Questions and answers in chronic urticaria: where do we stand and where do we go?

This supplement reports proceedings of the second international Global Urticaria Forum, which was held in Berlin, Germany in November 2015. In 2011, a report of the GA(2) LEN task force on urticaria outlined important and unanswered questions in chronic urticaria (CU). These included, but were not limited to, questions on the epidemiology and course of chronic spontaneous urticaria (CSU) [also called chronic idiopathic urticaria (CIU)], the resources allocated for the diagnosis and treatment of CSU, whether patients with angioedema as an isolated symptom can be regarded as a subgroup of CSU, and the efficacy and long-term safety of therapies. Many of these questions have been addressed by recent studies. Some of the answers obtained raise new questions. Here, we summarize some of the key insights on CU obtained over recent years, and we discuss old and new unmet needs and how to address them with future studies. We need to analyze the influence of recent advances in understanding of the burden of CU on patients and society, disease management and the CU patient journey. Our increased understanding of urticarial pathophysiology and consideration of the patient as a whole will need to be translated to better treatment algorithms and protocols. Actions to address these challenges include the 5th International Consensus Meeting on Urticaria, which will take place later this year. The formation of a global network of Urticaria Centers of Reference and Excellence over the next few years has also been proposed, with the aim of providing consistent excellence in urticaria management and a clear referral route, furthering knowledge of urticaria through additional research and educating/promoting awareness of urticaria.

Predicting altered pathways using extendable scaffolds.

Many diseases, especially solid tumors, involve the disruption or deregulation of cellular processes. Most current work using gene expression and other high-throughput data, simply list a set of differentially expressed genes. We propose a new method, PAPES (predicting altered pathways using extendable scaffolds), to computationally reverse-engineer models of biological systems. We use sets of genes that occur in a known biological pathway to construct component process models. We then compose these models to build larger scale networks that capture interactions among pathways. We show that we can learn process modifications in two coupled metabolic pathways in prostate cancer cells.

Assessing the value of the follow-through family project for students and families.

Although not a new teaching strategy, the follow-through family assignment is receiving renewed attention from maternity nursing faculty in light of shorter hospital stays and increased competition for clinical sites. The purpose of this evaluation study was to assess the project's value as a learning experience for students and to determine its benefits for participating families. The findings indicate that students enjoyed establishing therapeutic relationships with their families and helping child-bearing families answer health care questions. Students developed primary care skills, increased their self-confidence, and developed an appreciation of childbearing as a transition event for the family. Families appreciated students' educational support and individualized assistance. Families also enjoyed feeling that they had helped their student nurses learn. Overall, the benefits of the follow-through family project appear to outweigh the costs for both students and families.

Medicine and story: a novel clinical panorama arising from a unitary mind/body approach to physical illness.

Since 1987, all patients referred by family physicians for internal medicine consultation at the Institute for Integrative Health Studies (Christchurch, New Zealand) have been assessed by the author from both physical (normative internal medicine) and psychological (psychodynamic, interpersonal, object relations, and self psychological) perspectives. Depending upon the material emerging in each case, the treatment options available for the particular disorder, and patient preferences, many patients have gone on to mind/body oriented discussions or psychotherapy with the author (detailed in Broom 1997), or with one of a team of therapists supervised by the author. This clinical experience, mixing internal medicine and psychotherapy approaches to physical illnesses (with or without organic findings), points to the following: (1) Profound connections between the patients' perceptions of their life-events and experience and the development of illness in both organic and nonorganic illnesses; (2) a rich fund of information in the patients' verbal language about the meaning of the illnesses; (3) the crucial importance of clinical attunement to macro- and micro-life events surrounding symptom emergence; and (4) the decisive role a clinician's implicit paradigm of "personhood" plays in patient care. This paper broadly outlines the presuppositions for this integrative clinical approach, and illustrates the approach with case material. Additionally, it summarizes the kinds of listening, and other skills, that have proved clinically useful. In all, the material illustrates that a combination of orthodox biomedical approaches and a "story approach" (which focuses on meaning leading to illness) offers considerable potential benefits to patients with physical symptomatologies including those with organic findings.

