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Sample records for children undergoing hematopoietic

  1. Massage for Children Undergoing Hematopoietic Cell Transplantation: A Qualitative Report

    OpenAIRE

    Ackerman, Sara L.; E. Anne Lown; Dvorak, Christopher C.; Dunn, Elizabeth A.; Abrams, Donald I; Horn, Biljana N.; Marcia Degelman; Cowan, Morton J.; Mehling, Wolf E.

    2012-01-01

    Background. No in-depth qualitative research exists about the effects of therapeutic massage with children hospitalized to undergo hematopoietic cell transplantation (HCT). The objective of this study is to describe parent caregivers' experience of the effects of massage/acupressure for their children undergoing HCT. Methods. We conducted a qualitative analysis of open-ended interviews with 15 parents of children in the intervention arm of a massage/acupressure trial. Children received both p...

  2. Acute Kidney Injury and the Risk of Mortality in Children Undergoing Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Kizilbash, Sarah J; Kashtan, Clifford E; Chavers, Blanche M; Cao, Qing; Smith, Angela R

    2016-07-01

    Acute kidney injury (AKI) is a well-documented complication of pediatric hematopoietic stem cell transplantation (HSCT). Dialysis after HSCT is associated with a lower overall survival (OS); however, the association between less severe AKI and OS is unclear. We retrospectively studied 205 consecutive pediatric HSCT patients to determine the incidence and impact of all stages of AKI on OS in pediatric HSCT recipients. We used the peak pRIFLE grade during the first 100 days to classify AKI (ie, R = risk, I = injury, F = failure, L = loss of function, E = end-stage renal disease) and used the modified Schwartz formula to estimate glomerular filtration rate. AKI was observed in 173 of 205 patients (84%). The 1-year OS rate decreased significantly with an increasing severity of pRIFLE grades (P OS between patients without AKI and the R/I group. Regardless of the dialysis status, stages F/L/E had significantly lower rates of OS compared with patients without AKI or R/I (P OS among patients with dialysis and F/L/E without dialysis (P = .65). Stages F/L/E predicted mortality independent of acute graft-versus-host disease, gender, and malignancy. The OS of children after HSCT decreases significantly with an increasing severity of AKI within the first 100 days post-transplant. Although our data did not show an increased risk of mortality with stages R/I, stages F/L/E predicted mortality regardless of dialysis. Prevention and minimization of AKI may improve survival after pediatric HSCT. PMID:27034153

  3. Feasibility of an inpatient exercise intervention for children undergoing hematopoietic stem cell transplant.

    Science.gov (United States)

    Bogg, Tina Fung Ting; Broderick, Carolyn; Shaw, Peter; Cohn, Richard; Naumann, Fiona Leigh

    2015-12-01

    With improving survival rates following HSCT in children, QOL and management of short- and long-term effects need to be considered. Exercise may help mitigate fatigue and declines in fitness and strength. The aims of this study were to assess the feasibility of an inpatient exercise intervention for children undergoing HSCT and observe the changes in physical and psychological health. Fourteen patients were recruited, mean age 10 yr. A 6MWT, isometric upper and lower body strength, balance, fatigue, and QOL were assessed prior to Tx and six wk post-Tx. A supervised exercise program was offered five days per week during the inpatient period and feasibility assessed through uptake rate. The study had 100% program completion and 60% uptake rate of exercise sessions. The mean (± s.d.) weekly activity was 117.5 (± 79.3) minutes. Younger children performed significantly more minutes of exercise than adolescents. At reassessment, strength and fatigue were stabilized while aerobic fitness and balance decreased. QOL revealed a non-statistical trend towards improvement. No exercise-related adverse events were reported. A supervised inpatient exercise program is safe and feasible, with potential physiological and psychosocial benefits. PMID:26518227

  4. The Role of Social and Cognitive Processes in the Relationship between Fear Network and Psychological Distress among Parents of Children Undergoing Hematopoietic Stem Cell Transplantation

    OpenAIRE

    Virtue, Shannon Myers; Manne, Sharon; Mee, Laura; Bartell, Abraham; Sands, Stephen; Ohman-Strickland, Pamela; Gajda, Tina Marie

    2014-01-01

    The current study examined whether cognitive and social processing variables mediated the relationship between fear network and depression among parents of children undergoing hematopoietic stem cell transplant (HSCT). Parents whose children were initiating HSCT (N = 179) completed survey measures including fear network, Beck Depression Inventory (BDI), cognitive processing variables (positive reappraisal and self-blame) and social processing variables (emotional support and holding back from...

  5. Observational prospective study of viral infections in children undergoing allogeneic hematopoietic cell transplantation: a 3-year GETMON experience.

    Science.gov (United States)

    Verdeguer, A; de Heredia, C D; González, M; Martínez, A M; Fernández-Navarro, J M; Pérez-Hurtado, J M; Badell, I; Gómez, P; González, M E; Muñoz, A; Díaz, M A

    2011-01-01

    We studied surveillance, incidence and outcome of viral infections in children undergoing allogeneic hematopoietic cell transplantation (HCT) in the main pediatric transplant units in Spain. We prospectively collected data from first year post-HCT in every consecutive allogeneic HCT performed during 3 years (N = 215): first HCT = 188 and second HCT = 27; median age = 6.6 years (0.1-20.7). Most patients had acute leukemia (N = 137) and 135 recipients (63%) were CMV seropositive. A total of 46 patients underwent cord blood transplant, 133 patients underwent HCT from alternative donors (62%) and 101 patients received anti-thymocyte globulin. Observational time was completed in 137 patients, whereas the remaining 78 died after a median survival time of 99 days (3-352). CMV was monitored in all patients; adenovirus (ADV) and human herpesvirus 6 (HHV-6) were monitored in 101 and 33 patients, respectively. We found 145 viral infections in 103 patients: CMV (n = 42), ADV (n = 32), HHV-6 (n = 7), polyomavirus (n = 20), EBV (n = 6), VZV (n=17) and others (n = 8). CMV infection was significantly higher in seropositive patients (25 vs 7%) (P = 0.02). Extensive chronic GVHD (cGVHD) was significantly associated with an increased rate of viral infections (12 of 16 patients with cGVHD had infections vs 91 of 199 without GVHD) (P = 0.035). In total, 10 patients (4.6%) died of viral infections (CMV = 5, ADV = 3, respiratory = 2). We found a high incidence of viral infection, but mortality was low. PMID:20228849

  6. Oral changes in individuals undergoing hematopoietic stem cell transplantation

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    Regina Haddad Barrach

    2015-04-01

    Full Text Available INTRODUCTION: Patients undergoing hematopoietic stem cell transplantation receive high doses of chemotherapy and radiotherapy, which cause severe immunosuppression.OBJECTIVE: To report an oral disease management protocol before and after hematopoietic stem cell transplantation.METHODS: A prospective study was carried out with 65 patients aged > 18 years, with hematological diseases, who were allocated into two groups: A (allogeneic transplant, 34 patients; B (autologous transplant, 31 patients. A total of three dental status assessments were performed: in the pre-transplantation period (moment 1, one week after stem cell infusion (moment 2, and 100 days after transplantation (moment 3. In each moment, oral changes were assigned scores and classified as mild, moderate, and severe risks.RESULTS: The most frequent pathological conditions were gingivitis, pericoronitis in the third molar region, and ulcers at the third moment assessments. However, at moments 2 and 3, the most common disease was mucositis associated with toxicity from the drugs used in the immunosuppression.CONCLUSION: Mucositis accounted for the increased score and potential risk of clinical complications. Gingivitis, ulcers, and pericoronitis were other changes identified as potential risk factors for clinical complications.

  7. Changes in Body Composition and Their Related Factors of Children Undergoing Hematopoietic Stem Cell Transplantation%造血干细胞移植患儿急性期人体组分改变及其相关因素

    Institute of Scientific and Technical Information of China (English)

    朱晨临; 楼建华; 张冰花; 洪莉

    2013-01-01

    Objective To describe changes in body composition of children during acute period after hematopoietic stem transplantation and to analyze their related factors. Methods From January to September 2012,40 patients undergoing hematopoietic stem cell transplantation in Shanghai Children's Medical Center were prospectively enrolled into the study. Height, weight and body composition were measured by direct segmental multi-frequency bioelectrical impedance analysis (DSM-BIA) were recorded before transplantation and at the 30th, 60th and 100th day after transplantation. Sex, age, transplantation method, graft source,total body irradiation,use of methylprednisolone, infection, the grade of mucositis and acute graft-versus-host disease (aGVHD) grade were also recorded. Results After hematopoietic stem cell transplantation, no significant change was observed in height Z-scores (F=0. 75,P = 0. 3883); body mass index(BMI) Z-values and fat-free mass for height (FFM-Ht) were significantly decreased but fat mass for height(FM-Ht) was also significantly increased(P<0. 05 or P<0. 01). After controlling children's age, the graft source was a significant factor affecting BMI Z and the total body irradiation was a significant factor affecting FM-Ht and infection was the a risk factor of FFM-Ht. Conclusion Children have high risks of emaciation and obesity during the acute period after hematopoietic stem cell transplantation. Irradiation may increase their fat mass, while infection may decreases fat-free mass. BMI may not be a good indicator to assess nutrition status of children undergoing transplantation.%目的 了解造血干细胞移植患儿急性期的人体组分变化情况并分析其相关因素.方法 前瞻性收集2012年1月至2012年9月在上海儿童医学中心进行造血干细胞移植的40例患儿的临床资料,在患儿进行造血干细胞移植前、移植后的第30、60和100天测量其身高、体质指数及使用直接节段多频生物电阻抗分析

  8. Safety, Pharmacokinetics, and Efficacy of Palifermin in Children and Adolescents with Acute Leukemias Undergoing Myeloablative Therapy and Allogeneic Hematopoietic Stem Cell Transplantation: A Pediatric Blood and Marrow Transplant Consortium Trial.

    Science.gov (United States)

    Morris, Joan; Rudebeck, Mattias; Neudorf, Steven; Moore, Theodore; Duerst, Reggie; Shah, Ami J; Graham, Michael; Aquino, Victor; Morris, Christopher; Olsson, Birgitta

    2016-07-01

    Currently, effective pharmacologic treatment to reduce severe oral mucositis (OM) resulting from high-dose myeloablative cytotoxic therapy in the pediatric population is not available. Palifermin has been proven to decrease the incidence and duration of severe OM in adults with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT). In the pediatric population, however, data on palifermin treatment are limited. A phase I dose-escalation study of palifermin in pediatric patients with acute leukemias undergoing myeloablative HSCT with total body irradiation, etoposide, and cyclophosphamide was performed to determine a safe and tolerable dose and to characterize the pharmacokinetic (PK) profile and efficacy of palifermin. Twenty-seven patients in 3 age groups (1 to 2, 3 to 11, and 12 to 16 years) and 3 dose levels (40, 60, and 80 μg/kg/day) were studied. There were no deaths, dose-limiting toxicities, or treatment-related serious adverse events. Long-term safety outcomes did not differ from what would be expected in this population. PK data showed no differences between the 3 age groups. Exposure did not increase with increase in dose. The maximum severity of OM (WHO grade 4) occurred in 6 patients (22%), none of whom was in the 80-μg/kg/day dosing group. This study showed that all doses were well tolerated and a good safety profile in all 3 pediatric age groups was seen. PMID:26968792

  9. Iron Overload in Patients Undergoing Hematopoietic Stem Cell Transplantation

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    Vinod Pullarkat

    2010-01-01

    Full Text Available Recipients of hematopoietic stem cell transplantation (HSCT frequently have iron overload resulting from chronic transfusion therapy for anemia. In some cases, for example, in patients with myelodysplastic syndromes and thalassemia, this can be further exacerbated by increased absorption of iron from the gut as a result of ineffective erythropoiesis. Accumulating evidence has established the negative impact of elevated pretransplantation serum ferritin, a surrogate marker of iron overload, on overall survival and nonrelapse mortality after HSCT. Complications of HSCT associated with iron overload include increased bacterial and fungal infections as well as sinusoidal obstruction syndrome and possibly other regimen-related toxicities. Based on current evidence, particular attention should be paid to prevention and management of iron overload in allogeneic HSCT candidates, especially in patients with thalassemia and myelodysplastic syndromes. The pathophysiology of iron overload in the HSCT patient and optimum strategies to deal with iron overload during and after HSCT require further study.

  10. Tuberculosis in children undergoing hemodialysis

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    Gargah Tahar

    2010-04-01

    Full Text Available Gargah Tahar1, Goucha-Louzir Rim2, Lakhoua Mohamed Rachid11Department of Pediatric Nephrology, 2Department of Nephrology, Charles Nicolle Hospital, Tunis, TunisiaAbstract: Tuberculosis (TB remains a public health problem in Tunisia. Its incidence is higher in immunocompromised hosts than in the general population. In children and during hemodialysis, TB is characterized by the frequency of extrapulmonary localizations and diagnostic difficulties. The aim of this retrospective study is to evaluate the incidence of TB in Tunisian children undergoing hemodialysis and to determine its clinical features as well as the results of chemotherapy.Method: This retrospective study includes seven TB children among 112 children on hemodialysis at the pediatric nephrology department in Charles Nicolle Hospital from 2002 to 2008. The diagnosis of TB was established by a combination of clinical, radiological, biochemical, microbiological, and histological examinations. Treatment with anti-TB drugs, the results of therapy, and the outcome of patients were noted.Results: There were four girls and three boys aged 10 to 16 years (mean, 13 years. They had been on hemodialysis for 2 to 5 years (mean, 3 years. Noted clinical features were weight loss and fever in five cases, chest pain in one case, cervical lymph node in one case, and spinal pain in one case. The organ systems involved were pleural in two cases, pulmonary in one case, peritoneal in one case, cervical lymphatic in one case, and spinal in one case. One patient was treated empirically with a good response. Diagnosis was made by isolation of mycobacterium TB in three cases, by specific histological signs observed in a lymph node biopsy in one case, in peritoneal biopsy in one case, and in discovertebral biopsy in one case. In the remaining patient, the clinical and radiological presentations were compatible with pulmonary TB. All patients received four anti-TB drugs: isoniazid, rifampicin, pyrazinamide

  11. Stomatitis-Related Pain in Women with Breast Cancer Undergoing Autologous Hematopoietic Stem Cell Transplant

    OpenAIRE

    Fall-Dickson, Jane M.; Mock, Victoria; Berk, Ronald A.; Grimm, Patricia M.; Davidson, Nancy; Gaston-Johansson, Fannie

    2008-01-01

    The purpose of this cross-sectional, correlational study was to describe stomatitis-related pain in women with breast cancer undergoing autologous hematopoietic stem cell transplant. Hypotheses tested were that significant, positive relationships would exist between oral pain and stomatitis, state anxiety, depression, and alteration in swallowing. Stomatitis, sensory dimension of oral pain, and state anxiety were hypothesized to most accurately predict oral pain overall intensity. Thirty-two ...

  12. Fractionated stem cell infusions for patients with plasma cell myeloma undergoing autologous hematopoietic cell transplantation.

    Science.gov (United States)

    Landau, Heather; Wood, Kevin; Chung, David J; Koehne, Guenther; Lendvai, Nikoletta; Hassoun, Hani; Lesokhin, Alexander; Hoover, Elizabeth; Zheng, Junting; Devlin, Sean M; Giralt, Sergio

    2016-08-01

    We conducted a phase II trial investigating the impact of fractionated hematopoietic cell infusions on engraftment kinetics and symptom burden in patients with plasma cell myeloma (PCM) undergoing autologous hematopoietic cell transplant (AHCT). We hypothesized that multiple hematopoietic cell infusions would reduce duration of neutropenia and enhance immune recovery resulting in a better tolerated procedure. Twenty-six patients received high-dose melphalan followed by multiple cell infusions (Days 0, +2, +4, +6) and were compared to PCM patients (N = 77) who received high-dose melphalan and a single infusion (Day 0) (concurrent control group). The primary endpoint was number of days with ANC Inventory. Median duration of neutropenia was similar in study (4 days, range 3-5) and control patients (4 days, range 3-9) (p = 0.654). There was no significant difference in the number of red cell or platelet transfusions, days of fever, diarrhea, antibiotics, number of documented infections, or length of admission. Symptom burden surveys showed that AHCT was well-tolerated in both study and control patients. We conclude that fractionated stem cell infusions following high-dose melphalan do not enhance engraftment kinetics or significantly alter patients' clinical course following AHCT in PCM. PMID:26758672

  13. Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell differentiation.

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    Shuxian Jiang

    Full Text Available BACKGROUND: Mammary stem cells are maintained within specific microenvironments and recruited throughout lifetime to reconstitute de novo the mammary gland. Mammary stem cells have been isolated through the identification of specific cell surface markers and in vivo transplantation into cleared mammary fat pads. Accumulating evidence showed that during the reformation of mammary stem cell niches by dispersed epithelial cells in the context of the intact epithelium-free mammary stroma, non-mammary epithelial cells may be sequestered and reprogrammed to perform mammary epithelial cell functions and to adopt mammary epithelial characteristics during reconstruction of mammary epithelium in regenerating mammary tissue in vivo. METHODOLOGY/PRINCIPAL FINDINGS: To examine whether other types of progenitor cells are able to contribute to mammary branching morphogenesis, we examined the potential of murine embryonic stem (mES cells, undergoing hematopoietic differentiation, to support mammary reconstitution in vivo. We observed that cells from day 14 embryoid bodies (EBs under hematopoietic differentiation condition, but not supernatants derived from these cells, when transplanted into denuded mammary fat pads, were able to contribute to both the luminal and myoepithelial lineages in branching ductal structures resembling the ductal-alveolar architecture of the mammary tree. No teratomas were observed when these cells were transplanted in vivo. CONCLUSIONS/SIGNIFICANCE: Our data provide evidence for the dominance of the tissue-specific mammary stem cell niche and its role in directing mES cells, undergoing hematopoietic differentiation, to reprogram into mammary epithelial cells and to promote mammary epithelial morphogenesis. These studies should also provide insights into regeneration of damaged mammary gland and the role of the mammary microenvironment in reprogramming cell fate.

  14. Preoperative information needs of children undergoing tonsillectomy.

    LENUS (Irish Health Repository)

    Buckley, Aoife

    2012-02-01

    AIMS AND OBJECTIVES: To identify the information needs of children undergoing tonsillectomy with reference to content of information, method of delivery, information providers and timing of information provision. BACKGROUND: Tonsillectomy can be anxiety provoking for children and preoperative preparation programmes are long recognised to reduce anxiety. However, few have been designed from the perspectives of children and to date little is known about how best to prepare children in terms of what to tell them, how to convey information to them, who can best provide information and what is the best timing for information provision. DESIGN: A qualitative descriptive study. METHOD: Data were collected from nine children (aged 6-9) using interviews supported by a write and draw technique. Data were coded and categorised into themes reflecting content, method, providers and timing of information. RESULTS: Children openly communicated their information needs especially on what to tell them to expect when facing a tonsillectomy. Their principal concerns were about operation procedures, experiencing \\'soreness\\' and discomfort postoperatively and parental presence. Mothers were viewed as best situated to provide them with information. Children were uncertain about what method of information and timing would be most helpful to them. CONCLUSION: Preoperative educational interventions need to take account of children\\'s information needs so that they are prepared for surgery in ways that are meaningful and relevant to them. Future research is needed in this area. RELEVANCE TO CLINICAL PRACTICE: Practical steps towards informing children about having a tonsillectomy include asking them what they need to know and addressing their queries accordingly. Child-centred information leaflets using a question and answer format could also be helpful to children.

  15. Effect of titrated parenteral nutrition on body composition after allogeneic hematopoietic stem cell transplantation in children: a double-blind, randomized, multicenter trial123

    OpenAIRE

    Sharma, Tanvi S.; Bechard, Lori J.; Feldman, Henry A.; Venick, Robert; Gura, Kathleen; Gordon, Catherine M; Sonis, Andrew; Guinan, Eva C.; Duggan, Christopher

    2011-01-01

    Background: Children undergoing hematopoietic stem cell transplantation (HSCT) often require parenteral nutrition (PN) to optimize caloric intake. Standard approaches to nutritional supplementation provide 130–150% of estimated energy expenditure, but resting energy expenditure (REE) may be lower than expected after HSCT. Provision of PN exceeding energy needs may lead to overfeeding and associated complications.

  16. Extramedullary Relapse Following Total Marrow and Lymphoid Irradiation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

    International Nuclear Information System (INIS)

    Purpose: Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution. Methods and Materials: Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph node chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy. Results: A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years. Conclusions: EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk

  17. Extramedullary Relapse Following Total Marrow and Lymphoid Irradiation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

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    Kim, Ji Hyun [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Stein, Anthony [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Tsai, Nicole [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Schultheiss, Timothy E. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Palmer, Joycelynne [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Liu, An [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Rosenthal, Joseph [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Department of Pediatrics, City of Hope National Medical Center, Duarte, California (United States); Forman, Stephen J. [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Wong, Jeffrey Y.C., E-mail: jwong@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States)

    2014-05-01

    Purpose: Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution. Methods and Materials: Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph node chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy. Results: A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years. Conclusions: EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk.

  18. Clofarabine-associated acute kidney injury in patients undergoing hematopoietic stem cell transplant

    OpenAIRE

    Petri, Camille R.; O’Donnell, Peter H.; Cao, Hongyuan; Artz, Andrew S.; Stock, Wendy; Wickrema, Amittha; Hard, Marjie; van Besien, Koen

    2014-01-01

    We examined clofarabine pharmacokinetics and association with renal toxicity in 62 patients participating in a phase I–II study of clofarabine–melphalan–alemtuzumab conditioning for hematopoietic stem cell transplant (HSCT). Pharmacokinetic parameters, including clofarabine area under the concentration–time curve (AUC), maximum concentration and clearance, were measured, and patients were monitored for renal injury. All patients had normal pretreatment creatinine values, but over half (55%) e...

  19. Influence of oral health on mucositis in patients undergoing hematopoietic progenitor cell transplantation (HPCT)

    OpenAIRE

    Hernández-Fernández, Ana; Oñate-Sánchez, Ricardo E.; Cabrerizo-Merino, María C.; de Arriba de la Fuente, Felipe; Heras Fernando, Inmaculada; Vicente García, Vicente

    2011-01-01

    Aims: To establish whether or not the state of patient oral health can influence the occurrence and/or severity of oral mucositis during hematopoietic progenitor cell transplantation (HPCT). Materials and Methods: The study included 72 patients awaiting HPCT. Prior to transplantation, clinical exploration and radiology were carried out and oral photographs were taken. This evaluated the extent of caries present, the number of missing teeth and the number of dental fillings in each patient; CA...

  20. PROPHYLACTIC ADMINISTRATION OF DOXYCYCLINE REDUCES CENTRAL VENOUS CATHETER INFECTIONS IN PATIENTS UNDERGOING HEMATOPOIETIC CELL TRANSPLANTATION

    OpenAIRE

    Mohamed Kharfan-Dabaja; Mohamed Baydoun; Zaher Otrock; Samar Okaily; Rita Nehme; Racha Abu-Chahine; Ali Hamdan; Samar Noureddine; Souha Kanj; Zeina Kanafani; Ali Bazarbachi

    2013-01-01

    Hematopoietic stem cells are usually transfused through a central venous catheter (CVC), which also facilitates administration of medications and intravenous fluids. We had observed high rate of catheter-related blood-stream infection (CR-BSI) at our Bone Marrow Transplantation (BMT) unit despite prescribing fluoroquinolones for anti-bacterial prophylaxis. Accordingly, we implemented prophylactic use of a relatively inexpensive broad spectrum antibiotic, namely doxycycline to address this pro...

  1. Prophylactic Administration of Doxycycline Reduces Central Venous Catheter Infections in Patients Undergoing Hematopoietic Cell Transplantation

    OpenAIRE

    Baydoun, Mohamed; Otrock, Zaher K.; Okaily, Samar; Nehme, Rita; Abu-Chahine, Racha; Hamdan, Ali; Noureddine, Samar; Kanj, Souha; Kanafani, Zeina; Bazarbachi, Ali; Kharfan-Dabaja, Mohamed A.

    2013-01-01

    Hematopoietic stem cells are generally transfused through a central venous catheter (CVC), which also facilitates administration of medications and intravenous fluids. We had observed a high rate of CVC infections at our Bone Marrow Transplantation (BMT) unit. Accordingly, we evaluated the impact of administration of doxycycline as a prophylactic strategy to reduce CVC infection rates. Data was collected retrospectively on 54 consecutive patients, 26 who received doxycycline (doxycycline grou...

  2. Orofacial complications in children undergoing cancer therapy in Hong Kong

    OpenAIRE

    Nair, RG; Chu, CH; Chan, GCF

    2005-01-01

    Objectives. To investigate the orofacial complications in children undergoing cancer therapy and to increase their awareness of oral health. Methods. A randomly selected convenient sample of 46 children aged below 18 years undergoing combination chemotherapy for hematological malignancies or solid tumors at Queen Mary Hospital were recruited. Clinical examination and a parental questionnaire survey were performed. Parents were taught about oral health and received a talk that focused on the c...

  3. Selenium supplementation in patients undergoing hematopoietic stem cell transplantation: effects on pro-inflammatory cytokines levels

    OpenAIRE

    Daeian, Nesa; Radfar, Mania; Jahangard-Rafsanjani, Zahra; Hadjibabaie, Molouk; Ghavamzadeh, Ardeshir

    2014-01-01

    Background Pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) play an important role in the development of hematopoietic stem cell transplantation (HSCT) complications. We explored the effect of Selenium as an antioxidant and anti-inflammatory agent on pro-inflammatory cytokines levels in HSCT candidates. Findings Plasma concentrations of TNF-α, IL-1β and IL-6 were measured in 74 patients from a double-blind, randomized, p...

  4. PROPHYLACTIC ADMINISTRATION OF DOXYCYCLINE REDUCES CENTRAL VENOUS CATHETER INFECTIONS IN PATIENTS UNDERGOING HEMATOPOIETIC CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Mohamed Kharfan-Dabaja

    2013-02-01

    Full Text Available Hematopoietic stem cells are usually transfused through a central venous catheter (CVC, which also facilitates administration of medications and intravenous fluids. We had observed high rate of catheter-related blood-stream infection (CR-BSI at our Bone Marrow Transplantation (BMT unit despite prescribing fluoroquinolones for anti-bacterial prophylaxis. Accordingly, we implemented prophylactic use of a relatively inexpensive broad spectrum antibiotic, namely doxycycline to address this problem. We wanted to investigate whether doxycycline prophylaxis reduces CR-BSI rate. Data was collected retrospectively on 54 consecutive patients, 26 of whom received doxycycline (doxycycline group, and we compared their outcomes to a previous cohort of 28 patients who did not receive doxycycline (comparison group. The groups were comparable in regards to age, gender, hematopoietic cell transplant type, and primary diagnosis. No CVC infection (0% was observed in the doxycycline group, while 5 infection episodes (18.5% occurred in 4 patients in the comparison group (p<0.001. Episodes of CR-BSI were due to: Escherichia-coli (EC=1, coagulase-negative Staphylococcus-spp (CNSS=2, both EC & CNSS=1. Our results demonstrate that CR-BSI was reduced significantly after introducing doxycycline. This finding suggests a beneficial role for systemic use of doxycycline prophylaxis to prevent CR-BSI in adult BMT patients. Nevertheless, a randomized controlled study is warranted to confirm these findings.

  5. Time to Insurance Approval in Private and Public Payers Does Not Influence Survival in Patients Who Undergo Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Bhatt, Vijaya Raj; Loberiza, Fausto R; Schmit-Pokorny, Kim; Lee, Stephanie J

    2016-06-01

    In the United States, insurance status has been implicated as a barrier to obtaining timely treatment. In this retrospective cohort study of 521 patients who underwent first hematopoietic cell transplantation (HCT), we investigated the association between timeliness of HCT and overall survival. Timeliness was operationally defined in the following 3 ways: (1) payer approval, from request for approval to actual payer approval; (2) transplantation speed, from payer approval to time of actual HCT; and (3) total time, from request for approval to HCT. Patients with private insurance had longer time to payer approval (P HCT (P HCT (P HCT in lymphoma (n = 278), and autologous HCT in multiple myeloma (n = 121). Additional studies to evaluate the effect of insurance timeliness on all patients for whom HCT is recommended, not just those who undergo HCT, should be conducted. PMID:26988742

  6. The polyomaviruses WUPyV and KIPyV: a retrospective quantitative analysis in patients undergoing hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Motamedi Nasim

    2012-09-01

    Full Text Available Abstract Background The polyomaviruses WUPyV and KIPyV have been detected in various sample types including feces indicating pathogenicity in the gastrointestinal (GI system. However, quantitative viral load data from other simultaneously collected sample types are missing. As a consequence, primary replication in the GI system cannot be differentiated from swallowed virus from the respiratory tract. Here we present a retrospective quantitative longitudinal analysis in simultaneously harvested specimens from different organ sites of patients undergoing hematopoietic stem cell transplantation (HSCT. This allows the definition of sample types where deoxyribonucleic acid (DNA detection can be expected and, as a consequence, the identification of their primary replication site. Findings Viral DNA loads from 37 patients undergoing HSCT were quantified in respiratory tract secretions (RTS, stool and urine samples as well as in leukocytes (n = 449. Leukocyte-associated virus could not be found. WUPyV was found in feces, RTS and urine samples of an infant, while KIPyV was repeatedly detected in RTS and stool samples of 4 adult patients. RTS and stool samples were matched to determine the viral load difference showing a mean difference of 2.3 log copies/ml (p  Conclusions The data collected in this study suggest that virus detection in the GI tract results from swallowed virus from the respiratory tract (RT. We conclude that shedding from the RT should be ruled out before viral DNA detection in the feces can be correlated to GI symptoms.

  7. Physiological problems in patients undergoing autologous and allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Sevgisun Kapucu

    2014-01-01

    Full Text Available Objective: Stem cell transplantation is usually performed in an effort to extend the patient′s life span and to improve their quality of life. This study was conducted to determine the postoperative physiological effects experienced by patients who had undergone autologous and allogeneic stem cell transplantation. Methods: The research is a descriptive study conducted with a sample of 60 patients at Stem Cell Transplantation Units in Ankara. Percentile calculation and chi-square tests were used to evaluate the data. Results: When a comparison was made between patients who had undergone allogeneic Hematopoietic stem cell transplantation (HSCT and those who had undergone autologous HSCT, results indicated that problems occurred more often for the allogeneic HSCT patients. The problems included: Digestion (94.3%, dermatological (76.7%, cardiac and respiratory (66.7%, neurological (66.7%, eye (56.7%, infections (26.7% and Graft Versus Host Disease (5 patients. Furthermore, the problems with pain (50%, numbness and tingling (40%, and speech disorders (3 patients were observed more often in autologous BMT patients. Conclusion: Autologous and allogeneic patients experienced most of physical problems due to they receive high doses of chemotherapy. Therefore, it is recommended that an interdisciplinary support team approach should be usedtohelp reduce and manage the problems that may arise during patient care.

  8. Clofarabine-associated acute kidney injury in patients undergoing hematopoietic stem cell transplant.

    Science.gov (United States)

    Petri, Camille R; O'Donnell, Peter H; Cao, Hongyuan; Artz, Andrew S; Stock, Wendy; Wickrema, Amittha; Hard, Marjie; van Besien, Koen

    2014-12-01

    Abstract We examined clofarabine pharmacokinetics and association with renal toxicity in 62 patients participating in a phase I-II study of clofarabine-melphalan-alemtuzumab conditioning for hematopoietic stem cell transplant (HSCT). Pharmacokinetic parameters, including clofarabine area under the concentration-time curve (AUC), maximum concentration and clearance, were measured, and patients were monitored for renal injury. All patients had normal pretreatment creatinine values, but over half (55%) experienced acute kidney injury (AKI) after clofarabine administration. Age was the strongest predictor of AKI, with older patients at greater risk (p = 0.002). Clofarabine AUC was higher in patients who developed AKI, and patients with the highest dose-normalized AUCs experienced the most severe grades of AKI (p = 0.01). Lower baseline renal function, even when normal, was associated with lower clofarabine clearance (p = 0.008). These data suggest that renal-adjustment of clofarabine dosing should be considered for older and at-risk patients even when renal function is ostensibly normal. PMID:24564572

  9. Immune Reconstitution after Allogeneic Hematopoietic Cell Transplantation in Children.

    Science.gov (United States)

    de Koning, Coco; Plantinga, Maud; Besseling, Paul; Boelens, Jaap Jan; Nierkens, Stefan

    2016-02-01

    Allogeneic (allo) hematopoietic cell transplantation (HCT) has evolved into a potent curative treatment option for a variety of malignant and nonmalignant diseases. The occurrence of complications and mortality after allo-HCT is, however, still high and is strongly associated with immune reconstitution (IR). Therefore, detailed information on IR through immunomonitoring is crucial to improve survival chances after HCT. To date, information about the reconstituting immune system after allo-HCT in pediatric patients is mostly derived from routine standard-of-care measurements. More profound knowledge on IR may provide tools to better predict and modulate adverse reactions and, subsequently, improve survival chances. Here, we provide an overview of IR (eg, immune cell subsets and circulating chemokines/cytokines) after allo-HCT in children, taking into account different cell sources and serotherapy, and discuss strategies to enhance immunomonitoring. We conclude that available IR data after allo-HCT contain limited information on immune cell families (mostly only generic T, B, and NK cells), which would improve with more detailed information on reconstituting cell subsets or effector cell functionality at earlier time points (functionality and may even provide (early) biomarkers for individual disease outcome, such as viral reactivity, graft-versus-host disease, or graft-versus-leukemia. The present data and suggestions for more detailed, standardized, and harmonized immunomonitoring in future (pediatric) allo-HCT studies will pave the path to "precision transplantation:" an individualized HCT approach (including conditioning), based on detailed information on IR and biomarkers, aiming to reduce transplantation related mortality and relapse, and subsequently improve survival chances. PMID:26341398

  10. Nutritional consequences in children undergoing chemotherapy for malignant disease

    OpenAIRE

    Skolin, Inger

    2005-01-01

    Background: Chemotherapy has side effects that may interfere with food intake. Children suffering from a malignant disease are subjected to treatment with chemotherapy. They may therefore become at risk of undernutrition during the period of treatment. This in turn may increase the risk of infections, delayed therapy and influence the outcome of treatment. Few studies have investigated how children undergoing chemotherapy for cancer perceive food and eating. Attempts to improve food intake an...

  11. NRS2002 assesses nutritional status of leukemia patients undergoing hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Peng Liu; Zhao-Feng Zhang; Jing-Jing Cai; Bo-Shi Wang; Xia Yan

    2012-01-01

    Objective:To discuss whether nutritional risk screening 2002 (NRS2002) is appropriate for nutritional risk screening for leukemia patients before and after hematopoietic stem cell transplantation (HSCT),and whether there are risk differences in other conditions,such as age,gender and matching degree; to find the methods and indicators of nutritional risk screening for these patients before and after HSCT,in order to give timely intervention to guarantee the successful completion of the entire transplantation process.Methods:Nutritional risk of 99 leukemia patients was screened with NRS2002 before and after HSCT.The x2 test was applied to compare the risk differences between groups such as age,gender and matching degree,while the differences of other enumeration data,such as recent (1-3 months) weight loss,reduced food intake within one week and BMI,were compared by continuity correction.Results:Of the 99 leukemia patients,22 cases (22.2%) had nutritional risk before HSCT,while all patients had nutritional risk after HSCT; there is no significant difference in nutritional risk between male and female,and patients of less than 30 years old,not-full matched,recent (1-3 months) weight loss,reduced food intake within a week or BMI <18.5 were more likely to have nutritional risk; and 77 cases (77.8%) had weight loss,among which 49 patients (63.6%) had more than 5% weight loss within one month.Conclusions:This study showed that leukemia patients should receive the nutritional risk screening conventionally before and after HSCT,and NRS2002 was only appropriate for nutritional risk screening before HSCT.More attention should be paid to the patients less than 30 years old or not-full matched.Weight change was one of the important nutritional indicators for patients after HSCT.

  12. Anti-thymocyte globulin-induced hyperbilirubinemia in patients with myelofibrosis undergoing allogeneic hematopoietic cell transplantation.

    Science.gov (United States)

    Ecsedi, Matyas; Schmohl, Jörg; Zeiser, Robert; Drexler, Beatrice; Halter, Jörg; Medinger, Michael; Duyster, Justus; Kanz, Lothar; Passweg, Jakob; Finke, Jürgen; Bethge, Wolfgang; Lengerke, Claudia

    2016-10-01

    Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment option for myelofibrosis (MF) despite the emergence of novel targeted therapies. To reduce graft rejection and graft-versus-host disease (GvHD), current allo-HCT protocols often include in vivo T lymphocyte depletion using polyclonal anti-thymocyte globulin (ATG). Shortly after ATG administration, an immediate inflammatory response with fever, chills, and laboratory alterations such as cytopenias, elevation of serum C-reactive protein, bilirubin, and transaminases can develop. Here, we explore whether MF patients, who commonly exhibit extramedullary hematopoiesis in the liver, might be particularly susceptible to ATG-induced liver toxicity. To test this hypothesis, we analyzed 130 control and 94 MF patients from three transplant centers treated with or without ATG during the allo-HCT conditioning regimen. Indeed, hyperbilirubinemia was found in nearly every MF patient treated with ATG (MF-ATG 54/60 = 90 %) as compared to non-ATG treated MF (MF-noATG 15/34 = 44.1 %, p < 0.001) and respectively ATG-treated non-MF patients of the control group (control-ATG, 43/77 = 56 %, p < 0.001). In contrast, transaminases were only inconsistently elevated. Hyperbilirubinemia was in most cases self-limiting and not predictive of increased incidence of non-relapse mortality, hepatic sinusoidal obstruction syndrome (SOS) or liver GvHD. In sum, awareness of this stereotypic bilirubin elevation in MF patients treated with ATG provides a relatively benign explanation for hyperbilirubinemia occurring in these patients during the early transplant. However, attention to drug levels of biliary excreted drugs is warranted, since altered bile flow may influence their clearance and enhance toxicity (e.g., busulfan, antifungal agents). PMID:27480090

  13. Utility of an Australasian registry for children undergoing radiation treatment

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate the utility of an Australasian registry ('the Registry') for children undergoing radiation treatment (RT). Children under the age of 16years who received a course of radiation between January 1997 and December 2010 and were enrolled on the Registry form the subjects of this study. A total of 2232 courses of RT were delivered, predominantly with radical intent (87%). Registrations fluctuated over time, but around one-half of children diagnosed with cancer undergo a course of RT. The most prevalent age range at time of RT was 10–15years, and the most common diagnoses were central nervous system tumours (34%) and acute lymphoblastic leukaemia (20%). The Registry provides a reflection of the patterns of care of children undergoing RT in Australia and a mechanism for determining the resources necessary to manage children by RT (human, facilities and emerging technologies, such as proton therapy). It lacks the detail to provide information on radiotherapy quality and disease outcomes which should be the subject of separate audit studies. The utility of the Registry has been hampered by its voluntary nature and varying needs for consent. Completion of registry forms is a logical requirement for inclusion in the definition of a subspecialist in paediatric radiation oncology.

  14. Extracorporeal Photopheresis for the Prevention of Acute GVHD in Patients Undergoing Standard Myeloablative Conditioning and Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Shaughnessy, Paul J; Bolwell, Brian J; van Besien, Koen; Mistrik, Martin; Grigg, Andrew; Dodds, Anthony; Prince, H Miles; Durrant, Simon; Ilhan, Osman; Parenti, Dennis; Rogers, Jon; Gallo, Jose; Foss, Francine; Apperley, Jane; Zhang, Mei-Jie; Horowitz, Mary M; Abhyankar, Sunil

    2012-01-01

    Summary Graft-versus-host disease (GVHD) is partly mediated by host antigen presenting cells (APCs) that activate donor T-cells. Extracorporeal photopheresis (ECP) can modulate APC function and benefit some patients with GVHD. We report the results of a study using ECP administered prior to a standard myeloablative preparative regimen intended to prevent GVHD. Grade II-IV aGVHD developed in 9 (30%) of 30 recipients of HLA-matched related transplants and 13 (42%) of 31 recipients of HLA-matched unrelated or HLA-mismatched related donor transplants. Actuarial estimates of overall survival (OS) at day 100 and 1 year post transplant were 89% (95% CI, 78%-94%) and 77% (95% CI, 64%-86%), respectively. There were no unexpected adverse effects of ECP. Historical controls receiving similar conditioning and GVHD prophylaxis regimens but no ECP were identified from the database of the Center for International Blood and Marrow Transplant Research and multivariate analysis indicated a lower risk of grade II-IV aGVHD in patients receiving ECP (p=0.04). Adjusted OS at one year was 83% in the ECP study group and 67% in the historical control group (relative risk 0.44, 95% CI, 0.24-0.80) (p= 0.007). These preliminary data may indicate a potential survival advantage with ECP for transplant recipients undergoing standard myeloablative hematopoietic cell transplantation. PMID:19915634

  15. SECOND MALIGNANCIES AFTER AUTOLOGOUS HEMATOPOIETIC CELL TRANSPLANTATION IN CHILDREN

    OpenAIRE

    Danner-Koptik, Karina E; Majhail, Navneet S.; Brazauskas, Ruta; Wang, Zhiwei; Buchbinder, David; Cahn, Jean-Yves; Dilley, Kimberley J.; Frangoul, Haydar A.; Gross, Thomas G.; Hale, Gregory A.; Hayashi, Robert J.; Hijiya, Nobuko; Kamble, Rammurti T.; Lazarus, Hillard M.; Marks, David I.

    2012-01-01

    Childhood autologous hematopoietic cell transplant (AHCT) survivors can be at risk for secondary malignant neoplasms (SMNs). We assembled a cohort of 1,487 pediatric AHCT recipients to investigate the incidence and risk factors for SMNs. Primary diagnoses included neuroblastoma (39%), lymphoma (26%), sarcoma (18%), CNS tumors (14%), and Wilms tumor (2%). Median follow-up was 8 years (range,

  16. Lung function after allogeneic hematopoietic stem cell transplantation in children

    DEFF Research Database (Denmark)

    Uhlving, Hilde Hylland; Larsen Bang, Cæcilie; Christensen, Ib Jarle; Buchvald, Frederik Fouirnaies; Nielsen, Kim Gjerum; Heilmann, Carsten Johan; Müller, Klaus Gottlob

    2013-01-01

    Reduction in pulmonary function (PF) has been reported in up to 85% of pediatric patients during the first year after hematopoietic stem cell transplantation (HSCT). Our understanding of the etiology for this decrease in lung function is, however, sparse. The aim of this study was to describe PF...

  17. Interactions between the gut microbiota, short-chain fatty acids and the immune system in pediatric patients undergoing hematopoietic stem cell transplantation

    OpenAIRE

    Nastasi, Claudia

    2015-01-01

    The gut microbiota (GM) is essential for human health and contributes to several diseases; indeed it can be considered an extension of the self and, together with the genetic makeup, determines the physiology of an organism. In this thesis has been studied the peripheral immune system reconstitution in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (aHSCT) in the early phase; in parallel, have been also explored the gut microbiota variations as one of the...

  18. Clofarabine Combined with Busulfan Provides Excellent Disease Control in Adult Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

    OpenAIRE

    Kebriaei, P.; Basset, Roland; Ledesma, C.; Ciurea, S; Parmar, S.; Shpall, EJ; Hosing, C.; Khouri, Issa; Qazilbash, M; Popat, U; Alousi, A.; Nieto, Y; Jones, RB; Lima, M.; Champlin, RE

    2012-01-01

    We investigated the safety and early disease-control data obtained with intravenous busulfan (Bu) combined with clofarabine (Clo) in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (SCT). Fifty-one patients with median age 36 years (range 20–64) received a matched sibling (n=24), syngeneic (n=2) or matched unrelated donor transplant (n=25) for ALL in first complete remission (n=30), second complete remission (n=13), or with active...

  19. Late Effects Surveillance Recommendations among Survivors of Childhood Hematopoietic Cell Transplantation: A Children's Oncology Group Report.

    Science.gov (United States)

    Chow, Eric J; Anderson, Lynnette; Baker, K Scott; Bhatia, Smita; Guilcher, Gregory M T; Huang, Jennifer T; Pelletier, Wendy; Perkins, Joanna L; Rivard, Linda S; Schechter, Tal; Shah, Ami J; Wilson, Karla D; Wong, Kenneth; Grewal, Satkiran S; Armenian, Saro H; Meacham, Lillian R; Mulrooney, Daniel A; Castellino, Sharon M

    2016-05-01

    Hematopoietic cell transplantation (HCT) is an important curative treatment for children with high-risk hematologic malignancies, solid tumors, and, increasingly, nonmalignant diseases. Given improvements in care, there are a growing number of long-term survivors of pediatric HCT. Compared with childhood cancer survivors who did not undergo transplantation, HCT survivors have a substantially increased burden of serious chronic conditions and impairments involving virtually every organ system and overall quality of life. This likely reflects the joint contributions of pretransplantation treatment exposures and organ dysfunction, the transplantation conditioning regimen, and any post-transplantation graft-versus-host disease (GVHD). In response, the Children's Oncology Group (COG) has created long-term follow-up guidelines (www.survivorshipguidelines.org) for survivors of childhood, adolescent, and young adult cancer, including those who were treated with HCT. Guideline task forces, consisting of HCT specialists, other pediatric oncologists, radiation oncologists, organ-specific subspecialists, nurses, social workers, other health care professionals, and patient advocates systematically reviewed the literature with regards to late effects after childhood cancer and HCT since 2002, with the most recent review completed in 2013. For the most recent review cycle, over 800 articles from the medical literature relevant to childhood cancer and HCT survivorship were reviewed, including 586 original research articles. Provided herein is an organ system-based overview that emphasizes the most relevant COG recommendations (with accompanying evidence grade) for the long-term follow-up care of childhood HCT survivors (regardless of current age) based on a rigorous review of the available evidence. These recommendations cover both autologous and allogeneic HCT survivors, those who underwent transplantation for nonmalignant diseases, and those with a history of chronic GVHD. PMID

  20. Unrelated Hematopoietic Stem Cell Transplantation for Children with Acute Leukemia: Experience at a Single Institution

    OpenAIRE

    Lee, Jae Hee; Yoon, Hoi Soo; Song, Joon Sup; Choi, Eun Seok; Moon, Hyung Nam; Seo, Jong Jin; Im, Ho Joon

    2009-01-01

    We evaluate the outcomes in children with acute leukemia who received allogeneic hematopoietic stem cell transplantation (HCT) using unrelated donor. Fifty-six children in complete remission (CR) received HCT from unrelated donors between 2000 and 2007. Thirty-five had acute myeloid leukemia, and 21 had acute lymphoid leukemia. Stem cell sources included bone marrow in 38, peripheral blood in 4, and cord blood (CB) in 14. Four patients died before engraftment and 52 engrafted. Twenty patients...

  1. Cytogenetics Does Not Impact Outcomes in Adult Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Aldoss, Ibrahim; Tsai, Ni-Chun; Slovak, Marilyn L; Palmer, Joycelynne; Alvarnas, Joseph; Marcucci, Guido; Forman, Stephen J; Pullarkat, Vinod

    2016-07-01

    The prognostic relevance of cytogenetics at diagnosis on the outcome of allogeneic hematopoietic stem cell transplantation (alloHCT) for adult acute lymphoblastic leukemia (ALL) remains unclear. We retrospectively analyzed outcomes of 333 adult ALL patients who underwent alloHCT at our institution over a 10-year period. Patients were classified according to disease status at transplantation (complete response [CR] 1 [n = 202] or > CR1) and according to cytogenetic risk, defined as good (2%), intermediate (42%), poor (46%), or unknown (10%) based on available outcome data for each of the cytogenetic abnormalities. Three-year overall survival (OS), leukemia-free survival (LFS), and relapse incidence (RI) were 55.7%, 47.9% and 27.5%, respectively; 1-year nonrelapse mortality (NRM) was 17.3%. For patients undergoing alloHCT in CR1, 3-year OS, LFS, and RI were 69.8%, 62.3%, and 17.1%, respectively. In multivariable analysis, cytogenetic risk did not impact OS or LFS for the whole cohort or for patients who underwent transplantation in CR1. Disease status at alloHCT was an independent predictor for LFS (CR1 versus others: hazard ratio [HR], 3.17; P OS (CR1 versus others: HR, 2.90; P < .01). Graft-versus-host disease prophylaxis with tacrolimus/sirolimus was associated with a low NRM of 11.5% in the alloHCT recipients in CR1. Our data indicate that cytogenetic risk is not an independent predictor of outcomes in alloHCT performed to treat adult ALL. PMID:27044907

  2. Higher plasma bilirubin predicts veno-occlusive disease in early childhood undergoing hematopoietic stem cell transplantation with cyclosporine

    Science.gov (United States)

    Kim, Kwi Suk; Moon, Aree; Kang, Hyoung Jin; Shin, Hee Young; Choi, Young Hee; Kim, Hyang Sook; Kim, Sang Geon

    2016-01-01

    AIM: To analyze the association between plasma bilirubin levels and veno-occlusive disease (VOD) in non-adult patients undergoing hematopoietic stem cell transplantation (HSCT) during cyclosporine therapy. METHODS: A total of 123 patients taking cyclosporine were evaluated using an electronic medical system at the Seoul National University Children’s Hospital from the years 2004 through 2011. Patients were grouped by age and analyzed for incidence and type of adverse drug reactions (ADRs) including VOD. RESULTS: The HSCT patients were divided into three age groups: G#1 ≥ 18; 9 ≤ G#2 ≤ 17; and G#3 ≤ 8 years of age). The majority of transplant donor types were cord blood transplantations. Most prevalent ADRs represented acute graft-vs-host disease (aGVHD) and VOD. Although the incidences of aGVHD did not vary among the groups, the higher frequency ratios of VOD in G#3 suggested that an age of 8 or younger is a risk factor for developing VOD in HSCT patients. After cyclosporine therapy, the trough plasma concentrations of cyclosporine were lower in G#3 than in G#1, indicative of its increased clearance. Moreover, in G#3 only, a maximal total bilirubin level (BILmax) of ≥ 1.4 mg/dL correlated with VOD incidence after cyclosporine therapy. CONCLUSION: HSCT patients 8 years of age or younger are more at risk for developing VOD, diagnosed as hyperbilirubinemia, tender hepatomegaly, and ascites/weight gain after cyclosporine therapy, which may be represented by a criterion of plasma BILmax being ≥ 1.4 mg/dL, suggestive of more sensitive VOD indication in this age group. PMID:27358786

  3. Anxiety and personality characteristics in children undergoing dental interventions.

    Science.gov (United States)

    Pop-Jordanova, Nada; Sarakinova, Olivera; Markovska-Simoska, Silvana; Loleska, Sofija

    2013-01-01

    Anxiety about and fear of dental treatment have been recognized as sources of problems in the management of child dental patients. It has been suggested that some individuals who are fearful of or anxious about dental treatment have a constitutional vulnerability to anxiety disorders as is evidenced by the presence of multiple fears, generalized anxiety or panic disorders. Concerning the child population, maternal anxiety is considered to be a major factor affecting the behaviour of young children expecting dental intervention. The aim of the study was to the measure general anxiety of children undergoing dental intervention and to compare it with some personality characteristics, such as psychopathology, extroversion and neuroticism. The evaluated sample comprises 50 children (31 girls and 19 boys), randomly selected at the University Dental Hospital, Skopje. The mean age for girls was 11.4 (± 2.4) years, and for boys 10.7 (± 2.6) years. Two psychometric instruments were used: the General Anxiety Scale for Children (GASC) and the Eysenck Personality Questionnaire (EPQ). The study confirms the presence of a high anxiety level (evaluated with GASC) among all children undergoing dental intervention. It also confirmed differences in anxiety scores between girls and boys, girls having higher scores for anxiety. Personality characteristics (evaluated with EPQ) showed low psychopathological traits, moderate extroversion and neuroticism, but accentuated insincerity (evaluated with L scale). L scales are lower with increasing age, but P scores rise with age, which could be related to puberty. No correlation was found between personality traits (obtained scores for EPQ) and anxiety except for neuroticism, which is positively correlated with the level of anxiety. In the management of dental anxiety some response measures (psychological support, biofeedback, and relaxation techniques) are recommended. PMID:24566020

  4. Improved overall survival for pediatric patients undergoing allogeneic hematopoietic stem cell transplantation - A comparison of the last two decades.

    Science.gov (United States)

    Svenberg, Petter; Remberger, Mats; Uzunel, Mehmet; Mattsson, Jonas; Gustafsson, Britt; Fjaertoft, Gustav; Sundin, Mikael; Winiarski, Jacek; Ringdén, Olle

    2016-08-01

    Pediatric protocols for allogeneic hematopoietic SCT have been altered during the last two decades. To compare the outcomes in children (P1) and 2003-2013 (P2). We retrospectively analyzed 188 patients in P1 and 201 patients in P2. The most significant protocol changes during P2 compared with P1 were a decrease in MAC protocols, particularly those containing TBI, an increase in RIC protocols, and altered GvHD prophylaxis. In addition, P2 had more patients with nonmalignant diagnoses (p = 0.002), more mismatched (MM) donors (p = 0.01), and more umbilical CB grafts (p = 0.03). Mesenchymal or DSCs were used for severe acute GvHD during P2. Three-yr OS in P1 was 58%, and in P2, it was 78% (p < 0.001). Improved OS was seen in both malignant disorders (51% vs. 68%; p = 0.05) and nonmalignant disorders (77% vs. 87%; p = 0.04). Multivariate analysis showed that SCT during P2 was associated with reduced mortality (HR = 0.57; p = 0.005), reduced TRM (HR = 0.57; p = 0.03), unchanged relapse rate, similar rate of GF, less chronic GvHD (HR = 0.49; p = 0.01), and more acute GvHD (HR = 1.77, p = 0.007). During recent years, OS has improved at our center, possibly reflecting the introduction of less toxic conditioning regimens and a number of other methodological developments in SCT. PMID:27251184

  5. Analgesia and sedation for children undergoing burn wound care.

    Science.gov (United States)

    Bayat, Ahmad; Ramaiah, Ramesh; Bhananker, Sanjay M

    2010-11-01

    Standard care of burn wounds consists of cleaning and debridement (removing devitalized tissue), followed by daily dressing changes. Children with burns undergo multiple, painful and anxiety-provoking procedures during wound care and rehabilitation. The goal of procedural sedation is safe and efficacious management of pain and emotional distress, requiring a careful and systematic approach. Achieving the best results needs understanding of the mechanisms of pain and the physiologic changes in burn patients, frequent evaluation and assessment of pain and anxiety, and administration of suitable pharmacological and nonpharmacological therapies. Pharmacological therapies provide the backbone of analgesia and sedation for procedural pain management. Opioids provide excellent pain control, but they must be administered judiciously due to their side effects. Sedative drugs, such as benzodiazepines and propofol, provide excellent sedation, but they must not be used as a substitute for analgesic drugs. Ketamine is increasingly used for analgesia and sedation in children as a single agent or an adjuvant. Nonpharmacological therapies such as virtual reality, relaxation, cartoon viewing, music, massage and hypnosis are necessary components of procedural sedation and analgesia for children. These can be combined with pharmacological techniques and are used to limit the use of drugs (and hence side effects), as well as to improve patient participation and satisfaction. In this article, we review the pathophysiologic changes associated with major thermal injury in children, the options available for sedation and analgesia for wound care procedures in these children and our institutional guidelines for procedural sedation. PMID:20977331

  6. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Jeffrey Y.C., E-mail: jwong@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Forman, Stephen; Somlo, George [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Rosenthal, Joseph [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Department of Pediatrics, City of Hope National Medical Center, Duarte, California (United States); Liu An; Schultheiss, Timothy; Radany, Eric [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Palmer, Joycelynne [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Stein, Anthony [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States)

    2013-01-01

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on Day -5 (60 mg/kg), and cyclophosphamide (CY) on Day -3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days -12 to -8 (800 {mu}M min), TMI on Days -8 to -4, and VP16 on Day -3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible with BU/VP16 due to

  7. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    International Nuclear Information System (INIS)

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days −10 to −6, etoposide (VP16) on Day −5 (60 mg/kg), and cyclophosphamide (CY) on Day −3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days −12 to −8 (800 μM min), TMI on Days −8 to −4, and VP16 on Day −3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible

  8. [Prophylaxis against respiratory viral disease in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation].

    Science.gov (United States)

    Álvarez, Ana M; Catalán, Paula; Alba, Andrea; Zubleta, Marcela

    2012-09-01

    Respiratory viruses have been identified as a cause of morbidity and mortality in patients undergoing SOT and HSCT, specially in children. The most frequent are respiratory syncytial virus (RSV), influenza (FLU), parainfluenza (PI) and adenovirus (ADV). These infections are associated with progression to severe lower respiratory tract infections in up to 60% of the cases. It is advised to apply universal protection recommendations for respiratory viruses (A2) and some specific measures for FLU and AD. FLU: Annual anti-influenza vaccination (from 4-6 months post-transplantation in SOT, 6 months in HSCT (A2)); post- exposure prophylaxis in FLU (oseltamivir for 10 days (B2)). In lung transplantion, the prophylaxis should last as long as the risk period (B2). ADV: There is no vaccine nor valid chemoprophylaxis strategy to prevent ADV disease. In some specific HSCT recipients, weekly PCR monitoring is recommended until day+100 (A3). PMID:23282554

  9. Gastrointestinal Complications Following Hematopoietic Stem Cell Transplantation in Children

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Hye; Lim, Gye Yeon; Im, Soo Ah; Chung, Nak Gyun; Hahn, Seung Tae [St. Mary' s Hospital, The Catholic University of Korea, Seoul (Korea, Republic of)

    2008-10-15

    Gastrointestinal system involvement is one of the principal complications seen in the recipients of hematopoietic stem cell transplantation (HSCT), and it is also a major cause of morbidity and death in these patients. The major gastrointestinal complications include typhlitis (neutropenic enterocolitis), pseudomembranous enterocolitis, viral enteritis, graft-versus-host disease, benign pneumatosis intestinalis, intestinal thrombotic microangiopathy, and post-transplantation lymphoproliferative disease. As these patients present with nonspecific abdominal symptoms, evaluation with using such imaging modalities as ultrasonography and CT is essential in order to assess the extent of gastrointestinal involvement and to diagnose these complications. We present here a pictorial review of the imaging features and other factors involved in the diagnosis of these gastrointestinal complications in pediatric HSCT recipients.

  10. Vitamin D Deficiency and Survival in Children after Hematopoietic Stem Cell Transplant

    OpenAIRE

    Wallace, Gregory; Jodele, Sonata; Howell, Jonathan; Myers, Kasiani C.; Teusink, Ashley; Zhao, Xueheng; Setchell, Kenneth; Holtzapfel, Catherine; Lane, Adam; Taggart, Cynthia; Laskin, Benjamin L.; Davies, Stella M.

    2015-01-01

    Vitamin D has endocrine function as a key regulator of calcium absorption and bone homeostasis and also has intracrine function as an immunomodulator. Vitamin D deficiency before hematopoietic stem cell transplantation (HSCT) has been variably associated with higher risks of graft-versus-host disease (GVHD) and mortality. Children are at particular risk of growth impairment and bony abnormalities in the face of prolonged deficiency. There are few longitudinal studies of vitamin D deficient ch...

  11. Non-invasive anesthesia for children undergoing proton radiation therapy

    International Nuclear Information System (INIS)

    Background: Proton therapy is a newer modality of radiotherapy during which anesthesiologists face specific challenges related to the setup and duration of treatment sessions. Purpose: Describe our anesthesia practice for children treated in a standalone proton therapy center, and report on complications encountered during anesthesia. Materials and methods: A retrospective review of anesthetic records for patients ⩽18 years of age treated with proton therapy at our institution between January 2006 and April 2013 was performed. Results: A total of 9328 anesthetics were administered to 340 children with a median age of 3.6 years (range, 0.4–14.2). The median daily anesthesia time was 47 min (range, 15–79). The average time between start of anesthesia to the start of radiotherapy was 7.2 min (range, 1–83 min). All patients received Total Intravenous Anesthesia (TIVA) with spontaneous ventilation, with 96.7% receiving supplemental oxygen by non-invasive methods. None required daily endotracheal intubation. Two episodes of bradycardia, and one episode each of; seizure, laryngospasm and bronchospasm were identified for a cumulative incidence of 0.05%. Conclusions: In this large series of children undergoing proton therapy at a freestanding center, TIVA without daily endotracheal intubation provided a safe, efficient, and less invasive option of anesthetic care

  12. Accurate measurement of oxygen consumption in children undergoing cardiac catheterization.

    Science.gov (United States)

    Li, Jia

    2013-01-01

    Oxygen consumption (VO(2) ) is an important part of hemodynamics using the direct Fick principle in children undergoing cardiac catheterization. Accurate measurement of VO(2) is vital. Obviously, any error in the measurement of VO(2) will translate directly into an equivalent percentage under- or overestimation of blood flows and vascular resistances. It remains common practice to estimate VO(2) values from published predictive equations. Among these, the LaFarge equation is the most commonly used equation and gives the closest estimation with the least bias and limits of agreement. However, considerable errors are introduced by the LaFarge equation, particularly in children younger than 3 years of age. Respiratory mass spectrometry remains the "state-of-the-art" method, allowing highly sensitive, rapid and simultaneous measurement of multiple gas fractions. The AMIS 2000 quadrupole respiratory mass spectrometer system has been adapted to measure VO(2) in children under mechanical ventilation with pediatric ventilators during cardiac catheterization. The small sampling rate, fast response time and long tubes make the equipment a unique and powerful tool for bedside continuous measurement of VO(2) in cardiac catheterization for both clinical and research purposes. PMID:22488802

  13. Psychologists in preoperative programmes for children undergoing surgery.

    Science.gov (United States)

    Cuzzocrea, Francesca; Costa, Sebastiano; Gugliandolo, Maria Cristina; Larcan, Rosalba

    2016-06-01

    This study aimed to verify whether psychologists and game activities could reduce preoperative anxiety and promote compliance in paediatric patients. More specifically, we sought to evaluate whether it would be better to propose contextualized games or just distracting activities. A total of 104 children undergoing surgery were assigned to the following 4 conditions of treatment: (1) contextual games and psychological accompaniment, (2) only contextual games, (3) distracting activities, and (4) only psychological accompaniment. Observed children's anxiety was assessed using modified Yale Preoperative Anxiety Scale and compliant behaviours with modified form of Induction Compliance Checklist. Children in the first condition (complete intervention - contextual games and psychological accompaniment) were less anxious and more cooperative in the preoperative period and during the induction of anaesthesia than in the other three conditions. In particular, contextual activities (second condition) were found to be more efficient than psychological accompaniment (fourth condition), whereas the worst condition was proposing only distracting activities (third condition). In order to help young hospitalized patients in paediatric surgery structures, it is necessary to propose games that can prepare them for what will happen as well as the support of a psychologist. PMID:25469004

  14. Hematopoietic Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia

    OpenAIRE

    Ibrahim Bayram

    2014-01-01

    In children patients with acute lymphoblastic leukemia, according to the European bone marrow transplant handbook, the indications for stem cell transplantation, conditioning regimen, donor selection and information about sources of stem cells will be evaluated.

  15. Pain Measurement through Temperature Changes in Children Undergoing Dental Extractions.

    Science.gov (United States)

    Kolosovas-Machuca, Eleazar S; Martínez-Jiménez, Mario A; Ramírez-GarcíaLuna, José L; González, Francisco J; Pozos-Guillen, Amaury J; Campos-Lara, Nadia P; Pierdant-Perez, Mauricio

    2016-01-01

    Background and Objective. Pain evaluation in children can be a difficult task, since it possesses sensory and affective components that are often hard to discriminate. Infrared thermography has previously been used as a diagnostic tool for pain detection in animals; therefore, the aim of this study was to assess the presence of temperature changes during dental extractions and to evaluate its correlation with heart rate changes as markers of pain and discomfort. Methods. Thermographic changes in the lacrimal caruncle and heart rate measurements were recorded in healthy children scheduled for dental extraction before and during the procedure and compared. Afterwards, correlation between temperature and heart rate was assessed. Results. We found significant differences in temperature and heart rate before the procedure and during the dental extraction (mean difference 4.07°C, p < 0.001, and 18.11 beats per minute, p < 0.001) and no evidence of correlation between both measurements. Conclusion. Thermographic changes in the lacrimal caruncle can be detected in patients who undergo dental extractions. These changes appear to be stable throughout time and to possess very little intersubject variation, thus making them a candidate for a surrogate marker of pain and discomfort. Future studies should be performed to confirm this claim. PMID:27445611

  16. Pain Measurement through Temperature Changes in Children Undergoing Dental Extractions

    Directory of Open Access Journals (Sweden)

    Eleazar S. Kolosovas-Machuca

    2016-01-01

    Full Text Available Background and Objective. Pain evaluation in children can be a difficult task, since it possesses sensory and affective components that are often hard to discriminate. Infrared thermography has previously been used as a diagnostic tool for pain detection in animals; therefore, the aim of this study was to assess the presence of temperature changes during dental extractions and to evaluate its correlation with heart rate changes as markers of pain and discomfort. Methods. Thermographic changes in the lacrimal caruncle and heart rate measurements were recorded in healthy children scheduled for dental extraction before and during the procedure and compared. Afterwards, correlation between temperature and heart rate was assessed. Results. We found significant differences in temperature and heart rate before the procedure and during the dental extraction (mean difference 4.07°C, p<0.001, and 18.11 beats per minute, p<0.001 and no evidence of correlation between both measurements. Conclusion. Thermographic changes in the lacrimal caruncle can be detected in patients who undergo dental extractions. These changes appear to be stable throughout time and to possess very little intersubject variation, thus making them a candidate for a surrogate marker of pain and discomfort. Future studies should be performed to confirm this claim.

  17. Anxiety in Children Undergoing VCUG: Sedation or No Sedation?

    Directory of Open Access Journals (Sweden)

    David W. Herd

    2008-01-01

    Full Text Available Background. Voiding cystourethrograms are distressing for children and parents. Nonpharmacological methods reduce distress. Pharmacological interventions for VCUG focus on sedation as well as analgesia, anxiolysis, and amnesia. Sedation has cost, time, and safety issues. Which agents and route should we use? Are we sure that sedation does not influence the ability to diagnose vesicoureteric reflux? Methods. Literature search of Medline, EMBASE, and the Cochrane Database. Review of comparative studies found. Results. Seven comparative studies including two randomised controlled trials were reviewed. Midazolam given orally (0.5-0.6 mg/kg or intranasally (0.2 mg/kg is effective with no apparent effect on voiding dynamics. Insufficient evidence to recommend other sedating agents was found. Deeper sedating agents may interfere with voiding dynamics. Conclusion. Midazolam reduces the VCUG distress, causes amnesia, and does not appear to interfere with voiding dynamics. Midazolam combined with simple analgesia is an effective method to reduce distress to children undergoing VCUG.

  18. Neutrophil function in children following allogeneic hematopoietic stem cell transplant.

    Science.gov (United States)

    Kent, Michael W; Kelher, Marguerite R; Silliman, Christopher C; Quinones, Ralph

    2016-08-01

    HSCT is a lifesaving procedure for children with malignant and non-malignant conditions. The conditioning regimen renders the patient severely immunocompromised and recovery starts with neutrophil (PMN) engraftment. We hypothesize that children demonstrate minimal PMN dysfunction at engraftment and beyond, which is influenced by the stem cell source and the conditioning regimen. Peripheral blood was serially collected from children at 1 to 12 months following allogeneic HSCT. PMN superoxide (O2-) production, degranulation (elastase), CD11b surface expression, and phagocytosis were assessed. Twenty-five patients, mean age of 10.5 yr with 65% males, comprised the study and transplant types included: 14 unrelated cord blood stem cells (cords), seven matched related bone marrow donors, three matched unrelated bone marrow donors, and one peripheral blood progenitor cells. Engraftment occurred at 24 days. There were no significant differences between controls and patients in PMN O2- production, phagocytosis, CD11b surface expression, and total PMN elastase. Elastase release was significantly decreased <6 months vs. controls (p < 0.05) and showed normalization by six months for cords only. The conditioning regimen did not affect PMN function. PMN function returns with engraftment, save elastase release, which occurs later related to the graft source utilized, and its clinical significance is unknown. PMID:27114335

  19. The effect of a multimodal intervention on treatment-related symptoms in patients undergoing hematopoietic stem cell transplantation: a randomized controlled trial

    DEFF Research Database (Denmark)

    Jarden, Mary; Nelausen, Knud; Hovgaard, Doris;

    2009-01-01

    Studies applying exercise, relaxation training, and psychoeducation have each indicated a positive impact on physical performance and/or psychological factors in patients diagnosed with cancer. We explored the longitudinal effect of a combination of these interventions on treatment-related sympto...... in patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT). Forty-two patients (18-65 years) were randomized either to an intervention or a control group. The intervention group received standard treatment and care, and a supervised four- to six......-week structured exercise program, progressive relaxation, and psychoeducation during hospitalization, one hour per day for five days per week. The control group received standard treatment, care, and physiotherapy. A 24-item symptom assessment questionnaire was completed weekly during hospitalization, and at...

