Defective macrophage handling of Escherichia coli in Crohn's disease.

BACKGROUND AND AIM: Escherichia coli can be isolated from lamina propria macrophages in Crohn's disease (CD), and their intramacrophage persistence may provide a stimulus for inflammation. To further determine the contributions of macrophage dysfunction and E. coli pathogenicity to this, we aimed to compare in vitro functioning of macrophages from patients with CD and healthy controls (HC) in response to infection with CD-derived adherent-invasive E. coli (AIEC) and less pathogenic E. coli strains. METHODS: Monocyte-derived macrophages were cultured from patients with CD and HC. Intramacrophage survival of E. coli strains (CD-derived adherent-invasive [AI] and non-AI strains and laboratory strain K-12) was compared. Macrophage cytokine release (tumor necrosis factor alpha [TNFα], interleukin [IL]-23, IL-8 and IL-10) and monocyte phagoctyosis and respiratory burst function were measured after E. coli infection. For CD patients, laboratory data were correlated with clinical phenotype, use of immunomodulation, and CD risk alleles (NOD2, IL-23R, ATG16L1 and IRGM). RESULTS: Attenuated TNFα and IL-23 release from CD macrophages was found after infection with all E. coli strains. There was prolonged survival of CD-derived AIEC, CD-derived non-AIEC and E. coli K-12 in macrophages from CD patients compared to within those from HC. No abnormality of monocyte phagocytosis or respiratory burst function was detected in CD. Macrophage dysfunction in CD was not influenced by phenotype, use of immunomodulation or genotype. CONCLUSIONS: CD macrophage responses to infection with E. coli are deficient, regardless of clinical phenotype, CD genotype or E. coli pathogenicity. This suggests host immunodeficiency is an important contributor to intramacrophage E. coli persistence in CD.

Diet, cellular, and systemic homeostasis control the cycling of potassium stable isotopes in endothermic vertebrates.

The naturally occurring stable isotopes of potassium (41K/39K, expressed as δ41K) have the potential to make significant contributions to vertebrate and human biology. The utility of K stable isotopes is, however, conditioned by the understanding of the dietary and biological factors controlling natural variability of δ41K. This paper reports a systematic study of K isotopes in extant terrestrial endothermic vertebrates. δ41K has been measured in 158 samples of tissues, biofluids, and excreta from 40 individuals of four vertebrate species (rat, guinea pig, pig and quail) reared in two controlled feeding experiments. We show that biological processing of K by endothermic vertebrates produces remarkable intra-organism δ41K variations of ca. 1.6‰. Dietary δ41K is the primary control of interindividual variability and δ41K of bodily K is +0.5-0.6‰ higher than diet. Such a trophic isotope effect is expected to propagate throughout trophic chains, opening promising use for reconstructing dietary behaviors in vertebrate ecosystems. In individuals, cellular δ41K is related to the intensity of K cycling and effectors of K homeostasis, including plasma membrane permeability and electrical potential. Renal and intestinal transepithelial transports also control fractionation of K isotopes. Using a box-modeling approach, we establish a first model of K isotope homeostasis. We predict a strong sensitivity of δ41K to variations of intracellular and renal K cycling in normal and pathological contexts. Thus, K isotopes constitute a promising tool for the study of K dyshomeostasis.

An In Vitro Model of Gastric Inflammation and Treatment with Cobalamin.

Pernicious anaemia (PA) is an autoimmune condition where antibodies target intrinsic factor and parietal cells, reducing the patient's ability to absorb cobalamin promoting atrophic gastritis. Treatment guidelines are based on excretion data of hydroxocobalamin from healthy individuals obtained 50 years ago. This manuscript describes the use of phorbol 12-myristate 13-acetate (PMA) to stimulate low grade inflammation in an epithelial colorectal cell line to assess the efficacy of methylcobalamin and hydroxocobalamin. Nitric oxide increased significantly in cells exposed to higher doses of PMA (100 ng/ml, 150 ng/ml, and 200 ng/ml) accompanied by a loss of the characteristic cobblestone morphology with no negative effect on cell activity or viability. A significant reduction in nitric oxide production was associated with the addition of 200 pg/ml hydroxocobalamin, alongside a return to the characteristic cobblestone morphology. This study highlights the use of PMA to promote low grade inflammation in human cell lines to model gastric inflammation associated with autoimmunity; furthermore it raises questions regarding the concentration of cobalamin administered clinically to restore cell functionality, feasibly allowing the patient to receive reduced quantity of the vitamin more regularly, providing the patient with levels which are akin to dietary intake.

Dynamic processes in health outcomes among caregivers of patients with spinal cord injuries.

