bluuebunny/crossref_metadata_2025 huggingface dataset:
An immunohistochemical study of the antinociceptive effect of calcitonin in ovariectomized rats
Authors: Takayama Bunji , Kikuchi Shin-ichi , Konno Shin-ichi , Sekiguchi Miho
Published: December 2008

Background

Calcitonin is used as a treatment to reduce the blood calcium concentration in hypercalcemia and to improve bone mass in osteoporosis. An analgesic effect of calcitonin has been observed and reported in clinical situations. Ovariectomaized (OVX) rats exhibit the same hormonal changes as observed in humans with osteoporosis and are an animal model of postmenopousal osteoporosis. The aim of this study to investigate antinociceptive effect of calcitonin in OVX rats using the immunohistochemical study.

Methods

We assessed the antinociceptive effects of calcitonin in an ovariectomized (OVX) rat model, which exhibit osteoporosis and hyperalgesia, using the immunohistochemical method. Fifteen rats were ovariectomized bilaterally, and ten rats were received the same surgery expected for ovariectomy as a sham model. We used five groups: the OVX-CT (n = 5), the sham-CT (n = 5), and the OVX-CT-pcpa (n = 5) groups recieved calcitonin (CT: 4 U/kg/day), while OVX-vehi (n = 5) and the sham-vehi (n = 5) groups received vehicle subcutaneously 5 times a week for 4 weeks. The OVX-CT-pcpa-group was given traperitoneal injection of p-chlorophenylalanine (pcpa; an inhibitor of serotonin biosynthesis) (100 mg/kg/day) in the last 3 days of calcitonon injection. Two hours after 5% formalin (0.05 ml) subcutaneously into the hind paw, the L5 spinal cord were removed and the number of Fos-immunoreactive (ir) neurons were evaluated using the Mann-Whitney-U test.

Results

The numbers of Fos-ir neurons in the OVX-CT and sham-CT groups were significantly less than in the OVX-vehi and sham-vehi groups, respectively (p = 0.0090, p = 0.0090). The number of Fos-ir neurons in the OVX-CT-pcpa-group was significantly more than that of the OVX-CT-group (p = 0.0283), which means pcpa inhibits calcitonin induced reduction of c-Fos production.

Conclusion

The results in this study demonstrated that 1) the increase of c-Fos might be related to hyperalgesia in OVX-rats. 2) Calcitonin has an antinociceptive effect in both OVX and sham rats. 3) The central serotonergic system is involved in the antinociceptive properties of calcitonin.
Simultaneous tracking of fly movement and gene expression using GFP
Authors: Grover Dhruv , Yang Junsheng , Tavaré Simon , Tower John
Published: December 2008

Background

Green Fluorescent Protein (GFP) is used extensively as a reporter for transgene expression in Drosophila and other organisms. However, GFP has not generally been used as a reporter for circadian patterns of gene expression, and it has not previously been possible to correlate patterns of reporter expression with 3D movement and behavior of transgenic animals.

Results

We present a video tracking system that allows tissue-specific GFP expression to be quantified and correlated with 3D animal movement in real time. eyeless/Pax6 reporter expression had a 12 hr period that correlated with fly activity levels.

hsp70 and hsp22 gene reporters were induced during fly aging in circadian patterns (24 hr and 18 hr periods, respectively), and spiked in the hours preceding and overlapping the death of the animal. The phase of hsp gene reporter expression relative to fly activity levels was different for each fly, and remained the same throughout the life span.

Conclusion

These experiments demonstrate that GFP can readily be used to assay longitudinally fly movement and tissue-specific patterns of gene expression. The hsp22-GFP and hsp70-GFP expression patterns were found to reflect accurately the endogenous gene expression patterns, including induction during aging and circadian periodicity. The combination of these new tracking methods with the hsp-GFP reporters revealed additional information, including a spike in hsp22 and hsp70 reporter expression preceding death, and an intriguing fly-to-fly variability in the phase of hsp70 and hsp22 reporter expression patterns. These methods allow specific temporal patterns of gene expression to be correlated with temporal patterns of animal activity, behavior and mortality.
Efficacy of AZM therapy in patients with gingival overgrowth induced by Cyclosporine A: a systematic review
Authors: Clementini Marco , Vittorini Gianluca , Crea Alessandro , Gualano Maria Rosaria , Macrì Ludovica Antonella , Deli Giorgio , La Torre Giuseppe
Published: December 2008

Background

In daily clinical practice of a dental department it's common to find gingival overgrowth (GO) in periodontal patients under treatment with Cyclosporine A (CsA). The pathogenesis of GO and the mechanism of action of Azithromycin (AZM) are unclear. A systematic review was conducted in order to evaluate the efficacy of Azithromycin in patients with gingival overgrowth induced by assumption of Cyclosporine A.

Methods

A bibliographic search was performed using the online databases MEDLINE, EMBASE and Cochrane Central of Register Controlled Trials (CENTRAL) in the time period between 1966 and September 2008.

Results

The literature search retrieved 24 articles; only 5 were Randomised Controlled Trials (RCTs), published in English, fulfilled the inclusion criteria. A great heterogeneity between proposed treatments and outcomes was found, and this did not allow to conduct a quantitative meta-analysis. The systematic review revealed that a 5-day course of Azithromycin with Scaling and Root Planing reduces the degree of gingival overgrowth, while a 7-day course of metronidazole is only effective on concomitant bacterial over-infection.

