bluuebunny/crossref_metadata_2025 huggingface dataset:
Biopsy of musculoskeletal tumours − beware
Authors: Pollock Robin C. , Stalley Paul D.
Published: July 2004

Background:  Biopsy of musculoskeletal tumours is hazardous and, when poorly performed, can compromise limb salvage surgery and patient survival. The aim of the present paper is to examine the early management of such patients referred to the Department of Orthopaedic Surgery, Royal Prince Alfred Hospital, Sydney, Australia with particular reference to biopsy.

Methods:  We conducted a prospective audit of all patients referred to our musculoskeletal tumour service during 2002. Inclusion criteria were: all patients with primary tumours of the musculoskeletal system. We compared the outcome of patients biopsied prior to referral with that of patients biopsied in a recognized treatment centre.

Results:  One hundred and forty‐two patients were included. The referring surgeon performed biopsies in 29 cases, of which 20 were malignant lesions. The senior author biopsied the remaining 113 cases, of which 57 were malignant. Definitive treatment was hindered by a badly performed biopsy in 38% of patients biopsied by the referring surgeon. In 25% the definitive treatment had to be changed either to a more radical procedure than would have originally been necessary or to palliative rather than curative intent. Patients biopsied elsewhere were more likely to have an incomplete excision requiring re‐excision, more likely to require amputation, and more likely to require adjuvant radiotherapy.

Conclusions:  There is a high complication rate when patients with musculoskeletal tumours are biopsied by surgeons inexperienced in their management. These patients are better served by early referral to a specialist centre where staging investigations including biopsy can be performed with minimal morbidity.
Mobile phone photo messaging assisted communication in the assessment of hand trauma
Authors: Lam Tai Khoa , Preketes Angelo , Gates Robert
Published: July 2004

Background:  The aim of the present study was to incorporate the use of mobile phone photo‐messaging into clinical practice, in order to explore its potential advantages and limitations in the context of communication between the registrar and consultant for the assessment of hand trauma.

Methods:  Two Nokia 7650 mobile phones (Nokia, Sydney, Australia) were obtained. These were used for correspondence between the registrar and the consultant for all hand trauma seen in the emergency department over a 2‐month period.

Results:  There were 27 cases recorded. Deductions were drawn form the use of the phone and the collected data was qualitatively interpreted.

Conclusion:  The present paper describes our findings and approval of the use of mobile phones with photo‐messaging capabilities for the purpose of enhancing communication in a clinical setting. Low cost and ease of use make the phones easily incorporated into clinical practice.
Guidelines for the management of haemodynamically unstable pelvic fracture patients
Authors: Heetveld Martin J. , Harris Ian , Schlaphoff Glen , Sugrue Michael
Published: July 2004

Background:  Haemodynamically unstable pelvic fracture patients have a high mortality, and decision‐making is crucial. The present article discusses key clinical practice guidelines and options in the early management of these challenging patients.

Methods:  A multidisciplinary consensus committee developed guidelines following standard scientific methodology, comprehensive Medline searches and level of evidence grading. Clinical practice guidelines and options addressed four key questions: (i) how to determine the source of haemorrhage?; (ii) how to control haemorrhage?; (iii) what is the optimal angiography and embolization technique?; and (iv) what is the optimal pelvic stabilization technique?

Results:  The consensus best evidence recommends that the source of intra‐abdominal haemorrhage should be assessed using diagnostic peritoneal aspiration and/or focused abdominal sonography in trauma within 30 min of patient arrival. Immediate laparotomy and concomitant pelvic stabilization control intra‐abdominal haemorrhage and venous pelvic haemorrhage, followed by angiography if pelvic arterial bleeding is also present. If intra‐abdominal bleeding is absent, non‐invasive pelvic stabilization and transfer to angiography within 45 min of arrival is recommended to control venous and arterial pelvic haemorrhage. Optimal embolization is performed with steel coils or Gelfoam (Pharmacia & Upjohn, Peapack, NJ, USA) suspension. The optimal pelvic stabilization technique for rotationally unstable fractures with haemodynamic instability is non‐invasive.

Conclusion:  The consensus committee successfully developed best evidence recommendations identifying the issues and providing guidelines and options for this challenging condition.
Laser shock peening on fatigue crack growth behaviour of aluminium alloy
Authors: TAN Y. , WU G. , YANG J.‐M. , PAN T.
Published: July 2004

The effect of laser shock peening (LPS) in the fatigue crack growth behaviour of a 2024‐T3 aluminium alloy with various notch geometries was investigated. LPS was performed under a ‘confined ablation mode’ using an Nd: glass laser at a laser power density of 5 GW cm−2. A black paint coating layer and water layer was used as a sacrificial and plasma confinement layer, respectively. The shock wave propagates into the material, causing the surface layer to deform plastically, and thereby, develop a residual compressive stress at the surface. The residual compressive stress as a function of depth was measured by X‐ray diffraction technique. The fatigue crack initiation life and fatigue crack growth rates of an Al alloy with different preexisting notch configurations were characterized and compared with those of the unpeened material. The results clearly show that LSP is an effective surface treatment technique for suppressing the fatigue crack growth of Al alloys with various preexisting notch configurations.
Surface crack growth of silicon nitride bearings under rolling contact fatigue
Authors: KIDA K. , URAKAMI T. , YAMAZAKI T. , KITAMURA K.
Published: July 2004

