bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetic– pharmacodynamic analysis of the role of CYP2C19 genotypes in short‐term rabeprazole‐based triple therapy againstHelicobacter pylori
Authors: Yang Jyh‐Chin , Yang Yu‐Fan , Uang Yow‐Shieng , Lin Chun‐Jung , Wang Teh‐Hong
Published: February 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Asians have a higher percentage of CYP2C19 poor metabolizers (PMs) and a high percentage ofHelicobacter pyloriinfection compared with Whites.

• Although rabeprazole has been suggested to be least affected by CYP2C19 genotype, the pharmacokinetic properties of rabeprazole have been shown to correlate with the CYP2C19 genotype.

• Short‐term (i.e. <7 days) rabeprazole‐based triple therapy has been suggested for its use in eradicatingH. pylori, whereas the eradication rate has been reported variously as 90–27% without CYP2C19 genotyping.

WHAT THIS STUDY ADDS

• Population pharmacokinetic–pharmacodynamic analysis showed that the plasma rabeprazole levels, the values ofkeo(the first‐order rate constant for drug dissipation from the effect compartment), and the predicted gastrin‐time profile were higher in CYP2C19 PMs than in extensive metabolizers (EMs) after multiple dosing.

• Helicobacter pyloriwas eradicated in all CYP2C19 PMs except in one patient infected by a resistant strain, whereas the eradication rates ranged from 58 to 85% in CYP2C19 EMs.

AIMSThe aim was to explore the role of CYP2C19 polymorphism in short‐term rabeprazole‐based triple therapy againstHelicobacter pyloriinfection.

METHODSPatients withH. pyloriinfection were tested for CYP2C19 genotype as poor metabolizers (PMs) or extensive metabolizers (EMs, homozygous EM or heterozygous EM) and given rabeprazole for 7 days. Antibiotics (clarithromycin and amoxicillin) were given on days 1–4, days 4–7, or days 1–7. A direct link model with an effect compartment was used in the population pharmacokinetic–pharmacodynamic analysis. The status ofH. pyloriinfection was evaluated.

RESULTSRabeprazole clearance was lower in CYP2C19 PMs than in EMs (with average values of 10.7vs.16.8 l h−1in PMs and EMs, respectively), resulting in higher plasma levels in the former group. The values of EC50andkeoof gastrin response increased with multiple doses of rabeprazole. Thekeovalues were lower in CYP2C19 PMs than in EMs on day 1 (0.012vs.0.017 × 10−4 l min−1), and higher than in EMs on day 4 (0.804vs.0.169 × 10−4 l min−1) of rabeprazole treatment. The predicted gastrin‐time profile showed a higher response in CYP2C19 PMs than in EMs on days 4 and 7.Helicobacter pyloriwas eradicated in all CYP2C19 PMs except in one patient infected by a resistant strain. In contrast, in CYP2C19 EMs the eradication rates ranged from 58 to 85%.

CONCLUSIONSCYP2C19 genotypes play a role inH. pylorieradication therapy. Rabeprazole‐based short‐term triple therapy may be applicable in CYP2C19 PMs forH. pylorieradication.
Do educational interventions improve prescribing by medical students and junior doctors? A systematic review
Authors: Ross Sarah , Loke Yoon K
Published: February 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Recent studies have identified a problem with prescribing errors in hospitals.

• It is unclear to what extent educational interventions improve prescribing performance.

WHAT THIS STUDY ADDS

• A wide range of interventions have been tested, but most of them have been on small numbers of participants in single centres.

• The most widely tested intervention, with the greatest number of randomized controlled trials, is the WHO Good Prescribing Guide, which has demonstrated efficacy in international settings across a wide range of students.

• Further work is needed to produce high‐quality educational interventions and robust evaluations.

Our aim was to review systematically the literature on educational interventions to improve prescribing by medical students and junior doctors. MEDLINE, EMBASE, Educational Resource Information Center, British Education Index, PsycINFO, CINAHL, TIMELIT, Cochrane Trials Database and grey literature were searched. Inclusion criteria were: educational interventions to improve medical student and/or junior doctors' prescribing, in primary or secondary care settings, and published after 1990. After screening 3189 records, we retrieved 11 controlled and four ‘before‐and‐after’ trials. Ten controlled trials showed improvements in the scores of the intervention group on written scenarios or clinical examination stations, but one study in junior doctors showed no effect on real‐life prescription errors. Only one intervention [the World Health Organization (WHO) Good Prescribing Guide, in six randomized trials] had been tested in a variety of international settings and across a range of students at different levels. All four ‘before‐and‐after’ trials reported significant improvements in written tests or clinical stations. However, most studies tested only small numbers of participants and were affected by a range of methodological flaws. There is only moderate evidence in the literature to inform medical schools about how to prepare medical students for the challenges of prescribing. The WHO Good Prescribing Guide is the only model that has been widely used and shown to improve prescribing. Although it is based on sound principles, there is a need for further development. Robust methods of assessment are required to show clearly whether particular teaching interventions are successful.
Textilinin‐1, an alternative anti‐bleeding agent to aprotinin: Importance of plasmin inhibition in controlling blood loss
Authors: Flight Simone M. , Johnson Lambro A. , Du Qianyun S. , Warner Roscoe L. , Trabi Manuela , Gaffney Patrick J. , Lavin Martin F. , De Jersey John , Masci Paul P.
Published: February 2009

