bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic effect of telmisartan and losartan in hypertensive patients with metabolic syndrome
Authors: Vitale Cristiana , Mercuro Giuseppe , Castiglioni Carlotta , Cornoldi Alessandra , Tulli Arianna , Fini Massimo , Volterrani Maurizio , Rosano Giuseppe MC
Published: May 2005

Background

Metabolic syndrome is a cluster of common cardiovascular risk factors that includes hypertension and insulin resistance. Hypertension and diabetes mellitus are frequent comorbidities and, like metabolic syndrome, increase the risk of cardiovascular events. Telmisartan, an antihypertensive agent with evidence of partial peroxisome proliferator-activated receptor activity-gamma (PPARγ) activity, may improve insulin sensitivity and lipid profile in patients with metabolic syndrome.

Methods

In a double-blind, parallel-group, randomized study, patients with World Health Organization criteria for metabolic syndrome received once-daily doses of telmisartan (80 mg, n = 20) or losartan (50 mg, n = 20) for 3 months. At baseline and end of treatment, fasting and postprandial plasma glucose, insulin sensitivity, glycosylated haemoglobin (HBA1c) and 24-hour mean systolic and diastolic blood pressures were determined.

Results

Telmisartan, but not losartan, significantly (p < 0.05) reduced free plasma glucose, free plasma insulin, homeostasis model assessment of insulin resistance and HbAic. Following treatment, plasma glucose and insulin were reduced during the oral glucose tolerance test by telmisartan, but not by losartan. Telmisartan also significantly reduced 24-hour mean systolic blood pressure (p < 0.05) and diastolic blood pressure (p < 0.05) compared with losartan.

Conclusion

As well as providing superior 24-hour blood pressure control, telmisartan, unlike losartan, displayed insulin-sensitizing activity, which may be explained by its partial PPARγ activity.
Improvement of Escherichia coli production strains by modification of the phosphoenolpyruvate:sugar phosphotransferase system
Authors: Gosset Guillermo
Published: May 2005

The application of metabolic engineering in Escherichia coli has resulted in the generation of strains with the capacity to produce metabolites of commercial interest. Biotechnological processes with these engineered strains frequently employ culture media containing glucose as the carbon and energy source. In E. coli, the phosphoenolpyruvate:sugar phosphotransferase system (PTS) transports glucose when this sugar is present at concentrations like those used in production fermentations. This protein system is involved in phosphoenolpyruvate-dependent sugar transport, therefore, its activity has an important impact on carbon flux distribution in the phosphoenolpyruvate and pyruvate nodes. Furthermore, PTS has a very important role in carbon catabolite repression. The properties of PTS impose metabolic and regulatory constraints that can hinder strain productivity. For this reason, PTS has been a target for modification with the purpose of strain improvement. In this review, PTS characteristics most relevant to strain performance and the different strategies of PTS modification for strain improvement are discussed. Functional replacement of PTS by alternative phosphoenolpyruvate-independent uptake and phosphorylation activities has resulted in significant improvements in product yield from glucose and productivity for several classes of metabolites. In addition, inactivation of PTS components has been applied successfully as a strategy to abolish carbon catabolite repression, resulting in E. coli strains that use more efficiently sugar mixtures, such as those obtained from lignocellulosic hydrolysates.
A flexibly shaped spatial scan statistic for detecting clusters
Authors: Tango Toshiro , Takahashi Kunihiko
Published: May 2005

Background

The spatial scan statistic proposed by Kulldorff has been applied to a wide variety of epidemiological studies for cluster detection. This scan statistic, however, uses a circular window to define the potential cluster areas and thus has difficulty in correctly detecting actual noncircular clusters. A recent proposal by Duczmal and Assunção for detecting noncircular clusters is shown to detect a cluster of very irregular shape that is much larger than the true cluster in our experiences.

Methods

We propose a flexibly shaped spatial scan statistic that can detect irregular shaped clusters within relatively small neighborhoods of each region. The performance of the proposed spatial scan statistic is compared to that of Kulldorff's circular spatial scan statistic with Monte Carlo simulation by considering several circular and noncircular hot-spot cluster models. For comparison, we also propose a new bivariate power distribution classified by the number of regions detected as the most likely cluster and the number of hot-spot regions included in the most likely cluster.

Results

The circular spatial scan statistics shows a high level of accuracy in detecting circular clusters exactly. The proposed spatial scan statistic is shown to have good usual powers plus the ability to detect the noncircular hot-spot clusters more accurately than the circular one.

Conclusion

The proposed spatial scan statistic is shown to work well for small to moderate cluster size, up to say 30. For larger cluster sizes, the method is not practically feasible and a more efficient algorithm is needed.
Health-related quality of life measurement in pediatric clinical practice: An appraisal and precept for future research and application
Authors: Varni James W , Burwinkle Tasha M , Lane Mariella M
Published: May 2005

