bluuebunny/crossref_metadata_2025 huggingface dataset:
Foregrounding the Symbiosis of Power. A rhetorical strategy in some Chinese commemorative art
Authors: Liscomb Kathlyn
Published: December 2003

Although it can be useful to distinguish between official and personal spheres when studying Ming dynasty (1368–1644) China, here the author argues that Ming government officials sometimes found it advantageous to blur the boundaries of these two spheres. This rhetorical strategy foregrounded the officials’ participation in an ideally symbiotic relationship with the emperor they served. The author analyses instances in which leading bureaucrats recontextualized official occasions associated with the emperor to produce commemorations that clearly were not meant to be seen as positioned solely in the official sphere. They situated these works in their own personal spheres in terms of patronage, ownership and authorship of texts prominently featuring their own aims. This was done to enhance their own social status, reaffirm the prestige of office‐holding, and solidify their close relationship with the reigning emperor.
A slice of painting in Japan
Authors: Screech Timon
Published: December 2003

Book reviewed:

Quitman E. Phillips The Practices of Painting in Japan, 1475–1500
Classicism, Enlightenment and the ‘Other’: thoughts on decoding eighteenth–century visual culture
Authors: Umbach Maiken
Published: December 2003

Cultural historians have been slow to respond to the pictorial turn. They often find images too ambiguous to use as sources in their own right. This problem is aggravated by two characteristics shared by early modern and postmodern visual culture: both transgress boundaries of genre (such as the text/image divide), and both tend to be notoriously fluid and plural in terms of their ‘message’. The nineteenth–century Idealist notion of ‘art’, by contrast, celebrates unity of style and content, and tolerates multiple meanings only where they can be resolved in dialectical synthesis. This legacy continues to prevent us from understanding visual evidence which conforms to neither requirement. Drawing on readings of the contemporary landscape art of Ian Hamilton Finlay and Cy Twombly, this article proposes a new approach to visual culture of pre–Idealist periods, for which ambiguous allusive fields and transgressions of genre were constitutive. The eighteenth century’s use of classical culture is a case in point, here exemplified by a close reading of the multi‐layered trope of Arcadia. The conclusions that emerge from this reading call into question negative assumptions about the Enlightenment’s dogmatic rationalism which have dominated historiography from Romanticism to postmodernism. The ‘image–texts‘ of the eighteenth century destabilized hegemonic rationality without promoting its opposite, instead integrating the ‘other’ into a self–reflexive and self–critical Enlightenment ideology.
Progress versus the Picturesque: white women and the aesthetics of environmentalism in colonial Australia 1820–1860
Authors: Jordan Caroline
Published: December 2003

British artist–settlers steeped in the conventions of picturesque vision often found it difficult to create and preserve in the Australian colonies, in contrast to India. Colonists had to grapple not only with the patent Anglocentrism of their imported landscape aesthetic in a foreign, sometimes inhospitable environment, but with the appalling rate of destruction that accompanied the manifestations of ‘progress’, such as land clearing, on the colonial frontier. This essay argues that one aspect of an incipient environmental consciousness can be seen in the protests against progress made in the name of the picturesque by emigrants, in particular, amateur artists. It examines the classed and gendered dimensions of the inherent contest between progress and capitalist expansion and the picturesque and conservationism, through two Tasmanian artists, Louisa Meredith and Mary Allport. The essay concludes that the limits of aesthetic environmentalism for these women settlers are found in their attitudes to the indigenous Tasmanians.
Professionalizing women's practice
Authors: Macleod Dianne Sachko
Published: December 2003

Deborah Cherry Beyond the Frame. Feminism and Visual Culture, Britain 1850–1900
Awesome female muscle
Authors: Malvern Sue
Published: December 2003

Joanna Frueh, Laurie Fierstein and Judith Stein Picturing the Modern Amazon
The Dresden pioneers of the German avant garde?
Authors: Weikop Christian
Published: December 2003

Birgit Dalbajewa and Ulrich Bischoff(eds.) Die Brücke in Dresden, 1905–1911. Exhibition catalogue
Antiquity and Improvement in the National Landscape: The Bucks’ Views of Antiquities 1726–42
Authors: Kennedy Andrew
Published: December 2003

Andrew Kennedy studied at the Courtauld Institute and was awarded his PhD in 1998. His doctoral thesis was a study of British topographical print series 1720–1840, focusing on the marketing of an imagery of national and local identities to diverse and changing domestic audiences. He has a chapter, ‘Representing the Three Kingdoms: Hanoverianism and the Virtuosi’s Museum’, in the multi–authored volume to be published shortly, based on the proceedings of the 2001 ‘Landscape and Politics’ conference. His article, written jointly with Annie Richardson, ‘Blotting and Blurring One against the Other: Reynolds, Gainsborough and Narratives of the Artist’, was published in the Oxford Art Journal, January 2002. He has taught at Winchester School of Art and Reading University, among other institutions, and currently teaches at Kingston and East London Universities and the School of Oriental and African Studies, University of London.

