bluuebunny/crossref_metadata_2025 huggingface dataset:
TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand
Authors: Ito Tomoki , Wang Yui-Hsi , Duramad Omar , Hori Toshiyuki , Delespesse Guy J. , Watanabe Norihiko , Qin F. Xiao-Feng , Yao Zhengbin , Cao Wei , Liu Yong-Jun
Published: November 2005

We recently showed that dendritic cells (DCs) activated by thymic stromal lymphopoietin (TSLP) prime naive CD4+ T cells to differentiate into T helper type 2 (Th2) cells that produced high amounts of tumor necrosis factor-α (TNF-α), but no interleukin (IL)-10. Here we report that TSLP induced human DCs to express OX40 ligand (OX40L) but not IL-12. TSLP-induced OX40L on DCs was required for triggering naive CD4+ T cells to produce IL-4, -5, and -13. We further revealed the following three novel functional properties of OX40L: (a) OX40L selectively promoted TNF-α, but inhibited IL-10 production in developing Th2 cells; (b) OX40L lost the ability to polarize Th2 cells in the presence of IL-12; and (c) OX40L exacerbated IL-12–induced Th1 cell inflammation by promoting TNF-α, while inhibiting IL-10. We conclude that OX40L on TSLP-activated DCs triggers Th2 cell polarization in the absence of IL-12, and propose that OX40L can switch IL-10–producing regulatory Th cell responses into TNF-α–producing inflammatory Th cell responses.
Xenon measurement in breathing systems: a comparison of ultrasonic and thermal conductivity methods
Authors: King R. , Bretland M. , Wilkes A. , Dingley J.
Published: November 2005

Xenon is an anaesthetic and possibly neuroprotective gas that is impossible to measure using conventional anaesthetic gas analysers. We compared the performance of two commissioned xenon analysers using ultrasonic and thermal conductivity principles against a reference method of laser refractometry. An experimental gas circuit was constructed and xenon concentrations compared over a range of 0–100% in oxygen. Eighty‐two paired measurements were made comparing the experimental methods with laser refractometry. The ultrasonic method displayed good agreement with laser refractometry, with a mean difference of − 0.74% and two standard deviation limits of agreement of + 1.08% to − 2.56%. The agreement between laser refractometry and thermal conductivity was poor, the mean difference being − 5.37%, with two standard deviation limits of agreement of + 0.6% to − 11.3%. The ultrasonic method for measuring xenon concentrations can be used in breathing circuits. The thermal conductivity instrument may need further development.
N‐acetylcysteine – passe‐partout or much ado about nothing?
Authors: Aitio Mirja‐Liisa
Published: November 2005

In experimental studies, the old mucolytic agent N‐acetylcysteine (NAC) has had beneficial effects in disorders supposedly linked to oxidative stress. Numerous, mainly small clinical trials with variable doses have yielded inconsistent results in a wide variety of diseases. NAC added to the conventional therapy of human immunodeficiency virus infection might be of benefit; in respect of chronic obstructive pulmonary disease, systematic reviews and meta‐analyses suggested that prolonged treatment with NAC is efficacious, but a recent multicentre study has questioned this. In a large intervention trial on cancer recurrence, NAC was ineffective. NAC infusions have been widely used in acute hepatic failure but convincing evidence of its benefits is lacking. A preliminary study reported that NAC is effective in preventing radiocontrast‐induced nephropathy but thereafter highly mixed results have been published, and even meta‐analyses disagree on its efficacy. In intensive care NAC has mostly been a disappointment but recently it has ‘given promises’ in surgery with cardiopulmonary bypass. NAC therapy is routine only in paracetamol intoxication.
Regional variations in community consumption of antibiotics in Hungary, 1996–2003
Authors: Matuz Maria , Benko Ria , Doro Peter , Hajdu Edit , Nagy Gabor , Nagy Erzsebet , Monnet Dominique L. , Soos Gyongyver
Published: November 2005

Aims

To study regional differences and identify determinants of antibiotic consumption in ambulatory care in Hungary.

Methods

Regional distribution‐based antibiotic sales data were converted into a number of defined daily doses (DDD) per 1000 inhabitant‐days. Correlations were assessed with the Spearman rank test.

Results

There were large and stable interregional differences in antibiotic consumption. They were associated with socio‐economic determinants, e.g. the population receiving free access to medicines and receiving regular social assistance.

Conclusions

More detailed studies are needed to better understand the determinants of antibiotic use in these specific patient populations and to identify additional determinants at regional level.
Evaluation of proinflammatory cytokines and inflammation markers as biomarkers for the action of thiazolidinediones in Type 2 diabetes mellitus patients and healthy volunteers
Authors: Van Doorn Martijn , Kemme Michiel , Ouwens Margriet , Van Hoogdalem Ewoud J. , Jones Richard , Romijn Hans , De Kam Marieke , Schoemaker Rik , Burggraaf Koos , Cohen Adam
Published: November 2005

Aims

Thiazolidinediones (TZDs) not only enhance cellular glucose transport but are reported to have potent anti‐inflammatory effects. These effects may play an important role in the insulin sensitizing mechanism, and possibly precede the effects on parameters of glucoregulation. We sought to investigate whether these anti‐inflammatory effects could yield early responding biomarkers for TZD action in Type 2 diabetes mellitus (T2DM) patients and healthy volunteers (HV) to expedite early clinical development of novel compounds.

