SUMMARYIn the present investigation, the haematology and pathology of young broiler chicks with an ascitic syndrome were examined. Gross changes included cardiomegaly, ascites, congested lungs, shrunken livers, enlarged kidneys, dark breast muscle and congested intestines. Many blood parameters were significantly raised including the packed cell volume (PCV), haemoglobin (Hb), red (Rbc) and white blood cell (Wbc) counts. The heterophils and monocytes were also increased at the expense of the lymphocytes compared with control birds. The histopathology revealed degenerative changes in all organs examined which resembled lesions reported elsewhere in birds maintained at high altitude. In addition, large numbers of infiltrating leukocytes, in particular heterophils, were also present in the tissues. In many cases the syndrome was characterised by congestive heart failure.

Broiler chicks were subjected to experimentally-induced hypoxia and the haematology, together with the histopathology and ultrastructure of heart, liver, lung and kidney and the ultracytochemistry of heart tissues were examined. The haemoglobin concentration, packed cell volume and red blood cell counts were significantly increased compared with controls. The results resembled the haematology of similar aged broilers with an ascitic syndrome and also 1-day-old chicks after induced hypoxia. The morphological changes were also similar in all organs examined and compared with those described in ascitic syndromes. Lactate dehydrogenase was increased in the hearts of hypoxic and ascitic birds indicating reduced oxygen utilisation. It was suggested that hypoxia may be an important factor in the aetiology ascitic syndromes of flocks kept at low altitude.

1. White blood cells and thrombocyte values were examined in normal domestic fowls of layer and broiler strains fed restricted or ad libitum diets. 2. Basophils were the only white blood cells to increase significantly in number after the period of food restriction. It is suggested that the increase may have been associated with stress. 3. There were more basophils in broilers than layers, in males than females and in younger than older birds. 4. In contrast, a decrease in the total number of white blood cells was seen in birds maintained on a restricted diet compared with those fed ad libitum. 5. Stress may also have been responsible for an increased thrombocyte count in the restricted birds as well as a slightly lowered eosinophil count. 6. Heterophil/lymphocyte ratios were not significantly altered by the restriction of food.

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In the past 25 years, effective new drugs along with better treatment decisions based on disease factors have resulted in significantly improved clinical outcomes in acute lymphoblastic leukemia. Despite these successes in the last 2 decades, 15% to 25% of acute lymphoblastic leukemia patients relapse. Therefore, better dosing therapies are still needed. Insights in the pharmacokinetic and pharmacodynamic (PK-PD) contributions of licensed drugs may guide us into better protocol design and optimal use of existing combination drug regimens. Currently, 3 asparaginase formulations are available in the United States, Escherichia coli native asparaginase (ASNase), Pegaspargase, and Erwinase. On the basis of these clinical studies, PK and PD population modeling (NONMEM) have been used to delve into new insights as to the optimal dose, formulation, and time intervals of ASNases that may be used in future clinical trials. Pegaspargase 2500 IU/m2 Q2week dosing seems to be the "golden standard" as far as being safe and effective. Lower doses of this formulation Qweek may achieve better PK "steady-state" profiles in serum. Native E. coli or Erwinia ASNase at 6000 IU/m2 showed inferior PK parameters (peak, trough, and area under the curve) than Pegaspargase. Assuming linear handling of ASNase modeling, simulations of higher doses of these ASNase formulations on a daily or Q48 hours regimen are showing bioequivalency with Pegaspargase PK-PD parameters. Future clinical trial designs may prove these efforts useful.