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Using a convenience sampling, nurse educators representing 10 countries were surveyed to describe required clinical education for advanced practice beyond basic traditional nursing education. This article explores the many factors currently influencing the structure and diversity of these clinical experiences worldwide.

Background: The development of nursing research capacity and interactions with cultural and structural issues is at various stages throughout Europe. This process appears to be remarkably similar irrespective of the country. Sweden has developed this capacity since the 1990s, whereas France is experiencing a transition. Nevertheless, knowledge about how nurses conceive their learning about nursing research and transitioning toward being researchers is scarce., Objectives: The aim of this study was to explore French and Swedish RNs' conceptions of research education and educational passage toward research and to describe how learning research contributes to the understanding of their norms and practices., Design: A phenomenographic approach was used to understand and describe the qualitatively different ways in which French and Swedish RNs conceive research and its apprenticeship., Settings and Participants: A purposive maximum variation sampling of five French and five Swedish Nurse Researchers with PhDs., Methods: Individual in-depth interviews conducted in France and Sweden between November 2012 and March 2013 were analysed using phenomenography., Findings: The analysis revealed one main category, "Organisational factors to sustain individual apprenticeship". Three descriptive categories have emerged from the data and its variations amongst French and Swedish nurses: (1) entrance into research--modes of commitment; (2) nurses' engagement--the need for dedicated support; and (3) research as the means to resolve nursing situations., Conclusions: This study demonstrates how registered nurses have integrated nursing and researcher roles following different efficient paths. Education in nursing research is part of the strategy needed for the development of nursing research and is supported by the integration of research and practice., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aim: To report from a study aimed at illuminating how French Registered Nurses experience and engage in nursing research in clinical practice., Background: Nursing research in France is mainly conducted by nurses working at clinical research units rather than by dedicated nurse researchers. Education, i.e. advanced degrees, in the field of nursing research is still in its infancy and not yet consistent with the international context. Outside France, the general perception is that nursing research is a unified part of professional nursing. Consequently, in-depth knowledge about how nurses in a French clinical context might experience and engage in nursing research is still lacking., Design: The design of this study was influenced by an ethnographic approach as described by the French anthropologists Beaud and Weber., Method: Data, participatory observations, field notes and interviews (n = 6) were collected in a teaching hospital between April-August 2012. The field consisted of a wound-care unit and clinical research units. Collected data were analysed based on Beaud and Weber's description of analysis., Results: Three beliefs were identified: being a unified part of a research team, being an integral part of 'crosswise - across' activities and being part of research activities., Conclusion/implication for Research: Commitment to nursing research was strengthened by patient-related issues. Based on this context, nursing research would likely benefit from the support of a naturalized reciprocity between clinical practice and research., (© 2014 John Wiley & Sons Ltd.)

Nursing in France is undergoing a transition. In 2009, the preregistration nursing education program was reformed in line with the European Bologna Process, bringing nursing education to the universities. In 2010, the French Programme Hospitalier de Recherche Infirmière, the first national French nursing research funding program, was launched by the French Health Ministry. Of the 149 French research proposals submitted by registered nurses in 2010 and 2011, 13 were mixed-method proposals. The registered nurse principal investigator argued for a complementary use of qualitative and quantitative methods. These trends highlight major issues regarding mixed-method and nursing research. We can reasonably assume that mixed-method research has a broad appeal for nurse scholars, particularly for the exploration of complex phenomena related to nursing. Moreover, the recent movement in the domain of nursing education and research experienced in France highlights the need for dedicated research education in the development of nursing research capacity., (© The Author(s) 2014 Reprints and permissions:]br]sagepub.co.uk/journalsPermissions.nav.)

Maximal exercise test with gas exchange measurement evaluates exercise capacities with maximal oxygen uptake (VO(2) max) measurement. Measurements of lactate (L), lactate/pyruvate ratio (L/P) and ammonium (A) during rest, exercise and recovery enhance interpretative power of maximal exercise by incorporating muscular metabolism exploration. Maximal exercise test with gas exchange measurement is standardized in cardiopulmonary evaluations but, no reference data of blood muscular metabolites are available to evaluate the muscular metabolism. We determined normal values of L, L/P and A during a standardized maximal exercise and recovery in 48 healthy sedentary volunteers and compared with results obtained in four patients with exercise intolerance and a mitochondrial disease. In healthy subjects, L, L/P and A rose during exercise. In 98% of them L, L/P or A decreased between the fifth and the fifteenth minutes of recovery. In mitochondrial patients, VO(2) max was normal or low, and L, L/P and A had the same evolution as normal subjects or showed no decrease during recovery. We gave normal L, L/P and A values, which establish references for a maximal exercise test with muscular metabolism exploration. This test is helpful for clinicians in functional evaluation, management and treatment of metabolic myopathy and would be a useful tool in diagnosis of metabolic myopathy., (© 2012 The Authors Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

