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1.
Occup Med (Lond) ; 73(6): 324-331, 2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37523669

ABSTRACT

BACKGROUND: Little is known about the multi-dimensional nature of traumatic duty-related events encountered by firefighters in relation to their post-traumatic stress disorder (PTSD) risk. AIMS: To describe the types of duty-related events encountered by career firefighters and explore if years in the fire service or total event load moderated the association of trauma exposure to PTSD symptoms. METHODS: Participants included 755 career, male firefighters (19% of the department's firefighters and 76% of those who accessed the electronic anonymous survey). The Duty-Related Incident Stressors scale was used to assess exposure to 25 potentially traumatic events (event load) and self-appraisal of the stress associated with these events, grouped by type of event (indirect, direct and colleague-related). The Post-Traumatic Stress Disorder Checklist was used to assess PTSD symptoms. RESULTS: Firefighters rated colleague-related events as the most stressful, followed by indirect and direct events. Event load (r = 0.25) and indirect, direct and colleague-related events stress (r = 0.32-0.35) were positively associated with PTSD symptoms. Results of moderation analyses indicated that event load served as a risk factor in the relation of indirect events stress to PTSD symptoms, and as a buffer in the relation of direct events stress to PTSD symptoms. Years in the fire service were not associated with PTSD symptoms nor moderated the relation of event stress to PTSD symptoms. CONCLUSIONS: Findings underscored the importance of considering the differential effects that types of duty-related traumatic events and cumulative exposure to trauma may have on firefighters' PTSD symptoms.

2.
J Healthc Qual Res ; 35(5): 319-327, 2020.
Article in Spanish | MEDLINE | ID: mdl-32972901

ABSTRACT

Patient Blood Management (PBM) programs have proven to be successful in reducing overuse and improving patient safety, clinical outcomes and efficiency. Despite its benefits, PBM is still scarcely used in real clinical practice with a high variability among hospitals in Spain. Recent guidelines from the European Union on how to implement PBM, as well as recommendations from experts in the field, suggest that further development in PBM implementation requires not only the participation of healthcare professionals but also the commitment and support of Health Authorities and senior hospital management. This article provides some thoughts on health care management and policy strategies to help implement PBM throughout the Spanish autonomous healthcare systems.


Subject(s)
Anemia , Blood Transfusion , Health Policy , Humans , Spain
3.
Occup Med (Lond) ; 69(8-9): 577-585, 2019 Dec 31.
Article in English | MEDLINE | ID: mdl-31064010

ABSTRACT

BACKGROUND: Little is known regarding the mental health of women firefighters. AIMS: To identify demographic, work-related and mental health characteristics associated with post-traumatic stress disorder (PTSD) symptoms and lifetime suicidal ideation in female firefighters compared with male colleagues. METHODS: Participants were firefighters (75 women and 2564 men) employed in a large urban fire department in the USA. Chi-square, correlations, t-tests and analyses of variance were conducted to examine the predictors of PTSD symptoms and lifetime suicide ideation in men and women. RESULTS: Approximately 20% of women scored positively for PTSD and 30% reported lifetime suicidal ideation. Women with PTSD symptoms were more likely to be in their mid-career years (11-20) than in their first 10 years (87% versus 44%; χ2 = 8.77, P < 0.05) and to have received counselling (53% versus 14%; χ2 = 8.11, P < 0.01). Being single (73% versus 58%; χ2 = 6.02, P < 0.05), having a second job (68% versus 38%; χ2 = 5.79, P < 0.05) and having received counselling (41% versus 11%; χ2 = 8.51, P < 0.01) predicted suicide ideation. Depression and general stress positively predicted PTSD symptoms and suicide ideation. PTSD also predicted suicide ideation. CONCLUSIONS: Compared to male firefighters, women were at high risk for PTSD symptoms and suicide ideation. Particularly for women, few socio-demographic and work-related variables were associated with these outcomes. Mental health variables predicted depression and suicide ideation for both gender groups. Therefore, in screening and intervention efforts, it may be most fruitful to focus on mental health risk correlates of PTSD and suicide ideation.


Subject(s)
Firefighters/psychology , Stress Disorders, Post-Traumatic/psychology , Suicidal Ideation , Adult , Aged , Depression/epidemiology , Female , Humans , Male , Marital Status , Middle Aged , Risk Factors , Sex Factors , Stress Disorders, Post-Traumatic/epidemiology , Surveys and Questionnaires , United States/epidemiology
4.
Transpl Infect Dis ; 7(2): 93-6, 2005 Jun.
Article in English | MEDLINE | ID: mdl-16150099

ABSTRACT

The association between cytomegalovirus (CMV) infection and the development of Guillain-Barré syndrome (GBS) in the setting of allogeneic hematopoietic stem cell transplantation (alloSCT) has been reported only occasionally. We describe here a 23-year-old patient diagnosed with acute myelogenous leukemia who underwent a partially HLA-mismatched alloSCT and soon after developed GBS along with a CMV infection. Serum autoantibodies to several ganglioside antigens were concomitantly detected. Despite therapy with ganciclovir and plasma exchanges, the patient's clinical condition rapidly deteriorated, and he died 3 weeks later with persisting CMV antigenemia. Although a coincidental association cannot be excluded, it could be speculated that a pathogenetic link exists between the 2 disorders. In this sense, molecular mimicry between viral antigens and neural host tissues could be postulated as the hypothetical mechanism underlying the triggering of the autoimmune disease in the present case.