Surface crack growth of silicone nitride ceramic bearings under rolling contact fatigue has been investigated from the viewpoints of contact stresses (ring crack model) and fluid pressure (wedge effect model). The mechanisms of these two models have been investigated independently; however, it was impossible to separate the effects of contact stresses and fluid pressure on surface crack growth. In this paper the effects of contact stresses (ring crack model) on surface crack growth are investigated. In the ring crack model the crack growth is caused by contact stresses around the circumference of the contact circle. The growth of surface cracks located inside and outside the contact track was observed in order to obtain data from which we could reexamine the ring crack model. The outside cracks under rolling contact fatigue were propagated by contact stresses alone and also the inside cracks grew as slowly as the outside cracks. We concluded that the cracks are propagated by the single effect of contact stresses. Preliminary observations of surface crack growth showed that the cracks were unaffected by wear and residual stresses.
Structural integrity in electronics
Authors: PLUMBRIDGE W. J. , KARIYA Y.
Published: July 2004

With continuing miniaturisation, increased performance demands and the requirement to remove lead from solder alloys, the challenges to structural integrity and reliability of electronic equipment are substantial and increasing. This paper outlines typical features in electronic equipment of which the structural integrity community may be generally unaware. Potential failure modes in service are described, and the problems of scale and material characteristics are considered. Progress in the application of fracture mechanics to the life prediction of interconnections is reviewed. The limited evidence available suggests that the crack growth resistance of silver‐containing lead‐free solders is superior to that of the traditional Sn‐37Pb under cycle‐controlled conditions but there is no difference when time‐dependent conditions prevail. In several respects, it is contended that the electronics sector is faced with challenges at least equivalent to those encountered in gas turbines and nuclear power generation.
Analysis of the murine 5‐HT1A receptor gene promoter in vitro and in vivo
Authors: Ansorge Mark , Tanneberger Cornelia , Davies Benjamin , Theuring Franz , Kusserow Heike
Published: July 2004

The expression level of the 5‐HT1A receptor gene (htr1a) in the central nervous system (CNS) is implicated in the aetiology and treatment of anxiety disorders and depression. Previous studies of the murine htr1a have revealed that its proximal promoter is GC rich and TATA‐less. Several functional transcription factor binding sites, including MAZ and SP1 recognition sequences, have been identified. To further analyse the promoter of this receptor gene, additional upstream sequence information extending to −5.5 kb of the murine htr1a was generated and promoter fragments extending to −20 kb were analysed for activity in cell culture and transgenic animals. Promoter fragments greater than 4.5 kb in length were active in 5‐HT1A receptor mRNA positive cells and inactive in 5‐HT1A receptor mRNA negative cells. Smaller fragments were not able to confer this specificity. In agreement, using additive transgenesis to drive LacZ expression in vivo, CNS specific reporter gene expression was found with these longer constructs. Transgene expression in the 4.5‐ and 20‐kb mouse lines resembled the endogenous htr1a expression pattern, whereas the 5.5‐kb mouse lines surprisingly revealed strongly reduced expression. None of the three constructs was prone to confer ectopic expression, however, variation of expression between the transgenic lines was observed. Using colocalization studies we analysed the degree of concurrence of transgenic and endogenous htr1a expression brought about by these three different constructs. The highest degrees of colocalization were observed in mice harbouring the 20‐kb construct, suggesting a large promoter fragment is required to faithfully direct transgene expression in a 5‐HT1A receptor like pattern.
Intraocular delivery of BDNF following visual cortex lesion upregulates cytosolic branched chain aminotransferase (BCATc) in the rat dorsal lateral geniculate nucleus
Authors: Madeddu Federico , Naska Sibel , Menna Elisabetta , Chiellini Chiara , Sweatt Andrew J. , Hutson Susan M. , Benzi Luca , Maffei Margherita , Maffei Lamberto , Bozzi Yuri
Published: July 2004

Visual cortex ablation in newborn rats determines the almost complete degeneration of neurons in the dorsal lateral geniculate nucleus (dLGN), as a consequence of the axotomy of the geniculo‐cortical fibres. Death of dLGN neurons is massive and rapid, and occurs by apoptosis. We recently showed that exogenous administration of the neurotrophin brain‐derived neurotrophic factor (BDNF) in the eye prevents the degeneration of dLGN neurons occurring after visual cortex lesion in newborn rats. To elucidate the molecular mechanisms of BDNF‐mediated neuroprotection, we sought to identify novel genes regulated by BDNF in the rat dLGN after visual cortex lesion. By using mRNA fingerprinting, we isolated a cDNA fragment upregulated in the dLGN of lesioned rats treated with BDNF. This cDNA fragment shared 100% homology with the rat cytosolic branched chain aminotransferase (BCATc), a key enzyme of glutamate metabolism. Quantitative reverse transcription‐polymerase chain reaction and in situ hybridization confirmed that BCATc mRNA is markedly overexpressed by exogenous supply of BDNF to axotomized dLGNs. Immunohistochemical analysis showed that upregulation of BCATc in the dLGN of lesioned rats treated with BDNF takes place in astrocytes. These results suggest that modulation of glutamate metabolism by astrocytes might play an important role in BDNF‐mediated survival of axotomized dLGN neurons.
Inhibition of tyrosine kinase receptor type B synthesis blocks axogenic effect of estradiol on rat hypothalamic neurones in vitro
Authors: Brito V. I. , Carrer H. F. , Cambiasso M. J.
Published: July 2004

