bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient Advice and Liaison Services: results of an audit survey in England
Authors: Evans David , Powell Jane , Cross Tanya
Published: August 2008

Objective  To assess the extent national standards for Patient Advice and Liaison Services (PALS) were achieved across England.

Context  PALS are an important element of patient and public involvement strategy in England. Seven national standards for PALS were identified. Previous research has not assessed PALS across all trust types in England.

Design  Audit survey as part of a mixed method ‘realistic evaluation’ in which regularities of context, mechanism and outcome are hypothesized and tested.

Setting and participants  PALS based in 570 NHS trusts in England between October and December 2005.

Main outcome measures  Self reported achievement against PALS national standards.

Results  Three hundred and thirty‐six valid responses were received, a response rate of 65%. However because some PALS serve more than one trust, this represents an estimated 76% of trusts. Overall, PALS rated themselves highly against all the standards, though somewhat less highly against standard 2 (seamlessness across health and social care) and standard 6 (acting as a catalyst for culture change). There was a wide range of responses with regard to PALS budget, staffing and activity levels, and statistically significant associations between levels of funding and staffing and higher levels of performance.

Conclusions  The overall response rate was good so there can be a high degree of confidence in the reliability of the results. The results indicate the challenging context in which PALS are operating. Although the majority of PALS are single trust PALS, there is a high degree of variation in key mechanism factors such as budget and staffing.
When doctors disagree: a qualitative study of doctors’ and parents’ views on the risks of childhood food allergy
Authors: Hu Wendy , Grbich Carol , Kemp Andrew
Published: August 2008

Objective To examine the views of doctors which underpin clinical practice variation concerning an uncertain health risk, and the views of parents who had sought advice from these doctors, using the example of childhood food allergy.

Study design Qualitative study involving in‐depth interviews and participant observation over 16 months. Focus groups and consultation audio‐recordings provided corroborative data.

Setting Three specialist allergy clinics located in one metropolitan area.

Participants Eighteen medical specialists and trainees in allergy, and 85 parents (from 69 families) with food allergic children.

Results Doctors expressed a spectrum of views. The most divergent views were characterized by: scientific scepticism rather than precaution in response to uncertainty; emphasis on quantifiable physical evidence rather than parental histories; professional roles as providers of physical diagnosis and treatment rather than of information and advocacy; libertarian rather than communitarian perspectives on responsibility for risk; and values about allergy as a disease and normal childhood. Parents held a similar, but less divergent range of views. The majority of parents preferred more moderate doctors’ views, with 43% (30 of 69) of families expressing their dissatisfaction by seeking another specialist opinion. Many were confused by variation in doctors’ opinions, preferring relationships with doctors that recognized their concerns, addressed their information needs, and confirmed that they were managing their child’s allergy appropriately.

Conclusions In uncertain clinical situations, parents do not expect absolute certainty from doctors; inflexible certainty may not allow parental preferences to be acknowledged or accommodated, and is associated with the seeking of second opinions.
Clinical improvement and normalized Th1 cytokine profile in early and long‐term interferon‐α treatment in a suspected case of hyper‐IgE syndrome
Authors: Benninghoff Ulrike , Cattaneo Federica , Aiuti Alessandro , Flores‐D’Arcais Alberto , Gelmetti Carlo , Viscardi Matteo , Callegaro Luciano , Mirolo Massimiliano , Ambrosi Alessandro , Roncarolo Maria Grazia , Bacchetta Rosa
Published: August 2008

We are reporting on a 7‐months‐old boy with suspected hyper‐IgE syndrome, presenting with a therapy resistant severe eczema and an overall reduction of in vitro cytokine production. Interferon‐α (IFN‐α) treatment resulted in a marked and stable clinical improvement and normalization of in vitro T‐cell cytokine production, indicating a valid therapeutic potential of IFN‐α as immunomodulating drug.
Enhanced expression of IL‐27 mRNA in human newborns
Authors: Krumbiegel Doreen , Anthogalidis‐Voss Christina , Markus Helena , Zepp Fred , Meyer Claudius U.
Published: August 2008

Interleukin (IL)‐27, a heterodimer composed of Epstein–Barr virus‐induced gene 3 (EBI3) and p28, is an early product of activated dendritic cells (DC). Binding of IL‐27 to the WSX‐1 receptor initiates Th1 (Thelper 1) responses in naïve T cells. In order to assess the Th1 responses in human neonates with high susceptibility to infectious diseases, expression of EBI3‐, p28‐ and WSX‐1‐mRNA in response to Toll‐like receptor ligands was compared in neonate and adult monocyte‐derived (m)DC. Only the combined addition of ligands induced expression of IL‐27p28 mRNA. Surprisingly, neonatal mDC produced significantly more IL‐27p28 mRNA than that obtained from adults. Furthermore, there was enhanced expression of EBI3 mRNA in cord blood as compared with adult blood. In addition, the secretion of WSX‐1 mRNA in neonatal mDC and T cells was also significantly increased. Taken together, these findings indicate that the restricted Th1 responses in human newborns owing to deficient IL‐12 production may be compensated for, in part, by enhanced IL‐27 secretion.
Factors associated with non‐attendance at pediatric allergy clinics
Authors: Dreiher Jacob , Goldbart Aviv , Hershkovich Jacob , Vardy Daniel A. , Cohen Arnon D.
Published: August 2008