Health-related quality of life (HRQOL) measurement has emerged as an important health outcome in clinical trials, clinical practice improvement strategies, and healthcare services research and evaluation. HRQOL measures are also increasingly proposed for use in clinical practice settings to inform treatment decisions. In settings where HRQOL measures have been utilized with adults, physicians report such measures as useful, some physicians alter their treatment based on patient reports on such instruments, and patients themselves generally feel the instruments to be helpful. However, there is a dearth of studies evaluating the clinical utility of HRQOL measurement in pediatric clinical practice. This paper provides an updated review of the literature and proposes a precept governing the application of pediatric HRQOL measurement in pediatric clinical practice. Utilizing HRQOL measurement in pediatric healthcare settings can facilitate patient-physician communication, improve patient/parent satisfaction, identify hidden morbidities, and assist in clinical decision-making. Demonstrating the utility of pediatric HRQOL measurement in identifying children with the greatest needs, while simultaneously demonstrating the cost advantages of providing timely, targeted interventions to address those needs, may ultimately provide the driving force for incorporating HRQOL measurement in pediatric clinical practice.
Cytoskeleton reorganization mediates alpha6beta1 integrin-associated actions of laminin on proliferation and survival, but not on steroidogenesis of ovine granulosa cells
Authors: Bellego Frédérique Le , Fabre Stéphane , Pisselet Claudine , Monniaux Danielle
Published: May 2005

Background

Laminin (LN) is one of the most abundant extracellular matrix components of the basal lamina and granulosa cell layers of ovarian follicles. Culture of ovine granulosa cells (GC) on LN substratum induces cell spreading, enhances cell survival and proliferation, and promotes luteinization. Previous investigations have shown that these effects are mostly mediated by the alpha6beta1 integrin, but its signalization pathways have not been investigated. This study aimed to assess the importance of the cytoskeleton in the alpha6beta1 integrin-mediated actions of laminin on survival, proliferation and steroidogenesis of ovine GC.

Methods

The relationships between morphology and functions of ovine GC cultured on substrata containing LN or/and RGD peptides were investigated. The effects of (1) cytochalasin D, an actin cytoskeleton-disrupting drug, (2) a specific function-blocking antibody raised against alpha6 integrin subunit (anti-alpha6 IgG), and (3) an inhibitor of the ERK1/2 signalization pathway (PD98059) were assessed for GC shape, pyknosis and proliferation rates, oestradiol and progesterone secretions.

Results

Cytoskeleton disruption by cytochalasin D induced cell rounding, inhibited proliferation, promoted pyknosis, inhibited progesterone secretion and enhanced oestradiol secretion by GC cultured on LN. When GC were cultured on various substrata containing LN and/or RGD peptides in the presence or absence of anti-alpha6 IgG, both the existence of close correlations between the percentage of round cells, and the GC proliferation rate (r = -0.87) and pyknotic rate (r = 0.76) were established, but no relationship was found between cell shape and steroidogenesis. Inhibition of the ERK1/2 signalization pathway by PD98059 had no effect on GC shape, proliferation or pyknotic rates. However, it dramatically reduced progesterone secretion, expression of cytochrome P450 cholesterol side-chain cleavage and 3beta-hydroxysteroid deshydrogenase enzymes, and enhanced oestradiol secretion, thereby reproducing all the effects of the anti-alpha6 IgG on steroidogenesis of GC cultured on LN.

Conclusion

LN may participate in the paracrine control of follicular development through different mechanisms. It could enhance proliferation and survival of GC through its alpha6beta1 integrin-mediated actions on cytoskeleton. In contrast, its stimulating action on GC luteinization could be partly mediated by the ERK1/2 pathway, irrespective of cell shape.
Gene expression profile and synovial microcirculation at early stages of collagen-induced arthritis
Authors: Gierer Philip , Ibrahim Saleh , Mittlmeier Thomas , Koczan Dirk , Moeller Steffen , Landes Jürgen , Gradl Georg , Vollmar Brigitte
Published: May 2005

A better understanding of the initial mechanisms that lead to arthritic disease could facilitate development of improved therapeutic strategies. We characterized the synovial microcirculation of knee joints in susceptible mouse strains undergoing intradermal immunization with bovine collagen II in complete Freund's adjuvant to induce arthritis (i.e. collagen-induced arthritis [CIA]). Susceptible DBA1/J and collagen II T-cell receptor transgenic mice were compared with CIA-resistant FVB/NJ mice. Before onset of clinical symptoms of arthritis, in vivo fluorescence microscopy of knee joints revealed marked leucocyte activation and interaction with the endothelial lining of synovial microvessels. This initial inflammatory cell response correlated with the gene expression profile at this disease stage. The majority of the 655 differentially expressed genes belonged to classes of genes that are involved in cell movement and structure, cell cycle and signal transduction, as well as transcription, protein synthesis and metabolism. However, 24 adhesion molecules and chemokine/cytokine genes were identified, some of which are known to contribute to arthritis (e.g. CD44 and neutrophil cytosolic factor 1) and some of which are novel in this respect (e.g. CC chemokine ligand-27 and IL-13 receptor α1). Online in vivo data on synovial tissue microcirculation, together with gene expression profiling, emphasize the potential role played by early inflammatory events in the development of arthritis.
Drotrecogin alfa (activated) in patients with severe sepsis presenting with purpura fulminans, meningitis, or meningococcal disease: a retrospective analysis of patients enrolled in recent clinical studies
Authors: Vincent Jean-Louis , Nadel Simon , Kutsogiannis Demetrios J , Gibney RT Noel , Yan S Betty , Wyss Virginia L , Bailey Joan E , Mitchell Carol L , Sarwat Samiha , Shinall Stephen M , Janes Jonathan M
Published: May 2005

Introduction

We report data from adult and pediatric patients with severe sepsis from studies evaluating drotrecogin alfa (activated) (DrotAA) and presenting with purpura fulminans (PF), meningitis (MEN), or meningococcal disease (MD) (PF/MEN/MD). Such conditions may be associated with an increased bleeding risk but occur in a relatively small proportion of patients presenting with severe sepsis; pooling data across clinical trials provides an opportunity for improving the characterization of outcomes.

