A multidisciplinary perspective on physician-assisted dying in primary care in The Netherlands: A narrative interview study.

Most research on physician-assisted dying (PAD) in the Netherlands focuses on general practitioners (GPs). Less is known about the perspectives of other professionals. We performed narrative interviews with 10 professionals other than GPs to explore their perspectives on PAD in primary care. The results provide insight into PAD as an enacted practice involving many different actors, considerations, and expectations and into the intertwinement between PAD and palliative sedation. The study shows how a multidisciplinary perspective to PAD provides new avenues for practice, research, and ethics. It poses the question whether PAD can and should be considered merely a physicians' concern.

Living With Cardiovascular Disease: Existential Meaning of Lifestyle Change.

This study aims at exploring the perspectives of patients with cardiovascular disease (CVD) on the existential meaning of lifestyle change as an evidence base for spiritual care by nurses and other health professionals. This study has been carried out within the paradigm of phenomenological caring sciences. The sample of 18 participants was purposively selected. Data consisted of in-depth interviews among adults with an episode of CVD. Data analysis of transcribed audio recordings was done using the method of Reflective Lifeworld Approach. For patients with CVD, changing one's lifestyle is an experience of transition in self-image. This transition has a twofold dynamic. On the one hand, it entails alternating phases in what is meaningful for the patient: letting go (loss of the normal, of health, of bodily functions) and holding on (desire to be healthy and to be normal). On the other hand, through the vulnerability and loneliness patients often experience, patients report a need to be encouraged by and connected to others/the Other. Making brave choices and connecting to the patients' spiritual resources of inner strength are crucial for successful lifestyle changes and meaningful transition to a new lifestyle. Lifestyle change is not only a physical and psychological process for the patient with CVD but also an existential transition that involves fundamental views and values of being human. It is an experience that is in part socially influenced, that is, by encouragement from meaningful others. For the health care worker, knowledge of this experience may help provide spiritual care after CVD.

The Role of Spirituality in Lifestyle Changing Among Patients with Chronic Cardiovascular Diseases: A Literature Review of Qualitative Studies.

Chronic cardiovascular diseases (CVD) are diseases with marked morbidity. Patients are often advised to change their lifestyle to prevent complications and impairment of their diseases. Compliance, however, is influenced by multiple factors. Initial studies show that spirituality is an important aspect in health behavior and lifestyle changing, but to health professionals like nurses this is unknown. The aim of this review is to investigate and synthesize evidence about the role of spirituality in lifestyle changing in patients with chronic CVD. A comprehensive search was conducted in electronic databases Academic Search Premier, E-journals, Medline and PubMed, published between the years 2000-2015. After selection based on pre-set inclusion criteria, studies were retrieved and evaluated on quality using the criteria of the QOREC. Twelve studies with a qualitative empirical design and mixed methods were included. This review shows that spirituality, is related to the self-management of patients with chronic diseases. For instance, lifestyle changes are experienced as a continuous inner battle. Religion gives strength, but is also experienced as a struggle. Feelings of guilt and becoming a victim influence patients' experience. For effectively advising patients with CVD on lifestyle changes, nurses cannot ignore this factor but further investigation is required.

The importance of 'global meaning' for people rehabilitating from spinal cord injury.

STUDY DESIGN: Qualitative study. OBJECTIVES: To explore whether aspects of global meaning (that is, fundamental beliefs and life goals concerning core values, relationships, worldview, identity and inner posture) are associated with processes and outcomes in rehabilitation, as experienced by people with spinal cord injury (SCI). SETTING: People living in the community receiving outpatient rehabilitation in a Dutch rehabilitation center. METHODS: In-depth semi-structured interviews were conducted with 16 people with SCI. Interviews were analyzed using qualitative research methods: structural and provisional coding. RESULTS: Core values, relationships, worldview, identity and inner posture (that is, the way in which people relate to the facts of life) were associated with various processes and outcomes of rehabilitation. Elements of the rehabilitation process included motivation, regulation of emotion, making decisions and handling stress. Elements of the outcome of rehabilitation included physical functioning, emotional functioning, social functioning and subjective sense of meaning. The influence was positive, with the exception of one case in which worldview and inner posture were negatively associated with motivation. Besides that, respondents emphasized the importance of rehabilitation professionals attuning to their global meaning. CONCLUSION: All aspects of global meaning were positively associated with various processes and outcomes of rehabilitation. It is recommended that rehabilitation professionals are aware of the importance of global meaning to people with SCI and that they take people's fundamental beliefs and life goals into account.

Teaching medical students about fair distribution of healthcare resources.

