higher flexion angles. At 60° and 90° of flexion, there was a significant effect of posterior cruciate ligament sectioning and reconstruction on meniscal strain (P < .026). Average meniscal strain for both medial and lateral menisci increased between the intact and the posterior cruciate ligament–cut states. Posterior cruciate ligament reconstruction decreased strain values to that of the intact knee.

Conclusions

Meniscal strain increases with complete posterior cruciate ligament injury and is returned to posterior cruciate ligament–intact levels after posterior cruciate ligament reconstruction.

Clinical Relevance

Posterior cruciate ligament reconstruction may play an important role in reducing meniscal strain and sub-sequent degeneration within the posterior cruciate ligament–injured knee.
Incidence, Causes, and Severity of High School Football Injuries on FieldTurf versus Natural Grass
Authors: Meyers Michael C. , Barnhill Bill S.
Published: August 2004

Background

Numerous injuries have been attributed to playing on artificial turf. Recently, FieldTurf was developed to duplicate the playing characteristics of natural grass. No long-term study has been conducted comparing game-related, high school football injuries between the 2 playing surfaces.

Hypothesis

High school athletes would not experience any difference in the incidence, causes, and severity of game-related injuries between FieldTurf and natural grass.

Study Design

Prospective cohort study.

Methods

A total of 8 high schools were evaluated over 5 competitive seasons for injury incidence, injury category, time of injury, injury time loss, player position, injury mechanism, primary type of injury, grade and anatomical location of injury, type of tissue injured, head and knee trauma, and environmental factors.

Results

Findings per 10 team games indicated total injury incidence rates of 15.2 (95% confidence interval, 13.7-16.4) versus 13.9 (95% confidence interval, 11.9-15.6). Minor injury incidence rates of 12.1 (95% confidence interval, 10.5-13.6) versus 10.7 (95% confidence interval, 8.7-12.7), substantial injury incidence rates of 1.9 (95% confidence interval, 1.4-2.6) versus 1.3 (95% confidence interval, 0.8-2.1), and severe injury incidence rates of 1.1 (95% confidence interval, 0.7-1.7) versus 1.9 (95% confidence interval 1.2-2.8) were documented on FieldTurf versus natural grass, respectively. Multivariate analyses indicated significant playing surface effects by injury time loss, injury mechanism, anatomical location of injury, and type of tissue injured. Higher incidences of 0-day time loss injuries, noncontact injuries, surface/epidermal injuries, muscle-related trauma, and injuries during higher temperatures were reported on FieldTurf. Higher incidences of 1- to 2-day time loss injuries, 22+ days time loss injuries, head and neural trauma, and ligament injuries were reported on natural grass.

Conclusions

Although similarities existed between FieldTurf and natural grass over a 5-year period of competitive play, both surfaces also exhibited unique injury patterns that warrant further investigation.
A New Mechanical Testing Device for Measuring Anteroposterior Knee Laxity
Authors: Schuster Andreas J. , Mcnicholas Mike J. , Wachtl Stefan W. , McGurty Douglas W. , Jakob Roland P.
Published: August 2004

Background

The authors assessed a new instrument, the Rolimeter, for the measurement of anteroposterior translation in the knee; it was compared to the KT-1000 arthrometer.

Purpose

To determine if the Rolimeter offers a valid method for the measurement of anteroposterior translation that is as reproducible and reliable as the KT-1000 arthrometer.

Methods

Two of 3 observers examined 16 normal subjects (32 knees) and 36 patients (72 knees) with ligament ruptures twice, using both the Rolimeter and the KT-1000 arthrometers, 30 minutes apart. Total anteroposterior translation (manual maximal Lachman test) was recorded at 20° and 80° of knee flexion.

Results

On average, the Rolimeter measured approximately 1 mm less anteroposterior displacement than the KT-1000 arthrometer at manual maximum stress. Rolimeter measurements were more consistent than the KT-1000 measurements as measured by our observers. Specificity and sensitivity were equivalent between the Rolimeter and the KT-1000 arthrometer.

Conclusions

The Rolimeter is as reproducible and reliable as the KT-1000 arthrometer. It offers a valid method for the measurement of anteroposterior translation in the knee. Higher accuracy was obtained at 20° of flexion for the KT-1000 arthrometer and at 80° of flexion for the Rolimeter.
The Hotdog fold: wrapping up a superfamily of thioesterases and dehydratases
Authors: Dillon Shane C , Bateman Alex
Published: August 2004

Background

The Hotdog fold was initially identified in the structure of Escherichia coli FabA and subsequently in 4-hydroxybenzoyl-CoA thioesterase from Pseudomonas sp. strain CBS. Since that time structural determinations have shown a number of other apparently unrelated proteins also share the Hotdog fold.

Results

Using sequence analysis we unify a large superfamily of HotDog domains. Membership includes numerous prokaryotic, archaeal and eukaryotic proteins involved in several related, but distinct, catalytic activities, from metabolic roles such as thioester hydrolysis in fatty acid metabolism, to degradation of phenylacetic acid and the environmental pollutant 4-chlorobenzoate. The superfamily also includes FapR, a non-catalytic bacterial homologue that is involved in transcriptional regulation of fatty acid biosynthesis.