Genetic analysis of the age at menopause by using estimating equations and Bayesian random effects models.

Multi-wave self-report data on age at menopause in 2182 female twin pairs (1355 monozygotic and 827 dizygotic pairs), were analysed to estimate the genetic, common and unique environmental contribution to variation in age at menopause. Two complementary approaches for analysing correlated time-to-onset twin data are considered: the generalized estimating equations (GEE) method in which one can estimate zygosity-specific dependence simultaneously with regression coefficients that describe the average population response to changing covariates; and a subject-specific Bayesian mixed model in which heterogeneity in regression parameters is explicitly modelled and the different components of variation may be estimated directly. The proportional hazards and Weibull models were utilized, as both produce natural frameworks for estimating relative risks while adjusting for simultaneous effects of other covariates. A simple Markov chain Monte Carlo method for covariate imputation of missing data was used and the actual implementation of the Bayesian model was based on Gibbs sampling using the freeware package BUGS.

Parental sensitivity to infants and toddlers in dual-earner and single-earner families.

BACKGROUND: Concerns have been raised about the effects of maternal employment on parent-child relations. Some researchers have concluded that maternal employment status has no effect on children's maternal attachments; others have found that full-time employment initiated in the first year of life is associated with insecure patterns of attachment behavior. The evidence suggests that dual-earner parents who have young children have increased psychological distress, affecting marital quality and spousal and parenting behaviors. OBJECTIVES: To learn whether parental sensitivity and the determinants of parental sensitivity differ for first-time parents in single-earner and dual-earner families when their first-born children are 3 months of age and when they are 2 1/2 years old; and to learn the extent to which changes in parental sensitivity and the determinants of parental sensitivity differ for single-earner and dual-earner parents during the study interval. METHOD: This panel study compared marital quality, psychological well-being, and parental sensitivity of single-earner and dual-earner parents when their first-born children were 3 months of age and again when they were 2 1/2 years of age. RESULTS: Employed mothers were more sensitive to their 3-month olds than were nonemployed mothers. When children were 2 1/2 years of age, dual-earner parents had lower marital quality than single-earner parents. Marital quality was positively associated with parental sensitivity at both study phases. Regardless of maternal employment status, parents' marital quality declined during the study interval. CONCLUSIONS: Regardless of mothers' employment status, well-educated, middle-class parents tend to provide sensitive parenting. Marital quality and psychological well-being are important supports of sensitive parenting for dual-earner and single-earner families.

Predicting low-risk pregnant women's attendance at a preterm birth prevention class.

OBJECTIVE: To determine factors that predict attendance at a preterm birth prevention (PTBP) class in a sample of low-risk pregnant women. DESIGN: Predictive correlational. Discriminant function analysis with four predictor variables distinguished between women who did and did not attend a PTBP class. SETTING: A prenatal clinic in a large health maintenance organization. PARTICIPANTS: One hundred three pregnant women who were identified as being at low risk for preterm birth. MAIN OUTCOME MEASURES: Early in pregnancy, participants completed the Health Locus of Control scale, the Health Value Scale, the Perceived Barriers Scale, and a demographic questionnaire that included questions about prenatal education. Preterm birth prevention class attendance was determined by checking clients' electronic prenatal records at 26 weeks gestation. RESULTS: Women who attended the PTBP class had planned to attend pregnancy education classes, F(1, 98) = 5.18, p < .05, and perceived fewer barriers to class attendance, F(1, 98) = 13.53, p < .001, than did women who did not attend. CONCLUSIONS: Surveying clients to determine the most convenient times and locations and the availability of transportation can help nurses plan more accessible classes. Nurses should ascertain women's plans for attending pregnancy education classes and reinforce such plans.

Expanding nursing's role in helping new parents.

Nursing practice, research, and public policy currently do not recognize the important reciprocal nature of partner/marital relationships and parenting behavior. As partners adjust to parenthood they often experience significant tension in their relationship that affects their parenting. This article outlines indicators, timing, targets, and outcomes for research-based nursing interventions to help parents care for their couple relationship, thereby indirectly influencing parenting. The author also discusses implications for research to change practice and inform public policy.

