Aromatherapy in practice: creative nursing care--Daw House Hospice.
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Aromatherapy↗
Biomedical subjects
R Osborne
Publications and source records attributed to R Osborne.
Good manners for the pharmaceutical industry.
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Antineoplastic Combined Chemotherapy Protocols↗
Supernumerary status.
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Clinical Competence↗
A phase II study of leuprolide in advanced/recurrent endometrial cancer.
In order to determine the efficacy and toxicity of the gonadotrophin-releasing hormone agonist Leuprolide in the management of patients with recurrent or metastatic endometrial cancer, we performed a phase II study. Patients were included if there was clinical or radiological documentation of bidimensionally measurable recurrent or metastatic endometrial cancer that was deemed incurable. Treatment was 7.5 mg i.m. every 28 days, and was to continue for at least 2 courses until evidence of disease progression, patient requested withdrawal, or unacceptable toxicity. Twenty-five patients received Leuprolide for recurrent or metastatic endometrial cancer. The median age at study entry was 62 years, and the median time from initial diagnosis to first course of Leuprolide was 25 months. Six patients had received no systemic or radiotherapy prior to study entry, and 2 of these had not previously undergone hysterectomy. Fifteen patients received prior pelvic radiotherapy and 3 patients received prior whole abdominal radiotherapy. Nine of the 25 patients had received prior progestational agents, and 2 had received prior systemic chemotherapy. There were no responders, 8 patients had stable disease for a median 5 months (range 1-8), 14 patients progressed on therapy, and 3 patients were not evaluable for response due to receiving only 1 treatment. One patient experienced a grade 3 toxicity that was possibly attributable to Leuprolide (deep venous thrombosis). The median survival from study entry was 6 months. Twelve patients received progesterone after discontinuing this study, and none responded. Leuprolide does not appear to be a clinically active agent in the treatment of recurrent or metastatic endometrial cancer.
Adult↗
IRAG working group 3. Cell function-based assays. Interagency Regulatory Alternatives Group.
Cell function-based tests measure responses of cells at sublytic concentrations of test agents. The fluorescein leakage assay measures effects of substances on the barrier function of epithelial monolayers or multilayers (MDCK or NHEK cells) as in vitro models of corneal epithelial function. Two IRAG data submissions suggest that the fluorescein leakage assay shows promise as a screening test for surfactants and alcohols. The test method requires further optimization, standardization and evaluation to fully determine its utility as an in vitro ocular irritancy test. The silicon microphysiometer test measures effects of test substances on the metabolic rate of cells; although a large number of cell types have been evaluated, L929 cells have been used for irritancy screening. Three IRAG data submissions on the silicon microphysiometer test showed strong in vivo/in vitro correlations for surfactants and surfactant-based personal care and household cleaning products in a range of mild to moderate ocular irritancy. This and published information support the reproducibility of the method and its use as an ocular irritancy screening test for aqueous-soluble liquid, surfactant-based formulations.
Animal Testing Alternatives↗
IRAG working group 5. Other assays. Interagency Regulatory Alternatives Group.
As part of the Interagency Regulatory Alternatives Group (IRAG) program to evaluate the state of the art in the development of alternative (non-whole animal) eye irritation tests, academic and industrial organizations were invited to submit in vitro eye irritation data generated in their laboratories to one of several working groups for review. The assays reviewed in this report (from Working Group 5. "Other Assays") were the EYTEX assay, tissue equivalent assay, a cytotoxicity assay using three-dimensional human fibroblast constructs, the Microtox assay, and other miscellaneous assays. Each submission consisted of raw data for chemicals and products tested, a description of the methodology, and an analysis (generally by regression analysis and Pearson's correlation coefficient) for the performance of the in vitro test relative to its ability to predict individual ocular tissue scores or total ocular score. In vivo data were generated according to the scoring methods proposed by Draize. Working Group 5 evaluated the submissions and commented on the utility of the assays. The variability of the in vivo data made conclusions difficult in many situations. Most of these assays were deemed useful (within limited chemical classes) for screening purposes or for use in conjunction with other toxicological information.
Animal Testing Alternatives↗
Single-agent paclitaxel in patients with previously untreated stage IV epithelial ovarian cancer. London Gynaecological Oncology and North Thames Gynaecological Oncology Groups.
