bluuebunny/crossref_metadata_2025 huggingface dataset:
Practical Implications of Nonlinear Effects in Risk-Assessment Harmonization
Authors: Bukowski John A. , Lewis R. Jeffrey
Published: April 2004

Cancer and noncancer health effects have traditionally been handled differently in quantitative risk assessment. A threshold (i.e., safe exposure) has been assumed for noncancer health effects, and low-dose linearity without a threshold has been assumed for cancer. “Harmonization” attempts to reconcile these contrasting assumptions under one paradigm. Recent regulatory initiatives suggest that the U.S. Environmental Protection Agency may be leaning toward a harmonized, probabilistic/linear approach for noncancer health effects. Proponents of this approach cite variability in human susceptibility as an argument against thresholds (i.e., some individuals may be exquisitely sensitive at exposures well below threshold levels). They also cite the results of epidemiological models that suggest low-dose linearity for noncancer health effects. We will discuss the implications of these arguments and compare them to what is known about human biological variability in general. We will also touch on the regulatory implications of hormesis within this framework.
Dose-Response Curves in Chemical Carcinogenesis
Authors: Waddell William J.
Published: April 2004

Extrapolation from studies of chemical carcinogenicity in rodents, at high doses, to humans, at the typically low doses to which we are exposed, has been one of the most controversial issues in toxicology. Many chemical carcinogenesis experiments currently are evaluated on a linear scale for dose. Log dose has been the standard for decades in pharmacology and toxicology for noncancer toxicities and there is no reason to think that it should not apply to chemical carcinogenesis. Furthermore, log dose is consistent with fundamental principles of chemistry. Direct comparisons of linear and logarithmic scales for dose illustrate the deceptive nature of linear plots for dose; low doses, which is where our interest lies in comparing human exposures, are compressed beyond evaluation by a linear scale. Unequivocal thresholds for carcinogenicity are shown when the dose-response curves for animal studies done at high doses are evaluated on a log scale for dose. This observation now raises the issue of the relevance to human exposures of these high-dose experiments in animals. Studies analyzed by this log dose to linear response procedure demonstrate that the thresholds from animal experiments can be used to calculate safety factors for human exposure and that humans are more resistant than animals to carcinogenesis from chemicals.
Detoxication Strategy of Epoxide Hydrolase—The Basis for a Novel Threshold for Definable Genotoxic Carcinogens
Authors: Oesch Franz , Hengstler Jan Georg , Arand Michael
Published: April 2004

From our recent work on the three-dimensional structure of epoxide hydrolases we theoretically deduced the likelihood of a two-step catalytic mechanism that we and others have subsequently experimentally confirmed. Analysis of the rate of the two steps by us and by others show that the first step—responsible for removal of the reactive epoxide from the system—works extraordinarily fast (typically three orders of magnitude faster than the second step), sucking up the epoxide like a sponge. Regeneration of the free enzyme (the second step of the catalytic mechanism) is slow. This becomes a toxicological problem only at doses of the epoxide that titrate the enzyme out. Our genotoxicity work shows that indeed this generates a practical threshold below which no genotoxicity is observed. This shows that—contrary to old dogma—practical thresholds exist for definable genotoxic carcinogens.
Responses of Cultured Astrocytes, C6 Glioma and 1321NI Astrocytoma Cells to Amyloid β-Peptide Fragments
Authors: Pentreath V. W. , Mead C.
Published: April 2004

The effect of amyloid β-peptide (β AP), which can have both neurotrophic or neurotoxic effects on neurons and has been implicated in the pathogenesis of Alzheimer's disease (AD), was studied on astrocytes using primary cultures and astrocyte cell lines (rat C6 glioma, human 1321NI astrocytoma cells). The cultures were exposed to 0.0005–50 μg/ml) βAP fragments 1–40, 25–35, 31–35, or 40–41 (control) for 24 hr. Some of the fragments were maintained at 37°C for 48 hr to induce aggregation and some of the cell cultures were pretreated with the differentiating agent dBcAMP before the experiments. The astrocyte responses were evaluated for lysosome activity (neutral red assay) and levels of structural proteins, glial fibrillary acidic protein, vimentin, and S-100, which are altered in the dystrophic plaques with associated astrogliosis in AD. The cells frequently responded with biphasic responses, with initial (low-dose) activation-type responses (i.e., increases of indicator compared to controls), before reductions with altered morphology (increased branching of cells) at higher concentrations. However, cell death (with EC50 values) was not observed, even at the maximum concentrations of βAP fragments. The findings suggest that the astrocytes have a relatively high resistance against the β AP toxicity.
C‐peptide and Central Nervous System Complications in Diabetes
Authors: Li Zhen-guo , Sima Anders A. F.
Published: April 2004