Conclusion

Few RCTs on the efficacy of systemic antibiotic therapy in case of GO were found in the literature review. A systemic antibiotic therapy without plaque and calculus removal is not able to reduce gingival overgrowth. The great heterogeneity of diagnostic data and outcomes is due to the lack of precise diagnostic methods and protocols about GO. Future studies need to improve both diagnostic methods and tools and adequate classification aimed to determine a correct prognosis and an appropriate therapy for gingival overgrowth.
Host factors do not influence the colonization or infection by fluconazole resistant Candida species in hospitalized patients
Authors: Yang Yun-Liang , Cheng Ming-Fang , Chang Ya-Wen , Young Tzuu-Guang , Chi Hsin , Lee Sai Cheong , Cheung Bruno Man-Hon , Tseng Fan-Chen , Chen Tun-Chieh , Ho Yu-Huai , Shi Zhi-Yuan , Chan Chung-Huang Hubert , Lin Ju-Yu , Lo Hsiu-Jung
Published: December 2008

Nosocomial yeast infections have significantly increased during the past two decades in industrialized countries, including Taiwan. This has been associated with the emergence of resistance to fluconazole and other antifungal drugs. The medical records of 88 patients, colonized or infected with Candida species, from nine of the 22 hospitals that provided clinical isolates to the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) program in 1999 were reviewed. A total of 35 patients contributed fluconazole resistant strains [minimum inhibitory concentrations (MICs) ≧ 64 mg/l], while the remaining 53 patients contributed susceptible ones (MICs ≦ 8 mg/l). Fluconazole resistance was more frequent among isolates of Candida tropicalis (46.5%) than either C. albicans (36.8%) or C. glabrata (30.8%). There was no significant difference in demographic characteristics or underlying diseases among patients contributing strains different in drug susceptibility.
Normal mitochondrial respiratory function is essential for spatial remote memory in mice
Authors: Tanaka Daisuke , Nakada Kazuto , Takao Keizo , Ogasawara Emi , Kasahara Atsuko , Sato Akitsugu , Yonekawa Hiromichi , Miyakawa Tsuyoshi , Hayashi Jun-Ichi
Published: December 2008

Background

Mitochondrial DNA (mtDNA) with pathogenic mutations has been found in patients with cognitive disorders. However, little is known about whether pathogenic mtDNA mutations and the resultant mitochondrial respiration deficiencies contribute to the expression of cognitive alterations, such as impairments of learning and memory. To address this point, we used two groups of trans-mitochondrial mice (mito-mice) with heteroplasmy for wild-type and pathogenically deleted (Δ) mtDNA; the "low" group carried 50% or less ΔmtDNA, and the "high" group carried more than 50% ΔmtDNA.

Results

Both groups had normal phenotypes for not only spatial learning, but also memory at short retention delays, indicating that ΔmtDNA load did not affect learning and temporal memory. The high group, however, showed severe impairment of memory at long retention delays. In the visual cortex and dentate gyrus of these mice, we observed mitochondrial respiration deficiencies, and reduced Ca2+/calmodulin-dependent kinase II-α (α-CaMKII), a protein important for the establishment of spatial remote memory.

Conclusion

Our results indicated that normal mitochondrial respiratory function is necessary for retention and consolidation of memory trace; deficiencies in this function due to high loads of pathogenically mutated mtDNA are responsible for the preferential impairment of spatial remote memory.
Unusual cause of gastric outlet obstruction: giant gastric trichobezoar: a case report
Authors: Yetim Ibrahim , Ozkan Orhan Veli , Semerci Ersan , Abanoz Recep
Published: December 2008

Background

Trichobezoars are caused by hair ingestion. The usual presentation of a trichobezoar is with early satiety and malnutrition. Obstructive symptoms and manifestations of gastric outlet obstruction may occur. The diagnosis may be suspected in young females with malnutrition, who have a history of trichophagia.

Case presentation

We report a case of 12-year-old female admitted to the emergency room for abdominal pain. On physical examination, she was cachectic and an epigastric mass was palpated. An exploratory laparotomy was conducted. A giant trichobezoar was palpated in the stomach and was removed through an anterior gastrostomy.

Conclusion

There were no complications postoperatively and the patient was referred to a psychiatrist.
Incremental cost effectiveness of proton pump inhibitors for the prevention of non-steroidal anti-inflammatory drug ulcers: a pharmacoeconomic analysis linked to a case-control study
Authors: Vonkeman Harald E , Braakman-Jansen Louise MA , Klok Rogier M , Postma Maarten J , Brouwers Jacobus RBJ , van de Laar Mart AFJ
Published: December 2008

Introduction

We estimated the cost effectiveness of concomitant proton pump inhibitors (PPIs) in relation to the occurrence of non-steroidal anti-inflammatory drug (NSAID) ulcer complications.

Methods

This study was linked to a nested case-control study. Patients with NSAID ulcer complications were compared with matched controls. Only direct medical costs were reported. For the calculation of the incremental cost effectiveness ratio we extrapolated the data to 1,000 patients using concomitant PPIs and 1,000 patients not using PPIs for 1 year. Sensitivity analysis was performed by 'worst case' and 'best case' scenarios in which the 95% confidence interval (CI) of the odds ratio (OR) and the 95% CI of the cost estimate of a NSAID ulcer complication were varied. Costs of PPIs was varied separately.

Results

In all, 104 incident cases and 284 matched controls were identified from a cohort of 51,903 NSAID users with 10,402 NSAID exposition years. Use of PPIs was associated with an adjusted OR of 0.33 (95% CI 0.17 to 0.67; p = 0.002) for NSAID ulcer complications. In the extrapolation the estimated number of NSAID ulcer complications was 13.8 for non-PPI users and 3.6 for PPI users. The incremental total costs were € 50,094 higher for concomitant PPIs use. The incremental cost effectiveness ratio was € 4,907 per NSAID ulcer complication prevented when using the least costly PPIs.