The aim of this study was to evaluate the efficacy of high-dose paclitaxel in patients with previously untreated stage IV epithelial ovarian cancer. Paclitaxel was administered intravenously over 3 h at a dose of 225 mg m(-2) on a 21-day cycle for six courses. Thirty-six patients were entered into this study; all 36 were assessed for toxicity and 33 patients were evaluable for response. One patient had a complete response and 12 patients had partial responses (overall response rate 39.4%, 95% CI 23-58%). The overall median duration of response was 9 months (range 3.5-23+ months). The response rate to carboplatin following failure of paclitaxel within 1 year of stopping therapy was 57% (four out of seven patients). The median survival of patients was 17.2 months. The main toxicity encountered was neutropenia which was WHO grade 3 in 11 patients (31%) and WHO grade 4 in seven patients (19%). Granulocyte colony-stimulating factor (GCSF) was not given to any patient during the study. Other toxicities were: grade 3/4 infection (11%) and nausea and vomiting (11%); grade 3 bone pain (22%), fatigue (14%), diarrhoea (3%), myalgia/arthralgia (3%) and dry eyes (3%). Transient peripheral neuropathy occurred in 16 patients (44%), and alopecia was encountered in most patients (grade 2/3, 78%). Paclitaxel given at 225 mg m(-2) to patients with stage IV epithelial ovarian cancer is active, well tolerated and does not require GCSF support.
Adult↗
Review of autologous and allogeneic blood transfusion practices in patients undergoing radical hysterectomy.
To review the practice and predictors of autologous (AUT) and allogeneic blood transfusion in patients undergoing radical hysterectomy (RH). All patients undergoing RH between April 1, 1991 and March 31, 1995 were identified by the hospital blood bank. Clinical and tumour characteristics were abstracted from the charts of endometrial cancer patients, and amalgamated with our cervical cancer RH database. Pre and post-operative hemoglobin (Hg), the number of units of AUT blood requested, obtained, and transfused, and the number of units of allogeneic blood transfused were obtained from the blood bank records. Forty eight of the 111 patients undergoing RH during the study period predeposited AUT blood. There were no differences in the median age, quetelet index, American Society of Anaesthesiologists classification of physical status, or blood loss between the AUT and non-donors. The tumour size was greater in the AUT donors, and the preoperative Hg was greater in the non donors (p = 0.001, p < 0.04 respectively). Operative time was less in the AUT donors (2.1 hrs vs 2.7 hrs, p < 0.001), and there was a significant difference in the use of the AUT program between the 3 surgeons (0.5%, 68%, p < 0.0001). Despite similar blood loss, 98% and 33% of AUT and non-donors were transfused intra/postop respectively (p < 0.0001). Regression analysis revealed surgeon (p < 0.0001) to be the only predictor of AUT donation. Blood loss was found to be the only predictor of intraoperative/postoperative blood transfusion in the non donor group (p = 0.0006). The utilization of an AUT blood program differs significantly between surgeons. Physicians are more liberal to transfuse AUT than allogeneic blood.
Adult↗
Determination of the intra- and interlaboratory reproducibility of the low volume eye test and its statistical relationship to the Draize eye test.
The reproducibility of toxicologic test methods, including alternative tests, is a key scientific and regulatory concern. In the present work, historic rabbit eye irritation data were used to determine the intra- and interlaboratory reproducibility of the low volume eye test (LVET). The standard Draize eye irritation test was used as the basis for comparison. The LVET and Draize tests had similar degrees of intra- and interlaboratory reproducibility as determined by examination of their coefficients of variation, although the variability in LVET results was directionally lower. Results from 70 parallel Draize and LVET tests indicated a strong positive association between results from the two tests, for corneal, iridial, conjunctival, and maximum average scores (MAS). Correlation coefficients were 0.60, 0.73, 0.69, and 0.73, respectively (P </= 0.0001). The linear relationship between LVET and Draize MAS values was examined by regression analysis and found to follow the relationship LVET MAS = 0.522 (Draize MAS). Thus, the LVET is at least as reproducible as the Draize test and gives responses that are (linearly) correlated to the Draize. The previous findings that the LVET is more predictive of human eye responses than the Draize test lends additional support for its use as a refined alternative to the Draize test.
Alcohols↗
Conformational and receptor-binding properties of the insect neuropeptide proctolin and its analogues.
Proctolin (Arg-Tyr-Leu-Pro-Thr) was the first insect neuropeptide to be chemically characterised. It plays an essential role in insect neurophysiology and is involved in muscular contraction and neuromodulation. Elements of secondary structure in solution have been studied by comparing data obtained from NMR and molecular dynamics simulations. Different secondary structural requirements are associated with agonist and antagonist activities. A favoured conformation of proctolin has an inverse gamma-turn, comprising an intramolecular hydrogen bond near the C-terminal end between Thr NH and Leu CO. Antagonists have a more compact structure resembling a 'paperclip' loop, containing an intramolecular hydrogen bond between Tyr NH and Pro CO, possibly stabilised by a salt bridge between the N- and C-terminal groups. A cyclic analogue retains antagonist activity and resembles a beta-bulge loop, also comprising intramolecular hydrogen bonds between Tyr NH and Pro CO and Thr CO. These models may offer feasible starting points for designing novel compounds with proctolinergic activity.
