bluuebunny/crossref_metadata_2025 huggingface dataset:
A new method for calculating volume of excavated burrows: the geomorphic impact of Wedge‐Tailed Shearwater burrows on Rottnest Island
Authors: BANCROFT W. J. , HILL D. , ROBERTS J. D.
Published: September 2004

Studies of ecosystem engineering may use burrow volume and soil displacement rate to quantify the impact of burrowing vertebrates. Calculations of burrow volume from morphometric measurements have previously treated burrows as rectangular or elliptical prisms.

Here we use burrows of the Wedge‐Tailed Shearwater (Puffinus pacificusGmelin, 1789) to demonstrate a new method for collecting morphometric data, and for mathematically modelling burrow shape used to calculate burrow volume.

Our method improves on previous estimates by better estimating the cross‐sectional burrow shape, and by accounting for some of the variation in burrow width and height.

Wedge‐Tailed Shearwater burrows were parabolic in cross‐section, averaged 1·99 ± 0·04SE m in length and had a mean volume of 0·06 ± 0·00SE m3. The shearwaters excavate at a rate of 7·75 m3 ha−1 year−1(10·51 t ha−1 year−1) which ranks them above many geomorphic mammals. We suggest that this warrants further investigation into the role of burrowing seabirds as ecosystem engineers.
Maternal antibody transmission and breeding densities in the Black‐headed GullLarus ridibundus
Authors: MÜLLER WENDT , GROOTHUIS TON G. G. , DIJKSTRA COR , SIITARI HELI , ALATALO RAUNO V.
Published: September 2004

The offspring of avian species, especially those of colonial breeders, are exposed to a number of pathogens immediately after birth. The chick's immune system is, at that early stage still immature and inefficient. As a consequence, diseases can have a strong impact on chick survival.

The ability of mothers to transmit passive immunity in terms of antibodies of their own acquired immunity to their chicks is probably an essential pathway to enhance the chick survival. Since the production of antibodies is costly, females are expected to adjust the transmission of passive immunity to the local disease environment.

We found that in Black‐headed Gulls (Larus ridibundusL.) yolk antibody concentrations are positively correlated with local breeding density. This transmission pattern is likely to be adaptive, as the aggregation of birds will enhance the local presence of pathogens.

When birds were forced to re‐settle after the colony had been flooded (10–20% of the original number of breeding pairs re‐settled), this relationship was no longer present. The lack of such a relationship may be explained by the fact that females may retain certain levels of antibodies as a consequence of infections that occurred during the first breeding attempt at a different breeding density.

Within clutches, maternal antibodies decreased with laying sequence, in particular in eggs hatching male chicks. This transmission pattern may contribute to the observed mortality pattern found in gull species.
Growth efficiency and temperature in scallops: a comparative analysis of species adapted to different temperatures
Authors: HEILMAYER O. , BREY T. , PÖRTNER H. O.
Published: September 2004

Data were collected on metabolic activity and growth in pectinid bivalves from published studies. The resulting database comprised three types of data sets: (i) synoptic data (13 populations, 7 species), where both individual growth performance and metabolism are known, (ii) ‘metabolism only’ data (82 populations, 13 species), and (iii) ‘growth only’ data (198 populations, 26 species).

In pectinid bivalves belonging to different species and living under different environmental conditions metabolic activity (standard metabolic rate, SMRAvg,Q10 = 2·97) is more closely related to temperature than individual growth (overall growth performance, OGP index P,Q10 = 1·12).

The synthesis of the two corresponding Arrhenius equations shows that the relationship between the SMRAvg‐to‐OGP ratio and temperature follows the Arrhenius model, too, withQ10 = 2·26.

SMRAvg‐to‐OGP is an inverse proxy for growth efficiency, hence growth efficiency decreases with rising temperature across a wide range of pectinid populations and species. Thus, there is strong empirical evidence that elevated temperature constrains growth efficiency in scallops and that adaptation does not fully compensate for this effect.
Increased haemolymph osmolality suggests a new route for behavioural manipulation ofTalorchestia quoyana(Amphipoda: Talitridae) by its mermithid parasite
Authors: WILLIAMS C. M. , POULIN R. , SINCLAIR B. J.
Published: September 2004

Hairworms (phylum Nematomorpha) and mermithid nematodes (phylum Nematoda) have independently evolved almost identical life cycles: both parasites cause their terrestrial arthropod hosts to seek water, required for their aquatic free‐living adult stage. Hairworms achieve this by altering host neurotransmitters, but the mechanisms used by mermithids remain unknown.

The physiological effects of the mermithid nematodeThaumamermis zealandicaon its host, the supralittoral talitrid amphipodTalorchestia quoyana, are investigated. The parasite develops in the haemocoel, and induces the host to burrow more deeply than healthy amphipods and the adultT. zelandicaemerges from the host into moist sand at these greater depths.

Parasitized amphipods had higher haemolymph osmolality than unparasitized amphipods. There was no difference in haemolymph Na+, K+or Mg2+concentrations between parasitized and unparasitized amphipods.

Water content did not differ between parasitized and unparasitized amphipods. Lipid reserves were lower in parasitized male amphipods than in unparasitized males; there was no difference among females.