Impact of marital quality and psychological well-being on parental sensitivity.

The purpose of this study was to determine the extent to which marital quality influences psychological well-being, thereby contributing to parental sensitivity to infant cues among first-time mothers and fathers; the effects of parental age and infant sex on parental sensitivity; and whether the determinants of parental sensitivity differ between first-time mothers and first-time fathers. Data collections were done in the homes of 71 married couples with healthy, first-born 3-month-old infants. The maternal regression equation accounted for 17% of the variance in parental sensitivity, with perceptions of the spouse's participation in family life and maternal age explaining the most variance. The paternal equation accounted for 6% of the variance, with psychological well-being the only significant predictor. The sex of the infant was not a significant predictor of parental sensitivity for either parent.

Consensus about the marital relationship during transition to parenthood.

This research was designed to identify anticipated and actual postpartum concerns about the marriage relationship during the period of transition to parenthood. It also investigated: (1) the accuracy of prediction of postpartum concerns by the prenatal group; (2) states of consensus within the marital dyad regarding the importance of postpartum concerns; and (3) the relationship between communication about the concerns and the relative importance of concerns. Twenty-two couples expecting their first child were randomly assigned to either the prenatal or postpartum interview groups. Husbands and wives individually rank-ordered 35 postpartum concerns from Most Important to Least Important and estimated how their spouses would rank the concerns. Husbands and wives also indicated the three concerns they discussed the most and the three they discussed the least. Couples tended to discuss most often those concerns they ranked most important. However, there were only moderate levels of agreement on the importance of concerns, discrepancies between perceived agreement and actual agreement, and low to moderate levels of accuracy in estimating the importance of concerns for spouses.

Life-threatening inhalant allergy: typical anaphylaxis induced by inhalational allergen challenge in patients with idiopathic recurrent anaphylaxis.

Eight patients, referred to an allergy service because of anaphylactic syndromes, were investigated for the usual causes (drugs, foods, insect stings etc.) without satisfactory results. All were atopic by history and/or allergy skin testing. Inhalation challenges, using nebulized common inhalant allergens to which the patients were positive by skin tests, were performed to test whether such inhaled allergens could be causing the anaphylactic episodes. Four of the eight patients developed anaphylactic episodes similar to the spontaneous attacks. Two of the other four patients developed precipitous asthma with some suggestion of non-pulmonary anaphylactic features. It is suggested that inhaled allergens may be a common cause of recurrent anaphylaxis where other recognized causes have been excluded.

Atopy in medical students.

Personal and immediate family histories of symptomatic atopy (asthma, eczema or allergic rhinitis) and reactivities on allergen skin prick testing were assessed in 165 medical students. Over-all, 43.0% showed a positive skin prick test to one or more allergens, 32.7% had symptomatic atopy and 55.8% had positive immediate family histories. Although the over-all incidence of skin prick test atopy is comparable with previously reported studies, the prevalence of personal and family symptomatic atopy is high in this population, especially in the female students who were significantly more likely than the males to have atopic symptoms and immediate family histories of atopic symptoms.

Regulation of human cytotoxic lymphocyte responses. I. Non-cytolytic suppression mediated by alloantigen-activated cells.

Alloantigen sensitized human lymphocytes obtained from a 2-3 day mixed lymphocyte culture (MLC) suppressed the in vitro generation of alloreactive cytotoxic lymphocytes (CTL). The inhibition of CTL responses was demonstrated in MLC after both 1 day and 14 days' allosensitization. The suppressor cells were nylon wool non-adherent, lacked Fc receptors and adhered to histamine columns. The MLC-activated suppressor cell population had an associated very low and transient cytotoxic response directed against the allogeneic sensitizing cell. Several procedures were used to dissociate this activity from suppressor cell function: (1) donors were preselected which showed minimal cross-killing between allogeneic stimulating cells, (2) suppressor cultures were added to the test cultures prior to the development of maximal CTL activity, (3) suppressor cultures were irradiated preventing cell proliferation associated with differentiating CTL. Lastly, by increasing stimulating antigen concentration suppressor cell activity was increased rather than being competitively diminished, which would be predicted if suppression was occurring through a cytolytic or inactivation of stimulating antigen. It was therefore concluded that alloantigen stimulation in MLC activates a non-cytolytic regulatory cell population which is capable of inhibiting CTL responses to third-party allogeneic lymphocytes.