  20. Efficacy of oral cryotherapy on oral mucositis prevention in patients with hematological malignancies undergoing hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Li Wang

    Full Text Available Controversy exists regarding whether oral cryotherapy can prevent oral mucositis (OM in patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT. The aim of the present meta-analysis was to evaluate the efficacy of oral cryotherapy for OM prevention in patients with hematological malignancies undergoing HSCT.PubMed and the Cochrane Library were searched through October 2014. Randomized controlled trials (RCTs comparing the effect of oral cryotherapy with no treatment or with other interventions for OM in patients undergoing HSCT were included. The primary outcomes were the incidence, severity, and duration of OM. The secondary outcomes included length of analgesic use, total parenteral nutrition (TPN use, and length of hospital stay.Seven RCTs involving eight articles analyzing 458 patients were included. Oral cryotherapy significantly decreased the incidence of severe OM (RR = 0.52, 95% CI = 0.27 to 0.99 and OM severity (SMD = -2.07, 95% CI = -3.90 to -0.25. In addition, the duration of TPN use and the length of hospitalization were markedly reduced (SMD = -0.56, 95% CI = -0.92 to -0.19; SMD = -0.44, 95% CI = -0.76 to -0.13; respectively. However, the pooled results were uncertain for the duration of OM and analgesic use (SMD = -0.13, 95% CI = -0.41 to 0.15; SMD = -1.15, 95% CI = -2.57 to 0.27; respectively.Oral cryotherapy is a readily applicable and cost-effective prophylaxis for OM in patients undergoing HSCT.

  1. Prognostic Value of EMT-Circulating Tumor Cells in Metastatic Breast Cancer Patients Undergoing High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Michal Mego, Hui Gao, Bang-Ning Lee, Evan N. Cohen, Sanda Tin, Antonio Giordano, Qiong Wu, Ping Liu, Yago Nieto, Richard E. Champlin, Gabriel N. Hortobagyi, Massimo Cristofanilli, Naoto T. Ueno, James M. Reuben

    2012-01-01

    Full Text Available Background: Circulating tumor cells (CTCs are an independent prognostic factor in metastatic breast cancer (MBC patients treated by conventional dose chemotherapy. The aim of this study was to determine the role of CTCs and CTCs undergoing epithelial-mesenchymal transition (EMT in metastatic breast cancer. We used the platform of high-dose chemotherapy (HDCT and autologous hematopoietic stem cell transplantation (AHSCT to study the CTCs and CTCs with EMT.Patients and methods: CTCs were enumerated in 21 MBC patients before apheresis and 1 month after AHSCT. CD34-depleted apheresis products were analyzed for CD326+ epithelial and Aldefluor+ cancer stem cells (CSC by flow cytometry and were depleted of CD45+ cells and assessed for EMT-inducing transcription factors (EMT-TF by quantitative RT-PCR.Results: Patients with ≥ 5 CTCs/7.5 mL of peripheral blood 1 month after AHSCT had shorter progression-free survival (PFS (P=0.02 and overall survival (OS (P=0.02. Patients with apheresis products containing high percentages of CD326+ epithelial cells or overexpressing EMT-TF had shorter PFS. In multivariate analysis, low percentage of CD326+ epithelial cells and response to HDCT with AHSCT were associated with longer PFS, whereas lower CTCs after AHSCT was associated with longer OS. High CTCs, 1 month after AHSCT correlated with shorter PFS and OS in MBC patients undergoing HDCT and AHSCT, while CTCs with EMT and CSCs phenotype in apheresis products are associated with relapse.Conclusion: Our data suggest that CTC and CTCs with EMT are prognostic in MBC patients undergoing HDCT followed by AHSCT.

  2. Inflammatory Response Using Different Lipid Parenteral Nutrition Formulas in Children After Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Baena-Gómez, María Auxiliadora; de la Torre-Aguilar, María José; Aguilera-García, Concepción María; Olza, Josune; Pérez-Navero, Juan Luis; Gil-Campos, Mercedes

    2016-07-01

    Nutritional support is an integral part of the supportive care of hematopoietic stem cell transplantation (HSCT) patients. Omega-3 fatty acids (n-3 FA) emulsions in parenteral nutrition (PN) may modify the inflammatory response. The purpose of this study is to compare plasma cytokine levels in children after HSCT using an n-3 FA-containing lipid emulsion (LE) and a soybean oil-based formulation in PN. A randomized double-blind controlled trial was conducted on 14 children following HSCT. Children were randomized to receive either a fish oil or a soybean oil LE. Blood samples were drawn at baseline, on Day 10 and after completion of PN to analyze plasma interleukin 1 beta (IL-1β), 2 (IL-2), 6 (IL-6), 8 (IL-8), 10 (IL-10), and tumor necrosis factor alpha (TNF-α). After 10 days of PN, there were no significant changes in interleukins levels when comparing the two groups or time points (baseline vs. Day 10 of PN). In children requiring PN >21 days, IL-10 and TNF-α levels (P ≤ 0.05) were lower in the fish-oil-containing LE group. Fish oil- and soybean oil-supplemented PN administered for at least 10 days does not cause inflammatory changes. Prolonged PN based on fish oil LE may modulate the inflammatory response. PMID:27270245

  3. Beneficial effect of the CXCL12-3'A variant for patients undergoing hematopoietic stem cell transplantation from unrelated donors.

    Science.gov (United States)

    Bogunia-Kubik, Katarzyna; Mizia, Sylwia; Polak, Małgorzata; Gronkowska, Anna; Nowak, Jacek; Kyrcz-Krzemień, Sławomira; Markiewicz, Mirosław; Dzierżak-Mietła, Monika; Koclęga, Anna; Sędzimirska, Mariola; Suchnicki, Krzysztof; Duda, Dorota; Lange, Janusz; Mordak-Domagała, Monika; Kościńska, Katarzyna; Jędrzejczak, Wiesław Wiktor; Kaczmarek, Beata; Hellmann, Andrzej; Kucharska, Agnieszka; Kowalczyk, Jerzy; Drabko, Katarzyna; Warzocha, Krzysztof; Hałaburda, Kazimierz; Tomaszewska, Agnieszka; Mika-Witkowska, Renata; Witkowska, Agnieszka; Goździk, Jolanta; Mordel, Anna; Wysoczańska, Barbara; Jaskula, Emilia; Lange, Andrzej

    2015-12-01

    The present study aimed to assess the impact of the CXCL12 gene polymorphism (rs1801157) on clinical outcome of hematopoietic stem cell transplantation from unrelated donors. Toxic complications were less frequent among patients transplanted from donors carrying the CXCL12-3'-A allele (42/79 vs. 105/151, p=0.014 and 24/79 vs. 73/151, p=0.009, for grade II-IV and III-IV, respectively). Logistic regression analyses confirmed a role of donor A allele (OR=0.509, p=0.022 and OR=0.473, p=0.013 for grade II-IV and III-IV toxicity). In addition, age of recipients (OR=0.980, p=0.036 and OR=0.981, p=0.040, respectively) was independently protective while female to male transplantation and HLA compatibility were not significant. The incidence of aGvHD (grades I-IV) was lower in patients having A allele (52/119 vs. 113/204, p=0.043) and AA homozygous genotype (6/25 vs. 159/298, p=0.005). Independent associations of both genetic markers with a decreased risk of aGvHD were also seen in multivariate analyses (A allele: OR=0.591, p=0.030; AA homozygosity: OR=0.257, p=0.006) in which HLA compatibility seemed to play less protective role (pHHV-6 reactivation (2/34 vs. 19/69, p=0.026). The presence of the CXCL12-3'-A variant was found to facilitate outcome of unrelated HSCT. PMID:25982843

  4. Management of Viral Infections in Allogenic Hematopoietic Stem Cell Transplanted Children

    Directory of Open Access Journals (Sweden)

    Hatice Hale Gumus

    2014-02-01

    Full Text Available Viral infections such as herpes viruses (CMV, EBV, HHV-6, HSV-1 and 2, VZV, adenovirus, and polyomavirus (BK virus may lead to considerable morbidity and mortality in allogenic hematopoietic stem cell transplanted children (HSCT, mainly due to iatrogenic T cell dysfunction. To manage these infections, different strategies like matching of host and donor, viral surveillance, antiviral prophylaxis and preemptive antiviral treatment have been tried and combined, since these infections have become more recognised and can be monitored by quantitative real-time polymerase chain reaction. Viral infections associated with high morbidity and mortality in HSCT patients can be prevented by early diagnosis through the molecular diagnostic techniques and timely initiation of appropriate treatment options.

  5. Prevalence of Resistant Gram-Negative Bacilli in Bloodstream Infection in Febrile Neutropenia Patients Undergoing Hematopoietic Stem Cell Transplantation: A Single Center Retrospective Cohort Study.

    Science.gov (United States)

    Wang, Ling; Wang, Ying; Fan, Xing; Tang, Wei; Hu, Jiong

    2015-11-01

    Bloodstream infection (BSI) is an important cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). To evaluate the causative bacteria and identify risk factors for BSI associated mortality in febrile neutropenia patients undergoing HSCT, we collected the clinical and microbiological data from patients underwent HSCT between 2008 and 2014 and performed a retrospective analysis. Throughout the study period, among 348 episodes of neutropenic fever in patients underwent HSCT, 89 episodes in 85 patients had microbiological defined BSI with a total of 108 isolates. Gram-negative bacteria (GNB) were the most common isolates (76, 70.3%) followed by gram-positive bacteria (GPB, 29, 26.9%) and fungus (3, 2.8%). As to the drug resistance, 26 multiple drug resistance (MDR) isolates were identified. Resistant isolates (n = 23) were more common documented in GNB, mostly Escherichia coli (9/36, 25%) and Klebsiella pneumonia (6/24, 25%). A total of 12 isolated were resistant to carbapenem including 4 K pneumoniae (4/24, 16.7%), 3 Stenotrophomonas maltophilia, and 1 Pseudomonas aeruginosa and other 4 GNB isolates (Citrobacter freumdii, Pseudomonas stutzeri, Acinetobacter baumanii, and Chryseobacterium indologenes). As to the GPB, only 3 resistant isolates were documented including 2 methicillin-resistant isolates (Staphylococcus hominis and Arcanobacterium hemolysis) and 1 vancomycin-resistant Enterococcus faecium. Among these 85 patients with documented BSI, 11 patients died of BSI as primary or associated cause with a BSI-related mortality of 13.1 ± 3.7% and 90-day overall survival after transplantation at 80.0 ± 4.3%. Patients with high-risk disease undergoing allo-HSCT, prolonged neutropenia (≥15 days) and infection with carbapenem-resistant GNB were associated with BSI associated mortality in univariate and multivariate analyses. Our report revealed a prevalence of GNB in BSI of neutropenic patients undergoing

  6. Reduced intensity conditioning is superior to nonmyeloablative conditioning for older chronic myelogenous leukemia patients undergoing hematopoietic cell transplant during the tyrosine kinase inhibitor era.

    Science.gov (United States)

    Warlick, Erica; Ahn, Kwang Woo; Pedersen, Tanya L; Artz, Andrew; de Lima, Marcos; Pulsipher, Michael; Akpek, Gorgun; Aljurf, Mahmoud; Cahn, Jean-Yves; Cairo, Mitchell; Chen, Yi-Bin; Cooper, Brenda; Deol, Abhinav; Giralt, Sergio; Gupta, Vikas; Khoury, H Jean; Kohrt, Holbrook; Lazarus, Hillard M; Lewis, Ian; Olsson, Richard; Pidala, Joseph; Savani, Bipin N; Seftel, Matthew; Socié, Gerard; Tallman, Martin; Ustun, Celaettin; Vij, Ravi; Vindeløv, Lars; Weisdorf, Daniel

    2012-04-26

    Tyrosine kinase inhibitors (TKIs) and reduced intensity conditioning (RIC)/nonmyeloablative (NMA) conditioning hematopoietic cell transplants (HCTs) have changed the therapeutic strategy for chronic myelogenous leukemia (CML) patients. We analyzed post-HCT outcomes of 306 CML patients reported to the Center for International Blood and Marrow Transplant Research aged 40 years and older undergoing RIC/NMA HCT from 2001 to 2007: 117 (38%) aged 40 to 49 years, 119 (39%) 50 to 59 years, and 70 (23%) 60 years or older. The majority (74%) had treatment with imatinib before HCT. At HCT, most patients aged 40 to 49 years were in chronic phase (CP) 1 (74%), compared with 31% aged 60 years or older. Siblings were donors for 56% aged 40 to 49 years; older cohorts had more unrelated donors. The majority received peripheral blood grafts and RIC across all age groups. 3 year overall survival (54%, 52%, and 41%), day + 100 grade II-IV acute GVHD (26%, 32%, and 32%), chronic GVHD (58%, 51%, and 43%), and 1-year treatment-related mortality (18%, 20%, and 13%) were similar across ages. The 3-year relapse incidence (36%, 43%, and 66%) and disease-free survival (35%, 32%, and 16%) were inferior in the oldest cohort. Importantly, for CP1 patients, relapse and disease-free survival were similar across age cohorts. Allogeneic RIC HCT for older patients with CML can control relapse with acceptable toxicity and survival in TKI-exposed CML, especially if still in CP1. PMID:22408257

  7. Tolerability of 2.5% Lidocaine/Prilocaine Hydrogel in Children Undergoing Cryotherapy for Molluscum Contagiosum.

    Science.gov (United States)

    Gobbato, André A M; Babadópulos, Tainah; Gobbato, Cintia A R S; Moreno, Ronilson A; Gagliano-Jucá, Thiago; De Nucci, Gilberto

    2016-05-01

    The tolerability of a 2.5% lidocaine/prilocaine hydrogel (Nanorap, Biolab Indústria Farmacêutica Ltd., Sao Paulo, Brazil) was evaluated in 20 children ages 2 to 11 years undergoing cryotherapy for molluscum contagiosum (MC). The product was well tolerated, with only two children presenting with eczema at the application site. These adverse reactions were considered unlikely to be related to the test product, because a patch test was negative in one of the individuals and the other event occurred in only one of the two treated areas. Nanorap is an efficacious and well-tolerated option for topical anesthesia in children undergoing cryotherapy for MC. PMID:27041686

  8. Incidental pineal cysts in children who undergo 3-T MRI

    International Nuclear Information System (INIS)

    Pineal cysts, both simple and complex, are commonly encountered in children. More cysts are being detected with MR technology; however, nearly all pineal cysts are benign and require no follow-up. To discover the prevalence of pineal cysts in children at our institution who have undergone high-resolution 3-T MRI. We retrospectively reviewed 100 consecutive 3-T brain MRIs in children ages 1 month to 17 years (mean 6.8 ± 5.1 years). We evaluated 3-D volumetric T1-W imaging, axial T2-W imaging, axial T2-W FLAIR (fluid attenuated inversion recovery) and coronal STIR (short tau inversion recovery) sequences. Pineal parenchymal and cyst volumes were measured in three planes. Cysts were analyzed for the presence and degree of complexity. Pineal cysts were present in 57% of children, with a mean maximum linear dimension of 4.2 mm (range 1.5-16 mm). Of these cysts, 24.6% showed thin septations or fluid levels reflecting complexity. None of the cysts demonstrated complete T2/FLAIR signal suppression. No cyst wall thickening or nodularity was present. There was no significant difference between the ages of children with and without cysts. Cysts were more commonly encountered in girls than boys (67% vs. 52%; P = 0.043). There was a slight trend toward increasing pineal gland volume with age. Pineal cysts are often present in children and can be incidentally detected by 3-T MRI. Characteristic-appearing pineal cysts in children are benign, incidental findings, for which follow-up is not required if there are no referable symptoms or excessive size. (orig.)

  9. Incidental pineal cysts in children who undergo 3-T MRI

    Energy Technology Data Exchange (ETDEWEB)

    Whitehead, Matthew T. [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States); Le Bonheur Children' s Hospital, Department of Radiology, Memphis, TN (United States); Oh, Christopher C. [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States); Choudhri, Asim F. [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States); University of Tennessee Health Science Center, Department of Neurosurgery, Memphis, TN (United States)

    2013-12-15

    Pineal cysts, both simple and complex, are commonly encountered in children. More cysts are being detected with MR technology; however, nearly all pineal cysts are benign and require no follow-up. To discover the prevalence of pineal cysts in children at our institution who have undergone high-resolution 3-T MRI. We retrospectively reviewed 100 consecutive 3-T brain MRIs in children ages 1 month to 17 years (mean 6.8 {+-} 5.1 years). We evaluated 3-D volumetric T1-W imaging, axial T2-W imaging, axial T2-W FLAIR (fluid attenuated inversion recovery) and coronal STIR (short tau inversion recovery) sequences. Pineal parenchymal and cyst volumes were measured in three planes. Cysts were analyzed for the presence and degree of complexity. Pineal cysts were present in 57% of children, with a mean maximum linear dimension of 4.2 mm (range 1.5-16 mm). Of these cysts, 24.6% showed thin septations or fluid levels reflecting complexity. None of the cysts demonstrated complete T2/FLAIR signal suppression. No cyst wall thickening or nodularity was present. There was no significant difference between the ages of children with and without cysts. Cysts were more commonly encountered in girls than boys (67% vs. 52%; P = 0.043). There was a slight trend toward increasing pineal gland volume with age. Pineal cysts are often present in children and can be incidentally detected by 3-T MRI. Characteristic-appearing pineal cysts in children are benign, incidental findings, for which follow-up is not required if there are no referable symptoms or excessive size. (orig.)

  10. Oral Midazolam for Voiding Dysfunction in Children Undergoing Voiding Cystourethrography: A Controlled Randomized Clinical Trial

    OpenAIRE

    Azarfar, Anoush; Esmaeeili, Mohammad; Farrokh, Azadeh; Alamdaran, Ali; Keykhosravi, Aghilallah; Neamatshahi, Mahboobe; Hebrani, Alireza; Ravanshad, Yalda

    2014-01-01

    Background: Voiding Cystourethrography (VCUG) is the gold standard of detecting and grading the vesicoureteral reflux. Moreover, VCUG is a part of the standard review for infants and children with a urinary tract infection and urinary dysfunction. Objectives: The purpose of our study was to compare using oral midazolam in contrast to prescribing no sedative medication for voiding dysfunction in children undergoing VCUG. Patients and Methods: In a clinical trial, we studied 84 children referre...

  11. The effects of clown intervention on worries and emotional responses in children undergoing surgery.

    OpenAIRE

    Fernandes, Sara; Arriaga, Patrícia

    2010-01-01

    This study investigated whether clown intervention could reduce preoperative worries and the affective responses of children undergoing minor surgery. Parental anxiety was also tested. Child’s age, previous hospitalization, and temperament were tested as predictors of the child’s responses during this preoperative phase. Seventy children were assigned to one of two groups: children accompanied by their parents and a pair of clowns or, those accompanied by the parents but without the clowns. T...

  12. [Nursing care for children undergoing percutaneous endoscopic gastrostomy].

    Science.gov (United States)

    Huang, Mei-Jung; Lin, Chieh-Chung; Cheng, Shue-Lin

    2004-06-01

    Ever since percutaneous endoscopic gastronomy (PEG) was used for the first time in 1980 by Gauderer, Ponsky, Izant et al., It has been widely used in patients incapable of oral feeding. It is a safe and effective technique for long-term nutritional support in children, and easy to perform, as only local anesthesia or heavy sedation is required PEG can prevent children from suffering from nasopharyngeal and esophageal erosions due to repeated insertion of nasogastric tubes and the complication of aspiration pneumonia. It is therefore an alternative for children who need long-term feeding. In this article we review the literature on PEG and give a full description of its indications, complications, as well as advice on when to change gastrostomy tubes, and on nursing care, in the hope that this will be useful reference material for medical staff. PMID:15211780

  13. [Self-hypnosis, a resource for children undergoing painful treatment].

    Science.gov (United States)

    Restif, Anne-Sophie

    2010-01-01

    Learning self-hypnosis enables children to partially or totally manage the sensory and emotional components of pain, especially that linked to the use of a central line in paediatric onco-haematology. Specially trained paediatric nurses can teach this special technique. PMID:20518243

  14. Seriously clowning: Medical clowning interaction with children undergoing invasive examinations in hospitals.

    Science.gov (United States)

    Tener, Dafna; Ofir, Shoshi; Lev-Wiesel, Rachel; Franco, Nessia L; On, Avi

    2016-04-01

    This qualitative study examined the subjective experience of children undergoing an invasive examination in the hospital when accompanied by a medical clown. In-depth semi-structured interviews were conducted with nine such children and nine of their accompanying parents. The children were patients in two outpatient departments (Pediatric Gastroenterology and a Center for the Sexually Abused) in a hospital in Israel. Interviews were coded thematically using an Atlas.ti software program. Analysis of the interviews indicated that the intervention of the clown positively changed the children's perceptions of the hospital, of experiencing the examination, and of their life narrative. Medical clowns thus appear to be a central, meaningful, and therapeutic source for children undergoing invasive examinations in hospital, as well as for their parents. Therefore, it may be advisable to incorporate medical clowns as an integral part of medical teams performing invasive procedures and to include the clowns in all stages of the hospital visit. PMID:27123686

  15. Image-Guided Total-Marrow Irradiation Using Helical Tomotherapy in Patients With Multiple Myeloma and Acute Leukemia Undergoing Hematopoietic Cell Transplantation

    International Nuclear Information System (INIS)

    Purpose: Total-body irradiation (TBI) has an important role in patients undergoing hematopoietic cell transplantation (HCT), but is associated with significant toxicities. Targeted TBI using helical tomotherapy results in reduced doses to normal organs, which predicts for reduced toxicities compared with standard TBI. Methods and Materials: Thirteen patients with multiple myeloma were treated in an autologous tandem transplantation Phase I trial with high-dose melphalan, followed 6 weeks later by total-marrow irradiation (TMI) to skeletal bone. Dose levels were 10, 12, 14, and 16 Gy at 2 Gy daily/twice daily. In a separate allogeneic HCT trial, 8 patients (5 with acute myelogenous leukemia, 1 with acute lymphoblastic leukemia, 1 with non-Hodgkin's lymphoma, and 1 with multiple myeloma) were treated with TMI plus total lymphoid irradiation plus splenic radiotherapy to 12 Gy (1.5 Gy twice daily) combined with fludarabine/melphalan. Results: For the 13 patients in the tandem autologous HCT trial, median age was 54 years (range, 42-66 years). Median organ doses were 15-65% that of the gross target volume dose. Primarily Grades 1-2 acute toxicities were observed. Six patients reported no vomiting; 9 patients, no mucositis; 6 patients, no fatigue; and 8 patients, no diarrhea. For the 8 patients in the allogeneic HCT trial, median age was 52 years (range, 24-61 years). Grades 2-3 nausea, vomiting, mucositis, and diarrhea were observed. In both trials, no Grade 4 nonhematologic toxicity was observed, and all patients underwent successful engraftment. Conclusions: This study shows that TMI using helical tomotherapy is clinically feasible. The reduced acute toxicities observed compare favorably with those seen with standard TBI. Initial results are encouraging and warrant further evaluation as a method to dose escalate with acceptable toxicity or to offer TBI-containing regimens to patients unable to tolerate standard approaches

  16. Focal nodular hyperplasia of the liver: an emerging complication of hematopoietic SCT in children.

    Science.gov (United States)

    Pillon, M; Carucci, N S; Mainardi, C; Carraro, E; Zuliani, M; Chemello, L; Calore, E; Tumino, M; Varotto, S; Toffolutti, T; Destro, R; Gazzola, M V; Alaggio, R; Basso, G; Messina, C

    2015-03-01

    Hepatic focal nodular hyperplasia (FNH) is a nonmalignant condition rarely affecting children previously treated for cancer, especially those who received hematopoietic SCT (HSCT). Some aspects of its pathogenesis still remain unclear and a strong association with specific risk factors has not yet been identified. We report here a single institution's case series of 17 patients who underwent HSCT and were diagnosed with FNH, analyzing retrospectively their clinical features and the radiological appearance of their hepatic lesions. We aimed to compare the diagnostic accuracy of ultrasound (US) and magnetic resonance imaging (MRI) and to explore the role of transient elastography (FibroScan) to evaluate the degree of hepatic fibrosis in FNH patients. Our analysis showed an association of FNH with age at transplant ⩽12 years (hazard ratio (HR) 9.10); chronic GVHD (HR 2.99); hormone-replacement therapy (HR 4.02) and abdominal radiotherapy (HR 4.37). MRI proved to be a more accurate diagnostic tool compared with US. Nine out of 12 patients who underwent FibroScan showed hepatic fibrosis. Our study points out that FNH is an emerging complication of HSCT, which requires a lifelong surveillance to follow its course in cancer patients. PMID:25581411

  17. Development of an Individualized Yoga Intervention to Address Fatigue in Hospitalized Children Undergoing Intensive Chemotherapy.

    Science.gov (United States)

    Diorio, Caroline; Celis Ekstrand, Amanda; Hesser, Tanya; O'Sullivan, Cathy; Lee, Michelle; Schechter, Tal; Sung, Lillian

    2016-09-01

    Purpose Fatigue is an important problem in children receiving intensive chemotherapy and hematopoietic stem cell transplantation (HSCT). Exercise may be an effective intervention for fatigue. Individualized yoga represents an ideal intervention because it can be tailored according to an individual child's needs. Little is known about how to structure a standardized yoga program for intensivelytreated children. Therefore, this study describes the development of a yoga program and an approach to monitoring sessions suitable for hospitalized children receiving intensive chemotherapy or HSCT. Methods The yoga program was designed to increase mobility in hospitalized children and to provide children with relaxation techniques that could be used independently in a variety of environments. The program was founded on 4 key tenets: safety, adaptability, environmental flexibility, and appeal to children. We also developed quality and consistency assurance procedures. Results A menu format with a fixed structure was selected for the yoga program. Each yoga session contained up to 6 sections: breathing exercises, warmup exercises, yoga poses, balancing poses, cool-down poses, and final relaxation. Yoga instructors selected specific yoga poses for each session from a predetermined list organized by intensity level (low, moderate, or high). Monitoring procedures were developed using videotaping and multirater adjudication. Conclusion We created a standardized yoga program and an approach to monitoring that are now ready for incorporation in clinical trials. Future work should include the adaptation of the program to different pediatric populations and clinical settings. PMID:27146130

  18. Thyroid dose in children undergoing prophylactic cranial irradiation

    International Nuclear Information System (INIS)

    Purpose: To determine the radiation dose received by the thyroid gland as a result of prophylactic cranial irradiation (PCI) in childhood leukemia and the factors influencing that dose. Methods and Materials: The dose to the thyroid resulting from simulated cranial irradiation with parallel opposed lateral fields of an adult anthropomorphic (ART) phantom with both 6 MV X-rays and Cobalt-60 γ-rays was measured using thermoluminescent dosimeters (TLDs). The dependence of thyroid dose on the distance of the field from the thyroid and the proportions of thyroid dose from stray radiation (leakage, scatter from jaws, etc.) and tissue scattered radiation were measured. The effects of a shadow tray and shielding blocks were also determined. Calculation of thyroid dose using the Clarkson scatter integration method was performed for 6 MV X-rays to compare with the measured doses. In vivo thyroid dose estimates were made using TLD measurements for three children receiving PCI with 6 MV X-rays. Results: Using open, unshielded fields, the thyroid region of the phantom received 1.2-1.4% of the prescribed cranial dose for 6 MV X-rays and 1.5-1.7% for Cobalt-60. For both treatment units, stray radiation accounted for approximately two thirds of the thyroid dose and tissue scatter accounted for the remaining one third. The thyroid dose increased as the field moved closer to the thyroid, with an increasing proportion of the dose due to tissue scatter. Placement of a thyroid shielding block on a shadow tray reduced the thyroid dose by only 20% compared with the open, unshielded setup. Thyroid dose from 6 MV using open fields was affected by the orientation of the collimator. When the inferior field edge was defined by the lower jaw, the dose was reduced by 27% compared with the upper jaw. Good correlation of dose to the thyroid region was obtained between phantom measured doses, in vivo measured doses and calculation of dose using the Clarkson method. Conclusion: For PCI doses of

  19. Hematopoietic stem cell transplantation in children with hematological malignancies across HLA barriers--reasonable alternative?

    Science.gov (United States)

    Sedlácek, P; Starý, J; Vodváková, S; Poloucková, A; Gasová, Z; Marinov, I; Formánková, R

    2001-01-01

    The aim of this study was to evaluate the efficiency and risks of T-cell depletion in prevention of graft versus host disease (GVHD) using HLA haploidentical family donors as an alternative source of hematopoietic stem cells (HSC) in children with hematological malignancies without suitable matched donor. Ten children, median age 12 years (range, 3-17), were transplanted from haploidentical family donors for acute lymphoblastic leukemia (n = 4), acute myelogenous leukemia (n=2), chronic myelogenous leukemia (n = 2), non-Hodgkin lymphoma (n = 1) and myelodysplastic syndrome (n = 1). Parents were donors for nine, sibling for one patient. T-cell depletion of HSC was performed using CellPro followed by antiCD2/CD3 depletion in 7, and CliniMacs magnetic sorting in 3 grafts. Primary engraftment was achieved in nine patients. Patient with graft failure was successfully re-grafted. Primary acute GVHD was diagnosed in one patient who got higher amount of T-cells in the graft. Secondary GVHD was induced by add-backs of lymphocytes in four patients. Three patients developed chronic GVHD. Four patients died due to transplant related mortality (40%), one from veno-occlusive disease, two due to CMV pneumonia and one of aspergillosis with extensive chronic GVHD. Four patients relapsed with leukemia within 35-98 days post transplant, three without previous signs of GVHD, and all died. Two patients are alive and well 26 and 42 months after transplant. Haploidentical family donors appear to be a reasonable alternative option for patients with urgent indications for allogeneic transplant and/or without a matched donor. PMID:11712683

  20. Subclinical hypothyroidism in children and adolescents after hematopoietic stem cells transplantation without irradiation

    Directory of Open Access Journals (Sweden)

    Milenković Tatjana

    2014-01-01

    Full Text Available Background/Aim. Although total body irradiation (TBI was considered to be the primary cause of thyroid dysfunction following hematopoietic stem cells transplantation (HSCT, a significant prevalence of subclinical hypothyroidism after HSCT with chemotherapy-only conditioning regimens has been observed in several studies. The aim of this study was to assess changes in thyroid stimulating hormone (TSH levels in children after HSCT, without the use of irradiation at any time in the course of the treatment. Methods. Our cohort consisted of 41 children and adolescents who underwent autologous or allogeneic HSCT and were available for follow-up for at least one year after transplantation. Irradiation was not performed in any of the subjects, neither during pretransplatation therapy, nor during conditioning. The median duration of follow-up was 2.9 years. The indications for HSCT were hematologic malignancy (41.5%, solid malignant tumor (34.1%, and other disorders (24.4%. The thyroid status of all the subjects was assessed prior to HSCT and after follow-up period. Results. Thyroid dysfunction after HSCT was present in 27 (65.8% subjects. Subclinical hypothyroidism was the most common abnormality, presenting in 23 (56.1% patients, primary hypothyroidism was present in one (2.4% patient, while 3 (7.3% subjects had low free T4 with normal TSH values. Significantly (p < 0.01 higher elevations in TSH levels were present in the patients who received chemotherapy for the underlying disease prior to HSCT. Conclusion. Our findings emphasize the need for long-term monitoring of thyroid function following HSCT, regardless of whether or not irradiation was used.

  1. Effect of Chewing Gum on Oral Mucositis in Children Undergoing Chemotherapy: A Randomized Controlled Study

    OpenAIRE

    Eghbali, A.; Taherkhanchi, B; Bagheri, B; Sadeghi Sedeh, B

    2016-01-01

    Background Oral mucositis is an adverse effect of chemotherapy. Type of chemotherapy regimen is the most important factor causing mucositis. Oral mucositis is usually associated with transient decrease in saliva production. The goal was to study effects of gum consumption on oral mucositis in children undergoing chemotherapy. Materials and Method This randomized controlled trial was done in Amir Kabir Hospital, Arak, Iran. 130 children 5 to 15 years of age were studied. Control group was comp...

  2. An Assessment of Oral Hygiene in 7-14-Year-Old Children undergoing Orthodontic Treatment

    OpenAIRE

    Krupińska-Nanys, Magdalena; Zarzecka, Joanna

    2015-01-01

    Backround: The study is focused on increased risk of dental plaque accumulation among the children undergoing orthodontic treatment in consideration of individual hygiene and dietary habits. Materials and Methods: The study was conducted among 91 children aged 7-14 including 47 girls and 44 boys. The main objectives of the study were: API index, plaque pH, DMF index, proper hygiene and dietary habits. Statistical analysis was provided in Microsoft Office Exel spreadsheet and STATISTICA statis...

  3. Problems and challenges in care for children undergoing radiotherapy- A research paper

    International Nuclear Information System (INIS)

    for children undergoing radiotherapy and their parents, a paediatric radiographer may be one welcome solution to relieve the anxiety and stress during this difficult time in their lives. given the various factors, no one solution can be deemed ultimate in dealing with this complex situation. thus further efforts are needed to bring about workable solutions to this problem depending on the circumstances and situation

  4. Human Polyomaviruses in Children Undergoing Transplantation, United States, 2008–2010

    OpenAIRE

    Siebrasse, Erica A.; Bauer, Irma; Holtz, Lori R.; Le, Binh-minh; Lassa-Claxton, Sherry; Canter, Charles; Hmiel, Paul; Shenoy, Shalini; Sweet, Stuart; Turmelle, Yumirle; Shepherd, Ross; Wang, David

    2012-01-01

    Immunocompromised patients are at risk for disease caused by infection by some polyomaviruses. To define the prevalence of polyomaviruses in children undergoing transplantation, we collected samples from a longitudinal cohort and tested for the 9 known human polyomaviruses. All were detected; several were present in previously unreported specimen types.

  5. Gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy in the years 2000

    Science.gov (United States)

    Castagnola, Elio; Ruberto, Eliana; Guarino, Alfredo

    2016-01-01

    AIM: To review gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy. To look at gut microflora features in oncology children. METHODS: We selected studies published after year 2000, excluding trials on transplanted pediatric patients. We searched English language publications in MEDLINE using the keywords: “gastrointestinal infection AND antineoplastic chemotherapy AND children”, “gastrointestinal infection AND oncology AND children”, “liver infection AND antineoplastic chemotherapy AND children”, “liver abscess AND chemotherapy AND child”, “neutropenic enterocolitis AND chemotherapy AND children”, “thyphlitis AND chemotherapy AND children”, “infectious diarrhea AND children AND oncology”, “abdominal pain AND infection AND children AND oncology”, “perianal sepsis AND children AND oncology”, “colonic pseudo-obstruction AND oncology AND child AND chemotherapy”, “microflora AND children AND malignancy”, “microbiota AND children AND malignancy”, “fungal flora AND children AND malignancy”. We also analysed evidence from several articles and book references. RESULTS: Gastrointestinal and liver infections represent a major cause of morbidity and mortality in children undergoing antineoplastic chemotherapy. Antineoplastic drugs cause immunosuppression in addition to direct toxicity, predisposing to infections, although the specific risk is variable according to disease and host features. Common pathogens potentially induce severe diseases whereas opportunistic microorganisms may attack vulnerable hosts. Clinical manifestations can be subtle and not specific. In addition, several conditions are rare and diagnostic process and treatments are not standardized. Diagnosis may be challenging, however early diagnosis is needed for quick and appropriate interventions. Interestingly, the source of infection in those children can be exogenous or endogenous. Indeed, mucosal damage may allow the

  6. It Is Tough and Tiring but It Works-Children's Experiences of Undergoing Radiotherapy.

    Science.gov (United States)

    Engvall, Gunn; Ångström-Brännström, Charlotte; Mullaney, Tara; Nilsson, Kristina; Wickart-Johansson, Gun; Svärd, Anna-Maja; Nyholm, Tufve; Lindh, Jack; Lindh, Viveca

    2016-01-01

    Approximately 300 children ages 0 to 18 are diagnosed with cancer in Sweden every year, and 80 to 90 of them undergo radiotherapy treatment. The aim was to describe children's experiences of preparing for and undergoing radiotherapy, and furthermore to describe children's suggestions for improvement. Thirteen children between the ages of 5 and 15 with various cancer diagnoses were interviewed. Data was analyzed using qualitative content analysis. The findings revealed five categories: positive and negative experiences with hospital stays and practical arrangements; age-appropriate information, communication, and guidance to various degrees; struggle with emotions; use of distraction and other suitable coping strategies; and children's suggestions for improvement during radiotherapy. An overarching theme emerged: "It is tough and tiring but it works". Some key areas were: explanatory visits, the need for information and communication, being afraid, discomfort and suffering, the need for media distraction, dealing with emotions, and the need for support. A systematic, family-centered preparation program could possible help families prepare and individualized distraction during radiotherapy could contribute to reducing distress. Further studies with interventions could clarify successful programs. PMID:27055258

  7. The use of melatonin as an alternative to sedation in uncooperative children undergoing an MRI examination

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, K.; Page, A.; Williams, H.; Wassemer, E.; Whitehouse, W

    2002-06-01

    AIM: Children who are uncooperative, due either to their age or medical condition, usually require sedation or a general anaesthetic (GA) to ensure immobility during magnetic resonance imaging (MRI) examination. These procedures have a risk of respiratory compromise and loss of vital reflexes. Melatonin induces a natural sleep with no known complication or risk of respiratory compromise. We aimed to evaluate the use of melatonin in these uncooperative children. MATERIAL AND METHODS: An unselected group of 40 children, who had been referred for an MRI examination of the brain under sedation or GA, were chosen to receive melatonin instead. They all received 10 mg of melatonin and 17 children additionally underwent some form of sleep deprivation. The number of children who went to sleep and had a successful MRI examination was recorded. RESULTS: Twenty-six children (65%) went to sleep and of these 22 (55%) had a successful MRI examination. In the 17 children who underwent sleep deprivation, 13 (76%) went to sleep and had a successful MRI examination. There was no complication. CONCLUSIONS: Melatonin may provide an alternative to conventional sedation regimes and GA for uncooperative children undergoing an MRI examination. The use of sleep deprivation improves the success rate and there is no risk of respiratory compromise. Johnson, K. et al. (2002)

  8. Pre- and Postoperative Vomiting in Children Undergoing Video-Assisted Gastrostomy Tube Placement

    Directory of Open Access Journals (Sweden)

    Torbjörn Backman

    2014-01-01

    Full Text Available Background. The aim of this study was to determine the incidence of pre- and postoperative vomiting in children undergoing a Video-Assisted Gastrostomy (VAG operation. Patients and Methods. 180 children underwent a VAG operation and were subdivided into groups based on their underlying diagnosis. An anamnesis with respect to vomiting was taken from each of the children’s parents before the operation. After the VAG operation, all patients were followed prospectively at one and six months after surgery. All complications including vomiting were documented according to a standardized protocol. Results. Vomiting occurred preoperatively in 51 children (28%. One month after surgery the incidence was 43 (24% in the same group of children and six months after it was found in 40 (22%. There was a difference in vomiting frequency both pre- and postoperatively between the children in the groups with different diagnoses included in the study. No difference was noted in pre- and postoperative vomiting frequency within each specific diagnosis group. Conclusion. The preoperative vomiting symptoms persisted after the VAG operation. Neurologically impaired children had a higher incidence of vomiting than patients with other diagnoses, a well-known fact, probably due to their underlying diagnosis and not the VAG operation. This information is useful in preoperative counselling.

  9. COMPARATIVE EVALUATION OF ORAL MIDAZOLAM, BUTORPHANOL AND CLONIDINE AS PREMEDICANTS IN CHILDREN UNDERGOING ELECTIVE SURGERY

    Directory of Open Access Journals (Sweden)

    Mukta

    2015-06-01

    Full Text Available BACKGROUND: We compared the effects of oral midazolam, butorphanol and clonidine on preoperative sedation and anxiolysis and postoperative recovery profile of the children undergoing elective surgery. MATERIAL AND METHODS : 105 children of either sex, aged between 2 - 6 years, of ASA grade I scheduled for elective surgery were randomized into three groups. Group I: 35 children received midazolam 0.5 mg/kg body weight orally, Group II: 35 children received butorphanol 0.2 mg/kg orally, Group III: 35 children received cloni dine 4 μ/kg orally. Premedication was given 30 minutes before induction of anaesthesia. Children were assessed for attitude to venepuncture and face mask acceptance during induction of anaesthesia. RESULTS: The groups were statistically comparable (p>0.05 , regarding the patients’ demographic profile, hemodynamic variables, duration of surgery and awakening. Less time was required for the onset and time of maximum sedation in midazolam group. Sedation scores were highest in the clonidine group at the time o f induction (p0.05 and minimal with butorphanol. Reaction to i.v cannulation was minimal with clonidine whi le it was comparable in midazolam and butorphanol group. CONCLUSION: clonidine causes the best sedation among the three drugs and it causes minimum response to i.v cannulation and comparable mask acceptance with midazolam followed by butorphanol.

  10. The impact of preparation and support procedures for children with sickle cell disease undergoing MRI

    Energy Technology Data Exchange (ETDEWEB)

    Cejda, Katherine R. [St. Jude Children' s Research Hospital, Child Life Program, Memphis, TN (United States); Smeltzer, Matthew P. [St. Jude Children' s Research Hospital, Department of Biostatistics, Memphis, TN (United States); Hansbury, Eileen N. [Baylor International Hematology Center of Excellence and the Texas Children' s Center for Global Health, Houston, TX (United States); McCarville, Mary Elizabeth; Helton, Kathleen J. [St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); Hankins, Jane S. [St. Jude Children' s Research Hospital, Department of Hematology, Memphis, TN (United States)

    2012-10-15

    Children with sickle cell disease (SCD) often undergo MRI studies to assess brain injury or to quantify hepatic iron. MRI requires the child to lie motionless for 30-60 min, thus sedation/anesthesia might be used to facilitate successful completion of exams, but this poses additional risks for SCD patients. To improve children's ability to cope with MRI examinations and avoid sedation, our institution established preparation and support procedures (PSP). To investigate the impact of PSP in reducing the need for sedation during MRI exams among children with SCD. Data on successful completion of MRI testing were compared among 5- to 12-year-olds who underwent brain MRI or liver R2*MRI with or without receiving PSP. Seventy-one children with SCD (median age 9.85 years, range 5.57-12.99 years) underwent a brain MRI (n = 60) or liver R2*MRI (n = 11). Children who received PSP were more likely to complete an interpretable MRI exam than those who did not 30 of 33; 91% vs. 27 of 38; 71%, unadjusted OR = 4.1 (P = 0.04) and OR = 8.5 (P < 0.01) when adjusting for age. PSP can help young children with SCD complete clinically interpretable, nonsedated MRI exams, avoiding the risks of sedation/anesthesia. (orig.)

  11. The impact of preparation and support procedures for children with sickle cell disease undergoing MRI

    International Nuclear Information System (INIS)

    Children with sickle cell disease (SCD) often undergo MRI studies to assess brain injury or to quantify hepatic iron. MRI requires the child to lie motionless for 30-60 min, thus sedation/anesthesia might be used to facilitate successful completion of exams, but this poses additional risks for SCD patients. To improve children's ability to cope with MRI examinations and avoid sedation, our institution established preparation and support procedures (PSP). To investigate the impact of PSP in reducing the need for sedation during MRI exams among children with SCD. Data on successful completion of MRI testing were compared among 5- to 12-year-olds who underwent brain MRI or liver R2*MRI with or without receiving PSP. Seventy-one children with SCD (median age 9.85 years, range 5.57-12.99 years) underwent a brain MRI (n = 60) or liver R2*MRI (n = 11). Children who received PSP were more likely to complete an interpretable MRI exam than those who did not 30 of 33; 91% vs. 27 of 38; 71%, unadjusted OR = 4.1 (P = 0.04) and OR = 8.5 (P < 0.01) when adjusting for age. PSP can help young children with SCD complete clinically interpretable, nonsedated MRI exams, avoiding the risks of sedation/anesthesia. (orig.)

  12. Role of Pharmacogenetics in Hematopoietic Stem Cell Transplantation Outcome in Children

    OpenAIRE

    Raffaella Franca; Gabriele Stocco; Diego Favretto; Nagua Giurici; Giuliana Decorti; Marco Rabusin

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) is an established therapeutic procedure for several congenital and acquired disorders, both malignant and nonmalignant. Despite the great improvements in HSCT clinical practices over the last few decades, complications, such as graft vs. host disease (GVHD) and sinusoidal obstructive syndrome (SOS), are still largely unpredictable and remain the major causes of morbidity and mortality. Both donor and patient genetic background might influence the...

  13. Effect of preoperative oral midazolam sedation on separation anxiety and emergence delirium among children undergoing dental treatment under general anesthesia

    OpenAIRE

    El Batawi, Hisham Yehia

    2015-01-01

    Aim: To investigate the possible effects of preoperative oral Midazolam on parental separation anxiety, emergence delirium, and post-anesthesia care unit time on children undergoing dental rehabilitation under general anesthesia. Methods: Randomized, prospective, double-blind study. Seventy-eight American Society of Anesthesiology (ASA) I children were divided into two groups of 39 each. Children of the first group were premedicated with oral Midazolam 0.5 mg/kg, while children of the control...

  14. Ventilation and cardiac related impedance changes in children undergoing corrective open heart surgery.

    Science.gov (United States)

    Schibler, Andreas; Pham, Trang M T; Moray, Amol A; Stocker, Christian

    2013-10-01

    Electrical impedance tomography (EIT) can determine ventilation and perfusion relationship. Most of the data obtained so far originates from experimental settings and in healthy subjects. The aim of this study was to demonstrate that EIT measures the perioperative changes in pulmonary blood flow after repair of a ventricular septum defect in children with haemodynamic relevant septal defects undergoing open heart surgery. In a 19 bed intensive care unit in a tertiary children's hospital ventilation and cardiac related impedance changes were measured using EIT before and after surgery in 18 spontaneously breathing patients. The EIT signals were either filtered for ventilation (ΔZV) or for cardiac (ΔZQ) related impedance changes. Impedance signals were then normalized (normΔZV, normΔZQ) for calculation of the global and regional impedance related ventilation perfusion relationship (normΔZV/normΔZQ). We observed a trend towards increased normΔZV in all lung regions, a significantly decreased normΔZQ in the global and anterior, but not the posterior lung region. The normΔZV/normΔZQ was significantly increased in the global and anterior lung region. Our study qualitatively validates our previously published modified EIT filtration technique in the clinical setting of young children with significant left-to-right shunt undergoing corrective open heart surgery, where perioperative assessment of the ventilation perfusion relation is of high clinical relevance. PMID:24021191

  15. Ventilation and cardiac related impedance changes in children undergoing corrective open heart surgery

    International Nuclear Information System (INIS)

    Electrical impedance tomography (EIT) can determine ventilation and perfusion relationship. Most of the data obtained so far originates from experimental settings and in healthy subjects. The aim of this study was to demonstrate that EIT measures the perioperative changes in pulmonary blood flow after repair of a ventricular septum defect in children with haemodynamic relevant septal defects undergoing open heart surgery. In a 19 bed intensive care unit in a tertiary children's hospital ventilation and cardiac related impedance changes were measured using EIT before and after surgery in 18 spontaneously breathing patients. The EIT signals were either filtered for ventilation (ΔZV) or for cardiac (ΔZQ) related impedance changes. Impedance signals were then normalized (normΔZV, normΔZQ) for calculation of the global and regional impedance related ventilation perfusion relationship (normΔZV/normΔZQ). We observed a trend towards increased normΔZV in all lung regions, a significantly decreased normΔZQ in the global and anterior, but not the posterior lung region. The normΔZV/normΔZQ was significantly increased in the global and anterior lung region. Our study qualitatively validates our previously published modified EIT filtration technique in the clinical setting of young children with significant left-to-right shunt undergoing corrective open heart surgery, where perioperative assessment of the ventilation perfusion relation is of high clinical relevance. (paper)

  16. Providing Preoperative Information for Children Undergoing Surgery: A Randomized Study Testing Different Types of Educational Material to Reduce Children's Preoperative Worries

    Science.gov (United States)

    Fernandes, S. C.; Arriaga, P.; Esteves, F.

    2014-01-01

    This study developed three types of educational preoperative materials and examined their efficacy in preparing children for surgery by analysing children's preoperative worries and parental anxiety. The sample was recruited from three hospitals in Lisbon and consisted of 125 children, aged 8-12 years, scheduled to undergo outpatient surgery.…

  17. Psychosocial Changes Associated with Participation in Art Therapy Interventions for Siblings of Pediatric Hematopoietic Stem Cell Transplant Patients

    Science.gov (United States)

    Wallace, Jo; Packman, Wendy; Huffman, Lynne C.; Horn, Biljana; Cowan, Morton; Amylon, Michael D.; Kahn, Colleen; Cordova, Matt; Moses, Jim

    2014-01-01

    Hematopoietic stem cell transplantation (HSCT) is an accepted medical treatment for many serious childhood diseases. HSCT is a demanding procedure that creates both physical and emotional challenges for patients and their family members. Research has demonstrated that siblings of children undergoing HSCT are at risk for developing psychosocial…

  18. THE OCCURRENCE OF HIGH-LEVELS OF ACUTE BEHAVIORAL DISTRESS IN CHILDREN AND ADOLESCENTS UNDERGOING ROUTINE VENIPUNCTURES

    NARCIS (Netherlands)

    HUMPHREY, GB; BOON, CMJ; VANDENHEUVELL, GFECV; VANDEWIEL, HBM

    1992-01-01

    While there is no question that children dislike needles, there are very little data available on the occurrence of high levels of distress experienced by children undergoing routine venipunctures. To provide some insight into this problem, trained observers evaluated distress in 223 different child

  19. Evaluation of a virtual tour for children undergoing same-day surgery and their parents.

    Science.gov (United States)

    Tourigny, Jocelyne; Clendinneng, Debbie; Chartrand, Julie; Gaboury, Isabelle

    2011-01-01

    This study evaluated a virtual tour entitled, "Surgery Virtual Tour," offered on a Web site of a university-affiliated pediatric center. A pre-experimental one-group pretest-posttest design was used to assess the level of health care knowledge, emotional state, degree of utilization, and perceived usefulness of the Virtual Tour. The convenience sample consisted of 138 children having same-day surgery and their parents. The "Surgery Virtual Tour" was used by 55% of 138 families. Children who viewed the Web site had statistically significant higher knowledge scores than those who did not. Although there was no statistically significant difference in emotional distress for children in either group before the surgery (Time 1) to the day of the surgery (Time 2), parents' level of emotional distress increased significantly from Time 1 to Time 2 when they took the Virtual Tour. The results of this study will help clinicians and managers build virtual tours for children undergoing same-day surgery and their parents. PMID:21916345

  20. Can children undergoing ophthalmologic examinations under anesthesia be safely anesthetized without using an IV line?

    Directory of Open Access Journals (Sweden)

    Vigoda M

    2011-04-01

    Full Text Available Michael M Vigoda, Azeema Latiff, Timothy G Murray, Jacqueline L Tutiven, Audina M Berrocal, Steven GayerBascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USAPurpose: To document that with proper patient and procedure selection, children undergoing general inhalational anesthesia for ophthalmologic exams (with or without photos, ultrasound, laser treatment, peri-ocular injection of chemotherapy, suture removal, and/or replacement of ocular prosthesis can be safely anesthetized without the use of an intravenous (IV line. Children are rarely anesthetized without IV access placement. We performed a retrospective study to determine our incidence of IV access placement during examinations under anesthesia (EUA and the incidence of adverse events that required intraoperative IV access placement.Methods: Data collected from our operating room (OR information system includes but is not limited to diagnosis, anesthesiologist, surgeon, and location of IV catheter (if applicable, patient’s date of birth, actual procedure, and anesthesia/procedure times. We reviewed the OR and anesthetic records of children (>1 month and <10 years who underwent EUAs between January 1, 2003 and May 31, 2009. We determined the percentage of children who were anesthetized without IV access placement, as well as the incidence of any adverse events that required IV access placement, intraoperatively.Results: We analyzed data from 3196 procedures performed during a 77-month period. Patients’ ages ranged from 1 month to 9 years. Overall, 92% of procedures were performed without IV access placement. Procedure duration ranged from 1–39 minutes. Reasons for IV access placement included parental preference for antinausea medication and/or attending preference for IV access placement. No child who underwent anesthesia without an IV line had an intraoperative adverse event requiring insertion of an IV line.Conclusion: Our data suggest that for

  1. Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates capacity of hematopoietic stem cells to undergo lymphocyte differentiation

    International Nuclear Information System (INIS)

    The process of hematopoiesis, characterized by long-term self-renewal and multi-potent lineage differentiation, has been shown to be regulated in part by the ligand-activated transcription factor known as the aryl hydrocarbon receptor (AHR). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a ubiquitous contaminant and the most potent AHR agonist, also modulates regulation of adult hematopoietic stem and progenitor cell (HSC/HPC) homeostasis. However, the effect of developmental TCDD exposure on early life hematopoiesis has not been fully explored. Given the inhibitory effects of TCDD on hematopoiesis and lymphocyte development, we hypothesized that in utero exposure to TCDD would alter the functional capacity of fetal HSC/HPCs to complete lymphocyte differentiation. To test this hypothesis, we employed a co-culture system designed to facilitate the maturation of progenitor cells to either B or T lymphocytes. Furthermore, we utilized an innovative limiting dilution assay to precisely quantify differences in lymphocyte differentiation between HSC/HPCs obtained from fetuses of dams exposed to 3 μg/kg TCDD or control. We found that the AHR is transcribed in yolk sac hematopoietic cells and is transcriptionally active as early as gestational day (GD) 7.5. Furthermore, the number of HSC/HPCs present in the fetal liver on GD 14.5 was significantly increased in fetuses whose mothers were exposed to TCDD throughout pregnancy. Despite this increase in HSC/HPC cell number, B and T lymphocyte differentiation is decreased by approximately 2.5 fold. These findings demonstrate that inappropriate developmental AHR activation in HSC/HPCs adversely impacts lymphocyte differentiation and may have consequences for lymphocyte development in the bone marrow and thymus later in life

  2. Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates capacity of hematopoietic stem cells to undergo lymphocyte differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Ahrenhoerster, Lori S.; Tate, Everett R.; Lakatos, Peter A. [Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee (United States); Program in Environmental and Occupational Health, Milwaukee, WI 53211 (United States); Wang, Xuexia [Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee (United States); Program in Biostatistics, Milwaukee, WI 53211 (United States); Laiosa, Michael D., E-mail: laiosa@uwm.edu [Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee (United States); Program in Environmental and Occupational Health, Milwaukee, WI 53211 (United States)

    2014-06-01

    The process of hematopoiesis, characterized by long-term self-renewal and multi-potent lineage differentiation, has been shown to be regulated in part by the ligand-activated transcription factor known as the aryl hydrocarbon receptor (AHR). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a ubiquitous contaminant and the most potent AHR agonist, also modulates regulation of adult hematopoietic stem and progenitor cell (HSC/HPC) homeostasis. However, the effect of developmental TCDD exposure on early life hematopoiesis has not been fully explored. Given the inhibitory effects of TCDD on hematopoiesis and lymphocyte development, we hypothesized that in utero exposure to TCDD would alter the functional capacity of fetal HSC/HPCs to complete lymphocyte differentiation. To test this hypothesis, we employed a co-culture system designed to facilitate the maturation of progenitor cells to either B or T lymphocytes. Furthermore, we utilized an innovative limiting dilution assay to precisely quantify differences in lymphocyte differentiation between HSC/HPCs obtained from fetuses of dams exposed to 3 μg/kg TCDD or control. We found that the AHR is transcribed in yolk sac hematopoietic cells and is transcriptionally active as early as gestational day (GD) 7.5. Furthermore, the number of HSC/HPCs present in the fetal liver on GD 14.5 was significantly increased in fetuses whose mothers were exposed to TCDD throughout pregnancy. Despite this increase in HSC/HPC cell number, B and T lymphocyte differentiation is decreased by approximately 2.5 fold. These findings demonstrate that inappropriate developmental AHR activation in HSC/HPCs adversely impacts lymphocyte differentiation and may have consequences for lymphocyte development in the bone marrow and thymus later in life.

  3. Predictive Factors of Postoperative Pain and Postoperative Anxiety in Children Undergoing Elective Circumcision: A Prospective Cohort Study

    OpenAIRE

    Zavras, Nick; Tsamoudaki, Stella; Ntomi, Vasileia; Yiannopoulos, Ioannis; Christianakis, Efstratios; Pikoulis, Emmanuel

    2015-01-01

    Background Although circumcision for phimosis in children is a minor surgical procedure, it is followed by pain and carries the risk of increased postoperative anxiety. This study examined predictive factors of postoperative pain and anxiety in children undergoing circumcision. Methods We conducted a prospective cohort study of children scheduled for elective circumcision. Circumcision was performed applying one of the following surgical techniques: sutureless prepuceplasty (SP), preputial pl...

  4. COMPARATIVE STUDY OF SPINAL ANESTHESIA AND GENERAL ANESTHESIA IN CHILDREN UNDERGOING SURGERIES BELOW UMBILICUS

    Directory of Open Access Journals (Sweden)

    Ashish

    2014-09-01

    Full Text Available AIM: Aim of our study to compare the spinal anaesthesia and general anaesthesia in children undergoing surgeries below umbilicus. OBJECTIVE: to assess the patient comfort in pt. with GA and pt. with spinal anaesthesia, the adequate surgical condition, assess the hemodynamic change, assess the post op analgesia and to assess the post op complication. MATERIAL AND METHOD: 60 ASA grade I & II children of either sex, aged 5-12 yrs undergoing elective surgeries for the lower abdominal, perineal and lower limb surgeries were taken. After taking a detailed history, thorough general physical examination, all pertinent investigation were carried out to exclude any systemic disease. Patients were classified randomly into 2 groups (30 patients in each group. Group A: General anesthesia was given. Group P: subarachnoid block was given. Intraoperative monitoring consisted of SPO2, PR, NIBP, RR and assessment of duration of post-operative analgesia. P-value <0.05 consider significant. RESULT: Analysis revealed that there were no significant differences between the patients with respect to age, sex, duration and type of surgery In SAB since less general anaesthetic drug including parental opioid are used the risk and postoperative respiratory depression is minimal. The stress response to surgery is also limited and recovery is fast. Postoperatively complications like sore throat, laryngeal irritation, cough etc. was also less associated with it. CONCLUSION pediatric spinal anesthesia is not only a safe alternative to general anesthesia but often the anesthesia technique of choice in many lower abdominal and lower limb surgeries in children. The misconception regarding its safety and flexibility is broken and is now found to be even more cost effective. It is much preferred technique special for common day case surgeries generally performed in the pediatric age group.

  5. Effect of Chewing Gum on Oral Mucositis in Children Undergoing Chemotherapy: A Randomized Controlled Study

    Science.gov (United States)

    Eghbali, A; Taherkhanchi, B; Bagheri, B; Sadeghi Sedeh, B

    2016-01-01

    Background Oral mucositis is an adverse effect of chemotherapy. Type of chemotherapy regimen is the most important factor causing mucositis. Oral mucositis is usually associated with transient decrease in saliva production. The goal was to study effects of gum consumption on oral mucositis in children undergoing chemotherapy. Materials and Method This randomized controlled trial was done in Amir Kabir Hospital, Arak, Iran. 130 children 5 to 15 years of age were studied. Control group was composed of 65 children who received mucotoxic drugs. Test group was made up of 65 patients received similar drugs in addition to sugar free gums. Patients consumed 6 pieces of gums per day for 15 days. A standardized follow up form and World Health Organization (WHO) grading system for oral mucositis were used for evaluation of patients during 15 days of treatment. Results Severe oral mucositis occurred in 30 (46%) of 65 patients in the test group and in 26 of 65 (40%) patients in the control group. Difference was not statistically significant (P > 0.05). Rate of mild to moderate mucoitis (grade 1 and 2) was significantly lower in patients who used gums (15 % vs. 35%, P < 0.05). Conclusion Our study showed that stimulation of saliva flow by chewing gum could decrease mild to moderate inflammatory injuries of the oral mucosa during chemotherapy. However, it was not effective to subside severe mucositis.

  6. Role of Pharmacogenetics in Hematopoietic Stem Cell Transplantation Outcome in Children

    Directory of Open Access Journals (Sweden)

    Raffaella Franca

    2015-08-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is an established therapeutic procedure for several congenital and acquired disorders, both malignant and nonmalignant. Despite the great improvements in HSCT clinical practices over the last few decades, complications, such as graft vs. host disease (GVHD and sinusoidal obstructive syndrome (SOS, are still largely unpredictable and remain the major causes of morbidity and mortality. Both donor and patient genetic background might influence the success of bone marrow transplantation and could at least partially explain the inter-individual variability in HSCT outcome. This review summarizes some of the recent studies on candidate gene polymorphisms in HSCT, with particular reference to pediatric cohorts. The interest is especially focused on pharmacogenetic variants affecting myeloablative and immunosuppressive drugs, although genetic traits involved in SOS susceptibility and transplant-related mortality are also reviewed.

  7. Changes in Antioxidant Defense System Using Different Lipid Emulsions in Parenteral Nutrition in Children after Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    María Auxiliadora Baena-Gómez

    2015-08-01

    Full Text Available Background: Traditionally, lipids used in parenteral nutrition (PN are based on ω-6 fatty acid-rich vegetable oils, such as soybean oil, with potential adverse effects involving oxidative stress. Methods: We evaluated the antioxidant defense system in children, after hematopoietic stem cell transplantation (HSCT, who were randomized to use a lipid emulsion with fish oil or soybean oil. Blood samples at baseline, at 10 days, and at the end of the PN were taken to analyze plasma retinol, α-tocopherol, β-carotene, coenzyme Q9 and coenzyme Q10 levels, and catalase (CAT, glutathione reductase (GR, glutathione peroxidase (GPOX, and superoxide dismutase (SOD levels in lysed erythrocytes. Results: An increase in plasma α-tocopherol levels in the group of patients receiving the fish oil-containing emulsion (FO compared with the group receiving the soybean emulsion was observed at day 10 of PN. Concurrently, plasma α-tocopherol increased in the FO group and β-carotene decreased in both groups at day 10 compared with baseline levels, being more significant in the group receiving the FO emulsion. Conclusion: FO-containing emulsions in PN could improve the antioxidant profile by increasing levels of α-tocopherol in children after HSCT who are at higher risk of suffering oxidative stress and metabolic disorders.

  8. Outcomes of Allogeneic Hematopoietic Cell Transplantation in Children and Young Adults with Chronic Myeloid Leukemia: A CIBMTR Cohort Analysis.

    Science.gov (United States)

    Chaudhury, Sonali; Sparapani, Rodney; Hu, Zhen-Huan; Nishihori, Taiga; Abdel-Azim, Hisham; Malone, Adriana; Olsson, Richard; Hamadani, Mehdi; Daly, Andrew; Bacher, Ulrike; Wirk, Baldeep M; Kamble, Rammurti T; Gale, Robert P; Wood, William A; Hale, Gregory; Wiernik, Peter H; Hashmi, Shahrukh K; Marks, David; Ustun, Celalettin; Munker, Reinhold; Savani, Bipin N; Alyea, Edwin; Popat, Uday; Sobecks, Ronald; Kalaycio, Matt; Maziarz, Richard; Hijiya, Nobuko; Saber, Wael

    2016-06-01

    Chronic myeloid leukemia (CML) in children and young adults is uncommon. Young patients have long life expectancies and low morbidity with hematopoietic cell transplantation (HCT). Prolonged tyrosine kinase inhibitor (TKI) use may cause significant morbidity. In addition, indication for HCT in patients in the first chronic phase is not established. We hence retrospectively evaluated outcomes in 449 CML patients with early disease receiving myeloablative HCT reported to the CIBMTR. We analyzed various factors affecting outcome, specifically the effect of age and pre-HCT TKI in pediatric patients (age HCT probability rates of 5-year overall survival (OS) and leukemia-free survival (LFS) were 75% and 59%, respectively. Rates of OS and LFS were 76% and 57% in HCT TKI therapy on OS, LFS, transplant related mortality, or relapse. Favorable factors for OS were MSD (P HCT (2003 to 2010; P = .04). LFS was superior with MSD (P  90 (P = .03) compared with unrelated or mismatched peripheral blood stem cells donors and recipients with lower performance scores. Older age was associated with increased incidence of chronic graft-versus-host disease (P = .0002). In the current era, HCT outcomes are similar in young patients and children with early CML, and best outcomes are achieved with BM grafts and MSD. PMID:26964698

  9. Reduced intensity conditioning is superior to nonmyeloablative conditioning for older chronic myelogenous leukemia patients undergoing hematopoietic cell transplant during the tyrosine kinase inhibitor era

    DEFF Research Database (Denmark)

    Warlick, Erica; Ahn, Kwang Woo; Pedersen, Tanya L;

    2012-01-01

    the Center for International Blood and Marrow Transplant Research aged 40 years and older undergoing RIC/NMA HCT from 2001 to 2007: 117 (38%) aged 40 to 49 years, 119 (39%) 50 to 59 years, and 70 (23%) 60 years or older. The majority (74%) had treatment with imatinib before HCT. At HCT, most patients...

  10. Depressive Symptomatology in Children and Adolescents with Chronic Renal Insufficiency Undergoing Chronic Dialysis

    Directory of Open Access Journals (Sweden)

    Edith G. Hernandez

    2011-01-01

    Full Text Available This paper presents a descriptive study, using the Birleson Scale to determine the frequency of depressive symptomatology in children and adolescents with chronic renal insufficiency (CRI undergoing hemodialysis (HD and chronic peritoneal dialysis (CPD. There were 67 patients (40 female and 27 male with a mean age of 14.76±2.71 years, duration of illness ≥3 months, 43 (64.18% patients with CPD and 24 (35.82% undergoing HD. The frequency of high occurrence, low occurrence, and absence of depressive symptomatology was 10.45% (=7, 43.28% (=29, and 46.27% (=31, respectively; all of the seven (100% patients with high occurrence of depressive symptomatology were female (=0.04, and none of these (0% had a friend to confide in (=0.03. Depressive symptomatology in patients with CPD was associated with a lower weekly / compared to those without depressive symptomatology (2.15±0.68 versus 2.52±0.65; =0.01. There was no association with patient age, caregiver, time and dialysis type, anemia, bone disease, nutritional or financial status, origin, schooling, or employment.

  11. A Multimodal Approach to Post-Operative Pain Relief in Children Undergoing Ambulatory Eye Surgery

    Directory of Open Access Journals (Sweden)

    V V Jaichandran

    2008-01-01

    Full Text Available This study was carried to assess the efficacy of multimodal analgesia using ketorolac and fentanyl, for post-operative pain relief in children undergoing ambulatory eye surgery. Total of 161 children, aged 1 to 5 years, were randomly stratified to three different analgesic regimens: Group A Ketorolac 0.75 mg.kg -1 I.M. , Group B Fentanyl 0.75 µg.kg -1 I.V. and Group C Ketorolac 0.50mg.kg -1 I.M. and Fentanyl 0.50µg.kg -1 I.V. Ketorolac I.M. was given 45 minutes before extubation and fentanyl I.V. was given soon after extubation in the respective groups. Post-operative pain was assessed in a double blinded manner using Children′s Hospital of Eastern Onatario Pain Scale (CHEOPS scoring system and by recording the heart rate at 10, 30 and 60 minutes. If the score was above 8, the child was left with the parents. In case the score did not improve and persisted to be greater than 8, fentanyl 0.50µg.kg -1 I.V. was given as the rescue analgesia. The incidence of nausea, vomiting, sleep disturbances or any other complaints were recorded by a staff nurse 24 hours post operatively. Mean CHEOPS score at 10, 30 and 60 minutes and mean heart rate at 10 and 30 minutes were significantly higher for Group A compared with Group C. Mean pain score emerged significantly higher for Group B compared with Group C at 30 and 60 minutes, (P< 0.01. Rescue analgesia required was significantly higher in Group A compared to Groups B and C, (P< 0.0001. Post-operatively, significant incidence of drowsiness was reported in children in Group B compared to Groups A and C, (P< 0.01. A multimodal approach using both ketorolac and fentanyl at low doses produce effective and safe analgesia in children undergoing ambula-tory eye surgery.

  12. Comparison of Three Distinct Prophylactic Agents Against Invasive Fungal Infections in Patients Undergoing Haplo-identical Hematopoietic Stem Cell Transplantation and Post-transplant Cyclophosphamide

    OpenAIRE

    El-Cheikh, Jean; Crocchiolo, Roberto; Vai, Andrea; Furst, Sabine; Bramanti, Stefania; Sarina, Barbara; Granata, Angela; Faucher, Catherine; Mohty, Bilal; Harbi, Samia; Bouabdallah, Reda; Vey, Norbert; Santoro, Armando; Chabannon, Christian; Castagna, Luca

    2015-01-01

    Over the past decade, invasive fungal infections (IFIs) have remained an important problem in patients undergoing allogeneic haematopoietic stem cell transplantation (Allo-HSCT). The optimal approach for prophylactic antifungal therapy has yet to bedetermined. We conducted a retrospective analysis, comparing the safety and efficacy of micafungin 50mg/day vs. fluconazole 400mg/day vs. itraconazole 200mg/day as prophylaxis for adult patients with various haematological diseases receiving haploi...