We have defined 17 subfamilies, with some characterisation. Operon analysis has revealed numerous HotDog domain-containing proteins to be fusion proteins, where two genes, once separate but adjacent open-reading frames, have been fused into one open-reading frame to give a protein with two functional domains. Finally we have generated a Hidden Markov Model library from our analysis, which can be used as a tool for predicting the occurrence of HotDog domains in any protein sequence.

Conclusions

The HotDog domain is both an ancient and ubiquitous motif, with members found in the three branches of life.
Slowly developing depression of N-methyl-D-aspartate receptor mediated responses in young rat hippocampi
Authors: Dozmorov Mikhail , Li Rui , Xu Hui-Ping , Jilderos Barbro , Wigström Holger
Published: August 2004

Background

Activation of N-methyl-D-aspartate (NMDA) type glutamate receptors is essential in triggering various forms of synaptic plasticity. A critical issue is to what extent such plasticity involves persistent changes of glutamate receptor subtypes and many prior studies have suggested a main role for alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors in mediating the effect. Our previous work in hippocampal slices revealed that, under pharmacological unblocking of NMDA receptors, both AMPA and NMDA receptor mediated responses undergo a slowly developing depression. In the present study we have further adressed this phenomenon, focusing on the contribution via NMDA receptors. Pharmacologically isolated NMDA receptor mediated excitatory postsynaptic potentials (EPSPs) were recorded for two independent synaptic pathways in CA1 area using perfusion with low Mg2+ (0.1 mM) to unblock NMDA receptors.

Results

Following unblocking of NMDA receptors, there was a gradual decline of NMDA receptor mediated EPSPs for 2–3 hours towards a stable level of ca. 60–70 % of the maximal size. If such an experimental session was repeated twice in the same pathway with a period of NMDA receptor blockade in between, the depression attained in the first session was still evident in the second one and no further decay occurred. The persistency of the depression was also validated by comparison between pathways. It was found that the responses of a control pathway, unstimulated in the first session of receptor unblocking, behaved as novel responses when tested in association with the depressed pathway under the second session. In similar experiments, but with AP5 present during the first session, there was no subsequent difference between NMDA EPSPs.

Conclusions

Our findings show that merely evoking NMDA receptor mediated responses results in a depression which is input specific, induced via NMDA receptor activation, and is maintained for several hours through periods of receptor blockade. The similarity to key features of long-term depression and long-term potentiation suggests a possible relation to these phenomena. Additionally, a short term potentiation and decay (<5 min) were observed during sudden start of NMDA receptor activation supporting the idea that NMDA receptor mediated responses are highly plastic.
Synergic effect of chronic hepatitis C infection and beta thalassemia major with marked hepatic iron overload on liver fibrosis: a retrospective cross-sectional study
Authors: Ardalan Farid Azmoudeh , Osquei Mohammad RF , Toosi Mohsen N , Irvanloo Guiti
Published: August 2004

Background

Increased hepatic iron is assumed to potentiate progression towards liver fibrosis in chronic hepatitis C virus (HCV) infection. In this study we have evaluated the potentiating effect of marked hepatic iron overload and chronic HCV infection on hepatic fibrosis in thalassemic patients.

Methods

Liver biopsies of one group of patients with beta thalassemia major and chronic HCV infection (group 1) was compared with two groups of patients (groups 2&3) with either chronic HCV infection or thalassemia major, respectively (20 patients in each group). Necroinflammation, fibrosis, and iron overload were graded and compared.

Results

Stage of fibrosis in group 1 patients was significantly higher than the other two groups (p < 0.05). Necroinflammatory grade was significantly lower, but iron score was significantly higher in thalassemic patients (group 3) in comparison to groups 1 and 2 (p < 0.05).

Conclusion

Our results indicate that marked liver iron overload and HCV infection in thalassemic patients have potentiating effect on hepatic fibrogenesis.
Drop-out and mood improvement: a randomised controlled trial with light exposure and physical exercise [ISRCTN36478292]
Authors: Leppämäki Sami , Haukka Jari , Lönnqvist Jouko , Partonen Timo
Published: August 2004

Background

Combining bright light exposure and physical exercise may be an effective way of relieving depressive symptoms. However, relatively little is known about individual factors predicting either a good response or treatment failure. We explored background variables possibly explaining the individual variation in treatment response or failure in a randomised trial.

Methods

Participants were volunteers of working-age, free from prior mental disorders and recruited via occupational health centres. The intervention was a randomised 8-week trial with three groups: aerobics in bright light, aerobics in normal room lighting, and relaxation/stretching in bright light. Good response was defined as a 50% decrease in the symptom score on either the Hamilton Depression Rating Scale (HDRS) or 8-item scale of atypical symptoms. Background variables for the analysis included sex, age, body-mass index, general health habits, seasonal pattern, and sleep disturbances.

Results

Complete data were received from 98 subjects (11 men, 87 women). Of them, 42 (5 men, 37 women) were classified as responders on the HDRS. Overall, light had a significant effect on the number of responders, as assessed with the HDRS (X2 = .02). The number needed to treat (NNT) for light was 3.8.