Increase of host haemolymph osmolality byT. zealandicacould induce ‘thirst’, explaining why parasitized amphipods seek water‐saturated sand. This mechanism appears more parsimonious than that used by nematomorphs to achieve the same change in host behaviour.
Default Recovery Rates in Credit Risk Modelling: A Review of the Literature and Empirical Evidence
Authors: Altman Edward , Resti Andrea , Sironi Andrea
Published: September 2004

Evidence from many countries in recent years suggests that collateral values and recovery rates (RRs) on corporate defaults can be volatile and, moreover, that they tend to go down just when the number of defaults goes up in economic downturns. This link between RRs and default rates has traditionally been neglected by credit risk models, as most of them focused on default risk and adopted static loss assumptions, treating the RR either as a constant parameter or as a stochastic variable independent from the probability of default (PD). This traditional focus on default analysis has been partly reversed by the recent significant increase in the number of studies dedicated to the subject of recovery‐rate estimation and the relationship between default and RRs. This paper presents a detailed review of the way credit risk models, developed during the last 30 years, treat the RR and, more specifically, its relationship with the PD of an obligor. Recent empirical evidence concerning this issue is also presented and discussed.

(J.E.L.: G15, G21, G28).
The Co‐initial Swap Market Model
Authors: Galluccio Stefano , Hunter Christopher
Published: September 2004

In this paper, we introduce a novel approach to the pricing and the risk management of generic European style interest‐rate derivatives. This new model has great flexibility and has the advantage of avoiding complex model calibration techniques typical of standard short‐rate models. Dynamics is assigned on a set of co‐initial forward swap rates, and arbitrage‐free restrictions are determined in a normal and lognormal setup. Model implementation and calibration are discussed, and details of two example applications are also presented.

(J.E.L.: G12, G13).
Semi‐analytic Approaches to Collateralized Debt Obligation Modelling
Authors: Bluhm Christian , Overbeck Ludger
Published: September 2004

Collateralized debt obligations (CDOs) constitute an important class of asset‐backed securities. Most major banks use CDOs as portfolio management tools for achieving regulatory capital relief, economic risk transfer and funding. On the other side, banks and other financial institutions invest in CDO tranches with a risk/return profile matching their risk appetite and investment policies. For both sides (risk selling and risk buying) of a CDO transaction, sound mathematical tools are required for an evaluation of the deal. In this paper, we investigate some techniques for CDO modelling, paying special attention to approaches based on semi‐analytic approximations.
Preventing Systemic Crises through Bank Transparency
Authors: Hyytinen Ari , Takalo Tuomas
Published: September 2004

The banking system is known to be vulnerable to self‐fulfilling crises that are caused by depositors’ co‐ordination failure. We show that transparency regulation may prevent certain types of systemic crisis by eliminating the possibility of coordination failure.

(J.E.L.: G21, G28).
Pricing and Informational Efficiency of the MIB30 Index Options Market. An Analysis with High‐frequency Data
Authors: Cassese Gianluca , Guidolin Massimo
Published: September 2004

We analyse the pricing and informational efficiency of the Italian market for options written on the most important stock index, the MIB30. We report that a striking percentage of the data consists of option prices violating basic no‐arbitrage conditions. This percentage declines when we relax the no‐arbitrage restrictions to accommodate the presence of bid/ask spreads and other frictions but never becomes negligible. We also investigate the informational efficiency of the MIBO and conclude that option prices are poor predictors of the volatility of MIB30 returns. This conclusion is robust to a number of statistical and sampling methods.

(J.E.L.: G13, G14).
Cytochrome c oxidase as the target of the heat shock protective effect in septic liver
Authors: Chen Hsiang‐Wen , Kuo Hung‐Tien , Lu Tzong‐Shi , Wang Shu‐Jung , Yang Rei‐Cheng
Published: September 2004

Liver function failure is one of the characteristics of critically ill, septic patients and is associated with worse outcome. Our previous studies have demonstrated that heat‐shock response protects cells and tissue from subsequent insults and improves survival during sepsis. In this study, we have shown that mitochondrial cytochrome c oxidase (CCO) is one of the major sources of that protective effect. Experimental sepsis was induced by the cecal ligation and puncture (CLP) method. Heat‐shock treatment was induced in rats by hyperthermia 24 h before CLP operation. The results showed that ATP content of the liver declined significantly, and the enzymatic activity of mitochondrial CCO was apparently suppressed during the late stages of sepsis. The mitochondrial ultrastructure of septic liver showed the deformity, mild swelling and inner membrane budding. Heat‐shock treatment led to heat‐shock protein 72 overexpression and prevented the downregulation of Grp75 during sepsis. On the contrary, the expression of the enzyme complex and its activity were preserved, associated with the minimization of ultrastructural deformities. In conclusion, the maintenance of mitochondrial function, especially the CCO, may be an important strategy in therapeutic interventions of a septic liver.
Liver portal fibrosis in dioxin receptor‐null mice that overexpress the latent transforming growth factor‐β‐binding protein‐1
Authors: Corchero Javier , Martín‐Partido Gervasio , Dallas Sarah L. , Fernández‐Salguero Pedro M.
Published: September 2004

