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Find video protocols related to scientific articles indexed in Pubmed.
Phase I trial of a novel anti-GD2 monoclonal antibody, Hu14.18K322A, designed to decrease toxicity in children with refractory or recurrent neuroblastoma.
J. Clin. Oncol.
PUBLISHED: 04-07-2014
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The addition of immunotherapy, including a combination of anti-GD2 monoclonal antibody (mAb), ch14.18, and cytokines, improves outcome for patients with high-risk neuroblastoma. However, this therapy is limited by ch14.18-related toxicities that may be partially mediated by complement activation. We report the results of a phase I trial to determine the maximum-tolerated dose (MTD), safety profile, and pharmacokinetics of hu14.18K322A, a humanized anti-GD2 mAb with a single point mutation (K322A) that reduces complement-dependent lysis.
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Ethical considerations for pharmacogenomic testing in pediatric clinical care and research.
Pharmacogenomics
PUBLISHED: 06-23-2011
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The information gained from pharmacogenomic testing is becoming increasingly recognized as an opportunity to improve our current dosing strategies for children. The identification of gene polymorphisms that influence drug disposition and effect can be used to help predict a childs susceptibility to toxicity and/or response to a particular drug or therapeutic regimen. However, the potential consequences of performing genomic analysis in children raise important ethical considerations. Although the level of risk introduced remains partially hypothetical, awareness of the ethical concerns and protective legislation will be an important part of fully informing patients, families, clinicians, and researchers about the risks and benefits of pharmacogenomic testing in children. Where it can be done without loss of benefit, risk reduction is a moral imperative, and so the ethical complexities related to pharmacogenomics must be addressed in an ongoing way as we continue to learn more about the value of the technology to children.
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Spontaneous resolution of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.
Pediatr Blood Cancer
PUBLISHED: 09-01-2010
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Secondary hemophagocytic lymphohistiocytosis (sHLH) is a reactive, proliferative disorder of the immune system resulting in lymphohistiocytic proliferation, hemophagocytosis, and cytokine dysregulation. The most common infectious trigger in sHLH is Epstein-Barr virus (EBV-HLH). Current treatment protocols for EBV-HLH have a cure rate of approximately 75%; however, there are significant toxicities associated with these therapies. We present two patients with EBV-HLH who experienced spontaneous resolution of their disease prior to the initiation of therapy, suggesting there may be a subgroup of patients with EBV-HLH who do well with conservative management and can avoid potentially toxic therapies.
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Impact of continuous renal replacement therapy on oxygenation in children with acute lung injury after allogeneic hematopoietic stem cell transplantation.
Pediatr Blood Cancer
PUBLISHED: 07-27-2010
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Acute lung injury (ALI) continues to carry a high mortality rate in children after allogeneic hematopoietic stem cell transplant (HSCT). Continuous renal replacement therapy (CRRT) is often used for these patients for various indications including renal failure and fluid overload, and may have a beneficial effect on oxygenation and survival. Therefore, we sought to determine the effect of CRRT on oxygenation in mechanically ventilated pediatric allogeneic HSCT patients with ALI, and to document survival to intensive care unit discharge in this at-risk population receiving both mechanical ventilation and CRRT.
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Outcomes of hematopoietic stem cell transplant patients who received continuous renal replacement therapy in a pediatric oncology intensive care unit.
Pediatr Crit Care Med
PUBLISHED: 05-25-2010
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To assess the long-term benefits of continuous renal replacement therapy (CRRT) in this patient population and to analyze factors associated with survival. Hematopoietic stem cell transplantation is being utilized as curative therapy for a variety of disorders. However, organ dysfunction is commonly associated with this therapy. Continuous renal replacement therapy (CRRT) is increasingly being used in the treatment of this multiorgan dysfunction.
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Availability of palliative care services for children with cancer in economically diverse regions of the world.
Eur. J. Cancer
PUBLISHED: 03-23-2010
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We assessed the availability and quality of palliative care for children with cancer according to national income per capita.
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Anti-GD2 antibody therapy for GD2-expressing tumors.