Aprotinin has been used widely in surgery as an anti‐bleeding agent but is associated with a number of side effects. We report that textilinin‐1, a serine protease inhibitor from Pseudonaja textilis venom with sequence relatedness to aprotinin, is a potent but reversible plasmin inhibitor and has a narrower range of protease inhibition compared to aprotinin. Like aprotinin, textilinin‐1 at 5 μmol/l gave almost complete inhibition of tissue plasminogen activator‐induced fibrinolysis of whole blood clots. The activated partial thromboplastin time for plasma was markedly increased by aprotinin but unaffected by textilinin‐1. In a mouse tail‐vein bleeding model, intravenous textilinin‐1 and aprotinin caused similar decreases in blood loss but time to haemostasis in the textilinin‐treated animals was significantly shorter than in aprotinin‐treated mice. Based on these data, textilinin‐1 merits further investigation as a therapeutic alternative to aprotinin.
Beneficial and harmful effects of anthracyclines in the treatment of childhood acute lymphoblastic leukaemia: a systematic review and meta‐analysis
Authors: Childhood Acute Lymphoblastic Leukaemia Collaborative Group
Published: February 2009

Anthracyclines are used to treat childhood acute lymphoblastic leukaemia (ALL) but non‐randomized studies suggest that cardiotoxicity may be a problem. Individual patient data from trials in childhood ALL that randomized anthracyclines or methods of reducing cardiotoxicity were analysed by standard meta‐analysis methods. Results were grouped and combined according to: addition of an anthracycline to standard therapy, type of anthracycline, mode of administration, and the use of a cardioprotectant. Data from 958 patients in 4 trials, recruiting between 1972 and 1984, showed that addition of an anthracycline reduced bone marrow relapse and, non‐significantly, non‐bone marrow relapse, resulting in an increased relapse‐free interval. However there was a non‐significant increase in induction failures, and in deaths in first remission. Event‐free survival at 5 years was 56·7% with anthracycline versus 52·8% without (Odds Ratio = 0·91; 95% Confidence Interval = 0·76–1·10; P = 0·3). There were no significant differences found in other treatment comparisons. The limited data from trials did not demonstrate differences in clinically evident cardiotoxicity. Anthracyclines are effective against bone marrow relapse but have not been shown to significantly increase event free survival in childhood ALL. The evidence on type of anthracycline, method of administration or use of cardioprotectant was insufficient to be able to rule out important differences.
Ice age distributions of European small mammals: insights from species distribution modelling
Authors: Fløjgaard Camilla , Normand Signe , Skov Flemming , Svenning Jens‐Christian
Published: February 2009

Aim  In addition to the traditionally recognized Last Glacial Maximum (LGM, 21 ka) refuge areas in the Mediterranean region, more northerly LGM distributions for temperate and boreal taxa in central and eastern Europe are increasingly being discussed based on palaeoecological and phylogeographical evidence. Our aim was to investigate the potential refuge locations using species distribution modelling to estimate the geographical distribution of suitable climatic conditions for selected rodent species during the LGM.

Location  Eurasia.

Methods  Presence/absence data for seven rodent species with range limits corresponding to the limits of temperate or boreal forest or arctic tundra were used in the analysis. We developed predictive distribution models based on the species present‐day European distributions and validated these against their present‐day Siberian ranges. The models with the best predictors of the species distributions across Siberia were projected onto LGM climate simulations to assess the distribution of climatically suitable areas.

Results  The best distribution models provided good predictions of the present‐day Siberian ranges of the study species. Their LGM projections showed that areas with a suitable LGM climate for the three temperate species (Apodemus flavicollis, Apodemus sylvaticus and Microtus arvalis) were largely restricted to the traditionally recognized southern refuge areas, i.e. mainly in the Mediterranean region, but also southernmost France and southern parts of the Russian Plain. In contrast, suitable climatic conditions for the two boreal species (Clethrionomys glareous and Microtus agrestis) were predicted as far north as southern England and across southern parts of central and eastern Europe eastwards into the Russian Plain. For the two arctic species (Lemmus lemmus and Microtus oeconomus), suitable climate was predicted from the Atlantic coast eastward across central Europe and into Russia.

Main conclusions  Our results support the idea of more northerly refuge areas in Europe, indicating that boreal species would have found suitable living conditions over much of southern central and eastern Europe and the Russian Plain. Temperate species would have primarily found suitable conditions in the traditional southern refuge areas, but interestingly also in much of the southern Russian Plain.
Fatty acid acylation regulates trafficking of the unusual Plasmodium falciparum calpain to the nucleolus
Authors: Russo Ilaria , Oksman Anna , Goldberg Daniel E.
Published: February 2009