17‐β‐estradiol (E2) increases axonal growth and tyrosine kinase receptor (Trk)B levels of male‐derived hypothalamic neurones in vitro. To investigate whether the axogenic response depends on the upregulation of TrkB, we analysed neuritic growth and neuronal polarization in cultures treated with an antisense oligonucleotide against TrkB mRNA. In cultures without E2, treatment with 7.5 or 10 µm antisense reduced TrkB levels and the percentage of neurones showing an identifiable axon; the number and length of minor processes were increased. In cultures treated with 5 µm antisense, morphometric parameters were normal although total TrkB levels were reduced. The same dose prevented the E2‐dependent increase of TrkB levels and suppressed the axogenic effect of E2. These results indicate that TrkB is necessary for normal neuronal growth and maturation and further suggest that an increase in TrkB is necessary for E2 to exert its axogenic effect in male‐derived neurones.
Glutamatergic‐receptors blockade does not regularize the slow wave sleep bursty pattern of subthalamic neurons
Authors: Urbain Nadia , Vautrelle Nicolas , Dahan Lionel , Savasta Marc , Chouvet Guy
Published: July 2004

The subthalamic nucleus (STN) has been implicated in movement disorders observed in Parkinson's disease because of its pathological mixed burst firing mode and hyperactivity. In physiological conditions, STN bursty pattern has been shown to be dependent on slow wave cortical activity. Indeed, cortical ablation abolished STN bursting activity in urethane‐anaesthetized intact or dopamine depleted rats. Thus, glutamate afferents might be involved in STN bursting activity during slow wave sleep (SWS) when thalamic and cortical cells oscillate in a low‐frequency range. The present work was aimed to test, on non‐anaesthetized rats, if it was possible to regularize the SWS STN bursty pattern by microiontophoresis of kynurenate, a broad‐spectrum glutamate ionotropic receptors antagonist. As glutamatergic effects might be masked by GABAergic inputs arriving tonically and during the entire sleep‐wake cycle on STN neurons, kynurenate was also co‐iontophoresed with bicuculline, a GABAA receptors antagonist. Kynurenate iontophoretic applications had a weak inhibitory effect on the discharge rate of STN neurons whatever the vigilance state, and did not regularize the SWS STN bursty pattern. But, the robust bursty bicuculline‐induced pattern was impaired by kynurenate, which elicited the emergence of single spikes between remaining bursts. These data indicate that the bursty pattern exhibited by STN neurons specifically in SWS, does not seem to exclusively depend on glutamatergic inputs to STN cells. Furthermore, GABAA receptors may play a critical role in regulating the influence of excitatory inputs on STN cells.
Intravenous heroin self‐administration decreases GABA efflux in the ventral pallidum: an in vivo microdialysis study in rats
Authors: Caillé Stéphanie , Parsons Loren H.
Published: July 2004

Several lines of evidence suggest that opiate‐induced disinhibition of the ventral pallidum participates in the mediation of opiate reward, though direct in vivo evidence to support this hypothesis has been lacking. The present experiment tested this hypothesis by investigating alterations in ventral pallidal amino acid efflux using in vivo microdialysis during ongoing intravenous heroin self‐administration in rats. Concentrations of the inhibitory amino acid GABA in ventral pallidal dialysates were significantly reduced within the first 10 min of heroin self‐administration (0.02 mg per infusion; FR‐1), and remained ≈ 65% of presession baseline levels for the remainder of the 3‐h self‐administration session. Dialysate glutamate levels were unaltered during the first hour of heroin intake but significantly increased to a stable level of ≈ 120% presession values during the subsequent 2 h of self‐administration. Thus, heroin self‐administration is associated with both decreased GABA efflux and a late phase increase in glutamate efflux in the ventral pallidum. These observations are consistent with the hypothesis that heroin self‐administration results in a disinhibition and/or excitation of the ventral pallidum.
NMDA receptors are essential for the acquisition, but not expression, of conditional fear and associative spike firing in the lateral amygdala
Authors: Goosens Ki A. , Maren Stephen
Published: July 2004

We examined the contribution ofN‐methyl‐D‐aspartate (NMDA) receptors (NMDARs) to the acquisition and expression of amygdaloid plasticity and Pavlovian fear conditioning using single‐unit recording techniques in behaving rats. We demonstrate that NMDARs are essential for the acquisition of both behavioral and neuronal correlates of conditional fear, but play a comparatively limited role in their expression. Administration of the competitive NMDAR antagonist ±‐3‐(2‐carboxypiperazin‐4‐yl) propyl‐1‐phosphonic acid (CPP) prior to auditory fear conditioning completely abolished the acquisition of conditional freezing and conditional single‐unit activity in the lateral amygdala (LA). In contrast, CPP given prior to extinction testing did not affect the expression of conditional single‐unit activity in LA, despite producing deficits in conditional freezing. Administration of CPP also blocked the induction of long‐term potentiation in the amygdala. Together, these data suggest that NMDARs are essential for the acquisition of conditioning‐related plasticity in the amygdala, and that NMDARs are more critical for regulating synaptic plasticity and learning than routine synaptic transmission in the circuitry supporting fear conditioning.
Fear memories induce a switch in stimulus response and signaling mechanisms for long‐term potentiation in the lateral amygdala
Authors: Schroeder Bradley W. , Shinnick‐Gallagher Patricia
Published: July 2004