Conclusions

We investigated the effect of bright light and exercise on depressive symptoms. Problems with sleep, especially initial insomnia, may predict a good response to treatment using combined light and exercise. Bright light exposure and physical exercise, even in combination, seem to be well tolerated and effective on depressive symptoms.
Assessing computer skills in Tanzanian medical students: an elective experience
Authors: Samuel Miriam , Coombes John C , Miranda J Jaime , Melvin Rob , Young Eoin JW , Azarmina Pejman
Published: August 2004

Background

One estimate suggests that by 2010 more than 30% of a physician's time will be spent using information technology tools. The aim of this study is to assess the information and communication technologies (ICT) skills of medical students in Tanzania. We also report a pilot intervention of peer mentoring training in ICT by medical students from the UK tutoring students in Tanzania.

Methods

Design: Cross sectional study and pilot intervention study. Participants: Fourth year medical students (n = 92) attending Muhimbili University College of Health Sciences, Dar es Salaam, Tanzania. Main outcome measures: Self-reported assessment of competence on ICT-related topics and ability to perform specific ICT tasks. Further information related to frequency of computer use (hours per week), years of computer use, reasons for use and access to computers. Skills at specific tasks were reassessed for 12 students following 4 to 6 hours of peer mentoring training.

Results

The highest levels of competence in generic ICT areas were for email, Internet and file management. For other skills such as word processing most respondents reported low levels of competence. The abilities to perform specific ICT skills were low – less than 60% of the participants were able to perform the core specific skills assessed. A period of approximately 5 hours of peer mentoring training produced an approximate doubling of competence scores for these skills.

Conclusion

Our study has found a low level of ability to use ICT facilities among medical students in a leading university in sub-Saharan Africa. A pilot scheme utilising UK elective students to tutor basic skills showed potential. Attention is required to develop interventions that can improve ICT skills, as well as computer access, in order to bridge the digital divide.
The solution structure of ChaB, a putative membrane ion antiporter regulator from Escherichia coli
Authors: Osborne Michael J , Siddiqui Nadeem , Iannuzzi Pietro , Gehring Kalle
Published: August 2004

Background

ChaB is a putative regulator of ChaA, a Na+/H+ antiporter that also has Ca+/H+ activity in E. coli. ChaB contains a conserved 60-residue region of unknown function found in other bacteria, archaeabacteria and a series of baculoviral proteins. As part of a structural genomics project, the structure of ChaB was elucidated by NMR spectroscopy.

Results

The structure of ChaB is composed of 3 α-helices and a small sheet that pack tightly to form a fold that is found in the cyclin-box family of proteins.

Conclusion

ChaB is distinguished from its putative DNA binding sequence homologues by a highly charged flexible loop region that has weak affinity to Mg2+ and Ca2+ divalent metal ions.
Heat shock protein 70 expression, keratin phosphorylation and Mallory body formation in hepatocytes from griseofulvin-intoxicated mice
Authors: Fausther Michel , Villeneuve Louis , Cadrin Monique
Published: August 2004

Background

Keratins are members of the intermediate filaments (IFs) proteins, which constitute one of the three major cytoskeletal protein families. In hepatocytes, keratin 8 and 18 (K8/18) are believed to play a protective role against mechanical and toxic stress. Post-translational modifications such as phosphorylation and glycosylation are thought to modulate K8/18 functions. Treatment of mouse with a diet containing griseofulvin (GF) induces, in hepatocytes, modifications in organization, expression and phosphorylation of K8/18 IFs and leads, on the long term, to the formation of K8/18 containing aggregates morphologically and biochemically identical to Mallory bodies present in a number of human liver diseases. The aim of the present study was to investigate the relationship between the level and localization of the stress inducible heat shock protein 70 kDa (HSP70i) and the level and localization of K8/18 phosphorylation in the liver of GF-intoxicated mice. The role of these processes in Mallory body formation was studied, too. The experiment was carried out parallely on two different mouse strains, C3H and FVB/n.

Results

GF-treatment induced an increase in HSP70i expression and K8 phosphorylation on serines 79 (K8 S79), 436 (K8 S436), and K18 phosphorylation on serine 33 (K18 S33) as determined by Western blotting. Using immunofluorescence staining, we showed that after treatment, HSP70i was present in all hepatocytes. However, phosphorylated K8 S79 (K8 pS79) and K8 S436 (K8 pS436) were observed only in groups of hepatocytes or in isolated hepatocytes. K18 pS33 was increased in all hepatocytes. HSP70i colocalized with MBs containing phosphorylated K8/18. Phophorylation of K8 S79 was observed in C3H mice MBs but was not present in FVB/n MBs.

Conclusions

Our results indicate that GF intoxication represents a stress condition affecting all hepatocytes, whereas induction of K8/18 phosphorylation is not occurring in every hepatocyte. We conclude that, in vivo, there is no direct relationship between GF-induced stress and K8/18 phosphorylation on the studied sites. The K8/18 phosphorylation pattern indicates that different cell signaling pathways are activated in subpopulations of hepatocytes. Moreover, our results demonstrate that, in distinct genetic backgrounds, the induction of K8/18 phosphorylation can be different.
Regulatory role of E-NTPase/E-NTPDase in Ca2+/Mg2+ transport via gated channel
Authors: Schreiber Hans M , Kannan Subburaj
Published: August 2004

Background

E-NTPase/E-NTPDase is activated by millimolar concentrations of Ca2+ or Mg2+ with a pH optimum of 7.5 for the hydrolysis of extracellular NTP and NDP. It has been generally accepted that E-NTPase/E-NTPDase plays regulatory role in purinergic signalling, but other functions may yet be discovered.

