bluuebunny/crossref_metadata_2025 huggingface dataset:
An evidence‐based review and guidelines for patient self‐testing and management of oral anticoagulation
Authors: Fitzmaurice D. A. , Gardiner C. , Kitchen S. , Mackie I. , Murray E. T. , Machin S. J. ,   The British Society of Haematology Taskforce for Haemostasis and Thrombosis
Published: September 2005

There is a limited evidence base for self‐testing and ‐management for oral anticoagulation management. Available data suggest that these are credible models for a significant minority of patients if underpinned by structured training and follow‐up. The guidelines presented are necessarily consensual and outline procedures for patient selection, training, product procurement, product maintenance, quality assurance procedures, dosage adjustment and clinical supervision. The cost‐effectiveness of these models remains to be elucidated within the UK. Further data on both health economic and clinical outcomes are required from UK based studies before widespread implementation of self‐testing and management can be recommended on a wider scale.
Immune tolerance to hepatitis C virus acquired during engraftment of bone marrow transplant
Authors: Godkin A. , Openshaw P. , Thomas H. C.
Published: September 2005

Summary.  The CD4+ T‐cell response appears to be important for clearance of hepatitis C virus (HCV) in the majority of individuals. We have recently described a series of human leucocyte antigen (HLA)‐DR11‐restricted T‐cell epitopes derived from HCV proteins which enables distinct populations of memory CD4+ T cells to be detected and counted in all nonviraemic HCV subjects. We examined the case of an HLA‐DR11+ recipient of a haematopoietic stem‐cell transplant who was concurrently infected with HCV from an HLA‐DR11+ donor sibling. An acute HCV hepatitis developed and was treated with type I interferon. After successful viral clearance, the recipient demonstrated a selective lack of HCV epitope‐specific CD4+ T cells and absence of serological responses compared with the treated donor. The recipient had no evidence of any nonspecific immunosuppression. The subsequent effects of concurrent infection during immune reconstitution are not known in adult humans, but data from murine models suggest this can lead to a skewing of the T‐cell repertoire because of thymic selection. From the above observations, it is plausible that the introduction of foreign viral antigen into the thymus may lead to subsequent acquired central tolerance.
Response to hepatitis A vaccine in HIV‐positive patients1
Authors: Weissman S. , Feucht C. , Moore B. A.
Published: September 2005

Summary.  The USPHS/IDSA guidelines for Prevention of Opportunistic Infections in Persons with human immunodeficiency virus (HIV) recommends that all susceptible HIV+ patients at increased risk for hepatitis A virus (HAV) or with chronic liver disease, be vaccinated against HAV. Immune response to HAV vaccine has not been well studied in HIV+ patients. In particular, there is little information in the literature regarding the effect and relationship of the CD4 count and the immune response in HIV patients. A retrospective analysis of HIV+ patients who received HAV vaccine was performed, and the antibody response to HAV (anti‐HAV) measured. Univariate and multivariate analyses were performed to determine predictors of response to vaccine administration. Of the 503 patients evaluated, 138 patients completed their HAV vaccination series and 48% of them had postvaccine anti‐HAV positive results (responders). There was no difference in age, race, antiretroviral therapy use, or hepatitis C virus exposure between responders and nonresponders. In univariate analysis, responders were more likely to be female (40.3%vs 21.1%, P = 0.01), have a higher CD4 count at vaccine (508.6 cells/mm3vs 344.3 cells/mm3, P = 0.001) and marginally lower viral load at vaccine (2.65 log copies vs 2.94 log copies, P = 0.07). Multivariate analysis showed that female gender and higher CD4 count at vaccine were independent predictors of response to vaccine. Forty‐eight per cent of our HIV+ patients responded to HAV vaccine administration. This is much lower than reported rates of 100% in HIV‐negative patients. Female gender and CD4 count at vaccine, but not CD4 nadir, predicted response to vaccine.
Saccharin‐induced protection against powdery mildew in barley: effects on growth and phenylpropanoid metabolism
Authors: Boyle C. , Walters D. R.
Published: September 2005

Treatment of barley (Hordeum vulgare) with 3 mm saccharin, applied as a foliar treatment to the first leaf or as a soil drench, provided significant control of powdery mildew (Blumeria graminis f.sp. hordei) on first and second leaves. This was unlikely to be the result of a direct effect of saccharin on the fungus, as application of the chemical to first leaves 2 h before inoculation did not affect conidial germination or formation of appressoria. Saccharin treatment had no significant effect on plant growth, except for a reduction in total leaf area in plants treated with a saccharin drench 14 days before inoculation with mildew. Phenylalanine ammonia‐lyase activity was reduced significantly in second leaves 18 and 48 h after inoculation in plants treated with saccharin 14 days earlier. Peroxidase activity increased significantly in plants challenged with mildew within 6 days of saccharin application, although changes were not apparent until 48 h after pathogen challenge. On these occasions, treatment with saccharin resulted in a 33% increase in peroxidase activity compared with controls. In plants inoculated 10 or 14 days after saccharin application, cinnamyl alcohol dehydrogenase (CAD) activity increased prior to, and 18, 24 and 48 h after, inoculation of the barley plants with mildew. CAD activity increased approximately twofold compared with controls. However, in contrast to peroxidase, CAD activity was significantly higher in saccharin‐treated plants prior to and after inoculation with powdery mildew, suggesting that saccharin primes CAD activity prior to pathogen challenge.
Induction of root‐mat symptoms on cucumber plants by Rhizobium, but not by Ochrobactrum or Sinorhizobium, harbouring a cucumopine Ri plasmid
Authors: Weller S. A. , Stead D. E. , Young J. P. W.
Published: September 2005

