Index of pretreatment intensity predicts outcome of high-dose chemotherapy and autologous progenitor cell transplantation in chemosensitive relapse of Hodgkin's disease

Purpose To identify prognostic factors in patients with chemosensitive relapsed Hodgkin's disease treated by high-dose chemotherapy with autologous progenitor cell transplantation (HDC) and to compare the duration of treatment-free remission prior to HDC with the progression-free survival after HDC in individual patients. Patients and methods Forty-five consecutive patients were analyzed retrospectively. We devised an index of pretreatment intensity (IPTI) based number of different chemo- and radio-therapy regimens given between diagnosis and HDC and on the duration of disease. Results With a median follow-up of 47 months the post-transplant event-free survival (EFS) was 44% and the overall survival. (OAS) was 62% at four years. The IPTI allowed to discriminate between a low and a high-risk group with a four-year post-transplant EFS of 66% and 11% and a OAS of 87% and 28%, respectively (P = 0.0001). Of the 39 patients with sufficient follow-up after HDC, post-transplant EFS lasted on average ≥ 18.5 months longer than the pretransplant treatment-free remission. Conclusions HDC with the CBV regimen confers significant benefit to patients with chemosensitive relapsed Hodgkin's disease. The IPTI may help to select patients with a good response to HDC and to identify poor prognosis patients suitable for experimental protocols or palliative care onl

A high-precision polarimeter

We have built a polarimeter in order to measure the electron beam polarization in hall C at JLAB. Using a superconducting solenoid to drive the pure-iron target foil into saturation, and a symmetrical setup to detect the Moller electrons in coincidence, we achieve an accuracy of <1%. This sets a new standard for Moller polarimeters.Comment: 17 pages, 9 figures, submitted to N.I.

Hotel Intercontinental, en Ginebra (Suiza)

This is one of the largest hotels in Switzerland, having 400 bedrooms and a capacity for 800 guests, distributed in 15 storeys. There are also 3 restaurants, 3 bars, a dancing hall, a general hall, with installations for simultaneous translations, cinema shows, etc., with accommodation for 400 people, four lecture rooms, a number of luxurious shops, hairdressers and beauty salon, travelling agency, hot water pool, and other ameneties. Its main merit is the right choice of materials, and the simple, elegant style of its outer shape and interior decoration.Este hotel, que es uno de los mayores construidos en Suiza, cuenta, entre sus dependencias, con 400 habitaciones que pueden acoger a 800 huéspedes y distribuidas en 15 plantas; tres restaurantes; tres bares; un salón de baile; un salón para múltiples usos, equipado con instalaciones de traducción simultánea, de proyección, etc., y en el cual pueden ser servidos banquetes de 400 cubiertos; cuatro salas de conferencias; una serie de lujosas tiendas; peluquería y salón de belleza; agencias de viajes; piscina con agua caliente; etc. Su mayor atractivo reside en la acertada elección de los materiales empleados en su construcción, así como en la elegancia y sencillez de líneas exteriores y decoración interior

Hesperioidea e Papilionoidea (Lepidoptera) coligidos em expedição aos Rios Nhamundá e Abacaxis, Amazonas, Brasil: novos subsídios para o conhecimento da biodiversidade da Amazônia Brasileira

Hesperioidea e Papilionoidea (Lepidoptera) coligidos em expedição aos Rios Nhamundá e Abacaxis, Amazonas, Brasil: novos subsídios para o conhecimento da biodiversidade da Amazônia Brasileira. Objetivando um aprimoramento do conhecimento da lepidopterofauna diurna da Amazônia brasileira, este estudo lista 180 taxa coligidos em cinco pontos distintos de dois afluentes do Rio Amazonas, envolvendo as áreas de endemismo Guiana e Rondônia. As coletas foram passivas e ativas e as diferentes localidades comparadas através de análise de Escalonamento Multidimensional Não-Métrico (NMDS).Hesperioidea and Papilionoidea (Lepidoptera) collected in an expedition to the Nhamundá and Abacaxis rivers, Amazonas, Brazil: new insights for understanding the biodiversity of the Brazilian Amazon. Aiming at improving the knowledge of the diurnal lepidopterofauna of the Amazon rainforest, this study lists 180 taxa collected at five different points along two tributaries of the Amazon River, including the Guyana and Rondonia areas of endemism. The different localities were compared using Non-Metric Multidimensional Scaling analysis (NMDS)