Results

In this article it is proposed on the basis of published data that E-NTPase/E-NTPDase could play a role in the influx and efflux of Ca2+and Mg2+ in vivo.

Conclusions

Attenuation of extracellular Ca2+ influx by rat cardiac sarcoplasmic anti-E-NTPase antibodies and oligomerization studies on mammalian CD39 conclusively point towards the existence of a new channel in the membrane. Further studies on these properties of the E-NTPase/E-NTPDase may provide detailed mechanisms and identify the potential patho-physiological significance.
Increased expression of caspase-1 and interleukin-18 in peripheral blood mononuclear cells in patients with multiple sclerosis
Authors: Huang Wen-Xin , Huang Ping , Hillert Jan
Published: August 2004

Multiple sclerosis (MS) is supposedly a T-cell mediated autoimmune disorder of the central nervous system. Cytokines and other molecules involved in the regulation of apoptosis are thought to be of importance for the pathogenesis of MS. In this study, the mRNA levels of interleukin 18 (IL-18), IL-1b and their processing enzyme caspase-1 were quantified by a competitive RT-PCR method in unstimulated peripheral blood mononuclear cells (PBMCs) in MS patients never treated with disease modifying drugs. Western blot was used to support the expression pattern at the protein level. We found that the expression of caspase-1 and IL-18 was significantly increased in MS patients compared with healthy controls. Analysis of clinical subgroups revealed that caspase-1 was increased in all subgroups, whereas IL-18 was upregulated in chronic progression (P-0.001) and relapsing MS patients in remission (P-0.002) but not significantly during relapses (P-0.12). mRNA levels of IL-1b were not significantly altered in MS except for a possible decrease in chronic progression (P-0.03). An increased IL-18 expression, potentially augmented at the mature protein level, may indicate a pathway worth considering in future therapeutic strategies in MS.
An fMRI study of planning-related brain activity in patients with moderately advanced multiple sclerosis
Authors: Lazeron Richard HC , Rombouts Serge ARB , Scheltens Philip , Polman Chris H , Barkhof Frederik
Published: August 2004

Introduction: Cognitive impairment occurs in a substantial number of multiple sclerosis (MS) patients and often includes frontal lobe dysfunction. We used functional magnetic resonance imaging (fMRI) to study planning, an executive function, in moderately impaired MS patients. Methods: An fMRI version of the Tower of London (ToL) test was used to study patterns of brain activation in 23 MS patients and 18 healthy controls. The median score on the Expanded Disability Status Scale (EDSS) for the MS patients was 4. fMRI data were analysed using whole brain random effects analysis as well as region of interest (ROI)-based methods to assess group effects. Within the MS group, associations with behavioural data and measures of disease severity (lesion load from structural MRI) were examined. Results: Test performance in MS patients was significantly worse than in controls. Group analysis for the MS patients and the controls showed for both groups globally the same areas of activation, located in the frontal and parietal lobes bilaterally and the cerebellum. Although visual inspection suggested a larger extent of activation in the MS group, no statistically significant differences between groups were found. In the ROI analysis, statistically significant larger extent of activation was only found in the cerebellum. No association between disease severity and brain activity could be determined in the MS group. Conclusion: In MS patients with moderate disability and structural damage, the pattern and extent of brain activation during planning were maintained despite poorer performance. In contrast to other studies showing increased activity, the failure to do so in our group may reflect exhaustion of adaptive mechanisms.
Interferon-beta: the neutralizing antibody (NAb) titre predicts reversion to NAb negativity
Authors: Gneiss C , Reindl M , Lutterotti A , Ehling R , Egg R , Khalil M , Berger T , Deisenhammer F
Published: August 2004

Background: It has been reported that in some patients with MS who develop neutralizing antibodies (NAbs) against interferon beta (IFNb), antibody levels can initially increase and then decrease thereafter even when treatment is continued. Objective: To determine whether NAb titre correlates with time to reversion to NAb negativity in patients with multiple sclerosis (MS). Methods: Twenty-eight patients with MS who were NAb-positive during treatment with one of the currently available IFNbs were included in this retrospective study. NAb titres were determined by the myxovirus resistance protein A induction assay. Patients were considered NAb-positive if they had at least two consecutive samples with titres of]/20 neutralizing units (NU). Reversion to NAb-negative status was defined as two consecutive negative samples (NAb titre of B/20 NU) after NAb positivity. Results: When measured two years after treatment initiation, a NAb titre of B/75 NU had a 91.7% sensitivity and a 87.5% specificity for reversion to NAb negativity in the following two years (after a total of four years of treatment). In addition, somewhat surprisingly, patients whose serum converted to NAb-negative generally developed peak NAb titres earlier than patients who remained NAb-positive (mean time of first detection was 21 versus 38 months, respectively). Conclusion: The NAb titre might support treatment decisions in patients with MS whose test results are positive for NAbs.
Influence of HLA on progression of optic neuritis to multiple sclerosis: results of a four-year follow-up study
Authors: Kheradvar Arash , Tabassi Abdol Reza , Nikbin Behrouz , Khosravi Farideh , Naroueynejad Mehrnaz , Moradi Batool , Amirzargar Ali Akbar
Published: August 2004

