bluuebunny/crossref_metadata_2025 huggingface dataset:
Mimicking the Motion of Life: Catalytically Active Rotaxanes as Processive Enzyme Mimics
Authors: Thordarson Pall , Nolte Roeland J. M. , Rowan Alan E.
Published: April 2004

An often overlooked but essential architectural motif found in all living organisms is that of the toroid. Through evolution, nature has used the threading of biopolymers through toroidal assemblies, forming pseudo-rotaxanes, to impart a processive character on the synthesis, replication, repair, and even recombination of DNA. In spite of the fact that numerous processive enzymes have been reported and that life would not exist without such natural rotaxanes, there are virtually no examples of synthetic processive catalysts let alone biomimetic models of these essential and potentially useful systems. To rectify this omission we describe below our recent construction and study of the first catalytic rotaxane molecular machine, which can run along a polymer thread and carry out processive oxidative reactions.
Sexual reproduction in Chondrilla australiensis (Porifera:Demospongiae)
Authors: Usher Kayley M. , Sutton David C. , Toze Simon , Kuo John , Fromont Jane
Published: April 2004

Increasingly, sponges are being used as models for a wide range of biological systems. However, little is known about the reproductive biology of a group that has been shown to lack gonads or gonadal ducts. The development of gametes in the oviparous demosponge Chondrilla australiensis at Fremantle, Western Australia, was investigated using light microscopy and transmission electron microscopy over 5 years. Results indicate that C. australiensis is gonochoric and oviparous. Egg and sperm development were first apparent inside choanocyte chambers, with both types of gamete apparently developing from choanocytes. During egg development, large numbers of nurse cells appeared attached to eggs, with which they fused at the time of spawning. The origin of the nurse cells remains unclear, but they may also have a choanocyte origin. Eggs took 4 weeks to develop and sperm took approximately 2 weeks, during which time the nucleus condensed and the cytoplasm reduced. Mature sperm could occupy almost the entire matrix of fecund males and were not contained in cysts. Spawning occurred in late summer and autumn over a period of 4–5 days, when the tides were at the maximum height for the month.
Mechanistic studies of the molybdenum-catalyzed asymmetric alkylation reaction
Authors: Hughes David L. , Lloyd-Jones Guy C. , Krska Shane W. , Gouriou Laure , Bonnet Veronique D. , Jack Kevin , Sun Yongkui , Mathre David J. , Reamer Robert A.
Published: April 2004

Enantiomerically enriched, deuterated branched carbonates (
Z
)-(
S
)-PhCH(OCO
2
Me)-CH = CHD (1-D), (
Z
)-(
R
)-PhCH(OCO
2
Me)CH = CHD (2-D), and linear carbonate (
E
)-(
S
)-PhCH = CHCHD(OCO
2
Me) (3-D) were used as probes in the Mo-catalyzed asymmetric allylic alkylation with sodium dimethyl malonate, catalyzed by ligand-complex 11 derived from the mixed benzamide/picolinamide of (
S
,
S
)-transdiaminocyclohexane and (norbornadiene)Mo(CO)
4
. The results of these studies, along with x-ray crystallography and solution NMR structural analysis of the π-allyl intermediate, conclusively established the reaction proceeded by a retention–retention pathway. This mechanism contrasts with that defined for Pd-catalyzed allylic alkylations, which proceed by an inversion–inversion pathway. A proposed rationale for the retention pathway for nucleophilic substitution involves CO-coordination to form a tri-CO intermediate, followed by complexation with the anion of dimethyl malonate to produce a seven-coordinate intermediate, which reductively eliminates to afford product with retention of configuration.
A target site for template-based design of measles virus entry inhibitors
Authors: Plemper Richard K. , Erlandson Karl J. , Lakdawala Ami S. , Sun Aiming , Prussia Andrew , Boonsombat Jutatip , Aki-Sener Esin , Yalcin Ismail , Yildiz Ilkay , Temiz-Arpaci Ozlem , Tekiner Betul , Liotta Dennis C. , Snyder James P. , Compans Richard W.
Published: April 2004

Measles virus (MV) constitutes a principal cause of worldwide mortality, accounting for almost 1 million deaths annually. Although a live-attenuated vaccine protects against MV, vaccination efficiency of young infants is low because of interference by maternal antibodies. Parental concerns about vaccination safety further contribute to waning herd immunity in developed countries, resulting in recent MV outbreaks. The development of novel antivirals that close the vaccination gap in infants and silence viral outbreaks is thus highly desirable. We previously identified a microdomain in the MV fusion protein (F protein) that is structurally conserved in the paramyxovirus family and constitutes a promising target site for rationally designed antivirals. Here we report the template-based development of a small-molecule MV inhibitor, providing proof-of-concept for our approach. This lead compound specifically inhibits fusion and spread of live MV and MV glycoprotein-induced membrane fusion. The inhibitor induces negligible cytotoxicity and does not interfere with receptor binding or F protein biosynthesis or transport but prevents F protein-induced lipid mixing. Mutations in the postulated target site alter viral sensitivity to inhibition.In silicodocking of the compound in this microdomain suggests a binding model that is experimentally corroborated by a structure-activity analysis of the compound and the inhibition profile of mutated F proteins. A second-generation compound designed on the basis of the interaction model shows a 200-fold increase in antiviral activity, creating the basis for novel MV therapeutics. This template-based design approach for MV may be applicable to other clinically relevant members of the paramyxovirus family.
Comparative Recombination Rates in the Rat, Mouse, and Human Genomes
Authors: Jensen-Seaman Michael I. , Furey Terrence S. , Payseur Bret A. , Lu Yontao , Roskin Krishna M. , Chen Chin-Fu , Thomas Michael A. , Haussler David , Jacob Howard J.
Published: April 2004

