Long-term mortality in people with celiac disease diagnosed in childhood compared with adulthood: a population-based cohort study

INTRODUCTION: To explore whether the excess mortality in celiac disease is related directly to the disease and duration of gluten exposure before diagnosis we have examined the long-term mortality experience of people with celiac disease diagnosed as children and as adults. METHODS: Two hundred eighty-five children and 340 adults diagnosed with celiac disease were followed until death, loss to follow-up, or December 31, 2004. We calculated standardized mortality ratios (SMRs). RESULTS: All-cause mortality more than 5 yr after diagnosis was increased threefold in children (SMR 3.32, 95% CI 2.05-5.07) compared with only a 38% increase in adults (SMR 1.38, 95% CI 1.16-1.63). This excess mortality in children was primarily because of an increased risk of death from accidents, suicide, and violence (seven deaths, SMR 3.22, 95% CI 1.29-6.63), cancer (five deaths, SMR 3.72, 95% CI 1.21-8.67), and cerebrovascular disease (two deaths, SMR 10.03, 95% CI 1.21-36.00). CONCLUSIONS: Children diagnosed with celiac disease had a threefold increased risk of long-term mortality. This is in marked contrast to the experience of adult celiac disease where the long-term increase of mortality was modest. The increased mortality in children from external causes may reflect behavioral change associated with coping with a chronic disease and its treatment.     

The presence of both an energy deficiency and estrogen deficiency exacerbate alterations of bone metabolism in exercising women

BACKGROUND: Bone loss in amenorrheic athletes has been attributed to energy deficiency-related suppression of bone formation, but not increased resorption despite hypoestrogenism. OBJECTIVE: To assess the independent and combined effects of energy deficiency and estrogen deficiency on bone turnover markers in exercising women. DESIGN: PINP, osteocalcin, U-CTX-I, TT3, leptin, and ghrelin were measured repeatedly, and bone mineral density (BMD) was measured once in 44 exercising women. Resting energy expenditure (REE) was used to determine energy status (deficient or replete) and was corroborated with measures of metabolic hormones. Daily levels of urinary estrone and pregnanediol glucuronides (E1G, PdG), were assessed to determine menstrual and estrogen status. Volunteers were then retrospectively categorized into 4 groups: 1) Energy Replete+Estrogen Replete (EnR+E2R), (n=22), 2) Energy Replete+Estrogen Deficient (EnR+E2D), (n=7), 3) Energy Deficient+Estrogen Replete (EnD+E2R), (n=7), and 4) Energy Deficient+Estrogen Deficient (EnD+E2D), (n=8). RESULTS: The groups were similar (p>0.05) with respect to age (24.05+/-1.75 yrs), weight (57.7+/-2.2 kg), and BMI (21.05+/-0.7 kg/m2). By design, REE/FFM (p=0.028) and REE:pREE (p<0.001) were lower in the EnD vs. EnR group, and the E2D group had a lower REE:pREE (p=0.005) compared to the E2R group. The EnD+E2D group had suppressed PINP (p=0.034), and elevated U-CTX-I (p=0.052) and ghrelin (p=0.028) levels compared to the other groups. These same women also had convincing evidence of energy conservation, including TT3 levels that were 29% lower (p=0.057) and ghrelin levels that were 44% higher (p=0.028) than that observed in the other groups. Energy deficiency was associated with suppressed osteocalcin, and TT3 (p<0.05), whereas estrogen deficiency was associated with decreased E1G (p<0.02), and lower L2-L4 BMD (p=0.033). Leptin was significant in predicting markers of bone formation, but not markers of bone resorption. CONCLUSIONS: When the energy status of exercising women was adequate (replete), there were no apparent perturbations of bone formation or resorption, regardless of estrogen status. Estrogen deficiency in exercising women, in the presence of an energy deficiency, was associated with bone loss and involved suppressed bone formation and increased bone resorption. These findings underscore the importance of avoiding energy deficiency, which is associated with hypoestrogenism, to avoid bone health problems.     

Spontaneous coronary dissection in late pregnancy: a multidisciplinary approach to management

Spontaneous coronary dissection is a rare but potentially life-threatening condition. It often occurs in late pregnancy and may pose significant risks for the patient and the fetus. Its cause remains uncertain, and established guidelines for management have not been developed. In this report, close multidisciplinary collaboration has led to excellent outcomes in this condition.     

