Outcome of a multicenter treatment program including autologous or allogeneic bone marrow transplantation for de novo acute myeloid leukemia

Abstract: The results of an intensive treatment program for patients 16–60 yr of age with de novo acute myeloid leukemia are presented. The patients were given conventional induction treatment with daunorubicin and cytarabine. Patients not entering complete remission (CR) after 1 course of daunorubicin/cytarabine were given 1 course of amsacrine/etoposide/cytarabine. Those entering complete remission received 3 consolidation courses using mitoxantrone, etoposide, amsacrine and cytarabine. One hundred and eighteen patients were enrolled. Complete remission was attained after 1–2 courses in 90 patients (76%). Another 6 patients reached CR after 3–4 induction courses for a total CR rate of 81%. If feasible, patients were offered either allogeneic or unpurged autologous bone marrow transplantation. Twenty-four patients underwent allogeneic bone marrow transplantation; 15 in first remission, 8 in second remission, 1 in early relapse. Thirty patients below 56 yr of age underwent autologous bone marrow transplantation in first remission. The overall probability of survival at 4 yr was 34%, and for patients below 40 yr of age 50%. Leukemia-free survival was 35% for the whole cohort of patients; 52% for patients below 40 yr of age. Patients undergoing allogeneic or autologous bone marrow transplantation in first remission had an overall survival of 86% and 47%, respectively, while the probability of leukemia-free survival in these groups was 87% vs. 40% at 4 yr. The CR rate and long-term results of this intensive treatment program compare favorably with other recent studies using intensive consolidation with allogeneic or autologous bone marrow transplantation or high dose cytarabine.     

Electron Microscopy and Computed Microtomography Studies of in Vivo Implanted Mini-Tl Dosimeters

The need for direct methods of measuring the absorbed dose in vivo increases for systemic radiation therapy, and in more sophisticated methodologies developed for radioimmunotherapy. One method suggested is the use of mini-thermoluminescent dosimeters (TLD). Recent reports indicate a marked loss of signal when the dosimeters are used in vivo. We investigated the exterior surface of the dosimeters with scanning electron microscopy and the interior dosimeter volume with computed microtomography. The results show that the dosimeters initially have crystals uniformly embedded in the teflon matrix, with some of them directly exposed to the environment. After incubation in gel, holes appear in the dosimeter matrix where the crystals should have been. The computed microtomographic images show that crystals remain in the interior of the matrix, producing the remaining signal. We conclude that these dosimeters should be very carefully handled, and for practical use of mini-TLDs in vivo the dosimeters should be calibrated in equivalent milieus. An alternative solution to the problem of decreased TL efficiency, would be to coat the dosimeters with a thin layer, of Teflon, or other suitable material.     

Improved long-term bone-implant integration Experiments in transgenic mice overexpressing bovine growth hormone

Several recent studies have investigated the effects of growth hormone (GH) on the healing of fractures and bone ingrowth, but with conflicting results. The negative results may be due to antibody formation against injected GH or because some experimental models are able to prove only positive GH effects. In this study, we wanted to investigate the effect of GH on implant integration in bone. To avoid potential formation of antibodies against injected GH, we used a model with transgenic mice overexpressing bovine GH (bGH).

Titanium implants were inserted in the forehead of the mice. 4 months after insertion, the implants were cut out en bloc with the surrounding bone. The calcified specimens were cut and ground to a thickness of approximately 10m. Histomorphometry demonstrated significantly more direct bone-to-metal contact in the transgenic mice than in the nontransgenic littermates. Our findings indicate that systemic administration of GH in humans may improve implant integration in bone.     

Sex-specific effects for body mass index in the new Norwegian twin panel

Sex-specific effects for body mass index (BMI) were explored in a newly established, population-based Norwegian twin panel. The sample includes 5,864 individuals, aged 18–25 years, who responded to a questionnaire containing items for zygosity classification, height, weight, health, health-related behaviors, well-being, and demographic information. Among the 2,570 intact pairs who returned the questionnaire there were 416 identical (MZ) male pairs, 387 fraternal (DZ) male pairs, 528 MZ female pairs, 443 DZ female pairs, and 796 unlike-sexed pairs. Alternate sets of models testing for either sex-specific genetic or environmental parameters were evaluated using structural equation analysis. Results from the most parsimonious model indicated that the genes contributing to variation in BMI are not identical for men and women; rather, some genetic effects were shared by the sexes and some were unique to each sex. Total variation in BMI could be explained by sex-specific additive genetic effects, as well as genetic and non-shared environmental effects common to men and women. Estimates of heritability were .708 for men and .789 for women, and the male-female genetic correlation was 0.622. The series of models specifying sex-specific shared environment also fit the data and suggests that shared environmental factors may be important for males but not for females. The findings raise questions concerning the relationship between sex-specific effects for BMI and sex differences in health outcomes. ©1995 Wiley-Liss, Inc.     

Receptor binding of N-(methyl-11C) clozapine in the brain of rhesus monkey studied by positron emission tomography (PET)

By means of positron emission tomography the uptake and kinetics of N-(methyl-¹¹C)clozapine in different brain regions have been studied in Rhesus monkeys. ¹¹C-clozapine rapidly entered the brain and maximum radioactive uptake was seen 5–12 min after administration. Highest uptake was measured in the striatum. Other regions with an uptake higher than in the cerebellum were thalamus and mesencephalon. The radioactivity from different brain regions decreased with an elimination half-life of about 5 h and parallelled the plasma kinetics of unlabelled clozapine. The striatum/cerebellum ratio of ¹¹C-clozapine-derived radioactivity remained constant during the period studied and did not change after pretreatment with atropine. In contrast, the striatum/cerebellum ratio was somewhat lower after pretreatment with N-methylspiperone (NMSP), indicating competition for the same binding sites in the striatum. After pretreatment with increasing doses of clozapine, a dose-dependent protection of binding sites in the striatum for ¹¹C-NMSP was seen. It is concluded that clozapine is more loosely bound to dopamine receptors in the striatum than N-methylspiperone and that the kinetics of clozapine in the brain parallel that in the plasma. The binding properties of clozapine within the brain may explain some of the clinical properties of the drug.