Effect of negative pressure ventilation on arterial blood gas pressures and inspiratory muscle strength during an exacerbation of chronic obstructive lung disease.

The effects of intermittent negative pressure ventilation have been studied in 20 patients with chronic obstructive pulmonary disease during an exacerbation of their disease. Measurements of arterial blood gas tensions and maximal inspiratory pressure (MIP) were performed before and after six hours of negative pressure ventilation or standard treatment (control day) given in random order on two consecutive days. After negative pressure ventilation the mean (SD) value of MIP increased from 68.1 (21.5) to 74.8 (20) cm H2O;* arterial oxygen tension (PaCO2) fell from 60.6 (12.2) to 50.9 (8.9) mm Hg* but PaO2 changed little (from 48.4 (7.4) to 47.6 (8.2) mm Hg). There were no significant changes on the control day in arterial blood gas tensions (PaO2 47.8 (8.1) and 48.9 (9.4) and Paco2 59.8 (10.9) and 57.5 (8.06) mm Hg) or in MIP (69.4 (22.4) and 70.9 (22.9) cm H2O). Six patients tolerated negative pressure ventilation poorly and these patients showed less improvement after negative pressure ventilation. Our results suggest that intermittent negative pressure ventilation can increase alveolar ventilation in patients with an exacerbation of chronic obstructive lung disease, particularly in those who tolerate the procedure well. Most subjects showed a fall in PaCO2 and an increase in MIP. The fact that PaO2 was unchanged despite the fall in PaCO2 suggests that gas exchange may deteriorate with negative pressure ventilation in these patients.     

Combining the benefits of tele-rehabilitation and virtual reality-based balance training: a systematic review on feasibility and effectiveness

Purpose: A motivational surrounding is desirable in stroke rehabilitation considering the need to train repetitively to improve balance, even after discharge from rehabilitation facilities. This review aims to investigate whether it is feasible to combine virtual reality (VR) which allows exercising in game-like environments with tele-rehabilitation in a community-dwelling stroke population.

Methods: Literature searches were conducted in five databases, for example, PubMed and the Cochrane Library. Randomized controlled trial (RCT) and non-RCT investigating feasibility and effectiveness of VR-based tele-rehabilitation were included. Based on the risk of bias and study design, methodological quality is ranked according to the GRADE guidelines.

Results: Seven studies (n?=?120) were included, of which four are RCTs. Evidence regarding therapy adherence and perceived enjoyment of VR, as well as a cost–benefit of tele-rehabilitation emphasizes feasibility. Equal effects are reported comparing this approach to a therapist-supervised intervention in the clinical setting on balance and functional mobility.

Conclusions: Tele-rehabilitation could be a promising tool to overcome burdens that restrict accessibility to rehabilitation in the future. VR can increase motivation allowing longer and more training sessions in community-dwelling stroke survivors. Therefore, combining the benefits of both approaches seems convenient. Although evidence is still sparse, functional improvements seem to be equal compared to a similar intervention with therapist-supervision in the clinic, suggesting that for cost-efficient rehabilitation parts of therapy can be transferred to the homes.

• Implications for rehabilitation

• The use of tele-rehabilitation could be a promising tool to overcome burdens that restrict the access of stroke survivors to long-term rehabilitative care.

• VR-based interventions are game-like and therefore seem to provide a motivational environment which allows longer exercise sessions and greater adherence to therapy.

     

Risk factors for dislypidemia in obese children and adolescents

OBJECTIVE: To assess the risk of dislypidemia associated with obesity in children and adolescents. MATERIAL AND METHODS: A cross sectional study was conducted with 62 obese children (BMI > 95 centile and tricipital skinfold thickness > 90 centile) and 70 non-obese children (BMI 5-85 centile) ages 5-15 years, without chronic diseases. Subjects' characteristics and family background of chronic diseases were collected and a lipid profile was determined. The risk of lipid alterations in the obese children was calculated using odds ratio (OR) and multivariate analysis. RESULTS: Mean age was 9.8 +/- 2.7 years in both groups; 63 girls and 69 boys were included. Obesity was associated with abnormal values for cholesterol, triglycerides, LDL, HDL and dislypidemia (> 1 abnormal value) (OR 4.47-15.0). In obese children and adolescents the multivariate analysis showed that female gender was associated with dislypidemia. CONCLUSION: Obesity in children and adolescents is associated with high risk of dislypidemia; the risk is higher among females.     

In vitro induction of immune responses to shared tumor-associated antigens in rhabdomyosarcoma

Purpose

Currently, novel therapies to improve survival of patients with rhabdomyosarcoma (RMS) are being investigated. One of the new approaches involves immunotherapy using tumor-specific T-lymphocytes. An effective prolonged immune-mediated response against tumor cells is dependent upon the response of helper T-lymphocytes (HTLs) to tumor-associated antigens in the presence of histocompatibility lymphocyte antigen surface proteins.