Methods

We investigated the timing of treatment effects on several proinflammatory cytokines and markers of inflammation in comparison with effects on typical measures of glucoregulation in T2DM patients and HV receiving rosiglitazone 4 mg or placebo twice daily for 6 weeks.

Results

We found a significant reduction in interleukin (IL)‐6 [−39.4%, confidence interval (CI) − 60.0, − 8.2] and white blood cell count (−18.4%, CI − 30.2, − 4.5) after 4 weeks of treatment in the T2DM group. These anti‐inflammatory effects did not precede the effects on typical parameters of glucoregulation in the T2DM group and there was no significant anti‐inflammatory response in the HV group.

Conclusion

We could not identify biomarkers that precede the effects of rosiglitazone on parameters of glucoregulation in T2DM or that have a significant response in HV. However, the IL‐6 response observed in this study indicates a potential role for this cytokine as complementary biomarker in clinical ‘proof of concept’ studies with novel TZDs.
A likely molecular basis of the susceptibility of Giardia lambliaTowards oxygen
Authors: Li Lei , Wang Ching C.
Published: November 2005

Giardia lamblia is an amitochondrial protozoan susceptible to oxygen, but the molecular basis for it remains unclear. A Giardia NAD(P)H:menadione oxidoreductase (DT‐diaphorase) is known to catalyse a single electron transfer reaction with quinones as the likely two‐electron acceptor when oxygen is absent. Here we overexpressed this enzyme in GiardiaTrophozoites and observed a significantly enhanced susceptibility of the cells towards oxygen. A knock‐down of this enzyme resulted, however, in more oxygen‐tolerant Giardia cells growing equally well under anaerobic and aerobic conditions. The function of DT‐diaphorase could be thus a major, if not the only, cause for the oxygen susceptibility of Giardia. Overexpressed DT‐diaphorase is accompanied by increased intracellular hydrogen peroxide. An overexpression of Fe‐superoxide dismutase in Giardia led also to a similarly heightened sensitivity to oxygen. Thus, generation of H2O2 from superoxide anion likely produced from DT‐diaphorase catalysed reaction using oxygen as electron acceptor may constitute the molecular basis for Giardia susceptibility to oxygen. A functional homologue of DT‐diaphorase in Giardia, NADH oxidase, uses oxygen as the preferred electron acceptor and reduces it to water. Overexpression of this enzyme in Giardia resulted in significantly enhanced growth under aerobic conditions. Giarida NADH oxidase could be thus an instrumental enzyme for the organism to adapt to and to tolerate an aerobic living environment.
Binding of human plasma proteins to Streptococcus pyogenes M protein determines the location of opsonic and non‐opsonic epitopes
Authors: Sandin Charlotta , Carlsson Fredric , Lindahl Gunnar
Published: November 2005

Antibodies directed against a pathogenic microorganism may recognize either protective or non‐protective epitopes. Because antibodies elicited by a vaccine must be directed against protective epitopes, it is essential to understand the molecular properties that distinguish the two types of epitope. Here we analyse this problem for the antiphagocytic M protein of Streptococcus pyogenes, using the opsonizing capacity of antibodies to estimate their ability to confer protection in vivo. Our studies were focused on the M5 protein, which has three surface‐exposed regions: the amino‐terminal hypervariable region (HVR) and the B‐ and C‐repeat regions. We first analysed the role of different M5 regions in phagocytosis resistance under non‐immune conditions, employing chromosomal mutants expressing M5 proteins with internal deletions, and demonstrate that only the B‐repeat region is essential for phagocytosis resistance. However, only antibodies to the HVR were opsonic. This apparent paradox could be explained by the ability of fibrinogen and albumin to specifically bind to the B‐ and C‐repeats, respectively, causing inhibition of antibody binding under physiological conditions, while antibodies to the HVR could bind and promote deposition of complement. These data indicate that binding of human plasma proteins plays an important role in determining the location of opsonic and non‐opsonic epitopes in streptococcal M protein.
Pilus‐mediated adhesion of Neisseria meningitidis is negatively controlled by the pilus‐retraction machinery
Authors: Yasukawa Kazutoyo , Martin Patricia , Tinsley Colin R. , Nassif Xavier
Published: November 2005

The type IV pili (Tfp) of Neisseria meningitidis play an essential role in meningococcal virulence by mediating the initial interaction of bacteria with host cells. Tfp are also subject to retraction, which relies on the PilT protein. Among the other components of the Tfp machinery, PilC1, a pilus‐associated protein, is important for Tfp biogenesis and adhesion. Adhesion of N. meningitidis to living epithelial cells was previously shown to rely on the upregulation of the pilC1 gene. On the other hand the lack of induction of pilC1 is believed to be responsible for the low adhesion of N. meningitidis onto fixed dead cells. Surprisingly, a pilT mutant, unable to retract its pili, has been shown to adhere very efficiently onto both living and fixed epithelial cells. To elucidate the mechanisms by which the pilus retraction machinery mediates meningococcal adhesion onto fixed cells, an analysis of gene expression levels in wild‐type and pilT meningococci was performed using DNA microarrays. One of the upregulated genes in the pilT strain was pilC1. This result was confirmed using quantitative real‐time reverse‐transcription polymerase chain reaction (RT‐PCR) and immunoblot analysis. The transcription starting point responsible for the upregulation of pilC1 in a pilT background was shown to be different from those controlling the induction of pilC1 upon contact with living host cells. Subsequent work using a strain hyperproducing PilT confirmed that PilT downregulates the production of PilC1. Furthermore using a pilC1 allele under the control of IPTG, we demonstrated that the upregulation of pilC1 in a pilT background was responsible for the adhesive phenotype onto fixed dead cells. Taken together our results demonstrate that the pilus retraction machinery negatively controlled the adhesiveness of the Tfp via the expression of pilC1.
Herbarium collections and field data‐based plant diversity maps for Burkina Faso
Authors: Schmidt Marco , Kreft Holger , Thiombiano Adjima , Zizka Georg
Published: November 2005

