bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphatidylinositol‐3 kinase inhibitors reproduce the selective antiproliferative effects of imatinib on chronic myeloid leukaemia progenitor cells
Authors: Marley S. B. , Lewis J. L. , Schneider H. , Rudd C. E. , Gordon M. Y. 
Published: April 2004

SummaryWe investigated the role of the phosphatidylinositol‐3 kinase (PI‐3K) pathway in regulating the proliferation of primary chronic myeloid leukaemia (CML) progenitor cells by using imatinib to inhibit the activity of p210Bcr‐Abl. The effect of imatinib on the expression of PI‐3K pathway proteins was investigated by kinase assays and Western blotting; PI‐3K was inhibited by wortmannin or LY294002, Jak2 by AG490 and farnesylation by FTI II; progenitor cell proliferation (self‐renewal) was measured by growing myeloid colonies in vitro, then replating them to observe secondary colony formation. Suppression of p210Bcr‐Abl with imatinib indirectly suppressed the activity of PI‐3K and its downstream targets (Erk, Akt and p70S6 kinase), thereby implicating the PI‐3K pathway in p210Bcr‐Abl‐mediated signalling in primary CML progenitor cells. The PI‐3K inhibitors, wortmannin and LY294002 reproduced the differential effects of imatinib on normal and CML progenitor cell proliferation in vitro by increasing normal cell (P = 0·001) and reducing CML cell proliferation (P = 0·0003). This differential effect was attributable to dysregulated signalling by granulocyte colony‐stimulating factor in CML. The responses of individual patient's cells to wortmannin correlated with their responses to imatinib (P = 0·004) but not their responses to AG490 (Jak2 kinase inhibitor) or FTI II (farnesyltransferase inhibitor). Individual responses to wortmannin also correlated with responses to interferon α (IFNα) (P = 0·016). Imatinib‐resistant K562 cells were sensitive to LY294002. Inhibition of the PI‐3K pathway may be common to imatinib and IFNα and reflect dysregulated cytokine signalling. As imatinib‐resistant cells remained sensitive to wortmannin and LY294002, targeting the PI‐3K pathway may provide an alternative therapy for imatinib‐resistant patients.
Phase 2 study of arsenic trioxide in patients with relapsed or refractory multiple myeloma
Authors: Hussein Mohamad A. , Saleh Mansoor , Ravandi Farhad , Mason James , Rifkin Robert M. , Ellison Ralph 
Published: April 2004

SummaryDespite aggressive and innovative therapy, patients with multiple myeloma (MM) invariably relapse and die of their disease. New options for non‐cytotoxic salvage therapy and additional therapeutic strategies are needed. Arsenic trioxide, an antitumour agent with a multifaceted mechanism of action, induces apoptosis in vitro in MM cell lines and freshly isolated cells from MM patients and, in preliminary studies, displayed clinical activity in patients with late‐stage MM. A phase 2, multicentre, open‐label study of arsenic trioxide was conducted in 24 MM patients; eight had relapsed and 16 were refractory to prior therapy. Patients received arsenic trioxide 0·25 mg/kg/d for 5 d/week during the first 2 weeks of each 4‐week cycle. Sixteen patients had grade 3 or 4 neutropenia and one required antibiotics. Reductions (25% or more) in serum M‐protein levels occurred in eight of 24 (33%) patients. An additional six (25%) patients had stable disease. The median time to response was 67·5 d, with a median duration of response of 130 d. Arsenic trioxide therapy lowered serum creatinine levels in two patients with high baseline values. These data indicate that arsenic trioxide is active and reasonably well tolerated as a single‐agent salvage therapy, even in patients with late‐stage, relapsed and refractory MM.
Four pedigrees of the cation‐leaky hereditary stomatocytosis class presenting with pseudohyperkalaemia. Novel profile of temperature dependence of Na+–K+ leak in a xerocytic form
Authors: Gore D. M. , Layton Mark , Sinha A. K. , Williamson P. J. , Vaidya Bijay , Connolly V. , Mannix P. , Chetty M. C. , Nicolaou Anna , Stewart G. W. 
Published: April 2004