This article examines the possible contemporary meanings of the engraved views of English and Welsh antiquities published between 1726 and 1742 by Samuel and Nathaniel Buck. The category of ‘antiquity’ automatically existed in a binary relation to the category of ‘improvement’ at this period (as it still does, in some sense). William Stukeley, who was very much associated with the Bucks’ project, found that engravings were ideal for capturing and rendering manageable the promiscuous variety of Britain’s landscape, with its mixture of antiquity and improvement, as it presented itself to the traveller. The nation’s past history, as evidenced by these medieval remains, legitimated and was simultaneously redeemed by a dynamic, improving present, one which a number of the Bucks’ subscribers were actively involved in constructing. Not only are the plates invariably dedicated to the owners of the remains that they depict, but antiquarian study itself is linked to a wider state of propertied prosperity. Given this context, it does not seem so strange, for example, that a series depicting mainly ‘Gothic’ antiquities should attract subscriptions from leading proponents of English Palladianism, that classicizing, modernizing, improving style, when it might be thought that they would have patronized Romano–British antiquarianism exclusively.
Facing Down Medusa (An aetiology of the gaze)
Authors: Mack Rainer
Published: December 2003

Archaic and classical Greek images of the face of Medusa (gorgoneia) are typically understood as apotropaia, quasi–magical terror masks that instantiated the power of the monster’s petrifying gaze. This interpretation articulates the fiction of the image (its pictorialization of the threat posed by Medusa), but fails to account for its material condition as an object of visual consumption. The latter, constituted through practices of image–making and image–viewing, reverses Medusa’s mythological power by turning the objectifying gaze back upon the monster. A close reading of the Perseus legend indicates that this reversal articulated an aetiological discourse in which the hero retrieved the power of the gaze from Medusa by transforming it into the power of representation. By staging the key aetiological moment of the hero’s triumph, the gorgoneion interpellated its makers and viewers as ‘Perseus’ and worked thereby to reproduce the dominant masculine subject position he represented.
Mimesis, Materiality and The Shadow of Death
Authors: Jacobi Carol
Published: December 2003

This essay questions the apparent stylistic transparency of the ‘licked’ Victorian painting and proposes a cascade of connections between material, formal and iconographical concerns. It also offers a model of a relationship between the corporeal persona of the artist and the physical art. This shows that the physical properties of the work correspond, on several levels, to a physical self–image of the artist. The first section looks at the way style problematizes issues of mortality raised by the subject matter of the work and links this to so–far unrecognized expressions of doubt and frailty set out in private journals and letters. The second section will show how these ‘flesh and blood’ concerns inform medico–moral discussions of technique, and, lastly, it will reveal how the integrity of the paint surface itself comes to represent the integrity of the artist’s body.
Fulfilments of Desire in the Work of a Self–Taught Artist: the intimate existence of Malcolm McKesson
Authors: Rhodes Colin
Published: December 2003

This paper explores an artist whose substantial oeuvre was produced outside the usual structures of professional practice and the market. Malcolm McKesson (1909–1999) first became known around 1993 for his drawings, but there is also a significant related body of writing, most of which remains unpublished. He belongs to a category of artists now increasingly receiving serious attention, usually referred to as ‘Self–Taught’, or ‘Outsider’s. Though he was only a dozen years younger than Surrealism’ first generation, he came to artistic maturity late, in his early fifties. He is interesting partly because he seemingly embodies serendipitously certain Surrealist interests and practices, especially as espoused by Breton in texts like ‘The Automatic Message’. The relationships between image and text, and between intentionality and automatism are analysed through close readings of McKesson’ writings and drawings, with particular attention being paid to the short story, Lost. The discussion is framed in the context of McKesson’s transvestism and the complex of appropriations, fantasy and emotional uncertainty which contributed to his extraordinarily focused – and, for more than three decades, secret – creative project.
Taking dress seriously
Authors: Alfrey Penelope
Published: December 2003

Lou Taylor, The Study of Dress History
Return to Figuration: Władisław Strzemiński and the move from Idealism
Authors: Levinger Esther
Published: December 2003

Contrary to the homogeneous flat canvases of Unism, in which Władisław Strzeminński attempted to surpass the incidents and vagaries of sensory perception, in the nature‐inspired works he sought to represent a physiologically accurate vision. His purpose was to present humankind in the role of an active agent who formed the world and its concepts through observation and actual labour. An important contribution by Strzemiński to modern thought was therefore his introduction of the corporeal subject into the theory of art, a subject who perceived with the mechanics of his or her physiological eye. The return to figuration never signalled a distressing regression or a desperate act, but a fresh beginning and a mark of optimism: faith in the human capacity to change the world and faith in the transforming potential of human sight.
Plate 472. Sarcanthopsis hansemannii
Authors: Wood Jeffrey , Ormerod Paul
Published: December 2003

Sarcanthopsis hansemannii from the Bismarck Archipelago, Papua New Guinea, is illustrated. Its taxonomy, relationships, distribution and cultivation, and some problems of species delimitation in Sarcanthopsis, are discussed and a full description provided. Its formal transfer from Vandopsis to Sarcanthopsis is made. A preliminary key to the species of Sarcanthopsis occurring in Papua New Guinea and the Solomon Islands is provided. A brief account of the Kew expedition to New Ireland, during which the plant figured was collected, is given.
Plate 473. Dendrobium glomeratum
Authors: Wood Jeffrey
Published: December 2003

Dendrobium glomeratum Rolfe from Maluku and Sulawesi is illustrated. Its taxonomy, relationships, distribution and cultivation are discussed and a full description provided. The recently described Dendrobium sulawesiense J. Erfkamp & O. Gruss is considered conspecific. The status of the closely related D. crepidiferum J.J. Sm. is discussed. Background information on Maluku and Sulawesi is also provided.
Amherstia nobilis
Authors: Lyte Benedict
Published: December 2003