A map of plant species diversity in Burkina Faso is presented based on field observations and specimen data from the Ouagadougou University Herbarium (OUA) and the Herbarium Senckenbergianum (FR). A map of collecting intensity and field observations illustrates centres of botanical research activities in Burkina Faso. To overcome problems associated with biased sampling intensity, distributions of species have been modelled and extrapolated to maps of vascular plant diversity, life forms and diversity of four selected families (Poaceae, Cyperaceae, Dioscoreaceae and Rubiaceae). The area of most intensive collection and observation is around Gorom‐Gorom and Fada N’Gourma. Modelled diversity generally increases towards the south, as does the proportion of phanerophytes, lianas and hemicryptophytes, while the opposite trend is observed for therophytes. Poaceae diversity is highly correlated with total vascular plant diversity, making the family especially suitable as an indicator for overall plant diversity. Cyperaceae are rather evenly distributed throughout the country, Dioscoreaceae are restricted to the Sudanian Zone. Rubiaceae have their highest diversities in the very south.

Our approach can be transferred to areas with a similar database, certainly to other areas within West Africa. Future research should focus on distribution data for rare species, enabling our approach to evaluate the West African system of protected areas.
Plant species richness and diversity along an altitudinal gradient in the Sierra Nevada, Mexico
Authors: Sánchez‐González Arturo , López‐Mata Lauro
Published: November 2005

This article presents an analysis of plant species richness and diversity and its association with climatic and soil variables along a 1300‐m elevation gradient on the Cerro Tláloc Mountain in the northern Sierra Nevada in Mexico. Two 1000‐m2 tree sampling plots were created at each of 21 selected sampling sites, as well as two 250‐m2 plots for shrubs and six 9‐m2 plots for herbaceous plants. Species richness and diversity were estimated for each plant life form, and beta diversity between sites was estimated along the gradient. The relationship between species richness and diversity and environmental variables was modelled using simple linear correlation and regression trees. Species richness and diversity showed a unimodal pattern with a bias towards high values in the lower half of the elevation gradient under study. This response was consistent for all three life forms. Beta diversity increased steadily along the elevation gradient, being lower between contiguous sites at intermediate elevations and high – the species replacement rate was nearly 100%– between sites at the extremes of the gradient. Few species were adapted to the full spectrum of environmental variation along the elevation gradient studied. The regression tree suggests that differences in species richness are mainly influenced by elevation (temperature and humidity) and soil variables, namely A2 permanent wilting point, organic matter and horizon field capacity and A1 horizon Mg2+.
Modelling the distribution of Bonelli's eagle in Spain: implications for conservation planning
Authors: Muñoz A. Román , Real Raimundo , Barbosa A. Márcia , Vargas J. Mario
Published: November 2005

Bonelli's eagle, Hieraaetus fasciatus, has recently suffered a severe population decline and is currently endangered. Spain supports about 70% of the European population. We used stepwise logistic regression on a set of environmental, spatial and human variables to model Bonelli's eagle distribution in the 5167 UTM 10 × 10 km quadrats of peninsular Spain. We obtained a model based on 16 variables, which allowed us to identify favourable and unfavourable areas for this species in Spain, as well as intermediate favourability areas. We assessed the stepwise progression of the model by comparing the model's predictions in each step with those of the final model, and selected a parsimonious explanatory model based on three variables — slope, July temperature and precipitation — comprising 76% of the predictive capacity of the final model. The reported presences in favourable and unfavourable areas suggest a source–sink dynamics in Bonelli's eagle populations. The fragmented spatial structure of the favourable areas suggests the existence of a superimposed metapopulation dynamics. Previous LIFE (The Financial Instrument of the European Union for the Environment and Nature) projects for the conservation of this species have focused mainly on the northern limit of its range, where the sharpest population decline has been recorded. In these areas, favourability is low and Bonelli's eagle populations are probably maintained by the immigration of juveniles produced in more favourable zones. However, southern populations, although stable, show signs of reduction in productivity, which could menace the population sizes in the whole study area. We suggest that conservation efforts should focus also on known favourable areas, which might favour population persistence in unfavourable areas through dispersal.
The effects of fire, local environment and time on ant assemblages in fens and forests
Authors: Ratchford Jaime S. , Wittman Sarah E. , Jules Erik S. , Ellison Aaron M. , Gotelli Nicholas J. , Sanders Nathan J.
Published: November 2005