SummaryWe report four pedigrees of the group of Na+–K+‐leaky red cell disorders of the ‘hereditary stomatocytosis’ class. Each showed pseudohyperkalaemia because of temperature‐dependent loss of K+ from red cells on storage of whole blood at room temperature. All pedigrees showed an abnormality in the temperature dependence of the ‘passive leak’ of the membrane to K+. Two pedigrees, both of which showed a compensated haemolytic state with dehydrated red cells and target cells on the blood film, showed a novel pattern, in which the profile was flat between 37°C and about 32°C then dropped as the temperature was reduced to zero. The third showed the ‘shallow slope’ profile, with stomatocytes on the blood film and very markedly abnormal intracellular Na+ and K+ levels. Minimal haemolysis was present. The fourth pedigree, of Asian origin, showed the shoulder pattern (minimum at 32°C, maximum at 12°C) with essentially normal haematology. Both of these latter two forms have previously been seen in other pedigrees. The first variant represents a novel kind of temperature dependence of the passive leak found in these pedigrees presenting with pseudohyperkalaemia.
Chronic graft versus host disease
Authors: Higman Meghan A. , Vogelsang Georgia B. 
Published: April 2004

SummaryThe ability to cure increasing numbers of individuals for malignant and non‐malignant diseases with the use of stem cell transplantation has resulted in a growing number of long‐term survivors with unique medical issues. Chronic graft versus host disease (GvHD) continues to be a significant problem in the allogeneic stem cell transplant setting and, as we continue to use alternative stem cell sources and attempt to modulate the immune system to increase an anti‐tumour effect, we will probably see rising numbers of patients with this complication. The capacity to treat this problem and improve both the immediate quality of life as well as long‐term effects is imperative and requires the ability of haematologists/oncologists to identify chronic GvHD and its multi‐organ system presentations. We describe the risk factors for developing chronic GvHD, its presentation and the current treatment options for both initial therapy and secondary treatment.
Consequences count: against absolutism at the end of life
Authors: Snelling Paul C. 
Published: April 2004

Background.  There has been a considerable amount of debate in the nursing literature about euthanasia, and especially the distinctions between acts and omissions, and killing and letting die. These distinctions are required by opponents of euthanasia to justify allowing some cases of passive euthanasia while forbidding all cases of active euthanasia.Aim.  This paper adds to the debate by arguing that the position that absolutely forbids euthanasia is theoretically inconsistent.Methods.  The paper first considers the place of moral theory in analysing moral problems, within the framework of the principles of biomedical ethics. It is argued that despite a moral pluralism that operates in many areas, the legal status of euthanasia is based upon an absolute deontological position against deliberate killing, which cannot be overridden by appeals to favourable consequences. In order that certain forms of passive euthanasia can be allowed, this position allows distinctions within three pairs of concepts – acts and omissions, killing and letting die, and ordinary and extraordinary means. A further method of justifying certain actions near the end of life is the doctrine of double effect. These paired concepts and the doctrine of double effect are analysed with special reference to their consequences.Conclusion.  The application of the doctrine of double effect and the three distinctions relies on consideration of their consequences, allowing in practice what in theory is denied. This is important because it weakens the absolute case against euthanasia, which disallows any direct consequentialist appeal. If consequences count in the application of the doctrine and the distinctions, then they should also count directly prior to their application. This strengthens the argument for active euthanasia in certain cases.
Factors influencing decision to breastfeed
Authors: Kong Sarah K.F. , Lee Diana T.F. 
Published: April 2004