Levels of recombination vary among species, among chromosomes within species, and among regions within chromosomes in mammals. This heterogeneity may affect levels of diversity, efficiency of selection, and genome composition, as well as have practical consequences for the genetic mapping of traits. We compared the genetic maps to the genome sequence assemblies of rat, mouse, and human to estimate local recombination rates across these genomes. Humans have greater overall levels of recombination, as well as greater variance. In rat and mouse, the size of the chromosome and proximity to telomere have less effect on local recombination rate than in human. At the chromosome level, rat and mouse X chromosomes have the lowest recombination rates, whereas human chromosome X does not show the same pattern. In all species, local recombination rate is significantly correlated with several sequence variables, including GC%, CpG density, repetitive elements, and the neutral mutation rate, with some pronounced differences between species. Recombination rate in one species is not strongly correlated with the rate in another, when comparing homologous syntenic blocks of the genome. This comparative approach provides additional insight into the causes and consequences of genomic heterogeneity in recombination.
Regulatory Potential Scores From Genome-Wide Three-Way Alignments of Human, Mouse, and Rat
Authors: Kolbe Diana , Taylor James , Elnitski Laura , Eswara Pallavi , Li Jia , Miller Webb , Hardison Ross , Chiaromonte Francesca
Published: April 2004

We generalize the computation of the Regulatory Potential (RP) score from two-way alignments of human and mouse to three-way alignments of human, mouse, and rat. This requires overcoming technical challenges that arise because the complexity of the models underlying the score increases exponentially with the number of species. Despite the close evolutionary proximity of rat to mouse, we find that adding the rat sequence increases our ability to predict genomic sites that regulate gene transcription. A variant of the RP scoring scheme that accounts for local variation in neutral mutational patterns further improves our predictions.
Occurrence and Consequences of Coding Sequence Insertions and Deletions in Mammalian Genomes
Authors: Taylor Martin S. , Ponting Chris P. , Copley Richard R.
Published: April 2004

Nucleotide insertion and deletion (indel) events, together with substitutions, represent the major mutational processes of gene evolution. Through the alignment of 8148 orthologous genes from human, mouse, and rat, we have identified 1743 indel events within rodent protein-coding sequences. Using human as an out-group, we reconstructed the mutational event underlying each of these indels. Overall, we found an excess of deletions over insertions, particularly for the rat lineage (70% excess). Sequence slippage accounts for at least 52% of insertions and 38% of deletions. We have also evaluated the selective tolerance of identifiable protein structures to indels. Transmembrane domains are the least, and low complexity regions, the most tolerant. Mapping of indels onto known protein structures demonstrated that structural cores are markedly less tolerant to indels than are loop regions. There is a specific enrichment of CpG dinucleotides in close proximity to insertion events, and both insertions and deletions are more common in higher G+C content sequences.
Comparative Analysis of the α-Like Globin Clusters in Mouse, Rat, and Human Chromosomes Indicates a Mechanism Underlying Breaks in Conserved Synteny
Authors: Tufarelli Cristina , Hardison Ross , Miller Webb , Hughes Jim , Clark Kevin , Ventress Nicki , Frischauf Anna Maria , Higgs Douglas R.
Published: April 2004

We have sequenced and fully annotated a 65,871-bp region of mouse Chromosome 17 including the Hba-ps4 α-globin pseudogene. Comparative sequence analysis with the functional α-globin loci at human Chromosome 16p13.3 and mouse Chromosome 11 shows that this segment of mouse Chromosome 17 contains a group of three α-like pseudogenes (Hba-psm–Hba-ps4–Hba-q3), similar to the duplicated sets found at the functional mouse cluster on Chromosome 11. In addition, exons 7 to 12 of the mLuc7L gene are present just downstream from the pseudogene cluster, indicating that this clone contains the region in which human 16p13.3 switches in synteny between mouse Chromosomes 11 and 17. Comparison of the sequences around the α-like clusters on the two mouse chromosomes reveals the presence of conserved tandem repeats. We propose that these repetitive elements have played a role in the fragmentation of the mouse α cluster during evolution.
Dynamic Building of a BAC Clone Tiling Path for the Rat Genome Sequencing Project
Authors: Chen Rui , Sodergren Erica , Weinstock George M. , Gibbs Richard A.
Published: April 2004

