Hapten-induced colitis associated with maintained Th1 and inflammatory responses in IFN-gamma receptor-deficient mice

IFN-gamma is a potent pro-inflammatory cytokine thought to be involved in the pathogenesis of Crohn's disease. To further define the role of IFN-gamma in intestinal inflammation, we studied the effects of intra-colonic 2,4,6-trinitrobenzene sulfonic acid (TNBS) instillation in mice with a functionally inactivated IFN-gamma receptor 1 (IFN-gammaR1(- / -)). Our results indicate that IFN-gamma is not necessary for the induction of hapten-induced colitis: after TNBS administration both wild-type and IFN-gammaR1(- / -) mice lost body weight, and the histological features of TNBS-induced colitis were comparable. Colons of IFN-gammaR1(- / -) mice contained a greater number of cells, represented by macrophages and CD4(+) T cells; caudal lymph node cells produced more IFN-gamma and TNF-alpha upon stimulation in vitro. Moreover, IL-18 and IL-12 p40 RNA levels were comparably up-regulated after TNBS treatment in IFN-gammaR1(- / -) wild-type mice. These findings demonstrate that IFN-gamma is dispensable for the development of TNBS-induced colitis. Importantly, the production of Th1 cytokines (e. g. IFN-gamma and TNF-alpha) by caudal lymph node T lymphocytes was enhanced rather than decreased in IFNgammaR1(- / -) mice with no evidence for default Th2 development.     

An investigation of the disclosure process and support needs of BRCA1 and BRCA2 carriers

Disclosure of the results of a positive genetic mutation to offspring can be challenging. The purpose of this study was to investigate the content and process of disclosure from BRCA1/2 carriers to their offspring. A semi-structured questionnaire focused on the disclosure processes between parent and offspring. Thirty-one/40 mothers with BRCA1/2 mutations completed the cross-sectional survey. Sixteen carriers (51.6%) chose to disclose their results to all of their children, thirteen carriers (41.9%) chose not to disclose their results, and two carriers (6.5%) chose to disclose to some of their children. The age of a child appeared to be the most significant contributing factor in the decision to disclose. The mean age of the offspring who learned of the positive test result was 24.3 years with most carriers advocating the ideal age range for disclosure from 19 to 25 years. There was a discrepancy between actual and potential disclosure topics between those who had disclosed and those who had not disclosed at the time of the survey. Women who disclosed their result tended to do so alone, within a week of learning their own results, equally to male and female offspring and expressed that the relationships between themselves and their children had strengthened since revealing the presence of a genetic mutation in the family. Women who had not disclosed the results of their genetic test to offspring were significantly more interested in receiving additional individual counseling, educational videos, and email newsletters that focus on disclosure of this complex and life altering information compared to those who had already disclosed. Disclosure of BRCA1/2 results is determined primarily by age of offspring, is usually done by women alone, relatively soon after receiving results and appears to enhance the relationships between mothers and offspring. Both disclosed and non-disclosed carriers demonstrated significant interest in a variety of interventions to support the disclosure process.     

ALK expression in extranodal anaplastic large cell lymphoma favours systemic disease with (primary) nodal involvement and a good prognosis and occurs before dissemination

AIMS: In anaplastic large cell lymphoma (ALCL), the site of origin has been described as an important prognostic factor. Recently, a fusion protein containing anaplastic lymphoma kinase (ALK) was described in systemic nodal ALCL, and shown to be associated with a good prognosis. The aims of this study were to investigate whether the presence of ALK protein differs between ALCL of different sites of origin; to determine whether ALK expression occurs before dissemination to other sites; and, finally, to investigate whether the site of origin remains a prognostic parameter in ALK negative ALCL. METHODS: ALK expression, as detected by immunohistochemistry using the monoclonal antibodies ALK1 and ALKc, was studied in 85 ALCLs from different sites of origin. In 22 patients, ALK expression was studied in multiple biopsies from different sites (including 13 skin, 16 lymph node, and nine other). Overall survival time was analysed using the Kaplan Meier method. RESULTS: ALK expression was found in 20 of 51 systemic ALCLs with (primary) nodal involvement. No ALK expression was found in 15 primary cutaneous, 14 gastrointestinal, and five nasal ALCLs. Multiple and subsequent biopsies of patients showed ALK expression to be identical to that seen in the primary diagnostic biopsy. Kaplan Meier survival curves showed that in ALK negative ALCLs originating from different sites, primary cutaneous cases are associated with an excellent overall survival, whereas the other cases show a comparable five years survival of less than 40%. CONCLUSIONS: If present, ALK expression favours systemic ALCL with (primary) nodal involvement, and can be used in differentiating between extranodal involvement of systemic (nodal) ALCL and primary extranodal ALCL. ALK is expressed consistently in multiple biopsies of a given patient, indicating that the chromosomal abnormality leading to aberrant ALK expression occurs before dissemination to other sites. Finally, in ALK negative non-cutaneous ALCLs, different sites of origin show comparable poor survival.     