Background.  The low prevalence and short duration of breastfeeding in international studies have highlighted the need for more investigations into the problems. International studies have identified certain factors that affect breastfeeding intentions. Due to insufficient published studies on the local breastfeeding situation, this study specifically investigated factors influencing the breastfeeding decision among primipara women in Hong Kong.Aim.  The aim of this paper is to report a study investigating the personal, social, cultural, facilities and environmental and other factors contributing to women's decisions to breastfeed, and to exploring first‐time mothers’ knowledge of breastfeeding and its influence on their breastfeeding intentions.Methods.  Three private and 10 public hospitals in Hong Kong participated in the study. Both quantitative and qualitative data were collected through questionnaires and subsequently by in‐depth interviews with 230 first‐time mothers 24–48 hours after delivery.Results.  The results indicated that personal, cultural, social, and environmental factors are common influencing factors in the decision to breastfeed. Mother's knowledge and attitudes, followed by husband's support, were identified as important in influencing infant feeding choice. Expected local cultural differences were also identified.Discussion.  Acknowledgement of the influencing factors could lead to appropriate management of the promotion of breastfeeding. Further research into husband's role, recognition and support for infant feeding and the issue of ‘inadequate breast milk’ is necessary for a successful breastfeeding campaign. Some other interesting findings typical of the local culture, such as family communication and living environment relating to breastfeeding, are also discussed.Conclusions.  The study has identified the influencing factors that affect women's decision to breastfeed. Recommendations are made for health care professionals and the community to create a more baby‐friendly atmosphere and environment for the promotion of breastfeeding.
Nursing resistance as ethical action: literature review
Authors: Peter Elizabeth , Lunardi Valeria Lerch , Macfarlane Amy 
Published: April 2004

Background. Much has been written about nursing as a predominantly female profession whose members display passivity, submission, obedience and powerlessness. Alternatively, some authors have presented evidence of nurses’ capacity to exercise power, revealing the possible relationship between powerlessness and ethical compromise. Thus, empowerment strategies for nurses can yield ethical action.Aim. The aim of this paper is to use analysis of the literature to demonstrate how the actions and responses of nurses to ethical concerns are examples of nurses exercising power.Method. Empirical studies published in the nursing literature between 1990 and 2003 have been analysed to illustrate how nurses’ actions of resistance can ensure that moral values are realized in practice. Foucauldian notions of power relations and feminist ethics provide the theoretical framework.Conclusions. Nurses were found to resist in situations where they experienced moral conflicts in relation to the actions of health professionals; however, instances were cited where they did not. Consequently, strategies for nursing education and management are proposed to increase nurses’ understanding of the potential acts of resistance that they could employ in situations of moral conflict or concern.
New low back pain in nurses: work activities, work stress and sedentary lifestyle
Authors: Yip Vera Yin Bing 
Published: April 2004

Background. Low back pain is common among nurses. Previous studies have shown that the risk of low back pain increases rapidly with greater amounts of physical work and psychological stress, but is inversely related to leisure activities. However, these previous studies were predominantly retrospective in design and not many took account of three factors simultaneously.Aims. This 12‐month prospective study examined the relationships between work activities, work stress, sedentary lifestyle and new low back pain.Methods. A total of 144 nurses from six Hong Kong district hospitals completed a face‐to‐face baseline interview, which was followed‐up by a telephone interview. The main study measures were demographic characteristics, work activities, work stress, physical leisure activities and the nature of new low back pain during the 12‐month follow‐up period. Level of work stress, quality of relationships at work, level of enjoyment experienced at work, and work satisfaction were self‐reported.Results. Fifty‐six (38·9%) nurses reported experiencing new low back pain. Sedentary leisure time activity was not associated with new low back pain. Being comparatively new on a ward (adjusted relative risk 2·90), working in bending postures (adjusted relative risk 2·76) and poor work relationships with colleagues (adjusted relative risk 2·52) were independent predictors of new low back pain.Conclusion. The findings of this study suggest that low back pain is a common problem in the population of nurses in Hong Kong. Being comparatively new on a ward, bending frequently during work and having poor work relationships with colleagues are independent predictors of new low back pain. Training for high‐risk work activities and ergonomic assessment of awkward work postures are essential. Moreover, relaxation and team‐building workshops for nurses, especially those who are less experienced in the type of work on their current ward, are recommended.
Uptake of guidelines to avoid and report exposure to blood and body fluids
Authors: Cutter Jayne , Jordan Sue 
Published: April 2004