The Plasmodium falciparum genome encodes a single calpain. By generating P. falciparum clones expressing C‐terminally tagged calpain, we localized this protein to the nucleolus. Pf_calpain possesses an unusual and long N‐terminal domain in which we identified three subregions that are highly conserved among Plasmodium species. Two have putative targeting signals: a myristoylation motif and a nuclear localization sequence. We assessed their functionality. Our data show that the nuclear localization sequence is an active nuclear import motif that contains an embedded signal conferring nucleolar localization on various chimeras. The N‐terminus is myristoylated at Gly2 and palmitoylated at Cys3 and Cys22. Palmitoylation status has an important role in dictating P. falciparum calpain localization. The targeting signals function in mammalian cells as well as in the parasite. P. falciparum calpain is a unique nucleolar protein with an interesting mechanism of targeting.
Genome‐wide gene expression profiling and a forward genetic screen show that differential expression of the sodium ion transporter Ena21 contributes to the differential tolerance of Candida albicans and Candida dubliniensis to osmotic stress
Authors: Enjalbert Brice , Moran Gary P. , Vaughan Claire , Yeomans Tim , MacCallum Donna M. , Quinn Janet , Coleman David C. , Brown Alistair J. P. , Sullivan Derek J.
Published: February 2009

Candida albicans is more pathogenic than Candida dubliniensis. However, this disparity in virulence is surprising given the high level of sequence conservation and the wide range of phenotypic traits shared by these two species. Increased sensitivity to environmental stresses has been suggested to be a possible contributory factor to the lower virulence of C. dubliniensis. In this study, we investigated, in the first comparison of C. albicans and C. dubliniensis by transcriptional profiling, global gene expression in each species when grown under conditions in which the two species exhibit differential stress tolerance. The profiles revealed similar core responses to stresses in both species, but differences in the amplitude of the general transcriptional responses to thermal, salt and oxidative stress. Differences in the regulation of specific stress genes were observed between the two species. In particular, ENA21, encoding a sodium ion transporter, was strongly induced in C. albicans but not in C. dubliniensis. In addition, ENA21 was identified in a forward genetic screen for C. albicans genomic sequences that increase salt tolerance in C. dubliniensis. Introduction of a single copy of CaENA21 was subsequently shown to be sufficient to confer salt tolerance upon C. dubliniensis.
CRISPR families of the crenarchaeal genus Sulfolobus: bidirectional transcription and dynamic properties
Authors: Lillestøl Reidun K. , Shah Shiraz A. , Brügger Kim , Redder Peter , Phan Hien , Christiansen Jan , Garrett Roger A.
Published: February 2009

Clusters of regularly interspaced short palindromic repeats (CRISPRs) of Sulfolobus fall into three main families based on their repeats, leader regions, associated cas genes and putative recognition sequences on viruses and plasmids. Spacer sequence matches to different viruses and plasmids of the Sulfolobales revealed some bias particularly for family III CRISPRs. Transcription occurs on both strands of the five repeat‐clusters of Sulfolobus acidocaldarius and a repeat‐cluster of the conjugative plasmid pKEF9. Leader strand transcripts cover whole repeat‐clusters and are processed mainly from the 3′‐end, within repeats, yielding heterogeneous 40–45 nt spacer RNAs. Processing of the pKEF9 leader transcript occurred partially in spacers, and was incomplete, probably reflecting defective repeat recognition by host enzymes. A similar level of transcripts was generated from complementary strands of each chromosomal repeat‐cluster and they were processed to yield discrete ∼55 nt spacer RNAs. Analysis of the partially identical repeat‐clusters of Sulfolobus solfataricus strains P1 and P2 revealed that spacer‐repeat units are added upstream only when a leader and certain cas genes are linked. Downstream ends of the repeat‐clusters are conserved such that deletions and recombination events occur internally.
Effects of mitochondrial complex III disruption in the respiratory chain of Neurospora crassa
Authors: Duarte Margarida , Videira Arnaldo
Published: February 2009

In mitochondria from most organisms, including Neurospora crassa, dimeric complex III was found associated with complex I. Additional association of complex IV with this core structure leads to the formation of a respirasome. It was recently described for bacteria and mammals that complex III is needed for the assembly/stability of complex I. To elucidate the role of complex III in the organization of the respiratory chain of N. crassa, we analysed strains devoid of either the Rieske iron‐sulphur or the COREII polypeptide subunits. The mutants display reduced growth, are female sterile and lack active complex III. The supramolecular organization of the oxidative phosphorylation system was characterized by electrophoretic analyses and the efficiency of the respiratory chain analysed by oxygen consumption measurements. The results obtained indicate that absence of complex III activity is not associated with the absence of complex I or complex IV, and leads to the induction of alternative oxidase. Complex III mutant mitochondria are devoid of respirasomes but contain significant amounts of dimeric complex I (I2) and of the supercomplex I1IV1. Moreso, for the first time the alternative oxidase was found associated with dimeric complex IV and with supercomplex I1IV1.
Impairment of rectal afferent mechanosensitivity in experimental diabetes in the rat
Authors: Beyak M. J. , Bulmer D. C. E. , Sellers D. , Grundy D.
Published: February 2009