The history of the discovery and introduction to cultivation of the spectacular Burmese Amherstia nobilis Wall. (Leguminosae), which has not been seen in the wild since 1865, is presented; an early illustration and a description of the species is provided.
Forest products and traditional peoples: Economic, biological, and cultural considerations
Authors: Bennett Bradley C.
Published: December 2003

Conservationists and environmental economists have promoted the extraction of non–timber forest products (NTFP) as an alternative to forest conversion and as a means to benefit forest peoples. This article discusses the development of NTFP economic analyses and some economic, biological and socio–cultural constraints on the use of forest resources and methodological limitations of NTFP investigations. Several case studies document the importance of the forest in both North and South America. While studies differ in their conclusions regarding the sustainability of NTFP extraction, most researchers agree that sustainable harvesting is rare. The article argues for additional considerations that transcend the biological and economic concerns. While forests provide the basis of material culture for peoples that inhabit them, they are also linked intrinsically to the religion, mythology, and psyche of native peoples. Conservationists have an ethical obligation to consider the needs and desires of these people in conjunction with conservation and management plans.
The Legacy of Knut Wicksell to Capital Theory
Authors: Malinvaud Edmond
Published: December 2003

Wicksell's contributions to capital theory focused on stationary states in four distinct models intended to account for the time dimension of production in market economies. We now have a better understanding of the true challenges because of two developments: a full theory of intertemporal general equilibria and a methodology for comparative analysis as explained by Hicks. In Wicksell's equilibria, the real interest rate turns out to be equal to the marginal productivity of the volume of social capital, a concept that Wicksell could not master and hence avoided. Challenges remain, particularly regarding the best way to account for complementarities and substitutions over time.
Wicksell, Lindahl and the Theory of Public Goods
Authors: Silvestre Joaquim
Published: December 2003

Wicksell's and Lindahl's ideas on public goods and decisions are reviewed in light of later developments in the theoretical economics literature. I begin by discussing their normative ideals, in particular the notion of justness, and the sources of the difficulties in reaching them. Wicksell's and Lindahl's ideal states, as well as the obstacles that they perceive, are compared to more recent views on free riding and on the behavior of elected representatives. Their views on political bargaining are then related to later concepts, in particular to the core of the economy.
Multinational Companies, Technology Spillovers and Plant Survival*
Authors: Görg Holger , Strobl Eric
Published: December 2003

How does the presence of multinational companies affect plant survival in the host country? We postulate that multinational companies can impact positively on plant survival through technology spillovers. We examine the nature of the effect of multinationals using a Cox proportional hazard model, which we estimate using plant‐level data for Irish manufacturing industries. Our results show that the presence of multinationals has a life‐enhancing effect only on indigenous plants in high‐tech industries, suggesting the presence of technology spillovers. In contrast, multinationals compete with each other in low‐tech sectors in the host country.
Federal Monetary Policy
Authors: Hefeker Carsten
Published: December 2003

What is the optimal institutional structure for a federal central bank? The framework developed in this paper is used to analyze under what conditions an individual region will prefer a monetary union to be organized according to regional or common influences and how a combination of both can be rationalized. The implications of an enlargement of a monetary union for changes in its institutional setup are also derived.
Heroin Consumption, Prices and Addiction: Evidence from Self‐reported Panel Data*
Authors: Line Bretteville‐Jensen Anne , Biørn Erik
Published: December 2003

Estimation models of drug demand should encompass the aspect of addiction. Here, we consider two static panel data regression models and two cross‐section models with lags or leads in drug consumption as additional regressors. Heroin injectors attending a needle exchange service in Oslo were interviewed twice, with a one‐year interval. Despite our relatively small sample, we obtain statistically significant price and income responses for nearly all of the models and specifications applied. The sample is split by dealing status, with dealers obtaining price elasticities in the range of [−0.15, −1.51] and non‐dealers [−0.71, −1.69]. Somewhat surprisingly, the estimates of the variance of the latent individual‐specific variable are rather low in the panel data models, although higher for non‐dealers than for dealers.
Morphometry and composition of aragonite and vaterite otoliths of deformed laboratory reared juvenile herring from two populations
Authors: Tomás J. , Geffen A. J.
Published: December 2003

Vaterite otoliths were sampled from two reared populations (Celtic and Clyde Seas) of juvenile herring Clupea harengus. The crystallography, elemental composition and morphometry were analysed and compared with those of normal aragonite otoliths. The incidence of vaterite otoliths in the juveniles sampled (n = 601) ranged from 7·8% in the Clyde population to 13·9% in the Celtic Sea population, and was 5·5% in the small sample (n = 36) of wild adults examined. In all but one case fish had only one vaterite otolith; the corresponding otolith of the pair was completely aragonite. Although the majority of the juveniles sampled showed craniofacial deformities, there was no link between the skull or jaw malformation and the incidence of vaterite otoliths. All vaterite otoliths had an aragonite inner area, and vaterite deposition began sometime after the age of 90 days. The vaterite otoliths were larger and lighter than their corresponding aragonite partners, and were less dense as a consequence of the vaterite crystal structure. The vaterite areas of the otoliths were depleted in Sr, Na and K. Concentrations of Mn were higher in the vaterite areas. The transition between the aragonite inner areas and the vaterite areas was sharply delineated. Within a small spatial scale (20 μm3) in the vaterite areas, however, there was co‐precipitation of both vaterite and aragonite. The composition of the aragonite cores in the vaterite otoliths was the same as in the cores of the normal aragonite otoliths indicating that the composition of the aragonite cores did not seed the shift to vaterite. Vaterite is less dense than aragonite, yet the concentrations of Ca analysed with wavelength‐dispersive spectrometry (WDS) were the same between the two polymorphs, indicating that Ca concentrations measured with WDS are not a good indicator of hypermineralized zones with high mineral density. The asymmetry in density and size of the otoliths may cause disruptions of hearing and pressure sensitivity for individual fish with one vaterite otolith, however, the presence of vaterite otoliths did not seem to affect the growth of these laboratory reared juvenile herring.
Structure and enzymatic removal of the chorion of embryos of the Nile tilapia
Authors: Morrison C. M. , Pohajdak B. , Henry M. , Wright J. R.
Published: December 2003

