Need for follow up in coeliac disease

The use of follow up studies was evaluated in 128 patients with coeliac disease during their first visit to a department for adults. The original diagnosis had been made in childhood in all patients. Fifty eight (45%) of the subjects were following a gluten free diet, 23 (18%) were following a gluten free diet but with occasional gluten consumption, and 47 (37%) had adopted an unrestricted, gluten containing diet for a mean of 11.2 years. There was no correlation in individual subjects between the presence of symptoms, biochemical and immunological abnormalities, severity of histological findings, and the amount of dietary gluten, despite the greater frequency of symptoms in the group following an unrestricted diet than in the other two groups. Short stature and epilepsy with cerebral calcifications only occurred in patients following an unrestricted diet. As only diagnosis based on two or three biopsy samples and regular follow up correlated positively with dietary compliance, it is suggested that a histologically confirmed diagnosis of coeliac disease and regular lifelong follow up are essential in the management of these patients.     

The post-operative mortality of ruptured abdominal aortic aneurysm repair.

INTRODUCTION: Late peri-operative death after ruptured abdominal aortic aneurysm (RAAA) repair is usually due to multiple-organ failure. The aim of this study was to identify any factors that are associated with mortality in this group of patients. METHODS: A retrospective case-note review of a single decade's operative experience of RAAA repair in a single centre. Only those patients with confirmed rupture at laparotomy were included. Sixty-three pre- intra- and post-operative variables were recorded where possible for each patient who survived surgery and the initial 24-hours post-operatively. Multi-variate analysis was performed using stepwise logistic regression. The P-POSSUM, RAAA-POSSUM, RAAA-POSSUM (physiology only), V-POSSUM, and V-POSSUM (physiology only) models were all compared to determine how each performed in these patients. RESULTS: Two hundred and twenty-three cases of confirmed RAAA were identified, of whom 139 survived the operation and initial 24-hours post-operatively. In-hospital mortality in this group of patients was 32.4%. Variables significantly associated with mortality after multi-variate analysis, were low intra-operative systolic blood pressure, the presence of a consultant anaesthetist at the initial operation and the development of cardiac, renal or gastro-intestinal complications. All POSSUM models except the V-POSSUM and P-POSSUM (physiology only) models demonstrated no significant lack of fit in this dataset. DISCUSSION: Factors associated with delayed peri-operative death after RAAA are not the same as those previously found to be associated with overall peri-operative mortality after RAAA repair.     

Reduction in plasma or skin alpha-tocopherol concentration with long-term oral administration of beta-carotene in humans and mice.

BACKGROUND: Beta-carotene is one of the most commonly used compounds in clinical trials of chemopreventive agents in various neoplastic diseases. Animal studies, including our own, have documented that dietary beta-carotene can reduce plasma alpha-tocopherol (vitamin E) levels, but few published studies have examined the clinical or pharmacokinetic ramifications of long-term, high-dose beta-carotene regimens on other fat-soluble vitamins such as alpha-tocopherol. PURPOSE: This study was designed to determine the effects of long-term beta-carotene supplementation on plasma concentrations of alpha-tocopherol in normal human subjects and in an experimental C3H/HeN mouse model. METHODS: In a double-blind study, 45 normal subjects were randomly assigned to receive 0 (placebo), 15, 30, 45, or 60 mg of oral beta-carotene daily for approximately 9 months. Monthly plasma samples were collected. Thirty-five C3H/HeN mice were fed a basal diet with or without beta-carotene and treated topically with or without alpha-tocopherol, except for the control mice, which received UV radiation for 27 weeks from week 3 to week 30. Plasma and dorsal skin samples were taken after 40 weeks and were analyzed for alpha-tocopherol and/or beta-carotene by high-performance liquid chromatography. RESULTS: Long-term dietary beta-carotene administration resulted in statistically significant reductions in levels of alpha-tocopherol in the skin and plasma of UV-irradiated mice. In the human study, the decrease in plasma alpha-tocopherol levels was progressive and significant between 6 and 9 months of beta-carotene dosing in all dosage groups. The greatest decrease was observed during the 9th (last) month of dosing, with a decrease of 40% from baseline. All oral beta-carotene doses (15-60 mg/d), however, resulted in similar decreases in steady-state plasma levels of alpha-tocopherol and in only small differences in beta-carotene plasma levels. CONCLUSION: Long-term oral administration of beta-carotene decreased steady-state plasma concentrations of alpha-tocopherol. The lack of a significant dose-response effect between doses of beta-carotene and alpha-tocopherol plasma levels is not unexpected, given the small differences in steady-state beta-carotene plasma levels in the four beta-carotene dose groups. IMPLICATIONS: Studies are needed to determine how long-term beta-carotene dosing influences tissue distribution of dietary alpha-tocopherol. Careful surveillance for this and other potentially harmful nutrient interactions should become part of all long-term intervention studies.     

