High-dose busulfan, melphalan, thiotepa and peripheral blood stem cell infusion for the treatment of metastatic breast cancer

The purpose of this study was to determine the outcome of patients with metastatic breast cancer treated with high-dose busulfan (Bu), melphalan (Mel) and thiotepa (TT) followed by peripheral blood stem cell (PBSC) infusion. Fifty-one patients with chemotherapy refractory (n = 32) or responsive (n = 19) metastatic breast cancer received Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC collected after chemotherapy and growth factor (n = 43) or growth factor alone (n = 8). The 100 day treatment-related mortality was 8% including one death from cytomegalovirus pneumonia, one from aspiration pneumonia and two from regimen-related toxicity (RRT). Seven of 28 refractory (25%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft tissue disease with at least improvement in bone lesions (PR*). Fifteen of 51 patients (29%) are alive and progression-free a median of 423 days (range 353-934) after treatment, 5/32 (16%) with refractory disease and 10/19 (53%) with responsive disease. The probabilities of progression-free survival (PFS) at 1.5 years for the patients with refractory (n = 32) and responsive (n = 19) disease were 0.24 and 0.53, respectively. These preliminary data suggest that high-dose Bu/Mel/TT has significant activity in patients with advanced breast cancer and may be superior to some previously published regimens.     

Epitope specificity of CD44 for monoclonal antibody-dependent facilitation of marrow engraftment in a canine model

Primary graft rejection after marrow transplantation occurs more frequently in patients receiving HLA-haploidentical compared with HLA-identical sibling transplants. Both human and experimental animal data suggest that the cells responsible for this phenomenon are either host natural killer (NK) cells, T cells, or both. To investigate the mechanisms of graft rejection, we have developed a canine model of marrow transplantation, which uses DLA-nonidentical unrelated donors in the absence of postgrafting immunosuppression. In this model most animals rejected their marrow grafts after a preparative regimen of 9.2 Gy total body irradiation (TBI). However, engraftment of DLA-nonidentical marrow can be facilitated when the recipients are pretreated with monoclonal antibody (MoAb) S5, which recognizes CD44. In this report, we extended these observations by first cloning the canine CD44 and, next, mapping the epitope recognized by S5, which was located in a region conserved among human and canine CD44 and was distinct from the hyaluronan binding domain. However, in vitro binding of S5 caused a conformational change in CD44, which allowed increased hyaluronan binding. Then, we reexamined the in vivo model of marrow transplantation and compared results with MoAb S5 to those with two other anti-CD44 MoAbs, IM7 and S3. Only MoAb S5 significantly increased the engraftment rate of DLA-nonidentical unrelated marrow, whereas the two other anti-CD44 MoAbs were ineffective. The enhanced in vivo effect was not related to differences in the MoAbs' avidities, since both S5 and IM7 had equivalent binding to CD44, but most likely related to the specific epitope that S5 recognizes. Thus, this study shows that the effect of the anti-CD44 MoAb S5 in facilitating engraftment is epitope specific and if one is to use an anti-CD44 to facilitate engraftment of marrow in humans, one cannot assume that any anti-CD44 would work.     

Two studies of the long-term follow-up of minimal therapist contact treatments of vascular and tension headache.

Tension and vascular headache patients, initially treated with biofeedback and/or relaxation training in either a minimal therapist contact protocol (3 visits) or an intensive individual protocol (10 or 16 visits) were followed-up prospectively for 2 years. In the first study, for the first 6 months of follow-up, half of all patients continued to keep headache diaries and were seen monthly and the other half had only minimal contact. The results at 1-year follow-up, based on 4 weeks of daily headache diaries, revealed equally good maintenance from both treatment protocols and from both follow-up conditions. In Study 2, we found that patients remained improved over pretreatment baseline levels at the 2-year follow-up regardless of initial treatment intensity. Approximately three quarters of vascular patients who were initially improved at posttreatment remained improved at 2 years. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Antipneumococcal activities of levofloxacin and clarithromycin as determined by agar dilution, microdilution, E-test, and disk diffusion methodologies

The activities of levofloxacin and clarithromycin against 199 penicillin- and macrolide-susceptible and -resistant pneumococci were tested by agar and microdilution methods in air and by disk diffusion and E-test methods in air and CO2. For levofloxacin, >/=99. 0% of strains were susceptible at /=17 mm, regardless of incubation in air or CO2. Although zone sizes were smaller and E-test MICs were higher for clarithromycin in CO2 than those in air, category differences were minor, and susceptibility rates for clarithromycin were similar to those obtained by agar and microdilution in air (range, 76.9 to 80.9% by all methods). For clarithromycin, adjustment of breakpoints based upon distribution of results resulted in susceptibility rates which were similar by all methods (75.8 to 76.9% susceptible, 0 to 1.5% intermediate, 22.6 to 23.1% resistant). Minor discrepancies were obtained with levofloxacin for one strain (0.5%) by microdilution and two strains (1.0%) by disk diffusion in CO2. For clarithromycin, minor discrepancies were found in three strains (1.5%) by microdilution, seven strains (3.5%) by agar dilution, four strains (2.0%) by E-test in air, six strains (3.0%) by disk diffusion in air, and five strains (2.5%) by disk diffusion in CO2. Major discrepancies occurred with levofloxacin in one strain (0.5%) by microdilution but were not found with clarithromycin. Very major discrepancies were not seen with levofloxacin, but occurred with clarithromycin in five strains (2.5%) by microdilution, three strains (1.5%) by agar dilution, two strains (1.0%) by E-test in air, eight strains (4.0%) by disk diffusion in air, and one strain (0.5%) by disk diffusion in CO2.     