Dechorionation or partial digestion of the egg chorion is necessary for introducing embryonic stem cells into blastulas for chimera production and for harvesting blastulas. Several methods to digest the Nile tilapia Oreochromis niloticus chorion were tried and it was found that the chorions of most clutches of eggs were digested in <3 h using hatching medium [produced by allowing embryos to hatch in Hanks balanced salt solution (HBSS) in an incubator], or 2 mg ml−1 pronase P6911 in 10% Ca/Mg free HBSS. The chorion of Nile tilapia possesses multiple lamellae as found in most teleost species that have been studied. It was found to be thinner than that of medaka Oryzias latipes and thicker than that of zebrafish Danio rerio. During natural hatching the chorion was digested from the inner surface, and tail movements helped to break the remaining chorion; however, chorion digestion has to be complete for experimental dechorionation, because digestion starts at the external surface. The zona radiata externa remained intact after experimental digestion with hatching media but was disrupted by pronase. Embryos dechorionated at the cleavage or blastula stage only survived for 2 or 3 days, but some dechorionated at the gastrula stage or early segmentation stage developed until the natural hatching time. If the chorion was partially digested at the cleavage or blastula stage, some embryos survived to hatch.
Androgen levels of reproductive competitors in a co‐operatively breeding cichlid
Authors: Oliveira R. F. , Hirschenhauser K. , Canário A. V. M. , Taborsky M.
Published: December 2003

Androgen levels of family groups of Neolamprologus pulcher were assessed using non‐invasive methods. There were no significant differences in the excretion rates neither of testosterone nor of 11‐ketotestosterone between territorial and helper males.
Comparative morphology of the sagittal otolith in Serranus spp.
Authors: Tuset V. M. , Lombarte A. , González J. A. , Pertusa J. F. , Lorente MaJ.
Published: December 2003

Variations in the morphology of saccular otoliths (sagittae) among three sympatric species of the genus Serranus(S. atricauda, S. cabrilla and S. scriba) from the Canary Islands were investigated. Although the otolith gross morphology was similar among species, S. scriba was distinct in having a rostrum which had a slight turning at the tip and a more funnel‐like ostium. The shallower water species (S. scriba) had otolith and sulcus areas which were smaller than the deeper water species (S. cabrilla and S. atricauda). The sulcus acusticus and ostium size were correlated with the habit depth of the species, with the highest values in the deepest species, S. cabrilla. The otolith outline shape indices changed with size (total length) of the species, and allowed the separation of the species by means of a discriminate function.
Effects of a founder event and supplementary introductions on genetic variation in a captive breeding population of the endangered Spanish killifish
Authors: Schönhuth S. , Luikart G. , Doadrio I.
Published: December 2003

Twelve polymorphic allozyme loci were employed to assess the genetic change in a captive breeding population of the endangered killifish Aphanius baeticus in the Doñana National Park, south‐western Spain. The initial founder event did not significantly reduce the allelic richness or the expected heterozygosity. No genetic bottleneck signature was detected by tests for deviation from mutation‐drift equilibrium. The FST between the wild source and captive population, however, was relatively high (0·053 or 0·122 when excluding or including the locus IDHP‐1* respectively), after just two to three generations in captivity. Two generations after the incorporation of 68 new wild specimens (greater than five generations after founding) decreased the genetic differences and the FST(0·041 excluding IDHP‐1*). The restoration efforts appeared to be helpful and the study of 12 polymorphic loci and a sensitive parameter such as FST were useful for monitoring genetic changes in captivity. Nonetheless, future monitoring should include additional highly polymorphic loci (microsatellites) to achieve higher power to detect genetic change. Such restoration and monitoring efforts should help to avoid rapid inbreeding, adaptation to captivity, and to maintain the long‐term evolutionary potential in small isolated populations.
Predator avoidance behaviour in wild and hatchery‐reared brown trout: the role of experience and domestication
Authors: Álvarez D. , Nicieza A. G.
Published: December 2003

Juvenile brown troutSalmo truttafrom natural populations reacted to the presence of piscivorous brown trout by increasing the use of refuges. In contrast, second‐generation hatchery fish and the offspring of wild fish raised under hatchery conditions were insensitive to predation risk. The diel pattern of activity also differed between wild and hatchery brown trout. Second‐generation hatchery fish were predominantly active during daytime regardless of risk levels. Wild fish, however, showed a shift towards nocturnal activity in the presence of predators. These findings emphasize the potential role of domestication in weakening behavioural defences. They support the idea that the behavioural divergence between wild and domesticated individuals can arise from a process of direct or indirect selection on reduced responsiveness to predation risk, or as a lack of previous experience with predators.
Opercular differential pressure as a predictor of metabolic oxygen demand in the starry flounder
Authors: Dalla Valle A. Z. , Rivas‐Diaz R. , Claireaux G.
Published: December 2003