Methods

A retrospective analysis of placebo-controlled, open-label, and compassionate-use trials was conducted. Adult patients received infusions of either DrotAA or placebo. All pediatric patients (<18 years old) received DrotAA. 189 adult and 121 pediatric patients presented with PF/MEN/MD.

Results

Fewer adult patients with PF/MEN/MD met cardiovascular (68.3% versus 78.8%) or respiratory (57.8% versus 80.5%) organ dysfunction entry criteria than those without. DrotAA-treated adult patients with PF/MEN/MD (n = 163) had an observed 28-day mortality rate of 19.0%, a 28-day serious bleeding event (SBE) rate of 6.1%, and an intracranial hemorrhage (ICH) rate of 4.3%. Six of the seven ICHs occurred in patients with MEN (three of whom were more than 65 years old with a history of hypertension). DrotAA-treated adult patients without PF/MEN/MD (n = 3,088) had an observed 28-day mortality rate of 25.5%, a 28-day SBE rate of 5.8%, and an ICH rate of 1.0%. In contrast, a greater number of pediatric patients with PF/MEN/MD met the cardiovascular organ dysfunction entry criterion (93.5% versus 82.5%) than those without. DrotAA-treated PF/MEN/MD pediatric patients (n = 119) had a 14-day mortality rate of 10.1%, an SBE rate of 5.9%, and an ICH rate of 2.5%. DrotAA-treated pediatric patients without PF/MEN/MD (n = 142) had a 14-day mortality rate of 14.1%, an SBE rate of 9.2%, and an ICH rate of 3.5%.

Conclusion

DrotAA-treated adult patients with severe sepsis presenting with PF/MEN/MD had a similar SBE rate, a lower observed 28-day mortality rate, and a higher observed rate of ICH than DrotAA-treated patients without PF/MEN/MD. DrotAA-treated pediatric patients with severe sepsis with PF/MEN/MD may differ from adults, because all three outcome rates (SBE, mortality, and ICH) were lower in pediatric patients with PF/MEN/MD.
Quantity and quality of parental language input to late-talking toddlers during play
Authors: Vigil Debra C , Hodges Jennifer , Klee Thomas
Published: May 2005

This study compared the language behaviours of parents of toddlers with language delay (LD) and language ofparents of typically developing toddlers (LN). Results indicate that parents of children with a language delay and children with normal language produced comparable amounts of linguistic input, but differed on some qualitative measures. Parents of children with normal language used more responses, expansions and self-directed speech than parents of toddlers with language delay. Parents may adjust their conversational style to the communicative ability of their children. These results reinforce language behaviours taught in parent training programmes.
Aspects of the geomorphology, genesis and environmental significance of earth hummocks (thúfur, pounus): miniature cryogenic mounds
Authors: Grab Stefan
Published: May 2005

Miniature varieties of cryogenic mounds that are capable of forming in seasonally frozen ground are commonly referred to as earth hummocks (e.g., North America), thúfur (e.g., Greenland and Iceland) and pounus (Fennoscandia). Over the past few decades there has been a consistent interest to study earth hummocks from a variety of environmental settings. This review summarizes the current knowledge of earth hummocks, highlighting aspects on the external and internal morphology, and thermal characteristics, which may assist to explain hummock formation. Several hypotheses have been proposed for the genesis of earth hummocks, including the ‘cryoexpulsion’ of clasts, hydrostatic and cryostatic pressure, cellular circulation, and differential frost heave. These hypotheses are critically evaluated and some research gaps identified. It emerges that considerable advances have been made towards an improved understanding of earth hummock development, modification and disintegration. Much progress has been made in the application of earth hummock studies to a variety of environmental research approaches such as palaeoenvironmental reconstructions and assessing their impact on hillslope drainage.
Reviewing the origin of subglacial Lake Vostok and its sensitivity to ice sheet changes
Authors: Siegert Martin J.
Published: May 2005

The history of Lake Vostok, the huge East Antarctic subglacial lake, is critical to the unique biota expected in this extreme environment. One theory is that the lake existed prior to the mid-Miocene glaciation of the continent at around 15 million years ago, survived the subsequent period of ice growth intact, and then remained relatively stable beneath its thick ice cover to the present day. The alternative is that the lake was formed by subglacial water flow into an existing and/or glacially eroded trough after the ice sheet reached its present configuration. Here, the onset of persistent ice cover in Antarctica is reviewed and a simple model for continental ice growth discussed. This information is used to argue against the preglacial origin of subglacial lakes. Lake Vostok is large because ice flows essentially perpendicular to the trough’s long axis, permitting the slopes of the ice surface and the ice-water interface to be low. During the onset of glaciation ice flow across Lake Vostok would have been more akin to flow across an ice marginal trough such as the Astrolabe Subglacial Basin, which holds the thickest ice in Antarctica: 4776 m where the bed is over 2 km below the sea level. Hence, regardless of whether Lake Vostok was a lake prior to glaciation, its trough is likely to have been occupied by grounded ice during the period of ice growth. Although the lake is stable today, its size and extent will be affected by ice sheet changes that occur over glacial-interglacial cycles. Such changes are reviewed and the potential consequences for the lake’s volume are discussed.
A review of turbulence in the very stable nocturnal boundary layer and its implications for air quality
Authors: Salmond J. A. , McKendry I. G.
Published: May 2005

