Disrupted faces, disrupted identities? Embodiment, life stories and acquired facial 'disfigurement'.

Questions about the relationship between faces, 'disfigurement' and identity intensified following the first facial transplant (2005). Over a decade later, empirical research exploring the influence of acquired facial 'disfigurement' on embodied identity disruption and re-formation remains limited. A common strand of thinking assumes identities are contained within faces. Commentators have suggested that identities can be diminished through 'disfigurement' and restored or replaced through reconstruction or transplantation. The authors question this claim and provide a conceptually informed, empirical alternative drawing on the results of a phenomenologically located, narrative study exploring identity shift in British adults following acquired 'disfigurement'. Findings suggest that faces are important to humans and that identities can be disrupted in the aftermath of facial 'disfigurement'. Though, the relationship is not simple and cannot be predicted by the degree of corporeal change. Disrupted, liminal and contradictory strands of identity emerged; pre-existing identities were strengthened, new ones emerged, and other non-related experiences were also influential. Nuanced relationality was at the heart of participant sense-making. Consequently, the authors reject the idea that identities are contained within faces and call for the development of a wider social and relational facial phenomenology to more comprehensively explore this fascinating, multifaceted relationship.

Narrative approaches in mental health: Preserving the emancipatory tradition.

Narrative approaches have exercised an emancipatory influence within mental health. In this article, it is suggested that there is a risk that the emancipatory tradition associated with narrative may be co-opted through contemporary mental health strategy by a narrow agenda which promotes a particular Western and neoliberal form of citizenship. This may limit the way recovery can be imagined by equating it solely with the future-orientated individual who strives, above all, to be economically independent. To resist this, it is suggested that narrative in mental health should be approached with recourse to therapeutic thinking which promotes a relational ethos of 'recovery together'. The 'recovery together' model is subsequently considered in relation to narrative research on temporal understandings which have been conducted in disability studies and in the area of chronic illness. These studies point towards the value of a relational orientation towards well-being in the present, rather than fixating on future goals. It is suggested that a relational philosophy of the present might be usefully incorporated into narrative approaches when working therapeutically with people suffering from mental distress. It is argued that this might enable users and practitioners to extend the available narrative templates and to imagine recovery in diverse ways which support personal transformation and, ultimately, contribute to social change.

Revisiting the Panopticon: professional regulation, surveillance and sousveillance.

In this article, we will consider how the regulation of populations is not just a feature of prisons, but of all institutions and organisations that control members though hierarchies, divisions and norms. While nurses and other allied health professionals are considered to be predominantly self-regulatory, practice is guided by a code of conduct and codes of ethics that act as rules that serve to uphold the safety of the patient, whether they are a sick person in a hospital bed or an inmate in a prison. The codes of conduct espouse a number of rules that to a certain extent govern the behaviour of individual and groups of practitioners through reciprocal rewards and punishments. Supervision is one method of monitoring the effectiveness of the codes of conduct and ethics while regulating both the minimum standard of individual practice and of training organisations. It is posited that one of the possible effects of clinical supervision is to make the person effectively self-regulatory as, an autonomous practitioner. We take the view that professional autonomy is a highly problematic concept requiring closer examination.

Towards compassionate care through aesthetic rationality.

The Francis Report, which was based on the investigation of complaints regarding standards of care in the Staffordshire NHS Trust in the UK, was published in 2013. The Report revealed that while the Trust appeared to be compliant with the standards set by official regulating bodies, the quality of care provided to patients was often appalling. While the Report constituted a 'critical moment' in health care, its findings resonated with widespread concern in the UK and elsewhere that health care is sometimes characterised by a lack of compassion. The Francis Report partially attributed this lack of compassion to a task-based culture which tended to prioritise the meeting of targets over the quality of care provided to patients. Older patients, in particular, were identified as being vulnerable to neglect. This qualitative study of hospice volunteers responds to concerns regarding the quality of organisational forms of care by considering how motivations to care may be sustained and enhanced within organisational contexts. Charitable and third sector organisations, such as the hospice in this study, have been identified as potentially relevant to other health and social care contexts precisely because they emphasise values such as altruism and goodwill. Our sociological approach suggests that altruism or compassion can be encouraged within contexts that emphasise a sociability of care. We argue that a sociability of care may be encouraged in organisational contexts if dominant understandings of rationality are extended through the incorporation of aesthetic rationality, a feminist perspective taken from Roslyn Bologh. This, however, would require a degree of authentic emotional engagement on the part of formal caregivers, which is more typically associated with relationships in the private sphere.

