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.     

Sequence capture-PCR improves detection of mycobacterial DNA in clinical specimens

The rapid identification of mycobacterial DNA in clinical samples by PCR can be useful in the diagnosis of tuberculous infections, but several large studies have found that the sensitivity of this approach is not better than that of culture. In order to improve the sensitivity of detection of mycobacterial DNA in clinical specimens from patients with paucibacillary forms of tuberculosis, we have developed a procedure permitting the specific capture of mycobacterial DNA in crude samples prior to amplification, thereby concentrating the target sequences and removing irrelevant DNA and other potential inhibitors of the amplification reaction (sequence capture-PCR). By using this approach to capture and amplify two different sequences specific for organisms of the Mycobacterium tuberculosis complex (IS6110 and the direct repeat region), it was possible to detect as little as one genome of mycobacterial DNA in samples containing up to 750 micrograms of total DNA, representing a 10- to 100-fold increase in sensitivity compared with that obtained by purifying total DNA prior to amplification. Detection of the IS6110 sequence in pleural fluid samples from patients with tuberculous pleurisy by sequence capture-PCR gave positive results in 13 of 17 cases, including 3 of 3 culture-positive samples and 10 of 14 culture-negative samples. In contrast, when total DNA was purified from these samples by adsorption to a silica matrix prior to amplification, only the three culture-positive samples were positive by PCR. The sensitivity of detection of the direct repeat sequence in these samples by sequence capture-PCR was similar to that of IS6110 and, in addition, permitted immediate typing of the strains from some patients. We conclude that sequence capture-PCR improves the sensitivity of detection of mycobacterial DNA in paucibacillary samples. This approach should be useful in detecting rare target sequences from organisms implicated in other pathologic processes.     

Direct and indirect assessment of skeletal muscle blood flow in patients with congestive heart failure

Techniques which are currently used to measure skeletal muscle blood flow (SMBF) in patients with congestive heart failure (CHF) are neither convenient nor accurate. They have led to discrepant results in patients with congestive heart failure and are, in part, responsible for the ongoing debate regarding the factors which limit the rise in body oxygen consumption during exercise in these patients. However, direct measurement of SMBF may not be needed during exercise in patients with severe CHF. Their skeletal muscles maximally extract oxygen. Consequently, increase in oxygen consumption by the skeletal muscles is only mediated by a concomitant increase in SMBF. In patients with severe CHF, peak body oxygen consumption attained during maximal exercise closely depends on the rise in SMBF, and thus provides an indirect measurement of SMBF.     

New concept for applying edge line phase-shifting masks to arbitrary mask layouts

This paper explains the principle of a method which avoids printing of phantom resist lines due to undesired intensity minima appearing on Cr-less edge line phase-shifting masks. The method combines principles of grey-tone lithography and attenuated phase-shifting masks to give, what we call, a Cr-Less Attenuated Phase-shifting mask (CLAP). Rules for generating a CLAP design and a paradigm setup of a CLAP mask are presented. The capabilities and possible limitations of the CLAP method based on simulated results for a standard wafer stepper setup using the SOLID lithography simulator are being assessed.     

Tenascin-C and the development of articular cartilage

In comparison to the vast literature on articular cartilage structure and function, relatively little is known about how articular cartilage forms during embryogenesis and is endowed with unique phenotypic properties, most notably the ability to persist and function throughout postnatal life. In this minireview, we summarize recent studies from our laboratory suggesting that the extracellular matrix protein tenascin-C is involved in the genesis and function of articular chondrocytes. These and other data have led us to propose that tenascin-C may be part of in vivo mechanisms whereby articular chondrocytes develop at the epiphysis of long bone models, remain functional throughout postnatal life, and avoid the endochondral ossification process undertaken by the bulk of chondrocytes located in the metaphysis and diaphysis of skeletal models.     

The effects of growth hormone in children with a GH deficiency: a report of 5 cases

The authors describe 5 cases, 3 boys and 2 girls, with idiopathic growth hormone deficiency in prepubertal age, treated with human growth hormone. In four of five cases the response to treatment with GH was relevant. Only in one case (F1) the response was negative. The results of this study confirm that rhGH is a safe and effective therapy in children with GHD.     

Diffusion bonding of ferritic oxide dispersion strengthened alloys to austenitic superalloys

The superior high temperature mechanical strength and oxidation resistance of ferritic oxide dispersion strengthened (ODS) tubular alloys are compromised by the difficulties encountered in joining. Conventional fusion welding techniques generate a weld fusion zone which is devoid of the mechanical strength exhibited by the base material. Therefore, more sophisticated solid state joining techniques, such as diffusion bonding, must be employed when joining ODS materials. This paper describes a series of solid state diffusion bonding experiments carried out between two tubular ferritic ODS alloys and two high temperature austenitic alloys. Careful control of bonding conditions produced pressure retaining joints between one of the tubular ODS alloys and both austenitic alloys. The successful joint design was incorporated into the manufacture of a tubular creep component, which enabled a series of internally pressurized creep tests to be carried out. The microstructure developed at the bond interface of each of the four separate material couples is described and the high temperature performance of the pressure retaining joints is discussed.     

Interpolated smoothed pseudo Wigner-Ville distribution for accuratespectrum analysis

This paper deals with a new application of the time-domain windowed (smoothed version) of the pseudo Wigner-Ville distribution (PWD), that can be easily implemented in a dedicate digital instrument to be used as a spectral analyzer for time-frequency analysis of nonstationary signals. New computational algorithms are studied and developed to attain high time-frequency resolution, accuracy, flexibility and computational efficiency. Particularly, to reduce the negative effects due to leakage during frequency changes, a new interpolation formula is derived by using the windowing theory. The suggested technique allows the users to perform optimal evaluations of the instantaneous amplitudes and frequencies of analyzed signals     

Behavior of a vibrating wire near the liquid3He-vacuum interface and in a saturated3He-4He mixture

In this paper we describe the effect of the vicinity of a liquid³He-vacuum interface on the behavior of a vibrating wire viscometer. It was found that in the fluid near the liquid interface the quality factor is lower than in the bulk liquid. We further report on the observation of a doubling of the resonance peak of the wire in a saturated³He-⁴He mixture. The frequencies and amplitudes of the two peaks strongly depend on the distance between the phase boundary and the vibrating wire; the temperature and the velocity of the phase boundary have no significant influence on the peak frequencies. The observed peak doubling is attributed to the coupling of the vibrating wire with a standing second-sound wave in the dilute phase where the volume of the dilute phase can be regarded as a resonating cavity for second sound.