Non‐attendance for scheduled appointments is common in many medical specialties. However, there are no published reports on non‐attendance in pediatric allergy clinics. We investigated the factors for non‐attendance in pediatric allergy patients. We assessed the effects of age, gender, ethnic origin, waiting time for an appointment and the timing of the appointment on non‐attendance proportions. Chi‐square tests were used to analyze statistically significant differences of categorical variables. Logistic regression models were used for multivariate analyses. A total of 442 visits in a 21‐month period were included in the study. The overall proportion of non‐attendance at the pediatric allergy clinic was 33.0%. Jewish rural patients had 19.4% non‐attendance; Jewish urban patients had 35.6% non‐attendance; and Bedouin patients had 57.1% non‐attendance (p < 0.001). Non‐attendance was higher in spring and winter (43.5% and 36.7%, respectively) than in summer and autumn (26.9% and 26.5%, respectively) (p = 0.016). Non‐attendance was not significantly influenced by gender, age, hour of the appointment or waiting time for the appointment. A multivariate logistic regression model demonstrated that the ethnic origin of the patients and the season of the year were significantly associated with non‐attendance. We conclude that in children attending allergy clinics, factors that determine non‐attendance include the ethnic origin of the patients and the season of the year.
Latex allergy: Two educational cases
Authors: Baker L. , Hourihane J. O’B.
Published: August 2008

Natural rubber latex (NRL) allergy is a significant problem both for health care workers and for children with complex medical and surgical conditions that require multiple surgical interventions. Primary and secondary prophylaxis are effective measures in identified high risk groups, such as spina bifida (SB). It is therefore likely that with proper attention to prevention and secondary prophylaxis in the highest risk groups that the numbers of paediatric SB patients with NRL allergy will continue to decrease. In contrast medical awareness of established latex allergy needs to be maintained. The issue of latex sensitisation via fruit and food allergy will also remain, so some of the attention that SB patients have received in the past may need to be refocussed onto other emerging high risk groups. Innovative immunomodulatory approaches may soon translate to the clinic for latex sensitised or allergic subjects.
Susceptibility to Fas and tumor necrosis factor‐α receptor mediated apoptosis of anti‐CD3/anti‐CD28‐activated umbilical cord blood T cells
Authors: Lin Syh‐Jae , Lee Chen‐Cheng , Cheng Po‐Jen , See Lai‐Chu , Kuo Ming‐Ling
Published: August 2008

Decreased severity of graft‐versus‐host disease after mismatched umbilical cord blood (UCB) transplantation may be attributed in part to the increased propensity to apoptosis of UCB T cells following activation. Interleukin (IL)‐15, a pleiotropic cytokine that is essential for T‐cell proliferation and survival, may serve as promising immunomodulative therapy post‐CB transplantation for its anti‐apoptotic effect. This study aimed to determine the kinetics of Fas or tumor necrosis factor‐α receptor (TNFR) mediated caspase‐3 expression and apoptosis of anti‐CD3/anti‐CD28 activated UCB T cells in the influence of IL‐15. Activated caspase‐3 expression was analyzed by Western blotting and the percentage of apoptotic cells was determined by annexin‐V/propidium iodide (PI) flow cytometric staining. Significant expression of Fas and TNFR2 was detected on anti‐CD3/anti‐CD28 pre‐activated UCB T cells. These cells were susceptible to anti‐Fas but not TNF‐α‐induced apoptosis. Kinetic study shows that caspase‐3 expression became evident at 6th–8th h following anti‐Fas stimulation, while early apoptotic cells with annexin‐V+/PI− expression appeared at 12th–16th h. IL‐15, though successful in decreasing apoptosis in pre‐activated UCB T cells, failed to completely prevent Fas‐mediated caspase‐3 expression and apoptosis of CB T cells. The pre‐activated UCB and adult peripheral blood T cells behaved similarly with regard to death receptor expression, caspase‐3 expression and apoptosis upon Fas‐engagement. Although IL‐15 promotes overall activated UCB T‐cell survival, it did not particularly prevent Fas‐mediated activation‐induced cell death.
Sequencing of substance use and affective morbidity in 166 first‐episode bipolar I disorder patients
Authors: Baethge Christopher , Hennen John , Khalsa Hari‐Mandir Kaur , Salvatore Paola , Tohen Mauricio , Baldessarini Ross J
Published: August 2008

Objectives:  Since bipolar disorder (BPD) patients have high rates of comorbid substance abuse, and the temporal relationships involved are unclear, we evaluated the sequencing of specific substance use and affective morbidity.

Methods:  Prospective follow‐up (4.7 years) of 166 first‐episode DSM‐IV type I BPD patients with reliable, standardized assessments provided data for longitudinal analysis of temporal distribution of alcohol and cannabis use versus manic or depressive episodes or symptoms, using generalized estimating equation regression modeling.

Results:  By quarters, cannabis use selectively and strongly preceded and coincided with mania/hypomania, and alcohol use preceded or coincided with depression, whereas substance use was unassociated with mood states in preceding quarters.

Conclusions:  These preliminary findings suggest potentially predictive temporal associations, in which the abuse of cannabis or alcohol anticipated or corresponded with, but did not follow, affective morbidity, including selective association of cannabis with mania and alcohol with depression.
Short‐term course of neuropsychological abilities in middle‐aged and older adults with bipolar disorder
Authors: Depp Colin A , Savla Gauri N , Moore David J , Palmer Barton W , Stricker John L , Lebowitz Barry D , Jeste Dilip V
Published: August 2008

Objectives:  There are few longitudinal studies of neurocognition in bipolar disorder, and the short‐term course of cognitive deficits in later‐life bipolar disorder is unknown.