We investigated the pharmacological properties of a newly synthesised delta agonist AR-M1000390, derived from SNC-80 ((+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethyl-benzamide), in the neuroblastoma cell line SK-N-BE expressing only human delta-opioid receptors. Binding and functional experiments showed a weak affinity (K(i) = 106 +/- 34 nM) correlated with a weak potency (EC(50) = 111 +/- 31 nM) to inhibit the forskolin-stimulated cAMP accumulation. Sustained activation of opioid receptors in the presence of the maximal inhibitory concentration of AR-M1000390 produced a rapid and strong desensitization. In order to examine the contribution of internalization and down-regulation in the desensitization processes, binding and functional experiments were conducted in the presence or in the absence of hypertonic sucrose solution to block clathrin-dependent opioid receptor endocytosis. We observed both the inability of AR-M1000390 to down-regulate opioid receptors and the absence of any effect of sucrose on desensitization. The lack of delta-opioid receptor internalization by AR-M1000390 was further corroborated by confocal microscopy using antibodies directed either against the endogenous delta-opioid receptors or the FLAG-tagged delta-opioid receptors stably expressed in the SK-N-BE cells. These data suggest that uncoupling rather than internalization is responsible for delta-opioid receptors desensitization by AR-M1000390.

Using a particular model of apoptosis, we here demonstrate the ability of the comet assay to differentiate between different cell populations. In our study, the natural killer Kurloff cells, used as effector cells, recognize and bind to the tumoral L2C target cells. Formation of such conjugates leads to the death of the target cells by apoptosis, as previously described by different conventional techniques. With the alkaline comet assay, a conjugate could directly be visualized as an association of an undamaged cell joined to a highly damaged cell. The modified comet assay used in this study comprises specific labelling of Kurloff cells with immunomagnetic beads, which are visible as grey-dull spheres against the bright-red staining of nuclear origin on the comet preparation. The use of such labelled effector cells suggest the potential of the comet assay to visually identify different cell populations in an unique test.

L2C leukemia is a leukemia that occurs in strain two guinea pigs. The L2C cells are natural killer-sensitive. The Kurloff cell (KC), a guinea pig NK cell, develops a 3-fold increase in lysosomal enzyme activity and the number of KC cells increases during leukemogenesis, leading to KC cell-mediated L2C cytolysis. This paper shows that conjugates are produced by incubating KC and L2C for 4 h, with 34% of L2C showing chromatin compaction and shrinkage of the cytoplasm. There was also a reorientation of the KC cytoplasmic organelles to face the target cell and an elongation of the KC to produce arms that engulfed the L2C. The L2C had either necrotic or apoptotic characteristics. L2C DNA fragmentation was demonstrated in situ with the comet and the TUNEL assays. 22.2% of the viable L2C lost their membrane asymmetry during KC-L2C conjugation as shown by incubation with Annexin V-FITC. These results provide new evidence that the death of L2C is due, at least partly, to apoptosis. The cytolytic effect of the NKKC might be a model of the cytological changes that occur in NK cell-leukemic cell conjugates.

We examined the in vivo role of Kurloff cells (KC), guinea pig natural killer cells, during the development of L2C leukemia, by analysing changes in the arylsulfatases (Asases) in the lysosomal Kurloff body. The Kurloff body is rich in acid phosphatase, esterase and proteoglycans, as are large granular lymphocyte granules. Moreover, the Kurloff body contains lysosomal Asase B, with unusual anionic isoforms. Injection of L2C cells elicited a three-fold increase in KC Asase activity on day 6. The increase in KC Asase activity was correlated with the number of circulating L2C cells. The basic Asase form (pl 8) was lost, and a concomitant increase in anionic isoforms (pl 5-6) was observed on day 6. The role of the latter in cytolysis was investigated by examining their capacity to lyse L2C target cells. We conclude that Asase participates in cytolysis when lysis is mediated by the complete assembly of cytolytic proteins. Changing and increasing KC Asase activity during leukemia development may be a marker for activated KC in vivo. These findings suggest that the cytolytic activation of KC occurs during the preleukemic period.

The guinea pig Kurloff cell (KC) is an estradiol-dependent circulating mononuclear cell that had natural killer cytotoxic activity in vitro. We studied the variation of KC number during the development of transplanted leukemia in inbred strain 2 (S2) leukemia-sensitive guinea pigs. Grafts of leukemic cells (L2C) produced a significant increase in the number of KC. Leukemia occurred in 35.5% of non-estrogenized animals and in 18.3% of estrogenized guinea pigs. The increased number of KC seems to have antileukemia activity in vivo. This could be part of the general phenomenon of cancer resistance in guinea pigs.