Activity‐dependent modification of synapses is fundamental for information storage in the brain and underlies behavioral learning. Fear conditioning is a model of emotional memory and anxiety that is expressed as an enduring increase in synaptic strength in the lateral amygdala (LA). Here we analysed synaptic plasticity in the rat cortico‐LA pathway during maintenance of fear memory. We show for the first time that the stimulus frequency for synaptic potentiation is switched during maintenance of fear memory, and the underlying signaling mechanisms are altered in the cortico‐LA pathway. In slices from fear‐conditioned animals, high‐frequency stimulation‐induced (HFS) long‐term potentiation (LTP) was attenuated, whereas low‐frequency stimulation (LFS) elicited a long‐lasting potentiation. HFS generates robust LTP that is dependent onN‐methyl‐d‐aspartate receptor (NMDAR) andL‐type voltage‐gated calcium channel (VGCC) activation in control animals, whereas in fear‐conditioned animals HFS LTP is NMDAR‐ and VGCC‐independent. LFS‐LTP is partially NMDAR‐dependent, but VGCCs are necessary for potentiation in fear memory. Collectively, these results show that during maintenance of fear memory the stimulus requirements for amygdala afferents and critical signaling mechanisms for amygdala synaptic potentiation are altered, suggesting that cue‐engaged synaptic mechanisms in the amygdala are dramatically affected as a result of emotional learning.
Building a Scientific Community: The Need for Replication
Authors: Schneider Barbara
Published: July 2004

This article argues for the importance of replication and data sharing in educational research. Relying on standards set in other disciplines, such as sociology, the article discusses how professional associations can help to create norms and incentives for data sharing and data archiving. The author discusses the importance of data sharing across disciplines and points out how qualitative and quantitative data are currently being shared across a range of investigators. Data sharing is essential to replication and creates a vehicle through which researchers can build upon their designs, create and revise measures, and study different populations for purposes of developing new theories. The sharing of information about studies, including the actual data upon which findings are based, allows researchers to verify, extend, and generalize findings.
The role of orthographic analogies in reading for meaning: evidence from readers with dyslexia
Authors: Humphrey Neil , Richard Hanley J.
Published: July 2004

The aim of this experiment was to investigate the use of orthographic analogies in conditions that involved making sense of print (picture‐word matching) and pronouncing print (reading aloud) for readers with dyslexia. An adapted version of the classic clue‐word paradigm developed by Goswami was used. Participants were 40 readers with dyslexia and 40 reading‐age‐matched comparison readers. Based on previous theory and research in this area, we predicted that readers with dyslexia would read significantly fewer analogous words than their reading‐age‐matched counterparts. In light of the supposition that word‐picture matching does not require the synthesised pronunciation of a word, we also predicted that readers with dyslexia might be less impaired at analogy use in the picture‐word matching than in the reading aloud condition. However, we found that the dyslexic group read significantly fewer analogous words at post‐test than their reading‐age‐matched peers in both conditions. Also, performance in overall word reading was better for both groups in the word‐picture matching condition. The implications of these results for theory and practice in reading development are discussed, and methodological limitations are noted.
Morphological structures in visual word recognition: the case of Arabic
Authors: Abu‐Rabia Salim , Awwad Jasmin (Shalhoub)
Published: July 2004

This research examined the function within lexical access of the main morphemic units from which most Arabic words are assembled, namely roots and word patterns. The present study focused on the derivation of nouns, in particular, whether the lexical representation of Arabic words reflects their morphological structure and whether recognition of a word involves recognition of its morphological constituents. The morphology of Arabic language constitutes two main systems: inflectional morphology and derivational morphology. Inflectional morphology is used to express grammatical relations and derivational morphology deals with the formation of new words in language; it contains two types of word patterns: verbal and nominal. In this study, it was assumed that roots are lexical entities that can facilitate lexical access to a large cluster of words that derive from them, whereas word patterns are not lexical entities and have no role in access to words assembled by them. The lexical representations of the main morphemic units were examined in four experiments using skilled readers applying masked priming technique tasks: lexical decision and naming. The results indicated that previous exposure to a word sharing the same word pattern had no marked facilitating effect on lexical decision or on naming. The main conclusion of this study on the morphology of Arabic is that roots and word patterns have no essential role in word organisation in the mental lexicon. In addition, words in nominal pattern in derivational morphology are represented in their whole shape in the mental lexicon and each word has an independent representation.
Representations of Wales and the Welsh during the civil wars and Interregnum
Authors: Bowen Lloyd
Published: July 2004

This article examines how Wales and the Welsh were represented in the pamphlet literature of the civil war and early Interregnum. It considers the historical construction of the Welsh image in English minds, and traces how this image came to be politicized by Welsh support for Charles I during the sixteen-forties. An examination of the public controversies surrounding the state-sponsored evangelization programme in Wales during the early sixteen-fifties shows how the contested image of Wales in the public sphere interacted with high politics at the centre. This study contributes to our understanding of the interplay between ethnicity, identity and politics during the sixteen-forties and fifties, and demonstrates how imagery and representation informed political discourse in the mid seventeenth century.
The mobilization of manpower for Britain's mid-eighteenth-century wars
Authors: Conway Stephen
Published: July 2004

