Chronic myelogenous leukemia (CML) is characterized by the presence of a BcrAbl fusion protein with deregulated tyrosine kinase activity that is required for maintaining the malignant phenotype. Imatinib, a selective inhibitor of Bcr-Abl, induces major cytogenetic remission (MCR) or complete cytogenetic remission (CCR) in the majority of patients with CML in first chronic phase. However, thorough re-evaluation of cytogenetics in a cohort of patients in MCR or CCR demonstrated clonal karyotypic abnormalities in more than 10% of cases, some of which were clinically associated with a myelodysplastic syndrome (MDS). Further analysis identified previous exposure to cytarabine and idarubicin as significant risk factors for the subsequent occurrence of abnormalities in Philadelphia chromosome-negative (Ph ؊ ) cells. To investigate if cytogenetically normal but clonal hematopoiesis might be present in other patients in cytogenetic remission, we studied X-chromosome inactivation as a marker of clonality by polymerase chain reaction analysis of the human androgen receptor (HUMARA). We find that imatinib restores a polyclonal pattern in most patients in CCR and MCR. Nonetheless, our results are consistent with the notion that targeted therapy of CML with imatinib favors the manifestation of Ph ؊ clonal disorders in some patients. They indicate that patients on imatinib should be followed with conventional cytogenetics, even after induction of

Superparamagnetic iron-oxide nanoparticles can be used in medical applications like vascular or targeted imaging. Magnetic particle imaging (MPI) is a promising tomographic imaging technique that allows visualizing the 3D nanoparticle distribution concentration in a non-invasive manner. The two main strengths of MPI are high temporal resolution and high sensitivity. While the first has been proven in the assessment of dynamic processes like cardiac imaging, it is unknown how far the detection limit of MPI can be lowered. Within this work, we will present a highly sensitive gradiometric receive-coil unit combined with a noise-matching network tailored for the imaging of mice. The setup is capable of detecting 5 ng of iron in-vitro with an acquisition time of 2.14 sec. In terms of iron concentration we are able to detect 156 μg/L marking the lowest value that has been reported for an MPI scanner so far. In-vivo MPI mouse images of a 512 ng bolus and a 21.5 ms acquisition time allow for capturing the flow of an intravenously injected tracer through the heart of a mouse. Since it has been rather difficult to compare detection limits across MPI publications we propose guidelines to improve the comparability of future MPI studies.

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The aim of this retrospective study was to survey the spectrum of oral tumors and tumor-like lesions treated in a pediatric surgical unit. The clinical features and treatment outcome are presented, and guidelines for management discussed. Long-term follow-up was carried out both by re-examination and by means of a questionnaire. A total of 95 patients were encountered over a 30-year period. The age at presentation ranged from 1 day to 16 years, and the male to female ratio was 0.7:1. The lesions were located predominantly on the lips (22%), tongue (21%), and cheek (19%). Patients were divided into five groups based on histological diagnosis. Benign lesions accounted for 83 (87%) of the cases. Of these, 41 (43%) were benign tumors, the most common of which were the hemangiomas (17 cases). Hamartomas accounted for a further 22 benign lesions (23%), among which 12 were lymphangiomas. Furthermore, we saw 14 cases (15%) of mucoceles, ranula and dysontogenetic cysts, and a further 6 cases (6%) were classed as miscellaneous lesions. Simple surgical resection was successful in treating most benign lesions, with occasional re-excision being necessary in lymphangiomas. The long-term effects of treatment include reduction of the red volume of the lips, scarring following resection of parotid hemangiomas, a forked tongue after wedged resection, and partial facial nerve palsy. The group of 12 (13%) malignant tumors consisted of 5 rhabdomyosarcomas, 2 fibrosarcomas, 2 carcinomas of the parotid, 1 osteosarcoma, and 2 metastases. A multimodal approach was used in patients with rhabdomyosarcomas, while fibrosarcomas and parotid carcinomas were normally treated by surgical excision. Six of 12 patients with malignant tumors were alive after a median follow-up of 20.5 years. Re-examination of the malignant tumor group revealed scarring, impaired growth and function of the maxilla associated with local irradiation, and an external salivary fistula. In conclusion, while most oral and maxillofacial tumors of children are benign, malignant tumors of soft tissue, salivary glands and bones must be taken into account. There are specific aspects related to certain developmental and biological characteristics that make a mainly conservative approach preferable in these children.