The developmental trajectories of health outcomes in caregivers of patients with spinal cord injuries (SCIs) were studied as a function of caregiver and patient characteristics. Hierarchical linear modeling analysis examined (a) intraindividual developmental patterns of depressive behavior, anxiety, and physical symptoms over the 1st year of the caregiving career and (b) correlates of heterogeneity in the developmental patterns among 62 caregivers of persons with SCIs. Physical symptoms and anxiety were highly interdependent. Anxiety was a salient predictor of initial levels of and the rate of change in physical symptoms of caregivers. Physical symptoms and younger patient age were significantly predictive of initial levels of anxiety. Physical symptoms and positive affect predicted initial levels of depressive behavior among caregivers. Expressive support predicted the rate of change in anxiety and depressive behavior over time. These findings illustrate the value of studying caregiving as a developmental process.

Pain assessment in spinal cord injury.

Pain management is a serious problem for individuals with spinal cord injury (SCI). Recent developments in pain assessment indicate that multiaxial approaches, assessing medical, psychosocial, and behavioral/functional dimensions, are necessary to measure adequately the impact of chronic pain. The application of this multiaxial system to persons with SCI and chronic pain is presented. A review of the literature indicates that the psychometric properties and test utility for most pain measures have not been established for persons with SCI. The assessment task is further confounded by the functional limitations and psychosocial impairments that may accompany SCI. Recommendations are made for adapting established pain measures for use with SCI individuals. The choice of assessment tools for these patients is guided by the multidimensional nature of the pain experience, functional limitations, and the goals of treatment.

Negotiating reality after physical loss: hope, depression, and disability.

The utility of different reality negotiation strategies among 57 persons who had traumatically acquired severe physical disabilities was examined. It was predicted that a sense of goal-directed determination ("agency"; Snyder, 1989) would predict lower depression and psychosocial impairment scores soon after injury. To meet the demands of rehabilitation and social integration, however, it was hypothesized that a sense of ability to find ways to meet goals ("pathways") would predict lower depression and psychosocial impairment among persons who had been disabled for a longer period. The expected interaction was significant in the prediction of psychosocial impairment but not of depression. The sense of pathways was predictive of impairment and depression regardless of the time since injury. Results suggest that in the reality negotiation process the different components of hope as defined by Snyder have salient effects on perceptions of ability to function in social capacities.

Dysphoria: a major symptom factor in persons with disability or chronic illness.

Depression frequently is diagnosed in persons with chronic illness or following the onset of disability. The overlap of symptoms of many chronic illnesses and disabling conditions with depression may lead to an overestimation of depression in such populations. Some investigators have proposed revised criteria for diagnosing depression in these conditions without an understanding of the contribution of diagnostic criteria in disabling conditions. This study investigated the nature of depressive symptom criteria constellations by individually factor analyzing the Inventory to Diagnose Depression (based on DSM-III diagnostic criteria) in spinal cord injury (n = 134), rheumatoid arthritis (n = 78), student (n = 140), and community (n = 150) groups. A four-factor solution emerged, with the first factor labeled "dysphoria" being represented by symptoms of negative self-evaluations, depressed affect, and suicidal ideation. The results indicate that a core element of the syndrome of depression is dysphoria, which suggests that the contribution of somatic items may be less important to the identification of the depressive syndrome in chronic illness.

Efficient pain assessment in clinical settings.

The need for efficient and practical assessment techniques of the multidimensional nature of chronic pain remains paramount in clinical settings. Visual analogue scales (VASs) and simple behavioral observation methods have been proposed as efficient, reliable, and valid measures of the subjective (sensory and affective) and overt behavioral aspects of the pain experience. The relationships among VASs and the UAB Pain Behavior Scale were examined among 48 chronic pain patients. Ratings of overt behavior were significantly related to both the VAS sensory and VAS affective ratings. Regression analysis indicated that the VAS scores accounted for significant amount of the variance (27.7%) in UAB scores. Moreover, the affective dimension of self-reported pain tended to be more strongly related to the visible manifestations of pain than were ratings of pain intensity.

Self-appraised social problem solving abilities, emotional reactions and actual problem solving performance.

Self-report measures of social problem solving abilities have yet to be associated with objective problem solving performance in any consistent manner. In the present study, we investigated the relation of social problem solving abilities--as measured by the Social Problem Solving Skills Inventory--Revised (SPSI-R [Maydeu-Olivares, A. & D'Zurilla, T. J. (1996). A factor analytic study of the Social Problem Solving Inventory: an integration of theory and data. Cognitive Therapy and Research, 20, 115-133])--to performance on a structured problem solving task. Unlike previous studies, we examined the relation of problem solving skills to performance curves observed in repeated trials, while controlling for affective reactions to each trial. Using hierarchical modeling techniques, a negative problem orientation was significantly predictive of performance and this effect was not mediated by negative affectivity. Results are discussed as they pertain to contemporary models of social problem solving.

Assertiveness, social support, and psychological adjustment following spinal cord injury.

