The cycle of uncertainty: parents' experiences of childhood epilepsy.

Uncertainty has been highlighted as an important aspect of experiences of chronic conditions generally and epilepsy in particular. However, there is little research exploring the extent to which uncertainty features in the experiences of family members or the form that this uncertainty may take. Drawing on in-depth semi-structured interviews with 27 parents who had a child with epilepsy, this article explores parents' experiences of uncertainty and the way in which their views on childhood and epilepsy interacted and contributed to the uncertainties they experienced. It is argued that the occurrence of epilepsy during childhood shaped parents' experiences as they used their 'social clocks' in order to interpret symptoms. Furthermore, parents described what has been termed a 'cycle of uncertainty'. Indeed, the combination of epilepsy (a condition with various inherent forms of uncertainty) and childhood (a period in the life course that is seen as a time of development) meant that parents could not be sure which changes in their child were a result of the condition and which were a normal part of the ageing process. Overall, this article demonstrates that it is important to contextualise experiences of chronic conditions in relation to different stages in the life course.

Siblings' caring roles in families with a child with epilepsy.

Despite large amounts of care for chronic conditions being provided within the family, information regarding the extent to which siblings contribute to informal care practices in families where a child has a chronic condition is limited. This article draws on multiple perspective data from 24 families that had a child with epilepsy. In doing so, the article illustrates siblings' significant contribution to caring for their brother or sister and further develops the alert assistant concept. Two additional distinct caring roles that the siblings took on are also outlined - the substitute parent and parenting assistant roles. The relationship between siblings' socio-demographic characteristics and their caring responsibilities is also explored. The paper's findings are that siblings who were older, female and those in families with a higher child to parent ratio took on more caring responsibilities. Consequently, this article contributes to the currently limited literature on siblings who care for a chronically ill brother or sister by increasing understandings of different caring roles and experiences of chronic illness in families.

Similarities and differences in the meanings children and their parents attach to epilepsy medications.

By exploring the meanings children and their parents attached to two household treatments for childhood epilepsy (antiepileptic drugs and emergency medications), this paper broadens our understanding of the ways in which children view their medications and how these views can impact on their adherence to treatment. The paper draws on data collected during 2013 and 2014 from 24 families across the UK that had a child with epilepsy aged 3-13 years. In-depth semi-structured interviews were conducted with the parents and 10 children participated in autodriven photo-elicitation interviews. Parents' and children's perceptions of medications were compared and contrasted and the findings show that although both parents and children viewed medications as an unpleasant necessity, parents' concerns centred on the perceived side effects of medications, whereas the children commented on the process of ingesting medications. Additionally, some of the children had to learn that their medications were a preventative measure, as they originally viewed them as a cure. Furthermore, among the children, it was found that treatment could be seen as either a positive or negative symbol of difference. Lastly, emergency medications were often viewed as a saviour, particularly by parents. Through this analysis, the study shows that the meanings children attached to medications were often linked to the form the medication took and that the way in which children perceived their medications had implications for their adherence; indeed, those who viewed their medications as an unpleasant necessity and those who initially saw their treatment as a cure were most likely to stop taking their medications. Consequently, this paper contributes to the current literature on the meanings individuals attach to treatments by providing the first detailed insight into children's views on epilepsy medications and by illustrating the similarities and differences in children's and parents' perspectives.

Diet and identity: being a good parent in the face of contradictions presented by the ketogenic diet.

The ketogenic diet is a high-fat diet used to treat drug-resistant childhood epilepsy. Given that negative meanings tend to be attached to fatty foods and children's food consumption is seen to be the responsibility of parents, the ketogenic diet may be problematic for parenting identity. This article draws upon in-depth semi-structured interviews with 12 parents from 10 families that have a child whose epilepsy is being treated with the ketogenic diet. The main focus of the article is the meanings these parents attached to foods and how they were drawn upon or altered to overcome some of the contradictions presented by the diet. It will be argued that the diet was medicalised and parents came to view food as medicine. When viewing food in this way, negative associations with fat were reversed. Furthermore, parents also used food as a symbol of inclusion and prioritised portion size or the child's enjoyment of food in order to use food as a symbol of love. In turn this enabled parents to feel they were being good parents. Overall, it seems that diet can be medicalised and the identity of the good parent maintained if dietary treatment is successful.

Fc-independent phagocytosis: implications for IVIG and other therapies in immune-mediated thrombocytopenia.