We investigated the effects of the abiotic environment, plant community composition and disturbance by fire on ant assemblages in two distinct habitat types in the Siskiyou Mountains in northern California and southern Oregon, USA. Sampling over 2 years in burned and unburned Darlingtonia fens and their adjacent upland forests, we found that the effects of disturbance by fire depended on habitat type. In forests, fire intensity predicted richness in ant assemblages in both years after the fire, and plant community composition predicted richness 2 years after the fire. No factors were associated with richness in the species‐poor fen ant assemblages. Species‐specific responses to both habitat type and disturbance by fire were idiosyncratic. Assemblage composition depended on habitat type, but not disturbance by fire, and the composition of each assemblage between years was more dissimilar in burned than unburned sites.
Seed dispersal of fleshy‐fruited invasive plants by birds: contributing factors and management options
Authors: Gosper Carl R. , Stansbury Chris D. , Vivian‐Smith Gabrielle
Published: November 2005

The ecology of seed dispersal by vertebrates has been investigated extensively over recent decades, yet only limited research has been conducted on how suites of invasive plants and frugivorous birds interact. In this review, we examine how plant fruit traits (morphology, colour and display, nutritional quality, accessibility and phenology), avian traits (fruit handling techniques, gut passage time and effect, bird movements and social behaviour and dietary composition) and landscape structure (fruit neighbourhood, habitat loss and fragmentation and perch tree effects) affect frugivory and seed dispersal in invasive plants. This functional approach could be used to develop generic models of seed dispersal distributions for suites of invasive plant species and improve management efficiencies. Four broad research approaches are described that could direct management of bird‐dispersed invasive plants at the landscape scale, by manipulating dispersal. First, research is needed to quantify the effect of biological control agents on dispersal, particularly how changes in fruit production and/or quality affect fruit choice by frugivores, dispersal distributions of seed and post‐dispersal processes. Second, we explore how seed dispersal could be directed, such as by manipulating perch structures and/or vegetation density to attract frugivorous birds after they have been foraging on invasive plant fruits. Third, the major sources of seed spread could be identified and removed (i.e. targeting core or satellite infestations, particular habitats and creating barrier zones). Fourth, alternative food resources could be provided for frugivores, to replace fruits of invasive plants, and their use quantified.
Arthropod diversity and allochthonous‐based food webs on tiny oceanic islands
Authors: Morrison Lloyd W.
Published: November 2005

Very small islands, on the order of a few hundred square metres in area, have rarely been the focus of ecological investigations. I sampled nine such islands in the central Exumas, Bahamas for arthropod species abundance and diversity using a combination of pitfall traps, pan traps and sticky traps. Three islands had no terrestrial vegetation, three islands contained onlySesuvium portulacastrumL., a salt‐tolerant perennial that had been experimentally introduced 10 years ago, and three islands supported one or two naturally occurring plant species. A relatively diverse arthropod assemblage was discovered, including representatives of 10 different orders of Crustacea and Insecta. Land hermit crabs were the most abundant crustaceans, and dipterans were the most abundant and speciose insects. Two of the most common insects were previously undescribed species. Measures of arthropod species abundance and diversity were not significantly different for vegetated vs. non‐vegetated islands. All 10 orders were present on bare islands, and nine of them were present on vegetated islands. Measures of arthropod species abundance and diversity were positively associated with island area, and negatively associated with distance from the nearest large island. Hypothesized food webs consist of several trophic levels and have strong allochthonous inputs. Tiny islands such as these hold insights into early successional processes and the base of insular food webs.
Onset of pruritus relief with pimecrolimus cream 1% in adult patients with atopic dermatitis: a randomized trial
Authors: Kaufmann R. , Bieber T. , Helgesen A. L. , Andersen B. Lasthein , Luger T. , Poulin Y. , Al‐Hafidh J. , Paul C. ,   the multicentre investigator group
Published: November 2005

Background:  Pimecrolimus cream 1% (Elidel, Novartis Pharmaceuticals AG) effectively improves/relieves pruritus associated with atopic dermatitis (AD), but few data are available regarding the timing of relief. The purpose of this study was to investigate the timing of pruritus relief produced with pimecrolimus in adults with mild/moderate AD and moderate/severe pruritus.

Methods:  Patients were randomized to 7 days of treatment with pimecrolimus (n = 100) or vehicle (n = 98). Pruritus severity was assessed daily on a 4‐point scale (0 = absent, 3 = severe), reflecting the previous 24 h experience. Patients who completed this core study were eligible to enter a voluntary 5‐week, open‐label extension study.

Results:  A significant effect was noted within 48 h of treatment, with pruritus improving in 56% of pimecrolimus‐treated patients and 34% of vehicle‐treated patients (P = 0.003). Pruritus relief was maintained during the remainder of the core and extension phases, and was accompanied by an improvement in the Investigator's Global Assessment score.

Conclusion:  Pimecrolimus cream 1% significantly reduced pruritus within 48 h.
Viral safety of Nanogam®, a new 15 nm‐filtered liquid immunoglobulin product
Authors: Terpstra F. G. , Parkkinen J. , Tölö H. , Koenderman A. H. L. , Ter Hart H. G. J. , von Bonsdorff L. , Törmä E. , van Engelenburg F. A. C.
Published: November 2005

Background and Objectives  Producers of plasma derivatives continuously improve the viral safety of their products by, for example, introducing additional virus‐reducing steps into the manufacturing process. Here we present virus‐elimination studies undertaken for a number of steps employed in a new manufacturing process for liquid intravenous immunoglobulin (Nanogam®) that comprises two specific virus‐reducing steps: a 15‐nm filtration step combined with pepsin treatment at pH 4·4 (pH 4·4/15NF); and solvent–detergent (SD) treatment. The manufacturing process also includes precipitation of Cohn fraction III and viral neutralization, which contribute to the total virus‐reducing capacity of the manufacturing process. In addition, the mechanism and robustness of the virus‐reducing steps were studied.

