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1.
Am J Surg Pathol ; 47(1): 81-90, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36001451

RESUMO

Classic Hodgkin lymphoma (CHL) patients may infrequently present with a prior or recurrent disease with discordant histology resembling non-Hodgkin lymphomas. These include primary mediastinal large B-cell lymphoma (PMBL), diffuse large B-cell lymphoma (DLBCL), or mediastinal gray-zone lymphoma (MGZL). Such patients are often refractory to standard therapy and their diagnosis is hampered by significant morphologic and immunophenotypic overlap and insufficient molecular data. Among 509 CHL patients seen at an academic medical center, 6 patients had a prior or subsequent diagnosis different from CHL. Paired tissue samples were evaluated by targeted mutational analysis using a 164-gene panel. Our findings show multiple shared variants indicative of a clonal relationship between the CHL and the PMBL, DLBCL, or MGZL diagnoses. Most frequent mutated genes included TNFAIP3 (4 of 6, 66.7%), STAT6 (3 or 6, 50%), ARID1A (3 of 6, 50%), and XPO1 (3 of 5, 60%). Three patients showed the same oncogenic variant within the XPO1 gene (E571K), and mutations in TNFAIP3 and B2M were observed in 2 of the 5 patients with shared variants. In addition, differences in the mutation profile between the lymphoma pairs were also observed, which could represent clonal evolution. Mutational profiling could be of benefit in patients with recurrent/refractory disease with discordant histology, where the clonal relationship could be helpful to inform and guide therapeutic decisions. These findings provide further evidence of a true biological continuum surrounding CHL, PMBL, DLBCL, and MGZL and shed light on underlying genetic events and their clinical impact.


Assuntos
Doença de Hodgkin , Linfoma Difuso de Grandes Células B , Neoplasias do Mediastino , Humanos , Neoplasias do Mediastino/genética , Neoplasias do Mediastino/terapia , Neoplasias do Mediastino/diagnóstico , Doença de Hodgkin/diagnóstico , Linfoma Difuso de Grandes Células B/patologia , Imunofenotipagem , Mutação
2.
J Natl Compr Canc Netw ; 19(9): 1079-1109, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34551384

RESUMO

The NCCN Guidelines for Acute Lymphoblastic Leukemia (ALL) focus on the classification of ALL subtypes based on immunophenotype and cytogenetic/molecular markers; risk assessment and stratification for risk-adapted therapy; treatment strategies for Philadelphia chromosome (Ph)-positive and Ph-negative ALL for both adolescent and young adult and adult patients; and supportive care considerations. Given the complexity of ALL treatment regimens and the required supportive care measures, the NCCN ALL Panel recommends that patients be treated at a specialized cancer center with expertise in the management of ALL This portion of the Guidelines focuses on the management of Ph-positive and Ph-negative ALL in adolescents and young adults, and management in relapsed settings.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Humanos , Imunofenotipagem , Oncologia , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto Jovem
3.
Hematol Oncol Stem Cell Ther ; 14(3): 246-251, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32199933

RESUMO

Despite improvements in first-line treatment of T-cell acute lymphoblastic leukemia (T-ALL), the outcome of relapsed T-ALL remains dismal with less than 7% achieving a long-term survival. Thus, there is an unmet need for new treatment strategies to improve outcomes in this setting. Suppression of apoptosis is one of the hallmarks of anticancer drug resistance. Hence, over the past few years, antiapoptotic proteins have become an attractive target for therapeutic intervention in several hematologic malignancies. Venetoclax (ABT-199) is a novel, orally bioavailable small-molecule inhibitor of B-cell lymphoma 2 (BCL-2), a key regulator of the intrinsic apoptotic pathway. Recent preclinical studies have suggested that inhibition of BCL-2 may be a novel therapeutic strategy for patients with T-ALL. Herein, we report a case of clinical response to venetoclax in combination with a hypomethylating agent in a patient with relapsed T-ALL after allogeneic stem cell transplant and review the existing literature.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Transplante de Células-Tronco , Adulto , Aloenxertos , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Decitabina/administração & dosagem , Feminino , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Recidiva , Sulfonamidas/administração & dosagem
4.
Br J Haematol ; 189(5): e211-e213, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32236943
5.
Biol Blood Marrow Transplant ; 26(6): 1154-1159, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32105830