Conclusions

Concomitant use of PPIs for the prevention of NSAID ulcer complications costs € 4,907 per NSAID ulcer complication prevented when using the least costly PPIs. The price of PPIs highly influenced the robustness of the results.
Proteomic analysis of tumor necrosis factor-α resistant human breast cancer cells reveals a MEK5/Erk5-mediated epithelial-mesenchymal transition phenotype
Authors: Zhou Changhua , Nitschke Ashley M , Xiong Wei , Zhang Qiang , Tang Yan , Bloch Michael , Elliott Steven , Zhu Yun , Bazzone Lindsey , Yu David , Weldon Christopher B , Schiff Rachel , McLachlan John A , Beckman Barbara S , Wiese Thomas E , Nephew Kenneth P , Shan Bin , Burow Matthew E , Wang Guangdi
Published: December 2008

Introduction

Despite intensive study of the mechanisms of chemotherapeutic drug resistance in human breast cancer, few reports have systematically investigated the mechanisms that underlie resistance to the chemotherapy-sensitizing agent tumor necrosis factor (TNF)-α. Additionally, the relationship between TNF-α resistance mediated by MEK5/Erk5 signaling and epithelial-mesenchymal transition (EMT), a process associated with promotion of invasion, metastasis, and recurrence in breast cancer, has not previously been investigated.

Methods

To compare differences in the proteome of the TNF-α resistant MCF-7 breast cancer cell line MCF-7-MEK5 (in which TNF-α resistance is mediated by MEK5/Erk5 signaling) and its parental TNF-a sensitive MCF-7 cell line MCF-7-VEC, two-dimensional gel electrophoresis and high performance capillary liquid chromatography coupled with tandem mass spectrometry approaches were used. Differential protein expression was verified at the transcriptional level using RT-PCR assays. An EMT phenotype was confirmed using immunofluorescence staining and gene expression analyses. A short hairpin RNA strategy targeting Erk5 was utilized to investigate the requirement for the MEK/Erk5 pathway in EMT.

Results

Proteomic analyses and PCR assays were used to identify and confirm differential expression of proteins. In MCF-7-MEK5 versus MCF-7-VEC cells, vimentin (VIM), glutathione-S-transferase P (GSTP1), and creatine kinase B-type (CKB) were upregulated, and keratin 8 (KRT8), keratin 19 (KRT19) and glutathione-S-transferase Mu 3 (GSTM3) were downregulated. Morphology and immunofluorescence staining for E-cadherin and vimentin revealed an EMT phenotype in the MCF-7-MEK5 cells. Furthermore, EMT regulatory genes SNAI2 (slug), ZEB1 (δ-EF1), and N-cadherin (CDH2) were upregulated, whereas E-cadherin (CDH1) was downregulated in MCF-7-MEK5 cells versus MCF-7-VEC cells. RNA interference targeting of Erk5 reversed MEK5-mediated EMT gene expression.

Conclusions

This study demonstrates that MEK5 over-expression promotes a TNF-α resistance phenotype associated with distinct proteomic changes (upregulation of VIM/vim, GSTP1/gstp1, and CKB/ckb; and downregulation of KRT8/krt8, KRT19/krt19, and GSTM3/gstm3). We further demonstrate that MEK5-mediated progression to an EMT phenotype is dependent upon intact Erk5 and associated with upregulation of SNAI2 and ZEB1 expression.
The influence of menstrual risk factors on tumor characteristics and survival in postmenopausal breast cancer
Authors: Orgéas Chantal C , Hall Per , Rosenberg Lena U , Czene Kamila
Published: December 2008

Introduction

Hormonal factors are implicated in tumor progression and it is possible that factors influencing breast cancer induction could affect prognosis. Our study investigated the effects of menstrual risk factors on tumor characteristics and survival in postmenopausal breast cancer.

Methods

We used a nationwide, population-based, case-case design of 2,640 Swedish women who were 50 to 74 years old and had postmenopausal breast cancer during 1993 to 1995. Follow-up was conducted until 31 December 2000. We used polytomous multiple logistic regression to investigate the relationships between menstrual factors (age at menarche, cycle length, irregular menstruation, lifetime number of menstrual cycles, and age at menopause), tumor characteristics (size, grade, estrogen receptor and progesterone receptor [PR] status, lymph node involvement, and histology), and Cox proportional hazards modeling for 5-year survival.

Results

Younger ages at menarche were significantly associated with grade and lymph node involvement. Women with an age at menarche of 11 years or younger had a more than twofold excess risk of medium-grade (odds ratio [OR] = 2.05; 95% confidence interval [CI] 1.00 to 4.18) and high-grade (OR = 2.04; 95% CI 1.01 to 4.16) tumors. Early menarche significantly increased the risk of lymph node metastases. Survival was poorest in women with the earliest age at menarche, with a 72% increased risk of dying within 5 years after diagnosis (hazard ratio = 1.72; 95% CI 1.02 to 2.89). No significant associations were observed for other menstrual factors with tumor characteristics or survival.