Healthcare package decisions are complex. Different judgements about effectiveness, cost-effectiveness and disease burden influence the decision-making process. Moreover, different concepts of justice generate different ideas about fair distribution of healthcare resources. This paper presents a decision model that is used in medical school in order to familiarise medical students with the different concepts of justice and the ethical dimension of making concrete choices. The model is based on the four-stage decision model developed in the Netherlands by the Dunning Committee and the discussion that followed its presentation in 1991. Having to deal with 10 medical services, students working with the model learn to discern and integrate four different ideas of distributive justice that are integrated in a flow chart: libertarian, communitarian, egalitarian and utilitarian.

Boundaries, borders, and limits. A phenomenological reflection on ethics and euthanasia.

The subject of euthanasia divides both people and nations. It will always continue to do so because the arguments for and against this issue are intrinsically related to each other. This paper offers an analysis of the interrelation of the arguments, departing from a phenomenology of boundaries. From the participant perspective the boundary of euthanasia appears as a limit. From a helicopter perspective it appears as a border. Reflecting on both perspectives they turn out to complement each other: the positive effects of the former correspond to the negative effects of the latter. In order to see how this interrelation of viewpoints works out in the case of euthanasia a paradigmatic case is analysed from the perspective of the patient, the doctor, and the family. This phenomenological analysis does not directly lead to normative conclusions. It helps by both paying attention to, and dealing with, the complexity of the issue with intellectual honesty.

Avoiding evasion: medical ethics education and emotion theory.

Beginning with an exemplary case study, this paper diagnoses and analyses some important strategies of evasion and factors of hindrance that are met in the teaching of medical ethics to undergraduate medical students. Some of these inhibitions are inherent to ethical theories; others are connected with the nature of medicine or cultural trends. It is argued that in order to avoid an attitude of evasion in medical ethics teaching, a philosophical theory of emotions is needed that is able to clarify on a conceptual level the ethical importance of emotions. An approach is proposed with the help of the emotion theory Martha Nussbaum works out in her book Upheavals of thought. The paper ends with some practical recommendations.

Close phenotypic and functional similarities between human and murine alphabeta T cells expressing invariant TCR alpha-chains.

Several studies have demonstrated the existence of a murine NK1.1+ alphabeta T cell subset expressing V alpha14+ TCR alpha-chains with highly conserved invariant junctional sequences and able to secrete Th2 cytokines when exposed to CD1+ stimulator cells. In humans, alphabeta T cells carrying invariant V alpha24+ TCR alpha-chains highly homologous to those expressed by murine NK1.1 cells have been recently described. Here we show that these cells (referred to as V alpha24inv T cells) and murine NK1.1+ alphabeta T cells resemble each other in several ways. First, like their murine counterparts, T cells expressing high levels of V alpha24inv TCRs can be either CD4- CD8- double negative (DN) or CD4+, but they never express heterodimeric CD8 molecules. Second, most V alpha24inv T cells are brightly stained by NKRP1-specific mAb but not by mAb directed against other type II transmembrane proteins of the NK complex. Third, DN and particularly CD4+ V alpha24inv T cells are greatly enriched for IL-4 producers. The concomitant expression of highly conserved TCRs of a particular set of NK markers and of Th2 cytokines in human and murine alphabeta T cells suggests a coordinate acquisition of these phenotypic and functional properties. Furthermore, the relatively high frequency of human V alpha24inv T cells, which are presently shown to represent on average 1/500 PBL, and the high interindividual variations of the size of this cell subset under physiologic conditions go for a major role played by alphabeta T cells carrying invariant TCR in a large array of immune responses.

Reactivity of mouse T-cell hybridomas expressing human Vbeta gene segments with staphylococcal and streptococcal superantigens.

A panel of 15 mouse T-cell hybridomas, each expressing a different human Vbeta gene segment (hVbeta) in an otherwise mouse T-cell receptor (i.e., mouse alpha chain and CD3 complex), was constructed by transfection of hVbeta/mouse Cbeta chimeric T-cell receptor (TCR)-beta genes into a mouse T-cell hybridoma recipient lacking the endogenous TCR-beta chain. Several qualities that are conferred by the hVbeta chain of the TCR are retained in the chimeric human-mouse TCR complex: a large panel of hVbeta-specific antibodies specifically stained the hVbeta expressed by the mouse T-cell hybridomas. Moreover, hVbeta-transfected mouse cells could readily produce interleukin 2 when stimulated by superantigens presented by antigen-presenting cells. These characteristics made it possible to refine the reactivity of 17 superantigen preparations with the available transfected Vbetas. Each superantigen gave a characteristic pattern of reactivity on the transfectants. Positive reactivities with some of these transfectants, which differ only by the expressed hVbeta, demonstrate unambiguously the superantigenic character of a protein or fraction and its potential to react with the corresponding Vbetas. Therefore, these hVbeta-transfected cells constituted a valuable tool for determining "specificity fingerprints" of known or putative superantigens. First, commonly used, commercially available superantigens such as staphylococcal enterotoxin B and toxic shock syndrome toxin-1 (TSST-1) showed additional Vbeta reactivities, compared with those of their recombinant counterparts. This stresses the importance of using defined preparations of superantigens for the definition of Vbeta specificities. Second, the stimulatory pattern of a strain of Streptococcus pyogenes demonstrated that this strain, unlike others, produces a potent Vbeta 8-specific superantigen that is an yet undefined at the molecular level.

