Palliative chemotherapy with CMF after the same adjuvant regimen for breast cancer. The Breast Cancer Study Group

BACKGROUND: The results of palliative chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in patients with advanced breast cancer who received adjuvant therapy with the same regimen were investigated. RESULTS: Of 47 patients, 14 (30%) achieved an objective remission (median duration 9.5, range 5-21 months) and 8 (17%) stabilisation of disease (median duration 6, range 3-17 months). Objective remissions were observed in premenopausal as well as in postmenopausal women, in patients with all categories of dominant localisation of disease and regardless of the oestradiol receptor status of the primary tumour or eventual previous endocrine therapy. One of 4 and 13 of 43 patients who started palliative chemotherapy within or later than 12 months after the last adjuvant course obtained an objective remission. The median survival time from start of therapy of all treated patients was 12 (range 1-40) months. Patients with an objective remission or stable disease and patients with progressive disease had a median survival time of 20 (range 6-40) and 6 (range 1-35) months respectively (p < 0.0001). CONCLUSIONS: Palliative treatment with CMF should not be rejected for patients who have relapsed after adjuvant chemotherapy with the same modality.     

Fast order-recursive generalized Hermitian Toeplitz eigenspace decomposition

We present a parallel algorithm which computes recursively, in increasing order, the complete generalized eigendecompositions of the successive subpencils contained in a maximum size Hermitian Toeplitz generalized eigenproblem. At each order a number of independent, structurally identical, nonlinear problems are solved in parallel, facilitating fast implementation. The multiple and clustered minimum eigenvalue cases are treated in detail. In the application of our algorithm to narrowband array processing in colored noise, the direction-of-arrival containing eigenspace information is provided recursively in order. This permits estimation of the angles of arrival for subsequent orders, facilitating early estimation of the number of sources as well as verification of results obtained at previous orders. This research was supported in part by the Center for Innovative Technology Grant No. INF-86-018, Herndon, Virginia, and Unisys Corporation, Grant No. V120483, Reston, Virginia.     

Heterozygosity for a point mutation in an invariant splice donor site of dihydropyrimidine dehydrogenase and severe 5-fluorouracil related toxicity

Dihydropyrimidine dehydrogenase (DPD) is responsible for the breakdown of the widely used antineoplastic agent 5-fluorouracil (5-FU), thereby limiting the efficacy of the therapy. It has been suggested that patients suffering from 5-FU toxicities due to a low activity of DPD are genotypically heterozygous for a mutant allele of the gene encoding DPD. In this study we investigated the cDNA and a genomic region of the DPD gene of a cancer patient experiencing severe toxicity following 5-FU treatment for the presence of mutations. Although normal activity of DPD was observed in fibroblasts, the DPD activity in leucocytes of the cancer patient proved to be in the heterozygous range. Analysis of the DPD cDNA showed heterozygosity for a 165bp deletion that results from exon skipping. Sequence analysis of the genomic region encompassing the skipped exon showed that the tumour patient was heterozygous for a G-->A point mutation in the invariant GT splice donor sequence in the intron downstream of the skipped exon. So far, the G-->A point mutation has also been found in 8 out of 11 patients suffering from a complete deficiency of DPD. Considering the frequent use of 5-FU in the treatment of cancer patients, the severe 5-FU-related toxicities in patients with a low activity of DPD and the high frequency of the G-->A mutation in DPD deficient patients, analysis of the DPD activity and screening for the G-->A mutation should be routinely carried out prior to the start of the treatment with 5-FU.     

Increased use of immunohistochemistry for oestrogen receptor measurement in mammary carcinoma: the need for quality assurance

This paper outlines the changes which have occurred over the last 25 years in the methods employed for the measurement of oestrogen receptors to aid the management of women with breast cancer. Immunohistochemistry is now the method of choice and knowledge of oestrogen receptor status is being used with increasing frequency for the selection of adjuvant treatment as well as for the treatment of metastatic disease. It is essential that good quality assurance procedures are established so that results are reproducible and can be used with confidence in individual centres as well as being comparable with those produced elsewhere. A retrospective study of 170 women with metastatic breast cancer provides the basis for a discussion on the advantages and pitfalls of the immunohistochemical assay. Particular emphasis is paid to the choice of cut-off and how the results may be applied in patient management.     

