A multiphysics approach for modeling gas exchange in microperforated films for modified atmosphere packaging of respiring products

The objective of this work is to quantify, model and verify how the interactions between the respiring products and the surrounding atmosphere in a package affect the gas exchange through a microperforation. The pressure drop generated in a closed system by the metabolic activity of five different products has been determined by direct and indirect measurements. In this way, the estimated compensating hydrodynamic flows that can pass through the microperforated film ranged from 0.34 to 4.75 mL h(-1). A 3D model that considers the mass transfer coupled with the momentum transfer has been proposed to predict the gas concentration profiles around the microperforations originated by the diffusive and convective flows. A novel gas exchange measurement system, able to deliver small convective airflows comparable to those obtained for the different products and conditions, was assembled for the model verification. The model correctly predicts experimental data obtained for different convective flows

Individualized decision aid for diverse women with lupus nephritis (IDEA-WON): A randomized controlled trial.

BackgroundTreatment decision-making regarding immunosuppressive therapy is challenging for individuals with lupus. We assessed the effectiveness of a decision aid for immunosuppressive therapy in lupus nephritis.Methods and findingsIn a United States multicenter, open-label, randomized controlled trial (RCT), adult women with lupus nephritis, mostly from racial/ethnic minority backgrounds with low socioeconomic status (SES), seen in in- or outpatient settings, were randomized to an individualized, culturally tailored, computerized decision aid versus American College of Rheumatology (ACR) lupus pamphlet (1:1 ratio), using computer-generated randomization. We hypothesized that the co-primary outcomes of decisional conflict and informed choice regarding immunosuppressive medications would improve more in the decision aid group. Of 301 randomized women, 298 were analyzed; 47% were African-American, 26% Hispanic, and 15% white. Mean age (standard deviation [SD]) was 37 (12) years, 57% had annual income of <$40,000, and 36% had a high school education or less. Compared with the provision of the ACR lupus pamphlet (n = 147), participants randomized to the decision aid (n = 151) had (1) a clinically meaningful and statistically significant reduction in decisional conflict, 21.8 (standard error [SE], 2.5) versus 12.7 (SE, 2.0; p = 0.005) and (2) no difference in informed choice in the main analysis, 41% versus 31% (p = 0.08), but clinically meaningful and statistically significant difference in sensitivity analysis (net values for immunosuppressives positive [in favor] versus negative [against]), 50% versus 35% (p = 0.006). Unresolved decisional conflict was lower in the decision aid versus pamphlet groups, 22% versus 44% (p < 0.001). Significantly more patients in the decision aid versus pamphlet group rated information to be excellent for understanding lupus nephritis (49% versus 33%), risk factors (43% versus 27%), medication options (50% versus 33%; p ≤ 0.003 for all); and the ease of use of materials was higher in the decision aid versus pamphlet groups (51% versus 38%; p = 0.006). Key study limitations were the exclusion of men, short follow-up, and the lack of clinical outcomes, including medication adherence.ConclusionsAn individualized decision aid was more effective than usual care in reducing decisional conflict for choice of immunosuppressive medications in women with lupus nephritis.Trial registrationClinicaltrials.gov, NCT02319525

Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice

DYRK1A is the human orthologue of the Drosophila minibrain (mnb) gene, which is involved in postembryonic neurogenesis in flies. Because of its mapping position on chromosome 21 and the neurobehavioral alterations shown by mice overexpressing this gene, involvement of DYRK1A in some of the neurological defects of Down syndrome patients has been suggested. To gain insight into its physiological role, we have generated mice deficient in Dyrk1A function by gene targeting. Dyrk1A(−/−) null mutants presented a general growth delay and died during midgestation. Mice heterozygous for the mutation (Dyrk1A(+/−)) showed decreased neonatal viability and a significant body size reduction from birth to adulthood. General neurobehavioral analysis revealed preweaning developmental delay of Dyrk1A(+/−) mice and specific alterations in adults. Brains of Dyrk1A(+/−) mice were decreased in size in a region-specific manner, although the cytoarchitecture and neuronal components in most areas were not altered. Cell counts showed increased neuronal densities in some brain regions and a specific decrease in the number of neurons in the superior colliculus, which exhibited a significant size reduction. These data provide evidence about the nonredundant, vital role of Dyrk1A and suggest a conserved mode of action that determines normal growth and brain size in both mice and flies