CLONEPICKER is a software pipeline that integrates sequence data with BAC clone fingerprints to dynamically select a minimal overlapping clone set covering the whole genome. In the Rat Genome Sequencing Project (RGSP), a hybrid strategy of “clone by clone” and “whole genome shotgun” approaches was used to maximize the merits of both approaches. Like the “clone by clone” method, one key challenge for this strategy was to select a low-redundancy clone set that covered the whole genome while the sequencing is in progress. The CLONEPICKER pipeline met this challenge using restriction enzyme fingerprint data, BAC end sequence data, and sequences generated from individual BAC clones as well as WGS reads. In the RGSP, an average of 7.5 clones was identified from each side of a seed clone, and the minimal overlapping clones were reliably selected. Combined with the assembled BAC fingerprint map, a set of BAC clones that covered >97% of the genome was identified and used in the RGSP.
Low umbilical artery vascular flow resistance and fetal outcome
Authors: Olofsson Per , Olofsson Hanna , Molin Johan , Maršál Karel
Published: April 2004

Background.  An abnormally high [above mean + 2 standard deviations (SD)] umbilical artery (UA) pulsatility index (PI) indicates impaired fetal outcome, whereas the impact of an “abnormally” low (below mean −2 SD) PI is unknown.

Methods.  Perinatal outcome was compared between cases with a UA PI less than mean −2 SD (group A: high‐risk cases selected from a database, n = 330; group B: unselected cases, n = 39) and unselected controls (group C) with a PI within mean ± 2 SD (n = 863) at Doppler velocimetry. Groups B and C were retrieved from a population‐based sample. The unpaired t‐test, Mann–Whitney U‐test, χ2‐test and Fisher's exact probability test were used for statistical comparisons with a two‐tailed p < 0.05 being significant.

Results.  No significant differences were found between group A vs. group C and group B vs. group C regarding perinatal mortality, Apgar scores at 1, 5 or 10 min, or arterial or venous cord blood pH. Postterm pregnancy in group A carried no additional risk. For obvious reasons, operative delivery and neonatal intensive care were more common in group A than in group C, but no such differences were found between groups B and C. The mean birthweight was 3.7% higher in group B than in group C (p = 0.049).

Conclusions.  Deeming a UA PI below the lower reference limit as “abnormally” low is a statistical definition that was not reflected by a biological imperfection. Instead, a low UA PI promoted fetal growth.
The validity of self‐reported use of hormone replacement therapy among Danish nurses
Authors: Løkkegaard Ellen Leth , Johnsen SØren Påske , Heitmann Berit Lillienthal , Stahlberg Claudia , Pedersen Anette TØnnes , Obel Erik Bernhard , Hundrup Yrsa Andersen , Hallas Jesper , SØrensen Henrik Toft
Published: April 2004

Background.  Recent findings from randomized clinical trials on the effects of hormone replacement therapy (HRT) among postmenopausal women contradict findings from observational studies indicating a protective effect on the development of cardiovascular disease. Most observational studies on HRT are based on self‐reported data, although data on the validity of HRT in postmenopausal women are sparse.

Methods.  We examined self‐reported HRT use from questionnaires administered in 1993 (n = 2694) and again in 1999 (n = 2666) to a cohort of Danish nurses living in two Danish counties compared with prescription‐reimbursement data from two administrative databases through the Danish National Health Service.

Results.  The sensitivity and specificity of the self‐reported, current HRT use in 1993 were 78.4%[95% confidence interval (95% CI) 75.4–81.4] and 98.4% (95% CI 97.8–98.9), respectively. In 1999, the estimates were 74.8% (95% CI 72.0–77.7) and 98.0% (95% CI 97.3–98.8), respectively. None of the factors examined − including age, alcohol intake, physical activity, smoking, presence of hypertension, and body mass index − was strongly associated with validity. We found a relatively high validity of self‐reported data on HRT use. Furthermore, agreement between self‐reported and registry‐based data was not strongly associated with a range of demographic and lifestyle factors.

Conclusion.  These findings suggest that use of self‐reported data is not an important contributor to the apparent discrepancy between observational studies and randomized trials on the cardiovascular effects of HRT use.
Association of −634G/C and 936C/T polymorphisms of the vascular endothelial growth factor with spontaneous preterm delivery
Authors: Papazoglou Dimitrios , Galazios Georgios , Koukourakis Michael I. , Kontomanolis Emmanuel N. , Maltezos Efstratios
Published: April 2004

Background.  There is convincing evidence for a central role of vascular endothelial growth factor (VEGF) in fetal and placental angiogenesis. Our present study was undertaken to examine the possible relationship between two common functional VEGF gene polymorphisms (− 634G/C and 936C/T), linked with altered VEGF gene responsiveness, and spontaneous preterm delivery.

Methods.  Genomic DNA was extracted from whole blood from 54 women with preterm labor and 79 menopausal women with at least two term spontaneous labors. DNA samples were analyzed by polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP).

Results.  Individuals with 936T/T or 936C/T genotype demonstrated a statistically significant association with preterm delivery compared with those sharing 936C/C genotype [P = 0.0009, risk factor 2.05, 95% confidence interval (CI) 1.37–3.06]. There were no significant associations between spontaneous preterm delivery and − 634 genotypes.

