Long-term follow-up of a randomized post-induction therapy trial in acute myelogenous leukemia (a Southeastern Cancer Study Group trial)

A phase III clinical trial was designed to determine if more intensive induction and consolidation therapy for acute myeloblastic leukemia increases the remission rate and prolongs survival. A minor objective was to determine if the use of non-cross resistant drugs was more effective than the same drugs used for induction. Patients with untreated leukemia between the ages of 15 and 50 were given daunorubicin 45 mg/m2 for the first 3 days of a 10-day continuous infusion of cytosine arabinoside, initially at a dose of 2000 mg/m2 but reduced to 100 mg/m2 because of toxicity. Those under 36 achieving a complete remission and with an histocompatible donor were assigned to a transplant arm. The rest were randomized to receive one of three consolidation arms: A, cytosine arabinoside, 200 mg/m2 daily for 7 days and daunorubicin 45 mg/m2 daily for 3 days for three courses; B, one course as in Arm A followed by amsacrine, 120 mg/m2 daily for 5 days followed by a 5-day continuous infusion of azacytidine, 150 mg/m2/day; C, thioguanine and cytosine arabinoside, 100 mg/m2 every 12 h and daunorubicin 10 mg/m2 daily for 5 days for three courses followed by four maintenance courses of cytosine arabinoside, 100 mg/m2 daily for 5 days and daunorubicin, 45 mg/m2 for 2 days every 13 weeks. From 1981 to 1986, 398 eligible patients were enrolled and 219 achieved a complete remission. The initial induction dose of cytosine arabinoside was reduced after five of 29 patients exhibited fatal gastrointestinal toxicity. Only 11 patients were assigned to the transplant arm. There were no significant differences in the consolidation arms. The 5 year disease-free survivals were 38, 31 and 27% in arms A, B, and C respectively. Intensive consolidation therapy with the same or different drugs used in induction was as effective as lower dose consolidation followed by maintenance therapy.     

A comparison between different PMD compensation techniques

We quantify the benefits of using different techniques for compensation of polarization mode dispersion (PMD) in fiber-optic communication systems by means of numerical simulations. This is done both with respect to PMD-induced pulse broadening and in terms of system outage probability for different data formats [nonreturn-to-zero (NRZ) and return-to-zero (RZ)]. Attention is focused on simple and relevant single- and double-stage post-transmission compensators with a few degrees of freedom (DOF). It is generally believed that a PMD compensator with a polarization controller and a variable delay line can only compensate the PMD to the first order. We show, from analytical results, the counterintuitive fact that this scheme can also partially compensate for higher order PMD. We also investigate the benefit of using a polarizer as compensation element where the optical average power can be used as a feedback signal     

Tensile,creep, and low-cycle fatigue behavior of a cast γ-TiAl-based alloy for gas turbine applications

The influence of chemical composition on the microstructure of the γ-titanium aluminide alloy Ti-48Al-2W-0.5Si (at. pct) and the accompanying tensile, low-cycle fatigue, and creep properties has been evaluated. The study showed that small variations in chemical composition and casting procedures resulted in considerable variations in the microstructure, yielding vastly different mechanical properties. Low contents of aluminum and tungsten led to a coarse-grained lamellar (γ/α ₂) microstructure with high creep resistance. A composition close to the nominal one produced a duplex (γ+γ/α ₂) structure with favorable strength, ductility, and low-cycle fatigue properties. By controlling the solidification and cooling rates at casting, a pseudoduplex (PS-DP) microstructure with a unique combination of high strength and high fatigue and creep resistance can be obtained. These unique properties can be explained by the diffuse boundaries between the relatively small γ grains and the neighboring lamellar colonies, combined with semicoherent interfaces between the γ and α ₂ phases. At tensile and low-cycle fatigue loading, these boundaries act like high-angle boundaries, producing a virtually fine-grained material promoting strength, whereas at creep loading, grain-boundary sliding is hindered in the semicoherent interfaces leading to high creep resistance.     

Optimization of metal-based multilayers for transparent heat mirrors

Multilayer calculations by conventional matrix methods for dielectricum/noble metal/dielectricum systems on glass have been performed. The aim has been to maximize the integrated parameters for solar transmission, T_sol, and transmission of visible light, T_eye We have found that Ag is superior for maximizing the transmittance over the narrow visible wavelength range owing to the low internal absorptance. When solar energy transmission is considered multilayers based on Au are the best choice for metal film thicknesses above 15 nm. For thinner films, Ag is still to be preferred.     