Background: Genetic predisposition in multiple sclerosis (MS) has always been a critical concern in aetiology and progress of the disease. The present study looks into the relations between human leukocyte antigen (HLA), optic neuritis (ON) and MS in the Iranian population. Methods: Patients with potential diagnosis of acute ON underwent a standardized clinical examination for confirming the diagnosis. Selected patients were gathered for HLA typing and clinical follow up. Results: Of the 55 patients, 46 (83.6%) were female. The mean age was 25(± 7.3) with a range of 12-43. Twenty of the 55 (36%) were confirmed for the diagnosis of clinically definite MS (CDMS). Results show that A23, B21, A11 and B51 alleles were present in 4 (20%), 6 (30%), 2 (10%) and 1 (5%) of the CDMS patients, respectively. Ten (50%) and 17 (85%) CDMS patients were positive for HLA class II alleles, DR2 and DQ1, correspondingly. Conclusions: The study strongly suggests the association among DR2, A23 and B21 allele and the evolution of ON to MS. High prevalence of A23 and DR2 alleles in CDMS patients compared with the normal population may suggest an important role for these alleles in the development of MS. The study suggests B51 as a protective factor against development of ON in the normal population. In addition, results do not confirm previous studies considering A11 as a predisposing factor. The present study finally evokes that different classes of HLA have different roles in susceptibility to MS and confirms disease heterogeneity as an important emerging concept in MS.
Multiple Sclerosis Impact Scale (MSIS-29): relation to established measures of impairment and disability
Authors: Hoogervorst E LJ , Zwemmer J NP , Jelles B , Polman C H , Uitdehaag B MJ
Published: August 2004

Objective: To validate the newly developed Multiple Sclerosis Impact Scale (MSIS-29) in a large, well characterized, independent group of MS patients by investigating the relation between the MSIS-29 and the Guy’s Neurological Disability Scale (GNDS), the Expanded Disability Status Scale (EDSS) and the MS Functional Composite (MSFC). Methods: Two hundred MS patients were recruited at our outpatient department. At the same visit GNDS, EDSS, MSFC and MSIS-29 were assessed. Data obtained from GNDS, EDSS and MSFC assessment were compared to both physical and psychological impact scores of the MSIS-29. In addition the contribution of GNDS subcategories, EDSS functional systems and MSFC components to the physical and psychological impact scores of the MSIS-29 was studied. Results: Median scores were 37.5 for the physical and 22.2 for the psychological impact score of the MSIS-29, 13.0 for GNDS and 4.0 for EDSS. Mean MSFC was 0.07. The physical impact score showed good correlations with both GNDS (0.79) and EDSS (0.68) and a moderate correlation with the MSFC (- 0.53). The psychological impact score showed weak correlations with EDSS (0.22) and MSFC (-0.30) and a moderately strong correlation with the GNDS (0.58). In 50 (25%) patients, scores on physical and psychological impact scales diverted, i.e., a relative high score on one scale combined with a relative low score on the other scale. This was related to the clinical disease course. Conclusion: Our study supports the use of the MSIS-29 as a measure for the assessment of physical impact of MS on normal daily life. In addition, our data provides a deeper understanding of the factors that determine both physical and psychological disease impact. Discrepancies between the latter two aspects deserve further attention.
Intravenous corticosteroids in the postpartum period for reduction of acute exacerbations in multiple sclerosis
Authors: de Seze J , Chapelotte M , Delalande S , Ferriby D , Stojkovic T , Vermersch P
Published: August 2004

In order to assess the effectiveness of monthly intravenous corticosteroids in reducing childbirth-associated acute exacerbations in multiple sclerosis (MS), we compared pregnant patients followed up in our MS clinic. During the first period (1996-1998), 22 patients did not receive any treatment after delivery. During the second period (1999-2001), following the publication of the PRIMS study, 20 patients were treated monthly with 1 g of intravenous corticosteroids during the six months of the postpartum period. In both groups the relapse rate increased during the first trimester postpartum but it was higher in the untreated group (2±0.66 [mean±SD]) compared with the treated group (0.8±0.41) (P=0.018), suggesting a beneficial effect of monthly intravenous corticosteroids.
RANTES: a genetic risk marker for multiple sclerosis
Authors: Gade-Andavolu Radhika , Comings David E , MacMurray James , Vuthoori Ravi K , Tourtellotte Wallace W , Nagra Rashed M , Cone Lawrence A
Published: August 2004