Aqueous humor neutrophil gelatinase-associated lipocalin levels in patients with idiopathic acute anterior uveitis

Purpose: The purpose of this study was to evaluate the levels of neutrophil gelatinase-associated lipocalin (NGAL) in the aqueous humor in eyes with idiopathic acute anterior uveitis (AAU). Methods: A comparative control study. Aqueous humor was collected from 20 eyes of 20 patients with idiopathic AAU. The control group included 20 aqueous samples from 20 patients about to undergo cataract surgery and without any other ocular or systemic diseases. The level of NGAL was determined with a commercially available ELISA kit. Results: The concentration of NGAL in aqueous humor was markedly higher in patients with idiopathic AAU than in control subjects (Mann–Whitney U test, p<0.001). The level of NGAL was 139,197.38±183,426.36 (mean±SD) pg/ml in eyes with AAU and 3,169.96±1,595.78 pg/ml in the eyes of the control group. Conclusions: The aqueous humor NGAL level is increased in eyes with idiopathic AAU. These results imply that NGAL is associated with the regulation of inflammation in patients with AAU and could be used as a biomarker of ocular inflammation and immunomodulatory treatment response.Medicin

Improved syntheses of aromatase inhibitors and neuroactive steroids efficient oxidations and reductions at key positions for bioactivity

An Henbest reduction, followed by the preparation of a silyl enol ether and oxidation in situ with m-CPBA has led to the neurosteroids 3[alpha]-hydroxy- and 3[alpha],21-dihydroxy-5[alpha]-pregnanolones. Using testosterone as starting material, a new short synthesis of an aromatase inhibitor, 4-OHA, has been achieved through hydroboration/oxidation followed by a Swern type oxidation and epimerization. Another aromatase inhibitor, androst-4-ene-3,6-17-trione, has been efficiently prepared using PCC on montmorillonite K10, under ultrasonic irradiation.http://www.sciencedirect.com/science/article/B6THR-3WC46V7-8/1/5f915790e78df65f4c988ab78bf4f17

Stress hormones promote growth of B16-F10 melanoma metastases: an interleukin 6-and glutathione-dependent mechanism

