bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequence homology: A poor predictive value for profilins cross-reactivity
Authors: Sankian Mojtaba , Varasteh Abdolreza , Pazouki Nazanin , Mahmoudi Mahmoud 
Published: September 2005

Summary

Background
Profilins are highly cross-reactive allergens which bind IgE antibodies of almost 20% of plant-allergic patients. This study is aimed at investigating cross-reactivity of melon profilin with other plant profilins and the role of the linear and conformational epitopes in human IgE cross-reactivity.

Methods
Seventeen patients with melon allergy were selected based on clinical history and a positive skin prick test to melon extract. Melon profilin has been cloned and expressed in E. coli. The IgE binding and cross-reactivity of the recombinant profilin were measured by ELISA and inhibition ELISA. The amino acid sequence of melon profilin was compared with other profilin sequences. A combination of chemical cleavage and immunoblotting techniques were used to define the role of conformational and linear epitopes in IgE binding. Comparative modeling was used to construct three-dimensional models of profilins and to assess theoretical impact of amino acid differences on conformational structure.

Results
Profilin was identified as a major IgE-binding component of melon. Alignment of amino acid sequences of melon profilin with other profilins showed the most identity with watermelon profilin. This melon profilin showed substantial cross-reactivity with the tomato, peach, grape and Cynodon dactylon (Bermuda grass) pollen profilins. Cantaloupe, watermelon, banana and Poa pratensis (Kentucky blue grass) displayed no notable inhibition. Our experiments also indicated human IgE only react with complete melon profilin. Immunoblotting analysis with rabbit polyclonal antibody shows the reaction of the antibody to the fragmented and complete melon profilin. Although, the well-known linear epitope of profilins were identical in melon and watermelon, comparison of three-dimensional models of watermelon and melon profilins indicated amino acid differences influence the electric potential and accessibility of the solvent-accessible surface of profilins that may markedly affect conformational epitopes.

Conclusion
Human IgE reactivity to melon profilin strongly depends on the highly conserved conformational structure, rather than a high degree of amino acid sequence identity or even linear epitopes identity.
Application of a disease-specific mapping function to estimate utility gains with effective treatment of schizophrenia
Authors: Lenert Leslie A , Rupnow Marcia FT , Elnitsky Christine 
Published: September 2005

Abstract

Background
Most tools for estimating utilities use clinical trial data from general health status models, such as the 36-Item Short-Form Health Survey (SF-36). A disease-specific model may be more appropriate. The objective of this study was to apply a disease-specific utility mapping function for schizophrenia to data from a large, 1-year, open-label study of long-acting risperidone and to compare its performance with an SF-36-based utility mapping function.

Methods
Patients with schizophrenia or schizoaffective disorder by DSM-IV criteria received 25, 50, or 75 mg long-acting risperidone every 2 weeks for 12 months. The Positive and Negative Syndrome Scale (PANSS) and SF-36 were used to assess efficacy and health-related quality of life. Movement disorder severity was measured using the Extrapyramidal Symptom Rating Scale (ESRS); data concerning other common adverse effects (orthostatic hypotension, weight gain) were collected. Transforms were applied to estimate utilities.

Results
A total of 474 patients completed the study. Long-acting risperidone treatment was associated with a utility gain of 0.051 using the disease-specific function. The estimated gain using an SF-36-based mapping function was smaller: 0.0285. Estimates of gains were only weakly correlated (r = 0.2). Because of differences in scaling and variance, the requisite sample size for a randomized trial to confirm observed effects is much smaller for the disease-specific mapping function (156 versus 672 total subjects).

