bluuebunny/crossref_metadata_2025_split huggingface dataset:
Libertarian Bioethics and Religion: The Case of H. Tristram Engelhardt, Jr.
Authors: Merry Michael S. 
Published: August 2004

ABSTRACTThis paper is a critique of certain moral perspectives that are found in the second edition of Engelhardt's Foundation of Bioethics. These views are spelled out in explicit detail in his second edition, and follow on the heels of a profound religious conversion. Engelhardt is an eminent bioethicist with strong religious convictions that overlay much of his writing. The author wishes to question some of the conclusions that Engelhardt reaches as they touch upon moral frameworks, pluralism, and a ‘secular’ bioethics.
Research Ethics Committees: Differences and Moral Judgement
Authors: Edwards Sarah J.L. , Ashcroft Richard , Kirchin Simon 
Published: August 2004

ABSTRACTMany people argue that disagreements and inconsistencies between Research Ethics Committees are morally problematic and there has been much effort to ‘harmonise’ their judgements. Some inconsistencies are bad because they are due to irrationality, or carelessness, or the operation of conflicting interests, and so should be reduced or removed. Other inconsistencies, we argue, are not bad and should be left or even encouraged. In this paper we examine three arguments to reject the view that we should strive for complete consistency between committees. The first argument is that differences in judgement are not necessarily incompatible with ideas of justice for patients who are potential participants of research reviewed by different committees. We call this ‘the justice argument.’ The second argument is that such committees do not have access to a single moral truth, to which their judgement is supposed to correspond. We call this the ‘moral pluralism argument.’ The third argument is that the process of ethics committee review is also morally relevant and not solely the outcome. We call this the ‘due process argument.’ While we fall short of establishing exactly how much variation and on what substantive issues would be ethically permissible, we show that it is largely inevitable and that a certain amount of variation could be seen as a desirable part of the institution of medical research.
When Hope Makes Us Vulnerable: A Discussion of Patient–Healthcare Provider Interactions in the Context of Hope
Authors: Simpson Christy 
Published: August 2004

ABSTRACTWhen hope is discussed in bioethics’ literature, it is most often in the context of ‘false hopes’ and/or how to maintain hope while breaking bad news to patients. Little or no time is generally devoted to the description of hope that supports these analyses. In this paper, I present a detailed description of hope, one designed primarily for the healthcare context. Noting that hope is an emotional attitude, four key aspects are explored. In particular, the function of imagination in hope is discussed in depth. Through an examination of the relationship between hope and vulnerability, I demonstrate how adequately describing hope can broaden the normative inquiry into the role of hope in healthcare. Three ways in which persons with hope can be vulnerable are illustrated, and the challenge of how healthcare providers can attend in moral ways to the hopes of patients is identified.
Focus Group Interviews Examining Attitudes Towards Medical Research Among the Japanese: A Qualitative Study
Authors: Asai Atsushi , Ohnishi Motoki , Nishigaki Etsuyo , Sekimoto Miho , Fukuhara Shunichi , Fukui Tsuguya 
Published: August 2004

ABSTRACTObjectives: the purpose of this study is to explore laypersons’ attitudes towards and experiences of medical research, and to compare them with those of physicians in Japan.Designs and Participants: fourteen Japanese adults from the general public and seven physicians participated in one of three focus interviews.Setting: Osaka, Japan.Results: trust and distrust in the physician by whom the participants were invited to participate in research played a considerable role in their decisions about participation. That the participants felt an obligation to participate was also expressed. The lay participants perceived medical research as something entirely outside of their world. A greater willingness to volunteer for research was expressed if there were direct benefits to themselves or their families. Research methods such as use of placebos, double blinds, and randomisations seemed to cause negative attitudes to medical research. All physicians were convinced of the need for medical research, including double‐blinded randomised control trials, and its significant role in medical progress. Most physicians thought that the greater awareness of the need for medical research in the community and a better understanding of the psychology of potential research participants were necessary and urgent.Conclusions: there is a good possibility that the lay public and medical professionals have sharply different beliefs about and attitudes towards every aspect of medical research. Building up a better and equal patient‐doctor relationship based on trust is a key issue in medical research, and it is mandatory to fill the gap in perception regarding medical research between them through fully informed debates.
Results from the treatment of advanced stage squamous cell carcinoma of the nasal planum in cats, using a combination of intralesional carboplatin and superficial radiotherapy: a pilot study
Authors: De Vos J. P. , Burm A. G. O. , Focker B. P. 
Published: August 2004