Ochrobactrum CSL 2573, Rhizobium CSL 2411 and Sinorhizobium CSL 2611 strains harbouring the Agrobacterium cucumopine Ri plasmid (pRi), previously were shown to induce root‐mat symptoms in an in vitro cucumber cotyledon assay. In whole‐plant, rockwool‐grown cucumber host tests Rhizobium CSL 2411 was shown to be as efficient an inducer of root‐mat symptoms as the virulent Agrobacterium radiobacter strain NCPPB 4042, which also harbours a cucumopine pRi. Conjugal transfer of pRi to ingressing, avirulent Agrobacterium isolates was observed within root tissues with symptoms. Ochrobactrum CSL 2573 and Sinorhizobium CSL 2611 were not able to induce root‐mat symptoms on plants. Rhizobium CSL 2411 and Ochrobactrum CSL 2573 were reisolated from inoculated plants, but Sinorhizobium CSL 2611 was not detected or isolated from inoculated plants 68 days after inoculation. It was postulated that the differences in pathogenicity observed between the in vitro and in situ host tests were caused by a lack of proper attachment to inoculated root tissues by pRi‐harbouring Ochrobactrum and Sinorhizobium in the whole‐plant host tests.
A Late Paleoproterozoic (1.80 Ga) subduction‐related mafic igneous suite from Lomza, NE Poland
Authors: Krzemińska Ewa , Williams Ian , Wiszniewska Janina
Published: September 2005

The Lomza orthoamphibolites in the crystalline basement of NE Poland, dated at 1802 ± 9 Ma by SHRIMP zircon U–Pb, are characterized by high incompatible and REE element contents. These features, the low Nb, and the position of the rock compositions on La–Y–Nb, Zr–Nb/Zr and Zr–Nb–Y tectonomagmatic discrimination diagrams, suggest that the metavolcanics formed in a subduction setting, possibly within a continental margin island arc. The likely extension of the belt of Paleoproterozoic mafic magmatism from Latvia and Lithuania into NE Poland provides convincing evidence for the existence of an active plate margin in that region at that time.
Major perturbation of ocean chemistry and a ‘Strangelove Ocean’ after the end‐Permian mass extinction
Authors: Rampino Michael R. , Caldeira Ken
Published: September 2005

The severe mass extinction of marine and terrestrial organisms at the end of the Permian Period (c. 251 Ma) was accompanied by a rapid (<100 000 years and possibly <10 000 years) negative excursion of c. 3‰ in the δ13C of the global surface oceans and atmosphere that persisted for some 500 000 years into the Early Triassic. Simulations with an ocean–atmosphere/carbon‐cycle model suggest that the isotope excursion can be explained by collapse of ocean primary productivity, and changes in the delivery and cycling of carbon in the oceans and on land. Model results suggest that severe reduction of marine productivity led to an increase in surface‐ocean dissolved inorganic carbon and a rapid, short‐term increase in atmospheric pCO2 (from a Late Permian base of 850 ppm to c. 2500 ppm). Increase in surface ocean alkalinity may have stimulated the widespread microbial and abiotic shallow‐water carbonate deposition seen in the earliest Triassic. The model is also consistent with a long‐term (>1 Ma) decrease in sedimentary burial of organic carbon in the early Triassic.
Transcriptional gene silencing as a tool for uncovering gene function in maize
Authors: Mark Cigan A. , Unger‐Wallace Erica , Haug‐Collet Kristin
Published: September 2005

Transcriptional gene silencing has broad applications for studying gene function in planta. In maize, a large number of genes have been identified as tassel‐preferred in their expression pattern, both by traditional genetic methods and by recent high‐throughput expression profiling platforms. Approaches using RNA suppression may provide a rapid alternative means to identify genes directly related to pollen development in maize. The male fertility gene Ms45 and several anther‐expressed genes of unknown function were used to evaluate the efficacy of generating male‐sterile plants by transcriptional gene silencing. A high frequency of male‐sterile plants was obtained by constitutively expressing inverted repeats (IR) of the Ms45 promoter. These sterile plants lacked MS45 mRNA due to transcriptional inactivity of the target promoter. Moreover, fertility was restored to these promoter IR‐containing plants by expressing the Ms45 coding region using heterologous promoters. Transcriptional silencing of other anther‐expressed genes also significantly affected male fertility phenotypes and led to increased methylation of the target promoter DNA sequences. These studies provide evidence of disruption of gene activity in monocots by RNA interference constructs directed against either native or transformed promoter regions. This approach not only enables the correlation of monocot anther‐expressed genes with functions that are important for reproduction in maize, but may also provide a tool for studying gene function and identifying regulatory components unique to transcriptional gene control.
Plastid division is mediated by combinatorial assembly of plastid division proteins
Authors: Maple Jodi , Aldridge Cassie , Møller Simon Geir
Published: September 2005