  13. The Role Of Multidetector Computed Tomography In The Early Diagnosis Of Invasive Pulmonary Aspergıllosis In Patients With Febrile Neutropenia Undergoing Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Nazan Çiledağ

    2012-03-01

    Full Text Available OBJECTIVE: To evaluate the vessel involvement and the role of multidedector computed tomograpy (MDCT in the early diagnosis of invasive pulmonary aspergillosis (IPA at MDCT in autologous bone morrow transplantation patients with febrile neutropenia and antibiotic-resistant fever of unknown origin with clinically suspected IPA. METHODS: 74 pulmonary MDCT examinations of 37 consecutive hematopoietic stem cell transplantation patients with febrile neutropenia with clinically suspected IPA were retrospectively evaluated. RESULTS: The diagnosis of IPA was made according to according to the Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Consensus Group criteria and 0, 14, 11 patients were diagnosed as proven, probable, possible IPA, respectively. Among 25 cases accepted as probable and possible IPA, all patients had pulmonary MDCT findings consistent with IPA. Remaining 12 patients were accepted as having fever of unknown origin (FUO and in these 12, MDCT showed patent vessel. In patients with probable/possible IPA, 72 focal pulmonary lesions were detected. In 41 of 72 (57%, vascular occlusion was detected. The CT halo sign was present in 25 of 41 (61% lesions. A clinical improvement, resolution of fever was observed following antifungal therapy in 19 (76% of 25 patients with probable/possible IPA. Six (25% patients diagnosed as IPA died during follow-up. Transplant related mortality at day 100 in patients with IPA and FUO were found to be 24% and 0%, respectively. CONCLUSION: In conclusion, MDCT has a potential role in early diagnosis of IPA by detection of vessel occlusion.

  14. An empowerment health education program for children undergoing surgery for congenital heart diseases.

    Science.gov (United States)

    Ni, Zhihong; Chao, Yannfen; Xue, Xiaoling

    2016-09-01

    Since the surgery for congenital heart disease (CHD) is considered highly risky, appropriate postoperative care is crucial. After the surgery, children are often discharged with unhealed wounds, incomplete recovery, and continuing pain. Health education programs based on empowerment education model can assist clients to develop skills in self-management. This study aimed to evaluate the effectiveness of an empowerment health education program for improving caregiving knowledge, caring behaviors, and self-efficacy of parents caring for children after corrective surgery for CHD. This prospective clinical trial enrolled pediatric patients undergoing surgical correction for CHD. Patients were divided into two groups: the control group (n = 42), which received the standard education program, and the intervention group (n = 44), which participated in the empowerment theory-based education program. We collected data on left ventricular ejection fraction (LVEF); peripheral oxygen saturation (SpO2); New York Heart Association classification of the patients; and the parents' caregiving knowledge, caring behaviors, and self-efficacy before surgery and one month and three months after surgery. At one month and three months after surgery, the intervention group scored higher than the control group in caregiving knowledge, caring behavior, and self-efficacy. By the third month after surgery, the intervention group had significantly higher values of LVEF and SpO2 than the control group. PMID:26105060

  15. Higher Busulfan Dose Intensity Does Not Improve Outcomes of Patients Undergoing Allogeneic Hematopoietic Cell Transplantation Following Fludarabine, Busulfan-based Reduced Toxicity Conditioning

    OpenAIRE

    Hamadani, Mehdi; Craig, Michael; Gary S Phillips; Abraham, Jame; Tse, William; Cumpston, Aaron; Gibson, Laura; Remick, Scot C.; Bunner, Pamela; Leadmon, Sonia; Elder, Patrick; Hofmeister, Craig; Penza, Sam; Efebera, Yvonne; Andritsos, Leslie

    2011-01-01

    We evaluated the impact of busulfan dose-intensity in patients undergoing reduced toxicity/intensity conditioning allogeneic transplantation in a multicenter retrospective study of 112 consecutive patients. Seventy-five patients were conditioned with busulfan (0.8 mg/kg/dose IV × 8 doses), fludarabine (30mg/m2/day, days −7 to −3), and 6mg/kg of ATG (RIC group), while 37 patients received a more-intense conditioning with busulfan (130mg/m2/day IV, days −6 to −3), fludarabine (40mg/m2/day, days...

  16. Postoperative pain assessment using four behavioral scales in Pakistani children undergoing elective surgery

    Directory of Open Access Journals (Sweden)

    Faisal Shamim

    2015-01-01

    Full Text Available Background: Several measurement tools have been used for assessment of postoperative pain in pediatric patients. Self-report methods have limitations in younger children and parent, nurse or physician assessment can be used as a surrogate measure. These tools should be tested in different cultures as pain can be influenced by sociocultural factors. The objective was to assess the inter-rater agreement on four different behavioral pain assessment scales in our local population. Materials and Methods: This prospective, descriptive, observational study was conducted in Pakistan. American Society of Anesthesiologists I and II children, 3-7 years of age, undergoing elective surgery were enrolled. Four pain assessment scales were used, Children′s Hospital of Eastern Ontario Pain Scale (CHEOPS, Toddler Preschool Postoperative Pain Scale (TPPPS, objective pain scale (OPS, and Face, Legs, Activity, Cry, Consolability (FLACC. After 15 and 60 min of arrival in the postanesthesia care unit (PACU, each child evaluated his/her postoperative pain by self-reporting and was also independently assessed by the PACU nurse, PACU anesthetist and the parent. The sensitivity and specificity of the responses of the four pain assessment scales were compared to the response of the child. Results: At 15 min, sensitivity and specificity were >60% for doctors and nurses on FLACC, OPS, and CHEOPS scales and for FLACC and CHEOPS scale for the parents. Parents showed poor agreement on OPS and TPPS. At 60 min, sensitivity was poor on the OPS scale by all three observers. Nurses showed a lower specificity on FLACC tool. Parents had poor specificity on CHEOPS and rate of false negatives was high with TPPS. Conclusions: We recommend the use of FLACC scale for assessment by parents, nurses, and doctors in Pakistani children aged between 3 and 7.

  17. Idarubicin-intensified BUCY2 conditioning regimen improved survival in high-risk acute myeloid, but not lymphocytic leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: A retrospective comparative study.

    Science.gov (United States)

    Fang, Jun; Zhang, Ran; Wang, Huafang; Hong, Mei; Wu, Qiuling; Nie, Dimin; You, Yong; Zhong, Zhaodong; Li, Weiming; Hu, Yu; Xia, Linghui

    2016-07-01

    The intensity of conditioning regimen is highly correlated with outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We have previously reported that idarubicin (IDA) intensified BUCY2 regimen could reduce relapse and improve survival for high-risk hematological malignancies undergoing allo-HSCT. However, there is no published study comparing the efficacy of IDA-BUCY2 regimen for high-risk acute myeloid leukemia (AML) versus acute lymphocytic leukemia (ALL). We further retrospectively compared therapeutic outcomes of intensified conditioning regimen on 140 high-risk AML and ALL patients in the data analyses. IDA 15mg/m(2)/d was administered by continuous infusion from day -11 to -9, followed by intravenous injection of busulfan (BU) (3.2mg/kg/d) from day -6 to -4, and intravenous injection of cyclophosphamide (CY) (1.8g/m(2)/d) from day -3 to -2 in IDA-BUCY2 regimen. For high-risk AML, cumulative probabilities of 3-year relapse rates in IDA-BUCY2 and traditional BUCY2 regimens were 16.9%, 43.3% (P=0.016). Cumulative probabilities of 3-year overall survival (OS) and disease-free survival (DFS) were 69.2% vs 44.0% (P=0.024), and 66.9% vs 38.2% (P=0.01). However, two regimens showed no significant differences for high-risk ALL. Multivariate analysis also indicated that IDA intensified BUCY2 conditioning was the favorable variable to reduce relapse and elevate survival for high-risk AML patients. In conclusion, IDA-BUCY2 regimen reduces relapse and improves survival for high-risk AML undergoing allo-HSCT, but not presenting uniform therapeutic effects for high-risk ALL. PMID:27131062

  18. Immunotherapy of invasive fungal infection in hematopoietic stem cell transplant recipients

    OpenAIRE

    Lehrnbecher, Thomas; Schmidt, Stanislaw; Tramsen, Lars; Klingebiel, Thomas

    2013-01-01

    Despite the availability of new antifungal compounds, invasive fungal infection remains a significant cause of morbidity and mortality in children and adults undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Allogeneic HSCT recipients suffer from a long lasting defect of different arms of the immune system, which increases the risk for and deteriorates the prognosis of invasive fungal infections. In turn, advances in understanding these immune deficits have resulted in pro...

  19. COMPARISON OF THREE DISTINCT PROPHYLACTIC AGENTS AGAINST INVASIVE FUNGAL INFECTIONS IN PATIENTS UNDERGOING HAPLO-IDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION AND POST-TRANSPLANT CYCLOPHOSPHAMIDE

    Directory of Open Access Journals (Sweden)

    Jean Elcheikh

    2015-08-01

    Full Text Available Over the past decade, invasive fungal infections (IFI have remained an important problem in patients undergoing allogeneic haematopoietic stem cell transplantation (Allo-HSCT. The optimal approach for prophylactic antifungal therapy has yet to be determined. We conducted a retrospective, bi-institutional comparative clinical study, and compared the efficacy and safety of micafungin 50mg/day (iv with those of fluconazole (400mg/day or itraconazole 200mg/day (iv as prophylaxis for adult patients with various haematological diseases receiving haplo-identical allogeneic stem cell transplantation (haplo. Overall, 99 patients were identified; 30 patients received micafungin, and 69 patients received fluconazole or itraconazole. After a median follow-up of 13 months (range: 5-23, Proven or probable IFIs were reported in 3 patients (10% in the micafungin group and 8 patients (12% in the fluconazole or itraconazole group. Fewer patients in the micafungin group had invasive aspergillosis (1 [3%] vs. 5 [7%], P=0.6. A total of 4 (13% patients in the micafungin group and 23 (33% patients in the fluconazole or itraconazole group received empirical antifungal therapy (P = 0.14. No serious adverse events related to treatment were reported by patients and there was no treatment discontinuation because of drug-related adverse events in both groups. Despite the retrospective design of the study and limited sample, it contributes reassuring data to confirm results from randomised clinical trials, and to define a place for micafungin in prophylaxis after haplo.

  20. Immune reconstitution after allogeneic hematopoietic stem cell transplantation in children: a single institution study of 59 patients

    Directory of Open Access Journals (Sweden)

    Hyun O Kim

    2013-01-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; Lymphocyte subset recovery is an important factor that determines the success of hematopoietic stem cell transplantation (HSCT. Temporal differences in the recovery of lymphocyte subsets and the factors influencing this recovery are important variables that affect a patient's posttransplant immune reconstitution, and therefore require investigation. &lt;b&gt;Methods:&lt;/b&gt; The time taken to achieve lymphocyte subset recovery and the factors influencing this recovery were investigated in 59 children who had undergone HSCT at the Department of Pediatrics, The Catholic University of Korea Seoul St. Mary's Hospital, and who had an uneventful follow-up period of at least 1 year. Analyses were carried out at 3 and 12 months post-transplant. An additional study was performed 1 month post-transplant to evaluate natural killer (NK cell recovery. The impact of preand post-transplant variables, including diagnosis of Epstein-Barr virus (EBV DNAemia posttransplant,on lymphocyte recovery was evaluated. &lt;b&gt;Results:&lt;/b&gt; The lymphocyte subsets recovered in the following order: NK cells, cytotoxic T cells, B cells,and helper T cells. At 1 month post-transplant, acute graft-versus-host disease was found to contribute significantly to the delay of CD16+/56+ cell recovery. Younger patients showed delayed recovery of both CD3+/CD8+ and CD19+ cells. EBV DNAemia had a deleterious impact on the recovery of both CD3+ and CD3+/CD4+ lymphocytes at 1 year post-transplant. &lt;b&gt;Conclusion:&lt;/b&gt; In our pediatric allogeneic HSCT cohort, helper T cells were the last subset to recover. Younger age and EBV DNAemia had a negative impact on the post-transplant recovery of T cells and B cells.

  1. Impact of Psychological Interventions on Reducing Anxiety, Fear and the Need for Sedation in Children Undergoing Magnetic Resonance Imaging

    OpenAIRE

    Maria Pia Viggiano; Fiorenza Giganti; Arianna Rossi; Daniele Di Feo; Laura Vagnoli; Giovanna Calcagno; Claudio Defilippi

    2015-01-01

    Children undergoing magnetic resonance imaging examination frequently experience anxiety and fear before and during the scanning. The aim of the present study was to assess: i) whether and to what extent psychological interventions might reduce anxiety and fear levels; ii) whether the intervention is related to a decrease in the need for sedation. The interventions consisted of three activities: a clown show, dog interaction and live music. The emotional status (anxiety and fear) of the child...

  2. End-of-Life Care Patterns Associated with Pediatric Palliative Care among Children Who Underwent Hematopoietic Stem Cell Transplant.

    Science.gov (United States)

    Ullrich, Christina K; Lehmann, Leslie; London, Wendy B; Guo, Dongjing; Sridharan, Madhumitha; Koch, Richard; Wolfe, Joanne

    2016-06-01

    Stem cell transplantation (SCT) is an intensive therapy offering the possibility of cure for life-threatening conditions but with risk of serious complications and death. Outcomes associated with pediatric palliative care (PPC) for children who undergo SCT are unknown. Therefore, we evaluated whether PPC consultation is associated with differences in end-of-life (EOL) care patterns for children who underwent SCT and did not survive. Medical records of children who underwent SCT at Boston Children's Hospital/Dana-Farber Cancer Institute for any indication from September 2004 to December 2012 and did not survive were reviewed. Child demographic and clinical characteristics and PPC consultation and EOL care patterns were abstracted. Children who received PPC (PPC group) were compared with those who did not (non-PPC group). Children who received PPC consultation (n = 37) did not differ from the non-PPC group (n = 110) with respect to demographic or clinical characteristics, except they were more likely to have undergone unrelated allogeneic SCT (PPC, 68%; non-PPC, 39%; P = .02) or to have died from treatment-related toxicity (PPC, 76%; non-PPC, 54%; P = .03). PPC consultation occurred at a median of .7 months (interquartile range [IQR], .4 to 4.2) before death. PPC consultations most commonly addressed goals of care/decision-making (92%), psychosocial support (84%), pain management (65%), and non-pain symptom management (70%). Prognosis discussions (ie, the likelihood of survival) occurred more commonly in the PPC group (PPC, 97%; non-PPC, 83%; P = .04), as did resuscitation status discussions (PPC, 88%; non-PPC, 58%; P = .002). These discussions also occurred earlier in the PPC group, for prognosis a median of 8 days (IQR, 4 to 26) before death compared with 2 days (IQR, 1 to 13) in the non-PPC group and for resuscitation status a median of 7 days (IQR, 3 to 18) compared with 2 days (IQR, 1 to 5) in the non-PPC group (P cure-oriented SCT setting, PPC

  3. Allogeneic hematopoietic SCT in children with ALL: current concepts of ongoing prospective SCT trials.

    Science.gov (United States)

    Schrauder, A; von Stackelberg, A; Schrappe, M; Cornish, J; Peters, Christina

    2008-06-01

    The definition of indications for allogeneic SCT in children with high-risk (HR) ALL in the first remission or after the first or subsequent relapse depends on biological features, response to treatment and survival after chemotherapy alone. As the results of frontline and relapse protocols are improving over time, there is a strong need for prospective SCT trials, ensuring a well-standardized procedure regarding all relevant components that are potentially responsible for heterogeneity in post-SCT outcome. Therefore, in 2003, the ALL-BFM and the ALL-REZ BFM Study Group initiated a prospective, international, multicenter trial (ALL-SCT-BFM 2003). This trial will now be extended to a larger consortium, trial ALL-SCT-BFM-international (ALL-SCT-BFMi). Strict rules define HLA-typing, donor selection, conditioning regimen, GvHD prophylaxis and therapy as well as standards of supportive care to reduce treatment-related mortality and establish an early GVL effect. Moreover, comprehensive and closely reviewed documentation and serious adverse event reporting shall ensure high study quality. Case-by-case discussions of any fatal or critical course during annual meetings will improve the culture of failure management and lead to modifications of guidelines of supportive care. Finally, the results of these prospective trials will determine the current potential of the different SCT procedures in HR or relapsed childhood ALL. PMID:18545248

  4. Initial experience with intravenous pentobarbital sedation for children undergoing MRI at a tertiary care pediatric hospital: the learning curve

    International Nuclear Information System (INIS)

    Objective. Our purpose is to describe the initial experience with intravenous pentobarbital sedation in children undergoing MRI at a tertiary pediatric hospital to identify errors associated with inexperience. Subjects and methods. The study included the first 100 children sedated with intravenous pentobarbital prior to magnetic resonance examination at a tertiary pediatric hospital. The protocol included a maximum dose of 6 mg/kg administered in three divided doses with the total dose not to exceed 200 mg. Flow sheets documenting vital signs, administered drug doses, and adverse reactions were maintained contemporaneous to sedation. Results. Sedation was successful in 92 children. Of the eight children who failed sedation, three were at least 12 years old and three weighed more than 50 kg. χ2 tests identified significantly greater failure rates in children older than 11 years or weight greater than 50 kg. Two children had prolonged sedation after the maximum suggested dose was exceeded. Conclusions. The success rate was good, but could have been improved by restricting the use of pentobarbital to children less than 12 years of age and weighing less than 50 kg. Radiologists inexperienced with intravenous sedation should strictly observe the maximum suggested dose of pentobarbital to prevent prolonged sedation. (orig.)

  5. Allogeneic hematopoietic stem cells transplantation with reduced intensity conditioning regimen in children and adolescents with unfavorable forms of acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    E. V. Semenova

    2014-07-01

    Full Text Available Treatment results of allogeneic hematopoietic stem cells transplantation (allo-HSCT with myeloablative (MAC and reduced intensity (RIC conditioning regimen in children and adolescents with unfavorable forms of acute lymphoblastic leukemia (ALL were shown. One hundred and two ALL patients aged 1 to 21 years (mean – 12 years who received allo-HSCT from 2000 to 2010 (31 patients with RIC and 71 patients with MAC are included in the study. Analysis of overall and event-free survival in both groups showed comparable efficacy. The use of RIC as alternative conditioning regimen in children and adolescents with high risk ALL and poor general condition, comorbidities and infectious complications are discussed.

  6. Functional Decline in Children Undergoing Selective Dorsal Rhizotomy after Age 10

    Science.gov (United States)

    MacWilliams, Bruce A.; Johnson, Barbara A.; Shuckra, Amy L.; D'Astous, Jacques L.

    2011-01-01

    Aim: To compare function and gait in a group of children older than most children who received selective dorsal rhizotomy (SDR) with age- and function-matched peers who received either orthopedic surgery or no surgical intervention. Method: A retrospective study examined ambulatory children with diplegic cerebral palsy, aged between 10 years and…

  7. Judging Pain Intensity in Children with Autism Undergoing Venepuncture: The Influence of Facial Activity

    Science.gov (United States)

    Messmer, Rosemary L.; Nader, Rami; Craig, Kenneth D.

    2008-01-01

    The biasing effect of pain sensitivity information and the impact of facial activity on observers' judgments of pain intensity of children with autism were examined. Observers received information that pain experience in children with autism is either the same as, more intense than, or less intense than children without autism. After viewing six…

  8. Behavioral Distress in Children with Cancer Undergoing Medical Procedures: Developmental Considerations.

    Science.gov (United States)

    Katz, Ernest R.; And Others

    1980-01-01

    The amount of anxiety suggested the need for clinical intervention to reduce procedure-related distress in children with cancer. Younger children exhibited consistently higher levels of distress than older children and displayed a greater variety of anxious responses over a longer time span. (Author/BEF)

  9. Comparison between sevoflurane and desflurane on emergence and recovery characteristics of children undergoing surgery for spinal dysraphism

    Directory of Open Access Journals (Sweden)

    Priyanka Gupta

    2015-01-01

    Full Text Available Background and Aims: Rapid recovery is desirable after neurosurgery as it enables early post-operative neurological evaluation and prompt management of complications. Studies have been rare comparing the recovery characteristics in paediatric neurosurgical patients. Hence, this study was carried out to compare the effect of sevoflurane and desflurane anaesthesia on emergence and extubation in children undergoing spinal surgery. Methods: Sixty children, aged 1-12 years, undergoing elective surgery for lumbo-sacral spinal dysraphism were enrolled. Anaesthesia was induced with sevoflurane using a face mask. The children were then randomised to receive either sevoflurane or desflurane with oxygen and nitrous oxide, fentanyl (1 μg/kg/h and rocuronium. The anaesthetic depth was guided by bispectral index (BIS ® monitoring with a target BIS ® between 45 and 55. Perioperative data with regard to demographic profile, haemodynamics, emergence and extubation times, modified Aldrete score (MAS, pain (objective pain score, agitation (Cole′s agitation score, time to first analgesic and complications, thereof, were recorded. Statistical analysis was done using STATA 11.2 (StataCorp., College Station, TX, USA and data are presented as median (range or mean ± standard deviation. Results: The demographic profile, haemodynamics, MAS, pain and agitation scores and time to first analgesic were comparable in between the two groups (P > 0.05. The emergence time was shorter in desflurane group (2.75 [0.85-12] min as compared to sevoflurane (8 [2.5-14] min (P < 0.0001. The extubation time was also shorter in desflurane group (3 [0.8-10] min as compared to the sevoflurane group (5.5 [1.2-14] min (P = 0.0003. Conclusion: Desflurane provided earlier tracheal extubation and emergence as compared to sevoflurane in children undergoing surgery for lumbo-sacral spinal dysraphism.

  10. Population Pharmacokinetics of Busulfan in Pediatric and Young Adult Patients Undergoing Hematopoietic Cell Transplant: A Model-Based Dosing Algorithm for Personalized Therapy and Implementation into Routine Clinical Use

    Science.gov (United States)

    Long-Boyle, Janel; Savic, Rada; Yan, Shirley; Bartelink, Imke; Musick, Lisa; French, Deborah; Law, Jason; Horn, Biljana; Cowan, Morton J.; Dvorak, Christopher C.

    2014-01-01

    Background Population pharmacokinetic (PK) studies of busulfan in children have shown that individualized model-based algorithms provide improved targeted busulfan therapy when compared to conventional dosing. The adoption of population PK models into routine clinical practice has been hampered by the tendency of pharmacologists to develop complex models too impractical for clinicians to use. The authors aimed to develop a population PK model for busulfan in children that can reliably achieve therapeutic exposure (concentration-at-steady-state, Css) and implement a simple, model-based tool for the initial dosing of busulfan in children undergoing HCT. Patients and Methods Model development was conducted using retrospective data available in 90 pediatric and young adult patients who had undergone HCT with busulfan conditioning. Busulfan drug levels and potential covariates influencing drug exposure were analyzed using the non-linear mixed effects modeling software, NONMEM. The final population PK model was implemented into a clinician-friendly, Microsoft Excel-based tool and used to recommend initial doses of busulfan in a group of 21 pediatric patients prospectively dosed based on the population PK model. Results Modeling of busulfan time-concentration data indicates busulfan CL displays non-linearity in children, decreasing up to approximately 20% between the concentrations of 250–2000 ng/mL. Important patient-specific covariates found to significantly impact busulfan CL were actual body weight and age. The percentage of individuals achieving a therapeutic Css was significantly higher in subjects receiving initial doses based on the population PK model (81%) versus historical controls dosed on conventional guidelines (52%) (p = 0.02). Conclusion When compared to the conventional dosing guidelines, the model-based algorithm demonstrates significant improvement for providing targeted busulfan therapy in children and young adults. PMID:25162216

  11. Parent Outlook: How Parents View the Road Ahead as They Embark on Hematopoietic Stem Cell Transplantation for Their Child

    OpenAIRE

    Ullrich, Christina K.; Rodday, Angie Mae; Bingen, Kristin; Kupst, Mary Jo; Patel, Sunita K.; Syrjala, Karen L.; Harris, Lynnette L.; Recklitis, Christopher J.; Schwartz, Lisa; Davies, Stella; Guinan, Eva C.; Chang, Grace; Wolfe, Joanne; Parsons, Susan K

    2015-01-01

    Pediatric hematopoietic stem cell transplantation (HSCT) offers cure for high-risk malignancies and other conditions, but carries a risk of complications. Parental outlook regarding their child’s transplantation course and future health has been largely unexplored. This report presents the Parent Outlook Scale, describes its properties, and examines the outlook of parents embarking on their child’s transplantation course and the associated variables. Parents of children scheduled to undergo H...

  12. A population-based study relevant to seasonal variations in causes of death in children undergoing surgery for congenital cardiac malformations

    OpenAIRE

    Eskedal, Leif T.; Hagemo, Petter S.; Eskild, Anne; Frøslie, Kathrine F; Seiler, Stephen; Thaulow, Erik

    2007-01-01

    Aims: Our objectives were, first, to study seasonal distribution of perioperative deaths within 30 days after surgery, and late death, in children undergoing surgery for congenitally malformed hearts, and second, to study the causes of late death. Methods: We analysed a retrospective cohort of 1,753 children with congenital cardiac malformations born and undergoing surgery in the period from 1990 through 2002 with a special focus on the causes of late death. The data was obtained from the...

  13. Comparison of Hypnosis and Distraction in Severely Ill Children Undergoing Painful Medical Procedures.

    Science.gov (United States)

    Smith, Julien T.; And Others

    1996-01-01

    An ethnically diverse sample of high and low hypnotizable children (N=27) suffering from cancer or blood disorders were trained along with their parents to use both distraction and hypnosis to reduce pain and anxiety. Distraction produced significant positive effects for observer-rated distress scores for the low hypnotizable children. Discusses…

  14. Impact of psychological interventions on reducing anxiety, fear and the need for sedation in children undergoing magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Maria Pia Viggiano

    2015-03-01

    Full Text Available Children undergoing magnetic resonance imaging examination frequently experience anxiety and fear before and during the scanning. The aim of the present study was to assess: i whether and to what extent psychological interventions might reduce anxiety and fear levels; ii whether the intervention is related to a decrease in the need for sedation. The interventions consisted of three activities: a clown show, dog interaction and live music. The emotional status (anxiety and fear of the children was evaluated before and after the activities through a rating scale questionnaire. The results showed that the activities had high effectiveness in reducing the level of anxiety and fear and decreased the need for sedation in the experimental group compared to the control group. This approach proved to be a positive patient experience, helping to alleviate children’s anxiety and fear, decreasing the need for sedation, and was cost-effective.

  15. Sleep/sedation in children undergoing EEG testing: a comparison of chloral hydrate and music therapy.

    Science.gov (United States)

    Loewy, Joanne; Hallan, Cathrine; Friedman, Eliezer; Martinez, Christine

    2006-12-01

    This study included a total of 60 pediatric patients ranging from 1 month through 5 years of age. The effects of chloral hydrate and music therapy were evaluated and compared as means of safe and effective ways to achieve sleep/sedation in infants and toddlers undergoing EEG testing. The results of the study indicate that music therapy may be a cost-effective, risk-free alternative to pharmacological sedation. PMID:17285817

  16. GROWTH HORMONE LEVEL EVOLUTION IN CHILDREN WITH HEPATOBILIARY DISEASES, UNDERGOING LIVER TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    O. P. Shevchenko

    2012-01-01

    Full Text Available End stage liver disease is often associated with growth retardation in children with congenital and hereditary diseases of hepatobiliary system. The aim was to investigate the serum growth hormone level before and after liver transplantation in 52 children with congenital and hereditary diseases of hepatobiliary system. Data of our research work revealed increased serum level of growth hormone in children with liver cirrhosis (3,32 ± 7,7 ng/ml vs. 1,16 ± 1,46 ng/ml in healthy children, p = 0,01, which correlates with PELD score (r = 0,62, p < 0,001. In a month after liver transplantation growth hormone concentration decreases (p < 0,001 and in a year after transplantation it doesn’t differ from healthy children. There wasn’t revealed any interaction between serum growth hormone level and anthropometric parameters before liver transplantation, but in a year after there was significant correlation between growth hormone concentration and height (r = 0,79, p = 0,01. Investigation of growth hormone level in children with liver cirrhosis and its evolution after liver transplantation is of interest as objective criterion of recovery of physical development regulation and as an additional parameter, which cor- relates with severity of end-stage liver disease. 

  17. Chest computed tomography in children undergoing extra-corporeal membrane oxygenation: a 9-year single-centre experience

    Energy Technology Data Exchange (ETDEWEB)

    Goodwin, Susie J.; Calder, Alistair D. [Great Ormond Street Hospital for Children NHS Foundation Trust, Radiology Department, London (United Kingdom); Randle, Elise; Iguchi, Akane; Brown, Katherine; Hoskote, Aparna [Great Ormond Street Hospital for Children NHS Foundation Trust, Cardiac Intensive Care and ECMO, London (United Kingdom)

    2014-06-15

    We retrospectively reviewed the imaging findings, indications, technique and clinical impact in children who had undergone chest CT while undergoing extra-corporeal membrane oxygenation (ECMO). Radiology and ECMO databases were searched to identify all 19 children who had undergone chest CT (20 scans in total) while on ECMO at our institution between May 2003 and May 2012. We reviewed all CT scans for imaging findings. Chest CT is performed in a minority of children on ECMO (4.5% in our series). Timing of chest CT following commencement of ECMO varied among patient groups but generally it was performed earlier in the neonatal group. Clinically significant imaging findings were found in the majority of chest CT scans. Many scans contained several findings, with most cases demonstrating parenchymal or pleural abnormalities. Case examples illustrate the spectrum of imaging findings, including underlying pathology such as necrotising pneumonia and severe barotrauma, and ECMO-related complications such as tension haemothoraces and cannula migration. The results of chest CT led to a change in patient management in 16 of 19 children (84%). There were no adverse events related to patient transfer. An understanding of scan technique and awareness of potential findings is important for the radiologist to provide prompt and optimal image acquisition and interpretation in appropriate patients. (orig.)

  18. The role of blood lactate clearance as a predictor of mortality in children undergoing surgery for tetralogy of Fallot

    Science.gov (United States)

    Ladha, Suruchi; Kapoor, Poonam Malhotra; Singh, Sarvesh Pal; Kiran, Usha; Chowdhury, Ujjwal Kumar

    2016-01-01

    Background: The identification of biomarkers for predicting morbidity and mortality, particularly in pediatric population undergoing cardiac surgery will contribute toward improving the patient outcome. There is an increasing body of literature establishing the clinical utility of hyperlactatemia and lactate clearance as prognostic indicator in adult cardiac surgical patients. However, the relationship between lactate clearance and mortality risk in the pediatric population remains to be established. Objective: To assess the role of lactate clearance in determining the outcome in children undergoing corrective surgery for tetralogy of Fallot (TOF). Methods and Study Design: A prospective, observational study. Setting: A tertiary care center. Study Population: Two hundred children undergoing elective surgery for TOF. Study Method: Blood lactate levels were obtained as baseline before operation (T0), postoperatively at admission to the cardiac intensive care unit after surgery (T1), and then at every 6 h for the first 24 h of Intensive Care Unit (ICU) stay (T6, T12, T18, and T24, respectively). The lactate clearance in the study is defined by the equation ([lactate initial – lactate delayed]/lactate initial) ×100%. Lactate clearance was determined at T1–T6, T1–T12, T1–T18, and T1–T24 time interval, respectively. The primary outcome measured was mortality. Secondary outcomes measured were the duration of mechanical ventilation, duration of inotropic requirement, and duration of ICU stay. Results: Eleven out of the two hundred patients enrolled in the study died. Nonsurvivors had higher postoperative lactate concentration (P 10%, relative to patients with a lactate clearance 10%) after 6 h have improved outcome compared with those with lower lactate clearance. PMID:27052060

  19. The role of blood lactate clearance as a predictor of mortality in children undergoing surgery for tetralogy of Fallot

    Directory of Open Access Journals (Sweden)

    Suruchi Ladha

    2016-01-01

    Full Text Available Background: The identification of biomarkers for predicting morbidity and mortality, particularly in pediatric population undergoing cardiac surgery will contribute toward improving the patient outcome. There is an increasing body of literature establishing the clinical utility of hyperlactatemia and lactate clearance as prognostic indicator in adult cardiac surgical patients. However, the relationship between lactate clearance and mortality risk in the pediatric population remains to be established. Objective: To assess the role of lactate clearance in determining the outcome in children undergoing corrective surgery for tetralogy of Fallot (TOF. Methods and Study Design: A prospective, observational study. Setting: A tertiary care center. Study Population: Two hundred children undergoing elective surgery for TOF. Study Method: Blood lactate levels were obtained as baseline before operation (T0, postoperatively at admission to the cardiac intensive care unit after surgery (T1, and then at every 6 h for the first 24 h of Intensive Care Unit (ICU stay (T6, T12, T18, and T24, respectively. The lactate clearance in the study is defined by the equation ([lactate initial - lactate delayed]/lactate initial ×100%. Lactate clearance was determined at T1-T6, T1-T12, T1-T18, and T1-T24 time interval, respectively. The primary outcome measured was mortality. Secondary outcomes measured were the duration of mechanical ventilation, duration of inotropic requirement, and duration of ICU stay. Results: Eleven out of the two hundred patients enrolled in the study died. Nonsurvivors had higher postoperative lactate concentration (P 10%, relative to patients with a lactate clearance 10% after 6 h have improved outcome compared with those with lower lactate clearance.

  20. Efficacy and safety of oral triclofos as sedative for children undergoing sleep electroencephalogram: An observational study

    Science.gov (United States)

    Jain, Puneet; Sharma, Suvasini; Sharma, Ankita; Goel, Shaiphali; Jose, Anjali; Aneja, Satinder

    2016-01-01

    Objectives: Triclofos may be a better sedative in view of better palatability and less gastric irritation as compared to chloral hydrate. This study aimed to assess the efficacy of triclofos (a commonly used sedative in India) as a sedative for sleep electroencephalogram (EEG) study in children. Methods: This prospective observational study was carried out in a tertiary care pediatric center. Consecutive children aged 6 months to 5 years referred for sleep EEG evaluation were recruited. Their clinical details were noted in a proforma after an informed consent. After a trial for natural sleep, oral triclofos was administered. Sleep parameters and adverse effects were noted. Results: One-hundred and sixty children were then enrolled. EEG was successfully recorded in 149 (93.1%) children. Median latency of sleep onset was 30 min and median duration of sleep was 90 min. The adverse effects in the following 24 h were mild and included dizziness, irritability, and vomiting. Conclusions: Oral triclofos was found to be an effective sedative for EEG in children with minimal adverse effects.

  1. Clinical observation of parenteral nutrition support in patients undergoing hematopoietic stem cell transplantation%造血干细胞移植患者肠外营养支持的临床观察

    Institute of Scientific and Technical Information of China (English)

    余国攀; 孙竞; 江千里; 刘启发; 周红升; 范志平; 孟凡义; 曹睿

    2014-01-01

    目的 探讨肠外营养(PN)支持对造血干细胞移植患者的重要性及各种营养素的作用.方法 回顾性分析2008年1月至2009年9月106例接受造血干细胞移植患者的临床资料,根据营养支持方式不同分为PN组(n=42)和非PN组(n=64),比较两组患者在造血重建时间、口腔黏膜炎、肝功能异常、感染及移植物抗宿主病(GVHD)发生率等方面的差异;进一步分析核黄素、谷氨酰胺、结构脂肪乳等营养素的作用.结果 接受PN支持的42例患者中,包含接受核黄素的患者33例,谷氨酰胺24例,结构脂肪乳26例.PN组患者的口腔黏膜炎发生率显著低于非PN组(31.0%比51.6%,P=0.036),而两组的感染率(42.9%比46.9%,P=0.898)、GVHD发生率(21.4%比31.3%,P=0.267)、丙氨酸氨基转移酶(ALT)水平[(49.5±9.8) U/L比(69.9±10.9) U/L,P =0.196]、粒系重建时间[(11.6±0.3)d比(12.3±0.3)d,P=0.187]及血小板重建时间[(14.1±0.9)d比(13.3±0.4)d,P=0.386]差异均无统计学意义.核黄素组的口腔黏膜炎发生率为27.3%,有低于无核黄素组(44.4%)和非PN组(51.6%)的趋势,但差异无统计学意义(P =0.073).谷氨酰胺组、无谷氨酰胺组和非PN组在口腔黏膜炎发生率、感染率、GVHD发生率、ALT水平及造血重建时间方面的差异均无统计学意义(P均>0.05).结构脂肪乳组的ALT平均值为(38.7±4.9) U/L,有低于物理混合的中长链脂肪乳组[(68.5±23.0) U/L]和非PN组[(69.9±10.9) U/L]的趋势,但差异无统计学意义(P =0.243).结论 造血干细胞移植患者可从合理的PN中获益.核黄素对口腔黏膜炎的预防可能有益.结构脂肪乳与中长链脂肪乳对于肝脏功能具有同样的安全性.谷氨酰胺的作用有待进一步研究.%Objective To investigate the role of parenteral nutrition (PN) in patients undergoing hematopoietic stem cell transplantation (HSCT).Methods The clinical data of 106 patients who had undergone HSCT from January 2008 to

  2. A Critical Care and Transplantation-Based Approach to Acute Respiratory Failure after Hematopoietic Stem Cell Transplantation in Children.

    Science.gov (United States)

    Elbahlawan, Lama; Srinivasan, Ashok; Morrison, R Ray

    2016-04-01

    Acute respiratory failure contributes significantly to nonrelapse mortality after allogeneic hematopoietic stem cell transplantation. Although there is a trend of improved survival over time, mortality remains unacceptably high. An understanding of the pathophysiology of early respiratory failure, opportunities for targeted therapy, assessment of the patient at risk, optimal use of noninvasive positive pressure ventilation, strategies to improve alveolar recruitment, appropriate fluid management, care of the patient with chronic lung disease, and importantly, a team approach between critical care and transplantation services may improve outcomes. PMID:26409244

  3. Accuracy of the 'Paedfusor' in children undergoing cardiac surgery or catheterization

    NARCIS (Netherlands)

    Absalom, A; Amutike, D; Lal, A; White, M; Kenny, GNC

    2003-01-01

    Background. A prototype paediatric propofol target-controlled infusion (TCI) system, the 'Paedfusor' has been developed. This system incorporates a paediatric pharmacokinetic data set and algorithm specific for children in a Graseby 3500 anaesthesia syringe driver. In this study we have evaluated th

  4. Recent New Drug Approvals, Part 2: Drugs Undergoing Active Clinical Studies in Children

    OpenAIRE

    Chhim, Rebecca F.; Shelton, Chasity M.; Christensen, Michael L.

    2013-01-01

    The objective of this 2-part review is to provide information about drugs that have been recently approved by the US Food and Drug Administration. Part 1 reviewed recently approved drugs with pediatric indications. Part 2 reviews drugs recently approved only in adults and have published or ongoing studies in children.

  5. Propofol-remifentanil or sevoflurane for children undergoing magnetic resonance imaging?

    DEFF Research Database (Denmark)

    Pedersen, N A; Jensen, Anne Gert; Kilmose, L;

    2013-01-01

    Magnetic resonance imaging (MRI) of children is generally performed under sedation or with general anaesthesia (GA), but the ideal regimen has not been found. The aim of this study was to see if propofol-remifentanil would be a suitable alternative for the maintenance of anaesthesia in this...

  6. Music therapy to reduce pain and anxiety in children with cancer undergoing lumbar puncture: a randomized clinical trial.

    Science.gov (United States)

    Nguyen, Thanh Nhan; Nilsson, Stefan; Hellström, Anna-Lena; Bengtson, Ann

    2010-01-01

    A nonpharmacological method can be an alternative or complement to analgesics.The aim of this study was to evaluate if music medicine influences pain and anxiety in children undergoing lumbar punctures. A randomized clinical trial was used in 40 children (aged 7-12 years) with leukemia, followed by interviews in 20 of these participants. The participants were randomly assigned to a music group (n = 20) or control group (n = 20). The primary outcome was pain scores and the secondary was heart rate, blood pressure, respiratory rate, and oxygen saturation measured before, during, and after the procedure. Anxiety scores were measured before and after the procedure. Interviews with open-ended questions were conducted in conjunction with the completed procedures. The results showed lower pain scores and heart and respiratory rates in the music group during and after the lumbar puncture. The anxiety scores were lower in the music group both before and after the procedure. The findings from the interviews confirmed the quantity results through descriptions of a positive experience by the children, including less pain and fear. PMID:20386063

  7. The effect of scheduling in children undergoing prophylactic cranial irradiation for acute lymphoblastic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Costello, A.S.; Jones, R.D.; Barrett, A. (Western Infirmary, Glasgow (United Kingdom). Beatson Oncology Centre, Department of Radiation Oncology)

    1991-09-01

    Control of central nervous system disease and overall survival have been analysed in a group of 829 children with leukaemia entered into the UKALL VIII trial to determine whether scheduling of the cranial irradiation is of prognostic significance. It is shown that short gaps in treatment do not influence prognosis and that current radiotherapy practice need not be modified. (author). 20 refs., 1 fig., 2 tabs.

  8. Hematological Adverse events and Sustained Viral Response in Children Undergoing Therapy for Chronic Hepatitis C Infection

    Directory of Open Access Journals (Sweden)

    Malgorzata Pawlowska

    2011-12-01

    Full Text Available Background: Treatment of hepatitis C virus (HCV infection with interferon (IFN and ribavirin (RBV is associated with adverse events, which may affect the patient's adherence to the treatment regimen and the treatment efficacy.Objectives: The aim of this study was to assess the sustained viral response (SVR and interdependence between the haematological characteristics (leukocyte count, platelet count, and haemoglobin levels in patients with chronic hepatitis C (CHC infection during treatment with IFN and RBV.Patients and Methods: We conducted a retrospective cohort study of 170 children with CHC infection who completed treatment with IFN-α and RBV. The children were divided into 2 groups: the first group (group I, n = 119 underwent a 48-week course of treatment with recombinant IFN α-2b (Intron A at a dosage of 3 MU 3 times a week subcutaneously and RBV at a dosage of 15 mg/kg per day orally, and the second group (group II, n = 51 was administered pegylated IFN (peg-IFN-α-2b (PegIntron at a dosage of 1.5 μg/kg per week subcutaneously and RBV at a dosage of 15 mg/kg per day orally for 48 weeks. The dose of IFN was not adjusted but that of ribavirin was in 2 children from group II. Hematological growth factors and erythropoietin were not used. SVR was defined as undetectable serum HCV RNA 24 weeks after the end of treatment (study week 72. Serum HCV RNA was determined by performing polymerase chain reaction, and the HCV genotypes and hematological parameters were evaluated. Serum HCV RNA levels were analysed by descriptive statistics. Means and standard deviations were calculated for values collected at the baseline, on the 12th and 48th weeks during treatment, and after 24 weeks of untreated follow-up (study week 72.Results: Eighty-six (50% of the 170 patients who underwent treatment achieved SVR: 62 (51% out of 119 children from group I and 24 (47% out of 51 from group II. The mean serum hemoglobin levels and leukocyte and platelet counts at

  9. Emergence from anesthesia in children undergoing ambulatory surgery- a comparison between propofol and sevoflurane using single anesthetic technique

    International Nuclear Information System (INIS)

    Objective: To compare emergence from anesthesia using total intravenous anesthesia (TIVA) with propofol and volatile induction maintenance anesthesia (VIMA) with sevoflurane, in children undergoing ambulatory inguinal herniorrhaphy. Study Design: Randomized, controlled trials. Place and Duration of Study: Shifa Hospital of Pakistan Navy, from 1st Mar 2005 to 28th Feb 2006. Patients and Methods: Eighty children, aged 5-10 years of ASA physical status I or II were divided into two groups of 40 each using random numbers table. Group P received propofol 3mg/kg for induction and 100-400 micro g/kg/min infusion for maintenance of anesthesia, while group S received sevoflurane 8% (inspired concentration) in 100% oxygen for induction and 2-3% in oxygen for maintenance of anesthesia. No sedative premedication was given. Analgesia was provided with caudal block using 0.25% bupivacaine. Speed of emergence from anesthesia was assessed by time to extubation, time to eye opening, and time to crying / stating name. A modified aldrete score system was used to evaluate recovery while Pain/Discomfort scale to assess the quality of emergence from anesthesia. These were recorded by a separate consultant anesthetist blind to the anesthetic technique. Results: Emergence from anesthesia occurred significantly quicker in the S group as compared to P group, as evident by times in minutes (mean +- SD) to extubation: 8.3+-6.9 versus 4.7+-2.6(p=0.017), eye opening: 9.1 +- 5.3 vs. 5.6 +- 2.6 (p=0.043) and crying / state name: 14.7 +-7.2 vs.11.3 +- 4.6(p=0.039). Similarly, more patients in the S group scored maximum points in the modified aldrete score at 10 min: 17 (42.5%) vs.7 (17.5%) (p=0.015), 20 min: 32 (80%) vs.23 (57.5%) (p=0.030). Although, number of patients in the S group compared to P group scoring max points in Pain-discomfort scale at 10 min: 8 (20%) vs4 (10%), p=0.210; 20 min: 6 (15%) vs.2 (5%), p=0.136 and 30 min: 4 (10%) vs. 0, p=0.130 were more, these results were not

  10. Remote ischemic preconditioning (RIPC modifies the plasma proteome in children undergoing repair of tetralogy of fallot: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Michele Hepponstall

    Full Text Available Remote ischemic preconditioning (RIPC has been applied in paediatric cardiac surgery. We have demonstrated that RIPC induces a proteomic response in plasma of healthy volunteers. We tested the hypothesis that RIPC modifies the proteomic response in children undergoing Tetralogy of Fallot (TOF repair.Children (n=40 were randomized to RIPC and control groups. Blood was sampled at baseline, after cardiopulmonary bypass (CPB and 6, 12 and 24h post-CPB. Plasma was analysed by liquid chromatography mass spectrometry (LC-MS in an untargeted approach. Peptides demonstrating differential expression (p<0.01 were subjected to tandem LC-MS/MS and protein identification. Corresponding proteins were identified using the NCBI protein database. There was no difference in age (7.3±3.5vs6.8±3.6 months(p=0.89, weight (7.7±1.8vs7.5±1.9 kg(p=0.71, CPB time (104±7vs94±7 min(p=0.98 or aortic cross-clamp time (83±22vs75±20 min(p=0.36. No peptides were differentially expressed at baseline or immediately after CPB. There were 48 peptides with higher expression in the RIPC group 6h post-CPB. This was no longer evident at 12 or 24h, with one peptide down-regulated in the RIPC group. The proteins identified were: inter-alpha globulin inhibitor (42.0±11.8 vs 820.8±181.1, p=0.006, fibrinogen preproprotein (59.3±11.2 vs 1192.6±278.3, p=0.007, complement-C3 precursor (391.2±160.9 vs 5385.1±689.4, p=0.0005, complement C4B (151.5±17.8 vs 4587.8±799.2, p=0.003, apolipoprotein B100 (53.4±8.3 vs 1364.5±278.2, p=0.005 and urinary proteinase inhibitor (358.6±74.9 vs 5758.1±1343.1, p=0.009. These proteins are involved in metabolism, haemostasis, immunity and inflammation.We provided the first comprehensive analysis of RIPC-induced proteomic changes in children undergoing surgery. The proteomic changes peak 6h post-CPB and return to baseline within 24h of surgery.ACTR.org.au ACTRN12610000496011.

  11. Specific IgE response to different grass pollen allergen components in children undergoing sublingual immunotherapy

    Directory of Open Access Journals (Sweden)

    Marcucci Francesco

    2012-06-01

    Full Text Available Abstract Background Grass pollen is a major cause of respiratory allergy worldwide and contain a number of allergens, some of theme (Phl p 1, Phl p 2, Phl p 5, and Phl 6 from Phleum pratense, and their homologous in other grasses are known as major allergens. The administration of grass pollen extracts by immunotherapy generally induces an initial rise in specific immunoglobulin E (sIgE production followed by a progressive decline during the treatment. Some studies reported that immunotherapy is able to induce a de novo sensitisation to allergen component previously unrecognized. Methods We investigated in 30 children (19 males and 11 females, mean age 11.3 years, 19 treated with sublingual immunotherapy (SLIT by a 5-grass extract and 11 untreated, the sIgE and sIgG4 response to the different allergen components. Results Significant increases (p  Conclusions These findings confirm that the initial phase of SLIT with a grass pollen extract enhances the sIgE synthesis and show that the sIgE response concerns the same allergen components which induce IgE reactivity during natural exposure.

  12. Cardiac evaluation using {sup 123}I-BMIPP imaging in children undergoing a stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Hiroyuki; Yoshihara, Takao; Nakauchi, Shohei; Tsunamoto, Kentaro [Matsushita Memorial Hospital, Moriguchi, Osaka (Japan); Morimoto, Akira; Hibi, Shigeyoshi; Todo, Shinjiro; Kamiya, Yasutaka [Kyoto Prefectural Univ. of Medicine (Japan); Imashuku, Shinsaku [Inst. of Kyoto Health and Environmental Sciences (Japan)

    2003-02-01

    Sixteen children with hematological disease who had undergone allogeneic stem cell transplantation (SCT) were evaluated to determine the adverse effect of anthracycline (ATC) and cyclophosphamide (CY) used as the conditioning regimen on pre- and post-transplant cardiac function. Methods employed were resting electrocardiogram (ECG), echocardiography and {sup 123}I-BMIPP (beta-methyl-iodophenyl-pentadecanoic acid) imaging. A cumulative ATC dose over 300 mg/m{sup 2}, especially over 400 mg/m{sup 2}, was predictable for pre-transplant abnormal findings by parameters such as uptake score (US) and heart mediastinum ratio (H/M). However, the cumulative ATC dose and pre-transplant mild abnormal cardiac findings did not correlate with post-transplant cardiac function. A 200 mg/kg dose of CY was predictable for decreased summated QRS amplitude (QRS sum) and left ventricular mass index (LVMI), however, there was no correlation between the CY dose and the values obtained through BMIPP imaging. Moreover, the CY dose was not a risk factor for worsening post-transplant fractional shortening (FS) as evaluated by echocardiography. In summary, {sup 123}I-BMIPP imaging was useful for evaluating subclinical cardiac damage due to ATC before transplant, but not for predicting cardiac damage during the course of SCT. (author)

  13. Diagnostic Utility of Nodular Gastritis in Children with Chronic Abdominal Pain Undergoing Endoscopy

    Directory of Open Access Journals (Sweden)

    Seddiqe Amini-Ranjbar

    2008-01-01

    Full Text Available This study was aimed to describe the endoscopic picture and laboratory findings in children with chronic abdominal pain and to determine the utility of nodular gastritis in diagnosing HPI in these patients. This prospective study was done between November, 2004 and May, 2007. A total of 70 patients (36 male and 34 female aged 3-14 years, underwent upper endoscopy. H-pylori infection was diagnosed when both urease test and histology were positive for the infection. Seventy percent (n = 49 of them were diagnosed to have endoscopic nodular gastritis. HPI was confirmed in 33 (47.1% of 70 patients. The endoscopic antral nodularity had a sensitivity of 100%, specificity of 56.8%, positive predictive value of 67.3%, negative predictive value of 100% and a positive LR of 2.32 for diagnosis of HPI. It may be recommended that if nodular gastritis observed in a pediatric patient with chronic abdominal pain he/she should be investigated to exclude HPI otherwise no further work up is necessary to confirm HPI.

  14. Exposure Risks Among Children Undergoing Radiation Therapy: Considerations in the Era of Image Guided Radiation Therapy.

    Science.gov (United States)

    Hess, Clayton B; Thompson, Holly M; Benedict, Stanley H; Seibert, J Anthony; Wong, Kenneth; Vaughan, Andrew T; Chen, Allen M

    2016-04-01

    Recent improvements in toxicity profiles of pediatric oncology patients are attributable, in part, to advances in the field of radiation oncology such as intensity modulated radiation (IMRT) and proton therapy (IMPT). While IMRT and IMPT deliver highly conformal dose to targeted volumes, they commonly demand the addition of 2- or 3-dimensional imaging for precise positioning--a technique known as image guided radiation therapy (IGRT). In this manuscript we address strategies to further minimize exposure risk in children by reducing effective IGRT dose. Portal X rays and cone beam computed tomography (CBCT) are commonly used to verify patient position during IGRT and, because their relative radiation exposure is far less than the radiation absorbed from therapeutic treatment beams, their sometimes significant contribution to cumulative risk can be easily overlooked. Optimizing the conformality of IMRT/IMPT while simultaneously ignoring IGRT dose may result in organs at risk being exposed to a greater proportion of radiation from IGRT than from therapeutic beams. Over a treatment course, cumulative central-axis CBCT effective dose can approach or supersede the amount of radiation absorbed from a single treatment fraction, a theoretical increase of 3% to 5% in mutagenic risk. In select scenarios, this may result in the underprediction of acute and late toxicity risk (such as azoospermia, ovarian dysfunction, or increased lifetime mutagenic risk) in radiation-sensitive organs and patients. Although dependent on variables such as patient age, gender, weight, body habitus, anatomic location, and dose-toxicity thresholds, modifying IGRT use and acquisition parameters such as frequency, imaging modality, beam energy, current, voltage, rotational degree, collimation, field size, reconstruction algorithm, and documentation can reduce exposure, avoid unnecessary toxicity, and achieve doses as low as reasonably achievable, promoting a culture and practice of "gentle IGRT

  15. Ultrasound-guided ilioinguinal/iliohypogastric nerve blocks versus caudal block for postoperative analgesia in children undergoing unilateral groin surgery

    Directory of Open Access Journals (Sweden)

    Abualhassan A Abdellatif

    2012-01-01

    Full Text Available Context: Ultrasound (US guidance is strongly recommended when performing peripheral nerve blocks in infants and children. Aims: To assess whether US-guided ilioinguinal/iliohypogastric (II/IH nerve blocks with local anesthetic (LA would provide comparable postoperative analgesia to blind technique caudal block with LA following pediatric unilateral groin surgery. Secondary endpoints included analgesic consumption, parental satisfaction, and postoperative complications. Settings and Design: Prospective, crossover randomized controlled trial performed on children undergoing unilateral groin surgery. Methods: Fifty children aged 1-6 years scheduled for unilateral groin surgery were included in the study. After induction of general anesthesia and prior to surgical incision, patients were prospectively randomized into one of two groups: Group B received US-guided II/IH nerve blocks with 0.1 ml.kg−1 of 0.25% bupivacaine and Group C received a caudal blockade with 0.7 ml.kg−1 of 0.25% bupivacaine. Patients were assessed in the recovery room, the day-stay unit and for 24 h at home for pain score, analgesic consumption, and parental satisfaction. Statistical Analysis: Arithmetic mean and standard deviation values were calculated and statistical analyses were performed for each group. Independent sample t-test was used to compare continuous variables exhibiting normal distribution, and Chi-squared test or Fisher exact test for non-continuous variables. P0.05. The average time to first rescue analgesia was longer in group B 253±102.6 min as compared to 219.6±48.4 min in group C. In recovery room, four patients in group C required pain rescue medication compared to five patients in group B (P>0.05. Similarly eight patients in the group C and six patients in group B required pain rescue medication at day-stay unit or at home (P>0.05. Group C received 0.74 pain rescue medication doses (range 0-8, while group B received 0.65 pain rescue medication doses

  16. Engraftment syndrome after allogeneic hematopoietic cell transplantation predicts poor outcomes.

    Science.gov (United States)

    Chang, Lawrence; Frame, David; Braun, Thomas; Gatza, Erin; Hanauer, David A; Zhao, Shuang; Magenau, John M; Schultz, Kathryn; Tokala, Hemasri; Ferrara, James L M; Levine, John E; Reddy, Pavan; Paczesny, Sophie; Choi, Sung Won

    2014-09-01

    Engraftment syndrome (ES), characterized by fever, rash, pulmonary edema, weight gain, liver and renal dysfunction, and/or encephalopathy, occurs at the time of neutrophil recovery after hematopoietic cell transplantation (HCT). In this study, we evaluated the incidence, clinical features, risk factors, and outcomes of ES in children and adults undergoing first-time allogeneic HCT. Among 927 patients, 119 (13%) developed ES at a median of 10 days (interquartile range 9 to 12) after HCT. ES patients experienced significantly higher cumulative incidence of grade 2 to 4 acute GVHD at day 100 (75% versus 34%, P HCT outcomes. Despite early recognition of the syndrome and prompt institution of corticosteroid therapy, outcomes in ES patients were uniformly poor. This study suggests the need for a prospective approach of collecting clinical features combined with correlative laboratory analyses to better characterize ES. PMID:24892262

  17. Autologous hematopoietic stem cell transplantation and conventional insulin therapy in the treatment of children with newly diagnosed type 1 diabetes: long term follow-up

    Institute of Scientific and Technical Information of China (English)

    Gu Yi; Gong Chunxiu; Peng Xiaoxia; Wei Liya; Su Chang; Qin Miao; Wang Xi'ou

    2014-01-01

    Background It has been indicated that autologous hematopoietic stem cell transplantation (AHST) is a promising treatment to adults with type 1 diabetes,however,the application of AHST therapy to children with type 1 diabetes still needs more data.The aim of this study was to assess the clinical effect of immune intervention combined with AHST and conventional insulin therapy in the treatment of children with newly diagnosed type 1 diabetes.Methods This 1:2 matched case-control study was comprised of 42 children who were newly diagnosed with type 1 diabetes in the Department of Endocrinology,Beijing Children's Hospital from 2009-2010.The case group included 14 patients,who were treated with AHST within the first 3 months after being diagnosed with diabetes at request of their parents during 2009-2010.The control group included 28 patients with newly diagnosed type 1 diabetes at the same period of hospitalization.We compared the baseline and follow-up data of them,including ketoacidosis onset,clinical variables (glycosylated hemoglobin (HbA1c),insulin dosage and serum C-peptide).Results The clinical characteristics of the patients was comparable between the case group and the control group.At 6-12 months ((10.7±4.2) months) after AHST treatment,we found 11 patients in the case group did not stop the insulin therapy,three cases stopped insulin treatment for 2,3 and 11 months,respectively.No diabetic ketoacidosis (DKA) occurred after transplantation in all the patients in the case group.HbA1c in the control group was significant lower than that in the case group (P <0.01),while the insulin dosage and serum C-peptide were not significant different between the two groups (P >0.05).In order to eliminate the honeymoon effect,we performed final follow-up at the 3-5 years ((4.2±1.8) years) after AHST treatment,and found that HbA1c in the control group was still lower than that in the case group (P <0.01); however,the insulin dosage and serum C-peptide were not

  18. Value of bioimpedance analysis and anthropometry for complication prediction in children with malignant and non-malignant diseases after hematopoietic stem cells transplantation

    Directory of Open Access Journals (Sweden)

    G. Ya. Tseytlin

    2014-07-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is widely used in the treatment of malignant and autoimmune diseases. Various complications often develop during the post-transplantation period that can significantly impair the clinical outcomes, so the ability to predict therisk of severe complications is of great practical importance. Predictive value of some anthropometric indices and bioimpedance analysis(BIA measured before conditioning to assess the risks of serious complications and graft hypofunction in the early post-transplant period(100 days were analyzed. Anthropometry and BIA used in a comprehensive assessment of nutritional status in order to optimize the nutritional support of these patients. 101 patients were examined before conditioning and at different times during the early post-transplant period: 50 children (5–17 years of age were examined using BIA and anthropometry, 61 children (6 months – 4 years of age – using only anthropometry without BIA due to age restrictions. The prognostic value of the phase angle (FA, ratio of the active cell mass to lean body mass (ACM/LBM and shoulder muscle circumference (SMC was shown. Thus, in patients with FA ≤ 4, ACM/LBM < 0.45 and SMC ≤ 10th percentile before conditioning risk of severe complications during early post-transplant period was significantly higher (p < 0.05. Also, in patients with FA ≤ 4 and ACM/LBM < 0.45 a significantly higher risk of graft hypofunction developing was observed (p < 0.05.

  19. Prophylaxis of mucosal toxicity by oral propantheline and cryotherapy in children with malignancies undergoing myeloablative chemo-radiotherapy

    International Nuclear Information System (INIS)

    Mucosal toxicity is an incapacitating complication of intensive chemo-radiotherapy for children with malignant disorders, and is physically and psychologically distressful. It is therefore important to minimize mucosal toxicity in those patients. In this report, the effects of the combined prophylaxis of oral cooling (cryotherapy) and administration of propantheline, an anticholinergic drug, were studied in patients (aged 2-16 year) with acute leukemias or solid tumors, who underwent myeloablative chemo-radiotherapy and autologous peripheral blood stem cell rescue from 1993 to 1997. Patients were pretreated with the combined prophylaxis (n=12) or single prophylaxis (n=5), or left untreated (n=7). The combined prophylaxis significantly reduced the severe mucositis (combined, 8.3%; single, 20.0%; and untreated, 42.9%) and severe diarrhea (combined, 16.7%; single, 60.0%; and untreated, 57.1%). Moreover, the combined prophylaxis tended to shorten the periods of febrile episodes defined as temperature >38 deg C (combined, 3.8 days; single, 4.6 days; and untreated, 5.6 days). Therefore, the combination of propantheline and oral cryotherapy may be feasible and effective for reduction of mucosal toxicity in patients with malignancy who undergo high-dose chemotherapy. (author)

  20. Sevoflurane-emergence agitation: Effect of supplementary low-dose oral ketamine premedication in preschool children undergoing dental surgery

    Directory of Open Access Journals (Sweden)

    Khattab Ahmed

    2009-01-01

    : Adding a low dose of oral ketamine to midazolam-based oral premedication in preschool children undergoing dental surgery reduced sevoflurane-related emergence agitation without delaying discharge.

  1. The effectiveness of therapeutic play intervention in reducing perioperative anxiety, negative behaviors, and postoperative pain in children undergoing elective surgery: a systematic review.

    Science.gov (United States)

    He, Hong-Gu; Zhu, Lixia; Chan, Sally Wai Chi; Klainin-Yobas, Piyanee; Wang, Wenru

    2015-06-01

    Children undergoing surgical procedures commonly experience stress and anxiety, exhibit negative behaviors, and complain of postoperative pain. Parents also experience anxiety when their children undergo surgery. Therapeutic play intervention has been used to prepare hospitalized children for invasive medical procedures for decades. However, there has been no systematic review to examine the effectiveness of therapeutic play intervention for improving children's health-related outcomes such as perioperative anxiety and postoperative pain. The aim of this review was to synthesize current empirical evidence on the effectiveness of therapeutic play intervention in reducing perioperative anxiety, negative behaviors, and postoperative pain in children undergoing elective surgery and in reducing their parents' perioperative anxiety. Systematic searches of electronic databases of the Cumulative Index to Nursing and Allied Health Literature, PubMed, ProQuest Dissertations and Theses, Scopus, and Web of Science and screening of the reference lists of included articles from these databases identified studies on the topic. Relevant studies were methodologically assessed and appraised by two independent reviewers using the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument. Six studies were identified. The outcome measurements were heterogeneous across all six studies. These studies had conflicting outcomes regarding the effectiveness of therapeutic play intervention in children's perioperative anxiety, negative behaviors, and postoperative pain. Two studies showed that the intervention significantly reduced parents' preoperative anxiety. The current empirical evidence on the effectiveness of therapeutic play intervention in children's perioperative anxiety, negative behaviors, and postoperative pain is inconclusive. More studies on the effectiveness of therapeutic play intervention using rigorous designs and involving parents are needed. PMID

  2. End-of-life experience of children undergoing stem cell transplantation for malignancy: parent and provider perspectives and patterns of care.

    Science.gov (United States)

    Ullrich, Christina K; Dussel, Veronica; Hilden, Joanne M; Sheaffer, Jan W; Lehmann, Leslie; Wolfe, Joanne

    2010-05-13

    The end-of-life (EOL) experience of children who undergo stem cell transplantation (SCT) may differ from that of other children with cancer. To evaluate perspectives and patterns of EOL care after SCT, we surveyed 141 parents of children who died of cancer (response rate, 64%) and their physicians. Chart review provided additional information. Children for whom SCT was the last cancer therapy (n = 31) were compared with those for whom it was not (n = 110). SCT parents and physicians recognized no realistic chance for cure later than non-SCT peers (both P < .001) and were more likely to have a primary goal of cure at death (parents, P < .001; physicians, P = .02). SCT children were more likely to suffer highly from their last cancer therapy and die in the intensive care unit (both P < .001), with less opportunity for EOL preparation. SCT parents who recognized no realistic chance for cure more than 7 days before death along with the physician were more likely to prepare for EOL, and if their primary goal was to reduce suffering, to achieve this (P < .001). SCT is associated with significant suffering and less opportunity to prepare for EOL. Children and families undergoing SCT may benefit from ongoing discussions regarding prognosis, goals, and opportunities to maximize quality of life. PMID:20228275

  3. Subclinical left ventricular dysfunction in children after hematopoietic stem cell transplantation for severe aplastic anemia: a case control study using speckle tracking echocardiography

    Science.gov (United States)

    Kim, Beom Joon; Moon, Kyung Pil; Yoon, Ji-Hong; Lee, Eun-Jung; Kim, Seong Koo; Lee, Jae Wook; Chung, Nack Gyun; Cho, Bin; Kim, Hack Ki

    2016-01-01

    Purpose Severe aplastic anemia (SAA), a fatal disease, requires multiple transfusion, immunosuppressive therapy, and finally, hematopoietic stem cell transplantation (HSCT) as the definitive treatment. We hypothesized that iron overloading associated with multiple transfusions and HSCTrelated complications may adversely affect cardiac function. Left ventricular (LV) function was assessed in children after HSCT for SAA. Methods Forty-six consecutive patients with a median age of 9.8 years (range, 1.5-18 years), who received HSCT for SAA and who underwent comprehensive echocardiography before and after HSCT, were included in this study. The data of LV functional parameters obtained using conventional echocardiography, tissue Doppler imaging (TDI), and speckle-tracking echocardiography (STE) were collected from pre- and post-HSCT echocardiography. These data were compared to those of 40 age-matched normal controls. Results In patients, the LV ejection fraction, shortening fraction, end-diastolic dimension, mitral early diastolic E velocity, TDI mitral septal E' velocity, and STE LV longitudinal systolic strain rate (SSR) decreased significantly after HSCT. Compared to normal controls, patients had significantly lower post-HSCT early diastolic E velocity and E/A ratio. On STE, patients had significantly decreased LV deformational parameters including LV longitudinal systolic strain (SS), SSR, and diastolic SR (DSR), and circumferential SS and DSR. Serum ferritin levels showed weak but significant correlations (P<0.05) with LV longitudinal SS and SSR and circumferential SS and DSR. Conclusion Subclinical LV dysfunction is evident in patients after HSCT for SAA, and was associated with increased iron load. Serial monitoring of cardiac function is mandatory in this population. PMID:27186230

  4. On the development of a decision support intervention for mothers undergoing BRCA1/2 cancer genetic testing regarding communicating test results to their children

    OpenAIRE

    Peshkin, Beth N.; DeMarco, Tiffani A.; Tercyak, Kenneth P.

    2009-01-01

    Parent communication of BRCA1/2 test results to minor-age children is an important, yet understudied, clinical issue that is commonly raised in the management of familial cancer risk. Genetic counseling professionals and others who work with parents undergoing this form of testing often confront questions about the risks/benefits and timing of such disclosures, as well as the psychosocial impact of disclosure and nondisclosure on children’s health and development. This paper briefly reviews l...

  5. Human herpesvirus-6 viremia is not associated with poor clinical outcomes in children following allogeneic hematopoietic cell transplantation.

    Science.gov (United States)

    Violago, Leah; Jin, Zhezhen; Bhatia, Monica; Rustia, Evelyn; Kung, Andrew L; Foca, Marc D; George, Diane; Garvin, James H; Sosna, Jean; Robinson, Chalitha; Karamehmet, Esra; Satwani, Prakash

    2015-11-01

    HHV-6 is an evolving pathogen in the field of AlloHCT. However, the impact of HHV-6 on AlloHCT outcomes remains to be elucidated. We studied the incidence and clinical impact of HHV-6 viremia in children following AlloHCT. One hundred consecutive children were monitored weekly by plasma PCR for the first 180 days following AlloHCT for HHV-6, CMV, EBV, and ADV. HHV-6 viremia was defined as plasma PCR >1000 viral copies/mL. The median age was nine yr. Following AlloHCT, 19% (95% CI 11.3-26.7%) of patients had HHV-6 viremia, with the highest incidence of reactivation (14/19, 73%) occurring during day +15-day +98. The proportion of platelet engraftment by day +180 was lower in patients with HHV-6 viremia (58%) than in those without HHV-6 viremia (82%), p = 0.028. Delay in neutrophil and platelet engraftment was not associated with HHV-6 viremia in multivariate analysis. Similarly, HHV-6 viremia was not associated with TRM in multivariate analysis (p = 0.15). In summary, HHV-6 viremia is prevalent in pediatric AlloHCT recipients. Based on our study results, we recommend that HHV-6 PCR should only be performed on clinical suspicion. PMID:26329541

  6. Cotransplantation of ex vivo expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation.

    Science.gov (United States)

    Ball, Lynne M; Bernardo, Maria Ester; Roelofs, Helene; Lankester, Arjan; Cometa, Angela; Egeler, R Maarten; Locatelli, Franco; Fibbe, Willem E

    2007-10-01

    Haploidentical hematopoietic stem-cell transplantation (HSCT) is associated with an increased risk of graft failure. Adult bone marrow-derived mesenchymal stromal cells (MSCs) have been shown to support in vivo normal hematopoiesis and to display potent immune suppressive effects. We cotransplanted donor MSCs in 14 children undergoing transplantation of HLA-disparate CD34(+) cells from a relative. While we observed a graft failure rate of 15% in 47 historic controls, all patients given MSCs showed sustained hematopoietic engraftment without any adverse reaction. In particular, children given MSCs did not experience more infections compared with controls. These data suggest that MSCs, possibly thanks to their potent immunosuppressive effect on alloreactive host T lymphocytes escaping the preparative regimen, reduce the risk of graft failure in haploidentical HSC transplant recipients. PMID:17638847

  7. Change in Erythropoietin Pharmacokinetics Following Hematopoietic Transplantation

    OpenAIRE

    Widness, JA; Schmidt, RL; Hohl, RJ; Goldman, FD; Al-Huniti, NH; Freise, KJ; Veng-Pedersen, P.

