bluuebunny/crossref_metadata_2025 huggingface dataset:
Compressive creep behaviour of Mg–Li–Al alloy
Authors: Wei X. W. , Zu X. T. , Zhou W. L.
Published: May 2006

The compressive creep behaviour of as cast Mg–14Li–1·3Al (wt-%) alloy was investigated in the temperature range of 20−85°C and under different compressive stress in the range of 37·3–74·6 MPa with special apparatus. Primary creep deformation and steady creep rate increase with temperature and applied stress. The compressive creep behaviour obeys an empirical equation ln t= C− nln σ + Q/ RT, where t is the time to a selected creep strain, σ is the applied stress, T is the absolute temperature, R is the gas constant, and C, n, and Q are constants for the experimental alloy. The average values of the exponent n and the creep activation energy Q are 4·33 and 101·13 kJ mol−1 respectively. The creep rate controlling mechanism is the dislocation climb and the lattice diffusion of Li in the experimental alloy under the testing conditions.
Mechanical stabilisation of austenite
Authors: Chatterjee S. , Wang H.-S. , Yang J. R. , Bhadeshia H. K. D. H.
Published: May 2006

A theory has been developed for the mechanical stabilisation of plastically deformed austenite by balancing the force which drives the transformation interface against the resistance from dislocation debris in the austenite. The work has been used to explain why very large strains are required to mechanically stabilise certain stainless steels, and also to interpret the subunit mechanism of bainite growth.
Simple constitutive description of Al–5·5Mg alloy deformed at elevated temperatures and strain rates
Authors: Puchi-Cabrera E. S.
Published: May 2006

The constitutive description of a commercial Al–5·5Mg alloy is analysed on the basis of a zero internal state variable approach known as the Sellars–Tegart–Garofalo (STG) model, employing for this purpose a number of stress–strain curves obtained from tests conducted at almost constant deformation temperature and strain rate. It is shown that such a model provides a satisfactory description of the flow stress data of the material as a function of the deformation conditions and that its formulation requires the determination of a relatively small number of material constants from the experimental data. It is also shown that the constitutive analysis can be conducted from the actual stress, strain, temperature and strain rate data without the need of performing any previous temperature and/or strain rate correction of the flow stress. These findings have important implications, in the sense that the constitutive analysis of the materials that undergo dynamic recovery during hot deformation can be conducted from data obtained under variable deformation temperature and/or strain rate, and including tests carried out at constant crosshead speeds. The present work also shows that more accurate results are obtained if the definition of the Zener–Hollomon parameter is slightly modified in order to eliminate the trivial temperature dependence of the activation energy for deformation by normalising its value by the factor μb3.
Influence of carbon on aging response and tensile properties of eutectoid beta titanium alloy Ti–13Cr
Authors: Chu M. , Wu X. , Jones I. P. , Loretto M. H.
Published: May 2006

The influence of carbon addition on the aging response of quenched Ti–13Cr (wt-%) has been investigated using hardness tests, tensile tests, optical microscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). It has been found that carbon refines beta grain size, leads to fine and homogenous alpha precipitation and reduces grain boundary alpha. The carbon addition accelerates the rate at which hardening occurs during aging and increases the peak hardness of the aged specimens. A significant improvement in room temperature tensile strength and ductility has also been achieved in the carbon containing alloy after aging at 500°C. The effects of carbon on the aging response appear to be attributed to dislocations introduced by carbides during quenching, elastic strain created in the matrix by carbides and gettering effect of Ti2C carbides. The influence of each of those mechanisms has been demonstrated through experiments and the factors giving rise to the improvements in properties are also discussed in terms of the microstructural observations.
TRIP-assisted steels: Cracking of high-carbon martensite
Authors: Chatterjee S. , Bhadeshia H. K. D. H.
Published: May 2006

Modern TRIP assisted steels contain retained austenite with carbon concentrations in excess of 1 wt-%. Some of their mechanical properties, in particular the toughness and ductility, rely on the diffusionless transformation of this austenite into high-carbon martensite, induced by stress and strain. The properties can be excellent in spite of the fact that freshly formed high-carbon martensite is brittle. This contradictory behaviour has yet to be explained. In the present paper, the authors propose and show experimentally that the tendency of the martensite to crack in a mixed microstructure of austenite and martensite depends on its absolute size. It is demonstrated that in these mixtures, it is more difficult to crack fine martensite. It is the fine scale of the retained austenite in TRIP assisted steels that permits the martensite to be tolerated without endangering their mechanical properties.
Formation of Ti3AlC2 by mechanically induced self-propagating reaction in Ti–Al–C system at room temperature
Authors: Li S.-B. , Zhai H.-X. , Bei G. P. , Zhou Y. , Zhang Z. L.
Published: May 2006