Plastids arise by division from pre‐existing organelles, and with the recent characterization of several new components of plastid division our understanding of the division process in higher plants has improved dramatically. However, it is still not known how these different protein components act together during division. Here we analyse protein–protein interactions between all known stromal plastid division proteins. Using a combination of quantitative yeast two‐hybrid assays, in planta co‐localization studies, fluorescence resonance energy transfer and bimolecular fluorescence complementation assays we show that these proteins do not act in isolation but rather in protein complexes to govern appropriate plastid division. We have previously shown that AtMinD1 forms functional homodimers and we show here that in addition to homodimerization AtMinD1 also interacts with AtMinE1. Furthermore, AtMinE1 has the ability to homodimerize. We also demonstrate that proteins from both FtsZ families (AtFtsZ1‐1 and AtFtsZ2‐1) not only interact with themselves but also with each other, and we show that these interactions are not dependent on correct Z‐ring formation. Further to this we demonstrate that ARC6 specifically interacts with the core domain of AtFtsZ2‐1, but not with AtFtsZ1‐1, providing in planta evidence for a functional difference between the two FtsZ protein families in plants. Our studies have enabled us to construct a meaningful intraplastidic protein–protein interaction map of all known stromal plastid division proteins in Arabidopsis.
External control of transgene expression in tobacco plastids using the bacterial lac repressor
Authors: Mühlbauer Stefan K. , Koop Hans‐Ulrich
Published: September 2005

Although several induction systems have been described for plants containing transgenes in the nucleus, to date there is only one method for controlling transgene expression in plastids. This consists of chemical induction of a nuclear gene and import of the gene product into plastids, so that transformation of two cellular compartments is required. Here we describe a system for external control of plastid gene expression which is based entirely on plastid components and can therefore be established in a single transformation step. Our system uses modified promoters containing binding sites for the bacterial lac repressor. Chemical induction can be made with intact plants or after harvesting, which provides ecological and economic benefits.
The AtSUC5 sucrose transporter specifically expressed in the endosperm is involved in early seed development in Arabidopsis
Authors: Baud Sébastien , Wuillème Sylvie , Lemoine Rémi , Kronenberger Jocelyne , Caboche Michel , Lepiniec Loïc , Rochat Christine
Published: September 2005

The sucrose transporter gene AtSUC5 was studied as part of a programme aimed at identifying and studying the genes involved in seed maturation in Arabidopsis. Expression profiling of AtSUC5 using the technique of real‐time quantitative reverse transcriptase polymerase chain reaction (RT‐PCR) showed that the gene was specifically and highly induced during seed development between 4 and 9 days after flowering (DAF). Analysis of the activity of the AtSUC5 promoter in planta was consistent with this timing, and suggested that AtSUC5 expression is endosperm specific, spreading from the micropylar to the chalazal pole of the filial tissue. To demonstrate the function of AtSUC5, the corresponding cDNA was used to complement a sucrose uptake‐deficient yeast mutant, thus confirming its sucrose transport capacity. To investigate the function in planta, three allelic mutants disrupted in the AtSUC5 gene were isolated and characterized. A strong but transient reduction in fatty acid concentration was observed in mutant seeds 8 DAF. This biochemical phenotype was associated with a slight delay in embryo development. Taken together, these data demonstrated the role of the AtSUC5 carrier in the nutrition of the filial tissues during early seed development. However, additional sugar uptake systems, which remain to be characterized, must be functional in developing seeds, especially during maturation of the embryo.
Sucrose rescues seedling establishment but not germination of Arabidopsis mutants disrupted in peroxisomal fatty acid catabolism
Authors: Pinfield‐Wells Helen , Rylott Elizabeth L. , Gilday Alison D. , Graham Stuart , Job Kathleen , Larson Tony R. , Graham Ian A.
Published: September 2005

The Arabidopsis acyl‐CoA oxidase (ACX) family comprises isozymes with distinct fatty acid chain‐length specificities that together catalyse the first step of peroxisomal fatty acid β‐oxidation. We have isolated and characterized T‐DNA insertion mutants in the medium to long‐chain (ACX1) and long‐chain (ACX2) acyl‐CoA oxidases, and show that the corresponding endogenous activities are decreased in the mutants. Lipid catabolism during germination and early post‐germinative growth was unaltered in the acx1‐1 mutant, but slightly delayed in the acx2‐1 mutant, with 3‐day‐old acx2‐1 seedlings accumulating long‐chain acyl‐CoAs. In acx1‐1 and acx2‐1, seedling growth and establishment in the absence of an exogenous supply of sucrose was unaffected. Seedlings of the double mutant acx1‐1 acx2‐1 were unable to catabolize seed storage lipid, and accumulated long‐chain acyl‐CoAs. The acx1‐1 acx2‐1 seedlings were also unable to establish photosynthetic competency in the absence of an exogenous carbon supply, a phenotype that is shared with a number of other Arabidopsis mutants disrupted in storage lipid breakdown. Germination frequency of the double mutant was significantly reduced compared with wild‐type seeds. This was unaffected by the addition of exogenous sucrose, but was improved by dormancy‐breaking treatments such as cold stratification and after‐ripening. We show that the acx1‐1, acx2‐1 and acx1‐2 acx2‐1 double mutants and the ketoacyl‐CoA thiolase‐2 (kat2) mutant exhibit a sucrose‐independent germination phenotype comparable with that reported for comatose (cts‐2), a mutant in a peroxisomal ABC transporter which exhibits enhanced dormancy. This demonstrates an additional role beyond that of carbon provision for the β‐oxidation pathway during germination or in dormant seeds.
Cloning and characterization of micro‐RNAs from moss
Authors: Arazi Tzahi , Talmor‐Neiman Mali , Stav Ran , Riese Maike , Huijser Peter , Baulcombe David C.
Published: September 2005