Substantial evidence collected from clinical data and experimental
studies has indicated that CNS is not spared
from diabetes complications. Impairments in CNS function
are well documented in both type 1 and type 2 diabetic
patients as well as in various animal models of diabetes,
in terms of alterations in cognition, neuropsychology, neurobehavior,
electrophysiology, structure, neurochemistry
and apoptotic activities. These data suggest that primary
diabetic encephalopathy exists as a definable diabetic complication.
The mechanisms underlying this CNS complication
are not clear. Experimental studies have suggested that
neuronal apoptosis may play an important role in neuronal
loss and impaired cognitive function. In diabetes multiple
factors are responsible for neuronal apoptosis, such as a perturbed
IGF system, hyperglycemia and the aging process
itself. Recent data suggest that insulin/C‐peptide deficiency
may exert an eminent role. Administration of C‐peptide
partially corrects the perturbed IGF system in the brain
and prevents neuronal apoptosis in hippocampus of type 1
diabetes. In neuroblastoma SH‐SY5Y cells C‐peptide provides
a dose‐dependent stimulation on cell proliferation and
an anti‐apoptotic effect as well. These studies provide a basis
for administration of C‐peptide as a potentially effective
therapy for type 1 diabetes.
Degree performance of Economics students in UK universities: absolute and relative performance in prior qualifications
Authors: Naylor Robin , Smith Jeremy
Published: April 2004

We exploit individual‐level data on full cohorts of UK university leavers who were enrolled for an Economics degree during the period 1984–85 to 1992–93 or the academic year 1997–98. We analyse the determinants of degree performance and find that performance depends not only on prior qualifications as measured by A‐level scores, for example, but also on the individual student's ranking (based on their A‐level scores) within their cohort at their university. The students' performance is also enhanced by having previously studied mathematics, although there is no benefit from the prior study of Economics. We find that attendance at an Independent school has a negative effect on degree performance, and that there are comparatively few social class background effects. Females are more likely than males to obtain a good degree.
Are Higher Education Subsidies Second Best?
Authors: Wigger Berthold U.
Published: April 2004

An optimal taxation framework is considered in which part of the population can take advantage of investment in higher education. It is shown that social welfare can sometimes be increased by supplementing linear income taxes with a subsidy to material investment in higher education, but that social welfare can never be increased by supplementing a non‐linear income tax with such a subsidy.
The Taxation of Financial Capital under Asymmetric Information and the Tax‐competition Paradox
Authors: Eggert Wolfgang , Kolmar Martin
Published: April 2004

Information sharing between governments is examined in an optimal‐taxation framework. We introduce a taxonomy of alternative systems of international capital‐income taxation and characterize the choice of tax rates and information exchange. The model reproduces the conclusion found in earlier literature that integration of international caopital markets may lead to the under‐provision of publicly provided goods. However, in contrast to previous results in the literature, under‐provision occurs due to inefficiently coordinated expectations. We show that there exists a second equilibrium with an efficient level of public‐good provision as well as complete and voluntary information exchange between national tax authorities.
Dental pulp cells provide neurotrophic support for dopaminergic neurons and differentiate into neurons in vitro; implications for tissue engineering and repair in the nervous system
Authors: Nosrat Irina V. , Smith Christopher A. , Mullally Patrick , Olson Lars , Nosrat Christopher A.
Published: April 2004