Conclusion.  An association was demonstrated between the VEGF 936C/T polymorphism and deliveries before 37 weeks of gestation.
Evaluating Qualitative Research in Social Geography: Establishing ‘Rigour’ in Interview Analysis
Authors: Baxter Jamie , Eyles John
Published: April 2004

A review of 31 empirical and eighteen substantive papers by qualitative social geographers mainly using in‐depth interviews reveals little explicit reference to the principle(s) adopted to enhance ‘rigour’ and to ensure meaningful inference. Given the modest explicit discussion of evaluative criteria in these papers, a scheme from evaluation research itself is critically reviewed. A set of evaluation questions derived from this review and their application to an empirical piece of qualitative work frame an argument for a general set of criteria rather than rigid rules for assessing qualitative work. Such criteria can serve as anchor points for qualitative evaluation.
Debunking the Myth of Localized Agglomerations: The Development of a Regionalized Service Economy in South‐East England
Authors: Coe Neil M , Townsend Alan R
Published: April 2004

The central argument of this paper is that localized clusters of economic activity, or ‘agglomerations’, have been overemphasized in economic geography since the mid‐1980s. In particular, such analyses are too manufacturing‐biased, and place too much weight on the importance of local supply, market and partnership linkages. We will re‐emphasize the service‐based nature of growth in the core region of the UK economy, and will explore how a broad band of producer service activity is emerging in the Western Arc, owing largely to common locational logics, including back‐office decentralization and the new firm‐formation process. Such growth is both stimulated and supported by the high demand levels of the regional economy, but evidence suggests that the linkages of such firms extend well beyond the ‘local’, to cover at least the ‘Greater South‐East’. Furthermore, the international element in service growth needs to be recognized, as highlighted by the concentration of US foreign direct investment in the software industry along the M4 corridor. When areas outside the South‐East are considered (such as Edinburgh, Tyne and Wear, Cheshire), the evidence appears to support Allen's (1992) notion of a ‘regionalized mode of service growth’ in the South‐East.
Wild(er)ness: Reconfiguring the Geographies of Wildlife
Authors: Whatmore Sarah , Thorne Lorraine
Published: April 2004

Amidst millennial talk of the ‘end of nature’ (McKibben 1989), this paper examines the precarious geographies of ‘wildlife’ in rather less apocalyptic terms. Animal (and plant) species designated wild are placed categorically outside the ambit of ‘human society’, confined to inhabiting the margins and interstices of the social world. Yet, we contend, such animals have long been routinely imagined and organized within multiple circuits of social power, which (re)configure them in important ways. These social orderings of animal life confound the moral geographies of wilderness, which presuppose an easy coincidence between the species and spaces of a pristine nature. In this paper, we employ the fluid spatial vocabulary of topology to map a more volatile and relational conception of the fabrics of wildlife. Our arguments are worked through glimpses of two historically very different social orderings of ‘wild’ animals – those associated with the military vernacular of the gladiatorial games of Imperial Rome, and the scientific vernacular of endangered species listing and conservation under CITES (the Convention on the International Trade in Endangered Species). These ‘foldings’ of wildlife in distant time/space aim to disrupt the linear historical narratives of ‘civilization’ and ‘evolution’, which consign wildlife to marginal spaces with a teleological destiny of erasure.
The Partisan Impacts of Non‐Partisan Redistricting: Northern Ireland 1993–95
Authors: Rossiter D J , Johnston R J , Pattie C J
Published: April 2004

Space is manipulated for political purposes in a great variety of ways, and its restructuring is frequently a focus of conflict. The nature of such conflict is explored here.1 Legislation requires that all parliamentary constituencies in the United Kingdom are periodically reviewed by independent Boundary Commissions. The Fourth Periodic Review in Northern Ireland began in 1993 and coincided with a period of intense political activity, associated with what was commonly termed ‘the peace process’. Political parties, anxious to ensure that the resulting boundaries favoured their partisan interests (and, in the case of Sinn Fein, keen to establish their democratic bona fides), invested considerable effort in their attempts to influence the outcome. The Commissions' recommendations became the subject of claim and counter‐claim regarding bias towards one or other of the province's two main communities – Nationalist and Unionist – and as a result of that conflict, they were revised with priority given to a different criterion. This paper evaluates those claims with a close inspection of the redistricting process, illustrating how an ostensibly non‐partisan process is partisan in both its conduct and its outcome.
‘Hired Hands’ or ‘Local Voice’: Understandings and Experience of Local Participation in Conservation
Authors: Goodwin Philip
Published: April 2004

In recent years, the notion of local participation has emerged as a major force in both policy‐making and political philosophy. This paper explores the role that participation is playing in mediating relations between local people, conservation organizations and the ideas and practices of nature conservation in England. Drawing upon empirical research in the county of Kent, the paper argues that there are systematic discrepancies between the motives, experiences and understandings of the various policy actors towards the theory and practice of a participatory conservation. It argues that these apparent discrepancies have serious implications for both the credibility and the effectiveness of present initiatives, whereby participatory practice serves to reshape existing conceptions of conservation and rural space.
Reformulating Identities: British Settlers in Early Nineteenth‐Century South Africa
Authors: Lester Alan
Published: April 2004