Micro‐RNAs (miRNAs) are one class of endogenous tiny RNAs that play important regulatory roles in plant development and responses to external stimuli. To date, miRNAs have been cloned from higher plants such as Arabidopsis, rice and pumpkin, and there is limited information on their identity in lower plants including Bryophytes. Bryophytes are among the oldest groups of land plants among the earth's flora, and are important for our understanding of the transition to life on land. To identify miRNAs that might have played a role early in land plant evolution, we constructed a library of small RNAs from the juvenile gametophyte (protonema) of the moss Physcomitrella patens. Sequence analysis revealed five higher plant miRNA homologues, including three members of the miR319 family, previously shown to be involved in the regulation of leaf morphogenesis, and miR156, which has been suggested to regulate several members of the SQUAMOSA PROMOTER BINDING‐LIKE (SPL) family in Arabidopsis. We have cloned PpSBP3, a moss SPL homologue that contains an miR156 complementary site, and demonstrated that its mRNA is cleaved within that site suggesting that it is an miR156 target in moss. Six additional candidate moss miRNAs were identified and shown to be expressed in the gametophyte, some of which were developmentally regulated or upregulated by auxin. Our observations suggest that miRNAs play important regulatory roles in mosses.
A single amino acid insertion in the WRKY domain of the Arabidopsis TIR–NBS–LRR–WRKY‐type disease resistance protein SLH1 (sensitive to low humidity 1) causes activation of defense responses and hypersensitive cell death
Authors: Noutoshi Yoshiteru , Ito Takuya , Seki Motoaki , Nakashita Hideo , Yoshida Shigeo , Marco Yves , Shirasu Ken , Shinozaki Kazuo
Published: September 2005

In this study we characterized the sensitive to low humidity 1 (slh1) mutant of Arabidopsis ecotype No‐0 which exhibits normal growth on agar plate medium but which on transfer to soil shows growth arrest and development of necrotic lesions. cDNA microarray hybridization and RNA gel blot analysis revealed that genes associated with activation of disease resistance were upregulated in the slh1 mutants in response to conditions of low humidity. Furthermore, the slh1 mutants accumulate callose, autofluorescent compounds and salicylic acid (SA). We demonstrate that SA is required for the slh1 phenotype but not PAD4 or NPR1. SLH1 was isolated by map‐based cloning and it encodes a resistance (R)‐like protein consisting of a domain with Toll and interleukin‐1 receptor homology (TIR), a nucleotide‐binding domain (NB), leucine‐rich repeats (LRR) and a carboxy‐terminal WRKY domain. SLH1 is identical to the R gene RRS1‐R of the Arabidopsis ecotype Nd‐1, a gene which confers resistance to the bacterial pathogen Ralstonia solanacearum GMI1000 and also functions as an R gene to this pathogen in No‐0. We identified a 3 bp insertion mutation in slh1 that results in the addition of a single amino acid in the WRKY domain; thereby impairing its DNA‐binding activity. Our data suggest that SLH1 disease resistance signaling may be negatively regulated by its WRKY domain in the R protein and that the constitutive defense activation conferred by the slh1 mutation is inhibited by conditions of high humidity.
Lipid‐rich tapetosomes in Brassica tapetum are composed of oleosin‐coated oil droplets and vesicles, both assembled in and then detached from the endoplasmic reticulum
Authors: Hsieh Kai , Huang Anthony H.C.
Published: September 2005

Tapetosomes are abundant organelles in tapetum cells of floral anthers in Brassicaceae species. They contain triacylglycerols (TAGs), the amphipathic protein oleosins and putative vesicles and play a predominant role in pollen‐coat formation. Here we report the biogenesis and structures of tapetosomes in Brassica. Immunofluorescence confocal microscopy revealed that during early anther development, the endoplasmic reticulum (ER) luminal protein calreticulin existed as a network in tapetum cells, which contained no oleosins. Subsequently, oleosins appeared together with calreticulin in the ER network, which possessed centers with a higher ratio of oleosin to calreticulin. Finally, the ER network largely disappeared, and solitary tapetosomes containing oleosins and calreticulin became abundant. Transmission electron microscopy also revealed a close association between a maturing tapetosome and numerous ER cisternae. Mature, solitary tapetosomes were isolated and found to contain oleosins, calreticulin and the ER luminal binding protein (BiP). Isolated tapetosomes were treated with sodium carbonate and subfractionated by centrifugation. Two morphologically distinct constituents were isolated: low‐density oil droplets, which contained oleosins and TAGs, and relatively high‐density cisternae‐like vesicles, which possessed calreticulin and BiP. Thus, tapetosomes are composed of oleosin‐coated oil droplets and vesicles, both of which are assembled in and then detached from the ER. The structure and biogenesis of tapetosomes are unique among eukaryotic organelles. After tapetum cells lyzed, oleosins but not calreticulin and BiP of tapetosomes were transferred to the pollen surface.
OsMADS1, a rice MADS‐box factor, controls differentiation of specific cell types in the lemma and palea and is an early‐acting regulator of inner floral organs
Authors: Prasad Kalika , Parameswaran Sriram , Vijayraghavan Usha
Published: September 2005

Grass flowers are highly derived compared to their eudicot counterparts. To delineateOsMADS1functions in rice floret organ development we have examined its evolution and the consequences of its knockdown or overexpression. Molecular phylogeny suggests the co‐evolution ofOsMADS1with grass family diversification.OsMADS1knockdown perturbs the differentiation of specific cell types in the lemma and palea, creating glume‐like features, with severe derangements in lemma differentiation. Conversely, ectopicOsMADS1expression suffices to direct lemma‐like differentiation in the glume. Strikingly, in manyOsMADS1knockdown florets glume‐like organs occupy all the inner whorls. Such effects in the second and third whorl are unexplained, as wild‐type florets do not expressOsMADS1in these primordia and because transcripts for rice B and C organ‐identity genes are unaffected byOsMADS1knockdown. Through a screen forOsMADS1targets we identify a flower‐specificNt‐gh3type gene,OsMGH3, as a downstream gene. The delayed transcription activation ofOsMGH3by dexamethasone‐inducibleOsMADS1suggests indirect activation. TheOsMGH3floret expression profile suggests a novel role forOsMADS1as an early‐acting regulator of second and third whorl organ fate. We thus demonstrate the differential contribution ofOsMADS1for lemma versus palea development and provide evidence for its regulatory function in patterning inner whorl organs.
Changing association between schooling levels and HIV‐1 infection over 11 years in a rural population cohort in south‐west Uganda
Authors: de Walque Damien , Nakiyingi‐Miiro Jessica S. , Busingye June , Whitworth Jimmy A.
Published: September 2005

