bluuebunny/crossref_metadata_2025 huggingface dataset:
Expectations and experience of moving to a care home: Perceptions of older people with dementia
Authors: Nwe Winn Thein  , D'Souza Geraldine , Sheehan Bart
Published: March 2011

Large numbers of people with dementia live in care homes. Decisions about permanent care are usually made by family members and professionals with little involvement from people with dementia. This qualitative paper explores the personal experience of this move among people with dementia. Eighteen people with dementia were interviewed before and after a move into permanent care. Before moving into permanent care, a realization of one’s own difficulties, clearly expressed hopes and fears, and a wish for a role in preparation for the move were identified. After the move, both positive and negative experiences of the process were recalled, with participants clearly identifying what had helped them most in the process. Moving to a care home need not be a depressing process for people with dementia, who may be meaningfully involved in the process. Further research will profit from direct interviewing of the core people in the move, the people with dementia themselves.
Promise or Compromise? Education for Young People in Secure Institutions in England
Authors: Lanskey Caroline
Published: March 2011

In the light of recent legislative changes, this article offers an exposition of key issues relating to the positioning of education for young people under 18 years in secure institutions in England. It argues that interpretations of education have become overly narrow in criminal justice policy and practice and that, while the new legislation offers potential for improvement, further consideration needs to be given to the impact of existing penal and reform agendas which currently limit the conceptual reach and delivery of education in secure institutions.
Use of Complementary and Alternative Medicine by Cancer Patients at a Montreal Hospital
Authors: Sewitch Maida J. , Yaffe Mark , Maisonneuve Jenny , Prchal Jaroslav , Ciampi Antonio
Published: March 2011

Objectives: To assess feasibility of methods for a future study of complementary and alternative medicine (CAM) use by cancer patients treated in conventional health care settings. Methods: Patients aged 18 years and older, fluent in English or French, and diagnosed with cancer from St. Mary’s Hospital Center, Montreal, Canada participated. Feasibility was measured by the rates of participation and CAM use in the past 1 and 12 months. Following the survey, one patient focus group was held to better understand cancer patient perspectives on discussions of CAM that occur or not with their family physicians. Results: Of 103 patients approached, 100 (97.1%; 77% female, 87% white) participated. Overall, 86% and 91% of respondents used at least one CAM in the past 1 and 12 months, respectively. More patients with breast compared with colorectal and other cancers (90.2%, 86.2%, and 80%, respectively) used CAM in the previous year. In the past 1 and 12 months, natural health products were used by 70% and 80% of respondents, respectively; mind–body therapies by 61% and 64%, respectively, and CAM practitioners by 11% and 29%, respectively. More than 98% of patients used CAM to improve quality of life and 68% disclosed CAM use to their physicians. Four of 5 focus group participants used CAM. Patient–physician CAM discussions varied from receiving a CAM referral to complete dismissal of the topic. Conclusion: Recruitment methods were well accepted but a sampling strategy stratified by sex and ethnicity will ensure sufficient representation by males and non-whites. Whereas disclosure of natural health products use is occurring, informative CAM discussion is not.
Polarity Therapy for Cancer-Related Fatigue in Patients With Breast Cancer Receiving Radiation Therapy: A Randomized Controlled Pilot Study
Authors: Mustian Karen M. , Roscoe Joseph A. , Palesh Oxana G. , Sprod Lisa K. , Heckler Charles E. , Peppone Luke J. , Usuki Kenneth Y. , Ling Marilyn N. , Brasacchio Ralph A. , Morrow Gary R.
Published: March 2011

Background. Cancer-related fatigue (CRF) is the most frequently reported side effect of cancer and its treatment. In previous research, Polarity Therapy (PT), an energy therapy, was shown to reduce CRF in patients receiving radiation. This study reports on a small randomized clinical trial designed to collect preliminary data on the efficacy of PT compared with an active control (massage) and passive control (standard care) for CRF among cancer patients receiving radiation therapy. Methods. Forty-five women undergoing radiation therapy for breast cancer were randomized to 1 of 3 weekly treatment conditions. Patients received standard clinical care, 3 modified massages, or 3 PT treatments. CRF and health-related quality of life (HRQL) were assessed during baseline and the 3 intervention weeks. Results. TResults show CRF ratings were reduced after PT. The effect sizes for PT versus modified massage and versus standard care were small when using the primary measure of CRF (Brief Fatigue Inventory) and large when using the secondary measure of CRF (Daily CRF Diaries).The effect size was medium when assessing the benefit of PT on maintaining HRQL compared with standard care with very little difference between the PT and modified massage conditions. Patients’ feedback showed that both the modified massage and PT treatments were deemed useful by radiation patients. Conclusion. The present pilot randomized clinical trial supports previous experimental research showing that PT, a noninvasive and gentle energy therapy, may be effective in controlling CRF. Further confirmatory studies as well as investigations of the possible mechanisms of PT are warranted.
Effect of Long-Term Music Therapy Intervention on Autonomic Function in Anthracycline-Treated Breast Cancer Patients
Authors: Chuang Chih-Yuan , Han Wei-Ru , Li Pei-Chun , Song Mi-Yun , Young Shuenn-Tsong
Published: March 2011