Trunk Sway Measures of Postural Stability During Clinical Balance Tests: Effects of Age

Background. The major disadvantage of current clinical tests that screen for balance disorders is a reliance on an examiner's subjective assessment of equilibrium control. To overcome this disadvantage we investigated, using quantified measures of trunk sway, age-related differences of normal subjects for commonly used clinical balance tests. Methods. Three age groups were tested: young (15-25 years; n = 48), middle-aged (45-55 years; n = 50) and elderly (65-75 years; n = 49). Each subject performed a series of fourteen tasks similar to those included in the Tinetti and Clinical Test of Sensory Interaction in Balance protocols. The test battery comprised stance and gait tasks performed under normal, altered visual (eyes closed), and altered proprioceptive (foam support surface) conditions. Quantification of trunk sway was performed using a system that measured trunk angular velocity and position in the roll (lateral) and pitch (fore-aft) planes at the level of the lower back. Ranges of sway amplitude and velocity were examined for age-differences with ANOVA techniques. Results. A comparison between age groups showed several differences. Elderly subjects were distinguished from both middle-aged and young subjects by the range of trunk angular sway and angular velocity because both were greater in roll and pitch planes for stance and stance-related tasks (tandem walking). The most significant age group differences (F = 30, p < .0001) were found for standing on one leg on a normal floor or on a foam support surface with eyes open. Next in significance was walking eight tandem steps on a normal floor (F = 13, p < .0001). For gait tasks, such as walking five steps while rotating or pitching the head or with eyes closed, pitch and roll velocity ranges were influenced by age with middle-aged subjects showing the smallest ranges followed by elderly subjects and then young subjects (F = 12, p < .0001). Walking over a set of low barriers also yielded significant differences between age groups for duration and angular sway. In contrast, task duration was the only variable significantly influenced when walking up and down a set of stairs. An interesting finding for all tasks was the different spread of values for each population. Population distributions were skewed for all ages and broadened with age. Conclusions. Accurate measurement of trunk angular sway during stance and gait tasks provides a simple way of reliably measuring changes in balance stability with age and could prove useful when screening for balance disorders of those prone to fal

Long-term results of a multicenter SAKK trial on high-dose ifosfamide and doxorubicin in advanced or metastatic gynecologic sarcomas

Background: Dose intensive chemotherapy has not been tested prospectively for the treatment of gynecologic sarcomas. We investigated the antitumor activity and toxicity of high-dose ifosfamide and doxorubicin, in the context of a multidisciplinary strategy for the treatment of advanced and metastatic, not pretreated, gynecologic sarcomas. Patients and methods: Thirty-nine patients were enrolled onto a phase I-II multicenter trial of ifosfamide, 10 g/m2 as a continuous infusion over 5 days, plus doxorubicin intravenously, 25 mg/m2/day for 3 days with Mesna and granulocyte-colony-stimulating factor every 21 days. Salvage therapy was allowed after chemotherapy. Results: Among the 37 evaluable patients, the tumor was locally advanced (n = 11), with concomitant distant metastases (n = 5) or with distant metastases only (n = 21). After a median of three (range 1-7) chemotherapy cycles, six patients experienced a complete response and 12 a partial response for an overall response rate of 49% (95% CI 32% to 66%). The response rate was higher in poorly differentiated tumors (62%) compared with moderately well differentiated ones (18%), but was not different according to histology subtypes. Eleven patients had salvage therapy, either immediately following chemotherapy (n = 7) or at time of progression (n = 4). With a median follow-up time of 5 years, the median overall survival was 30.5 months. Hematological toxicity was as expected neutropenia, thrombopenia and anemia ≥grade 3 at 50%, 34% and 33% of cycles respectively. No toxic death occurred. Conclusions: High-dose ifosfamide plus doxorubicin is an active regimen for all subtypes of gynecological sarcomas. Its toxicity was manageable in a multicentric setting. The prolonged survival might be due to the multidisciplinary strategy that was possible in one-third of the patient

Feldversuch zur Eradikation von Methicillin-resistenten Staphylococcus aureus (MRSA) mittels Bakteriophagen in einem Schweinezuchtbetrieb