Animals↗
Immunogenicity of a peptide from a major neutralising determinant of the feline immunodeficiency virus surface glycoprotein.
The third variable region (V3) of the feline immunodeficiency virus (FIV) surface glycoprotein is predicted to have similar physical properties to that of HIV and has been shown to contain immunodominant and neutralizing epitopes. Immunological characteristics of this region were investigated further using a peptide corresponding to the middle of the putative FIV V3 loop. The peptide was recognized in ELISA by sera from the majority of naturally FIV-infected cats, and absorbed a significant fraction of the virus neutralizing activity from a pool of sera of cats naturally infected with FIV, confirming the immunogenic nature of this region. A sheep immunized with an octameric form of the peptide (multiple antigenic peptide; MAP) in Freund's complete adjuvant generated neutralizing antibody to a higher titre than infected cats. However, immunization of cats with the same MAP in an acceptable adjuvant formulation (Quil A) induced antibody and cytotoxic T-cell responses to the immunizing peptides but only minimal neutralizing activity. These responses did not significantly alter the kinetics of infection or the proviral load after challenge with a homologous strain of FIV, compared with naive controls. While the potential efficacy of peptide vaccines to lentiviruses remains to be determined, this study shows that the immune response evoked may be highly dependent on the delivery and adjuvant regime used.
Amino Acid Sequence↗
Aorto-iliac reconstruction without arteriography.
BACKGROUND: Duplex imaging has been shown to be as accurate as arteriography in detecting hemodynamically significant aorto-iliac stenosis or occlusions. METHODS: Review of the duplex scan and arteriogram reports for all primary aorto-iliac reconstructions performed during an 18-month period was undertaken. Deviations from the preoperatively planned procedure were determined. The role of the duplex scan on procedure selection was assessed. RESULTS: Of the 54 patients identified, 13 had both duplex scan and arteriography (group I), 30 had only arteriography (group II), and 11 had only duplex scans (group III). Ten group I, 15 group II, and 9 group III patients had an occluded aorta or iliac artery. Two patients (3 anastomosis) required placement of the distal anastomosis on the common femoral rather than the external iliac artery as planned preoperatively. Both had been arteriogrammed. No group III patient required deviation from the preoperative plan. CONCLUSION: Aorto-iliac reconstruction can be performed without arteriography when a totally occluded aorta or iliac artery is identified by duplex scanning.
Aortic Diseases↗
Vaccination with fixed feline immunodeficiency virus (FIV) infected cells: protection, breakthrough and specificity of response.
Infection of cats with feline immunodeficiency virus (FIV), a naturally occurring lentivirus infection of cats which causes an AIDS-like disease, has generated considerable interest as an animal model for HIV vaccination. This paper reports on experiments performed to examine the potential of a fixed infected cell vaccine to confer protection against intraperitoneal challenge with cell-free FIV. The cell vaccine was highly immunogenic and elicited antibody responses to virus core antigen, p24, high virus neutralizing (VN) antibody titres, and antibodies which recognized cellular components of the vaccine. Whilst protection, assessed by the inability to detect infectious virus by virus isolation or polymerase chain reaction, against homologous but not heterologous FIV isolates was apparent up to week 12 post-challenge, when cats were monitored longer up to week 50 post-challenge a breakthrough in vaccine protection against homologous virus was observed. Protection could not be correlated with levels of antibody to p24 or VN antibody titres. In contrast with simian immunodeficiency virus vaccine studies in macaques there was no clear evidence that antibodies recognizing cellular components of the vaccine, including MHC class I and II antigens, conferred any protective effect following challenge. These results indicate that long-term post-challenge monitoring for infection is essential in lentivirus vaccine trials.
Animals↗
Development of an in vitro method for skin corrosion testing.