Background.  Mucocutaneous and percutaneous exposure to blood and body fluids (inoculation injury) are major risk factors for occupational acquisition of bloodborne infection in health care professionals. Compliance with prescribed ‘universal precautions’ during exposure‐prone procedures has been shown to reduce the risk of acquiring bloodborne viral infection. In addition, reporting such exposures facilitates prophylaxis.Aim.  The aim of this paper is to report a study to identify strategies to minimize professionals’ risks of acquiring bloodborne infections during exposure‐prone procedures.Method.  All surgeons, theatre nurses who scrub for surgery and midwives employed in general operating theatres and delivery suites within one UK National Health Service trust (n = 276) were surveyed by postal questionnaire. Data were analysed using univariate and bivariate techniques in SPSS version 10. Content analysis was undertaken on the one open‐ended question.Findings.  The response rate was 72·5% (200/276). Only 1·5% (3/200) of respondents adopted universal precautions for all patients irrespective of whether their bloodborne viral status was known. On average, only half the recommended theatre‐specific precautions were always adopted (mean 3·725/7, sd = 1·385). Most respondents (63·3%) admitted making judgements related to nationality, lifestyle or sexual orientation when making decisions about protective clothing. Many respondents (74%, 145/196) reported sustaining an inoculation injury in the 10 years prior to the study. However, under‐reporting of injuries was common, and 32·4% (47/145) admitted failing to report injuries. Guideline adherence was influenced by profession, but not by time since qualification.Conclusions.  The findings suggest that strategies must be developed to improve compliance with universal precautions and reporting guidelines by all health care professionals. The extent of, and reasons for, non‐compliance with both local and national guidelines remain relatively unexplored.
Home care needs of patients with long‐term conditions: literature review
Authors: Algera Marco , Francke Anneke L. , Kerkstra Ada , Van Der Zee Jouke 
Published: April 2004

Background.  There is a widely felt need to improve the match between long‐term patients’ care needs and actual use of home care. As this match is not always adequate, it is important to know what factors influence it.Aim.  The aim of this paper is to provide insight into long‐term patients’ need and actual use of home care, and the factors influencing these.Method.  A literature review was carried out, based on database searches in PubMed, CINAHL and the Nivel online library catalogue. A total of 114 papers were retrieved, but only 13 clearly dealt with use of professional home care (rather than informal home care or residential care) by people with long‐term conditions.Results.  There is a dearth of publications on factors influencing the match between care need and actual use of professional home care among people with long‐term conditions. Most of the 13 publications reviewed concerned determinants of professional home care use, rather than the match between patients’ felt needs and the home care delivered. From these studies, a profile of people with long‐term conditions who used home care emerged. In general, older, non‐white women, with multiple chronic diseases and impairments, and who had recently had inpatient care, tended to make more use of professional home care.Conclusion.  Future research in this field is recommended, particularly into system‐ and patient‐related characteristics that may be responsible for the mismatch between care need and use.
Effect of Environmental Enrichment on Stress Related Systems in Rats
Authors: Moncek F. , Duncko R. , Johansson B. B. , Jezova D. 
Published: April 2004

AbstractThe aim of this study was to test whether environmental enrichment alters the status and responsiveness of pituitary‐adrenocortical and sympathetic‐adrenomedullary hormones in rats. Previous studies have shown that rats kept in an enriched environment differ from those kept in standard cages in dendritic branching, synaptogenesis, memory function, emotionality and behaviour. In male Wistar rats kept in an enriched environment for 40 days, we studied basal concentrations of hormones, endocrine responses to 5‐HT1A challenge and responsiveness and adaptation to repeated handling. Environmental enrichment consisted of large plexiglass cages with 10 rats per cage, which contained variety of objects exchanged three times a week. Rats kept in this enriched environment had higher resting plasma concentrations of corticosterone, larger adrenals and increased corticosterone release to buspirone challenge compared to controls. Lower adrenocorticotropic hormone, corticosterone and adrenaline responses to handling were noticed in rats kept in an enriched environment. Exposure to repeated handling led to a more rapid extinction of corticosterone responses in rats kept in an enriched environment. Thus, environmental enrichment leads to pronounced changes in neuroendocrine regulation, including larger adrenals and increased adrenocortical function, which are so far considered to be indication of chronic stress.
Gonadotroph Heterogeneity, Density and Distribution, and Gonadotroph–Lactotroph Associations in the Pars Distalis of the Male Equine Pituitary Gland
Authors: Townsend J. , Sneddon C. L. , Tortonese D. J. 
Published: April 2004