Conclusion
Application of a disease-specific mapping function was feasible. Differences in scaling and precision suggest the clinically based mapping function has greater power than the SF-36-based measure to detect differences in utility.
The epidemiological impact of antiretroviral use predicted by mathematical models: a review
Authors: Baggaley Rebecca F , Ferguson Neil M , Garnett Geoff P 
Published: September 2005

AbstractThis review summarises theoretical studies attempting to assess the population impact of antiretroviral therapy (ART) use on mortality and HIV incidence. We describe the key parameters that determine the impact of therapy, and argue that mathematical models of disease transmission are the natural framework within which to explore the interaction between antiviral use and the dynamics of an HIV epidemic. Our review focuses on the potential effects of ART in resource-poor settings. We discuss choice of model type and structure, the potential for risk behaviour change following widespread introduction of ART, the importance of the stage of HIV infection at which treatment is initiated, and the potential for spread of drug resistance. These issues are illustrated with results from models of HIV transmission. We demonstrate that HIV transmission models predicting the impact of ART use should incorporate a realistic progression through stages of HIV infection in order to capture the effect of the timing of treatment initiation on disease spread. The realism of existing models falls short of properly reproducing patterns of diagnosis timing, incorporating heterogeneity in sexual behaviour, and describing the evolution and transmission of drug resistance. The uncertainty surrounding certain effects of ART, such as changes in sexual behaviour and transmission of ART-resistant HIV strains, demands exploration of best and worst case scenarios in modelling, but this must be complemented by surveillance and behavioural surveys to quantify such effects in settings where ART is implemented.
Melatonin, a potent agent in antioxidative defense: Actions as a natural food constituent, gastrointestinal factor, drug and prodrug
Authors: Hardeland Rüdiger , Pandi-Perumal SR 
Published: September 2005

Abstract
Melatonin, originally discovered as a hormone of the pineal gland, is also produced in other organs and represents, additionally, a normal food constituent found in yeast and plant material, which can influence the level in the circulation. Compared to the pineal, the gastrointestinal tract contains several hundred times more melatonin, which can be released into the blood in response to food intake and stimuli by nutrients, especially tryptophan. Apart from its use as a commercial food additive, supraphysiological doses have been applied in medical trials and pure preparations are well tolerated by patients. Owing to its amphiphilicity, melatonin can enter any body fluid, cell or cell compartment. Its properties as an antioxidant agent are based on several, highly diverse effects. Apart from direct radical scavenging, it plays a role in upregulation of antioxidant and downregulation of prooxidant enzymes, and damage by free radicals can be reduced by its antiexcitatory actions, and presumably by contributions to appropriate internal circadian phasing, and by its improvement of mitochondrial metabolism, in terms of avoiding electron leakage and enhancing complex I and complex IV activities. Melatonin was shown to potentiate effects of other antioxidants, such as ascorbate and Trolox. Under physiological conditions, direct radical scavenging may only contribute to a minor extent to overall radical detoxification, although melatonin can eliminate several of them in scavenger cascades and potentiates the efficacy of antioxidant vitamins. Melatonin oxidation seems rather important for the production of other biologically active metabolites such as N
1-acetyl-N
2-formyl-5-methoxykynuramine (AFMK) and N
1-acetyl-5-methoxykynuramine (AMK), which have been shown to also dispose of protective properties. Thus, melatonin may be regarded as a prodrug, too. AMK interacts with reactive oxygen and nitrogen species, conveys protection to mitochondria, inhibits and downregulates cyclooxygenase 2.
Pain and pain treatments in European palliative care units. A cross sectional survey from the European Association for Palliative Care Research Network
Authors: Klepstad Pa , Kaasa Stein , Cherny Nathan , Hanks Geoffrey , de Conno Franco ,   Research Steering Committee of the EAPC
Published: September 2005