    2007-01-01

    Pre-clinical studies have demonstrated that bone marrow ablation has a profound effect in decreasing erythropoietin (EPO) elimination. The study’s objective was to determine in humans if EPO pharmacokinetics (PKs) are perturbed following bone marrow ablation. EPO PK studies were performed in eight subjects, aged 4 to 61 years, undergoing fully myeloablative hematopoietic stem cell transplantation. Serial PK studies using intravenous injection of recombinant human EPO (92±2.0 U/kg) (mean±SEM) ...

  8. Nasopharyngeal and Adenoid Colonization by Haemophilus influenzae and Haemophilus parainfluenzae in Children Undergoing Adenoidectomy and the Ability of Bacterial Isolates to Biofilm Production.

    Science.gov (United States)

    Kosikowska, Urszula; Korona-Głowniak, Izabela; Niedzielski, Artur; Malm, Anna

    2015-05-01

    Haemophili are pathogenic or opportunistic bacteria often colonizing the upper respiratory tract mucosa. The prevalence of Haemophilus influenzae (with serotypes distribution), and H. parainfluenzae in the nasopharynx and/or the adenoid core in children with recurrent pharyngotonsillitis undergoing adenoidectomy was assessed. Haemophili isolates were investigated for their ability to biofilm production.Nasopharyngeal swabs and the adenoid core were collected from 164 children who underwent adenoidectomy (2-5 years old). Bacteria were identified by the standard methods. Serotyping of H. influenzae was performed using polyclonal and monoclonal antisera. Biofilm formation was detected spectrophotometrically using 96-well microplates and 0.1% crystal violet.Ninety seven percent (159/164) children who underwent adenoidectomy were colonized by Haemophilus spp. The adenoid core was colonized in 99.4% (158/159) children, whereas the nasopharynx in 47.2% (75/159) children (P parainfluenzae and 14 isolates of other Haemophilus spp. were selected. In 20.1% (32/159) children 2 or 3 phenotypically different isolates of the same species (H. influenzae or H. parainfluenzae) or serotypes (H. influenzae) were identified in 1 child. 67.2% (129/192) isolates of H. influenzae, 56.3% (54/96) isolates of H. parainfluenzae and 85.7% (12/14) isolates of other Haemophilus spp. were positive for biofilm production. Statistically significant differences (P = 0.0029) among H. parainfluenzae biofilm producers and nonproducers in the adenoid core and the nasopharynx were detected.H. influenzae and H. parainfluenzae carriage rate was comparatively higher in the adenoid core than that in the nasopharynx in children undergoing adenoidectomy, suggesting that their involvement in chronic adenoiditis. The growth in the biofilm seems to be an important feature of haemophili colonizing the upper respiratory tract responsible for their persistence. PMID:25950686

  9. The predictive value of plasma B-type natriuretic peptide levels on outcome in children with pulmonary hypertension undergoing congenital heart surgery

    Directory of Open Access Journals (Sweden)

    Ayse Baysal

    2014-09-01

    Full Text Available Background and objectives: In children undergoing congenital heart surgery, plasma brain natriuretic peptide levels may have a role in development of low cardiac output syndrome that is defined as a combination of clinical findings and interventions to augment cardiac output in children with pulmonary hypertension. Methods: In a prospective observational study, fifty-one children undergoing congenital heart surgery with preoperative echocardiographic study showing pulmonary hypertension were enrolled. The plasma brain natriuretic peptide levels were collected before operation, 12, 24 and 48 h after operation. The patients enrolled into the study were divided into two groups depending on: (1 Development of LCOS which is defined as a combination of clinical findings or interventions to augment cardiac output postoperatively; (2 Determination of preoperative brain natriuretic peptide cut-off value by receiver operating curve analysis for low cardiac output syndrome. The secondary end points were: (1 duration of mechanical ventilation ≥72 h, (2 intensive care unit stay >7days, and (3 mortality. Results: The differences in preoperative and postoperative brain natriuretic peptide levels of patients with or without low cardiac output syndrome (n = 35, n = 16, respectively showed significant differences in repeated measurement time points (p = 0.0001. The preoperative brain natriuretic peptide cut-off value of 125.5 pg mL−1 was found to have the highest sensitivity of 88.9% and specificity of 96.9% in predicting low cardiac output syndrome in patients with pulmonary hypertension. A good correlation was found between preoperative plasma brain natriuretic peptide level and duration of mechanical ventilation (r = 0.67, p = 0.0001. Conclusions: In patients with pulmonary hypertension undergoing congenital heart surgery, 91% of patients with preoperative plasma brain natriuretic peptide levels above 125.5 pg mL−1 are at risk of developing low cardiac

  10. Short-Term Changes in Postoperative Cognitive Function in Children Aged 5 to 12 Years Undergoing General Anesthesia: A Cohort Study.

    Science.gov (United States)

    Aun, Cindy S T; McBride, Catherine; Lee, Anna; Lau, Angel S C; Chung, Raymond C K; Yeung, Chung Kwong; Lai, Kelly Y C; Gin, Tony

    2016-04-01

    Due to the neurotoxicity effects of general anesthesia (GA) and sedatives found in animal studies, there is a general recommendation to avoid nonurgent surgical procedures requiring anesthesia in children younger than 3 years of age. The aim of this study was to determine the incidence of anesthesia-related postoperative cognitive dysfunction (POCD) on the first day (Day 1) and at 6 weeks after elective noncardiac surgery in school-age children.This was a prospective cohort study of 118 children undergoing GA and 126 age-matched controls of school children aged 5 to 12 years. All children were given a panel of 4 neuropsychological assessments (Hong Kong List Learning for verbal memory, Visual Matching for processing speed, Visual Memory, and General Comprehension Skill from the Hong Kong Wechsler Intelligence Scale for Children). The primary outcome was the incidence of POCD on Day 1 and at 6 weeks after surgery. POCD was defined as when at least 2 of the 4 cognitive function tests showed individual Z-scores ≤-1.96 or a combined Z-score ≤-1.96.Using the combined Z-score definition, the incidence of POCD in the GA group on Day 1 and at 6 weeks were 5.1% (95% confidence interval [CI]: 2.1-10.3) and 3.4% (95% CI: 1.1-8.0), respectively. No POCD was found using the other definition. The incidences of decline and improvement in neuropsychological tests were similar between groups over time except for a higher risk in visual matching impairment in the anesthesia group (11.9%) versus control group (1.6%) on Day 1 (P definitions and relative risk ratio methodology, we found no anesthesia-related POCD per se in school-age children. PMID:27057869

  11. Hematopoietic stem cell transplantation: clinical use and perspectives

    OpenAIRE

    Francisco Barriga; Pablo Ramírez; Angélica Wietstruck; Nicolás Rojas

    2012-01-01

    Hematopoietic stem cell transplantation is the accepted therapy of choice for a variety of malignant and non-malignant diseases in children and adults. Initially developed as rescue therapy for a patient with cancer after high doses of chemotherapy and radiation as well as the correction of severe deficiencies in the hematopoietic system, it has evolved into an adoptive immune therapy for malignancies and autoimmune disorders. The procedure has helped to obtain key information about the bone ...

  12. Comparison of children versus adults undergoing mini-percutaneous nephrolithotomy: large-scale analysis of a single institution.

    Directory of Open Access Journals (Sweden)

    Guohua Zeng

    Full Text Available OBJECTIVE: As almost any version of percutaneous nephrolithotomy (PCNL was safely and efficiently applied for adults as well as children without age being a limiting risk factor, the aim of the study was to compare the different characteristics as well as the efficacy, outcome, and safety of the pediatric and adult patients who had undergone mini-PCNL (MPCNL in a single institution. METHODS: We retrospective reviewed 331 renal units in children and 8537 renal units in adults that had undergone MPCNL for upper urinary tract stones between the years of 2000-2012. The safety, efficacy, and outcome were analyzed and compared. RESULTS: The children had a smaller stone size (2.3 vs. 3.1 cm but had smilar stone distribution (number and locations. The children required fewer percutaneous accesses, smaller nephrostomy tract, shorter operative time and less hemoglobin drop. The children also had higher initial stone free rate (SFR (80.4% vs. 78.6% after single session of MPCNL (p0.05. Both groups had low rate of high grade Clavien complications. There was no grade III, IV, V complications and no angiographic embolization required in pediatric group. One important caveat, children who required multiple percutaneous nephrostomy tracts had significant higher transfusion rate than in adults (18.8% vs. 4.5%, p = 0.007. CONCLUSIONS: This contemporary largest-scale analysis confirms that the stone-free rate in pediatric patients is at least as good as in adults without an increase of complication rates. However, multiple percutaneous nephrostomy tracts should be practiced with caution in children.

  13. FNIRS-based evaluation of cortical plasticity in children with cerebral palsy undergoing constraint-induced movement therapy

    Science.gov (United States)

    Cao, Jianwei; Khan, Bilal; Hervey, Nathan; Tian, Fenghua; Delgado, Mauricio R.; Clegg, Nancy J.; Smith, Linsley; Roberts, Heather; Tulchin-Francis, Kirsten; Shierk, Angela; Shagman, Laura; MacFarlane, Duncan; Liu, Hanli; Alexandrakis, George

    2015-03-01

    Sensorimotor cortex plasticity induced by constraint-induced movement therapy (CIMT) in six children (10.2 ± 2.1 years old) with hemiplegic cerebral palsy (CP) was assessed by functional near-infrared spectroscopy (fNIRS). The activation laterality index and time-to-peak/duration during a finger tapping task were quantified before, immediately after, and six months after CIMT. Five age-matched healthy children (9.8 ± 1.3 years old) were also imaged at the same time points to provide comparative activation metrics for normal controls. In children with CP the activation time-to-peak/duration for all sensorimotor centers displayed significant normalization immediately after CIMT that persisted six months later. In contrast to this longer term improvement in localized activation response, the laterality index that depended on communication between sensorimotor centers improved immediately after CIMT, but relapsed six months later.

  14. [Local anesthesia in the children undergoing the fibroendoscopic study of the nasal cavity, nasopharynx, and larynx: are topical anesthetics needed?].

    Science.gov (United States)

    Soldatsky, Yu L; Denisova, O A; Mazur, E M

    2015-01-01

    This prospective randomized study with double blind control was designed to evaluate the effectiveness of various anesthetic techniques employed prior to fibroendoscopy of the nose, nasopharynx, and larynx of the children. The study included 160 children at the age varying from 3 to 14 (mean 7.4±2.96) years randomly allocated to four statistically comparable groups matched for age and sex. The following preparations were used to treat the children prior to fibroendoscopy: physiological solution (group 1), a 0.05% xylometazoline solution (group 2), a 10% lidocaine solution (group 3), and a mixture of 0.05% xylometazoline and 10% lidocaine solutions (group 4). The evaluation of the tolerance to the pretreatment of the nasal cavity with lidocaine and lidocaine plus xylometazoline (groups 3 and 4) showed that it was significantly (p0.05). The doctors found the tolerance of fibroendoscopy to be the worst following pretreatment with the physiological solution (group 1) and the best after pretreatment with a mixture of lidocaine and xylometazoline (group 4) (p=0.03). The children comprising groups 2 and 3 were not significantly different in terms of the tolerance to fibroendoscopy (p>0.05). It is concluded that the pretreatment of the nasal cavity of the children with a 10% lidocaine solution before fibroendoscopy has no advantage over the pretreatment with a 0.05% xylometazoline solution; at the same time, insuflation of lidocaine as an anesthetic induces more pronounced negative emotions compared with the application of 0.05% xylometazoline. PMID:26525473

  15. Evolution of the biochemical profile of children treated or undergoing treatment for moderate or severe stunting: consequences of metabolic programming?

    Directory of Open Access Journals (Sweden)

    Jullyana F.R. Alves

    2014-07-01

    Full Text Available OBJECTIVE: to evaluate changes in the biochemical profile of children treated or being treated for moderate or severe stunting in a nutrition recovery and education center. METHODS: this was a retrospective longitudinal study of 263 children treated at this center between August of 2008 to August of 2011, aged 1 to 6 years, diagnosed with moderate (z-score of height-for-age [HAZ] < -2 or severe stunting (HAZ < -3. Data were collected on socioeconomic conditions, dietary habits, and biochemical changes, as well as height according to age. RESULTS: the nutritional intervention showed an increase in HAZ of children with moderate (0.51 ± 0.4, p = 0.001 and severe (0.91 ± 0.7, p = 0.001 stunting during the monitoring. Increased levels of insulin-like growth factor 1 (IGF-1 (initial: 71.7 ng/dL; final: 90.4 ng/dL; p = 0.01 were also observed, as well as a reduction in triglycerides (TG in both severely (initial: 91.8 mg/dL; final: 79.1 mg/dL; p = 0.01 and in moderately malnourished children (initial: 109.2 mg/dL; final 88.7 mg/dL; p = 0.01, and a significant increase in high-density lipoprotein cholesterol HDL-C only in the third year of intervention (initial: 31.4 mg/dL; final: 42.2 mg/dL. The values of total cholesterol (TC and low-density lipoprotein cholesterol (LDL-C levels remained high throughout the treatment (initial: 165.1 mg/dL; final: 163.5 mg/dL and initial: 109.0 mg/dL; final: 107.3 mg/dL, respectively. CONCLUSION: the nutritional treatment for children with short stature was effective in reducing stunting and improving TG and HDL-C after three years of intervention. However, the levels of LDL-C and TC remained high even in treated children. It is therefore speculated that these changes may result from metabolic programming due to malnutrition.

  16. Itraconazole for secondary prophylaxis of invasive fungal infection in patients undergoing chemotherapy and stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    施继敏

    2013-01-01

    Objective To evaluate the efficacy and safety of itraconazole for secondary prophylaxis of previous proven or probable invasive fungal infection (IFI) in patients undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) in agranulocytosis state.

  17. Estimation of radiation dose and risk to children undergoing cardiac catheterization for the treatment of a congenital heart disease using Monte Carlo simulations

    Energy Technology Data Exchange (ETDEWEB)

    Yakoumakis, Emmanuel; Kostopoulou, Helen; Dimitriadis, Anastastios; Georgiou, Evaggelos [University of Athens, Medical Physics Department, Medical School, Athens (Greece); Makri, Triantafilia [' Agia Sofia' Hospital, Medical Physics Unit, Athens (Greece); Tsalafoutas, Ioannis [Anticancer-Oncology Hospital of Athens ' Agios Savvas' , Medical Physics Department, Athens (Greece)

    2013-03-15

    Children diagnosed with congenital heart disease often undergo cardiac catheterization for their treatment, which involves the use of ionizing radiation and therefore a risk of radiation-induced cancer. The purpose of this study was to calculate the effective and equivalent organ doses (H{sub T}) in those children and estimate the risk of exposure-induced death. Fifty-three children were divided into three groups: atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA). In all procedures, the exposure conditions and the dose-area product meters readings were recorded for each individual acquisition. Monte Carlo simulations were run using the PCXMC 2.0 code and mathematical phantoms simulating a child's anatomy. The H{sub T} values to all irradiated organs and the resulting E and risk of exposure-induced death values were calculated. The average dose-area product values were, respectively, 40 {+-} 12 Gy.cm{sup 2} for the ASD, 17.5 {+-} 0.7 Gy.cm{sup 2} for the VSD and 9.5 {+-} 1 Gy.cm{sup 2} for the PDA group. The average E values were 40 {+-} 12, 22 {+-} 2.5 and 17 {+-} 3.6 mSv for ASD, VSD and PDA groups, respectively. The respective estimated risk of exposure-induced death values per procedure were 0.109, 0.106 and 0.067%. Cardiac catheterizations in children involve a considerable risk for radiation-induced cancer that has to be further reduced. (orig.)

  18. Estimation of radiation dose and risk to children undergoing cardiac catheterization for the treatment of a congenital heart disease using Monte Carlo simulations

    International Nuclear Information System (INIS)

    Children diagnosed with congenital heart disease often undergo cardiac catheterization for their treatment, which involves the use of ionizing radiation and therefore a risk of radiation-induced cancer. The purpose of this study was to calculate the effective and equivalent organ doses (HT) in those children and estimate the risk of exposure-induced death. Fifty-three children were divided into three groups: atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA). In all procedures, the exposure conditions and the dose-area product meters readings were recorded for each individual acquisition. Monte Carlo simulations were run using the PCXMC 2.0 code and mathematical phantoms simulating a child's anatomy. The HT values to all irradiated organs and the resulting E and risk of exposure-induced death values were calculated. The average dose-area product values were, respectively, 40 ± 12 Gy.cm2 for the ASD, 17.5 ± 0.7 Gy.cm2 for the VSD and 9.5 ± 1 Gy.cm2 for the PDA group. The average E values were 40 ± 12, 22 ± 2.5 and 17 ± 3.6 mSv for ASD, VSD and PDA groups, respectively. The respective estimated risk of exposure-induced death values per procedure were 0.109, 0.106 and 0.067%. Cardiac catheterizations in children involve a considerable risk for radiation-induced cancer that has to be further reduced. (orig.)

  19. Plasma Levels of 2% Lidocaine with 1:100,000 Epinephrine with Young Children Undergoing Dental Procedures

    OpenAIRE

    Jurevic, Richard; Milgrom, Peter; Karl, Helen W.; Weinstein, Philip; Coldwell, Susan E.; Evan D. Kharasch; Mautz, Douglas; Domoto, Peter

    1998-01-01

    Lidocaine levels were determined for 12 children, aged 55 to 150 mo, who received routine dental treatment, including multiple intraoral injections of 2% lidocaine (2.6 to 6.4 mg/kg) with 1:100,000 epinephrine. Peak plasma concentrations of lidocaine ranged from 0.7 to 3.8 μg/ml at 5 to 15 min postinjection. Generally accepted threshold concentrations for the onset of central nervous system toxicity are 5 to 10 μg/ml. In this study, no child approached these levels when given local anesthesia...

  20. Plasma Levels of 2% Lidocaine with 1:100,000 Epinephrine with Young Children Undergoing Dental Procedures

    Science.gov (United States)

    Jurevic, Richard; Milgrom, Peter; Karl, Helen W.; Weinstein, Philip; Coldwell, Susan E.; Kharasch, Evan D.; Mautz, Douglas; Domoto, Peter

    1998-01-01

    Lidocaine levels were determined for 12 children, aged 55 to 150 mo, who received routine dental treatment, including multiple intraoral injections of 2% lidocaine (2.6 to 6.4 mg/kg) with 1:100,000 epinephrine. Peak plasma concentrations of lidocaine ranged from 0.7 to 3.8 μg/ml at 5 to 15 min postinjection. Generally accepted threshold concentrations for the onset of central nervous system toxicity are 5 to 10 μg/ml. In this study, no child approached these levels when given local anesthesia for dental procedures. PMID:19598719

  1. Comparison of the Effects of Fentanyl and Midazolam as a Premedication in Children Undergoing Inguinal Hernial Surgery

    Directory of Open Access Journals (Sweden)

    MH Abdollahi

    2011-04-01

    Full Text Available Introduction: Premedication with midazolam can occasionally result in increased pediatric anxiety. In this study, we compared the effects of intravenous midazolam and fentanyl as pediatric premedication in children posted for inguinal hernia surgery. Methods: In this double blind randomized clinical trial study, sixty pediatric patients were randomly allocated to two study groups. Anesthesia was similar in both groups. Sedation score by Richmond agitation sedation scale was repeatedly measured on arrival to the preoperative part of the operating room, during drug administration, separation of the child from parent for transfer to the operating room, induction of anesthesia, time of transfer to the recovery room and discharge from the recovery room. Post-operative nausea and vomiting was also recorded. The collected data was analyzed with SPSS 15 and P value<0.05 was considered meaningful. Results: Baseline characteristics of the two study groups were similar. Mean RASS at separation of patients from parents; the time between the study drug administrations till separation from parents, induction of anesthesia and end of operation and need for additional drug during separation was significantly lower in the midazolam group. Opioid need in the fentanyl group was higher. Other findings were similar in the two groups. Conclusion: Use of fentanyl instead of midazolam as a premedication is not a priority in children posted for surgery.

  2. The Effect of Age of Cochlear Implantation on the Improvement of the Auditory Performance in the Children Undergoing Cochlear Implantation

    Directory of Open Access Journals (Sweden)

    L Monshizadeh

    2013-03-01

    Full Text Available Introduction: Hearing is one of the premier human senses. Being deprived from hearing is not only being unable to hear the sounds, but it is also the disability to gain a lot of helpful experiences. Cochlear implantation is introduced worldwide in order to treat the severe to profound hearing loss. Therefore, the present study aims to determine the effect of age of cochlear implantation on improvement of the auditory performance. Methods: The present follow-up study was conducted on 96 children who had referred to Fars Cochlear Implantation Center. The patients’ information was gathered from their profiles both before and after the operation. In addition, the auditory performance score was obtained in 3 stages – 6 months, 1 year, and 2 years after the implantation – through the Cap test. Also, non-parametric tests of Fridman, Willcoxon, and Mann-Withney U were utilized in order to analyze the data of the study. Results: The mean of the children’s auditory performance 6 months, 1 year, and 2 years after the implantation was measured as 2.8+1.03, 4.36+1.04, and 5.34+1.02, respectively. Besides, the median of their auditory performance 6 months, 1 year, and 2 years after the implantation was calculated as 3, 5, and 5, respectively. Also, a statistically significant relationship was observed between the independent variable of age of cochlear implantation and the auditory performance score 6 months, 1 year, and 2 years after the implantation. Conclusion: In line with other studies conducted on the issue, the present study showed the improvement of the auditory performance in the children who benefited from cochlear implantation. Moreover, the results of the present study revealed that the age of cochlear implantation can be of great help in determining the candidates of cochlear implantation. In other words, it can be a major prognostic factor of the response to the treatment

  3. Chiaroscuro hematopoietic stem cell.

    OpenAIRE

    Quesenberry, P.; Habibian, M. (PhD); Dooner, M; Zhong, S.; Reilly, J; Peters, S.; De Becker, P; Grimaldi, C.; Carlson, J; REDDY, P; Nilsson, S.; Stewart, F. M.

    1998-01-01

    These observations suggest several immediate clinical strategies. In gene therapy, approaches could be targeted to obtain cycling of hematopoietic stem cells and gene-carrying retrovirus vector integration followed by engraftment at an appropriate time interval which favors engraftment. The same type of approach can be utilized for stem cell expansion approaches. Alternatively marrow or peripheral stem cell engraftment can be obtained with minimal to no toxicity in allochimeric strategies in ...

  4. Hematopoietic stem cell transplantation

    OpenAIRE

    Eleftheria Hatzimichael; Mark Tuthill

    2010-01-01

    Eleftheria Hatzimichael1, Mark Tuthill21Department of Haematology, Medical School of Ioannina, University of Ioannina, Ioannina, Greece; 2Department of Medical Oncology, Hammersmith Hospital, Imperial College National Health Service Trust, London, UKAbstract: More than 25,000 hematopoietic stem cell transplantations (HSCTs) are performed each year for the treatment of lymphoma, leukemia, immune-deficiency illnesses, congenital metabolic defects, hemoglobinopathies, and myelodysplastic and mye...

  5. Nasopharyngeal vs. adenoid cultures in children undergoing adenoidectomy: prevalence of bacterial pathogens, their interactions and risk factors.

    Science.gov (United States)

    Korona-Glowniak, I; Niedzielski, A; Kosikowska, U; Grzegorczyk, A; Malm, A

    2015-03-01

    Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus colonization of the adenoids and nasopharynx in 103 preschool children who underwent adenoidectomy for recurrent upper respiratory tract infections was examined. Bacterial interactions and risk factors for bacterial colonization of the nasopharynx and adenoids, separately, were analysed statistically. The prevalence of simultaneous isolation from both anatomical sites was 45·6% for S. pneumoniae, 29·1% for H. influenzae, 15·5% for M. catarrhalis and 18·4% for S. aureus. Three pathogens were significantly more frequent together from adenoid samples; nasopharyngeal swabs more often yielded a single organism, but without statistical significance. M. catarrhalis and S. aureus significantly more frequently co-existed with S. pneumoniae and H. influenzae than with each other and a positive association of S. pneumoniae and H. influenzae in adenoid samples was evident. Several differences between risk factors for nasopharyngeal and adenoid colonization by the individual pathogens were observed. We conclude that the adenoids and nasopharynx appear to differ substantially in colonization by pathogenic microbes but occurrence of H. influenzae and S. pneumoniae in the nasopharynx could be predictive of upper respiratory tract infections. PMID:25703401

  6. Sequential myeloablative autologous stem cell transplantation and reduced intensity allogeneic hematopoietic cell transplantation is safe and feasible in children, adolescents and young adults with poor-risk refractory or recurrent Hodgkin and non-Hodgkin lymphoma.

    Science.gov (United States)

    Satwani, P; Jin, Z; Martin, P L; Bhatia, M; Garvin, J H; George, D; Chaudhury, S; Talano, J; Morris, E; Harrison, L; Sosna, J; Peterson, M; Militano, O; Foley, S; Kurtzberg, J; Cairo, M S

    2015-02-01

    The outcome of children, adolescents and young adults (CAYA) with poor-risk recurrent/refractory lymphoma is dismal (⩽30%). To overcome this poor prognosis, we designed an approach to maximize an allogeneic graft vs lymphoma effect in the setting of low disease burden. We conducted a multi-center prospective study of myeloablative conditioning (MAC) and autologous stem cell transplantation (AutoSCT), followed by a reduced intensity conditioning (RIC) and allogeneic hematopoietic cell transplantation (AlloHCT) in CAYA, with poor-risk refractory or recurrent lymphoma. Conditioning for MAC AutoSCT consisted of carmustine/etoposide/cyclophosphamide, RIC consisted of busulfan/fludarabine. Thirty patients, 16 Hodgkin lymphoma (HL) and 14 non-Hodgkin lymphoma (NHL), with a median age of 16 years and median follow-up of 5years, were enrolled. Twenty-three patients completed both MAC AutoSCT and RIC AlloHCT. Allogeneic donor sources included unrelated cord blood (n=9), unrelated donor (n=8) and matched siblings (n=6). The incidence of transplant-related mortality following RIC AlloHCT was only 12%. In patients with HL and NHL, 10 year EFS was 59.8% and 70% (P=0.613), respectively. In summary, this approach is safe, and long-term EFS with this approach is encouraging considering the poor-risk patient characteristics and the use of unrelated donors for RIC AlloHCT in the majority of cases. PMID:24938649

  7. Predictors of seizure outcomes in children with tuberous sclerosis complex and intractable epilepsy undergoing resective epilepsy surgery: an individual participant data meta-analysis.

    Directory of Open Access Journals (Sweden)

    Aria Fallah

    Full Text Available OBJECTIVE: To perform a systematic review and individual participant data meta-analysis to identify preoperative factors associated with a good seizure outcome in children with Tuberous Sclerosis Complex undergoing resective epilepsy surgery. DATA SOURCES: Electronic databases (MEDLINE, EMBASE, CINAHL and Web of Science, archives of major epilepsy and neurosurgery meetings, and bibliographies of relevant articles, with no language or date restrictions. STUDY SELECTION: We included case-control or cohort studies of consecutive participants undergoing resective epilepsy surgery that reported seizure outcomes. We performed title and abstract and full text screening independently and in duplicate. We resolved disagreements through discussion. DATA EXTRACTION: One author performed data extraction which was verified by a second author using predefined data fields including study quality assessment using a risk of bias instrument we developed. We recorded all preoperative factors that may plausibly predict seizure outcomes. DATA SYNTHESIS: To identify predictors of a good seizure outcome (i.e. Engel Class I or II we used logistic regression adjusting for length of follow-up for each preoperative variable. RESULTS: Of 9863 citations, 20 articles reporting on 181 participants were eligible. Good seizure outcomes were observed in 126 (69% participants (Engel Class I: 102(56%; Engel class II: 24(13%. In univariable analyses, absence of generalized seizure semiology (OR = 3.1, 95%CI = 1.2-8.2, p = 0.022, no or mild developmental delay (OR = 7.3, 95%CI = 2.1-24.7, p = 0.001, unifocal ictal scalp electroencephalographic (EEG abnormality (OR = 3.2, 95%CI = 1.4-7.6, p = 0.008 and EEG/Magnetic resonance imaging concordance (OR = 4.9, 95%CI = 1.8-13.5, p = 0.002 were associated with a good postoperative seizure outcome. CONCLUSIONS: Small retrospective cohort studies are inherently prone to bias, some of which are overcome using individual participant data. The

  8. 慢性肾脏病及透析患儿的疫苗接种%Immunization in children with chronic renal diseases and undergoing dialysis

    Institute of Scientific and Technical Information of China (English)

    刘小荣; 姚开虎; 杨永弘

    2013-01-01

    Most children patients with chronic kidney disease show immune disorders and defects of immune functionality.There are significant increases in various pathogen infections,especially streptococcus pneumonia,hepatitis B virus,and influenza virus.Streptococcus pneumonia is the most common cause of bacterial pneumonia and otitis media worldwide,and the main pathogens of bacterial meningitis as well.Children treated by hemodialysis are in high risk circumstance susceptible to hepatitis B virus.Influenza is a highly contagious disease with extremely strong dissemination capability.The organizations of U.S.Advisory Committee on Immunization Practices (ACIP),and Kidney Disease:Improving Global Outcomes (KDIGO) specifically recommends 3 vaccines,namely,hepatitis B virus,influenza virus (inactivated),and pneumococcal vaccine for patients with chronic kidney disease and chronic dialysis.Vaccination is a specific preventive and an effective protective measure for patients of chronic kidney disease and undergoing dialysis.%慢性肾脏病患儿大多存在免疫紊乱及免疫功能缺陷.各种病原菌的感染率明显增高,尤其容易感染肺炎链球菌、HBV及流感病毒.在全球范围内,肺炎链球菌是细菌性肺炎和中耳炎的最常见病原,是细菌性脑膜炎的主要病原菌.血液透析的患儿更是HBV易感染的高危人群.流感是具有高度传染性及极其广泛的传播性疾病.美国免疫实践指南咨询委员会(ACIP)及改善全球肾脏病预后(KDIGO)特别推荐慢性肾脏病及慢性透析的患者接种的3种疫苗是HBV疫苗、灭活流感病毒疫苗及肺炎链球菌疫苗.接种疫苗是特异性的预防措施,可对慢性肾脏病及透析患者提供有效的预防保护.

  9. Cytokine signaling for proliferation, survival, and death in hematopoietic cells.

    Science.gov (United States)

    Miyajima, A; Ito, Y; Kinoshita, T

    1999-04-01

    The survival, proliferation, and differentiation of hematopoietic cells are regulated by cytokines. In the absence of cytokines, hematopoietic cells not only stop proliferation, but undergo apoptosis. This strict dependency of hematopoietic cells on cytokines is an important mechanism that maintains the homeostasis of blood cells. Cytokines induce various intracellular signaling pathways by activating the receptor-associated Janus kinases (Jaks), and distinct signals are responsible for cell cycle progression and cell survival. Induction of signals for cell cycle progression without suppressing apoptosis results in apoptotic cell death, indicating the essential role of anti-apoptotic signaling for cell growth. In hematopoietic cells, Ras, a cellular protooncogen product, and phosphatidylinositol 3 kinase are involved in the suppression of apoptosis. Cytokine depletion not only turns off anti-apoptotic signaling, but also actively induces cell death by activating caspases, a distinct family of cysteine proteases. Alterations in the mechanisms of cytokine signaling for cell cycle progression and anti-apoptotic function are implicated in hematological disorders. PMID:10222650

  10. Thrombopoietin and hematopoietic stem cells

    OpenAIRE

    de Graaf, Carolyn A.; Metcalf, Donald

    2011-01-01

    Thrombopoietin (TPO) is the cytokine that is chiefly responsible for megakaryocyte production but increasingly attention has turned to its role in maintaining hematopoietic stem cells (HSCs). HSCs are required to initiate the production of all mature hematopoietic cells, but this differentiation needs to be balanced against self-renewal and quiescence to maintain the stem cell pool throughout life. TPO has been shown to support HSC quiescence during adult hematopoiesis, with the loss of TPO s...

  11. Improving access to preparatory information for children undergoing general anaesthesia for tooth extraction and their families: study protocol for a Phase III randomized controlled trial

    OpenAIRE

    Hosey, Marie Therese; Donaldson, Ana Nora; Huntington, Corinne; Liossi, Christina; Reynolds, Patricia A; Alharatani, Reham; Newton, J Timothy

    2014-01-01

    Background Children can find anaesthesia induction especially distressing and postoperative psychological and physical morbidity are common. Preparation programmes for general anaesthesia (GA) are highly effective in reducing this distress. A Phase II study has already verified the effectiveness of a prototype preoperative GA-coping computer game to help children cope with induction in a dental GA setting. The biggest patient users of pediatric GA services in the UK are children who need to h...

  12. Perioperative effects of oral midazolam premedication in children undergoing skin laser treatment. A double-blinded randomized placebo-controlled trial

    NARCIS (Netherlands)

    Shoroghi, Mehrdad; Arbabi, Shahriyar; Farahbakhsh, Farshid; Sheikhvatan, Mehrdad; Abbasi, Ali

    2011-01-01

    Purpose: To investigate and compare the efficacy of oral midazolam with two different dosages in orange juice on perioperative hemodynamics and behavioral changes in children who underwent skin laser treatment in an academic educational Hospital. Methods: Ninety children, candidates for skin laser t

  13. Critical early events in hematopoietic cell seeding and engraftment.

    Directory of Open Access Journals (Sweden)

    Jerry Stein

    2005-12-01

    Full Text Available Durable hematopoietic stem cell engraftment requires efficient homing to and seeding in the recipient bone marrow. Dissection of cellular and molecular mechanisms by retrospective analysis of functional engraftment studies imposes severe limitations on the understanding of the early stages of this process. We have established an experimental approach for in vivo functional imaging of labeled cells at the level of recipient bone marrow in real time. The adhesive interaction of hematopoietic cells with the bone marrow stroma evolves as the most important early event. Adhesion to the marrow, rather than the vascular endothelium, determines the efficiency of both homing and seeding, and is absolutely essential to maintain cell viability in the marrow. Seeding and engraftment may be improved either by bypassing homing or by localized transplant of a large number of cells in a relatively small marrow space. There is functional redundancy in the molecular pathways that mediate the cell-stroma interaction, such that blockage of a single pathway has only minor effect on homing and seeding. We hypothesize that successfully seeding-engrafting cells undergo extensive phenotypic changes as a consequence of interaction with the stroma, without engaging in rapid proliferation. Surprisingly, Fas-ligand appears to promote hematopoietic cell engraftment by immunomodulatory and trophic effects.

  14. A Time Series Observation of Chinese Children Undergoing Rigid Bronchoscopy for an Inhaled Foreign Body: 3149 Cases in 1991-2010

    OpenAIRE

    Xu Zhang; Wen-Xian Li; Yi-Rong Cai

    2015-01-01

    Background: In China, tracheobronchial foreign body (TFB) aspiration, a major cause of emergency episode and accident death in children, remains a challenge for anesthetic management. Here, we share our experience and discuss the anesthetic consideration and management of patients with TFB aspiration. Methods: This was a single-institution retrospective study in children with an inhaled foreign body between 1991 and 2010 that focused on the complications following rigid bronchoscopy (RB)....

  15. Association between down syndrome and in-hospital death among children undergoing surgery for congenital heart disease a us population-based study

    OpenAIRE

    Evans, JM; Dharmar, M; Meierhenry, E; Marcin, JP; Raff, GW

    2014-01-01

    Background-The prevalence of Down syndrome (DS)-affected births has increased during the past 30 years; moreover, children with DS have a higher incidence of congenital heart disease compared with their peers. Whether children with DS have better or worse outcomes after repair of congenital heart disease is unclear. We sought to identify differences in in-hospital mortality after cardiac surgery in pediatric patients with and without DS using a large national database. Methods and Results-Chi...

  16. Risk assessment of relapse by lineage-specific monitoring of chimerism in children undergoing allogeneic stem cell transplantation for acute lymphoblastic leukemia

    Science.gov (United States)

    Preuner, Sandra; Peters, Christina; Pötschger, Ulrike; Daxberger, Helga; Fritsch, Gerhard; Geyeregger, Rene; Schrauder, André; von Stackelberg, Arend; Schrappe, Martin; Bader, Peter; Ebell, Wolfram; Eckert, Cornelia; Lang, Peter; Sykora, Karl-Walter; Schrum, Johanna; Kremens, Bernhard; Ehlert, Karoline; Albert, Michael H.; Meisel, Roland; Lawitschka, Anita; Mann, Georg; Panzer-Grümayer, Renate; Güngör, Tayfun; Holter, Wolfgang; Strahm, Brigitte; Gruhn, Bernd; Schulz, Ansgar; Woessmann, Wilhelm; Lion, Thomas

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation is required as rescue therapy in about 20% of pediatric patients with acute lymphoblastic leukemia. However, the relapse rates are considerable, and relapse confers a poor outcome. Early assessment of the risk of relapse is therefore of paramount importance for the development of appropriate measures. We used the EuroChimerism approach to investigate the potential impact of lineage-specific chimerism testing for relapse-risk analysis in 162 pediatric patients with acute lymphoblastic leukemia after allogeneic stem cell transplantation in a multicenter study based on standardized transplantation protocols. Within a median observation time of 4.5 years, relapses have occurred in 41/162 patients at a median of 0.6 years after transplantation (range, 0.13–5.7 years). Prospective screening at defined consecutive time points revealed that reappearance of recipient-derived cells within the CD34+ and CD8+ cell subsets display the most significant association with the occurrence of relapses with hazard ratios of 5.2 (P=0.003) and 2.8 (P=0.008), respectively. The appearance of recipient cells after a period of pure donor chimerism in the CD34+ and CD8+ leukocyte subsets revealed dynamics indicative of a significantly elevated risk of relapse or imminent disease recurrence. Assessment of chimerism within these lineages can therefore provide complementary information for further diagnostic and, potentially, therapeutic purposes aiming at the prevention of overt relapse. This study was registered at clinical.trials.gov with the number NC01423747. PMID:26869631

  17. Radiation detriment ascribable to infants and children undergoing micturating cystourethrograms - A review of studies in Spain, Britain, New Zealand and Venezuela

    International Nuclear Information System (INIS)

    The detriment, due to ionizing irradiation, ascribable to infants and children may be as high as three times that to adults. Recent interest in dose reduction, in part associated with the advent of the Diamentor dose-area product meter, has led to several studies reporting average dose-area products at a number of centres for micturating cystourethrograms (MCUGS) and other radiological examinations. In this review the data has been further processed to yield the ICRP 60 Equivalent Doses and a detriment factor applied to yield the numbers of infants and children likely to suffer detriment in future life as a result of having undergone the procedure at the centres reviewed. (author)

  18. Canonical Wnt signaling promotes early hematopoietic progenitor formation and erythroid specification during embryonic stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Anuradha Tarafdar

    Full Text Available The generation of hematopoietic stem cells (HSCs during development is a complex process linked to morphogenic signals. Understanding this process is important for regenerative medicine applications that require in vitro production of HSC. In this study we investigated the effects of canonical Wnt/β-catenin signaling during early embryonic differentiation and hematopoietic specification using an embryonic stem cell system. Our data clearly demonstrates that following early differentiation induction, canonical Wnt signaling induces a strong mesodermal program whilst maintaining a degree of stemness potential. This involved a complex interplay between β-catenin/TCF/LEF/Brachyury/Nanog. β-catenin mediated up-regulation of TCF/LEF resulted in enhanced brachyury levels, which in-turn lead to Nanog up-regulation. During differentiation, active canonical Wnt signaling also up-regulated key transcription factors and cell specific markers essential for hematopoietic specification, in particular genes involved in establishing primitive erythropoiesis. This led to a significant increase in primitive erythroid colony formation. β-catenin signaling also augmented early hematopoietic and multipotent progenitor (MPP formation. Following culture in a MPP specific cytokine cocktail, activation of β-catenin suppressed differentiation of the early hematopoietic progenitor population, with cells displaying a higher replating capacity and a propensity to form megakaryocytic erythroid progenitors. This bias towards erythroid lineage commitment was also observed when hematopoietic progenitors were directed to undergo myeloid colony formation. Overall this study underscores the importance of canonical Wnt/β-catenin signaling in mesodermal specification, primitive erythropoiesis and early hematopietic progenitor formation during hematopoietic induction.

  19. Immunological characteristics and T-cell receptor clonal diversity in children with systemic juvenile idiopathic arthritis undergoing T-cell-depleted autologous stem cell transplantation.

    Science.gov (United States)

    Wu, Qiong; Pesenacker, Anne M; Stansfield, Alka; King, Douglas; Barge, Dawn; Foster, Helen E; Abinun, Mario; Wedderburn, Lucy R

    2014-06-01

    Children with systemic Juvenile Idiopathic Arthritis (sJIA), the most severe subtype of JIA, are at risk from destructive polyarthritis and growth failure, and corticosteroids as part of conventional treatment can result in osteoporosis and growth delay. In children where there is failure or toxicity from drug therapies, disease has been successfully controlled by T-cell-depleted autologous stem cell transplantation (ASCT). At present, the immunological basis underlying remission after ASCT is unknown. Immune reconstitution of T cells, B cells, natural killer cells, natural killer T cells and monocytes, in parallel with T-cell receptor (TCR) diversity by analysis of the β variable region (TCRVb) complementarity determining region-3 (CDR3) using spectratyping and sequencing, were studied in five children with sJIA before and after ASCT. At time of follow up (mean 11.5 years), four patients remain in complete remission, while one child relapsed within 1 month of transplant. The CD8(+) TCRVb repertoire was highly oligoclonal early in immune reconstitution and re-emergence of pre-transplant TCRVb CDR3 dominant peaks was observed after transplant in certain TCRVb families. Further, re-emergence of pre-ASCT clonal sequences in addition to new sequences was identified after transplant. These results suggest that a chimeric TCR repertoire, comprising T-cell clones developed before and after transplant, can be associated with clinical remission from severe arthritis. PMID:24405357

  20. Severe fludarabine neurotoxicity after reduced intensity conditioning regimen to allogeneic hematopoietic stem cell transplantation: a case report

    OpenAIRE

    C. Annaloro; Costa, A.; N.S. Fracchiolla; G. Mometto; S. Artuso; G. Saporiti; Tagliaferri, E.; GRIFONI, F.; Onida, F.; Cortelezzi, A.

    2015-01-01

    Key Clinical Message We present a case of severe, irreversible neurotoxicity in a 55-year-old-patient with myelofibrosis undergoing hematopoietic stem cell transplantation following a reduced intensity conditioning including fludarabine. The patient developed progressive sensory-motor, visual and consciousness disturbances, eventually leading to death. MRI imaging pattern was unique and attributable to fludarabine neurotoxicity.

  1. Severe fludarabine neurotoxicity after reduced intensity conditioning regimen to allogeneic hematopoietic stem cell transplantation: a case report.

    Science.gov (United States)

    Annaloro, Claudio; Costa, Antonella; Fracchiolla, Nicola S; Mometto, Gabriella; Artuso, Silvia; Saporiti, Giorgia; Tagliaferri, Elena; Grifoni, Federica; Onida, Francesco; Cortelezzi, Agostino

    2015-07-01

    We present a case of severe, irreversible neurotoxicity in a 55-year-old-patient with myelofibrosis undergoing hematopoietic stem cell transplantation following a reduced intensity conditioning including fludarabine. The patient developed progressive sensory-motor, visual and consciousness disturbances, eventually leading to death. MRI imaging pattern was unique and attributable to fludarabine neurotoxicity. PMID:26273463

  2. Routine Surveillance for Bloodstream Infections in a Pediatric Hematopoietic Stem Cell Transplant Cohort: Do Patients Benefit?

    Directory of Open Access Journals (Sweden)

    Heather Rigby

    2007-01-01

    Full Text Available BACKGROUND: Hematopoietic stem cell transplant (HSCT recipients are at a high risk for late bloodstream infection (BSI. Controversy exists regarding the benefit of surveillance blood cultures in this immunosuppressed population. Despite the common use of this practice, the practical value is not well established in non-neutropenic children following HSCT.

  3. Single-Cell RNA-Sequencing Reveals a Continuous Spectrum of Differentiation in Hematopoietic Cells

    Directory of Open Access Journals (Sweden)

    Iain C. Macaulay

    2016-02-01

    Full Text Available The transcriptional programs that govern hematopoiesis have been investigated primarily by population-level analysis of hematopoietic stem and progenitor cells, which cannot reveal the continuous nature of the differentiation process. Here we applied single-cell RNA-sequencing to a population of hematopoietic cells in zebrafish as they undergo thrombocyte lineage commitment. By reconstructing their developmental chronology computationally, we were able to place each cell along a continuum from stem cell to mature cell, refining the traditional lineage tree. The progression of cells along this continuum is characterized by a highly coordinated transcriptional program, displaying simultaneous suppression of genes involved in cell proliferation and ribosomal biogenesis as the expression of lineage specific genes increases. Within this program, there is substantial heterogeneity in the expression of the key lineage regulators. Overall, the total number of genes expressed, as well as the total mRNA content of the cell, decreases as the cells undergo lineage commitment.

  4. Rinossinusites em crianças infectadas pelo HIV sob terapia anti-retroviral Rhinosinusitis in HIV-infected children undergoing antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Carlos Diógenes Pinheiro Neto

    2009-02-01

    Full Text Available A associação dos inibidores de protease (IP à terapia anti-retroviral provocou mudanças importantes na morbidade e mortalidade de pacientes infectados pelo HIV. OBJETIVOS: Avaliar o impacto desta associação na prevalência de rinossinusite (RS e na contagem sérica de linfócitos CD4 em crianças infectadas pelo HIV. CASUÍSTICA E MÉTODOS: A forma de estudo foi cross-sectional com 471 crianças infectadas pelo HIV. Em 1996, inibidores de protease foram liberados para terapia anti-retroviral. Desta forma, dois grupos de crianças foram formados: as que não fizeram uso de IP e as que fizeram uso desta droga após 1996. A prevalência de RS e a contagem sérica de linfócitos CD4 foram comparadas entre estes grupos. RESULTADOS: 14,4% das crianças infectadas pelo HIV apresentaram RS. A RS crônica foi mais prevalente que a RS aguda em ambos os grupos. Crianças menores de 6 anos tratadas com a associação de IP apresentaram maior prevalência de RS aguda. A associação de IP esteve associada à maior contagem de linfócitos CD4 séricos com menor prevalência de RS crônica. CONCLUSÕES: A terapia com IP esteve associada ao aumento na contagem de linfócitos CD4. Crianças abaixo dos 6 anos em uso de IP apresentaram menor tendência à cronificação da doença.The association of protease inhibitors (PI to antiretroviral therapy has generated sensible changes in morbidity and mortality of HIV-infected patients. AIM: Aims at evaluating the impact of this association on the prevalence of rhinosinusitis (RS and CD4+ lymphocyte count in HIV-infected children. METHODS: Retrospective cross-sectional study of the medical charts of 471 HIV-infected children. In 1996, protease inhibitors were approved for use as an association drug in antiretroviral therapy. Children were divided into two groups: one which did not receive PI and another which received PI after 1996. The prevalence of RS and CD4+ lymphocyte counts were compared between these groups

  5. Fluid balance of pediatric hematopoietic stem cell transplant recipients and intensive care unit admission.

    Science.gov (United States)

    Benoit, Geneviève; Phan, Véronique; Duval, Michel; Champagne, Martin; Litalien, Catherine; Merouani, Aicha

    2007-03-01

    Fluid administration is essential in patients undergoing hematopoietic stem cell transplant (HSCT). Admission to pediatric intensive care unit (PICU) is required for 11-29% of pediatric HSCT recipients and is associated with high mortality. The objective of this study was to determine if a positive fluid balance acquired during the HSCT procedure is a risk factor for PICU admission. The medical records of 87 consecutive children who underwent a first HSCT were reviewed retrospectively for the following periods: from admission for HSCT to PICU admission for the first group (PICU group), and from admission for HSCT to hospital discharge for the second group (non-PICU group). Fluid balance was determined on the basis of weight gain (WG) and fluid overload (FO). PICU group consisted of 19 patients (21.8%). Among these, 13 (68.4%) developed>or=10% WG prior to PICU admission compared with 15 (22.1%) in the non-PICU group (por=10% FO prior to PICU admission compared with 31 (45.6%) in the non-PICU group (p=0.075). Following multivariate analysis, >or=10% WG (p=0.018) and cardiac dysfunction on admission for HSCT (p=0.036) remained independent risk factors for PICU admission. Smaller children (p=0.033) and patients with a twofold increase in serum creatinine (p=0.026) were at risk of developing>or=10% WG. This study shows that WG is a risk factor for PICU admission in pediatric HSCT recipients. Further research is needed to better understand the pathophysiology of WG in these patients and to determine the impact of WG prevention on PICU admission. PMID:17123119

  6. Evaluation of cortical plasticity in children with cerebral palsy undergoing constraint-induced movement therapy based on functional near-infrared spectroscopy

    Science.gov (United States)

    Cao, Jianwei; Khan, Bilal; Hervey, Nathan; Tian, Fenghua; Delgado, Mauricio R.; Clegg, Nancy J.; Smith, Linsley; Roberts, Heather; Tulchin-Francis, Kirsten; Shierk, Angela; Shagman, Laura; MacFarlane, Duncan; Liu, Hanli; Alexandrakis, George

    2015-04-01

    Sensorimotor cortex plasticity induced by constraint-induced movement therapy (CIMT) in six children (10.2±2.1 years old) with hemiplegic cerebral palsy was assessed by functional near-infrared spectroscopy (fNIRS). The activation laterality index and time-to-peak/duration during a finger-tapping task and the resting-state functional connectivity were quantified before, immediately after, and 6 months after CIMT. These fNIRS-based metrics were used to help explain changes in clinical scores of manual performance obtained concurrently with imaging time points. Five age-matched healthy children (9.8±1.3 years old) were also imaged to provide comparative activation metrics for normal controls. Interestingly, the activation time-to-peak/duration for all sensorimotor centers displayed significant normalization immediately after CIMT that persisted 6 months later. In contrast to this improved localized activation response, the laterality index and resting-state connectivity metrics that depended on communication between sensorimotor centers improved immediately after CIMT, but relapsed 6 months later. In addition, for the subjects measured in this work, there was either a trade-off between improving unimanual versus bimanual performance when sensorimotor activation patterns normalized after CIMT, or an improvement occurred in both unimanual and bimanual performance but at the cost of very abnormal plastic changes in sensorimotor activity.

  7. Hepatitis B-related events in autologous hematopoietic stem cell transplantation recipients

    Institute of Scientific and Technical Information of China (English)

    zcan; eneli; Zübeyde; Nur; zkurt; Kadir; Acar; Seyyal; Rota; Sahika; Zeynep; Aki; Zeynep; Arzu; Yegin; Münci; Yagci; Seren; zenirler; Gülsan; Türkz; Sucak

    2010-01-01

    AIM: To investigate the frequency of occult hepatitis B, the clinical course of hepatitis B virus (HBV) reactivation and reverse seroconversion and associated risk factors in autologous hematopoietic stem cell transplantation (HSCT) recipients. METHODS: This study was conducted in 90 patients undergoing autologous HSCT. Occult HBV infection was investigated by HBV-DNA analysis prior to transplantation, while HBV serology and liver function tests were screened prior to and serially after transplantation. HBV...

  8. Hemorrhagic cystitis after hematopoietic stem cell trans-plantation: much progress and many remaining issues

    Institute of Scientific and Technical Information of China (English)

    Edmund K. Waller

    2007-01-01

    @@ The manuscript by Xu et al1 addresses an important question in the field of allogeneic hematopoietic progenitor cell transplantation (HPCT): how to identify those patients at risk for hemmoraghic cystitis. The authors performed a retrospective analysis of 250 patients undergoing allogeneic HPCT following myeloablative conditioning with busulfan and cyclophosphamide using a standard post-transplant immunoprophylaxis with cyclosporine, short-course methotrexate and mycophenylate.

  9. Incidence and predictors of congestive heart failure after autologous hematopoietic cell transplantation

    OpenAIRE

    Armenian, Saro H; Sun, Can-Lan; Shannon, Tabitha; Mills, George; Francisco, Liton; Venkataraman, Kalyanasundaram; Wong, F. Lennie; Forman, Stephen J.; Bhatia, Smita

    2011-01-01

    Advances in autologous hematopoietic cell transplantation (HCT) strategies have resulted in a growing number of long-term survivors. However, these survivors are at increased risk of developing cardiovascular complications due to pre-HCT therapeutic exposures and conditioning and post-HCT comorbidities. We examined the incidence and predictors of congestive heart failure (CHF) in 1244 patients undergoing autologous HCT for a hematologic malignancy between 1988 and 2002. The cumulative inciden...

  10. Allogeneic Hematopoietic Cell Transplantation in Patients with Myelodysplastic Syndrome and Concurrent Lymphoid Malignancy

    OpenAIRE

    Zimmerman, Zachary; Scott, Bart L.; Gopal, Ajay K.; Sandmaier, Brenda M.; Maloney, David G; Deeg, H. Joachim

    2011-01-01

    Allogeneic hematopoietic cell transplantation (HCT) can be curative for both myelodysplastic syndromes (MDS) and lymphoid malignancies. Little is known about the efficacy of allogeneic HCT in patients in whom both myeloid and lymphoid disorders are present at the time of HCT. We analyzed outcomes in 21 patients with MDS and concurrent lymphoid malignancy when undergoing allogeneic HCT. Seventeen patients had received extensive prior cytotoxic chemotherapy, including autologous HCT in seven, f...

  11. Histocompatibility and Hematopoietic Transplantation in the Zebrafish

    Directory of Open Access Journals (Sweden)

    Jill L. O. de Jong

    2012-01-01

    Full Text Available The zebrafish has proven to be an excellent model for human disease, particularly hematopoietic diseases, since these fish make similar types of blood cells as humans and other mammals. The genetic program that regulates the development and differentiation of hematopoietic cells is highly conserved. Hematopoietic stem cells (HSCs are the source of all the blood cells needed by an organism during its lifetime. Identifying an HSC requires a functional assay, namely, a transplantation assay consisting of multilineage engraftment of a recipient and subsequent serial transplant recipients. In the past decade, several types of hematopoietic transplant assays have been developed in the zebrafish. An understanding of the major histocompatibility complex (MHC genes in the zebrafish has lagged behind transplantation experiments, limiting the ability to perform unbiased competitive transplantation assays. This paper summarizes the different hematopoietic transplantation experiments performed in the zebrafish, both with and without immunologic matching, and discusses future directions for this powerful experimental model of human blood diseases.

  12. Fertility issues following hematopoietic stem cell transplantation.

    Science.gov (United States)

    Tichelli, André; Rovó, Alicia

    2013-08-01

    With the improvement of the outcome, the number of long-term survivors of hematopoietic stem cell transplantation (HSCT) is continuously increasing. However, there is still a high burden of late morbidity and mortality. Two-thirds of the transplant survivors develop at least one late effect interfering with their physical or psychological health. Infertility is common after myeloablative HSCT conditioned with total body irradiation and high doses of gonadotoxic drugs. Other factors, such as the age of the patient at transplantation, the treatment modality received before HSCT or the onset of chronic graft versus host disease, may play an additional role. Accordingly, the number of pregnancies observed after HSCT is very low when compared to a general population in childbearing age. Furthermore, complications during pregnancy and at delivery occur significantly more frequently, probably because of the uterine damages caused by irradiation therapy. However, there is no excess of congenital abnormalities observed among newborn children. Today there are good possibilities for fertility preservation. In male patients cryopreservation of sperm, and in female patients cryopreservation of fertilized embryos or of mature oocytes, are well-established treatment options. Patients' and physicians' attitude toward discussion on fertility issues play a key role in the success of fertility preservation after HSCT. PMID:23991924

  13. A Time Series Observation of Chinese Children Undergoing Rigid Bronchoscopy for an Inhaled Foreign Body: 3149 Cases in 1991-2010

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    Xu Zhang

    2015-01-01

    Full Text Available Background: In China, tracheobronchial foreign body (TFB aspiration, a major cause of emergency episode and accident death in children, remains a challenge for anesthetic management. Here, we share our experience and discuss the anesthetic consideration and management of patients with TFB aspiration. Methods: This was a single-institution retrospective study in children with an inhaled foreign body between 1991 and 2010 that focused on the complications following rigid bronchoscopy (RB. Data including the clinical characteristics of patients and TFB, anesthetic method, and postoperative severe complications were analyzed by different periods. Results: During the 20-year study period, the charts of 3149 patients who underwent RB for suspected inhaled TFB were reviewed. There were 2079 male and 1070 female patients (1.94:1. A nut (84% was the most commonly inhaled object. The study revealed a 9% (n = 284 overall rate of severe postoperative complications related to severe hypoxemia, laryngeal edema, complete laryngospasm, pneumothorax, total segmental atelectasis, and death with incidences of 3.2%, 0.9%, 1.3%, 0.3%, 0.3%, and 0.1%, respectively. The rates of preoperative airway impairment, negative findings of TFB, and adverse postoperative events have been on the rise in the past 5 years. Conclusions: The survey results confirmed that hypoxemia remains the most common postoperative complication in different periods. Both controlled ventilation and spontaneous ventilation were effective during the RB extraction of the foreign body at our hospital in the modern technique period. An active respiratory symptom was commonly seen in the groups with negative findings.

  14. A Time Series Observation of Chinese Children Undergoing Rigid Bronchoscopy for an Inhaled Foreign Body: 3149 Cases in 1991-2010

    Institute of Scientific and Technical Information of China (English)

    Xu Zhang; Wen-Xian Li; Yi-Rong Cai

    2015-01-01

    Background:In China,tracheobronchial foreign body (TFB) aspiration,a major cause of emergency episode and accident death in children,remains a challenge for anesthetic management.Here,we share our experience and discuss the anesthetic consideration and management of patients with TFB aspiration.Methods:This was a single-institution retrospective study in children with an inhaled foreign body between 1991 and 2010 that focused on the complications following rigid bronchoscopy (RB).Data including the clinical characteristics of patients and TFB,anesthetic method,and postoperative severe complications were analyzed by different periods.Results:During the 20-year study period,the charts of 3149 patients who underwent RB for suspected inhaled TFB were reviewed.There were 2079 male and 1070 female patients (1.94:1).A nut (84%) was the most commonly inhaled object.The study revealed a 9% (n =284) overall rate of severe postoperative complications related to severe hypoxemia,laryngeal edema,complete laryngospasm,pneumothorax,total segmental atelectasis,and death with incidences of 3.2%,0.9%,1.3%,0.3%,0.3%,and 0.1%,respectively.The rates of preoperative airway impairment,negative findings of TFB,and adverse postoperative events have been on the rise in the past 5 years.Conclusions:The survey results confirmed that hypoxemia remains the most common postoperative complication in different periods.Both controlled ventilation and spontaneous ventilation were effective during the RB extraction of the foreign body at our hospital in the modern technique period.An active respiratory symptom was commonly seen in the groups with negative findings.

  15. Hypothermia During Cardiopulmonary Bypass Increases Need for Inotropic Support but Does Not Impact Inflammation in Children Undergoing Surgical Ventricular Septal Defect Closure.

    Science.gov (United States)

    Schmitt, Katharina Rose Luise; Fedarava, Katsiaryna; Justus, Georgia; Redlin, Mathias; Böttcher, Wolfgang; Delmo Walter, Eva Maria; Hetzer, Roland; Berger, Felix; Miera, Oliver

    2016-05-01

    Minimizing the systemic inflammatory response caused by cardiopulmonary bypass is a major concern. It has been suggested that the perfusion temperature affects the inflammatory response. The aim of this prospective study was to compare the effects of moderate hypothermia (32°C) and normothermia (36°C) during cardiopulmonary bypass on markers of the inflammatory response and clinical outcomes (time on ventilator) after surgical closure of ventricular septal defects. During surgical closure of ventricular septal defects under cardiopulmonary bypass, 20 children (median age 4.9 months, range 2.3-38 months; median weight 7.2 kg, range 5.2-11.7 kg) were randomized to a perfusion temperature of either 32°C (Group 1, n = 10) or 36°C (Group 2, n = 10). The clinical data and blood samples were collected before cardiopulmonary bypass, directly after aortic cross-clamp release, and 4 and 24 h after weaning from cardiopulmonary bypass. Time on ventilation as primary outcome did not differ between the two groups. Other clinical outcome parameters like fluid balance or length of stay in the intensive care were also similar in the two groups. Compared with Group 2, Group 1 needed significantly higher and longer inotropic support (P Perfusion temperature did not influence cytokine release, organ injury, or coagulation. Cardiopulmonary bypass temperature does not influence time on ventilation or inflammatory marker release. However, in the present study, with a small patient cohort, patients operated under hypothermic bypass needed higher and longer inotropic support. The use of hypothermic cardiopulmonary bypass in infants and children should be approached with care. PMID:26581834

  16. A PROSPECTIVE, RANDOMIZED, DOUBLE BLIND, CONTROLLED CLINICAL STUDY OF ADJUVANT EFFECT OF FENTANYL (1 µg/kg OR CLONIDINE (2µg / kg TO ROPIVACAINE 0.2% 1ML/KG FOR CAUDAL ANALGESIA IN CHILDREN UNDERGOING LOWER ABDOMINAL SURGERIES

    Directory of Open Access Journals (Sweden)

    Manjunath

    2014-10-01

    Full Text Available Ropivacaine having better safety profile and less motor blockade than bupivacaine is well suited for caudal analgesia. Since studies done regarding the effect of fentanyl and clonidine as adjuvants to ropivacaine for prolongation of caudal analgesia are scant and have shown conflicting results, the present study was conducted. METHODS: A total of 90 children aged between 3-6yrs belonging to ASA class I and II undergoing surgical procedures below the umbilicus were randomly allocated to one of two groups: Group R received ropivacaine 0.2%, 1 ml/kg with saline 0.02ml/kg and Group RF received ropivacaine 0.2%, 1 ml/kg with fentanyl 1 μg/kg (0.02ml/kg and Group RC (clonidine received 1ml/kg of 0.2% Ropivacaine plus clonidine 2µg / kg caudally after induction of general endotracheal anaesthesia. The pain score was evaluated using Hannallah pain scale, motor blockade using modified bromage scale and sedation assessed using 4 point sedation score at 30 minutes after extubation and at 1, 2, 4, 6, 12 and 24 h. The time to awakening, first analgesic requirement time, number of doses of rescue analgesic and side-effects in a 24 hours period were also recorded. The results were evaluated using SPSS 17 statistical method. RESULTS: There were no differences in demographic characteristics between the groups. However, mean duration of caudal analgesia was 659.5 minutes in group R, 784.5 minutes in group RF and 960.5 minutes in group RC which was statistically highly significant (P<0.01.The total dose of rescue analgesic in 24 hours was lower in groups RF and RC. Also the number of children receiving rescue analgesia at 12 hours was higher in placebo group than fentanyl group and clonidine group which was statistically highly significant (P<0.01. Increased incidence of urinary retention and pruritis was noted in group RF which was statistically not significant (P=0.366. CONCLUSION: Addition of inj. Fentanyl 1µg/kg or clonidine 2µg/kg to Ropivacaine 0.2% 1ml

  17. Thrombotic obstruction of the central venous catheter in patients undergoing hematopoietic stem cell transplantation Obstrucción trombótica del catéter venoso central en pacientes sometidos al trasplante de células-tronco hematopoyéticas Obstrução trombótica do cateter venoso central em pacientes submetidos ao transplante de células-tronco hematopoéticas

    Directory of Open Access Journals (Sweden)

    Kátia Michelli Bertoldi Arone

    2012-08-01

    Full Text Available This is an integrative literature review with the aim of summarizing the prevention measures and treatment of thrombotic obstruction of long-term semi-implanted central venous catheters, in patients undergoing hematopoietic stem cell transplantation. The sample consisted of seven studies, being two randomized controlled clinical trials, three cohort studies and two case series. Regarding the prevention measures, one single study demonstrated effectiveness, which was a cohort study on the oral use of warfarin. In relation to the treatment measures, three studies evidenced effectiveness, one highlighted the efficacy of streptokinase or urokinase, one demonstrated the benefit of using low-molecular-weight heparin and the other treated the obstruction with heparin or urokinase. Catheter patency research shows a restricted evolution that does not follow the evolution of transplantations, mainly regarding nursing care.Se trata de una revisión integradora de la literatura con objeto de sintetizar las medidas de prevención y tratamiento de obstrucción trombótica del catéter venosos central de larga permanencia y semi-implantado, en pacientes sometidos al trasplante de células-tronco hematopoyéticas. La muestra abarcó a siete estudios: dos ensayos clínicos controlados aleatorizados, tres estudios de cohorte y dos series de casos. Respecto a las medidas de prevención, fue identificado un único estudio efectivo, uno cohorte sobre el uso de la warfarina oral. Sobre las medidas de tratamiento, tres estudios evidenciaron efectividad, uno apuntó la eficacia de la estreptoquinasa o uroquinasa, otro mostró beneficio del uso de heparina de bajo peso molecular y otro trató la obstrucción con heparina o uroquinasa. Se observa que la evolución de la investigación sobre la permeabilidad del catéter fue limitada, no acompañando la evolución del trasplante, principalmente respecto a los cuidados de enfermería.Trata-se de revisão integrativa da

  18. The role of the embryonic microenvironment in hematopoietic cell development

    NARCIS (Netherlands)

    E. Haak (Esther)

    2007-01-01

    textabstractThe adult hematopoietic system is comprised of a hierarchy of cells with the hematopoietic stem cell (HSC) at its foundation. HSCs give rise to progenitors that differentiate into mature hematopoietic cells, which perform the physiological functions of the hematopoietic system. The matur

  19. Serum Krebs Von Den Lungen-6 as a Biomarker for Early Detection of Bronchiolitis Obliterans Syndrome in Children Undergoing Allogeneic Stem Cell Transplantation.

    Science.gov (United States)

    Gassas, Adam; Schechter, Tal; Krueger, Joerg; Craig-Barnes, Hayley; Sung, Lillian; Ali, Muhammad; Dell, Sharon; Egeler, R Maarten; Zaidman, Irina; Palaniyar, Nades

    2015-08-01

    Bronchiolitis obliterans syndrome (BOS) is a devastating complication after allogeneic stem cell transplantation (allo-SCT). Early identification of high-risk patients is pivotal for success. Lung proteins, KL-6, CCSP, SP-A, and SP-D, measured in the serum may identify high-risk patients for BOS earlier than pulmonary function tests (PFTs) can identify changes or clinical symptoms. Lung proteins were measured in patients' serum at baseline and at 1, 3, 6, 9, 12, 18, and 24 months after transplantation along with history, clinical examination, and PFTs. Serum levels of lung proteins were also measured in healthy control subjects. The primary endpoint was the development of BOS confirmed by pathological biopsy or National Institutes of Health criteria. Between September 2009 and September 2011, 39 patients were enrolled. Six children developed BOS at a median time of 200 days (range, 94 to 282). KL-6 levels were low in control subjects, at a median of .1 U/mL (range, .1 to 1.5). Pre-SCT and 1-month KL-6 levels were significantly higher in surviving patients who developed BOS (n = 6) versus those who did not (n = 18) (pre-SCT: mean, 32.6 U/mL [IQR, 9.7 to 89.3] versus 5.8 U/mL [IQR, 2.1 to 12.6], P = .03; at 1 month: mean, 52.5 U/mL [IQR, 20.2 to 121.3] versus 11.4 U/mL [IQR, 5.7 to 36.0], P = .04). Three- and 6-month KL-6 levels continued to be higher in BOS group but were not statistically significant. CCSP, SP-A, and SP-D were not predictive. KL-6 measured in the serum of children receiving allo-SCT may identify patients at high risk for the development of BOS. These patients will benefit from intensive surveillance protocol and early therapy before irreversible lung damage. PMID:25963919

  20. CONTENTS OF LYMPHOCYTE SUB-POPULATIONS IN THE CHILDREN WITH ACUTE LEUKEMIA AND LYMPHOMAS DEPENDENT ON INFECTIOUS COMPLICATION AND NEUTROPENIA

    Directory of Open Access Journals (Sweden)

    M. V. Peshikova

    2005-01-01

    Full Text Available Abstract. The aim of the present work was to evaluate the contents of some lymphocyte sub-populations in peripheral blood of the children with tumors of hematopoietic and lymphoid tissues, depending on infectious complication of cytostatic therapy and neutropenia. In all children undergoing cytostatic therapy for acute lympho-blastic leukemia and non-B cell non-Hodgkinґs lymphomas, we found significant decrease in the numbers of CD95 lymphocytes, absolute amounts of natural killer cells (CD16, CD56-lymphocytes and activated lymphocytes (СD11b, HLA-DR-cells, irrespective of neutrophile numbers in their blood and infectious complications. However, absolute number of CD25- lymphocytes was significantly decreased in the children with neutropenia. Relative contents of CD16, CD56, СD11b, HLA-DR, CD25-lymphocytes did not significantly differ from those in healthy children, or they were found to be significantly increased.

  1. CONTENTS OF LYMPHOCYTE SUB-POPULATIONS IN THE CHILDREN WITH ACUTE LEUKEMIA AND LYMPHOMAS DEPENDENT ON INFECTIOUS COMPLICATION AND NEUTROPENIA

    Directory of Open Access Journals (Sweden)

    M. V. Peshikova

    2014-07-01

    Full Text Available Abstract. The aim of the present work was to evaluate the contents of some lymphocyte sub-populations in peripheral blood of the children with tumors of hematopoietic and lymphoid tissues, depending on infectious complication of cytostatic therapy and neutropenia. In all children undergoing cytostatic therapy for acute lympho-blastic leukemia and non-B cell non-Hodgkinґs lymphomas, we found significant decrease in the numbers of CD95 lymphocytes, absolute amounts of natural killer cells (CD16, CD56-lymphocytes and activated lymphocytes (СD11b, HLA-DR-cells, irrespective of neutrophile numbers in their blood and infectious complications. However, absolute number of CD25- lymphocytes was significantly decreased in the children with neutropenia. Relative contents of CD16, CD56, СD11b, HLA-DR, CD25-lymphocytes did not significantly differ from those in healthy children, or they were found to be significantly increased.

