16. Animal care and monitoring Report any expected or unexpected adverse events. examples

“Murine lymph node tumors arose in 11 of 12 mice that received N2-transduced human cells. The neo gene could be detected in murine cells as well as in human cells. Significant lymphoproliferation could be seen only in the murine pre-T cells. It took 5 months for murine leukemia to arise; the affected mice displayed symptoms of extreme sickness rapidly, with 5 of the 12 mice becoming moribund on exactly the same day (Figure…), and 6 others becoming moribund within a 1-month period…Of the 12 mice that had received N2-transduced human cells, 11 had to be killed because they developed visibly enlarged lymph nodes and spleen, hunching, and decrease in body weight, as shown in Figure…The 12th mouse was observed carefully for 14 months; it did not show any signs of leukemia or other adverse events, and had no abnormal tissues when it was autopsied…The mice were observed at least once daily for signs of illness, which were defined as any one or more of the following: weight loss, hunching, lethargy, rapid breathing, skin discoloration or irregularities, bloating, hemi-paresis, visibly enlarged lymph nodes, and visible solid tumors under the skin. Any signs of illness were logged as “adverse events” in the experiment, the mouse was immediately killed, and an autopsy was performed to establish the cause of illness.” [1]

“Although procedures were based on those reported in the literature, dogs under Protocol 1 displayed high levels of stress and many experienced vomiting. This led us to significantly alter procedures in order to optimize the protocol for the purposes of our own fasting and postprandial metabolic studies.” [2]