Abstract  Diabetes mellitus results in neuropathy of both somatic and visceral nerves. In diabetic patients with faecal incontinence, impaired rectal sensory function, manifested by a decreased sensitivity to balloon distention is common. This may contribute to unawareness of rectal filling and incontinence. There has been little study to date of visceral mechanosensation in experimental diabetes however. We hypothesized that experimental diabetes would impair mechanosensitivity in rectal afferent nerves. Diabetes was induced in rats by i.p. injection of streptozotocin. Controls were injected with citrate. In vitro recordings were performed from rectal afferent nerves innervating isolated segments of rectum. In control animals, three distinct populations of mechanosensitive fibres were identified. Low threshold fibres responded at low intensity stretch and reached a maximal firing rate at less than 10 g of stretch (11/24 units). Wide dynamic sensitivity units responded at low intensity stretch (<2 g) but encoded stimulus intensity in a linear fashion up to 20 g (12/24 units). High threshold units responded at greater than 5 g. In diabetic animals there was a near complete loss of LT units (1/19) and most (16/29) had properties similar to WD units. However, their response threshold was significantly increased. Firing rates in response to maximal distention did not change in diabetic animals. We conclude that experimental diabetes selectively affects the detection of low threshold ‘physiologic’ rectal distention, such as that which might occur during rectal filling, prior to defaecation.
Secretin‐induced gastric relaxation is mediated by vasoactive intestinal polypeptide and prostaglandin pathways
Authors: Lu Y. , Owyang C.
Published: February 2009

Abstract Secretin has been shown to delay gastric emptying and inhibit gastric motility. We have demonstrated that secretin acts on the afferent vagal pathway to induce gastric relaxation in the rat. However, the efferent pathway that mediates the action of secretin on gastric motility remains unknown. We recorded the response of intragastric pressure to graded doses of secretin administered intravenously to anaesthetized rats using a balloon attached to a catheter and placed in the body of the stomach. Secretin evoked a dose‐dependent decrease in intragastric pressure. The threshold dose of secretin was 1.4 pmol kg−1h−1and the effective dose, 50% was 5.6 pmol kg−1h−1. Pretreatment with hexamethonium markedly reduced gastric relaxation induced by secretin (5.6 pmol kg−1h−1). Bilateral vagotomy also significantly reduced gastric motor responses to secretin. Administration ofNG‐nitro‐l‐arginine methyl ester (10 mg kg−1) did not affect gastric relaxation induced by secretin. In contrast, intravenous administration of a vasoactive intestinal polypeptide (VIP) antagonist (30 nmol kg−1) reduced the gastric relaxation response to secretin (5.6 pmol kg−1h−1) by 89 ± 5%. Indomethacin (2 mg kg−1) reduced gastric relaxation induced by secretin (5.6 pmol kg−1h−1) by 87 ± 5%. Administration of prostaglandin (48 mg kg−1h−1) prevented this inhibitory effect. Indomethacin also reduced gastric relaxation induced by VIP (300 pmol kg−1) by 90 ± 7%. These observations indicate that secretin acts through stimulation of presynaptic cholinergic neurons in a vagally mediated pathway. Through nicotinic synapses, secretin stimulates VIP release from postganglionic neurons in the gastric myenteric plexus, which in turn induces gastric relaxation through a prostaglandin‐dependent pathway.
Patients with physiological acid exposure and positive symptom association scores: a distinct group within the GORD spectrum
Authors: De Vries D. R. , Van Herwaarden M. A. , Smout A. J. P. M. , Samsom M.
Published: February 2009

Abstract  Studies comparing pH‐metrically well‐characterized gastro‐oesophageal reflux disease (GORD) patients with physiological reflux to GORD patients with pathological reflux, with regard to clinical and epidemiological data, are lacking. We included 273 GORD patients with pathological 24‐h pH‐monitoring (pH+), defined as pH<4 ≥ 6% of time. A symptom index (SI) ≥ 50% was considered positive, as well as a symptom association probability (SAP) ≥ 95%. We included 84 GORD patients with physiological acid exposure (pH−) and a positive SI and/or SAP. Manometry and endoscopy reports were reviewed. Subjects completed questionnaires about demographics and medical history, functional dyspepsia and irritable bowel syndrome, the Nepean Dyspepsia Index symptom score and the RAND‐36 quality of life scale. pH− patients were younger (45 vs 50 years, P = 0.003), more often female (60%vs 39%, P = 0.001), smoked more (31%vs 19%, P = 0.021) and reported proton pump inhibition failure more often (47%vs 32%, P = 0.027). A hypotensive lower oesophageal sphincter was less common in pH− patients (18%vs 34%, P = 0.008) and distal oesophageal contraction amplitude was higher (11 vs 9.5 kPa, P = 0.045). pH− patients had hiatal hernia and oesophagitis less often (48%vs 73%, P < 0.0005; 36%vs 54%, P = 0.012 respectively). pH− patients less often reported no other symptoms besides GORD (20%vs 34%, P = 0.015). pH− patients scored worse at the Nepean (reflux 19 vs 12 out of 39, P < 0.0005; dyspepsia 54 vs 38 out of 156, P < 0.0005). In the subgroup of patients who have physiological oesophageal acid exposure the enhancement of the perceived symptom burden appears to be the most important mechanism in GORD pathogenesis.
Modelling the formation of residual dune ridges behind barchan dunes in North‐east Brazil
Authors: LEVIN NOAM , TSOAR HAIM , HERRMANN HANS JÜRGEN , MAIA LUIS P. , CLAUDINO‐SALES VANDA
Published: February 2009