Regulated upon activation, normal T-cell expressed and secreted (RANTES) is a beta-chemokine and has been detected in brain lesions of multiple sclerosis (MS) patients. Considering its potential role in MS, we screened two functional polymorphisms in the proximal promoter region of the RANTES in MS patients versus controls. Methods: We examined 140 postmortem brain samples from subjects with a primary diagnosis of MS, and peripheral blood samples from 216 control subjects. The RANTES-28C/G and -403G/A promoter polymorphisms were examined. All subjects were non-Hispanic Caucasians. Results: MS cases differed from controls showing a significant association with the 403G/A polymorphism (odds ratio, 2.359, [1.465-3.799]; P-0.0001), but not the -28C/G (P-NS) polymorphism. There was a significant association of the -28G allele with both early onset (P-0.031) and longer survival (P-0.006). Conclusion: There is a significant but complex association of the RANTES gene with MS.
Regulation of differentiation and functional properties of monocytes and monocyte-derived dendritic cells by interferon beta in multiple sclerosis
Authors: Zang Ying CQ , Skinner Sheri M , Robinson Rachel R , Li Sufang , Rivera Victor M , Hutton George J , Zhang Jingwu Z
Published: August 2004

Interferon beta (IFN beta) has complex immune regulatory properties that contribute to its treatment effect on multiple sclerosis (MS). In this study, we investigated the role of IFN beta in differentiation and functional properties of monocytes and monocyte-derived dendritic cells that are critical to the inflammatory process in MS. The results revealed that IFN beta inhibited intracellular production of interleukin (IL)-1b (PB/0.01) in both monocytes exposed toin vitro treatment of IFN beta and monocytes analysedex vivo from MS patients treated with IFN beta. IFN beta was shown to modulate differentiation of monocytes into dendritic cells in the presence of IL-4 and GM-CSF, which resulted in a delayed differentiation process. Furthermore, it characteristically altered the phenotypic features of differentiated dendritic cells by inhibiting the expression of CD1a, CD11b, CD11c, CD123 and CD209 while upregulating costimulatory molecules, such as CD86. The selective regulatory properties of IFN beta appeared to render the function of differentiated dendritic cells to produce an increased amount (PB/0.01) while their ability to secrete proinflammatory IL-12 and TGF beta was significantly reduced. The observed collective effects of IFN beta seemed to correlate with Th2 immune deviation. The study has provided new insights into the regulatory mechanisms of IFN beta in the treatment of MS.
Multiple sclerosis gender issues: clinical practices of women neurologists
Authors: Coyle P K , Christie S , Fodor P , Fuchs K , Giesser B , Gutierrez A , Lynn J , Weinstock-Guttman B , Pardo L ,   Women Neurologists MS Initiative (WNMSI)
Published: August 2004

Substantially more women than men develop multiple sclerosis (MS), but information about the effects of MS and gender-specific issues such as pregnancy, breastfeeding, menstruation and hormone use is lacking. A survey study of neurologists’ practice patterns was undertaken to elicit information about gender-specific topics and the use of disease-modifying MS therapies (DMT) including the interferons and glatiramer acetate (GA). A total of 147 surveys were returned. Half of respondents require patients to discontinue DMT during pregnancy, while 35% encourage discontinuation. Among those who allow patients to continue therapy, half consider GA to be safer during pregnancy than the interferons. Nearly 86% of respondents do not use DMT in patients who are breastfeeding. Among the 11% who actually prescribe during breastfeeding, most recommend GA. Neurologists generally leave the decision to breastfeed up to patients, and most refer patients to obstetrician/gynaecologists for counselling about contraception or hormone replacement therapy. The survey results described here provide insight into how neurologists manage reproductive health issues among women with MS.
Prevalence and treatment of spasticity reported by multiple sclerosis patients
Authors: Rizzo M A , Hadjimichael O C , Preiningerova J , Vollmer T L
Published: August 2004

The objective of this study was to characterize the population of multiple sclerosis (MS) patients suffering from spasticity and to evaluate treatment patterns, including intrathecal baclofen (ITB) delivery, related to patient quality of life (QOL). We conducted a cross-sectional, two-level study using data from the Patient Registry of the North American Research Committee on MS (NARCOMS). In addition, we surveyed a subgroup of 198 preselected patients who are using ITB (ITBG) and a random sample of 315 oral drug users (ORALG). Among the registrants, 16% reported no spasticity, 31% minimal, 19% mild, 17% moderate (frequently affects activities), 13% severe (daily forced to modify activities) and 4% total (prevents daily activities). Patients experiencing greater severity included by proportion males, and those older and with longer duration of MS. QOL scores decreased inversely with severity. In the focused survey, ITBG reported lower levels of spasticity than ORALG, less stiffness in the legs, less pain and fewer spasms at any time. They scored significantly lower in the SF-36 physical component, yet reported less fatigue on the MFIS scale. Prevalence data reveal that one third of MS patients modify or eliminate daily activities as a result of spasticity. Treatment of spasticity can significantly impact QOL parameters by reducing spasms, pain and fatigue.
A prospective study of conditions associated with multiple sclerosis in a cohort of 658 consecutive outpatients attending a multiple sclerosis clinic
Authors: Edwards L J , Constantinescu C S
Published: August 2004

The cause of multiple sclerosis (MS) remains unknown. It is largely regarded as being an inflammatory autoimmune disease and has been reported in association with other inflammatory/autoimmune diseases. We performed a prospective study in 658 consecutive patients diagnosed with MS attending our outpatient MS management clinic between June 2002 and June 2003. Prevalence of associated conditions in these patients was calculated and compared with values from population studies using chi-square tests, odds ratios and confidence intervals. The MS population had significantly increased rates of asthma, inflammatory bowel disease, type I diabetes mellitus, pernicious anaemia, autoimmune thyroid disease, uveitis, seronegative spondyloarthropathies, bipolar disorder and melanoma compared to the general population. Both T helper type 1 (Th1)-mediated and T helper type 2 (Th2)-mediated diseases were significantly increased compared to the general population. There were also interesting associations seen with polyglandular autoimmune syndrome and rare single case associations.