Association between oxygen delivery and consumption in patients undergoing cardiac surgery. Is there supply dependence?

Numerous investigators have suggested that cell glycoconjugates are modified by the development of cancer and the progression of this to a malignant form. Accordingly, in the present work, beta-D-galactosidase, alpha-L-fucosidase, beta-N-acetyl-D-glucosaminidase and beta-N-acetyl-D-galactosaminidase activities were studied in human thyroid and gastric tumours. Samples were obtained from human gastric mucosa and thyroid gland tumours together with a part of the surrounding normal tissue (control). Enzyme activity was determined spectrophotometrically based on the release of p-nitrophenol from suitable p-nitrophenyl-derivative substrates. Results showed that beta-D-galactosidase, alpha-L-fucosidase, beta-N-acetyl-D-glucosaminidase and beta-N-acetyl-D-galactosaminidase activities were detected in tumour and control samples from thyroid and gastric tissues. The gastric mucosa also showed alpha-L-mannosidase activity. The specific activities of these glycosidases were higher (two- or three-fold) in tumour tissues as compared with their controls. beta-D-galactosidase, beta-N-acetyl-D-glucosaminidase and beta-N-acetyl-D-galactosaminidase activities from thyroid and gastric tumours showed a significant increase in V(max) as compared with their respective controls (P < 0.05 or P < 0.001). Thyroid alpha-L-fucosidase activity showed a statistically and significantly increased affinity (lower K(m)) in tumour samples as compared to normal tissue. In conclusion both gastric and thyroid tumours showed enhanced glycosidase activity as compared with enzyme activity observed in normal tissue. These results are in agreement with the notion of a markedly raised degradation within lysosomes of tumour cells.     

Effects of quinine on the mechanical frequency response of the cupula in the fish lateral line

Quinine induces changes in the motion of the cupula in the lateral line canal of the African knife-fish in response to sinusoidal water movements. Two different phases in the action of quinine on the cupular frequency response can be discerned. In the first phase the best frequency, i.e., the frequency at which the cupular vibratory displacement is maximal in response to constant-amplitude sinusoidal canal fluid displacement, shifts toward higher frequencies. During this phase, lasting about 70-100 min, the best frequency increases by a factor between 1.3 and 1.5. In the second phase, during roughly the following 90 min, the best frequency decreases gradually to a value 0.3-0.5 times that observed before the application of quinine.     

Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B

BACKGROUND: About 65 percent of previously untreated adults with primary acute myeloid leukemia (AML) enter complete remission when treated with cytarabine and an anthracycline. However, such responses are rarely durable when conventional postremission therapy is administered. Uncontrolled trials have suggested that intensive postremission therapy may prolong these complete remissions. METHODS: We treated 1088 adults with newly diagnosed AML with three days of daunorubicin and seven days of cytarabine and randomly assigned patients who had a complete remission to receive four courses of cytarabine at one of three doses: 100 mg per square meter of body-surface area per day for five days by continuous infusion, 400 mg per square meter per day for five days by continuous infusion, or 3 g per square meter in a 3-hour infusion every 12 hours (twice daily) on days 1, 3, and 5. All patients then received four courses of monthly maintenance treatment. RESULTS: Of the 693 patients who had a complete remission, 596 were randomly assigned to receive postremission cytarabine. After a median follow-up of 52 months, the disease-free survival rates in the three treatment groups were significantly different (P = 0.003). Relative to the 100-mg group, the hazard ratios were 0.67 for the 3-g group (95 percent confidence interval, 0.53 to 0.86) and 0.75 for the 400-mg group (95 percent confidence interval, 0.60 to 0.94). The probability of remaining in continuous complete remission after four years for patients 60 years of age or younger was 24 percent in the 100-mg group, 29 percent in the 400-mg group, and 44 percent in the 3-g group (P = 0.002). In contrast, for patients older than 60, the probability of remaining disease-free after four years was 16 percent or less in each of the three postremission cytarabine groups. CONCLUSIONS: These data support the concept of a dose-response effect for cytarabine in patients with AML who are 60 years of age or younger. The results with the high-dose schedule in this age group are comparable to those reported in similar patients who have undergone allogeneic bone marrow transplantation during a first remission.