National and international regulations require that chemicals must be properly classified, labeled, packaged, and transported based on their ability to damage or destroy tissue, e.g., skin. Traditionally, skin corrosion assessments were based on tests involving topical application of test substances to the skin of rabbits. In the present work, an in vitro skin corrosion test based on the use of reconstructed human skin cultures was developed as a potential replacement for in vivo rabbit skin tests for corrosion. In the in vitro method, test substances were applied topically to the stratum corneum surface of human skin cultures. Skin culture damage or cytotoxicity was measured as decreased 3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyltetrazolium bromide (MTT) vital dye metabolism. In time-course experiments, the time (in minutes) of test material exposure eliciting a 50% reduction of MTT metabolism (i.e., t50 value) was calculated. Using this method we evaluated 24 chemicals and found that the 9 corrosive chemicals were accurately distinguished from 15 strong, moderate, or mild skin irritants, using an in vitro cutoff of t50 < 3 min. Histologic examination of the cultures indicated gradations of epidermal necrosis quantitated using a specially designed grading scale, which correlated well with the corrosivity of treatment chemicals and cytotoxicity measurements. The predictivity of the method was confirmed and was consistent in skin culture models from two suppliers. Thus, the utility of human skin equivalent cultures as a screening tool for prediction of skin corrosivity appears to be independent of the commercial source of the cultures. We conclude that the in vitro assay using human skin equivalent cultures is a promising alternative to in vivo rabbit skin corrosion tests for assessment of the corrosivity of chemicals to human skin.
Animal Testing Alternatives↗
Development and intralaboratory evaluation of an in vitro human cell-based test to aid ocular irritancy assessments.
A human cell-based in vitro method was developed to screen for ocular irritancy potential of aqueous compatible and incompatible test agents, such as liquids, insoluble solids, powders, granulars, emulsions, and acids/alkalis. Methods were developed for topical application (an exposure that mimics in vivo testing) and wash-off of test substances on the epithelial surface of human skin derived epithelial-fibroblast cocultures (Skin2 Model ZK1200 from Advanced Tissue Sciences). These cultures contain noncornified stratified squamous epithelium, providing a three-dimensional in vitro model that resembles noncornified mucosal epithelium, such as cornea and conjunctiva. The hypothesis tested and confirmed in this work was that the rate of cytotoxicity induced by topical application of test substances to the stratified epithelial cell cultures would correlate with ocular irritancy. Test substances were applied to the cell system for up to 30 min, and cytotoxicity was measured as decreased 3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide (MTT) vital dye metabolism. The time (in minutes) of exposure to test agent that reduced MTT metabolism to 50% of control levels (the t50 value) was calculated for each test substance, and these values showed a good correlation (r = 0.87) with historic rabbit low-volume eye test maximum average scores (MAS) for a range of liquid, solid, granular, powder, and other test materials, including consumer product formulations and ingredient chemicals. Additionally, t50 values confirmed the mild nature of selected cosmetic formulations. Taken together, these data indicate that this in vitro test, termed the tissue equivalent assay, is a valuable tool to screen for irritancy of test substances to mucosal tissues, such as cornea and conjunctiva.
Animal Testing Alternatives↗
Does aggressive therapy improve survival in suboptimal stage IIIc/IV ovarian cancer? A Canadian-American comparative study.
In an effort to determine if differences exist in the treatment and outcome of patients with suboptimally debulked stage IIIc and IV epithelial ovarian cancer between two tertiary-care cancer centers in Canada and the United States, we conducted a comparative study. The records of all patients who underwent treatment for epithelial ovarian cancer at two tertiary-care cancer centers in Canada and the United States between 1987 and 1989 were abstracted onto a common datasheet which was then entered into a computerized database for analysis. Only patients with suboptimally debulked stage IIIc disease (residual tumor diameter > 1 cm) or stage IV were included in the comparative study. There was a total of 129 evaluable patients (61 Canadian, 68 American). There were no statistically significant differences between the centers in mean age, performance status, histology, grade, or stage distribution. During the period of this study there was no statistically significant difference between the two institutions in the proportion of patients in whom optimal debulking was achieved (Canadian 19%, American 26%). The American patients were heavier than the Canadian patients (Quetelet index 27.3 vs 23.8, P < 0.006). Primary chemotherapy included a platin-containing regimen in 98 and 93% of Canadian and American patients, respectively. The average number of laparotomies each patient received during her course of illness was 1.7 and 2.5 at the Canadian and the American centers, respectively (P < 0.0001). Similarly, the American patients received a higher mean number of different chemotherapy regimens and total number of courses of chemotherapy during the course of their disease (3.0 and 12.6) than did the Canadian patients (2.4 and 8.8) (P < 0.01 and P < 0.001, respectively). The median survival was 21 months and 20 months in the Canadian and the American patients, respectively (no significant difference), and the 5-year survival was 10% for the Canadian and 11% for the American patients. Despite significant differences in the overall aggressiveness of treatment between the two centers, there was no difference in the survival of these patients. Until effective salvage agents or treatment strategies are realized, "more is not necessarily better."
Actuarial Analysis↗