Background  Previous studies have found that in Africa, a greater risk of HIV infection is often found in groups with higher educational attainment. However, some serial cross‐sectional studies have found greater reductions in HIV prevalence among more educated groups, especially in cohorts of young adults. More recent studies have found some instances where higher schooling levels are associated with lower HIV prevalence.

Methods  We describe changes in the association between schooling levels, HIV prevalence and condom use in a rural population‐based cohort between 1989/1990 and 1999/2000, in Masaka District, Uganda.

Results  In 1989–1990, higher educational attainment was associated with higher risk of HIV‐1 infection, especially among males, but once odds ratios are adjusted for age, no significant relation between schooling and HIV infection remains. In 1999–2000, there is, for females aged 18–29 years, a significant relationship between higher educational attainment and lower HIV prevalence, even after adjustment for age, gender, marital status and wealth (P for trend 0.01). Tests for interaction, significant for males and both genders combined, show that more schooling has been shifting towards an association with less HIV infection between 1989–1990 and 1999–2000, especially for young individuals. Condom use increased during the study period and this increase has been concentrated among more educated individuals.

Conclusions  These findings suggest that over a decade more educated young adults, especially females, have become more likely to respond to HIV/AIDS information and prevention campaigns by effectively reducing their sexual risk behaviour.
Adoption of the new antimalarial drug policy in Tanzania – a cross‐sectional study in the community
Authors: Eriksen Jaran , Nsimba Stephen E. D. , Minzi Omary M. S. , Sanga Anku J. , Petzold Max , Gustafsson Lars L. , Warsame Marian Y. , Tomson Göran
Published: September 2005

Objective  To assess the diffusion of the change of first line antimalarial drug from chloroquine (CQ) to sulphadoxine/pyrimethamine (SP) at household level in a rural district of Tanzania less than a year after the policy implementation.

Methods  Caretakers in 729 households were interviewed on knowledge of the new policy, home stocking of antimalarials, home‐treatment practices of children younger than 5 years with fever, health‐seeking behaviour and experience of SP. SP and CQ levels in blood were analysed from 328 children younger than 5 years in the households. Twelve focus group discussions (FGD) were performed with mothers, fathers and health workers.

Results  About 51% of the population knew that SP was the first line antimalarial. Only 8% of mothers stocked antimalarials, and only 4% stated self‐treatment as the first action. We estimated that 84% of the children who had had fever during the last 4 weeks sought care at public health facilities. SP was detectable in 18% of the total child population and in 32% of those with reported fever, CQ in only 5% and 7%, respectively. The FGDs revealed negative perceptions of SP and fear of severe adverse reactions with mass media reported as key informant.

Conclusion  The policy had diffused to the communities in the sense that CQ had been changed to SP, which was well known as first line treatment. Moreover, there was a reported dramatic change from self‐treatment with CQ to seeking care at public health facilities where SP was given under observation.
Fulminating varicella despite prophylactic immune globulin and intravenous acyclovir in a renal transplant recipient: should renal patients be vaccinated against VZV before transplantation?
Authors: Robertson Susan , Newbigging Karen , Carman William , Jones Gwyneth , Isles Chris ,   on behalf of the Scottish Renal Registry
Published: September 2005

Abstract:  We describe a case of fulminating varicella despite prophylactic immune globulin and intravenous acyclovir in a renal transplant recipient. This promoted a survey of all 383 adult patients awaiting a renal transplant in Scotland, which showed a low level of Varicella zoster virus (VZV) awareness but a willingness to consider vaccination if non immune. 359/363 serum samples tested were seropositive for VZV antibody giving a susceptibility to VZV of 1.2%. Although data on vaccination in adults with chronic kidney disease are limited, expert opinion is of the view that the benefits of vaccinating immunocompetent seronegative patients before transplantation are likely to outweigh the risks. We believe that adult patients awaiting a transplant in the UK should be tested for their susceptibility to VZV and that early vaccination should be offered to those who are both immunocompetent and seronegative.
B cells: a rational target in alloantibody‐mediated solid organ transplantation rejection
Authors: Pescovitz Mark D
Published: September 2005

Abstract:  Loss of allografts over time remains a barrier to achieving successful outcomes in solid organ transplantation. Although the role of donor‐specific alloantibody‐mediated mechanisms in hyperacute rejection is well known, research and management of early and late post‐transplant rejection have traditionally focused on T cell‐mediated mechanisms. However, available agents that affect T‐cell pathways have minimal impact on long‐term graft survival, suggesting that other effector mechanisms are involved. A growing body of evidence now supports a role for alloantibody‐mediated mechanisms in early and late graft rejection, which can significantly impact on long‐term graft survival. The important role of B cells in generating and perpetuating alloantibody production provides a rationale for B‐cell depletion therapy as an approach to prevent or reduce alloantibody formation before transplantation and to treat or prevent early and late alloantibody‐mediated rejection. The use of monoclonal antibodies that directly target B cells, in combination with standard alloantibody‐depleting therapies and/or immunosuppression, has been investigated in several small non‐controlled studies. Promising results suggest that this strategy warrants further investigation in larger controlled studies.
Application of the weakest‐link concept to the endurance limit of notched and multiaxially loaded specimens of carburized steel 16MnCrS5
Authors: BOMAS H. , SCHLEICHER M.
Published: September 2005