Conclusions

Age at menarche has a significant impact on breast cancer prognosis and survival. It remains to be established whether the associations are attributable to age at menarche directly or are associated with the early-life physiological events of breast development and carcinogenesis also taking place during childhood and puberty, as menarche is only the culmination of this series of events.
Evolutionary-new centromeres preferentially emerge within gene deserts
Authors: Lomiento Mariana , Jiang Zhaoshi , D'Addabbo Pietro , Eichler Evan E , Rocchi Mariano
Published: December 2008

Background

Evolutionary-new centromeres (ENCs) result from the seeding of a centromere at an ectopic location along the chromosome during evolution. The novel centromere rapidly acquires the complex structure typical of eukaryote centromeres. This phenomenon has played an important role in shaping primate karyotypes. A recent study on the evolutionary-new centromere of macaque chromosome 4 (human 6) showed that the evolutionary-new centromere domain was deeply restructured, following the seeding, with respect to the corresponding human region assumed as ancestral. It was also demonstrated that the region was devoid of genes. We hypothesized that these two observations were not merely coincidental and that the absence of genes in the seeding area constituted a crucial condition for the evolutionary-new centromere fixation in the population.

Results

To test our hypothesis, we characterized 14 evolutionary-new centromeres selected according to conservative criteria. Using different experimental approaches, we assessed the extent of genomic restructuring. We then determined the gene density in the ancestral domain where each evolutionary-new centromere was seeded.

Conclusions

Our study suggests that restructuring of the seeding regions is an intrinsic property of novel evolutionary centromeres that could be regarded as potentially detrimental to the normal functioning of genes embedded in the region. The absence of genes, which was found to be of high statistical significance, appeared as a unique favorable scenario permissive of evolutionary-new centromere fixation in the population.
Annotating genomes with massive-scale RNA sequencing
Authors: Denoeud France , Aury Jean-Marc , Da Silva Corinne , Noel Benjamin , Rogier Odile , Delledonne Massimo , Morgante Michele , Valle Giorgio , Wincker Patrick , Scarpelli Claude , Jaillon Olivier , Artiguenave François
Published: December 2008

Next generation technologies enable massive-scale cDNA sequencing (so-called RNA-Seq). Mainly because of the difficulty of aligning short reads on exon-exon junctions, no attempts have been made so far to use RNA-Seq for building gene models de novo, that is, in the absence of a set of known genes and/or splicing events. We present G-Mo.R-Se (Gene Modelling using RNA-Seq), an approach aimed at building gene models directly from RNA-Seq and demonstrate its utility on the grapevine genome.
American Society of Clinical Oncology Policy Statement: The Role of the Oncologist in Cancer Prevention and Risk Assessment
Authors: Zon Robin T. , Goss Elizabeth , Vogel Victor G. , Chlebowski Rowan T. , Jatoi Ismail , Robson Mark E. , Wollins Dana S. , Garber Judy E. , Brown Powel , Kramer Barnett S.
Published: December 2008

Oncologists have a critical opportunity to utilize risk assessment and cancer prevention strategies to interrupt the initiation or progression of cancer in cancer survivors and individuals at high risk of developing cancer. Expanding knowledge about the natural history and prognosis of cancers positions oncologists to advise patients regarding the risk of second malignancies and treatment-related cancers. In addition, as recognized experts in the full spectrum of cancer care, oncologists are afforded opportunities for involvement in community-based cancer prevention activities.

Although oncologists are currently providing many cancer prevention and risk assessment services to their patients, economic barriers exist, including inadequate or lack of insurance, that may compromise uniform patient access to these services. Additionally, insufficient reimbursement for existing and developing interventions may discourage patient access to these services.

The American Society of Clinical Oncology (ASCO), the medical society representing cancer specialists involved in patient care and clinical research, is committed to supporting oncologists in their wide-ranging involvement in cancer prevention. This statement on risk assessment and prevention counseling, although not intended to be a comprehensive overview of cancer prevention describes the current role of oncologists in risk assessment and prevention; provides examples of risk assessment and prevention activities that should be offered by oncologists; identifies potential opportunities for coordination between oncologists and primary care physicians in prevention education and coordination of care for cancer survivors; describes ASCO's involvement in education and training of oncologists regarding prevention; and proposes improvement in the payment environment to encourage patient access to these services.
Sequential Therapy With Fludarabine, High-Dose Cyclophosphamide, and Rituximab in Previously Untreated Patients With Chronic Lymphocytic Leukemia Produces High-Quality Responses: Molecular Remissions Predict for Durable Complete Responses
Authors: Lamanna Nicole , Jurcic Joseph G. , Noy Ariela , Maslak Peter , Gencarelli Alison N. , Panageas Katherine S. , Heaney Mark L. , Brentjens Renier J. , Golde David W. , Scheinberg David A. , Zelenetz Andrew D. , Weiss Mark A.
Published: December 2008

Purpose

Modern combination strategies are active in chronic lymphocytic leukemia (CLL) but can have significant myelosuppression and immunosuppression that may require dose attenuation for safety. We explored a sequential treatment strategy to allow safe delivery of active agents at full doses. Previously, we studied sequential therapy with fludarabine followed by cyclophosphamide (F→C). In that study, cyclophosphamide consolidation improved the frequency of complete response (CR) four-fold. Subsequently, rituximab was added to this regimen (F→C→R).

Patients and Methods

Thirty-six previously untreated CLL patients received therapy with fludarabine 25 mg/m2 on days 1 through 5 every 4 weeks for six cycles, followed by consolidation with cyclophosphamide 3,000 mg/m2 administered every 3 weeks for three cycles, followed by consolidation with weekly rituximab 375 mg/m2 for four cycles. Evaluation for minimal residual disease included flow cytometry and a highly sensitive clonotypic polymerase chain reaction (PCR). The median age was 59 years (range, 37 to 71 years), 61% of patients had high-risk disease, and 58% had unmutated IgVH genes.