The formation of Ti3AlC2 was first investigated by mechanically induced self-propagating reaction (MSR) in Ti–Al–C system at room temperature. The effects of the milling parameters on the formation of Ti3AlC2 were discussed. The phase composition and microstructure were analysed and observed by using X-ray diffraction and scanning electron microscopy, respectively. The formation mechanism of Ti3AlC2 was analysed. An MSR was ignited during mechanical alloying of Ti, Al and C powders after a short time. An exothermic reaction between Ti and Al in the Ti–Al–C system first occurred after a certain milling time. Then, Ti–C reaction was induced at high temperature. All of the above reactions were exothermic that resulted in Ti–Al liquid formation. The previously formed TiC dissolved into and nucleated in the Ti–Al liquid. At last, Ti3AlC2 formed between the Ti–Al melt and the TiC. The final products consist of Ti3AlC2, TiC and Al3Ti.
Evidence for subcomplexes in the Fanconi anemia pathway
Authors: Medhurst Annette L. , Laghmani El Houari , Steltenpool Jurgen , Ferrer Miriam , Fontaine Chantal , de Groot Jan , Rooimans Martin A. , Scheper Rik J. , Meetei Amom Ruhikanta , Wang Weidong , Joenje Hans , de Winter Johan P.
Published: May 2006

Fanconi anemia (FA) is a genomic instability disorder, clinically characterized by congenital abnormalities, progressive bone marrow failure, and predisposition to malignancy. Cells derived from patients with FA display a marked sensitivity to DNA cross-linking agents, such as mitomycin C (MMC). This observation has led to the hypothesis that the proteins defective in FA are involved in the sensing or repair of interstrand cross-link lesions of the DNA. A nuclear complex consisting of a majority of the FA proteins plays a crucial role in this process and is required for the monoubiquitination of a downstream target, FANCD2. Two new FA genes, FANCB and FANCL, have recently been identified, and their discovery has allowed a more detailed study into the molecular architecture of the FA pathway. We demonstrate a direct interaction between FANCB and FANCL and that a complex of these proteins binds FANCA. The interaction between FANCA and FANCL is dependent on FANCB, FANCG, and FANCM, but independent of FANCC, FANCE, and FANCF. These findings provide a framework for the protein interactions that occur “upstream” in the FA pathway and suggest that besides the FA core complex different subcomplexes exist that may have specific functions other than the monoubiquitination of FANCD2.
Compound heterozygosity of novel missense mutations in the gamma-glutamyl-carboxylase gene causes hereditary combined vitamin K–dependent coagulation factor deficiency
Authors: Darghouth Dhouha , Hallgren Kevin W. , Shtofman Rebecca L. , Mrad Amel , Gharbi Youssef , Maherzi Ahmed , Kastally Radhia , LeRicousse Sophie , Berkner Kathleen L. , Rosa Jean-Philippe
Published: May 2006

Hereditary combined vitamin K–dependent (VKD) coagulation factor deficiency is an autosomal recessive bleeding disorder associated with defects in either the γ-carboxylase, which carboxylates VKD proteins to render them active, or the vitamin K epoxide reductase (VKORC1), which supplies the reduced vitamin K cofactor required for carboxylation. Such deficiencies are rare, and we report the fourth case resulting from mutations in the carboxylase gene, identified in a Tunisian girl who exhibited impaired function in hemostatic VKD factors that was not restored by vitamin K administration. Sequence analysis of the proposita did not identify any mutations in the VKORC1 gene but, remarkably, revealed 3 heterozygous mutations in the carboxylase gene that caused the substitutions Asp31Asn, Trp157Arg, and Thr591Lys. None of these mutations have previously been reported. Family analysis showed that Asp31Asn and Thr591Lys were coallelic and maternally transmitted while Trp157Arg was transmitted by the father, and a genomic screen of 100 healthy individuals ruled out frequent polymorphisms. Mutational analysis indicated wild-type activity for the Asp31Asn carboxylase. In contrast, the respective Trp157Arg and Thr591Lys activities were 8% and 0% that of wild-type carboxylase, and their compound heterozygosity can therefore account for functional VKD factor deficiency. The implications for carboxylase mechanism are discussed.
Impaired “outside-in” integrin αIIbβ3 signaling and thrombus stability in TSSC6-deficient mice
Authors: Goschnick Matt W. , Lau Lai-Man , Wee Janet L. , Liu Yong S. , Hogarth P. Mark , Robb Lorraine M. , Hickey Michael J. , Wright Mark D. , Jackson Denise E.
Published: May 2006

We investigated the role of the hematopoietic-specific tetraspanin superfamily member, TSSC6, in platelet function using wild-type mice and TSSC6-deficient mice. TSSC6 is expressed on the surface of murine platelets and is up-regulated by thrombin stimulation, indicating an intracellular pool of TSSC6. Immunoprecipitation/Western blot studies reveal a constitutive physical association of TSSC6 with the integrin αIIbβ3 complex under strong detergent conditions. In vivo evaluation of hemostasis by tail bleeding revealed increased bleeding time, volume of blood lost, and evidence of tail rebleeds in TSSC6 null mice, indicating unstable hemostasis. Using ex vivo techniques, we showed that TSSC6-deficient platelets exhibited impaired kinetics of clot retraction, platelet aggregation at lower doses of PAR-4, and collagen and platelet spreading on fibrinogen in the presence of normal integrin αIIbβ3 expression. TSSC6-deficient platelets showed normal alpha granule secretion, normal “insideout” integrin αIIbβ3 signaling (fluorescein isothiocyanate [FITC]–fibrinogen and JON/A binding), and normal platelet adhesion on fibrinogen. Furthermore, we show that absence of platelet TSSC6 affects the secondary stability of arterial thrombi in vivo upon vascular injury. These data demonstrate that TSSC6 appears to regulate integrin αIIbβ3 “outside-in” signaling events in platelets and is necessary for stability of arterial thrombi in vivo.
Impaired megakaryocytopoiesis in type 2B von Willebrand disease with severe thrombocytopenia
Authors: Nurden Paquita , Debili Najet , Vainchenker William , Bobe Regis , Bredoux Raymonde , Corvazier Elisabeth , Combrie Robert , Fressinaud Edith , Meyer Dominique , Nurden Alan T. , Enouf Jocelyne
Published: May 2006