Glial cell line‐derived neurotrophic factor (GDNF) mRNA is highly expressed by dental pulp cells (DPCs) prior to the initiation of dental pulp innervation. We show that radioactively labelled exogenous GDNF is retrogradely transported from neonatal teeth and vibrissae to the trigeminal neurons, indicating that GDNF acts as a classical neurotrophic factor in the trigeminal system. We also show that DPCs from both rats and humans produce nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF) and GDNF mRNAs in vitro, promote the survival and phenotypic characteristics of embryonic dopaminergic (DA) neurons and protect DA neurons against the neurotoxin 6‐hydroxy‐dopamine (6‐OHDA) in vitro. By using inhibitory antibodies to NGF, BDNF and GDNF, we show that the promotion of DA neuron survival relates to the production and release of neurotrophic proteins by DPCs in vitro. We suggest that in vivo production of neurotrophic factors by DPCs play roles in tooth innervation. However, continued production of neurotrophic factors by the DPCs might have wider implications. We propose that the dental pulp is a viable source of easily attainable cells with possible potential for development of autologous cell transplantation therapies. We also show that a population of neural crest‐derived dental pulp cells acquire clear neuronal morphology and protein expression profile in vitro, indicating the presence of a cell population in the dental pulp with neuronal differentiation capacity that might provide additional benefits when grafted into the CNS.
Locus coeruleus activation shortens synaptic drive while decreasing spike latency and jitter in sensorimotor cortex. Implications for neuronal integration
Authors: Lecas Jean‐Claude
Published: April 2004

Chronic recording of locus coeruleus (LC) neurons in rat and monkey have pointed out that brief, phasic LC discharges, but not sustained activity, are specifically related to salient stimuli and attention. However, the sensory consequences of phasic activation of the noradrenergic system by a brief conditioning stimulation of the LC have not been fully investigated. This study examined the effect of LC activation on synaptic and neuronal responses to a tactile stimulus in the sensorimotor cortex of the anaesthetized rat, by analysing the fine temporal structure of sensory discharges and current source‐density profiles recorded from the same electrodes. LC stimulation, with minimal EEG effects, consistently reduced the synaptic input in layers IV and V–VI, by decreasing the amplitude and duration of short‐latency current sinks, but not the slope of their early rising phase. Simultaneously, most multiple and single unit excitatory responses were shortened by the suppression of their late component after 25–30 ms, whereas robust temporal facilitation of the early discharge was found for spike latency mean and variance, spike timing and synchronization to the stimulus, but leaving the number of spikes unaffected. These two apparently opposite effects on the synaptic drive and neuronal response are reminiscent of the noradrenergic depression of afferent synaptic potentials observed with an increased neuronal excitability in vitro. They are interpreted as a noradrenergic sharpening of thalamocortical processing consistent with a presumed role of synchronous discharges in perception that would depend on activated states, particularly when LC activity is correlated with vigilance or attention.
Ligand‐gated channels in early mesencephalic neuronal precursors: immunocytochemical and electrophysiological analysis
Authors: Schlesinger F. , Meywirth J. , Krampfl K. , Grosskreutz J. , Petri S. , Mauth C. , Just L. , Bader A. , Bufler J.
Published: April 2004

Neuronal precursors play an important role in potential regenerative therapeutic strategies in different neurodegenerative diseases, e.g. Parkinson's disease. To understand proliferation and differentiation of these cells in vitro and in vivo, it is important to characterize functional properties of neuronal precursors in detail. The aim of the present study was to analyse the electrophysiological characteristics of ligand‐gated channels of neuronal precursors prepared from the rat ventral mesencephalon (VM) of embryonic stage 12.5 during their in vitro differentiation. For the experiments we used the patch‐clamp technique in combination with a system for ultrafast solution exchange and immunocytochemistry. It could be shown that functional active AMPA‐type glutamate as well as GABAA receptor channels are expressed at an early stage of neuronal development. In culture we observed excitatory as well as inhibitory postsynaptic currents (defined by their different kinetics) which correspond to the activation of AMPAergic and GABAergic receptor channels. Two populations of glutamate‐activated currents could be differentiated by their different time course of desensitization whereas the time course of resensitization and deactivation was normally distributed in all cells. GABAergic currents could be blocked by bicuculline and their kinetics correspond to that of GABAA receptor channel currents. Summarizing the results, in the present study it was shown for the first time that neuronal embryonic precursors of the rat VM express both functional AMPA‐type glutamate and functional GABAA receptor channels in vitro.
Left hemisphere motor facilitation in response to manual action sounds
Authors: Aziz‐Zadeh Lisa , Iacoboni Marco , Zaidel Eran , Wilson Stephen , Mazziotta John
Published: April 2004