The Research Network of the European Association for Palliative Care (EAPC) performed a survey of 3030 cancer patients from 143 palliative care centres in 21 European countries. The survey addressed pain intensity and the use of non-opioid analgesics, adjuvant analgesics and opioids. Patients were treated with analgesics corresponding to the WHO pain ladder step I (n / 855), step II (n / 509) and step III (n / 1589). The investigators assessed 32% of the patients as having moderate or severe pain. In general there were small differences between pain intensities across different countries. Cancer primary sites and the presence of metastasis had only minor influences on pain intensity. The most frequently used nonopioid analgesics were NSAIDs (26%) and paracetamol (23%). Adjuvant analgesics or coanalgesics used by / 1% of the patients were corticosteroids (39%), tricylic antidepressants (11%), gabapentin (5%), bisphosphonates (4%), clonazepam (2%), carbamazepine (4%) and phenytoin (2%). The use of non-opioid analgesics and co-analgesics varied widely between countries. Opioids administered for mild to moderate pain were codeine (8%), tramadol (8%), dextropropoxyphene (5%) and dihydrocodeine (2%). Morphine was the most frequently used opioid for moderate to severe pain (oral normal release morphine: 21%; oral sustained-release morphine: 19%; iv or sc morphine: 10%). Other opioids for moderate to severe pain were transdermal fentanyl (14%), oxycodone (4%), methadone (2%), diamorphine (2%) and hydromorphone (1%). We observed large variations in the use of opioids across countries. Finally, we observed that only a minority of the patients who used morphine needed very high doses.
The healthcare needs of chronic obstructive pulmonary disease patients in the last year of life
Authors: Elkington Helena , White Patrick , Addington-Hall Julia , Higgs Roger , Edmonds Polly 
Published: September 2005

Chronic obstructive pulmonary disease (COPD) causes almost as many deaths as lung cancer, yet evidence about the impact of COPD in the latter stages of illness is limited. We assessed the healthcare needs of COPD patients in the last year of life through a retrospective survey of the informants of 399 deaths from COPD in four London health authorities between January and May 2001. We assessed symptoms, day to day functioning, contact with health and social services, formal and informal help with personal care, information received and place of death. We obtained data on 209 (52%) deceased subjects (55% male), average age at death was 76.8 years. Based on the reports of informants of the deaths: 98% were breathless all the time or sometimes in the last year of life; other symptoms reported all the time or sometimes included fatigue or weakness (96%), low mood (77%) and pain (70%); breathlessness was partly relieved in over 50% of those treated; control of other symptoms was poor, with low mood relieved in 8% and no treatment for low mood received by 82% of sufferers; 41% left the house less than once a month or never; 47% were admitted to hospital at least twice in the last year of life; 51% received regular check-ups for their chest; 36% had check-ups by a hospital consultant; 35% saw their general practitioner (GP) less than once every three months or never; 63% knew they might die; 67% died in hospital. Patients who died from COPD lacked surveillance and received inadequate services from primary and secondary care in the year before they died. The absence of palliative care services highlights the need for research into appropriate models of care to address uncontrolled symptoms, information provision and end of life planning in COPD.
The House of Lords Select Committee on the Assisted Dying for the Terminally Ill Bill: implications for specialist palliative care
Authors: Finlay I G , Wheatley V J , Izdebski C 
Published: September 2005

The Assisted Dying for the Terminally Ill Bill proposed to legalise both euthanasia and physician-assisted suicide for those with a terminal illness in the UK. A House of Lords Select Committee was convened to scrutinise this Bill and has recently published its report, which will be debated in Parliament on October 10th 2005. The written and oral evidence submitted to the Select Committee represented a wide range of views on 'assisted dying'. Much of the evidence from those countries which have legalised euthanasia/physician-assisted suicide (The Netherlands, Belgium, Switzerland and Oregon, USA) dealt with the practicalities of ending life, and the legal procedures and safeguards instigated in these countries. All the written and oral evidence in the public domain was scrutinised by the authors whilst the Select Committee was sitting. We have extracted those themes relevant to specialist palliative care practice and present them in this paper. We hope that this will provide a useful resource to inform the forthcoming public debate on assisted dying. The evidence of harms inherent in making such a change in the law, as presented to the Select Committee, has moved all three authors to oppose a change in the law.
Clinical Trial Results of a HER2/neu (E75) Vaccine to Prevent Recurrence in High-Risk Breast Cancer Patients
Authors: Peoples George E. , Gurney Jennifer M. , Hueman Matthew T. , Woll Mike M. , Ryan Gayle B. , Storrer Catherine E. , Fisher Christine , Shriver Craig D. , Ioannides Constantin G. , Ponniah Sathibalan 
Published: September 2005