  2. Exercise as an Adjuvant Therapy for Hematopoietic Stem Cell Mobilization

    Science.gov (United States)

    Emmons, Russell; Niemiro, Grace M.; De Lisio, Michael

    2016-01-01

    Hematopoietic stem cell transplant (HSCT) using mobilized peripheral blood hematopoietic stem cells (HSPCs) is the only curative strategy for many patients suffering from hematological malignancies. HSPC collection protocols rely on pharmacological agents to mobilize HSPCs to peripheral blood. Limitations including variable donor responses and long dosing protocols merit further investigations into adjuvant therapies to enhance the efficiency of HSPCs collection. Exercise, a safe and feasible intervention in patients undergoing HSCT, has been previously shown to robustly stimulate HSPC mobilization from the bone marrow. Exercise-induced HSPC mobilization is transient limiting its current clinical potential. Thus, a deeper investigation of the mechanisms responsible for exercise-induced HSPC mobilization and the factors responsible for removal of HSPCs from circulation following exercise is warranted. The present review will describe current research on exercise and HSPC mobilization, outline the potential mechanisms responsible for exercise-induced HSPC mobilization, and highlight potential sites for HSPC homing following exercise. We also outline current barriers to the implementation of exercise as an adjuvant therapy for HSPC mobilization and suggest potential strategies to overcome these barriers. PMID:27123008

  3. Molecular mechanisms underlying adhesion and migration of hematopoietic stem cells

    OpenAIRE

    Sahin, Aysegul Ocal; Buitenhuis, Miranda

    2012-01-01

    Hematopoietic stem cell transplantation is the most powerful treatment modality for a large number of hematopoietic malignancies, including leukemia. Successful hematopoietic recovery after transplantation depends on homing of hematopoietic stem cells to the bone marrow and subsequent lodging of those cells in specific niches in the bone marrow. Migration of hematopoietic stem cells to the bone marrow is a highly regulated process that requires correct regulation of the expression and activit...

  4. Parasitic Infections in Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Jarque, Isidro; Salavert, Miguel; Pemán, Javier

    2016-01-01

    Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients. PMID:27413527

  5. PARASITIC INFECTIONS IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

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    Isidro Jarque

    2016-07-01

    Full Text Available Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However, they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients.

  6. Bone Marrow Vascular Niche: Home for Hematopoietic Stem Cells

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    Ningning He

    2014-01-01

    Full Text Available Though discovered later than osteoblastic niche, vascular niche has been regarded as an alternative indispensable niche operating regulation on hematopoietic stem cells (HSCs. As significant progresses gained on this type niche, it is gradually clear that the main work of vascular niche is undertaking to support hematopoiesis. However, compared to what have been defined in the mechanisms through which the osteoblastic niche regulates hematopoiesis, we know less in vascular niche. In this review, based on research data hitherto we will focus on component foundation and various functions of vascular niche that guarantee the normal hematopoiesis process within bone marrow microenvironments. And the possible pathways raised by various research results through which this environment undergoes its function will be discussed as well.

  7. Generation of axolotl hematopoietic chimeras

    Directory of Open Access Journals (Sweden)

    David Lopez

    2015-02-01

    Full Text Available Wound repair is an extremely complex process that requires precise coordination between various cell types including immune cells.  Unfortunately, in mammals this usually results in scar formation instead of restoration of the original fully functional tissue, otherwise known as regeneration.  Various animal models like frogs and salamanders are currently being studied to determine the intracellular and intercellular pathways, controlled by gene expression, that elicit cell proliferation, differentiation, and migration of cells during regenerative healing.  Now, the necessary genetic tools to map regenerative pathways are becoming available for the axolotl salamander, thus allowing comparative studies between scarring and regeneration.  Here, we describe in detail three methods to produce axolotl hematopoietic cell-tagged chimeras for the study of hematopoiesis and regeneration.

  8. The Biology of Allogeneic Hematopoietic Cell Resistance

    Science.gov (United States)

    Shizuru, Judith A.; Bhattacharya, Deepta; Cavazzana-Calvo, Marina

    2016-01-01

    At the most basic level, success of an allogeneic hematopoietic cell transplantation (HCT) procedure relies upon the engraftment of recipients with donor hematopoietic stem cells (HSCs) that will generate blood formation for the life of that individual. The formula to achieve durable HSC engraftment involves multiple factors including the recipient conditioning regimen, the nature of the genetic disparity between donor and recipient, and the content of the hematopoietic graft. Animal and clinical studies have shown that the biology of host resistance is complex, involving both immune and nonimmune elements. In this article, we review the factors that contribute to host resistance, describe emerging concepts on the basic biology of resistance, and discuss hematopoietic resistance as it relates specifically to patients with severe combined immunodeficiencies (SCID)— disorders that bring unique insights into the dynamics of cell replacement by allogeneic HSCs and progenitor cells. PMID:19913629

  9. Return to the hematopoietic stem cell origin

    OpenAIRE

    Samokhvalov, Igor M.

    2012-01-01

    Studying embryonic hematopoiesis is complicated by diversity of its locations in the constantly changing anatomy and by the mobility of blood cell precursors. Embryonic hematopoietic progenitors are identified in traditional in vivo and in vitro cell potential assays. Profound epigenetic plasticity of mammalian embryonic cells combined with significant inductive capacity of the potential assays suggest that our understanding of hematopoietic ontogenesis is substantially distorted. Non-invasiv...

  10. Thrombopoietin expands hematopoietic stem cells after transplantation

    OpenAIRE

    Fox, Norma; Priestley, Greg; Papayannopoulou, Thalia; Kaushansky, Kenneth

    2002-01-01

    Multiple lines of evidence indicate that thrombopoietin (TPO) contributes to the development of hematopoietic stem cells (HSC), supporting their survival and proliferation in vitro. To determine whether TPO supports the impressive expansion of HSC observed following transplantation, we transplanted normal marrow cells into lethally irradiated Tpo–/– and Tpo+/+ mice and quantified HSC self-renewal and expansion and hematopoietic progenitor cell homing. Although essentially identical numbers of...

  11. SNP Array in Hematopoietic Neoplasms: A Review

    Science.gov (United States)

    Song, Jinming; Shao, Haipeng

    2015-01-01

    Cytogenetic analysis is essential for the diagnosis and prognosis of hematopoietic neoplasms in current clinical practice. Many hematopoietic malignancies are characterized by structural chromosomal abnormalities such as specific translocations, inversions, deletions and/or numerical abnormalities that can be identified by karyotype analysis or fluorescence in situ hybridization (FISH) studies. Single nucleotide polymorphism (SNP) arrays offer high-resolution identification of copy number variants (CNVs) and acquired copy-neutral loss of heterozygosity (LOH)/uniparental disomy (UPD) that are usually not identifiable by conventional cytogenetic analysis and FISH studies. As a result, SNP arrays have been increasingly applied to hematopoietic neoplasms to search for clinically-significant genetic abnormalities. A large numbers of CNVs and UPDs have been identified in a variety of hematopoietic neoplasms. CNVs detected by SNP array in some hematopoietic neoplasms are of prognostic significance. A few specific genes in the affected regions have been implicated in the pathogenesis and may be the targets for specific therapeutic agents in the future. In this review, we summarize the current findings of application of SNP arrays in a variety of hematopoietic malignancies with an emphasis on the clinically significant genetic variants.

  12. RESULTS OF HEMATOPOIETIC CELL TRANSPLANTATION IN PEDIATRIC LEUKEMIA

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    A. Mousavi

    2008-05-01

    Full Text Available Hematopoietic cell transplantation (HCT is an accepted treatment for acute myeloid leukemia (AML in first remission, the treatment of choice for chronic myeloid leukemia (CML and high risk groups of ALL who relapse with conventional chemotherapy. We assessed results of HCT for pediatric leukemia in our center. A total of 92 children, 63 with diagnose of AML, 23 with ALL and 6 with CML received allogeneic transplantation from HLA full matched siblings (57.6% and autologous transplantation (42.4%. Source of hematopoietic cells were peripheral blood 83.7%, bone marrow 15.2% and cord blood 1.6%. The median transplanted nucleated cells were 6.4 ± 4.7 ×108 /Kg (body weight of patients and mononuclear cells were 5.5 ± 2.9×108/Kg. The most common conditioning regimens were cyclophosphamide + busulfan. Prophylaxis regimen for GVHD was cyclosporin ± methotrexate. GVHD occurred in 50 (54.3% patients. Eighty five of children had engraftment, 26 (28.6% relapsed and 57 (62% are alive. The most common cause of death was relapse (68.6%. Five years overall survival of patients with AML and ALL were 49% and 44% respectively and disease free survival of them were 52% and 49%. One year overall survival and disease free survival of CML was 57%. Overall survival increased with increasing age of patients at transplantation time (P = 0.06. Longer survival significantly related to earlier WBC and platelet recovery (P < 0.0001 and P = 0.006 respectively. Considering acceptable overall and disease free survival of patients after HCT, we concluded that is a good modality in treatment of leukemia of children.

  13. Advance in hematopoietic stem cells transplantation for leukemia

    Institute of Scientific and Technical Information of China (English)

    HUANG Xiao-jun

    2008-01-01

    @@ During the past 50 years, intensive studies into the characteristics of hematopoietic stem cell transplantation immunology and the emergence of new immunosuppressant and anti-infective drugs have significantly improved the clinical result of hematopoietic stem cell transplantation (HSCT).

  14. Lentivirus-mediated Gene Transfer in Hematopoietic Stem Cells Is Impaired in SHIV-infected, ART-treated Nonhuman Primates

    OpenAIRE

    Younan, Patrick M; Peterson, Christopher W.; Polacino, Patricia; Kowalski, John P.; Obenza, Willimark; Miller, Hannah W.; Milless, Brian P; Gafken, Phil; DeRosa, Stephen C; Hu, Shiu-Lok; Kiem, Hans-Peter

    2015-01-01

    Recent studies have demonstrated that genetically modified hematopoietic stem cells (HSCs) can reduce HIV viremia. We have developed an HIV/AIDS-patient model in Simian/human immunodeficiency virus (SHIV)-infected pigtailed macaques that are stably suppressed on antiretroviral therapy (ART: raltegravir, emtricitabine and tenofovir). Following SHIV infection and ART, animals undergo autologous HSC transplantation (HSCT) with lentivirally transduced cluster of differentiation (CD)34+ cells expr...

  15. Hematopoietic Cell Transplant and Use of Massage for Improved Symptom Management: Results from a Pilot Randomized Control Trial

    Directory of Open Access Journals (Sweden)

    Wolf E. Mehling

    2012-01-01

    Discussion. Feasibility of studying massage-acupressure was established in children undergoing HCT. Larger studies are needed to test the efficacy of such interventions in reducing HCT-associated symptoms in children.

  16. Promoter methylation and expression levels of selected hematopoietic genes in pediatric B-cell acute lymphoblastic leukemia

    OpenAIRE

    Musialik, Ewa; Bujko, Mateusz; Kober, Paulina; Agnieszka WYPYCH; Gawle-Krawczyk, Karolina; Matysiak, Michal; Siedlecki, Janusz Aleksander

    2015-01-01

    Background Precursor B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common neoplasm in children and is characterized by genetic and epigenetic aberrations in hematopoietic transcription factor (TF) genes. This study evaluated promoter DNA methylation and aberrant expression levels of early- and late-acting hematopoietic TF genes homeobox A4 and A5 (HOXA4 and HOXA5), Meis homeobox 1 (MEIS1), T-cell acute lymphocytic leukemia 1 (TAL1), and interferon regulatory factors 4 and 8 (IR...

  17. Human hematopoietic cell culture, transduction, and analyses

    DEFF Research Database (Denmark)

    Bonde, Jesper; Wirthlin, Louisa; Kohn, Donald B;

    2008-01-01

    This unit provides methods for introducing genes into human hematopoietic progenitor cells. The Basic Protocol describes isolation of CD34(+) cells, transduction of these cells with a retroviral vector on fibronectin-coated plates, assaying the efficiency of transduction, and establishing long......-term cultures. Support protocols describe methods for maintenance of vector-producing fibroblasts (VPF) and supernatant collection from these cells, screening medium components for the ability to support hematopoietic cell growth, and establishing colonies from long-term cultures. Other protocols provide PCR...

  18. Transplante de células-tronco hematopoéticas em crianças e adolescentes com leucemia aguda: experiência de duas instituições Brasileiras Hematopoietic stem cell transplantation in children and adolescents with acute leukemia: experience of two Brazilian institutions

    Directory of Open Access Journals (Sweden)

    Juliane Morando

    2010-01-01

    acute lymphocytic leukemia (ALL and 89 had acute myeloid leukemia (AML. Early disease was considered for CR1 and CR2 cases and advanced disease >CR3 and refractory and relapse disease. Ninety patients are alive between 258 and 6068 days after hematopoietic stem cell transplantation (M: 1438 days. The overall survival (OS was 45% (3 years and event free survival (EFS was 39% (3 years. Primary graft failure occurred in 14/195 patients (8%. There were no differences in the overall survival and event free survival between patients with acute lymphocytic leukemia and acute myeloid leukemia, between sources of cells used or between those who developed acute or chronic graft-versus-host disease (GVHD. When comparing transplants from related and unrelated donors, there was no difference in the overall survival. Patients with acute lymphocytic leukemia receiving the total body irradiation (TBI conditioning regimen had better overall survival and event free survival (p<0.001. One hundred and eighteen patients died between 0 and 1654 days after hematopoietic stem cell transplantation (M: 160 days. Transplantation-related-mortality (TRM at D+100 was 16% and cumulative incidence of relapse was 40% (3 years. Patients with advanced disease had lower 3-year overall survival and event free survival (p<0.001. Multivariate analysis showed that disease status was the most significant factor associated with higher event free survival and overall survival . Our results show that children and adolescents transplanted with early disease can achieve considerable overall survival and also highlights the inefficacy of hematopoietic stem cell transplantation for patients with advanced disease.

  19. Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation.

    Science.gov (United States)

    Bernardo, M E; Ball, L M; Cometa, A M; Roelofs, H; Zecca, M; Avanzini, M A; Bertaina, A; Vinti, L; Lankester, A; Maccario, R; Ringden, O; Le Blanc, K; Egeler, R M; Fibbe, W E; Locatelli, F

    2011-02-01

    When compared with BMT, umbilical cord blood transplantation (UCBT) is associated with a lower rate of engraftment and delayed hematological/immunological recovery. This leads to increased risk of TRM in the early post transplantation period due to infection. Acute GVHD, although occurring less frequently in UCBT compared with BMT, is also significantly associated with increased rate of early TRM. BM MSCs are known to support normal in vivo hematopoiesis, and co-transplantation of MSCs has been shown to enhance engraftment of human cord blood hematopoietic cells in nonobese diabetic/SCID mice. In 13 children with hematological disorders (median age 2 years) undergoing UCBT, we co-transplanted paternal, HLA-disparate MSCs with the aim of improving hematological recovery and reducing rejection. We observed no differences in hematological recovery or rejection rates compared with 39 matched historical controls, most of whom received G-CSF after UCBT. However, the rate of grade III and IV acute GVHD was significantly decreased in the study cohort when compared with controls (P=0.05), thus resulting in reduced early TRM. Although these data do not support the use of MSCs in UCBT to support hematopoietic engraftment, they suggest that MSCs, possibly because of their immunosuppressive effect, may abrogate life-threatening acute GVHD and reduce early TRM. PMID:20400983

  20. Application of children's toothbrush combined with warm water washing method in oral nursing of children undergoing orotracheal intubation%儿童牙刷刷牙结合温开水冲洗法在经口气管插管病人口腔护理中的应用

    Institute of Scientific and Technical Information of China (English)

    刘琼; 刘静兰; 刘敏; 周瑞; 吕娟

    2012-01-01

    [目的]探讨儿童牙刷刷牙结合冲洗法对经口气管插管病人口腔护理的临床效果.[方法]将150例经口气管插管病人随机分为对照组和观察组各75例,现察组采用儿童牙刷刷牙结合温开水冲洗法进行口腔护理,对照组采用常规口腔护理方法.比较两组病人口腔清洁效果、牙菌斑指数及口腔并发症发生情况.[结果]两组口腔清洁度、牙菌斑指数和并发症的发生情况比较,差异有统计学意义.[结论]儿童牙刷刷牙结合温开水冲洗法能有效清除牙菌斑,提高口腔清洁度,预防及降低口腔并发症的发生.%Objective;To probe into the clinical effect of children's tooth-brush combined with warm water washing method for oral nursing in chil-dren undergoing orotracheal intubation. Methods; A total of 150 patients undergoing endotracheal intubation were randomly divided into control group and observation group,75 cases in each. The observation group cases accepted the oral nursing with children's toothbrush combined with warm boiling water washing method. The conventional oral nursing method was carried out for the control group cases. The oral hygiene effects,plaque in-dex and oral complications were compared between the two groups. Re-sults :There was statistical significant difference in oral hygiene effects, plaque index and oral complications occurrence between the two groups. Conclusion: Children' s toothbrush combined with warm water washing boiling method can effectively remove plaque, improve oral cleanness, pre-vent and reduce oral complications.

  1. Clinical use of statins in hematopoietic stem cell transplantation: Old drugs and new horizons.

    Science.gov (United States)

    Mohammadi, Mehdi; Vaezi, Mohammad; Mirrahimi, Bahador; Hadjibabaie, Molouk

    2016-01-01

    Hydroxymethylglutaryl Co-enzyme A reductase inhibitors, also known as statins, are a class of anti-hyperlipidemic agents. These drugs have been employed vastly to reduce the morbidity and mortality of cardiovascular disorders. Soon after their introduction, benefits other than their primary actions were discovered. Along with these pleiotropic properties, a series of mainly favorable effects has been proposed in patients intended to undergo hematopoietic stem cell transplantation. These actions address some complications encountered by this special population such as graft-versus-host disease, efficacy of chemotherapy, infections, etc. This review presents the current evidence surrounding these issues. PMID:27047650

  2. Drosophila Rabex-5 restricts Notch activity in hematopoietic cells and maintains hematopoietic homeostasis

    OpenAIRE

    Reimels, Theresa A.; Cathie M. Pfleger

    2015-01-01

    ABSTRACT Hematopoietic homeostasis requires the maintenance of a reservoir of undifferentiated blood cell progenitors and the ability to replace or expand differentiated blood cell lineages when necessary. Multiple signaling pathways function in these processes, but how their spatiotemporal control is established and their activity is coordinated in the context of the entire hematopoietic network are still poorly understood. We report here that loss of the gene Rabex-5 in Drosophila causes se...

  3. Unrelated hematopoietic stem cell registry and the role of the Hematopoietic Stem Cell Bank

    OpenAIRE

    Beom, Su-Hee; Kim, Eung Jo; Kim, Miok; Kim, Tai-Gyu

    2016-01-01

    Background The hematopoietic stem cell bank has been actively recruiting registrants since 1994. This study systematically reviews its operations and outcomes over the last 20 years. Methods Retrospective data on a total of 47,711 registrants were reviewed. Relevant data were processed using PASW Statistics for Windows, version 18.0. Results As of 2013, the Korean Network for Organ Sharing database contained 265,307 registrants. Of these, 49,037 (18%) registrants committed to hematopoietic ce...

  4. Study of Pulmonary Complications in Pediatric Patients With Storage Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    2005-06-23

    I Cell Disease; Fucosidosis; Globoid Cell Leukodystrophy; Adrenoleukodystrophy; Mannosidosis; Niemann-Pick Disease; Pulmonary Complications; Mucopolysaccharidosis I; Mucopolysaccharidosis VI; Metachromatic Leukodystrophy; Gaucher's Disease; Wolman Disease

  5. Hematopoiesis and hematopoietic organs in arthropods.

    Science.gov (United States)

    Grigorian, Melina; Hartenstein, Volker

    2013-03-01

    Hemocytes (blood cells) are motile cells that move throughout the extracellular space and that exist in all clades of the animal kingdom. Hemocytes play an important role in shaping the extracellular environment and in the immune response. Developmentally, hemocytes are closely related to the epithelial cells lining the vascular system (endothelia) and the body cavity (mesothelia). In vertebrates and insects, common progenitors, called hemangioblasts, give rise to the endothelia and blood cells. In the adult animal, many differentiated hemocytes seem to retain the ability to proliferate; however, in most cases investigated closely, the bulk of hemocyte proliferation takes place in specialized hematopoietic organs. Hematopoietic organs provide an environment where undifferentiated blood stem cells are able to self-renew, and at the same time generate offspring that differentiate into different blood cell types. Hematopoiesis in vertebrates, taking place in the bone marrow, has been subject to intensive research by immunologists and stem cell biologists. Much less is known about blood cell formation in invertebrate animals. In this review, we will survey structural and functional properties of invertebrate hematopoietic organs, with a main focus on insects and other arthropod taxa. We will then discuss similarities, at the molecular and structural level, that are apparent when comparing the development of blood cells in hematopoietic organs of vertebrates and arthropods. Our comparative review is intended to elucidate aspects of the biology of blood stem cells that are more easily missed when focusing on one or a few model species. PMID:23319182

  6. Autonomous behavior of hematopoietic stem cells

    NARCIS (Netherlands)

    Kamminga, LM; Akkerman, [No Value; Weersing, E; Ausema, A; Dontje, B; Van Zant, G; de Haan, G

    2000-01-01

    Objective. Mechanisms that affect the function of primitive hematopoietic stem cells with long-term proliferative potential remain largely unknown. Here we assessed whether properties of stem cells are cell-extrinsically or cell-autonomously regulated. Materials and Methods. We developed a model in

  7. Cellular memory and, hematopoietic stem cell aging

    NARCIS (Netherlands)

    Kamminga, Leonie M.; de Haan, Gerald

    2006-01-01

    Hematopoietic stem cells (HSCs) balance self-renewal and differentiation in order to sustain lifelong blood production and simultaneously maintain the HSC pool. However, there is clear evidence that HSCs are subject to quantitative and qualitative exhaustion. In this review, we briefly discuss sever

  8. Hematopoietic stem cell transplantation in multiple sclerosis

    DEFF Research Database (Denmark)

    Rogojan, C; Frederiksen, J L

    2009-01-01

    Intensive immunosuppresion followed by hematopoietic stem cell transplantation (HSCT) has been suggested as potential treatment in severe forms of multiple sclerosis (MS). Since 1995 ca. 400 patients have been treated with HSCT. Stabilization or improvement occurred in almost 70% of cases at least...

  9. 用多感官型分心装置缓解患儿伤口处理时疼痛的研究%Multimodal distraction to relieve pain in children undergoing acute medical procedures

    Institute of Scientific and Technical Information of China (English)

    Kate Miller; Sylvia Rodger; Sam Bucolo; Xue-Qing WANG; Roy M Kim-ble

    2009-01-01

    Objective Non-pharmacological approaches to pain management have been used by therapists for decades to reduce the anxiety and pain experienced by children during burn care procedures. With a greater understanding of pain and the principles behind what causes a child to be distracted, com-bined with access to state of the art technology, we have developed an easy to use, hand held multimodal distraction device (MMD). MMD is an interactive device that prepares the child for a procedure and uses developmentally appropriate distraction stories and games during the procedures to alleviate anxiety and pain. This paper summarizes the results of three randomized control trials. The trials aimed to understand the effec-tiveness of MMD as a distraction and preparation tool in reducing anxiety and pain in children undergoing burns and non-burns medical procedures compared to pure pharmacological approaches Standard Distraction (SD) and off the shelf video games (VG). Methods Three separate prospective randomized control tri-als involving 182 children having 354 dressing changes were conducted in the burns and orthopedic depart-ments at Royal Children's Hospital, Brisbane, Australia, to address the above aims. Pain and anxiety scores were completed for the child, caregivcr and nursing staff according to the Modified Faces, Legs, Activity, Cry and Consolability Scale, Faces Pain Scale-Revised, Visual Analogue Scale and Wong-Baker Faces Pain Rating Scale. Procedural length was recorded. Results MMD as a preparation and distraction tool were shown to have a significant impact on child, parent and nursing staff reported anxiety and pain daring proce-dures compared to standard care and video games (P<0.01). The MMD had a positive effect on clinical time and was shown to sustain its impact on pain and time with further dressing changes. Conclusions MMD is more effective in reducing the pain and anxiety experienced by children in acute medical procedures as compared with SD and VG

  10. Clinical and In Vitro Studies on Impact of High-Dose Etoposide Pharmacokinetics Prior Allogeneic Hematopoietic Stem Cell Transplantation for Childhood Acute Lymphoblastic Leukemia on the Risk of Post-Transplant Leukemia Relapse.

    Science.gov (United States)

    Sobiak, Joanna; Kazimierczak, Urszula; Kowalczyk, Dariusz W; Chrzanowska, Maria; Styczyński, Jan; Wysocki, Mariusz; Szpecht, Dawid; Wachowiak, Jacek

    2015-10-01

    The impact of etoposide (VP-16) plasma concentrations on the day of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on leukemia-free survival in children with acute lymphoblastic leukemia (ALL) was studied. In addition, the in vitro effects of VP-16 on the lymphocytes proliferation, cytotoxic activity and on Th1/Th2 cytokine responses were assessed. In 31 children undergoing allo-HSCT, VP-16 plasma concentrations were determined up to 120 h after the infusion using the HPLC-UV method. For mentioned in vitro studies, VP-16 plasma concentrations observed on allo-HSCT day were used. In 84 % of children, VP-16 plasma concentrations (0.1-1.5 μg/mL) were quantifiable 72 h after the end of the drug infusion, i.e. when allo-HSCT should be performed. In 20 (65 %) children allo-HSCT was performed 4 days after the end of the drug infusion, and VP-16 was still detectable (0.1-0.9 μg/mL) in plasma of 12 (39 %) of them. Post-transplant ALL relapse occurred in four children, in all of them VP-16 was detectable in plasma (0.1-0.8 μg/mL) on allo-HSCT day, while there was no relapse in children with undetectable VP-16. In in vitro studies, VP-16 demonstrated impact on the proliferation activity of stimulated lymphocytes depending on its concentration and exposition time. The presence of VP-16 in plasma on allo-HSCT day may demonstrate an adverse effect on graft-versus-leukemia (GvL) reaction and increase the risk of post-transplant ALL relapse. Therefore, if 72 h after VP-16 administration its plasma concentration is still above 0.1 μg/mL then the postponement of transplantation for next 24 h should be considered to protect GvL effector cells from transplant material. PMID:26040247

  11. Care of patients undergoing external radiotherapy

    International Nuclear Information System (INIS)

    The anxiety and associated depression suffered by most patients undergoing radiotherapy is discussed and the possibilities open to the nurse to encourage and reassure patients thus facilitating physical care are considered. The general symptoms of anorexia, nausea, tiredness, skin problems, alopecia, bonemarrow depresssion and rapid tumour destruction are described and nursing care prescribed. The side-effects which may occur following radiation of the brain, head and neck region, eyes, oesophagus, lung, abdomen, pelvis, bones, skin, spine, and spinal cord are considered from the nursing standpoint. The specialised subject of radiotherapy in children is discussed briefly. (U.K.)

  12. Hematopoietic stem cell transplantation monitoring in childhood. Hematological diseases in Serbia: STR-PCR techniques

    Directory of Open Access Journals (Sweden)

    Krstić Aleksandra D.

    2007-01-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is a very successful method of treatment for children with different aquired or inborn diseases. The main goal of post-transplantation chimerism monitoring in HSCT is to predict negative events (such as disease relapse and graft rejection, in order to intervene with appropriate therapy and improve the probability of long-term DFS (disease free survival. In this context, by quantifying the relative amounts of donor and recipient cells present in the peripheral blood sample, it can be determined if engraftment has taken place at all, or if full or mixed chimerism exists. In a group of patients who underwent hematopoietic stem cell transplantation at the Mother and Child Health Care Institute, we decided to use standard human identfication tests based on multiplex PCR analyses of short tandem repeats (STRs, as they are highly informative, sensitive, and fast and therefore represent an optimal methodological approach to engraftment analysis.

  13. Characterization of Selectin Ligands on Hematopoietic Stem Cells

    KAUST Repository

    Mahmood, Hanan

    2013-05-18

    Successful bone marrow (BM) transplantation requires the homing of the transplanted hematopoietic stem/progenitor cells (HSPCs) to their bone marrow niche, where they undergo differentiation to form mature cells that are eventually released into the peripheral blood. However, the survival rate of patients receiving BM transplants is poor since many of the transplanted HSPCs do not make it to their BM niches in the recipient’s body. Since the availability of HSPCs from traditional sources is limited, transplanting more number of HSPCs is not a solution to this problem. This study aims to characterize the adhesion molecules mediating cell migration in order to better understand the adhesion mechanisms of HSCs with the bone marrow endothelium. This will aid in developing future tools to improve the clinical transplantation of HSPCs. This study also aims to understand the factors that influence HSPC proliferation in the bone marrow niche. E-selectin plays an important role in the process of homing; however, its ligands on HSPCs are not well characterized. We used western blotting and immunoprecipitation to show that endomucin is expressed on HSPCs and plays a role in the binding of HSPCs to E-selectin. We also studied the effect of recombinant E-selectin on the expression of a newly characterized E-selectin ligand in our lab, CD34, in HSPCs. This will provide us insight into novel roles for endomucin and E-selectin and help us to understand the factors influencing HSPC migration to BM endothelium.

  14. Secondary solid cancer screening following hematopoietic cell transplantation

    Science.gov (United States)

    Inamoto, Y; Shah, NN; Savani, BN; Shaw, BE; Abraham, AA; Ahmed, IA; Akpek, G; Atsuta, Y; Baker, KS; Basak, GW; Bitan, M; DeFilipp, Z; Gregory, TK; Greinix, HT; Hamadani, M; Hamilton, BK; Hayashi, RJ; Jacobsohn, DA; Kamble, RT; Kasow, KA; Khera, N; Lazarus, HM; Malone, AK; Lupo-Stanghellini, MT; Margossian, SP; Muffly, LS; Norkin, M; Ramanathan, M; Salooja, N; Schoemans, H; Wingard, JR; Wirk, B; Wood, WA; Yong, A; Duncan, CN; Flowers, MED; Majhail, NS

    2016-01-01

    Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients. PMID:25822223

  15. Proliferative capacity of murine hematopoietic stem cells

    International Nuclear Information System (INIS)

    The present study demonstrates a decrease in self-renewal capacity with serial transfer of murine hematopoietic stem cells. Production of differentiated cell progeny is maintained longer than stem cell self-renewal. In normal animals the capacity for self-renewal is not decreased with increasing donor age. The stem cell compartment in normal animals, both young and old, appears to be proliferatively quiescent. After apparent recovery from the alkylating agent busulfan, the probability of stem cell self-renewal is decreased, there is a permanent defect in the capacity of the bone marrow for serial transplantation, and the stem cells are proliferatively active. These findings support a model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation, and increasing proliferative activity. Cells progress in the continuum in one direction and such progression is not reversible

  16. Recent advances in hematopoietic stem cell biology

    DEFF Research Database (Denmark)

    Bonde, Jesper; Hess, David A; Nolta, Jan A

    2004-01-01

    made recently in the field of stem cell biology, researchers now have improved tools to define novel populations of stem cells, examine them ex vivo using conditions that promote self-renewal, track them into recipients, and determine whether they can contribute to the repair of damaged tissues......PURPOSE OF REVIEW: Exciting advances have been made in the field of hematopoietic stem cell biology during the past year. This review summarizes recent progress in the identification, culture, and in vivo tracking of hematopoietic stem cells. RECENT FINDINGS: The roles of Wnt and Notch proteins...... in regulating stem cell renewal in the microenvironment, and how these molecules can be exploited in ex vivo stem cell culture, are reviewed. The importance of identification of stem cells using functional as well as phenotypic markers is discussed. The novel field of nanotechnology is then discussed...

  17. Immunoselection techniques in hematopoietic stem cell transplantation.

    Science.gov (United States)

    Li Pira, Giuseppina; Biagini, Simone; Cicchetti, Elisabetta; Merli, Pietro; Brescia, Letizia Pomponia; Milano, Giuseppe Maria; Montanari, Mauro

    2016-06-01

    Hematopoietic Stem Cells Transplantation (HSCT) is an effective treatment for hematological and non-hematological diseases. The main challenge in autologous HSCT is purging of malignant cells to prevent relapse. In allogeneic HSCT graft-versus-host disease (GvHD) and opportunistic infections are frequent complications. Two types of graft manipulation have been introduced: the first one in the autologous context aimed at separating malignant cells from hematopoietic stem cells (HSC), and the second one in allogeneic HSCT aimed at reducing the incidence of GvHD and at accelerating immune reconstitution. Here we describe the manipulations used for cell purging in autologous HSCT or for T Cell Depletion (TCD) and T cell selection in allogeneic HSCT. More complex manipulations, requiring a Good Manufacturing Practice (GMP) facility, are briefly mentioned. PMID:27209628

  18. Proteomic cornerstones of hematopoietic stem cell differentiation

    DEFF Research Database (Denmark)

    Klimmeck, Daniel; Hansson, Jenny; Raffel, Simon;

    2012-01-01

    Regenerative tissues such as the skin epidermis, the intestinal mucosa or the hematopoietic system are organized in a hierarchical manner with stem cells building the top of this hierarchy. Somatic stem cells harbor the highest self-renewal activity and generate a series of multipotent progenitors...... which differentiate into lineage committed progenitors and subsequently mature cells. In this report, we applied an in-depth quantitative proteomic approach to analyze and compare the full proteomes of ex vivo isolated and FACS-sorted populations highly enriched for either multipotent hematopoietic stem....../progenitor cells (HSPCs, Lin(neg)Sca-1(+)c-Kit(+)) or myeloid committed precursors (Lin(neg)Sca-1(-)c-Kit(+)). By employing stable isotope dimethyl labeling and high-resolution mass spectrometry, more than 5,000 proteins were quantified. From biological triplicate experiments subjected to rigorous statistical...

  19. Exogenous endothelial cells as accelerators of hematopoietic reconstitution

    Directory of Open Access Journals (Sweden)

    Mizer J

    2012-11-01

    Full Text Available Abstract Despite the successes of recombinant hematopoietic-stimulatory factors at accelerating bone marrow reconstitution and shortening the neutropenic period post-transplantation, significant challenges remain such as cost, inability to reconstitute thrombocytic lineages, and lack of efficacy in conditions such as aplastic anemia. A possible means of accelerating hematopoietic reconstitution would be administration of cells capable of secreting hematopoietic growth factors. Advantages of this approach would include: a ability to regulate secretion of cytokines based on biological need; b long term, localized production of growth factors, alleviating need for systemic administration of factors that possess unintended adverse effects; and c potential to actively repair the hematopoietic stem cell niche. Here we overview the field of hematopoietic growth factors, discuss previous experiences with mesenchymal stem cells (MSC in accelerating hematopoiesis, and conclude by putting forth the rationale of utilizing exogenous endothelial cells as a novel cellular therapy for acceleration of hematopoietic recovery.

  20. Ex vivo Expansion of Hematopoietic Stem Cells

    OpenAIRE

    Farahbakhshian, Elnaz

    2013-01-01

    textabstractHematopoiesis is a complex cellular differentiation process resulting in the formation of all blood cell types. In this process, hematopoietic stem cells (HSCs) reside at the top of the hematopoiesis hierarchy and have the capacity to differentiate into all blood cell lineages (multipotency) as well as maintaining themselves (self-renewal) during the lifespan of an individual. Mouse primitive HSCs are first found in the blood islands of the extra-embryonic yolk sac at day 7.5 of g...

  1. Hematopoietic Stem Cells Contribute to Lymphatic Endothelium

    OpenAIRE

    Jiang, Shuguang; Bailey, Alexis S.; Goldman, Devorah C.; Swain, John R.; Wong, Melissa H.; Streeter, Philip R; Fleming, William H.

    2008-01-01

    Background Although the lymphatic system arises as an extension of venous vessels in the embryo, little is known about the role of circulating progenitors in the maintenance or development of lymphatic endothelium. Here, we investigated whether hematopoietic stem cells (HSCs) have the potential to give rise to lymphatic endothelial cells (LEC). Methodology/Principal Findings Following the transfer of marked HSCs into irradiated recipients, donor-derived LEC that co-express the lymphatic endot...

  2. Nonmyeloablative allogeneic hematopoietic stem cell transplantation.

    OpenAIRE

    Baron, Frédéric; Beguin, Yves

    2002-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective treatment for selected hematological malignancies. Its curative potential is largely mediated by an immune-mediated destruction of malignant cells by donor lymphocytes termed graft-versus-leukemia (GVL) effect. However, because of its toxicity, conventional allogeneic HSCT is restricted to younger and fitter patients. These observations led several groups to set up new (less toxic) transplant protocols (nonmyeloab...

  3. Placenta as a source of hematopoietic stem cells

    OpenAIRE

    Dzierzak, Elaine; Robin, Catherine

    2010-01-01

    The placenta is a large, highly vascularised hematopoietic tissue that functions during the embryonic and foetal development of eutherian mammals. Although recognised as the interface tissue important in the exchange of oxygen, nutrients and waste products between the foetus and mother, the placenta has increasingly become a focus of research concerning the ontogeny of the blood system. Here, we describe recent data showing the intrinsic hematopoietic potential and appearance of hematopoietic...

  4. Placenta as a source of hematopoietic stem cells

    OpenAIRE

    Dzierzak, Elaine; Robin, Catherine

    2010-01-01

    The placenta is a large, highly vascularized hematopoietic tissue that functions during embryonic and foetal development of eutherian mammals. Although recognized as the interface tissue important in the exchange of oxygen, nutrients and waste products between the foetus and mother, the placenta has increasingly become a focus of research concerning the ontogeny of the blood system. Here, we describe recent data showing the intrinsic hematopoietic potential and appearance of hematopoietic cel...

  5. Genotoxic sensitivity of the developing hematopoietic system.

    Science.gov (United States)

    Udroiu, Ion; Sgura, Antonella

    2016-01-01

    Genotoxic sensitivity seems to vary during ontogenetic development. Animal studies have shown that the spontaneous mutation rate is higher during pregnancy and infancy than in adulthood. Human and animal studies have found higher levels of DNA damage and mutations induced by mutagens in fetuses/newborns than in adults. This greater susceptibility could be due to reduced DNA repair capacity. In fact, several studies indicated that some DNA repair pathways seem to be deficient during ontogenesis. This has been demonstrated also in murine hematopoietic stem cells. Genotoxicity in the hematopoietic system has been widely studied for several reasons: it is easy to assess, deals with populations cycling also in the adults and may be relevant for leukemogenesis. Reviewing the literature concerning the application of the micronucleus test (a validated assay to assess genotoxicity) in fetus/newborns and adults, we found that the former show almost always higher values than the latter, both in animals treated with genotoxic substances and in those untreated. Therefore, we draw the conclusion that the genotoxic sensitivity of the hematopoietic system is more pronounced during fetal life and decreases during ontogenic development. PMID:27036061

  6. Prostaglandin E2 regulates hematopoietic stem cell

    International Nuclear Information System (INIS)

    Prostaglandin E2 (PGE2) is a bioactive lipid molecule produced by cyclooxygenase (COX), which plays an important role on hematopoiesis. While it can block differentiation of myeloid progenitors but enhance proliferation of erythroid progenitors. Recent research found that PGE2 have the effects on hematopoietic stem cell (HSC) function and these effects were independent from effects on progenitor cells. Exposure of HSC cells to PGE2 in vitro can increase homing efficiency of HSC to the murine bone marrow compartment and decrease HSC apoptosis, meanwhile increase long-term stem cell engraftment. In-vivo treatment with PGE2 expands short-term HSC and engraftment in murine bone marrow but not long-term HSC.In addition, PGE2 increases HSC survival after radiation injury and enhance hematopoietic recovery, resulting maintains hematopoietic homeostasis. PGE2 regulates HSC homeostasis by reactive oxygen species and Wnt pathway. Clinical beneficial of 16, 16-dimethyl-prostaglandin E2 treatment to enhance engraftment of umbilical cord blood suggest important improvements to therapeutic strategies. (authors)

  7. Hepatic complications of allogeneic hematopoietic cell transplantation

    Directory of Open Access Journals (Sweden)

    Ramazan Idilman

    2008-09-01

    Full Text Available Hepatic complications of allogeneic hematopoietic cell transplantation contribute substantially to the overall success of the procedure and represent a major cause of morbidity and mortality. Early hepatic complications consist of the sinusoidal obstruction syndrome, drug toxicities, infections, and acute graft-versus-host disease, while late hepatic complications consist of chronic graft-versus host disease, chronic viral hepatitis, and iron overload states. Successful management of the hepatic complications of allogeneic hematopoietic cell transplantation is dependent on several factors. These include the recognition and elimination of any pre-transplant risk factors for these problems and the development of strategies to evaluate and prevent them in both the early and later post-transplant periods. The aims of the present review are 1 to identify the early and late hepatic complications of allogeneic hematopoietic cell transplantation, in the chronological order in which they occur, 2 to characterize the diagnostic procedures used to identify them, and finally 3 to present the current therapeutic approaches used to manage these problems.

  8. Acute respiratory failure in 3 children with juvenile myelomonocytic leukemia

    DEFF Research Database (Denmark)

    Gustafsson, Britt; Hellebostad, Marit; Ifversen, Marianne;

    2011-01-01

    Juvenile myelomonocytic leukemia is a rare hematopoietic stem cell disease in children with features of both myelodysplasia and myeloproliferation. Extramedullary involvement has been reported and pulmonary involvement secondary to leukemic infiltration is an initial manifestation, which may result...

  9. Acute Respiratory Failure in 3 Children With Juvenile Myelomonocytic Leukemia

    DEFF Research Database (Denmark)

    Gustafsson, Britt; Hellebostad, Marit; Ifversen, Marianne;

    2011-01-01

    Juvenile myelomonocytic leukemia is a rare hematopoietic stem cell disease in children with features of both myelodysplasia and myeloproliferation. Extramedullary involvement has been reported and pulmonary involvement secondary to leukemic infiltration is an initial manifestation, which may result...

  10. Effect of dietary supplementation with Agaricus sylvaticus fungus on the hematology and immunology systems of breast cancer patients undergoing chemotherapy

    OpenAIRE

    Valadares, Fabiana; Novaes, Maria Rita Carvalho Garbi; Roberto Cañete VILLAFRANCA; Marília da Cunha MENEZES; Mariana Campos REIS; Gonçalves, Daniella Rodrigues

    2011-01-01

    Objective: Patients with cancer tend to develop hematological and immunological alterations during the disease process. Medicinal fungi can stimulate the immune and hematopoietic systems, promoting improvements in the prognosis and physiological response. In this trial it is aimed to evaluate changes in hematological and immunological parameters in patients with breast cancer undergoing chemotherapy after dietary supplementation with Agaricus sylvaticus. Method: A randomized, double-blind, pl...

  11. Comparison of itraconazole, voriconazole, and posaconazole as oral antifungal prophylaxis in pediatric patients following allogeneic hematopoietic stem cell transplantation

    OpenAIRE

    M. Döring; Blume, O; Haufe, S.; Hartmann, U; Kimmig, A.; Schwarze, C.-P.; Lang, P; Handgretinger, R; Müller, I

    2013-01-01

    Oral antifungal prophylaxis with extended-spectra azoles is widely used in pediatric patients after allogeneic hematopoietic stem cell transplantation (HSCT), while controlled studies for oral antifungal prophylaxis after bone marrow transplantation in children are not available. This survey analyzed patients who had received either itraconazole, voriconazole, or posaconazole. We focused on the safety, feasibility, and initial data of efficacy in a cohort of pediatric patients and adolescents...

  12. Less vasoocclusive disease after intravenous ersus oral busulfan for autologous hematopoietic cell transplantation : the Belgian pediatric experience

    OpenAIRE

    Huybrechts, S.; Beguin, Yves; Ferster, A; Laureys, G; UYTTEBROECK, A; Vermeylen, C

    2012-01-01

    Busulfan is commonly used in preparative conditioning regimens prior to hematopoietic stem cell transplantation in children and young adults for malignant and non-malignant disorders. For many years Busulfan was only available in an oral form, resulting in large inter- and intra-patients variability in plasma exposure, associated with higher graft failure rate as well as higher toxicity such as venoocclusive disease. With the development of an intravenous formulation of Busulfan, a more accur...

  13. Circulating hematopoietic progenitors and CD34+ cells predicted successful hematopoietic stem cell harvest in myeloma and lymphoma patients: experiences from a single institution

    Directory of Open Access Journals (Sweden)

    Yu JT

    2016-02-01

    Full Text Available Jui-Ting Yu,1,2,* Shao-Bin Cheng,3,* Youngsen Yang,1 Kuang-Hsi Chang,4 Wen-Li Hwang,1 Chieh-Lin Jerry Teng,1,5,6 1Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, 2Division of Hematology/Medical Oncology, Tungs' Taichung MetroHarbor Hospital, 3Division of General Surgery, Department of Surgery, 4Department of Medical Research and Education, Taichung Veterans General Hospital, 5Department of Life Science, Tunghai University, 6School of Medicine, Chung Shan Medical University, Taichung, Taiwan, Republic of China *These authors contributed equally to this work Background: Previous studies have shown that the numbers of both circulating hematopoietic progenitor cell (HPC and CD34+ cell are positively correlated with CD34+ cell harvest yield. However, the minimal numbers of both circulating HPCs and CD34+ cells required for performing an efficient hematopoietic stem cell (HSC harvest in lymphoma and myeloma patients have not been defined in our institution. Patients and methods: Medical records of 50 lymphoma and myeloma patients undergoing peripheral blood HSC harvest in our institution were retrospectively reviewed. The minimal and optimal HSC harvest yield required for the treatment was considered to be ≥2×106 CD34+ cells/kg and ≥5×106 CD34+ cells/kg, respectively. Results: The minimally required or optimal HSC yield obtained was not influenced by age (≥60 years, sex, underlying malignancies, disease status, multiple rounds of chemotherapy, or history of radiotherapy. The numbers of both circulating HPC and CD34+ cell were higher in patients with minimally required HSC yields (P=0.000 for HPC and P=0.000 for CD34+ cell and also in patients with optimal HSC yields (P=0.011 for HPC and P=0.006 for CD34+ cell. The cell count cutoff for obtaining minimally required HSC harvest was determined to be 20/mm3 for HPCs and 10/mm3 for CD34+ cells. Furthermore, the cell count cutoff for obtaining

  14. Hematopoietic potential cells in skeletal muscle

    Institute of Scientific and Technical Information of China (English)

    Atsushi Asakura

    2007-01-01

    @@ During mouse embryogenesis,the formation of primi-tive hematopoiesis begins in the yolk sac on embryonic day 7.5(E7.5).Thereafter,definitive hematopoietic stem cell(HSC)activity is first detectable in the aorta-gonad-mesonephros(AGM)region on E10,followed by fetal liver and yolk sac.Subsequently,the fetal liver by E12 becomes the main tissue for definitive hematopoiesis.At a later time,HSC population in the fetal liver migrates to the bone marrow,which becomes the maior site of he-matopoiesis throughout normal adult life[1].

  15. Mechanism of hematopoietic stem cell homing

    International Nuclear Information System (INIS)

    The clinical transplantation of hematopoietic stem cell (HSC) originating from many sources such as bone marrow, peripheral blood and cord blood has been widely applied in recent years. At the same time, the development of the study on the mechanism of HSC homing which involves multi-procedures has been achieved. And a lot of molecular and cytokines on the surface or in the microenvironment of HSC are functioning in homing. The purpose of is to review those molecular and cytokines on which more studies have been focused in the past

  16. Radiation response of human hematopoietic cells

    International Nuclear Information System (INIS)

    The radiosensitivity and capacity to accumulate and repair sub-lethal damage has been studied in hematopoietic cell lines of human origin and in stem cells derived from blood and bone narrow of normal human donors. The results were analysed in terms of the linear quadratic and multitarget models. For the cell lines intrinsic radiosensitivity varied widely with D/sub o/'s ranging from 0.53 to 1.39 Gy. Five of the cell lines showed same capacity to accumulate sub-lethal damage and in three of these survival was enhanced by dose fractionation or reduction of dose rate. Among the cell lines of leukemic origin, several did not conform in one or more respects with the highly radiosensitive and repair deficient model associated with hematopoietic cells. There was no apparent correlation between radiation response and the phenotype (myeloid, lymphoid or undifferentiated) of the cell lines studied. Variability of radiation response and in some cases an unpredicted degree of radioresistance and capacity to repair sub-lethal damage has now been demonstrated for both cultured and primary explants of human leukemic cells. These observations have implications for the design of Total Body Irradiation protocols for use prior to bone narrow transplant

  17. Epigenetic regulation of hematopoietic stem cell aging

    Energy Technology Data Exchange (ETDEWEB)

    Beerman, Isabel, E-mail: isabel.beerman@childrens.harvard.edu [Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 (United States); Department of Pediatrics, Harvard Medical School, Boston, MA 02115 (United States); Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children' s Hospital, MA 02116 (United States); Rossi, Derrick J. [Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 (United States); Department of Pediatrics, Harvard Medical School, Boston, MA 02115 (United States); Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children' s Hospital, MA 02116 (United States)

    2014-12-10

    Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and play a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks – DNA methylation and histone modifications – but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging.

  18. The biology of hematopoietic stem cells.

    Science.gov (United States)

    Szilvassy, Stephen J

    2003-01-01

    Rarely has so much interest from the lay public, government, biotechnology industry, and special interest groups been focused on the biology and clinical applications of a single type of human cell as is today on stem cells, the founder cells that sustain many, if not all, tissues and organs in the body. Granting organizations have increasingly targeted stem cells as high priority for funding, and it appears clear that the evolving field of tissue engineering and regenerative medicine will require as its underpinning a thorough understanding of the molecular regulation of stem cell proliferation, differentiation, self-renewal, and aging. Despite evidence suggesting that embryonic stem (ES) cells might represent a more potent regenerative reservoir than stem cells collected from adult tissues, ethical considerations have redirected attention upon primitive cells residing in the bone marrow, blood, brain, liver, muscle, and skin, from where they can be harvested with relative sociological impunity. Among these, it is arguably the stem and progenitor cells of the mammalian hematopoietic system that we know most about today, and their intense study in rodents and humans over the past 50 years has culminated in the identification of phenotypic and molecular genetic markers of lineage commitment and the development of functional assays that facilitate their quantitation and prospective isolation. This review focuses exclusively on the biology of hematopoietic stem cells (HSCs) and their immediate progeny. Nevertheless, many of the concepts established from their study can be considered fundamental tenets of an evolving stem cell paradigm applicable to many regenerating cellular systems. PMID:14734085

  19. Epigenetic regulation of hematopoietic stem cell aging

    International Nuclear Information System (INIS)

    Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and play a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks – DNA methylation and histone modifications – but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging

  20. Progress toward curing HIV infection with hematopoietic cell transplantation

    Directory of Open Access Journals (Sweden)

    Petz LD

    2015-07-01

    Full Text Available Lawrence D Petz,1 John C Burnett,2 Haitang Li,3 Shirley Li,3 Richard Tonai,1 Milena Bakalinskaya,4 Elizabeth J Shpall,5 Sue Armitage,6 Joanne Kurtzberg,7 Donna M Regan,8 Pamela Clark,9 Sergio Querol,10 Jonathan A Gutman,11 Stephen R Spellman,12 Loren Gragert,13 John J Rossi2 1StemCyte International Cord Blood Center, Baldwin Park, CA, USA; 2Department of Molecular and Cellular Biology, Irell and Manella Graduate School of Biological Sciences, 3Department of Molecular and Cellular Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA; 4CCR5-Δ32/Δ32 Research Department, StemCyte International Cord Blood Center, Baldwin Park, CA, USA; 5Department of Stem Cell Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 6MD Anderson Cord Blood Bank, Department of Stem Cell Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 7Carolinas Cord Blood Bank, Duke University Medical Center, Durham, NC, USA; 8St Louis Cord Blood Bank, SSM Cardinal Glennon Children's Medical Center, St Louis, MO, USA; 9Enhance Quality Consulting Inc., Oviedo, FL, USA; 10Cell Therapy Service and Cord Blood Bank, Banc de Sang i Teixits, Barcelona, Spain; 11BMT/Hematologic Malignancies, University of Colorado, Aurora, CO, USA; 12Immunobiology and Observational Research, CIBMTR, Minneapolis, MN, USA; 13National Marrow Donor Program/Be The Match, Minneapolis, MN, USA Abstract: HIV-1 infection afflicts more than 35 million people worldwide, according to 2014 estimates from the World Health Organization. For those individuals who have access to antiretroviral therapy, these drugs can effectively suppress, but not cure, HIV-1 infection. Indeed, the only documented case for an HIV/AIDS cure was a patient with HIV-1 and acute myeloid leukemia who received allogeneic hematopoietic cell transplantation (HCT from a graft that carried the HIV-resistant CCR5-Δ32/Δ32 mutation. Other attempts to establish a cure for HIV

  1. Prostaglandin E2 increases hematopoietic stem cell survival and accelerates hematopoietic recovery after radiation injury

    OpenAIRE

    Porter, Rebecca L.; Georger, Mary; Bromberg, Olga; McGrath, Kathleen E.; Frisch, Benjamin J.; Becker, Michael W.; Calvi, Laura M.

    2013-01-01

    Hematopoietic stem and progenitor cells (HSPCs), which continuously maintain all mature blood cells, are regulated within the marrow microenvironment. We previously reported that pharmacologic treatment of naïve mice with prostaglandin E2 (PGE2) expands HSPCs. However, the cellular mechanisms mediating this expansion remain unknown. Here we demonstrate that PGE2 treatment in naïve mice inhibits apoptosis of HSPCs without changing their proliferation rate. In a murine model of sub-lethal total...

  2. Ikaros deficiency in host hematopoietic cells separates GVL from GVHD after experimental allogeneic hematopoietic cell transplantation

    OpenAIRE

    Toubai, Tomomi; Guoqing, Hou; Rossi, Corrine; Mathewson, Nathan; Oravecz-Wilson, Katherine; Cummings, Emily; Wu, Julia; Sun, Yaping; Choi, Sung; Reddy, Pavan

    2015-01-01

    The graft-versus-leukemia (GVL) effect following allogeneic hematopoietic stem cell transplantation (allo-HCT) is critical for its curative potential. Hwever, GVL is tightly linked to graft-versus-host disease (GVHD). Among hematological malignancies, acute lymphoblastic leukemia (ALL) is the most resistant to GVL, although the reasons for this remain poorly understood. Clinical studies have identified alterations in Ikaros (Ik) transcription factor as the major marker associated with poor ou...

  3. Incidence of venous thromboembolism in the setting of hematopoietic cell transplantation.

    Science.gov (United States)

    O'Hara, V J Daphne; Miller, Trent; Mehta, Rakesh; Swartzendruber, Evonne; Kiel, Patrick J

    2014-01-01

    The underlying risk of venous thromboembolism (VTE) is unclear in patients undergoing hematopoietic cell transplantation (HCT). As such, these patients should still be considered at risk for development of VTE due to factors such as their underlying malignancy and the marked inflammatory state that develops from treatment. The purpose of this study was to characterize the incidence of VTE in patients undergoing HCT. Retrospective chart review of patients from the Indiana University Stem Cell Transplant Unit treated between January 1, 2008, and May 24, 2011. Patients were older than 18 years and had undergone HCT. The primary objective was to analyze the incidence of VTE in patients undergoing autologous HCT versus allogeneic HCT. Secondary objectives included documentation of VTE treatment strategies and time to occurrence of VTE. Of the 567 patients who underwent autologous HCT, 14 developed VTE (2.5%), whereas 5 of the 180 patients who underwent allogeneic HCT developed VTE (2.8%; P = 1.000). The median time to development of VTE from admission for HCT was 12 days in the autologous HCT arm versus 19 days in the allogeneic HCT arm (P = 0.610). The most commonly used VTE treatment strategy was enoxaparin (12 out of 19 VTEs). This study illustrates that VTE does occur rarely in patients who have undergone HCT. The optimal treatment regimen in this population requires further evaluation. Until a reliable protocol for treatment and evidence for risk factors are established, providers should be vigilant for occurrence of VTE in these patients. PMID:24061558

  4. Tritium contamination of hematopoietic stem cells alters long-term hematopoietic reconstitution

    International Nuclear Information System (INIS)

    Purpose: In vivo effects of tritium contamination are poorly documented. Here, we study the effects of tritiated Thymidine ([3H] Thymidine) or tritiated water (HTO) contamination on the biological properties of hematopoietic stem cells (HSC). Materials and methods: Mouse HSC were contaminated with concentrations of [3H] Thymidine ranging from 0.37-37.03 kBq/ml or of HTO ranging from 5-50 kBq/ml. The biological properties of contaminated HSC were studied in vitro after HTO contamination and in vitro and in vivo after [3H] Thymidine contamination. Results: Proliferation, viability and double-strand breaks were dependent on [3H] Thymidine or HTO concentrations used for contamination but in vitro myeloid differentiation of HSC was not affected by [3H] Thymidine contamination. [3H] Thymidine contaminated HSC showed a compromised long-term capacity of hematopoietic reconstitution and competition experiments showed an up to two-fold decreased capacity of contaminated HSC to reconstitute hematopoiesis. These defects were not due to impaired homing in bone marrow but to an initial decreased proliferation rate of HSC. Conclusion: These results indicate that contaminations of HSC with doses of tritium that do not result in cell death, induce short-term effects on proliferation and cell cycle and long-term effects on hematopoietic reconstitution capacity of contaminated HSC. (authors)

  5. Basic oral care for hematology–oncology patients and hematopoietic stem cell transplantation recipients

    DEFF Research Database (Denmark)

    Elad, Sharon; Raber-Durlacher, Judith E; Brennan, Michael T;

    2015-01-01

    PURPOSE: Hematology-oncology patients undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT) recipients are at risk for oral complications which may cause significant morbidity and a potential risk of mortality. This emphasizes the importance of basic oral care prior to, during...... and following chemotherapy/HSCT. While scientific evidence is available to support some of the clinical practices used to manage the oral complications, expert opinion is needed to shape the current optimal protocols. METHODS: This position paper was developed by members of the Oral Care Study Group......, Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT) in attempt to provide guidance to the health care providers managing these patient populations. RESULTS: The protocol on basic oral care...

  6. Engineering Hematopoietic Stem Cells: Lessons from Development.

    Science.gov (United States)

    Rowe, R Grant; Mandelbaum, Joseph; Zon, Leonard I; Daley, George Q

    2016-06-01

    Cell engineering has brought us tantalizingly close to the goal of deriving patient-specific hematopoietic stem cells (HSCs). While directed differentiation and transcription factor-mediated conversion strategies have generated progenitor cells with multilineage potential, to date, therapy-grade engineered HSCs remain elusive due to insufficient long-term self-renewal and inadequate differentiated progeny functionality. A cross-species approach involving zebrafish and mammalian systems offers complementary methodologies to improve understanding of native HSCs. Here, we discuss the role of conserved developmental timing processes in vertebrate hematopoiesis, highlighting how identification and manipulation of stage-specific factors that specify HSC developmental state must be harnessed to engineer HSCs for therapy. PMID:27257760

  7. The Neuropsychiatry of Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Mitchell R. Levy

    2006-06-01

    Full Text Available BACKGROUND AND OBJECTIVES: Regimens incorporating hematopoietic stem cell transplantation (HSCT have become widely utilized in disease treatments, particularly for cancer. These complex treatment programs also expose patients to central nervous system (CNS toxicities from chemotherapy, irradiation, infection, metabolic effects and immunosuppression. METHODS: Relevant recent medical literature from Medline and bibliographies in pertinent publications are reviewed with a focus on those cases and studies pertaining to neuropsychiatric effects of HSCT. RESULTS: High rates of neuropsychiatric sequelae occur on a continuum from acute to chronic. Adverse outcomes include focal CNS deficits and severe global manifestations such as seizures, encephalopathy and delirium. More graduated effects on cognition, energy and mood are frequently seen, impacting patient function. CONCLUSIONS: Additional research on neuropsychiatric outcomes and treatment interventions is needed in the HSCT setting. Risks for neuropsychiatric deficits should be part of an ongoing informed consent discussion among treating physicians, patients and families.

  8. HLA-mismatched hematopoietic stem cell tranplantation for pediatric solid tumors

    Directory of Open Access Journals (Sweden)

    Andrea Pession

    2011-06-01

    Full Text Available Even if the overall survival of children with cancer is significantly improved over these decades, the cure rate of high-risk pediatric solid tumors such as neuroblastoma, Ewing’s sarcoma family tumors or rhabdomiosarcoma remain challenging. Autologous hematopoietic stem cell transplantation (HSCT allows chemotherapy dose intensification beyond marrow tolerance and has become a fundamental tool in the multimodal therapeutical approach of these patients. Anyway this procedure does not allow to these children an eventfree survival approaching more than 50% at 5 years. New concepts of allogeneic HSCT and in particular HLA-mismatched HSCT for high risk solid tumors do not rely on escalation of chemo therapy intensity and tumor load reduction but rather on a graft-versus-tumor effect. We here report an experimental study design of HLA-mismatched HSCT for the treatment of pediatric solid tumors and the inherent preliminary results.

  9. Renal function in high dose chemotherapy and autologous hematopoietic cell support treatment for breast cancer.

    Science.gov (United States)

    Merouani, A; Shpall, E J; Jones, R B; Archer, P G; Schrier, R W

    1996-09-01

    Autologous and allogeneic bone marrow grafting both require cytoreductive therapy but only the allogeneic procedure requires immunosuppressive agents. Allogeneic bone marrow transplantation has been reported to be associated with a high incidence of both renal failure and veno-occlusive disease (VOD) of the liver, the combination of which is associated with a high morbidity and mortality. There is less known about the frequency and severity of these complications in patients undergoing autologous bone marrow transplantation. In the present study renal, hepatic and other complications were examined in 232 patients with Stages II/III and IV breast cancer who were treated with high-dose chemotherapy and autologous hematopoietic cell support with either marrow or peripheral blood progenitor cells. The post-treatment severity of the renal dysfunction was classified as follows: Grade 0, normal renal function [ 25% decrement in GFR but twofold rise in serum creatinine but no need for dialysis; Grade 3 > than twofold rise in serum creatinine and need for dialysis. There were 102 patients (44%) who were classified as Grade 0 and 81 patients (35%) who were classified as Grade 1 renal dysfunction. Severe renal dysfunction (Grades 2 and 3) was observed in 49 of the 232 patients (21%). This severe renal dysfunction of 21% compares with a previously reported 53% incidence of severe renal dysfunction for allogeneic bone marrow transplantation. Similarly, the frequency of hepatic VOD was less (4.7% or 11 of 232 patients) in this autologous bone marrow transplant study as compared to a reported incidence of hepatic VOD ranging from 22 to 53% in large series of allogeneic bone marrow transplant patients. The severe renal dysfunction (Grades 2 and 3) in the present autologous hematopoietic cell support study correlated most significantly with sepsis, liver and pulmonary dysfunction. The major fall in GFR occurred during chemotherapy but before hematopoietic cell support, thus

  10. Comparison of efficacy of pressure-controlled ventilation and volume-controlled ventilation in children undergoing laparoscopic surgery%腹腔镜手术患儿压力控制通气和容量控制通气效果的比较

    Institute of Scientific and Technical Information of China (English)

    冯继峰; 郑剑秋; 周蜀克

    2014-01-01

    Objective To compare the efficacy of pressure-controlled ventilation and volume-controlled ventilation in children undergoing laparoscopic surgery.Methods Thirty ASA Ⅰ or Ⅱ children of both sexes,aged 12-36 months,weighing 9-15 kg,scheduled for laparoscopic surgery,were randomly divided into two groups (n =15 each):pressure-controlled ventilation group (group P) and volume-controlled ventilation group (group Ⅴ).After anesthesia was induced with propofol 2-4 mg/kg,vecuronium 0.1 mg/kg and fentanyl 2 μg/kg,the children received endotracheal intubation and mechanical ventilation.The maximum inspiratory pressure was adjusted to make the tidal volume (VT) achieve 12 ml/kg in group P and the VT was set at 12 ml/kg in group V.The end-tidal pressure of carbon dioxide (PET CO2) was controlled at 35-45 mm Hg.The mean arterial blood pressure (MAP),heart rate (HR),arterial carbpn dioxide tension (PaCO2),PETCO2,minute ventilation and peak airway pressure were recorded immediately after intubation (T0),immediately before skin incision (T1),after 30 minutes of pneumoperitoneum (T2) and 15 minutes after the end of pneumoperitoneum (T3).Arterial blood samples were taken at the same time points mentioned above for blood gas analysis.Dynamic lung compliance and the ratio of the physiological dead space to the tidal volume were calculated.Results Compared with group Ⅴ,PaCO2 and PET CO2 were significantly decreased and dynamic lung compliance was significantly increased at T1-2,and minute ventilation and peak airway pressure were significantly decreased at T0-3 in group P (P < 0.01).There was no significant difference in MAP,HR and the ratio of the physiological dead space to the tidal volume between the two groups (P > 0.05).Conclusion Compared with volume-controlled ventilation,pressure-controlled ventilation can better improve the ventilatory efficacy,is more beneficial to gas exchange and reduces the influence of pneumoperitoneum on respiratory function in children

  11. Critical early events in hematopoietic cell seeding and engraftment.

    OpenAIRE

    Jerry Stein; Isaac Yaniv; Nadir Askenasy

    2005-01-01

    Durable hematopoietic stem cell engraftment requires efficient homing to and seeding in the recipient bone marrow. Dissection of cellular and molecular mechanisms by retrospective analysis of functional engraftment studies imposes severe limitations on the understanding of the early stages of this process. We have established an experimental approach for in vivo functional imaging of labeled cells at the level of recipient bone marrow in real time. The adhesive interaction of hematopoietic ce...

  12. Eicosanoid Regulation of Hematopoiesis and Hematopoietic Stem and Progenitor Trafficking

    OpenAIRE

    Hoggatt, Jonathan; Pelus, Louis M.

    2010-01-01

    Hematopoietic stem cell (HSC) transplantation is a potentially curative treatment for numerous hematologic malignancies. The transplant procedure as performed today takes advantage of HSC trafficking; either egress of HSC from the bone marrow to the peripheral blood, i.e. mobilization, for acquisition of the hematopoietic graft, and/or trafficking of HSC from the peripheral blood to bone marrow niches in the recipient patient, i.e. HSC homing. Numerous studies, many of which are reviewed here...

  13. Circulation and chemotaxis of fetal hematopoietic stem cells.

    OpenAIRE

    Christensen, Julie L.; Wright, Douglas E.; Wagers, Amy J.; Weissman, Irving L.

    2004-01-01

    The major site of hematopoiesis transitions from the fetal liver to the spleen and bone marrow late in fetal development. To date, experiments have not been performed to evaluate functionally the migration and seeding of hematopoietic stem cells (HSCs) during this period in ontogeny. It has been proposed that developmentally timed waves of HSCs enter the bloodstream only during distinct windows to seed the newly forming hematopoietic organs. Using competitive reconstitution assays to measure ...

  14. Induction of embryonic stem cells to hematopoietic cells in vitro

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In order to get hematopoietic cells from embryonic stem (ES) cells and to study development mechanisms of hematopoietic cells, the method of inducing embryonic stem cells to hematopoietic cells was explored by differenciating mouse ES cells and human embryonic cells in three stages. The differentiated cells were identified by flow cytometry, immunohistochemistry and Wright's staining. The results showed that embryoid bodies (EBs) could form when ES cells were cultured in the medium with 2-mercaptoethanol (2-ME). However, cytokines, such as stem cell factor (SCF), thrombopoietin (TPO), interleukin-3 (IL-3), interleukin-6 (IL-6), erythropoietin (EPO) and granular colony stimulating factor (G-CSF), were not helpful for forming EBs. SCF, TPO and embryonic cell conditional medium were useful for the differentiation of mouse EBs to hematopoietic progenitors. Eighty-six percent of these cells were CD34+ after 6-d culture. Hematopoietic progenitors differentiated to B lymphocytes when they were cocultured with primary bone marrow stroma cells in the DMEM medium with SCF and IL-6. 14 d later, most of the cells were CD34-CD38+. Wright's staining and immunohistochemistry showed that 80% of these cells were plasma-like morphologically and immunoglubolin positive. The study of hematopoietic cells from human embryonic cells showed that human embryonic cell differentiation was very similar to that of mouse ES cells. They could form EBs in the first stage and the CD34 positive cells account for about 48.5% in the second stage.

  15. Therapeutic approaches of hematopoietic syndrome after serious accidental global irradiation. Ex vivo expansion interest of hematopoietic cells

    International Nuclear Information System (INIS)

    Aplasia is one of the main syndrome, appearing after one global accidental irradiation by one ionizing radiation source. The hematopoietic syndrome is characterized by a peripheric blood cell number fall; the cell marrow is reduced too

  16. Impact of Pretransplant Donor and Recipient Cytomegalovirus Serostatus on Outcome for Multiple Myeloma Patients Undergoing Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation

    OpenAIRE

    El-Cheikh, Jean; Devillier, Raynier; Crocchiolo, Roberto; Fürst, Sabine; Calmels, Boris; Faucher, Catherine; Stoppa, Anne Marie; Granata, Angela; Castagna, Luca; Ladaique, Patrick; Lemarie, Claude; Bouabdallah, Reda; Zandotti, Christine; Merlin, Michele; Berger, Pierre

    2013-01-01

    Scope of the study was to investigate the impact of pre-transplant CMV serostatus of the donor and/or recipient on the outcome of patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-SCT) for Multiple Myeloma (MM). To our knowledge no data are available in the literature about this issue. We retrospectively followed 99 consecutive patients who underwent reduced-intensity conditioning (RIC) Allo-SCT for MM in our cancer center at Marseille between January 2000 and Janua...