AbstractSix cats with an advanced stage squamous cell carcinoma (SCC) of the nasal planum were treated with a combination of superficial radiotherapy and intralesional carboplatin therapy. This multimodality protocol was well tolerated by the majority of cats and resulted in complete responses in all cats (100%). Median follow‐up for all cats is 268 days, and the median time‐to‐recurrence, time‐to‐progression and overall survival have not yet been reached. Our study, although limited in number of animals and with a relatively short median follow‐up compared to other studies for this disease, suggests that a combination of radiotherapy and intralesional carboplatin is a useful treatment option for an advanced stage SCC of the nasal planum in cats and warrants further application of the multimodality approach presented here.
Investigating the in vitro interactive effects of ionizing radiation and pamidronate in a canine osteosarcoma cell line
Authors: Charney S. C. , Fan T. M. , De Lorimier L. P. , Lacoste H. I. 
Published: August 2004

Introduction:  Dogs with osteosarcoma suffer intense bone pain. Conventional palliative treatment options include ionizing radiation with or without systemic chemotherapy. Intravenous pamidronate is a first‐line therapeutic agent in people with painful skeletal metastases and is currently being evaluated for the management of osteolytic pain associated with canine osteosarcoma. The theoretical combination of radiation and pamidronate for managing bone pain appears to be a rational treatment option, however, in vitro experiments demonstrating additive or supraadditve cytotoxic effects of these two modalities would further support the clinical institution of this novel combination therapy. The purpose of this study was to evaluate the in vitro cytotoxicity of ionizing radiation and pamidronate in a canine OSA cell line and to characterize the interaction between these two therapeutic modalities when used in combination.Methods:  The canine osteosarcoma cell line, HMPOS, was subjected independently to varying doses of ionizing radiation (100 cGy, 300 cGy, 400 cGy, 600 cGy, 800 cGy, or 1000 cGy) or different concentrations of pamidronate (10, 25, 50, 66, 75, 100, 150, 200, and 250 μM). Cells were harvested following 48 hours of incubation and cell viability was assessed by flow cytometric analysis. Dose‐response curves were generated, and a theoretical ED50 for each treatment modality calculated. An ED50 isobologram was created to determine if different combinations of ionizing radiation and pamidronate (isoboles) would demonstrate subadditive, additive, or supraadditve cytotoxic effects.Results:  The ED50 of ionizing radiation and pamidronate were 614 cGy and 65.3 μM, respectively. Of the six different isobole combinations evaluated, three produced supraadditve effects, one produced a subadditive effect, and two produced additive effects.Conclusions:  Both ionizing radiation and pamidronate independently exert in vitro cytotoxic effects. Positive interactive effects can be generated, but only with specific isobole combinations. The results from this in vitro study support the use of specific combinations of ionizing radiation and pamidronate in order to maximize the cytotoxic properties of both treatment modalities.
The effects of cyclooxygenase‐2 inhibition on apoptosis and cell cycle distribution using two in vitro models of nasal squamous cell carcinoma
Authors: Heller D. A. , Fan T. M. , Charney S. C. , De Lorimier L. P. , Wallig M. A. 
Published: August 2004

Objective:  Despite numerous attempts using a variety of therapeutic modalities, response rates and survival times for canine nasal squamous cell carcinoma remain poor. The goals of this study are to determine if a COX‐2 selective inhibitor induces apoptosis and alters cell cycle distribution in two in vitro models of nasal squamous cell carcinoma, and to establish a basis for future clinical trials using COX‐2 inhibitors as radiosensitizing agents.Methods:  The nasal squamous cell carcinoma cell lines FAT‐7 (rat) and RPMI 2650 (human) were purchased from ATCC (Manassas, VA). Cell pellets were stained for COX‐2 expression using standard immunohistochemical techniques. Following the determination of growth kinetics for each cell line, cells were plated in triplicate using 25 cm2 tissue culture flasks and incubated with different concentrations of a COX‐2 selective inhibitor (0, 1, 10, 50 and 100 μM) for 72 hours. Cells were stained with Annexin‐V and propidium iodide (Oncogene Research Products) and analyzed with flow cytometry to assess cell viability. Cell cycle distribution was determined using a propidium iodide methodology and flow cytometric analysis.Results:  Preliminary results show that the addition of a COX‐2 selective inhibitor caused a dose‐dependent cytotoxicity on the FAT‐7 cells. Viability at 72 hours ranged from 95.4% for control samples to 7.46% for cells incubated at 100 μM. Changes in cell cycle distribution were also detected.Conclusions:  Future study is warranted to determine if the addition of a COX‐2 selective inhibitor will increase response rates and overall survival in a population of spontaneously arising canine nasal squamous cell carcinomas.
Phase I clinical trial evaluating STI571 in tumor bearing cats
Authors: Lachowicz J. L. , Post G. S. 
Published: August 2004