Methods:  We administered a battery of neurocognitive tests, repeated 1–3 years after baseline, to 35 community‐dwelling outpatients with bipolar disorder (mean age = 58), and compared their performance on a composite measure of cognitive functioning to that of demographically matched samples of normal comparison subjects (NCs; n = 35) and patients with schizophrenia (n = 35). Using regression analyses, we examined group differences in baseline performance, trajectory of change over time, and variability in performance across time. Within the bipolar group, we examined the impact of baseline severity and change in severity of psychiatric symptoms on intra‐individual change in neurocognitive performance.

Results:  At baseline, the group with bipolar disorder differed in overall neurocognitive functioning from the NCs, but did not differ significantly from the schizophrenia group. The bipolar group did not differ from the NCs or schizophrenia group in the mean trajectory of change between time‐points, but the bipolar patients showed more intra‐individual variability over time than the NCs or schizophrenia group. In the bipolar group, change in neurocognitive function was not related to baseline or change in psychiatric symptom severity.

Conclusions:  Middle‐aged and older community‐dwelling adults with bipolar disorder have greater short‐term variability in level of neurocognitive functioning relative to NCs or people with schizophrenia. The developmental course of and risk factors for cognitive deficits in bipolar disorder should be examined in future longitudinal studies.
Service delivery in older patients with bipolar disorder: a review and development of a medical care model
Authors: Kilbourne Amy M , Post Edward P , Nossek Agnes , Sonel Elif , Drill Larry J , Cooley Susan , Bauer Mark S
Published: August 2008

Objectives:  Medical comorbidities, especially cardiovascular disease (CVD), occur disproportionately in older patients with bipolar disorder. We describe the development, implementation, and feasibility/tolerability results of a manual‐based medical care model (BCM) designed to improve medical outcomes in older patients with bipolar disorder.

Methods:  The BCM consisted of (i) self‐management sessions focused on bipolar disorder symptom control, healthy habits, and provider engagement, (ii) telephone care management to coordinate care and reinforce self‐management goals, and (iii) guideline dissemination focused on medical issues in bipolar disorder. Older patients with bipolar disorder and a CVD‐related risk factor (n = 58) were consented, enrolled, and randomized to receive BCM or usual care.

Results:  Baseline assessment (mean age = 55, 9% female, 9% African American) revealed a vulnerable population: 21% were substance users, 31% relied on public transportation, and 22% reported problems accessing medical care. Evaluation of BCM feasibility revealed high overall patient satisfaction with the intervention, high fidelity (e.g., majority of self‐management sessions and follow‐up contacts completed), and good tolerability (dropout rate <5%). Use of telephone contacts may have mitigated barriers to medical care (e.g., transportation).

Conclusions:  The BCM is a feasible model for older, medically ill patients with bipolar disorder, and could be an alternative to more costly treatment models that involve co‐location and/or additional hiring of medical providers in mental health clinics. Future research directions pertinent to the development of the BCM and other medical care models for older patients with bipolar disorder include assessment of their long‐term effects on physical health and their cost‐effectiveness across different treatment settings.
Missed bipolarity and psychiatric comorbidity in women with postpartum depression
Authors: Sharma Verinder , Khan Mustaq , Corpse Cynthia , Sharma Priya
Published: August 2008

Objective:  To investigate the diagnostic profile of women referred for postpartum depression.

Methods:  Fifty‐six women seen consecutively with the referral diagnosis of postpartum depression were administered structured instruments to gather information about their DSM‐IV Axis I diagnoses.

Results:  In terms of frequency of occurrence, the primary diagnoses in this sample were: major depressive disorder (46%), bipolar disorder not otherwise specified (29%), bipolar II disorder (23%), and bipolar I disorder (2%). A current comorbid disorder, with no lifetime comorbidity, occurred among 32% of the sample; by contrast, lifetime comorbidity alone (i.e., with no currently comorbid disorder) was found among 27%. Both a lifetime and a current comorbidity were found among 18% of the women, and 23% had no comorbid disorder. The most frequently occurring current comorbid disorder was an anxiety disorder (46%), with obsessive‐compulsive disorder (62%) being the most common type of anxiety disorder. For lifetime comorbidity, substance use (20%) and anxiety disorders (12%) were the two most common. Over 80% of patients who scored positive on either the Highs Scale or the Mood Disorder Questionnaire met the diagnostic criteria for a bipolar disorder.

Conclusion:  The results suggest that postpartum depression is a heterogeneous entity and that misdiagnosis of bipolar disorder in the postpartum period may be quite common. The findings have important clinical implications, which include the need for early detection of bipolarity through the use of reliable and valid assessment instruments, and implementation of appropriate prevention and treatment strategies.
Double‐blind randomized controlled study comparing short‐term efficacy of bifrontal and bitemporal electroconvulsive therapy in acute mania
Authors: Hiremani Raja M , Thirthalli Jagadisha , Tharayil Biju S , Gangadhar Bangalore N
Published: August 2008

Background: Bifrontal electrode placement is as efficacious as bitemporal placement during electroconvulsive therapy (ECT) in depression but is associated with fewer cognitive adverse effects. There are no studies comparing these techniques in acute mania. This study compared the short‐term efficacy and adverse effects of bifrontal and bitemporal ECT in the treatment of acute mania.