AbstractThe intrapituitary mechanisms regulating gonadotrophin secretion in the horse remain unclear. Here, we examined seasonal and gonadal effects on the gonadotroph and lactotroph populations of male horses with the aim of defining a possible morphological basis for the differential release of gonadotrophins. Pituitaries were collected from: (i) gonadal‐intact horses in the breeding season (GBS); (ii) orchidectomized horses in the breeding season (OBS); and (iii) orchidectomized horses in the nonbreeding season (ONBS). Immunohistochemistry was performed using antibodies to the luteinizing hormone (LH) β subunit, follicle‐stimulating hormone (FSH) β subunit and prolactin. In all groups, gonadotrophs were distributed throughout the pars distalis, with dense populations detected near the borders with the pars tuberalis and pars intermedia. The numbers of LH‐monohormonal, FSH‐monohormonal and bihormonal cells/field were greater in GBS than in OBS and ONBS horses. Similarly, the proportion of gonadotrophs in relation to all pituitary cells was larger in gonadal‐intact than orchidectomized horses. In the absence of the gonads, no effects of season were observed on these variables. Interestingly, the relative proportions of gonadotroph subtypes and the LH/FSH gonadotroph ratio were similar among groups. Furthermore, while specific gonadotroph–lactotroph associations were identified in all groups, significant gonadal effects within the breeding season and direct effects of season within orchidectomized horses were detected for the number of lactotrophs. This study reveals a gonadal‐independent effect of season on the lactotroph, but not the gonadotroph population of the equine pituitary, and a clear gonadal stimulation of both cell types within the breeding season. We suggest that alterations in intercellular arrangements, rather than changes in the incidence of gonadotroph subtypes, may contribute to the differential release of gonadotrophins and, accordingly, to the intrapituitary control of fertility throughout the male equine annual reproductive cycle.
Diverse Effects of Stress and Additional Adrenocorticotropic Hormone on Digitalis‐Like Compounds in Normal and Nude Mice
Authors: Weidemann H. , Salomon N. , Avnit‐Sagi T. , Weidenfeld J. , Rosen H. , Lichtstein D. 
Published: April 2004

AbstractDigitalis‐like compounds (DLC) are steroidal hormones that are synthesized in, and released from, the adrenal gland, whose regulation may be directed by the hypothalamic‐pituitary‐adrenal (HPA) axis. Increasing evidence points to antitumour properties of these compounds and we hypothesized that the establishment of tumours in athymic nude mice may be facilitated by an abnormal synthesis or secretion of DLC. To explore this hypothesis, DLC concentrations were determined in the plasma, and in adrenal and hypothalamic tissues of nude compared to normal mice under basal conditions, and 30 min after a stress stimulus (i.p. injection of 100 µl saline) with or without additional adrenocorticotropic hormone (ACTH) 1 µg/per animal. Simultaneously, plasma corticosterone and serum adrenocorticotropic hormone (ACTH) concentrations were analysed. The basal DLC concentrations were similar in the plasma and the hypothalamus of both strains, whereas the basal adrenal DLC concentration was significantly lower in the nude mice compared to normal mice. The stress stimulus induced in normal mice a significant increase in DLC concentrations in the adrenal gland, the plasma and the hypothalamus. However, in nude mice, it caused an increase only in the adrenal gland and the hypothalamus, whereas the plasma DLC concentration was not affected. In both strains, the administration of ACTH in addition to injection stress did not provoke a further increase in DLC concentrations while inducing a significant increase in plasma corticosterone concentration. Regardless of the applied stimulus, the nude mice expressed significant lower DLC concentrations in the adrenal gland and the plasma compared to normal mice. The low basal adrenal DLC concentration in nude mice and their impaired DLC response towards stress‐ and ACTH stimulation both support an involvement of DLC in tumorigenesis.