The feasibility of using a differential pressure sensor connected to an acoustic telemetry device to monitor opercular activity as a correlate of oxygen consumption was investigated. Four starry flounders Platichthys stellatus were fitted with a miniature differential pressure sensor mounted close to the operculum. A cannula was connected to the sensor and inserted under the operculum, inside the branchial cavity. Measurements of oxygen consumption and opercular activity were carried out over a broad range of metabolic activity, from the post‐surgery stress (high metabolic rate) to routine metabolic rate the following day. Relationships between differential pressure changes (rate and amplitude) were highly correlated with oxygen consumption (r2 = 0·74 and 0·60 respectively). The results indicate that monitoring opercular activity offers an alternative method for measuring aerobic metabolism in free‐swimming fishes in nature.
Southernmost occurrence of Epinephelus marginatus in the south‐west Atlantic
Authors: Rico M. R. , Acha E. M.
Published: December 2003

The southernmost occurrence of the dusky grouper Epinephelus marginatus in the south‐west Atlantic (Argentina) was recorded at 36°S, expanding its range 1200 km southward from that previously reported.
Changes in mucus cell numbers in the epidermis of the Atlantic salmon at the onset of smoltification
Authors: O'Byrne‐Ring N. , Dowling K. , Cotter D. , Whelan K. , MacEvilly U.
Published: December 2003

A sharp decrease to <50% in the numbers of mucus cells mm−2 of epidermis was observed in the skin of Atlantic salmon Salmo salar at the beginning of the smoltification period in 1997 and 1999. Average numbers decreased in 1997 from 662 mm−2 on 6 March to 275 mm−2 on 20 March and in 1999 from 828 mm−2 on 3 March to 388 mm2 on 24 March. A second smaller decrease was observed towards the end of smoltification in both years.
Anaesthetic management of childhood thyrotoxicosis and the use of esmolol
Authors: Knighton J. D. , Crosse M. M.
Published: December 2003

We report a case of infantile thyrotoxicosis requiring thyroidectomy while biochemically hyperthyroid, detailing the use of esmolol to control a thyrotoxic episode.
Involvement of multiple human cytochromes P450 in the liver microsomal metabolism of astemizole and a comparison with terfenadine
Authors: Matsumoto Shigeki , Yamazoe Yasushi
Published: December 2003

Aims  The aims of the present study were to investigate the metabolism of astemizole in human liver microsomes, to assess possible pharmacokinetic drug‐interactions with astemizole and to compare its metabolism with terfenadine, a typical H1 receptor antagonist known to be metabolized predominantly by CYP3A4.

Methods  Astemizole or terfenadine were incubated with human liver microsomes or recombinant cytochromes P450 in the absence or presence of chemical inhibitors and antibodies.

Results  Troleandomycin, a CYP3A4 inhibitor, markedly reduced the oxidation of terfenadine (26% of controls) in human liver microsomes, but showed only a marginal inhibition on the oxidation of astemizole (81% of controls). Three metabolites of astemizole were detected in a liver microsomal system, i.e. desmethylastemizole (DES‐AST), 6‐hydroxyastemizole (6OH‐AST) and norastemizole (NOR‐AST) at the ratio of 7.4 : 2.8 : 1. Experiments with recombinant P450s and antibodies indicate a negligible role for CYP3A4 on the main metabolic route of astemizole, i.e. formation of DES‐AST, although CYP3A4 may mediate the relatively minor metabolic routes to 6OH‐AST and NOR‐AST. Recombinant CYP2D6 catalysed the formation of 6OH‐AST and DES‐AST. Studies with human liver microsomes, however, suggest a major role for a mono P450 in DES‐AST formation.

Conclusions  In contrast to terfenadine, a minor role for CYP3A4 and involvement of multiple P450 isozymes are suggested in the metabolism of astemizole. These differences in P450 isozymes involved in the metabolism of astemizole and terfenadine may associate with distinct pharmacokinetic influences observed with coadministration of drugs metabolized by CYP3A4.
Effect of diuretics on fetal growth: A drug effect or confounding by indication? Pooled Danish and Scottish cohort data
Authors: Olesen Charlotte , De Vries Corinne S. , Thrane Nana , MacDonald Tom M. , Larsen Helle , Sørensen Henrik Toft , Group The EuroMap
Published: December 2003

Aims  The diabetogenic effect of diuretics, as well as the indication for prescribing them, may impact on fetal growth. We analysed whether the purchase of prescription drugs for diuretics during pregnancy was associated with measures of fetal growth.

Methods  During 1991–98 all women who purchased prescription drugs for diuretics during pregnancy were identified in the Northern Jutland Prescription Database (NJDP), Denmark, and in the Medicines Monitoring Unit's Database (MEMO), Scotland. Information on birth weight and gestational age was obtained from the Danish Birth Registry, the Danish Hospital Discharge Registry and the Scottish Tayside Neonatal Database. Information on diabetes, hypertension and prepregnancy weight were obtained by hospital record review in a sample of women in the Danish cohort. Women who did not purchase prescription diuretics during pregnancy were used as a reference group in both cohorts.