Method: Thirty‐six DSM‐IV mania inpatients referred for ECT were recruited for study. They were randomized to receive bifrontal (BFECT; n = 17) or bitemporal (BTECT; n = 19) ECT. None of the subjects were on mood stabilizers during the course of ECT. Severity of mania was measured on the Young Mania Rating Scale (YMRS) before beginning ECT and then on Days 3, 7, 11, 14, and 21 of treatment. Cognitive functions were assessed eight hours after the fifth ECT session using the Mini‐Mental Status Examination (MMSE), Paired Associate Learning Test, Complex Figure Test, Verbal Fluency Test (animals and fruits categories), and Trail Making Test, Part A.

Results: The subjects in the two groups were comparable on sociodemographic and clinical variables, including severity of mania at baseline. They were also similar in ECT parameters, including seizure threshold and seizure duration. Mean YMRS scores showed faster decline in the BFECT than in the BTECT group. Kaplan–Meier survival analysis showed that a greater proportion of subjects in the BFECT group responded (50% reduction in YMRS score) significantly earlier than in the BTECT group. There were no significant differences between the groups in performance on cognitive function tests.

Conclusion: In this pilot study, mania patients treated with BFECT responded faster than those treated with BTECT, with comparable cognitive adverse effects. Since ECT is usually prescribed for rapid control of symptoms, BFECT may be preferred over BTECT in the treatment of acute mania.
Treatment‐emergent mania/hypomania in unipolar patients
Authors: Benvenuti Antonella , Rucci Paola , Miniati Mario , Papasogli Alessandra , Fagiolini Andrea , Cassano Giovanni B , Swartz Holly , Frank Ellen
Published: August 2008

Objective:  The aim of this study was to estimate the incidence of treatment‐emergent mania/hypomania (TEMH) and to describe the clinical characteristics of patients with major depression experiencing this event during treatment with a selective serotonin reuptake inhibitor (SSRI) and/or interpersonal psychotherapy (IPT).

Methods:  Following an algorithm‐based protocol, 344 patients with major depression confirmed with the Structured Clinical Interview for DSM‐IV disorders were treated with an SSRI, interpersonal psychotherapy, or their combination for nine months. The emergence of mania/hypomania was carefully monitored throughout the study using the Young Mania Rating Scale and clinical assessment.

Results:  Overall, eight patients experienced TEMH. The incidence of this event was 3.0% in patients treated with an SSRI and 0.9% in patients treated with IPT alone. Among patients treated with an SSRI, the difference between sites was higher than expected by chance alone (6.8% at Pisa and 0% at Pittsburgh, p = 0.002). Despite the adoption of an identical protocol at the two sites, some demographic and clinical characteristics of participants may account for this unexpected result. Alternatively, the greater number of episodes and earlier age of onset at the Pittsburgh site suggests that the unipolar course of illness was more clearly established prior to study entry.

Conclusions:  TEMH is an infrequent event, occurring in 2.3% of patients treated for major depression. Nevertheless, its consequences are clinically relevant and require prompt and appropriate therapeutic interventions. For this reason, recognising those patients at risk for such an event is of paramount clinical significance. The observed difference in the incidence of TEMH between the two sites requires further investigation.
Quetiapine for the treatment of bipolar mania in older adults
Authors: Sajatovic Martha , Calabrese Joseph R , Mullen Jamie
Published: August 2008

Objectives:  A post hoc analysis of pooled data from two quetiapine monotherapy clinical trials was conducted to evaluate the efficacy and tolerability of quetiapine therapy (twice daily, 400–800 mg/day) among bipolar manic adults aged 55 years and older. The primary efficacy endpoint was the change from baseline in Young Mania Rating Scale (YMRS) total score at Day 21. A secondary endpoint was change from baseline in YMRS score at Day 84.

Methods:  A total of 407 patients made up the safety population, consisting of 59 older adults (aged ≥55 years) and 348 younger adults. A total of 403 patients made up the efficacy population, consisting of 59 older adults and 344 younger adults. Efficacy outcomes were analyzed using covariance models (ANCOVA); descriptive statistics are presented for safety outcomes.

Results:  Both older and younger individuals treated with quetiapine had significant improvement from baseline on YMRS scores compared with placebo‐treated patients. The older adult group demonstrated a sustained reduction in YMRS score compared with placebo that was apparent by Day 4 of treatment. For the quetiapine treatment groups, the most common adverse effects (at a frequency ≥10%) were dry mouth, somnolence, postural hypotension, insomnia, weight gain, and dizziness in older adults, and dry mouth, somnolence, and insomnia in younger adults. For the placebo treatment groups, insomnia was the most common adverse event in both older and younger adults.

Conclusions:  This secondary analysis suggests that quetiapine represents a potentially useful treatment option among older adults with bipolar I mania. Studies with a primary focus of geriatric bipolar mania, and including larger patient numbers, are needed to confirm these findings.
Regional brain changes in bipolar I depression: a functional magnetic resonance imaging study
Authors: Altshuler Lori , Bookheimer Susan , Townsend Jennifer , Proenza Manuel A , Sabb Fred , Mintz Jim , Cohen Mark S
Published: August 2008

Objective:  To investigate neural activity in prefrontal cortex and amygdala during bipolar depression.

Methods:  Eleven bipolar I depressed and 17 normal subjects underwent functional magnetic resonance imaging (fMRI) while performing a task known to activate prefrontal cortex and amygdala. Whole brain activation patterns were determined using statistical parametric mapping (SPM) when subjects matched faces displaying neutral or negative affect (match condition) or matched a geometric form (control condition). Contrasts for each group for the match versus control conditions were used in a second‐level random effects analysis.