Residual dune ridges are often formed by vegetation growing along a line some distance upwind of the lower stoss slope of migrating dunes. This process is common in areas where vegetation germinates along the edge of the water during the rainy period when the water level is higher and interdune areas are flooded. The phenomenon occurs on a large scale in North‐east Brazil, because of the rise and fall in groundwater level at the end of the rainy season. Each residual dune ridge corresponds to the position of the dune during the wet period in each year. Therefore, variations in the distance between these residual dune ridges could be used potentially to monitor climatic fluctuations in rainfall and wind. To examine the potential use of these residual dune ridges for the reconstruction of past climatic fluctuations, a model that simulates them under varying conditions of wind, rainfall and evaporation rates was formulated. The model was tested for sensitivity to climatic variability in North‐east Brazil and validated against residual dune ridge displacements as measured in the field and from high spatial resolution satellite images. Based on the results, it is concluded that residual dune ridges may not form in North‐east Brazil in years which are exceptionally dry, as may happen during El‐Niño events. When this type of event happens, the distance between adjacent residual dune ridges corresponds to more than one year and, therefore, the correlation between dune displacements and wind power becomes weak or even disappears. Additionally, because of biotic, aeolian and hydrological processes, these arcuate residual dune ridges may not preserve their initial shape for long periods. The presence of residual dune ridges testifies to the temporary flooding which may or may not be seasonal. However, the potential for using residual dune ridges to reconstruct the palaeo‐climate of wind regime on a yearly basis or to identify past El‐Niño events seems to be limited.
The household costs of health care in rural South Africa with free public primary care and hospital exemptions for the poor
Authors: Goudge Jane , Gilson Lucy , Russell Steve , Gumede Tebogo , Mills Anne
Published: February 2009

Objective  To measure the direct cost burdens (health care expenditure as a percent of total household expenditure) for households in rural South Africa, and examine the expenditure and use patterns driving those burdens, in a setting with free public primary health care and hospital exemptions for the poor.

Methods  Data on illness events, treatment patterns and health expenditure in the previous month were assessed from a cross‐sectional survey of 280 households conducted in the Agincourt Health and Demographic Surveillance site, South Africa.

Results  On average, a household experiencing illness incurred a direct cost burden of 4.5% of total household expenditure. A visit to a public clinic generated a mean burden of 1.3%. Complex sequences of treatments led 20% of households to incur a burden over 10%, with transport costs generating 42% of this burden. An outpatient public hospital visit generated a burden of 8.2%, as only 58% of those eligible obtained an exemption; inpatient stays incurred a burden of 45%. Consultations with private providers incurred a mean burden of 9.5%. About 38% of individuals who reported illness did not take any treatment action, 55% of whom identified financial and perceived supply‐side barriers as reasons.

Conclusion  The low overall mean cost burden of 4.5% suggests that free primary care and hospital exemptions provided financial protection. However, transport costs, the difficulty of obtaining hospital exemptions, use of private providers, and complex treatment patterns meant state‐provided protection had limitations. The significant non‐use of care shows the need for other measures such as more outreach services and more exemptions in rural areas. The findings also imply that fee removal anywhere must be accompanied by wider measures to ensure improved access.
Influences of herbicides, uprooting and use as cut flowers on sexual reproduction of Solidago canadensis
Authors: GUO S L , JIANG H W , FANG F , CHEN G Q
Published: February 2009

Solidago canadensis is a noxious invasive species in China. We examined the influences of herbicides on pollen germination and pollen tube growth and the effects of cutting flowers and herbicides on seed production and quality. We also determined the seed production and resource allocation to different organs of S. canadensis after uprooting the plants during their reproductive periods. The main results were as follows: (i) 49% pollen of S. canadensis was able to germinate on an appropriate medium; (ii) compared with paraquat, ethephon and 2,4‐D, glyphosate had an ideal inhibitory effect on pollen germination and the formation of seeds of S. canadensis; (3) cut flowering branches, when placed in water or nutrient solution, were still able to produce viable seeds; (4) resources were allocated more to the inflorescences to facilitate seed maturation after plants were uprooted at the flowering stage. Uprooted flower branches were still able to produce viable seeds, especially those in full flower. Therefore, in order to reduce the seed production of S. canadensis and spread of the species we suggest: (i) apply glyphosate at the flower bud stage, (ii) completely destroy uprooted plants at flowering stages and (iii) avoid using the flowering branches as ornamental materials.
Mutual influence in shared decision making: a collaborative study of patients and physicians
Authors: Lown Beth A. , Hanson Janice L. , Clark William D.
Published: February 2009

Objective  To explore how patients and physicians describe attitudes and behaviours that facilitate shared decision making.

Background  Studies have described physician behaviours in shared decision making, explored decision aids for informing patients and queried whether patients and physicians want to share decisions. Little attention has been paid to patients’ behaviors that facilitate shared decision making or to the influence of patients and physicians on each other during this process.

Methods  Qualitative analysis of data from four research work groups, each composed of patients with chronic conditions and primary care physicians.

Results  Eighty‐five patients and physicians identified six categories of paired physician/patient themes, including act in a relational way; explore/express patient’s feelings and preferences; discuss information and options; seek information, support and advice; share control and negotiate a decision; and patients act on their own behalf and physicians act on behalf of the patient. Similar attitudes and behaviours were described for both patients and physicians. Participants described a dynamic process in which patients and physicians influence each other throughout shared decision making.