Results  Danish women who purchased prescription loop diuretics during pregnancy gave birth to infants with higher birth weights than women who did not use diuretics; mean difference 104.7 g (95% CI; 2.6, 206.9). However, the high prevalence of diabetes (10.3%) among Danish women who purchased prescription loop diuretics during pregnancy might explain this result. Both the Danish and the Scottish women who purchased prescription diuretics during their pregnancy were at increased risk of preterm delivery (< 37 completed weeks); ORs: 1.8 (CI; 1.2, 2.7)NJDP, 1.9 (CI; 0.9, 4.3)MEMO. The proportion of hypertension among women who purchased prescription thiazides was 15.8%, and the risk of having an infant with a birth weight (BW) < 2500 g was increased; ORs: 2.6 (CI; 1.4, 5.0)NJDP, 2.4 (CI; 0.8, 7.8)MEMO.

Conclusions  Prescribing diuretics during pregnancy was associated with differences in birth weight and incidence of preterm delivery. Confounding by indication may explain the findings.
Disposition and metabolism of the flavonoid chrysin in normal volunteers
Authors: Walle T. , Otake Y. , Brubaker J. A. , Walle U. K. , Halushka P. V.
Published: December 2003

Aims  To describe the oral disposition of the dietary flavonoid chrysin in healthy volunteers.

Methods  Oral 400 mg doses of chrysin were administered to seven subjects. Chrysin and metabolites were assayed in plasma, urine and faeces by h.p.l.c.

Results  Peak plasma chrysin concentrations were only 3–16 ng ml−1 with AUCs of 5–193 ng ml−1 h. Plasma chrysin sulphate concentrations were 30‐fold higher (AUC 450–4220 ng ml−1 h). In urine, chrysin and chrysin glucuronide accounted for 0.2–3.1 mg and 2–26 mg, respectively. Most of the dose appeared in faeces as chrysin. Parallel experiments in rats showed high bile concentrations of chrysin conjugates.

Conclusions  These findings, together with previous data using Caco‐2 cells, suggest that chrysin has low oral bioavailability, mainly due to extensive metabolism and efflux of metabolites back into the intestine for hydrolysis and faecal elimination.
Acetylsalicylic acid and other salicylates in relation to Stevens–Johnson syndrome and toxic epidermal necrolysis
Authors: Kaufman David W. , Kelly Judith P.
Published: December 2003

Aims  Various nonsteroidal anti‐inflammatory drugs are known to increase the risk of Stevens–Johnson syndrome and toxic epidermal necrolysis. The relationship between salicylate treatment and these conditions is not known.

Methods  A case‐control study was conducted in four countries in Europe from 1989 to 1995.

Results  Among 373 cases and 1720 controls, the multivariate relative risk estimate for any salicylate use in the previous week was 1.3 (95% confidence interval, 0.8–2.2); no statistically significant elevations were observed for single ingredient preparations or for salicylate‐containing combination products.

Conclusions  Acetylsalicylic acid and other salicylates are not associated with a measurable increase in the risk of these rare but severe reactions.
Influence of gender and oral contraceptives on CYP2D6 and CYP2C19 activity in healthy volunteers
Authors: Hägg Staffan , Spigset Olav , Dahlqvist Rune
Published: December 2003

Aims
 The study was carried out in order to assess the effects of gender and the use of oral contraceptives (OCs) on CYP2D6 and CYP2C19 activities in healthy volunteers.

Methods
 Six hundred and eleven Caucasian volunteers (330 males and 281 females; age range 18–49 years) were phenotyped with respect to CYP2D6 and CYP2C19 by means of the probe drugs dextromethorphan and mephenytoin, respectively. Extensive metabolisers were selected for this study.

Results
 The median dextromethorphan/dextrorphan metabolic ratio in non‐OC using females was significantly lower than in males (0.067 vs 0.080; P = 0.033) (mean difference in ln dextromethorphan/dextrorphan metabolic ratio 0.023, 95% CI 0.03–0.43). For the mephenytoin S/R ratio, no such difference was observed. However, OC using females had a significantly higher median mephenytoin S/R ratio than non‐OC using females (0.230 vs 0.090; P < 0.001) (mean difference in ln mephenytoin S/R ratio 0.082, 95% CI 0.60–1.04). Moreover, females using combined OCs had a significantly higher median ratio than females using OCs with progestins only (median 0.258 vs 0.135; P = 0.008) (mean difference in ln mephenytoin S/R ratio 0.82, 95% CI 0.21–1.34).

Conclusions
 Given certain assumptions, the study indicates that females in the fertile age have a slightly higher CYP2D6 activity compared with males. There was no evidence of a gender difference in CYP2C19 activity. The use of combined OCs reduces the activity of CYP2C19, an effect that seems to be related to the ethinyloestradiol component.
Prescribing patterns in patients using new antidepressants
Authors: Meijer Welmoed E. E. , Heerdink Eibert R. , Pepplinkhuizen Lolke P. , Van Eijk Jacques ThM. , Leufkens Hubert G. M.
Published: December 2003

Aims  To study possible selective prescribing (‘channelling’) we compared characteristics of patients using the SSRI sertraline with patients using longer available SSRIs.

Methods  An observational cohort study in 1251 patients being prescribed an SSRI.