  17. Hematopoietic tissue repair under chronic low daily dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.M.

    1994-12-01

    The capacity of the hematopoietic system to repair constantly accruing cellular damage under chronic, low daily dose gamma irradiation is essential for the maintenance of a functional hematopoietic system, and, in turn, long term survival. In certain individuals, however, such continuous cycles of damage and repair provide an essential inductive environment for selected types of hematopathologies, e.g., myeloid leukemia (ML). We have been studying temporal and causal relationships between hematopoietic capacity, associated repair functions, and propensities for hematologic disease in canines under variable levels of chronic radiation stress (0.3{minus}26.3 cGy d{sup {minus}1}). Results indicate that the maximum exposure rate tolerated by the hematopoietic system is highly individual-specific and is based largely on the degree to which repair capacity, and, in turn, hematopoietic restoration, is augmented under chronic exposure. In low-tolerance individuals (prone to aplastic anemia, subgroup (1), the failure to augment basic m-pair functions seemingly results in a progressive accumulation of genetic and cellular damage within vital progenitorial marrow compartments particularly marked within erythroid compartments. that results in loss of reproductive capacity and ultimately in collapse of the hematopoietic system. The high-tolerance individuals (radioaccomodated and either prone- or not prone to ML, subgroup 2 & 3 appear to minimize the accumulating damage effect of daily exposures by extending repair functions, which preserves reproductive integrity and fosters regenerative hematopoietic responses. As the strength of the regenerative response manifests the extent of repair augmentation, the relatively strong response of high- tolerance individuals progressing to patent ML suggests an insufficiency of repair quality rather than repair quantity.

  18. Hematopoietic tissue repair under chronic low daily dose irradiation

    International Nuclear Information System (INIS)

    The capacity of the hematopoietic system to repair constantly accruing cellular damage under chronic, low daily dose gamma irradiation is essential for the maintenance of a functional hematopoietic system, and, in turn, long term survival. In certain individuals, however, such continuous cycles of damage and repair provide an essential inductive environment for selected types of hematopathologies, e.g., myeloid leukemia (ML). We have been studying temporal and causal relationships between hematopoietic capacity, associated repair functions, and propensities for hematologic disease in canines under variable levels of chronic radiation stress (0.3-26.3 cGy d-1). Results indicate that the maximum exposure rate tolerated by the hematopoietic system is highly individual-specific and is based largely on the degree to which repair capacity, and, in turn, hematopoietic restoration, is augmented under chronic exposure. In low-tolerance individuals (prone to aplastic anemia, subgroup (1), the failure to augment basic m-pair functions seemingly results in a progressive accumulation of genetic and cellular damage within vital progenitorial marrow compartments particularly marked within erythroid compartments. that results in loss of reproductive capacity and ultimately in collapse of the hematopoietic system. The high-tolerance individuals (radioaccomodated and either prone- or not prone to ML, subgroup 2 ampersand 3 appear to minimize the accumulating damage effect of daily exposures by extending repair functions, which preserves reproductive integrity and fosters regenerative hematopoietic responses. As the strength of the regenerative response manifests the extent of repair augmentation, the relatively strong response of high- tolerance individuals progressing to patent ML suggests an insufficiency of repair quality rather than repair quantity

  19. MiR-24 promotes the survival of hematopoietic cells.

    Directory of Open Access Journals (Sweden)

    Tan Nguyen

    Full Text Available The microRNA, miR-24, inhibits B cell development and promotes myeloid development of hematopoietic progenitors. Differential regulation of cell survival in myeloid and lymphoid cells by miR-24 may explain how miR-24's affects hematopoietic progenitors. MiR-24 is reported to regulate apoptosis, either positively or negatively depending on cell context. However, no role for miR-24 in regulating cell death has been previously described in blood cells. To examine miR-24's effect on survival, we expressed miR-24 via retrovirus in hematopoietic cells and induced cell death with cytokine or serum withdrawal. We observed that miR-24 enhanced survival of myeloid and B cell lines as well as primary hematopoietic cells. Additionally, antagonizing miR-24 with shRNA in hematopoietic cells made them more sensitive to apoptotic stimuli, suggesting miR-24 functions normally to promote blood cell survival. Since we did not observe preferential protection of myeloid over B cells, miR-24's pro-survival effect does not explain its promotion of myelopoiesis. Moreover, expression of pro-survival protein, Bcl-xL, did not mimic miR-24's impact on cellular differentiation, further supporting this conclusion. Our results indicate that miR-24 is a critical regulator of hematopoietic cell survival. This observation has implications for leukemogenesis. Several miRNAs that regulate apoptosis have been shown to function as either tumor suppressors or oncogenes during leukemogenesis. MiR-24 is expressed highly in primary acute myelogenous leukemia, suggesting that its pro-survival activity could contribute to the transformation of hematopoietic cells.

  20. Fiberoptic monitoring of central venous oxygen saturation (PediaSat in small children undergoing cardiac surgery: continuous is not continuous [v3; ref status: indexed, http://f1000r.es/3qt

    Directory of Open Access Journals (Sweden)

    Francesca G. Iodice

    2014-06-01

    Full Text Available Background: Monitoring of superior vena cava saturation (ScvO2 has become routine in the management of pediatric patients undergoing cardiac surgery. The objective of our study was to evaluate the correlation between continuous ScvO2 by the application of a fiber-optic oximetry catheter (PediaSat and intermittent ScvO2 by using standard blood gas measurements. These results were compared to those obtained by cerebral near infrared spectroscopy (cNIRS. Setting: Tertiary pediatric cardiac intensive care unit (PCICU. Methods and main results: A retrospective study was conducted in consecutive patients who were monitored with a 4.5 or 5.5 F PediaSat catheter into the right internal jugular vein. An in vivo calibration was performed once the patient was transferred to the PCICU and re-calibration took place every 24 hours thereafter. Each patient had a NIRS placed on the forehead. Saturations were collected every 4 hours until extubation. Ten patients with a median age of 2.2 (0.13-8.5 years and a weight of 12.4 (3.9-24 kg were enrolled. Median sampling time was 32 (19-44 hours: 64 pairs of PediaSat and ScVO2 saturations showed a poor correlation (r=0.62, 95% CI 44-75; p<0.0001 and Bland Altman analysis for repeated measures showed an average difference of 0.34 with a standard deviation of 7,9 and 95% limits of agreement from -15 to 16. Thirty-six pairs of cNIRS and ScVO2 saturations showed a fair correlation (r=0.79, 95% CI 0.60-0.89; p<0.0001 an average difference of -1.4 with a standard deviation of 6 and 95% limits of agreement from -13 to 10. Analysis of median percentage differences between PediaSat and ScvO2 saturation over time revealed that, although not statistically significant, the change in percentage saturation differences was clinically relevant after the 8th hour from calibration (from -100 to +100%. Conclusion: PediaSat catheters showed unreliable performance in our cohort. It should be further investigated whether repeating

  1. Retinopatia da prematuridade limiar em crianças submetidas à terapia com surfactante exógeno endotraqueal Threshold retinopathy of prematurity in children undergoing exogenous endotracheal surfactant therapy

    Directory of Open Access Journals (Sweden)

    Mário Martins dos Santos Motta

    2008-12-01

    Full Text Available OBJETIVO: Estudar a freqüência da retinopatia da prematuridade (ROP em qualquer estadiamento e da retinopatia da prematuridade limiar em prematuros que usaram ou não surfactante endotraqueal, para tratamento da síndrome da membrana hialina e avaliar a resposta dos olhos que necessitaram tratamento de ablação da retina periférica. MÉTODOS: Cento e sessenta e oito prematuros, nascidos com 1.500 gramas ou menos e/ou idade gestacional de 32 semanas ou menos, foram triados para a ROP por avaliação oftalmoscópica. Foram comparados os achados de 40 crianças tratadas pelo surfactante endotraqueal com os de 128 que não precisaram desta terapia. A ablação da retina periférica, com laser ou crioterapia, foi realizada nos pacientes com ROP limiar. Para análise estatística foram usados os testes t de Student, qui-quadrado e Kruskal-Wallis, além do teste exato de Fisher com significância para pOBJECTIVE: To study the frequency of retinopathy of prematurity (ROP in any stage and its threshold form in premature infants, either treated or non-treated with exogenous surfactant to neonatal respiratory distress syndrome, and evaluate the response of eyes with threshold retinopathy to ablation treatment. METHODS: One hundred and sixty eight premature infants who weighed 1500 grams or less and/or who had a gestational age of 32 weeks or less, were screened for ROP by ophthalmoscopy. We compared findings in 40 patients treated with exogenous endotracheal surfactant, with those of 128 patients who did not require such therapy. Ablation of ischaemic peripheral retina, either with laser or cryotherapy, was applied in cases of threshold ROP. For statistical analysis Student's t, qui-square, Kruskal-Wallins and Fisher's exact tests were used, with p value of < 0.05 considered as significant. RESULTS: ROP, in any stage, occurred in 51,2% of children. Threshold ROP, requiring treatment, was found in 12 (7,4% of them and regressed in 9. There was no

  2. In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells

    OpenAIRE

    Amabile, Giovanni; Welner, Robert S.; Nombela-Arrieta, Cesar; D'Alise, Anna Morena; Di Ruscio, Annalisa; Ebralidze, Alexander K.; Kraytsberg, Yevgenya; Ye, Min; Kocher, Olivier; Neuberg, Donna S.; Khrapko, Konstantin; Silberstein, Leslie E.; Tenen, Daniel G

    2013-01-01

    Human hematopoietic cells develop within human iPSC-derived teratomas in immunodeficient mice.Co-transplantation of OP9 stromal cells along with human iPSCs increases hematopoietic specification within teratomas.

  3. Complications of central venous catheter in patients transplanted with hematopoietic stem cells in a specialized service

    Directory of Open Access Journals (Sweden)

    Lidiane Miotto Barretta

    2016-01-01

    Full Text Available Abstract Objective: to identify the model, average length of stay on site and complications of central venous catheter in patients undergoing transplant of hematopoietic stem cells and verify the corresponding relationship between the variables: age, gender, medical diagnosis, type of transplant, implanted catheter and insertion site. Method: a retrospective and quantitative study with a sample of 188 patients transplanted records between 2007 and 2011. Results: the majority of patients used Hickman catheter with an average length of stay on site of 47.6 days. The complication fever/bacteremia was significant in young males with non-Hodgkin's lymphoma undergoing autologous transplant, which remained with the device for a long period in the subclavian vein. Conclusion: nurses should plan with their team the minimum waiting time, recommended between the catheter insertion and start of the conditioning regimen, as well as not to extend the length of time that catheter should be on site and undertake their continuing education, focusing on the prevention of complications.

  4. Complications of central venous catheter in patients transplanted with hematopoietic stem cells in a specialized service

    Science.gov (United States)

    Barretta, Lidiane Miotto; Beccaria, Lúcia Marinilza; Cesarino, Cláudia Bernardi; Pinto, Maria Helena

    2016-01-01

    Abstract Objective: to identify the model, average length of stay on site and complications of central venous catheter in patients undergoing transplant of hematopoietic stem cells and verify the corresponding relationship between the variables: age, gender, medical diagnosis, type of transplant, implanted catheter and insertion site. Method: a retrospective and quantitative study with a sample of 188 patients transplanted records between 2007 and 2011. Results: the majority of patients used Hickman catheter with an average length of stay on site of 47.6 days. The complication fever/bacteremia was significant in young males with non-Hodgkin's lymphoma undergoing autologous transplant, which remained with the device for a long period in the subclavian vein. Conclusion: nurses should plan with their team the minimum waiting time, recommended between the catheter insertion and start of the conditioning regimen, as well as not to extend the length of time that catheter should be on site and undertake their continuing education, focusing on the prevention of complications. PMID:27276021

  5. The Hematopoietic Stem Cell Niche—Home for Friend and Foe?

    OpenAIRE

    Daniela S Krause; Scadden, David T.; Preffer, Frederic I.

    2012-01-01

    The hematopoietic stem cell (HSC) niche is involved in the maintainance and regulation of quiescence, self-renewal and differentiation of hematopoietic stem cells and the fate of their progeny in mammals dealing with the daily stresses to the hematopoietic system. From the discovery that perturbations of the HSC niche can lead to hematopoietic disorders, we have now arrived at the prospect that the HSC niche may play a role in hematological malignancies and that this HSC niche may be a target...

  6. Elevated fluoride levels and periostitis in pediatric hematopoietic stem cell transplant recipients receiving long-term voriconazole.

    Science.gov (United States)

    Tarlock, Katherine; Johnson, Darren; Cornell, Cathy; Parnell, Shawn; Meshinchi, Soheil; Baker, K Scott; Englund, Janet A

    2015-05-01

    Azole therapy is widely utilized in hematopoietic stem cell transplant (HCT) recipients for the treatment of aspergillus. Complications of voriconazole treatment related to its elevated fluoride content have been described in adults, including reports of symptomatic skeletal fluorosis. We review fluoride levels, clinical, and laboratory data in five pediatric HCT recipients on long-term voriconazole therapy, all found to have elevated serum fluoride levels. Two patients had toxic fluoride levels, one infant had symptoms of significant pain with movement and radiographs confirmed skeletal fluorosis. Monitoring fluoride levels in children, especially with skeletal symptoms, should be considered in patients on long-term voriconazole. PMID:25327935

  7. Variation in Prescribing Patterns and Therapeutic Drug Monitoring of Intravenous Busulfan in Pediatric Hematopoietic Cell Transplant Recipients

    Science.gov (United States)

    McCune, Jeannine S.; Baker, K. Scott; Blough, David K.; Gamis, Alan; Bemer, Meagan J.; Kelton-Rehkopf, Megan C.; Winter, Laura; Barrett, Jeffrey S.

    2016-01-01

    Personalizing intravenous (IV) busulfan doses in children using therapeutic drug monitoring (TDM) is an integral component of hematopoietic cell transplant. The authors sought to characterize initial dosing and TDM of IV busulfan, along with factors associated with busulfan clearance, in 729 children who underwent busulfan TDM from December 2005 to December 2008. The initial IV busulfan dose in children weighing ≤12 kg ranged 4.8-fold, with only 19% prescribed the package insert dose of 1.1 mg/kg. In those children weighing >12 kg, the initial dose ranged 5.4-fold, and 79% were prescribed the package insert dose. The initial busulfan dose achieved the target exposure in only 24.3% of children. A wide range of busulfan exposures were targeted for children with the same disease (eg, 39 target busulfan exposures for the 264 children diagnosed with acute myeloid leukemia). Considerable heterogeneity exists regarding when TDM is conducted and the number of pharmacokinetic samples obtained. Busulfan clearance varied by age and dosing frequency but not by underlying disease. The authors’ group is currently evaluating how using population pharmacokinetics to optimize initial busulfan dose and TDM (eg, limited sampling schedule in conjunction with maximum a posteriori Bayesian estimation) may affect clinical outcomes in children. PMID:23444282

  8. Hematopoietic stem cell transplantation for infantile osteopetrosis.

    Science.gov (United States)

    Orchard, Paul J; Fasth, Anders L; Le Rademacher, Jennifer; He, Wensheng; Boelens, Jaap Jan; Horwitz, Edwin M; Al-Seraihy, Amal; Ayas, Mouhab; Bonfim, Carmem M; Boulad, Farid; Lund, Troy; Buchbinder, David K; Kapoor, Neena; O'Brien, Tracey A; Perez, Miguel A Diaz; Veys, Paul A; Eapen, Mary

    2015-07-01

    We report the international experience in outcomes after related and unrelated hematopoietic transplantation for infantile osteopetrosis in 193 patients. Thirty-four percent of transplants used grafts from HLA-matched siblings, 13% from HLA-mismatched relatives, 12% from HLA-matched, and 41% from HLA-mismatched unrelated donors. The median age at transplantation was 12 months. Busulfan and cyclophosphamide was the most common conditioning regimen. Long-term survival was higher after HLA-matched sibling compared to alternative donor transplantation. There were no differences in survival after HLA-mismatched related, HLA-matched unrelated, or mismatched unrelated donor transplantation. The 5- and 10-year probabilities of survival were 62% and 62% after HLA-matched sibling and 42% and 39% after alternative donor transplantation (P = .01 and P = .002, respectively). Graft failure was the most common cause of death, accounting for 50% of deaths after HLA-matched sibling and 43% of deaths after alternative donor transplantation. The day-28 incidence of neutrophil recovery was 66% after HLA-matched sibling and 61% after alternative donor transplantation (P = .49). The median age of surviving patients is 7 years. Of evaluable surviving patients, 70% are visually impaired; 10% have impaired hearing and gross motor delay. Nevertheless, 65% reported performance scores of 90 or 100, and in 17%, a score of 80 at last contact. Most survivors >5 years are attending mainstream or specialized schools. Rates of veno-occlusive disease and interstitial pneumonitis were high at 20%. Though allogeneic transplantation results in long-term survival with acceptable social function, strategies to lower graft failure and hepatic and pulmonary toxicity are urgently needed. PMID:26012570

  9. Proton MR spectroscopy of hyperplastic hematopoietic marrow in aplastic anemia

    Energy Technology Data Exchange (ETDEWEB)

    Amano, Yasuo; Kumazaki, Tatsuo [Nippon Medical School, Tokyo (Japan); Arai, Nobuyuki

    1997-04-01

    The purpose of this study was to compare the findings of magnetic resonance (MR) spectroscopy of hyperplastic hematopoietic marrow with those of normal bone marrow. Twenty-four samples of normal marrow from eight control subjects and 19 samples of hyperplastic marrow in aplastic anemia were examined with a 1.5 T MR unit. The former showed low intensity on opposed-phase T1-weighted images, while the latter showed high intensity on both fast STIR and opposed-phase T1-weighted images. MR spectroscopy quantitatively confirmed that the water; fat ratio was increased and the transverse relaxation time of water was changed in hyperplastic bone marrow, compared with normal bone marrow. In summary, MR imaging is able to detect hematopoietic regions among a wide range of bone marrow of aplastic anemia, while MR spectroscopy allowed us to quantitatively analyze the cell population of hyperplastic hematopoietic marrow in aplastic anemia. (author)

  10. Proton MR spectroscopy of hyperplastic hematopoietic marrow in aplastic anemia

    International Nuclear Information System (INIS)

    The purpose of this study was to compare the findings of magnetic resonance (MR) spectroscopy of hyperplastic hematopoietic marrow with those of normal bone marrow. Twenty-four samples of normal marrow from eight control subjects and 19 samples of hyperplastic marrow in aplastic anemia were examined with a 1.5 T MR unit. The former showed low intensity on opposed-phase T1-weighted images, while the latter showed high intensity on both fast STIR and opposed-phase T1-weighted images. MR spectroscopy quantitatively confirmed that the water; fat ratio was increased and the transverse relaxation time of water was changed in hyperplastic bone marrow, compared with normal bone marrow. In summary, MR imaging is able to detect hematopoietic regions among a wide range of bone marrow of aplastic anemia, while MR spectroscopy allowed us to quantitatively analyze the cell population of hyperplastic hematopoietic marrow in aplastic anemia. (author)

  11. Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation

    Science.gov (United States)

    Goode, Debbie K.; Obier, Nadine; Vijayabaskar, M.S.; Lie-A-Ling, Michael; Lilly, Andrew J.; Hannah, Rebecca; Lichtinger, Monika; Batta, Kiran; Florkowska, Magdalena; Patel, Rahima; Challinor, Mairi; Wallace, Kirstie; Gilmour, Jane; Assi, Salam A.; Cauchy, Pierre; Hoogenkamp, Maarten; Westhead, David R.; Lacaud, Georges; Kouskoff, Valerie; Göttgens, Berthold; Bonifer, Constanze

    2016-01-01

    Summary Metazoan development involves the successive activation and silencing of specific gene expression programs and is driven by tissue-specific transcription factors programming the chromatin landscape. To understand how this process executes an entire developmental pathway, we generated global gene expression, chromatin accessibility, histone modification, and transcription factor binding data from purified embryonic stem cell-derived cells representing six sequential stages of hematopoietic specification and differentiation. Our data reveal the nature of regulatory elements driving differential gene expression and inform how transcription factor binding impacts on promoter activity. We present a dynamic core regulatory network model for hematopoietic specification and demonstrate its utility for the design of reprogramming experiments. Functional studies motivated by our genome-wide data uncovered a stage-specific role for TEAD/YAP factors in mammalian hematopoietic specification. Our study presents a powerful resource for studying hematopoiesis and demonstrates how such data advance our understanding of mammalian development. PMID:26923725

  12. The Genetic Landscape of Hematopoietic Stem Cell Frequency in Mice

    Directory of Open Access Journals (Sweden)

    Xiaoying Zhou

    2015-07-01

    Full Text Available Prior efforts to identify regulators of hematopoietic stem cell physiology have relied mainly on candidate gene approaches with genetically modified mice. Here we used a genome-wide association study (GWAS strategy with the hybrid mouse diversity panel to identify the genetic determinants of hematopoietic stem/progenitor cell (HSPC frequency. Among 108 strains, we observed ∼120- to 300-fold variation in three HSPC populations. A GWAS analysis identified several loci that were significantly associated with HSPC frequency, including a locus on chromosome 5 harboring the homeodomain-only protein gene (Hopx. Hopx previously had been implicated in cardiac development but was not known to influence HSPC biology. Analysis of the HSPC pool in Hopx−/− mice demonstrated significantly reduced cell frequencies and impaired engraftment in competitive repopulation assays, thus providing functional validation of this positional candidate gene. These results demonstrate the power of GWAS in mice to identify genetic determinants of the hematopoietic system.

  13. Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation.

    Science.gov (United States)

    Goode, Debbie K; Obier, Nadine; Vijayabaskar, M S; Lie-A-Ling, Michael; Lilly, Andrew J; Hannah, Rebecca; Lichtinger, Monika; Batta, Kiran; Florkowska, Magdalena; Patel, Rahima; Challinor, Mairi; Wallace, Kirstie; Gilmour, Jane; Assi, Salam A; Cauchy, Pierre; Hoogenkamp, Maarten; Westhead, David R; Lacaud, Georges; Kouskoff, Valerie; Göttgens, Berthold; Bonifer, Constanze

    2016-03-01

    Metazoan development involves the successive activation and silencing of specific gene expression programs and is driven by tissue-specific transcription factors programming the chromatin landscape. To understand how this process executes an entire developmental pathway, we generated global gene expression, chromatin accessibility, histone modification, and transcription factor binding data from purified embryonic stem cell-derived cells representing six sequential stages of hematopoietic specification and differentiation. Our data reveal the nature of regulatory elements driving differential gene expression and inform how transcription factor binding impacts on promoter activity. We present a dynamic core regulatory network model for hematopoietic specification and demonstrate its utility for the design of reprogramming experiments. Functional studies motivated by our genome-wide data uncovered a stage-specific role for TEAD/YAP factors in mammalian hematopoietic specification. Our study presents a powerful resource for studying hematopoiesis and demonstrates how such data advance our understanding of mammalian development. PMID:26923725

  14. Extracorporeal Photopheresis for the Prevention of Acute GVHD in Patients Undergoing Standard Myeloablative Conditioning and Allogeneic Hematopoietic Stem Cell Transplantation

    OpenAIRE

    Shaughnessy, Paul J; Bolwell, Brian J.; van Besien, Koen; Mistrik, Martin; Grigg, Andrew; Dodds, Anthony; Prince, H. Miles; Durrant, Simon; Ilhan, Osman; Parenti, Dennis; Rogers, Jon; Gallo, Jose; Foss, Francine; Apperley, Jane; Zhang, Mei-Jie

    2009-01-01

    Graft-versus-host disease (GVHD) is partly mediated by host antigen presenting cells (APCs) that activate donor T-cells. Extracorporeal photopheresis (ECP) can modulate APC function and benefit some patients with GVHD. We report the results of a study using ECP administered prior to a standard myeloablative preparative regimen intended to prevent GVHD. Grade II-IV aGVHD developed in 9 (30%) of 30 recipients of HLA-matched related transplants and 13 (42%) of 31 recipients of HLA-matched unrela...

  15. Mitigation of radiation induced hematopoietic injury via regulation of Nrf-2 and increasing hematopoietic stem cells

    International Nuclear Information System (INIS)

    Therapeutic doses of ionizing radiation (IR) that can be delivered to tumors are restricted due to radiation induced damage to surrounding normal tissues thereby limiting the effectiveness of radiotherapy. Strategies to develop agents that selectively protect normal cells yielded limited success in the past. There is pressing need to develop safe, syndrome specific and effective radiation countermeasures to prevent or mitigate the harmful consequences of radiation exposure. Survival of bone marrow stem cells (HSCs) play a key role in protecting against IR induced hematopoietic injury. Many studies have shown manipulation of HSC frequency and/or survival as principal mechanism of radioprotection. It is known that, Nrf-2 plays crucial role in HSC survival and maintenance under oxidative stress conditions. In the present study, we have investigated the radioprotective ability of a flavonoid baicalein (5,6,7-trihydroxyflavone), extracted from the root of Scutellaria baicalensis Georgi, a medicinal plant traditionally used in Oriental medicine. There are numerous reports showing anti-inflammatory, anti-apoptotic, anti-oxidant, anti-cancer, anti-microbial, anti-mutagenic and neuroprotective properties of baicalein. Based on these reports, we have investigated the ability of baicalein to protect against radiation induced hematopoietic injury. Baicalein administration to mice protected against WBI induced mortality. Interestingly, the stem cell frequency increased in bone marrow cells obtained from baicalein administered mice as compared to vehicle treated mice. Baicalein treatment led to increased phospho-Nrf-2 levels in lineage negative BM-MNC. Administration of mice with Nrf-2 inhibitor prior to baicalein treatment led to significant abrogation of radioprotective ability of baicalein. This result suggests that, Nrf-2 may be playing a key role in baicalein mediated radioprotection. Here, we have shown that baicalein administration augments stem cell frequency, induces

  16. HOXB4 can enhance the differentiation of embryonic stem cells by modulating the hematopoietic niche

    DEFF Research Database (Denmark)

    Jackson, Melany; Axton, Richard A; Taylor, A Helen; Wilson, Julie A; Gordon-Keylock, Sabrina A M; Kokkaliaris, Konstantinos D; Brickman, Joshua M; Schulz, Herbert; Hummel, Oliver; Hubner, Norbert; Forrester, Lesley M

    2012-01-01

    Hematopoietic differentiation of embryonic stem cells (ESCs) in vitro has been used as a model to study early hematopoietic development, and it is well documented that hematopoietic differentiation can be enhanced by overexpression of HOXB4. HOXB4 is expressed in hematopoietic progenitor cells...... ESCs. To test our hypothesis, we developed a conditionally activated HOXB4 expression system using the mutant estrogen receptor (ER(T2)) and showed that a pulse of HOXB4 prior to HPC emergence in differentiating ESCs led to an increase in hematopoietic differentiation. Expression profiling revealed an...

  17. [The decision to undergo tubal ligation].

    Science.gov (United States)

    Fontaine, J G

    1984-07-01

    Gynecologists frequently seek the opinion of a psychiatrist before performing tubal ligations. The case of a 25-year-old childless divorcee whose gynecologist feared that her request for sterilization was actually a sign of depression is described to illustrate different aspects of psychiatric evaluation of women seeking sterilization. The patient's appearance and comportment during the interview, husband, family, attitude toward children, and dreams appeared normal. A traditional psychiatric evaluation shed little light on her reasons for seeking sterilization. A scale developed in the course of a few years of interviewing sterilization candidates to try to achieve a degree of objectivity was applied to the case. The scale requires assessment of the client's motivation, contraceptive usage, self-image, psychosexual development, the economic value of the ligation, and the consequences for the patient's sexual, social, and professional life. The psychiatrist summarizes his detailed findings and states them in comprehensible and practical terms for the sterilization practitioner. In this case, the client was raised rather coldly in a large family of 13 children where she received little attention from her father or mother. Her family background caused her to enter the work force at a very early age and to seek affection from an older man whom she married at 19 after 2 years of living together. She soon realized that he could not fill her need for affection and decided to leave him as he was demanding a child. Her 2nd partner was an alcoholic whom she left for the same reasons. She could not accept the idea of having a child who would be demanding when her own needs were so pressing. Her position was reinforced by her belief that she could not use oral contraceptives because of recurrent infections and that the IUD is unreliable. Deep psychotherapy could probably lower her resistence to motherhood but the client had no motivation for it. There was little reason not to

  18. Anesthetic considerations for adults undergoing fontan conversion surgery.

    Science.gov (United States)

    Mossad, Emad B; Motta, Pablo; Vener, David F

    2013-06-01

    There are currently in North America more adults with congenital heart disease than children. This article discusses the anesthetic considerations in adults with single-ventricle physiology and prior repairs who present for Fontan conversion surgery as a demonstration of the challenges of caring for adults undergoing interventions for the repair of congenital heart defects. The care of these patients requires an understanding of the impact of passive pulmonary blood flow and single systemic ventricular physiology. The perioperative morbidity in this patient population remains high. PMID:23711650

  19. Fetal liver stromal cells promote hematopoietic cell expansion

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Kun; Hu, Caihong [Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China); Zhou, Zhigang [Shanghai 1st People Hospital, Shanghai Jiao Tong University, Shanghai 201620 (China); Huang, Lifang; Liu, Wenli [Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China); Sun, Hanying, E-mail: shanhum@163.com [Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China)

    2009-09-25

    Future application of hematopoietic stem and progenitor cells (HSPCs) in clinical therapies largely depends on their successful expansion in vitro. Fetal liver (FL) is a unique hematopoietic organ in which hematopoietic cells markedly expand in number, but the mechanisms involved remain unclear. Stromal cells (StroCs) have been suggested to provide a suitable cellular environment for in vitro expansion of HSPCs. In this study, murine StroCs derived from FL at E14.5, with a high level of Sonic hedgehog (Shh) and Wnt expression, were found to have an increased ability to support the proliferation of HSPCs. This effect was inhibited by blocking Shh signaling. Supplementation with soluble Shh-N promoted the proliferation of hematopoietic cells by activating Wnt signaling. Our findings suggest that FL-derived StroCs support proliferation of HSPCs via Shh inducing an autocrine Wnt signaling loop. The use of FL-derived StroCs and regulation of the Shh pathway might further enhance HPSC expansion.

  20. A new image of the hematopoietic stem cell vascular niche

    OpenAIRE

    Silberstein, Leslie E.; Lin, Charles P.

    2013-01-01

    The microenvironment within the bone marrow that maintains hematopoietic stem cell (HSC) quiescence is the subject of intense study. In a recent Nature paper, Kunisaki et al combine imaging techniques and computational modeling to define a novel arteriolar niche for quiescent HSCs within the bone marrow.

  1. Primary Immunodeficiency Diseases and Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Ayse Ozkan

    2014-02-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is the only curative therapy for primary immunodeficiency diseases. Early diagnosis, including prenatally, and early transplantation improve HSCT outcomes. Survival rates improve with advances in the methods of preparing hosts and donor cells, and in supportive and conditioning regimes.

  2. The hematopoietic system in the context of regenerative medicine.

    Science.gov (United States)

    Porada, Christopher D; Atala, Anthony J; Almeida-Porada, Graça

    2016-04-15

    Hematopoietic stem cells (HSC) represent the prototype stem cell within the body. Since their discovery, HSC have been the focus of intensive research, and have proven invaluable clinically to restore hematopoiesis following inadvertent radiation exposure and following radio/chemotherapy to eliminate hematologic tumors. While they were originally discovered in the bone marrow, HSC can also be isolated from umbilical cord blood and can be "mobilized" peripheral blood, making them readily available in relatively large quantities. While their ability to repopulate the entire hematopoietic system would already guarantee HSC a valuable place in regenerative medicine, the finding that hematopoietic chimerism can induce immunological tolerance to solid organs and correct autoimmune diseases has dramatically broadened their clinical utility. The demonstration that these cells, through a variety of mechanisms, can also promote repair/regeneration of non-hematopoietic tissues as diverse as liver, heart, and brain has further increased their clinical value. The goal of this review is to provide the reader with a brief glimpse into the remarkable potential HSC possess, and to highlight their tremendous value as therapeutics in regenerative medicine. PMID:26319943

  3. Placenta as a source of hematopoietic stem cells

    NARCIS (Netherlands)

    E.A. Dzierzak (Elaine); C. Robin (Catherine)

    2010-01-01

    textabstractThe placenta is a large, highly vascularised hematopoietic tissue that functions during the embryonic and foetal development of eutherian mammals. Although recognised as the interface tissue important in the exchange of oxygen, nutrients and waste products between the foetus and mother,

  4. Longitudinal Assessment of Hematopoietic Stem Cell Transplantation and Hyposalivation

    DEFF Research Database (Denmark)

    Laaksonen, Matti; Ramseier, Adrian; Rovó, Alicia;

    2011-01-01

    Hyposalivation is a common adverse effect of anti-neoplastic therapy of head and neck cancer, causing impaired quality of life and predisposition to oral infections. However, data on the effects of hematopoietic stem cell transplantation (HSCT) on salivary secretion are scarce. The present study...

  5. Sexual function 1-year after allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Noerskov, K H; Schjødt, I; Syrjala, K L;

    2016-01-01

    Treatment with allogeneic hematopoietic stem cell transplantation (HSCT) is associated with short and long-term toxicities that can result in alterations in sexual functioning. The aims of this prospective evaluation were to determine: (1) associations between HSCT and increased sexual dysfunction...

  6. Hematopoietic growth factors for the treatment of myelodysplastic syndromes

    DEFF Research Database (Denmark)

    Hansen, P B; Penkowa, M; Johnsen, H E

    1998-01-01

    of leukemic myelopoiesis and subsequent progression into overt acute myeloid leukemia. In conclusion, combinations of hematopoietic growth factors may be of clinical benefit in some patients with MDS. However, due to the cost and unpredictable clinical outcome there is a need for extended laboratory research...... to understand the functional defects of MDS stem cells and progenitors....

  7. Hematopoietic organ tumors post exposure and AML1 transcription factor

    International Nuclear Information System (INIS)

    This review describes the functions of AML1 transcription factor (tf) in hemopoiesis and the mechanism of hematopoietic organ tumorigenesis related with the product of chimaeric AML1 gene caused by chromosomal translocation and with AML1 mutation. Abnormality of AML1 (RUNX1) tf, an important factor for development and maintenance of hemopoiesis, is a representative cause of leukemia and is shown to be frequently observed in hematopoietic organ tumors of A-bomb survivors and radiation- and anticancer agent-treated patients. The dimmer via β-subunit (CDFβ) of AML1 product binds to DNA and functions at the budding of adult-type hematopoietic stem cells from aortic endothelial cells. Point mutations of AML1 are recognized in 46% A-bomb survivors with marrow dysplastic syndrome. Their distance from the explosion site is mostly 1.5-2.7 km and their exposure dose is low. Since histone acetylation is a key for hematopoietic cell tumorigenesis and differentiation by chimaeric AML/ETO tf, agent to control its activity is a target strategy for a new treatment. For this, analysis is important in such models as conditional knock-in mice. (K.H.)

  8. DNA Damage Response in Hematopoietic Stem Cell Ageing.

    Science.gov (United States)

    Li, Tangliang; Zhou, Zhong-Wei; Ju, Zhenyu; Wang, Zhao-Qi

    2016-06-01

    Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically regulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing. PMID:27221660

  9. DNA Damage Response in Hematopoietic Stem Cell Ageing

    Institute of Scientific and Technical Information of China (English)

    Tangliang Li; Zhong-Wei Zhou; Zhenyu Ju; Zhao-Qi Wang

    2016-01-01

    Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employ-ing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically reg-ulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing.

  10. Lentiviral hematopoietic stem cell gene therapy in inherited metabolic disorders

    NARCIS (Netherlands)

    G. Wagemaker (Gerard)

    2014-01-01

    textabstractAfter more than 20 years of development, lentiviral hematopoietic stem cell gene therapy has entered the stage of initial clinical implementation for immune deficiencies and storage disorders. This brief review summarizes the development and applications, focusing on the lysosomal enzyme

  11. Toll-like receptor polymorphisms in allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Kornblit, Brian; Enevold, Christian; Wang, Tao; Spellman, Stephen; Haagenson, Mike; Lee, Stephanie J; Müller, Klaus

    2014-01-01

    To assess the impact of the genetic variation in toll-like receptors (TLRs) on outcome after allogeneic myeloablative conditioning hematopoietic cell transplantation (HCT), we investigated 29 single nucleotide polymorphisms across 10 TLRs in 816 patients and donors. Only donor genotype of TLR8 rs...... of TLR8 rs3764879 of the donor is associated with outcome after myeloablative conditioned allogeneic HCT....

  12. Assessing the Influence of Different Comorbidities Indexes on the Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in a Developing Country.

    Directory of Open Access Journals (Sweden)

    Gustavo Machado Teixeira

    Full Text Available Although the application of Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI has enabled better prediction of transplant-related mortality (TRM in allogeneic hematopoietic stem cell transplants (AHSCT, data from developing countries are scarce. This study prospectively evaluated the HCT-CI and the Adult Comorbidity Evaluation (ACE-27, in its original and in a modified version, as predictors of post-transplant complications in adults undergoing a first related or unrelated AHSCT in Brazil. Both bone marrow (BM and peripheral blood stem cells (PBSC as graft sources were included. We analyzed the cumulative incidence of granulocyte and platelet recovery, sinusoidal obstructive syndrome, acute and chronic graft-versus-host disease, relapse and transplant-related mortality, and rates of event-free survival and overall survival. Ninety-nine patients were assessed. Median age was 38 years (18-65 years; HCT-CI ≥ 3 accounted for only 8% of cases; hematologic malignancies comprised 75.8% of the indications for AHSCT. There was no association between the HCT-CI or the original or modified ACE-27 with TRM or any other studied outcomes after AHSCT. These results show that, in the population studied, none of the comorbidity indexes seem to be associated with AHSCT outcomes. A significantly low frequency of high-risk (HCT-CI ≥ 3 in this Brazilian population might justify these results.

  13. Heterogeneous Nuclear Ribonucleoprotein L is required for the survival and functional integrity of murine hematopoietic stem cells

    Science.gov (United States)

    Gaudreau, Marie-Claude; Grapton, Damien; Helness, Anne; Vadnais, Charles; Fraszczak, Jennifer; Shooshtarizadeh, Peiman; Wilhelm, Brian; Robert, François; Heyd, Florian; Möröy, Tarik

    2016-01-01

    The proliferation and survival of hematopoietic stem cells (HSCs) has to be strictly coordinated to ensure the timely production of all blood cells. Here we report that the splice factor and RNA binding protein hnRNP L (heterogeneous nuclear ribonucleoprotein L) is required for hematopoiesis, since its genetic ablation in mice reduces almost all blood cell lineages and causes premature death of the animals. In agreement with this, we observed that hnRNP L deficient HSCs lack both the ability to self-renew and foster hematopoietic differentiation in transplanted hosts. They also display mitochondrial dysfunction, elevated levels of γH2AX, are Annexin V positive and incorporate propidium iodide indicating that they undergo cell death. Lin-c-Kit+ fetal liver cells from hnRNP L deficient mice show high p53 protein levels and up-regulation of p53 target genes. In addition, cells lacking hnRNP L up-regulated the expression of the death receptors TrailR2 and CD95/Fas and show Caspase-3, Caspase-8 and Parp cleavage. Treatment with the pan-caspase inhibitor Z-VAD-fmk, but not the deletion of p53, restored cell survival in hnRNP L deficient cells. Our data suggest that hnRNP L is critical for the survival and functional integrity of HSCs by restricting the activation of caspase-dependent death receptor pathways. PMID:27271479

  14. Identification of a Hematopoietic Cell Dedifferentiation-Inducing Factor.

    Science.gov (United States)

    Li, Yunyuan; Adomat, Hans; Guns, Emma Tomlinson; Hojabrpour, Payman; Duronio, Vincent; Curran, Terry-Ann; Jalili, Reza Baradar; Jia, William; Delwar, Zahid; Zhang, Yun; Elizei, Sanam Salimi; Ghahary, Aziz

    2016-06-01

    It has long been realized that hematopoietic cells may have the capacity to trans-differentiate into non-lymphohematopoietic cells under specific conditions. However, the mechanisms and the factors for hematopoietic cell trans-differentiation remain unknown. In an in vitro culture system, we found that using a conditioned medium from proliferating fibroblasts can induce a subset of hematopoietic cells to become adherent fibroblast-like cells (FLCs). FLCs are not fibroblasts nor other mesenchymal stromal cells, based on their expression of type-1 collagen, and other stromal cell marker genes. To identify the active factors in the conditioned medium, we cultured fibroblasts in a serum-free medium and collected it for further purification. Using the fractions from filter devices of different molecular weight cut-offs, and ammonium sulfate precipitation collected from the medium, we found the active fraction is a protein. We then purified this fraction by using fast protein liquid chromatography (FPLC) and identified it by mass spectrometer as macrophage colony-stimulating factor (M-CSF). The mechanisms of M-CSF-inducing trans-differentiation of hematopoietic cells seem to involve a tyrosine kinase signalling pathway and its known receptor. The FLCs express a number of stem cell markers including SSEA-1 and -3, OCT3/4, NANOG, and SOX2. Spontaneous and induced differentiation experiments confirmed that FLCs can be further differentiated into cell types of three germ layers. These data indicate that hematopoietic cells can be induced by M-CSF to dedifferentiate to multipotent stem cells. This study also provides a simple method to generate multipotent stem cells for clinical applications. J. Cell. Physiol. 231: 1350-1363, 2016. © 2015 Wiley Periodicals, Inc. PMID:26529564

  15. Determination of the psychiatric symptoms and psychological resilience levels of hematopoietic stem cell transplant patients and their relatives.

    Science.gov (United States)

    Çuhadar, D; Tanriverdi, D; Pehlivan, M; Kurnaz, G; Alkan, S

    2016-01-01

    This study was performed to evaluate psychiatric symptoms and resilience levels of the hematopoietic stem cell transplant patients and their relatives. The study enrolled 51 patients and 45 relatives undergoing bone marrow transplantation. Data were collected using Personal Information Form, Brief Symptom Inventory and Resilience Scale for Adults. Psychiatric symptoms of both patients and their relatives were negatively associated with resilience levels. Patients and their relatives with a higher degree of resilience showed a lower degree of psychiatric symptoms. The study results demonstrate that haematopoietic stem cell transplantation is a process that affects patients as well as their families. We suggest that patients and their family members be evaluated for psychiatric symptoms by nurses during this process and resilience level of patients be increased by helping them improve their coping and problem-solving skills for adaptation throughout the process. PMID:25040559

  16. The Impact of HLA-E Polymorphisms in Graft-versus-Host Disease following HLA-E Matched Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Ehteramolsadat Hosseini

    2012-03-01

    Full Text Available The  non-classical MHC  class-I mainly involves in the  regulation of  innate  immune responses where HLA-E  plays a significant role in the cell identification by natural killer cells. HLA-E is a main regulatory ligand for natural killer cells and given the importance of these effector cells in hematopoietic stem cell transplantation, we investigated the effect of HLA-E polymorphisms on post-hematopoietic stem cell transplantation outcomes.The study group included 56 donor-patient pairs with underlying malignant hematological disorders undergoing HLA-E  matched allogeneic hematopoietic stem cell transplantation. They were genotyped for HLA-E locus using a sequence specific primer-polymerase chain reaction. The  median follow-up was 20.6 months  (range 0.2-114.8 and  the  parameters assessed were acute and chronic graft-versus-host disease and overall survival.We showed a lower frequency of acute graft-versus-host disease (grade II or more; p=0.02and chronic graft-versus-host disease (extensive; p=0.04 in the patients with HLA- E*0103/0103 genotype compared to other genotypes of HLA-E. There was also an association between HLA-E*0103/0103 and improved overall survival (p=0.001.Conclusively, our  results  suggest a  protective  role  for  HLA-E*0103/0103  genotypeagainst acute graft-versus-host disease (grade II or more and chronic graft-versus-host disease (extensive as well as an association between this genotype and a better overall survival after HLA-E matched allogeneic hematopoietic stem cell transplantation.

  17. Satisfação corporal e características de lipodistrofia em crianças e adolescentes com HIV/AIDS em uso de terapia antirretroviral de alta potência Body satisfaction and lipodystrophy characteristics in HIV/AIDS children and teenagers undergoing highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Querino Haesbaert da Silva

    2011-09-01

    Full Text Available OBJETIVO: Verificar a presença de alterações metabólicas e corporais e satisfação corporal em crianças e adolescentes em uso de terapia antirretroviral. MÉTODOS: Estudo transversal de 38 jovens entre seis e 18 anos infectados por HIV e atendidos entre dezembro de 2009 e maio de 2010. A satisfação corporal foi avaliada por escala de silhuetas, composta por 11 figuras. O estado nutricional foi avaliado por meio de mensurações de peso, altura, circunferências e pregas cutâneas. A presença de características de lipodistrofia foi avaliada pelo exame físico e o perfil lipídico e glicêmico foi solicitado no dia da consulta. Na análise estatística, aplicou-se o teste t e do qui-quadrado, sendo significante pOBJECTIVE: To verify the presence of body and metabolic alterations as well as body satisfaction in children and teenagers undergoing antiretroviral therapy. METHODS: This cross-sectional study enrolled 38 HIV infected young individuals (aged six to 18 years old treated from December 2009 to May 2010. The body satisfaction was assessed by the silhouette rating scale with 11 figures. The nutritional status was assessed by weight, height, circumferences and skinfolds. The presence of lipodystrophy characteristics was determined by the physical exam, and lipid profile and glycemia were requested during consultation. The statistical analysis used t-test and chi-square test, being significant p<0.05. RESULTS: Most of the 38 patients were eutrophic with length adequate for age; 26% of them presented overweight/obesity. The total cholesterol was within the normal range in 29% of the sample. The most expressive changes were cheek and abdominal lipohypertrophy. The body dissatisfaction prevalence was 84%. Children and teenagers had similar dissatisfaction levels; however, those dissatisfied by an excessive body weight had higher mean body mass index and tricipital skinfold thickness than the satisfied ones. The dissatisfaction was not

  18. Treatment of Oral Mucositis in Hematologic Patients Undergoing Autologous or Allogeneic Transplantation of Peripheral Blood Stem Cells: a Prospective, Randomized Study with a Mouthwash Containing Camelia Sinensis Leaf Extract

    OpenAIRE

    Giovanni Carulli; Melania Rocco; Alessia Panichi; Chiara Feira Chios; Ester Ciurli; Chiara Mannucci; Elisabetta Sordi; Francesco Caracciolo; Federico Papineschi; Edoardo Benedetti; Mario Petrini

    2013-01-01

    Oral mucositis is an important side effect of hematopoietic stem cell transplantation (HCST), mainly due to toxicity of conditioning regimens. It produces significant pain and morbidity. The present study reports a prospective, randomized, non-blinded study testing the efficacy of a new mouthwash, called Baxidil Onco® (Sanitas Farmaceutici Srl, Tortona, Italy) in 60 hematologic patients undergoing HCST (28 autologous, 32 allogeneic). Baxidil Onco®, used three times a day from Day -1 to Day +3...

  19. Markers of coagulation activation and acute kidney injury in patients after hematopoietic cell transplantation.

    Science.gov (United States)

    Hingorani, S R; Seidel, K; Pao, E; Lawler, R; McDonald, G B

    2015-05-01

    Acute kidney injury (AKI) is common after hematopoietic cell transplant (HCT). The etiology of AKI is unknown because biopsies are rarely performed. The pathophysiology of injury is inferred from clinical data. Thrombotic microangiopathy (TMA) is often invoked as the cause of renal injury. Patients >2 years old undergoing their first HCT at Fred Hutchinson Cancer Research Center participated in this study. We prospectively measured plasma markers of coagulation activation, (PAI-1 and tPA) and fibrinolyis (D-dimer) weekly in 149 patients during the first 100 days post transplant. Cox proportional hazards modeling was used to determine associations between these markers and AKI (doubling of baseline serum creatinine). Kruskal-Wallis test was used to determine the associations between day 100 urinary albumin to creatinine ratios and these markers. Thirty one percent of patients developed AKI. Though elevations in these markers occurred frequently, neither PAI-1 nor tPA were associated with the development of AKI. D-dimer was associated with a slightly increased risk of AKI (relative risk=1.76; P-value 0.04). None of these markers were associated with micro- or macroalbuminuria at day 100. The lack of an association with AKI suggests that endothelial injury in the form of TMA is not a common cause of AKI early after transplant. PMID:25665045

  20. Incidence, etiology, and outcome of pleural effusions in allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Modi, Dipenkumar; Jang, Hyejeong; Kim, Seongho; Deol, Abhinav; Ayash, Lois; Bhutani, Divaya; Lum, Lawrence G; Ratanatharathorn, Voravit; Manasa, Richard; Mellert, Kendra; Uberti, Joseph P

    2016-09-01

    Pleural effusion is a known entity in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT); however, the incidence, risk factors, and morbidity-mortality outcomes associated with pleural effusions remain unknown. We retrospectively evaluated pleural effusions in 618 consecutive adult patients who underwent allogeneic HSCT from January 2008 to December 2013 at our institution. Seventy one patients developed pleural effusion at a median of 40 days (range, 1 - 869) post-HSCT with the cumulative incidence of 9.9% (95% CI, 7.7 - 12.5%) at 1 year. Infectious etiology was commonly associated with pleural effusions followed by volume overload and serositis type chronic GVHD. In multivariate analysis, higher comorbidity index (P = 0.03) and active GVHD (P = 0.018) were found to be significant independent predictors for pleural effusion development. Higher comorbidity index, very high disease risk index, ≤7/8 HLA matching, and unrelated donor were associated with inferior overall survival (OS) (P < 0.03). More importantly, patients with pleural effusion were noted to have poor OS in comparison to patients without pleural effusion (P < 0.001). Overall, pleural effusion is a frequently occurring complication after allogeneic HSCT, adding to morbidity and mortality and hence, early identification is required. Am. J. Hematol. 91:E341-E347, 2016. © 2016 Wiley Periodicals, Inc. PMID:27238902

  1. Invasive aspergillosis in hematopoietic stem cell transplant recipients: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Viviane Maria Hessel Carvalho-Dias

    2008-10-01

    Full Text Available Invasive aspergillosis (IA currently is an important cause of mortality in subjects undergoing hematopoietic stem cell transplants (HSCT and is also an important cause of opportunistic respiratory and disseminated infections in other types of immunocompromised patients. We examined the medical records of 24 cases of proven and probable invasive aspergillosis (IA at the Hospital de Clinicas of the Federal University of Parana, Brazil, from January 1996 to October 2006. During this period occurred a mean of 2.2 cases per year or 3.0 cases per 100 HSTC transplants. There was a significant relationship between structural changes in the bone marrow transplant (BMT Unit and the occurrence of IA cases (p=0.034, relative risk (RR = 2.47. Approximately 83% of the patients died due to invasive fungal infection within 60 days of follow up. Some factors tended to be associated with mortality, but these associations were not significant. These included corticosteroid use, neutropenia (<100 cells/mm³ at diagnosis, patients that needed to change antifungal therapy because of toxicity of the initial first-line regimen and disseminated disease. These factors should be monitored in BMT units to help prevent IA. Physicians should be aware of the risk factors for developing invasive fungal infections and try to reduce or eliminate them. However, once this invasive disease begins, appropriate diagnostic and treatment measures must be implemented as soon as possible in order to prevent the high mortality rates associated with this condition.

  2. Improving Outcome of Hodgkins Disease with Autologous Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Raut, Shreeniwas; Shah, Sandip; Shah, Kamalesh; Patel, Kinnari; Talati, Shailesh; Parikh, Sonia; Anand, Asha; Panchal, Harsha; Patel, Apurva; Jain, Akhil

    2016-06-01

    We report analysis of all consecutive Hodgkins disease patients undergoing autologous hematopoietic stem cell transplant from September 1999 to December 2014. Out of total 38 patients 26 were males and 12 were females. 32 were adults and 6 were pediatric (<18 years). None were elderly. Median age was 28 years (9-61). All received BEAM protocol as conditioning regimen. Median engraftment time for granulocytes was 12 and 14 days for platelets. Thirty three (86.84 %) patients achieved complete remission out of which 8 (24.24 %) had further relapse. Transplant related mortality occurred in 4 (10 %) patients. Finally 26 (78.78 %) patients were disease free at median follow up of 60 months and median disease free survival (DFS) was 35 months. DFS was 66.66 and 65 %, respectively on 3 and 5 years. While overall survival was 70.83 and 70 % on 3 and 5  years, respectively. PMID:27065579

  3. Effects of T-Cell Depletion on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in AML Patients

    Directory of Open Access Journals (Sweden)

    Gabriela Soriano Hobbs

    2015-03-01

    Full Text Available Graft versus host disease (GVHD remains one of the leading causes of morbidity and mortality associated with conventional allogeneic hematopoietic stem cell transplantation (HCT. The use of T-cell depletion significantly reduces this complication. Recent prospective and retrospective data suggest that, in patients with AML in first complete remission, CD34+ selected grafts afford overall and relapse-free survival comparable to those observed in recipients of conventional grafts, while significantly decreasing GVHD. In addition, CD34+ selected grafts allow older patients, and those with medical comorbidities or with only HLA-mismatched donors to successfully undergo transplantation. Prospective data are needed to further define which groups of patients with AML are most likely to benefit from CD34+ selected grafts. Here we review the history of T-cell depletion in AML, and techniques used. We then summarize the contemporary literature using CD34+ selection in recipients of matched or partially mismatched donors (7/8 or 8/8 HLA-matched, and provide a summary of the risks and benefits of using T-cell depletion.

  4. [Human herpesvirus-6-associated diseases in hematopoietic stem cell transplantation: an update].

    Science.gov (United States)

    Ogata, Masao

    2016-03-01

    Human herpesvirus (HHV)-6 belongs to the Betaherpesvirinae subfamily of human herpesviruses. Primary HHV-6 infection commonly causes exanthem subitum. Like other herpesviruses, HHV-6 is capable of persisting in the host after the primary infection. Under conditions of immunosuppression, latent HHV-6 can be reactivated. Between 30% and 70% of patients who undergo allogeneic hematopoietic cell transplantation (allo-HCT) experience HHV-6 reactivation at 2-4 weeks after transplantation. Accumulating evidence indicates that HHV-6 is an actual cause of encephalitis after allo-HCT. Risk factors for HHV-6 encephalitis include cord blood transplantation and an inflammatory milieu, which occurs in the early period after allo-HCT. Although HHV-6 encephalitis is associated with a poor prognosis, no validated treatments or preventative measures have as yet been established. HHV-6 reactivation may also cause myelitis, bone marrow suppression, lung disease, hepatitis, delirium, and graft-versus-host disease. However, such associations have not been consistently demonstrated and causality remains uncertain. This review updates the latest information regarding the clinical syndrome accompanying HHV-6 reactivation, with a particular focus on HHV-6 encephalitis, in the form of a series of questions and answers. PMID:27076241

  5. Metabolic reprogramming of alloantigen-activated T cells after hematopoietic cell transplantation.

    Science.gov (United States)

    Nguyen, Hung D; Chatterjee, Shilpak; Haarberg, Kelley M K; Wu, Yongxia; Bastian, David; Heinrichs, Jessica; Fu, Jianing; Daenthanasanmak, Anusara; Schutt, Steven; Shrestha, Sharad; Liu, Chen; Wang, Honglin; Chi, Hongbo; Mehrotra, Shikhar; Yu, Xue-Zhong

    2016-04-01

    Alloreactive donor T cells are the driving force in the induction of graft-versus-host disease (GVHD), yet little is known about T cell metabolism in response to alloantigens after hematopoietic cell transplantation (HCT). Here, we have demonstrated that donor T cells undergo metabolic reprograming after allogeneic HCT. Specifically, we employed a murine allogeneic BM transplant model and determined that T cells switch from fatty acid β-oxidation (FAO) and pyruvate oxidation via the tricarboxylic (TCA) cycle to aerobic glycolysis, thereby increasing dependence upon glutaminolysis and the pentose phosphate pathway. Glycolysis was required for optimal function of alloantigen-activated T cells and induction of GVHD, as inhibition of glycolysis by targeting mTORC1 or 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) ameliorated GVHD mortality and morbidity. Together, our results indicate that donor T cells use glycolysis as the predominant metabolic process after allogeneic HCT and suggest that glycolysis has potential as a therapeutic target for the control of GVHD. PMID:26950421

  6. Impact of prior imatinib mesylate on the outcome of hematopoietic cell transplantation for chronic myeloid leukemia

    Science.gov (United States)

    Kukreja, Manisha; Wang, Tao; Giralt, Sergio A.; Szer, Jeffrey; Arora, Mukta; Woolfrey, Ann E.; Cervantes, Francisco; Champlin, Richard E.; Gale, Robert Peter; Halter, Joerg; Keating, Armand; Marks, David I.; McCarthy, Philip L.; Olavarria, Eduardo; Stadtmauer, Edward A.; Abecasis, Manuel; Gupta, Vikas; Khoury, H. Jean; George, Biju; Hale, Gregory A.; Liesveld, Jane L.; Rizzieri, David A.; Antin, Joseph H.; Bolwell, Brian J.; Carabasi, Matthew H.; Copelan, Edward; Ilhan, Osman; Litzow, Mark R.; Schouten, Harold C.; Zander, Axel R.; Horowitz, Mary M.; Maziarz, Richard T.

    2008-01-01

    Imatinib mesylate (IM, Gleevec) has largely supplanted allogeneic hematopoietic cell transplantation (HCT) as first line therapy for chronic myeloid leukemia (CML). Nevertheless, many people with CML eventually undergo HCT, raising the question of whether prior IM therapy impacts HCT success. Data from the Center for International Blood and Marrow Transplant Research on 409 subjects treated with IM before HCT (IM+) and 900 subjects who did not receive IM before HCT (IM−) were analyzed. Among patients in first chronic phase, IM therapy before HCT was associated with better survival but no statistically significant differences in treatment-related mortality, relapse, and leukemia-free survival. Better HLA-matched donors, use of bone marrow, and transplantation within one year of diagnosis were also associated with better survival. A matched-pairs analysis was performed and confirmed a higher survival rate among first chronic phase patients receiving IM. Among patients transplanted with advanced CML, use of IM before HCT was not associated with treatment-related mortality, relapse, leukemia-free survival, or survival. Acute graft-versus-host disease rates were similar between IM+ and IM− groups regardless of leukemia phase. These results should be reassuring to patients receiving IM before HCT. PMID:18664621

  7. A prognostic index for survival among mechanically ventilated hematopoietic cell transplant recipients.

    Science.gov (United States)

    Solh, Melhem; Oommen, Sanjay; Vogel, Rachel Isaksson; Shanley, Ryan; Majhail, Navneet S; Burns, Linda J

    2012-09-01

    The prognosis of recipients of allogeneic hematopoietic cell transplantation (HCT) who require mechanical ventilation (MV) has historically been poor. Of 883 adults undergoing allogeneic HCT at the University of Minnesota between 1998 and 2009, 179 (20%) required MV before day 100 posttransplantation. We evaluated the outcomes of these patients to develop a prognostic index to predict the 100-day post-MV overall survival (OS) based on factors present at the time of MV. The 179 patients were divided at random into a training set (n = 119) and a validation set (n = 60). The 100-day postventilation OS was 17% for the total population. Multivariate Cox regression on the training set identified creatinine 20 × 10(9)/L as significant predictors of better OS. Recursive partitioning classified patients with these good prognostic criteria into class A (n = 76); all other patients were classified as class B (n = 103). Among class A patients, 100-day OS was 29% in the training set and 30% in the validation set. Corresponding OS in class B patients was 5% and 15%, respectively. This prognostic index should help guide physicians in counseling HCT patients and their families regarding the use of MV and potential outcomes. PMID:22387348

  8. How I treat respiratory viral infections in the setting of intensive chemotherapy or hematopoietic cell transplantation.

    Science.gov (United States)

    Waghmare, Alpana; Englund, Janet A; Boeckh, Michael

    2016-06-01

    The widespread use of multiplex molecular diagnostics has led to a significant increase in the detection of respiratory viruses in patients undergoing cytotoxic chemotherapy and hematopoietic cell transplantation (HCT). Respiratory viruses initially infect the upper respiratory tract and then progress to lower respiratory tract disease in a subset of patients. Lower respiratory tract disease can manifest itself as airflow obstruction or viral pneumonia, which can be fatal. Infection in HCT candidates may require delay of transplantation. The risk of progression differs between viruses and immunosuppressive regimens. Risk factors for progression and severity scores have been described, which may allow targeting treatment to high-risk patients. Ribavirin is the only antiviral treatment option for noninfluenza respiratory viruses; however, high-quality data demonstrating its efficacy and relative advantages of the aerosolized versus oral form are lacking. There are significant unmet needs, including data defining the virologic characteristics and clinical significance of human rhinoviruses, human coronaviruses, human metapneumovirus, and human bocavirus, as well as the need for new treatment and preventative options. PMID:26968533

  9. Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate

    Science.gov (United States)

    Grover, Amit; Mancini, Elena; Moore, Susan; Mead, Adam J.; Atkinson, Deborah; Rasmussen, Kasper D.; O’Carroll, Donal; Jacobsen, Sten Eirik W.

    2014-01-01

    The erythroid stress cytokine erythropoietin (Epo) supports the development of committed erythroid progenitors, but its ability to act on upstream, multipotent cells remains to be established. We observe that high systemic levels of Epo reprogram the transcriptomes of multi- and bipotent hematopoietic stem/progenitor cells in vivo. This induces erythroid lineage bias at all lineage bifurcations known to exist between hematopoietic stem cells (HSCs) and committed erythroid progenitors, leading to increased erythroid and decreased myeloid HSC output. Epo, therefore, has a lineage instructive role in vivo, through suppression of non-erythroid fate options, demonstrating the ability of a cytokine to systematically bias successive lineage choices in favor of the generation of a specific cell type. PMID:24493804

  10. Allogeneic hematopoietic stem-cell transplantation for leukocyte adhesion deficiency

    DEFF Research Database (Denmark)

    Qasim, Waseem; Cavazzana-Calvo, Marina; Davies, E Graham;

    2009-01-01

    of leukocyte adhesion deficiency who underwent hematopoietic stem-cell transplantation between 1993 and 2007 was retrospectively analyzed. Data were collected by the registries of the European Society for Immunodeficiencies/European Group for Blood and Marrow Transplantation, and the Center for International......, with full donor engraftment in 17 cases, mixed multilineage chimerism in 7 patients, and mononuclear cell-restricted chimerism in an additional 3 cases. CONCLUSIONS: Hematopoietic stem-cell transplantation offers long-term benefit in leukocyte adhesion deficiency and should be considered as an early...... therapeutic option if a suitable HLA-matched stem-cell donation is available. Reduced-intensity conditioning was particularly safe, and mixed-donor chimerism seems sufficient to prevent significant symptoms, although careful long-term monitoring will be required for these patients....

  11. Aging, Clonality, and Rejuvenation of Hematopoietic Stem Cells.

    Science.gov (United States)

    Akunuru, Shailaja; Geiger, Hartmut

    2016-08-01

    Aging is associated with reduced organ function and increased disease incidence. Hematopoietic stem cell (HSC) aging driven by both cell intrinsic and extrinsic factors is linked to impaired HSC self-renewal and regeneration, aging-associated immune remodeling, and increased leukemia incidence. Compromised DNA damage responses and the increased production of reactive oxygen species (ROS) have been previously causatively attributed to HSC aging. However, recent paradigm-shifting concepts, such as global epigenetic and cytoskeletal polarity shifts, cellular senescence, as well as the clonal selection of HSCs upon aging, provide new insights into HSC aging mechanisms. Rejuvenating agents that can reprogram the epigenetic status of aged HSCs or senolytic drugs that selectively deplete senescent cells provide promising translational avenues for attenuating hematopoietic aging and, potentially, alleviating aging-associated immune remodeling and myeloid malignancies. PMID:27380967

  12. Expansion of hematopoietic stem cells for transplantation: current perspectives

    Directory of Open Access Journals (Sweden)

    Schuster Jessica A

    2012-05-01

    Full Text Available Abstract Hematopoietic stem cells (HSCs are rare cells that have the unique ability to self-renew and differentiate into cells of all hematopoietic lineages. The expansion of HSCs has remained an important goal to develop advanced cell therapies for bone marrow transplantation and many blood disorders. Over the last several decades, there have been numerous attempts to expand HSCs in vitro using purified growth factors that are known to regulate HSCs. However, these attempts have been met with limited success for clinical applications. New developments in the HSC expansion field coupled with gene therapy and stem cell transplant should encourage progression in attractive treatment options for many disorders including hematologic conditions, immunodeficiencies, and genetic disorders.

  13. Lnk deficiency partially mitigates hematopoietic stem cell aging

    OpenAIRE

    Bersenev, Alexey; Rozenova, Krasimira; Balcerek, Joanna; JIANG, JING; Wu, Chao; Tong, Wei

    2012-01-01

    Upon aging, the number of hematopoietic stem cells (HSCs) in the bone marrow increases while their repopulation potential declines. Moreover, aged HSCs exhibit lineage bias in reconstitution experiments with an inclination towards myeloid at the expense of lymphoid potential. The adaptor protein Lnk is an important negative regulator of HSC homeostasis, as Lnk deficiency is associated with a 10-fold increase in HSC numbers in young mice. However, the age-related increase in functional HSC num...

  14. Imaging of complications from hematopoietic stem cell transplant

    OpenAIRE

    Tarun Pandey; Suresh Maximin; Puneet Bhargava

    2014-01-01

    Stem cell transplant has been the focus of clinical research for a long time given its potential to treat several incurable diseases like hematological malignancies, diabetes mellitus, and neuro-degenerative disorders like Parkinson disease. Hematopoietic stem cell transplantation (HSCT) is the oldest and most widely used technique of stem cell transplant. HSCT has not only been used to treat hematological disorders including hematological malignancies, but has also been found useful in tream...

  15. Bone Marrow Vascular Niche: Home for Hematopoietic Stem Cells

    OpenAIRE

    Ningning He; Lu Zhang; Jian Cui; Zongjin Li

    2014-01-01

    Though discovered later than osteoblastic niche, vascular niche has been regarded as an alternative indispensable niche operating regulation on hematopoietic stem cells (HSCs). As significant progresses gained on this type niche, it is gradually clear that the main work of vascular niche is undertaking to support hematopoiesis. However, compared to what have been defined in the mechanisms through which the osteoblastic niche regulates hematopoiesis, we know less in vascular niche. In this rev...

  16. Hematopoietic Stem Cell Targeting with Surface-Engineered Lentiviral Vectors

    OpenAIRE

    sprotocols

    2014-01-01

    Authors: Els Verhoeyen and Francois-Loic Cosset Adapted from [*Gene Transfer: Delivery and Expression of DNA and RNA*](http://www.cshlpress.com/link/genetrnp.htm) (eds. Friedmann and Rossi). CSHL Press, Cold Spring Harbor, NY, USA, 2007. ### INTRODUCTION In the protocol presented here, hematopoietic stem cells (HSCs) are specifically transduced with a vector displaying the HSC-activating polypeptides, stem cell factor (SCF) and thrombopoietin (TPO). Targeted HSC transduction is e...

  17. Radioprotection of hematopoietic progenitors by low dose amifostine prophylaxis

    OpenAIRE

    Seed, Thomas M.; Inal, Cynthia E.; Singh, Vijay K

    2014-01-01

    Purpose Amifostine is a highly efficacious cytoprotectant when administered in vivo at high doses. However, at elevated doses, drug toxicity manifests for general, non-clinical radioprotective purposes. Various strategies have been developed to avoid toxic side-effects: The simplest is reducing the dose. In terms of protecting hematopoietic tissues, where does this effective, non-toxic minimum dose lie? Material and methods C3H/HEN mice were administered varying doses of amifostine (25–100 mg...

  18. FIFTY YEARS OF MELPHALAN USE IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

    OpenAIRE

    Bayraktar, Ulas D.; Bashir, Qaiser; Qazilbash, Muzaffar; Champlin, Richard E.; Ciurea, Stefan O.

    2012-01-01

    Melphalan remains the most widely used agent in preparative regimens for hematopoietic stem-cell transplantation. From its initial discovery more than 50 years ago, it has been gradually incorporated in the conditioning regimens for both autologous and allogeneic transplantation due to its myeloablative properties and broad antitumor effects as a DNA alkylating agent. Melphalan remains the mainstay conditioning for multiple myeloma and lymphomas; and has been used successfully in preparative ...

  19. Regulation of Hematopoietic Stem Cells by Bone Marrow Stromal Cells

    OpenAIRE

    Anthony, Bryan; Link, Daniel C.

    2013-01-01

    Hematopoietic stem cells (HSCs) reside in specialized microenvironments (niches) in the bone marrow. The stem cell niche is thought to provide signals that support key HSC properties, including self-renewal capacity and long-term multilineage repopulation ability. The stromal cells that comprise the stem cell niche and the signals that they generate that support HSC function are the subjects of intense investigation. Here we review the complex and diverse stromal cell populations that reside ...