Identity, emotion and the internal goods of practice: a study of learning disability professionals.

Contemporary transitions in the delivery of health and social care are a global phenomenon. They prompt a particular need to reconsider how quality in relation to professional practice should be understood and whether greater importance should be attached to values such as goodwill, altruism and commitment. Based on a qualitative study of a small voluntary sector organisation in the North of England, this paper addresses how changes in policy articulate with the identities of professionals who work in learning disability services. Drawing on MacIntyre's After Virtue, which is discussed in relation to some recent sociological debates on emotion, it is suggested that professionals have an emotionally based commitment to their work as well as to the people they work with. Professional commitment is embedded in a coherent sense of self that problematises traditional binaries between the private and the public, and the cognitive and affective. The participants in this study appeared to pursue what MacIntyre terms the 'internal goods' of practice; they valued being able to work innovatively and responsively with service users. It is suggested that this requires a particular type of relationship with oneself, with others, and with practice, which engenders a criticality towards dominant professional discourses.

Warfarin sensitivity genotyping: a review of the literature and summary of patient experience.

The antithrombotic benefits of warfarin are countered by a narrow therapeutic index that contributes to excessive bleeding or cerebrovascular clotting and stroke in some patients. This article reviews the current literature describing warfarin sensitivity genotyping and compares the results of that review to the findings of our study in 189 patients at Mayo Clinic conducted between June 2001 and April 2003. For the review of the literature, we identified relevant peer-reviewed articles by searching the Web of Knowledge using key word warfarin-related adverse event. For the 189 Mayo Clinic patients initiating warfarin therapy to achieve a target international normalized ratio (INR) in the range of 2.0 to 3.5, we analyzed the CYP2C9 (cytochrome P450 2C9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genetic loci to study the relationship among the initial warfarin dose, steady-state dose, time to achieve steady-state dose, variations in INR, and allelic variance. Results were compared with those previously reported in the literature for 637 patients. The relationships between allelic variants and warfarin sensitivity found in our study of Mayo Clinic patients are fundamentally the same as in those reported by others. The Mayo Clinic population is predominantly white and shows considerable allelic variability in CYP2C9 and VKORC1. Certain of these alleles are associated with increased sensitivity to warfarin. Polymorphisms in CYP2C9 and VKORC1 have a considerable effect on warfarin dose in white people. A correlation between steady-state warfarin dose and allelic variants of CYP2C9 and VKORC1 has been demonstrated by many previous reports and is reconfirmed in this report. The allelic variants found to most affect warfarin sensitivity are CYP2C9*1*1-VKORC1BB (less warfarin sensitivity than typical); CYP2C9*1*1-VKORC1AA (considerable variance in INR throughout initiation); CYP2C9*1*2-VKORC1AB (more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1AB (much more sensitivity to warfarin than typical); CYP2C9*1*2-VKORC1AB (much more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1AA (much more sensitivity to warfarin than typical); and CYP2C9*2*2-VKORC1AB (much more sensitivity to warfarin than typical). Although we were unable to show an association between allelic variants and initial warfarin dose or dose escalation, an association was seen between allelic variant and steady-state warfarin dose. White people show considerable variance in CYP2C9 allele types, whereas people of Asian or African descent infrequently carry CYP2C9 allelic variants. The VKORC1AA allele associated with high warfarin sensitivity predominates in those of Asian descent, whereas white people and those of African descent show diversity, carrying either the VKORC1BB, an allele associated with low warfarin sensitivity, or VKORC1AB or VKORC1AA, alleles associated with moderate and high warfarin sensitivity, respectively.