RESUMO

Hematopoietic stem cell transplantation (HCT) survivors are burdened by a high prevalence and early onset of chronic diseases. Healthy dietary patterns have been associated with lower risks of chronic health conditions in the general population. HCT survivors are susceptible to multiple complications that may result in chronic illness. Unfortunately, no study to date has comprehensively documented the adherence of HCT survivors to the Dietary Guidelines for Americans (DGA), which are designed specifically to provide guidance for making healthy food choices. The primary aim of this study was to evaluate diet quality and nutrient intake adequacy of HCT survivors. A secondary aim was to assess these survivors' willingness to take part in a future dietary intervention. The dietary intake of adults who had undergone autologous or allogeneic HCT for a hematologic disease and were at least 1 year post-transplantation was assessed using the Block 2014 food frequency questionnaire, and diet quality was estimated using the Healthy Eating Index 2015. Nutrient intake adequacies of the group were estimated by the estimated average requirement cutpoint method. Survivors' (n = 90) HEI-2015 scores averaged 61.6 ± 1.1. Adherence to a good-quality diet was reported by only 10% of survivors. Intakes of vitamins A, C, and D, as well as magnesium and calcium, suggested inadequacy. Fiber intake at 8.9 g per 1000 kcal/day fell below the recommended adequate intake. "Change in taste" was associated with lower quality of diet (P = .02). HCT survivors within 2 years post-transplantation were more receptive than survivors beyond 2 years to participating in a dietary intervention (95% versus 65%; P = .0013). Adult HCT survivors reported less-than-optimal adherence to the 2015-2020 DGA and had numerous shortfall nutrient intakes; however, their willingness to participate in a dietary intervention was relatively high. These findings reinforce the need to incorporate nutrition into HCT survivor care.


Assuntos
Dieta , Transplante de Células-Tronco Hematopoéticas , Adulto , Ingestão de Alimentos , Ingestão de Energia , Humanos , Sobreviventes
6.
Middle East Afr J Ophthalmol ; 26(2): 95-100, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31543667

RESUMO

PURPOSE: The purpose of the study is to determine the safety and efficacy of corneal collagen cross-linking for keratoconus in pediatric patients with and without vernal keratoconjunctivitis (VKC). METHODS: This is a retrospective analysis of 89 eyes of 58 patients <18 years of age that underwent corneal collagen cross-linking for progressive keratoconus; inclusion criteria included a minimum of 2-year follow-up after cross-linking. The main outcomes measures included keratometry, pachymetry, vision, and complications following epithelial-off cross-linking with the Dresden protocol. RESULTS: VKC patients were more likely to be male; 81.6% of the non-VKC patients and 96.3% of VKC patients were male (P = 0.038). Comparing pretreatment to the 2-year follow-up, there was no statistically significant change in the mean steep or flat keratometry, corneal thickness, and uncorrected visual acuity or best spectacle-corrected visual acuity in either group. There were no statistically significant differences in the mean visual, keratometric, or adverse event outcomes between the two groups. The proportion exhibiting progression of ectasia at 2 years was 18.5% in the VKC group and 16.7% in the non-VKC group (P = 0.83). CONCLUSIONS: Cross-linking appears to be as safe and effective in pediatric patients with vernal keratoconjunctivits as in those without, with similar outcomes, adverse events, and progression of keratoconus after treatment. The proportion of patients exhibiting progression appears to be higher in pediatric patients than adults, and there is an association between male sex and diagnosis of VKC.


