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Find video protocols related to scientific articles indexed in Pubmed.
Fortification of blood plasma from cancer patients with human serum albumin decreases the concentration of cisplatin-derived toxic hydrolysis products in vitro.
Metallomics
PUBLISHED: 09-26-2014
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While cisplatin (CP) is still one of the world's bestselling anticancer drugs, its intravenous administration is inherently associated with severe, dose limiting toxic side-effects. Although the molecular basis of the latter are not well understood, biochemical transformations of CP in blood and the interaction of the generated platinum species with plasma proteins likely play a critical role since these processes will ultimately determine which platinum-species reach the intended tumor cells as well as non-target cells. Compared to healthy subjects, cancer patients often have decreased plasma human serum albumin (HSA) concentrations. Little, however, is known about how the plasma HSA concentration will affect the metabolism of CP. To gain insight, we obtained blood plasma from healthy adults (n = 20, 42 ± 4 g HSA per L) and pediatric cancer patients (n = 11, 26 ± 7 g HSA per L). After the incubation of plasma at 37 °C, a pharmacologically relevant dose of CP was added and the Pt-distribution therein was determined by size-exclusion chromatography coupled on-line to an inductively coupled plasma atomic emission spectrometer. At the 2 h time point, a 5.9% increase of toxic CP-derived hydrolysis products was detected in pediatric cancer patient plasma, while 9.8% less platinum was protein bound compared to plasma from healthy controls. These in vitro results suggest that the elevated concentration of highly reactive free CP-derived hydrolysis products in plasma may cause the toxic side-effects in cancer patients. More importantly, the deliberate increase of the plasma HSA concentration in cancer patients prior to CP treatment would represent a simple strategy to possibly alleviate the fraction of patients that suffer from drug induced toxic side-effects.
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Outcomes after hematopoietic stem cell transplantation for children with I-cell disease.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-13-2014
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Mucolipidosis type II (MLII), or I-cell disease, is a rare but severe disorder affecting localization of enzymes to the lysosome, generally resulting in death before the 10th birthday. Although hematopoietic stem cell transplantation (HSCT) has been used to successfully treat some lysosomal storage diseases, only 2 cases have been reported on the use of HSCT to treat MLII. For the first time, we describe the combined international experience in the use of HSCT for MLII in 22 patients. Although 95% of the patients engrafted, overall survival was low, with only 6 patients (27%) alive at last follow-up. The most common cause of death post-transplant was cardiovascular complications, most likely due to disease progression. Survivors were globally delayed in development and often required complex medical support, such as gastrostomy tubes for nutrition and tracheostomy with mechanical ventilation. Although HSCT has demonstrated efficacy in treating some lysosomal storage disorders, the neurologic outcome and survival for patents with MLII were poor. Therefore, new medical and cellular therapies should be sought for these patients.
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Conserved behavioral and genetic mechanisms in the pre-hatching molt of the nematode Pristionchus pacificus.
Evodevo
PUBLISHED: 01-01-2014
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During development, juvenile nematodes undergo four molts. Although the number of molts appears to be constant within the Nematoda, the timing of the first molt can occur either before or after hatching. A previous study indicates that, as in some parasitic nematode lineages, a pre-hatching juvenile stage also exists in Diplogastrid nematodes. A detailed description of these sequence of events has yet to be shown for any single species.
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Allogeneic Human Mesenchymal Stem Cell Therapy (Remestemcel-L, Prochymal) as a Rescue Agent for Severe Refractory Acute Graft-versus-Host Disease in Pediatric Patients.
Biol. Blood Marrow Transplant.