[EN] Background: Interleukin (IL)-6 (mainly of tumor origin) activates glutathione (GSH) release from hepatocytes and its interorgan transport to B16-F10 melanoma metastatic foci. We studied if this capacity to overproduce IL-6 is regulated by cancer cell-independent mechanisms. Methods: Murine B16-F10 melanoma cells were cultured, transfected with red fluorescent protein, injected i.v. into syngenic C57BL/6J mice to generate lung and liver metastases, and isolated from metastatic foci using high-performance cell sorting. Stress hormones and IL-6 levels were measured by ELISA, and CRH expression in the brain by in situ hybridization. DNA binding activity of NF-kappa B, CREB, AP-1, and NF-IL-6 was measured using specific transcription factor assay kits. IL-6 expression was measured by RT-PCR, and silencing was achieved by transfection of anti-IL-6 small interfering RNA. GSH was determined by HPLC. Cell death analysis was distinguished using fluorescence microscopy, TUNEL labeling, and flow cytometry techniques. Statistical analyses were performed using Student's t test. Results: Plasma levels of stress-related hormones (adrenocorticotropin hormone, corticosterone, and noradrenaline) increased, following a circadian pattern and as compared to non-tumor controls, in mice bearing B16-F10 lung or liver metastases. Corticosterone and noradrenaline, at pathophysiological levels, increased expression and secretion of IL-6 in B16-F10 cells in vitro. Corticosterone- and noradrenaline-induced transcriptional up-regulation of IL-6 gene involves changes in the DNA binding activity of nuclear factor-kappa B, cAMP response element-binding protein, activator protein-1, and nuclear factor for IL-6. In vivo inoculation of B16-F10 cells transfected with anti-IL-6-siRNA, treatment with a glucocorticoid receptor blocker (RU-486) or with a beta-adrenoceptor blocker (propranolol), increased hepatic GSH whereas decreased plasma IL-6 levels and metastatic growth. Corticosterone, but not NORA, also induced apoptotic cell death in metastatic cells with low GSH content. Conclusions: Our results describe an interorgan system where stress-related hormones, IL-6, and GSH coordinately regulate metastases growthThis research was supported by grant (SAF2009-07729 and IPT-010000-2010-21) from the Ministerio de Economia y Competitividad (http://www.idi.mineco.gob.es), Spain.Valles, SL.; Benlloch, M.; Rodriguez, ML.; Mena-Mollá, S.; Pellicer, JA.; Asensi-Miralles, MÁ.; Obrador, E.... (2013). Stress hormones promote growth of B16-F10 melanoma metastases: an interleukin 6-and glutathione-dependent mechanism. Journal of Translational Medicine. 11:1-14. https://doi.org/10.1186/1479-5876-11-72S11411Meister, A. (1983). Selective modification of glutathione metabolism. Science, 220(4596), 472-477. doi:10.1126/science.6836290Estrela, J. M., Ortega, A., & Obrador, E. (2006). Glutathione in Cancer Biology and Therapy. Critical Reviews in Clinical Laboratory Sciences, 43(2), 143-181. doi:10.1080/10408360500523878Obrador, E., Benlloch, M., Pellicer, J. A., Asensi, M., & Estrela, J. M. (2011). Intertissue Flow of Glutathione (GSH) as a Tumor Growth-promoting Mechanism. Journal of Biological Chemistry, 286(18), 15716-15727. doi:10.1074/jbc.m110.196261Meister, A. (1991). Glutathione deficiency produced by inhibition of its synthesis, and its reversal; Applications in research and therapy. Pharmacology & Therapeutics, 51(2), 155-194. doi:10.1016/0163-7258(91)90076-xHanigan, M. H. (1995). Expression of gamma-glutamyl transpeptidase provides tumor cells with a selective growth advantage