Assuntos
Conjuntivite Alérgica/tratamento farmacológico , Substância Própria/metabolismo , Reagentes de Ligações Cruzadas , Ceratocone/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/uso terapêutico , Adolescente , Criança , Colágeno/metabolismo , Conjuntivite Alérgica/metabolismo , Paquimetria Corneana , Topografia da Córnea , Dilatação Patológica , Progressão da Doença , Feminino , Seguimentos , Humanos , Ceratocone/metabolismo , Masculino , Fármacos Fotossensibilizantes/efeitos adversos , Exame Físico , Estudos Retrospectivos , Riboflavina/efeitos adversos , Raios Ultravioleta , Acuidade Visual
7.
Cancer Genet ; 239: 33-35, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31520998

RESUMO

Familial adenomatous polyposis (FAP) is an autosomal dominant condition that predisposes to multiple malignancies, most commonly colorectal carcinoma, but has rarely been associated with lymphoma. We discuss one patient found to have Burkitt-like Lymphoma (BLL) with 11q aberration in the setting of previously undiagnosed FAP. We review the literature of FAP and associated malignancies and the provisional WHO classification of Burkitt-like lymphoma with 11q aberration. Both FAP and Burkitt-like lymphoma with 11q aberration involve perturbation of the MYC network and this may provide insight into a connection between these two diagnoses. However, further study is needed to elucidate if there is an increased risk of BLL and other subtypes of lymphoma among patients with FAP in order to provide optimal counseling and surveillance for patients with FAP.


Assuntos
Polipose Adenomatosa do Colo , Linfoma de Burkitt , Abdome/diagnóstico por imagem , Abdome/patologia , Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/genética , Adolescente , Linfoma de Burkitt/complicações , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/genética , Aberrações Cromossômicas , Humanos , Masculino
8.
J Clin Apher ; 33(1): 29-37, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28556233

RESUMO

BACKGROUND: Peripheral blood stem cell (PBSC) mobilization is routinely undertaken prior to autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). A number of studies have identified risk factors for poor PBSC mobilization, however, little data exists to correlate mobilization with disease-specific outcomes in this patient population. Prospective work in MM has demonstrated similar outcomes in a homogenous patient population. METHODS: In this single institution analysis, we retrospectively studied the impact of poor PBSC mobilization on progression free survival (PFS) and OS in MM patients undergoing PBSC mobilization. Poor mobilizers are defined as patients that collected < 4 × 106 CD34+ cells/kg over maximum of 5 apheresis days, or those that required ≥2 mobilization cycles to achieve this target. RESULTS: We confirm that poor PBSC mobilization is significantly associated with a shortened PFS (P = .0012) and OS (P = .0005) compared with good mobilizers. Our univariate analysis also shows that independent risk factors for poor mobilization include male gender, higher ideal body weight, and a greater median number of lines of chemotherapy prior to PBSC mobilization. However, by multivariate analysis, only number of prior lines of chemotherapy remains significantly predictive of poor mobilization (Odds ratio 1.857, P = .0095). The use of high-dose G-CSF (> 10 mcg/kg/day) and/or plerixafor can significantly improve mobilization and ASCT chances in this population. DISCUSSION: These data indicate that poor mobilization can be predictable and is associated with more aggressive disease biology and worse outcomes, warranting intensive post-ASCT management.


Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Células-Tronco de Sangue Periférico/citologia , Estudos Retrospectivos , Análise de Sobrevida , Transplante Autólogo , Adulto Jovem
9.
Middle East Afr J Ophthalmol ; 24(3): 156-158, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29279657

RESUMO

A 55-year-old male presented with reduced vision due to senile cataract. The patient consented to undergo real-time intraoperative anterior segment-optical coherence tomography (AS-OCT) during phacoemulsification with intraocular lens (IOL) implantation. Images were captured at various points during the surgery. The use of AS-OCT incorporated into the surgical microscope was evaluated as an adjunct to cataract surgery. We were able to successfully evaluate, in real-time, wound architecture, the attachment of Descemet's membrane, the posterior capsule, and IOL position. Real-time AS-OCT can be used to proactively address potential complications and verify IOL placement intraoperatively.