PUBLISHED: 08-13-2013
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Severe steroid-refractory acute graft-versus-host disease (aGVHD) is related to significant mortality and morbidity after allogeneic stem cell transplantation. Early clinical trials of therapy with human mesenchymal stem cells (hMSCs) in pediatric patients with severe aGVHD resistant to multiple immunosuppressive agents showed promising results. In this study, we evaluated the risk/benefit profile of remestemcel-L (Prochymal), a third-party, off-the-shelf source of hMSCs, as a rescue agent for treatment-resistant aGVHD in pediatric patients. Children with grade B-D aGVHD failing steroids and, in most cases, other immunosuppressive agents were eligible for enrollment. Patients received 8 biweekly i.v. infusions of 2 × 10(6) hMSCs/kg for 4 weeks, with an additional 4 weekly infusions after day +28 for patients who achieved either a partial or mixed response. The enrolled patients compose a very challenging population with severe disease that was nonresponsive to the standard of care, with 88% of the patients experiencing severe aGVHD (grade C or D). Seventy-five patients (median age, 8 yr; 58.7% male; and 61.3% Caucasian) were treated in this study. Sixty-four patients (85.3%) had received an unrelated hematopoietic stem cell graft, and 28 patients (37.3%) had received a cord blood graft. At baseline, the distribution of aGVHD grades B, C, and D was 12.0%, 28.0%, and 60.0%, respectively. The median duration of aGVHD before enrollment was 30 d (range, 2 to 1639 d), and patients failed a median of 3 immunosuppressive agents. Organ involvement at baseline was 86.7% gastrointestinal, 54.7% skin, and 36.0% liver. Thirty-six patients (48.0%) had 2 organs involved, and 11 patients (14.7%) had all 3 organs involved. When stratified by aGVHD grade at baseline, the rate of overall response (complete and partial response) at day +28 was 66.7% for aGVHD grade B, 76.2% for grade C, and 53.3% for grade D. Overall response for individual organs at day +28 was 58.5% for the gastrointestinal system, 75.6% for skin, and 44.4% for liver. Collectively, overall response at day +28 for patients treated for severe refractory aGVHD was 61.3%, and this response was correlated with statistically significant improved survival at day +100 after hMSC infusion. Patients who responded to therapy by day +28 had a higher Kaplan-Meier estimated probability of 100-d survival compared with patients who did not respond (78.1% versus 31.0%; P < .001). Prochymal infusions were generally well tolerated, with no evidence of ectopic tissue formation.
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Infections in children with down syndrome and acute myeloid leukemia: a report from the Canadian infections in AML research group.
Infect. Agents Cancer
PUBLISHED: 07-23-2013
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Children with Down syndrome (DS) are at high risk of infectious toxicity when treated with acute lymphoblastic leukemia chemotherapy protocols optimized in children without DS. Our objective was to determine if children with DS and acute myeloid leukemia (AML) have a different risk of infection when treated with chemotherapy protocols developed for children with DS compared to AML treatment protocols developed for children without DS.
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Clostridium difficile infection in pediatric acute myeloid leukemia: from the Canadian Infections in Acute Myeloid Leukemia Research Group.
Pediatr. Infect. Dis. J.
PUBLISHED: 07-11-2013
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The prevalence and severity of Clostridium difficile infection (CDI) has increased over time in adult patients, but little is known about CDI in pediatric cancer. The primary objectives were to describe the incidence and characteristics of CDI in children with de novo acute myeloid leukemia (AML). The secondary objective was to describe factors associated with CDI.
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Infections in pediatric acute promyelocytic leukemia: from the canadian infections in acute myeloid leukemia research group.
BMC Cancer
PUBLISHED: 05-29-2013
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BACKGROUND: It is not known whether children with acute promyelocytic leukemia (APL) have an infection risk similar to non- APL acute myeloid leukemia. The objective was to describe infectious risk in children with newly diagnosed APL and to describe factors associated with these infections. METHODS: We conducted a retrospective, population-based cohort study that included children <= 18 years of age with de novo APL treated at 15 Canadian centers. Thirty-three children with APL were included; 78.8% were treated with APL -specific protocols. RESULTS: Bacterial sterile site infection occurred in 12 (36.4%) and fungal sterile site infection occurred in 2 (6.1%) children. Of the 127 chemotherapy courses, 101 (79.5%) were classified as intensive and among these, the proportion in which a sterile site microbiologically documented infection occurred was 14/101 (13.9%). There was one infection-related death. CONCLUSIONS: One third of children with APL experienced at least one sterile site bacterial infection throughout treatment and 14% of intensive chemotherapy courses were associated with a microbiologically documented sterile site infection. Infection rates in pediatric APL may be lower compared to non- APL acute myeloid leukemia although these children may still benefit from aggressive supportive care during intensive chemotherapy.