In recent years, Livestock Associated Methicillin-Resistant Staphylococcus aureus (LA-MRSA) are found frequently in pigs. The colonization of the care staff with LA-MRSA is strongly associated with the intensity and duration of animal contact and LA-MRSA herd prevalence. In human medicine, staphylococcal infections have been controlled successfully by topical or systemic administration of Staphylococcus - associated bacteriophages. Therefore, the present study investigated the effect of a bacteriophage cocktail on skin and mucosal colonization of pigs with MRSA in a pig farm with high MRSA prevalence. In a first experiment, the sows were washed with a bacteriophage cocktail and nose, mouth and vagina were rinsed before the sows were admitted to the farrowing house. Then, 10 ml of the bacteriophage cocktail was administered daily to the sows over the feed until weaning. The suckling piglets were sprayed and sampled twice a week during the suckling period and treated with the bacteriophage cocktail over the feed during the weaning period. In further experiments, the weaning room was nebulized three times a day with a bacteriophage cocktail and different concentrations of bacteriophages were added to the drinking water via Dosatron®. None of the experiments, however, showed an eradication of MRSA neither in nose nor in feces

Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study

Background: Relapsed or refractory diffuse large B-cell and mantle-cell lymphoma have a poor prognosis. The EPOCH regimen and rituximab monotherapy have demonstrated activity as salvage therapies. Because of their non-overlapping toxicity, we evaluated their combination as salvage therapy in a phase II study. Patients and methods: Patients with relapsed or refractory CD20-positive large B-cell and mantle-cell lymphoma were offered treatment with rituximab 375 mg/m2 intravenously (i.v.) on day 1, doxorubicin 15 mg/m2 as a continuous i.v. infusion on days 2-4, etoposide 65 mg/m2 as a continuous i.v. infusion on days 2-4, vincristine 0.5 mg as a continuous i.v. infusion on days 2-4, cyclophosphamide 750 mg/m2 i.v. on day 5 and prednisone 60 mg/m2 orally on days 1-14. Results: Fifty patients, with a median age of 56 years (range 23-72), entered the study. Twenty-five had primary diffuse large B-cell lymphoma, 18 transformed large B-cell lymphoma and seven mantle-cell lymphoma. The median number of prior chemotherapy regimens was 1.7 (range one to four). The median number of treatment cycles was four (range one to six). Possible treatment-related death occurred in two patients. Objective responses were obtained in 68% of patients (28% complete responses, 40% partial responses). Nineteen patients received consolidating high-dose chemotherapy with autologous stem-cell transplantation. The median follow-up was 33 months. Three patients developed a secondary myelodysplastic syndrome. The median overall survival was 17.9 months; the projected overall survival at 1, 2 and 3 years was 66, 42 and 35%, respectively. The median event-free survival was 11.8 months; the projected event-free survival at 1, 2 and 3 years was 50, 30 and 26%, respectively. Conclusion: The rituximab-EPOCH regimen is effective and well tolerated, even in extensively pretreated patients with relapsed or refractory large B-cell lymphoma and mantle-cell lymphom

Stabilization and humanization of a single-chain Fv antibody fragment specific for human lymphocyte antigen CD19 by designed point mutations and CDR-grafting onto a human framework

A single-chain Fv (scFv) fragment derived from the murine antibody 4G7, specific for human lymphocyte CD19, was engineered for stability and expression in Escherichia coli in view of future use as a therapeutic protein. We compared two orthogonal knowledge-based procedures. In one approach, we designed a mutant with 14 single amino-acid substitutions predicted to correct destabilizing residues in the 4G7-wt sequence to create 4G7-mut. In the second variant, the murine CDRs were grafted to the human acceptor framework huVκ3-huVH3, with 11 additional point mutations introduced to obtain a better match between CDR graft and acceptor framework, to arrive at 4G7-graft. Compared to 4G7-wt, 4G7-mut showed greater thermodynamic stability in guanidinium chloride-induced equilibrium denaturation experiments and somewhat greater stability in human serum. The loop graft maintained the comparatively high stability of the murine loop donor, but did not improve it further. Our analysis indicates that this is due to subtle strain introduced between CDRs and framework, mitigating the otherwise highly favorable properties of the human acceptor framework. This slight strain in the loop graft is also reflected in the binding affinities for CD19 on leukemic cells of 8.4 nM for 4G7-wt, 16.4 nM for 4G7-mut and 30.0 nM for 4G7-graft. This comparison of knowledge-based mutation and loop-grafting-based approaches will be important, when moving molecules forward to therapeutic application