This article seeks to assess the size and social composition of the armed forces from Britain and Ireland employed in the wars of 1739–63. The number of men serving in a military or naval capacity was larger than is usually recognized – especially during the Seven Years' War – and the background of such men was much more varied than most general accounts suggest. The ‘middling’ and artisan contribution was far from insignificant, especially in unofficial volunteer formations, but even in the regular armed forces.
‘No-one telling us what to do’: anarchist schools in Britain, 1890–1916
Authors: Thomas Matthew
Published: July 2004

This article seeks to analyse the intentions of anarchists in organizing schools in London and Liverpool between 1890 and 1916. It will also address the various teaching practices and methods of management adopted, and the experience of the children within the schools. Although they formulated many original ideas, the anarchist educators failed to break out of their own milieu and influence a wider community. The experiments in counter-education, meant to be a starting point for an alternative culture, embraced mostly foreign children who had already been brought up within an anarchist sub-culture. This was despite the fact that the libertarian schools belonged to a wider tradition of independent, working-class education that at times was in tune with anarchist thinking.
Regulation of RANTES/CCL5 expression in human astrocytes by interleukin‐1 and interferon‐β
Authors: Kim Mee‐Ohk , Suh Hyeon‐Sook , Brosnan Celia F. , Lee Sunhee C.
Published: July 2004

In the CNS, astrocytes are significant sources of RANTES/CCL5 (regulated upon activation, normal T cell expressed and secreted), a CC‐chemokine with important biological function. Astrocyte RANTES/CCL5 has been shown to be induced by interleukin‐1 (IL‐1), with interferon‐γ (IFNγ) as a primer, but whether type I interferons play any role in the expression of RANTES/CCL5 is not known. In this report, we studied the detailed mechanism of RANTES/CCL5 induction in primary human astrocytes activated with IL‐1 and IFNβ. Ribonuclease protection assay and ELISA showed that IFNβ, although not effective alone, increased IL‐1‐induced RANTES/CCL5 expression, but did not antagonize IFNγ. IL‐1 or IL‐1/IFNβ‐induced RANTES/CCL5 expression was inhibited by the super‐repressor IκBα or inhibitors of p38 or c‐Jun N‐terminal kinase (JNK) MAPKs (mitogen‐activated protein kinases), but not by extracellular signal regulated kinases (ERK) inhibitors. IFNβ enhanced IL‐1‐induced phosphorylation of p38 MAPK, but was not effective alone. Transfection with mutated RANTES/CCL5 promoter‐reporter constructs revealed that κB, interferon‐stimulated response element (ISRE) and CAATT‐enhancer binding protein‐β (C/EBPβ) sites all contributed to IL‐1/IFNβ‐induced RANTES/CCL5 transcription. IFNβ synergized with IL‐1 to induce nuclear accumulation of C/EBPβ protein. They also synergized to form nuclear ISRE complexes with Stat1, Stat2 and interferon regulatory factor‐1 (IRF‐1) proteins. Together, our results demonstrate that IFNβ plays a positive regulatory role in the expression of RANTES/CCL5 in human astrocytes through several distinct mechanisms.
Shift in the localization of sites of hydrogen peroxide production in brain mitochondria by mitochondrial stress
Authors: Gyulkhandanyan Armen V. , Pennefather Peter S.
Published: July 2004

We have determined the underlying sites of H2O2generation by isolated rat brain mitochondria and how these can shift depending on the presence of respiratory substrates, electron transport chain modulators and exposure to stressors. H2O2production was determined using the fluorogenic Amplex red and peroxidase system. H2O2production was higher when succinate was used as a respiratory substrate than with another FAD‐dependent substrate, α‐glycerophosphate, or with the NAD‐dependent substrates, glutamate/malate. Depolarization by the uncouplerp‐trifluoromethoxyphenylhydrazone decreased H2O2production stimulated by all respiratory substrates. H2O2production supported by succinate during reverse transfer of electrons was decreased by inhibitors of complex I (rotenone and diphenyleneiodonium) whereas in glutamate/malate‐oxidizing mitochondria diphenyleneiodonium decreased while rotenone increased H2O2generation. The complex III inhibitors antimycin and myxothiazol decreased succinate‐induced H2O2production but stimulated H2O2production in glutamate/malate‐oxidizing mitochondria. Antimycin and myxothiazol also increased H2O2production in mitochondria using α‐glycerophosphate as a respiratory substrate. In substrate/inhibitor experiments maximal stimulation of H2O2production by complex I was observed with the α‐glycerophosphate/antimycin combination. In addition, three forms ofin vitromitochondrial stress were studied: Ca2+overload, cold storage for more than 24 h and cytochromecdepletion. In each case we observed (i) a decrease in succinate‐supported H2O2production by complex I and an increase in succinate‐supported H2O2production by complex III, (ii) increased glutamate/malate‐induced H2O2generation by complex I and (iii) increased α‐glycerophosphate‐supported H2O2generation by complex III. Our results suggest that all three forms of mitochondrial stress resulted in similar shifts in the localization of sites of H2O2generation and that, in both normal and stressed states, the level and location of H2O2production depend on the predominant energetic substrate.
Modulation of feeding‐related peptide/protein signals by the blood–brain barrier
Authors: Pan Weihong , Akerstrom Victoria , Zhang Jian , Pejovic Vojislav , Kastin Abba J.
Published: July 2004