Multidimensional scaling of spouses' attributions for marital conflicts

Attributional dimensions for marital conflicts were derived using a multidimensional scaling of spouses' explanations for relationships problems. Four dimensions for husbands and four dimensions for wives were interpreted by using visual inspection and their relation to attributional dimensions drawn from the literature. Most of the dimensions reflected the locus of factors affecting relationship problems. However, the dimensions seemed to have additional meaning beyond the causal dimensions used in many past studies. Particularly noteworthy were dimensions (one for the husbands and one for the wives) that reflected attributions torelationship schism, or the “poor state of the relationship.” Additionally, one of the husbands' attributional dimensions reflected a denial of serious problems in the relationship. Initial evidence suggested that attributional dimensions in the present study were associated with marital distress. The results are interpreted in light of existing research, and the implications of the findings for future investigations are discussed.     

Suppression of allergic airway disease using mycobacterial lipoglycans

BACKGROUND: Administration of heat-killed mycobacteria can suppress allergic disease in mice and humans. The active components of mycobacteria mediating these effects remain unresolved. OBJECTIVE: We sought to identify the active components of mycobacteria mediating suppression of allergic disease and to determine structural features important for function. METHODS: Using a murine model of allergic airway disease, we tested the ability of the lipoglycan fractions of the mycobacterial cell wall to suppress airway eosinophilia. Lipoglycans isolated from different strains of mycobacteria and chemical modifications were used to explore structure-function relationships. Markers of allergic disease including bronchoalvealor lavage cytokines, spleen and lymph node T-cell cytokine production, and serum specific immunoglobulin (Ig) E/IgG1 were examined. RESULTS: We identified the mycobacterial cell wall lipoglycans lipoarabinomannan and phosphatidylinositol mannan as components of mycobacteria capable of suppressing airway disease (>70% reduction in airway eosinophilia; P <.03). Structure-function analysis identified the acyl chains and mannose groups of the molecules as having a role in mediating this effect. Mechanistic studies provided no evidence for a T-helper cell (Th) 1-mediated suppression of an ongoing Th2 response. An increased capacity of T cells to secrete interleukin 10 in the spleen and lymph node of treated animals was identified, suggesting a potential T-cell-mediated suppression mechanism. CONCLUSION: We have identified immunomodulatory component(s) of mycobacteria responsible for the protective effects observed in allergic disease; these findings will lead to the generation of synthetic compounds or agonists devoid of the unwanted characteristics of whole mycobacteria for evaluation in a human clinical setting.     

The skull beneath the skin: cancer survival and awareness of death

Terror management theory predicts that people made aware of their own mortality (mortality salience) will seek to boost their self-esteem in order to buffer the anxiety they feel. One common resource to achieve this is strengthening social bonds with an admired in-group. It would also seem to predict that cancer survivors and those close to them would be driven to a greater closeness. A similar closeness might be predicted between those with terminal illness and their families and other supporters. Some empirical observations suggest that there are other forms of death-related salience which do not conform to the predictions of terror management theory.We suggest that some of those who have recovered from cancer may be made death salient, while those close to them remain mortality salient. Death salience seems to turn people inward to the resources and challenges of their deep (subconscious and unconscious) minds, and confronts them with the realities of their deep identities. A third form of salience, dying salience, affects those who have terminal illness. Distinguishing between death salience and mortality salience provides one explanation for the frequency with which close relationships break down after recovery from cancer. The distinctive nature of dying salience raises important questions about the inappropriateness of survivors as providers of support for the dying.