A number of common metastatic cancers are associated with marked weight loss at the time of diagnosis. Cancer patients with weight loss at the time of diagnosis have decreased mean survival compared to similar cancer patients without weight loss. Provision of excess calories alone does not appear to change median survival in patients with advanced cancer and many patients either maintain body weight or lose weight while receiving calories which would be predicted to result in weight gain. The authors recently have extended their studies to head and neck cancer patients without detectable metastatic disease in order to detect systemic metabolic effects of a localized tumor. These patients failed to gain weight despite the administration of apparently adequate calories by continuous enteral alimentation. Abnormalities of carbohydrate metabolism with secondary effects on fat and protein metabolism have been identified in several populations of patients with common cancers. These abnormalities offer potential points of intervention which may enhance nutritional therapy as rehabilitation and as a potential biological modifier of the response of specific cancers to chemotherapy, radiation therapy, or surgery.

Hydrazine sulfate was evaluated using 24-hour dietary recalls and body weight determinations before and after 30 days of either placebo or hydrazine (60 mg, 3 times/d) oral administration in 101 heavily pretreated cancer patients with weight loss. After 1 month, 83% of hydrazine and only 53% of placebo patients completing repeat evaluation maintained or increased their weight (P less than 0.05). In addition, appetite improvement was more frequent in the hydrazine group (63% versus 25%, P less than 0.05). Although caloric intake was only slightly greater in hydrazine-treated patients, an increased caloric intake was more commonly associated with weight gain in patients receiving hydrazine compared with those receiving placebo (81% versus 53%, respectively). Hydrazine toxicity was mild, with 71% of patients reporting no toxic effects. Hydrazine sulfate circulatory levels were obtained from a subset of 14 patients who completed 30 days of treatment, with a single sample obtained in the morning at least 9 hours after the last dose. Mean maintenance hydrazine sulfate levels, determined using a spectrofluorometric assay, ranged from 0 to 89 ng/ml (mean 45 +/- 16 ng/ml). These data, which demonstrate an association between 1 month of hydrazine sulfate administration and body weight maintenance in patients with cancer, suggest future clinical trials of hydrazine sulfate are indicated to definitively assess its long-term impact on important clinical outcome parameters in defined cancer populations.

Cachexia is a phenomenon commonly observed in patients with cancer, but its etiology is poorly understood. Abnormalities of insulin action and metabolism that have been hypothesized to promote cancer cachexia were investigated in this study using a computerized euglycemic clamp and modified frequently sampled intravenous glucose tolerance test (FSIGT) in a group of malnourished patients with localized head and neck cancer, and in healthy, well-nourished, age- and, sex-matched controls. Glucose disposal rates, determined by the euglycemic clamp at three different rates of insulin infusion did not differ significantly between the two groups. However, mean plasma insulin concentrations at each level of insulin infused were significantly lower in the patients with cancer than in the control subjects resulting in unexpectedly higher calculated insulin metabolic clearance rate in the patients with cancer. Peripheral insulin sensitivity calculated from the slope of glucose disposal versus plasma insulin concentration did not differ between the two groups. Results from the FSIGT demonstrated no difference in insulin sensitivity or insulin-independent glucose disappearance between the two groups. However, whole body glucose appearance was significantly elevated in the patients with cancer. Thus, increased whole body glucose utilization in the absence of insulin resistance or increased insulin-dependent glucose disposal was observed. These data are consistent with the concept of a localized tumor acting as a glucose drain in which case increased glucose appearance and increased insulin clearance would defend against hypoglycemia.

Relaxor ferroelectrics are a unique class of materials that can be identified by their high dielectric constants, low hysteresis, large electrostrictive strains, and diffuse paraelectric to ferroelectric phase transitions [1]. The outstanding electromechanical response of relaxor ferroelectrics is attributed to the presence of "polar nanoregions" (PNRs), nanoscale domains that coexist within normal ferroelectric domains. Although relaxors have been extensively studied, the structural and chemical origins of PNRs are not yet fully understood.In this talk, we will present an investigation of local distortion and its relationship with local chemistry in the prototypical relaxor, Pb(Mg 1/3 Nb 2/3 )O 3 (PMN). In this perovskite structured material, the A sublattice contains Pb, while the B sub-lattice contains Mg/Nb at a 1:2 ratio. In addition to PNRs, chemical ordering has also been observed in PMN in the form of chemically ordered regions (CORs) which are ~2-5 nm in size. CORs can be characterized by a charge balanced "random site" model that assumes a 1:1 Pb(B I 1/2 B II 1/2 )O 3 ordered structure where B I is a random mixture of (Mg 2/3 Nb 1/3 ) and B II contains only Nb [2]. Through the application of annular dark-field scanning transmission electron microscopy (ADF-STEM) in figure 1a, we identify distinct B I and B II positions across the image, as in figure 1b. As is evident, B I (blue circles) and B II (red circles) positions can be identified and classified into unique domains across the entire image, separated by antiphase boundaries (green circles). Further, we will discuss and justify the development of an "ordering metric", here defined as the standard deviation of local B-site intensities. Figure 1c highlights how highly ordered regions transition diffusely to less order. Minimum values of local ordering correspond to antiphase regions. These results are also discussed in the context of multislice STEM image simulations, where the effect of chemical fluctuations on the ordering metric is determined [3].The relationship between chemical ordering and local distortion is elucidated through the application of spatial statistics. Assuming a rigid B-sub lattice, we determine local A-site distortions as shown in figure 2a. The application of revolving STEM (RevSTEM) enables picometer precision when measuring distortions [4]. The square roots of the A-site distortions are then correlated with the local means and local standard deviations of the B-site intensities. Utilizing multiple linear regression and a Bayesian fit of a spatial linear model, non-random correlation between distortion and intensity is evident. Spatial correlation between A-site distortion and B-site intensity is then found to be ~1.5-2.0 nm, the expected size of a PNR (figure 2b). Finally, we will discuss the broad applications of these techniques and implications in the wider relaxor ferroelectric community [5].