The peptide urocortin is a member of the corticotropin‐releasing factor (CRF) family and a potent satiety signal to the brain. Urocortin in blood does not reach the brain significantly by itself, but its permeation across the blood–brain barrier (BBB) can be enhanced by leptin. How leptin facilitates the influx of urocortin has not been elucidated. In this study, we tested the hypothesis that leptin activates receptor‐mediated endocytosis of urocortin. We measured the kinetics of permeation of radioactively labeled urocortin across the mouse BBB and determined the specific effects of leptin and receptor antibodies. The results show that the influx transfer constant of urocortin was enhanced in the presence of leptin and mediated by CRF‐2β, the specific receptor for urocortin. To determine the specificity of this modulation, the effect of leptin was compared with that of TNFα. Both TNFα and leptin independently facilitated receptor‐mediated transport of urocortin across the BBB. Even though TNFα and leptin have similar effects on urocortin transport, leptin did not significantly affect the influx of TNFα across the BBB. The results indicate that permeation of ingestive peptides and cytokines across the BBB can be acutely modulated, consistent with a role of BBB in regulating feeding behavior. Thus, sites of action of leptin, urocortin, and TNFα exist not only in the brain but also at the BBB where they each control the flow of other ingestive signals to CNS targets.
Substitution of conserved glycine residue by alanine in natural and synthetic neuropeptide ligands causes partial agonism at the stomoxytachykinin receptor
Authors: Poels Jeroen , Van Loy Tom , Franssens Vanessa , Detheux Michel , Nachman Ronald J. , Oonk Hendrica B. , Åkerman Karl E. , Vassart Gilbert , Parmentier Marc , De Loof Arnold , Torfs Herbert , Broeck Jozef Vanden
Published: July 2004

A few naturally occurring insect tachykinin‐related peptides, such as stomoxytachykinin (Stc‐TK), contain an Ala‐residue instead of the highly conserved Gly‐residue that is present in most other members of this peptide family. Stc‐TK is a potent, partial agonist of the stable fly (Stomoxys calcitrans) tachykinin receptor, STKR. By means of synthetic analogues, the Gly/Ala exchange, representing the addition of a single methyl group in the active core region of these peptides, was shown to be fully responsible for the generation of this partial agonism, which was also accompanied by an increase in agonistic potency. Surprisingly, this Ala‐dependent reduction in maximal response levels was only observed for the agonist‐induced cellular calcium rise. Stomoxytachykinin, Stc‐TK, did not display partial agonism for the STKR‐mediated cyclic AMP response. A possible explanation for this differential partial agonism is that the Gly‐containing and Ala‐replaced peptides recognize and stabilize active receptor conformations that differ in their functional coupling efficacies towards these response pathways. Drosotachykinins, Drm‐TK, tachykinin‐like peptides encoded in the fruit fly genome, were shown to be STKR‐agonists. Interestingly, one of these peptides, which contains an Ala‐residue instead of the conserved Gly‐residue, also proved to be a potent, partial agonist for STKR.
Composition of the early Oligocene ocean from coral stable isotope and elemental chemistry
Authors: IVANY LINDA C. , PETERS STEPHEN C. , WILKINSON BRUCE H. , LOHMANN KYGER C. , REIMER BETH A.
Published: July 2004

A sectioned and polished specimen of the coral Archohelia vicksburgensis from the early Oligocene Byram Formation (∼30 Ma) near Vicksburg, Mississippi, reveals 12 prominent annual growth bands. Stable oxygen isotopic compositions of 77 growth‐band‐parallel microsamples of original aragonite exhibit well‐constrained fluctuations that range between −2.0 and −4.8. Variation in δ18O of coral carbonate reflects seasonal variation in temperature ranging from 12 to 24 °C about a mean of 18 °C. These values are consistent with those derived from a bivalve and a fish otolith from the same unit, each using independently derived palaeotemperature equations. Mg/Ca and Sr/Ca ratios were determined for 40 additional samples spanning five of the 12 annual bands. Palaeotemperatures calculated using elemental‐ratio thermometers calibrated on modern corals are consistently lower; mean temperature from Mg/Ca ratios are 12.5 ± 1 °C while those from Sr/Ca are 5.8 ± 2.2 °C. Assuming that δ18O‐derived temperatures are correct, relationships between temperature and elemental ratio for corals growing in today's ocean can be used to estimate Oligocene palaeoseawater Mg/Ca and Sr/Ca ratios. Calculations indicate that early Oligocene seawater Mg/Ca was ∼81% (4.2 mol mol−1) and Sr/Ca ∼109% (9.9 mmol mol−1) of modern values. Oligocene seawater with this degree of Mg depletion and Sr enrichment is in good agreement with that expected during the Palaeogene transition from ‘calcite’ to ‘aragonite’ seas. Lower Oligocene Mg/Ca probably reflects a decrease toward the present day in sea‐floor hydrothermal activity and concomitant decrease in scavenging of magnesium from seawater. Elevated Sr/Ca ratio may record lesser amounts of Oligocene aragonite precipitation and a correspondingly lower flux of strontium into the sedimentary carbonate reservoir than today.
Acute effects of smoking on left ventricular function and neuro‐humoral responses in patients with known or suspected ischaemic heart disease
Authors: Høilund‐Carlsen Poul Flemming , Marving Jens , Gadsbøll Niels , Rasmussen Sten , Lønborg‐Jensen Harald , Nielsen Meta Damkjær , Christensen Niels Juel , Jensen Birte Hjort
Published: July 2004