Materials and Methods  Selected process steps were studied with spiking experiments using a range of lipid enveloped (LE) and non‐lipid‐enveloped (NLE) viruses. The LE viruses used were bovine viral diarrhoea virus (BVDV), human immunodeficiency virus (HIV) and pseudorabies virus (PRV); the NLE viruses used were parvovirus B19 (B19), canine parvovirus (CPV) and encephalomyocarditis virus (EMC). After spiking, samples were collected and tested for residual infectivity, and the reduction factors were calculated. For B19, however, removal of B19 DNA was measured, not residual infectivity. To reveal the contribution of viral neutralization, bovine parvovirus (BPV) and hepatitis A virus (HAV) were used.

Results  For the pH 4·4/15NF step, complete reduction (> 6 log10) was demonstrated for all viruses, including B19, but not for CPV (> 3·4 but ≤ 4·2 log10). Robustness studies of the pH 4·4/15NF step with CPV showed that pH was the dominant process parameter. SD treatment for 10 min resulted in complete inactivation (> 6 log10) of all LE viruses tested. Precipitation of Cohn fraction III resulted in the significant removal (3–4 log10) of both LE and NLE viruses. Virus‐neutralization assays of final product revealed significant reduction (≥ 3 log10) of both BPV and HAV.

Conclusions  The manufacturing process of Nanogam® comprises two effective steps for the reduction of LE viruses and one for NLE viruses. In addition, the precipitation of Cohn fraction III and the presence of neutralizing antibodies contribute to the total virus‐reducing capacity of Nanogam®. The overall virus‐reducing capacity was > 15 log10 for LE viruses. For the NLE viruses B19, CPV and EMC, the overall virus‐reducing capacities were > 10, > 7 and > 9 log10, respectively. Including the contribution of immune neutralization, the overall virus‐reducing capacity for B19 and HAV is estimated to be > 10 log10.
The relevance of natural killer cell human leucocyte antigen epitopes and killer cell immunoglobulin‐like receptors in bone marrow transplantation
Authors: Witt C. S. , Christiansen F. T.
Published: November 2005

The discovery that killer cell immunoglobulin‐like receptors (KIR) interact with genetically polymorphic epitopes on class I human leucocyte antigen (HLA) molecules and that the KIR receptor repertoire itself is genetically variable has led to investigation of the relevance of the KIR system to stem cell transplantation. A number of retrospective studies of transplant outcome have now demonstrated either beneficial or deleterious effects of mismatching for class I natural killer (NK) epitopes. A smaller number of studies have shown effects of the donor and/or patient KIR repertoire on outcome, irrespective of the patient and donor HLA type. The most parsimonious interpretation of the data, which are often conflicting, is that the effect of NK epitope matching is very much dependent on transplant protocols, with the extent of donor T‐cell depletion possibly being the most important variable. A clearer picture of the role of matching for NK epitopes and the KIR‐receptor repertoire of the donor is needed.
Genetic and environmental parameters for racing time at different distances in Brazilian Thoroughbreds
Authors: Mota M.D.S. , Abrahão A.R. , Oliveira H.N.
Published: November 2005

The aim of the present study was to investigate genetic parameters for racing time in Thoroughbred horses racing at distances between 1000 and 1600 m subdivided into 100‐m intervals. The data provided by TURFETOTAL Ltda comprised races that occurred in the Gávea and Cidade Jardim race tracks over a period of 11 years (1992–2002) and consisted of 32 145 races and 238 890 time records. The variance components necessary to obtain the heritability and repeatability estimates of the traits studied were estimated with the MTDFREML program, and animal age at race (3 years old or younger, 4, 5 and older than 5 years), sex (male and female), number of races (1–32 145), and postposition at start (1–11) as fixed effects, and animal and permanent environmental random effects were included in a one‐trait animal model. Males were significantly superior to females at all distances. Excluding the 1100 m distance, animals 4 years of age were significantly faster than the mean of the other ages for all distances analysed. Horses older than 5 years showed a significantly lower performance than the mean of the other ages for all distances analysed, except for the 1100 m. Postpositions one and two did not differ significantly from one another for any of the distances analysed. These two inner positions both together varied from the other positions depending on race length. The components of additive genetic and permanent environmental variance varied in a similar way, tending to decrease with increasing racing distance, and the other temporary environmental variance almost doubled from 1000 to 1600 m. As was the case for the additive genetic and environmental variances, heritability and repeatability estimates tended to decrease with increasing distance, indicating that selection based on racing time will be less successful when the racing distance increases.
A genotype probability index for multiple alleles and haplotypes
Authors: Percy A. , Kinghorn B.P.
Published: November 2005

We use linear algebra to calculate an index of information content in genotype probabilities which has previously been calculated using trigonometry. The new method can be generalized allowing the index to be calculated for loci with more than two alleles. Applications of this index include its use in genotyping strategies, strategies to manage genetic disorders and in estimation of genotype effects.
NKT cells are not critical for HSV‐1 disease resolution
Authors: Cornish Ann L , Keating Rachael , Kyparissoudis Konstantinos , Smyth Mark J , Carbone Francis R , Godfrey Dale I
Published: November 2005