MS is associated with several other conditions. This work does not give evidence for the hypothesis that MS and atopy, reflecting Th1 and Th2 polarization, respectively, are mutually exclusive. Further work, ideally with a matched control population, is indicated.
The 14-3-3 protein in multiple sclerosis: a marker of disease severity
Authors: Colucci M , Roccatagliata L , Capello E , Narciso E , Latronico N , Tabaton M , Mancardi G L
Published: August 2004

Context: In multiple sclerosis (MS) axonal damage is an early event and is probably to be considered the most relevant cause of permanent and progressive disability. Objectives: To investigate the value of the increase of 14-3-3 and tau proteins in the cerebrospinal fluid (CSF) as peripheral markers of axonal pathology and predictors of disease evolution. Patients and methods: In the CSF samples obtained from 63 patients with demyelinating diseases (DD), including 20 clinically isolated syndromes (CIS) and 43 clinically defined MS, as well as from 56 controls, we analysed the presence of 14-3-3 reactivity by immunoblot analysis along with the concentration of tau protein by sandwich ELISA. Results: The percentage of DD subjects showing a positive 14-3-3 protein CSF reactivity (38%) was significantly higher than the one previously detected, and was correlated in the MS patients with a more severe clinical phenotype in terms of degree of disability and rate of disease progression, during a 10-month mean clinical follow-up. On the contrary, the levels of the CSF-tau protein were highly variable in DD and control subjects, and the mean CSF-tau concentration was similar in both groups. Conclusions: The immunoblot analysis of 14-3-3 protein in the CSF could be a useful marker to identify a subgroup of DD patients with high risk of developing severe disability.
Macrophage brain infiltration in experimental autoimmune encephalomyelitis is not completely compromised by suppressed T-cell invasion: in vivo magnetic resonance imaging illustration in effective anti-VLA-4 antibody treatment
Authors: Deloire Mathilde SA , Touil Tarik , Brochet Bruno , Dousset Vincent , Caillé Jean-Marie , Petry Klaus G
Published: August 2004

Large inflammatory infiltrates of T cells, macrophages and B cells in the central nervous system (CNS) contribute to the pathogenesis of multiple sclerosis (MS). The passage of T cells through the blood-brain barrier can be suppressed with antibodies directed against alpha-4 integrins (VLA-4) that mediate T-cell adherence. This treatment, in phase III of clinical trial evaluation, reduces lesion development in MS patients. In the ongoing inflammatory disease process the consequences of T-cell inhibitory anti-VLA-4 antibodies on inflammatory compounds are still poorly investigated. We show that anti-VLA-4 antibody treatment during the late preclinical phase of the acute experimental autoimmune encephalomyelitis (EAE) MS rat model interrupts T-cell egress out of the vascular compartment and suppresses clinical disease and histological alterations but macrophage recruitment in the CNS is not fully compromised. Among the treated EAE animals not developing disease, none presented foci of T-cell infiltration in CNS. However, in 75% of the treated EAE rats monocyte ingress in CNS was observedin vivo by magnetic resonance imaging with the ultrasmall superparamagnetic iron oxide contrast agent. Our data shed new light on the role of remaining macrophage brain infiltration in an induced but interrupted T-cell-mediated EAE disease process.
Waldenström's macroglobulinemia developing in a patient with multiple sclerosis: coincidence or association?
Authors: Deftereos S , Farmakis D , Papadogianni A , Besleme B , Diamanti-Kandarakis E , Polymeropoylos E , Georgonikou D , Aessopos A
Published: August 2004

Multiple sclerosis (MS) has been reported in association with haematological abnormalities, including monoclonal gammopathies. We present a 54-year-old male patient with a 30-year history of MS who was admitted to our hospital for investigation of anaemia and increased erythrocyte sedimentation rate. A monoclonal IgM protein was detected by serum protein immunofixation, while bone marrow biopsy indicated a 70% infiltration by small lymphoplasmacytoid cells, in the context of a lymphoplasmacytoid immunocytoma, findings compatible to the diagnosis of Waldenström's macroglobulinemia (WM). To our knowledge, this is the first report of WM in a patient with MS. Further to the coexistence of the two diseases observed in the case presented here, there is additional evidence suggesting that the association of MS with plasma cell dyscrasias may not be coincidental.
In Search of the Song Template
Authors: ADRET PATRICE
Published: August 2004