Results

There were 32 responses (89%), including 22 CRs (61%). Consolidation with cyclophosphamide improved responses in 13 patients (36%); nine patients (25%) further improved their response with rituximab. Twenty patients (56%) achieved flow cytometric CRs, and 12 patients (33%) achieved a molecular CR (PCR negative). Patients achieving molecular CRs had an excellent prognosis with a plateau in the response duration curve, and 90% remain in clinical CR at 5 years. For the entire group, 5-year survival rate is 71% compared with a rate of 48% with our prior F→C regimen (P = .10).

Conclusion

Sequential therapy with F→C→R yields improvement in quality of response, with many patients achieving a PCR-negative state.
Relevance of Breast Cancer Antiestrogen Resistance Genes in Human Breast Cancer Progression and Tamoxifen Resistance
Authors: van Agthoven Ton , Sieuwerts Anieta M. , Meijer-van Gelder Marion E. , Look Maxime P. , Smid Marcel , Veldscholte Jos , Sleijfer Stefan , Foekens John A. , Dorssers Lambert C.J.
Published: December 2008

Purpose

We have previously identified a set of breast cancer antiestrogen resistance (BCAR) genes causing estrogen independence and tamoxifen resistance in vitro using a functional genetic screen. Here, we explored whether these BCAR genes provide predictive value for tamoxifen resistance and prognostic information for tumor aggressiveness in breast cancer patients.

Patients and Methods

mRNA levels of 10 BCAR genes (AKT1, AKT2, BCAR1, BCAR3, EGFR, ERBB2, GRB7, SRC, TLE3, and TRERF1) were measured in estrogen receptor–positive breast tumors using quantitative reverse-transcriptase polymerase chain reaction. Normalized mRNA levels were evaluated for association with progression-free survival (PFS) in 242 patients receiving tamoxifen as first-line monotherapy for recurrent disease, and with distant metastasis-free survival (MFS) in 413 lymph node-negative (LNN) primary breast cancer patients who did not receive systemic adjuvant therapy.

Results

Concerning tamoxifen resistance, BCAR3, ERBB2, GRB7, and TLE3 mRNA levels were predictive for PFS, independent of traditional predictive factors. By combining GRB7 (or ERBB2) and TLE3 mRNA levels, patients could be classified in three subgroups with distinct PFS. For the evaluation of tumor aggressiveness, AKT2, EGFR, and TRERF1 mRNA levels were all significantly associated with MFS, independent of traditional prognostic factors. Using the combined AKT2 and EGFR mRNA status, four prognostic groups were identified with different MFS outcomes.

Conclusion

The majority of BCAR genes, which were revealed to confer tamoxifen resistance and estrogen independence in vitro by functional screening, have clinical relevance, and associate with tamoxifen resistance and/or tumor aggressiveness in breast cancer patients.
Randomized Trial of 13-cis Retinoic Acid Compared With Retinyl Palmitate With or Without Beta-Carotene in Oral Premalignancy
Authors: Papadimitrakopoulou Vassiliki A. , Lee J. Jack , William William N. , Martin Jack W. , Thomas Margaret , Kim Edward S. , Khuri Fadlo R. , Shin Dong M. , Feng Lei , Hong Waun Ki , Lippman Scott M.
Published: December 2008

Purpose

To investigate whether retinyl palmitate (RP) alone or plus beta-carotene (BC) would be as effective and less toxic than low-dose 13-cis retinoic acid (13cRA) in treating oral premalignant lesions (OPLs) and reducing the risk of oral cancer.

Patients and Methods

Initially, patients were randomly assigned to receive low-dose 13cRA or BC plus RP for 3 years (plus 2 years follow-up). After other randomized trials established an adverse effect of BC on lung cancer incidence/mortality, BC was dropped (patients randomly assigned to 13cRA or RP alone). The primary end point was OPL clinical response at 3 months.

Results

We randomly assigned 162 eligible patients. The 3-month clinical response rate of the combined BC plus RP and RP alone arm (32.5%) was not statistically equivalent to that of 13cRA (48.1%). The clinical response rate of RP alone (20.0%) was significantly lower than that of BC plus RP (42.9%; P = .03). Similar oral cancer–free survival rates were observed across all arms. There was no significant association between 3-month OPL response and subsequent oral cancer development (P = .11). Grades 2 and higher adverse events were more common in the 13cRA than other groups (P < .0001).

Conclusion

This large chemoprevention trial did not establish the equivalence of RP plus BC or RP alone with low-dose 13cRA in reducing the long-term risk of oral cancer. At present, 13cRA, BC plus RP, and RP alone cannot be recommended for chemoprevention, and new, better agents are needed in this setting. Our results did not establish short-term OPL response as a surrogate end point for oral cancer–free survival.
Oregovomab Maintenance Monoimmunotherapy Does Not Improve Outcomes in Advanced Ovarian Cancer
Authors: Berek Jonathan , Taylor Peyton , McGuire William , Smith L. Mary , Schultes Birgit , Nicodemus Christopher F.
Published: December 2008

Purpose

This phase III study tested the hypothesis that the CA-125–specific murine monoclonal antibody, oregovomab, administered as a monoimmunotherapy after front-line therapy in a selected ovarian cancer population would prolong time to relapse (TTR) and, ultimately, survival.

