The aim of this study was to determine the activity of anthracycline rechallenge using pegylated liposomal doxorubicin (PLD) in patients with metastatic breast cancer (MBC) previously treated with ...conventional anthracyclines.
Pooled individual data from four prospective trials were used, and the primary end point of the pooled analysis was clinical benefit rate (CBR). The studies comprised 935 patients, of whom 274 had received PLD in the metastatic setting after prior exposure to conventional anthracyclines (rechallenge population).
The majority of patients were heavily pretreated. Previous anthracycline therapy was administered in the adjuvant (14%) or metastatic setting (46%), or both (40%). The overall CBR from rechallenge with PLD was 37.2% (95% CI, 32.4-42.0). In univariate analyses, the CBR was significantly higher in patients with less exposure to prior chemotherapy, in taxane-naive patients, and in patients with a favourable Eastern Cooperative Group performance status of 0 vs 1 vs 2 (53.3 vs 35.5 vs 18.2%; P<0.001). In multivariate analyses, performance status proved to be the only independent predictor of the CBR achieved with PLD rechallenge (P=0.038). There was no statistically significant difference in CBR regarding the setting, cumulative dose of and/or resistance to prior anthracyclines, or time since prior anthracycline administration.
Anthracycline rechallenge using PLD is effective in patients with MBC who have a favourable performance status, regardless of setting, resistance, cumulative dose or time since prior conventional anthracycline therapy.
The central complex is a brain specific structure involved in multimodal information processing and in coordinating motor behaviour. It possesses a highly organized neuroarchitecture, which is ...remarkably conserved across insect species. A prominent feature of this neuroarchitecture is the stereotypic projection of axons from clusters of neurons in the pars intercerebralis to the central body via the so-called w, x, y and z tracts. Despite extensive analyses of this neuroarchitecture in adults, little is known about its ontogeny in any insect. In this paper we use the expression pattern of the segment polarity gene
engrailed to identify those neuroblasts belonging to the protocerebrum of the early embryonic brain of the grasshopper
Schistocerca gregaria. We present a new map for this brain region in which the 95 protocerebral neuroblasts in each hemisphere are organized into seven rows, as they are in the neuromeres of the ventral nerve cord. We then identify a subset of four of these neuroblasts as being the progenitor cells for four clusters of neurons, some of whose axons we show project via discrete tracts (w, x, y, z) into the central complex. These tracts begin to form prior to 39% of embryogenesis. We show further, that the cells from one of these clusters (the Z cluster) are organized according to age, and direct axons topologically according to age into the appropriate z tract. This pattern is repeated in each of the other three clusters, thus establishing a clonally based modular system of fibre tracts consistent with the model proposed for this brain region in the adult.
Zusammenfassung
Hintergrund
Die Harnsteine, die als Votivgaben zur Wallfahrtskirche Grafrath gebracht wurden, bieten durch die Möglichkeit der Komponentenanalyse durch Infrarotspektroskopie Einblicke ...über die Harnsteinzusammensetzung der damaligen Harnsteinträger zu gewinnen. Es wurden 166 Proben an 139 Objekten (davon 5 Knochen, 4 Gipssteine), bei größeren Steinen z. T. in mehreren Schichten, abgenommen.
Material und Methode
Bei 127 Harnsteinen wurden typische Harnsteinspektren gefunden und wurden einer Gruppe von 98 zugesandten Steinproben (77 männlich, 21 weiblich) aus den Jahren 2007/2008 gegenüber gestellt.
Ergebnisse
Das prozentuale Vorkommen von Ammoniumhydrogenurat (NH
4
U) war mit 68,0% in Grafrath deutlich höher als in der Kontrollgruppe 2007/2008 (1,0%), während das der Harnsäure sich nur wenig unterschied. Die Oxalate Whewellit (Whe) und Weddelit (Wed) waren damals deutlich seltener (Whe 18,1%–69,4%, Wed 7,9%–26,5%). Die Phosphate unterschieden sich in ihrer Zusammensetzung zu Gunsten von Brushit bei den alten Harnsteinen.Der hohe NH
4
U-Gehalt der Harnsteine von Grafrath ist vergleichbar mit den NH
4
U-Komponenten der Sammlung aus Norwich vor 1900 und der Harnsteine aus endemischen Harnsteingebieten unterentwickelter Länder, wie Nordost-Thailand. Angaben über Alter, Geschlecht und Art des Abgangs finden sich in Grafrath nur indirekt durch die dort vorliegenden Mirakelbücher (1444–1728) mit 12.131 Eintragungen der Gebetserhörungen, davon 1165=8,6% mit urologischen Leiden. Über 70% der Harnsteinkranken waren Kinder, z. T schon vor dem 2. Lebensjahr.
Schlussfolgerung
Grafrath mit dem Einzugsgebieten Oberbayern, Schwaben kann anhand der hohen NH
4
U-Komponenten als ein endemisches Blasensteingebiet angesehen werden, mit häufigem Auftreten im frühen Kindesalter. Frühe Mehlbreibeikost, mangelndes Stillen und relativer Eiweißmangel könnten eine Ursache sein.
In Germany, many processing, modeling and interpreting methodologies for studying the earth's magnetic and gravity fields were developed under a specific program using satellites. This book presents ...results of studies in that program from 2005-2008.