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Autologous haematopoietic cell transplantation for non-Hodgkin lymphoma with secondary CNS involvement.
Br. J. Haematol.
PUBLISHED: 03-04-2013
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Pre-existing central nervous system (CNS) involvement may influence referral for autologous haematopoietic cell transplantation (AHCT) for patients with non-Hodgkin lymphoma (NHL). The outcomes of 151 adult patients with NHL with prior secondary CNS involvement (CNS(+) ) receiving an AHCT were compared to 4688 patients without prior CNS lymphoma (CNS(-) ). There were significant baseline differences between the cohorts. CNS(+) patients were more likely to be younger, have lower performance scores, higher age-adjusted international prognostic index scores, more advanced disease stage at diagnosis, more aggressive histology, more sites of extranodal disease, and a shorter interval between diagnosis and AHCT. However, no statistically significant differences were identified between the two groups by analysis of progression-free survival (PFS) and overall survival (OS) at 5 years. A matched pair comparison of the CNS(+) group with a subset of CNS(-) patients matched on propensity score also showed no differences in outcomes. Patients with active CNS lymphoma at the time of AHCT (n = 55) had a higher relapse rate and diminished PFS and OS compared with patients whose CNS lymphoma was in remission (n = 96) at the time of AHCT. CNS(+) patients can achieve excellent long-term outcomes with AHCT. Active CNS lymphoma at transplant confers a worse prognosis.
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Infectious events prior to chemotherapy initiation in children with acute myeloid leukemia.
PLoS ONE
PUBLISHED: 01-01-2013
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The primary objective was to describe infectious complications in children with acute myeloid leukemia from presentation to the healthcare system to initiation of chemotherapy and to describe how these infections differ depending on neutropenia.
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Endocrine complications following pediatric bone marrow transplantation.
J. Pediatr. Endocrinol. Metab.
PUBLISHED: 08-10-2011
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Pediatric bone marrow transplantation (BMT) for various diseases can lead to endocrine system dysfunction owing to preparative regimens involving chemotherapy and radiation therapy. We assessed the prevalence of post-BMT endocrine complications in children treated at the Alberta Childrens Hospital (ACH) from 1991 to 2001. Time of onset of endocrine dysfunction, underlying disease processes, chemotherapy, radiation therapy and age at BMT were characterized. Subjects of <18 years of age at the time of allogeneic or autologous BMT for whom 1-year follow-up through the ACH and a chart were available for review were included in the study. Subjects with a pre-existing endocrine condition were excluded. Of the 194 pediatric BMT procedures performed at the ACH between January 1, 1991 and December 31, 2001, 150 complete charts were available for review. Sixty five subjects received follow-up care at other centers and were excluded. Therefore, a total of 85 subjects were included in the review. The prevalence of endocrine complications identified was: primary hypothyroidism 1.2%, compensated hypothyroidism 7.0%, hyperthyroidism 2.4%, hypergonadotrophic hypogonadism 22.4%, abnormal bone density 2.4%, and secondary diabetes mellitus 1.2%. These findings emphasize the need to screen for endocrine system dysfunction, particularly hypergonadotrophic hypogonadism, in children who have undergone BMT. Children need long-term follow-up so that endocrine complications can be diagnosed and treated promptly.