Based on the weakest‐link concept a method is developed, from which the endurance probability of every surface and volume element of a case‐hardened part, which is loaded near the endurance limit, can be calculated. A prerequisite for the calculation is knowledge of the hardness and residual stress distribution, the surface roughness and the surface oxidation depth. By multiplication of the endurance probabilities of neighboured elements the endurance probability of a limited region or of the whole part can be calculated, which includes an endurance limit determination. It is shown, that this model can be applied successfully to specimens of a carburized steel. The necessary model parameters can be gained from a set of reference specimens. Because of the possibility to formulate an endurance probability for every volume and surface element, there are no geometrical restrictions on the parts to be assessed.
Improved glycaemic control with dipeptidyl peptidase‐4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response
Authors: Ristic S. , Byiers S. , Foley J. , Holmes D.
Published: September 2005

Objective:  A novel treatment option for diabetic patients is the enhancement of incretin hormone activity by inhibition of the enzyme dipeptidyl peptidase‐4 (DPP‐4). This study was designed to establish a dose of the DPP‐4‐inhibitor vildagliptin (LAF237) that was effective in reducing HbA1c levels and was safe and well tolerated in patients with type 2 diabetes.

Patients and Methods:  The study of 279 patients with type 2 diabetes consisted of a 4‐week run‐in phase where patients received placebo and a 12‐week active treatment phase where they received one of the following dosages of vildagliptin: 25 mg twice daily, 25, 50 or 100 mg once daily (qd), or placebo.

Results:  There was a statistically significant reduction in HbA1c levels in the vildagliptin 50 mg qd (p = 0.003) and 100 mg qd groups (p = 0.004) compared with the placebo group. The mean 4‐h postprandial glucose level was significantly reduced from placebo in the vildagliptin 50 mg qd group (p = 0.012) and mean 4‐h postprandial insulin was significantly increased from baseline vs. placebo in the vildagliptin 100 mg qd group (p = 0.022). The assessment of β‐cell function (HOMA‐B) was significantly increased in the vildagliptin 100 mg qd treatment group (p = 0.007). The incidence of adverse events was similar in all treatment groups including placebo.

Conclusions:  Vildagliptin, at 50 and 100 mg qd, was effective in reducing HbA1c levels compared with placebo in patients with type 2 diabetes. Vildagliptin at dosages up to 100 mg qd appeared safe and well tolerated.
Carotid artery intima‐media thickness in patients with Type 2 diabetes mellitus and impaired glucose tolerance: a systematic review
Authors: Brohall G. , Odén A. , Fagerberg B.
Published: September 2005

Aims  To review the difference in carotid artery intima media thickness (IMT) between patients with Type 2 diabetes (DM) or impaired glucose tolerance (IGT), and control subjects.

Methods  Systematic reviews were made in order to identify cross‐sectional studies using the ultrasound method. The differences between IMT in DM or IGT and control subjects were calculated. Meta‐analysis using random‐effects modelling was used to calculate summary measures.

Results  Twenty‐three studies included 24 111 subjects; 4019 with DM and 1110 with IGT. In 20 of 21 studies, the diabetic patients had greater carotid artery IMT than the subjects in the control groups. The estimated mean difference in IMT was 0.13 (95% CI: 0.12–0.14) mm. Heterogeneity was observed and likely sources of variation were study size, diabetes duration, and ultrasound method. In three out of nine studies, the IGT patients had significant greater carotid artery IMT than the subjects in the control groups. The estimated mean difference in IMT was 0.04 (95% CI: 0.014–0.071) mm.

Conclusions  Type 2 diabetes was associated with an 0.13 mm increase in IMT compared with control subjects. In patients with IGT, the increase in IMT was about one‐third of that observed in diabetes. The observed difference in IMT can be interpreted as if the diabetes patients were more than 10 years older than the control groups, and that the relative risks of myocardial infarction and stroke were increased by almost 40%, respectively.
IL‐18 gene polymorphism confers susceptibility to the development of anti‐GAD65 antibody in Graves’ disease
Authors: Hiromatsu Y. , Mukai T. , Kaku H. , Miyake I. , Ichimura M. , Fukutani T. , Nakayama H. , Takata K. , Imamura Y. , Shoji S. , Yamada K. , Koda Y. , Bednarczuk T.
Published: September 2005

Aims  This study aimed to investigate whether interleukin‐18 (IL‐18) gene polymorphisms are associated with the development of antibody against the 65‐kDa isoform of recombinant human glutamic acid decarboxylase (GAD65Ab) in patients with Graves’ disease.

Methods  A total of 398 unrelated Japanese patients with Graves’ disease, with and without GAD65Ab, were recruited. Three single nucleotide polymorphisms in the IL‐18 gene were examined and the polymorphic allele and the genotype and haplotype frequencies calculated.

Results  The frequency of the GG genotype at position −4675 of the IL‐18 gene was significantly lower in Graves’ disease patients with GAD65Ab than those without (4% vs. 24%, P = 0.0126). The −4675C allele frequency was significantly greater in patients with GAD65Ab than those without (69% vs. 53%, P = 0.0168). The homozygous −4675G/−607A/−137G haplotype was less common in Graves’ disease patients with GAD65Ab than those without (4% vs. 23%, P = 0.0144).