Introduction:  STI571 (Gleevec, imatinib mesylate) is a receptor tyrosine kinase inhibitor with selectivity for Bcr‐Abl, platelet‐derived growth factor (PDGF), stem cell factor (SCF), and c‐Kit. Side effects with use in humans include vomiting, diarrhea, nausea, myalgia, edema, and cutaneous reactions. Renal and hepatic toxicity have also been reported. In dogs, there is significant hepatic toxicity at sub‐clinical doses. The purpose of this prospective study was to determine the toxicity level and potential treatment protocol in tumor bearing cats.Methods:  A phase I clinical trial was performed in client owned cats using an escalating dose of STI571 in tumor bearing cats. Cats included in the study had a histologic diagnosis of fibrosarcoma or other tumors and were staged with CBC, biochemical profile, thoracic radiographs, and abdominal ultrasound. None of the cats received concurrent chemotherapy, but those previously treated with surgery, radiation therapy, or chemotherapy, were not excluded. The initial starting dose was 5 mg/cat PO SID and was gradually increased to 10 and 20 mg/cat PO SID at a 2–6 week interval depending on laboratory work and disease progression. A repeat physical examination, CBC, and biochemical profile, were performed every 2 weeks for 2 rechecks, then every 4 weeks.Results:  Six cats were enrolled in the study. Four cats had oral squamous cell carcinoma, and two cats had cutaneous fibrosarcoma. One cat demonstrated leukocytosis, increased liver enzymes, and signs of acute renal failure two weeks after initiating therapy (5 mg PO SID). No dose escalation was made in this cat. Five cats endured dose escalations of 10 mg PO SID in two cats and 20 mg PO SID in three cats and were treated for 2–4 months. None of these cats experienced any signs of toxicity as measured by CBC and biochemical profile.Conclusions:  Only one cat experienced toxicity that may have been associated with low dose administration of STI571. As most cats tolerated the drug without an adverse effect, further evaluation of STI571 in a phase II clinical trial is warranted.
A comparison of two pamidronate dosing protocols on bone turnover in normal dogs and dogs with osteosarcoma
Authors: Lacoste H. I. , Fan T. M. , De Lorimier L. P. , Charney S. C. 
Published: August 2004

Introduction:  Dogs with appendicular osteosarcoma (OSA) excrete higher concentrations of urine cross‐linked N‐telopeptide of type I collagen (NTx) than normal dogs. NTx is a specific biochemical marker of osteoclastic activity. Pamidronate is a bone‐modulating agent that exerts potent inhibitory effects on osteoclasts. The use of pamidronate is currently being evaluated for the management of osteolytic bone pain in dogs with appendicular osteosarcoma. Despite pamidronate's increasing usage in veterinary oncology, optimal dosing has yet to be determined. Commonly utilized dosages range from 1–2 mg/kg, given intravenously (IV) as a 2‐hour constant rate infusion every 28 days. The purpose of this prospective study was to compare the biological activity of two pamidronate doses (1 mg/kg vs. 2 mg/kg) in the suppression of urine NTx excretion in normal dogs and dogs with appendicular osteosarcoma.Methods:  Seventeen OSA dogs receiving single‐agent pamidronate as palliative therapy were evaluated. Group 1A (n = 10) received a dose of 1 mg/kg and group 2A (n = 7) received a dose of 2 mg/kg IV. Urine NTx level were measured at day 0 and 28 using a commercial ELISA (Ostex International). Urine NTx level were also measured in 6 normal dogs: Group 1B (n = 3) received a dose of 1 mg/kg and group 2B (n = 3) received a dose of 2 mg/kg. In normal dogs, urine NTx levels were recorded weekly for six consecutive weeks.Results:  In dogs with osteosarcoma, greater reductions in urine NTx excretion from baseline values were demonstrated at 2 mg/kg versus 1 mg/kg (57% and 23%, respectively). Likewise, in normal dogs, urine NTx excretion was suppressed to a greater extent with a dosage of 2 mg/kg versus 1 mg/kg (69% and 23%, respectively).Conclusion:  Pamidronate possesses biologic activity in both normal dogs and in dogs with osteosarcoma, as assessed by reductions in urine NTx excretion. Based upon reductions in urine NTx excretion, a dosage of 2 mg/kg appears more effective than 1 mg/kg.
Proteomic profiling using SELDI‐TOF mass spectrometry: a diagnostic tool for canine B‐cell lymphoma
Authors: Lana S. E. , Powell T. D. , Gaines P. J. , Wisnewski N. , Stinchcomb D. T. , Withrow S. J. 
Published: August 2004