Methods

Rhabdomyosarcoma tumor lysate-pulsed human dendritic cells were used to stimulate HTL precursors (naive CD4+ T-cells) in vitro. After 3 rounds of antigen stimulation with antigen-presenting cells, the T-cells were tested for reactivity (T-cell proliferation assays) against a large panel of tumor lysate-pulsed autologous antigen-presenting cells.

Results

Using peripheral blood mononuclear cells from normal naive donors, we have been able to generate HTL clones that recognize and proliferate to multiple tumor cell lines. The HTLs were induced using lysate from a single alveolar RMS tumor cell line (RMS13). The clones generated recognized all of the alveolar RMS cell lines (RMS13, Rh18, Rh28, Rh30, and Rh41), prostate cancer cell lines (LNCAP and LAPC4), melanoma cell lines (Mel 624 and G361), and breast cancer cell line (SKBR3). Helper T-lymphocytes recognition was also confirmed by interferon-γ production. The clones did not recognize colon, lymphoma, ovarian carcinoma, ERMS or Epstein-Barr virus (EBV) transformed B-cells. This recognition was histocompatibility lymphocyte antigen class II restricted and was not an allogeneic response.

Conclusion

The results of this work demonstrate that HTLs, exposed to RMS lysate, are able to recognize and respond to a broad range of tumor types suggesting that a common antigen exist among these different tumors. These findings suggest novel treatment strategies for patients with RMS using tumor lysate to induce antitumor immune responses.     

Ectopic lymphoid neogenesis in psoriatic arthritis

BACKGROUND: Ectopic lymphoid neogenesis (LN) occurs in rheumatoid synovium, where it is thought to drive local antigen-dependent B cell development and autoantibody production. This process involves the expression of specific homing chemokines and the development of high endothelial venules (HEV). OBJECTIVE: To investigate whether these mechanisms occur in psoriatic arthritis (PsA) synovium, where autoantibodies have not been described and the organisation and function of B cells is not clear, and to analyse their clinical correlates. METHODS: Arthroscopic synovial biopsy specimens from patients with PsA before and after tumour necrosis factor alpha blockade were characterised by immunohistochemical analysis for T/B cell segregation, peripheral lymph node addressin (PNAd)-positive HEV, and the expression of CXCL13, CCL21 and CXCL12 chemokines in relation to the size of lymphoid aggregates. RESULTS: Lymphoid aggregates of variable sizes were observed in 25 of 27 PsA synovial tissues. T/B cell segregation was often observed, and was correlated with the size of lymphoid aggregates. A close relationship between the presence of large and highly organised aggregates, the development of PNAd+ HEV, and the expression of CXCL13 and CCL21 was found. Large organised aggregates with all LN features were found in 13 of 27 tissues. LN in PsA synovitis was not related to the duration, pattern or severity of the disease. The synovial LN pattern remained stable over time in persistent synovitis, but a complete response to treatment was associated with a regression of the LN features. CONCLUSIONS: LN occurs frequently in inflamed PsA synovial tissues. Highly organised follicles display the characteristic features of PNAd+ HEV and CXCL13 and CCL21 expression, demonstrating that the microanatomical bases for germinal centre formation are present in PsA. The regression of LN on effective treatment indicates that the pathogenic and clinical relevance of these structures in PsA merits further investigation.     

Expression, specificity and immunotherapy potential of prostate-associated genes in murine cell lines

The TRAMP-C1 (C1) and TRAMP-C2 (C2) cell lines were derived from a prostate tumor that arose in a mouse from the transgenic adenocarcinoma mouse prostate (TRAMP) model. However, their similarity to primary prostate tumors and therefore their usefulness in immunotherapy studies has not been clearly defined. We showed using RT-PCR that these cell lines exhibited a variety of prostate-specific genes expressed by human prostate tumors that may be used as tumor-associated antigens for immunotherapy. Interestingly, several of these genes are also expressed in cell lines that are not prostatic in origin. The prostate cell lines were also shown to grow in an androgen-independent manner, to be capable of expressing MHC class I and to be susceptible to specific lysis by cytotoxic T lymphocytes. Therefore, these cell lines will provide us with the ability to evaluate immune responses to and tolerance of prostate-specific protein peptides in an animal model.     

‘Tackling cancer in the EU: The role of innovation’

The objective of the workshop was to examine what Cancer Innovation in Europe means and what it should be standing for in the future. The panel discussion brought together patients, researchers, politicians and industry in order to examine what cancer innovation represents to them, what the challenges are to innovation, and how innovation in this research area can be encouraged and developed in the EU.