1H MRS identifies specific metabolite profiles associated with MYCN-amplified and non-amplified tumour subtypes of neuroblastoma cell lines.

Neuroblastoma is the most common extracranial solid malignancy in children. The disease possesses a broad range of clinical phenotypes with widely varying prognoses. Numerous studies have sought to identify the associated genetic abnormalities in the tumour, resulting in the identification of useful prognostic markers. In particular, the presence of multiple copies of the MYCN oncogene (referred to as MYCN amplification) has been found to confer a poor prognosis. However, the molecular pathways involved are as yet poorly defined. Metabolite profiles generated by in vitro (1)H MRS provide a means of investigating the downstream metabolic consequences of genetic alterations and can identify potential targets for new agents. Thirteen neuroblastoma cell lines possessing multiple genetic alterations were investigated; seven were MYCN amplified and six MYCN non-amplified. In vitro magic angle spinning (1)H MRS was performed on cell suspensions, and the spectra analysed to obtain metabolite concentration ratios relative to total choline (tCho). A principal component analysis using these concentration ratios showed that MYCN-amplified and non-amplified cell lines form separate classes according to their metabolite profiles. Phosphocholine/tCho and taurine/tCho were found to be significantly raised (p < 0.05) and glycerophosphocholine/tCho significantly reduced (p < 0.05) in the MYCN-amplified compared with the MYCN non-amplified cell lines (two-tailed t test). (1)H MRS of the SH-EP1 cell line and an isogenic cell line transfected with the MYCN oncogene also showed that MYCN oncogene over-expression causes alterations in phosphocholine, glycerophosphocholine and taurine concentrations. Molecular pathways of choline and taurine metabolism are potential targets for new agents tailored to MYCN-amplified neuroblastoma.

Post-traumatic stress disorder after critical illness requiring general intensive care.

OBJECTIVE: To determine the incidence and severity of symptoms related to the diagnosis of post-traumatic stress disorder (PTSD) in a cohort of general ICU patients. DESIGN: A prospective cohort study 3 months after general ICU discharge. SETTING: A general ICU in a teaching hospital in northern Scotland. PATIENTS AND PARTICIPANTS: Seventy-eight ICU survivors of general ICU. INTERVENTIONS: Patients were contacted 3 months after ICU discharge and asked to complete a telephone assessment of the Davidson Trauma Scale. MEASUREMENTS AND RESULTS: The median score was 8, with 22% recording a score of at least 27 and 14% meeting the full diagnostic criteria for PTSD. The overall score was not correlated with sex, ICU length of stay, or APACHE II score but was inversely correlated with age and directly correlated with length of mechanical ventilation. The overall score was also related to the patient reporting having visited a GP or a mental health professional for psychological distress previous to ICU. CONCLUSIONS: We found a high incidence of symptoms consistent with PTSD 3 months after ICU discharge in this general ICU cohort. This was associated with younger patients and those who visited their GP or a mental health professional complaining of psychological symptoms. Further research and a greater liaison between ICU staff and family practitioners and mental health practitioners is required to better identify individuals at risk and reduce psychological morbidity in this group.