This paper examines the formation of a colonial identity among settlers from the British Isles who were relocated to the eastern frontier of the Cape Colony in 1820. It suggests that material aspirations united certain of the settlers in a political programme, and thus began the erosion of imported class (and other) divisions. However, it argues that their establishment as a capitalist colonial class is an insufficient explanation for their construction of a shared and emotive British settler identity. The settlers modified their inherited discourses of class, race, gender and nationality in order to forge solidarity, and the imperative for solidarity derived not so much from their mutual desire for accumulation, but from a corresponding collective insecurity. Not only were settlers afraid of Khoikhoi labour rebellion and Xhosa reprisals for land loss; they also feared abandonment by a seemingly unsympathetic metropole. Their aggressive capitalist endeavour, and collective fear of its destabilizing consequences, were two sides of the same coin, informing the development of a unifying social identity. The paper goes on to consider the mechanisms through which that identity was sustained, including acts of landscape representation, the textual generation of collective memory and the practice of communally binding, quotidian, gendered routines.
How New is the New Local Governance? Lessons from the United Kingdom
Authors: Imrie Rob , Raco Mike
Published: April 2004

In recent times, a conventional wisdom concerning the governance of cities has emerged. It revolves around the contention that policy and planning frameworks are increasingly closed off from public and democratic accountability, in order to facilitate the pursuit of efficiency over equity objectives. The implication is that ‘old’ styles of governance were more open and accountable, while the ‘new’ seek to close off debate and streamline procedures. Yet the evidence to sustain such claims seems limited; this paper situates the policies and practices of local government in the UK within a historical perspective, and develops the contention that the claimed differences between old and new styles of governance are overdrawn. Using empirical material from two UK cities, we demonstrate that there are significant continuities in the procedures and practices of policy‐makers, in terms of policy objectives, styles and modes of accountability. In this sense, greater clarity is required in terms of what constitutes both the old and new modes of local governance in the British cities.
Embodiment, Power and the Politics of Mobility: The Case of Female Tramps and Hobos
Authors: Cresswell Tim
Published: April 2004

Mobility and travel have recently attracted the interest of many people, both inside and outside geography. This interest has often focused on issues of gender. Mobile women, in particular, have been seen to be indicative of wider social and cultural themes of power, exclusion, resistance and emancipation. In this paper, I consider the gendered dimensions of a moral panic in the United States between 1869 and 1940, known as the ‘tramp scare’. I argue that the construction of the panic around threats to women's bodies and the actual experience of female tramps illuminates a clearly gendered and embodied politics of mobility.
The Location and Concentration of Businesses in Britain: Business Clusters, Business Services, Market Coverage and Local Economic Development
Authors: Bennett Robert J , Graham Daniel J , Bratton William
Published: April 2004

An important debate has recently developed around the significance of business clusters for the development of the economy. This paper assesses the extent to which concentrated clusters of businesses exist in Britain, using the fine spatial mesh of postcode districts. It identifies the major clusters using a development of the methodology to define local labour market areas. The paper demonstrates the high degree of localization and uneven development of businesses in Britain. It also shows that business service firms are even more highly localized and clustered than other businesses. Moreover, the larger the business centre, the more localized and clustered the firms. The pattern suggests that there is a strong influence of increasing returns of scale, and that, as well as local clusters, much of the British economy is covered by one metacluster. Implications from these results are drawn for the likely future development of the economy, the location of business service suppliers in order to develop their market coverage, and local economic development policy.
Pattern and regulation of cell proliferation during murine ureteric bud development
Authors: Michael Lydia , Davies Jamie A.
Published: April 2004

Branched epithelia determine the anatomy of many mammalian organs; understanding how they develop is therefore an important element of understanding organogenesis as a whole. In recent years, much progress has been made in identifying paracrine factors that regulate branching morphogenesis in many organs, but comparatively little attention has been paid to the mechanisms of morphogenesis that translate these signals into anatomical change. Localized cell proliferation is a potentially powerful mechanism for directing the growth of a developing system to produce a specific final morphology. We have examined the pattern of cell proliferation in the ureteric bud system of the embryonic murine metanephric kidneys developing in culture. We detect a zone of high proliferation at the site of the presumptive ureteric bud even before it emerges from the Wolffian duct and later, as ureteric bud morphogenesis continues, proliferation is localized mainly in the very tips of the branching epithelium. Blocking cell cycling using methotrexate inhibits ureteric bud emergence. The proliferative zone is present at ureteric bud tips only when they are undergoing active morphogenesis; if branching is inhibited either by treatment with natural negative regulators (TGF‐β) or with antagonists of natural positive regulators (GDNF, glycosaminoglycans) then proliferation at the tips falls back to levels characteristic of the stalks behind them. Our results suggest that localized proliferation is an important morphogenetic mechanism in kidney development.
Topical corticosteroid allergy in an urban Australian centre
Authors: Keegel Tessa , Saunders Helen , Milne Roger , Sajjachareonpong Praneet , Fletcher Ashley , Nixon Rosemary
Published: April 2004