Abstract:The auditory template theory—the conversion of memorized song to produced song using feedback as an error‐correction mechanism—is central to neurobiological studies of birdsong learning. The essence of the theory is the construction of a complex sound replica based on a set of both genetic and environmental instructions. These premises, as yet unchallenged, have stimulated much research on the process of vocal imitation. Two somewhat distinct, but closely related streams of research have emerged. One seeks to determine the neural mechanisms that underlie the formation, storage, and retrieval of vocal memories as a consequence of experience during a sensitive phase—the template concept in its purest form. The other aims at establishing an explanatory basis for genetically based species differences in auditory responsiveness; here, the prime focus is on innately specified templates that guide learning preferences in young, naïve birds. The chapter begins with an historical overview of conceptual issues. Then recent progress in the attempt to characterize template properties is reviewed, focusing on selected studies of sparrows, nightingales, and zebra finches. The chapter concludes with a discussion of research strategy and tactics, including suggestions for criteria that must be met in identifying neural substrates for template specification and localization. The chapter is intended to provide a conceptual framework for further progress in this critical area.
Plasticity of the Adult Avian Song Control System
Authors: BRENOWITZ ELIOT A.
Published: August 2004

Abstract:There is extensive plasticity of the song behavior of birds and the neuroendocrine circuit that regulates this behavior in adulthood. One of the most pronounced examples of plasticity, found in every species of seasonally breeding bird examined, is the occurrence of large seasonal changes in the size of song control nuclei and in their cellular attributes. This seasonal plasticity of the song circuits is primarily regulated by changes in the secretion and metabolism of gonadal testosterone (T). Both androgenic and estrogenic sex steroids contribute to seasonal growth of the song system. These steroids act directly on the forebrain song nucleus HVC, which then stimulates growth of its efferent target nuclei transsynaptically. Seasonal growth and regression of the song circuits occur rapidly and sequentially following changes in circulating T and its metabolites. As the neural song circuits change across seasons, there are changes in different aspects of song behavior, including the structural stereotypy of songs, their duration, and the rate of production. The burden of evidence supports a model in which changes in song behavior are a consequence rather than a cause of the changes in the song circuits of the brain. Seasonal plasticity of the song system may have evolved as an adaptation to reduce the energetic demands imposed by these regions of the brain outside the breeding season, when the use of song for mate attraction and territorial defense is reduced or absent. The synaptic plasticity that accompanies seasonal changes in the song system may have acted as a preadaptation that enabled the evolution of adult song learning in some species of birds.
The Avian Song System in Comparative Perspective
Authors: FARRIES MICHAEL A.
Published: August 2004

Abstract: The song system of oscine birds has become a versatile model system that is used to study diverse problems in neurobiology. Because the song system is often studied with the intention of applying the results to mammalian systems, it is important to place song system brain nuclei in a broader context and to understand the relationships between these avian structures and regions of the mammalian brain. This task has been impeded by the distinctiveness of the song system and the vast apparent differences between the forebrains of birds and mammals. Fortunately, accumulating data on the development, histochemistry, and anatomical organization of avian and mammalian brains has begun to shed light on this issue. We now know that the forebrains of birds and mammals are more alike than they first appeared, even though many questions remain unanswered. Furthermore, the song system is not as singular as it seemed—it has much in common with other neural systems in birds and mammals. These data provide a firmer foundation for extrapolating knowledge of the song system to mammalian systems and suggest how the song system might have evolved.
Peripheral Motor Dynamics of Song Production in the Zebra Finch
Authors: GOLLER FRANZ , COOPER BRENTON G.
Published: August 2004

Abstract:Singing behavior in songbirds is a model system for motor control of learned behavior. The target organs of its central motor programs are the various muscle systems involved in sound generation. Investigation of these peripheral motor mechanisms of song production is the first step toward an understanding of how different motor systems are coordinated. Here we review physiological studies of all major motor systems that are involved in song production and modification in the zebra finch (Taeniopygia guttata). Acoustic syllables of zebra finch song are produced by a characteristic air sac pressure pattern. Electromyographic (EMG) and sonomicrometric recording of expiratory muscle activity reveals that respiratory motor control is tightly coordinated with syringeal gating of airflow. Recordings of bronchial airflow demonstrate that most of the song syllables are composed of simultaneous independent contributions from the two sides of the syrinx. Sounds generated in the syrinx can be modified by the resonance properties of the upper vocal tract. Tracheal length affects resonance, but dynamic changes of tracheal length are unlikely to make a substantial contribution to sound modification. However, beak movements during song contribute to sound modification and, possibly, affect the vibratory behavior of the labia. Rapid beak aperture changes were associated with nonlinear transitions in the acoustic structure of individual syllables. The synergy between respiratory and syringeal motor systems, and the unique bilateral, simultaneous, and independent sound production, combined with dynamic modification of the acoustic structure of song, make the zebra finch an excellent model system for exploring mechanisms of sensorimotor integration underlying a complex learned behavior.
The Role of Auditory Feedback in Birdsong
Authors: KONISHI MASAKAZU
Published: August 2004

Abstract: Young songbirds memorize a tutor song and use the memory trace as a template to shape their own song by auditory feedback. Major issues in birdsong research include the neural sites and mechanisms for song memory and auditory feedback. The brain song control system contains neurons with both premotor and auditory function. Yet no evidence so far shows that they respond to the bird's own song during singing. Also, no neurons have been found to respond to perturbation of auditory feedback in the brain area that is thought to be involved in the feedback control of song. The phenomenon of gating in which neurons respond to playback of the bird's own song only during sleep or under anesthesia is the sole known evidence for control of auditory input to the song system. It is, however, not known whether the gating is involved in switching between the premotor and auditory function of neurons in the song control system.