NKT cells are a minor subset of T cells that have important roles in controlling immune responses in disease states including cancer, autoimmunity and pathogenic infections. In contrast to conventional T cells, NKT cells express an invariant TCR and respond to glycolipids presented by CD1d. In this study, we sought to investigate the role of NKT cells in regulating the response to infection with HSV‐1, and the mechanism involved, in well‐established mouse models. Previous studies of HSV‐1 disease in mice have shown clear roles for CD4+ and CD8+ T cells. The role of NKT cells in the resolution of HSV‐1 (KOS strain) infection was investigated through flank zosteriform or footpad infection in wild‐type versus CD1d‐deficient mice, by measurement of viral plaque‐forming units at different sites after infection, lesion severity and HSV‐1‐specific T‐cell responses. In contrast to a previous study using a more virulent strain of HSV‐1 (SC16 strain), no differences were observed in disease magnitude or resolution, and furthermore, the T‐cell response to HSV‐1 (KOS strain) was unaltered in the absence of NKT cells. In conclusion, this study shows that NKT cells do not play a general role in controlling the resolution or severity of HSV‐1 infection. Instead, the resolution or severity of the infection may depend on the HSV‐1 strain under investigation.
The outcome of surgery in fulminant Clostridium difficile colitis
Authors: Koss K. , Clark M. A. , Sanders D. S. A. , Morton D. , Keighley M. R. B. , Goh J.
Published: November 2005

Background  The clinical presentation of Clostridium difficile infection ranges from asymptomatic carriage, colitis with or without pseudomembranes, to fulminant colitis. Although not common, fulminant C. difficile colitis can result in bowel perforation and peritonitis with a high mortality rate. Colectomy is often indicated in these cases.

Methods  We retrospectively analysed the outcome of 14 patients who underwent surgery for fulminant C. difficile colitis in the period 1996–2003 in our Unit.

Results  The indications for surgery were systemic toxicity and peritonitis (n = 10), radiological and clinical evidence of progressive toxic colonic dilatation (n = 3) and progressive colonic dilatation with bowel perforation (n = 1). C. difficile infection as the cause of colitis was diagnosed pre‐operatively in seven (50%) patients, six of whom underwent a total colectomy and one a right hemicolectomy. Overall mortality in our series was 35.7%. Total colectomy was associated with a lower mortality rate of 11·1% (1/9) when compared with left hemicolectomy was 100% (4/4) (P = 0·01). One patient who underwent a right hemicolectomy (on the basis of deceptively normal external appearance of the rest of the colon intra‐operatively) survived after a prolonged hospital stay.

Conclusions  Early or pre‐operative microbiological diagnosis of C. difficile infection can be difficult in patients with a fulminant presentation. Those patients with C. difficile colitis, who develop signs of toxicity, peritonitis or perforation, should undergo a total colectomy as the operation of choice.
A Sleep Study in Cluster Headache
Authors: Marca G Della , Vollono C , Rubino M , Capuano A , Di Trapani G , Mariotti P
Published: November 2005

Cluster headache (CH) is a primary headache with a close relation to sleep. CH presents a circa-annual rhythmicity; attacks occur preferably during the night, in rapid eye movement (REM) sleep, and they are associated with autonomic and neuroendocrine modifications. The posterior hypothalamus is the key structure for the biological phenomenon of CH. Our aim is to describe a 55-year-old man presenting a typical episodic CH, in whom we performed a prolonged sleep study, consisting of a 9-week actigraphic recording and repeated polysomnography, with evaluation of both sleep macrostructure and microstructure. During the acute bout of the cluster we observed an irregular sleep-wake pattern and abnormalities of REM sleep. After the cluster phase these alterations remitted. We conclude that CH was associated, in this patient, with sleep dysregulation involving the biological clock and the arousal mechanisms, particularly in REM. All these abnormalities are consistent with posterior hypothalamic dysfunction.
Cardiorespiratory Regulation in Migraine. Results in Children and Adolescents and Review of the Literature
Authors: Ebinger F , Kruse M , Just U , Rating D
Published: November 2005

To investigate autonomic regulation in juvenile migraine we studied 70 children and adolescents with migraine during the headache-free period and 81 healthy controls by cardiorespiratory function tests. Heart rate variability was analysed with time and frequency domain indices during spontaneous breathing at rest and during metronomic breathing. Changes of heart rate and blood pressure were studied during tilt-table test, active standing, Valsalva manoeuvre and sustained handgrip. We found significant differences in metronomic breathing, tilt-table test and Valsalva manoeuvre. We interpret our findings and results reported in the literature as pointing to a restricted ability of the system to rest, which supports therapies intending to further this ability. In autonomic tests, hyperreactivity in juvenile migraineurs changes to hyporeactivity and passive coping in adults. This might be explained by disturbances of raphe nuclei and the periaqueductal grey. It corresponds to psychological findings in juvenile migraineurs reporting hypersensitivity and repressed aggression and claiming learned helplessness.
Does Earlier Headache Response Equate to Earlier Return to Functioning in Patients Suffering from Migraine?
Authors: Pradel FG , Subedi P , Varghese AA , Mullins CD , Weis KA
Published: November 2005