Patients and Methods

Patients with stage III to IV ovarian cancer with preoperatively elevated CA-125 and objectively defined characteristics were randomly assigned 4 to 12 weeks after front-line carboplatin and paclitaxel chemotherapy to maintenance monoimmunotherapy in a fully blinded protocol. Two mg of oregovomab or placebo was infused over 20 minutes at weeks 0, 4, and 8 and then 12 weeks until recurrence or up to year 5. Patients were evaluated with serial imaging and clinical evaluation for evidence of recurrence at quarterly visits. TTR was the primary end point.

Results

Three hundred seventy-three patients were accrued at more than 60 centers; 251 patients were assigned to oregovomab and 120 patients were assigned to placebo. The treatment arms were well balanced. There were no differences in the clinical outcomes between treatment groups. Median TTR measured from randomization after completion of chemotherapy for the integrated study was 10.3 months (95% CI, 9.7 to 13.0 months) for oregovomab and 12.9 months (95% CI, 10.1 to 17.4 months) for placebo (P = .29, log-rank test). The treatment was well tolerated. Grade 3 to 4 toxicity was reported in 24.6% of patients in the placebo group and 20.1% of patients in the oregovomab group, respectively.

Conclusion

Although oregovomab has demonstrated bioactivity, the strategy of monoimmunotherapy is not effective as maintenance therapy after front-line treatment of a favorable subset of patients with advanced ovarian cancer. Future studies of this or other tumor-antigen specific immunization strategies should seek ways to further augment induced immunity.
Phase III Randomized, Placebo-Controlled, Double-Blind Trial of Risedronate for the Prevention of Bone Loss in Premenopausal Women Undergoing Chemotherapy for Primary Breast Cancer
Authors: Hines Stephanie L. , Mincey Betty Anne , Sloan Jeff A. , Thomas Sachdev P. , Chottiner Elaine , Loprinzi Charles L. , Carlson Mark D. , Atherton Pamela J. , Salim Muhammad , Perez Edith A.
Published: December 2008

Purpose

Risedronate prevents bone loss in postmenopausal women. The purpose of this study was to determine whether risedronate prevents bone loss in premenopausal women undergoing chemotherapy for breast cancer.

Patients and Methods

Premenopausal women undergoing chemotherapy for breast cancer were treated with oral calcium 600 mg and vitamin D 400 U daily and randomly assigned to receive oral risedronate 35 mg weekly or placebo, with all these therapies beginning within a month of the start of chemotherapy. Most chemotherapy regimens included anthracyclines, taxanes, or cyclophosphamide. Bone mineral density (BMD) was measured at baseline and 1 year. The primary end point was the change in lumbar spine (LS) BMD from baseline to 1 year.

Results

A total of 216 women enrolled; 170 women provided BMD data at 1 year. There was no difference in the mean change or percent change in LS BMD between groups, with a loss of 4.3% in the risedronate arm and 5.4% for placebo at 1 year (P = .18). Loss of BMD at the femoral neck and total hip were also similar between treatment groups. Risedronate was well tolerated, with no significant differences in adverse events compared with placebo, except that arthralgias and chest pain were worse in those receiving the placebos.

Conclusion

Risedronate did not prevent bone loss in premenopausal women undergoing adjuvant chemotherapy for breast cancer.
Decreased precision contributes to the hypoxic thermoregulatory response in lizards
Authors: Cadena Viviana , Tattersall Glenn J.
Published: December 2008

The decrease in body temperature (Tb) observed in most vertebrate classes in response to hypoxia has been attributed to a regulated decrease in set-point, protecting organs against tissue death due to oxygen depletion. Hypoxia, however, imparts particular challenges to metabolic function which may, in turn, affect thermoregulation. In ectotherms, where thermoregulation is mainly behavioural, stressors that influence the propensity to move and respond to temperature gradients are expected to have an impact on thermoregulatory control. Using low oxygen as a potent stressor,we evaluated the variability and level of thermoregulation of inland bearded dragons. To examine the source of thermoregulatory variability, we studied their behaviour in an electronically controlled temperature-choice shuttle box, a constant temperature dual-choice shuttle box, and a linear thermal gradient. A significant increase in the size of the Tbrange was observed at the lowest oxygen concentration (4% O2),reflecting a decrease in thermoregulatory precision in the temperature-choice shuttle box. This was also accompanied by a drop of ∼2–4°C in Tb, the drop being greatest in situations where Tb must be actively defended. Situations that force the lizards to continually choose temperatures, rather than passively remain at a given temperature, lead to an increase in the variability in the manifested Tb, which is further exaggerated in hypoxia. This study reveals that a decrease in thermoregulatory precision caused by a diminished propensity to move or effect appropriate thermoregulatory responses may be a contributing component in the lowering of selected body temperatures observed in many hypoxic ectotherms.
Wear and frictional performance of betelnut fibre-reinforced polyester composite
Authors: Singh Gill N , Yousif B F
Published: December 2008