Anthracyclines are potent antineoplastic agents associated with cardiotoxicity, which may lead to congestive heart failure, causing impairment of autonomic cardiovascular function as assessed by heart rate variability (HRV). This decreases survival rates. This study aimed to determine whether music therapy intervention improves autonomic function in anthracycline-treated breast cancer patients, and if so, whether such improvements persist after cessation of the intervention. Participants were 12 women with breast cancer who had undergone mastectomy or breast-conserving treatment and adjuvant chemotherapy; they attended 8 weekly music therapy sessions, each lasting 2 hours. Electrocardiogram traces (5 minutes) for HRV analysis were recorded 4 times: prior to the first music session, T1; after the fourth music session, T2; after the eighth music session, T3; and 4 weeks after the completion of music therapy, T4. HRV parameters were subjected to a nonparametric Friedman test on the differences between T1 and T2, T3, and T4. The standard deviation of normal intervals and the total power of HRV parameters, related to global autonomic function, were significantly higher at T3 than at T1. The root-mean-square differences of successive normal R–R intervals and high-frequency (HF) HRV parameters, related to parasympathetic activity, were significantly increased, but no change was seen in the LF/HF ratio of HRV parameters (which is related to sympathetic activity) during the music therapy. Global autonomic function and parasympathetic activity had not changed significantly at T4 relative to T1. The authors provide preliminary evidence of the benefits of music therapy for anthracycline-treated breast cancer survivors.
Anti-inflammatory modulation of immune response by probiotic Escherichia coli Nissle 1917 in human blood mononuclear cells
Authors: Güttsches Anne-Katrin , Löseke Stefan , Zähringer Ulrich , Sonnenborn Ulrich , Enders Corinne , Gatermann Sören , Bufe Albrecht
Published: March 2011

Escherichia coli Nissle 1917 (EcN) bears a defect in its LPS biosynthesis leading to truncated variable oligosaccharide-antigen chains and a semi-rough phenotype. It is effectively inactivated by complement factors due to resolved serum resistance and is, therefore, safe as a probiotic strain, i.e. for the treatment of inflammatory gastrointestinal diseases. It is unknown whether the modification of LPS in EcN contributes to its probiotic properties. Purified LPS from EcN and wild-type LPS from uropathogenic E. coli W536 together with raw lysates of both strains were analyzed for their gene expression activity with human PBMCs measured by microarrays. Comparing the two LPS molecules and the two lysate variants with each other, respectively, no differences of transcriptional patterns were observed. However, when comparing LPS with lysate patterns, pro-inflammatory cytokine IL-12p40 was up-regulated by both LPS molecules and anti-inflammatory IL-10 by both lysates. The higher the lysate concentration, the higher IL-10 release from PBMCs, clearly exceeding LPS induced IL-12p40 release. Furthermore, inflammatory chemokine CCL24 (eotaxin) was down-regulated by lysates and quantitative real-time PCR revealed that EcN compared to wild-type LPS was 8 times stronger in down-regulation of CCL24. We conclude that truncated LPS may down-regulate CCL24-mediated inflammation and that EcN lysate contains as yet unidentified factors which preferably induce anti-inflammatory activity. Both effects may contribute to the probiotic properties of EcN.
An outbreak of group A streptococcal infection
Authors: Adams Debra , Yee Lian , Heseltine Allison , Afza Musarrat
Published: March 2011

Group A streptococcal (GAS) infection is responsible for a wide range of infections including sore G throat, skin infections, septicaemia, streptococcal toxic shock syndrome and necrotising fasciitis.

During April 2010, three patients on a medical ward in a small acute hospital in the United Kingdom had GAS identified in samples obtained from a blood culture and various lesions.

The investigation and management of this outbreak included effective antimicrobial management and treatment of identified cases, establishment of an outbreak control team (OCT), epidemiological investigation and screening of staff for throat carriage and staff and patients on the ward for skin lesions and dermatitis. Isolate typing by the Health Protection Agency (HPA), Centre for Infections laboratory, confirmed the three cases had identical strains — type M/ emm44. The prompt treatment and effective management of the outbreak ensured that no further cases in the extended surveillance period were identified.
Safety (toxicity), pharmacokinetics, immunogenicity, and impact on elements of the normal immune system of recombinant human IL-15 in rhesus macaques
Authors: Waldmann Thomas A. , Lugli Enrico , Roederer Mario , Perera Liyanage P. , Smedley Jeremy V. , Macallister Rhonda P. , Goldman Carolyn K. , Bryant Bonita R. , Decker Jean M. , Fleisher Thomas A. , Lane H. Clifford , Sneller Michael C. , Kurlander Roger J. , Kleiner David E. , Pletcher John M. , Figg William D. , Yovandich Jason L. , Creekmore Stephen P.
Published: March 2011

IL-15 uses the heterotrimeric receptor IL-2/IL-15Rβ and the γ chain shared with IL-2 and the cytokine-specific IL-15Rα. Although IL-15 shares actions with IL-2 that include activation of natural killer (NK) and CD8 T cells, IL-15 is not associated with capillary leak syndrome, activation-induced cell death, or with a major effect on the number of functional regulatory T cells. To prepare for human trials to determine whether IL-15 is superior to IL-2 in cancer therapy, recombinant human IL-15 (rhIL-15) was produced under current good manufacturing practices. A safety study in rhesus macaques was performed in 4 groups of 6 animals each that received vehicle diluent control or rhIL-15 at 10, 20, or 50 μg/kg/d IV for 12 days. The major toxicity was grade 3/4 transient neutropenia. Bone marrow examinations demonstrated increased marrow cellularity, including cells of the neutrophil series. Furthermore, neutrophils were observed in sinusoids of enlarged livers and spleens, suggesting that IL-15 mediated neutrophil redistribution from the circulation to tissues. The observation that IL-15 administration was associated with increased numbers of circulating NK and CD8 central and effector-memory T cells, in conjunction with efficacy studies in murine tumor models, supports the use of multiple daily infusions of rhIL-15 in patients with metastatic malignancies.
A differential interplay between the expression of Th1/Th2/Treg related cytokine genes in Teladorsagia circumcincta infected DRB1*1101 carrier lambs
Authors: Hassan Musa , Hanrahan James P , Good Barbara , Mulcahy Grace , Sweeney Torres
Published: March 2011