In type 2B von Willebrand disease, there is spontaneous binding of mutated von Willebrand factor (VWF) multimers to platelets. Here we report a family in which severe thrombocytopenia may also be linked to abnormal megakaryocytopoiesis. A heterozygous mutation in the VWF A1 domain gave a R1308P substitution in an interactive site for glycoprotein Ibα (GPIbα). Electron microscopy showed clusters of platelets in close contact. Binding of antibodies to the GPIbα N-terminal domain was decreased, whereas GPIX and GPV were normally detected. In Western blotting (WB), GPIbα, αIIb, and β3 were normally present. Proteins involved in Ca2+ homeostasis were analyzed by quantitating platelet mRNA or by WB. Plasma membrane Ca2+ ATPase (PMCA)-4b and type III inositol trisphosphate receptor (InsP3-R3) were selectively increased. The presence of degradation products of polyadenosine diphosphate (ADP)-ribose polymerase protein (PARP) suggested ongoing caspase-3 activity. These were findings typical of immature normal megakaryocytes cultured from peripheral blood CD34+ cells with TPO. Significantly, megakaryocytes from the patients in culture produced self-associated and interwoven proplatelets. Immunolocalization showed VWF not only associated with platelets, but already on the megakaryocyte surface and within internal channels. In this family, type 2B VWD is clearly associated with abnormal platelet production.
Thrombin-induced endothelial microparticle generation: identification of a novel pathway involving ROCK-II activation by caspase-2
Authors: Sapet Cédric , Simoncini Stéphanie , Loriod Béatrice , Puthier Denis , Sampol José , Nguyen Catherine , Dignat-George Françoise , Anfosso Francine
Published: May 2006

Thrombin exerts pleiotropic effects on endothelial cells, including the release of microparticles (EMPs) that disseminate and exchange information with vascular cells. Nevertheless, the mechanisms leading to their generation are not elucidated. We performed microarray analysis to identify genes involved in EMP release by the endothelial cell line HMEC-1 in response to thrombin. We identified a group of genes linked to the cytoskeleton reorganization family. Among these, the Rho-kinase ROCK-II presented a high transcription rate. ROCK-I, another Rho-kinase isoform, was not modulated by thrombin. Pharmacologic inhibition of Rho-kinases or specific depletion of ROCK-II by short interfering (si) RNA inhibited thrombin-induced EMP release. In contrast, ROCK-I mRNA silencing did not modify EMP generation by thrombin. Exposure of HMEC-1 to thrombin in presence of the caspase-2 selective inhibitor Z-VDVAD-FMK prevented ROCK-II cleavage and inhibited the thrombin-induced EMP release. These events were observed in absence of cell death. Our data clearly identified ROCK-II as a target of thrombin in EMP generation. They indicated that the 2 Rho-kinases did not share identical functions. The involvement of caspase-2 in ROCK-II activation independently of cell death points out a novel signaling pathway that emphasizes the proteolytic activity of caspase in EMP generation in response to cell activation.
Evaluation of the safety and pharmacodynamics of Hematide, a novel erythropoietic agent, in a phase 1, double-blind, placebo-controlled, dose-escalation study in healthy volunteers
Authors: Stead Richard B. , Lambert John , Wessels Dawie , Iwashita Julie S. , Leuther Kerstin K. , Woodburn Kathryn W. , Schatz Peter J. , Okamoto Douglas M. , Naso Robert , Duliege Anne-Marie
Published: May 2006

Hematide is an investigational pegylated synthetic peptide that stimulates erythropoiesis in animal models and is being developed for the treatment of anemia associated with chronic renal failure and cancer. This study evaluated the safety and pharmacodynamics of single, intravenous doses (0.025, 0.05, and 0.1 mg/kg) of Hematide in 28 healthy male volunteers. All doses of Hematide were well tolerated, with safety profiles similar to those of placebo. Hematide showed a dose-dependent increase in reticulocytes. The 0.1-mg/kg dose was associated with a statistically significant increase in hemoglobin (Hgb) from baseline compared to the placebo group (13.6 ± 3.9 g/L [1.36 ± 0.39 g/dL] versus 3.9 ± 3.8 g/L [0.39 ± 0.38 g/dL]; P < .001) that was sustained for longer than 1 month. These results support phase 2 studies in patients with anemia associated with chronic kidney disease or cancer and suggest that Hematide administered as infrequently as once a month may result in a sustained elevation of Hgb levels. (Please note that Hematide is a proposed trade name; the compound does not yet have a nonproprietary name.)
Identification of a Bacillus thuringiensis Cry11Ba toxin-binding aminopeptidase from the mosquito, Anopheles quadrimaculatus
Authors: Abdullah Mohd Amir F , Valaitis Algimantas P , Dean Donald H
Published: May 2006

Background

Aminopeptidase N (APN) type proteins isolated from several species of lepidopteran insects have been implicated as Bacillus thuringiensis (Bt) toxin-binding proteins (receptors) for Cry toxins. We examined brush border membrane vesicle (BBMV) proteins from the mosquito Anopheles quadrimaculatus to determine if APNs from this organism would bind mosquitocidal Cry toxins that are active to it.