Structural analysis of gamma delta TCR using a novel set of TCR gamma and delta chain-specific monoclonal antibodies generated against soluble gamma delta TCR. Evidence for a specific conformation adopted by the J delta 2 region and for a V delta 1 polymorphism.

We recently showed that secretion of non-chimeric disulfide-linked human gamma delta TCR ('soluble' TCR, sTCR) comprising V gamma 9 and V delta 2 regions could be achieved by simply introducing translational termination codons upstream from the sequences encoding TCR transmembrane region. Here we extended these findings by demonstrating efficient secretion and heterodimerization of gamma delta sTCR comprising V gamma 8, V delta 1 and V delta 3 regions, obtained via the same strategy. After immunization against immunoaffinity-purified soluble TCR, several hundreds of TCR-specific monoclonal antibodies (mAb) were generated, which fell in at least seven groups. One set of mAb was directed against a V gamma 8-specific epitope. Strikingly, despite the high degree of sequence homology between V gamma 8 and other V gamma I domains, none of these mAb were crossreactive with other members of the V gamma I family. Three other sets of mAbs were shown to recognize delta chains comprising V delta 1, V delta 2 and V delta 3 regions respectively, regardless of their junctional sequence or of the gamma chain to which they were paired. Among the V delta 1-specific mAb, some specifically recognized V delta 1D delta J delta C delta chains while others reacted with both V delta 1 D delta J delta C delta and V delta 1J alpha C alpha chains, which suggested V domain conformational alterations induced by the C region. Moreover, reactivity of one V delta 1-specific mAb (#R6.11) was affected by a polymorphic residue located on the predicted CDR4 loop of the V delta region. Two delta chain-specific mAb (#178 and #515) showed a highly unusual reactivity, which was negatively affected by particular V delta and J delta sequences: (i) mAb #515 and #178 recognized all TCR delta chains except those comprising V delta 1 or V delta 2 regions, respectively and (ii) within TCR delta chains carrying 'permissive' V delta regions, none of those comprising the J delta 2 region were recognized by #515 and/or #178 mAbs, which suggested a highly specific conformation adopted by this particular J delta sequence. Apart from its usefulness in TCR structural studies, this novel set of mAb represents an important tool for the characterization and isolation of gamma delta T cells expressing particular combinations of V gamma/V delta regions and for analysis of V alpha/V delta usage by alpha beta T cells. Moreover, since our present data strongly suggest that gamma delta TCR are easier to obtain in a soluble form than alpha beta TCR, an efficient strategy for the generation of V alpha region-specific mAb might be to immunize with chimeric gamma delta sTCR comprising particular V alpha regions.

Repertoire analysis of human peripheral blood lymphocytes using a human V delta 3 region-specific monoclonal antibody. Characterization of dual T cell receptor (TCR) delta-chain expressors and alpha beta T cells expressing V delta 3J alpha C alpha-encoded TCR chains.

V delta 3 usage and combinatorial expression of V gamma and V delta regions was studied on peripheral T cells with a novel V delta 3-specific mAb (p11.10b), generated against a soluble V gamma 9V delta 3 TCR. V delta 3+ cells represented the vast majority of V delta 1/V delta 2- gamma delta T cells within peripheral blood and mucosal lymphocytes. No preferential V gamma region expression was noted within V delta 3+ cells, but the frequency of V gamma 9+ cells was significantly lower among V delta 3+ than among V delta 1+ or V delta 2+ PBL. Phenotypic analysis of cultured V delta 3+ cells sorted with p11.10b mAb revealed the presence of T lymphocytes with unusual phenotypes. First, cells carrying two distinct surface TCR delta-chains, recognized by both V delta 1- and V delta 3-specific mAbs, were detected in most T cell lines, though at frequencies much lower than that of dual gamma expressors, indicating that allelic exclusion of delta genes is more tightly regulated than that of gamma genes. Moreover, a significant fraction of V delta 3+ cells were recognized by C beta- but not C delta-specific mAbs. Molecular analysis of V delta 3+C beta+ clones revealed the presence of V delta 3J alpha C alpha transcripts in all of them. Given the peculiar location of the V delta 3 gene between the delta Rec/psi J alpha elements, those observations formally demonstrate that activation of rearrangements with J alpha elements is not necessarily preceded by a delta Rec/psi J alpha-mediated deletion of the delta locus on the same chromosome.