The reported prevalence of allergic contact dermatitis from topical corticosteroids in clinical populations, in the period 1993–2002, varied from 0.55 to 5.98%. This study is a retrospective analysis of 1153 individuals undergoing routine patch testing in an Occupational Dermatology Clinic in Melbourne, Australia. We report a rate of 0.52% for positive patch test reactions to 5 corticosteroids. Corticosteroids tested were betamethasone‐17‐valerate, budesonide, Diprosone® cream (betamethasone diproprionate 0.05%) (Essex‐Pharma, a division of Schering‐Plough Pty Ltd, Sydney, Australia), tixocortol‐21‐pivalate and triamcinolone acetonide. Population characteristics were described using the MOAHL (M = percentage of males tested; O = occupational; A = atopics; H = patients with hand eczema; L = patients with leg ulcers or stasis eczema) index. Prescribing patterns, rate of referral and rate of relevant positive patch test reactions were characterized for the region. These results were compared to the rates of corticosteroid allergy and patch testing methodologies from published international studies. It was noted that many high‐sensitization potential corticosteroids were not available in our region. Although a low percentage of leg ulcers and stasis dermatitis may be associated with a lower rate of corticosteroid allergy, this association may be confounded by regional factors such as prescribing habits and the local availability of corticosteroids. We conclude that the low rate of topical corticosteroid contact allergy reported by our clinic is associated with regional availability and prescribing practices and the scarcity of stasis dermatitis and leg ulcers in our clinic population.
Reproducibility of atopy patch tests with Dermatophagoides: a study on 85 patients with atopic dermatitis
Authors: Giusti Francesca , Seidenari Stefania
Published: April 2004

Atopy patch tests (APTs) are considered a useful addition to standard testing procedures for the identification of allergens triggering the appearance of eczema in patients with atopic dermatitis (AD). The aim of the study was to evaluate the reproducibility of APTs with house dust mites by simultaneously patch testing AD patients. 85 subjects affected by AD, 36 males and 48 females, aged from 1 to 52 years, were patch tested with Dermatophagoides mix (D. pteron/D. farinae) 20% pet. In our patients, the percentage of agreement between the frequency of positive and negative responses to Dermatophagoides mix was 96.7%. Reproducibility was highly satisfactory, as evaluated by k‐value (0.953). As regards the agreement in the intensity of APT responses to Dermatophagoides mix between the right and left sides, we found that reproducibility was also highly satisfactory (k = 0.851). In conclusion, for Dermatophagoides APTs, the agreement rate was similar to that of standard patch tests, and therefore APTs may be considered sufficiently reproducible to be employed as a diagnostic testing procedure.
Palpable arciform migratory erythema in an HIV patient, a CD8+ pseudolymphoma
Authors: Muche J. M. , Toppe E. , Sterry W. , Haas N.
Published: April 2004

Background:  Palpable arciform migratory erythema (PAME) is characterized by large, elevated, reddish annular lesions localized on the upper trunk. As its infiltrate consists predominantly of dense infiltrates of CD4+ lymphocytes with polyclonal T‐cell receptor (TCR) gene rearrangement, it has been grouped as a rare member of the T‐cell pseudolymphomas.

Methods:  We performed histology, immunophenotyping, and TCR‐γ gene rearrangement studies in an human immunodeficiency virus (HIV)‐positive patient, CDC stage IIIB, who showed a clinically typical PAME.

Results:  While TCR‐γ gene rearrangement studies showed a polyclonal infiltrate confirming a pseudolymphoma, 85% of skin‐infiltrating lymphocytes were CD8+ T cells.

Conclusion:  PAME may also occur in HIV‐positive patients with CD4+ deficiency. Our case demonstrates that regular CD4 counts and immunocompetence are not necessary for its pathogenesis.
Emergency thoracotomy and the military surgeon
Authors: MacFarlane Campbell
Published: April 2004

Emergency thoracotomy might be necessary in battle surgery and might, in an era of superspecialization, be a challenge for the present day military surgeon. He or she might, nonetheless, be the only surgeon in the austere circumstances of a forward field surgical team. This paper provides assistance and guidelines for a military surgeon in such circumstances, including surgical indications and approaches, surgical procedures and techniques. It includes recent advances in this area and principles of ‘damage control’.
Is palliative resection of the primary tumour, in the presence of advanced rectal cancer, a safe and useful technique for symptom control?
Authors: Al‐Sanea Nasser , Isbister William H.
Published: April 2004

Introduction:  At some time, every general surgeon will be faced with the task of trying to decide what to do with a patient who presents with rectal cancer and unresectable distant metastases. How safe is resectional surgery? What sort of palliation may be expected following resection of the primary tumour? In an attempt to answer these questions, the management and outcomes of all patients with rectal cancer and distant metastases, who were primarily referred to the colorectal unit at King Faisal Specialist Hospital were examined.