The current work is an attempt to use betelnut fibres as reinforcement for tribo-polyester composite. The composite was fabricated using hand lay-up technique. It consists of 13 layers of randomly distributed betelnut fibre mats and 15 layers of polyester. Wear and frictional behaviours of the composite were studied against a polished stainless steel counterface using a newly developed block-on-disc machine. Tests were conducted at 2.8 m/s sliding velocity, different applied loads (5-30 N), and sliding distances (0-6.72 km). In addition, the orientation of the fibre mats, with respect to the sliding direction of the counterface, was considered, i.e. anti-parallel (AP-O), parallel (P-O), and normal (N-O). The worn surface morphology was studied using a scanning electron microscope. Optical microscopy was used to observe the wear track surface on the counterface. In addition, the modifications on the counterface roughness were studied. This work revealed that the presence of betelnut fibre in the matrix, namely P-O, enhanced the wear and frictional performance of the polyester by about 98 and 73 per cent. Applied load has less effect on the specific wear rate and friction coefficient of the composite, especially in P-O and AP-O. The composite behaved differently in N-O in which the wear and friction increased when the applied load and sliding distance increased. The composite exhibited higher wear performance in P-O compared with AP-O followed by N-O. In N-O, poor support of the fibres to the resinous was observed, i.e delamination, pullout, and breakage in the fibres. In AP-O, the wear mechanism was predominated by plastic deformation, micro- and macro-cracks in the resinous regions associated with pullout, and breakage of the fibre. In P-O, debonding of fibres was the main wear mechanism.
Comparison of the Effect of Denosumab and Alendronate on BMD and Biochemical Markers of Bone Turnover in Postmenopausal Women With Low Bone Mass: A Randomized, Blinded, Phase 3 Trial
Authors: Brown Jacques P , Prince Richard L , Deal Chad , Recker Robert R , Kiel Douglas P , de Gregorio Luiz H , Hadji Peyman , Hofbauer Lorenz C , Álvaro-Gracia Jose M , Wang Huei , Austin Matthew , Wagman Rachel B , Newmark Richard , Libanati Cesar , San Martin Javier , Bone Henry G
Published: December 2008

Denosumab is a fully human monoclonal antibody that inhibits bone resorption by neutralizing RANKL, a key mediator of osteoclast formation, function, and survival. This phase 3, multicenter, double-blind study compared the efficacy and safety of denosumab with alendronate in postmenopausal women with low bone mass. One thousand one hundred eighty-nine postmenopausal women with a T-score ≤ −2.0 at the lumbar spine or total hip were randomized 1:1 to receive subcutaneous denosumab injections (60 mg every 6 mo [Q6M]) plus oral placebo weekly (n = 594) or oral alendronate weekly (70 mg) plus subcutaneous placebo injections Q6M (n = 595). Changes in BMD were assessed at the total hip, femoral neck, trochanter, lumbar spine, and one-third radius at 6 and 12 mo and in bone turnover markers at months 1, 3, 6, 9, and 12. Safety was evaluated by monitoring adverse events and laboratory values. At the total hip, denosumab significantly increased BMD compared with alendronate at month 12 (3.5% versus 2.6%; p < 0.0001). Furthermore, significantly greater increases in BMD were observed with denosumab treatment at all measured skeletal sites (12-mo treatment difference: 0.6%, femoral neck; 1.0%, trochanter; 1.1%, lumbar spine; 0.6%, one-third radius; p ≤ 0.0002 all sites). Denosumab treatment led to significantly greater reduction of bone turnover markers compared with alendronate therapy. Adverse events and laboratory values were similar for denosumab- and alendronate-treated subjects. Denosumab showed significantly larger gains in BMD and greater reduction in bone turnover markers compared with alendronate. The overall safety profile was similar for both treatments.
Darfur: coverage of a genocide by three major US TV networks on their evening news
Authors: Eke Chinedu
Published: December 2008

This article examines the conflict in Darfur, which has been described by many including the President of the United States, as an ongoing genocide. To this end, I argue that the lack of adequate coverage of the killings in Darfur particularly in US network television evening news, has kept the public in the dark. This lack of information provided to the public has the potential to prolong the plight of Darfurians who have been killed, raped, starved and displaced, because there is little public pressure on policy makers, or outcry from the international community to stop the atrocities. It is also argued here that these television networks have the capacity to influence US foreign relations by mobilizing public opinion on pressing international issues such as the genocide in Darfur. Suggestions of how the news media can improve coverage are offered.
Boy, 15, tells of romps with magical seductive Ren aged 32: reporting allegations of female sexual abuse in the British press
Authors: Ndangam Lilian
Published: December 2008

This article examines British press coverage of Renate Williams a female teacher accused of sexually assaulting her adolescent male pupil during a school trip. On the basis of a textual analysis of tabloid and broadsheet reporting of the case, I argue that through focus on her appearance, marital status, background and mental health, the press representation worked to construct Williams as guilty even though she was subsequently acquitted of all charges by the criminal justice system. The frame of Williams transgressing both gender and professional expectations was central to the press reporting in this case. Relating the media reports in the Williams case to existing feminist scholarship on gender, crime and the media, the article argues that her gender was used as a source of titillation to diminish her accusation, thereby exposing the potential contradictions in press representations of allegations of sexual abuse by women.
‘Bibeldichtung’ und dichterische Darstellung. Kain in der Literatur um 1800: Klopstock, Gessner, Coleridge, Byron
Authors: Weidner Daniel
Published: December 2008

Biblical poetry is a still neglected genre in literary history. The current approaches are misleading both systematically and historically because they tend to split literary matter and biblical form, and they see biblical poetry as part of a broad secularization process. Four rewritings of Cain's biblical story, all written around 1800, show that literary approaches to the bible tended to produce new forms and innovative genres, such as an “undramatic” drama (Klopstock), a pastoral that implicitly criticises the pastoral worldview (Gessner), a prose poem that systematically blurs the border between poetry and prose (Coleridge), and a drama that combines the radial rebellion of Cain with the reinforcement of the biblical norms (Byron).
Reisen durch Raum und Zeit: Joseph Conrads Heart of Darkness und die Vernetzung der Welt um 1900
Authors: Frank Michael C.
Published: December 2008