Previous studies indicate that the motor areas of both hemispheres are active when observing actions. Here we explored how the motor areas of each hemisphere respond to the sounds associated with actions. We used transcranial magnetic stimulation (TMS) to measure motor corticospinal excitability of hand muscles while listening to sounds. Sounds associated with bimanual actions produced greater motor corticospinal excitability than sounds associated with leg movements or control sounds. This facilitation was exclusively lateralized to the left hemisphere, the dominant hemisphere for language. These results are consistent with the hypothesis that action coding may be a precursor of language.
Plasticity of somatostatin and somatostatin sst2A receptors in the rat dentate gyrus during kindling epileptogenesis
Authors: Csaba Zsolt , Richichi Cristina , Bernard Véronique , Epelbaum Jacques , Vezzani Annamaria , Dournaud Pascal
Published: April 2004

Increasing evidence suggests that somatostatin may control neuronal excitability during epileptogenesis. In the hippocampus, sst2A receptors are likely to mediate somatostatin inhibitory actions but little is known about their status in kindled tissues. In the present study, sst2A receptor and somatostatin immunoreactivity were examined by confocal microscopy in the hippocampus during and after kindling acquisition. In control rats, somatostatin‐positive axon terminals were mainly found in the stratum lacunosum moleculare of CA1 area and in the outer molecular layer of the dentate gyrus. sst2A receptor immunoreactivity was diffusely distributed in the strata radiatum and oriens of CA1 and in the stratum moleculare of the dentate gyrus. Immunogold electron microscopy revealed that sst2A receptors were predominantly localized postsynaptically, at the plasma membrane of dendritic shafts and spines of principal neurons. During kindling epileptogenesis, qualitative and semiquantitative analysis revealed a progressive decrease of sst2A immunoreactivity in the outer molecular layer, which was spatially associated with an increase in somatostatin immunoreactivity. No obvious changes in sst2A receptor immunoreactivity were observed in other hippocampal subfields. These results suggest that the decrease of sst2A receptor immunoreactivity in the outer molecular layer reflects receptor down‐regulation in distal dendrites of granule cells in response to chronic somatostatin release. Because the sst2A receptor appears to mediate anticonvulsant and antiepileptogenic effects of somatostatin, this may represent a pivotal mechanism contributing to epileptogenesis.
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

We 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

Despite 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

We 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

The 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

The 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

The 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

Digitalis‐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.
Acute Intracarotid Glucose Injection Towards the Brain Induces Specific c‐fos Activation in Hypothalamic Nuclei: Involvement of Astrocytes in Cerebral Glucose‐Sensing in Rats
Authors: Guillod‐Maximin E. , Lorsignol A. , Alquier T. , Pénicaud L.
Published: April 2004

The detection of changes in glucose level constitutes the first step of the control of glucose homeostasis. Glucose sensors are therefore expected to be present in different parts of the body and particularly in the central nervous system. Some studies have already attempted to determine glucose‐sensitive cerebral structures either after a glucoprivic stimulus or after prolonged hyperglycaemia. By analogy to beta cells, it was postulated that the glucose sensors in the brain could involve GLUT2, glucokinase and/or ATP‐sensitive K+ channels. Surprisingly, GLUT2 was mainly found in astrocytes. Thus, the aims of the present investigation were to determine, in awake rats: (i) the hypothalamic areas that respond to acute hyperglycaemic condition induced by an intracarotid injection of glucose and (ii) the involvement of astrocytes in glucose‐sensing by the use of a glial drug, methionine sulfoximine. Rats were given intracarotid injections of glucose solution to trigger a transient insulin secretion without change in peripheral glycaemia, thus involving only central nervous regulation. Hypothalamic activation was determined by immunodetection of the immediate early gene c‐fos protein. Acute glucose injection induces significant activation of arcuate and paraventricular nuclei. This stimulation mainly affects neurones in both nuclei, but also astrocytes in the former as illustrated by double immunohistochemistry (Fos and neuronal nuclei or glial fibrillary acidic protein). After specific impairment of astrocyte metabolism by methionine sulfoximine, cerebral activation disappears in the arcuate nucleus, correlated with the lack of cerebral glucose‐induced insulin secretion. Therefore, arcuate and paraventricular hypothalamic nuclei are able to detect acute cerebral hyperglycaemia, leading to a peripheral stimulation of insulin secretion. Arcuate nucleus and more especially astrocytes in this nucleus play a pivotal role in glucose‐sensing.
Relationships Between Aromatase Activity in the Brain and Gonads and Behavioural Deficits in Homozygous and Heterozygous Aromatase Knockout Mice
Authors: Bakker J. , Baillien M. , Honda S. , Harada N. , Balthazart J.
Published: April 2004