Purpose E75 is an immunogenic peptide from the HER2/neu protein that is highly expressed in breast cancer. We are conducting a clinical trial of an E75 + granulocyte-macrophage colony-stimulating factor vaccine to assess safety, immunologic response, and the prevention of clinical recurrences in patients with disease-free, node-positive breast cancer (NPBC). Patients and Methods Fifty-three patients with NPBC were enrolled and HLA typed. HLA-A2+ patients (n = 24) were vaccinated, and HLA-A2− patients (n = 29) are observed prospectively as clinical controls. Local/systemic toxicities, immunologic responses, and time to recurrence are being measured. Results Only minor toxicities have occurred (one grade 3 [4%]). All patients have demonstrated clonal expansion of E75-specific CD8+T cells that lysed HER2/neu-expressing tumor cells. An optimal dosage and schedule have been established. Patients have developed delayed-type hypersensitivity reactions to E75 postvaccination compared with controls (33 v 7 mm; P < .01). HLA-A2+ patients have been found to have larger, more poorly differentiated, and more hormonally insensitive tumors compared to HLA-A2− patients. Despite this, the only two deaths have occurred in the control group. The disease-free survival in the vaccinated group is 85.7% compared to 59.8% in the controls at 22 months' median follow-up with a recurrence rate of 8% compared to 21%, respectively (P < .19). Median time to recurrence in the vaccinated patients was prolonged (11 v 8 months), and recurrence correlated with a weak delayed-type hypersensitivity response. Conclusion This HER2/neu (E75) vaccine is safe and effective in eliciting a peptide-specific immune response in vivo. Induced HER2/neu immunity seems to reduce the recurrence rate in patients with NPBC.
Prediction of Response to Neoadjuvant Chemotherapy by Sequential F-18-Fluorodeoxyglucose Positron Emission Tomography in Patients With Advanced-Stage Ovarian Cancer
Authors: Avril Norbert , Sassen Stefanie , Schmalfeldt Barbara , Naehrig Joerg , Rutke Stephan , Weber Wolfgang A. , Werner Martin , Graeff Henner , Schwaiger Markus , Kuhn Walther 
Published: September 2005

Purpose The aim of this study was to evaluate sequential F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) to predict patient outcome after the first and third cycle of neoadjuvant chemotherapy in advanced-stage (International Federation of Gynecology and Obstetrics stages IIIC and IV) ovarian cancer. Patients and Methods Thirty-three patients received three cycles of carboplatin-based chemotherapy, followed by cytoreductive surgery. Quantitative FDG-PET of the abdomen and pelvis was acquired before treatment and after the first and third cycle of chemotherapy. Changes in tumoral FDG uptake, expressed as standardized uptake values (SUV), were compared with clinical and histopathologic response; overall survival served as a reference. Results A significant correlation was observed between FDG-PET metabolic response after the first (P = .008) and third (P = .005) cycle of chemotherapy and overall survival. By using a threshold for decrease in SUV from baseline of 20% after the first cycle, median overall survival was 38.3 months in metabolic responders compared with 23.1 months in metabolic nonresponders. At a threshold of 55% decrease in SUV after the third cycle median overall survival was 38.9 months in metabolic responders compared with 19.7 months in nonresponders. There was no correlation between clinical response criteria (P = .7) or CA125 response criteria (P = .5) and overall survival. There was only a weak correlation (P = .09) between histopathologic response criteria and overall survival. Conclusion Sequential FDG-PET predicted patient outcome as early as after the first cycle of neoadjuvant chemotherapy and was more accurate than clinical or histopathologic response criteria including changes in tumor marker CA125. FDG-PET appears to be a promising tool for early prediction of response to chemotherapy.
American Society of Clinical Oncology Guideline Recommendations for Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer
Authors: Lyman Gary H. , Giuliano Armando E. , Somerfield Mark R. , Benson Al B. , Bodurka Diane C. , Burstein Harold J. , Cochran Alistair J. , Cody Hiram S. , Edge Stephen B. , Galper Sharon , Hayman James A. , Kim Theodore Y. , Perkins Cheryl L. , Podoloff Donald A. , Sivasubramaniam Visa Haran , Turner Roderick R. , Wahl Richard , Weaver Donald L. , Wolff Antonio C. , Winer Eric P. 
Published: September 2005