Conclusions  This study is unique in that clinicians and patients collaboratively defined and described attitudes and behaviours that facilitate shared decision making and expand previous descriptions, particularly of patient attitudes and behaviours that facilitate shared decision making. Study participants described relational, contextual and affective behaviours and attitudes for both patients and physicians, and explicitly discussed sharing control and negotiation. The complementary, interactive behaviours described in the themes for both patients and physicians illustrate mutual influence of patients and physicians on each other.
Getting ready for user involvement in a systematic review
Authors: Smith Elizabeth , Donovan Sheila , Beresford Peter , Manthorpe Jill , Brearley Sally , Sitzia John , Ross Fiona
Published: February 2009

Objective  This paper aims to support the critical development of user involvement in systematic reviews by explaining some of the theoretical, ethical and practical issues entailed in ‘getting ready’ for user involvement.

Background  Relatively few health or social care systematic reviews have actively involved service users. Evidence from other research contexts shows that user involvement can have benefits in terms of improved quality and outcomes, hence there is a need to test out different approaches in order to realize the benefits of user involvement and gain a greater understanding of any negative outcomes.

Design  Setting up a service‐user reference group for a review of user involvement in nursing, midwifery and health visiting research involved conceptualizing user involvement, developing a representation framework, identifying and targeting service users and creating a sense of mutuality and reciprocity.

Setting and participants  Recruitment was undertaken across England by two researchers. Members from 24 national consumer organizations were selected to participate in the review.

Main variables studied  Learning was gained about finding ways of navigating consumer networks and organizations, how best to communicate our goals and intentions and how to manage selection and ‘rejection’ in circumstances where we had stimulated enthusiasm.

Results and conclusions  Involving service users helped us to access information, locate the findings in issues that are important to service users and to disseminate findings. User involvement is about relationships in social contexts: decisions made at the early conceptual level of research design affect service users and researchers in complex and personal ways.
Information and behavioural instruction along the health‐care pathway: the perspective of people undergoing hernia repair surgery and the role of formal and informal information sources
Authors: Powell Rachael , McKee Lorna , Bruce Julie
Published: February 2009

Background Provision of information and behavioural instruction has been demonstrated to improve recovery after surgery. However, patients draw on a range of information sources and it is important to establish which sources patients use and how this influences perceptions and behaviour as they progress along the surgical pathway. In this qualitative, exploratory and longitudinal study, the use of information and instruction were explored from the perspective of people undergoing inguinal hernia repair surgery.

Methods Seven participants undergoing inguinal hernia repair surgery were interviewed using semi‐structured interviews 2 weeks before surgery and 2 weeks and 4 months post‐surgery. Nineteen interviews were conducted in total. Topic guides included sources of knowledge, reasons for help‐seeking and opting for surgery and factors influencing return to activity. Data were analysed thematically according to Interpretative Phenomenological Analysis.

Findings and conclusions Participants sought information from a range of sources, focusing on informal information sources before surgery and using information and instruction from health‐care professionals post‐surgery. This information influenced behaviours including deciding to undergo surgery, use of pain medication and returning to usual activity. Anxiety and help‐seeking resulted when unexpected post‐surgical events occurred such as extensive bruising. Findings were consistent with psychological and sociological theories. Overall, participants were positive about the information and instruction they received but expressed a desire for more timely information on post‐operative adverse events.
Response to antiviral therapy in liver transplant recipients with recurrent hepatitis C viral infection: a single center experience
Authors: Jain Ashok , Sharma Rajeev , Ryan Charlotte , Safadjou Saman , Kashyap Randeep , Mantry Parvez , Maliakkal Benedict , Orloff Mark
Published: February 2009

Jain A, Sharma R, Ryan C, Safadjou S, Kashyap R, Mantry P, Maliakkal B, Orloff M. Response to antiviral therapy in liver transplant recipients with recurrent hepatitis C viral infection: a single center experience. Clin Transplant 2010: 24: 104–111. © 2009 John Wiley & Sons A/S.

Abstract:  Introduction:  Recurrence of hepatitis C virus (HCV) in hepatic allograft is a major concern after successful liver transplant (LTx).

Aim:  To examine the response rate to pegylated interferon (PEG–IFN) and ribavirin in post‐LTx patients with HCV recurrence.

Patients and methods:  Between January 2003 and September 2006, 60 patients with biopsy proven HCV recurrence (46 males and 14 females) received PEG–IFN 2a (n = 40) or IFN 2b (n = 20) with ribavirin. All patients were followed until July 2007.

Results:  Fourteen patients (23.3%) tolerated antiviral therapy for less than six months and 10 (16.7%) discontinued therapy between six and 11 months. PEG–IFN dose was reduced in 21 (35%) patients and ribavirin dose was reduced in 16 (26.7%) patients. Overall, 55% patients achieved end of treatment response (EOT) and 35% sustained virological response (SVR). Mean Hepatitis Activity Index and Fibrosis Score pre‐therapy was 5.8 ± 1.9 and 1.7 ± 1.3 and post‐therapy, it was 4.4 ± 2.1 and 2.4 ± 1.6, respectively. Overall, three yr patient and graft survival was 73.9% and 69.2%, respectively. The patients with SVR had significantly lower viral load compared with other groups (p = 0.028).