It is a truism among historians, sociologists, and anthropologists that, in the West, the advent of modern technologies of travel and communication led to an “overcoming of distance” and even a gradual “annihilation of space and time”. Whereas turn-of-the-century geographers like George R. Parkin and H. J. Mackinder suggest that this is also true for much of the non-Western world, Joseph Conrad's Heart of Darkness dramatizes the Congo region as an “other space” that, although no longer white on the map, resists European attempts at empire-building and economic-technological expansion. Conrad's work shows that the perception of distance depends not only on the actual advances in travel and communication technologies, but also – and perhaps more importantly – on the construction of “imaginative geographies”. Around 1900, Central Africa was both spatially and temporarily distanced; it represented a different state of cultural development – a chronotope not (yet) part of the global network.
Die Ausschließlichkeit des Heiligen. Narrative Inklusions- und Exklusionsstrategien im mhd. ›Passional‹
Authors: Hammer Andreas , Seidl Stephanie
Published: December 2008

The article focuses on narrative strategies of inclusion and exclusion and their realisation in vernacular hagiographical texts. In the Life of St. Cecily in the Middle High German ›Passional‹, the exclusion from the secular culture can be shown in the refusing of the aristocratic conception of life by the protagonist; her turning to Christianity is reflected in selective, even exclusive strategies of perception: only by participating in the ›communio sanctorum‹, in Christianity, certain transcendent phenomena can be noticed; unbaptised persons keep being excluded. In contrast, in the Life of St. Martin of Tours, the protagonist's exclusion from the sphere of aristocratic culture is reflected in the confrontation of disparate body-concepts; the different forms of perception presented in this vita are excluding the saint from the other Christians. If the criteria of distinction become more diverse, if – as it is the case in the Life of St. Martin – the distinction between Pagan and Christian is not solely decisive any longer, strategies of inclusion and exclusion are operative on several levels: on the level of perception as well as on the level of body-concepts.
Effect of surface sizing on the surface chemistry of paper containing eucalyptus pulp
Authors: Teixeira Moutinho Isabel Maria , Kleen Anne Marjatta , Lopes Figueiredo Maria Margarida , Tavares Ferreira Paulo Jorge
Published: December 2008

The effect of different surface sizing formulations on the chemical features of surfaces of the papers produced from Eucalyptus kraft pulp was studied. The surface analysis techniques, electron spectroscopy for chemical analysis and time-of-flight secondary ion mass spectrometry were applied. An uncoated base paper, the reference material, was sized with blends of cationic starch with either co-acrylonitrile-acrylate or co-styrene-acrylate. The results of both techniques are in good agreement and complete each other. It was possible not only to detect the presence of the surface sizing agents on the paper surface but also to distinguish them and evaluate their distribution and relative concentration. In addition, it was found that application of higher amounts of the sizing formulations, at a constant ratio of 20% copolymer to starch, did not significantly change the chemical properties of the paper surfaces.
Using High Speed Video Imaging in the Study of Cracking Processes in Rock
Authors: Wong L. N. Y. , Einstein H. H.
Published: December 2008

This paper presents the use of a high speed video system (high speed camera) in studying the crack initiation, propagation, and coalescence in rocks. Prismatic laboratory-molded gypsum and Carrara marble specimens, which contained either a single artificial flaw or a pair of artificial flaws, were tested in uniaxial compression. The front face of the specimen was monitored by a high speed camera. By adopting an appropriate frame rate (1000 to 24 000 frames/s) and image resolution (256 by 512 to 1024 by 1024 pixels) of the high speed camera, we were able to observe the abrupt and violent cracking processes in rocks. In particular, it was possible to distinguish shear and tensile crack mechanisms, which so far was not possible and subject to many discussions in rock mechanics. Distinguishing the cracking details allowed us to record and interpret the entire cracking sequence. The aims of this paper are twofold. First, it briefly addresses the capability of the high speed camera technology to set the stage. Second, and this is the major contribution, it presents two comprehensive examples of how the interpretation of high speed videos is carried out to retrieve useful information on the cracking processes in rocks.
Serum adiponectin is associated with family history of diabetes independently of obesity and insulin resistance in healthy Korean men and women
Authors: Sull Jae Woong , Kim Hee Jin , Yun Ji Eun , Kim Grace , Park Eun Jung , Kim Soriul , Lee Hee Yeon , Jee Sun Ha
Published: December 2008

Background

Adiponectin has been reported as a new risk factor for the development of diabetes. However, it is not clear whether adiponectin levels are associated with family history of diabetes (FHD).

Objective

The objective of this study was to measure the independent association of serum adiponectin with FHD in relation to insulin resistance and obesity.

Methods

In 2006, a cross-sectional study was conducted in which waist circumference (WC), body mass index (BMI), and serum adiponectin were measured in 5919 healthy Korean men and women. Multiple linear regression models were used to assess the association of serum adiponectin levels with FHD. The population was classified into two groups according to median values for each of the following variables: WC, BMI, and homeostasis model assessment of insulin resistance (HOMA-IR).

Results

The positive FHD group had higher HOMA-IR and lower adiponectin levels in both men and women than those without FHD. Adiponectin levels were significantly associated with FHD in men and women respectively, after adjusting for age, BMI, and alcohol consumption (P=0.0123 and 0.0004). The relationship between adiponectin and FHD was similar between the high and low insulin resistance, BMI, and WC groups in male non-smokers and in all Korean women.

Conclusion

These results confirm that adiponectin levels are associated with FHD. These data also suggest that the association of serum adiponectin with FHD may be independent of obesity and insulin resistance.