The present study was carried out to determine whether aromatase knockout (ArKO) mice are completely devoid of aromatase activity in their brain and gonads and to compare aromatase activity in wild‐type and ArKO mice, as well as in heterozygous (HET) mice of both sexes that were previously shown to display a variety of reproductive behaviours at levels intermediate between wild‐type and ArKO mice. Aromatase activity was extremely low, and undetectable by the tritiated water assay, in homogenates of the preoptic area‐hypothalamus of adult wild‐type mice, but was induced following a 12‐day treatment with testosterone. The induction of aromatase activity by testosterone was significantly larger in males than in females. Even after 12 days exposure to testosterone, no aromatase activity was detected in the brain of ArKO mice of either sex whereas HET mice showed intermediate levels of activity between ArKO and wild‐type. Aromatase activity was also undetectable in the ovary of adult ArKO females but was very high in the wild‐type ovary and intermediate in the HET ovary. In wild‐type mice, a high level of aromatase activity was detected on the day of birth even without pretreatment with testosterone. This neonatal activity was higher in males than in females, but females nevertheless appear to display a substantial level of oestrogen production in their brain. Aromatase activity was undetectable in the brain of newborn ArKO males and females and was intermediate between wild‐type and ArKO in HET mice. In conclusion, the present study confirms that ArKO mice are unable to synthesize any oestrogens, thereby validating the ArKO mouse as a valuable tool in the study of the physiological roles of oestradiol. In addition, it demonstrates that the intermediate behaviour of HET mice presumably reflects the effect of gene dosage on aromatase expression and activity, that aromatase activity is sexually differentiated in mice during the neonatal period as well as in adulthood and, finally, that the neonatal female brain produces substantial amounts of oestrogens that could play a significant role in the sexual differentiation of the female brain early in life.
Effects of interferon and ribavirin combination therapy on CD4+ proliferation, lymphocyte activation, and Th1 and Th2 cytokine profiles in chronic hepatitis C
Authors: Marinho R. T. , Pinto R. , Santos M. L. , Lobos I. V. , Moura M. C.
Published: April 2004

Summary.  We studied the relationship between immunological markers such as CD4+ proliferation, cytokines profile and lymphocyte activation markers in patients with chronic hepatitis C, having different responses to interferon (IFN) and ribavirin (RBV) treatment. A prospective study of 20 patients was conducted, six had received IFN‐alpha‐2b alone and 14 IFN in combination with RBV.

The proliferative immune responses of peripheral blood mononuclear cells to hepatitis C virus peptides and the lymphocyte activation markers (CD25+, CD38+ and CD69+) were assessed before treatment, at 1 week, and 1, 3 and 6 months of treatment. Cytokines interleukin (IL)‐2, IFN‐γ, IL‐4 and IL‐10 were determined in supernatants before onset of treatment and at 1 and 6 months thereafter.

Stimulation indices (SI) were higher in the sustained responders (SR), in comparison with those with no response (NR), before treatment (5.2 ± 3.7 to 3.3 ± 1.9, P = 0.028) and also at 6 months (7.8 ± 1.9 to 4.1 ± 1.2, P = 0.021). Patients with SR also had high SI to NS3 when compared with those with transitory response or no response (NR) (4.9 ± 2.5 and 3.3 ± 1.1, P = 0.033). At 1 month, SR had higher supernatant IL‐2 than those with NR (133.8 ± 119.2 to 56.0 ± 89.3 pg/mL, P = 0.023) and lower levels of IL‐10 (13.8 ± 10.1 and 167.1 ± 272.0 pg/mL, P = 0.023) in response to NS3. Combination therapy induced a higher percentage of the lymphocyte activation markers CD69+ and CD38+.

In conclusion, we found that SR is associated with higher CD4+ proliferation particularly in response to the NS3 region, promoting a T‐helper (Th)1/Th0 profile of cytokines, and that combination therapy induced a higher percentage of lymphocyte activation than therapy with IFN alone.