Turbulence in the very stable nocturnal boundary layer is weak and typically characterized by intermittent bursts of activity. It often exists in isolated layers or pockets generated primarily from localized shear instabilities. As a result, turbulence is rarely in equilibrium with the conditions of the underlying surface. Given the layered structure of the nocturnal boundary layer, the spatial and temporal characteristics of turbulent activity (and resulting vertical mixing) can have a significant affect on local air quality at hourly to diurnal scales. However, while there is a wealth of information concerning turbulent processes operating during daytime conditions, until recently comparatively few studies have focused on the nocturnal case. Nevertheless the three-dimensional distribution of pollutants in the nocturnal boundary layer may have a significant impact on local pollutant budgets at a variety of temporal and spatial scales. This paper reviews recent progress in our understanding of the structure of, and processes operating in, the very stable nocturnal boundary layer. Then, drawing upon case studies from the Lower Fraser Valley, of British Columbia, Canada, it considers the implications of these developments for pollutant transport and surface air quality.
Impact of plant roots on the resistance of soils to erosion by water: a review
Authors: Gyssels G. , Poesen J. , Bochet E. , Li Y.
Published: May 2005

Vegetation controls soil erosion rates significantly. The decrease of water erosion rates with increasing vegetation cover is exponential. This review reveals that the decrease in water erosion rates with increasing root mass is also exponential, according to the equation SEP e b RP where SEP is a soil erosion parameter (e.g., interrill or rill erosion rates relative to erosion rates of bare topsoils without roots), RP is a root parameter (e.g., root density or root length density) and b is a constant that indicates the effectiveness of the plant roots in reducing soil erosion rates. Whatever rooting parameter is used, for splash erosion b equals zero. For interrill erosion the average b-value is 0.1195 when root density (kg m 3) is used as root parameter, and 0.0022 when root length density (km m 3) is used. For rill erosion these average b-values are 0.5930 and 0.0460, respectively. The similarity of this equation for root effects with the equation for vegetation cover effects is striking, but it is yet impossible to determine which plant element has the highest impact in reducing soil losses, due to incomparable units. Moreover, all the studies on vegetation cover effects attribute soil loss reduction to the above-ground biomass only, whereas in reality this reduction results from the combined effects of roots and canopy cover. Based on an analysis of available data it can be concluded that for splash and interrill erosion vegetation cover is the most important vegetation parameter, whereas for rill and ephemeral gully erosion plant roots are at least as important as vegetation cover.
Thermal history of the Arctic Ocean environs adjacent to North America during the last 3.5 Ma and a possible mechanism for the cause of the cold events (major glaciations and permafrost events)
Authors: Harris Stuart A.
Published: May 2005

At 3.5 Ma, the Arctic Ocean was unfrozen, and only during the second Pliocene cold event (Californian - 3.0 Ma) did an extensive glaciation occur in Alaska-Yukon and Iceland. The sea froze during the third (Alaskan - 2.58 Ma) event as the western Arctic cooled rapidly. Baffin Island and Labrador were the centres of ice sheets, and ice-rafted debris appeared in the North Atlantic. Shrub-tundra replaced boreal forest in the west during the next warm episode but forested-shrubtundra persisted in north Greenland during the next (Wyoming - 2.2 Ma) cold event. During the last Pliocene (Montanan - 1.9 Ma) cold event, tundra surrounded the Arctic basin with widespread permafrost in unglaciated areas. Quaternary cold events were more frequent, with tundra persisting on land during warm episodes, although coastal seas usually thawed seasonally. There was a continuous cooling trend due to the demise of the Tethyan sea, but the18O marine curve shows about 130 fluctuations compared with 14 major cold events on land. The cause of the terrestrial changes seems to be the interaction of many cyclical controls with different periodicities. When enough cycles are synchronized for air temperature to cross a critical threshold, a climatic change occurs. The critical thresholds are dependent on local environments and latitude.
Glacier fluctuations, equilibrium-line altitudes and palaeoclimate in Lyngen, northern Norway, during the Lateglacial and Holocene
Authors: Bakke Jostein , Dahl Svein Olaf , Paasche Øyvind , Løvlie Reidar , Nesje Atle
Published: May 2005

Based on lacustrine and morpho-stratigraphical evidence from Lyngen in Troms, northern Norway, 13 marginal moraines have been mapped in front of Lenangsbreene in Strupskardet. Moraines M1-M13 are inferred to represent glacier halts or advance/readvance taking place during the Lateglacial and Holocene. The presence of collapse depressions suggests that some of them were ice cored (M1-M3). A chronological framework, taking into account a combination of former shorelines and related glacier-meltwater channels, lichenometry and AMS radiocarbon-dated lacustrine sediments spanning the last 20 000 cal. yr BP, has been established. The distal glacier-fed lake Aspvatnet was isolated from the sea c 10 300 cal. yr BP, and the lacustrine sediments have been investigated by use of loss-on-ignition (LOI) magnetic susceptibility, water content, wet and dry bulk density (DBD), and the magnetic parameters anhysteretic remanent magnetization (ARM) and saturation remanent magnetization (SIRM). There is, in general, good agreement between physical sediment parameters and magnetic parameters. DBD, a combination of medium and fine silt and the two statistical parameters ‘sorting’ and ‘mean’ have been used to construct a high-resolution glacier-fluctuation curve for the last 3800 cal. yr BP. Based on an accumulation-area ratio (AAR) of 0.6 and an ablation-accumulation balance ratio (ABR) approach, a continuous temperature-precipitation-wind equilibrium-line altitude (TPW-ELA) curve for the last 20000 cal. yr BP has been constructed. Using an established exponential relationship between mean ablation-season temperature and mean annual solid precipitation at the ELA of Norwegian glaciers, variations in mean winter precipitation (snow) are quantified using an independent proxy for summer temperature. Mean annual winter precipitation varied from 500 to 5000 mm water equivalent, and on average, Holocene estimates are c. 50% higher than similar figures from the Lateglacial. The two driest periods occurred during Heinrich events 1 (HI) (17 500-16 500) and 0 (HO) (13 000-12 200), whereas freshwater pulses to the North Atlantic had apparently no systematic impact on mean winter precipitation. Based on the winter precipitation curve from Lyngen, the atmospheric circulation responded to the sea surface temperature (SST) lowering associated with HI and HO. The dry and cold climate during the events led to formation of talus-derived rock glaciers at sea level.
Trends in twentieth-century tree growth at high elevations in the Sierra Nevada and White Mountains, USA
Authors: Bunn Andrew G. , Graumlich Lisa J. , Urban Dean L.
Published: May 2005