Results  In contrast to other studies, we found no evidence for channeling of sertraline. Sertraline was mainly prescribed for the labelled indication (depressive disorder), while older SSRIs were more often prescribed also for other indications. Time on the market was inversely associated to the proportion of patients treated for depressive disorder.

Conclusions  We found no evidence for channeling of sertraline compared with prescribing patterns of older SSRIs.
Prescribers prefer people: The sources of information used by doctors for prescribing suggest that the medium is more important than the message
Authors: McGettigan P. , Golden J. , Fryer J. , Chan R. , Feely J.
Published: December 2003

Aims  The sources of prescribing information are legion but there is little knowledge about which are actually used in practice by doctors when prescribing. The aims of this study were to determine the sources of prescribing information considered important by doctors, establish which were used in practice, and investigate if hospital and primary care physicians differed in their use of the sources.

Methods  Two hundred general practitioners (GPs) and 230 hospital doctors were asked to rate information sources in terms of their importance for prescribing ‘old’ and ‘new’ drugs, and then to name the source from which information about the last new drug prescribed was actually derived.

Results  Among 108 GPs, the Drugs and Therapeutics Bulletin and medical journal articles were most frequently rated as important for information on both old and new drugs while pharmaceutical representatives and hospital/consultant recommendations were more important for information on new drugs, as opposed to old. In practice, information on the last new drug prescribed was derived from pharmaceutical representatives in 42% of cases and hospital/consultant recommendations in 36%, with other sources used infrequently. Among 118 hospital doctors, the British National Formulary (BNF) and senior colleagues were of greatest theoretical importance. In practice, information on the last new drug prescribed was derived from a broad range of sources: colleagues, 29%; pharmaceutical representatives, 18%; hospital clinical meetings, 15%; journal articles, 13%; lectures, 10%. GPs and hospital doctors differed significantly in their use of pharmaceutical representatives (42% vs 18%) and colleagues (7% vs 29%) as sources of prescribing information (P < 0.0001 for both).

Conclusions  The sources most frequently rated important in theory were not those most used in practice, especially among GPs. Both groups under‐estimated the importance of pharmaceutical representatives. Most importantly, the sources of greatest practical importance were those involving the transfer of information through the medium of personal contact.
Population pharmacokinetics of antifibroblast activation protein monoclonal antibody F19 in cancer patients
Authors: Tanswell Paul , Garin‐Chesa Pilar , Rettig Wolfgang J. , Welt Sydney , Divgi Chaitanya R. , Casper Ephraim S. , Finn Ronald D. , Larson Steven M. , Old Lloyd J. , Scott Andrew M.
Published: December 2003

Aims  The population pharmacokinetics of 131I‐mAbF19, a radiolabelled murine monoclonal antibody against fibroblast activation protein and a potential antitumour stroma agent, were investigated during two phase I studies in cancer patients.

Methods  131I‐mAbF19 serum concentration‐time data were obtained in 16 patients from two studies involving imaging and dosimetry in colorectal carcinoma and soft tissue sarcoma. Doses of 0.2, 1 and 2 mg antibody were administered as 60 min intravenous infusions. The data were analysed by nonlinear mixed effect modelling.

Results  The data were described by a two‐compartment model. Population mean values were 109 ml h−1 for total serum clearance, 3.1 l for the volume of distribution of the central compartment, and 4.9 l for the volume of distribution at steady state. Mean terminal half‐life was 38 h. Intersubject variability was high, but no patient covariates could be identified that further explained this variability. In particular, there was no influence of tumour type or mAbF19 dose.

Conclusions  The pharmacokinetics of antistromal mAbF19 were well defined in these two studies with different solid tumour types, and were comparable with those of other murine monoclonal antibodies that do not bind to normal tissue antigens or blood cells.
Human autoimmune anti-proteinase 3 scFv from a phage display library
Authors: FINNERN R , PEDROLLO E , FISCH I , WIESLANDER J , MARKS J D , LOCKWOOD C M , OUWEHAND W H
Published: December 2003

This is the first study describing recombinant human antibody fragments directed to the autoantigen proteinase 3 (PR3) from an immune B cell source. Detection of these autoantibodies has proven valid for the diagnosis and monitoring of Wegener's granulomatosis. The described antibody fragment (scFv) was isolated from a phage display library prepared from the IgG-positive splenic lymphocytes of a patient with systemic autoimmunity. The cloning strategy was designed to maintain the diversity of the antibody variable gene repertoire, and sequencing of several variable genes demonstrated that all major heavy and light chain families were represented. We found an over-representation of particular heavy chain variable domains in splenic lymphocytes which differ from the ones frequently found in peripheral blood lymphocytes. It was possible to obtain specific scFv to PR3 after a single round of selection and the binding could be inhibited by the patients' sera. Although the antibody fragments in the splenic repertoire were found to be highly mutated, it was interesting to find that the selected scFv showed only limited somatic mutation. Furthermore, we could demonstrate that the removal of the mutations had no effect on binding specificity.
Proinflammatory cytokines regulate FcαR expression by human mesangial cells in vitro
Authors: BAGHERI N , CHINTALACHARUVU S R , EMANCIPATOR S N
Published: December 2003