at physiologic concentrations of cyst(e)ine. Carcinogenesis, 16(2), 181-185. doi:10.1093/carcin/16.2.181Obrador, E. (2002). γ-Glutamyl transpeptidase overexpression increases metastatic growth of B16 melanoma cells in the mouse liver. Hepatology, 35(1), 74-81. doi:10.1053/jhep.2002.30277Ballatori, N., & Rebbeor, J. (1998). Roles of MRP2 and oatp1 in Hepatocellular Export of Reduced Glutathione. Seminars in Liver Disease, 18(04), 377-387. doi:10.1055/s-2007-1007171Hodge, D. R., Hurt, E. M., & Farrar, W. L. (2005). The role of IL-6 and STAT3 in inflammation and cancer. European Journal of Cancer, 41(16), 2502-2512. doi:10.1016/j.ejca.2005.08.016Barton, B. E. (2005). Interleukin-6 and new strategies for the treatment of cancer, hyperproliferative diseases and paraneoplastic syndromes. Expert Opinion on Therapeutic Targets, 9(4), 737-752. doi:10.1517/14728222.9.4.737Rose-John, S., Waetzig, G. H., Scheller, J., Grötzinger, J., & Seegert, D. (2007). The IL-6/sIL-6R complex as a novel target for therapeutic approaches. Expert Opinion on Therapeutic Targets, 11(5), 613-624. doi:10.1517/14728222.11.5.613Ara, T., & DeClerck, Y. A. (2010). Interleukin-6 in bone metastasis and cancer progression. European Journal of Cancer, 46(7), 1223-1231. doi:10.1016/j.ejca.2010.02.026Emmenegger, U., & Kerbel, R. S. (2010). Chemotherapy counteracted. Nature, 468(7324), 637-638. doi:10.1038/468637aWang, Y., Niu, X. L., Qu, Y., Wu, J., Zhu, Y. Q., Sun, W. J., & Li, L. Z. (2010). Autocrine production of interleukin-6 confers cisplatin and paclitaxel resistance in ovarian cancer cells. Cancer Letters, 295(1), 110-123. doi:10.1016/j.canlet.2010.02.019Sternberg, E. M. (1997). Neural-immune interactions in health and disease. Journal of Clinical Investigation, 100(11), 2641-2647. doi:10.1172/jci119807Reiche, E. M. V., Nunes, S. O. V., & Morimoto, H. K. (2004). Stress, depression, the immune system, and cancer. The Lancet Oncology, 5(10), 617-625. doi:10.1016/s1470-2045(04)01597-9Besedovsky, H. O., Del Rey, A., Klusman, I., Furukawa, H., Monge Arditi, G., & Kabiersch, A. (1991). Cytokines as modulators of the hypothalamus-pituitary-adrenal axis. The Journal of Steroid Biochemistry and Molecular Biology, 40(4-6), 613-618. doi:10.1016/0960-0760(91)90284-cBethin, K. E., Vogt, S. K., & Muglia, L. J. (2000). Interleukin-6 is an essential, corticotropin-releasing hormone-independent stimulator of the adrenal axis during immune system activation. Proceedings of the National Academy of Sciences, 97(16), 9317-9322. doi:10.1073/pnas.97.16.9317Herr, I., & Pfitzenmaier, J. (2006). Glucocorticoid use in prostate cancer and other solid tumours: implications for effectiveness of cytotoxic treatment and metastases. The Lancet Oncology, 7(5), 425-430. doi:10.1016/s1470-2045(06)70694-5Bernabé, D. G., Tamae, A. C., Biasoli, É. R., & Oliveira, S. H. P. (2011). Stress hormones increase cell proliferation and regulates interleukin-6 secretion in human oral squamous cell carcinoma cells. Brain, Behavior, and Immunity, 25(3), 574-583. doi:10.1016/j.bbi.2010.12.012Antoni, M. H., Lutgendorf, S. K., Cole, S. W., Dhabhar, F. S., Sephton, S. E., McDonald, P. G., … Sood, A. K. (2006). The influence of bio-behavioural factors on tumour biology: pathways and mechanisms. Nature Reviews Cancer, 6(3), 240-248. doi:10.1038/nrc1820Yang, E. V., Kim, S., Donovan, E. L., Chen, M., Gross, A. C., Webster Marketon, J. I., … Glaser, R. (2009). Norepinephrine upregulates VEGF, IL-8, and IL-6 expression in human melanoma tumor cell lines: Implications for stress-related enhancement of tumor progression. Brain, Behavior, and