Mice lacking aryl hydrocarbon (dioxin) receptor (AhR) had variable degree of hepatic fibrosis and altered liver architecture. Transforming growth factor‐β (TGF‐β), a major profibrogenic molecule in the liver, is localized to the extracellular matrix by its association to the latent TGF‐β‐binding protein‐1 (LTBP‐1). Very recently, LTBP‐1 has been shown to be negatively regulated by the AhR. Embryonic fibroblasts from AhR‐null (AhR–/–) mice overexpress LTBP‐1 and secrete four times more active TGF‐β than wild‐type fibroblasts. To test whether TGF‐β and LTBP‐1 overexpression colocalize within the fibrotic nodule of AhR–/– liver, we have characterized this hepatic portal fibrosis using collagen protein staining, immunohistochemistry and in situ hybridization. LTBP‐1 mRNA and protein were overexpressed in the fibrotic region and colocalized with other indicators of fibrosis such as collagen and fibronectin and the fibroblast marker proteins α‐actin and vimentin. TGF‐β protein also colocalized with fibrosis, although in contrast, TGF‐β mRNA expression, rather than restricted to the fibrotic compartment, was present throughout the hepatic parenchyma and exhibited similar levels in wild‐type and AhR–/– mice. These results suggest that LTBP‐1 targets TGF‐β to specific areas of the liver and that the AhR could be a negative regulator of liver fibrosis, possibly through the control of LTBP‐1 and TGF‐β activities.
The effect of enalapril on the cardiac remodelling in ovariectomized spontaneously hypertensive rats
Authors: Santos Wellington V. , Pereira Leila M.M. , Mandarim‐de‐Lacerda Carlos A.
Published: September 2004

Angiotensin‐converting enzyme inhibitors reduce the blood pressure (BP) and inhibit the generation of the angiotensin II from the inactive angiotensin I. Ten 28‐week‐old spontaneously hypertensive rats (SHRs) had their ovaries bilaterally removed and five rats were left intact and studied for 7 additional weeks: intact group, ovariectomized group (ovx SHRs) and ovariectomized + enalapril group (ovx + en). BP was higher in ovx SHRs and lower in treated ovx SHRs. Left ventricular (LV) mass index was greater in untreated ovx SHRs and smaller in ovx + en group. The LV cardiomyocyte (cmy) mean cross‐sectional area, measured by stereology, was greater in ovx SHRs and smaller in both intact and ovx + en SHRs. Ovx significantly decreased the density of intramyocardial blood vessels (ive), but administration of enalapril was able to restore the density of the ive to that seen in intact group. The worst ive:cmy ratio was found in untreated ovx SHRs, the intact group showed a 90% greater ratio, and the treated ovx group showed a 150% greater ratio than the untreated ovx group. In conclusion, ovariectomy, in SHRs, causes cardiac hypertrophy and an unfavourable myocardial remodelling. Of the spectrum of changes seen, the major effect of enalapril appears to be mediated via an increase in the density of ive.
Factor XIII V34L polymorphism modulates the risk of chronic venous leg ulcer progression and extension
Authors: Gemmati Donato , Tognazzo Silvia , Serino Maria L. , Fogato Luisella , Carandina Sergio , De Palma Massimiliano , Izzo Marcello , De Mattei Monica , Ongaro Alessia , Scapoli Gian L. , Caruso Angelo , Liboni Alberto , Zamboni Paolo
Published: September 2004

Low Factor XIII (FXIII) activity has been reported in the blood of patients with chronic venous leg ulcer (CVU). In vivo studies have described increased wound healing in CVU patients treated with FXIII concentrate, and in vitro studies have shown increased regenerative capacity in FXIII‐treated fibroblasts. In addition, a common G‐to‐T polymorphism in the FXIIIA‐subunit gene (V34L) significantly increases the activity and modifies the cross‐linking properties of the FXIII molecule and this variant has been investigated as a protective factor against thrombosis, a recognized risk factor for CVU establishment. Therefore, the role of FXIII levels, FXIII V34L, FVR506Q, and FIIG20210A, common gene polymorphisms in the pathogenesis of CVU was investigated. Ninety‐one patients with CVU and 195 healthy controls (91 of them sex‐ and age‐matched) were PCR‐genotyped for the FXIIIV34L, FVR506Q, and FIIG20210A substitutions and FXIIIA‐subunit levels were determined by immuno‐electrophoresis. The extent of the venous ulcer surface in patients was measured by computer software. The allele frequency and the genotype distribution of the FXIII polymorphism did not show significant differences between the whole group of cases and controls as well as prothrombin variants did. On the contrary, the FVR506Q variant (FV Leiden) allele was more frequent in patients, yielding a significant OR value of 5.93 (95 percent CI, 1.83–19.17; p= 0.003). Considering only CVU cases secondary to a post–thrombotic syndrome (n= 24), FV Leiden yielded a greater OR value of 16.08 (95 percent CI, 4.33‐59.6; p < 0.0001). When the CVU cases were stratified by the three possible FXIII genotypes, a significant trend toward a lower mean value of the ulcerated area was clearly evident as the number of the polymorphic alleles (L34) increased in the genotype of patients (VV = 11.9 cm2,± 23.6; VL = 6.1 cm2,± 6.9; LL = 4.1 cm2,± 2.8; p= 0.01). On the other hand, FXIIIA antigen levels were similar between CVU cases and matched controls, but 11 percent of cases had FXIII deficiency (FXIIIA ≤ 0.65 U/ml; p= 0.003) and they showed a greater mean extension of the lesion if compared with the remaining cases without FXIIIA deficiency (14.5 cm2, ± 20.2 vs. 9.0 cm2, ± 6.3; p= 0.08). We conclude that FXIII antigen levels and FXIII V34L polymorphism may play a crucial role in the complex cascade of CVU pathophysiology, being significantly related to the CVU progression and extension because of the direct effects they have on the FXIII molecular activity.
Modulation of scar tissue formation using different dermal regeneration templates in the treatment of experimental full‐thickness wounds
Authors: Druecke Daniel , Lamme Evert N. , Hermann Sonja , Pieper Jeroen , May Paul S. , Steinau Hans‐Ulrich , Steinstraesser Lars
Published: September 2004