This study explored the association between headache response and return to functioning, and identified migraine-associated symptoms related to functional status and acceptability of migraine treatment as reported by patients. Data from migraineurs enrolled in the active arms of a randomized, double-blind, parallel group, placebo-controlled, clinical trial were analysed. The relationships between headache response and functional response, and clinical factors and treatment acceptability were assessed using X2 tests of proportions and logistic regressions. A greater proportion of patients with headache response at 0.5 h were functioning at 0.5, 1 and 2 h compared with patients who did not attain a headache response at 0.5 h ( P < 0.0001). These patients also were more likely to find their treatment acceptable ( P < 0.05). The results suggest a direct temporal relationship among the key determinants of migraine resolution. Rapid headache response is associated with faster return to functioning; rapid headache and functional responses are significant attributes of treatment acceptability.
Prophylactic Treatment of Migraine in Children. Part 1. A Systematic Review of non-Pharmacological Trials∗
Authors: Damen L , Bruijn J , Koes BW , Berger MY , Passchier J , Verhagen AP
Published: November 2005

The aim of this study was to assess the efficacy of non-pharmacological prophylactic treatments of migraine in children. Databases were searched from inception to June 2004 and references were checked. We selected controlled trials reporting the effects of non-pharmacological prophylactic treatments in children with migraine. We assessed trial quality using the Delphi list and extracted data. Analyses were carried out according to type of intervention. A total of 19 trials were included. Relaxation, relaxation + biofeedback, relaxation + biofeedback + cognitive behavioural treatment were more effective compared with waiting list controls. Relaxation + behavioural therapy was more effective than placebo. There is conflicting evidence for the use of oligoantigenic diets. A few non-pharmacological treatments such as relaxation may be effective as prophylactic treatment for migraine in children. Because of the small number of studies and the methodological shortcomings, conclusions on effectiveness have to be drawn with caution.
Topical use of calcitriol 3 µg/g ointment in the treatment of mild‐to‐moderate psoriasis: results from an open‐label study
Authors: Carboni I , De Felice C , Bergamin A , Chimenti S
Published: November 2005

Background  Calcitriol is the active metabolite and hormonal analogue of vitamin D3. It is widely used for the topical treatment of psoriasis showing good tolerability and effectiveness.

Objectives  To assess the efficacy, tolerability and safety of calcitriol 3 µg/g ointment in mild to moderate plaque psoriasis involving sensitive areas.

Methods  Sixty patients with a body surface area < 35% were enrolled into a prospective open label clinical study. Patients were treated for 12 weeks with a twice daily calcitriol 3 µg/g topical ointment application. Efficacy and safety were assessed during the therapy and during a 6‐month follow‐up period.

Results  The study demonstrated a high clinical remission rate which progressively increased throughout therapy (11.6% at week 4, 28.3% at week 8 and 63.3% at week 12). No serious adverse events and clinically relevant changes of calcium/phosphorus homeostasis were reported.

Conclusions  The study suggests that calcitriol 3 µg/g ointment, applied twice daily, is an effective topical treatment for chronic psoriatic plaques involving less than 35% of the body surface and sensitive areas.
Chronic venous insufficiency – a potential trigger for localized scleroderma
Authors: Ludwig RJ , Werner RJ , Winker W , Boehncke W‐H , Wolter M , Kaufmann R
Published: November 2005

Localized scleroderma is a cutaneous disease that is characterized by an initial inflammatory response, followed by sclerosis of the skin. The cause of localized scleroderma has not yet been determined. Seifarth et al. reported two cases of localized scleroderma at sites of chronic venous insufficiency. We document here three more patients in whom localized scleroderma was located at insufficient veins. Treatment of underlying chronic venous insufficiency (CVI) leads to a substantial clinical improvement of scleroderma at the site of insufficient veins, but not elsewhere. Experimental data support the concept of chronic venous insufficiency creating a microenvironment, which may lead to localized scleroderma. Local hypoxaemia, which is present in CVI, induces the release of endothelium‐derived cytokines, such as IL‐1. Subsequently, expression of endothelial adhesion molecules and consequently leucocyte extravasation are induced. Infiltrating leucocytes secrete a number of inflammatory mediators, including transforming growth factor β, which is a potent stimulus for collagen synthesis. Therefore, it may well be that CVI is a potential trigger factor for localized scleroderma. In addition, localized scleroderma may only develop if a certain amount of trigger factors are present – and resolves if one or more of the contributing factors (i.e. CVI) can be treated.
The Changing Epidemiology of Autism
Authors: Fombonne Eric
Published: November 2005

This article reviews epidemiological studies of autism and related disorders. Study designs and sample characteristics are summarized. Currently, conservative prevalence estimates are: 13/10000 for autistic disorder, 21/10000 for pervasive developmental disorders not otherwise specified, 2.6/10000 for Asperger disorder, and 2/100000 for childhood disintegrative disorder. Newer surveys suggest that the best estimate for the prevalence of all autistic spectrum disorders is close to 0.6%. A detailed analysis of time trends in rates of pervasive developmental disorders in then provided. It is concluded that most of the increase is accounted for by changes in diagnostic concepts and criteria, and by improved identification. Whether or not there is, in addition to these factors, a true increase in the incidence of the disorder cannot be examined from available data.
Disability Statistics in the Developing World: A Reflection on the Meanings in our Numbers
Authors: Fujiura Glenn T. , Park Hye J. , Rutkowski‐Kmitta Violet
Published: November 2005

Background  The imbalance between the sheer size of the developing world and what little is known about the lives and life circumstances of persons with disabilities living there should command our attention.