Regulation of human cytotoxic lymphocyte responses. II. Suppression by a soluble factor produced by primed lymphocytes.

A soluble supernatant factor is elaborated from in vitro primed human allogeneic lymphocytes which suppresses the development of alloreactive cytotoxic lymphocytes (CTL). In contrast, supernatants obtained from primary mixed lymphocyte cultures (MLC) and primed autologous cultures were unable to suppress CTL activation, indicating that antigen restimulation was required to elicit the factor. The suppressor factor (SF) functioned in a dose-dependent manner. When the SF was added 24 or 48 hr after MLC initiation it was ineffective. However, adding the SF at culture initiation significantly reduced CTL activity, suggesting that suppression occurs either during antigen recognition or early in the CTL differentiation pathway. The SF did not function by altering the kinetics of the CTL response. Preincubation experiments showed that the SF operates by partially inactivating both MLC responder and stimulator cell populations.

Intracellular immunoglobulin production in vitro by lymphocytes from patients with hypogammaglobulinaemia and their effect on normal lymphocytes.

The ability of peripheral blood lymphocytes from twenty-two patients with late onset (acquired or common variable) hypogammaglobulinaemia to produce immunoglobulin was assessed by the immunofluorescent detection of intracytoplasmic immunoglobulin (Ic-Ig) in cultures stimulated with pokeweed mitogen (PWM). Intracellular immunoglobulin was found in 4-9-26% of cultured cells from eighteen out of nineteen controls. In contrast nineteen out of twenty-two patients with hypogammaglobulinaemia showed values less than 1% and in ten no Ic-Ig was detected. Two of the remaining three patients showed normal values. Lymphocytes from eleven patients showing less than 1% positive cells were selected for mixture experiments. Lymphocytes from five of the eleven patients strongly depressed immunoglobulin synthesis by normal lymphocytes when mixed together in the presence of PWM. However, lymphocytes from these individual patients did not depress immunoglobulin production in all normal controls.

Dichotomy between immunoglobulin synthesis by cells in gut and blood of patients with hypogammaglobulinaemia.

Eleven of fifteen patients with late-onset hypogammaglobulinaemia were found to have significant numbers of immunoglobulin-containing cells in the lamina propria of the gut. In six of them typical plasma cells were detected. In contrast the blood lymphocytes of only two of these patients could be induced to synthesise immunoglobulin by stimulation with pokeweed mitogen in vitro. Moreover, one patient in whom immunoglobulin-containing cells and plasma cells were detected in the rectum and jejunum failed to show similar cells in a peripheral lymph-node even after immunisation with pneumococcal polysaccharide type-III antigen in the drainage area of the node. It is possible, therefore, that the gut is a privileged site for the differentiation of B cells in these patients.

Rat tumour allografts evoke anaphylactic antibody responses.

In vitro assays of release of histamine from peritoneal mast cells showed that Wistar rats produced anaphylactic antibody in response to a single immunization with an allogeneic sarcoma. The response occurs early after immunization, and no adjuvant is needed. The thermolability of the anaphylactic antibody suggests that it is IgE.

Mast cell and anaphylactic antibody responses in inbred rats to syngeneic fibrosarcomas.

The mast cell content of sarcomata induced chemically in inbred rats showed wide variation. After first passage into a normal syngeneic recipient, primary tumours which were heavily infiltrated showed a complete absence of mast cells. Moreover, detectable anaphylactic antibody to passaged tumours was only occasionally detected. An important immunological role for the IgE/mast cell system in host-tumour defence is not supported.