The recovery of skin function is the goal of each burn surgeon. Split‐skin graft treatment of full‐thickness skin defects leads to scar formation, which is often vulnerable and instable. Therefore, the aim of this study was to analyze wound healing and scar tissue formation in acute full‐thickness wounds treated with clinically available biopolymer dermal regeneration templates. Full‐thickness wounds (3 × 3 cm) on both flanks of Gottingen mini pigs (n= 3) were treated with split‐thickness skin graft alone or in combination with a 1‐ethyl‐3‐(3‐dimethylaminopropyl)‐carbodiimide (EDC) cross‐linked‐collagen scaffold, Integra, or a polyethyleneglycol terephthalate‐polybutylene terephthalate (PEGT/PBT) scaffold. The wounds (n= 12 per group) were examined weekly for six weeks to evaluate graft take, contraction (planimetry), and cosmetic appearance. Histologic samples taken after one and six weeks were used to assess scaffold angiogenesis, biocompatibility, and scar tissue quality. In all wounds, one week postwounding graft take was between 93 and 100 percent. The control wound, treated with split‐skin graft, showed little granulation tissue formation, whereas the EDC‐collagen treated wounds showed two to three times more granulation tissue formation. The collagen scaffold was completely degraded within one week. The Integra and PEGT/PBT scaffolds showed angiogenesis only through two‐thirds of the scaffold, which resulted in loss of integrity of the epidermis. Only basal cells survived, proliferated, and regenerated a fully differentiated epidermis within three weeks. Granulation thickness was comparable to collagen scaffold‐treated wounds. After six weeks, control wounds showed a wound contraction of 27.2 ± 6.1 percent, Integra‐treated wounds 34.6 ± 6.4 percent, collagen scaffold‐treated wounds 38.1 ± 5.0 percent, and PEGT/PBT scaffold‐treated wounds 54.5 ± 3.9 percent. The latter wounds had significantly more contraction than wounds of other treatment groups. Microscopically, the control and collagen scaffold‐treated wounds showed an immature scar tissue that was two times thicker in the EDC‐collagen treated wounds. The Integra‐treated wounds showed nondegraded collagen scaffold fibers with partly de novo dermal tissue formation and partly areas with giant cells and other inflammatory cells. The PEGT/PBT scaffold was almost completely degraded. Scaffold particles were phagocytosized and degraded intracellularly by clusters of macrophages. The scar tissue was in the early phase of ECM remodeling. In conclusion, this study showed that the rate of dermal tissue formation and scarring is influenced by the rate of scaffold angiogenesis, degradation, and host response induced by the scaffold materials.
Histologic evaluation of skin‐derived and collagen‐based substrates implanted in palatal wounds
Authors: Ophof Ricardo , Maltha Jaap C. , Von Den Hoff Johannes W. , Kuijpers‐Jagtman Anne‐Marie
Published: September 2004

Tissue shortage complicates the surgery of cleft lip and palate anomalies and the healing of defects on the palate impairs growth of the dento‐alveolar complex due to scar tissue formation. Implantation of substitutes into the wound area might overcome this adverse effect. The aim of this study was to compare the tissue response to three collagen‐based (collagen type I substrate alone, or collagen coated with elastin or chondroitin‐6‐sulfate) and two skin‐derived substrates (unprocessed dermis and AlloDerm) after implantation into 12 dogs. Histology was performed at 3, 10, and 20 days postsurgery. We showed that all substrates were well tolerated. However, it is unclear whether AlloDerm was rapidly degraded or if it was sequestrated. There was no elastin or collagen present in these wounds. All collagen‐based substrates showed good epithelial regeneration, although heparan sulfate (JM 403) was absent. Wounds treated with the collagen‐based substrates contained fewer myofibroblasts at 20 days postsurgery and the type III collagen fibers in the immature scar tissue were more randomly oriented than in an untreated wound. In conclusion, palatal wounds with a dermal substrate heal with fewer indications of scar tissue formation and evoke only a mild inflammatory reaction, which is preferred over the tissue reaction in an untreated wound.
Fascial fibroblast kinetic activity is increased during abdominal wall repair compared to dermal fibroblasts
Authors: Dubay Derek A. , Wang Xue , Kirk Sofia , Adamson Belinda , Robson Martin C. , Franz Michael G.
Published: September 2004

Abdominal wall fascial wound healing failure is a common clinical problem for general surgeons, manifesting in early postoperative fascial dehiscence as well as delayed development of incisional hernias. We previously reported that abdominal wall fascial incisions normally recover breaking strength faster than simultaneous dermal incisions in a rodent model. The accelerated fascial repair was associated with greater fibroblast cellularity within fascial wounds and increased wound collagen deposition. The current study was designed to determine whether accelerated fascial healing is the result of increased fascial fibroblast kinetic activity as measured by a more efficient fibroblast phenotype for binding to and remodeling a collagen matrix. Using a new model of abdominal wall repair, fibroblast cell cultures were developed from uninjured and wounded fascia and compared to dermal fibroblasts in order to define the fibroproliferative kinetic properties of abdominal wall fibroblasts. Fascial wound fibroblasts produced a more efficient and greater overall collagen lattice compaction compared to dermal fibroblasts. Acute fascial wound fibroblasts also showed enhanced cell proliferation compared to dermal fibroblasts but no significant differences in collagen production when normalized to cell number. These results suggest that fascial fibroblasts express distinct acute repair phenotypes and therefore a specific mechanism for fascial repair following injury.
Complex epithelial–mesenchymal interactions modulate transforming growth factor‐β expression in keloid‐derived cells
Authors: Xia Wei , Phan Toan‐Thang , Lim Ivor J. , Longaker Michael T. , Yang George P.
Published: September 2004