Curr Cancer Drug Targets
PUBLISHED: 03-06-2010
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In the development of novel immune therapies for high-risk cancers, one goal is to find tumor targets that are not widely shared by normal cells. One such target is the surface disialoganglioside GD2. This antigen is expressed on the surface of a variety of tumors for which no curative therapies exist for patients with advanced disease. In childhood, the most common GD2-expressing tumor is neuroblastoma. GD2 is also expressed on several other high-risk tumors, including those of neuroectodermal or epithelial origin, virtually all melanomas, and approximately 50% of tumor samples from osteosarcoma and soft-tissue sarcomas. Because of the tumor-selective expression of this molecule, it is an attractive target for tumor-specific therapies such as antibody therapy. Over the last 2 decades, several anti-GD2 antibodies have been developed. To reduce both the toxicity of the antibody and the development of human anti-mouse antibodies (HAMA), research efforts have primarily focused on exploring anti-GD2 antibodies that have progressively more human elements while at the same time reducing the mouse components. This review will examine antibodies currently undergoing clinical testing as well as the most recent advances to improve antibody therapy for patients with GD2-expressing tumors.
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Agency and communication challenges in discussions of informed consent in pediatric cancer research.
Qual Health Res
PUBLISHED: 02-12-2010
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In this article we examine the discourse of four focus groups we conducted at a pediatric research hospital in which we queried teenage patients, parents, nurses, and physicians about their perceptions of the informed consent process in research. Autonomy, as the goal of informed consent, is a murky concept, with some ethicists questioning the possibility that it can ever be attained. We argue that it might be more productive to consider agency, which we define as language and action that are constructed, negotiated, and maintained through effective communication. Our goal was to understand how individuals rhetorically constructed agency in discussions of informed consent experiences. After transcribing and coding the focus group interviews, we identified six aspects of agency in participants discourse: (a) defining roles, (b) seeking information, (c) providing information, (d) supporting others, (e) making decisions, and (f) claiming agency for self. Examining these aspects of agency indicated that efforts to improve the informed consent process must address: (a) status differentials, (b) role definitions, (c) information flow, and (d) relationships.
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Anti-GD(2) with an FC point mutation reduces complement fixation and decreases antibody-induced allodynia.
Pain
PUBLISHED: 01-27-2010
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Monoclonal antibodies against GD(2) ganglioside, such as ch14.18, the human-mouse chimeric antibody, have been shown to be effective for the treatment of neuroblastoma. However, treatment is associated with generalized, relatively opiate-resistant pain. We investigated if a point mutation in ch14.18 antibody (hu14.18K332A) to limit complement-dependent cytotoxicity (CDC) would ameliorate the pain behavior, while preserving antibody-dependent cellular cytotoxicity (ADCC). In vitro, CDC and ADCC were measured using europium-TDA assay. In vivo, allodynia was evaluated by measuring thresholds to von Frey filaments applied to the hindpaws after injection of either ch14.18 or hu14.18K332 into wild type rats or rats with deficient complement factor 6. Other rats were pretreated with complement factor C5a receptor antagonist and tested following ch14.18 injection. The mutation reduces the antibodys ability to activate complement, while maintaining its ADCC capabilities. Injection of hu14.18K322 (1 or 3mg/kg) produced faster resolving allodynia than that engendered by ch14.18 (1mg/kg). Injection of ch14.18 (1mg/kg) into rats with C6 complement deficiency further reduced antibody-induced allodynia, while pre-treatment with complement factor C5a receptor antagonist completely abolished ch14.18-induced allodynia. These findings showed that mutant hu14.18 K322 elicited less allodynia than ch14.18 and that ch14.18-elicited allodynia is due to activation of the complement cascade: in part, to formation of membrane attack complex, but more importantly to release of complement factor C5a. Development of immunotherapeutic agents with decreased complement-dependent lysis while maintaining cellular cytotoxicity may offer treatment options with reduced adverse side effects, thereby allowing dose escalation of therapeutic antibodies.
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Decision-making by adolescents and parents of children with cancer regarding health research participation.
Pediatrics
PUBLISHED: 08-10-2009
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Low rates of participation of adolescents and young adults (AYAs) in clinical oncology trials may contribute to poorer outcomes. Factors that influence the decision of AYAs to participate in health research and whether these factors are different from those that affect the participation of parents of children with cancer.
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Iron overload in survivors of childhood leukemia after allogeneic hematopoietic stem cell transplantation.