Results:  Random effects between‐group analysis revealed significant attenuation in right and left orbitofrontal cortex (BA47) and right dorsolateral prefrontal cortex (DLPFC) (BA9) in bipolar depressed subjects. Additionally, random effects analysis showed a significantly increased activation in left lateral orbitofrontal cortex (BA10) in the bipolar depressed versus control subjects. Within‐group contrasts demonstrated significant amygdala activation in the controls and no significant amygdala activation in the bipolar depressed subjects. The amygdala between‐group difference, however, was not significant.

Conclusions:  Bipolar depression is associated with attenuated bilateral orbitofrontal (BA47) activation, attenuated right DLPFC (BA9) activation and heightened left orbitofrontal (BA10) activation. BA47 attenuation has also been reported in mania and may thus represent a trait feature of the disorder. Increased left prefrontal (BA10) activation may be a state marker to bipolar depression. Our findings suggest dissociation between mood‐dependent and disease‐dependent functional brain abnormalities in bipolar disorder.
Brain lithium, N‐acetyl aspartate and myo‐inositol levels in older adults with bipolar disorder treated with lithium: a lithium‐7 and proton magnetic resonance spectroscopy study
Authors: Forester Brent P , Finn Chelsea T , Berlow Yosef A , Wardrop Megan , Renshaw Perry F , Moore Constance M
Published: August 2008

Objectives:  We investigated the relationship between brain lithium levels and the metabolites N‐acetyl aspartate (NAA) and myo‐inositol (myo‐Ino) in the anterior cingulate cortex of a group of older adults with bipolar disorder (BD).

Methods:  This cross‐sectional assessment included nine subjects (six males and three females) with bipolar I disorder and currently treated with lithium, who were examined at McLean Hospital’s Geriatric Psychiatry Research Program and Brain Imaging Center. The subjects’ ages ranged from 56 to 85 years (66.0 ± 9.7 years) and all subjects had measurements of serum and brain lithium levels. Brain lithium levels were assessed using lithium magnetic resonance spectroscopy. All subjects also had proton magnetic resonance spectroscopy to obtain measurements of NAA and myo‐Ino.

Results:  Brain lithium levels were associated with higher NAA levels [df = (1, 8), Β = 12.53, t = 4.09, p < 0.005] and higher myo‐Ino levels [df = (1, 7), F = 16.81, p < 0.006]. There were no significant effects of serum lithium levels on any of the metabolites.

Conclusion:  Our findings of a relationship between higher brain lithium levels and elevated NAA levels in older adult subjects with BD may support previous evidence of lithium’s neuroprotective, neurotrophic, and mitochondrial function‐enhancing effects. Elevated myo‐Ino related to elevated brain lithium levels may reflect increased inositol monophosphatase (IMPase) activity, which would lead to an increase in myo‐Ino levels. This is the first study to demonstrate alterations in NAA and myo‐Ino in a sample of older adults with BD treated with lithium.
Evolution of grasping among anthropoids
Authors: POUYDEBAT E. , LAURIN M. , GORCE P. , BELS V.
Published: August 2008

The prevailing hypothesis about grasping in primates stipulates an evolution from power towards precision grips in hominids. The evolution of grasping is far more complex, as shown by analysis of new morphometric and behavioural data. The latter concern the modes of food grasping in 11 species (one platyrrhine, nine catarrhines and humans). We show that precision grip and thumb‐lateral behaviours are linked to carpus and thumb length, whereas power grasping is linked to second and third digit length. No phylogenetic signal was found in the behavioural characters when using squared‐change parsimony and phylogenetic eigenvector regression, but such a signal was found in morphometric characters. Our findings shed new light on previously proposed models of the evolution of grasping. Inference models suggest that Australopithecus, Oreopithecus and Proconsul used a precision grip.
The stimulation of immune defence accelerates development in the red flour beetle (Tribolium castaneum)
Authors: ROTH O. , KURTZ J.
Published: August 2008

The timing of the transition between life stages is of key importance for an organism. Depending on the environmental conditions, maturing earlier at a smaller size or maturing later at a larger size can be advantageous for fitness. Exposure to parasites and subsequent immune activation may lead to alterations in development. Immune defence often comes at a cost, such as energy drain towards immune function, which is likely to delay development. On the other hand, animals may react to an anticipated risk of infection with a phenotypically plastic shift in life history, which may more likely lead to accelerated development and earlier maturation. We tested these alternatives in the red flour beetle, Tribolium castaneum. Young larvae were exposed to a non‐infectious immune challenge with heat‐killed bacteria (either Escherichia coli or Bacillus thuringiensis) and they were followed up for their development, survival, adult size and reproduction. We found that animals that had experienced a bacterial challenge developed into adults earlier than sham‐treated beetles, while they did not differ significantly in survival or adult size. Beetles exposed to E. coli produced fewer offspring, while exposure to B. thuringiensis did not affect offspring number. Taken together, our results indicate that T. castaneum is able to speed up its development when facing a risk of infection.
Maternal allocation strategies and differential effects of yolk carotenoids on the phenotype and viability of yellow‐legged gull (Larus michahellis) chicks in relation to sex and laying order
Authors: ROMANO M. , CAPRIOLI M. , AMBROSINI R. , RUBOLINI D. , FASOLA M. , SAINO N.
Published: August 2008