Substantial debate exists on whether the immune response between sheep resistant and susceptible to gastrointestinal nematodes can be differentiated into a Th1 and Th2 phenotype. The present study addresses the hypothesis that variation in resistance toTeladorsagia circumcinctabetweenDRB1*1101(associated with reduced faecal egg count and worm burden) carriers and non-carriers is due to a differential interplay in the expression of Th1/Th2 and regulatory T (Treg) related cytokine genes. Lambs from each genotype were either slaughtered at day 0 (un-infected control) or infected with 3 × 104Teladorsagia circumcinctaL3 and slaughtered at 3, 7, 21, and 35 days later. Lambs carrying theDRB1*1101allele had a significantly lower worm burden (P < 0.05) compared to the non-carriers. Abomasal mucosal cytokine gene expression was evaluated by quantitative real-time PCR and comparison made for time and genotype effects. The response generated varied through the course of infection and was affected by genotype.DRB1*1101carriers had an up-regulated expression of the Th1-related cytokine genes (IL-1β, TNFα, and IFN-γ) at day 3, but this was replaced by an up-regulated expression of Th2-related cytokine genes (IL-10 and IL-13) and Treg-related cytokine genes (IL-2RA-CD25, TGFα, TGFβ, Arg2, MIF and FOXP3) by day 7. Conversely, in the non-carriers these changes in gene expression were delayed until days 7 and 21 post infection (pi), respectively. It is concluded that resistance toTeladorsagia circumcinctain animals carrying theDRB1*1101allele is influenced by an earlier interplay between Th1, Th2 and T regulatory immune response genes.
Exceptional lability of a genomic complex in rice and its close relatives revealed by interspecific and intraspecific comparison and population analysis
Authors: Tian Zhixi , Yu Yanjun , Lin Feng , Yu Yeisoo , SanMiguel Phillip J , Wing Rod A , McCouch Susan R , Ma Jianxin , Jackson Scott A
Published: March 2011

Background

Extensive DNA rearrangement of genic colinearity, as revealed by comparison of orthologous genomic regions, has been shown to be a general concept describing evolutionary dynamics of plant genomes. However, the nature, timing, lineages and adaptation of local genomic rearrangement in closely related species (e.g., within a genus) and haplotype variation of genomic rearrangement within populations have not been well documented.

Results

We previously identified a hotspot for genic rearrangement and transposon accumulation in the Orp region of Asian rice (Oryza sativa, AA) by comparison with its orthologous region in sorghum. Here, we report the comparative analysis of this region with its orthologous regions in the wild progenitor species (O. nivara, AA) of Asian rice and African rice (O. glaberrima) using the BB genome Oryza species (O. punctata) as an outgroup, and investigation of transposon insertion sites and a segmental inversion event in the AA genomes at the population level. We found that Orp region was primarily and recently expanded in the Asian rice species O. sativa and O. nivara. LTR-retrotransposons shared by the three AA-genomic regions have been fixed in all the 94 varieties that represent different populations of the AA-genome species/subspecies, indicating their adaptive role in genome differentiation. However, LTR-retrotransposons unique to either O. nivara or O. sativa regions exhibited dramatic haplotype variation regarding their presence or absence between or within populations/subpopulations.

Conclusions

The LTR-retrotransposon insertion hotspot in the Orp region was formed recently, independently and concurrently in different AA-genome species, and that the genic rearrangements detected in different species appear to be differentially triggered by transposable elements. This region is located near the end of the short arm of chromosome 8 and contains a high proportion of LTR-retrotransposons similar to observed in the centromeric region of this same chromosome, and thus may represent a genomic region that has recently switched from euchromatic to heterochromatic states. The haplotype variation of LTR-retrotransposon insertions within this region reveals substantial admixture among various subpopulations as established by molecular markers at the whole genome level, and can be used to develop retrotransposon junction markers for simple and rapid classification of O. sativa germplasm.
Endosomal accumulation of APP in wobbler motor neurons reflects impaired vesicle trafficking: Implications for human motor neuron disease
Authors: Palmisano Ralf , Golfi Panagiota , Heimann Peter , Shaw Christopher , Troakes Claire , Schmitt-John Thomas , Bartsch Jörg W
Published: March 2011

Background

The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown but hypotheses about disease mechanisms include oxidative stress, defective axonal transport, mitochondrial dysfunction and disrupted RNA processing. Whereas familial ALS is well represented by transgenic mutant SOD1 mouse models, the mouse mutant wobbler (WR) develops progressive motor neuron degeneration due to a point mutation in the Vps54 gene, and provides an animal model for sporadic ALS. VPS54 protein as a component of a protein complex is involved in vesicular Golgi trafficking; impaired vesicle trafficking might also be mechanistic in the pathogenesis of human ALS.