Three cases of male infants with hypoplasia and aplasia of the right lung and dextrocardia are reported. The infants developed increasing obstructive respiratory distress in the first 4 months of ...life. In all three cases, there was an opaque right hemithorax with overinflation of the left lung, a posterior deviation of the trachea with pulsatile stenosis, and a posteriorly located aortic arch. Hypoplasia (two cases) or aplasia (one case) of the right pulmonary artery and an absence or a remnant of the right main bronchus were also observed. Associated malformations were esophageal atresia with an abnormal high pouch of the proximal esophagus in case 1, and hypertelorismus syndrome in case 2. Because of severe respiratory distress in all three patients, an aortopexy was performed at the ages of 5 months (one infant) and 10 months (two infants). The obstructive respiratory signs disappeared postoperatively in the following weeks. It has been observed that tracheal stenosis in aplasia or hypoplasia of the right lung may be caused by the dislocated aortic arch. An aortopexy can release the airway compression in such cases. Because of associated malformations, a careful evaluation of the airway and vessels is recommended.
Background: A recent magnetic resonance imaging (MRI) stratification algorithm based on three monthly sequential MRIs classifies multiple sclerosis (MS) patients into four `MRI phenotypes' based on ...the presence or absence of central nervous system inflammation and the presence or absence of focal and/or general tissue damage. Objective: To assess whether the MRI-based stratification algorithm can be adapted to a setting in which imaging resources are limited. Methods: We performed a meta-analysis with clinical trial placebo patients included in the Sylvia Lawry Centre database. 141 patients with three monthly sequential MRIs were available for this study. The stratification into low ( less than or equal to 1 Gd-lesion/month) and high inflammatory (>1 Gd-lesion/month) based on three MRIs was taken as gold standard and compared with stratification algorithms with limited imaging resources. Accuracy measures were compared among the stratification algorithms and put into relation to costs of MRIs. Results: The misclassification rate for a stratification into high or low inflammation based on two MRIs was 5.7% in comparison with the defined gold standard. Further reduction of imaging resources to a single scan results in misclassification rates ranging from 10.6% to 18.4%. All stratification algorithms were conservative and misclassification rates were lower in secondary progressive MS (SPMS) patients. Costs are reduced by more than 55% when (1) only one scan was performed in patients with SPMS and (2) a second scan was performed in relapsing-remitting MS patients with high inflammation in the first scan. The misclassification rate of the new adaptive design was 8.46%. Conclusions: As imaging resources are limited an adaptive design for the performance of MRIs provides a trade-off between classification accuracy into high and low inflammatory and imaging costs, yielding an improved cost-benefit ratio. The proposed adaptive design can be applied to enhance clinical trial designs and to provide evidence-based decision support to improve all aspects of patient care from prognostic estimates to treatment individualization.
Deformability of red blood cells (RBC) is an important determinant of microcirculation, of oxygen transport and release to the tissues, and of RBC life span. Deformability of RBC from five fetuses, ...20 preterm infants, 20 term neonates, and 20 adults was determined by direct microscopic observation of RBC subjected to shear stresses of 6 to 85 dyn/cm2 using a counter-rotating rheoscope. There was no significant difference in deformability among RBC from the fetuses, the preterm and term neonates, and the adults at any shear stress. More than 95% of fetal, neonatal, and adult RBC were capable of tank-tread motion. Compared to adults, the frequency distribution of RBC deformability was slightly broader in the fetuses and neonates because of the presence of more highly and poorly deformable RBC. The increased number of rigid RBC may contribute to the shortened life span of fetal RBC.
In this paper, we propose an ontogeny for previously identified cells from the median domain in the midline of the embryonic brain of the grasshopper
Schistocerca gregaria. The so-called lateral ...cells (LCs) are characteristically located laterally within the median domain at its border with the protocerebral hemispheres. The LC occurs singly and can be identified in the early embryo on the basis of their expression of the cell surface lipocalin Lazarillo. Using immunocytochemical, dye injection, electron microscopical and histological methods, we show that these LC are neurons and derive as postmitotic cells directly from the epithelium of the median domain. Further, they and the other identified cells of the median domain such as the protocerebral commissure pioneers (PCP), co-express the Mes-3 antigen, consistent with a derivation from the mesectodermal germ layer of the embryo. Subsequent to axogenesis, electron microscopy reveals that these Mes-3-expressing LC fasciculate with the co-expressing PCPs within the developing protocerebral commissure. We present a model for the origin of all these cells based on histological data and bromodeoxyuridine incorporation. The model suggests a delamination of cells from the mesectoderm followed by a migration to their ultimate sites within the median domain.
The old urinary calculi of the votive offerings in the pilgrimage church at Grafrath offer the possibility of analysing the components by infrared spectroscopy to give insights into factors that ...might influence their formation. A total of 166 specimens were taken from 139 objects (134 stones, 5 bones), in some stones from different layers.
Spectral analysis showed typical components for urinary calculi in 127 stones. These were compared with a control group of 98 urinary stones from carriers (77 male, 21 female) during 2007/2008 in Bavaria.
The percentage of occurrence of ammonium acid urate (NH(4)U) was high in the old stones (68.0%) versus the 2007/2008 group (1.0%). In uric acid (HS) there was no relevant difference between the two groups, whereas the occurrence of the oxalates whewellite (Whe) and weddellite (Wed) was much less in the old stones (Whe 18.1-69.4%, Wed 7.9-26.5 %). The phosphates differ in the components in favour of brushite in the old stones. The high occurrence of NH(4) in the old stones is comparable with (a) the old pre-1900 collection of Norwich (England), especially with the pre-1800 juvenile bladder stones, and (b) urinary stones in endemic areas of stone disease in children such as in North Thailand. Data about the Grafrath stone carriers (name, age, hometown) are not available but can indirectly be derived from the miracle books (1444-1728) of Grafrath with 12,131 reports; 1,165 had urologic disease of which 70% were children with urinary calculi coming from areas of Upper Bavaria and Swabia.
The finding of a high NH(4)U content indicates that this area might have been a stone belt for bladder stones in children. Under- or malnutrition with low protein and low fluid intake may be the aetiologic factor.
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