Results

A 100-kDa protein with APN activity (APNAnq 100) was isolated from the brush border membrane of Anopheles quadrimaculatus. Native state binding analysis by surface plasmon resonance shows that APNAnq 100 forms tight binding to a mosquitocidal Bt toxin, Cry11Ba, but not to Cry2Aa, Cry4Ba or Cry11Aa.

Conclusion

An aminopeptidase from Anopheles quadrimaculatus mosquitoes is a specific binding protein for Bacillus thuringiensis Cry11Ba.
Expression of carbonic anhydrases IX and XII during mouse embryonic development
Authors: Kallio Heini , Pastorekova Silvia , Pastorek Jaromir , Waheed Abdul , Sly William S , Mannisto Susanna , Heikinheimo Markku , Parkkila Seppo
Published: May 2006

Background

Of the thirteen active carbonic anhydrase (CA) isozymes, CA IX and XII have been linked to carcinogenesis. It has been suggested that these membrane-bound CAs participate in cancer cell invasion, which is facilitated by an acidic tumor cell environment. Since active cell migration is a characteristic feature of embryonic development, we set out to explore whether these isozymes are expressed in mouse embryos of different ages. The studies were focused on organogenesis stage.

Results

Immunohistochemistry demonstrated that both CA IX and XII are present in several tissues of the developing mouse embryo during organogenesis. Staining for CA IX revealed a relatively wide distribution pattern with moderate signals in the brain, lung, pancreas and liver and weak signals in the kidney and stomach. The expression pattern of CA XII in the embryonic tissues was also relatively broad, although the intensity of immunostaining was weak in most tissues. The CA XII-positive tissues included the brain, where the most prominent staining was seen in the choroid plexus, and the stomach, pancreas, liver and kidney.

Conclusion

Membrane-bound CA isozymes IX and XII are expressed in various tissues during mouse organogenesis. These enzymes may regulate ion and pH homeostasis within the developing embryo.
Comparative genomic mapping of the bovine Fragile Histidine Triad (FHIT) tumour suppressor gene: characterization of a 2 Mb BAC contig covering the locus, complete annotation of the gene, analysis of cDNA and of physiological expression profiles
Authors: Uboldi Cristina , Guidi Elena , Roperto Sante , Russo Valeria , Roperto Franco , Di Meo Giulia Pia , Iannuzzi Leopoldo , Floriot Sandrine , Boussaha Mekki , Eggen André , Ferretti Luca
Published: May 2006

Background

The Fragile Histidine Triad gene (FHIT) is an oncosuppressor implicated in many human cancers, including vesical tumors. FHIT is frequently hit by deletions caused by fragility at FRA3B, the most active of human common fragile sites, where FHIT lays. Vesical tumors affect also cattle, including animals grazing in the wild on bracken fern; compounds released by the fern are known to induce chromosome fragility and may trigger cancer with the interplay of latent Papilloma virus.

Results

The bovine FHIT was characterized by assembling a contig of 78 BACs. Sequence tags were designed on human exons and introns and used directly to select bovine BACs, or compared with sequence data in the bovine genome database or in the trace archive of the bovine genome sequencing project, and adapted before use. FHIT is split in ten exons like in man, with exons 5 to 9 coding for a 149 amino acids protein. VISTA global alignments between bovine genomic contigs retrieved from the bovine genome database and the human FHIT region were performed. Conservation was extremely high over a 2 Mb region spanning the whole FHIT locus, including the size of introns. Thus, the bovine FHIT covers about 1.6 Mb compared to 1.5 Mb in man. Expression was analyzed by RT-PCR and Northern blot, and was found to be ubiquitous. Four cDNA isoforms were isolated and sequenced, that originate from an alternative usage of three variants of exon 4, revealing a size very close to the major human FHIT cDNAs.

Conclusion

A comparative genomic approach allowed to assemble a contig of 78 BACs and to completely annotate a 1.6 Mb region spanning the bovine FHIT gene. The findings confirmed the very high level of conservation between human and bovine genomes and the importance of comparative mapping to speed the annotation process of the recently sequenced bovine genome. The detailed knowledge of the genomic FHIT region will allow to study the role of FHIT in bovine cancerogenesis, especially of vesical papillomavirus-associated cancers of the urinary bladder, and will be the basis to define the molecular structure of the bovine homologue of FRA3B, the major common fragile site of the human genome.
Causal inference of regulator-target pairs by gene mapping of expression phenotypes
Authors: Kulp David C , Jagalur Manjunatha
Published: May 2006

Background

Correlations between polymorphic markers and observed phenotypes provide the basis for mapping traits in quantitative genetics. When the phenotype is gene expression, then loci involved in regulatory control can theoretically be implicated. Recent efforts to construct gene regulatory networks from genotype and gene expression data have shown that biologically relevant networks can be achieved from an integrative approach. In this paper, we consider the problem of identifying individual pairs of genes in a direct or indirect, causal, trans-acting relationship.