  20. Endothelio-hematopoietic relationship: getting closer to the beginnings

    OpenAIRE

    Gordon-Keylock Sabrina; Medvinsky Alexander

    2011-01-01

    Abstract The close association between hematopoietic and endothelial cells during embryonic development led to the proposal that they may originate from a common ancestor - the hemangioblast. Due to a lack of unique specific markers for in vivo cell fate tracking studies, evidence supporting this theory derives mainly from in vitro differentiation studies. Teixeira and colleagues describe a novel enhancer that drives specific eGFP expression in blood islands of the electroporated chick embryo...

  1. Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Ursula; M; Gehling; Marc; Willems; Kathleen; Schlagner; Ralf; A; Benndorf; Maura; Dandri; Jrg; Petersen; Martina; Sterneck; Joerg-Matthias; Pollok; Dieter; K; Hossfeld; Xavier; Rogiers

    2010-01-01

    AIM:To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells. METHODS:Peripheral blood samples from 72 patients with liver cirrhosis of varying etiology were analyzed by flow cytometry.Identified progenitor cell subsets were immunoselected and used for functional assays in vitro. Plasma levels of stromal cell-derived factor-1(SDF-1) were measured using an enzyme linked immunosorbent assay.RESULTS:Progenitor cells with a CD133 + /CD45 + CD14 + phenotype we...

  2. NON-TRANSFERRIN-BOUND IRON IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

    OpenAIRE

    Sahlstedt, Leila

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) is an intensive treatment often complicated by organ injuries. Non-transferrin-bound iron (NTBI), as an inducer of free oxygen radicals, is a potential factor in the pathogenesis of these complications. We studied the appearance and timing of NTBI in transplant patients and the possibility to prevent the occurrence of NTBI by binding it with apotransferrin administration. We showed that NTBI appears regularly during the peritransplantation period...

  3. Large Animal Models of Hematopoietic Stem Cell Gene Therapy

    OpenAIRE

    Trobridge, Grant D.; Kiem, Hans-Peter

    2010-01-01

    Large animal models have been instrumental in advancing hematopoietic stem cell (HSC) gene therapy. Here we review the advantages of large animal models, their contributions to the field of HSC gene therapy, and recent progress in this field. Several properties of human HSCs including their purification, their cell-cycle characteristics, their response to cytokines, and the proliferative demands put on them after transplantation are more similar in large animal models than in mice. Progress i...

  4. Regulation of hematopoietic stem cells by their mature progeny

    OpenAIRE

    de Graaf, Carolyn A.; Kauppi, Maria; Baldwin, Tracey; D. Hyland, Craig; Metcalf, Donald; Willson, Tracy A.; Carpinelli, Marina R.; Smyth, Gordon K; Alexander, Warren S.; Hilton, Douglas J.

    2010-01-01

    Thrombopoietin (TPO), acting through its receptor Mpl, has two major physiological roles: ensuring production of sufficient platelets via stimulation of megakaryocyte production and maintaining hematopoietic stem cell (HSC) quiescence. Mpl also controls circulating TPO concentration via receptor-mediated internalization and degradation. Here, we demonstrate that the megakaryocytosis and increased platelet mass in mice with mutations in the Myb or p300 genes causes reduced circulating TPO conc...

  5. Comparison of efficacy of pressure-controlled ventilation and volume-controlled ventilation in children undergoing laparoscopic surgery%腹腔镜手术患儿压力控制通气和容量控制通气效果的比较

    Institute of Scientific and Technical Information of China (English)

    冯继峰; 郑剑秋; 周蜀克; 兰江丽

    2011-01-01

    Objective To compare the efficacy of pressure-controlled ventilation and volume-controlled ventilation in children undergoing laparoscopic surgery. Methods Thirty ASA Ⅰ or Ⅱ children of both sexes,aged 12-36 months, weighing 9-15 kg, scheduled for laparoscopic surgery, were randomly divided into 2 groups (n = 15 each): pressure-controlled ventilation group (group P) and volume-controlled ventilation group (group V) . Anesthesia was induced with propofol 2-4 mg/kg, vecuronium 0.1 mg/kg and fentanyl 2 μg/kg. The children were tracheal intubated and mechanically ventilated. The maximum inspiratory pressure was adjusted to make the tidal volume (VT ) achieve 12 ml/kg in group P and the VT was set at 12 ml/kg in group V. PETCO2 was maintained at 35-45 mm Hg. MAP, HR, PETCO2 , minute ventilation and peak airway pressure were recorded immediately after intubation (T0 ) , immediately before skin incision (T1 ) , 30 min of pneumoperitoneum (T2 ) and 15 min after the end of pneumoperitoneum (T3 ) . Arterial blood samples were taken at the same time points mentioned above for blood gas analysis. Dynamic lung compliance and physiological dead space to tidal volume ratio were calculated.Results Compared with group V, PaCO2 and PETCO2 were significantly decreased and dynamic lung compliance was significantly increased at T1,2 , and minute ventilation and peak airway pressure were significantly decreased at T0-3 in group P ( P 0.05) . Conclusion Compared with volume-controlled ventilation, pressure-controlled ventilation can better improve the ventilatory efficacy, is more beneficial to gas exchange and reduces the influence of pneumoperitoneum on respiratory function in children undergoing laparoscopic surgery.%目的 比较腹腔镜手术患儿压力控制通气和容量控制通气的效果.方法 择期行腹腔镜手术患儿30例,性别不限,年龄12~36月,ASA分级Ⅰ或Ⅱ级,体重9~15 kg,采用随机数字表法,将其随机分为2组(n=15):压力控制通气

  6. Bone Marrow GvHD after Allogeneic Hematopoietic Stem Cell Transplantation

    OpenAIRE

    Szyska, Martin; Na, Il-Kang

    2016-01-01

    The bone marrow is the origin of all hematopoietic lineages and an important homing site for memory cells of the adaptive immune system. It has recently emerged as a graft-versus-host disease (GvHD) target organ after allogeneic stem cell transplantation (alloHSCT), marked by depletion of both hematopoietic progenitors and niche-forming cells. Serious effects on the restoration of hematopoietic function and immunological memory are common, especially in patients after myeloablative conditioni...

  7. Experiments on Gene Transferring to Primary Hematopoietic Cells by Liposome

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Liposomes have showed many advantages in mediating exogenous gene into many cell types in vitro and in vivo. But few data are available concerning gene transfer into hematopoietic cells. In this report, we described two-marker genes (Neo R and Lac Z) co-transferred into hematopoietic cells of human and mouse by using liposome in vitro. The efficiency of gene transfer was tested by Xgal staining and observation of colony formation. The X-gal blue staining rate of transduced cells was about (13.33±2. 68) % in human and about (16. 28±2.95) % in mouse without G418 selection. After G418 selection, the blue cell rate was (46. 06±3.47)%in human and (43. 45±4. 1) % in mouse, which were markedly higher than those before selection, suggesting that high-efficiency gene transfer and expression could be attained in primary hematopoietic cells using this easy and harmless transduction protocol. At the same time, this protocol provided experimental data for clinicians to investigate the biology of marrow reconstitution and trace the origin of relapse after autologous bone marrow transplantation for the patients with leukemia.

  8. Measuring microRNA expression in mouse hematopoietic stem cells.

    Science.gov (United States)

    Hu, Wenhuo; Park, Christopher Y

    2014-01-01

    MicroRNAs (miRNAs) are important regulators of diverse biologic processes. In the hematopoietic system, miRNAs have been shown to regulate lineage fate decisions, mature immune effector cell function, apoptosis, and cell cycling, and a more limited number of miRNAs has been shown to regulate hematopoietic stem cell (HSC) self-renewal. Many of these miRNAs were initially identified as candidate regulators of HSC function by comparing miRNA expression in hematopoietic stem and progenitors cells (HSPCs) to their mature progeny. While the measurement of miRNA expression in rare cell populations such as HSCs poses practical challenges due to the low amount of RNA present, a number of techniques have been developed to measure miRNAs in small numbers of cells. Here, we describe our protocol for measuring miRNAs in purified mouse HSCs using a highly sensitive real-time quantitative PCR strategy that utilizes microfluidic array cards containing pre-spotted TaqMan probes that allows the detection of mature miRNAs in small reaction volumes. We also describe a simple data analysis method to evaluate miRNA expression profiling data using an open-source software package (HTqPCR) using mouse HSC miRNA profiling data generated in our lab. PMID:25062625

  9. Protracted radiation-induced alterations in hematopoietic repair and recovery

    International Nuclear Information System (INIS)

    Pathologic predisposition of beagle dogs under chronic, low daily dose (7.5 cGy day-1) whole-body gamma irradiation has been studied relative to molecular repair and hematopoietic competency. Molecular repair, assessed by a microscopy-based unscheduled DNA synthesis (UDS) response, was measured within proliferative and nonproliferative marrow myeloid elements of dogs with markedly different hematopoietic capacities (low capacity, aplasia-prone [AA+] versus high capacity, myeloproliferative disease-prone [MPD+]) under protracted radiation stress. Results indicated that protracted exposure elicited a net increase in UDS-repair capacity that was largely independent of exposure duration. This enhanced capacity resulted from the increased strength of the UDS signal together with an expanded number of positively responding cells. The combined response was strong in primitive blasts and weak in more differentiated myelocytic cells. The UDS repair response of the MPD+ dogs was significantly greater than that of the AA+ animals and was clearly modified relative to the controls. These results suggest that both resiliency and pathologic potential of the hematopoietic system under protracted radiation stress is, in part, associated with an augmentable DNA repair within the more primitive myeloid marrow elements. (author)

  10. Preparação psicológica e o estresse de crianças submetidas a cirurgias Preparación psicológica y el estrés de los niños sometidos a cirugía Psychological preparation and stress of children undergoing surgery

    Directory of Open Access Journals (Sweden)

    Camilla Volpato Broering

    2011-03-01

    ños en pre-quirúrgicos y las limitaciones a considerar en la investigación de esta área de la psicología pediátrica.This paper aims to present a study that assessed the effects of psychological preparation on pre-surgical stress in children undergoing elective surgery, using two separate programs of preparation. The research was conducted with 30 participants, divided into two groups, users of a children's hospital and it used the Child Stress Scale (ESI. There were three distinct stages: a Implementation of ESI before preparation, the day before the surgery, b the preparation itself, in both groups submitted to different programs of preparation, and c a reapplication of ESI, after preparation. The results showed that significant reduction in the level of stress after preparation, although there was no significant difference on the type of program used. There are practical implications for the psychological attendance of children in pre-surgical situation and limitations to consider when researching this area of pediatric psychology.

  11. Financial analysis of Serbian companies undergoing privatization

    Directory of Open Access Journals (Sweden)

    Nino Vesković

    2016-05-01

    Full Text Available This study presents a financial analysis of companies undergoing the process of privatization in the Republic of Serbia (RS. A total of 182 of such companies were examined and compared to an equal number of randomly chosen companies of comparable size. The results revealed a significant gap between the financial performances of the two samples. For that reason, the companies undergoing privatization need to undergo radical changes for the purpose of achieving a higher level of profitability and preventing further losses. Given that these companies pose a significant challenge for the Serbian economy, the author believes that this study will serve as a reference for further research. In addition, this manuscript shall present the comparative analysis of the total net loss of the observed companies and the gross domestic product of the RS, as well as between the corresponding number of employees for the year 2013.

  12. Effects of tramadol combined with acetaminophen suppository for the prevention of emergence agitation in children undergoing sevoflurane general anesthesia%曲马多复合对乙酰氨基酚栓剂防治小儿七氟醚全麻苏醒期躁动的效果

    Institute of Scientific and Technical Information of China (English)

    卿朝辉; 徐波; 尧新华; 王保; 鲁义; 陈陈燕

    2014-01-01

    目的::观察曲马多复合对乙酰氨基酚栓剂防治小儿七氟醚全麻苏醒期躁动的效果。方法:择期七氟醚全麻下手术患儿90例随机分为3组,每组各30例。3组均用8%七氟醚、芬太尼2μg/kg和维库溴铵0.1 mg/kg全麻诱导,术中以七氟醚(1~1.5 MAC)维持麻醉。 A组:术前10 min对乙酰氨基酚栓剂20 mg/kg塞肛+手术结束前20 min静注曲马多1 mg/kg;B组:手术结束前20 min静注曲马多2 mg/kg;C组:手术结束前20 min静注等量生理盐水。观察3组手术时间,术后清醒时间、拔管时间、镇静评分、躁动发生情况及药物不良反应。结果:3组手术时间、清醒时间、拔管时间等指标比较,差异无统计学意义(P>0.05)。 A组躁动发生率、恶心呕吐发生率和躁动评分明显低于B组和C组,而Remesay镇静评分明显高于B组和C组( P0.05) . The incidence of agitation, nausea and vomiting, and agitation score in group A were significantly lower than those in group B and group C. However, the Remesay sedation score in group A was significantly higher than that in group B and group C ( P<0.05) . Conclusion:The effects of 1mg/kg of tramadol combined with 20mg/kg of acetaminophen suppository for the prevention of emergence agitation in children undergoing sevoflurane general anesethesia were safe and effective.

  13. Effects of hematopoietic growth factors on purified bone marrow progenitor cells

    NARCIS (Netherlands)

    F.J. Bot (Freek)

    1992-01-01

    textabstractWe have used highly enriched hematopoietic progenitor cells and in-vitro culture to examine the following questions: 1. The effects of recombinant lL-3 and GM-CSF on proliferation and differentiation of enriched hematopoietic progenitor cells have not been clearly defined: - how do IL~3

  14. Analysis and manipulation of hematopoietic progenitor and stem cells from murine embryonic tissues

    NARCIS (Netherlands)

    A. Medvinsky (Alexander); S. Taoudi (Samir); S.C. Mendes (Sandra); E.A. Dzierzak (Elaine)

    2008-01-01

    textabstractHematopoietic development begins in several locations in the mammalian embryo: yolk sac, aorta-gonad-mesonephros region (AGM), and the chorio-allantoic placenta. Generation of the most potent cells, adult definitive hematopoietic stem cells (HSCs), occurs within the body of the mouse emb

  15. A novel complex, RUNX1-MYEF2, represses hematopoietic genes in erythroid cells

    NARCIS (Netherlands)

    B. van Riel (Boet); T. Pakozdi (Tibor); R.W.W. Brouwer; R. Monteiro (Rui); E. Tuladhar (Era); V. Franke (Vedran); J.C. Bryne; R.J.J. Jorna (Ruud); E.J. Rijkers; W.F.J. van IJcken (Wilfred); C. Andrieu-Soler (Charlotte); J.A.A. Demmers (Jeroen); R. Patient; E. Soler (Eric); B. Lenhard (Boris); F.G. Grosveld (Frank)

    2012-01-01

    textabstractRUNX1 is known to be an essential transcription factor for generating hematopoietic stem cells (HSC), but much less is known about its role in the downstream process of hematopoietic differentiation. RUNX1 has been shown to be part of a large transcription factor complex, together with L

  16. Directed differentiation of definitive hemogenic endothelium and hematopoietic progenitors from human pluripotent stem cells.

    Science.gov (United States)

    Ditadi, Andrea; Sturgeon, Christopher M

    2016-05-15

    The generation of hematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) remains a major goal for regenerative medicine and disease modeling. However, hPSC differentiation cultures produce mostly hematopoietic progenitors belonging to the embryonic HSC-independent hematopoietic program, which may not be relevant or accurate for modeling normal and disease-state adult hematopoietic processes. Through a stage-specific directed differentiation approach, it is now possible to generate exclusively definitive hematopoietic progenitors from hPSCs showing characteristics of the more developmentally advanced fetal hematopoiesis. Here, we summarize recent efforts at generating hPSC-derived definitive hematopoiesis through embryoid body differentiation under defined conditions. Embryoid bodies are generated through enzymatic dissociation of hPSCs from matrigel-coated plasticware, followed by recombinant BMP4, driving mesoderm specification. Definitive hematopoiesis is specified by a GSK3β-inhibitor, followed by recombinant VEGF and supportive hematopoietic cytokines. The CD34+ cells obtained using this method are then suitable for hematopoietic assays for definitive hematopoietic potential. PMID:26439174

  17. Estradiol increases hematopoietic stem and progenitor cells independent of its actions on bone

    NARCIS (Netherlands)

    Illing, Anett; Liu, Peng; Ostermay, Susanne; Schilling, Arndt; de Haan, Gerald; Krust, Andree; Amling, Michael; Chambon, Pierre; Schinke, Thorsten; Tuckermann, Jan P.

    2012-01-01

    Hematopoietic stem and progenitor cells reside in vascular and endosteal niches in the bone marrow. Factors affecting bone remodeling were reported to influence numbers and mobilization of hematopoietic stem cells. We therefore analyzed the effects of estradiol acting anabolic on bone integrity. Her

  18. Of lineage and legacy: The development of mammalian hematopoietic stem cells

    NARCIS (Netherlands)

    E.A. Dzierzak (Elaine); N.A. Speck (Nancy)

    2008-01-01

    textabstractThe hematopoietic system is one of the first complex tissues to develop in the mammalian conceptus. Of particular interest in the field of developmental hematopoiesis is the origin of adult bone marrow hematopoietic stem cells. Tracing their origin is complicated because blood is a mobil

  19. Aspirin in patients undergoing noncardiac surgery

    DEFF Research Database (Denmark)

    Devereaux, P J; Mrkobrada, Marko; Sessler, Daniel I;

    2014-01-01

    BACKGROUND: There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not. METHODS: Using a 2-by-2 factorial trial design, we randomly assigned 10,010...

  20. File list: DNS.Bld.20.AllAg.CD34_Hematopoietic_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. Repurposing Treprostinil for Enhancing Hematopoietic Progenitor Cell Transplantation.

    Science.gov (United States)

    Kazemi, Zahra; Bergmayr, Christian; Prchal-Murphy, Michaela; Javaheri, Tahereh; Themanns, Madeleine; Pham, Ha T T; Strohmaier, Wolfgang; Sexl, Veronika; Freissmuth, Michael; Zebedin-Brandl, Eva

    2016-06-01

    Activation of Gs-coupled receptors enhances engraftment of hematopoietic stem and progenitor cells (HSPCs). We tested the hypothesis that treprostinil, a prostacyclin analog approved for the treatment of pulmonary hypertension, can be repurposed to improve hematopoietic stem cell transplantation. Murine and human HSPCs were isolated from bone marrow and umbilical cord blood, respectively. Prostanoid receptor agonists and the combination thereof with forskolin were tested for their capacity to stimulate [(3)H]cAMP accumulation in HSPCs. Three independent approaches were employed to verify the ability of agonist-activated HSPCs to reconstitute the bone marrow in lethally irradiated recipient mice. The underlying mechanism was explored in cellular migration assays and by blocking C-X-C motif chemokine receptor 4 (CXCR4). Among several prostanoid agonists tested in combination with forskolin, treprostinil was most efficacious in raising intracellular cAMP levels in murine and human HPSCs. Injection of murine and human HSPCs, which had been pretreated with treprostinil and forskolin, enhanced survival of lethally irradiated recipient mice. Survival was further improved if recipient mice were subcutaneously administered treprostinil (0.15 mg kg(-1) 8 h(-1)) for 10 days. This regimen also reduced the number of HSPCs required to rescue lethally irradiated mice. Enhanced survival of recipient mice was causally related to treprostinil-enhanced CXCR4-dependent migration of HSPCs. Treprostinil stimulates the engraftment of human and murine hematopoietic stem cells without impairing their capacity for self-renewal. The investigated dose range corresponds to the dose approved for human use. Hence, these findings may be readily translated into a clinical application. PMID:26989084

  14. The Hematopoietic Stem Cell Therapy for Exploration of Space

    Science.gov (United States)

    Roach, Allana Nicole; Brezo, Jelena

    2002-01-01

    Astronauts experience severe/invasive disorders caused by space environments. These include hematological/cardiac abnormalities, bone and muscle losses, immunodeficiency, neurological disorders and cancer. While the cause of these symptoms are not yet fully delineated, one possible explanation could be the inhibition of hematopoietic stem cell (HSC) growth and hematopoiesis in space. HSCs differentiate into all types of blood cells, and growing evidence indicates that the HSCs also have the ability to transdifferentiate to various tissues, including muscle, skin, liver, neuronal cells and possibly bone. Therefore, a hypothesis was advanced in this laboratory that the hematopoietic stem cell-based therapy, herein called the hematopoietic stem cell therapy (HSCT), could mitigate some of the disorders described above. Due to the magnitude of this project our laboratory has subdivided it into 3 sections: a) HSCT for space anemia; b) HSCT for muscle and bone losses; and c) HSCT for immunodeficiency. Toward developing the HSCT protocol for space anemia, the HSC transplantation procedure was established using a mouse model of beta thalassemia. In addition, the NASA Rotating Wall Vessel (RWV) culture system was used to grow HSCs in space condition. To investigate the HSCT for muscle loss and bone loss, donor HSCs were genetically marked either by transfecting the beta-galactosidase-containing plasmid, pCMV.SPORT-beta-gal or by preparing from b-galactosidase transgenic mice. The transdifferentiation of HSCs to muscle is traced by the reporter gene expression in the hindlimb suspended mice with some positive outcome, as studied by the X-gal staining procedure. The possible structural contribution of HSCs against muscle loss is being investigated histochemically.

  15. Endothelio-hematopoietic relationship: getting closer to the beginnings

    Directory of Open Access Journals (Sweden)

    Gordon-Keylock Sabrina

    2011-12-01

    Full Text Available Abstract The close association between hematopoietic and endothelial cells during embryonic development led to the proposal that they may originate from a common ancestor - the hemangioblast. Due to a lack of unique specific markers for in vivo cell fate tracking studies, evidence supporting this theory derives mainly from in vitro differentiation studies. Teixeira and colleagues describe a novel enhancer that drives specific eGFP expression in blood islands of the electroporated chick embryo, thereby presenting a tool potentially suitable for analysis of hemangioblast differentiation and development of blood islands. See research article: http://www.biomedcentral.com/1471-213X/11/76

  16. The Hematopoietic Stem Cell Therapy for Exploration of Deep Space

    Science.gov (United States)

    Ohi, Seigo; Roach, Allana-Nicole; Fitzgerald, Wendy; Riley, Danny A.; Gonda, Steven R.

    2003-01-01

    It is hypothesized that the hematopoietic stem cell therapy (HSCT) might countermeasure various space-caused disorders so as to maintain astronauts' homeostasis. If this were achievable, the HSCT could promote human exploration of deep space. Using animal models of disorders (hindlimb suspension unloading system and beta-thalassemia), the HSCT was tested for muscle loss, immunodeficiency and space anemia. The results indicate feasibility of HSCT for these disorders. To facilitate the HSCT in space, growth of HSCs were optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

  17. Gelatinous marrow transformation and hematopoietic atrophy in a miniature horse stallion.

    Science.gov (United States)

    Beeler-Marfisi, J; Gallastegui Menoyo, A; Beck, A; König, J; Hewson, J; Bienzle, D

    2011-03-01

    Gelatinous marrow transformation, or serous atrophy of bone marrow fat, has been noted in livestock, laboratory animals, and wildlife in association with an inadequate plane of nutrition, inanition, or intoxication. This is a report of gelatinous marrow transformation and hematopoietic marrow atrophy in a 5-year-old miniature horse stallion. The horse had oral malformations leading to poor food assimilation and emaciation. A bone marrow biopsy obtained to investigate persistent anemia and leukopenia showed hematopoietic atrophy and replacement of fat with a granular extracellular substance, which stained with alcian blue, consistent with acidic mucopolysaccharide content. Surgical correction of the dental abnormalities resulted in improved food assimilation, weight gain, and resolution of cytopenias. In humans, gelatinous bone marrow transformation and hematopoietic atrophy are commonly associated with malnutrition from anorexia nervosa and other causes. The cause of hematopoietic atrophy is unknown but may relate to a nonsupportive marrow microenvironment and inadequate hematopoietic substrate availability. Similar pathogenic mechanisms were suspected in this horse. PMID:20587692

  18. Thrombopoietin Induces HOXA9 Nuclear Transport in Immature Hematopoietic Cells: Potential Mechanism by Which the Hormone Favorably Affects Hematopoietic Stem Cells

    OpenAIRE

    Kirito, Keita; Fox, Norma; Kaushansky, Kenneth

    2004-01-01

    Members of the homeobox family of transcription factors are major regulators of hematopoiesis. Overexpression of either HOXB4 or HOXA9 in primitive marrow cells enhances the expansion of hematopoietic stem cells (HSCs). However, little is known of how expression or function of these proteins is regulated during hematopoiesis under physiological conditions. In our previous studies we demonstrated that thrombopoietin (TPO) enhances levels of HOXB4 mRNA in primitive hematopoietic cells (K. Kirit...

  19. Optimized patient-trajectory for patients undergoing treatment with high-dose chemotherapy and autologous stem cell transplantation

    DEFF Research Database (Denmark)

    Bartels, Frederik Reith; Smith, Nicholas Simon; Gørløv, Jette Sønderskov;

    2015-01-01

    PURPOSE: Before, during and after autologous hematopoietic stem cell transplantation (HD-ASCT) patients suffer from significant loss of physical function, and experience multiple complications during and after hospitalization. Studies regarding safety and feasibility of physical exercise interven......PURPOSE: Before, during and after autologous hematopoietic stem cell transplantation (HD-ASCT) patients suffer from significant loss of physical function, and experience multiple complications during and after hospitalization. Studies regarding safety and feasibility of physical exercise...... interventions for patients undergoing treatment with HD-ASCT are missing. METHODS: Forty patients referred to HD-ASCT treatment, suffering from multiple myeloma, lymphoma or amyloidosis aged 23-70 years were enrolled in a prospective longitudinal study. The study consisted of a home-based exercise program for...... use in the ambulatory setting and supervised exercise sessions Monday to Friday for 30-40 minutes during admission. Safety of the exercise program and physical tests were assessed by using a weekly questionnaire and report of inadvertent incidences. Adherence to the home-based exercise program was...

  20. Pilot experience with opebacan/rBPI21 in myeloablative hematopoietic cell transplantation [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Eva Guinan

    2015-12-01

    Full Text Available Bacterial infection and inflammation contribute significantly to the morbidity and mortality of myeloablative allogeneic hematopoietic cell transplantation (HCT. Endotoxin, a component of the outer membrane of Gram-negative bacteria, is a potent inflammatory stimulus in humans. Bactericidal/permeability increasing protein (BPI, a constituent of human neutrophil granules, binds endotoxin thereby precluding endotoxin-induced inflammation and also has direct anti-infective properties against bacteria. As a consequence of myeloablative therapy used in preparation for hematopoietic cell infusion, patients experience gastrointestinal leak of bacteria and bacterial toxins into the systemic circulation and a period of inflammatory cytokine elevation associated with subsequent regimen-related toxicities.  Patients frequently become endotoxemic and febrile as well as BPI-deficient due to sustained neutropenia. To examine whether enhancing endotoxin-neutralizing and anti-infective activity by exogenous administration of a recombinant N-terminal fragment of BPI (rBPI21, generic name opebacan might ameliorate regimen-related toxicities including infection, we recruited patients scheduled to undergo myeloablative HCT to participate in a proof-of-concept prospective phase I/II trial. After the HCT preparative regimen was completed, opebacan was initiated 18-36 hours prior to administration of allogeneic hematopoietic stem cells (defined as Day 0 and continued for 72 hours. The trial was to have included escalation of rBPI21 dose and duration but was stopped prematurely due to lack of further drug availability.  Therefore, to better understand the clinical course of opebacan-treated patients (n=6, we compared their outcomes with a comparable cohort meeting the same eligibility criteria and enrolled in a non-interventional myeloablative HCT observational study (n = 35.  Opebacan-treated participants had earlier platelet engraftment (p=0.005, mirroring

  1. Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency.

    Science.gov (United States)

    De Ravin, Suk See; Wu, Xiaolin; Moir, Susan; Anaya-O'Brien, Sandra; Kwatemaa, Nana; Littel, Patricia; Theobald, Narda; Choi, Uimook; Su, Ling; Marquesen, Martha; Hilligoss, Dianne; Lee, Janet; Buckner, Clarissa M; Zarember, Kol A; O'Connor, Geraldine; McVicar, Daniel; Kuhns, Douglas; Throm, Robert E; Zhou, Sheng; Notarangelo, Luigi D; Hanson, I Celine; Cowan, Mort J; Kang, Elizabeth; Hadigan, Coleen; Meagher, Michael; Gray, John T; Sorrentino, Brian P; Malech, Harry L

    2016-04-20

    X-linked severe combined immunodeficiency (SCID-X1) is a profound deficiency of T, B, and natural killer (NK) cell immunity caused by mutations inIL2RGencoding the common chain (γc) of several interleukin receptors. Gamma-retroviral (γRV) gene therapy of SCID-X1 infants without conditioning restores T cell immunity without B or NK cell correction, but similar treatment fails in older SCID-X1 children. We used a lentiviral gene therapy approach to treat five SCID-X1 patients with persistent immune dysfunction despite haploidentical hematopoietic stem cell (HSC) transplant in infancy. Follow-up data from two older patients demonstrate that lentiviral vector γc transduced autologous HSC gene therapy after nonmyeloablative busulfan conditioning achieves selective expansion of gene-marked T, NK, and B cells, which is associated with sustained restoration of humoral responses to immunization and clinical improvement at 2 to 3 years after treatment. Similar gene marking levels have been achieved in three younger patients, albeit with only 6 to 9 months of follow-up. Lentiviral gene therapy with reduced-intensity conditioning appears safe and can restore humoral immune function to posthaploidentical transplant older patients with SCID-X1. PMID:27099176

  2. The effects of hematopoietic growth factors on neurite outgrowth.

    Directory of Open Access Journals (Sweden)

    Ye Su

    Full Text Available Stem cell factor (SCF and granulocyte colony-stimulating factor (G-CSF are initially discovered as the essential hematopoietic growth factors regulating bone marrow stem cell proliferation and differentiation, and SCF in combination with G-CSF (SCF+G-CSF has synergistic effects on bone marrow stem cell mobilization. In this study we have determined the effect of SCF and G-CSF on neurite outgrowth in rat cortical neurons. Using molecular and cellular biology and live cell imaging approaches, we have revealed that receptors for SCF and G-CSF are expressed on the growth core of cortical neurons, and that SCF+G-CSF synergistically enhances neurite extension through PI3K/AKT and NFκB signaling pathways. Moreover, SCF+G-CSF induces much greater NFκB activation, NFκB transcriptional binding and brain-derived neurotrophic factor (BDNF production than SCF or G-CSF alone. In addition, we have also observed that BDNF, the target gene of NFκB, is required for SCF+G-CSF-induced neurite outgrowth. These data suggest that SCF+G-CSF has synergistic effects to promote neurite growth. This study provides new insights into the contribution of hematopoietic growth factors in neuronal plasticity.

  3. Arrhythmias in the setting of hematopoietic cell transplants.

    Science.gov (United States)

    Tonorezos, E S; Stillwell, E E; Calloway, J J; Glew, T; Wessler, J D; Rebolledo, B J; Pham, A; Steingart, R M; Lazarus, H; Gale, R P; Jakubowski, A A; Schaffer, W L

    2015-09-01

    Prior studies report that 9-27% of persons receiving a hematopoietic cell transplant develop arrhythmias, but the effect on outcomes is largely unknown. We reviewed data from 1177 consecutive patients ⩾40 years old receiving a hematopoietic cell transplant at one center during 1999-2009. Transplant indication was predominately leukemia, lymphoma and multiple myeloma. Overall, 104 patients were found to have clinically significant arrhythmia: 43 before and 61 after transplant. Post-transplant arrhythmias were most frequently atrial fibrillation (N=30), atrial flutter (N=7) and supraventricular tachycardia (N=11). Subjects with an arrhythmia post transplant were more likely to have longer median hospital stays (32 days vs 23, P=transplant (41% vs 15%; Ptransplant, diagnosis, history of pretransplant arrhythmia, and transplant-related variables, post-transplant arrhythmia was associated with a greater risk for death within a year of transplant (odds ratio 3.5, 95% confidence interval: 2.1, 5.9; Ptransplants are associated with significant morbidity and mortality. A prospective study of arrhythmia in the transplant setting is warranted. PMID:26030046

  4. SHIPi Enhances Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Sandra Fernandes

    2015-03-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is a highly effective procedure enabling long-term survival for patients with hematologic malignancy or heritable defects. Although there has been a dramatic increase in the success rate of HSCT over the last two decades, HSCT can result in serious, sometimes untreatable disease due to toxic conditioning regimens and Graft-versus-Host-Disease. Studies utilizing germline knockout mice have discovered several candidate genes that could be targeted pharmacologically to create a more favorable environment for transplant success. SHIP1 deficiency permits improved engraftment of hematopoietic stem-progenitor cells (HS-PCs and produces an immunosuppressive microenvironment ideal for incoming allogeneic grafts. The recent development of small molecule SHIP1 inhibitors has opened a different therapeutic approach by creating transient SHIP1-deficiency. Here we show that SHIP1 inhibition (SHIPi mobilizes functional HS-PC, accelerates hematologic recovery, and enhances donor HS-PC engraftment in both allogeneic and autologous transplant settings. We also observed the expansion of key cell populations known to suppress host-reactive cells formed during engraftment. Therefore, SHIPi represents a non-toxic, new therapeutic that has significant potential to improve the success and safety of therapies that utilize autologous and allogeneic HSCT.

  5. Radioprotective effect of genistein on hematopoietic system of mice

    International Nuclear Information System (INIS)

    Objective: To study the radioprotective effect of genistein on mice hematopoietic system. Methods: Adult male BALB/c mice were administered orally with genistein 24 h before exposure to a sublethal dose of 6.0 Gy gamma irradiation. The 30-day survival rate and some indices with relation to hematogenesis were examined after irradiation and pathologic changes of bone marrow were detected by hematotoxylin-eosin staining. Results: Bone marrow was damaged slightly, and the numbers of peripheral blood WBC, bone marrow nucleated cells and CFU-S were all significantly higher and restored more rapidly in genistein-treated groups than those in the corresponding irradiated controls (P<0.05). Meanwhile, genistein could also increase the 30-days survival rate and the average survival days of dead mice (P<0.05). All results were similar to those in diethylstilbestrol-treated groups. In addition, genistein could promote recovery of spleen/body weight ratio (P<0.05). Conclusion: These observations suggest that genistein has the capability of reducing the damage of hematopoietic system in irradiated mice and has significant protective effect on mice against radiation injury. (authors)

  6. Sphingolipid signaling and hematopoietic malignancies: to the rheostat and beyond.

    Science.gov (United States)

    Loh, Kenneth C; Baldwin, Dianna; Saba, Julie D

    2011-11-01

    Sphingosine-1-phosphate (S1P) is a bioactive lipid with diverse functions including the promotion of cell survival, proliferation and migration, as well as the regulation of angiogenesis, inflammation, immunity, vascular permeability and nuclear mechanisms that control gene transcription. S1P is derived from metabolism of ceramide, which itself has diverse and generally growth-inhibitory effects through its impact on downstream targets involved in regulation of apoptosis, senescence and cell cycle progression. Regulation of ceramide, S1P and the biochemical steps that modulate the balance and interconversion of these two lipids are major determinants of cell fate, a concept referred to as the "sphingolipid rheostat." There is abundant evidence that the sphingolipid rheostat plays a role in the origination, progression and drug resistance patterns of hematopoietic malignancies. The pathway has also been exploited to circumvent the problem of chemotherapy resistance in leukemia and lymphoma. Given the broad effects of sphingolipids, targeting multiple steps in the metabolic pathway may provide possible therapeutic avenues. However, new observations have revealed that sphingolipid signaling effects are more complex than previously recognized, requiring a revision of the sphingolipid rheostat model. Here, we summarize recent insights regarding the sphingolipid metabolic pathway and its role in hematopoietic malignancies. PMID:21707493

  7. Epidemiological characteristics of infectious hematopoietic necrosis virus (IHNV): a review.

    Science.gov (United States)

    Dixon, Peter; Paley, Richard; Alegria-Moran, Raul; Oidtmann, Birgit

    2016-01-01

    Infectious hematopoietic necrosis virus (IHNV, Rhabdoviridae), is the causative agent of infectious hematopoietic necrosis (IHN), a disease notifiable to the World Organisation for Animal Health, and various countries and trading areas (including the European Union). IHNV is an economically important pathogen causing clinical disease and mortalities in a wide variety of salmonid species, including the main salmonid species produced in aquaculture, Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss). We reviewed the scientific literature on IHNV on a range of topics, including geographic distribution; host range; conditions required for infection and clinical disease; minimum infectious dose; subclinical infection; shedding of virus by infected fish; transmission via eggs; diagnostic tests; pathogen load and survival of IHNV in host tissues. This information is required for a range of purposes including import risk assessments; parameterisation of disease models; for surveillance planning; and evaluation of the chances of eradication of the pathogen to name just a few. The review focuses on issues that are of relevance for the European context, but many of the data summarised have relevance to IHN globally. Examples for application of the information is presented and data gaps highlighted. PMID:27287024

  8. Perturbation of the Hematopoietic Profile by Anabolic Androgenic Steroids

    Directory of Open Access Journals (Sweden)

    Jenny Erkander Mullen

    2014-01-01

    Full Text Available Objective. The aim of this study was to investigate the hematopoietic profile in AAS abusers, during or short after their last abuse and approximately six months later. Moreover, we studied if supraphysiological doses of testosterone influence the concentration of hemoglobin and erythropoietin in healthy volunteers. Design and Methods. Subjects (N=31 were recruited through an antidoping hotline. The hematological profile was measured when the subjects entered the study and approximately 6 months later. Testosterone enanthate (500 mg was administered to healthy volunteers (N=24. Gene expression was studied in human hek293 cells exposed to 1 μM testosterone. Results. Decreased levels of hemoglobin, erythrocyte volume fraction, and erythrocyte counts were observed after 6 months without the use of AAS. Results in volunteers show that hemoglobin increased 3% four and 15 days after testosterone administration, whereas EPO was significantly increased by 38% four days after dose. Agreeingly, in vitro study shows that testosterone induces the mRNA level of EPO with 65% after 24-hour exposure. Conclusion. These results indicate that supraphysiological doses of testosterone may cause a perturbation in the hematopoietic profile. This is of interest in relation to the adverse cardiovascular effects observed in AAS abusers.

  9. Design inspections for systems undergoing design modifications

    International Nuclear Information System (INIS)

    The US Nuclear Regulatory Commission's (NRC's) Office of Inspection and Enforcement (IE) has conducted direct inspections (integrated design inspections) of the technical aspects of the nuclear plant design process for several plants under construction. It has also evaluated independent design verification programs and engineering assurance programs at a number of other plants under construction. Many of the lessons learned from these construction phase efforts are directly applicable to operating plants undergoing major modifications. This has been confirmed by IE direct inspections of the design aspects of safety systems outage modifications, which have identified significant potential safety-related deficiencies. The paper discusses methodology for design inspections; failure to maintain up-to-date design basis documentation; and lessons learned common to plants under construction and undergoing major modifications

  10. Mitigation of Late Renal and Pulmonary Injury After Hematopoietic Stem Cell Transplantation

    International Nuclear Information System (INIS)

    Purpose: To update the results of a clinical trial that assessed whether the angiotensin-converting enzyme inhibitor captopril was effective in mitigating chronic renal failure and pulmonary-related mortality in subjects undergoing total body irradiation (TBI) in preparation for hematopoietic stem cell transplantation (HSCT). Methods and Materials: Updated records of the 55 subjects who were enrolled in this randomized controlled trial were analyzed. Twenty-eight patients received captopril, and 27 patients received placebo. Definitions of TBI-HSCT-related chronic renal failure (and relapse) were the same as those in the 2007 analysis. Pulmonary-related mortality was based on clinical or autopsy findings of pulmonary failure or infection as the primary cause of death. Follow-up data for overall and pulmonary-related mortality were supplemented by use of the National Death Index. Results: The risk of TBI-HSCT-related chronic renal failure was lower in the captopril group (11% at 4 years) than in the placebo group (17% at 4 years), but this was not statistically significant (p > 0.2). Analysis of mortality was greatly extended by use of the National Death Index, and no patients were lost to follow-up for reasons other than death prior to 67 months. Patient survival was higher in the captopril group than in the placebo group, but this was not statistically significant (p > 0.2). The improvement in survival was influenced more by a decrease in pulmonary mortality (11% risk at 4 years in the captopril group vs. 26% in the placebo group, p = 0.15) than by a decrease in chronic renal failure. There was no adverse effect on relapse risk (p = 0.4). Conclusions: Captopril therapy produces no detectable adverse effects when given after TBI. Captopril therapy reduces overall and pulmonary-related mortality after radiation-based HSCT, and there is a trend toward mitigation of chronic renal failure.

  11. The consensus sequence of FAMLF alternative splice variants is overexpressed in undifferentiated hematopoietic cells

    Directory of Open Access Journals (Sweden)

    W.L. Chen

    2015-07-01

    Full Text Available The familial acute myeloid leukemia related factor gene (FAMLF was previously identified from a familial AML subtractive cDNA library and shown to undergo alternative splicing. This study used real-time quantitative PCR to investigate the expression of the FAMLF alternative-splicing transcript consensus sequence (FAMLF-CS in peripheral blood mononuclear cells (PBMCs from 119 patients with de novo acute leukemia (AL and 104 healthy controls, as well as in CD34+ cells from 12 AL patients and 10 healthy donors. A 429-bp fragment from a novel splicing variant of FAMLF was obtained, and a 363-bp consensus sequence was targeted to quantify total FAMLF expression. Kruskal-Wallis, Nemenyi, Spearman's correlation, and Mann-Whitney U-tests were used to analyze the data. FAMLF-CS expression in PBMCs from AL patients and CD34+ cells from AL patients and controls was significantly higher than in control PBMCs (P<0.0001. Moreover, FAMLF-CS expression in PBMCs from the AML group was positively correlated with red blood cell count (rs =0.317, P=0.006, hemoglobin levels (rs =0.210, P=0.049, and percentage of peripheral blood blasts (rs =0.256, P=0.027, but inversely correlated with hemoglobin levels in the control group (rs =–0.391, P<0.0001. AML patients with high CD34+ expression showed significantly higher FAMLF-CS expression than those with low CD34+ expression (P=0.041. Our results showed that FAMLF is highly expressed in both normal and malignant immature hematopoietic cells, but that expression is lower in normal mature PBMCs.

  12. Standard sub-thermoneutral caging temperature influences radiosensitivity of hematopoietic stem and progenitor cells.

    Directory of Open Access Journals (Sweden)

    Benjamin J Povinelli

    Full Text Available The production of new blood cells relies on a hierarchical network of hematopoietic stem and progenitor cells (HSPCs. To maintain lifelong hematopoiesis, HSPCs must be protected from ionizing radiation or other cytotoxic agents. For many years, murine models have been a valuable source of information regarding factors that either enhance or reduce the survival of HSPCs after exposure of marrow to ionizing radiation. In a recent series of studies, however, it has become clear that housing-related factors such as the cool room temperature required for laboratory mice can exert a surprising influence on the outcome of experiments. Here we report that the mild, but chronic cold-stress endured by mice housed under these conditions exerts a protective effect on HSPCs after both non-lethal and lethal doses of total body irradiation (TBI. Alleviation of this cold-stress by housing mice at a thermoneutral temperature (30°C resulted in significantly greater baseline radiosensitivity to a lethal dose of TBI with more HSPCs from mice housed at thermoneutral temperature undergoing apoptosis following non-lethal TBI. Cold-stressed mice have elevated levels of norepinephrine, a key molecule of the sympathetic nervous system that binds to β-adrenergic receptors. We show that blocking this signaling pathway in vivo through use of the β-blocker propanolol completely mitigates the protective effect of cold-stress on HSPC apoptosis. Collectively this study demonstrates that chronic stress endured by the standard housing conditions of laboratory mice increases the resistance of HSPCs to TBI-induced apoptosis through a mechanism that depends upon β-adrenergic signaling. Since β-blockers are commonly prescribed to a wide variety of patients, this information could be important when predicting the clinical impact of HSPC sensitivity to TBI.

  13. Mitigation of Late Renal and Pulmonary Injury After Hematopoietic Stem Cell Transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, Eric P., E-mail: Eric.Cohen2@va.gov [Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Bedi, Manpreet; Irving, Amy A. [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Jacobs, Elizabeth; Tomic, Rade [Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Klein, John [Department of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Lawton, Colleen A.; Moulder, John E. [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States)

    2012-05-01

    Purpose: To update the results of a clinical trial that assessed whether the angiotensin-converting enzyme inhibitor captopril was effective in mitigating chronic renal failure and pulmonary-related mortality in subjects undergoing total body irradiation (TBI) in preparation for hematopoietic stem cell transplantation (HSCT). Methods and Materials: Updated records of the 55 subjects who were enrolled in this randomized controlled trial were analyzed. Twenty-eight patients received captopril, and 27 patients received placebo. Definitions of TBI-HSCT-related chronic renal failure (and relapse) were the same as those in the 2007 analysis. Pulmonary-related mortality was based on clinical or autopsy findings of pulmonary failure or infection as the primary cause of death. Follow-up data for overall and pulmonary-related mortality were supplemented by use of the National Death Index. Results: The risk of TBI-HSCT-related chronic renal failure was lower in the captopril group (11% at 4 years) than in the placebo group (17% at 4 years), but this was not statistically significant (p > 0.2). Analysis of mortality was greatly extended by use of the National Death Index, and no patients were lost to follow-up for reasons other than death prior to 67 months. Patient survival was higher in the captopril group than in the placebo group, but this was not statistically significant (p > 0.2). The improvement in survival was influenced more by a decrease in pulmonary mortality (11% risk at 4 years in the captopril group vs. 26% in the placebo group, p = 0.15) than by a decrease in chronic renal failure. There was no adverse effect on relapse risk (p = 0.4). Conclusions: Captopril therapy produces no detectable adverse effects when given after TBI. Captopril therapy reduces overall and pulmonary-related mortality after radiation-based HSCT, and there is a trend toward mitigation of chronic renal failure.

  14. Specialised care in patients undergoing pancreatoduodenectomy

    OpenAIRE

    Gouma, D. J.; Busch, O.R.C.; Tol, J.A.M.G.

    2014-01-01

    This thesis studies the controversies in the management of patients with pancreatic cancer undergoing pancreatoduodenectomy and determines different factors that will improve this management and thereby the postoperative outcomes. The studies were performed in both the pre-, peri- and postoperative phase. The improvement of preoperative care is analysed by studying the impact of preoperative biliary drainage (PBD) by using metal stents instead of plastic stents, whether the type of stent infl...

  15. Perioperative Education of Patient Undergoing Cardiac Surgery

    OpenAIRE

    Alexandros Zacharis; Aikaterini Kampourelli

    2011-01-01

    In recent years, the number of patients undergoing cardiac surgeries is steadily increasing. In Greece, approximately 10,500 patients per year are admitted to some kind of cardiac operation. Constant evolution of heart surgery techniques calls for adaptation of the perioperative nursing care given. Patient education, as an important part of the perioperative care, is directly related to the reduction of postoperative complications and stress management, thus promoting the patient's overall po...

  16. Severe venous air embolism in a paediatric patient undergoing neurosurgical procedure

    Directory of Open Access Journals (Sweden)

    Naresh Dua

    2007-01-01

    Full Text Available Venous air embolism (VAE is a well-recognized complication and twice much common in children undergoing neurosurgical operations. A case of catastrophic presentation of venous air embolism during perioperative period is hereby reported. Early detection by adequate vigilant monitoring techniques and appropriate management of VAE as well as massive blood transfusion to replace the severe blood loss made the successful outcome.

  17. Obliging children.

    Science.gov (United States)

    Lyons, Barry

    2011-01-01

    Children may sometimes undergo healthcare procedures that are not intended to improve their health status. Such interventions might include the use of young children as bone marrow donors or their enrolment in non-therapeutic research. One of the justifications used to legitimise these interventions is the premise that children have obligations to others; to their family in the case of related bone marrow transplantation, and to wider society in the case of non-therapeutic research. However, this 'obligation model' (the notion that children possess positive obligations to advance the health status of others) fails as a justificatory paradigm because it is based upon a confusion, identified by Hart, between two notions; that of 'being under an obligation to do something' and that of 'being obliged to do something'. Instead the 'obligation model' is a device employed to put a justificatory gloss upon a consequentialist decision-making process; removing the legitimising gloss allows for a more transparent look at the conflict between parental rights and an individual child's right to bodily integrity. PMID:21289034

  18. Insulin-Like Growth Factor 1 Mitigates Hematopoietic Toxicity After Lethal Total Body Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Dunhua; Deoliveira, Divino; Kang, Yubin; Choi, Seung S. [Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Li, Zhiguo [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Chao, Nelson J. [Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Department of Pathology, Duke University Medical Center, Durham, North Carolina (United States); Department of Immunology, Duke University Medical Center, Durham, North Carolina (United States); Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Chen, Benny J., E-mail: chen0032@mc.duke.edu [Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States)

    2013-03-15

    Purpose: To investigate whether and how insulin-like growth factor 1 (IGF-1) mitigates hematopoietic toxicity after total body irradiation. Methods and Materials: BALB/c mice were irradiated with a lethal dose of radiation (7.5 Gy) and treated with IGF-1 at a dose of 100 μg/dose intravenously once a day for 5 consecutive days starting within 1 hour after exposure. Survival and hematopoietic recovery were monitored. The mechanisms by which IGF-1 promotes hematopoietic recovery were also studied by use of an in vitro culture system. Results: IGF-1 protected 8 of 20 mice (40%) from lethal irradiation, whereas only 2 of 20 mice (10%) in the saline control group survived for more than 100 days after irradiation. A single dose of IGF-1 (500 μg) was as effective as daily dosing for 5 days. Positive effects were noted even when the initiation of treatment was delayed as long as 6 hours after irradiation. In comparison with the saline control group, treatment with IGF-1 significantly accelerated the recovery of both platelets and red blood cells in peripheral blood, total cell numbers, hematopoietic stem cells, and progenitor cells in the bone marrow when measured at day 14 after irradiation. IGF-1 protected both hematopoietic stem cells and progenitor cells from radiation-induced apoptosis and cell death. In addition, IGF-1 was able to facilitate the proliferation and differentiation of nonirradiated and irradiated hematopoietic progenitor cells. Conclusions: IGF-1 mitigates radiation-induced hematopoietic toxicity through protecting hematopoietic stem cells and progenitor cells from apoptosis and enhancing proliferation and differentiation of the surviving hematopoietic progenitor cells.

  19. Perioperative concerns in pediatric patients undergoing different types of scoliosis correction surgery: A retrospective observational study

    Directory of Open Access Journals (Sweden)

    Anjolie Chhabra

    2013-01-01

    Patients and Methods: After taking parental consent, data were collected retrospectively for 33 patients who underwent 37 procedures (four patients had both anterior and posterior procedures on 2 days of the week mainly from August 2008 to February 2010 at a tertiary care institution. Results: Children undergoing GR surgery were younger (8.1 ± 2.1 years than patients undergoing AR (12.9 ± 1.7 years or posterior fusion (14.2 ± 2.2 years. AR children had a significantly higher Cobb′s angle and more rigid curves. (P = 0.057 Associated congenital abnormalities especially neurological were commoner in the GR children. Surgical duration and blood loss was significantly more for PF (2207.5 ± 1224.13 ml than GR (456 ± 337.5 ml, or AR (642.85 ± 304.72 ml, (P = 0.0002. PF patients needed Intensive care unit (ICU care mainly due to the blood loss and prolonged surgery (35%. AR performed via thoracotomy was associated with the need for mechanical ventilation in 28.6%. The GR patients had major intraoperative hemodynamic events and 20% needed ICU care. Conclusions: Post-operative ventilation may be required in 20-35% patients undergoing procedures for scoliosis correction. Despite GR insertion involving lesser blood loss; younger age, congenital abnormalities, positioning, and surgical manipulation resulted in life threatening events in these patients.

  20. Viridans Group Streptococcal Infections in Children After Chemotherapy or Stem Cell Transplantation: A 10-year Review From a Tertiary Pediatric Hospital.

    Science.gov (United States)

    Nielsen, Maryke J; Claxton, Sarah; Pizer, Barry; Lane, Steven; Cooke, Richard P D; Paulus, Stéphane; Carrol, Enitan D

    2016-03-01

    Viridans Group Streptococci (VGS) are associated with high mortality rates in febrile neutropenia; yet there are no recent European pediatric studies to inform antimicrobial therapy. The aim of this study was to describe the characteristics, outcome, and resistance patterns of children with VGS bacteremia (VGSB) undergoing treatment of malignancy or hematopoietic stem cell transplant.Patients aged 0 to 18 years, admitted to a tertiary pediatric hemato-oncology center with VGSB, from 2003 to 2013, were included in the study. All data were collected retrospectively from medical records.A total of 54 bacteremic episodes occurred in 46 patients. The most common underlying diagnosis was relapsed acute lymphoblastic leukemia.Streptococcus mitis was the most frequent organism. A total of 30% of isolates were resistant to penicillin and 100% sensitive to vancomycin. There were 8 episodes (14.8%) of Viridans Group Streptococcal Shock Syndrome; 6 resulted in admission to intensive care and 3 of these patients died of multiorgan failure.The potentially fatal nature of VGSB is confirmed. The high risk in relapsed acute lymphoblastic leukemia is of note. Research is needed to develop risk-stratification scores that identify children at risk of Viridans Group Streptococcal Shock Syndrome to guide empirical antimicrobial therapy in febrile neutropenia. PMID:26945409

  1. Disseminated Bacillus Calmette-Guérin (BCG) infection following allogeneic hematopoietic stem cell transplant in a patient with Bare Lymphocyte Syndrome type II

    Science.gov (United States)

    Abu-Arja, R.F.; Gonzalez, B.E.; Jacobs, M.R.; Cabral, L.; Egler, R.; Auletta, J.; Arnold, J.; Cooke, K.R.

    2016-01-01

    We describe the first case, to our knowledge, of disseminated Mycobacterium bovis Bacillus Calmette-Guérin infection in a child with Bare Lymphocyte Syndrome type II after undergoing hematopoietic stem cell transplantation (HSCT). The patient presented 30 days post HSCT with fever and lymphadenitis. Lymph node, blood, and gastric aspirates were positive for M. bovis. The patient received a prolonged treatment course with a combination of isoniazid, levofloxacin, and ethambutol. Her course was further complicated by granulomatous lymphadenitis and otitis media associated with M. bovis that developed during immune suppression taper and immune reconstitution. Ultimately, the patient recovered fully, in association with restoration of immune function, and has completed 12 months of therapy. PMID:24995715

  2. Cellular Barcoding Links B-1a B Cell Potential to a Fetal Hematopoietic Stem Cell State at the Single-Cell Level

    DEFF Research Database (Denmark)

    Kristiansen, Trine A; Jaensson Gyllenbäck, Elin; Zriwil, Alya;

    2016-01-01

    Hematopoietic stem cells (HSCs) undergo a functional switch in neonatal mice hallmarked by a decrease in self-renewing divisions and entry into quiescence. Here, we investigated whether the developmental attenuation of B-1a cell output is a consequence of a shift in stem cell state during ontogeny....... Using cellular barcoding for in vivo single-cell fate analyses, we found that fetal liver definitive HSCs gave rise to both B-1a and B-2 cells. Whereas B-1a potential diminished in all HSCs with time, B-2 output was maintained. B-1a and B-2 plasticity could be reinitiated in a subset of adult HSCs...... by ectopic expression of the RNA binding protein LIN28B, a key regulator of fetal hematopoiesis, and this coincided with the clonal reversal to fetal-like elevated self-renewal and repopulation potential. These results anchor the attenuation of B-1a cell output to fetal HSC behavior and demonstrate...

  3. Oral surgery in patients undergoing chemoradiation therapy.

    Science.gov (United States)

    Demian, Nagi M; Shum, Jonathan W; Kessel, Ivan L; Eid, Ahmed

    2014-05-01

    Oral health care in patients undergoing chemotherapy and/or radiation therapy can be complex. Care delivered by a multidisciplinary approach is timely and streamlines the allocation of resources to provide prompt care and to attain favorable outcomes. A hospital dentist, oral and maxillofacial surgeon, and a maxillofacial prosthodontist must be involved early to prevent avoidable oral complications. Prevention and thorough preparation are vital before the start of chemotherapy and radiation therapy. Oral complications must be addressed immediately and, even with the best management, can cause delays and interruption in treatment, with serious consequences for the outcome and prognosis. PMID:24794266

  4. Cartilage Aggrecan Can Undergo Self-Adhesion

    OpenAIRE

    Han, Lin; Dean, Delphine; Daher, Laura A.; Grodzinsky, Alan J.; Ortiz, Christine

    2008-01-01

    Here it is reported that aggrecan, the highly negatively charged macromolecule in the cartilage extracellular matrix, undergoes Ca2+-mediated self-adhesion after static compression even in the presence of strong electrostatic repulsion in physiological-like solution conditions. Aggrecan was chemically end-attached onto gold-coated planar silicon substrates and gold-coated microspherical atomic force microscope probe tips (end radius R ≈ 2.5 μm) at a density (∼40 mg/mL) that simulates physiolo...

  5. Dermatillomania: In patient undergoing orthodontic treatment

    Directory of Open Access Journals (Sweden)

    Adit

    2014-01-01

    Full Text Available Dermatillomania is a disorder in which a person habitually picks their skin, and this is a form of self-injury. It can involve any part of the body, but usually involves the face, neck, arms and shoulders. Symptoms often follow an event that has caused severe emotional distress. A dermatillomania or compulsive skin picking episode may be a conscious response to anxiety or depression but is frequently done as an unconscious habit. In this case report, a patient undergoing orthodontic treatment was found to be suffering from dermatillomania and was treated using psychological counseling.

  6. Thromboprophylaxis for women undergoing caesarean section.

    LENUS (Irish Health Repository)

    Kennedy, C

    2012-02-01

    Thromboprophylaxis for women undergoing caesarean section (CS) was introduced in the hospital in 1995. This study audited the use of tinzaparin prophylaxis in a nested cohort of women who screened negative for diabetes mellitus at 28 weeks gestation. All the women had their weight measured and BMI calculated at the first antenatal visit. Of the 284 women, 68 (24%) had a CS and all received tinzaparin. Of the 68, however, 94% received a dose lower than recommended. Compliance with prophylaxis was complete but compliance with the recommended dosage was suboptimal, which may result in venous thromboembolism after CS despite thromboprophylaxis.

  7. Imaging of complications from hematopoietic stem cell transplant

    Directory of Open Access Journals (Sweden)

    Tarun Pandey

    2014-01-01

    Full Text Available Stem cell transplant has been the focus of clinical research for a long time given its potential to treat several incurable diseases like hematological malignancies, diabetes mellitus, and neuro-degenerative disorders like Parkinson disease. Hematopoietic stem cell transplantation (HSCT is the oldest and most widely used technique of stem cell transplant. HSCT has not only been used to treat hematological disorders including hematological malignancies, but has also been found useful in treamtent of genetic, immunological, and solid tumors like neuroblastoma, lymphoma, and germ cell tumors. In spite of the rapid advances in stem cell technology, success rate with this technique has not been universal and many complications have also been seen with this form of therapy. The key to a successful HSCT therapy lies in early diagnosis and effective management of complications associated with this treatment. Our article aims to review the role of imaging in diagnosis and management of stem cell transplant complications associated with HSCT.

  8. Imaging Macrophage and Hematopoietic Progenitor Proliferation in Atherosclerosis

    DEFF Research Database (Denmark)

    Ye, Yu-Xiang; Calcagno, Claudia; Binderup, Tina;

    2015-01-01

    atherosclerotic lesions, spleen, and bone marrow (standardized uptake values wild-type versus apolipoprotein E knock out mice, 0.05 ± 0.01 versus 0.17 ± 0.01, P<0.05 in aorta; 0.13 ± 0.01 versus 0.28 ± 0.02, P<0.05 in bone marrow; 0.06 ± 0.01 versus 0.22 ± 0.01, P<0.05 in spleen), corroborated by ex vivo...... scintillation counting and autoradiography. Flow cytometry confirmed significantly higher proliferation of macrophages in aortic lesions and hematopoietic stem and progenitor cells in the spleen and bone marrow in these mice. In addition, (18)F-FLT plaque signal correlated with the duration of high cholesterol...

  9. The Hematopoietic Stem Cell Therapy for Exploration of Space

    Science.gov (United States)

    Ohi, S.

    Departments of Biochemistry &Molecular Biology, Genetics &Human Genetics, Pediatrics &Child Long-duration space missions require countermeasures against severe/invasive disorders in astronauts that are caused by space environments, such as hematological/cardiac abnormalities, bone/muscle losses, immunodeficiency, neurological disorders, and cancer. Some, if not all, of these disorders may be amenable to hematopoietic stem cell therapy and gene therapy. Growing evidence indicates that hematopoietic stem cells (HSCs) possess extraordinary plasticity to differentiate not only to all types of blood cells but also to various tissues, including bone, muscle, skin, liver and neuronal cells. Therefore, our working hypothesis is that the hematopoietic stem cell-based therapy, herein called as the hematopoietic stem cell therapy (HSCT), might provide countermeasure/prevention for hematological abnormalities, bone and muscle losses in space, thereby maintaining astronauts' homeostasis. Our expertise lies in recombinant adeno-associated virus (rAAV)-mediated gene therapy for the hemoglobinopathies, -thalassemia and sickle cell disease (Ohi S, Kim BC, J Pharm Sci 85: 274-281, 1996; Ohi S, et al. Grav Space Biol Bull 14: 43, 2000). As the requisite steps in this protocol, we established procedures for purification of HSCs from both mouse and human bone marrow in 1 G. Furthermore, we developed an easily harvestable, long-term liquid suspension culture system, which lasts more than one year, for growing/expanding HSCs without stromal cells. Human globin cDNAs/gene were efficiently expressed from the rAAVs in the mouse HSCs in culture. Additionally, the NASA Rotating Wall Vessel (RWV) culture system is being optimized for the HSC growth/expansion. Thus, using these technologies, the above hypothesis is being investigated by the ground-based experiments as follows: 1) -thalassemic mice (C57BL/6-Hbbth/Hbbth, Hbd-minor) are transplanted with normal isologous HSCs to correct the

  10. COST OF HEMATOPOIETIC STEM CELL TRANSPLANTATION IN INDIA

    Directory of Open Access Journals (Sweden)

    Sanjeev Kumar Sharma

    2014-06-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is the definite cure for many hematological diseases. With the increasing indications for HSCT and its relatively low cost in Indian subcontinent, an increasing number of patients are opting for this procedure. We retrospectively analyzed the cost of one hundred sixty two HSCTs done at our center in the last three years. The median cost of autologous transplant was INR 7,52,294 (USD, $ 12,500 (range INR 6,19,850-14,17,212 and the median cost of allogenic transplant was INR 10,74,881 ($18,000 (range INR 6,49,944-23,82,227. The cost of HSCT is cheaper here compared to that in developed countries and success rates are nearly equivalent. The major factors contributing to the cost are related to the complications post-transplant mainly infections and graft versus host disease, which are also the reasons for the increased stay in the hospital.

  11. Graft rejection after hematopoietic cell transplantation with nonmyeloablative conditioning

    DEFF Research Database (Denmark)

    Masmas, T.N.; Petersen, S.L.; Madsen, H.O.; Ryder, L.P.; Kornblit, B.; Svejgaard, A.; Andersen, P.; Dickmeiss, E.; Vindelov, L.L.

    2008-01-01

    Graft rejection after hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning is a rare but serious clinical problem. Graft rejection and salvage therapy in eight patients in a retrospective analysis of 124 consecutive patients is reported. The patients were conditioned with low......-dose fludarabine and total body irradiation (TBI). The association of pretransplantation risk factors with rejection and the effect of chimerism and graft-versus-host disease on rejection were analyzed. Overall survival (OS) and progression free survival (PFS) were compared between patients with and without......, patients are at greater risk of dying from infections and progression/relapse of their malignancy. Retransplantation is feasible and well tolerated after HCT with nonmyeloablative conditioning and should be performed without delay in patients with imminent and manifest graft rejection Udgivelsesdato: 2008/7...

  12. Bullous pemphigoid after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Kato, Keisuke; Koike, Kazutoshi; Kobayashi, Chie; Iijima, Shigeruko; Hashimoto, Takashi; Tsuchida, Masahiro

    2015-06-01

    Bullous pemphigoid (BP) is an autoimmune skin disorder characterized by subepidermal blisters due to deposit of autoantibody against dermal basement membrane protein. It has been reported that BP can occur after allogeneic hematopoietic stem cell transplantation (HSCT). We describe a patient with BP having autoantibody against BP180 after unrelated-donor HSCT against T lymphoblastic leukemia. The patient was treated with steroid leading to complete resolution of BP, but T lymphoblastic leukemia progressed rapidly after steroid hormone treatment. Given that immunosuppressant may reduce graft-versus-tumor effect, immunomodulatory agents such as nicotinamide and tetracycline, erythromycin, and immunoglobulin may be appropriate as soon as typical blister lesions are seen after HSCT. PMID:26113316

  13. [Physiological regulation of hematopoietic stem cell and its molecular basis].

    Science.gov (United States)

    Dong, Fang; Hao, Sha; Cheng, Hui; Cheng, Tao

    2016-08-25

    As a classical type of tissue stem cells, hematopoietic stem cell (HSC) is the earliest discovered and has been widely applied in the clinic as a great successful example for stem cell therapy. Thus, HSC research represents a leading field in stem cell biology and regenerative medicine. Self-renewal, differentiation, quiescence, apoptosis and trafficking constitute major characteristics of functional HSCs. These characteristics also signify different dynamic states of HSC through physiological interactions with the microenvironment cues in vivo. This review covers our current knowledge on the physiological regulation of HSC and its underlying molecular mechanisms. It is our hope that this review will not only help our colleagues to understand how HSC is physiologically regulated but also serve as a good reference for the studies on stem cell and regenerative medicine in general. PMID:27546503

  14. Imaging of complications from hematopoietic stem cell transplant.

    Science.gov (United States)

    Pandey, Tarun; Maximin, Suresh; Bhargava, Puneet

    2014-10-01

    Stem cell transplant has been the focus of clinical research for a long time given its potential to treat several incurable diseases like hematological malignancies, diabetes mellitus, and neuro-degenerative disorders like Parkinson disease. Hematopoietic stem cell transplantation (HSCT) is the oldest and most widely used technique of stem cell transplant. HSCT has not only been used to treat hematological disorders including hematological malignancies, but has also been found useful in treamtent of genetic, immunological, and solid tumors like neuroblastoma, lymphoma, and germ cell tumors. In spite of the rapid advances in stem cell technology, success rate with this technique has not been universal and many complications have also been seen with this form of therapy. The key to a successful HSCT therapy lies in early diagnosis and effective management of complications associated with this treatment. Our article aims to review the role of imaging in diagnosis and management of stem cell transplant complications associated with HSCT. PMID:25489126

  15. Sexual Health in Hematopoietic Stem Cell Transplant Recipients

    Science.gov (United States)

    Li, Zhuoyan; Mewawalla, Prerna; Stratton, Pamela; Yong, Agnes S.M.; Shaw, Bronwen E.; Hashmi, Shahrukh; Jagasia, Madan; Mohty, Mohamad; Majhail, Navneet S.; Savani, Bipin N.; Rovó, Alicia

    2016-01-01

    Hematopoietic stem cell transplantation (HSCT) plays a central role in patients with malignant and, increasingly, nonmalignant conditions. As the number of transplants increases and the survival rate improves, long-term complications are important to recognize and treat to maintain quality of life. Sexual dysfunction is a commonly described but relatively often underestimated complication after HSCT. Conditioning regimens, generalized or genital graft-versus-host disease, medications, and cardiovascular complications as well as psychosocial problems are known to contribute significantly to physical and psychological sexual dysfunction. Moreover, it is often a difficult topic for patients, their significant others, and health care providers to discuss. Early recognition and management of sexual dysfunction after HSCT can lead to improved quality of life and outcomes for patients and their partners. This review focuses on the risk factors for and treatment of sexual dysfunction after transplantation and provides guidance concerning how to approach and manage a patient with sexual dysfunction after HSCT. PMID:26372459

  16. Hematopoietic ontogeny and its relevance for pediatric leukemias.

    Science.gov (United States)

    Udroiu, Ion; Sgura, Antonella

    2016-03-01

    Fetal and infant hematopoiesis display characteristics different from the adult one: our suggestion is that these features may help to explain the peculiar incidence rates of acute leukemias. Hematopoietic stem cells (HSCs) are fast-cycling (those in adults instead are largely quiescent) and studies in mice demonstrated that their relative contribution to myelo- and lymphopoiesis varies during development. We hypothesize that during development some of the "hits" needed for the onset of leukemia are usually occurring (being part of the normal development), so leukemogenesis needs less mutations than in adults to take place and therefore it's more probable. The switch between the relative incidence of acute myeloid and lymphoid leukemias may be related to the changes of the percentage of lymphoid-deficient and lymphoid-proficient sub-set of HSCs during development. Further investigations may clarify this hypothesis, elucidating also the roles of the different microenvironments in determining the myeloid/lymphoid predisposition of the HSCs. PMID:26880643

  17. Venous thromboembolism in hematopoietic stem cell transplant recipients.

    Science.gov (United States)

    Chaturvedi, S; Neff, A; Nagler, A; Savani, U; Mohty, M; Savani, B N

    2016-04-01

    Venous thromboembolism (VTE) is an increasingly recognized problem in the post-hematopoietic stem cell transplantation (HSCT) setting, with a lack of high-quality evidence-based data to recommend best practices. Few patients with hematologic malignancies and even fewer post-HSCT patients were included in randomized trials of VTE prophylaxis and treatment. Prior VTE, GVHD, infections and indwelling venous catheters are risk factors for thrombosis. The increasing use of post-transplant maintenance therapy with lenalidomide in patients with multiple myeloma adds to this risk after autologous HSCT. These patients are also at high risk of bleeding complications because of prolonged thrombocytopenia and managing the competing risks of bleeding and thrombosis can be challenging. This review aims to provide a practical, clinician-focused approach to the prevention and treatment of VTE in the post-HSCT setting. PMID:26691425

  18. Analysis of the motivation for hematopoietic stem cell donation.

    Science.gov (United States)

    Aurelio, M T; Aniasi, A; Haworth, S E; Colombo, M B; Dimonopoli, T; Mocellin, M C; Poli, F; Torelli, R; Crespiatico, L; Serafini, M; Scalamogna, M

    2011-05-01

    The Italian Bone Marrow Donor Register is the institutional organization for management of unrelated hematopoietic stem cell donors. The law requires only a donor's clinical history, but not a psychosocial profile for registration. We have studied the donor's motivation for enlistment on the donor registry and the medical staff's need for this information to interact correctly with the donor. For this purpose we distributed a questionnaire to new donors at the 20 centers in the Lombardy Region over a period of 1 year. The analysis of the responses revealed a prevalence of extrinsic motivations that would not ensure continued registration for donation. Therefore, it is necessary that the donor be well informed and better educated about all aspects of donation, in order to produce a shift to an intrinsic motivation. This objective can be facilitated via professional training of health workers in communication. PMID:21620031

  19. The Hematopoietic Stem Cell Therapy for Exploration of Deep Space

    Science.gov (United States)

    Ohi, Seigo; Roach, Allana-Nicole; Ramsahai, Shweta; Kim, Bak C.; Fitzgerald, Wendy; Riley, Danny A.; Gonda, Steven R.

