Amalgam Restorations And Mercury Toxicity

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a barrier to more widespread application of allogeneic haemopoietic stem-cell transplantation. Vorinostat is an inhibitor of histone deacetylases and was shown to attenuate GVHD in preclinical models. We aimed to study the safety and activity of vorinostat, in combination with standard immunoprophylaxis, for prevention of GVHD in patients undergoing related-donor reduced-intensity conditioning haemopoietic stem-cell transplantation. METHODS: Between March 31, 2009, and Feb 8, 2013, we did a prospective, single-arm, phase 1/2 study at two centres in the USA. We recruited adults (aged >/=18 years) with high-risk haematological malignant diseases who were candidates for reduced-intensity conditioning haemopoietic stem-cell transplantation and had an available 8/8 or 7/8 HLA-matched related donor. All patients received a conditioning regimen of fludarabine (40 mg/m(2) daily for 4 days) and busulfan (3.2 mg/kg daily for 2 days) and GVHD immunoprophylaxis of mycophenolate mofetil (1 g three times a day, days 0-28) and tacrolimus (0.03 mg/kg a day, titrated to a goal level of 8-12 ng/mL, starting day -3 until day 180). Vorinostat (either 100 mg or 200 mg, twice a day) was initiated 10 days before haemopoietic stem-cell transplantation until day 100. The primary endpoint was the cumulative incidence of grade 2-4 acute GVHD by day 100. This trial is registered with ClinicalTrials.gov, number NCT00810602. FINDINGS: 50 patients were assessable for both toxic effects and response; eight additional patients were included in the analysis of toxic effects. All patients engrafted neutrophils and platelets at expected times after haemopoietic stem-cell transplantation. The cumulative incidence of grade 2-4 acute GVHD by day 100 was 22% (95% CI 13-36). The most common non-haematological adverse events included electrolyte disturbances (n=15), hyperglycaemia (11), infections (six), mucositis (four), and increased activity of liver enzymes (three). Non-symptomatic thrombocytopenia after engraftment was the most common haematological grade 3-4 adverse event (nine) but was transient and all cases resolved swiftly. INTERPRETATION: Administration of vorinostat in combination with standard GVHD prophylaxis after related-donor reduced-intensity conditioning haemopoietic stem-cell transplantation is safe and is associated with a lower than expected incidence of severe acute GVHD. Future studies are needed to assess the effect of vorinostat for prevention of GVHD in broader settings of haemopoietic stem-cell transplantation. FUNDING: Merck, Leukemia and Lymphoma Society, National Institutes of Health, St Baldrick's Foundation, Michigan Institute for Clinical and Health Research

What determines levels of passive smoking in children with asthma?

BACKGROUND: Children with parents who smoke are often exposed to high levels of environmental tobacco smoke, and children with asthma are particularly susceptible to the detrimental effects of passive smoking. Data were collected from parents who smoke and from their asthmatic children. The families are currently taking part in a randomised controlled trial to test an intervention designed to reduce passive smoking in children with asthma. This paper reports on the baseline data. Questionnaire data and cotinine levels were compared in an attempt to assess exposure and to identify factors which influence exposure of the children. The aim of the study was to identify the scope for a reduction in passive smoking by these children. METHODS: A sample of 501 families with an asthmatic child aged 2-12 years was obtained. Factors influencing passive smoking were assessed by interviewing parents. Cotinine levels were measured from saliva samples using gas liquid chromatography with nitrogen phosphorous detection. RESULTS: Cotinine levels in children were strongly associated with the age of the child, the number of parents who smoked, contact with other smokers, the frequency of smoking in the same room as the child, and crowding within the home. Parental cotinine levels, the amount smoked in the home, and whether the home had a garden also exerted an independent effect on cotinine levels in the children. CONCLUSIONS: Many children are exposed to high levels of environmental tobacco smoke and their cotinine levels are heavily dependent upon proximity to the parent who smokes. Parents who smoke have a unique opportunity to benefit their child's health by modifying their smoking habits within the home. 



Psychiatric and psychosocial challenges in patients undergoing haematopoietic stem cell transplants

Haematological malignancies are often treated with haematopoietic stem cell transplants (HSCT). The disease and its treatment are challenging and life threatening, as they not only affect the recipients, but also their families. This review highlights the available data on the psychological, psychiatric and social impact of these illnesses and their treatment on recipients and families. There are robust data that correlate HSCT with emotional distress, as emotional and physical functioning significantly affect quality of life. Psychiatric co-morbidity including anxiety, depression, adjustment and post-traumatic stress disorder, delirium and cognitive deficits have been reported at different stages in the transplant process. This review will highlight the psychosocial and clinical research findings relevant to HSCT patients and will summarize recommendations for future psychosocial research in this population