Conclusions  These findings in a Japanese population indicate that Graves’ disease patients carrying the GG genotype at position −4657 of the promoter of the IL‐18 gene or a gene in linkage disequilibrium with the −4675G/−607A/−137G haplotype have a low risk for the development of GAD65Ab in Graves’ disease.
Plasma anhydro‐d‐glucitol (1,5‐AG) as an indicator of hyperglycaemic excursions in pregnant women with diabetes
Authors: Dworacka M. , Wender‐Ożegowska E. , Winiarska H. , Borowska M. , Zawiejska A. , Pietryga M. , Brazert J. , Szczawinska K. , Bobkiewicz‐Kozłowska T.
Published: September 2005

Aims  To evaluate the use of the plasma 1,5‐anhydro‐d‐glucitol (1,5‐AG) level as a possible marker for glucose excursions in pregnant women with diabetes.

Methods  The study group consisted of 55 pregnant women with diabetes (gestational diabetes mellitus—GDM, n = 28 or pre‐gestational diabetes mellitus —PGDM, n = 27), without hepatic or renal insufficiency, gestational age range 5–38 weeks. In each patient, 24‐h glucose profile, glycated haemoglobin and 1,5‐AG plasma levels were measured. Mean blood glucose (MBG) and M‐value (by Schlichtkrull) were calculated. MBG, M‐value and maximal daily glycaemia (MxG) were used as indexes of daily glycaemic excursions.

Results  A significant correlation was found between the 1,5‐AG plasma level and MxG [r = (−0.3)] and between the 1,5‐AG level and M‐value [r = (−0.36)]. There was no association between the 1,5‐AG level and gestational age. Multivariate regression analysis, with 24‐h glucose profile, gestational age and MxG as independent variables, showed that MxG was the main parameter determining the 1,5‐AG plasma level [β = (−0.68)]. The M‐value, the coefficient of glucose fluctuations, also determined the 1,5‐AG level but with lower statistical power [β = (0.41)]. No statistical differences were found in the group with HbA1c < 6% or > 6% for 1,5‐AG and M‐value, while MBG was higher in poorly controlled patients (HbA1c > 6%).

Conclusions  The plasma 1,5‐AG level may be a useful marker of daily glucose excursion in pregnant women with diabetes, as an adjunct to HbA1c monitoring.
Mobile diabetes education and care: intervention for children and young people with Type 1 diabetes in rural areas of northern Germany
Authors: Von Sengbusch S. , Müller‐Godeffroy E. , Häger S. , Reintjes R. , Hiort O. , Wagner V.
Published: September 2005

Aims  To improve the quality of care in children with Type 1 diabetes who have limited access to specialized diabetes care in rural areas, by providing a mobile diabetes education and care team, affiliated with a University hospital paediatric diabetes centre.

Methods  A cohort of 107 children and their families from eight rural hospitals was followed between July 2000 and July 2002. Parameters on quality of metabolic control (HbA1c, hospitalization rate and number of episodes of severe hypoglycaemia), diabetes knowledge and quality of life at baseline (t0), 6 weeks (t1) and 6 months (t2) after the interventions were measured.

Results  Mean HbA1c was 7.9 ± 1.4% at t0. The proportion of HbA1c values < 6.8% increased significantly (P < 0.05) and of values > 8.0% decreased significantly (P < 0.01) at t1 and t2. The rate of hospitalization fell significantly by 9.4%, from 16.2% at baseline to 6.8% at t2 (P < 0.05). The children reported significantly better diabetes‐specific quality of life (P < 0.05) and higher self‐esteem (P < 0.01) after the intervention. Theoretical diabetes knowledge was increased both in the short and long term (P < 0.05).

Conclusions  The intervention improved metabolic control, diabetes knowledge and diabetes‐specific quality of life. We conclude that high‐quality diabetes care in a rural area can be provided by a mobile diabetes education and care team.
Short‐term effects of severe dietary carbohydrate‐restriction advice in Type 2 diabetes—a randomized controlled trial
Authors: Daly M. E. , Paisey R. , Paisey R. , Millward B. A. , Eccles C. , Williams K. , Hammersley S. , MacLeod K. M. , Gale T. J.
Published: September 2005

Objective  This study sought to examine the effects of a 3‐month programme of dietary advice to restrict carbohydrate intake compared with reduced‐portion, low‐fat advice in obese subjects with poorly controlled Type 2 diabetes.

Research design and methods  One hundred and two patients with Type 2 diabetes were recruited across three centres and randomly allocated to receive group education and individual dietary advice. Weight, glycaemic control, lipids and blood pressure were assessed at baseline and 3 months. Dietary quality was assessed at the end of study.

Results  Weight loss was greater in the low‐carbohydrate (LC) group (−3.55 ± 0.63, mean ± sem) vs. −0.92 ± 0.40 kg, P = 0.001) and cholesterol : high‐density lipoprotein (HDL) ratio improved (−0.48 ± 0.11 vs. −0.10 ± 0.10, P = 0.01). However, relative saturated fat intake was greater (13.9 ± 0.71 vs. 11.0 ± 0.47% of dietary intake, P < 0.001), although absolute intakes were moderate.