Keloids are proliferative dermal growths representing a pathologic wound healing response. We have previously demonstrated that coculture of fibroblasts derived from either keloid or normal skin have an elevated proliferation rate when cocultured with keloid‐derived keratinocytes vs. normal keratinocytes. In these studies, we examined the contribution of transforming growth factor‐β (TGF‐β) to this phenomenon using a two‐chamber coculture system. Fibroblast proliferation in coculture was slower with the addition of a pan‐TGF‐β neutralizing antibody. Keloid keratinocytes in coculture expressed more TGF‐β1, ‐β3, and TGF‐β receptor 1 than normal keratinocytes. Keloid fibroblasts cocultured with keloid keratinocytes expressed more mRNA for TGF‐β1, ‐β2, TGF‐β receptor 1, and Smad2. Keloid fibroblasts also produced more type I collagen, connective tissue growth factor, and insulin‐like growth factor‐II/mannose‐6‐phosphate receptor when cocultured with keloid keratinocytes vs. normal keratinocytes. Levels of total and activated TGF‐β activity increased when fibroblasts were cocultured with keratinocytes, correlating with the changes in transcriptional activity of TGF‐β. In conclusion, we find a complex paracrine interaction regulates TGF‐β mRNA expression and activation between keratinocytes and fibroblasts. These data suggest that keloid pathogenesis may result from both an increased TGF‐β production and activation by the keloid keratinocyte, and elevated TGF‐β expression, utilization, and signaling in keloid fibroblasts.
Fluorescence imaging of reepithelialization from skin explant cultures on acellular dermis
Authors: Lu Hongguang , Rollman Ola
Published: September 2004

Reconstituted skin models are valuable tools in studies of cutaneous biology although they are not generally devised to visualize and quantify the time course of reepithelialization. We describe a skin explant culture technique coupled with vital microscopy allowing sequential imaging of epithelial outgrowth while maintaining the tissue in culture. Radial expansion of neo‐epidermis was initiated from a 2‐mm skin punch biopsy explanted onto acellular human dermis and maintained at the air–liquid interface in serum‐containing keratinocyte medium. Microscopic viewings and surface area measurements of newly formed epidermis were performed repeatedly using fluorescein‐based cell staining and subsequent image analysis. The labeling and visualization procedures did not interfere with neo‐epidermal growth or tissue architecture. In order to appraise the versatility of the model, we studied the effect of epidermal growth factor supplementation on the course of skin resurfacing as related to tissue morphology and proliferative activity over a 10‐day cultivation period. Exogenous epidermal growth factor at 10 ng/ml increased the radial outgrowth rate (mean, + 13.3 percent), papillomatosis index (+ 19.2 percent), epithelial thickness (+ 49.8 percent), and fraction of Ki‐67 positive basal cells (+ 18.4 percent) in neo‐epidermis produced from a biopsy of normal human skin. The contribution of this miniaturized and convenient format for concurrent studies of dynamic and qualitative features of neo‐epidermis should be a useful complement to existing assays of epidermalization.
Adenoviral mediated gene transfer of PDGF‐B enhances wound healing in type I and type II diabetic wounds
Authors: Keswani Sundeep G. , Katz Anna B. , Lim Foong‐Yen , Zoltick Philip , Radu Antoneta , Alaee Datis , Herlyn Meenhard , Crombleholme Timothy M.
Published: September 2004

We have shown that the genetically diabetic mouse (C57BLKS/J‐m+/+Leprdb) has a wound healing and neovascularization deficit associated with an inability to recruit endothelial precursor cells (EPCs) to the wound. This may account for a fundamental mechanism in impaired diabetic wound healing. We hypothesized that the adenoviral mediated overexpression of platelet‐derived growth factor‐B (PDGF‐B) would enhance wound healing, improve neovascularization, and recruit EPCs to the epithelial wound in three diabetic mouse models. Eight‐mm full‐thickness flank wounds were made in db/db, nonobese NOD/Ltj, streptozotocin, and C57BLKS/J mice. Wounds were treated with either 1 × 108 PFU Ad‐PDGF‐B or Ad LacZ or phosphate buffered saline solution. Wounds harvested at seven days were analyzed for epithelial gap, blood vessel density, granulation tissue area, and EPCs per high powered field. All three diabetic models have a significant wound healing and neovascularization defect compared to C57BLKS/J controls. Adenoviral‐PDGF‐B treatment significantly enhanced epithelial gap closure in db/db, streptozotocin, and nonobese NOD/Ltj mice as compared to diabetic phosphate buffered saline solution or Ad LacZ controls. A similar increase in the formation of granulation tissue and vessel density was also observed. All three models had reduced levels of GATA‐2 positive EPCs in the wound bed that was corrected by the adenoviral mediated gene transfer of PDGF. EPC recruitment was positively correlated with neovascularization and wound healing. Three different diabetic models have a wound healing impairment and a decreased ability to recruit EPCs. The vulnerary effect of adenoviral mediated gene therapy with PDGF‐B significantly enhanced wound healing and neovascularization in diabetic wounds. The PDGF‐B mediated augmentation of EPC recruitment to the wound bed may be a fundamental mechanism of these results.
The role of the hiatus hernia in gastro‐oesophageal reflux disease
Authors: Gordon C. , Kang J. Y. , Neild P. J. , Maxwell J. D.
Published: September 2004

