Adoptive transfer of gene-engineered CD4+ helper T cells induces potent primary and secondary tumor rejection

Because CD4+ T cells play a key role in aiding cellular immune responses, we wanted to assess whether increasing numbers of gene-engineered antigen-restricted CD4+ T cells could enhance an antitumor response mediated by similarly gene-engineered CD8+ T cells. In this study, we have used retroviral transduction to generate erbB2-reactive mouse T-cell populations composed of various proportions of CD4+ and CD8+ cells and then determined the antitumor reactivity of these mixtures. Gene-modified CD4+ and CD8+ T cells were shown to specifically secrete Tc1 (T cytotoxic-1) or Tc2 cytokines, proliferate, and lyse erbB2+ tumor targets following antigen ligation in vitro. In adoptive transfer experiments using severe combined immunodeficient (scid) mice, we demonstrated that injection of equivalent numbers of antigen-specific engineered CD8+ and CD4+ T cells led to significant improvement in survival of mice bearing established lung metastases compared with transfer of unfractionated (largely CD8+) engineered T cells. Transferred CD4+ T cells had to be antigen-specific (not just activated) and secrete interferon gamma (IFN-gamma) to potentiate the antitumor effect. Importantly, antitumor responses in these mice correlated with localization and persistence of gene-engineered T cells at the tumor site. Strikingly, mice that survived primary tumor challenge could reject a subsequent rechallenge. Overall, this study has highlighted the therapeutic potential of using combined transfer of antigen-specific gene-modified CD8+ and CD4+ T cells to significantly enhance T-cell adoptive transfer strategies for cancer therapy.     

Repetitive transcranial magnetic stimulation in schizophrenic patients reporting auditory hallucinations

Auditory hallucinations are experienced by 60-80% of person with schizophrenia and can often cause significant distress behavioural dyscontrol. The application of rTMS in the left temporoparietal cortex could modulate the neuronal activation and reduce the occurrence of auditory disperceptions. Sixteen schizophrenic patients (treated with atypical antipsycothic drugs) reporting auditory hallucinations were included in the study. Low frequency rTMS (1 Hz) was performed at the 90% of resting motor threshold (MT), during 4 sessions in four consecutive days for 15 minutes each application. Eight patients received active stimulation, while eight patients received sham stimulation. Scale for the assessment of positive symptoms (SAPS), scale for the assessment of negative symptoms (SANS) and a scale to asses the severity of the auditory hallucinations (SAH) were administered at the beginning and at regular intervals during the follow-up. The present study confirms the reduction in auditory hallucinations by means of rTMS. The main finding was the long-term reduction in auditory hallucinations in the active group, with a return to the baseline in the sham group. The negative symptomatology improved only in the later sessions and lasted during the follow-up. The improvements in auditory hallucinations and positive symptomatology increased and lasted during the follow-up till the end-point. These data suggest that this approach may lead to an alternative somatic intervention for auditory hallucination in patients with schizophrenia.     

Participatory action research to understand and reduce health disparities

Participatory action research (PAR) is an excellent way to systematically learn about the conditions under which people experience health disparities, what it is like from the perspective of those experiencing such disparities and, even more importantly, how to ameliorate this major public health problem and create a more equitable and effective health care system. This article describes the method of PAR, supports the appropriateness of PAR to learn about and reduce health disparities, and then presents some specific examples of research projects that have employed or are planning to employ PAR. These examples are from the work of several authors of this article, who are members of an interdisciplinary working group that serves as a forum for discussion of issues related to qualitative research methods and facilitates the development of qualitative studies. All of the authors of this article are part of a task force of this working group that is focusing specifically on community outreach with the goal of reducing health disparities within specific communities.     

Validity of pedometers for measuring exercise adherence in heart failure patients

BACKGROUND: Measuring adherence to exercise is important to clinicians and researchers because inadequate adherence can adversely affect the effectiveness of an exercise program and cloud the relationship between exercise and clinical outcomes. Hence, assessment strategies for adherence to exercise, as with assessment strategies for other outcomes, must have demonstrated validity if they are to be employed with confidence. We conducted this study to determine the validity of pedometers as a measure of exercise adherence to a home-based walking program in heart failure patients. METHODS AND RESULTS: Exercise adherence was measured using pedometers in 38 patients (74% men) age 54.1 +/- 11.7 years who participated in a 12-month home-based walking program. A comparison of functional status as measured by the 6-minute walk distance and peak oxygen uptake (VO2 max) at 6 months into the exercise training program was made between 2 groups of participants who were thought to represent adherers and nonadherers: participants who demonstrated > or = 10% change in pedometer scores (n = 20) and those who showed no change in pedometer scores (n = 18) from baseline to 6 months. Patients who showed improvements in their pedometer scores over 6 months had better functional status at 6 months (6-minute walk distance 1718 +/- 46 versus 1012 +/- 25 meters, F = 5.699, P = .022; VO 2 max 17 +/- 0.7 versus 10 +/- 0.5 units, F = 7.162, P = .011) when compared with patients whose pedometers reflected minimal change in distance walked (ie, < or = 10%). CONCLUSION: Pedometers are inexpensive and readily available to both clinicians and researchers. The results of this study suggest that they may be a valid indicator of exercise adherence in heart failure patients who participate in a home-based walking program.