Conclusions  Carbohydrate restriction was an effective method of achieving short‐term weight loss compared with standard advice, but this was at the expense of an increase in relative saturated fat intake.
Boundary Value Problems for Third‐Order Nonlinear Ordinary Differential Equations
Authors: Sachdev P. L. , Bujurke N. M. , Awati V. B.
Published: September 2005

In this paper, we describe how to analyze boundary value problems for third‐order nonlinear ordinary differential equations over an infinite interval. Several physical problems of interest are governed by such systems. The seminumerical schemes described here offer some advantages over solutions obtained by using traditional methods such as finite differences, shooting method, etc. These techniques also reveal the analytic structure of the solution function. For illustrative purposes, several physical problems, mainly drawn from fluid mechanics, are considered; they clearly demonstrate the efficiency of the techniques presented here.
The Tallest Column—A Dynamical System Approach Using a Symmetry Solution
Authors: Farjoun Yossi , Neu John
Published: September 2005

A classic problem, the design of the tallest column, is solved again using a different method. By the use of a similarity solution the equations are transformed and the difficult singularity at the endpoint is peeled away. The resulting autonomous system has a critical point and the solution must be on its stable manifold. The solution is found by starting near the critical point in the direction of the stable manifold, and solving backward numerically. This removes the need for an iterative integration method that was previously used. The method is shown to work for clamped or hinged boundary condition and can also be used for other problems involving singularities at the endpoints.
Pyoderma gangrenosum coexisting with acute myelogenous leukaemia
Authors: Krauze E , Brzezińska‐Wcisło L , Kamińska‐Winciorek G , Wyglȩdowska‐Kania M , Sygula E
Published: August 2005

The frequency of occurrence of malignant neoplasms in the cases of pyoderma gangrenosum is not exactly determined, but it can be assessed to be at 7%.

The aim of the study was to report a 26‐year‐old male patient with pyoderma gangrenosum coexisting with acute myelogenous leukaemia.

The first skin lesions on both tibia occurred in June 2001. Prior to the proper diagnosis of pyoderma gangrenosum, the patient was treated surgically. Because of the dramatic dermatological and general condition in November 2001, the patient was admitted to the Dermatological Department of the Silesian Medical Academy in Katowice where the diagnosis of pyoderma gangrenosum was established.

On the clinical and biochemical picture, the diagnosis of pyoderma gangrenosum within acute myelogenous leukaemia was made.

Initially, cyclosporin A 200 mg orally per day in the therapy of pyoderma gangrenosum was administered to achieve a slight clinical improvement. Although chemotherapy leukaemia was performed, the patient died after 4 months of the confirmation of the acute myelogenous leukaemia diagnosis.
Merkel cell carcinoma: a clinicopathological study of 11 cases
Authors: Acebo E , Vidaurrazaga N , Varas C , Burgos‐Bretones JJ , Díaz‐Pérez JL
Published: August 2005

Objective  To report our 12‐year experience with Merkel cell carcinomas (MCCs) from a clinical and pathological point of view.

Subjects and setting  Eleven MCCs were diagnosed at our institution between 1991 and 2002.

Methods  A retrospective clinical, histopathological and immunohistochemical study was performed. Age, gender, location, size, stage, treatment and follow‐up data were collected. Histopathological pattern and immunohistochemical study with CAM 5.2, cytokeratin 20 (CK20), CK7, Ber EP4, neurofilaments, synaptophysin, chromogranin, S100 protein, p53 protein, CD117, leucocyte common antigen (LCA) and Ki‐67 were accomplished.

Results  Six females and five males with a mean age of 82 years were identified. Tumours were located on the face (n = 6), extremities (n = 3) and trunk (n = 1). At diagnosis, one patient was in stage Ia, six in stage Ib, three in stage II and one in stage III. All but one patient experienced wide surgical excision of the tumour. Additional treatment consisted of lymph node dissection in two patients, radiotherapy in four patients and systemic chemotherapy in one patient. Local recurrence developed in five patients. Three patients died because of MCC after 14 months of follow‐up. Intermediate‐size round cell proliferation was found in all cases. Additional small‐size cell pattern and trabecular pattern were observed in seven and six cases, respectively. Eccrine and squamous cell differentiation were found in three cases. A dot‐like paranuclear pattern was observed in all cases with CAM 5.2 and neurofilaments, and in 89% of cases with CK20. Seventy‐five per cent of cases reacted with Ber EP4, chromogranin and synaptophysin, 70% with p53, 22% with S100 protein, 55% with CD117 and none with LCA. Ki‐67 was found in 75% of tumoral cells on average. Fifty per cent of MCCs reacted with CK7 and showed eccrine differentiation areas.

Conclusions  MCC is an aggressive neuroendocrine tumour of the elderly. Wide surgical excision is the recommended treatment. Lymph node dissection, adjuvant radiotherapy and chemotherapy decrease regional recurrences but have not been demonstrated to increase survival. Immunohistochemically, MCC is an epithelial tumour with neuroendocrine features.
Alopecia areata treatment with a phototoxic dose of UVA and topical 8‐methoxypsoralen
Authors: Mohamed Z , Bhouri A , Jallouli A , Fazaa B , Kamoun MR , Mokhtar I
Published: August 2005

Twenty‐five patients with alopecia totalis (AT) or alopecia universalis and 124 patients with alopecia areata (AA) were treated with photochemotherapy, combining topical 8‐methoxypsoralen (8‐MOP) with UV irradiation of the scalp at a phototoxic dose. The mean energy required was 15 J/cm2 for AA and 42 J/cm2 for AT. Ninety‐four patients had multiple bald patches and 12 with AT had complete or > 50% hair regrowth. Positive treatment results did not seem to depend on the age of onset or the duration of the disease. Few side‐effects of topical psoralens plus UVA (PUVA) treatment were noted, except a for few days of slight erythema caused by the high dose of UV.