Results

In motor neurons of homozygous symptomatic WR mice, a massive number of endosomal vesicles significantly enlarged (up to 3 μm in diameter) were subjected to ultrastructural analysis and immunohistochemistry for the endosome-specific small GTPase protein Rab7 and for amyloid precursor protein (APP). Enlarged vesicles were neither detected in heterozygous WR nor in transgenic SOD1(G93A) mice; in WR motor neurons, numerous APP/Rab7-positive vesicles were observed which were mostly LC3-negative, suggesting they are not autophagosomes.

Conclusions

We conclude that endosomal APP/Rab7 staining reflects impaired vesicle trafficking in WR mouse motor neurons. Based on these findings human ALS tissues were analysed for APP in enlarged vesicles and were detected in spinal cord motor neurons in six out of fourteen sporadic ALS cases. These enlarged vesicles were not detected in any of the familial ALS cases. Thus our study provides the first evidence for wobbler-like aetiologies in human ALS and suggests that the genes encoding proteins involved in vesicle trafficking should be screened for pathogenic mutations.
steve bAccumulation of nerve growth factor and its receptors in the uterus and dorsal root ganglia in a mouse model of adenomyosis
Authors: Li Yan , Zhang Shao-fen , Zou Shi-en , Xia Xian , Bao Lei
Published: March 2011

Background

Adenomyosis is a common gynecological disease, which is accompanied by a series of immunological and neuroendocrinological changes. Nerve growth factor (NGF) plays a critical role in producing pain, neural plasticity, immunocyte aggregation and release of inflammatory factors. This study aimed to investigate the expression of NGF and its two receptors in uteri and dorsal root ganglia (DRG) in an adenomyosis mouse model, as well as their relationship with the severity of adenomyosis.

Methods

Forty newborn ICR mice were randomly divided into the adenomyosis model group and control group (n = 20 in each group). Mice in the adenomyosis model group were orally dosed with 2.7 μmol/kg tamoxifen on days 2-5 after birth. Experiments were conducted to identify the expression of NGF- beta and its receptors, tyrosine kinase receptor (trkA) and p75 neurotrophin receptor (p75NTR), in the uterus and DRG in four age groups (90+/-5 d, 140+/-5 d, 190+/-5 d and 240+/-5 d; n = 5 mice in each group) by western bolt, immunochemistry and real time reverse transcription-polymerase chain reaction.

Results

Adenomyosis, which became more serious as age increased, was successfully induced in dosed ICR mice. NGF-beta, trkA and p75NTR protein levels in the uterus and trkA mRNA levels in DRG were higher in the older aged adenomyosis model group than those in controls (190+/-5 d and 240+/-5 d groups, P < 0.05). The expression of NGF-beta and its receptors in the uterus increased gradually as age increased for adenomyosis mice (190+/-5 d and 240+/-5 d, P < 0.05, compared with 90+/-5 d) but it showed little change in control mice. The mRNA level of trkA in DRG also increased as age increased in the adenomyosis model group (190+/-5 d and 240+/-5 d, P < 0.05, compared with 90+/-5 d) but was unchanged in controls. The mRNA level of p75NTR in DRG was not different between the adenomyosis and control groups and was stable from young to old mice.

Conclusions

NGF- beta can be used as an indicator for the severity of adenomyosis. The gradually increasing level of NGF- beta and its receptors while the disease becomes more severe suggests an effect of NGF- beta on pathogenic mechanisms of adenomyosis.
Rectal microbicides: clinically relevant approach to the design of rectal specific placebo formulations
Authors: Wang Lin , Schnaare Roger L , Dezzutti Charlene , Anton Peter A , Rohan Lisa C
Published: March 2011

Background

The objective of this study is to identify the critical formulation parameters controlling distribution and function for the rectal administration of microbicides in humans. Four placebo formulations were designed with a wide range of hydrophilic characteristics (aqueous to lipid) and rheological properties (Newtonian, shear thinning, thermal sensitive and thixotropic). Aqueous formulations using typical polymers to control viscosity were iso-osmotic and buffered to pH 7. Lipid formulations were developed from lipid solvent/lipid gelling agent binary mixtures. Testing included pharmaceutical function and stability as well as in vitro and in vivo toxicity.

Results

The aqueous fluid placebo, based on poloxamer, was fluid at room temperature, thickened and became shear thinning at 37°C. The aqueous gel placebo used carbopol as the gelling agent, was shear thinning at room temperature and showed a typical decrease in viscosity with an increase in temperature. The lipid fluid placebo, myristyl myristate in isopropyl myristate, was relatively thin and temperature independent. The lipid gel placebo, glyceryl stearate and PEG-75 stearate in caprylic/capric triglycerides, was also shear thinning at both room temperature and 37°C but with significant time dependency or thixotropy. All formulations showed no rectal irritation in rabbits and were non-toxic using an ex vivo rectal explant model.

Conclusions

Four placebo formulations ranging from fluid to gel in aqueous and lipid formats with a range of rheological properties were developed, tested, scaled-up, manufactured under cGMP conditions and enrolled in a formal stability program. Clinical testing of these formulations as placebos will serve as the basis for further microbicide formulation development with drug-containing products.
Antibody dependent enhancement infection of Enterovirus 71 in vitro and in vivo
Authors: Han Jian-Feng , Cao Rui-Yuan , Deng Yong-Qiang , Tian Xue , Jiang Tao , Qin E-De , Qin Cheng-Feng
Published: March 2011

Background

Human enterovirus 71 (EV71) has emerged as a significant cause of acute encephalitis and deaths in young children. The clinical manifestations caused by EV71 varied from mild hand, foot and mouth disease to severe neurological complications and deaths, but its pathogenesis remains elusive. Antibody dependent enhancement (ADE) infection has been reported in various viruses and has been shown to contribute to disease severity.