We analysed a multispecies tree-ring data base to assess the degree to which twentieth-century growth trends reflect tree growth of the last millennium. We examined ∼1000-yr chronologies for five species of high-elevation conifers at 13 sites in western North America. Using non-parametric ordination and cluster analysis, we decomposed the variability at annual to decadal timescales into two dimensions, both of which are significantly correlated to temperature and precipitation variation. Tree-ring sites map onto the ordination axes according to species and relative position on the landscape. A spectral analysis of the ordination axes indicates a secular trend and significant quasi-periodic variation on scales of years to decades. Further, we find that the pattern of high-elevation conifer growth rates during the last half of the twentieth century are different than any time in the past 1000 years, indicating a distinct biological signature of global climate change.
Last glacial to Holocene evolution of semi-arid rangelands in southeastern Australia
Authors: Cupper Matthew L.
Published: May 2005

Pollen sequences from playa lakes in the Darling Anabranch dunefields of southwestern New South Wales record vegetation changes over the last glacial period and into the Holocene. This interval was one of marked taxonomic and structural reorganization, with the plant communities that became established after the last glacial maximum (LGM; ~24-18 ka) distinct from those that had prevailed over the build-up to full glacial conditions (~70-24 ka). The glacial period was characterized by a gradual reduction of woodland and tall shrubland cover. Recolonization of the dunefields involved a similar, gradual succession from herbfields and low shrublands to tall shrublands and, finally, woodlands. These changes are likely to have been driven by climatic change, particularly fluctuations in temperature, precipitation and atmospheric CO2, as global climate systems entered and emerged from the last glaciation.
Relationships between calibrated ages and depth in stratigraphical sequences: an estimation procedure by mixed-effect regression
Authors: Heegaard Einar , Birks H. J.B. , Telford Richard J.
Published: May 2005

We present a procedure for estimating age-depth relationships in stratigraphical sequences by means of a generalized mixed-effect regression using an ancillary function for the partitioning of the fixed effect and the random effect corresponding to the degree of representativity of the individual calibrated dates for a particular section of the sedimentary sequence. The procedure uses mid-point estimates of the calibrated ages in combination with the central distributional range as the basis for estimating the fixed relationship between age and depth. Further, it combines the variability of the calibrated age at individual layers (within-object variance) with estimation of the variability of the calibrated age distribution as a whole between the layers standardized by the fixed effect (between-object variance). These components of random variability can be considered independent, and hence the uncertainty of the estimated fixed relationship between age and depth can be estimated by combining the two random variables. The procedure follows the logic of mixed-effects models, but with prior information about the expected variance within each dated object.
The association between FcgRIIIB polymorphisms and systemic lupus erythematosus in Korea
Authors: Hong C-H , Lee J-S , Lee H-S , Bae S-C , Yoo D-H
Published: May 2005

Polymorphisms of FcgR have been proposed as genetic factors that influence susceptibility to SLE. FcgRIIIB polymorphism in systemic lupus erythematosus (SLE) have been studied in various populations, but the results were inconsistent. The aim of this study was to determine the association of FcgRIIIB polymorphism in Korean lupus patients. One-hundred and eighty-three SLE patients (166 female, 17 male) meeting 1982 ACR criteria and 300 Korean disease-free controls were enrolled. Genotyping for the FcgRIIIB NA1/NA2 was performed by PCR of genomic DNA using allele-specific primers. There was no significant skewing in the distribution of the three FcgRIIIB genotypes, and alleles between SLE and the controls. The frequency of FcgRIIIB genotypes in SLE patients and controls was FcgRIIIB NA1/NA1 27.9% versus 26%, NA1/NA2 55.2% versus 51.7%, NA2/NA2 16.9% versus 22.3%, respectively. The gene frequencies of NA1 allele were 0.56 in the SLE and 0.52 in controls, respectively. Among clinical manifestations, thrombocytopenia was more common in FcgRIIIB NA2/NA2 genotype ( P = 0.04, OR 2.4, 95% CI 1.0-5.4), and NA2 allele ( P = 0.03, OR 1.7, 95% CI 1.1-2.8). Although FcgRIIIB polymorphism was not associated with the development of SLE in Korean, thrombocytopenia was associated with FcgRIIIB NA2/NA2 genotype, and NA2 allele.
Polymorphisms of the renin-angiotensin system genes in Brazilian patients with lupus nephropathy
Authors: Sprovieri S RS , Sens Y AS
Published: May 2005