Methods:  All patients who underwent primary surgery for rectal cancer in the presence of metastatic disease were identified. The charts of these patients were examined and their morbidity, mortality and survival were determined.

Results:  Over an 8‐year period 22 patients (average age 54 years) underwent rectal resectional surgery in the presence of metastatic disease. There were 13 men and nine women. The commonest complaint was rectal bleeding. All patients had chest radiographs. Pulmonary metastases were identified in four patients. Nineteen abdominal and pelvic computed tomography scans were performed and eight showed evidence of metastases. Skeletal radiographs in two patients showed evidence of bone metastasis. At operation, intraperitoneal metastases were found in 18 patients. Nine of these were not identified preoperatively. Six patients underwent abdomino‐perineal resection, nine anterior resection and seven a Hartmann's procedure. Eight patients developed a significant postoperative complication and one died 42 days after surgery. The mean length of hospital stay was 18.6 days. Nine patients received preoperative radiotherapy. Four patients had palliative radiotherapy, two for bony, one for liver and one for peritoneal metastases. Patients were followed up for a mean of 1.1 years. During follow up, 11 returned to the emergency room on 24 occasions. Two patients required readmission. No patient had further rectal bleeding. The mean survival was 1.3 years.

Conclusion:  Patients with rectal cancer and unresectable distant metastases can be successfully palliated by resection of the primary tumour with low morbidity and mortality. The early involvement of a palliative care team facilitates patient management and helps patients enjoy what remains of the rest of their lives at home, in comfort and with good symptom control.
Ureteric stenting 25 years on: routine or risky?
Authors: Lawrentschuk Nathan , Russell John M.
Published: April 2004

Background:  Ureteric stents have been used in urological practice for over 25 years and in many cases have become almost routine. The purpose of the present review is to highlight the uses, complications and risk management issues associated with their use.

Methods:  An extensive literature review was conducted and knowledge from past experience was accessed to give a summary of past and current ureteric stent use in urology.

Results:  Broadly, there are stone and non‐stone indications for stenting. Complications may range from the commonly experienced ‘stent syndrome’ to the medico‐legal dilemma of the forgotten stent. Risk management must be applied to all uses of stenting to minimize complications and achieve best practice.

Conclusion:  Although almost routine in many areas of urological practice, the complications and implications for risk management of ureteric stenting cannot be ignored.
Carotid endarterectomy in octogenarians
Authors: Varghese Raphael , Norman Paul
Published: April 2004

Background:  The role of carotid endarterectomy in octogenarians is unclear as this age group was not included in the major trials of carotid surgery. The aim of the present study was to determine the trends and early outcome of carotid endarterectomy performed in octogenarians at a single institution.

Methods:  A retrospective review of all carotid endarterectomies performed between 1990 and 2001 was conducted as part of a clinical audit. Trends in procedure numbers, length of stay, age and early outcome were assessed. The results of octogenarians were analysed separately.

Results:  Three hundred and fifty‐nine carotid endarterectomies were performed in 329 patients including 33 octogenarians. The number of cases and the mean age of patients increased and length of stay decreased during the study period. There was a significant increase in the proportion of octogenarians undergoing carotid endarterectomy (P = 0.03) in the second half of the study period. The combined rate of stroke and death was higher in octogenarians compared with patients under 80 years old, but the difference was not statistically significant (8.8%vs 5.8%; P = 0.59).

Conclusion:  The mean age of patients and the proportion of octogenarians undergoing carotid endarterectomy has increased over the 12‐year study period.
Zymosan induces nitric oxide production by peritoneal mesothelial cells
Authors: Yao Veronica , McCauley Rosalie , Cooper Deborah , Platell Cameron , Hall John C.
Published: April 2004

Introduction:  The production of nitric oxide is an important peritoneal defense mechanism. We have evaluated the effect of various putative stimulants on nitric oxide production by peritoneal mesothelial cells.

Methods:  Wistar rats were randomized to either a control group or a peritonitis group (5 mg zymosan intraperitoneally). Groups of five animals were sacrificed at 4, 18, 24, 48 and 96 h after the induction of peritonitis and their peritoneal fluid was harvested for assay. Cultures of peritoneal mesothelial cells were stimulated with lipopolysaccharide, myeloperoxidase, TNFα, zymosan, peritoneal fluid from a control animal and peritoneal fluid from a peritonitis animal. Supernatants were collected after incubation for 4, 24 and 48 h for assay. The assay for nitric oxide was based upon the nitrite content of the samples.

Results:  The intraperitoneal administration of zymosan was associated with an increased production of nitric oxide (NO) when compared with control animals (P < 0.01). In cultures of peritoneal mesothelial cells, zymosan, but not the other putative stimulants, was associated with a marked output of nitric oxide (P < 0.001).