Phagocytes were first described by Dr. Metchnikoff in 1873. The roles of phagocytes in innate and adaptive immunity have been well established to date, although the molecular mechanisms involved in initiating phagocytosis (through Fc or other receptors) remain to be further explored. Phagocytes in the reticuloendothelial system, particularly macrophages, have been implicated in the clearance of senescent blood cells. The destruction of these cells may be primarily mediated via an Fc-independent pathway. Fc-independent phagocytosis may also play an important role in platelet clearance, including in autoimmune thrombocytopenia (ITP), and in clearance of platelet-rich emboli detached from sites of vascular injury. In ITP, the two major platelet auto-antigens have been located on glycoprotein (GP)IIbIIIa and the GPIb complex. It has been demonstrated that anti-GPIb antibodies, in contrast to anti-GPIIbIIIa, can induce thrombocytopenia in an Fc-independent manner. We further demonstrated in an animal model that intravenous IgG (IVIG) is unable to ameliorate thrombocytopenia caused by most anti-GPIb antibodies, despite its efficacy in anti- GPIIbIIIa-mediated thrombocytopenia. Our data was supported by subsequent retrospective studies with ITP patients by several independent groups. Most recently, we found that anti-GPIb-mediated ITP was also resistant to steroid therapy and that platelet activation and apoptosis induced by anti-GPIb antibodies may be involved in the Fc-independent platelet clearance. Therefore, identification of antibody specificity in patients, e.g. anti-GPIIbIIIa (Fc-dependent) versus anti-GPIb (Fc-independent), may be important for therapies against ITP, as well as other immune-mediated thrombocytopenias.

A murine model of severe immune thrombocytopenia is induced by antibody- and CD8+ T cell-mediated responses that are differentially sensitive to therapy.

Immune thrombocytopenia (ITP) is a bleeding disorder characterized by antibody-opsonized platelets being prematurely destroyed in the spleen, although some patients with ITP may have a cell-mediated form of thrombocytopenia. Although several animal models of ITP have been developed, few mimic primary chronic ITP nor have any shown cell-mediated platelet destruction. To create this type of model, splenocytes from CD61 knockout mice immunized against CD61(+) platelets were transferred into severe combined immunodeficient (SCID) (CD61(+)) mouse recipients, and their platelet counts and phenotypes were observed. As few as 5 x 10(4) splenocytes induced a significant thrombocytopenia and bleeding mortality (80%) in recipients within 3 weeks after transfer. Depletion of lymphocyte subsets before transfer showed that the splenocyte's ability to induce thrombocytopenia and bleeding completely depended on CD4(+) T helper cells and that both CD19(+) B cell (antibody)- and CD8(+) T cell (cell)-mediated effector mechanisms were responsible. Treatment of the SCID mouse recipients with intravenous gamma-globulins raised platelet counts and completely prevented bleeding mortality induced by antibody-mediated effector mechanisms but did not affect cell-mediated disease. This novel model not only shows both antibody- and cell-mediated ITP and bleeding but also suggests that these 2 effector mechanisms have a differential response to therapy.

Fc-independent phagocytosis: implications for intravenous IgG therapy in immune thrombocytopenia.

Phagocytes were first described 120 years ago. Although the molecular mechanisms involved in initiating phagocytosis (through Fc or other receptors) are still not fully understood, the roles of phagocytes in innate and adaptive immunity have been well studied. Phagocytes in the reticuloendothelial system, particularly macrophages, have been implicated in the clearance of senescent blood cells. The destruction of these cells may be primarily mediated through an Fc-independent pathway. Fc-independent phagocytosis may also play an important role in platelet clearance, including immune thrombocytopenia (ITP). The two major platelet antigens targeted in ITP are GPIIbIIIa and the GPIb complex. It has been demonstrated that anti-GPIbalpha antibodies, in contrast to anti-GPIIbIIIa, can induce thrombocytopenia in an Fc-independent manner. We further demonstrated in an animal model that intravenous IgG is not able to ameliorate thrombocytopenia caused by most anti-GPIbalpha antibodies, though it is effective in anti-GPIIbIIIa mediated thrombocytopenia. Our data was supported by a recent retrospective study of ITP patients. Therefore, identification of antibody specificity (e.g. anti-GPIIbIIIa (Fc-dependent) versus anti-GPIbalpha (Fc-independent)) in patients may be important for ITP therapy.

