Neonatal colon insult alters growth factor expression and TRPA1 responses in adult mice

Inflammation or pain during neonatal development can result in long-term structural and functional alterations of nociceptive pathways, ultimately altering pain perception in adulthood. We have developed a mouse model of neonatal colon irritation (NCI) to investigate the plasticity of pain processing within the viscerosensory system. Mouse pups received an intracolonic administration of 2% mustard oil (MO) on postnatal days 8 and 10. Distal colons were processed at subsequent timepoints for myeloperoxidase (MPO) activity and growth factor expression. Adult mice were assessed for visceral hypersensitivity by measuring the visceromotor response during colorectal distension. Dorsal root ganglion (DRG) neurons from adult mice were retrogradely labeled from the distal colon and calcium imaging was used to measure transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) responses to acute application of capsaicin and MO, respectively. Despite the absence of inflammation (as indicated by MPO activity), neonatal exposure to intracolonic MO transiently maintained a higher expression level of growth factor messenger RNA (mRNA). Adult NCI mice displayed significant visceral hypersensitivity, as well as increased sensitivity to mechanical stimulation of the hindpaw, compared to control mice. The percentage of TRPA1-expressing colon afferents was significantly increased in NCI mice, however they displayed no increase in the percentage of TRPV1-immunopositive or capsaicin-sensitive colon DRG neurons. These results suggest that early neonatal colon injury results in a long-lasting visceral hypersensitivity, possibly driven by an early increase in growth factor expression and maintained by permanent changes in TRPA1 function.     

Gender differences in characteristics and outcomes of smokers diagnosed with psychosis participating in a smoking cessation intervention

While research has identified gender differences in characteristics and outcomes of smokers in the general population, no studies have examined this among smokers with psychosis. This study aimed to explore gender differences among 298 smokers with psychosis (schizophrenia, schizoaffective and bipolar affective disorder) participating in a smoking intervention study. Results revealed a general lack of gender differences on a range of variables for smokers with psychosis including reasons for smoking/quitting, readiness and motivation to quit, use of nicotine replacement therapy, and smoking outcomes including point prevalence or continuous abstinence, and there were no significant predictors of smoking reduction status according to gender at any of the follow-up time-points. The current study did find that female smokers with psychosis were significantly more likely than males to report that they smoked to prevent weight gain. Furthermore, the females reported significantly more reasons for quitting smoking and were more likely to be driven by extrinsic motivators to quit such as immediate reinforcement and social influence, compared to the male smokers with psychosis. Clinical implications include specifically focussing on weight issues and enhancing intrinsic motivation to quit smoking for female smokers with psychosis; and strengthening reasons for quitting among males with psychosis.     

Monitoring CD4+ T cell responses against viral and tumor antigens using T cells as novel target APC

CD4+ T cells play an important role in the induction and maintenance of an effective antiviral and antitumor immune response. However, standardized monitoring of antigen-specific CD4+ T cells has not been established at the single-cell level. We now present a sensitive, specific, and simple methodology in which purified memory CD4+ T cells are expanded from PBMC in a single cycle of antigen-driven stimulation and quantitatively assayed by interferon-gamma ELISPOT. Issues of nonspecific background in assays were resolved with the use of innovative target cells, autologous PHA-expanded CD4+ T cells (T-APC). Remarkably, T-APC could not only present peptide epitopes from model antigens NY-ESO-1 and influenza nucleoprotein, but could also process full-length antigen endogenously expressed from recombinant fowlpox vector. This approach makes it possible to monitor CD4+ T cells in large series of patients, regardless of HLA haplotype, against the full peptide repertoire of a given antigen.     

Proficiency of nucleic acid tests for avian influenza viruses, Australasia

An avian influenza quality assurance program was used to provide information for laboratories on the sensitivity and specificity of their avian influenza nucleic acid testing. Most laboratories were able to correctly detect clinically relevant amounts of influenza virus (H5N1), and results improved as each subsequent panel was tested.     

Single-lung transplantation in patients with previous contralateral pneumonectomy: technical aspects and results

Objective: Single-lung transplantation (SLTX) in patients with previous contralateral pneumonectomy (PN) is a rarely observed situation. Intrathoracic anatomical changes caused by mediastinal shift may complicate the surgical procedure. We collected observations from different transplantation centres to analyse the technical aspects and results. Patients and methods: Between July 1990 and September 2008, 14 patients (seven women and seven men) with previous PN underwent SLTX for end-stage pulmonary failure. Patients were categorised in three groups according to lung disease: cystic fibrosis bronchiectasis (group 1; n = 4), non-cystic fibrosis bronchiectasis (group 2; n = 6) and bronchioloalveolar carcinoma (group 3; n = 4). We reviewed patients’ characteristics according to mediastinal shift, thoracic approach, bypass cannula procedure, perioperative difficulties and immediate and long-term results. Results: Median age was 19.5, 33.5 and 52.5 years in groups 1, 2 and 3, respectively; there were nine left and five right cases of SLTX. Surgery was performed by sternotomy (n = 4), anterolateral thoracotomy (n = 4), clamshell (n = 4) or posterolateral thoracotomy (n = 2). Cannulas for bypass were inserted into femoral (n = 7) or central vessels (n = 5) or both (n = 2). Mediastinal shift did not complicate surgical procedure but rendered cannulation more difficult with ensuing cardiopulmonary bypass dysfunction (n = 3) and early bronchial complications (n = 2). In-hospital mortality rate was 29% (4 out of 14 patients), including two deaths due to perioperative difficulties linked to mediastinal shift. Median global survival was 108 months. Median survival was higher in group 2 (108 months vs 1 month in the other groups) and in case of PN during childhood (n = 6, median survival 108 months corresponding to one death). Conclusions: SLTX after PN is associated with high perioperative morbidity and mortality due to mediastinal shift. Best results are observed in patients undergoing PN for non-cystic fibrosis bronchiectasis and during childhood. Anatomical changes induced by PN must be anticipated to adapt the thoracic approach and cardiopulmonary bypass access.