A sliding hiatus hernia disrupts both the anatomy and physiology of the normal antireflux mechanism. It reduces lower oesophageal sphincter length and pressure, and impairs the augmenting effects of the diaphragmatic crus. It is associated with decreased oesophageal peristalsis, increases the cross‐sectional area of the oesophago‐gastric junction, and acts as a reservoir allowing reflux from the hernia sac into the oesophagus during swallowing. The overall effect is that of increased oesophageal acid exposure. The presence of a hiatus hernia is associated with symptoms of gastro‐oesophageal reflux, increased prevalence and severity of reflux oesophagitis, as well as Barrett's oesophagus and oesophageal adenocarcinoma. The efficacy of treatment with proton pump inhibitors is reduced. Our view on the significance of the sliding hiatus hernia in gastro‐oesophageal reflux disease has changed enormously in recent decades. It was initially thought that a hiatus hernia had to be present for reflux oesophagitis to occur. Subsequently, the hiatus hernia was considered an incidental finding of little consequence. We now appreciate that the hiatus hernia has major patho‐physiological effects favouring gastro‐oesophageal reflux and hence contributing to oesophageal mucosal injury, particularly in patients with severe gastro‐oesophageal reflux disease.
Meta‐analysis: budesonide treatment for collagenous colitis
Authors: Feyen B. , Wall G. C. , Finnerty E. P. , DeWitt J. E. , Reyes R. S.
Published: September 2004

Background : Collagenous colitis is typified by chronic watery diarrhoea and characteristic histological alterations of the colonic mucosa without endoscopic abnormalities. Budesonide, a corticosteroid with high first‐pass metabolism has been examined in collagenous colitis, but studies to date have had small numbers, and relatively low statistical power.

Aim : A meta‐analysis of existing published trials was undertaken to evaluate the treatment effect of budesonide in collagenous colitis.

Methods : All pertinent literature sources were searched for published reports in English of budesonide use in collagenous colitis. MEDLINE and EMBASE databases were reviewed, as well as bibliographies from published articles and available abstracts from relevant meetings. Literature that met prespecified criteria was selected for the meta‐analysis.

Results : Three trials were included in the meta‐analysis. Budesonide significantly decreased stool frequency (budesonide vs. placebo OR: 20.1, 95% CI: 7.0–57.5, P < 0.0001). In general, budesonide treatment was well‐tolerated.

Conclusions : Budesonide is clinically effective short‐term in collagenous colitis, and seems to be relatively well‐tolerated. Clinicians can consider this drug as a reasonable option for patients with this disorder.
Natural history of gastro‐oesophageal reflux disease diagnosed in general practice
Authors: Ruigómez A. , García Rodríguez L. A. , Wallander M.‐A. , Johansson S. , Graffner H. , Dent J.
Published: September 2004

Background : Cross‐sectional studies indicate that gastro‐oesophageal reflux disease symptoms have a prevalence of 10–20% in Western countries and are associated with obesity, smoking, oesophagitis, chest pain and respiratory disease.

Aim : To determine the natural history of gastro‐oesophageal reflux disease presenting in primary care in the UK.

Methods : Patients with a first diagnosis of gastro‐oesophageal reflux disease during 1996 were identified in the UK General Practice Research Database and compared with age‐ and sex‐matched controls. We investigated the incidence of gastro‐oesophageal reflux disease, potential risk factors and comorbidities, and relative risk for subsequent oesophageal complications and mortality.

Results : The incidence of a gastro‐oesophageal reflux disease diagnosis was 4.5 per 1000 person‐years (95% confidence interval: 4.4–4.7). Prior use of non‐steroidal anti‐inflammatory drugs, smoking, excess body weight and gastrointestinal and cardiac conditions were associated with an increased risk of gastro‐oesophageal reflux disease diagnosis. Subjects with gastro‐oesophageal reflux disease had an increased risk of respiratory problems, chest pain and angina in the year after diagnosis, and had a relative risk of 11.5 (95% confidence interval: 5.9–22.3) of being diagnosed with an oesophageal complication. There was an increase in mortality in the gastro‐oesophageal reflux disease cohort only in the year following the diagnosis.

Conclusions : Gastro‐oesophageal reflux disease is a disease associated with a range of potentially serious oesophageal complications and extra‐oesophageal diseases.
There is no difference in the disease severity of gastro‐oesophageal reflux disease between patients infected and not infected with Helicobacter pylori
Authors: Fallone C. A. , Barkun A. N. , Mayrand S. , Wakil G. , Friedman G. , Szilagyi A. , Wheeler C. , Ross D.
Published: September 2004

Background : The role of Helicobacter pylori in gastro‐oesophageal reflux disease (GERD) is controversial.

Aim : To compare the severity of GERD in infected vs. non‐infected patients, as part of an ongoing randomized controlled trial that examines the impact of H. pylori eradication on GERD‐related outcomes.

Methods : Consecutive GERD patients underwent urea breath testing and completed validated GERD symptom severity, and quality of life questionnaires as well as, 24‐h pH‐metry. These parameters, as well as demographics and endoscopic findings were assessed in double‐blinded fashion and compared between H. pylori‐infected and non‐infected subjects.

Results : Helicobacter pylori‐infected GERD patients (n = 50) were significantly older and less educated than non‐infected patients (n = 51). They also used proton pump inhibitors less often but had no difference in symptoms (as measured with both the Spechler's Activity Index and the Gastrointestinal Symptom Rating Scale), quality of life, endoscopic findings or 24‐h pH‐metry findings.