Results

In this study, the presence of sub-neutralizing antibody was demonstrated to enhance EV71 infection in THP-1 cells and increase the mortality of EV71 infection in a suckling mouse model. Further, a secondary infection model was established to characterize the correlation between ADE and disease severity, and primary asymptomatic EV71 infection was shown to increase the mortality of the secondary EV71 infection in suckling mice.

Conclusions

Together, these in vitro and in vivo experiments strongly supported the hypothesis of ADE infection of EV71. The present findings indicate ADE might contribute to the pathogenesis of severe EV71 infection, and raise practical issues of vaccine development and antibody-based therapy.
Proteomic analysis of swine serum following highly virulent classical swine fever virus infection
Authors: Sun Jin-fu , Shi Zi-xue , Guo Huan-cheng , Li Su , Tu Chang-chun
Published: March 2011

Background

Classical swine fever virus (CSFV) belongs to the genusPestiviruswithin the familyFlaviviridae. Virulent strains of classical swine fever virus (CSFV) cause severe disease in pigs characterized by immunosuppression, thrombocytopenia and disseminated intravascular coagulation, which causes significant economic losses to the pig industry worldwide.

Methods

To reveal proteomic changes in swine serum during the acute stage of lethal CSFV infection, 5 of 10 pigs were inoculated with the virulent CSFV Shimen strain, the remainder serving as uninfected controls. A serum sample was taken at 3 days post-infection from each swine, at a stage when there were no clinical symptoms other than increased rectal temperatures (≥40°C). The samples were treated to remove serum albumin and immunoglobulin (IgG), and then subjected to two-dimension differential gel electrophoresis.

Results

Quantitative intensity analysis revealed 17 protein spots showing at least 1.5-fold quantitative alteration in expression. Ten spots were successfully identified by MALDI-TOF MS or LTQ MS. Expression of 4 proteins was increased and 6 decreased in CSFV-infected pigs. Functions of these proteins included blood coagulation, anti-inflammatory activity and angiogenesis.

Conclusion

These proteins with altered expression may have important implications in the pathogenesis of classical swine fever and provide a clue for identification of biomarkers for classical swine fever early diagnosis.
Single-Dose Fosaprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting Associated With Cisplatin Therapy: Randomized, Double-Blind Study Protocol—EASE
Authors: Grunberg Steven , Chua Daniel , Maru Anish , Dinis José , DeVandry Suzanne , Boice Judith A. , Hardwick James S. , Beckford Elizabeth , Taylor Arlene , Carides Alexandra , Roila Fausto , Herrstedt Jørn
Published: March 2011

Purpose

Addition of aprepitant, a neurokinin-1 receptor antagonist (NK1RA), to an ondansetron and dexamethasone regimen improves prevention of chemotherapy-induced nausea/vomiting (CINV), particularly during the delayed phase (DP; 25 to 120 hours). Therefore, recommended antiemetic regimens include multiple-day NK1RA administration. Preliminary data suggested that single-dose aprepitant before chemotherapy could provide CINV protection throughout the overall risk phase (OP; 0 to 120 hours). This study compared a 3-day oral aprepitant schedule to a regimen containing a single dose of the intravenous NK1RA fosaprepitant.

Patients and Methods

A randomized, double-blind, active-control design was used to test whether fosaprepitant is noninferior to aprepitant. Patients receiving cisplatin ≥ 70 mg/m2 for the first time received ondansetron and dexamethasone with a standard aprepitant regimen (125 mg on day 1, 80 mg on day 2, 80 mg on day 3) or a single-dose fosaprepitant regimen (150 mg on day 1). The primary end point was complete response (CR; no vomiting, no rescue medication) during OP. Secondary end points were CR during DP and no vomiting during OP. Accrual of 1,113 evaluable patients per treatment arm was planned to confirm noninferiority with expected CR of 67.7% and noninferiority margin of minus 7 percentage points.

Results

A total of 2,322 patients were randomly assigned, and 2,247 were evaluable for efficacy. Antiemetic protection with aprepitant and fosaprepitant was equivalent within predefined bounds for noninferiority. Both regimens were well tolerated, although more frequent infusion site pain/erythema/thrombophlebitis was seen with fosaprepitant relative to aprepitant (2.7% v 0.3%, respectively).

Conclusion

Given with ondansetron and dexamethasone, single-dose intravenous fosaprepitant (150 mg) was noninferior to standard 3-day oral aprepitant in preventing CINV during OP and DP.
At What Cost Does a Potential Survival Advantage of Bevacizumab Make Sense for the Primary Treatment of Ovarian Cancer? A Cost-Effectiveness Analysis
Authors: Cohn David E. , Kim Kenneth H. , Resnick Kimberly E. , O'Malley David M. , Straughn J. Michael
Published: March 2011

Purpose

To determine whether the addition of bevacizumab to paclitaxel and carboplatin for the primary treatment of advanced ovarian cancer can be cost effective.

Methods

A cost-effectiveness analysis compared the three arms of the Gynecologic Oncology Group (GOG) 218 study (paclitaxel plus carboplatin [PC], PC plus bevacizumab [PCB], and PCB plus bevacizumab maintenance [PCB+B]). Actual and estimated costs of treatment plus the potential costs of complications were established for each strategy. Progression-free survival (PFS) and bowel perforation rates were taken from recently reported results of GOG 218. Sensitivity analysis was performed for pertinent uncertainties in the model. Incremental cost-effectiveness ratios (ICERs) per progression-free life-year saved (PF-LYS) were estimated.

