Citations

Insulin regulates many cellular processes, but the full impact of insulin deficiency on cellular functions remains to be defined. Applying a mass spectrometry–based nontargeted metabolomics approach, we report here alterations of 330 plasma metabolites representing 33 metabolic pathways during an 8-h insulin deprivation in type 1 diabetic individuals. These pathways included those known to be affected by insulin such as glucose, amino acid and lipid metabolism, Krebs cycle, and immune responses and those hitherto unknown to be altered including prostaglandin, arachidonic acid, leukotrienes, neurotransmitters, nucleotides, and anti-inflammatory responses. A significant concordance of metabolome and skeletal muscle transcriptome–based pathways supports an assumption that plasma metabolites are chemical fingerprints of cellular events. Although insulin treatment normalized plasma glucose and many other metabolites, there were 71 metabolites and 24 pathways that differed between nondiabetes and insulin-treated type 1 diabetes. Confirmation of many known pathways altered by insulin using a single blood test offers confidence in the current approach. Future research needs to be focused on newly discovered pathways affected by insulin deficiency and systemic insulin treatment to determine whether they contribute to the high morbidity and mortality in T1D despite insulin treatment.

SUMMARY Chromosomally integrated human herpesvirus 6 (ciHHV‐6) is a condition in which the complete HHV‐6 genome is integrated into the host germ line genome and is vertically transmitted in a Mendelian manner. The condition is found in less than 1% of controls in the USA and UK, but has been found at a somewhat higher prevalence in transplant recipients and other patient populations in several small studies. HHV‐6 levels in whole blood that exceed 5.5 log10 copies/ml are strongly suggestive of ciHHV‐6. Monitoring DNA load in plasma and serum is unreliable, both for identifying and for monitoring subjects with ciHHV‐6 due to cell lysis and release of cellular DNA. High HHV‐6 DNA loads associated with ciHHV‐6 can lead to erroneous diagnosis of active infection. Transplant recipients with ciHHV‐6 may be at increased risk for bacterial infection and graft rejection. ciHHV‐6 can be induced to a state of active viral replication in vitro . It is not known whether ciHHV‐6 individuals are put at clinical risk by the use of drugs that have been associated with HHV‐6 reactivation in vivo or in vitro . Nonetheless, we urge careful observation when use of such drugs is indicated in individuals known to have ciHHV‐6. Little is known about whether individuals with ciHHV‐6 develop immune tolerance for viral proteins. Further research is needed to determine the role of ciHHV‐6 in disease. Copyright © 2011 John Wiley & Sons, Ltd.

Abstract Lymphedema (LE) is a common complication of cancer treatment, and has been identified as the number one issue by breast cancer survivors with incidence as high as 70%. Given the long-term survivorship of these women, LE is a widely prevalent condition. Irradiation of axillary and supraclavicular lymph nodes increases a patient's risk of LE onset and progression by as much as 2-fold. It is anticipated that a more individualized approach to post-surgical irradiation of breast cancer patients may reduce radiation-induced lymph node (LN) damage without sacrificing control rates, although it is noted that a definitive radiation exposure threshold below which LNs physiological integrity will be preserved is currently lacking. To identify the locations of the small, non-pathological but physiologically relevant LNs which drain the arm after breast cancer surgery and incorporate them into radiation planning, filtered 99mTc sulfur colloid (TcSC) was administered and a SPECT-CT scan was acquired for 22 patients immobilized in the treatment position. These images were registered with the Radiation Oncology planning CT scan, and draining LN were contoured automatically using a threshold of 50% maximum intensity. Two treatment plans were generated for each patient, one per routine clinical practice (STD) and the other (MOD) with treatment fields modified to minimize dose to the LNs visible on SPECT/CT images while ensuringthat ≥50Gy or biologic equivalent is delivered to target tissues. 53 draining LN were identified, 54% of which were inside the STD plan fields but could be blocked in the MOD plan fields. 62% of LN in the STD plans vs. 17% in the MOD plans receiving a mean of ≥10Gy, and 27% in the STD plans vs. 6% in the MOD plans receiving a mean of ≥40Gy. Patient-specific LN dose reduction can be achieved through integration of SPECT/CT images into the radiation planning process. These patients will be followed for the development of LE, to estimate an exposure threshold below which LN preservation is assured. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-20.