Immunity, 23(2), 267-275. doi:10.1016/j.bbi.2008.10.005Carretero, J., Obrador, E., Anasagasti, M. J., Martin, J. J., Vidal-Vanaclocha, F., & Estrela, J. M. (1999). Clinical and Experimental Metastasis, 17(7), 567-574. doi:10.1023/a:1006725226078Lachize, S., Apostolakis, E. M., van der Laan, S., Tijssen, A. M. I., Xu, J., de Kloet, E. R., & Meijer, O. C. (2009). Steroid receptor coactivator-1 is necessary for regulation of corticotropin-releasing hormone by chronic stress and glucocorticoids. Proceedings of the National Academy of Sciences, 106(19), 8038-8042. doi:10.1073/pnas.0812062106Veenema, A. H., Reber, S. O., Selch, S., Obermeier, F., & Neumann, I. D. (2008). Early Life Stress Enhances the Vulnerability to Chronic Psychosocial Stress and Experimental Colitis in Adult Mice. Endocrinology, 149(6), 2727-2736. doi:10.1210/en.2007-1469Asensi, M., Sastre, J., Pallardo, F. V., Delaasuncion, J. G., Estrela, J. M., & Vina, J. (1994). A High-Performance Liquid Chromatography Method for Measurement of Oxidized Glutathione in Biological Samples. Analytical Biochemistry, 217(2), 323-328. doi:10.1006/abio.1994.1126Ortega, A. L., Carretero, J., Obrador, E., Gambini, J., Asensi, M., Rodilla, V., & Estrela, J. M. (2003). Tumor Cytotoxicity by Endothelial Cells. Journal of Biological Chemistry, 278(16), 13888-13897. doi:10.1074/jbc.m207140200SAKAKIBARA, H., KOYANAGI, A., SUZUKI, T., SUZUKI, A., LING, L., & SHIMOI, K. (2010). Effects of Animal Care Procedures on Plasma Corticosterone Levels in Group-Housed Mice during the Nocturnal Active Phase. Experimental Animals, 59(5), 637-642. doi:10.1538/expanim.59.637Lucot, J. B., Jackson, N., Bernatova, I., & Morris, M. (2005). Measurement of plasma catecholamines in small samples from mice. Journal of Pharmacological and Toxicological Methods, 52(2), 274-277. doi:10.1016/j.vascn.2004.11.004Dobos, J., Kenessey, I., Tímár, J., & Ladányi, A. (2011). Glucocorticoid Receptor Expression and Antiproliferative Effect of Dexamethasone on Human Melanoma Cells. Pathology & Oncology Research, 17(3), 729-734. doi:10.1007/s12253-011-9377-8Tsuji, M., Kuno, T., Tanaka, C., Ichihashi, M., & Mishima, Y. (1983). Beta-adrenergic receptors of B16 melanoma cell. Archives of Dermatological Research, 275(6), 415-416. doi:10.1007/bf00417345Im, A., & Appleman, L. J. (2010). Mifepristone: pharmacology and clinical impact in reproductive medicine, endocrinology and oncology. Expert Opinion on Pharmacotherapy, 11(3), 481-488. doi:10.1517/14656560903535880Smoak, K. A., & Cidlowski, J. A. (2004). Mechanisms of glucocorticoid receptor signaling during inflammation. Mechanisms of Ageing and Development, 125(10-11), 697-706. doi:10.1016/j.mad.2004.06.010Cole, S. W., & Sood, A. K. (2011). Molecular Pathways: Beta-Adrenergic Signaling in Cancer: Figure 1. Clinical Cancer Research, 18(5), 1201-1206. doi:10.1158/1078-0432.ccr-11-0641Matsusaka, T., Fujikawa, K., Nishio, Y., Mukaida, N., Matsushima, K., Kishimoto, T., & Akira, S. (1993). Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8. Proceedings of the National Academy of Sciences, 90(21), 10193-10197. doi:10.1073/pnas.90.21.10193McEwen, B. S. (2007). Physiology and Neurobiology of Stress and Adaptation: Central Role of the Brain. Physiological Reviews, 87(3), 873-904. doi:10.1152/physrev.00041.2006Lee, J.-H., Yoo, S. B., Kim, N. Y., Cha, M. J., & Jahng, J. W. (2008). Interleukin-6 and the Hypothalamic-Pituitary-Adrenal Activation in a Tumor Bearing Mouse. International Journal of Neuroscience, 118(3), 355-364. doi:10.1080/00207450701592915Li, Y.-F., He, R.-R., Tsoi, B., Li, X.