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Classifying cytogenetics in patients with acute myelogenous leukemia in complete remission undergoing allogeneic transplantation: a Center for International Blood and Marrow Transplant Research study.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-26-2011
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Cytogenetics play a major role in determining the prognosis of patients with acute myelogenous leukemia (AML). However, existing cytogenetics classifications were developed in chemotherapy-treated patients and might not be optimal for patients undergoing allogeneic hematopoietic cell transplantation (HCT). We studied 821 adult patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) who underwent HCT for AML in first or second complete remission between 1999 and 2004. We compared the ability of the 6 existing classifications to stratify patients by overall survival. We then defined a new scheme specifically applicable to patients undergoing HCT using this patient cohort. Under this scheme, inv(16) is favorable, a complex karyotype (4 or more abnormalities) is adverse, and all other classified abnormalities are intermediate in predicting survival after HCT (5-year overall survival, 64%, 18%, and 50%, respectively; P = .0001). This scheme stratifies patients into 3 groups with similar nonrelapse mortality, but significantly different incidences of relapse, overall and leukemia-free survival. It applies to patients regardless of disease status (first or second complete remission), donor type (matched related or unrelated), or conditioning intensity (myeloablative or reduced intensity). This transplantation-specific classification could be adopted for prognostication purposes and to stratify patients with AML and karyotypic abnormalities entering HCT clinical trials.
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Outcomes of pediatric bone marrow transplantation for leukemia and myelodysplasia using matched sibling, mismatched related, or matched unrelated donors.
Blood
PUBLISHED: 07-29-2010
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Although some trials have allowed matched or single human leukocyte antigen (HLA)-mismatched related donors (mmRDs) along with HLA-matched sibling donors (MSDs) for pediatric bone marrow transplantation in early-stage hematologic malignancies, whether mmRD grafts lead to similar outcomes is not known. We compared patients < 18 years old reported to the Center for International Blood and Marrow Transplant Research with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and myelodysplastic syndrome undergoing allogeneic T-replete, myeloablative bone marrow transplantation between 1993 and 2006. In total, patients receiving bone marrow from 1208 MSDs, 266 8/8 allelic-matched unrelated donors (URDs), and 151 0-1 HLA-antigen mmRDs were studied. Multivariate analysis showed that recipients of MSD transplants had less transplantation-related mortality, acute graft-versus-host disease (GVHD), and chronic GVHD, along with better disease-free and overall survival than the URD and mmRD groups. No differences were observed in transplant-related mortality, acute and chronic GVHD, relapse, disease-free survival, or overall survival between the mmRD and URD groups. These data show that mmRD and 8/8 URD outcomes are similar, whereas MSD outcomes are superior to the other 2 sources. Whether allele level typing could identify mmRD recipients with better outcomes will not be known unless centers alter practice and type mmRD at the allele level.
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Nasal epithelial cells of donor origin after allogeneic hematopoietic cell transplantation are generated at a faster rate in the first 3 months compared with later posttransplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-18-2010
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Detection of donor-type epithelial cells (ECs) after allogeneic hematopoietic cell transplantation (allo-HCT) using XY chromosome fluorescein in situ hybridization (FISH) has suggested that hematopoietic stem cells carry a degree of developmental plasticity. This is controversial, given artifacts of XY-based detection and the possibility of hematopoietic-nonhematopoietic cell fusion. Moreover, the kinetics of donor-type ECs (quantity at different time points after transplant) is unknown. Here, we document unequivocally the existence of donor-type ECs using a method obviating the artifacts of XY-FISH and study their kinetics. Nasal scrapings and blood specimens were collected from 60 allo-HCT survivors between 7 days and 22 years posttransplantation. DNA extracted from laser-captured nasal ECs (ie, CK(+)CD45(-) cells) and blood leukocytes was polymerase chain reaction-amplified for a panel of 16 short tandem repeat markers. The median percentage of donor-type ECs (among nasal ECs) was 0% on day 7 posttransplantation, 2.8% at 3 months posttransplantation, and 8.5% at 12-22 years posttransplantation. Cell fusion was ruled out by FISH analysis for two autosomes. We conclude that donor-type nasal ECs exist after HCT, and that their percentage rises rapidly in the first 3 months posttransplantation and more slowly thereafter.
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The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first and second complete remission.