Assuntos
Catarata/diagnóstico por imagem , Microscopia/instrumentação , Facoemulsificação , Cirurgia Assistida por Computador , Tomografia de Coerência Óptica/instrumentação , Humanos , Período Intraoperatório , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade
10.
Case Rep Hematol ; 2017: 7815095, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28270940

RESUMO

Chronic myeloid leukemia (CML) and mantle cell lymphoma (MCL) are hematologic malignancies that originate from different oligopotent progenitor stem cells, namely, common myeloid and lymphoid progenitor cells, respectively. Although blastic transformation of CML can occur in the lymphoid lineage and CML has been related to non-Hodgkin lymphoma on transformation, to our knowledge, de novo and synchronous occurrence of CML and MCL has not been reported. Herein, we report the first case of synchronous CML and MCL in an otherwise healthy 38-year-old man. Potential etiologies and pathological relationships between the two malignancies are explored, including the possibility that the downstream effects of BCR-ABL may link it to an overexpression of cyclin D1, which is inherent to the etiology of MCL.

11.
Middle East Afr J Ophthalmol ; 23(4): 329-331, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27994401

RESUMO

A 25-year-old Syrian male with a previous episode of Stevens-Johnson syndrome with bilateral corneal cicatrization previously underwent surgery for Type 1 Boston Keratoprosthesis (K-Pro). Sixteen months after the K-Pro surgery, the patient presented with decreased vision to hand motion and microbial keratitis of the graft around the K-Pro with purulent discharge. Corneal scrapings were nonrevealing. B-scan in 3 days showed increased debris in the vitreous cavity and thickened retinochoroidal layer. Intravitreal tap and injections of vancomycin and ceftazidime were performed. The vitreous culture revealed ß-hemolytic Streptococcus agalactiae; fungal cultures were negative. Repeat B-scan 3 days later demonstrated decreased vitreous opacity, and the patient felt more comfortable and was without pain. His visual acuity improved to 20/70, ocular findings have been stable for 9 months, and the patient continues to be monitored.


Assuntos
Bioprótese , Córnea , Endoftalmite/microbiologia , Infecções Oculares Bacterianas/microbiologia , Síndrome de Stevens-Johnson/cirurgia , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/isolamento & purificação , Adulto , Antibacterianos/uso terapêutico , Ceftazidima/uso terapêutico , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/microbiologia , Combinação de Medicamentos , Endoftalmite/diagnóstico , Endoftalmite/tratamento farmacológico , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Humanos , Masculino , Implantação de Prótese , Estudos Retrospectivos , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico , Vancomicina/uso terapêutico , Corpo Vítreo/microbiologia
12.
Middle East Afr J Ophthalmol ; 23(3): 259-61, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27555712

RESUMO

We present a unique method of retrocorneal membrane removal with a femtosecond laser (FSL). A 22-year-old male who had undergone penetrating keratoplasty had a retained retrocorneal membrane and a double anterior chamber postoperatively. The membrane was dissected completely with the FSL and the free-floating membrane was removed. Histopathological evaluation confirmed the diagnosis of retained Descemets membrane (DM). There was improvement in uncorrected visual acuity from 20/300 to 20/50. Central corneal endothelial cell count was 810 cells/mm(2) preoperatively and 778 cells/mm(2) postoperatively. Inadvertent retention of DM may be safely treated with the FSL. Clarity and viability of the existing graft can be maintained.


Assuntos
Lâmina Limitante Posterior/cirurgia , Ceratocone/cirurgia , Ceratoplastia Penetrante , Terapia a Laser/métodos , Complicações Pós-Operatórias , Câmara Anterior/patologia , Lâmina Limitante Posterior/diagnóstico por imagem , Lâmina Limitante Posterior/patologia , Humanos , Masculino , Microscopia Acústica , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/cirurgia , Acuidade Visual/fisiologia , Adulto Jovem
13.
Middle East Afr J Ophthalmol ; 22(3): 356-61, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26180477