Conclusion:  PEG–IFN and ribavirin therapy achieved 55% EOT and 35% SVR; 60% patients tolerated therapy. Biochemical response was observed in all groups of patients irrespective of virological response.
Food allergy after liver transplantation in children: a prospective study
Authors: Ozbek Ozlem Yilmaz , Ozcay Figen , Avci Zekai , Haberal Aysegul , Haberal Mehmet
Published: February 2009

Food allergy has been increasingly reported in children who had orthotopic liver transplantation (OLT). We aimed to conduct a prospective study to investigate the prevalence of sensitizations and food allergy in pediatric OLT recipients. We also aimed to identify potential risk factors. The study group consisted of 28 children (14 male, 14 female, mean age 4.96 ± 0.76 yrs) who had OLT. Total eosinophil count (TEC), total IgE, and specific IgEs were studied before and 3, 6, 12 months after OLT. Six patients (21%) developed multiple food allergies. Mean age of six patients at OLT who developed food allergy was younger compared to the non‐food allergy group (10.2 months vs. 68.9 months, p < 0.05). Food allergy has been developed within 1 yr in 5, and in 20 months in one patient after OLT. All six patients had cow’s milk and egg allergy after OLT. Five children developed wheat, one children developed lentil and another one developed peach allergy in addition to cow’s milk and egg allergy. Out of six food‐allergic patients after OLT, four children developed Epstein–Barr virus (EBV) infection prior to food allergy. Before OLT, TECs and total IgE levels were not differed among food allergic and non‐food allergic patients (p > 0.05). Mean of TECs were significantly higher in food allergic group compared to non‐food allergic group at each time point after OLT (p < 0.05). Though statistically insignificant, mean of total IgE levels were also higher in the food allergic group (p > 0.05). These findings suggest that food allergy should be considered after OLT in patients who are younger than 1 yr of age, who developed hypereosinophilia, high total IgE levels or EBV viremia.
Detection and treatment of Strongyloides hyperinfection syndrome following lung transplantation
Authors: Balagopal A. , Mills L. , Shah A. , Subramanian A.
Published: February 2009

Abstract: Strongyloides hyperinfection syndrome has not been reported in lung transplant recipients. We describe the case of a 61‐year‐old Peruvian man, who received bilateral lung transplants for idiopathic pulmonary fibrosis, and subsequently developed persistent fever with pulmonary infiltrates, ventilator dependence, and pneumothoraces. Bronchoalveolar lavage (BAL) cultures for bacteria, viruses, and fungi were negative, but testing for ova and parasites from BAL fluid revealed Strongyloides stercoralis larvae on day 16 post transplant. He was successfully treated with albendazole and ivermectin, and immunosuppression was reduced. BAL fluid also grew Mycobacterium kansasii, for which he received combination anti‐mycobacterial therapy. This case illustrates the importance of screening for parasitic infections before transplantation in the appropriate clinical setting, and demonstrates the utility of direct diagnostic evaluation for parasitic infections in at‐risk post‐transplant patients with unexplained illnesses.
Vasopressin decreases intestinal mucosal perfusion: a clinical study on cardiac surgery patients in vasodilatory shock
Authors: NYGREN A. , THORÉN A. , RICKSTEN S.‐E.
Published: February 2009

Background: Low to moderate doses of vasopressin have been used in the treatment of cathecholamine‐dependent vasodilatory shock in sepsis or after cardiac surgery. We evaluated the effects of vasopressin on jejunal mucosal perfusion, gastric‐arterial pCO2 gradient and the global splanchnic oxygen demand/supply relationship in patients with vasodilatory shock after cardiac surgery.

Methods: Eight mechanically ventilated patients, dependent on norepinephrine to maintain mean arterial pressure (MAP) ≥60 mmHg because of septic/post‐cardiotomy vasodilatory shock and multiple organ failure after cardiac surgery, were included. Vasopressin was sequentially infused at 1.2, 2.4 and 4.8 U/h for 30‐min periods. Norepinephrine was simultaneously decreased to maintain MAP at 75 mmHg. At each infusion rate of vasopressin, data on systemic hemodynamics, jejunal mucosal perfusion, jejunal mucosal hematocrit and red blood cell velocity (laser Doppler flowmetry) as well as gastric‐arterial pCO2 gradient (gastric tonometry) and splanchnic oxygen and lactate extraction (hepatic vein catheter) were obtained.

Results: The cardiac index, stroke volume index and systemic oxygen delivery decreased and systemic vascular resistance and systemic oxygen extraction increased significantly, while the heart rate or global oxygen consumption did not change with increasing vasopressin dose. Jejunal mucosal perfusion decreased and the arterial‐gastric‐mucosal pCO2 gradient increased, while splanchnic oxygen or lactate extraction or mixed venous–hepatic venous oxygen saturation gradient were not affected by increasing infusion rates of vasopressin.