Results

For the 600 patients entered onto each arm of GOG 218 at the baseline estimates of PFS and bowel perforation, the cost of PC was $2.5 million, compared with $21.4 million for PCB and $78.3 million for PCB+B. These costs led to an ICER of $479,712 per PF-LYS for PCB and $401,088 per PF-LYS for PCB+B. When the cost of bevacizumab was reduced to 25% of baseline, the ICER of PCB+B fell below $100,000 per PF-LYS. ICERs were not substantially reduced when the perforation rate was equal across all arms.

Conclusion

The addition of bevacizumab to standard chemotherapy in patients with advanced ovarian cancer is not cost effective. Treatment with maintenance bevacizumab leads to improved PFS but is associated with both direct and indirect costs. The cost effectiveness of bevacizumab in the adjuvant treatment of ovarian cancer is primarily dependent on drug costs.
Impact of Concordant and Discordant Bone Marrow Involvement on Outcome in Diffuse Large B-Cell Lymphoma Treated With R-CHOP
Authors: Sehn Laurie H. , Scott David W. , Chhanabhai Mukesh , Berry Brian , Ruskova Anna , Berkahn Leanne , Connors Joseph M. , Gascoyne Randy D.
Published: March 2011

Purpose

In diffuse large B-cell lymphoma (DLBCL), prior studies suggest that concordant bone marrow involvement with DLBCL portends a poorer prognosis, whereas discordant bone marrow involvement with small B-cell lymphoma does not. We examined the significance of bone marrow involvement in patients treated in the current era of therapy including rituximab.

Patients and Methods

We performed a retrospective analysis of the prognostic impact of bone marrow involvement in an unselected population of patients with newly diagnosed DLBCL treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in British Columbia and Auckland, New Zealand, with complete clinical information and evaluable staging bone marrow biopsies.

Results

In total, 795 patients were identified. Six hundred seventy (84.3%) of 795 had a negative bone marrow, 67 patients (8.4%) had concordant and 58 (7.3%) had discordant involvement. Median follow-up was 41 months (range, 1 to 115). Progression-free survival (PFS) was inferior in those with concordant (P < .001) and discordant (P = .019) involvement while overall survival (OS) was inferior in those with concordant involvement (P < .001) only. In a multivariate analysis controlling for the International Prognostic Index (IPI) score, concordant involvement remained an independent predictor of PFS (P < .001) and OS (P = .007). Discordant involvement was associated with older age, elevated lactate dehydrogenase, advanced stage, and increased number of extranodal sites and was not a negative prognostic factor independent of the IPI score.

Conclusion

The negative prognostic impact of discordant involvement is adequately represented by the IPI score, while the risk with concordant involvement is greater than that encompassed by this predictor. The results emphasize the need for accurate staging assessment of bone marrow involvement in DLBCL.
Restriction of hepatic competence by Fgf signaling
Authors: Shin Donghun , Lee Yoonsung , Poss Kenneth D. , Stainier Didier Y. R.
Published: March 2011

Hepatic competence, or the ability to respond to hepatic-inducing signals, is regulated by a number of transcription factors broadly expressed in the endoderm. However, extrinsic signals might also regulate hepatic competence, as suggested by tissue explant studies. Here, we present genetic evidence that Fgf signaling regulates hepatic competence in zebrafish. We first show that the endoderm posterior to the liver-forming region retains hepatic competence: using transgenic lines that overexpress hepatic inducing signals following heat-shock, we found that at late somitogenesis stages Wnt8a, but not Bmp2b, overexpression could induce liver gene expression in pancreatic and intestinal bulb cells. These manipulations resulted in the appearance of ectopic hepatocytes in the intestinal bulb. Second, by overexpressing Wnt8a at various stages, we found that as embryos develop, the extent of the endodermal region retaining hepatic competence is gradually reduced. Most significantly, we found, using gain- and loss-of-function approaches, that Fgf10a signaling regulates this gradual reduction of the hepatic-competent domain. These data provide in vivo evidence that endodermal cells outside the liver-forming region retain hepatic competence and show that an extrinsic signal, Fgf10a, negatively regulates hepatic competence.
FGF/MAPK/Ets signaling renders pigment cell precursors competent to respond to Wnt signal by directly controllingCi-Tcftranscription
Authors: Squarzoni Paola , Parveen Fateema , Zanetti Laura , Ristoratore Filomena , Spagnuolo Antonietta
Published: March 2011