Systolic left ventricular function was examined by radionuclide ventriculography in 12 habitual smokers with known or suspected ischaemic heart disease, aged 33–69 years, before, during, and after smoking of two cigarettes in a row and was repeated on a non‐smoking control day. Plasma concentrations of adrenaline, noradrenaline, renin, and angiotensin II were determined on the smoking day, before and immediately after smoking. During smoking, there were significant increases in heart rate (+27%), rate‐pressure product (+23%), and cardiac output (+14%) in the face of a significant increase in left ventricular end‐systolic volume (+5%) and significant decreases in ejection fraction (−6%) and stroke volume (−8%). Blood pressure was virtually unchanged, and total peripheral resistance remained constant. Plasma adrenaline increased by 100%, renin decreased by 21%, and noradrenaline and angiotensin II did not change. The humoral changes were not correlated to changes in any of the haemodynamic variables. Areas of myocardial hypokinesis emerged or widened during smoking in 11 of 12 patients. Thus, in patients with known or suspected ischaemic heart disease, smoking was associated with an acute decrease in systolic ventricular function and development of widespread hypokinesis despite adrenaline stimulation.
Influence of repeated isometric contractions on muscle deoxygenation and pulmonary oxygen uptake kinetics in humans
Authors: Bringard Aurélien , Perrey Stéphane
Published: July 2004

The purpose of the present study was to compare simultaneously vastus lateralis (VL) deoxygenation and pulmonary O2 uptake (O2) kinetics during fatiguing knee extension exercise with minimal cardiac load. Eight healthy subjects realized an intermittent bilateral knee‐extension exercise (3‐s contraction/3‐s relaxation) at 40% of maximum voluntary contraction for 10 min. VL deoxygenation was recorded by near infrared spectroscopy at 2 Hz (NIRO‐300, Hamamatsu Photonics, Japan) and O2 was determined breath‐by‐breath (K4b2, Cosmed, Italy). After a time delay of 16 ± 5 s, deoxygenation kinetics at the onset of exercise followed an exponential time course at a significant faster rate than O2 (time constant of 5·4 ± 4·0 s vs. 31·6 ± 10·4 s, P<0·01) reflecting a mismatch between local O2 consumption and perfusion. Thereafter, a rise in O2 of 223 ± 123 ml min−1 (consistent with the mathematical model, 259 ± 126 ml min−1) was observed between minutes 2 and 10. During the same exercise time, changes in tissue oxygenation index decreased significantly and were individually correlated with the corresponding increased O2 (P<0·05), suggesting that the majority of the slow rise of O2 arose from the exercising limbs. Averaged heart rate increased from 67 ± 11 to 116 ± 20 beats min−1 during exercise. Knee extension exercise may be relevant to estimate the cardiopulmonary and deoxygenation of working skeletal muscle responses for assessment of exercise limiting factors in clinical settings or in the exercise physiology.
Brain glucose and lactate levels during ventilator‐induced hypo‐ and hypercapnia*
Authors: van Hulst R. A. , Lameris T. W. , Haitsma J. J. , Klein J. , Lachmann B.
Published: July 2004

Objective:  Levels of glucose and lactate were measured in the brain by means of microdialysis in order to evaluate the effects of ventilator‐induced hypocapnia and hypercapnia on brain metabolism in healthy non‐brain‐traumatized animals.

Design and setting:  Prospective animal study in a university laboratory.

Subjects:  Eight adult Landrace/Yorkshire pigs.

Interventions:  The microdialysis probe was inserted in the brain along with a multiparameter sensor and intracranial pressure (ICP) probe. The animals were ventilated in a pressure‐controlled mode according to the open lung concept with an inspired oxygen fraction of 0·4/1·0. Starting at normoventilation (PaCO2 ±40 mmHg) two steps of both hypercapnia (PCO2 ± 70 and 100 mmHg) and hypocapnia (PaCO2 ± 20 and 30 mmHg) were performed. Under these conditions, brain glucose and lactate levels as well as brain oxygen (PbrO2), brain carbon dioxide (PbrCO2), brain pH (brpH), brain temperature and ICP were measured.

Results:  At hypercapnia (PaCO2 = 102·7 mmHg) there were no significant changes in brain glucose and lactate but there was a significant increase in PbrCO2, PbrO2 and ICP. In contrast, at hypocapnia (PCO2 = 19·8 mmHg) there was a significant increase in brain lactate and a significant decrease in both brain glucose and PbrCO2.