Egg quality may mediate maternal allocation strategies according to progeny sex. In vertebrates, carotenoids have important physiological roles during embryonic and post‐natal life, but the consequences of variation in yolk carotenoids for offspring phenotype in oviparous species are largely unknown. In yellow‐legged gulls, yolk carotenoids did not vary with embryo sex in combination with egg laying date, order and mass. Yolk lutein supplementation enhanced the growth of sons from first eggs but depressed that of sons from last eggs, enhanced survival of daughters late in the season, and promoted immunity of male chicks and chicks from small eggs. Lack of variation in egg carotenoids in relation to sex and egg features, and the contrasting effects of lutein on sons and daughters, do not support the hypothesis of optimal sex‐related egg carotenoid allocation. Carotenoids transferred to the eggs may rather result from a trade‐off between opposing effects on sons or daughters.
Premating isolation is determined by larval rearing substrates in cactophilicDrosophila mojavensis. VIII. Mating success mediated by epicuticular hydrocarbons within and between isolated populations
Authors: ETGES W. J. , TRIPODI A. D.
Published: August 2008

We tested the hypothesis that intrademic sexual selection has caused sexual isolation between populations of geographically isolated populations of cactophilicDrosophila mojavensis, and was mediated by epicuticular hydrocarbons (EHCs), contact pheromones in this system. Sexual selection and sexual isolation were estimated using a Baja California and mainland population by comparing the number of mated and unmated males and females in each of four pairwise population mating trials. EHC profiles were significantly different in mated and unmated males in the interdemic (Baja♀ × Mainland♂ and Mainland♀ × Baja♂), but not the intrademic mating trials. A small number of EHCs was identified that best discriminated among mated and unmated males, mostly alkadienes with 34 and 37 carbons. Females showed population‐specific preferences for male EHC profiles. However, EHC profiles between mated and unmated males in the intrademic mating trials were not significantly different, consistent with undetectable sexual selection estimated directly from numbers of copulating pairs vs. unmated adults. Thus, sexual isolation among populations was much stronger than sexual selection within these populations ofD. mojavensis.
Progress in large‐scale purification of factor VIII/von Willebrand factor concentrates using ion‐exchange chromatography
Authors: Mori F. , Nardini I. , Rossi P. , Nardini C. , Farina C.
Published: August 2008

Background and Objectives  We investigated and optimized the parameters of a chromatographic process suitable for industrial scale to obtain a highly purified factor VIII (FVIII)/von Willebrand factor (VWF) concentrate.

Materials and Methods  Several chromatographic runs were performed on the same production intermediate using different anion‐exchange supports. The best matrix was selected and the final product was characterized. Once the chromatographic medium was chosen, the other parameters were evaluated to obtain the highest purified product and to modulate the VWF content in the FVIII/VWF complex.

Results  Fractogel EMD TMAE was the best support among those tested. It was the only one maintaining good results either with standard or double loading and flow rate conditions with respect to a typical industrial process. The chromatographic recovery of FVIII co‐purified with VWF was at least 86% with a specific activity not lower than 140 IU/mg. The FVIII/VWF complex obtained is highly pure and, with the exception of immunoglobulin M (IgM), all investigated contaminant proteins are under the detection limit. Different concentrates characterized by variable FVIII/VWF ratios were purified by varying the chromatographic conditions.

Conclusions  Several highly purified products, suitable for haemophilia A and von Willebrand disease management, can be obtained, through the same chromatographic process, on an industrial scale.
A new gene conferring resistance to anthracnose in Andean common bean (Phaseolus vulgaris L.) cultivar ‘Jalo Vermelho’
Authors: Gonçalves‐Vidigal M. C. , Lacanallo G. F. , Vidigal Filho P. S.
Published: August 2008

‘Jalo Vermelho’ is a large seeded Andean landrace of common bean (Phaseolus vulgaris L.) that constitutes an important source of anthracnose resistance, disease caused by Colletotrichum lindemuthianum. This landrace has different resistance spectrum, when compared with cultivars of Andean origin, indicating the presence of an anthracnose‐resistant gene different from Co‐1 locus. This anthracnose resistance was characterized by inheritance and allelism tests were carried out on the following genes: Co‐1, Co‐12, Co‐13, Co‐15, Co‐2, Co‐3, Co‐4, Co‐5, Co‐6, Co‐7, Co‐9, Co‐10, Co‐11 and Co‐13. Resistance to races 23, 55, 89 and 453 in ‘Jalo Vermelho’ was conditioned by a single dominant gene. Allelism tests in F2 populations demonstrated that ‘Jalo Vermelho’ carries a dominant gene located at a distinct locus, differing from previously characterized genes. Based on its independence from previously described loci, the authors propose that the ‘Jalo Vermelho’s gene should be named Co‐12. This new gene is a valuable source of resistance to anthracnose which can be transferred to commercial cultivars to enhance the effectiveness of resistance gene pyramiding in bean breeding programmes.
Correlation of hepatocyte expression of hepatitis B viral antigens with histological activity and viral titer in chronic hepatitis B virus infection: An immunohistochemical study
Authors: Ramakrishna Banumathi , Mukhopadhya Ashis , Kurian George
Published: August 2008

Background and Aim:  The localization of hepatitis B virus (HBV) core antigen to the nucleus or cytoplasm of hepatocytes has biological implications for viral packaging and persistence. This study examined the relationship between the localization of hepatitis B virus antigens, histological activity, and viral titer in patients with chronic HBV infection.