FGF and Wnt pathways constitute two fundamental signaling cascades, which appear to crosstalk in cooperative or antagonistic fashions in several developmental processes. In vertebrates, both cascades are involved in pigment cell development, but the possible interplay between FGF and Wnt remains to be elucidated. In this study, we have investigated the role of FGF and Wnt signaling in development of the pigment cells in the sensory organs of C. intestinalis. This species possesses the basic features of an ancestral chordate, thus sharing conserved molecular developmental mechanisms with vertebrates. Chemical and targeted perturbation approaches revealed that a FGF signal, spreading in time from early gastrulation to neural tube closure, is responsible for pigment cell precursor induction. This signal is transmitted via the MAPK pathway, which activates the Ci-Ets1/2 transcription factor. Targeted perturbation of Ci-TCF, a downstream factor of the canonical Wnt pathway, indicated its contribution to pigment cell differentiation Furthermore, analyses of the Ci-Tcf regulatory region revealed the involvement of the FGF effector, Ci-Ets1/2, in Ci-Tcf transcriptional regulation in pigment cell precursors. Our results indicate that both FGF and the canonical Wnt pathways are involved in C. intestinalis pigment cell induction and differentiation. Moreover, we present a case of direct transcriptional regulation exerted by the FGF signaling cascade, via the MAPK-ERK-Ets1/2, on the Wnt downstream gene Ci-Tcf. Several examples of FGF/Wnt signaling crosstalk have been described in different developmental processes; however, to our knowledge, FGF-Wnt cross-interaction at the transcriptional level has never been previously reported. These findings further contribute to clarifying the multitude of FGF-Wnt pathway interactions.
Conditional ablation of Pten in osteoprogenitors stimulates FGF signaling
Authors: Guntur Anyonya R. , Reinhold Martina I. , Cuellar Joe , Naski Michael C.
Published: March 2011

Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a direct antagonist of phosphatidylinositol 3 kinase. Pten is a well recognized tumor suppressor and is one of the most commonly mutated genes in human malignancies. More recent studies of development and stem cell behavior have shown that PTEN regulates the growth and differentiation of progenitor cells. Significantly, PTEN is found in osteoprogenitor cells that give rise to bone-forming osteoblasts; however, the role of PTEN in bone development is incompletely understood. To define how PTEN functions in osteoprogenitors during bone development, we conditionally deleted Pten in mice using the cre-deleter strain Dermo1cre, which targets undifferentiated mesenchyme destined to form bone. Deletion of Pten in osteoprogenitor cells led to increased numbers of osteoblasts and expanded bone matrix. Significantly, osteoblast development and synthesis of osteoid in the nascent bone collar was uncoupled from the usual tight linkage to chondrocyte differentiation in the epiphyseal growth plate. The expansion of osteoblasts and osteoprogenitors was found to be due to augmented FGF signaling as evidenced by (1) increased expression of FGF18, a potent osteoblast mitogen, and (2) decreased expression of SPRY2, a repressor of FGF signaling. The differentiation of osteoblasts was autonomous from the growth plate chondrocytes and was correlated with an increase in the protein levels of GLI2, a transcription factor that is a major mediator of hedgehog signaling. We provide evidence that increased GLI2 activity is also a consequence of increased FGF signaling through downstream events requiring mitogen-activated protein kinases. To test whether FGF signaling is required for the effects of Pten deletion, we deleted one allele of fibroblast growth factor receptor 2 (FGFR2). Significantly, deletion of FGFR2 caused a partial rescue of the Pten-null phenotype. This study identifies activated FGF signaling as the major mediator of Pten deletion in osteoprogenitors.
The Drosophila homologue of SRF acts as a boosting mechanism to sustain FGF-induced terminal branching in the tracheal system
Authors: Gervais Louis , Casanova Jordi
Published: March 2011

Recent data have demonstrated a crucial role for the transcription factor SRF (serum response factor) downstream of VEGF and FGF signalling during branching morphogenesis. This is the case for sprouting angiogenesis in vertebrates, axonal branching in mammals and terminal branching of the Drosophila tracheal system. However, the specific functions of SRF in these processes remain unclear. Here, we establish the relative contributions of the Drosophila homologues of FGF [Branchless (BNL)] and SRF [Blistered (BS)] in terminal tracheal branching. Conversely to an extended view, we show that BNL triggers terminal branching initiation in a DSRF-independent mechanism and that DSRF transcription induced by BNL signalling is required to maintain terminal branch elongation. Moreover, we report that increased and continuous FGF signalling can trigger tracheal cells to develop full-length terminal branches in the absence of DSRF transcription. Our results indicate that DSRF acts as an amplifying step to sustain the progression of terminal branch elongation even in the wild-type conditions of FGF signalling.
Consumptive hypothyroidism: a case report and review of the literature
Authors: Jassam N , Visser T J , Brisco T , Bathia D , McClean P , Barth J H
Published: March 2011

Hepatic haemangioendothelioma is a rare vascular tumour in infants and may be associated with a unique form of thyroid function abnormalities. Hepatic haemangioendotheliomata is capable of producing an excess of the thyroid hormone inactivating enzyme, type 3 iodothyronine deiodinase. The increased enzyme activity leads to rapid degradation of thyroid hormones, resulting in frank hypothyroidism. We report a case of a three-month-old neonate with multiple hepatic haemangioendotheliomata and associated hypothyroidism. The patient required increasing doses of thyroid hormone.
Sexual abuse in childhood and postoperative depression in women with breast cancer who opt for immediate reconstruction after mastectomy
Authors: Clark Louise , Holcombe Christopher , Hill Jonathan , Krespi-Boothby Margorit Rita , Fisher Jean , Seward Joanna , Salmon Peter
Published: March 2011

INTRODUCTION

Breast reconstruction is routinely offered to women who undergo mastectomy for breast cancer. However, patient-reported outcomes are mixed. Child abuse has enduring effects on adults’ well-being and body image. As part of a study into damaging effects of abuse on adjustment to breast cancer, we examined: (i) whether women with history of abuse would be more likely than other women to opt for reconstruction; and (ii) whether mood problems in women opting for reconstruction can be explained by greater prevalence of abuse.

PATIENTS AND METHODS

We recruited 355 women within 2-4 days after surgery for primary breast cancer; 104 had mastectomy alone and 29 opted for reconstruction. Using standardised questionnaires, women self-reported emotional distress and recollections of childhood sexual abuse. Self-report of distress was repeated 12 months later.