The effect of pitch tracking on automatic dialect identification

Pitch tracking is one of the most important research topics in the recognition and identification area. This study concerns the effect of the pitch tracking technique used on the accuracy and speed of automatic dialect identification. This effort was carried out using the TIMIT database. The pitch tracking procedures investigated are the Boersma algorithm, the iterative adaptive inverse filtering approach, and the summation of residual harmonics method. All else being equal, the summation of residual harmonics provided the highest accuracy as well as the fastest performance of the three methods.     

Complexes between urokinase-type plasminogen activator and its receptor in blood as determined by enzyme-linked immunosorbent assay

Microvascular endothelial cells actively participate in local regulation of blood flow and blood-tissue exchange by producing various vasoactive substances including nitric oxide (NO). This study examined microcirculatory changes in the early stage of thermal injury and the NO-related mechanisms. Resistance arterioles of rat cremaster muscle were observed using intravital microscopy. Arteriolar diameter and flow velocity were measured and flow rate was calculated after administration of various vasoactive agonists in burns. In fluid-resuscitated rats with stable systemic blood pressure, microvascular caliber and blood flow were not significantly altered in the first hour following a 25% total body surface area full-thickness scald burn. Topical application of acetylcholine (ACh), an endothelium-dependent vasodilator, increased arteriolar diameter and flow rate in a dose-dependent fashion. The dose-responsive effects of ACh were significantly greater in burned rats than in sham-burned rats, and the augmentation was blocked by inhibition of NO production with NG-monomethyl-l-arginine (L-NMMA). Topical application of adenosine, an endothelium-independent vasodilator, and sodium nitroprusside, an exogenous NO donor, markedly increased arteriolar diameter and flow rate. The effects were not significantly different in burned and sham-burned animals, and the adenosine-induced vasodilation was not blocked by L-NMMA. These data suggest that endothelium-dependent and NO-mediated arteriolar dilation is enhanced in the early stage of thermal injury. This effect may play an important role in the pathophysiological events of microcirculation and blood-tissue exchange in burns.     

Numbness of the chin, sometimes an ominous sign

Delirium was demonstrated after cataract surgery in a 64-year-old man (case 1). The patient struck his head against the floor; thereafter an extradural hematoma was found and extracted. Postoperative delirium was also noted in a 58-year-old woman (case 2) and in a 26-year-old woman (case 3) with rhegmatogenous retinal detachment. All 3 patients recovered from their psychiatric complications within 1 month.     

A quasicontinuum methodology for multiscale analyses of discrete microstructural models

Many studies in different research fields use lattice models to investigate the mechanical behavior of materials. Full lattice calculations are often performed to determine the influence of localized microscale phenomena on large‐scale responses but they are usually computationally expensive. In this study the quasicontinuum (QC) method (Phil. Mag. A 1996; 73 :1529–1563) is extended towards lattice models that employ discrete elements, such as trusses and beams. The QC method is a multiscale approach that uses a triangulation to interpolate the lattice model in regions with small fluctuations in the deformation field, while in regions of high interest the exact lattice model is obtained by refining the triangulation to the internal spacing of the lattice. Interpolation ensures that the number of unknowns is reduced while summation ensures that only a selective part of the underlying lattice model must be visited to construct the governing equations. As the QC method has so far only been applied to atomic lattice models, the existing summation procedures have been revisited for structural lattice models containing discrete elements. This has led to a new QC method that makes use of the characteristic structure of the considered truss network. The proposed QC method is, to the best of the authors' knowledge, the only QC method that does not need any correction at the interface between the interpolated and the fully resolved region and at the same time gives exact results unlike the cluster QC methods. In its present formulation, the proposed QC method can only be used for lattice models containing nearest neighbor interactions, but with some minor adaptations it can also be used for lattices with next‐nearest neighbor interactions such as atomic lattices. Copyright © 2011 John Wiley & Sons, Ltd.