Conclusions: Infusion of low to moderate doses of vasopressin in patients with norepinephrine‐dependent vasodilatory shock after cardiac surgery induces an intestinal and gastric mucosal vasoconstriction.
Role of fibrinogen‐, factor VIII‐ and XIII‐mediated clot propagation in gelatin haemodilution
Authors: SCHRAMKO A. A. , KUITUNEN A. H. , SUOJARANTA‐YLINEN R. T. , NIEMI T. T.
Published: February 2009

Background: Gelatin solution impairs coagulation. The mechanism of coagulopathy is incompletely defined. The purpose of this study was to evaluate the capacity of single coagulation factors to reverse gelatin‐promoted whole‐blood coagulation disorders in vitro.

Methods: Venous blood was withdrawn from 12 volunteers in a crossover study. Four percent succinylated gelatin was added to citrated whole‐blood samples to make a 40 vol% end‐concentration of gelatin. The baseline and 40 vol% samples, and samples with addition of fresh‐frozen plasma (FFP), fibrinogen, coagulation factors XIII (FXIII) or VIII, together with the von Willebrand factor (FVIII+vWF), were analysed by thromboelastometry (ROTEM®). Coagulation was initiated by tissue thromboplastin (ExTEM®) with and without cytochalasin to determine the functional component of fibrinogen (FibTEM®).

Results: Initiation of coagulation and fibrin formation were delayed at 40 vol% gelatin dilution. At this stage, the median (25th–75th percentiles) maximum clot firmness (MCF) was 76.3 (65.9–80.0) and 32.5 (27.4–45.0)% of the pre‐dilution value in ExTEM® and FibTEM® thromboelastometry, respectively. Coagulation time was corrected by addition of fibrinogen and FFP in ExTEM® and FibTEM® analysis, whereas FVIII or FXIII had minimal effects. MCF was partly restored only by FFP in ExTEM®. In FibTEM® analysis, MCF improved more by fibrinogen than by FVIII+VWF, FXIII or FFP.

Conclusions: Gelatin‐induced whole‐blood coagulation disorder in vitro is mainly dependent on the initial fibrinogen–fibrin interaction. The proposed mechanism might suggest not to reverse gelatin coagulopathy solely by fibrinogen administration. The administration of FFP, a mixture of different coagulation factors, reversed the gelatin‐induced in vitro coagulopathy the best.
Behavioural, ecological and genetic evidence confirm the occurrence of host‐associated differentiation in goldenrod gall‐midges
Authors: DORCHIN N. , SCOTT E. R. , CLARKIN C. E. , LUONGO M. P. , JORDAN S. , ABRAHAMSON W. G.
Published: February 2009

Host‐associated differentiation (HAD) is considered a step towards ecological speciation and an important mechanism promoting diversification in phytophagous insects. Although the number of documented cases of HAD is increasing, these still represent only a small fraction of species and feeding guilds among phytophagous insects, and most reports are based on a single type of evidence. Here we employ a comprehensive approach to present behavioural, morphological, ecological and genetic evidence for the occurrence of HAD in the gall midge Dasineura folliculi (Diptera: Cecidomyiidae) on two sympatric species of goldenrods (Solidago rugosa and S. gigantea). Controlled experiments revealed assortative mating and strong oviposition fidelity for the natal‐host species. Analysis of mitochondrial DNA showed an amount of genetic divergence between the two host‐associated populations compatible with cryptic species rather than host races. Lower levels of within‐host genetic divergence, gall development and natural‐enemy attack in the S. gigantea population suggest this is the derived host.
SNP deserts of Asian cultivated rice: genomic regions under domestication
Authors: WANG L. , HAO L. , LI X. , HU S. , GE S. , YU J.
Published: February 2009

When performing a genome‐wide comparison between indica (93‐11) and japonica (Nipponbare), we find 8% of the genome, which have an extremely low SNP rate (< 1 SNP/kb). Inside these ‘SNP deserts’, experimentally confirmed genes show increased Ka/Ks that indicate adaptive selection. To further elucidate this connection, we survey the level and pattern of genetic variation in both cultivated and wild rice groups, using 155 noncoding regions located within SNP deserts. The results suggest that cultivated rice has greatly reduced genetic variation within SNP deserts as compared to either the nondesert or corresponding genomic regions in wild rice. Consistent with this reduction in genetic variation, we find a biased distribution of derived allele frequency in the cultivated group, indicative of positive selection. Furthermore, over half of the confirmed, domestication‐related genes are found within SNP deserts, also suggesting that SNP deserts are strongly related to domestication, and might be the key sites in the process of domestication.
How ecology shapes caste evolution: linking resource use, morphology, performance and fitness in a superorganism
Authors: POWELL S.
Published: February 2009

Caste evolution is a central process in the adaptive diversification of insect superorganisms. Nevertheless, how ecology shapes adaptive caste evolution remains poorly understood. Recent work with the ant genusCephaloteshas provided new comparative evidence that ecological specialization may drive adaptive caste specialization. Here, three key predictions of this adaptive hypothesis are supported, using a representative of the highest level of ecological specialization and the most specialized soldier phenotype. First, soldier defensive performance was maximal for the specific nesting resource used most often in nature. Second, colonies only used a specialized subset of available nesting resources and preferred the specific resource that maximizes soldier performance. Third, soldier performance and its limitations on resource use were found to have both direct and indirect consequences for colony reproduction. These findings suggest that the most specialized soldier phenotype inCephalotesis indeed an adaptation to ecological specialization on a narrowly defined subset of available nesting resources.