RESUMO

PURPOSE: We present the visual outcomes 6 weeks following Femtosecond laser assisted cataract surgery (FLACS) and conventional phacoemulsification cataract extraction (CE) cataract surgeries in 2013. MATERIALS AND METHODS: This was a review of health record type of study. Eyes operated by FLACS and an equal number of conventional phacoemulsification (CE) on the same day by same surgeon were included in the study. Demographics, preoperative status, operative details and the best-corrected visual acuity (BCVA) at 6-8 weeks following surgery were noted. BCVA of >20/60 was considered as excellent. The rate and determinants of excellent vision were calculated. RESULT: Study population comprised of 154 eyes. Both FLACS and CL groups had 77 eyes. Visual acuity at 6-8 weeks was excellent in 44 (60%) eyes of FLACS group and 36 (40%) eyes of CE. Visual outcome following FLACS and conventional surgery was not different (Odd's ratio [OR] 1.5 [95% confidence intervals [CI]: 0.8-2.9]). Operating surgeon did not significantly influence the visual outcomes following FLACS (OR = 1.6) and CE (OR = 0.4). Association of the grade of lens opacities to the visual outcome was not affected by type of surgery (χ(2) = 0.5, P = 0.2). The duration of surgery in CE and FLACS groups was not significantly different (-3.2 min [95% CI: -13; 6.6]). CONCLUSION: Visual outcomes at 6-8 weeks following CE were not different from FLACS. Visual outcomes following FLACS and CE were not influenced by the operating surgeon or severity of the cataract. The time required for FLACS was greater than that required for CE.


Assuntos
Extração de Catarata/métodos , Terapia a Laser/métodos , Implante de Lente Intraocular , Facoemulsificação/métodos , Pseudofacia/fisiopatologia , Acuidade Visual/fisiologia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
PLoS One ; 8(12): e80060, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24312454

RESUMO

Despite intensive treatment with chemotherapy, radiotherapy and surgery, over 70% of patients with metastatic Ewing's Sarcoma Family of Tumors (EFT) will die of their disease. We hypothesize that properly characterized laboratory models reflecting the drug resistance of clinical tumors will facilitate the application of new therapeutic agents to EFT. To determine resistance patterns, we studied newly established EFT cell lines derived from different points in therapy: two established at diagnosis (CHLA-9, CHLA-32), two after chemotherapy and progressive disease (CHLA-10, CHLA-25), and two at relapse after myeloablative therapy and autologous bone marrow transplantation (post-ABMT) (CHLA-258, COG-E-352). The new lines were compared to widely studied EFT lines TC-71, TC-32, SK-N-MC, and A-673. These lines were extensively characterized with regard to identity (short tandem repeat (STR) analysis), p53, p16/14 status, and EWS/ETS breakpoint and target gene expression profile. The DIMSCAN cytotoxicity assay was used to assess in vitro drug sensitivity to standard chemotherapy agents. No association was found between drug resistance and the expression of EWS/ETS regulated genes in the EFT cell lines. No consistent association was observed between drug sensitivity and p53 functionality or between drug sensitivity and p16/14 functionality across the cell lines. Exposure to chemotherapy prior to cell line initiation correlated with drug resistance of EFT cell lines in 5/8 tested agents at clinically achievable concentrations (CAC) or the lower tested concentration (LTC): (cyclophosphamide (as 4-HC) and doxorubicin at CAC, etoposide, irinotecan (as SN-38) and melphalan at LTC; P<0.1 for one agent, and P<0.05 for four agents. This panel of well-characterized drug-sensitive and drug-resistant cell lines will facilitate in vitro preclinical testing of new agents for EFT.


Assuntos
Antineoplásicos/farmacologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sarcoma de Ewing/metabolismo , Proteína Supressora de Tumor p14ARF/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Tumoral , Inibidor p16 de Quinase Dependente de Ciclina/genética , Resistencia a Medicamentos Antineoplásicos/genética , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologia , Proteína Supressora de Tumor p14ARF/genética , Proteína Supressora de Tumor p53/genética
15.
PLoS One ; 8(7): e68416, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23894304