Conclusion : This prospective, double‐blind study demonstrates, using excellent GERD quantifying measures including validated symptom severity scores, endoscopy, and 24‐h pH‐metry, that there exist no clinically significant differences in clinical or laboratory‐related GERD manifestations between H. pylori‐infected and non‐infected GERD patients.
The effect of Helicobacter pylori and its eradication on gastro‐oesophageal reflux disease in patients with duodenal ulcers or reflux oesophagitis
Authors: Raghunath A. S. , Hungin A. P. S. , Wooff D. , Childs S.
Published: September 2004

Background : The effect of Helicobacter pylori in provoking or protecting against gastro‐oesophageal reflux disease is unclear and studies have given conflicting results. Recent guidelines recommend H. pylori eradication in patients on long‐term proton pump inhibitors.

Aim : To ascertain the effect of H. pylori eradication on gastro‐oesophageal reflux disease outcomes (reflux oesophagitis and heartburn) in patients with duodenal ulcer disease, and to ascertain the effect of H. pylori infection on reflux oesophagitis concerning heartburn, pH, severity, healing and relapse rates.

Methods : A systematic review of electronic databases was undertaken to September 2003. Experts in the field, pharmaceutical companies and journals were contacted about unpublished trials. Studies were reviewed according to predefined eligibility and quality criteria. Twenty‐seven studies/trials were included in the systematic review.

Results : Study variation rather than therapy‐influenced results in relation to the presence or absence of oesophagitis in patients with duodenal ulcer who underwent H. pylori eradication at 6–48 months follow‐up. In patients with reflux oesophagitis no obvious differences were discovered in heartburn scores, 24‐h pH values, healing and relapse rates between H. pylori‐positive and ‐negative cases.

Conclusion : There is no evidence to indicate that H. pylori eradication in duodenal ulcer disease provokes reflux oesophagitis or worsens heartburn; (ii) there are insufficient data to draw firm conclusions about the impact of H. pylori in patients with reflux oesophagitis.
Risk of malignancy in diagnosed coeliac disease: a 24‐year prospective, population‐based, cohort study
Authors: T. R. Card , J. West , G. K. T. Holmes
Published: September 2004

Background : There is recent evidence from studies of hospitalized and of undiagnosed patients that the risk of lymphoma for people with coeliac disease may be lower than previously thought. In addition, there have been no precise estimates of small bowel lymphoma risk due to a lack of population data.

Aim : To examine these and other malignant risks in a cohort of patients more typical of those seen in routine clinical practice.

Methods : A prospective cohort study of incident malignancy rates in patients with coeliac disease in southern Derbyshire compared with general population figures.

Results : During 5684 person years of follow‐up 31 malignancies (excluding non‐melanoma skin cancer) occurred in comparison with 30.30 expected [standardized incidence ratio (SIR) 1.02 (0.69–1.45)]. There were four non‐Hodgkin's lymphomas (0.69 expected) SIR 5.81 (1.58–14.86), of which one originated in small bowel (0.02 expected) SIR 40.51 (1.03–225.68). GI malignancy occurred in nine (5.71 expected) SIR 1.58 (0.72–2.99), and breast cancer in three (5.08 expected) SIR 0.59 (0.12–1.73).

Conclusions : There is no increase in the risk of incident malignancy in this population and the risk of non‐Hodgkin's lymphoma in general or of the small bowel is lower than previously found from UK coeliac cohorts.
Barrett's oesophagus with predominant intestinal metaplasia correlates with superficial cyclo‐oxygenase‐2 expression, increased proliferation and reduced apoptosis: changes that are partially reversed by non‐steroidal anti‐inflammatory drugs usage
Authors: Amano Y. , Ishihara S. , Kushiyama Y. , Yuki T. , Takahashi Y. , Chinuki D. , Miyake T. , Miyaoka Y. , Rumi M. A. K. , Ishimura N. , Adachi K. , Kinoshita Y.
Published: September 2004

Background : Cyclo‐oxygenase‐2 expression has been reported to play an important role in the metaplasia‐dysplasia‐carcinoma sequence in Barrett's oesophagus. However, the existence of cyclo‐oxygenase‐2 expressing cells in Barrett's epithelium is still uncertain.

Aim : To identify the cells that express cyclo‐oxygenase‐2 protein and to investigate the relationship between cyclo‐oxygenase‐2 expression and mucin‐phenotype of Barrett's epithelium.

Methods : Sections from 466 biopsy samples of Barrett's epithelium from 358 non‐medicated patients were immunohistochemically examined for the cyclo‐oxygenase‐2 expression, mucin‐phenotype, cell proliferation and apoptosis.

Results : Cyclo‐oxygenase‐2 expression was detected in 71.0% of Barrett's epithelium biopsy samples. In Barrett's epithelium with the gastric predominant mucin‐phenotype, cyclo‐oxygenase‐2 expression was mainly found in stromal and deep epithelial cells, whereas in intestinal predominant mucin‐phenotype, it was mostly in superficial epithelial cell. A significant elevation of proliferating cell nuclear antigen index and suppression of apoptotic index was observed in Barrett's epithelium with superficial epithelial cyclo‐oxygenase‐2 expression. Neither such elevation of proliferating cell nuclear antigen index nor the suppression of apoptotic index could be found in chronic non‐steroidal anti‐inflammatory drugs users.

Conclusions : Barrett's epithelium with intestinal mucin and superficial epithelial cyclo‐oxygenase‐2 expression possess a higher proliferation potential, but this risk may be thwarted by non‐steroidal anti‐inflammatory drugs administration.
Onset and disappearance of reflux symptoms in a Chinese population: a 1‐year follow‐up study
Authors: Wong W. M. , Lai K. C. , Lam K. F. , Hui W. M. , Huang J. Q. , Xia H. H. X. , Hu W. H. C. , Lam C. L. K. , Chan C. K. , Lam S. K. , Wong B. C. Y.
Published: September 2004

Background : The natural history of gastro‐oesophageal reflux disease in Asian population has not been studied before.