Pediatr Transplant
PUBLISHED: 08-07-2009
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Iron overload has not been studied extensively and prospectively in pediatric survivors of allogeneic hematopoietic stem cell transplantation (HSCT); therefore, we conducted a prospective long-term study of 133 survivors of childhood leukemia to assess the incidence of and risk factors for iron overload and to investigate its association with organ dysfunction. One yr after HSCT, the mean serum ferritin level was 1158 ng/mL (range, 22-3264 ng/mL), with 124 patients (93.2%) having a serum ferritin level that exceeded the upper limit of the normal range (110 ng/mL). Thereafter, the serum ferritin level declined over time. There was a positive correlation between the level of serum ferritin and that of total bilirubin (r = 0.21, p < 0.001) and glutamate pyruvate transaminase (r = 0.17, p < 0.001). A high concentration of serum ferritin was associated with low cardiac fractional shortening (r = -0.15, p = 0.047). In addition, patients with hypothyroidism and GH deficiency had a higher level of serum ferritin than those without (p < 0.02). We conclude that iron overload is common after HSCT and is associated with hepatic, cardiac, and endocrine dysfunction.
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Immune therapies for neuroblastoma.
Cancer Biol. Ther.
PUBLISHED: 05-09-2009
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Neuroblastoma, a solid tumor arising from developing cells of the sympathetic nervous system, is the most common extracranial tumor in children. The prognosis for high-risk neuroblastoma remains poor with conventional treatment, and new approaches are therefore being explored to treat this disease. One such alternative therapy that holds promise is immune therapy. We review here the recent advances in four types of immune therapy-cytokine, vaccine, antibody and cellular therapy-to treat neuroblastoma. We present preclinical research and clinical trials on several promising candidates such as IL-12, dendritic cell vaccines, anti-GD2 antibodies and allogeneic hematopoietic stem cell transplant. An optimal treatment plan for neuroblastoma will most likely involve multimodal approaches and combinations of immune therapies.
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Challenges faced by research ethics committees in El Salvador: results from a focus group study.
Dev World Bioeth
PUBLISHED: 04-18-2009
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To identify perceived barriers to capacity building for local research ethics oversight in El Salvador, and to set an agenda for international collaborative capacity building.
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Clinical utility of computed tomography screening of chest, abdomen, and sinuses before hematopoietic stem cell transplantation: the St. Jude experience.
Biol. Blood Marrow Transplant.
PUBLISHED: 02-12-2009
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All allogeneic (allo) and autologous (auto) hematopoietic stem cell transplantation (HSCT) recipients at St. Jude Childrens Research Hospital undergo pre-HSCT computed tomography (CT) of the sinuses, chest, and abdomen because they are at significant risk for opportunistic infections. We studied whether this extensive routine imaging is warranted to detect infection despite the risk of additional radiation exposure. We reviewed the medical records of all children receiving allo- and auto-HSCT at St. Jude in 2004 and 2005. Of the 184 eligible patients who received 187 transplants, 131 received allografts and 56 autografts. Solid tumors and lymphomas were removed from the final analysis of the chest and abdomen CT as this imaging is typically warranted as part of disease restaging; thus, 111 allogeneic participants were included in this analysis. Both auto- and allo-recipients were evaluated by sinus CT and included in this final analysis. Most allo- and auto-HSCT recipients (> or =80%) did not have sinus, pulmonary, cardiac, or gastrointestinal symptoms; >85% of the evaluable allo-recipients had no prior fungal infection. Eighty-eight allo- and 31 auto-HSCT recipients had abnormal sinus CT findings, all unrelated to the underlying disease. Sixty-two (55.9%) of the allo-recipients had normal chest CT and 85 (76.6%) had normal abdominal CT. Of the 18 allo-recipients who began new therapy based on these findings, only 2 (11.1%) were related to chest CT findings and the other 16 were related to sinus findings. Our findings suggest that pre-HSCT routine CT imaging of the abdomen may not be warranted in a subset of allogeneic recipients who are asymptomatic and without previous infectious findings. Thus, these patients may be spared unnecessary radiation exposure. Recipients undergoing auto-HSCT or allo-HSCT for lymphomas or solid tumors will routinely undergo chest and abdominal CT imaging as part of their disease evaluation. The decision to perform chest CT should be made judiciously based on a careful history and physical examination. Sinus imaging, which was frequently abnormal, may be justified in all patients to plan post-HSCT care.