Results

Inspired by epistatic models of multi-locus quantitative trait (QTL) mapping, we propose a unified model of expression and genotype to identify quantitative trait genes (QTG) by extending the conventional linear model to include both genotype and expression of regulator genes and their interactions. The model provides mapping of specific genes in contrast to standard linkage approaches that implicate large QTL intervals typically containing tens of genes. In simulations, we found that the method can often detect weak trans-acting regulators amid the background noise of thousands of traits and is robust to transcription models containing multiple regulator genes. We reanalyze several pleiotropic loci derived from a large set of yeast matings and identify a likely alternative regulator not previously published. However, we also found that many regulators can not be so easily mapped due to the presence of cis-acting QTLs on the regulators, which induce close linkage among small neighborhoods of genes. QTG mapped regulator-target pairs linked to ARN1 were combined to form a regulatory module, which we observed to be highly enriched in iron homeostasis related genes and contained several causally directed links that had not been identified in other automatic reconstructions of that regulatory module. Finally, we also confirm the surprising, previously published results that regulators controlling gene expression are not enriched for transcription factors, but we do show that our more precise mapping model reveals functional enrichment for several other biological processes related to the regulation of the cell.

Conclusion

By incorporating interacting expression and genotype, our QTG mapping method can identify specific regulator genes in contrast to standard QTL interval mapping. We have shown that the method can recover biologically significant regulator-target pairs and the approach leads to a general framework for inducing a regulatory module network topology of directed and undirected edges that can be used to identify leads in pathway analysis.
No direct effect of the -521 C/T polymorphism in the human dopamine D4 receptor gene promoter on transcriptional activity
Authors: Kereszturi Eva , Kiraly Orsolya , Barta Csaba , Molnar Noemi , Sasvari-Szekely Maria , Csapo Zsolt
Published: May 2006

Background

The human dopamine D4 receptor (DRD4) gene has been studied extensively as a candidate gene for certain psychological traits and several behavioural and psychiatric disorders. Both the 5' regulatory region and the coding sequence contain a number of polymorphisms. The promoter variants have received particular attention in the past few years due to their possible role in the regulation of gene transcription. Previously, the -521C/T SNP was shown to influence promoter activity. The aim of this study is to perform an in-depth analysis of this effect in the context of various neural cell lines.

Results

Endogenous mRNA expression of the DRD4 gene was demonstrated in two neuroblastoma (SK-N-F1, IMR32) and one retinoblastoma cell line (Y79) by RT-PCR. In addition, very low DRD4 mRNA levels were also detected in HeLa cells. The transcriptional activity of a series of 5' promoter deletion mutants was determined by transient transfection of luciferase reporter constructs. The activity profile of these promoter fragments was similar in each of the cell lines tested. The highest luciferase reporter activity was obtained with a construct containing promoter sequences between nucleotides -668 to -389, while a putative silencer region was localised spanning from nucleotide -1571 to -800. Surprisingly, the -521 C/T polymorphism had no significant effect on transcriptional activity of the reporter construct with the highest activity (-668 to -389) in any of the three cell lines tested.

Conclusion

Our results do not confirm previous data assigning different transcriptional activities to the -521 C/T alleles of the human DRD4 promoter. Furthermore, these findings highlight the need for further characterization of the 5' regulatory region of the DRD4 gene and identification of additional functional promoter polymorphic sites, especially in the context of haplotype.
An exploratory study of GP awareness of carer emotional needs in Western Australia
Authors: Bulsara Caroline E , Fynn Noreen
Published: May 2006

Background

The impact of caring for a family member or friend is a life changing experience. Often carers are struggling to cope with ongoing demands of caring for someone. At some point, most carers will approach their family physician for advice on aspects of their role. Carers Western Australia sought information and opinions of General Practitioners (GPs) regarding being a carer. This exploratory survey was to assess the perceptions of Western Australian GPs regarding their role in providing information and support to carers and their awareness of carer needs and issues.

Methods

A telephone survey design of an opportunistic sample of 66 Western Australian GPs was conducted. The responses were both closed and open-ended questions to allow for probing of responses. Responses were analysed using both qualitative and quantitative analysis.

Results

GPs are generally aware of their role in regard to carers and most doctors (88%) said that they had been approached for help in accessing services by carers. A majority of respondents said that carers and spoken to them (70%) and asked for help with (77%) emotional needs. However, when asked how these needs are met, GPs tended to provide practical assistance for the care recipient and carer as a means of addressing those needs. This primarily included providing referral to services to ensure that the carer has practical assistance in caring for the person. However, GPs are less able to provide the necessary emotional or psychological support needed by carers before crisis point is reached. Most doctors said that they had experienced difficulties in providing assistance to carers (84%) at some time.

Conclusion

GPs may be unable or unwilling to provide the necessary assistance to carers who are showing signs of carer burnout and stress. The GP needs to adopt a more holistic approach when treating a patient as to the interaction with the caregiver.
Recurrent bacteremia with Helicobacter cinaedi: case report and review of the literature
Authors: Uçkay Ilker , Garbino Jorge , Dietrich Pierre-Yves , Ninet Béatrice , Rohner Peter , Jacomo Véronique
Published: May 2006

Background

Helicobacter cinaedi is a rare pathogen in humans, occurring mostly in immuno-compromised patients, with a high potential for recurrence. We describe a case of a patient with lymphoma hospitalized for chemotherapy.