Genetic polymorphisms of the renin-angiotensin system (RAS) has been associated with cardiovascular events and the progression of nephropathy in several diseases. The objective of this study was to evaluate a possible association of the genetic polymorphisms of RAS with the development and/or progression of lupus nephritis in a Brazilian population. Seventy-five SLE patients with lupus nephropathy (LN group) were compared to 72 SLE patients without LN (SLE group) and 65 healthy individuals (CONTROL group), of sex and ethnic matched, in a Brazilian population sample. Mean global follow-up was 9 + 6 years for lupus without nephropathy and 11 + 7 years for lupus nephropathy. Following the extraction of genomic DNA from the leukocytes in the peripheral blood, angiotensin converting enzyme (ACE I/D), angiotensinogen (AGT M235T) and angiotensin II type 1 receptor (AGTR1 A1166C) genotypes were determined by the polymerase chain reaction.

No significant difference of ACE, AGT and AGTR1 genotypes distribution between groups was observed in this study. There was no significant association between the variables of the RAS genotypes and the presence of hypertension in SLE. However, an increased frequency of DD genotype (ACE I/D) was observed in SLE patients with LN who progressed to CRF compared to healthy controls (DD 60%, DI 26.7%, II 13.3% versus 27.7%, 60% and 12.3%, respectively; x2 = 6.299, P = 0.0429). In the population studied, there was no influence of the RAS genetic polymorphisms in the development of lupus nephropathy, but the progression to CRF was associated with ACE DD polymorphism.
Orthopaedic manifestations of the antiphospholipid (Hughes) syndrome
Authors: Vasoo S , Sangle S , Zain M , D’Cruz D , Hughes G
Published: May 2005

The antiphospholipid (Hughes) syndrome (APS), is characterized by arterial and/or venous thrombosis and pregnancy morbidity in association with antiphospholipid antibodies (aPL). Since its classical description 21 years ago, the clinical spectrum of Hughes syndrome has embraced the realms of obstetrics, nephrology, cardiology, neurology, gastroenterology and now, possibly orthopaedics. This is not surprising, given that this disease can affect virtually any organ system and blood vessel of any size and nature. Just as venous thrombosis may affect limbs and internal organs, arterial thrombosis has been shown to affect organs such as the brain, eye, heart, kidney, liver and may also involve the skeleton. In this review, the skeletal aspects of Hughes syndrome, postulated pathogenesis and possible implications of anticoagulation will be discussed. Finally, the approach to APS patients undergoing orthopaedic surgery shall also be outlined.
25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis
Authors: Soilu-Hänninen M , Airas L , Mononen I , Heikkilä A , Viljanen M , Hänninen A
Published: May 2005

Past sun exposure and vitamin D supplementation have been associated with a reduction in the risk of MS. We measured the serum concentration of 25-hydroxyvitamin D (25[OH]D) at the time of MS diagnosis in 40 MS patients and 40 controls. We found no difference in the serum levels of 25(OH)D between MS patients and controls when all samples or samples obtained during winter months were compared, but MS patients had significantly lower serum 25(OH)D concentrations in June to September than the controls. The vitamin D stores were adequate for bone metabolism (> 37 nmol/L) in 70% of MS patients throughout the year and within the hypovitaminosis level (< 37 nmol/L) in 30% of MS patients at some time of the year. During MS-relapses, 25(OH)D levels were lower than in remission, but mostly within the reference range observed in relation with normal bone metabolism. We conclude that the vitamin D stores in most MS patients are adequate for their normal bone metabolism. However, lower vitamin D levels during MS relapses than in remission suggest that vitamin D could be involved in the regulation of the clinical disease activity of MS. The optimal serum levels of vitamin D for the regulation of immune responses remain to be determined.
Tau protein level in cerebrospinal fluid is increased in patients with early multiple sclerosis
Authors: Brettschneider J , Maier M , Arda S , Claus A , Süssmuth S D , Kassubek J , Tumani H
Published: May 2005

Axonal damage has been proposed as the major substrate of permanent clinical disability in multiple sclerosis. Tau protein, a microtubule-associated protein localised in neuronal axons, may serve as a biochemical surrogate marker to evaluate axonal damage in vivo.We intended to determine the extent of axonal damage in different stages and clinical subtypes of MS by investigating cerebrospinal fluid tau concentrations. Tau was measured using an immunoassay in 35 patients with relapsing—remitting MS, eight patients with secondary progressive MS, nine patients with primary progressive MS, 50 patients with clinically isolated syndrome suggestive of early MS and 46 normal controls. Cerebrospinal fluid tau was significantly elevated in MS compared with normal controls (median 206.0 pg/mL versus152.0 pg/mL;P=0.002). No significant difference among different subtypes of MS could be detected, although highest levels were found in very early disease stages. There was a significant elevation of CSF tau among patients with gadolinium-enhancing brain lesions in magnetic resonance imaging (P=0.02) and a tendency towards higher CSF tau levels in patients with pronounced intrathecal IgG synthesis, supporting the notion that axonal damage is influenced by inflammatory activity.
Accuracy of two electronic pedometers for measuring steps taken under controlled conditions among ambulatory individuals with multiple sclerosis
Authors: Motl Robert W , McAuley Edward , Snook Erin M. , Scott Jennifer A.
Published: May 2005