Is nicotine replacement therapy for smoking cessation effective in the “real world”? Findings from a prospective multinational cohort study

BACKGROUND: Increasing smoking cessation rates is an important goal in preventing lung cancer and chronic obstructive pulmonary disease. Nicotine replacement therapy (NRT) has been found in clinical trials to improve the chances of success at stopping, but recent cross-sectional survey data have raised doubts as to whether it is effective when used by smokers making quit attempts unsupervised outside clinical trials. Because of biases inherent in cross-sectional surveys, this issue can only be adequately addressed using longitudinal studies. This paper reports the first study of its kind to examine the issue. METHODS: The ATTEMPT cohort is a multinational cohort study with data collection by the internet which recruited smokers of > or = 5 cigarettes per day aged 35-65 years who were intending to stop smoking within the next 3 months. Phase 1 began in spring 2003 and involved 2009 smokers from the USA, UK, Canada and France. Phase 2 involved 3645 smokers and included the same countries plus Spain. Follow-up assessments were carried out every 3 months. 492 smokers who made a quit attempt without formal behavioural support or bupropion in the first 3-month follow-up period were identified from phase 1, 357 of whom were followed up for a further 6 months. The phase 2 sample involved 906 smokers making quit attempts, 732 of whom were followed up. At baseline, demographic characteristics, smoking history and nicotine dependence were assessed. Smokers who made quit attempts were questioned on methods used to aid them. The main outcome measure was self-report of complete abstinence throughout both the 3-month periods following the quit date. RESULTS: 35.6% of smokers followed up in phase 1 and 29.6% of those followed up in phase 2 used NRT. The odds ratios comparing abstinence for 6 months in those using and those not using NRT, adjusting for nicotine dependence, were 3.0 (95% CI 1.2 to 7.5) for the phase 1 sample and 2.1 (95% CI 1.0 to 4.1) for the phase 2 sample. The difference in success rates between those using NRT and those not using it, adjusted for the Fagerstrom test for nicotine dependence (FTND) score, was 6% in the phase 1 sample and 3.7% in the phase 2 sample. The improved odds of success were not explicable in terms of motivation to use some form of aid to cessation or differential loss to follow-up. CONCLUSION: NRT use by smokers making self-initiated quit attempts without formal behavioural support is associated with improved long-term abstinence rates.     

Group interventions for anger in people with intellectual disabilities

This paper describes an evaluation of a group intervention for reducing inappropriately expressed anger (as aggression) in people with intellectual disabilities. Group intervention was compared to a treatment as usual group consisting of people referred to the group but who had to wait to participate. The intervention used was based on the work of Novaco (1976; 1978) and Benson (1994). However, further modifications to the group that emphasized the contextual perspective of anger, such as the participants being accompanied by a support worker and more collaborative recording procedures, were devised. A reduction in expressed anger and measured levels of depression occurred after group treatment. Reductions in expressed anger were maintained at 6 and 12 months follow up. However, scores on the depression scale tended to increase on follow up. While caution must be expressed when considering these results, this type of intervention shows promise for reducing inappropriately expressed anger in people with intellectual disabilities Suggestions are made for future research and clinical practice.     

Prevalence of herpes simplex type 2 and syphilis serology among young adults in a rural Gambian community

OBJECTIVES: To estimate prevalence and risk factors for herpes simplex 2 (HSV2) positivity, syphilis and Chlamydia trachomatis infection among rural people aged 15-34 in the Gambia. METHODS: Questionnaires and serum samples were collected from 1076 men and women aged 15-34 during a cross sectional prevalence survey in a rural area of the Gambia. Sera were screened for antibodies to herpes simplex virus type 2 (HSV2), and for syphilis using Treponema pallidum haemagglutination assay (TPHA) and rapid plasma reagin (RPR) tests. Urine was tested by polymerase chain reaction (PCR) for C trachomatis infection. RESULTS: 28% of women and 5% of men were HSV2 ELISA positive; 10% of women and 2% of men were TPHA positive; and 7% of women and 1% of men were both RPR and TPHA positive. Out of 1030 urine sample tested only six were positive for C trachomatis. 7% of those who reported never having sex were positive for one or other of these tests. Prevalences of all STIs increased with age and were higher in women than men. Women were much less likely than men to seek treatment for STI symptoms at a health centre. Married people were at increased risk of an STI compared with single people. Jola and Fula women had a higher prevalence of HSV2 than women from other ethnic groups, and Fulas also had a higher prevalence of RPR/TPHA positivity. The limited number of sexual behaviour questions were not significantly associated with STIs after adjustment for age, marital status, and ethnic group. CONCLUSIONS: The prevalences of the ulcerative infections HSV2 and syphilis in this population are a cause for concern. In a setting where HIV1 prevalence remains low this indicates an urgent need for STI control and behaviour change programmes to prevent an HIV epidemic. Concerns about the validity of reported sexual behaviour data high light the necessity of biological markers in the evaluation of behaviour change programmes.     