Methods:  Liver biopsies from 110 patients with chronic HBV infection were studied. Ishak's scoring system was used for the histological analysis. The localization of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) and the percentage of hepatocytes stained positive by immunohistochemistry were correlated with viral titer, histological activity, and fibrosis indices using Spearman rank correlation.

Results:  In 88 hepatitis B e‐antigen (HBeAg)‐positive individuals, the nuclear localization of HBcAg correlated significantly with DNA titer (r = 0.435, P = 0.001) and negatively with fibrosis (r = −0.297, P = 0.005). The cytoplasmic localization correlated significantly with histological activity (r = 0.211, P = 0.049). In 22 HBeAg‐negative individuals, the nuclear localization of HBcAg correlated significantly with histological activity (r = 0.625, P = 0.002), DNA titer (r = 0.651, P = 0.009), and fibrosis (r = 0.447, P = 0.042). The cytoplasmic localization correlated significantly with DNA titer (r = 0.524, P = 0.045) and fibrosis (r = 0.528, P = 0.012). There was no correlation of HBsAg expression with DNA titer, histological activity index, or fibrosis in both groups. HBeAg‐positive patients presented at a younger age.

Conclusion:  In HBeAg‐positive individuals, nuclear core antigen correlated with DNA titer, and cytoplasmic localization with histological activity, whereas in HBeAg‐negative individuals, nuclear localization correlated with DNA titer, histological activity, and fibrosis, and cytoplasmic localization correlated with DNA titer and fibrosis, but not with histological activity. These observations suggest biological differences between HBeAg‐positive and ‐negative disease.
Imaging of liver disease: Comparison between quadruple‐phase multidetector computed tomography and magnetic resonance imaging
Authors: Balci N Cem , Befeler Alex S , Leiva Paula , Pilgram Thomas K , Havlioglu Necat
Published: August 2008

Background and Aim:  To compare quadruple‐phase multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) for the assessment of focal and diffuse liver disease.

Methods:  Quadruple‐phase contrast‐enhanced MDCT and MRI of 37 consecutive patients were retrospectively reviewed by two readers (R1 and R2). In patients with focal liver lesions, the gold standard was histopathology (n = 17) and/or long‐term (>6 months) follow‐up imaging (n = 27) or transarterial chemoembolization (n = 1). Diffuse liver disease was confirmed by histopathology in all patients, when present.

Results:  Both readers identified 60 focal liver lesions on MDCT and 56 focal liver lesions on MRI. Gold standard diagnoses revealed 48 focal liver lesions in 25 patients. Diagnosis of malignant liver lesions revealed a sensitivity of 88% (R1) and 91% (R2) for MRI; 63% (R1) and 66% (R2) for MDCT; and a specificity of 75% (R1) and 79% (R2) for MRI; 50% (R1) and 64% (R2) for MDCT. MRI was superior to MDCT for the diagnosis of malignant focal liver lesions, when the mean areas under the alternative free‐response receiver operating characteristic curves (AZ) were compared (MRI = 0.93 vs CT = 0.69), (P < 0.00001). Thirty‐three patients had histopathologically confirmed diffuse liver disease. Overall diagnosis of diffuse liver disease revealed a sensitivity of 88% (R1) and 92% (R2) for MRI; 75% (R1) and 74% (R2) for MDCT; and a specificity of 100% for both modalities by both readers.

Conclusions:  MRI is superior for the assessment of malignant focal liver lesions and diffuse liver disease compared to quadruple‐phase MDCT, and can be considered as primary diagnostic imaging modality for liver imaging.
Diabetes mellitus worsens the recurrence rate after potentially curative therapy in patients with hepatocellular carcinoma associated with nonviral hepatitis
Authors: Kawamura Yusuke , Ikeda Kenji , Arase Yasuji , Yatsuji Hiromi , Sezaki Hitomi , Hosaka Tetsuya , Akuta Norio , Kobayashi Masahiro , Saitoh Satoshi , Suzuki Fumitaka , Suzuki Yoshiyuki , Kumada Hiromitsu
Published: August 2008

Background and Aim:  The aim of this retrospective study was to examine the relationship between diabetes mellitus and recurrence of hepatocellular carcinoma after potentially curative therapy for hepatocellular carcinoma with nonviral hepatitis.

Methods:  We studied 40 consecutive hepatocellular carcinoma patients who were diagnosed between 1980 and 2006 with hepatocellular carcinoma associated with non‐B, non‐C hepatitis, and later underwent surgical resection or radiofrequency ablation.

Results:  Twenty‐two out of the 40 patients developed hepatocellular carcinoma recurrence within a median of 3.7 years. In the 18 patients with diabetes mellitus, the cumulative rates of hepatocellular carcinoma recurrence were 22.2% at the first year, 55.6% at the second year, 61.1% at the third year, 61.1% at the fourth year, and 80.6% at the fifth year. The cumulative rates of hepatocellular carcinoma recurrence in 22 nondiabetic patients were 24.6% at the first year, 24.6% at the second year, 31.5% at the third year, 31.5% at the fourth year, and 31.5% at the fifth year. The hepatocellular carcinoma recurrence rate was significantly higher in diabetic patients than in nondiabetics (P = 0.026). The multivariate Cox proportional model identified old age and diabetes as the only significant predictors for recurrence. The hazard ratio of hepatocellular carcinoma recurrence in diabetic patients was 4.61 (P = 0.007). There was no significant difference in overall survival rate between diabetic and nondiabetic patients (P = 0.392).