Conclusions:  Hypocapnia decreases brain glucose and increases brain lactate concentration, indicating anaerobic metabolism, whereas hypercapnia has no influence on levels of brain glucose and brain lactate.
Developing an integrated paediatric low vision service*
Authors: Rudduck Gillian , Corcoran Helen , Davies Kay
Published: July 2004

A survey of usage of low vision aids (LVAs) by 56 children with visual impairment, who were attending mainstream schools in Wirral, was undertaken. A total of 25% of children owned an LVA and 5% were using these on a regular basis. These low levels of ownership and usage led to the development of a low vision service involving the collaboration of education and health care. This paper describes the development of that service, its elements and implementation. The results from the new service show that of the 29 children issued with an LVA, 82.7% are using them on a regular basis. Having an integrated service is shown to significantly improve LVA usage in the group of children seen so far. The service results are discussed with suggestions for future service development.
Multihospital System Membership and Patient Treatments, Expenditures, and Outcomes
Authors: Madison Kristin
Published: July 2004

Objective. To determine the relationship between hospital membership in systems and the treatments, expenditures, and outcomes of patients.

Data Sources. The Medicare Provider Analysis and Review dataset, for data on Medicare patients admitted to general medical‐surgical hospitals between 1985 and 1998 with a diagnosis of acute myocardial infarction (AMI); the American Hospital Association Annual Survey, for data on hospitals.

Study Design. A multivariate regression analysis. An observation is a fee‐for‐service Medicare AMI patient admitted to a study hospital. Dependent variables include patient transfers, catheterizations, angioplasties or bypass surgeries, 90‐day mortality, and Medicare expenditures. Independent variables include system participation, other admission hospital and patient traits, and hospital and year fixed effects. The five‐part system definition incorporates the size and location of the index admission hospital and the size and distance of its partners.

Principal Findings. While the effects of multihospital system membership on patients are in general limited, patients initially admitted to small rural system hospitals that have big partners within 100 miles experience lower mortality rates than patients initially admitted to independent hospitals. Regression results show that to the extent system hospital patients experience differences in treatments and outcomes relative to patients of independent hospitals, these differences remain even after controlling for the admission hospital's capacity to provide cardiac services.

Conclusions. Multihospital system participation may affect AMI patient treatment and outcomes through factors other than cardiac service offerings. Additional investigation into the nature of these factors is warranted.
Adoption of Liquid‐Based Cervical Cancer Screening Tests by Family Physicians and Gynecologists
Authors: Rappaport Karen M. , Forrest Christopher B. , Holtzman Neil A.
Published: July 2004

Objective. To examine reasons for the adoption of liquid‐based cervical cancer screening tests.

Data Sources/Study Setting. A mailed survey of 250 family physicians and 250 gynecologists in Maryland in 2000. Additional data were obtained from the AMA Master File of Physicians.

Study Design. Key outcome variables in this cross‐sectional survey were early adoption of a liquid‐based test by the end of 1997 and overall adoption by the time of the survey. Adoption was viewed in terms of a supply and demand theoretical framework with marketing influencing physician and patient demand as well as supply by insurance companies and laboratories.

Data Collection. Random samples of family physicians and gynecologists were selected from the AMA Master File of Physicians. The overall response rate was 61.9 percent.

Principal Findings. By 2000, 96 percent of gynecologists and 75 percent of family physicians in Maryland were using liquid‐based cervical cancer screening tests, most commonly the ThinPrep® Pap Test™. Gynecologists were more likely than family physicians to have been early adopters (34 percent versus 5 percent, p<.01). Part of this variation in adoption was due to aggressive marketing to gynecologists, who were more likely than family physicians to receive information in the mail from the test manufacturer (89 percent versus 56 percent, p<.01) and to have been informed by the manufacturer that a patient had inquired about physicians' use of the test (22 percent versus 8 percent, p<.01).

Conclusions. The rapid diffusion of liquid‐based cervical cancer screening tests occurred despite general agreement that the Pap smear has been one of the most successful cancer prevention interventions ever. Commercial marketing campaigns appear to contribute to the more rapid rate of diffusion of technology among specialists compared with generalists.
Development of the Patient Activation Measure (PAM): Conceptualizing and Measuring Activation in Patients and Consumers
Authors: Hibbard Judith H. , Stockard Jean , Mahoney Eldon R. , Tusler Martin
Published: July 2004

Background. Controlling costs and achieving health care quality improvements require the participation of activated and informed consumers and patients.

Objectives. We describe a process for conceptualizing and operationalizing what it means to be “activated” and delineate the process we used to develop a measure for assessing “activation,” and the psychometric properties of that measure.

Methods. We used the convergence of the findings from a national expert consensus panel and patient focus groups to define the concept and identify the domains of activation. These domains were operationalized by constructing a large item pool. Items were pilot‐tested and initial psychometric analysis performed using Rasch methodology. The third stage refined and extended the measure. The fourth stage used a national probability sample to assess the measure's psychometric performance overall and within different subpopulations.

Study Sample. Convenience samples of patients with and without chronic illness, and a national probability sample (N=1,515) are included at different stages in the research.

Conclusions. The Patient Activation Measure is a valid, highly reliable, unidimensional, probabilistic Guttman‐like scale that reflects a developmental model of activation. Activation appears to involve four stages: (1) believing the patient role is important, (2) having the confidence and knowledge necessary to take action, (3) actually taking action to maintain and improve one's health, and (4) staying the course even under stress. The measure has good psychometric properties indicating that it can be used at the individual patient level to tailor intervention and assess changes.