Blood
PUBLISHED: 04-19-2010
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We examined the efficacy of reduced-intensity conditioning (RIC) and compared outcomes of 93 patients older than 16 years after RIC with 1428 patients receiving full-intensity conditioning for allografts using sibling and unrelated donors for Philadelphia-negative acute lymphoblastic leukemia (ALL) in first or second complete remission. RIC conditioning included busulfan 9 mg/kg or less (27), melphalan 150 mg/m(2) or less (23), low-dose total body irradiation (TBI; 36), and others (7). The RIC group was older (median 45 vs 28 years, P < .001) and more received peripheral blood grafts (73% vs 43%, P < .001) but had similar other prognostic factors. The RIC versus full-intensity conditioning groups had slightly, but not significantly, less acute grade II-IV graft-versus-host disease (39% vs 46%) and chronic graft-versus-host disease (34% vs 42%), yet similar transplantation-related mortality. RIC led to slightly more relapse (35% vs 26%, P = .08) yet similar age-adjusted survival (38% vs 43%, P = .39). Multivariate analysis showed that conditioning intensity did not affect transplantation-related mortality (P = .92) or relapse risk (P = .14). Multivariate analysis demonstrated significantly improved overall survival with: Karnofsky performance status more than 80, first complete remission, lower white blood count, well-matched unrelated or sibling donors, transplantation since 2001, age younger than 30 years, and conditioning with TBI, but no independent impact of conditioning intensity. RIC merits further investigation in prospective trials of adult ALL.
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Childhood acute lymphoblastic leukemia (ALL) presenting with severe osteolysis: a model to study leukemia-bone interactions and potential targeted therapeutics.
Pediatr Hematol Oncol
PUBLISHED: 04-07-2010
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Interference with the molecular mechanisms that generate tumor supportive niches in the bone microenvironment is a rational approach to inhibit the growth of hematological malignancies. However, the advancement of knowledge in this area has been slowed down by the lack of in vitro models to facilitate the screening of potential candidate agents. The rare cases of acute lymphoblastic leukemia (ALL) in children presenting with extensive bone involvement may represent an exaggerated form of some aspects of the normal tumor-bone interactions. Thus, these cases can provide insight into processes that are otherwise challenging to uncover. The authors describe the case of a 6-year-old child who presented with severe osteopenia that resolved at the time of leukemic remission. Compared to control sera, serum taken at disease presentation contained increased levels of a group of osteolytic cytokines and was effective in activating preosteoclast cells in culture. Based on these findings, the authors describe an experimental model to identify agents that would interfere with leukemia mediated osteolytic process.
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Cytotoxicity, drug combinability, and biological correlates of ABT-737 against acute lymphoblastic leukemia cells with MLL rearrangement.
Pediatr Blood Cancer
PUBLISHED: 01-27-2010
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ABT-737 is a BH3 mimetic small-molecule inhibitor that binds with high affinity to Bcl-2 to induce apoptosis in malignant cells and has shown promise as an effective anti-leukemic agent in pediatric preclinical tests. This study focuses on the effects of ABT-737 on leukemia cells with MLL rearrangement and identifies some of the biological correlates of its activity.
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The use of argon beam coagulation in pressure sore reconstruction.
J Plast Reconstr Aesthet Surg
PUBLISHED: 12-24-2009
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Pressure sores are a significant source of physical and financial burden for debilitated patients. When conservative measures fail, surgical reconstruction with myocutaneous flaps may be the last hope for cure and/or improved quality of life in these patients. Adequate haemostasis is an integral component of these reconstructive procedures, as bleeding and haematoma formation can lead to increased morbidity. This study was designed to investigate the use of argon beam coagulation in patients undergoing bony debridement and subsequent pressure sore reconstruction with myocutaneous flaps.
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Targeting the Bcl-2 family of proteins in Hodgkin lymphoma: in vitro cytotoxicity, target modulation and drug combination studies of the Bcl-2 homology 3 mimetic ABT-737.