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Total and active rabbit antithymocyte globulin (rATG;Thymoglobulin) pharmacokinetics in pediatric patients undergoing unrelated donor bone marrow transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-27-2009
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Rabbit antithymocyte globulin (rATG; Thymoglobulin) is currently used to prevent or treat graft-versus-host disease (GVHD) during hematopoietic stem cell transplantation (HSCT). The dose and schedule of rATG as part of the preparative regimen for unrelated donor (URD) bone marrow transplantation (BMT) have not been optimized in pediatric patients. We conducted a prospective study of 13 pediatric patients with hematologic malignancies undergoing URD BMT at St. Jude Childrens Research Hospital from October 2003 to March 2005, to determine the pharmacokinetics and toxicities of active and total rATG. The conditioning regimen comprised total body irradiation (TBI), thiotepa, and cyclophosphamide (Cy); cyclosporine (CsA) and methotrexate (MTX) were administered as GVHD prophylaxis. Patients received a total dose of 10 mg/kg rATG, and serial blood samples were assayed for total rATG by enzyme linked immunosorbent assay (ELISA) and active rATG by florescein activated cell sorting (FACS). We found that our weight-based dosing regimen for rATG was effective and well tolerated by patients. The half-lives of total and active rATG were comparable to those from previous studies, and despite high doses our patients had low maximum concentrations of active and total rATG. There were no occurrences of grade iii-iv GVHD even in patients having low peak rATG levels, and the overall incidence of grade II GVHD was only 15%. None of the patients had serious infections following transplantation. These data support the use of a 10 mg/kg dose of rATG in children with hematologic malignancies because it can be administered without increasing the risk of graft rejection, or serious infection in pediatric patients with a low rate of GVHD. These conclusions may not apply to patients with nonmalignant disorders.
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Providing research results to participants: attitudes and needs of adolescents and parents of children with cancer.
J. Clin. Oncol.
PUBLISHED: 01-21-2009
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There is an increasing demand for researchers to provide research results to participants. Our aim was to define an appropriate process for this, based on needs and attitudes of participants.
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64Cu-p-NH2-Bn-DOTA-hu14.18K322A, a PET radiotracer targeting neuroblastoma and melanoma.
J. Nucl. Med.
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The hu14.18K322A variant of the GD2-targeting antibody hu14.18 has been shown to elicit a level of antibody-dependent cell-mediated cytotoxicity toward human neuroblastoma cells similar to that of the parent antibody. However, hu14.18K322A exhibited a decreased complement activation and associated pain, the dose-limiting toxicity in neuroblastoma immunotherapy. PET with a radiolabeled analog of the same antibody used in treatment will provide insight into the ability of hu14.18K322A to reach its target, as well as nontarget uptake that may cause side effects. Such antibody radiotracers might also provide a method for measuring GD2 expression in tumors, thus enabling the prediction of response to anti-GD2 therapy for individual patients.
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Addressing parental bereavement support needs at the end of life for infants with complex chronic conditions.
J Palliat Med
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Health care providers understandings of parental bereavement needs before and in the acute period following the death of an infant with a complex chronic condition are based upon models that outline the process of grief and provide direction for possible points of intervention. These models do not address prospective factors along the illness trajectory that may contribute to the depth and debilitating nature of grief, and fail to clarify the influence of social structures on parents experience and construct of grief, loss, and mourning. The purpose of this study was to prospectively describe the bereavement experience of parents whose infants die in acute care settings with a complex chronic condition.
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Association of IL-1? -511 polymorphism with severe veno-occlusive disease in pediatric-matched allogeneic hematopoietic stem cell transplantation.
J. Pediatr. Hematol. Oncol.
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Single nucleotide polymorphisms (SNPs) of the interleukin 1 (IL-1) family have been implicated in acute graft-versus-host disease and mortality postallogeneic hematopoietic stem cell transplantation (HSCT) in adults. Hepatic veno-occlusive disease (VOD) is a well-known complication of HSCT and can result in an increased risk of mortality. In this study, we sought to investigate the association of both patient and donor genotypes at the IL-1? -511 cytidine/thymidine (C/T) polymorphic site with hepatic VOD and mortality in an exclusive pediatric cohort undergoing matched myeloablative allogeneic HSCT. Donor TT genotype was associated with higher cumulative incidence of grade III-IV hepatic VOD at 3 months after transplantation relative to donor CT and CC genotypes (25±13.1% in TT, 2.9±2.9% in CT, and 3.6±3.6% in CC; P=0.024). Neither recipient nor donor IL-1? -511 single nucleotide polymorphisms genotypes were associated with mortality or relapse. Our findings suggest that donor, rather than host, genotype at the IL-1? -511 polymorphic site may associate with higher risk for severe VOD after matched allogeneic HSCT. Our findings challenge the assumption that host factors are exclusively responsible for VOD and suggest a novel role for the donor inflammasome pathway in inducing injury and microvascular disease after HSCT, which merits further study in a larger cohort analysis.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.