The assembly of tiny magnetic particles in external magnetic fields is important for many applications ranging from data storage to medical technologies. The development of ever smaller magnetic structures is restricted by a size limit, where the particles are just barely magnetic. For such particles we report the discovery of a kind of solution assembly hitherto unobserved, to our knowledge. The fact that the assembly occurs in solution is very relevant for applications, where magnetic nanoparticles are either solutionprocessed or are used in liquid biological environments. Induced by an external magnetic field, nanocubes spontaneously assemble into 1D chains, 2D monolayer sheets, and large 3D cuboids with almost perfect internal ordering. The self-assembly of the nanocubes can be elucidated considering the dipole-dipole interaction of small superparamagnetic particles. Complex 3D geometrical arrangements of the nanodipoles are obtained under the assumption that the orientation of magnetization is freely adjustable within the superlattice and tends to minimize the binding energy. On that basis the magnetic moment of the cuboids can be explained.M agnetic particles show an intriguing self-assembly behavior, due to mutual magnetic interactions or interaction with external magnetic fields. This can already be experienced by playing with toy magnets, which can assemble into strings or clusters. For much smaller magnetic particles, the knowledge about the magnetic assembly is crucial for technical applications involving magnetorheological fluids (1), high-density magnetic storage devices, hyperthermal cancer therapy, and magnetic resonance imaging (2). These applications use small magnetic particles, in the micrometer size range for magnetorheological fluids and down to 10 nm for magnetic resonance imaging or magnetothermal cancer therapy. Decreasing the size of the particles further decreases their magnetic moment to an extent that they are not considered in those applications anymore. In consequence, the assembly of sub-15-nm magnetic nanoparticles has been scarcely explored (3). Only recently, it was reported that cube-shaped magnetic nanoparticles of 13 nm showed a surprising magnetic-field-induced assembly into helices at the air-liquid interface (4) and 9-nm magnetic nanoparticles in the presence of a magnetic field uniquely assembled into very large, nearly defectfree monolayers and 3D cubic assemblies on solid substrates (5). This triggers the question about the arrangement of the magnetic dipoles in such assemblies where an amazing answer was recently found in the case of only eight dipoles (6), and where for larger magnetic nanoparticles and their assemblies considerable complexity was observed (7, 8).Here we report very small (sub-15-nm diameter) spherical and cube-shaped iron-oxide nanoparticles with respect to their magnetic assembly behavior. The nanoparticles are sterically stabilized by oleic acid, have very narrow size distributions, and very regular shapes (SI Appendix). The controlled synthesis of...

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Summary:Sclerodermoid chronic graft-versus-host disease (sGVHD) is a well-known complication in patients with a long history of chronic GVHD. Pulmonary involvement in chronic GVHD presents typically as bronchiolitis obliterans (BO). Pulmonary fibrosis after allogeneic hematopoietic stem cell transplantation (HSCT) is presumed to be caused by the long-term toxicity of the conditioning regimen or the result of lung injury elicited predominantly by viral infections or GVHD. We present two patients with late onset pulmonary fibrosis associated with moderate sGVHD of the skin after HSCT. At the initial diagnosis of chronic GVHD both patients presented with symptoms of interstitial pneumonia. Years later both patients developed moderate to severe interstitial pulmonary fibrosis in association with sGVHD. One patient showed additional clinical and histological signs of BO. While one patient responded to increased immunosuppression including total nodal irradiation (1 Gy), the other patient died due to complications related to pulmonary fibrosis. Bone Marrow Transplantation (2002) 29, 357-360. DOI: 10.1038/sj/bmt/1703386 Keywords: bone marrow transplantation; lung fibrosis; graft-versus-host disease; progressive systemic sclerosis; bronchiolitis obliterans; total nodal irradiation Sclerodermoid chronic GVHD (sGVHD) is a well-known late complication in patients with chronic GVHD. 1 It resembles progressive systemic sclerosis and involves the skin, fasciae, as well as the gastrointestinal tract. Furthermore data on cutaneous microchimerism in females with progressive systemic sclerosis may indicate a related pathophysiology. Progressive systemic sclerosis typically affects the kidneys and the lungs with development of alveolitis and pulmonary fibrosis. 5 However, pulmonary or renal involvement have not been reported in sGVHD. In chronic GVHD pulmonary changes are well known. Bronchiolitis obliterans (BO) is the typical and threatening pulmonary manifestation of chronic GVHD with progressive obstruction of the small bronchioles due to proliferation of the peribronchiolar tissue. [6][7][8][9][10][11] The occurrence of pulmonary fibrosis is mainly considered a manifestation of late toxicity of total body irradiation or chemotherapy during conditioning for allogeneic stem cell transplantation or the result of interstitial pneumonitis (IP) mainly due to viral infections or acute GVHD. 12-13 Here, we report two patients with sGVHD and late onset progressive pulmonary fibrosis. Patients Patient 1A 32-year-old male with a 15 pack-year smoking history received a peripheral stem cell graft from his HLA-identical sister for T-ALL in 2nd CR, after conditioning with TBI (12 Gy in six fractions with shielding of the lung, total pulmonary dose 10 Gy) and cyclophosphamide 60 mg/kg once daily i.v. on days 1 and 2. Patient and donor were CMVnegative by serology. GVHD prophylaxis consisted of cyclosporine A (CsA), MTX and prednisone. On day 90, the patient developed primary extensive chronic GVHD of the skin, oral mucosa, salivary glands an...