Pedometers are inexpensive and user-friendly devices that might be practical for measuring physical activity among individuals with multiple sclerosis (MS). This study involved an evaluation of the accuracy of two pedometers against actual steps taken under controlled laboratory conditions (five minute bouts of walking at five different treadmill speeds [41, 54, 67, 80, and 94 m—min-1]) among 23 individuals with MS who were ambulatory without an aide. Both pedometers exhibited good accuracy with the 67, 80, and 94 m=min-1 speeds, but poor accuracy with the 41 and 54 m=min-1 speeds. Those results support the quantification of physical activity using pedometers among those with MS who are ambulatory without an aide.
Motor cortex excitability and fatigue in multiple sclerosis: a transcranial magnetic stimulation study
Authors: Liepert J , Mingers D , Heesen C , Bäumer T , Weiller C
Published: May 2005

We investigated electrophysiological correlates of fatigue in patients with multiple sclerosis (MS). Transcranial magnetic stimulation (TMS) was used to explore motor excitability in three groups of subjects: MS patients with fatigue (MS-F), MS patients without fatigue (MS-NF) and healthy control subjects. All participants had to perform a fatiguing hand-grip exercise. TMS was performed prior to and after the exercise. Prior to the motor task, MS-F patients had less inhibition in the primary motor cortex compared to both other groups. Postexercise, intracortical inhibition was still reduced in the MS-F patients compared to the MS-NF patients. In MS-F patients the postexercise time interval for normalization of the motor threshold was correlated with the fatigue severity. We conclude that MS patients with fatigue have an impairment of inhibitory circuits in their primary motor cortex. The results also indicate that fatigue severity is associated with an exercise-induced reduction of membrane excitability.
Hereditary Melkersson-Rosenthal syndrome and multiple sclerosis
Authors: Cabrera-Gómez J A , Echazabal-Santana N , Real-González Y , García K Romero , Sobrinho Manuel Junior , Ocaña M A Gil , González-Valdes N , de Oca M L Valdes-Montes , Cristofol-Corominas M , de la Nuez J González , Lahera J García , Şuárez C Ugarte
Published: May 2005

The revision of MEDLINE from 1966 to 2003 did not report any association between multiple sclerosis (MS) and Melkersson—Rosenthal syndrome (MRS). This is a case report of a 51-year-old woman, with history of four recurrent Bell’s palsies. In 1999 she developed a right facial paralysis due to a supranuclear pyramidal lesion with right monoparesis. The family history showed five relatives with recurrent Bell’s paralysis and plicata tongue. Physical examination: right Bell’s paralysis, left supranuclear facial paralysis, furrowed tongue, right hemiparesis with pallor of the optic disks. Brain magnetic resonance imaging (MRI) demonstrated the typical lesions of MS and CSF oligoclonal bands. This is the first observation of a patient with hereditary MRS and MS. The link between both diseases is discussed.
Severity of chronic pain and its relationship to quality of life in multiple sclerosis
Authors: Kalia Lorraine V , OConnor Paul W
Published: May 2005

Introduction: This study used reliable and validated instruments to compare pain severity in multiple sclerosis (MS) to that in other chronic painful conditions, and to examine relationships between chronic pain in MS and health-related quality of life (HRQOL). Methods: Ninety-nine MS patients completed a self-administered survey comprised of the Medical Outcomes 36-Item Short-Form Health Survey, the Short-Form McGill Pain Questionnaire, and the Hospital Anxiety and Depression Scale. Results: Pain severity was not different between MS patients with pain and rheumatoid arthritis (P=0.77) or osteoarthritis (P=0.98) patients. Chronic pain in MS was less often neurogenic than non-neurogenic, although severity of neurogenic pain was greater than that of non-neurogenic pain (P=0.048). Chronic pain in MS was found to have no significant relationship to age, disease duration or disease course. Instead, we found that pain was correlated with aspects of HRQOL, particularly mental health (r=0.44, P<0.0001) versus physical functioning (r=0.19, P>0.05). Chronic pain was significantly related to anxiety and depression for females but not for males with MS. Conclusions: Chronic pain in MS is as severe as pain in arthritic conditions and is associated with reduced HRQOL. Thus, pain can be a significant symptom for MS patients and the need for treatment may be underestimated.
Factors related with treatment adherence to interferon b and glatiramer acetate therapy in multiple sclerosis
Authors: Río Jordi , Porcel Joana , Téllez Nieves , Sánchez-Betancourt Angela , Tintoré M ar , Arévalo M Jesús , Nos Carlos , Montalban Xavier
Published: May 2005

Background: Awareness of the factors influencing discontinuation of immunomodulatory drugs (IMD) treatment in multiple sclerosis (MS) can help to find approaches to patient management with the aim of establishing more specific indications and also attaining more optimal patient selection in future clinical trials. Objective: To identify the causes that influence adhesion to IMD therapy within the clinical practice in a large cohort of patients with MS. Patients and methods: We have studied all MS patients who have initiated IMD in our hospital. All patients took part in training sessions where treatment expectations and side effects were explained and they received training in the administration technique. Reasons for stopping therapy were recorded during follow-up. Results: We studied 632 MS patients (mean follow-up was 47.1 (28.7) months). At the time of analysis, 107/632 patients (17%) were no longer receiving IMD. Almost half of the patients who stopped IMD (52/107) did so within the first two years on therapy. Fifty-six patients stopped IMD because of lack of efficacy. Only 27 patients (4.3%) discontinued treatment for reasons other than inefficacy or side effects. The proportion of patients with secondary progressive MS that stopped IMD therapy was 30%, while only 13.5% of the patients with relapsing—remitting MS stopped therapy (P= 0.0001). Expanded Disability Status Scale (EDSS) score at entry was the main factor that predicted interruption of therapy. Conclusions: The proportion of patients interrupting IMD in our centre is low, possibly due to individualized care. Higher EDSS, mainly in the first two years of treatment, is the main factor related with interruption. Close follow-up of these patients would be useful in avoiding early discontinuation of therapy.
Elevated endothelial microparticle—monocyte complexes induced by multiple sclerosis plasma and the inhibitory effects of interferon-β1b on release of endothelial microparticles, formation and transendothelial migration of monocyte-endothelial microparticle complexes
Authors: Jimenez Joaquin J , Jy Wenche , Mauro Lucia M , Horstman Lawrence L , Ahn Eugene R , Ahn Yeon S , Minagar Alireza
Published: May 2005