Acute cytomegalovirus infection and the host immune response. II. Relationship of suppressed in vitro lymphocyte reactivity to bacterial recall antigens and mitogens with the development of cytomegalovirus-induced lymphocyte reactivity

Cellular immunity in cytomegalovirus (CMV) infection was studied in eighteen patients with CMV infection in the acute stage and thereafter. Peripheral blood lymphocyte reactivity (LR) to mitogens, bacterial recall antigens and CMV was tested sequentially in fourteen out of eighteen patients and once in four patients and sex and age-matched healthy controls. LR to a cocktail of bacterial recall antigens was impaired (P<0·01) during the acute phase of the CMV infection (<50 days after onset of illness symptoms). Despite a gradual improvement during the first (convalescent and post-convalescent, 50–250 days) and second (follow-up) period (>250 days) it still remained markedly impaired as opposed to LR of the controls (P<0·01 and P<0·02 respectively). In ten out of eighteen patients twelve superinfections were suspected clinically and two viral and eight bacterial infections documented during the observation period of 1 year after onset of CMV infection. In vitro LR to Con A and PWM appeared grossly disturbed as opposed to PHA-LR which was decreased only slightly in the acute phase. Although a gradual improvement of mitogenic LR was seen after the acute phase, PWM-LR remained decreased during the follow-up period as opposed to that of the controls (P<0·05). CMV-specific LR to heat-inactivated AD 169 strain virion antigens was generally negative or lowgrade initially but a positive CMV-LR test was obtained in all patients studied sequentially during or after the acute phase. To a certain extent, the appearance of positive CMV-LR was associated with improvement of LR to bacterial recall antigens and mitogens. In individual cases CMV-LR development apparently preceded the restoration of the generalized immunosuppression as reflected by LR tests with mitogens and bacterial recall antigens. It is concluded that CMV infection of adults causes a (relatively) longlasting cellular immunosuppression. Possible pathogenetic mechanisms are discussed. A relationship with increased sensitivity to infections of an opportune nature after CMV infection is suggested.     

How are different types of continuity achieved? A mixed methods longitudinal study

BACKGROUND: In the context of developments in healthcare services that emphasise swift access to care, concern has been expressed about whether and how continuity of care, particularly interpersonal continuity, will continue to be achieved. AIM: To explore how patients regard and use primary care services in relation to continuity of provider and access to care, to identify factors that promote or hinder their success in achieving their preferences, and to describe what this means for how different types of continuity are achieved. DESIGN OF STUDY: Longitudinal, mixed methods. SETTING: Community in London and Leicester. METHOD: Purposive sample of 31 patients recruited from general practices, walk-in centres and direct advertising. Data collection involved in-depth interviews, consultation record booklets completed over 6 months and general practice records for the year including the study period. Data were analysed qualitatively. RESULTS: Four patterns were identified in the way patients used primary care. These were shaped by their own preferences, by the organisation and culture of their primary care practices, and by their own and their provider's efforts to achieve their preferences. Different configurations of these factors gave rise to different types of continuity. Patients were not always able to achieve the type they wanted. Patients with apparently similar consulting patterns could experience them differently. CONCLUSION: Within a programme of modernisation, policies that promote a commitment to meeting the preferences of different patients with flexibility and understanding are most likely to provide continued support for interpersonal and other types of continuity of care.     

Racial Identity Clusters and Their Relation to Postpartum Maternal Functioning in Black Women

Maternal and Child Health Journal - Racial identity, which is the degree that individuals define themselves regarding their racial group membership, may influence the mental well-being of Black...     

Variability in cesarean delivery rates among individual labor and delivery nurses compared to physicians at three attribution time points

ObjectiveTo examine the variability in the cesarean delivery (CD) rates of individual labor and delivery nurses compared with physicians at three attribution time points.Data SourcesMedical record data from nine hospitals in Washington State from January 2016 through September 2018.Study DesignRetrospective, observational cohort design using an aggregated database of birth records.Data Collection/Extraction MethodsChart‐abstracted clinical data from a subset of nulliparous, term, singleton, vertex births attributed at admission, labor management, and delivery to nurses and physicians. Two classification methods were used to categorize nurse‐ and physician‐level CD rates at three attribution time points and the reliability of these methods compared.Principal FindingsThe sample included 12 556 births, 319 nurses, and 126 physicians. Overall, variation in nurse‐level CD rates did not differ significantly across the three attribution time points, and the extent of variation was similar to that observed in physicians. However, agreement between attribution time points varied between 35 percent and 65 percent when classifying individual nurses into the top and bottom deciles. The average reliability of nurse‐level CD rates was 32 percent at admission (IQR 22.0 percent to 38.7 percent), 32.6 percent at labor (IQR 23.1 percent to 40.9 percent), and 29.3 percent (IQR 20.9 percent to 35.8 percent) at delivery. The average reliability of physician‐level CD rates was higher: 54.2 percent (IQR 38.7 percent to 71.4 percent) at admission, 62.5 percent (IQR 49.0 percent to 79.6 percent) at labor management, and 66.1 percent (IQR 53.7 percent to 81.2 percent) at delivery.ConclusionFeedback on nurse‐level CD rates as part of routine clinical quality audits can provide insight into nurse performance in the context of other individual‐level and unit‐level information. To reliably distinguish individual nurse performance, larger sample sizes are needed.