CYP2D6: novel genomic structures and alleles.

OBJECTIVE: CYP2D6 is a polymorphic gene. It has been observed to be deleted, to be duplicated and to undergo recombination events involving the CYP2D7 pseudogene and surrounding sequences. The objective of this study was to discover the genomic structure of CYP2D6 recombinants that interfere with clinical genotyping platforms that are available today. METHODS: Clinical samples containing rare homozygous CYP2D6 alleles, ambiguous readouts, and those with duplication signals and two different alleles were analyzed by long-range PCR amplification of individual genes, PCR fragment analysis, allele-specific primer extension assay, and DNA sequencing to characterize alleles and genomic structure. RESULTS: Novel alleles, genomic structures, and the DNA sequence of these structures are described. Interestingly, in 49 of 50 DNA samples that had CYP2D6 gene duplications or multiplications where two alleles were detected, the chromosome containing the duplication or multiplication had identical tandem alleles. CONCLUSION: Several new CYP2D6 alleles and genomic structures are described which will be useful for CYP2D6 genotyping. The findings suggest that the recombination events responsible for CYP2D6 duplications and multiplications are because of mechanisms other than interchromosomal crossover during meiosis.

Empowering interventions in health and social care: recognition through 'ecologies of practice'.

This article considers findings from two recent qualitative studies in the UK, identifying parallels in the ways in which 'ecologies of practice' in two high-profile areas of health-related intervention underpin processes of empowerment and recognition. The first project focused on policy and practice in relation to teenage motherhood in a city in the North of England. The second project was part of a larger research programme, Changing Families, Changing Food, and investigated the ways in which 'family' is constructed through policy and practice interventions concerning food and health. While UK Government health policy stresses that health and social care agencies should 'empower' service users, it is argued here that this predominantly reflects a managerialist discourse, equating citizenship with individualised self-sufficiency in the 'public' sphere. Drawing critically on Honneth's politics of recognition (Honneth, A. (2001). Recognition or redistribution? Changing perspective on the moral order of society. Theory, Culture and Society, 18(2-3), 43-55.), we suggest that formal health policy overlooks the inter-subjective processes that underpin a positive sense of self, emphasising instead an individualised ontology. While some research has positioned practitioners as one-dimensional in their adherence to the current audit culture of the public sector in the UK, our study findings demonstrate how practitioners often circumvent audit-based 'economies of performance' with more flexible 'ecologies of practice.' The latter open up spaces for recognition through inter-subjective processes of identification between practitioners and service users. Ecologies of practice are also informed by practitioners' experiential knowledge. However, this process is largely unacknowledged, partly because it does not fall within a managerialist framework of 'performativity' and partly because it often reflects taken-for-granted, gendered patterns. It is argued here that a critical understanding of 'empowerment', in community-based health initiatives, requires clear acknowledgment of these inter-subjective and gendered dimensions of 'ecologies of practice'.

Wellbeing and empowerment: the importance of recognition.

Health and wellbeing are now located within a policy framework that emphasises the empowerment of the individual 'consumer'. Within this paradigm, empowerment is writ large and wellbeing is seen as a 'civic duty'. The role of the health and social care services has been identified as one of enabling service users to promote their own wellbeing. In this paper, it is argued that dominant narratives relating to 'achievement' and 'normality' may result in forms of 'misrecognition' that act to undermine the positive sense of self that is crucial for self-empowerment. It is suggested that while the parents of disabled babies often act reflexively to create empowering life narratives within the private sphere, this is not always facilitated by their encounters with health and social care organisations where neo-liberal ideas and biomedical narratives, based on a modernist view of identity as individual and existing prior to society, mean that parents and children are attributed 'deficient' identities in ways that undermine empowerment. With reference to 'the politics of recognition', it is argued that services that seek to empower must value diversity and alterity whilst respecting human dependency on intersubjective recognition.