The Kurloff cell (KC) of the guinea-pig develops natural killer cytotoxic activity in heterologous systems. We report in this paper the effective in vitro cytotoxic activity of the KC in a homologous guinea-pig system, i.e. against the guinea-pig target leukemic L2C cells. A dual-color flow analysis of homologous effector-target conjugates, using calcein-labeled KC and hydroethidine-labeled L2C shows a 40% frequency KC-L2C conjugation. The specific cytotoxicity of KC against L2C (78%) was estimated as the target-loss of green fluorescence due to hydrolysed carboxy-fluorescein diacetate after 4 hours at 37 degrees C. We propose that the Kurloff cell could be involved in surveillance against spontaneously arising leukemic cells, and this could be an explanation for the high degree of resistance to spontaneous or experimentally-induced cancers, in the guinea-pig.

Sex hormones have an effect on various immune responses but the mechanisms of action are unknown. One of these mechanisms might be a modification of expression of major histocompatibility complex (MHC) antigens in blood leucocytes. Estradiol-induced variations of the expression of guinea pig blood leukocytes MHC antigens (GPL-A) was studied. Class I and class II MHC antigens were detected by a sensitive rosetting method using specific alloimmune sera (AIS) and staphylococcal protein A-coated sheep red blood cells (SPA-SRBC) and evaluated by counting the number of bound SPA-SRBC per 100 cells. MHC antigens decreased after estrogen treatment. Estradiol modifies the expression of GPL-A antigens on the mononuclear cells including the Kurloff cells, which are involved in immunity or in a natural killer effect, but did not affect the expression of polymorphonuclear cells, ones which are not involved in immunity.

The relationship of the Kurloff cell (KC), guinea pig blood mononuclear cell with natural killer (NK) activity, to a known cell lineage was established. Using indirect immunoperoxidase staining and flow cytometric analysis, numerous monoclonal antibodies directed against guinea pig macrophage antigen, Ia antigen or different T lymphocyte markers and a polyclonal anti-IgM serum were tested in unimmunized estrogenized animals. We excluded any relationship between KC and the monocytic macrophage lineage (MR-1-) and between KC and the B lymphocyte lineage (CT10- and IgM-). The KC immunophenotype was pan T CT7 positive but 8BE6 (mature thymocyte) and CT6 (cytotoxic suppressor T lymphocyte) negative. Since KC displays an NK activity, this cell may be classified among the NK effector cells exhibiting some T lymphocyte markers.

In order to study their natural killer effect, guinea pig splenic Kurloff cells were fractionated by Percoll discontinuous density gradient centrifugation. Kurloff cells were collected and tested for cytotoxicity in a 24-hr chromium-release test. Comparison of different splenic cellular samples (of males or estrogenized females) with increasing percentage of Kurloff cells, revealed a highly significant positive correlation (r = 0.93, alpha less than 0.01) with the cellular cytotoxicity developed against the K 562 target cells.

We made red cell and white cell counts in an homogeneous sample of more than 250 healthy, non gravid, adult, female guinea-pigs. Up to the present it is the highest number of guinea-pigs on which systematic blood counts have been taken. Each category of cells was studied statistically. Our mean of the red cells (5.03 X 106/mm3) is close to most of the means reported in the literature for both sexes; the distribution apparently follows the Gauss normal distribution. The mean of the white cells that we obtained (11.800/mm3) is greater than those of many authors in both sexes. The total number of lymphocytes and monocytes (6.180/mm3) is larger than that of the granulocytes (4.970/mm3). The mean Kurloff cells is 422/mm3. The distribution curves of the aggregate of white cells and those of the granulocytes, the lymphocytes and monocytes, the Kurloff cells are asymmetrical and spread towards the right; the normality hypothesis is rejected for each of them.

Large populations of splenic Kurloff (150 - 200 X 10(6) Kurloff cells) were obtained from estrogenized guinea pigs by isopycnic centrifugation in a Percoll solution of 1.085 g/ml starting density. The Kurloff cells settled at a buoyant density of about 1.100 g/ml. The purity of these cell suspensions reached 95%, as assessed by phase contrast microscopy and by specific staining. The viability assessed by Trypan blue exclusion test was also about 95%. Moreover, the good transmission electron microscopic appearance of these Kurloff cells and their ability to take up 35S-methionine in culture confirmed their physiological integrity. By autohistoradiography, this protein labeling was localized between the nucleus and the Kurloff body, and also on the Kurloff body itself. This data reinforces the hypothesis of de novo synthesis of the Kurloff body.

The exceptional carcinoresistance of guinea-pigs is well known and only a few cases of spontaneous leukaemia and several very rare cases of lymphoma have been reported in the literature. A spontaneous malignant tumor in an old male hybrid guinea-pig is described. The monomorphous aspect of the tumour, the cellular cohesiveness, the "starry-sky" pattern and the immunocytological characterization of tumour cells as B lymphocytes bearing IgM, lead to describe this tumour as a probable spontaneous Burkitt-type malignant lymphoblastic lymphoma.