PurposeTo develop a guideline for the use of sentinel node biopsy (SNB) in early stage breast cancer.MethodsAn American Society of Clinical Oncology (ASCO) Expert Panel conducted a systematic review of the literature available through February 2004 on the use of SNB in early-stage breast cancer. The panel developed a guideline for clinicians and patients regarding the appropriate use of a sentinel lymph node identification and sampling procedure from hereon referred to as SNB. The guideline was reviewed by selected experts in the field and the ASCO Health Services Committee and was approved by the ASCO Board of Directors.ResultsThe literature review identified one published prospective randomized controlled trial in which SNB was compared with axillary lymph node dissection (ALND), four limited meta-analyses, and 69 published single-institution and multicenter trials in which the test performance of SNB was evaluated with respect to the results of ALND (completion axillary dissection). There are currently no data on the effect of SLN biopsy on long-term survival of patients with breast cancer. However, a review of the available evidence demonstrates that, when performed by experienced clinicians, SNB appears to be a safe and acceptably accurate method for identifying early-stage breast cancer without involvement of the axillary lymph nodes.ConclusionSNB is an appropriate initial alternative to routine staging ALND for patients with early-stage breast cancer with clinically negative axillary nodes. Completion ALND remains standard treatment for patients with axillary metastases identified on SNB. Appropriately identified patients with negative results of SNB, when done under the direction of an experienced surgeon, need not have completion ALND. Isolated cancer cells detected by pathologic examination of the SLN with use of specialized techniques are currently of unknown clinical significance. Although such specialized techniques are often used, they are not a required part of SLN evaluation for breast cancer at this time. Data suggest that SNB is associated with less morbidity than ALND, but the comparative effects of these two approaches on tumor recurrence or patient survival are unknown.
Defining Cancer Patients As Being in the Terminal Phase: Who Receives a Formal Diagnosis, and What Are the Effects?
Authors: Aabom B. , Kragstrup J. , Vondeling H. , Bakketeig L.S. , Stovring H. 
Published: September 2005

Purpose Physicians either do not define cancer patients as being terminal, or their prognostic estimates tend to be optimistic. This might affect patients' appropriate and timely referral to specialist palliative care services or can lead to unintended acute hospitalization. Patients and Methods We used the Danish Cancer Register and four administrative registers to perform a retrospective cohort study in 3,445 patients who died as a result of cancer. We used the Danish “terminal declaration” issued by a physician as a proxy for a formal terminal diagnosis (prognosis of death within 6 months). The terminal declaration gives right to economic benefits and increased care for the dying. We investigated patient-related factors of receiving an explicit terminal diagnosis by logistic regression and then analyzed the effects of such a diagnosis on admission rate per week and place of death. Results Thirty-four percent of patients received a formal terminal diagnosis. Age of ≥ 70 years (odds ratio [OR], 0.44; 95% CI, 0.34 to 0.56; P < .001), women (OR, 0.81; 95% CI, 0.69 to 0.96; P = .02), hematologic cancer (OR, 0.20; 95% CI, 0.09 to 0.41; P < .001), and a less than 1-month survival time (OR, 0.10; 95% CI, 0.07 to 0.15; P < .001) were associated with a lesser likelihood of receiving a formal terminal diagnosis. Explicit terminal diagnosis was associated with lower admission rate and an adjusted OR of hospital death of 0.25 (95% CI, 0.21 to 0.29). Conclusion Women and the elderly were less likely to receive a formal terminal diagnosis. The formal terminal diagnosis reduced hospital admissions and increased the possibilities of dying at home.