The linear medical model of disability: mothers of disabled babies resist with counter-narratives.

This paper draws on the narratives of parents of disabled babies in order to conceptualise notions of enabling care. This analysis emerges from the Sheffield site of an ESRC research project Parents, Professionals and Disabled Babies: Identifying Enabling Care, which brings together the Universities of Sheffield and Newcastle-upon-Tyne. The linear heroic narrative is a dominant theme within Western culture. It is competitive and individualistic and tends to be future-orientated in that actions conducted in the present are evaluated according to later outcomes. This linear narrative places much store on modernist interventions such as medicine, and tends to uphold professional boundaries and hierarchies. In the lifeworlds of parents, usually mothers, of disabled babies, this narrative can reinforce disempowering interpretations of disability and impairment. On the basis of 25 in-depth interviews, accompanying stories and ethnographic data, this paper suggests that parents are developing counter-narratives which, at times, resist linear life models and free parents to enjoy their children as they are. If life is perceived as an open book rather than as a concluding chapter, parents are able to develop stories that are neither linear nor heroic but present and becoming.

Mechanisms of MAdCAM-1 gene expression in human intestinal microvascular endothelial cells.

Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is a homing receptor preferentially expressed on gut-associated endothelial cells that plays a central role in leukocyte traffic into the mucosal immune compartment. Although the molecular mechanisms underlying endothelial ICAM-1 or E-selectin expression have been intensively investigated, the mechanisms that regulate human MAdCAM-1 expression have not been defined. We report MAdCAM-1 gene and protein expression in primary cultures of human intestinal microvascular endothelial cells (HIMEC) that was not demonstrated in human umbilical vein endothelial cells. Similar to ICAM-1 and E-selectin expression, MAdCAM-1 gene expression in HIMEC was inducible with TNF-alpha, IL-1beta, or LPS activation. However, in striking contrast to ICAM-1 and E-selectin expression, MAdCAM-1 mRNA and protein expression in HIMEC was heavily dependent on culture duration and/or cellular density, suggesting a prominent role for cell-cell interaction among these endothelial cells in the expression of the mucosal addressin. MAdCAM-1 expression was inhibited by both SN-50 (NF-kappaB inhibitor) and LY-294002 [phosphatidylinositol 3-kinase (PI3-K) inhibitor], whereas ICAM-1 and E-selectin expression was inhibited by SN-50 but not by LY-294002. The Akt phosphorylation by TNF-alpha or LPS was greater at higher cell density, demonstrating a pattern similar to that of MAdCAM-1 expression. NF-kappaB activation was not affected by cellular density in HIMEC. MAdCAM-1 expression in human gut endothelial cells is regulated by distinct signaling mechanisms involving both NF-kappaB and PI3-K/Akt. These data also suggest that PI3-K/Akt is involved in the gut-specific differentiation of HIMEC, which results in expression of the mucosal addressin MAdCAM-1.

Cyclosporin A differentially inhibits multiple steps in VEGF induced angiogenesis in human microvascular endothelial cells through altered intracellular signaling.