Erythrocyte membrane phosphorylation in untreated and in etretinate-treated psoriatic patients

Levels of phosphorylation were decreased in bands 2 to 2.1, 2.9 to 3 and 4.5 to 4.8 of erythrocyte membranes from psoriatic patients compared with control values. In addition, higher than control levels of 32P were incorporated into a new polypeptide band (mol.wt. 18-20,000 daltons) of red cell membranes from patients. Uptake of 32P by these bands returned towards normal after the patients received oral etretinate treatment. These results suggest there is a generalized plasma membrane defect in psoriasis and that etretinate may affect the metabolism of red cell membrane proteins.     

The art of auscultation: evaluating a patient's respiratory pathology

This article considers national policy drivers promoting the development of advanced assessment skills and practical procedures for the safe and effective use of the stethoscope in the clinical area. The evidence base underpinning effective use of the stethoscope in clinical practice is explored, including the preparation of the patient and the environment, applying infection control policies, and placing an emphasis on privacy and dignity. This is followed by a practical guide to auscultation technique of the respiratory system for nurses developing advanced practice skills.     

Functional activities of the upper extremity of young adults with cerebral palsy: a limiting factor for participation?

Purpose. To assess functional activities of the upper extremity of young adults with cerebral palsy (CP) and to determine their relations with participant characteristics and participation.

Method. Assessment of functional activities of the upper extremity was performed on 103 participants (aged 16 - 20 years) with the Melbourne assessment and the Abilhand Questionnaire. Participation was measured with the Life Habits Questionnaire. Participant characteristics included age, gender, limb distribution of the spastic paresis, educational level and gross and fine motor function. Relations among these variables were studied by means of correlation coefficients and linear regression analysis.

Results. Limitations in functional activities of the upper extremity were related to the limb distribution of the spastic paresis and were especially present in quadriplegic participants. Significant correlations between participant characteristics and measures of functional activities were present. Limitations in functional activities of the upper extremity, measured with the Abilhand Questionnaire, were an important determinant for participation, in addition to the gross motor function and educational level.

Conclusion. Limitations in functional activities of the upper extremity are an important determinant for restrictions in participation in young adults with CP. It is recommended to include assessment of functional activities of the upper extremity in patients with CP.     

Optimization of dendritic cell loading with tumor cell lysates for cancer immunotherapy

The immune response to cancer is critically determined by the way in which tumor cells die. As necrotic, stress-associated death can be associated with activation of antitumor immunity, whole tumor cell antigen loading strategies for dendritic cell (DC)-based vaccination have commonly used freeze-thaw "necrotic" lysates as an immunogenic source of tumor-associated antigens. In this study, the effect of such lysates on the ability of DCs to mature in response to well-established maturation stimuli was examined, and methods to enhance lysate-induced DC activation explored. Freeze-thaw lysates were prepared from murine tumor cell lines and their effects on bone marrow-derived DC maturation and function examined. Unmodified freeze-thaw tumor cell lysates inhibited the toll-like receptor-induced maturation and function of bone marrow-derived DCs, preventing up-regulation of CD40, CD86, and major histocompatibility complex class II, and reducing secretion of inflammatory cytokines [interleukin (IL)-12 p70, tumor necrosis factor-alpha, and IL-6]. Although IL-10 secretion was increased by lysate-pulsed DCs, this was not responsible for the observed suppression of IL-12. Although activation of the nuclear factor-kappaB pathway remained intact, the kinase activity of phosphorylated p38 mitogen-activated protein kinase was inhibited in lysate-pulsed DCs. Lysate-induced DC suppression was partially reversed in vitro by induction of tumor cell stress before lysis, and only DCs loaded with stressed lysates afforded protection against tumor challenge in vivo. These data suggest that ex vivo freeze-thaw of tumor cells does not effectively mimic in vivo immunogenic necrosis, and advocates careful characterization and optimization of tumor cell-derived vaccine sources for cancer immunotherapy.