Case presentation

At admission, the patient presented with an indolent and non-prurigenic macular rash around her implantable venous access device. Gram staining of blood cultures revealed the presence of spiral-shaped gram-negative rods that could not be grown upon subculture. Helicobacter cinaedi was identified by PCR. No other symptoms or pathology were observed in a whole body CT scan. The implantable venous access device was removed and empiric therapy by ceftriaxone and gentamicin for 2 weeks was initiated, followed by peroral clarithromycin 2 × 500 mg/day and later by levofloxacin 2 × 500 mg/day for 7 weeks. Oncologic remission was achieved 3 months later. However, the patient was re-hospitalized 2 months later for fever, shivering, reappearance of the macular non-prurigenic rash, diarrhea, cough and asthenia. Blood cultures grew H. cinaedi. Multiple investigations could not identify the source. Empiric antibiotic therapy of ceftriaxone and doxycycline was started for 2 weeks with resolution of symptoms, followed by an oral combination of amoxicillin, metronidazole and doxycycline for 2 months; doxycycline was continued for another month. Bacteremia has not recurred for a period of 19 months.

Conclusion

Although H. cinaedi is considered to be a low virulent bacteria, its potential to cause recurrent bacteremia should not be underestimated. H. cinaedi could have an endovascular source of infection and should be treated for an adequate duration with combined antibiotherapy.
Cost-effectiveness analysis of colorectal cancer screening with stool DNA testing in intermediate-incidence countries
Authors: Wu Grace Hui-Min , Wang Yi-Ming , Yen Amy Ming-Fang , Wong Jau-Min , Lai Hsin-Chih , Warwick Jane , Chen Tony Hsiu-Hsi
Published: May 2006

Background

The aim of this study is to compare the cost-effectiveness of screening with stool DNA testing with that of screening with other tools (annual fecal occult blood testing, flexible sigmoidoscopy every 5 years, and colonoscopy every 10 years) or not screening at all.

Methods

We developed a Markov model to evaluate the above screening strategies in the general population 50 to 75 years of age in Taiwan. Sensitivity analyses were performed to assess the influence of various parameters on the cost-effectiveness of screening. A third-party payer perspective was adopted and the cost of $13,000 per life-year saved (which is roughly the per capita GNP of Taiwan in 2003) was chosen as the ceiling ratio for assessing whether the program is cost-effective.

Results

Stool DNA testing every three, five, and ten years can reduce colorectal cancer mortality by 22%, 15%, and 9%, respectively. The associated incremental costs were $9,794, $9,335, and $7,717, per life-year saved when compared with no screening. Stool DNA testing strategies were the least cost-effective with the cost per stool DNA test, referral rate with diagnostic colonoscopy, prevalence of large adenoma, and discount rate being the most influential parameters.

Conclusion

In countries with a low or intermediate incidence of colorectal cancer, stool DNA testing is less cost-effective than the other currently recommended strategies for population-based screening, particularly targeting at asymptomatic subjects.
A pilot trial on safety and efficacy of erythrocyte-mediated steroid treatment in CF patients
Authors: Lucidi V , Tozzi AE , Bella S , Turchetta A
Published: May 2006

Background

Chronic neutrophil inflammation of the respiratory tract tissues plays a key role in the pathogenesis and in prognosis of cystic fibrosis (CF). It is evident that an anti-inflammatory therapy represents an important step in the treatment of CF patients. Corticosteroids and ibuprofen have been proven to slow down the impairment of the pulmonary function in CF patients but their use is limited by the frequency of adverse events. A novel strategy for delivering low doses of steroids for long periods through the infusion of autologous erythrocytes loaded with dexamethasone has been recently set up. A recent study suggested the feasibility of therapy with low doses of corticosteroids delivered through engineered erythrocytes in CF patients. This study presents a further analysis of safety and efficacy of this therapy.

Methods

The treatment group was not randomised and the assignment was based on the patient's consent. Patients entered the study if they had a forced expiratory volume in 1 second (FEV1) <70%, puberty development completed, pancreatic insufficiency, and chronic pulmonary infection requiring frequent cycles of intravenous antibiotic therapy. Patients were excluded if they underwent systemic corticosteriod therapy in the three months preceding the experimental treatment or were on therapy with non-steroidal anti inflammatory drugs (NASDs), or if they had liver CF disease, allergic bronchopulmonary aspergillosis, or positive tuberculin test. Controls were patients who followed a standard treatment, who fulfilled the enrolment criteria, and who were matched to the experimental group by gender, age, and severity of the disease.

Results

Nine patients in the experimental group received the treatment once a month for a period of 24 month. Patients did not develop diabetes, cataract, or hypertension, or other typical side effects of steroid treatment during the follow up period. There was a constant improvement of FEV1 in patients undergoing the experimental treatment compared to a gradual decrease of the same parameter in the standard therapy group (P = 0.04). The average of clinic and radiological indexes did not vary. The number of infective relapses that have required antibiotic intravenous therapy was not different in the two groups, although the average of these episodes was slightly higher in the experimental therapy group.

Conclusion

Intraerythrocyte corticosteroid treatment may stabilize the respiratory function in CF patients but is often considered too invasive by patients. The results obtained by our study may help planning an experimental, controlled, randomised study. A sample size of 150 patients per group would be sufficient for demonstrating such a difference with a 95% confidence interval and a power of 90%.
Posttraumatic stress disorder among female street-based sex workers in the greater Sydney area, Australia
Authors: Roxburgh Amanda , Degenhardt Louisa , Copeland Jan
Published: May 2006

Background

This paper examines rates of exposure to work-related violence and other trauma, and the prevalence of lifetime and current posttraumatic stress disorder (PTSD) among female street-based sex workers. It also investigates associations between current PTSD symptoms and: demographic characteristics, psychiatric comorbidity, injecting and sex risk behaviours, and trauma history.