Conclusion:  Diabetes is a significant predictor of tumor recurrence after potentially curative therapy for hepatocellular carcinoma in patients with nonviral hepatitis.
Endoscopic fibrin sealing of gastrocutaneous fistulas after sleeve gastrectomy and biliopancreatic diversion with duodenal switch
Authors: Papavramidis Theodossis S , Kotzampassi Katerina , Kotidis Efstathios , Eleftheriadis Efthymios E , Papavramidis Spiros T
Published: August 2008

Background and Aim:  Gastrocutaneous fistulas (GCF) are uncommon complications accounting for 0.5–3.9% of gastric operations. When their management is not effective, the mortality rate is high. This study reports the conservative treatment of GCF in morbidly obese patients who underwent biliopancreatic diversion with duodenal switch.

Methods:  Ninety‐six morbidly obese patients were treated in our department with biliopancreatic diversion with duodenal switch (Marceau technique) and, in six of them, a high‐output GCF developed. A general protocol was applied to all patients presenting a GCF. Everyone was treated by total parenteral nutrition (TPN) and somatostatin for at least 7 days after the appearance of the leak. If the leak continued, then fibrin glue was used as a tissue adhesive. Endoscopic application of the sealant was accomplished under direct vision via a double‐lumen catheter passed through a forward‐viewing gastroscope.

Results:  All patients were treated successfully with conservative treatment (either solely with TPN and somatostatin, or with endoscopic fibrin sealing sessions). No evidence of fistula was observed at gastroscopy 3 and 24 months after therapy.

Conclusion:  The conservative treatment of GCF following biliopancreatic diversion with duodenal switch is highly effective. All patients should enter a protocol that includes TPN and somatostatin. When the GCF persist, endoscopic sealing glue should be considered before operation because it is simple, safe, effective and, in some cases, life‐saving. Therefore, conservative treatment should be employed as a therapeutic option in GCF developing after bariatric surgery.
Role of intestinal metaplasia subtyping in the risk of gastric cancer in Korea
Authors: Kang Kyung P , Lee Hye S , Kim Nayoung , Kang Hyung M , Park Young S , Lee Dong H , Choe Gheeyoung , Kim Joo S , Jung Hyun C , Song In S
Published: August 2008

Background and Aim:  Gastric cancer is believed to develop by a multistage process. Intestinal metaplasia (IM) is regarded as a premalignant condition; it is classified into subtypes I, II and III. The aim of this study was to evaluate whether the subtypes of IM were associated with progression to gastric cancer.

Methods:  The study cohort consisted of 861 subjects, categorized as controls, gastric ulcers, dysplasia and cancer. The IM was scored histologically using the Sydney classification for the antrum and the body of the stomach. The biopsies were stained with high iron diamine and alcian blue (pH 2.5) (HID‐AB2.5), and the IM was subtyped as I, II or III.

Results:  The proportion of IM subtypes I, II and III were 14.5%, 47.2% and 38.3% in the antrum, and 28.1%, 57.8% and 14.1% in the body of the stomach, respectively. These distributions did not show significant differences depending on disease or Helicobacter pylori positivity. In cases that were H. pylori‐positive, the prevalence of IM subtype II in the cancer and dysplasia groups was higher than in the control group in the body of the stomach (P < 0.05). The proportion of IM subtype III in the antrum increased in proportion with age (P = 0.036).

Conclusions:  IM subtyping was not found to play a major role in the prediction of gastric cancer development in Korea. IM subtype III was associated with aging, and IM subtype II appeared to be related to gastric carcinogenesis in the presence of H. pylori infection.
Can computed tomography with coronal reconstruction improve the diagnosis of choledocholithiasis?
Authors: Tseng Chih‐Wei , Chen Chun‐Chia , Chen Tseng‐Shing , Chang Full‐Young , Lin Han‐Chieh , Lee Shou‐Dong
Published: August 2008

Background and Aim:  Many technical developments of computed tomography (CT) made in recent years have improved imaging quality. However, the diagnostic efficacy of CT with coronal reconstruction for choledocholithiasis remains uncertain. This study aimed to investigate if CT with coronal reconstruction can aid in the diagnosis of choledocholithiasis.

Methods:  Two hundred and sixty‐six patients with clinically suspected choledocholithiasis undergoing abdominal CT before endoscopic retrograde cholangiopancreatography were recruited. Among them, 163 patients confirmed with choledocholithiasis were divided into three groups: group 1, 92 patients undergoing CT using 5‐mm thick sections with coronal reconstruction; group 2, 32 patients undergoing CT using 5‐mm thick sections without coronal reconstruction; and group 3, 39 patients undergoing CT using 7‐mm thick sections without coronal reconstruction. The diagnostic rate of CT for choledocholithiasis, the stone size and biochemical data among the three groups were analyzed.

Results:  The sensitivity and specificity of CT in diagnosing choledocholithiasis were 77.3% and 72.8%. There was no significant difference of CT diagnostic rate among the three groups (75.0%, 81.2% and 79.5%, respectively). The diameter of common bile duct (CBD), size of CBD stones and white cell count showed significant differences between CT true‐positive and false‐negative cases in group 1 patients. The CT diagnostic rate was significantly lower in patients with choledocholithiasis of less than 5 mm than in patients with choledocholithiasis of 5 mm or more (56.5% vs 81.2%).

Conclusion:  The coronal reconstruction of CT imaging did not increase its diagnostic efficacy on choledocholithiasis. The stone size affects the diagnostic rate of abdominal CT for detecting choledocholithiasis.