    2004-02-01

    Astronauts experience severe/invasive disorders caused by space environments. These include hematological and cardiac abnormalities, bone and muscle losses, immunodeficiency, neurological disorders and cancer. Exploiting the extraordinary plasticity of hematopoietic stem cells (HSCs), which differentiate not only to all types of blood cells, but also to various tissues, including muscle, bone, skin, liver, and neuronal cells, we advanced a hypothesis that some of the space-caused disorders might be amenable to hematopoietic stem cell therapy (HSCT) so as to maintain astronauts' homeostasis. If this were achievable, the HSCT could promote human exploration of deep space. Using mouse models of human anemia (β-thalassemia) and spaceflight (hindlimb suspension unloading system), we have obtained feasibility results of HSCT for space anemia, muscle loss, and immunodeficiency. For example, the β-thalassemic mice were successfully transplanted with isologous HSCs, resulting in chimerism of hemoglobin species and alleviation of the hemoglobinopathy. In the case of HSCT for muscle loss, β-galactosidase-marked HSCs, which were prepared from β-galactosidase-transgenic mice, were detected by the X-gal wholemount staining procedure in the hindlimbs of unloaded mice following transplantation. Histochemical and physical analyses indicated structural contribution of HSCs to the muscle. To investigate HSCT for immunodeficiency, β-galactosidase-transformed Escherichia coli was used as the reporter bacteria, and infected to control and the hindlimb suspended mice. Results of the X-gal stained tissues indicated that the HSCT could help eliminate the E. coli infection. In an effort to facilitate the HSCT in space, growth of HSCs has been optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

  20. Hematopoietic differentiation: a coordinated dynamical process towards attractor stable states

    Directory of Open Access Journals (Sweden)

    Rossi Simona

    2010-06-01

    Full Text Available Abstract Background The differentiation process, proceeding from stem cells towards the different committed cell types, can be considered as a trajectory towards an attractor of a dynamical process. This view, taking into consideration the transcriptome and miRNome dynamics considered as a whole, instead of looking at few 'master genes' driving the system, offers a novel perspective on this phenomenon. We investigated the 'differentiation trajectories' of the hematopoietic system considering a genome-wide scenario. Results We developed serum-free liquid suspension unilineage cultures of cord blood (CB CD34+ hematopoietic progenitor cells through erythroid (E, megakaryocytic (MK, granulocytic (G and monocytic (Mo pathways. These cultures recapitulate physiological hematopoiesis, allowing the analysis of almost pure unilineage precursors starting from initial differentiation of HPCs until terminal maturation. By analyzing the expression profile of protein coding genes and microRNAs in unilineage CB E, MK, G and Mo cultures, at sequential stages of differentiation and maturation, we observed a coordinated, fully interconnected and scalable character of cell population behaviour in both transcriptome and miRNome spaces reminiscent of an attractor-like dynamics. MiRNome and transcriptome space differed for a still not terminally committed behaviour of microRNAs. Conclusions Consistent with their roles, the transcriptome system can be considered as the state space of a cell population, while the continuously evolving miRNA space corresponds to the tuning system necessary to reach the attractor. The behaviour of miRNA machinery could be of great relevance not only for the promise of reversing the differentiated state but even for tumor biology.

  1. How do I perform hematopoietic progenitor cell selection?

    Science.gov (United States)

    Avecilla, Scott T; Goss, Cheryl; Bleau, Sharon; Tonon, Jo-Ann; Meagher, Richard C

    2016-05-01

    Graft-versus-host disease remains the most important source of morbidity and mortality associated with allogeneic stem cell transplantation. The implementation of hematopoietic progenitor cell (HPC) selection is employed by some stem cell processing facilities to mitigate this complication. Current cell selection methods include reducing the number of unwanted T cells (negative selection) and/or enriching CD34+ hematopoietic stem/progenitors (positive selection) using immunomagnetic beads subjected to magnetic fields within columns to separate out targeted cells. Unwanted side effects of cell selection as a result of T-cell reduction are primary graft failure, increased infection rates, delayed immune reconstitution, possible disease relapse, and posttransplant lymphoproliferative disease. The Miltenyi CliniMACS cell isolation system is the only device currently approved for clinical use by the Food and Drug Administration. It uses magnetic microbeads conjugated with a high-affinity anti-CD34 monoclonal antibody capable of binding to HPCs in marrow, peripheral blood, or umbilical cord blood products. The system results in significantly improved CD34+ cell recoveries (50%-100%) and consistent 3-log CD3+ T-cell reductions compared to previous generations of CD34+ cell selection procedures. In this article, the CliniMACS procedure is described in greater detail and the authors provide useful insight into modifications of the system. Successful implementation of cell selection procedures can have a significant positive clinical effect by greatly increasing the pool of donors for recipients requiring transplants. However, before a program implements cell selection techniques, it is important to consider the time and financial resources required to properly and safely perform these procedures. PMID:26919388

  2. O transplante de células-tronco hematopoéticas na infância: situação atual e perspectivas Hematopoietic stem cell transplantation in childhood: current status and perspectives

    Directory of Open Access Journals (Sweden)

    Adriana Seber

    2009-05-01

    Full Text Available O transplante de células-tronco hematopoéticas (TCTH é uma opção terapêutica para um grande número de crianças com doenças malignas e não malignas. O objetivo deste artigo é apresentar a situação atual dos TCTH em pediatria para o tratamento de doenças hematológicas malignas, incluindo dados de nosso país e perspectivas futuras.Hematopoietic stem cell transplantation is a treatment option for a large number of children with malignant and non-malignant diseases. The objective of this article is to present the current status of hematopoietic stem cell transplantation in the treatment of malignant hematological diseases in pediatrics, including results in Brazil, and future perspectives.

  3. Quantification of Acute Lymphoblastic Leukemia Clonotypes in Leukapheresed Peripheral Blood Progenitor Cells Predicts Relapse Risk after Autologous Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Mannis, Gabriel N; Martin, Thomas G; Damon, Lloyd E; Andreadis, Charalambos; Olin, Rebecca L; Kong, Katherine A; Faham, Malek; Hwang, Jimmy; Ai, Weiyun Z; Gaensler, Karin M L; Sayre, Peter H; Wolf, Jeffrey L; Logan, Aaron C

    2016-06-01

    Since the incorporation of tyrosine kinase inhibitors into the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), the notion that all patients with "high-risk" ALL uniformly require allogeneic (allo) hematopoietic cell transplantation (HCT) has received increasing scrutiny. Although multiple studies have shown superiority of alloHCT over autologous (auto) hematopoietic cell transplantation for high-risk patients, these findings may be explained, in part, by contamination of the peripheral blood progenitor cell (PBPC) leukapheresis product by residual leukemic cells in patients undergoing autoHCT. We retrospectively evaluated minimal residual disease (MRD) using next-generation sequencing (NGS) in the PBPC leukapheresis product of 32 ALL patients who underwent autoHCT. Twenty-eight patients (88%) had diagnostic samples with quantifiable immunoreceptor rearrangements to follow for MRD. Twelve (38%) patients had Ph+ B-ALL, 12 (38%) had Philadelphia chromosome-negative (Ph-) B-ALL, and 4 (14%) had T cell ALL. With a median follow-up of 41 months (range, 3 to 217), median relapse-free survival (RFS) and overall survival for the entire cohort were 3.2 and 4.2 years, respectively; at 5 years after transplantation, 42% of patients remain alive and relapse free. Using MRD detection at a threshold of ≥ 1 × 10(-6), median RFS for patients with detectable MRD was 6.5 months and was not reached for patients without detectable disease (P = .0005). In multivariate analysis, the only factor significantly associated with relapse was the presence of MRD ≥1 × 10(-6) (odds ratio, 23.8; confidence interval, 1.8 to 312.9; P = .0158). Our findings suggest that NGS for MRD detection can predict long-term RFS in patients undergoing autoHCT for high-risk ALL. PMID:26899561

  4. Oral features and dental health in Hurler Syndrome following hematopoietic stem cell transplantation.

    LENUS (Irish Health Repository)

    McGovern, Eleanor

    2010-09-01

    Hurler Syndrome is associated with a deficiency of a specific lysosomal enzyme involved in the degradation of glycosaminoglycans. Hematopoietic stem cell transplantation (HSCT) in early infancy is undertaken to help prevent the accumulation of glycosaminoglycans and improve organ function.

  5. The role of hematopoietic growth factors in nuclear and radiation accidents

    International Nuclear Information System (INIS)

    Molecularly cloned hematopoietic growth factors are likely to be useful in treating persons with bone marrow failure resulting from radiation exposure. Some effects, such as increased granulocytes or platelets, are of clear therapeutic benefit. Other effects, such as a direct action on survival of hematopoietic stem cells and improved granulocyte function, may also increase survival. Many important areas remain to be studied, including which molecularly cloned hematopoietic growth factor(s) to use, optimal dose and timing, and others. Some of these issues can be studied in clinical trials; others require in vitro or animal models. Despite the limited data currently available, it is clear that the availability of molecularly cloned hematopoietic growth factors heralds a new era in treating radiation and nuclear accidents.70 references

  6. TET2 deficiency inhibits mesoderm and hematopoietic differentiation in human embryonic stem cells

    DEFF Research Database (Denmark)

    Langlois, Thierry; da Costa Reis Monte Mor, Barbara; Lenglet, Gaëlle;

    2014-01-01

    profile, including abnormal expression of neuronal genes. Intriguingly, when TET2 was knockdown in hematopoietic cells, it increased hematopoietic development. In conclusion, our work suggests that TET2 is involved in different stages of human embryonic development, including induction of the mesoderm and......Ten-Eleven-Translocation 2 (TET2) belongs to the TET protein family that catalyzes the conversion of 5-methylcytosine into 5-hydroxymethylcytosine and plays a central role in normal and malignant adult hematopoiesis. Yet, the role of TET2 in human hematopoietic development remains largely unknown....... Here, we show that TET2 expression is low in human embryonic stem (ES) cell lines and increases during hematopoietic differentiation. ShRNA-mediated TET2 knockdown had no effect on the pluripotency of various ES cells. However, it skewed their differentiation into neuroectoderm at the expense of...

  7. Immunophenotyping of hematopoietic progenitor cells: Comparison between cord blood and adult mobilized blood grafts

    OpenAIRE

    2011-01-01

    AIM: To study the immunophenotype of hematopoietic progenitor cells from cord blood (CB) grafts (n = 39) in comparison with adult apheresis grafts (AG, n = 229) and pre-apheresis peripheral blood (PAPB) samples (n = 908) using flow cytometry analysis.

  8. Expression of human adenosine deaminase in mice reconstituted with retrovirus-transduced hematopoietic stem cells

    International Nuclear Information System (INIS)

    Recombinant retroviruses encoding human adenosine deaminase have been used to infect murine hematopoietic stem cells. In bone marrow transplant recipients reconstituted with the genetically modified cells, human ADA was detected in peripheral blood mononuclear cells of the recipients for at least 6 months after transplantation. In animals analyzed in detail 4 months after transplantation, human ADA and proviral sequences were detected in all hematopoietic lineages; in several cases, human ADA activity exceeded the endogenous activity. These studies demonstrate the feasibility of introducing a functional human ADA gene into hematopoietic stem cells and obtaining expression in multiple hematopoietic lineages long after transplantation. This approach should be helpful in designing effective gene therapies for severe combined immunodeficiency syndromes in humans

  9. The role of citrulline in patients following hematopoietic stem cell transplantation

    NARCIS (Netherlands)

    Herbers, A.H.E.

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) provides effective treatment of hematological malignancies and other disorders. However, the procedure temporarily compromises the immune system resulting in damage to the gastrointestinal (GI) tract, called mucosal barrier injury (MBI), and neutropenia

  10. Boosting Hematopoietic Engraftment after in Utero Transplantation through Vascular Niche Manipulation.

    Science.gov (United States)

    Mokhtari, Saloomeh; Colletti, Evan J; Atala, Anthony; Zanjani, Esmail D; Porada, Christopher D; Almeida-Porada, Graça

    2016-06-14

    In utero hematopoietic stem/progenitor cell transplantation (IUHSCT) has only been fully successful in the treatment of congenital immunodeficiency diseases. Using sheep as a large animal model of IUHSCT, we demonstrate that administration of CD146(+)CXCL12(+)VEGFR2(+) or CD146(+)CXCL12(+)VEGFR2(-) cells prior to, or in combination with, hematopoietic stem/progenitor cells (HSC), results in robust CXCL12 production within the fetal marrow environment, and significantly increases the levels of hematopoietic engraftment. While in the fetal recipient, donor-derived HSC were found to reside within the trabecular bone, the increased expression of VEGFR2 in the microvasculature of CD146(+)CXCL12(+)VEGFR2(+) transplanted animals enhanced levels of donor-derived hematopoietic cells in circulation. These studies provide important insights into IUHSCT biology, and demonstrate the feasibility of enhancing HSC engraftment to levels that would likely be therapeutic in many candidate diseases for IUHSCT. PMID:27304918

  11. Cough: are children really different to adults?

    OpenAIRE

    Chang, Anne B

    2005-01-01

    Worldwide paediatricians advocate that children should be managed differently from adults. In this article, similarities and differences between children and adults related to cough are presented. Physiologically, the cough pathway is closely linked to the control of breathing (the central respiratory pattern generator). As respiratory control and associated reflexes undergo a maturation process, it is expected that the cough would likewise undergo developmental stages as well. Clinically, th...

  12. Leukoencephalopathy in childhood hematopoietic neoplasm caused by moderate-dose methotrexate and prophylactic cranial radiotherapy -- an MR analysis

    International Nuclear Information System (INIS)

    Purpose: The main purpose of this study was to determine influential factors related to minor leukoencephalopathy (LEP) caused by moderate-dose methotrexate (MTX) and prophylactic cranial radiotherapy (CRT) in childhood hematopoietic malignancies. We also compared the incidence of LEP following this treatment to that reported in the literature following treatment with high-dose MTX alone. Methods and Materials: Thirty-eight pediatric patients of hematopoietic malignancies (37 acute lymphoblastic leukemias, 1 non-Hodgkin lymphoma) who were given CRT (18-24 Gy) as well as prophylactic intrathecal and per os MTX were studied for leukoencephalopathy by magnetic resonance (MR) imaging. All the patients were free from grave neuropsychiatric disturbances. The data were examined to elucidate the influential ones of five factors (patients' age, doses of intrathecal and per os MTX, dose of CRT, interval between treatment, and MR study) to develop LEP using multiple regression analysis. To compare the effect of moderate-dose MTX and prophylactic CRT on LEP to that of high-dose MTX alone, we conducted literature review. Results: Seven out of 38 patients (18%) developed LEP. From multiple regression analysis and partial correlation coefficients, the age and CRT dose seemed influential in the subsequent development of LEP. The incidence of LEP following treatment with moderate-dose MTX and prophylactic CRT appears to be less than that reported in the literature following treatment with intravenous high-dose MTX. However, even moderate-dose MTX in combination with CRT can result in a significant incidence of MR-detectable LEP, particularly in children 6 years of age or younger receiving 24 Gy. Conclusion: Leukoencephalopathy was caused by moderate-dose MTX and prophylactic CRT in pediatric patients, probably less frequently than by high-dose MTX treatment alone. The influential factors were patient's age and CRT dose

  13. Leukoencephalopathy in childhood hematopoietic neoplasm caused by moderate-dose methotrexate and prophylactic cranial radiotherapy - an MR analysis

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Ko [Tohoku Univ. (Japan)]|[Miyagi Cancer Center (Japan); Takahashi, Shoki; Higano, Shuichi [Tohoku Univ. (Japan)] [and others

    1995-07-15

    The main purpose of this study was to determine influential factors related to minor leukoencephalopathy (LEP) caused by moderate-dose methotrexate (MTX) and prophylactic cranial radiotherapy (CRT) in childhood hematopoietic malignancies. We also compared the incidence of LEP following this treatment to that reported in the literature following treatment with high-dose MTX alone. Thirty-eight pediatric patients of hematopoietic malignancies (37 acute lymphoblastic leukemias, 1 non-Hodgkin lymphoma) who were given CRT (18-24 Gy) as well as prophylactic intrathecal and per os MTX were studied for leukoencephalopathy by magnetic resonance (MR) imaging. All the patients were free from grave neuropsychiatric disturbances. The data were examined to elucidate the influential ones of five factors (patients` age, doses of intrathecal and per os MTX, dose of CRT, interval between treatment, and MR study) to develop LEP using multiple regression analysis. To compare the effect of moderate-dose MTX and prophylactic CRT on LEP to that of high-dose MTX alone, we conducted a literature review. Seven out of 38 patients (18%) developed LEP. From multiple regression analysis and partial correlation coefficients, the age and CRT dose seemed influential in the subsequent development of LEP. The incidence of LEP following treatment with moderate-dose MTX and prophylactic CRT appears to be less than that reported in the literature following treatment with intravenous high-dose MTX. However, even moderate-dose MTX in combination with CRT can result in a significant incidence of MR-detectable LEP, particularly in children 6 years of age or younger receiving 24 Gy. Leukoencephalopathy was caused by moderate-dose MTX and prophylactic CRT in pediatric patients, probably less frequently than by high-dose MTX treatment alone. The influential factors were patient`s age and CRT dose. 26 refs., 6 figs., 2 tabs.

  14. Effect of cotransplantation of hematopoietic stem cells and embryonic AGM stromal cells on hematopoietic reconstitution in mice after bone marrow transplantation

    International Nuclear Information System (INIS)

    Objective: To explore the effects of cotransplantation of hematopoietic stem cells and stromal cells derived from aorta-gonad-mesonephros (AGM) region on hematopoietic reconstitution in mice after bone marrow transplantation (BMT). Methods: The typical mice model of syngeneic BMT was established and the mice were randomly divided into 4 groups: the control group, the BMT group, the group of cotransplantation of HSC with AGM stromal cells (the cotransplantation group) and the ligustrazine group (the LT group). On days 3, 7, 10, 14, 21 and 28 after BMT, the peripheral blood cells and bone marrow mononuclear cells (BMMNC) were counted, and histology changes of bone marrow were detected. Results: The levels of peripheral WBC, RBC, platelet, and BMMNC in the contransplantation group were significantly higher than those in the single BMT group and the LT group (P<0.05). Conclusions: Cotransplantation with AGM stromal cells could significantly promote hematopoietic reconstruction in mice after BMT. (authors)

  15. Critical Role of Jak2 in the Maintenance and Function of Adult Hematopoietic Stem Cells

    OpenAIRE

    Akada, Hajime; Akada, Saeko; Hutchison, Robert E.; Sakamoto, Kazuhito; Wagner, Kay-Uwe; Mohi, Golam

    2014-01-01

    Jak2, a member of the Janus kinase family of non-receptor protein tyrosine kinases, is activated in response to a variety of cytokines, and functions in survival and proliferation of cells. An activating JAK2V617F mutation has been found in most patients with myeloproliferative neoplasms, and patients treated with Jak2 inhibitors show significant hematopoietic toxicities. However, the role of Jak2 in adult hematopoietic stem cells (HSCs) has not been clearly elucidated. Using a conditional Ja...

  16. Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation

    OpenAIRE

    Kim, Sung-Yong; Le Rademacher, Jennifer; Antin, Joseph H.; Anderlini, Paolo; Ayas, Mouhab; Battiwalla, Minoo; Carreras, Jeanette; Kurtzberg, Joanne; Nakamura, Ryotaro; Eapen, Mary; Deeg, H. Joachim

    2014-01-01

    A proportion of patients with aplastic anemia who are treated with immunosuppressive therapy develop clonal hematologic disorders, including post-aplastic anemia myelodysplastic syndrome. Many will proceed to allogeneic hematopoietic stem cell transplantation. We identified 123 patients with post-aplastic anemia myelodysplastic syndrome who from 1991 through 2011 underwent allogeneic hematopoietic stem cell transplantation, and in a matched-pair analysis compared outcome to that in 393 patien...

  17. Improvement in the quality of hematopoietic prostaglandin D synthase crystals in a microgravity environment

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Hiroaki, E-mail: tanakah@confsci.co.jp [Confocal Science Inc. (Japan); Tsurumura, Toshiharu; Aritake, Kosuke [Osaka Bioscience Institute (Japan); Furubayashi, Naoki [Maruwa Foods and Biosciences Inc. (Japan); Takahashi, Sachiko; Yamanaka, Mari; Hirota, Erika [Confocal Science Inc. (Japan); Sano, Satoshi; Sato, Masaru; Kobayashi, Tomoyuki; Tanaka, Tetsuo [Japan Aerospace Exploration Agency (Japan); Inaka, Koji [Maruwa Foods and Biosciences Inc. (Japan); Urade, Yoshihiro [Osaka Bioscience Institute (Japan)

    2011-01-01

    Crystals of hematopoietic prostaglandin D synthase grown in microgravity show improved quality. Human hematopoietic prostaglandin synthase, one of the better therapeutic target enzymes for allergy and inflammation, was crystallized with 22 inhibitors and in three inhibitor-free conditions in microgravity. Most of the space-grown crystals showed better X-ray diffraction patterns than the terrestrially grown ones, indicating the advantage of a microgravity environment on protein crystallization, especially in the case of this protein.

  18. Single-Cell Cytokine Profiling to Investigate Cellular Functional Diversity in Hematopoietic Malignancies.

    Science.gov (United States)

    Chen, Jonathan J; Kwak, Minsuk; Fan, Rong

    2016-01-01

    Single-cell analysis of cytokine production is increasingly recognized as an important method to understand the inflammatory microenvironment and hematopoietic disease state. Certain cytokines are critical to the regulation of lineage specification, and the aberrant production of these cytokines can contribute to lineage reprogramming. Here, we describe of a platform combining subnanoliter microchambers and a high-density antibody barcode array for the study of single-cell cytokine secretions in hematopoietic cancer cell populations. PMID:27581152

  19. Recovery from Hematopoietic Injury by Modulating Prostaglandin E2 Signaling Post-Irradiation

    OpenAIRE

    Hoggatt, Jonathan; Singh, Pratibha; Stilger, Kayla N.; Plett, P. Artur; Sampson, Carol H.; Chua, Hui Lin; Orschell, Christie M.; Pelus, Louis M.

    2012-01-01

    While high dose total body irradiation (TBI) is used therapeutically, the proliferation of nuclear weapons, increasing use of nuclear power, and worldwide radical terrorism underscore the need to develop countermeasures to a radiological mass casualty event. The hematopoietic syndrome of the acute radiation syndrome (HS-ARS) results from severe compromise to the hematopoietic system, including lymphocytopenia, neutropenia, thrombocytopenia, and possible death from infection and/or hemorrhage....

  20. A highly conserved regulatory element controls hematopoietic expression of GATA-2 in zebrafish

    OpenAIRE

    Zhang Michael Q; Sakamoto Kathleen M; Shankar Deepa B; Zhao Fang; Jiang Hong; Yang Zhongan; Lin Shuo

    2007-01-01

    Abstract Background GATA-2 is a transcription factor required for hematopoietic stem cell survival as well as for neuronal development in vertebrates. It has been shown that specific expression of GATA-2 in blood progenitor cells requires distal cis-acting regulatory elements. Identification and characterization of these elements should help elucidating transcription regulatory mechanisms of GATA-2 expression in hematopoietic lineage. Results By pair-wise alignments of the zebrafish genomic s...

  1. Production of human glucocerebrosidase in mice after retroviral gene transfer into multipotential hematopoietic progenitor cells.

    OpenAIRE

    Correll, P H; Fink, J K; Brady, R O; Perry, L K; S. Karlsson

    1989-01-01

    The human glucocerebrosidase (GC) gene has been transferred efficiently into spleen colony-forming unit (CFU-S) multipotential hematopoietic progenitor cells, and production of human GC RNA and protein has been achieved in transduced CFU-S colonies. High-titer retroviral vectors containing the human GC cDNA were constructed. Mouse bone marrow cells were stimulated with hematopoietic growth factors, infected by coculture with producer cells, and injected into lethally irradiated animals. Four ...

  2. Vector design for expression of O6-methylguanine-DNA methyltransferase in hematopoietic cells

    OpenAIRE

    Schambach, Axel; Baum, Christopher

    2007-01-01

    Enhancing DNA repair activity of hematopoietic cells by stably integrating gene vectors that express O(6)-methylguanine-DNA-methyltransferase (MGMT) is of major interest for innovative approaches in tumor chemotherapy and for the control of hematopoietic chimerism in the treatment of multiple other acquired or inherited disorders. Crucial determinants of this selection principle are the stringency of treatment with O(6)-alkylating agents and the level of transgenic MGMT expression. Attempts t...

  3. Expression Levels of Histone Deacetylases Determine the Cell Fate of Hematopoietic Progenitors*

    OpenAIRE

    Wada, Taeko; Kikuchi, Jiro; Nishimura, Noriko; Shimizu, Rumi; Kitamura, Toshio; Furukawa, Yusuke

    2009-01-01

    Histone deacetylases (HDACs) are globally implicated in the growth and differentiation of mammalian cells; however, relatively little is known about their specific roles in hematopoiesis. In this study, we investigated the expression of HDACs in human hematopoietic cells and their functions during hematopoiesis. The expression of HDACs was very low in hematopoietic progenitor cells, which was accompanied by histone hyperacetylation. HDACs were detectable in more differentiated progenitors and...

  4. Transcriptional, epigenetic and retroviral signatures identify regulatory regions involved in hematopoietic lineage commitment

    OpenAIRE

    Romano, Oriana; Peano, Clelia; Tagliazucchi, Guidantonio Malagoli; Petiti, Luca; Poletti, Valentina; Cocchiarella, Fabienne; Rizzi, Ermanno; Severgnini, Marco; Cavazza, Alessia; Rossi, Claudia; Pagliaro, Pasqualepaolo; Ambrosi, Alessandro; Ferrari, Giuliana; Bicciato, Silvio; De Bellis, Gianluca

    2016-01-01

    Genome-wide approaches allow investigating the molecular circuitry wiring the genetic and epigenetic programs of human somatic stem cells. Hematopoietic stem/progenitor cells (HSPC) give rise to the different blood cell types; however, the molecular basis of human hematopoietic lineage commitment is poorly characterized. Here, we define the transcriptional and epigenetic profile of human HSPC and early myeloid and erythroid progenitors by a combination of Cap Analysis of Gene Expression (CAGE...

  5. Dysregulated Gene Expression During Hematopoietic Differentiation From Human Embryonic Stem Cells

    OpenAIRE

    Dravid, Gautam; Zhu, Yuhua; Scholes, Jessica; Evseenko, Denis; Crooks, Gay M

    2010-01-01

    The generation of hematopoietic cells from human embryonic stem cells (hESC) has raised the possibility of using hESC as an alternative donor source for transplantation. However, functional defects identified in hESC-derived cells limit their use for full lymphohematopoietic reconstitution. The purpose of the present study was to define and quantitate key functional and molecular differences between CD34+ hematopoietic progenitor subsets derived from hESC and CD34+ subsets from umbilical cord...

  6. Sox17 Dependence Distinguishes the Transcriptional Regulation of Fetal from Adult Hematopoietic Stem Cells

    OpenAIRE

    Kim, Injune; Saunders, Thomas L.; Morrison, Sean J

    2007-01-01

    Fetal stem cells differ phenotypically and functionally from adult stem cells in diverse tissues. However, little is known about how these differences are regulated. To address this we compared the gene expression profiles of fetal versus adult hematopoietic stem cells (HSCs) and discovered that the Sox17 transcriptional regulator is specifically expressed in fetal and neonatal but not adult HSCs. Germline deletion of Sox17 led to severe fetal hematopoietic defects, including a lack of detect...

  7. Current state and future directions of autologous hematopoietic stem cell transplantation in systemic lupus erythematosus

    OpenAIRE

    Illei, Gabor G.; Cervera, Ricard; Burt, Richard K.; Doria, Andrea; Hiepe, Falk; Jayne, David; Pavletic, Steven; Martin, Thierry; Marmont, Alberto; Saccardi, Riccardo; Voskuyl, Alexandre E; Farge, Dominique

    2011-01-01

    Autologous hematopoietic stem cell transplantation (AHSCT) has been proposed as a treatment modality which may arrest the autoimmune disease process and lead to sustained treatment-free remissions. Since the first consensus statement in 1997, approximately 200 autologous bone marrow or hematopoietic stem cell transplantations have been reported world-wide for SLE. The current state of AHSCT in SLE was reviewed at a recent meeting of the Autoimmune Working Party of the European Group for Blood...

  8. Mobilization of hematopoietic stem cells from the bone marrow niche to the blood compartment

    OpenAIRE

    Hoggatt, Jonathan; Pelus, Louis M.

    2011-01-01

    The vast majority of hematopoietic stem cells (HSCs) reside in specialized niches within the bone marrow during steady state, maintaining lifelong blood cell production. A small number of HSCs normally traffic throughout the body; however, exogenous stimuli can enhance their release from the niche and entry into the peripheral circulation. This process, termed mobilization, has become the primary means to acquire a stem cell graft for hematopoietic transplant at most transplant centers. Curre...

  9. Radioprotective potential of primitive hematopoietic precursors forming colonies in diffusion chambers in mice

    International Nuclear Information System (INIS)

    The purpose of this study was to determine the radioprotective ability of primitive hematopoietic precursors which form colonies in diffusion chambers in mice (CFU-D). Thirty-two lethally irradiated female ICR mice were injected with 5 to 7 male ICR mouse bone marrow-derived CFU-D colonies each. Fourteen of these mice survived over 30 days and were sacrificed at intervals up to a year. As a control, 20 lethally irradiated female ICR mice received cells from intercolony areas. All of these mice died before day 20. DNA samples obtained from hematopoietic organs and liver from 8 sacrificed mice were analyzed for the presence of CFU-D colony-derived cells. Only in 1 ICR mouse was CFU-D colony origin DNA detected by Southern analysis in all hematopoietic organs: bone marrow, spleen, thymus and lymph nodes. In 6 mice, only selected hematopoietic organs were repopulated by CFU-D colony-derived cells ad judged by Southern analysis. In some of these mice, the remaining hematopoietic organs contained small CDU-D-derived cell populations which could be detected by more sensitive polynmerase chain reaction (PCR). In 1 mouse, the presence of DFU-C-derived cells in all hematopoietic organs was only demonstrated by PCR. These findings suggest that lethally irradiated mice can be rescued by DFU-D-derived daughter cells. They appear to have the potential to give rise to clones containing lymphoid and myeloid cells in all hematopoietic organs, at least temporarily. Thus, it can be concluded that CFU-D represents a very primitive hematopoietic precursor cell with radioprotective capability. (au)

  10. Hematopoietic Defects in rps29 Mutant Zebrafish Depend Upon p53 Activation

    OpenAIRE

    Taylor, Alison Marie; Humphries, Jessica M.; White, Richard; Murphey, Ryan D.; Burns, Caroline Erter; Zon, Leonard Ira

    2012-01-01

    Disruption of ribosomal proteins is associated with hematopoietic phenotypes in cell culture and animal models. Mutations in ribosomal proteins are seen in patients with Diamond Black- fan anemia, a rare congenital disease characterized by red cell aplasia and distinctive cranio- facial anomalies. A zebrafish screen uncovered decreased hematopoietic stem cells in embryos with mutations in ribosomal protein rps29. Here, we determined that rps29L/L embryos also have red blood cell defects and i...

  11. Quality of life of hospitalized patients submitted to hematopoietic stem cells transplantation

    OpenAIRE

    Vanessa da Rocha; Luciana Puchalski Kalinke; Jorge Vinicius Cestari Felix; Maria de Fátima Montovani; Mariluci Alves Maftum; Paulo Ricardo Bittencourt Guimarães

    2015-01-01

    The objective of this study was to assess the quality of life and to identify the altered domains of adult patients with blood cancer, submitted to hematopoietic stem cells transplantation during hospitalization time. A longitudinal, observation and analytical study, conducted in a reference hospital for hematopoietic stem cell transplant. The data collection was during September of 2013 and September of 2014, including 25 patients and using questionnaires for sociodemographic and clinic char...

  12. A problem-solving education intervention in caregivers and patients during allogeneic hematopoietic stem cell transplantation

    OpenAIRE

    Bevans, Margaret; Wehrlen, Leslie; Castro, Kathleen; Prince, Patricia; Shelburne, Nonniekaye; Soeken, Karen; Zabora, James; Wallen, Gwenyth R.

    2013-01-01

    The aim of this study was to determine the effect of problem-solving education on self-efficacy and distress in informal caregivers of allogeneic hematopoietic stem cell transplantation patients. Patient/caregiver teams attended three 1-hour problem-solving education sessions to help cope with problems during hematopoietic stem cell transplantation. Primary measures included the Cancer Self-Efficacy Scale–transplant and Brief Symptom Inventory–18. Active caregivers reported improvements in se...

  13. Donor parity no longer a barrier for female-to-male hematopoietic stem cell transplantation

    OpenAIRE

    van Halteren, Astrid GS; Miranda P Dierselhuis; Netelenbos, Tanja; Fechter, Mirjam

    2014-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a widely applied treatment for disorders mainly involving the hematopoietic system. The success of this treatment depends on many different patient- and donor-specific factors. Based on higher CD34+ yields and superior clinical outcomes associated with the use of male donors, males are generally seen as the preferred HSCT donor. In addition, female donors are notorious for bearing memory type lymphocytes induced by previous pregnanc...

  14. Treatment with thrombopoietin of the hematopoietic syndrome induced by lethal irradiation

    International Nuclear Information System (INIS)

    The therapeutical efficacy of thrombopoietin, an hematopoietic cytokine, has been evaluated on improvement of hematopoietic syndrome, hematopoietic recovery and survival in C57BL6J mice following total body irradiation with a 60Co source (7-10 Gy). A single administration of 0.3 μg thrombopoietin 2 h after an irradiation of 9 Gy increased the 30-day survival. The survival enhancement was related to an accelerated hematopoietic recovery for all lineages and a decrease in bacterial infections. However, when the administration was delayed to 24 h after irradiation, thrombopoietin had a lower efficiency on both survival and hematopoietic recovery. We observed that half of the thrombopoietic-treated mice died between the 2 nd and the 6. month after irradiation. This long-term mortality was likely to be due to thrombosis formation. In fact, we have demonstrated that thrombopoietin activates platelets which in turn enhance thrombosis formation in irradiated mice. In order to avoid thrombosis, we administrated ticlopidine, an antagonist of platelet activation, to mice before irradiation. Almost all of the 9 Gy irradiated mice which received both thrombopoietin and ticlopidine survived up to 6 months, reaching the same efficiency than a bone marrow graft. In summary, we have shown that thrombopoietin treatment enhances survival of lethally irradiated mice in relation with protection form hematopoietic syndrome. Nonetheless, an anti-platelet drug might be associated with thrombopoietin to avoid thrombosis formation which might be lethal on a long term basis. (author)

  15. Donor Dependent Variations in Hematopoietic Differentiation among Embryonic and Induced Pluripotent Stem Cell Lines

    Science.gov (United States)

    Féraud, Olivier; Valogne, Yannick; Melkus, Michael W.; Zhang, Yanyan; Oudrhiri, Noufissa; Haddad, Rima; Daury, Aurélie; Rocher, Corinne; Larbi, Aniya; Duquesnoy, Philippe; Divers, Dominique; Gobbo, Emilie; Brunet de la Grange, Philippe; Louache, Fawzia; Bennaceur-Griscelli, Annelise; Mitjavila-Garcia, Maria Teresa

    2016-01-01

    Hematopoiesis generated from human embryonic stem cells (ES) and induced pluripotent stem cells (iPS) are unprecedented resources for cell therapy. We compared hematopoietic differentiation potentials from ES and iPS cell lines originated from various donors and derived them using integrative and non-integrative vectors. Significant differences in differentiation toward hematopoietic lineage were observed among ES and iPS. The ability of engraftment of iPS or ES-derived cells in NOG mice varied among the lines with low levels of chimerism. iPS generated from ES cell-derived mesenchymal stem cells (MSC) reproduce a similar hematopoietic outcome compared to their parental ES cell line. We were not able to identify any specific hematopoietic transcription factors that allow to distinguish between good versus poor hematopoiesis in undifferentiated ES or iPS cell lines. There is a relatively unpredictable variation in hematopoietic differentiation between ES and iPS cell lines that could not be predicted based on phenotype or gene expression of the undifferentiated cells. These results demonstrate the influence of genetic background in variation of hematopoietic potential rather than the reprogramming process. PMID:26938212

  16. Comparative study of hematopoietic differentiation between human embryonic stem cell lines.

    Science.gov (United States)

    Melichar, Heather; Li, Ou; Ross, Jenny; Haber, Hilary; Cado, Dragana; Nolla, Hector; Robey, Ellen A; Winoto, Astar

    2011-01-01

    Directed differentiation of human embryonic stem cells (hESCs) into any desired cell type has been hailed as a therapeutic promise to cure many human diseases. However, substantial roadblocks still exist for in vitro differentiation of hESCs into distinct cell types, including T lymphocytes. Here we examined the hematopoietic differentiation potential of six different hESC lines. We compare their ability to develop into CD34(+) or CD34(+)CD45(+) hematopoietic precursor populations under several differentiation conditions. Comparison of lymphoid potential of hESC derived- and fetal tissue derived-hematopoietic precursors was also made. We found diverse hematopoietic potential between hESC lines depending on the culture or passage conditions. In contrast to fetal-derived hematopoietic precursors, none of the CD34(+) precursors differentiated from hESCs were able to develop further into T cells. These data underscore the difficulties in the current strategy of hESC forward differentiation and highlight distinct differences between CD34(+) hematopoietic precursors generated in vitro versus in vivo. PMID:21603627

  17. Comparative study of hematopoietic differentiation between human embryonic stem cell lines.

    Directory of Open Access Journals (Sweden)

    Heather Melichar

    Full Text Available Directed differentiation of human embryonic stem cells (hESCs into any desired cell type has been hailed as a therapeutic promise to cure many human diseases. However, substantial roadblocks still exist for in vitro differentiation of hESCs into distinct cell types, including T lymphocytes. Here we examined the hematopoietic differentiation potential of six different hESC lines. We compare their ability to develop into CD34(+ or CD34(+CD45(+ hematopoietic precursor populations under several differentiation conditions. Comparison of lymphoid potential of hESC derived- and fetal tissue derived-hematopoietic precursors was also made. We found diverse hematopoietic potential between hESC lines depending on the culture or passage conditions. In contrast to fetal-derived hematopoietic precursors, none of the CD34(+ precursors differentiated from hESCs were able to develop further into T cells. These data underscore the difficulties in the current strategy of hESC forward differentiation and highlight distinct differences between CD34(+ hematopoietic precursors generated in vitro versus in vivo.

  18. DNA Damage: A Sensible Mediator of the Differentiation Decision in Hematopoietic Stem Cells and in Leukemia

    Directory of Open Access Journals (Sweden)

    Cary N. Weiss

    2015-03-01

    Full Text Available In the adult, the source of functionally diverse, mature blood cells are hematopoietic stem cells, a rare population of quiescent cells that reside in the bone marrow niche. Like stem cells in other tissues, hematopoietic stem cells are defined by their ability to self-renew, in order to maintain the stem cell population for the lifetime of the organism, and to differentiate, in order to give rise to the multiple lineages of the hematopoietic system. In recent years, increasing evidence has suggested a role for the accumulation of reactive oxygen species and DNA damage in the decision for hematopoietic stem cells to exit quiescence and to differentiate. In this review, we will examine recent work supporting the idea that detection of cell stressors, such as oxidative and genetic damage, is an important mediator of cell fate decisions in hematopoietic stem cells. We will explore the benefits of such a system in avoiding the development and progression of malignancies, and in avoiding tissue exhaustion and failure. Additionally, we will discuss new work that examines the accumulation of DNA damage and replication stress in aging hematopoietic stem cells and causes us to rethink ideas of genoprotection in the bone marrow niche.

  19. Serum after autologous transplantation stimulates proliferation and expansion of human hematopoietic progenitor cells.

    Directory of Open Access Journals (Sweden)

    Thomas Walenda

    Full Text Available Regeneration after hematopoietic stem cell transplantation (HSCT depends on enormous activation of the stem cell pool. So far, it is hardly understood how these cells are recruited into proliferation and self-renewal. In this study, we have addressed the question if systemically released factors are involved in activation of hematopoietic stem and progenitor cells (HPC after autologous HSCT. Serum was taken from patients before chemotherapy, during neutropenia and after hematopoietic recovery. Subsequently, it was used as supplement for in vitro culture of CD34(+ cord blood HPC. Serum taken under hematopoietic stress (4 to 11 days after HSCT significantly enhanced proliferation, maintained primitive immunophenotype (CD34(+, CD133(+, CD45(- for more cell divisions and increased colony forming units (CFU as well as the number of cobblestone area-forming cells (CAFC. The stimulatory effect decays to normal levels after hematopoietic recovery (more than 2 weeks after HSCT. Chemokine profiling revealed a decline of several growth-factors during neutropenia, including platelet-derived growth factors PDGF-AA, PDGF-AB and PDGF-BB, whereas expression of monocyte chemotactic protein-1 (MCP-1 increased. These results demonstrate that systemically released factors play an important role for stimulation of hematopoietic regeneration after autologous HSCT. This feedback mechanism opens new perspectives for in vivo stimulation of the stem cell pool.

  20. ESAM is a novel human hematopoietic stem cell marker associated with a subset of human leukemias.

    Science.gov (United States)

    Ishibashi, Tomohiko; Yokota, Takafumi; Tanaka, Hirokazu; Ichii, Michiko; Sudo, Takao; Satoh, Yusuke; Doi, Yukiko; Ueda, Tomoaki; Tanimura, Akira; Hamanaka, Yuri; Ezoe, Sachiko; Shibayama, Hirohiko; Oritani, Kenji; Kanakura, Yuzuru

    2016-04-01

    Reliable markers are essential to increase our understanding of the biological features of human hematopoietic stem cells and to facilitate the application of hematopoietic stem cells in the field of transplantation and regenerative medicine. We previously identified endothelial cell-selective adhesion molecule (ESAM) as a novel functional marker of hematopoietic stem cells in mice. Here, we found that ESAM can also be used to purify human hematopoietic stem cells from all the currently available sources (adult bone marrow, mobilized peripheral blood, and cord blood). Multipotent colony-forming units and long-term hematopoietic-reconstituting cells in immunodeficient mice were found exclusively in the ESAM(High) fraction of CD34(+)CD38(-) cells. The CD34(+)CD38(-) fraction of cord blood and collagenase-treated bone marrow contained cells exhibiting extremely high expression of ESAM; these cells are likely to be related to the endothelial lineage. Leukemia cell lines of erythroid and megakaryocyte origin, but not those of myeloid or lymphoid descent, were ESAM positive. However, high ESAM expression was observed in some primary acute myeloid leukemia cells. Furthermore, KG-1a myeloid leukemia cells switched from ESAM negative to ESAM positive with repeated leukemia reconstitution in vivo. Thus, ESAM is a useful marker for studying both human hematopoietic stem cells and leukemia cells. PMID:26774386

  1. CELLULAR AND MOLECULAR BASIS OF HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THE SUCCESSFUL TREATMENT OF HIGH RISK LEUKEMIAS.

    Directory of Open Access Journals (Sweden)

    FRANCO eLOCATELLI

    2013-02-01

    Full Text Available Natural Killer (NK cells are involved in innate immune responses and play a major role in tumor surveillance and in defence against viruses. Human NK cells recognize HLA-class I molecules via surface receptors (KIR and NKG2A delivering signals that inhibit NK cell function and kill HLA-class I-deficient target cells, a frequent event in tumors or virus-infected cells. NK cell triggering is mediated by activating receptors that recognize ligands expressed primarily on tumors or virus-infected cells. NK cells play also a key role in the cure of high-risk leukemias. Thus, donor-derived alloreactive NK cells are fundamental effectors in adult acute myeloid leukemia (AML and in pediatric acute lymphoblastic leukemia (ALL patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT. Alloreactive NK cells mediate killing of leukemia cells and patient’s DC, thus preventing respectively leukemic relapses and graft-versus-host responses. FACS analysis of KIRs expressed by NK cells allows to define the size of the alloreactive NK subset and the selection of the best potential donor. Recently, it has been shown that also the expression of activating KIRs, in particular the (C2-specific KIR2DS1, may contribute to donor NK alloreactivity. It has also been established a correlation between the size of the alloreactive NK cell population and the clinical outcome. Notably, the alloreactive NK cells derived from donor’s HSC are generated and persist in patients over time. The high survival rates of patients undergoing haploidentical HSCT highlight an important new reality in the setting of allograft performed to cure otherwise fatal leukemias. Novel approaches are in progress to further improve the clinical outcome based on the infusion of donor alloreactive NK cells either as a component of the transplanted cell population or as in vitro expanded NK cells.

  2. High incidence of oral squamous cell carcinoma independent of HPV infection after allogeneic hematopoietic SCT in Taiwan.

    Science.gov (United States)

    Chen, M H; Chang, P M; Li, W Y; Hsiao, L T; Hong, Y C; Liu, C Y; Gau, J P; Liu, J H; Chen, P M; Chiou, T J; Tzeng, C H

    2011-04-01

    Hematopoietic SCT (HSCT) is a well-recognized therapeutic procedure to prolong life and cure patients with life-threatening hematological malignancies; however, the risk of developing secondary carcinoma may increase in long-term survivors. The objective of this study was to determine the incidence and risk factors for secondary squamous carcinoma after HSCT. Between 1984 and 2004, 170 allogeneic HSCT recipients aged >15 years, who had survived for >5 years were enrolled. Demographic data and the characteristics of secondary carcinoma were collected and analyzed for the determination of the incidence and risk of developing secondary carcinoma. Eight patients developed secondary carcinoma, including five oral squamous cell carcinomas, one esophageal, one gastric and one ovarian carcinoma, but no cutaneous carcinomas were detected at a median follow-up of 14.1 years (range, 5.1-23.3 years) after HSCT. The accrual 10-year cumulative incidence of secondary carcinoma was 2.89%. In univariate and multivariate analyses, chronic GVHD and age >40 years at the time of HSCT were both significant risk factors independently associated with the development of secondary carcinoma. Thus, the occurrence of secondary carcinoma is one of the late complications in patients undergoing HSCT. Oral squamous cell carcinoma was more common in our patients after HSCT, indicating the need for lifelong surveillance of the oral cavity. Moreover, because of the relatively long latency in developing secondary carcinoma, extended follow-up is required for a thorough understanding of the incidence and characteristics of secondary carcinoma after HSCT. PMID:20622906

  3. Radiation exposure distribution in patients undergoing CT brain scans

    International Nuclear Information System (INIS)

    The distribution of surface exposures in patients undergoing single and multiple computerized tomographic brain scans with Hitachi CT-W500 was measured by LiF(Mg, Ti) thermoluminescent dosimetry. It was found that there was no significant difference in the sufrace exposures from different scanning slices. However, the exposure doses at different scanning angles around the head were different significantly. The reference point of the maximum surface exposure was at the temporal part of the head. the maximum surface exposure was at 1.65 x 10-3 C·kg-1 while the average exposure was 1.55 x 10-3 C·kg-1. The ratio of the average dose resulting from nine scans to that from a single scan was 1.3, and the surface exposure contribution of scattered radiation was computed. At the same time the radiation doses to eyes, thyroid, chest and gonads of patiens at corresponding position were also measured and were compared with those from CT cranial scans in children and skull radiographic procedures respectively

  4. Quantitative and qualitative assessment of reactive hematopoietic bone marrow in aplastic anemia using MR spectroscopy with variable echo times

    Energy Technology Data Exchange (ETDEWEB)

    Amano, Yasuo; Kumazaki, Tatsuo [Department of Radiology, Nippon Medical School, Tokyo (Japan)

    2002-01-01

    Objective: To assess quantitative and qualitative differences in water components between normal bone marrow and reactive hematopoietic marrow in aplastic anemia using magnetic resonance (MR) spectroscopy with variable echo times (TEs). Design: Water content, T2 value of the water component, and signal change in water related to TE were assessed in normal bone marrow and reactive hematopoietic bone marrow by a stimulated echo acquisition mode with TEs of 30, 45, 60, and 90 ms. Patients: Six patients with aplastic anemia (13-84 years) and seven normal volunteers (25-38 years) were examined. Results and conclusion: Reactive hematopoietic marrow showed significantly higher water content than normal bone marrow. The T2 value of water components tended to be longer in reactive hematopoietic marrow. Water signal ratio related to TE was significantly higher in reactive hematopoietic marrow. These results suggest a quantitative and qualitative difference in water components between normal and reactive hematopoietic bone marrow. (orig.)

  5. Quantitative and qualitative assessment of reactive hematopoietic bone marrow in aplastic anemia using MR spectroscopy with variable echo times

    International Nuclear Information System (INIS)

    Objective: To assess quantitative and qualitative differences in water components between normal bone marrow and reactive hematopoietic marrow in aplastic anemia using magnetic resonance (MR) spectroscopy with variable echo times (TEs). Design: Water content, T2 value of the water component, and signal change in water related to TE were assessed in normal bone marrow and reactive hematopoietic bone marrow by a stimulated echo acquisition mode with TEs of 30, 45, 60, and 90 ms. Patients: Six patients with aplastic anemia (13-84 years) and seven normal volunteers (25-38 years) were examined. Results and conclusion: Reactive hematopoietic marrow showed significantly higher water content than normal bone marrow. The T2 value of water components tended to be longer in reactive hematopoietic marrow. Water signal ratio related to TE was significantly higher in reactive hematopoietic marrow. These results suggest a quantitative and qualitative difference in water components between normal and reactive hematopoietic bone marrow. (orig.)

  6. Efficacy and Safety of Oral Lactoferrin Supplementation in Combination with rHuEPO-β for the Treatment of Anemia in Advanced Cancer Patients Undergoing Chemotherapy: Open-Label, Randomized Controlled Study

    Science.gov (United States)

    Madeddu, Clelia; Gramignano, Giulia; Mulas, Carlo; Sanna, Eleonora; Mantovani, Giovanni

    2010-01-01

    Advanced-stage cancer patients often suffer from anemia that closely resembles the anemia of chronic inflammatory diseases characterized by specific changes in iron homeostasis and absorption. i.v. iron improves the efficacy of recombinant human erythropoietin (rHuEPO) in anemic cancer patients undergoing chemotherapy. We report the results of an open-label, randomized, prospective trial aimed at testing the efficacy and safety of treatment with oral lactoferrin versus i.v. iron, both combined with rHuEPO, for the treatment of anemia in a population of 148 advanced cancer patients undergoing chemotherapy. All patients received s.c. rHuEPO-β, 30,000 UI once weekly for 12 weeks, and were randomly assigned to ferric gluconate (125 mg i.v. weekly) or lactoferrin (200 mg/day). Both arms showed a significant hemoglobin increase. No difference in the mean hemoglobin increase or the hematopoietic response, time to hematopoietic response, or mean change in serum iron, C-reactive protein, or erythrocyte sedimentation rate were observed between arms. In contrast, ferritin decreased in the lactoferrin arm whereas it increased in the i.v. iron arm. In conclusion, these results show similar efficacy for oral lactoferrin and for i.v. iron, combined with rHuEPO, for the treatment of anemia in advanced cancer patients undergoing chemotherapy. PMID:20647390

  7. Astrovirus infection in hospitalized infants with severe combined immunodeficiency after allogeneic hematopoietic stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Werner Wunderli

    Full Text Available Infants with severe primary combined immunodeficiency (SCID and children post-allogeneic hematopoietic stem cell transplantation (HSCT are extremely susceptible to unusual infections. The lack of generic tools to detect disease-causing viruses among more than 200 potential human viral pathogens represents a major challenge to clinicians and virologists. We investigated retrospectively the causes of a fatal disseminated viral infection with meningoencephalitis in an infant with gamma C-SCID and of chronic gastroenteritis in 2 other infants admitted for HSCT during the same time period. Analysis was undertaken by combining cell culture, electron microscopy and sequence-independent single primer amplification (SISPA techniques. Caco-2 cells inoculated with fecal samples developed a cytopathic effect and non-enveloped viral particles in infected cells were detected by electron microscopy. SISPA led to the identification of astrovirus as the pathogen. Both sequencing of the capsid gene and the pattern of infection suggested nosocomial transmission from a chronically excreting index case to 2 other patients leading to fatal infection in 1 and to transient disease in the others. Virus-specific, real-time reverse transcription polymerase chain reaction was then performed on different stored samples to assess the extent of infection. Infection was associated with viremia in 2 cases and contributed to death in 1. At autopsy, viral RNA was detected in the brain and different other organs, while immunochemistry confirmed infection of gastrointestinal tissues. This report illustrates the usefulness of the combined use of classical virology procedures and modern molecular tools for the diagnosis of unexpected infections. It illustrates that astrovirus has the potential to cause severe disseminated lethal infection in highly immunocompromised pediatric patients.

  8. In Vivo Repopulating Activity Emerges at the Onset of Hematopoietic Specification during Embryonic Stem Cell Differentiation

    OpenAIRE

    Stella Pearson; Sara Cuvertino; Maud Fleury; Georges Lacaud; Valerie Kouskoff

    2015-01-01

    Summary The generation of in vivo repopulating hematopoietic cells from in vitro differentiating embryonic stem cells has remained a long-standing challenge. To date, hematopoietic engraftment has mostly been achieved through the enforced expression of ectopic transcription factors. Here, we describe serum-free culture conditions that allow the generation of in vivo repopulating hematopoietic cells in the absence of ectopically expressed factors. We show that repopulating activity arises imme...

  9. Brain tumor - children

    Science.gov (United States)

    Glioblastoma multiforme - children; Ependymoma - children; Glioma - children; Astrocytoma - children; Medulloblastoma - children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children)

  10. Response of hematopoietic stem cells to ionizing radiation

    International Nuclear Information System (INIS)

    Hematopoietic stem cells (HSCs) maintain blood and immune system throughout life and restore them after hematological injuries. Exposure of an organism to ionizing radiation (IR) causes rapid and acute myelosuppression and challenges the replenishment capacity of HSCs. Yet, the precise damages that are generated remain largely unexplored. To better understand these effects, phenotypic and functional changes in the stem/progenitor compartments of sublethally irradiated mice were monitored over a ten week period after radiation exposure. We report that shortly after sublethal IR-exposure, HSCs, defined by their repopulating ability, still segregate in the Hoechst dye excluding side population (SP); yet, their Sca-1 (S) and c-Kit (K) expression levels are increased and severely reduced, respectively, with a concurrent increase in the proportion of SPSK cells positive for established indicators of HSC presence: CD150+ and CD105+. A great proportion of HSCs quickly but transiently enter the cell cycle to replenish the bone marrow of myelo-ablated mice. Ten weeks after, whereas bone marrow cellularity has recovered and hematopoietic homeostasis is restored, major phenotypic modifications can be observed within the Lin-/low Sca-1+ c-Kit+ (LSK) stem/progenitor compartment: CD150+/Flk2- and CD150-/Flk2+ LSK cell frequencies are increased and dramatically reduced, respectively. CD150+ LSK cells also show impaired reconstitution capacity, accrued number of γ-H2AX foci and increased tendency to apoptosis. This demonstrates that the LSK compartment is not properly restored 10 weeks after sublethal exposure, and that long-term IR-induced injury to the bone marrow proceeds, at least partially, through direct damage to the stem cell pool. Thrombopoietin (TPO) has been shown to promote the survival of lethally irradiated mice when administrated quickly after exposure. We investigated the mechanisms underlying this effect, and found in a competitive transplant experiment that a

  11. OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo.

    Science.gov (United States)

    Chen, Xiaoli; Zhao, Qianhao; Li, Chen; Geng, Yang; Huang, Ke; Zhang, Jian; Wang, Xiaoshan; Yang, Jiaqi; Wang, Tongjie; Xia, Chengxiang; Liu, Xiaofei; Meng, Minghui; Yang, Dan; Zheng, Yi; Du, Juan; Zhang, Xiangzhong; Chen, Jiekai; Pan, Guangjin; Wang, Jinyong

    2015-09-01

    Generating engraftable hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) is an ideal approach for obtaining induced HSCs for cell therapy. However, the path from PSCs to robustly induced HSCs (iHSCs) in vitro remains elusive. We hypothesize that the modification of hematopoietic niche cells by transcription factors facilitates the derivation of induced HSCs from PSCs. The Lhx2 transcription factor is expressed in fetal liver stromal cells but not in fetal blood cells. Knocking out Lhx2 leads to a fetal hematopoietic defect in a cell non-autonomous role. In this study, we demonstrate that the ectopic expression of Lhx2 in OP9 cells (OP9-Lhx2) accelerates the hematopoietic differentiation of PSCs. OP9-Lhx2 significantly increased the yields of hematopoietic progenitor cells via co-culture with PSCs in vitro. Interestingly, the co-injection of OP9-Lhx2 and PSCs into immune deficient mice also increased the proportion of hematopoietic progenitors via the formation of teratomas. The transplantation of phenotypic HSCs from OP9-Lhx2 teratomas but not from the OP9 control supported a transient repopulating capability. The upregulation of Apln gene by Lhx2 is correlated to the hematopoietic commitment property of OP9-Lhx2. Furthermore, the enforced expression of Apln in OP9 cells significantly increased the hematopoietic differentiation of PSCs. These results indicate that OP9-Lhx2 is a good cell line for regeneration of hematopoietic progenitors both in vitro and in vivo. PMID:26339946

  12. OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Xiaoli Chen

    2015-09-01

    Full Text Available Generating engraftable hematopoietic stem cells (HSCs from pluripotent stem cells (PSCs is an ideal approach for obtaining induced HSCs for cell therapy. However, the path from PSCs to robustly induced HSCs (iHSCs in vitro remains elusive. We hypothesize that the modification of hematopoietic niche cells by transcription factors facilitates the derivation of induced HSCs from PSCs. The Lhx2 transcription factor is expressed in fetal liver stromal cells but not in fetal blood cells. Knocking out Lhx2 leads to a fetal hematopoietic defect in a cell non-autonomous role. In this study, we demonstrate that the ectopic expression of Lhx2 in OP9 cells (OP9-Lhx2 accelerates the hematopoietic differentiation of PSCs. OP9-Lhx2 significantly increased the yields of hematopoietic progenitor cells via co-culture with PSCs in vitro. Interestingly, the co-injection of OP9-Lhx2 and PSCs into immune deficient mice also increased the proportion of hematopoietic progenitors via the formation of teratomas. The transplantation of phenotypic HSCs from OP9-Lhx2 teratomas but not from the OP9 control supported a transient repopulating capability. The upregulation of Apln gene by Lhx2 is correlated to the hematopoietic commitment property of OP9-Lhx2. Furthermore, the enforced expression of Apln in OP9 cells significantly increased the hematopoietic differentiation of PSCs. These results indicate that OP9-Lhx2 is a good cell line for regeneration of hematopoietic progenitors both in vitro and in vivo.

  13. Hematopoietic-supportive effect of (2S, 3R)-ent-catechin on marrow-depressed mice

    Institute of Scientific and Technical Information of China (English)

    CHEN Yi-hong; WANG Dong-xiao; LIU Ping; CHEN Ruo-yun; CHEN Meng-li; CHENG Liu-fang; YIN Jian-fen; CHEN Gui-yun

    2005-01-01

    @@ Hematopoiesis is an active process of cell proliferation, differentiation and release. It is the process during which hematopoietic stem cells (HSCs) proliferate and differentiate to mature blood cells under the effect of hemetopoietic growth factors (HGFs) in certain hematopoietic microenvironment. HSCs are sources of hematopoiesis of a body that can self-renew, differentiate to blood cells of every lineage and maintain the constancy of them. As the major tissue of hematopoiesis bone marrow is filled with all kinds of blood cells in various developmental stages. Under the normal conditions, the ordered proliferation and differentiation of hematopoietic stem cells/hematopoietic progenitor cells (HSC/HPC) depend on the regulation of cytokine network.

  14. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies

    DEFF Research Database (Denmark)

    Sorror, Mohamed L; Sandmaier, Brenda M; Storer, Barry E;

    2011-01-01

    A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions....

  15. Oral Complications and Management Strategies for Patients Undergoing Cancer Therapy

    OpenAIRE

    2014-01-01

    With cancer survival rate climbing up over the past three decades, quality of life for cancer patients has become an issue of major concern. Oral health plays an important part in one’s overall quality of life. However, oral health status can be severely hampered by side effects of cancer therapies including surgery, chemotherapy, radiotherapy, and hematopoietic stem cell transplantation. Moreover, prevention and treatment of these complications are often overlooked in clinical practice. The ...

  16. Administration of interleukin-6 stimulates multilineage hematopoiesis and accelerates recovery from radiation-induced hematopoietic depression

    International Nuclear Information System (INIS)

    Hematopoietic depression and subsequent susceptibility to potentially lethal opportunistic infections are well-documented phenomena following radiotherapy. Methods to therapeutically mitigate radiation-induced myelosuppression could offer great clinical value. In vivo studies have demonstrated that interleukin-6 (IL-6) stimulates pluripotent hematopoietic stem cell (CFU-s), granulocyte-macrophage progenitor cell (GM-CFC), and erythroid progenitor cell (CFU-e) proliferation in normal mice. Based on these results, the ability of IL-6 to stimulate hematopoietic regeneration following radiation-induced hematopoietic injury was also evaluated. C3H/HeN female mice were exposed to 6.5 Gy 60Co radiation and subcutaneously administered either saline or IL-6 on days 1 through 3 or 1 through 6 postexposure. On days 7, 10, 14, 17, and 22, femoral and splenic CFU-s, GM-CFC, and CFU-e contents and peripheral blood white cell, red cell, and platelet counts were determined. Compared with saline treatment, both 3-day and 6-day IL-6 treatments accelerated hematopoietic recovery; 6-day treatment produced the greater effects. For example, compared with normal control values (N), femoral and splenic CFU-s numbers in IL-6-treated mice 17 days postirradiation were 27% N and 136% N versus 2% N and 10% N in saline-treated mice. At the same time, bone marrow and splenic GM-CFC values were 58% N and 473% N versus 6% N and 196% N in saline-treated mice; bone marrow and splenic CFU-e numbers were 91% N and 250% N versus 31% N and 130% N in saline-treated mice; and peripheral blood white cell, red cell, and platelet values were 210% N, 60% N, and 24% N versus 18% N, 39% N, and 7% N in saline-treated mice. These studies demonstrate that therapeutically administered IL-6 can effectively accelerate multilineage hematopoietic recovery following radiation-induced hematopoietic injury

  17. Perfil das crianças submetidas à correção de cardiopatia congênita e análise das complicações respiratórias Perfil de los niños sometidos a la corrección de cardiopatía congénita y análisis de las complicaciones respiratorias Profile of children undergoing congenital heart surgery and analysis of their respiratory complications

    Directory of Open Access Journals (Sweden)

    Priscila Mara N. Oliveira

    2012-01-01

    Full Text Available OBJETIVO: Descrever as características demográficas e clínicas de crianças submetidas à cirurgia de correção de cardiopatia congênita (CC em um hospital universitário, comparando pacientes com e sem complicações respiratórias no pós-operatório. MÉTODOS: Estudo retrospectivo, realizado por meio de consulta de prontuários de crianças submetidas à cirurgia corretiva de CC em hospital universitário brasileiro no período de novembro de 2006 a setembro de 2007. Foram analisados dados relativos a idade, sexo, peso, comorbidades e tipo de CC das crianças incluídas no estudo, comparando pacientes com e sem complicações respiratórias no pós-operatório. Foram utilizados o teste de Mann-Whitney e exato de Fisher, considerando-se significante pOBJETIVO: Describir las características demográficas y clínicas de niños sometidos a la cirugía de corrección de cardiopatía congénita (CC en un hospital universitario, comparando pacientes con y sin complicaciones respiratorias en el post-operatorio. MÉTODOS: Estudio retrospectivo, realizado por medio de consulta de prontuarios de niños sometidos a la cirugía correctiva de CC, en el Hospital de Clínicas de la Universidad Estadual de Campinas (Unicamp, en el periodo de noviembre de 2006 a septiembre de 2007. Se analizaron datos relativos a la edad, sexo, peso, comorbidades y tipo de CC de los niños incluidos en el estudio, comparando pacientes con y sin complicaciones respiratorias en el post-operatorio. Se utilizaron el test de Mann-Whitney y el exacto de Fisher, considerándose significante pOBJECTIVE: To describe the profile of children that undergo surgical correction of congenital heart disease (CHD in a university hospital and to compare patients with and without postoperative respiratory complications. METHOD: This observational analytical study reviewed the records of children that underwent corrective surgery for CHD a Brazilian University Hospital during 11 months. The

  18. [Neutrophil disorders: diagnosis and hematopoietic stem cell transplantation].

    Science.gov (United States)

    Kobayashi, Masao

    2015-10-01

    Neutrophil disorders are classified into abnormal neutrophil function and granulopoiesis. The identification of genetic defects causing neutropenia and neutrophil dysfunction has revealed the mechanisms controlling myeloid differentiation and their functions. The International Union of Immunological Societies of Primary Immunodeficiencies represents the most current catalog of approximately 30 neutrophil disorders. In this report, we show the progress made in studies of the pathophysiology and treatment of these disorders, focusing on chronic granulomatous disease (CGD) and severe congenital neutropenia (SCN). Hematopoietic stem cell transplantation (HSCT) is the only available curative therapy for CGD and SCN. However, the use of HSCT as treatment for both diseases is limited by transplant-related mortality (TRM) because of active infections and intractable inflammatory complications. Recently, reduced-intensity conditioning regimens have been introduced to minimize the TRM and the late adverse effects of HSCT for both diseases. The results of HSCT using the RIC regimen for 40 patients with CGD and SCN in Hiroshima University Hospital are summarized herein. Determining the optimal line of treatment will require further accumulation to cases to refine HSCT for both diseases. PMID:26458464

  19. HSC-explorer: a curated database for hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Corinna Montrone

    Full Text Available HSC-Explorer (http://mips.helmholtz-muenchen.de/HSC/ is a publicly available, integrative database containing detailed information about the early steps of hematopoiesis. The resource aims at providing fast and easy access to relevant information, in particular to the complex network of interacting cell types and molecules, from the wealth of publications in the field through visualization interfaces. It provides structured information on more than 7000 experimentally validated interactions between molecules, bioprocesses and environmental factors. Information is manually derived by critical reading of the scientific literature from expert annotators. Hematopoiesis-relevant interactions are accompanied with context information such as model organisms and experimental methods for enabling assessment of reliability and relevance of experimental results. Usage of established vocabularies facilitates downstream bioinformatics applications and to convert the results into complex networks. Several predefined datasets (Selected topics offer insights into stem cell behavior, the stem cell niche and signaling processes supporting hematopoietic stem cell maintenance. HSC-Explorer provides a versatile web-based resource for scientists entering the field of hematopoiesis enabling users to inspect the associated biological processes through interactive graphical presentation.

  20. Systematic Nutritional Support in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

    Science.gov (United States)

    Fuji, Shigeo; Einsele, Hermann; Savani, Bipin N; Kapp, Markus

    2015-10-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) has become an established treatment modality for various hematological diseases. However, in allogeneic HSCT, patients often suffer from severe gastrointestinal complications caused by the conditioning regimen and acute/chronic graft-versus-host disease, which requires support by multidisciplinary nutritional support teams (NST). In addition, pretransplantation nutritional status can affect the clinical outcome after allogeneic HSCT. Therefore, it is important to refer the patient to a NST when becoming aware of nutritional problems before allogeneic HSCT. It is also important to follow nutritional status over the long term, as patients often suffer from various nutritional problems, such as malnutrition and metabolic syndrome, even late after allogeneic HSCT. In summary, NST can contribute to the improvement of nutritional status and possibly prognosis at every stage before and after allogeneic HSCT. Here, we aim to give a comprehensive overview of current understanding about nutritional support in allogeneic HSCT and try to provoke a constructive discussion to stimulate further investigation. PMID:26172477