IgA nephropathy (IgAN) is defined by the predominant deposition of IgA immune complexes (IC) in the glomerular mesangium. Interaction between IgA immune complexes and mesangial cells (MC) could be a linchpin for the genesis of IgAN. We studied the modulation of MC expression of IgA receptors (FcαR) by selected cytokines. Binding of 125I-IgA to quiescent human MC showed 2.55 ×105 sites/cell with an affinity (Ka) of 3.2 ×107 M−1. Addition of selected recombinant cytokines had no significant influence on Ka, but increased the number of sites/cell relative to unstimulated cells. Northern hybridization using the pHuFcαR cDNA probe showed time-dependent increases in mRNA expression in stimulated versus control cells. IL-6 and tumour necrosis factor-alpha (TNF-α) had a biphasic effect on the FcαR mRNA level; at 48 h, IL-6 increased steady state mRNA levels about six-fold relative to control, TNF-α increased mRNA four-fold, and interferon-gamma (IFN-γ) induced FcαR mRNA two-fold. By reverse transcriptase-polymerase chain reaction (RT-PCR), the FcαR expressed on human MC appears highly homologous to that expressed by U937 cells. Altered FcαR expression in response to cytokines may influence the pathogenesis of IgAN by affecting deposition and/or clearance of IgA-IC in the mesangium.
Diagnostic value of CD45RO expression on circulating T lymphocytes of fetuses and newborn infants with pre-, peri- or early post-natal infections
Authors: BRU¨NING T , DAIMINGER A , ENDERS G
Published: December 2003

We examined the expression of the CD45RO antigen, which characterizes the antigen primed/memory phenotype of T lymphocytes, as a marker for congenital infection in blood samples of newborns and fetuses. CD45RO expression on T cells was determined by triple-colour fluorescence flow cytometry. In total 537 blood samples of newborns and infants up to an age of 3 months and 89 fetal blood samples from gestational weeks 19–31 were analysed. Of the newborns and infants, 74 had a clinically, serologically and/or antigenically evident infection, and four of the fetuses had a confirmed intra-uterine infection. In 35 infants with acute predominantly bacterial infections such as sepsis or pneumonia, 17 (48.6%) had elevated CD45RObright expression. In 39 infants with proven pre-, peri- or early post-natal infections with toxoplasmosis, cytomegalovirus (CMV), rubella, herpes simplex virus (HSV) or human herpes virus type 6 (HHV6), 25 (64.1%) exhibited enhanced CD45RObright expression. Three of four fetuses with confirmed intra-uterine infection (three with CMV, one with parvovirus B19) exhibited elevated CD45RObright expression. The specificity of the CD45RO assay for detecting microbial infections was 94.6% for newborns and infants up to 3 months and 90.6% for fetuses. It is concluded that elevated numbers of CD45RObright T cells in infants up to 3 months of age strongly suggest an infection. However, the sensitivity of the CD45RO assay is not sufficient to enable the test to be used as a general marker for prescreening infants to detect pre-, peri- or early post-natally acquired infections.
Systemic acute-phase reactants, C-reactive protein and haptoglobin, in adult periodontitis
Authors: EBERSOLE J L , MACHEN R L , STEFFEN M J , WILLMANN D E
Published: December 2003

Capture ELISAs with biotinylated monospecific antibodies were developed to detect both C-reactive protein (CRP) and haptoglobin (Hp) in serum of adult periodontitis (AP) patients and normal subjects. Each acute-phase reactant was significantly increased in serum from AP patients with CRP at 9.12 ±1.61 mg/l versus 2.17 ± 0.41 mg/l (P < 0.001) and Hp at 3.68 ± 0.37 g/l versus 1.12 ± 0.78 g/l (P < 0.001). Assessment of clinical characteristics of the patients' periodontal disease indicated that CRP and Hp levels were significantly increased in patients with the most frequent disease active episodes (P < 0.02 and P < 0.001, respectively). Longitudinal examination of the Hp levels showed a significant decrease following scaling and root planing (3.68 versus 2.38 g/l; P < 0.01). After a 2-year administration of 50 mg/b.i.d. Flurbiprofen (a non-steroidal anti-inflammatory drug), significantly decreased Hp levels were noted (P < 0.005). CRP levels declined by 35–40% after 1–2 years of treatment with the drug (P < 0.05). The findings indicated that localized infections resulting in increased inflammation and tissue loss in the periodontium elicit systemic host changes manifest by increases in two acute-phase reactants. The conclusions are that either these molecules are formed locally and distributed to the serum, or these presumably localized infections impact upon the systemic components of the host protective responses.
Induction of hypoglycaemia in Japanese encephalitis virus infection: the role of T lymphocytes
Authors: KHANNA N , MATHUR A , BHARADWAJ M , CHATURVEDI U C
Published: December 2003

We report here development of hypoglycaemia in the convalescent phase of Japanese encephalitis virus (JEV) infection in mice by the induction of antigen-specific Ly1−2+ T cells in the spleen which mediate hypoglycaemia through the generation of soluble T cell hypoglycaemic factor (TCHF). The TCHF acted in a dose-dependent manner and was found to be trypsin-sensitive and thermolabile. It was purified on Superose-12 high performance liquid chromatography (HPLC) gel filtration column and purified protein migrated as a ∼25-kD band on SDS–PAGE. The JEV-induced hypoglycaemia coincided with an increased circulating glucagon level, without any alterations in blood insulin and growth hormone concentrations. These effects were mimicked by TCHF. These results indicate that JEV-primed T lymphocytes mediate hypoglycaemia through the production of a soluble hypoglycaemic factor.