Tested predictions that assertiveness and social support would be significantly predictive of psychological adjustment. Furthermore, it was anticipated that assertiveness and certain types of social relationships would differentially interact to predict adjustment, since positive and negative effects of both variables have been noted in prior research. Trained raters interviewed 156 persons receiving either in-patient or out-patient care for cord injuries and administered measures of assertiveness, social support, depression and psychosocial impairment. Persons who reported a keen sense of responsibility for the welfare of another reported more depression and impairment. Persons reporting higher levels of support facilitating social integration and reassuring personal worth were less depressed. Several significant interactions between assertiveness and different social support relationships revealed beneficial and deleterious effects on depressive behavior and impairment secondary to the disability. Results are discussed as they advance theoretical understanding of the effects of assertiveness and social support. Implications for discriminate cue learning in assertion training for persons with physical disability are proposed.

Spinal cord injury model systems of care: the legacy and the promise.

The Spinal Cord Injury Model Systems of Care have served a unique role in the provision of integrated and coordinated care for persons with spinal cord injuries (SCI), and in collaborative research efforts to advance available technologies. Although the basic mission of the model systems remains viable, contemporary issues and trends indicate that the model systems concept ought to be expanded in terms of roles and functions to meet current needs.

Social problem-solving telephone partnerships with family caregivers of persons with stroke.

As individuals with significant functional deficits are discharged earlier from the hospital, health care professionals are challenged to develop cost-effective intervention programmes that will assist family members to manage caregiving problems in the home. The literature suggests that social problem-solving can positively influence the physical and psychological well-being of individuals. This paper describes a social problem-solving training procedure provided primarily by telephone to assist family caregivers to manage caregiving issues in the home.

A pilot study of effects of cardiopulmonary resuscitation training on participants' self-concepts.

The administration of cardiopulmonary resuscitation (CPR) was taught to a group of 12 adults. The Tennessee Self-concept Scale Form-C and the Fundamental Interpersonal Relations Orientation-Behavior Scale (FIRO-B) were administered before and after their training. A control group of 12 was administered both scales twice with one day between administrations. Analysis indicated both groups showed significant differences between the pre- and posttest administrations on expressed affection on the FIRO-B. However, participants in a brief CPR course did not score significantly differently from a control group on these measures, as expected.

Long-term outcome following pneumatic dilatation as initial therapy for idiopathic achalasia: an 18-year single-centre experience.

BACKGROUND: Relapse after treatment for idiopathic achalasia is common and long-term outcome data are limited. AIM: To determine the cumulative relapse rate and long-term outcome after pneumatic dilatation (PD) for achalasia in a tertiary referral centre. METHODS: A retrospective study of 301 patients with achalasia treated with PD as first-line therapy. Short-term outcome was measured at 12 months. Long-term outcome was assessed in those who were in remission at 12 months by cumulative relapse rate and cross-sectional analysis of long-term remission rate regardless of any interval therapy, using a validated achalasia-specific questionnaire. RESULTS: Eighty-two percent of patients were in remission 12 months following initial PD. Relapse rates thereafter were 18% by 2 years; 41% by 5 years and 60% by 10 years. Whilst 43% patients underwent additional treatments [PD (29%), myotomy (11%) or botulinum toxin (3%)] beyond 12 months, 32% of those who had not received interval therapy had relapsed at cross-sectional analysis. After a mean follow-up of 9.3 years, regardless of nature, timing or frequency of any interval therapy, 71% (79/111) patients were in remission. The perforation rate from PD was 2%. Chest pain had a poor predictive value (24%) for perforation. CONCLUSIONS: Long-term relapse is common following pneumatic dilatation. While on-demand pneumatic dilatation for relapse yields a good response, one-third of relapsers neither seek medical attention nor receive interval therapy. Close follow-up with timely repeat dilatation is necessary for a good long-term outcome. Given the poor predictive value of chest pain for perforation, routine gastrografin swallow is recommended postdilatation.

Life stress and psychologic adjustment following spinal cord injury.

Previous research on psychologic adjustment following spinal cord injury has not systematically investigated the impact of negative life events from contemporary perspectives. In order to examine the effects of life stress on adjustment, 53 spinal cord injured patients were assessed by the Symptom Checklist-90, Beck Depression Inventory, and a measure of life events. Patients who were experiencing higher subjective levels of life stress displayed more distress than those reporting lower levels of life stress. The findings were not mediated by the passage of time since injury.

Spinal cord injury and health locus of control beliefs.

Individual beliefs about control over their health were assessed in 53 patients with spinal cord injury. Patients who believed they exercised control over their health were less depressed than patients who were fatalistic. A significant number of patients were found to be higher in their internal attributions of health control (N = 31) than those who believed in chance (N = 5) and those who believed medical personnel were in control of their health (N = 11). The results are integrated with a past study of depression following spinal cord injury and locus of control beliefs.