A total gastrectomy with omentectomy and resection of the distal oesophagus in a 69-year-old haemophilia A patient with high inhibitor of 128 Bethesda units is described. Surgery was successfully performed after infusion of 112 microg kg-1 bw of recombinant FVIIa. Ninety-two microg kg-1 were given thereafter at time intervals of 2 h until 12 h, then every 3 h until 24 h, and every 4 h until 48 h after surgery. Doses were gradually reduced in the following days and finally discontinued on day 28 after surgery. The complete treatment schedule required the administration of a total of 708 mg of recombinant FVIIa. Using this approach, we observed normal haemostasis, and there were no signs of excessive postoperative bleeding or wound haematoma. No clinical side-effects or evidence of systemic activation of coagulation occurred during the treatment. As judged from the clinical course of this major surgery, recombinant FVIIa appears to be highly efficacious and safe and should be used as first line treatment in high titre inhibitor patients with cross-reactivity to porcine factor VIII, undergoing surgery.
A multivariate survival analysis including gender, age, log white blood cell (WBC) count, liver and spleen size at diagnosis, mean log WBC count during maintenance therapy, and the prescribed cumulative doses of 6-mercaptopurine (6-MP), methotrexate (MTX), vincristine (VCR), and prednisone (PDN) during maintenance therapy was performed on 53 children with average-risk acute lymphoblastic leukemia (ALL). The 6-MP cumulative dose prescribed during maintenance therapy resulted in the most important statistically significant independent prognostic factor. Patients who received less than the median cumulative dose of 6-MP (86% of planned protocol dose) fared significantly worse than the other patients, regardless of WBC count at diagnosis, gender, age, and other factors studied. Therefore, 6-MP cumulative dose during maintenance therapy may be the critical factor for effective maintenance therapy in childhood ALL.
lhe biological effectiveness of cobalt-60 y-irradiation relative to 250 kVp X-irradiation for six different responses in CF, mice was found to be: 30-day lethality, 0.79 f 0.06; mean survival time, 0.79 0.04; body weight loss, 0.80 f 0.04; intestinal weight loss, 1.00; splenic weight loss, 1.00 f 0.06; and testicular weight loss, 0.63 f 0.06. The RBE for intestinal weight loss varied with the level of the effect resulting in an average RBE determined for this response. Possible considerations for the observed differences in RBE are discussed. Z I R K L E~~) and BoAG(~) have published excellent review articles on the relative biological effectiveness (RBE) of various ionizing radiations. Early experiments with mammals relied mainly on lethality as a biologic end-point. Since the radiosensitivity of certain organs and portions of the body varies considerably, it seemed advisable that a number of responses other than lethality be studied. Such studies would indicate the role of the specific organ or portion of the body in the over-all observed effect. These values for relative biological effectiveness would help facilitate decisions of permissible exposure of other mammals, including humans, to various ionizing radiations.The experiments reported here evaluate the relative biological effectiveness of cobalt-60 y-irradiation and 250 kVp X-irradiation for the following responses in CF, mice: 30-day lethality; mean survival time; body weight loss; intestinal, splenic and testicular weight loss. MATERIALS AND METHODSThe cobalt-60 y-rays and 250 kVp X-rays used have approximate linear energy transfer (LET) values of 0.3 keV/p and 3.0 keV/p, respectively.X-rays were delivered by a General ElectricMaxitron Unit operated at 250 kVp, 15 mA, 4.75 mm Be inherent filtration, 1 mm A1 + 0.5 mm Cu added filtration, HVL 1.1 mm Cu, and tube targetsample distance of 50 cm. y-Rays (1.17 and 1.33 MeV energy) were supplied by a 1000 c cobalt-60 unit. HVL of radiation is 12 mm Pb and tube target-sample distance of 47 cm was used. Dose rates of 81 rads/min and 63 rads/min, measured with a 100 r Victoreen ionization chamber placed in a paraffin phantom located at the center of the lucite cage (6 in. diameter), were found for the X-rays and C060 y-rays, respectively. The roentgen dose was converted to rads by assuming that 1 r is equivalent to 0.96 rad for X-rays and 0.98 rad for Co60 y-rays. The 6 m m thick lucite cage cover was more than sufficient to provide electronic equilibrium for the y-dose measurements. Adult female and male (used only for the testicular weight loss study) CF, mice, weighing 21-23 g, were used. The mice were acclimatized to laboratory conditions for at least 2 weeks prior to use. Prior to and following irradiation exposure, the mice were fed water and Purina Laboratory Chow ad libitum.The mice were irradiated ten at a time in a shallow lucite cage. Radiation exposure was unilateral to dorsal surface in all cases.The biological responses measured must be of a type which respond more or less quantitatively with dose ...
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