Introduction:  Surface enhanced laser desorption ionization time of flight (SELDI‐TOF) mass spectrometry is a powerful new tool for biomarker discovery and diagnostic test development. In this process, proteins in biological samples are selectively bound to chip surfaces that have various chemistries and then subjected to mass spectrometry. Selectively bound proteins are separated by mass and the relative quantities of each protein compared among samples. Unlike conventional diagnostic test formats that commonly use single biomarkers, SELDI‐TOF technology allows multiple biomarkers to be used in a single assay to improve sensitivity and specificity. This technology has been used to improve diagnostic tests for human prostate and ovarian cancers. The objective of this study is to investigate the utility of this technology for the proteomic profiling of canine B‐cell lymphoma. Developing a diagnostic serum screening test for B‐cell lymphoma in dogs would be valuable as early diagnosis and treatment may confer a more favorable outcome.Methods:  Serum samples were collected from 26 dogs diagnosed with B‐cell lymphoma prior to treatment and from 26 apparently healthy dogs that were similar in age, breed, and sex to the test group. Serum proteins were selectively bound to weak cationic, strong anionic, and nickel chelating chip surface chemistries under optimized buffer conditions, and subjected to mass spectrometry. The protein profiles were then compared using Biomarker Wizard and classification trees developed using Biomarker Patterns software from Ciphergen Biosystems, Inc (Fremont, CA).Results:  To date several putative biomarkers have been identified. These putative biomarkers have been used to build classification tree models that predict disease in test samples. Preliminary results using cross‐validation of the test and control sample sets indicate that trees built with two or more biomarkers have greater than 90% sensitivity and specificity.Conclusions:  Proteomic profiling using SELDI‐TOF technology in canine serum is feasible. Further testing is planned to confirm these initial results.
Detection of retinoid receptor expression patterns in canine normal lymph nodes and in nodal lymphomas
Authors: Souza C. H. M. , Valli V. E. O. , Fan T. M. , Vail D. M. 
Published: August 2004

Introduction:  Retinoids are derivatives of vitamin A, which are essential for cell growth and differentiation of a variety of cells. Retinoid activity occurs after binding to a class of nuclear receptors termed retinoic acid receptor (RAR) and retinoid X receptor (RXR). Receptor‐ligand interactions ultimately activate the transcription of target genes. Retinoids have been shown in vitro to participate in both lymphocyte activation and apoptosis. In human cancer patients, specific ligands to retinoid receptors have been approved for the treatment of T‐cell cutaneous lymphomas. The use of retinoids for the treatment of additional lymphoid malignancies, both of B and T‐cell types, has been speculated. In vitro experiments demonstrating lymphocyte apoptosis subsequent to treatment with both natural and synthetic retinoids further support the potential utility of retinoid therapy in spontaneous lymphoid malignancies.Objectives:  To detect the pattern of retinoid receptor expression (RAR and RXR) and their isoforms (α, β, and γ) in normal lymph nodes and in nodal lymphomas in dogs.Methods:  Immunohistochemistry was performed in tissue specimens derived from naturally occurring cases of nodal lymphomas and normal lymph nodes from dogs. Rabbit polyclonal antibodies (Santa Cruz Biotechnology), previously demonstrated to be cross‐reactive with canine tissue, were utilized to assess the expression patterns of RAR/RXR and their respective isoforms (α, β, and γ) in all pathologic and normal tissue samples evaluated.Results:  Normal lymph nodes were consistently negative for all isoforms. In hyperplastic nodes, macrophages were positive for all isoforms. Lymphomas both of B and T‐cell type stained strongly positive for the isoforms RARα and RXRγ.Conclusions:  A distinctive pattern of expression between lymphomas, lymphoid hyperplasia, and normal lymph nodes was detected in dogs. Different retinoid receptor expression profiles from normal lymph nodes and nodal lymphomas seem to be of diagnostic importance. Further investigation with larger number of lymphoma cases is warranted to thoroughly characterize retinoid receptor expression patterns in lymphoid malignancies with the possibility of using specific retinoid receptor ligands for the treatment of canine nodal lymphomas.
Thalidomide for the treatment of hemangiosarcoma in dogs
Authors: Woods J. P. , Mathews K. A. , Binnington A. G. 
Published: August 2004