Monocyte migration through the disrupted cerebral endothelial cell (EC) junctions plays an essential role in formation of multiple sclerosis (MS) demyelinating lesions. During pathogenesis of MS, activated ECs release endothelial microparticles (EMP), which possibly facilitate transendothelial migration (TEMIG) of monocytes. To assess functional roles of EMP in MS, specifically, their (i) interaction with monocytes, (ii) effect on monocyte TEMIG in an in vitro model of the brain microvascular endothelial cells (BMVEC), (iii) phenotypic profiles of EMP elicited by MS plasma and (iv) the effects of IFN-b1b on release of EMP and on TEMIG of monocytes (mono) and monocytes:EMP complexes (mono:EMP) through the BMVEC. The effect of IFN-b1b on the release of EMP and the TEMIG of mono and mono:EMP was assessed by preincubating BMVEC cultures of IFN-b1b prior to addition of plasma. Three EMP phenotypes, CD54, CD62E and CD31 were assayed. Plasma specimens from 20 patients with relapsing—remitting MS (11 in exacerbation, MS-E, and 9 in remission, ME-R) and 10 healthy controls were studied. Incubation of BMVEC with MS-E plasma yielded elevated levels of EMPCD54, EMP62E and EMPCD31 relative to MS-R and control plasmas. MS-E but not MS-R or control plasma also augmented TEMIG of monocytes, respectively. Mono:EMP complexes further augmented TEMIG relative to mono alone, but only in the presence of MS-E plasma; there was no significant effect with MS-R or control plasmas. The presence of IFN-b1b inhibited TEMIG of mono and mono:EMP by 20% and 30%, respectively. MS-E but not MS-R plasma elicited release of activation-derived EMP and enhanced TEMIG of mono and mono:EMP. IFN-b1b inhibited TEMIG and release of EMP, suggesting a role of EMP and a novel therapeutic mechanism for IFN-β1b in MS.
A randomized clinical trial of valacyclovir in multiple sclerosis
Authors: Friedman J E , Zabriskie J B , Plank C , Ablashi D , Whitman J , Shahan B , Edgell R , Shieh M , Rapalino O , Zimmerman R , Sheng D
Published: May 2005

Objective: The human Herpesvirus type-6 (HHV-6) has been implicated in multiple sclerosis (MS). Valacyclovir is an antiviral agent with an excellent safety profile. A two-year, placebo-controlled, double-blind study was conducted to (1) ascertain if high-dose, prolonged treatment with valacyclovir would be safe and (2) observe if valacyclovir would delay the progression of MS clinically or by magnetic resonance imaging (MRI). Design/methods: Fifty-eight patients were stratified as to severity and randomly assigned to receive valacyclovir (3000 mg/day) or placebo for a period of two years. Patients were followed clinically over the two-year period by means of the Expanded Disability Status Scale (EDSS), the Ambulation Index (AI) and brain MRI scans. Patients underwent routine lab studies every three months. Patients continued on the medication for two years unless they had a sustained progression or repeated exacerbations. Results: No patient discontinued the study due to side effects or toxicity. In Relative Ranking of Progression, time to first attack, attack rate, and time to withdrawal there were trends (but not statistically significant) toward drug effect over placebo in the Severe clinical category. MRI evaluation showed no significant drug effect. Conclusions: Although not statistically significant, positive trends were detected for acyclovir by clinical measures, but not by MRI.
Industry Preparedness for Earthquakes and Earthquake-Triggered Hazmat Accidents in the 1999 Kocaeli Earthquake
Authors: Cruz Ana Maria , Steinberg Laura J.
Published: May 2005

In this study, we report on the results of a random mail survey of 400 industrial facilities affected by the Turkey earthquake of 17 August 1999. The survey asked questions concerning damage and economic losses, hazardous materials and hazardous materials releases during the earthquake, and risk management and emergency response practices for hazmats prior to and after the earthquake. The study results indicate a high toll on industrial facilities in the region with more than 56% of industrial facilities reporting structural damage and over 60% reporting economic losses. A significantly higher number of industrial facilities built prior to the introduction of the first seismic building codes in 1975 suffered damage. In a logistic regression, older facilities and facilities owned by multinational firms were found to be more likely to suffer damages than Turkish-owned facilities or newer facilities. Eight percent of facilities handling hazardous materials suffered an earthquake-triggered hazardous materials release. Preparedness for earthquake-triggered hazardous materials releases prior to the earthquake was low, but increased significantly in the aftermath of the earthquake, especially for those facilities that had suffered earthquake damage.