RESUMO

BACKGROUND: To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of irinotecan administered in combination with vincristine, temozolomide and bevacizumab in children with refractory solid tumors. METHODS: The study design included two dose levels (DL) of irinotecan given intravenously once daily for 5 consecutive days (DL1: 30 mg/m(2), and DL2: 50 mg/m(2)), combined with vincristine 1.5 mg/m(2) on days 1 and 8, temozolomide 100 mg/m(2) on days 1-5, and bevacizumab 15mg/kg on day 1, administered every 21 days for a maximum of 12 cycles. RESULTS: Thirteen patients were enrolled and 12 were evaluable for toxicity Dose limiting toxicity observed included grade 3 hyperbilirubinemia in 1 of 6 patients on DL1, and grade 3 colitis in 1 of 6 patients on DL2. DL 2 was the determined MTD. A total of 87 cycles were administered. Myelosuppression was mild. Grade 1-2 diarrhea occurred in the majority of cycles with grade 3 diarrhea occurring in only one cycle. Grade 2 hypertension developed in two patients. Severe hemorrhage, intestinal perforation, posterior leukoencephalopathy or growth plate abnormalities were not observed. Objective responses were noted in three Wilms tumor patients and one each of medulloblastoma and hepatocellular carcinoma. Five patients completed all 12 cycles of protocol therapy. CONCLUSIONS: Irinotecan 50 mg/m(2)/day for 5 days was the MTD when combined with vincristine, temozolomide and bevacizumab administered on a 21 day schedule. Encouraging anti-tumor activity was noted. TRIAL REGISTRATION: ClinicalTrials.gov; NCT00993044; http://clinicaltrials.gov/show/NCT00993044.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Adolescente , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Bevacizumab , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Criança , Pré-Escolar , Dacarbazina/efeitos adversos , Dacarbazina/análogos & derivados , Dacarbazina/farmacologia , Dacarbazina/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Humanos , Irinotecano , Masculino , Dose Máxima Tolerável , Recidiva , Temozolomida , Vincristina/efeitos adversos , Vincristina/farmacologia , Vincristina/uso terapêutico , Adulto Jovem
16.
J Pediatr ; 163(2): 601-3, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23582141

RESUMO

We describe a 12-year-old girl, simultaneously presenting with colonic adenocarcinoma and medulloblastoma from bialleic deletions in the mismatch repair gene PMS2. Her distinctive physical and clinical findings are characteristic of constitutional mismatch repair deficiency syndrome. Earlier recognition of such findings may permit better screening and more effective treatment.


Assuntos
Adenocarcinoma/genética , Adenosina Trifosfatases/genética , Neoplasias Cerebelares/genética , Neoplasias do Colo/genética , Enzimas Reparadoras do DNA/genética , Proteínas de Ligação a DNA/genética , Deleção de Genes , Meduloblastoma/genética , Neoplasias Primárias Múltiplas/genética , Alelos , Criança , Feminino , Humanos , Endonuclease PMS2 de Reparo de Erro de Pareamento
17.
PLoS One ; 8(1): e54556, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23365673

RESUMO

Ewing Family Tumors (Ewing Sarcoma and peripheral Primitive Neuroectodermal Tumor) are common bone and soft tissue malignancies of childhood, adolescence and young adulthood. Chromosomal translocation in these tumors produces fusion oncogenes of the EWS/ETS class, with EWS/FLI1 being by far the most common. EWS/ETS chimera are the only well established driver mutations in these tumors and they function as aberrant transcription factors. Understanding the downstream genes whose expression is modified has been a central approach to the study of these tumors. FOXM1 is a proliferation associated transcription factor which has increasingly been found to play a role in the pathogenesis of a wide range of human cancers. Here we demonstrate that FOXM1 is expressed in Ewing primary tumors and cell lines. Reduction in FOXM1 expression in Ewing cell lines results in diminished potential for anchorage independent growth. FOXM1 expression is enhanced by EWS/FLI1, though, unlike other tumor systems, it is not driven by expression of the EWS/FLI1 target GLI1. Thiostrepton is a compound known to inhibit FOXM1 by direct binding. We show that Thiostrepton diminishes FOXM1 expression in Ewing cell lines and this reduction reduces cell viability through an apoptotic mechanism. FOXM1 is involved in Ewing tumor pathogenesis and may prove to be a useful therapeutic target in Ewing tumors.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Fusão Oncogênica/genética , Proteína Proto-Oncogênica c-fli-1/genética , Proteína EWS de Ligação a RNA/genética , Sarcoma de Ewing/genética , Adolescente , Animais , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/metabolismo , Biópsia , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Adesão Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Criança , Proteína Forkhead Box M1 , Fatores de Transcrição Forkhead/antagonistas & inibidores , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Células NIH 3T3 , Proteínas de Fusão Oncogênica/metabolismo , Proteína Proto-Oncogênica c-fli-1/metabolismo , RNA Interferente Pequeno/genética , Proteína EWS de Ligação a RNA/metabolismo , Sarcoma de Ewing/metabolismo , Sarcoma de Ewing/patologia , Transdução de Sinais/efeitos dos fármacos , Tioestreptona/farmacologia , Translocação Genética , Adulto Jovem
18.
Cardiol Young ; 23(4): 546-52, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23040535