-D., Li, W.-X., Abe, K., & Kurihara, H. (2012). Anti-Stress Effects of Carnosine on Restraint-Evoked Immunocompromise in Mice through Spleen Lymphocyte Number Maintenance. PLoS ONE, 7(4), e33190. doi:10.1371/journal.pone.0033190Sarabdjitsingh, R. A., Kofink, D., Karst, H., de Kloet, E. R., & Joëls, M. (2012). Stress-Induced Enhancement of Mouse Amygdalar Synaptic Plasticity Depends on Glucocorticoid and ß-Adrenergic Activity. PLoS ONE, 7(8), e42143. doi:10.1371/journal.pone.0042143Moreno-Smith, M., Lutgendorf, S. K., & Sood, A. K. (2010). Impact of stress on cancer metastasis. Future Oncology, 6(12), 1863-1881. doi:10.2217/fon.10.142Tissing, W. J. E., Meijerink, J. P. P., den Boer, M. L., & Pieters, R. (2003). Molecular determinants of glucocorticoid sensitivity and resistance in acute lymphoblastic leukemia. Leukemia, 17(1), 17-25. doi:10.1038/sj.leu.2402733Anderer, G., Schrappe, M., Brechlin, A. M., Lauten, M., Muti, P., Welte, K., & Stanulla, M. (2000). Polymorphisms within glutathione S-transferase genes and initial response to glucocorticoids in childhood acute lymphoblastic leukaemia. Pharmacogenetics, 10(8), 715-726. doi:10.1097/00008571-200011000-00006Thaker, P. H., & Sood, A. K. (2008). Neuroendocrine influences on cancer biology. Seminars in Cancer Biology, 18(3), 164-170. doi:10.1016/j.semcancer.2007.12.005Takeda, T., Kurachi, H., Yamamoto, T., Nishio, Y., Nakatsuji, Y., Morishige, K., … Murata, Y. (1998). Crosstalk between the interleukin-6 (IL-6)-JAK-STAT and the glucocorticoid-nuclear receptor pathway: synergistic activation of IL-6 response element by IL-6 and glucocorticoid. Journal of Endocrinology, 159(2), 323-330. doi:10.1677/joe.0.1590323Rodriguez-Rocha, H., Garcia Garcia, A., Zavala-Flores, L., Li, S., Madayiputhiya, N., & Franco, R. (2012). Glutaredoxin 1 Protects Dopaminergic Cells by Increased Protein Glutathionylation in Experimental Parkinson’s Disease. Antioxidants & Redox Signaling, 17(12), 1676-1693. doi:10.1089/ars.2011.4474Tome, M. E., Jaramillo, M. C., & Briehl, M. M. (2011). Hydrogen peroxide signaling is required for glucocorticoid-induced apoptosis in lymphoma cells. Free Radical Biology and Medicine, 51(11), 2048-2059. doi:10.1016/j.freeradbiomed.2011.09.002Lázár-Molnár, E., Hegyesi, H., Tóth, S., & Falus, A. (2000). AUTOCRINE AND PARACRINE REGULATION BY CYTOKINES AND GROWTH FACTORS IN MELANOMA. Cytokine, 12(6), 547-554. doi:10.1006/cyto.1999.0614Sansone, P., & Bromberg, J. (2012). Targeting the Interleukin-6/Jak/Stat Pathway in Human Malignancies. Journal of Clinical Oncology, 30(9), 1005-1014. doi:10.1200/jco.2010.31.8907Arrigo, A.-P. (1999). Gene expression and the thiol redox state. Free Radical Biology and Medicine, 27(9-10), 936-944. doi:10.1016/s0891-5849(99)00175-6Antelmann, H., & Helmann, J. D. (2011). Thiol-Based Redox Switches and Gene Regulation. Antioxidants & Redox Signaling, 14(6), 1049-1063. doi:10.1089/ars.2010.3400Leibowitz, B., & Yu, J. (2010). Mitochondrial signaling in cell death via the Bcl-2 family. Cancer Biology & Therapy, 9(6), 417-422. doi:10.4161/cbt.9.6.11392Powe, D. G., Voss, M. J., Habashy, H. O., Zänker, K. S., Green, A. R., Ellis, I. O., & Entschladen, F. (2011). Alpha- and beta-adrenergic receptor (AR) protein expression is associated with poor clinical outcome in breast cancer: an immunohistochemical study. Breast Cancer Research and Treatment, 130(2), 457-463. doi:10.1007/s10549-011-1371-zPowe, D. G., & Entschladen, F. (2011). Using β-blockers to inhibit breast cancer progression. Nature Reviews Clinical Oncology, 8(9), 511-512. doi:10.1038/nrclinonc.2011.12