Adoptively transferred dendritic cells restore primary cell-mediated inflammatory competence to acutely malnourished weanling mice.

Immune depression associated with prepubescent malnutrition underlies a staggering burden of infection-related morbidity. This investigation centered on dendritic cells as potentially decisive in this phenomenon. C57BL/6J mice, initially 19 days old, had free access for 14 days to a complete diet or to a low-protein formulation that induced wasting deficits of protein and energy. Mice were sensitized by i.p. injection of sheep red blood cells on day 9, at which time one-half of the animals in each dietary group received a simultaneous injection of 10(6) syngeneic dendritic cells (JAWS II). All mice were challenged with the immunizing antigen in the right hind footpad on day 13, and the 24-hour delayed hypersensitivity response was assessed as percentage increase in footpad thickness. The low-protein diet reduced the inflammatory immune response, but JAWS cells, which exhibited immature phenotypic and functional characteristics, increased the response of both the malnourished group and the controls. By contrast, i.p. injection of 10(6) syngeneic T cells did not influence the inflammatory immune response of mice subjected to the low-protein protocol. Antigen-presenting cell numbers limited primary inflammatory cell-mediated competence in this model of wasting malnutrition, an outcome that challenges the prevailing multifactorial model of malnutrition-associated immune depression. Thus, a new dendritic cell-centered perspective emerges regarding the cellular mechanism underlying immune depression in acute pediatric protein and energy deficit.

Relative efficacy of intravenous immunoglobulin G in ameliorating thrombocytopenia induced by antiplatelet GPIIbIIIa versus GPIbalpha antibodies.

Intravenous immunoglobulin G (IVIG) is used to treat idiopathic thrombocytopenic purpura (ITP). Although many patients benefit from IVIG, some are refractory to this therapy. ITP is characterized by platelet clearance mediated primarily by antiplatelet antibodies against GPIIbIIIa and/or the GPIbalpha complex. These 2 groups of antibodies may induce ITP through different mechanisms. We tested the hypothesis that IVIG may not be equally effective in preventing ITP caused by anti-GPIIbIIIa versus anti-GPIbalpha antibodies in mice. Thrombocytopenia was induced in BALB/c mice using monoclonal antibodies against either mouse GPIIbIIIa (JON1, JON2, and JON3) or GPIbalpha (p0p3, p0p4, p0p5, p0p9, and p0p11). Pretreatment with IVIG significantly ameliorated ITP in all anti-GPIIbIIIa-injected animals. Conversely, IVIG failed to prevent ITP in all anti-GPIbalpha-treated mice, except for p0p4. These results were repeated in C57BL/6 mice, and with different IVIG preparations. These data in mice suggest that patients with ITP mediated by anti-GPIbalpha antibodies may be less responsive to IVIG treatment.

Polarized Th2 like cells, in the absence of Th0 cells, are responsible for lymphocyte produced IL-4 in high IgE-producer schistosomiasis patients.

BACKGROUND: Human resistance to re-infection with S. mansoni is correlated with high levels of anti-soluble adult worm antigens (SWAP) IgE. Although it has been shown that IL-4 and IL-5 are crucial in establishing IgE responses in vitro, the active in vivo production of these cytokines by T cells, and the degree of polarization of Th2 vs. Th0 in human schistosomiasis is not known. To address this question, we determined the frequency of IL-4 and IFN-gamma or IL-5 and IL-2 producing lymphocytes from schistosomiasis patients with high or low levels of IgE anti-SWAP. RESULTS: Our analysis showed that high and low IgE-producers responded equally to schistosomiasis antigens as determined by proliferation. Moreover, patients from both groups displayed similar percentages of circulating lymphocytes. However, high IgE-producers had an increased percentage of activated CD4+ T cells as compared to the low IgE-producers. Moreover, intracellular cytokine analysis, after short-term stimulation with anti-CD3/CD28 mAbs, showed that IgE high-producers display an increase in the percentage of T lymphocytes expressing IL-4 and IL-5 as compared to IgE low-responders. A coordinate control of the frequency of IL-4 and IL-5 producing lymphocytes in IgE high, but not IgE low-responders, was observed. CONCLUSIONS: High IgE phenotype human schistosomiasis patients exhibit a coordinate regulation of IL-4 and IL-5 producing cells and the lymphocyte derived IL-4 comes from true polarized Th2 like cells, in the absence of measurable Th0 cells as measured by co-production of IL-4 and IFN-gamma.