Method  International development initiatives routinely give great priority to the collection of statistical indicators yet even the most basic data on intellectual disability is lacking. In response to the recent adoption of the ‘international classification of function’, numerous initiatives are attempting to expand and improve the quality of disability surveillance.

Results  We argue that these efforts must not lose sight of the core focus and promise of disability statistics – that of advocacy and the elevation of a disability policy agenda.

Conclusions  To this end, we weave throughout our analysis of the technical features of surveillance, reflections on the meanings we attach to disability statistics and by extension, disability itself.
Telomere length in white blood cells is not associated with morbidity or mortality in the oldest old: a population‐based study
Authors: Martin‐Ruiz Carmen M. , Gussekloo Jacobijn , van Heemst Diana , von Zglinicki Thomas , Westendorp Rudi G. J.
Published: November 2005

Cross‐sectional studies have repeatedly suggested peripheral blood monocyte telomere length as a biomarker of aging. To test this suggestion in a large population‐based follow‐up study of the oldest old, we measured telomere length at baseline in 598 participants of the Leiden 85‐plus Study (mean age at baseline 89.8 years). We also obtained second telomere measurements from 81 participants after an average time span of between 3.9 and 12.9 years. Telomere length at baseline was not predictive for mortality (P > 0.40 for all‐cause, cardiovascular causes, cancer or infectious diseases, Cox regression for gender‐adjusted tertiles of telomere length) or for the incidence of dementia (P = 0.78). Longitudinally, telomere length was highly unstable in a large fraction of participants. We conclude that blood monocyte telomere length is not a predictive indicator for age‐related morbidity and mortality at ages over 85 years, possibly because of a high degree of telomere length instability in this group.
Raised cortisol:DHEAS ratios in the elderly after injury: potential impact upon neutrophil function and immunity
Authors: Butcher Stephen K. , Killampalli Vijay , Lascelles David , Wang Keqing , Alpar E. Kaya , Lord Janet M.
Published: November 2005

The detrimental effect of stress on the immune response increases with age, though the mechanisms responsible are not fully understood. The physiological response to stress is regulated in part by the adrenocortical system. Adrenal hormones dehydroepiandrosterone sulphate (DHEAS) and cortisol have opposing effects on the innate immune system, DHEAS enhances while cortisol suppresses immunity and the molar ratio of cortisol to DHEAS increases with age. We found that elderly hip fracture patients produced a robust neutrophilia after injury, but circulating neutrophils showed an impaired antibacterial response. We therefore proposed that adrenocortical hormones mediate the heightened immunosuppression seen in the elderly after injury. We examined neutrophil function and adrenocortical hormone levels in elderly (> 65 years) hip fracture patients and age‐matched healthy controls. Thirteen out of 35 elderly patients acquired infections following hip fracture. Neutrophil superoxide production was lower in elderly hip fracture patients compared with controls (P < 0.005) and lower in patients who acquired infection following injury compared with those who did not (P < 0.05). Serum cortisol:DHEAS ratio was higher in elderly hip fracture patients (0.56 ± 0.38) compared with either age‐matched controls (0.36 ± 0.21; P < 0.05) or young fracture patients (0.087 ± 0.033; P < 0.0001). Moreover, cortisol: DHEAS was increased in elderly patients who succumbed to infection compared with those who did not (0.803 ± 0.42 vs. 0.467 ± 0.28; P < 0.02). In vitro cortisol significantly decreased neutrophil superoxide generation (P < 0.05) and this was prevented by coincubation with DHEAS. We propose that increased cortisol:DHEAS ratios may contribute to reduced immunity following physical stress in the elderly.
Behavioral, physical, and demographic changes in Drosophila populations through dietary restriction
Authors: Bross Tyson G. , Rogina Blanka , Helfand Stephen L.
Published: November 2005

Dietary restriction (DR) is a valuable experimental tool for studying the aging process. Primary advancement of research in this area has relied on rodent models, but attention has recently turned toward Drosophila melanogaster. However, little is known about the baseline effects of DR on wild‐type Drosophila and continued experimentation requires such information. The findings described here survey the effects of DR on inbred, wild‐type populations of Canton‐S fruit flies and demonstrate a robust effect of diet on longevity. Over a circumscribed range of dietary conditions, healthy lifespan varies by as much as 121% for wild‐type Drosophila females. Significant differences are also observed for male flies, but the magnitude of the DR effect is less robust. Mortality analyses of the survivorship data reveal that this variation in lifespan can be attributed to a modulation of the rate parameter for the mortality function – a change in the demographic rate of aging. Since the feeding of fruit flies is less easily controlled than that of rodents, this research also addresses the validity of applying a DR model to Drosophila populations. Feeding and body weight data for flies given the various dietary conditions surveyed indicate that Drosophila on higher‐calorie diets consume a similar volume of food to those on a low‐calorie diet, resulting in different levels of calorie intake. Fertility and activity levels demonstrate that the diets surveyed are comparable, and that increasing the calorie content of laboratory food up to twice the normal concentration is not pathologic for experimental fly populations.