Leucemia linfocítica crônica: anormalidades cromossômicas e a sua relação com o estágio clínico CD38 e o ZAP-70

Chronic lymphocytic leukemia is the most prevalent type of leukemia in the West. It is characterized by an extremely variable clinical course. The aim of the study was to detect the most frequent chromosomal abnormalities in patients with CLL using FISH, and assess them regarding age, gender, clinical stage and CD38 and ZAP-70 expressions. We found 51.7% of the patients with chromosome abnormalities. The most frequent one was del 13q14 in 34.5% of cases. It was associated to other alterations in 17.2%. 17p13 deletions were found in 17.2% and trisomy 12 in 13.8% (in isolation in 6.9% and associated to del 13q14, in 6.9% of the cases). An 11q22 deletion was found in one case associated to a 13q14 deletion. To better evaluate the relationship between chromosome aberrations and other prognostic factors in CLL, two cytogenetics groups were considered: favorable (13q deletion in isolation and no alteration) and unfavorable outcomes (trisomy 12, 17p13 deletion, 11q22 deletion and two simultaneous alterations).The unfavorable alterations were more frequently seen among young individuals (<60y). There were more females (70%) than males in this group (p=0.04). In relation to the Binet's staging system, patients with unfavorable cytogenetic alterations, tended to be B and C stages, while in the favorable group prevailed patients in stage A. Additionally, patients with poor prognostic cytogenetics tended to express CD38 and ZAP-70 proteins.A leucemia linfocítica crônica (LLC) é o tipo de leucemia mais prevalente no Ocidente e é caracterizada por curso clínico extremamente variável. O objetivo deste estudo foi detectar as anomalias cromossômicas mais freqüentes em pacientes com LLC, empregando a técnica FISH, e correlacioná-las com idade, sexo, estádio clínico, expressão de CD 38 e ZAP-70. Foram encontradas alterações cromossômicas em 51,7% dos pacientes. A mais freqüente foi a del 13q14, observada em 34,5% dos casos e que esteve associada a outras anomalias em 17,2%. Deleção 17p13 foi encontrada em 17,2% e trissomia 12 em 13,8% (isolada em 6,9% e associada à del 13q14 em 6,9%). Deleção 11q22 foi observada em um caso em concomitância à del 13q14. Para melhor avaliar a relação entre alteração cromossômica e outros fatores prognósticos em LLC, dois grupos citogenéticos foram considerados: favorável (deleção 13q isolada e ausência de alterações) e desfavorável (trissomia 12, deleção 17p13, deleção 11q22 e duas anomalias simultâneas). As alterações desfavoráveis foram mais freqüentemente observadas em indivíduos jovens (<60 anos) e em mulheres (70%)(p=0,04). Em relação ao sistema de estadiamento de Binet, houve tendência dos pacientes com alterações cromossômicas desfavoráveis apresenteram-se nos estágios B e C enquanto no grupo favorável prevaleceram aqueles com estágio A. Em adição, pacientes com achados citogenéticos de prognóstico desfavorável tiveram tendência a expressar proteínas CD 38 e ZAP-70.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Characteristics of two conditioning regimens cyclophosphamide plus antithymocyte globulin versus cyclophosphamide plus busulfan in allogeneic stem cell transplantation for severe aplastic anemia

Universidade Federal de São Paulo, São Paulo, BrazilHosp Santa Marcelina, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc