IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H)

Phase II clinical trials revealed that the lymphocyte-depleting humanized monoclonal antibody alemtuzumab (Campath-1H) is highly effective in the treatment of early relapsing-remitting multiple sclerosis. However, 30% of patients develop autoimmunity months to years after pulsed exposure to alemtuzumab, usually targeting the thyroid gland and, more rarely, blood components. In this study, we show that autoimmunity arose in those patients with greater T cell apoptosis and cell cycling in response to alemtuzumab-induced lymphocyte depletion, a phenomenon that is driven by higher levels of IL-21. Before treatment, patients who went on to develop secondary autoimmunity had more than 2-fold greater levels of serum IL-21 than the nonautoimmune group. We suggest that serum IL-21 may, therefore, serve as a biomarker for the risk of developing autoimmunity months to years after alemtuzumab treatment. This has implications for counseling those patients with multiple sclerosis who are considering lymphocyte-depleting therapy with alemtuzumab. Finally, we demonstrate through genotyping that IL-21 expression is genetically predetermined. We propose that, by driving cycles of T cell expansion and apoptosis to excess, IL-21 increases the stochastic opportunities for T cells to encounter self antigen and, hence, for autoimmunity.     

Beverage intake improvement by high school students in Saskatchewan,Canada

Certain beverages contribute energy, protein, vitamins, and minerals. North American adolescents have shifted their beverage intake from predominantly milk to predominantly sugary beverages. Intake of these sugary beverages, in sufficient quantity, may increase the risk of bone fractures, may contribute to obesity, and may lead to tooth decay. This study evaluated the effectiveness of a school-nutrition education program (Fluids Used Effectively for Living) on nutrition knowledge, attitude, and self-reported behavior of grade 9 students in Saskatchewan, Canada. Two classes of grade 9 students, 1 (n = 33) in a high school in Saskatoon (n = 33) and 1 (n = 24) in a large high school in Prince Albert, Saskatchewan, received the peer educator intervention. Two other classes in the 2 cities (n = 24 and n = 24, respectively) were controls. Six sessions of Fluids Used Effectively for Living nutrition education were delivered by using 2 peer educator models (multiple and single), and the intervention was delivered in a 45-minute weekly class session over a 6-week period. After the intervention, students in these 2 peer educator classes decreased their sugary beverage intake significantly, which was sustained for 3 months. Students in the control self-taught class increased their juice intake at the end of the year. The significant decrease of juice and sugary beverage intakes in the single model peer educator class disappeared after Bonferroni correction. Carbonated sugary beverage intake of students in the control self-taught classes declined, but it was not sustainable at the 3-month follow-up. A peer educator school-based nutrition education approach can lead to a decrease in sugary beverage intake in high school children.     

Informed choice in cancer pain: empowering the patient

Cancer and palliative care service users can often feel isolated and disempowered. (Tower, 1999). Physical changes, medical interventions and pain can mean that they no longer feel in control of their bodies or their futures. In recognition of this, many health professionals within cancer and palliative care have adopted the mantra of 'patient empowerment', but it is not always clear what it means for either the patients or the professionals. Empowerment is an interactive process that develops and increases power through cooperation, sharing and working together (Marquis and Huston, 2000), and it plays a central role in health professionals' personal and working lives. A person's ability to make decisions and choices demonstrates control of his or her own destiny. This article aims to direct health professionals' participation and involvement in restoring this ability to patients who have pain related to cancer.     

The role of the duodenal microflora as a determinant of persistent diarrhoea

It has been suggested that proliferation of enterobacteriaceae and/or anaerobes in the duodenum of some children with acute diarrhoea determines whether the episode becomes persistent. A review of published studies and the comparison of cultures of duodenal aspirates from Peruvian children with acute and persistent diarrhoea and diarrhoea-free children did not support this hypothesis. Although many children had enterobacteriaceae and/or anaerobes cultured there was no correlation with clinical and nutritional outcome. Age, nutritional status, the environment and the aetiology of the episode were determinants of the duodenal microflora independent of diarrhoea. Culture of the duodenal aspirates did not increase the yield of enteropathogens which were isolated more frequently from stools than from the duodenum. Despite the presence of a single strain or serotype of enterobacteriaceae suggesting that these bacteria were colonizing the duodenum, we were unable to demonstrate any adherence mechanisms in the majority of them. Two often bacteria with no other evidence of virulence caused diarrhoea in the RITARD rabbit model.     

Social network and social support among poor elderly ill in Guadalajara, Mexico

This paper examines social networks and social support among poor elderly ill in Guadalajara, Mexico. We interviewed 40 hospitalized elderly patients. The mean size of social networks was 7.5, basically involving women, multiple generations, and members of the extended family. Emotional support was more frequent than other types of social support. Elderly women had larger social networks and received more social support than men. Married elderly also had larger social networks and more social support than single patients. There were no differences between age and living arrangements with social networks and social support. Future studies are needed on the social and cultural environment of social support for the elderly.     

Closed heart surgery for congenital heart disease in infancy

Closed heart surgery in congenital heart disease can be palliative or corrective. Palliative surgery aims at improving the physiologic deficit rather than the anatomic defect of the heart. Palliative procedures aim to increase pulmonary blood flow in cyanotic children with decreased pulmonary blood flow (Blalock-Taussig shunt), decrease pulmonary blood flow when there is unrestricted flow (pulmonary artery banding), or improve venous mixing in cyanotic children that require pulmonary and systemic venous mixing for survival (atrial septectomy). The indications for palliation over corrective surgery have changed over time. Now we reserve palliation for children that require low pulmonary vascular resistance for correction, a conduit that will require replacement as the child grows, or where the risk of the corrective procedure decreases rapidly with age. For palliation with systemic to pulmonary artery shunts, we prefer to perform a Blalock-Taussig subclavian to pulmonary artery shunt using a synthetic (PTFE) tube graft in infants. The operative mortality is higher in infants under 1 month of age but is not affected by weight or diagnosis. Palliative surgery to decrease pulmonary blood flow is restricted primarily to infants with large left-to-right shunts where the risk of correction in infancy is high (multiple VSDs) or not feasible (univentricular heart). The operative risk for pulmonary artery banding is affected mostly by the complexity of the cardiac defect and the clinical state of the infant (severe congestive failure) at the time of surgery. A trial septectomy to improve venous mixing is used mostly in infants with univentricular heart in whom a balloon septostomy was ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)