RESUMO

We designed a pilot study of a training module for nurses to perform rheumatic heart disease echocardiography screening in a resource-poor setting. The aim was to determine whether nurses given brief, focused, basic training in echocardiography could follow an algorithm to potentially identify cases of rheumatic heart disease requiring clinical referral, by undertaking basic two-dimensional and colour Doppler scans. Training consisted of a week-long workshop, followed by 2 weeks of supervised field experience. The nurses' skills were tested on a blinded cohort of 50 children, and the results were compared for sensitivity and specificity against echocardiography undertaken by an expert, using standardised echocardiography definitions for definite and probable rheumatic heart disease. Analysis of the two nurses' results revealed that when a mitral regurgitant jet length of 1.5 cm was used as the trigger for rheumatic heart disease identification, they had a sensitivity of 100% and 83%, respectively, and a specificity of 67.4% and 79%, respectively. This pilot supports the principle that nurses, given brief focused training and supervised field experience, can follow an algorithm to undertake rheumatic heart disease echocardiography in a developing country setting to facilitate clinical referral with reasonable accuracy. These results warrant further research, with a view to developing a module to guide rheumatic heart disease echocardiographic screening by nurses within the existing public health infrastructure in high-prevalence, resource-poor regions.


Assuntos
Insuficiência da Valva Aórtica/diagnóstico por imagem , Ecocardiografia Doppler em Cores/enfermagem , Educação em Enfermagem/métodos , Insuficiência da Valva Mitral/diagnóstico por imagem , Estenose da Valva Mitral/diagnóstico por imagem , Cardiopatia Reumática/diagnóstico por imagem , Insuficiência da Valva Aórtica/etiologia , Criança , Países em Desenvolvimento , Ecocardiografia/enfermagem , Fiji , Recursos em Saúde , Humanos , Programas de Rastreamento , Insuficiência da Valva Mitral/etiologia , Estenose da Valva Mitral/etiologia , Projetos Piloto , Padrões de Prática em Enfermagem , Cardiopatia Reumática/complicações , Sensibilidade e Especificidade
19.
Rev. AMRIGS ; 55(4): 333-338, out.-dez. 2011. tab
Artigo em Português | LILACS | ID: biblio-835383

RESUMO

A depressão é uma condição presente em 20% dos portadores de doenças crônicas, estando associada à incapacitação funcional e comprometimento da saúde física. A doença renal crônica faz parte desse escopo, com prevalência de 405 pacientes por milhão de habitantes submetidos a hemodiálise no Brasil. Objetiva-se avaliar prevalência de sintomatologia depressiva e suas características em pacientes sob tratamento dialítico. Métodos: Estudo transversal, realizado entre junho e agosto de 2010, incluindo os pacientes submetidos a hemodiálise no Hospital Geral de Caxias do Sul, que preencheram os critérios de inclusão. Procedeu-se a aplicação de instrumentos de coleta de dados. O ponto de corte para depressão foi de 16 pontos no Inventário de Depressão de Beck. O estudo foi aprovado por Comitê de Ética em Pesquisa. Resultados: A amostra foi constituída por 64 pacientes. A média de idade foi de 53,66 ± 15,82 anos; 51,7% eram do sexo feminino. A prevalência de depressão foi de 44,8%. Os pacientes com IDB < 16 apresentaram escore médio de 7,23 ± 3,5; já aqueles com IDB > 16 apresentaram média de 26,43 ± 9,35 (p < 0,001). Os pacientes que necessitavam cuidador apresentaram maiores índices de depressão (p< 0,001). Nos pacientes com IDB > 16 os fatores mais influentes foram sono, cansaço e incapacidade de tomar decisões. Conclusão: A prevalência de depressão nos pacientes em hemodiálise é alta. Os pacientes que necessitam de cuidadores apresentam maior escore no IDB. Alterações do sono, cansaço e incapacidade de tomar decisões são os principais fatores para o humor depressivo.