Leuk. Lymphoma
PUBLISHED: 06-27-2009
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With currently available treatment, patients with refractory Hodgkin lymphoma (HL) or those who relapse multiple times have an extremely poor prognosis. Therefore, new agents and novel therapeutic approaches are urgently needed. Anti-apoptotic proteins such as Bcl-2 and Bcl-x have been associated with the growth and survival of Hodgkin Reed-Sternberg cells and are potential therapeutic targets. ABT-737 is a small molecule that inhibits the Bcl-2 family of apoptosis regulators. In this study, we show the concentration-dependent and time-dependent cytotoxicity of ABT-737 against cell lines derived from patients with HL. A concurrent reduction in a number of intracellular cell growth and survival related molecules, such as Bcl-2, Bcl-xl, NF-kappaB and survivin was also seen. Drug combination studies using a panel of conventional and novel therapeutic agents show that ABT-737 potentiates the activity of agents that have inherent anti-lymphoma activity and provide support for the evaluation of ABT-737 in the clinical setting.
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Reconstruction of the zygomatic arch using a mandibular adaption plate.
J Craniofac Surg
PUBLISHED: 06-26-2009
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Zygomatic complex fractures are one of the most common facial fractures treated by maxillofacial surgeons. Because of the importance of the zygomatic complex in midfacial skeletal orientation, comminuted zygomatic arch fractures can lead to significant morbidity and deformity. Common repair modalities include closed reduction via a Gilles approach, open reduction and internal fixation with screws and/or plating systems, primary bone grafting, and/or biosynthetics. In patients with significant comminution and arch defects, who are poor candidates for bone grafting, reconstruction can be difficult. In this clinical report, we present 2 patients with comminuted zygomatic arch fractures and significant bony defects, who were reconstructed with mandibular adaption plates alone without primary bone grafting. Over a mean follow-up period of 12.5 months, both patients healed well without any complications and had acceptable cosmetic outcomes.
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Allogeneic hematopoietic stem cell transplantation of patients with FA and high risk features using fludarabine without radiation.
Pediatr Blood Cancer
PUBLISHED: 01-22-2009
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Several factors unique to Fanconi anemia (FA) limit the success of allogeneic hematopoietic stem cell transplantation (HSCT) in this population. In this report, we describe a multi-center pilot study of five consecutive FA patients with high-risk features for transplant prepared with fludarabine, without radiation. Four patients engrafted quickly, experienced minimal toxicity and are well at 43-65 months post-transplant. One patient had a C-mismatched unrelated donor transplant and had unsustained engraftment. This fludarabine based regimen without radiation was safe and effective for four high-risk patients, suggesting that eliminating radiation should be further studied as an approach to HSCT in children with FA.
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Occurrence and modulation of therapeutic targets of Aurora kinase inhibition in pediatric acute leukemia cells.
Leuk. Lymphoma
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Acute lymphoblastic leukemia (ALL) is one of the most prevelant pediatric malignancies. Although cure rates have improved in recent decades, approximately one in five children relapse, and survival rates post-relapse remain low. Therefore, more effective and innovative therapeutic strategies are needed in order to improve the outcome in these children. Aurora kinases, a family of serine/threonine kinases essential for regulated mitosis, are overexpressed in many forms of cancer, and have been identified as potential targets for cancer therapeutics. Based on this premise, we evaluated the activity of the Aurora-A/B inhibitor AT9283 against pediatric leukemia cells. It was found that AT9283 significantly inhibited the growth and survival of cell lines derived from patients with pediatric leukemia. Specifically, AT9283 promoted Flt-3 dephosphorylation, inhibiting the activity of downstream effectors such as Erk and Mek. In addition, apoptotic markers were also identified, providing a panel of markers for biological correlative analysis for drug activity. Lastly, drug combination studies demonstrated the potential of several novel and conventional agents to synergize with AT9283, including apicidin, 17-allylamino-17-demethoxygeldanamycin (17-AAG) and doxorubicin. These data provide a rationale for further studies and the formulation of a clinical trial of AT9283 for the treatment of refractory pediatric ALL.