Conclusion:  Zymosan has a direct effect on peritoneal mesothelial cells, which are able to generate nitric oxide in the absence of co‐stimulatory molecules. This suggests that it may be possible to use some form of external stimulation to up‐regulate the NO response by peritoneal mesothelial cells.
Infarcted intestine: a diagnostic void
Authors: Glenister Kristen M. , Corke Charlie F.
Published: April 2004

The diagnostic approaches to infarction of the small intestine are reviewed in the present paper. The inadequacy of current methods, especially biochemical methods, are highlighted. Additionally, the benefits of a sensitive and specific test of intestinal infarction are discussed.
Medical practice and medical education 1500−2001: an overview
Authors: Magee Reginald
Published: April 2004

Up to the middle of the nineteenth century medicine was practised by a variety of people: physicians, surgeons, apothecaries, bone setters and various irregular practitioners or quacks. Physicians were well educated and learned men who had studied the classics and the works of Galen. The surgeons attended lectures and demonstrations in anatomy. In reality, medical knowledge regarding disease and its management was minimal. The present paper is an overview of the education and training of those who practised in medicine before the subject began to develop into a science.
Exploring the paradox of unionised worker dissatisfaction
Authors: Guest David E. , Conway Neil
Published: April 2004

This paper explores the apparent paradox that while unions exist to promote the interests and well‐being of their members, UK survey evidence consistently shows that union members report lower levels of job satisfaction than non‐union workers. A review and further analysis of the evidence confirms that this difference persists after controlling for other factors such as type of work. If union member dissatisfaction reflects a form of voice, then we might expect to see resulting gains. An analysis of data from the 1998 Workplace Employee Relations Survey indicates that any gains are modest. Evidence is presented to suggest that although management has become less hostile to trade unions, a degree of anti‐union sentiment remains, sometimes leading to a muffling of the union voice, and this helps to account for some of the union member dissatisfaction.
Worker representation and health and safety in small enterprises in Europe
Authors: Walters David
Published: April 2004

The aim of this paper is to review the role that representative worker participation can play in contributing to better health and safety performance in small enterprises. The relevance of representative participation to health and safety in small enterprises is addressed and the challenges that the sector poses are discussed. Using a number of examples, including legislative approaches, trade union initiatives and joint trade union employer schemes in various countries, the paper explores some of the ways in which such challenges have been tackled.
Sideroblastic anaemia during fusidic acid treatment
Authors: Vial T. , Grignon M. , Daumont M. , Guy C. , Zenut M. , Germain M. L. , Jaubert J. , Ruivard M. , Guyotat D. , Descotes J.
Published: April 2004

Objectives and Methods:  To describe cases of fusidic acid‐associated sideroblastic anaemia from the French Pharmacovigilance database.

Results:  Six cases of sideroblastic anaemia associated with oral fusidic acid treatment were retrieved. Four females and two males (mean age 65.3 yr) developed severe anaemia (mean haemoglobin level: 6.9 g/dL) within 32–190 d (mean: 81 d) of treatment. Bone marrow aspirates showed dyserythropoiesis and ringed sideroblasts in all patients. Four patients required repeated blood transfusions. After fusidic acid discontinuation in five patients, complete recovery was obtained. In one patient, rechallenge with fusidic acid resulted in recurrence of anaemia that resolved after definitive discontinuation of the drug.

Conclusion:  Our data indicate that fusidic acid should be added to the list of drugs that can cause sideroblastic anaemia.
Acute cardiorespiratory collapse from heparin: a consequence of heparin‐induced thrombocytopenia
Authors: Mims Martha P. , Manian Prasad , Rice Lawrence
Published: April 2004

Background:  Heparin has rarely been reported to cause acute cardiorespiratory reactions or collapse. Some reports relate this to underlying heparin‐induced thrombocytopenia.

Objective:  To confirm and increase awareness of acute life‐threatening cardiopulmonary events when patients with heparin‐induced thrombocytopenia are re‐exposed to heparin.

Design:  Retrospective observational case series.

Patients/setting:  Four cardiovascular surgery patients were identified in two adjacent large urban hospitals over a 2‐yr‐period who experienced eight episodes of cardiorespiratory collapse immediately following heparin administration. All had underlying heparin‐induced thrombocytopenia.

Results:  Intravenous boluses of unfractionated heparin were given to four patients with known or previously unrecognized heparin‐induced thrombocytopenia. Two patients experienced severe respiratory distress within 15 min for which they required endotracheal intubation. Two other patients experienced cardiac arrest or a lethal arrhythmia within minutes of receiving intravenous heparin. Serologic tests for heparin‐induced antibodies were positive in all patients. In three cases, the platelet count was normal or near normal but fell dramatically (71%) immediately following the heparin bolus. Three cases had prior diagnoses of heparin‐induced thrombocytopenia, but health care workers administered heparin either unaware of the diagnosis or ignorant of its significance. No patients died, but all required some form of cardiopulmonary resuscitation and subsequent intensive care.

Conclusions:  Heparin administration to patients with heparin‐induced antibodies can result in life‐threatening pulmonary or cardiac events. Appreciation of this phenomenon can unmask cases of heparin‐induced thrombocytopenia and strengthens the mandate to avoid any heparin exposure in affected patients. Recognition is crucial to avoiding disastrous outcomes.