Parameter estimation and screening of solar cells

The aggregation (sorting) of the individual solar cells into an array is commonly based on a single operating point on the current-voltage (I-V) characteristic curve. an alternative approach for cell performance prediction and cell screening is provided by modelling the cell using an equivalent electrical circuit, in which the parameters involved are related to the physical phenomena in the device. These analytical models may be represented by a double exponential I-V characteristic with seven parameters, by a double exponential model with five parameters or by a single exponential equation with four or five parameters. In this article we address issues concerning methodologies for the determination of solar cell parameters based on measured data points of the I-V characteristic, and introduce a procedure for screening solar cells for arrays. We show that common curve-fitting techniques, e.g. least-squares, may produce many combinations of parameter values while maintaining a good fit between the fitted and measured I-V characteristics of the cell. Therefore, techniques relying on curve-fitting criteria alone cannot be used directly for cell parameterization. We propose a consistent procedure that takes into account the entire set of parameter values for a batch of cells. This procedure is based on a definition of a mean cell representing the batch, and takes into account the relative contribution of each parameter to the overall goodness of fit. the procedure is demonstrated on a batch of 50 silicon cells for Space Station Freedom.     

Analyse einer Regelungsschaltung für Wechselstromspannungen mittels Steller

Übersicht Es wird eine neue Regelungsmethode der Spannung am Wechselstromverbraucher vorgestellt und analysiert. Diese Methode ist der in den Gleichstromkreisen verwendeten Methode ähnlich, mit dem Vorteil, daß dank der geringen Blindleistungszirkulation, der Leistungsfaktor der Anlage höher ist als derjenige in den klassischen Regelkreisen. Die mathematische Analyse wurde mit einem Digitalrechner durchgeführt.

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Contents The paper describes and analyses a novel regulation technique for alternating voltages, similar to those applied in d. c. circuits, but with a higher power factor than in conventional regulating circuits, owing to the negligible circulation of the reactive power. The mathematical calculation was carried out on a digital computer.

     

Validation of language subtypes in learning disabled children.

Hypothesized that children characterized by deficits in narrative skills, relative to other language skills (e.g., syntactic and semantic), would be most at risk for general academic problems, especially in reading comprehension. Using data from a previous longitudinal study by the 1st author and J. D. McKinney (see record 1985-02522-001), different subtypes of language disability were identified in 63 6- and 7-yr-old learning disabled (LD) children. Comparison data had been obtained from 66 non-LD children matched to the LD sample on age, race, and sex. Results, obtained with hierarchical cluster analysis, indicate that 6 language subtypes were derived and that these were both internally consistent and externally valid, being differentially linked to reading and math achievement over a 3-yr period. Narrative ability was shown to be relatively important in predicting academic outcomes. The 3 subtypes showing the poorest academic outcomes had the highest relative scores in syntax and semantics. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pharmacokinetics of cyclophosphamide and its metabolites in bone marrow transplantation patients

Classical swine fever virus infection of pigs causes a severe leukopenia and immunosuppression. In the present study, the kinetics of virus infection, and identification of target cells for the virus in peripheral blood were analysed. Virus infection was often not detectable before 5-7 days p.i. A minority of animals yielded detectable infected cells at 3 days p.i., but < 5% PBMC. It was not until 10 days p.i. that this figure increased-to 35-70% PBMC depending on the animal. Detailed analysis of Ficoll-Hypaque-purified PBMC identified the major population to be SWC3+SWC8+CD14+MHCII- granulocytic cells. Microscopic observations determined that these low density granulocytic cells in the PBMC from CSFV infected animals were indeed immature cells. Both the low density granulocytic cells and monocytes were major targets for CSFV infection in the peripheral blood. This is the first demonstration that low density granulocytic cells dominate the blood leukocyte population during CSF, and that such cells are targets for virus infection. The present work also demonstrates that the leukocyte population changes, such as B lymphocyte depletion and the relative dominance of myeloid cells in the blood during CSF, occur before virus infection of the affected cells. Thus, the pathological mechanism therein is not a direct consequence of virus infection.     

Prevalence of antimicrobial-resistant pathogens in middle ear fluid: multinational study of 917 children with acute otitis media

The management of acute otitis media is complicated by the emergence of resistance to beta-lactam and other antibiotics among common pathogens. We conducted a large, international study of infants and children with acute otitis media to identify pathogens and susceptibility patterns. During the winter of 1994 to 1995, middle ear fluid samples were collected from 917 patients with acute otitis media in Bulgaria, the Czech Republic, Hungary, Romania, Slovakia, Israel, and the United States. A single reference laboratory performed in vitro susceptibility testing. Pathogens were isolated from 62% of the patients. For Streptococcus pneumoniae (30% of the patients), untypeable Haemophilus influenzae (17%), and Moraxella catarrhalis (4%), there was significant variation among geographic regions (P < 0.001). The composite susceptibilities of these three organisms to amoxicillin ranged from 62% in the United States to 89% in Eastern and Central Europe; the corresponding susceptibilities to amoxicillin-clavulanate ranged from 90% in Israel to 95% in Eastern and Central Europe. beta-Lactamase was produced by 31 and 100% of the isolates of H. influenzae and M. catarrhalis, respectively. More isolates of S. pneumoniae were susceptible to amoxicillin (90%) or amoxicillin-clavulanate (90%) than to penicillin (70%; P = 0.002). The prevalence of resistant S. pneumoniae was highest in patients less than 12 months of age. S. pneumoniae, H. influenzae, and M. catarrhalis remain the most important bacterial pathogens in patients with acute otitis media; however, their prevalence is variable and resistance patterns are changing.