Depression is a condition present in 20% of patients with chronic diseases and is associated with functional disability and impaired physical health. Chronic kidney disease is part of this scope, with an estimated prevalence of 405 patients per million undergoing hemodialysis in Brazil. The objective of this study was to evaluate the prevalence of depressive symptoms and their characteristics in patients on dialysis. Methods: A cross-sectional study conducted between June and August 2010, including patients undergoing hemodialysis at the General Hospital of Caxias do Sul, who met the inclusion criteria. The data collection instruments (questionnaire, Mini Mental State Examination and the Beck Depression Inventory–BDI) were administered individually during a hemodialysis session. The cut-off point for depression was 16 points in the BDI. Results: We studied 64 patients. The mean age was 53.66 ± 15.82 years, 51.7% were females. The prevalence of depression was 44.8. Patients with BDI<16 had a mean score of 7.23 ± 3.5, whereas those with BDI>16 had an average of 26.43 ± 9.35 (p <0.001). Patients who needed caregivers had higher levels of depression (p <0.001). In patients with BDI>16, the most influent factors were sleep, fatigue and inability to make decisions. Conclusion: The prevalence of depression in hemodialysis patients is high. Patients who need caregivers had higher scores on the BDI. Sleep disorders, fatigue and inability to make decisions are the main factors for depressed mood.


Assuntos
Humanos , Depressão , Insuficiência Renal Crônica , Transtorno Depressivo
20.
J Cataract Refract Surg ; 37(6): 1140-6, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21497050

RESUMO

PURPOSE: To determine the effectiveness of a single radial suture placement in 2 clear corneal incision (CCI) configurations in preventing inflow of bacterial-sized particles. SETTING: Wilmer Eye Institute, Baltimore, Maryland, USA. DESIGN: Experimental study. METHODS: Ten human globes were used. Two 25-gauge needles connected to a saline solution bag and to a digital manometer were inserted through the limbus 120 degrees apart. Four incision-suture combinations were evaluated sequentially in each cornea. All incisions had the same dimensions (2.75 mm width, 3.00 mm length). Two incisions were single plane, and 2 were biplane. One incision from each configuration was left unsutured, and the other was sutured (10-0 nylon). With a preset 10 mm Hg intraocular pressure (IOP), India ink was applied to the incision site and a sudden IOP fluctuation was induced. Inflow was outlined and measured by planimetry. RESULTS: There was a significant increase in area and linear distance of India-ink inflow after pressure challenge in all groups (P < .05), but with important differences among them. When the sutured and unsutured groups from each CCI were compared, there was a significantly smaller area of inflow in the 2-step unsutured group (P < .05). The linear inflow was higher in both sutured groups; however, the difference was significant for the 2-step incision configuration only (P < .05). CONCLUSIONS: A single radial suture reduced the area of inflow of bacterial-sized particles but increased the linear distance of inflow in single-plane 3.0 mm incisions. Suture placement in a stepped incision increased inflow of bacterial-sized particles. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.


Assuntos
Carbono/metabolismo , Extração de Catarata , Córnea/metabolismo , Córnea/cirurgia , Deiscência da Ferida Operatória/metabolismo , Técnicas de Sutura , Humanos , Pressão Intraocular , Modelos Biológicos , Nylons , Suturas , Cicatrização/fisiologia
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