The immunosuppressive agent cyclosporin A (CsA), a calcineurin inhibitor which blocks T cell activation has provided the pharmacologic foundation for organ transplantation. CsA exerts additional effects on non-immune cell populations and may adversely effect microvascular endothelial cells, contributing to chronic rejection, a long-term clinical complication and significant cause of mortality in solid-organ transplants, including patients with small bowel allografts. Growth of new blood vessels, or angiogenesis, is a critical homeostatic mechanism in organs and tissues, and regulates vascular populations in response to physiologic requirements. We hypothesized that CsA would inhibit the angiogenic capacity of human gut microvessels. Primary cultures of human intestinal microvascular endothelial cells (HIMEC) were used to evaluate CsA's effect on four in vitro measures of angiogenesis, including endothelial stress fiber assembly, migration, proliferation and tube formation, in response to the endothelial growth factor VEGF. We characterized the effect of CsA on intracellular signaling mechanisms following VEGF stimulation. CsA affected all VEGF induced angiogenic events assessed in HIMEC. CsA differentially inhibited signaling pathways which mediated distinct steps of the angiogenic process. CsA blocked VEGF induced nuclear translocation of the transcription factor NFAT, activation of p44/42 MAPK, and partially inhibited JNK and p38 MAPK. CsA differentially affected signaling cascades in a dose dependent fashion and completely blocked expression of COX-2, which was integrally linked to HIMEC angiogenesis. These data suggest that CsA inhibits the ability of microvascular endothelial cells to undergo angiogenesis, impairing vascular homeostatic mechanisms and contributing to the vasculopathy associated with chronic rejection.

Sodium butyrate inhibits angiogenesis of human intestinal microvascular endothelial cells through COX-2 inhibition.

We examined the effect of sodium butyrate on in vitro angiogenesis and cyclooxygenase (COX) expression using primary cultures of human intestinal microvascular endothelial cells (HIMEC). Butyrate inhibited VEGF-induced cellular proliferation, transmigration and tube formation of HIMEC. Butyrate also inhibited COX-2 expression as well as prostaglandin (PG)E2 and PGI2 production, and administration of PGI2 analog partially reversed the effect of butyrate on HIMEC angiogenesis. These results indicate that sodium butyrate inhibits HIMEC angiogenesis through down-regulation of COX-2 expression and PG production, and suggest that anti-angiogenic mechanisms may also be involved in the inhibitory effect of sodium butyrate on tumor growth.

Butyrate modulates gene and protein expression in human intestinal endothelial cells.

We hypothesized that sodium butyrate, a product of enteric bacterial fermentation, modulates gene expression in gut microvascular endothelium which plays a central role in mucosal immunity. We examined sodium butyrate's effect on LPS-induced gene and protein expression in primary cultures of human intestinal microvascular endothelial cells. cDNA array analysis revealed that sodium butyrate augmented ICAM-1 mRNA expression, while it inhibited IL-6 and COX-2 expression in response to LPS stimulation. These results were confirmed at the protein level. Prostaglandin E2 production by LPS was also strongly inhibited by butyrate. The pattern of altered gene expression by butyrate was reproduced by the histone deacetylase inhibitor tricostatin A, suggesting that the regulatory mechanism of butyrate on HIMEC gene expression involves histone deacetylase inhibition. IkappaBalpha degradation and NF-kappaB activation were unaffected by butyrate. In addition to effects on epithelium, sodium butyrate modulates the innate mucosal immune response towards LPS through effects on microvascular endothelial function.

Isolation and characterization of human esophageal microvascular endothelial cells: mechanisms of inflammatory activation.

Gastroesophageal reflux disease is the most common malady of the esophagus, affecting 7% of the United States population. Histological assessment demonstrates classic inflammatory mechanisms including selective leukocyte recruitment and hemorrhage, suggesting a prominent role for the microvasculature. We isolated and characterized human esophageal microvascular endothelial cells (EC) (HEMEC), examined inflammatory activation in response to cytokines, LPS, and acidic pH exposure, and identified signaling pathways that underlie activation. HEMEC displayed characteristic morphological and phenotypic features including acetylated LDL uptake. TNF-alpha/LPS activation of HEMEC resulted in upregulation of the cell adhesion molecules (CAM) ICAM-1, VCAM-1, E-selectin, and mucosal addressin CAM-1 (MAdCAM-1), increased IL-8 production, and enhanced leukocyte binding. Both acid and TNF-alpha/LPS activation lead to activation of SAPK/JNK in HEMEC that was linked to VCAM-1 expression and U-937 leukocyte adhesion. Expression of constitutive inducible nitric oxide synthase in HEMEC was in marked contrast to intestinal microvascular endothelial cells. In this study, we demonstrate that HEMECs are phenotypically and functionally distinct from lower gut-derived endothelial cells and will facilitate understanding of inflammatory mechanisms in esophageal inflammation.

Mechanisms of endotoxin tolerance in human intestinal microvascular endothelial cells.

Lipopolysaccharide (endotoxin) tolerance is well described in monocytes and macrophages, but is less well characterized in endothelial cells. Because intestinal microvascular endothelial cells exhibit a strong immune response to LPS challenge and play a critical regulatory role in gut inflammation, we sought to characterize the activation response of these cells to repeated LPS exposure. Primary cultures of human intestinal microvascular endothelial cells (HIMEC) were stimulated with LPS over 6-60 h and activation was assessed using U937 leukocyte adhesion, expression of E-selectin, ICAM-1, VCAM-1, IL-6, IL-8, manganese superoxide dismutase, HLA-DR, and CD86. Effect of repeat LPS stimulation on HIMEC NF-kappaB and mitogen-activated protein kinase (MAPK) activation, generation of superoxide anion, and Toll-like receptor 4 expression was characterized. LPS pretreatment of HIMEC for 24-48 h significantly decreased leukocyte adhesion after subsequent LPS stimulation. LPS pretreatment inhibited expression of E-selectin, VCAM-1, IL-6, and CD86, while ICAM-1, IL-8, and HLA-DR were not altered. Manganese superoxide dismutase expression increased with repeated LPS stimulation, with a reduction in intracellular superoxide. NF-kappaB activation was transiently inhibited by LPS pretreatment for 6 h, but not at later time points. In contrast, p44/42 MAPK, p38 MAPK, and c-Jun N-terminal kinase activation demonstrated inhibition by LPS pretreatment 24 or 48 h prior. Toll-like receptor 4 expression on HIMEC was not altered by LPS. HIMEC exhibit endotoxin tolerance after repeat LPS exposure in vitro, characterized by diminished activation and intracellular superoxide anion concentration, and reduced leukocyte adhesion. HIMEC possess specific mechanisms of immunoregulatory hyporesponsiveness to repeated LPS exposure.

Cyclosporine A enhances leukocyte binding by human intestinal microvascular endothelial cells through inhibition of p38 MAPK and iNOS. Paradoxical proinflammatory effect on the microvascular endothelium.

The calcineurin inhibitor cyclosporine A (CsA) modulates leukocyte cytokine production but may also effect nonimmune cells, including microvascular endothelial cells, which regulate the inflammatory process through leukocyte recruitment. We hypothesized that CsA would promote a proinflammatory phenotype in human intestinal microvascular endothelial cells (HIMEC), by inhibiting inducible nitric-oxide synthase (iNOS, NOS2)-derived NO, normally an important mechanism in limiting endothelial activation and leukocyte adhesion. Primary cultures of HIMEC were used to assess CsA effects on endothelial activation, leukocyte interaction, and the expression of iNOS as well as cell adhesion molecules. CsA significantly increased leukocyte binding to activated HIMEC, but paradoxically decreased endothelial expression of cell adhesion molecules (E-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule-1). In contrast, CsA completely inhibited the expression of iNOS in tumor necrosis factor-alpha/lipopolysaccharide-activated HIMEC. CsA blocked p38 MAPK phosphorylation in activated HIMEC, a key pathway in iNOS expression, but failed to inhibit NFkappaB activation. These studies demonstrate that CsA exerts a proinflammatory effect on HIMEC by blocking iNOS expression. CsA exerts a proinflammatory effect on the microvascular endothelium, and this drug-induced endothelial dysfunction may help explain its lack of efficacy in the long-term treatment of chronically active inflammatory bowel disease.