Aim : To study the onset and disappearances of reflux symptoms over a 1‐year period in the Chinese population.

Methods : A population‐based telephone survey was performed in 2002 and repeated 1 year later. The change in prevalence rate, onset and disappearance of gastro‐oesophageal reflux disease, and the change in diagnoses were assessed. Factors associated with the onset and disappearance of gastro‐oesophageal reflux disease were studied.

Results : A total of 712 subjects completed the first and second survey. The annual, monthly and weekly prevalence of gastro‐oesophageal reflux disease were 34.1%, 10.1% and 2.7% respectively. The onset rate (per 1000 person‐year) and disappearance rate of any gastro‐oesophageal reflux disease and frequent gastro‐oesophageal reflux disease (≥ monthly symptoms) were 209, 40; and 395, 243 respectively. Forty‐four percentage of gastro‐oesophageal reflux disease subjects changed their diagnoses in 2003. By multiple logistic regression analysis, high anxiety score (OR: 1.2, 95% CI: 1.1–1.2) and higher educational level (OR: 2.7, 95% CI: 1.3–6.3) were associated with the onset of gastro‐oesophageal reflux disease; while the frequency of acid regurgitation (OR: 0.35, 95% CI: 0.17–0.70) and use of antisecretory therapy (OR: 0.50, 95% CI: 0.28–0.89) were associated with the disappearance of gastro‐oesophageal reflux disease.

Conclusion : The prevalence of gastro‐oesophageal reflux disease is stable over 1 year. Higher anxiety score and higher educational level were associated with the onset of gastro‐oesophageal reflux disease, while lower frequency of reflux symptoms and infrequent use of antisecretory therapy were associated with the disappearance of gastro‐oesophageal reflux disease in a Chinese population.
Tumour lysis syndrome: new therapeutic strategies and classification
Authors: Cairo Mitchell S. , Bishop Michael
Published: September 2004

Tumour lysis syndrome (TLS) describes the metabolic derangements that occur with tumour breakdown following the initiation of cytotoxic therapy. TLS results from the rapid destruction of malignant cells and the abrupt release of intracellular ions, nucleic acids, proteins and their metabolites into the extracellular space. These metabolites can overwhelm the body's normal homeostatic mechanisms and cause hyperuricaemia, hyperkalaemia, hyperphosphaetemia, hypocalcaemia and uraemia. TLS can lead to acute renal failure and can be life‐threatening. Early recognition of patients at risk and initiation of therapy for TLS is essential. There is a high incidence of TLS in tumours with high proliferative rates and tumour burden such as acute lymphoblastic leukaemia and Burkitt's lymphoma. The mainstays of TLS prophylaxis and treatment include aggressive hydration and diuresis, control of hyperuricaemia with allopurinol prophylaxis and rasburicase treatment, and vigilant monitoring of electrolyte abnormalities. Urine alkalinization remains controversial. Unfortunately, there have been few comprehensive reviews on this important subject. In this review, we describe the incidence, pathophysiological mechanisms of TLS and risk factors for its development. We summarise recent advances in the management of TLS and provide a new classification system and recommendations for prophylaxis and/or treatment based on this classification scheme.
Tetramolecular immune complexes are more efficient than IVIg to prevent antibody‐dependent in vitro and in vivo phagocytosis of blood cells
Authors: Bazin Renée , Lemieux Réal , Tremblay Tony , St‐Amour Isabelle
Published: September 2004

Intravenous immunoglobulins (IVIg) have immunomodulatory effects in vivo and are widely used in the treatment of autoimmune diseases, such as idiopathic thrombocytopenic purpura (ITP). The mechanisms by which IVIg can prevent platelet clearance in ITP patients are not fully understood but are known to require the participation of low affinity Fcγ receptors (FcγRs), which interact poorly with monomeric immunoglobulin G (IgG). Given the importance of low affinity FcγRs in the treatment of ITP, we hypothesized that immune complexes (IC) produced in vitro could reproduce the effects of IVIg. Small‐size tetramolecular IC were prepared using mouse monoclonal anti‐human IgG and human Fc fragments. The effects of tetramolecular IC and IVIg on the in vitro and in vivo inhibition of phagocytosis of opsonized blood cells were compared. The results obtained showed that tetramolecular IC were at least six times more efficient than IVIg to prevent phagocytosis of opsonized red blood cells in vitro, and clearance of platelets in the thrombocytopenic mouse model.
Dose and response in haemophilia – optimization of factor replacement therapy
Authors: Srivastava Alok
Published: September 2004

The mainstay of the management of haemophilia is the replacement of clotting factors, using clotting factor concentrates (CFC) in a way that prevents bleeding and its complications. Beginning with small doses, as whole blood and plasma over 50 years ago, highly purified CFCs are now administered frequently in large doses to effectively treat this condition so that even people with severe haemophilia can lead near normal lives. However, with such regimens, compliance and expense have both become significant issues. The question therefore is whether the current models of clotting factor replacement are optimal. This article reviews the literature on the dose–response relationship in haemophilia, with particular reference to management of musculoskeletal bleeding and surgical haemostasis. Current practices are based on uncontrolled observational data. Less intensive protocols could achieve similar outcomes. Large multi‐centre prospective studies are needed to provide comparative data on unresolved issues so that factor replacement therapy can be optimized, based on evidence.