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The incidence of methicillin-resistant Staphylococcus aureus in pressure ulcers.
Adv Skin Wound Care
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Colonization of chronic wounds with methicillin-resistant Staphylococcus aureus continues to be an important healthcare concern. Aside from the morbidity associated with infections, colonization alone can contribute to outbreaks at long-term-care facilities and within hospitals. Despite the prevalence of pressure ulcers, the incidence of S aureus in these chronic wounds is unknown.
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Corticosteroids, behavior, and quality of life in children treated for acute lymphoblastic leukemia; a multicentered trial.
J. Pediatr. Hematol. Oncol.
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The aim of this study was to investigate the effects of high-dose corticosteroids on behavior and quality of life of children with acute lymphoblastic leukemia (ALL) in maintenance therapy. Forty-three families (patient and/or parent) completed the Child Behavior Checklist (CBCL), the Pediatric Quality of Life Inventory (PedsQL) Cancer module questionnaires, a checklist of common complaints, and a descriptive intervention data questionnaire, on and off steroids, each child serving as his/her own control. Children 5 years and younger had higher CBCL scores in the somatic complaints, affective problems, internalizing, externalizing, and total problem scales, when comparing "on-steroid" to "off-steroid" periods (P<0.01). Children 6 years and above had higher CBCL scores in the externalizing, aggressive, and oppositional defiant problem scales on steroids compared with off steroids (P<0.05). Older children had larger changes on dexamethasone, compared with prednisone (P<0.05). On the PedsQL questionnaire, parents reported more pain and hurt (P<0.001), nausea (P=0.042), and procedural anxiety (P=0.013) when children were on steroids compared with off steroids. Corticosteroid treatment during ALL maintenance therapy is associated with behavior and emotional disturbances and adversely affects quality of life. Dexamethasone is associated with more significant behavioral changes in older children.
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Impact of immune modulation with in vivo T-cell depletion and myleoablative total body irradiation conditioning on outcomes after unrelated donor transplantation for childhood acute lymphoblastic leukemia.
Blood
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To determine whether in vivo T-cell depletion, which lowers GVHD, abrogates the antileukemic benefits of myeloablative total body irradiation-based conditioning and unrelated donor transplantation, in the present study, we analyzed 715 children with acute lymphoblastic leukemia. Patients were grouped for analysis according to whether conditioning included antithymocyte globulin (ATG; n = 191) or alemtuzumab (n = 132) and no in vivo T-cell depletion (n = 392). The median follow-up time was 3.5 years for the ATG group and 5 years for the alemtuzumab and T cell-replete groups. Using Cox regression analysis, we compared transplantation outcomes between groups. Compared with no T-cell depletion, grade 2-4 acute and chronic GVHD rates were significantly lower after in vivo T-cell depletion with ATG (relative risk [RR] = 0.66; P = .005 and RR = 0.55; P < .0001, respectively) or alemtuzumab (RR = 0.09; P < .003 and RR = 0.21; P < .0001, respectively). Despite lower GVHD rates after in vivo T-cell depletion, nonrelapse mortality, relapse, overall survival, and leukemia-free survival (LFS) did not differ significantly among the treatment groups. The 3-year probabilities of LFS after ATG-containing, alemtuzumab-containing, and T cell-replete transplantations were 43%, 49%, and 46%, respectively. These data suggest that in vivo T-cell depletion lowers GVHD without compromising LFS among children with acute lymphoblastic leukemia who are undergoing unrelated donor transplantation with myeloablative total body irradiation-based regimens.
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Predictors and Outcomes of Viridans Group Streptococcal Infections in Pediatric Acute Myeloid Leukemia: From the Canadian Infections in AML Research Group.
Pediatr. Infect. Dis. J.
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Viridans group streptococci (VGS) cause significant morbidity in children treated for acute myeloid leukemia (AML). Our goals were to determine the occurrence and impact of these infections in children treated for AML and to understand the factors that increase the risk of VGS infections and viridans streptococcal shock syndrome (VSSS) in this population.
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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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