Introduction:  Hemangiosarcoma is a malignant neoplasm of vascular endothelium occurring most frequently in older large breed dogs. Noncutaneous hemangiosarcoma is highly metastatic (>80% at diagnosis). Surgery is the primary method of treatment; however, even with adjuvant chemotherapy the prognosis for long‐term survival is low. Hence, new therapies are needed.The sedative‐hypnotic drug thalidomide (alpha‐N‐phthalimidoglutarimide) was withdrawn from general distribution in the 1960's after recognition of its teratogenicity and association with phocomelia. Recently, discredited thalidomide is making a comeback for its immunomodulatory and antiangiogenesis properties to treat inflammatory, infectious, and neoplastic diseases in people. Thalidomide can inhibit the proliferation of blood vessels associated with tumour development, thereby stopping or slowing tumour growth (similar to the devastating effect of the in utero interference with the blood supply of the developing limbs of the fetus).Therefore, the purpose of this study was to retrospectively obtain the results of thalidomide therapy for canine hemangiosarcoma. A prospective study for the use of thalidomide therapy for the treatment of canine hemangiosarcoma was also planned.Materials and Methods:  Fourteen dogs with histologically diagnosed hemangiosarcoma were retrospectively entered into the study. Dogs were treated at 100–400 mg per day. Unfortunately, a legal, consistent source of thalidomide for treatment of dogs could not be obtained; therefore, the prospective study was postponed.Results:  The median survival was 61 days with a range of 0 days to 2 years.Conclusions:  Only limited efficacy data are available so far to define the clinical utility of thalidomide in canine hemangiosarcoma. However, in this pilot study there were prolonged responses to thalidomide in some patients which prompts a phase 2 investigation of thalidomide in canine hemangiosarcoma. The optimal dose and schedule of administration in dogs remains to be determined but the absence of myelosuppressive and other important adverse effects suggests thalidomide could be used in combination with chemotherapy. We conclude that thalidomide (or its analogues) could open the possibility for novel treatment that targets tumours and their microenvironment.
Evaluation of red blood cells stored at −80°C in excess of 10 years
Authors: Lecak J. , Scott K. , Young C. , Hannon J. , Acker J.P. 
Published: August 2004

BACKGROUND:  RBCs frozen in 40 percent (wt/vol) glycerol are currently approved by the FDA and the AABB for storage at −80°C for up to 10 years.STUDY DESIGN AND METHODS:  This study examined 20 RBC units that had been cryopreserved in 40 percent (wt/vol) glycerol and stored at −80°C for up to 22 years. Measures of the freeze‐thaw‐wash (FTW) recovery, ATP, 2,3‐DPG, methemoglobin, RBC indices, morphology, and osmotic fragility were made immediately after deglycerolization and after 24 hours of storage at 4°C.RESULTS:  RBCs frozen for longer than 10 years had acceptable mean FTW recovery, normal oxygen transport function, RBC morphology, RBC indices, methemoglobin, and osmotic fragility. Statistical analysis indicated that the in‐vitro viability and function of cryopreserved RBCs was not dependent on the length of frozen storage or postthaw storage at 4°C but did correlate with the storage length at 4°C before cryopreservation.CONCLUSION:  The data reported in this study demonstrate that RBCs can be stored at −80°C beyond 10 years with acceptable in‐vitro quality and suggest that more defined criteria for the cryopreservation process be adopted.