Methods

Cross sectional data collected from 72 women via face to face structured interviews. The interview included structured diagnostic assessment of DSM-IV PTSD; drug dependence; depression; experience of childhood trauma; and an assessment of sex working history.

Results

All but one of the women interviewed reported experiencing trauma, with the majority reporting multiple traumas that typically began in early childhood. Child sexual abuse, adult sexual assault and work related violence were commonly reported. Just under half of the women met DSM-IV criteria for PTSD and approximately one-third reported current PTSD symptoms. Adult sexual assault was associated with current PTSD symptoms. Depression and drug dependence were also highly prevalent; cocaine dependence in particular was associated with elevated rates of injecting risk and sexual risk behaviours.

Conclusion

These women reported complex trauma histories and despite ongoing opportunities for clinical intervention, they continued to experience problems, suggesting that current models of treatment may not be appropriate. More targeted interventions, and integrated mental health and drug treatment services are needed to address the problems these women are experiencing. Outreach services to these women remain a priority. Education strategies to reduce risky injecting and sexual behaviours among sex workers should also remain a priority.
The effect of a worksite based walking programme on cardiovascular risk in previously sedentary civil servants [NCT00284479]
Authors: Murphy Marie H , Murtagh Elaine M , Boreham Colin AG , Hare Lesley G , Nevill Alan M
Published: May 2006

Background

A significant proportion of Europeans do not meet the recommendations for 30 mins of physical activity 5 times per week. Whether lower frequency, moderate intensity exercise alters cardiovascular disease (CVD) risk has received little attention. This study examined the effects of 45 minutes self-paced walking, 2 d· wk-1 on aerobic fitness, blood pressure (BP), body composition, lipids and C-Reactive Protein (CRP) in previously sedentary civil servants.

Methods

37 subjects (24 women) aged 41.5 ± 9.3 years were randomly assigned to either two 45 minute walks per week (walking group) or no training (control group). Aerobic fitness, body composition, blood pressure (BP), CRP and lipoprotein variables were measured at baseline and following 8 weeks. Steps counts were measured at baseline and during weeks 4 and 8 of the intervention.

Results

Compared to the control group, the walking group showed a significant reduction in systolic BP and maintained body fat levels (P < 0.05). There were no changes other risk factors. Subjects took significantly more steps on the days when prescribed walking was performed (9303 ± 2665) compared to rest days (5803 ± 2749; P < 0.001).

Conclusion

These findings suggest that walking twice per week for 45 minutes at ~ 62% HRmax, improves activity levels, reduces systolic BP and prevents an increase in body fat in previously sedentary adults. This walking prescription, however, failed to induce significant improvements in other markers of cardiovascular disease risk following eight weeks of training.
ALIFE@Work: a randomised controlled trial of a distance counselling lifestyle programme for weight control among an overweight working population [ISRCTN04265725]
Authors: van Wier Marieke F , Ariëns Geertje AM , Dekkers Johanna C , Hendriksen Ingrid JM , Pronk Nico P , Smid Tjabe , van Mechelen Willem
Published: May 2006

Background

The prevalence of overweight is increasing and its consequences will cause a major public health burden in the near future. Cost-effective interventions for weight control among the general population are therefore needed. The ALIFE@Work study is investigating a novel lifestyle intervention, aimed at the working population, with individual counselling through either phone or e-mail. This article describes the design of the study and the participant flow up to and including randomisation.

Methods/Design

ALIFE@Work is a controlled trial, with randomisation to three arms: a control group, a phone based intervention group and an internet based intervention group. The intervention takes six months and is based on a cognitive behavioural approach, addressing physical activity and diet. It consists of 10 lessons with feedback from a personal counsellor, either by phone or e-mail, between each lesson. Lessons contain educational content combined with behaviour change strategies. Assignments in each lesson teach the participant to apply these strategies to every day life.

The study population consists of employees from seven Dutch companies. The most important inclusion criteria are having a body mass index (BMI) ≥ 25 kg/m2 and being an employed adult.

Primary outcomes of the study are body weight and BMI, diet and physical activity. Other outcomes are: perceived health; empowerment; stage of change and self-efficacy concerning weight control, physical activity and eating habits; work performance/productivity; waist circumference, sum of skin folds, blood pressure, total blood cholesterol level and aerobic fitness. A cost-utility- and a cost-effectiveness analysis will be performed as well.

Physiological outcomes are measured at baseline and after six and 24 months. Other outcomes are measured by questionnaire at baseline and after six, 12, 18 and 24 months.

Statistical analyses for short term (six month) results are performed with multiple linear regression. Analyses for long term (two year) results are performed with multiple longitudinal regression. Analyses for cost-effectiveness and cost-utility are done at one and two years, using bootstrapping techniques.

Discussion

ALIFE@Work will make a substantial contribution to the development of cost-effective weight control- and lifestyle interventions that are applicable to and attractive for the large population at risk.
The hypoactive corpora cavernosa with degenerative erectile dysfunction: a new syndrome
Authors: Shafik Ahmed , Ahmed Ismail , El Sibai Olfat , Shafik Ali A
Published: May 2006

Background

In a group of 22 patients with erectile dysfunction, vasculogenic, neurogenic, endocrinologic or psychogenic investigations failed to find a cause for their erectile dysfunction. The electro-cavernosograms of these patients recorded a diminished activity. We investigated the hypothesis that diminished corpus cavernosum electromyography activity was the cause of erectile dysfunction in these patients.