RESULTS

Women who had reconstruction were younger than those who did not. Controlling for this, they reported greater prevalence of abuse and more distress than those having mastectomy alone. They were also more depressed postoperatively, and this effect remained significant after controlling for abuse.

CONCLUSIONS

One interpretation of these findings is that history of abuse influences women's decisions about responding to the threat of mastectomy, but it is premature to draw inferences for practice until the findings are replicated. If they are replicated, it will be important to recognise increased vulnerability of some patients who choose reconstruction. Studying the characteristics and needs of women who opt for immediate reconstruction and examining the implications for women's adjustment should be a priority for research.
A review of needle core biopsy diagnosed radial scars in the Welsh Breast Screening Programme
Authors: Osborn G , Wilton F , Stevens G , Vaughan-Williams E , Gower-Thomas K
Published: March 2011

INTRODUCTION

Radial scars are benign breast lesions; their appearance on mammography may, however, mimic carcinoma. Needle core biopsy is performed for pre-operative diagnosis and, currently in Wales, all lesions with benign biopsy results are surgically excised. We have reviewed all cases of needle core biopsy-diagnosed radial scars from the Welsh breast screening programme, Breast Test Wales (BTW), and investigated the outcome of radial scars based on histology from surgical excision in order to evaluate the appropriateness of the current management of these lesions in Wales.

PATIENTS AND METHODS

All needle core biopsy diagnosed radial scars were identified from the BTW screening database from the start of screening in 1989 until the end of 2007.

RESULTS

A total of 118 patients were diagnosed with radial scars on needle core biopsy; two patients had bilateral radial scars. Median patient age was 54 years (range, 49-68 years). Ninety-five lesions (79%) were thought to be pure radial scars on needle core biopsy; however, only 81 pure radial scars were identified on excision biopsy histology. Carcinoma was present in seven patients and ductal carcinoma in situ in nine patients at excision biopsy. In two patients, the cancers occurred in lesions reported as pure radial scars on needle core biopsy. Twenty-two lesions showed atypical ductal or lobular hyperplasia (ADH/ALH) or both on excision biopsy; 14 of these lesions were classed as pure radial scars by needle core biopsy.

CONCLUSIONS

All core biopsy diagnosed radial scars, presenting as screen detected abnormalities, should be excised due to their association with premalignant and malignant conditions.
A comparison of the effect of different surgical gloves on objective measurement of fingertip cutaneous sensibility
Authors: Bucknor A , Karthikesalingam A , Markar SR , Holt PJ , Jones I , Allen-Mersh TG
Published: March 2011

INTRODUCTION

The prudent selection of surgical gloves can deliver significant efficiency savings. However, objective data are lacking to compare differences in cutaneous sensibility between competing gloves. Therefore, the present study examined the use of a single comparable model of sterile surgical glove from two competing providers, Gammex PF HyGrip® (Ansell Limited, Red Bank, NJ, USA) with Biogel® (Mölnlycke Health Care AB, Göteborg, Sweden).

SUBJECTS AND METHODS

Cutaneous pressure threshold, static and moving two-point discrimination were measured as indices of objective surgical glove performance in 52 blinded healthcare professionals.

RESULTS

The mean cutaneous pressure threshold was 0.0680 ± 0.0923 g for skin, 0.411 ± 0.661 g for Ansell gloves and 0.472 ± 0.768 g for Biogel gloves. Skin was significantly more sensitive than Ansell (P< 0.0001) or Biogel (P< 0.0001) gloves (Wilcoxon signed rank test). There was no statistical difference between Biogel and Ansell gloves (P = 0.359). There was no significant difference between static or moving 2-point discrimination of skin and Ansell gloves (P= 0.556, P = 0.617; Wilcoxon signed rank test), skin and Biogel gloves (P= 0.486, P= 0.437; Wilcoxon signed rank test) or Ansell and Biogel gloves (P= 0.843, P= 0.670; Wilcoxon signed rank test).

CONCLUSIONS

No demonstrable objective difference was found between competing gloves in the outcome measures of cutaneous sensibility and two-point discrimination. However, a difference in subjective preference was noted. Untested factors may underlie this discrepancy, and further research should employ more sophisticated measurements of surgical performance using competing models of surgical glove.
State diagrams for improving processing and storage of foods, biological materials, and pharmaceuticals (IUPAC Technical Report)
Authors: Buera Maria Pilar , Roos Yrjö , Levine Harry , Slade Louise , Corti Horacio R. , Reid David S. , Auffret Tony , Angell C. Austen
Published: March 2011

Supplemented temperature/composition phase diagrams include the non-equilibrium glass-transition temperature (Tg) curve and equilibrium ice-melting and solubility curves. The inclusion of the non-equilibrium curve allows one to establish relationships with the time coordinate and, thus, with the dynamic behavior of systems, provided that the thermal history of such systems is known. The objective of this report is to contribute to the potential applications of supplemented state diagrams for aqueous glass-formers, in order to describe the influence of water content, nature of vitrifying agents, and temperature on the physico-chemical properties of foods and biological and pharmaceutical products. These data are helpful to develop formulations, processing strategies, or storage procedures in order to optimize the stability of food ingredients and pharmaceutical formulations. Reported experimental data on phase and state transitions for several food and pharmaceutical systems were analyzed. Some methodological aspects and the effect of phase and state transitions on the main potential chemical reactions that can alter those systems during processing and/or storage are discussed.