Methods

The study comprised the above mentioned 22 patients (study group, 43.8 ± 5.9 SD years) and 15 healthy volunteers (control group, 41.8 ± 5.1 SD years). The electro-cavernosograms were recorded in the flaccid, erectile and detumescent phases by 2 electrodes inserted into the corpus cavernosum.

Results

The electro-cavernosogram of the healthy volunteers registered in the flaccid phase regular slow waves and random action potentials. The wave variables declined significantly in the erectile phase (p < 0.01). In the study group, the slow wave variables in the flaccid phase exhibited a significant decrease (p < 0.05) compared to the healthy volunteers, and the rhythm was irregular. Erection did not occur with sildenafil administration or intracavernosal papaverine injection, and penile implant was performed. Biopsy examination showed degenerated muscle fibers, and fragmented collagen and elastic fibers with areas of fibrosis.

Conclusion

A novel concept of the cause of erectile dysfunction was presented. Corpora cavernosa showed degenerative changes on histopathologic examination and exhibited diminished electromyography activity. They did not respond to sildenafil administration or intracavernosal papaverine injection. Penile implants were the only treatment. The condition is given the name 'hypoactive corpus cavernosum'. The cause of corpus cavernosum degenerative changes needs further study.
Using the Ages and Stages Questionnaire to teach medical students developmental assessment: a descriptive analysis
Authors: Nicol Pam
Published: May 2006

Background

After a survey of medical graduates' skills found a lack of confidence in developmental assessment, a program was introduced with the broad aims of increasing medical student confidence and respect for the parents' role in childhood developmental assessment. Research has shown that parents' concerns are as accurate as quality screening tests in assessing development, so the program utilised the Ages and Stages Questionnaire, a parent completed, child development assessment tool.

Method

To evaluate the program, an interpretative analysis was completed on the students' reports written during the program and a questionnaire was administered to the parents to gain their perception of the experience. As well, student confidence levels in assessing growth and development were measured at the end of the paediatric term.

Results

Although there was an increase in student confidence in developmental assessment at the end of the term, it was not statistically significant. However the findings indicated that students gained increased understanding of the process and enhanced recognition of the parental role, and the study suggested there was increased confidence in some students. Parents indicated that they thought they should be involved in the teaching of students.

Conclusion

The ASQ was shown to have been useful in an education program at the level of advanced beginners in developmental assessment.
Racial and ethnic disparities in the control of cardiovascular disease risk factors in Southwest American veterans with type 2 diabetes: the Diabetes Outcomes in Veterans Study
Authors: Wendel Christopher S , Shah Jayendra H , Duckworth William C , Hoffman Richard M , Mohler M Jane , Murata Glen H
Published: May 2006

Background

Racial/ethnic disparities in cardiovascular disease complications have been observed in diabetic patients. We examined the association between race/ethnicity and cardiovascular disease risk factor control in a large cohort of insulin-treated veterans with type 2 diabetes.

Methods

We conducted a cross-sectional observational study at 3 Veterans Affairs Medical Centers in the American Southwest. Using electronic pharmacy databases, we randomly selected 338 veterans with insulin-treated type 2 diabetes. We collected medical record and patient survey data on diabetes control and management, cardiovascular disease risk factors, comorbidity, demographics, socioeconomic factors, psychological status, and health behaviors. We used analysis of variance and multivariate linear regression to determine the effect of race/ethnicity on glycemic control, insulin treatment intensity, lipid levels, and blood pressure control.

Results

The study cohort was comprised of 72 (21.3%) Hispanic subjects (H), 35 (10.4%) African Americans (AA), and 226 (67%) non-Hispanic whites (NHW). The mean (SD) hemoglobin A1c differed significantly by race/ethnicity: NHW 7.86 (1.4)%, H 8.16 (1.6)%, AA 8.84 (2.9)%, p = 0.05. The multivariate-adjusted A1c was significantly higher for AA (+0.93%, p = 0.002) compared to NHW. Insulin doses (unit/day) also differed significantly: NHW 70.6 (48.8), H 58.4 (32.6), and AA 53.1 (36.2), p < 0.01. Multivariate-adjusted insulin doses were significantly lower for AA (-17.8 units/day, p = 0.01) and H (-10.5 units/day, p = 0.04) compared to NHW. Decrements in insulin doses were even greater among minority patients with poorly controlled diabetes (A1c ≥ 8%). The disparities in glycemic control and insulin treatment intensity could not be explained by differences in age, body mass index, oral hypoglycemic medications, socioeconomic barriers, attitudes about diabetes care, diabetes knowledge, depression, cognitive dysfunction, or social support. We found no significant racial/ethnic differences in lipid or blood pressure control.

Conclusion

In our cohort, insulin-treated minority veterans, particularly AA, had poorer glycemic control and received lower doses of insulin than NHW. However, we found no differences for control of other cardiovascular disease risk factors. The diabetes treatment disparity could be due to provider behaviors and/or patient behaviors or preferences. Further research with larger sample sizes and more geographically diverse populations are needed to confirm our findings.