Subject(s)
Cytomegalovirus Infections/complications , Guillain-Barre Syndrome/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Transplantation, Homologous/adverse effects , Adult , Humans , Male
5.
Bone Marrow Transplant ; 36(10): 847-53, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16113660

ABSTRACT

The optimal approach to obtain an adequate graft for transplantation in patients with poor peripheral blood stem cell (PBSC) mobilization remains unclear. We retrospectively assessed the impact of different strategies of second-line stem cell harvest on the transplantation outcome of patients who failed PBSC mobilization in our institution. Such patients were distributed into three groups: those who proceeded to steady-state bone marrow (BM) collection (group A, n = 34); those who underwent second PBSC mobilization (group B, n = 41); those in whom no further harvesting was carried out (group C, n = 30). PBSC harvest yielded significantly more CD34+ cells than BM collection. Autologous transplantation was performed in 30, 23 and 11 patients from groups A, B and C, respectively. Engraftment data and transplantation outcome did not differ significantly between groups A and C. By contrast, group B patients had a faster neutrophil recovery, required less platelet transfusions and experienced less transplant-related morbidity, as reflected by lower antibiotics needs and shorter hospital stays. In conclusion, remobilization of PBSC constitutes an effective approach to ensure a rapid hematopoietic engraftment and a safe transplantation procedure for poor mobilizers, whereas unprimed BM harvest does not provide any clinical benefit in this setting.


Subject(s)
Hematopoietic Stem Cell Mobilization , Leukapheresis/methods , Peripheral Blood Stem Cell Transplantation/methods , Adult , Aged , Antigens, CD34 , Blood Cells/cytology , Blood Cells/drug effects , Bone Marrow Cells/cytology , Bone Marrow Cells/drug effects , Bone Marrow Transplantation/methods , Cell Count , Female , Granulocyte Colony-Stimulating Factor/pharmacology , Granulocyte Colony-Stimulating Factor/therapeutic use , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Mobilization/methods , Hematopoietic Stem Cell Mobilization/standards , Humans , Leukapheresis/standards , Male , Middle Aged , Retrospective Studies , Transplantation, Autologous , Treatment Outcome
6.
An Pediatr (Barc) ; 58(3): 268-72, 2003 Mar.
Article in Spanish | MEDLINE | ID: mdl-12628100

ABSTRACT

BACKGROUND: The progressive increase in eating disorders suggests the need to begin health education in early childhood. However, the prevention of eating disorders has been a complicated and, perhaps for this reason, elusive goal for researchers. Restrictive behavior and body image distortion are two basic criteria in the diagnosis of eating disorders. OBJECTIVE: The aim of this study was to explore the relationship between appearance schema and restrictive behavior such as preoccupation with weight and dieting in a random sample of 373 adolescents. METHODS: The instruments used were the Appearance Schemas Inventory (ASI) and the Restraint Scale (RS). Statistical analysis included Pearson's correlation coefficient, Student's t-test, and analysis of variance with the post hoc Tukey contrast test. RESULTS: Body image and restrictive behavior scores were positively correlated (p < 0.0001). Body image distortions were significantly greater in younger adolescents and in those with a higher RS score (i.e. those involved in following restrictive diets and who experienced frequent weight fluctuations) than in older adolescents and in those with a lower RS score. CONCLUSIONS: The results of this study suggest the importance of working in primary prevention and of concentrating efforts on the identification and subsequent modification of body image distortions in children and adolescents.


Subject(s)
Body Image , Diet , Adolescent , Female , Humans , Male
7.
An. pediatr. (2003, Ed. impr.) ; 58(3): 268-272, mar. 2003.
Article in Es | IBECS | ID: ibc-19972

ABSTRACT

Antecedentes. El progresivo incremento de los trastornos alimentarios sugiere la necesidad de comenzar los esfuerzos de educación para la salud en la infancia. Sin embargo, la prevención de los problemas alimentarios ha sido un objetivo complicado y, tal vez por eso, eludido por los investigadores. La conducta restrictiva y la alteración de la imagen corporal son dos criterios fundamentales en el diagnóstico de los trastornos alimentarios. Objetivo. El propósito de este trabajo fue explorar en una muestra de 373 adolescentes las relaciones existentes entre sus esquemas acerca de la apariencia y actitudes restrictivas como la preocupación por el peso y la dieta. Métodos. Los instrumentos utilizados fueron Appearance Schemas Inventory (ASI) (Inventario sobre los Esquemas acerca de la apariencia) y Restraint Scale (RS) (Escala de restricción).Para el análisis estadístico de los datos se utilizó el coeficiente de correlación de Pearson, la prueba t de Student y el análisis de varianza con la prueba de contraste de Tukey. Resultados. Los resultados indicaron correlaciones significativas y positivas entre una excesiva valoración de la apariencia física y las conductas restrictivas (p < 0,0001). Los adolescentes más jóvenes y los adolescentes restrictivos (aquellos que se implicaban en mayor medida en la práctica de dietas y en la fluctuación de su peso) presentaron de forma significativa (p < 0,0001) más alteraciones en la imagen corporal que los adolescentes no restrictivos y que los adolescentes de mayor edad. Conclusiones. A la luz de estos datos, se concluye la importancia de trabajar en un nivel de prevención primaria, centrando los esfuerzos en la identificación y posterior modificación de las distorsiones de la imagen corporal en niños y adolescentes (AU)


Subject(s)
Adolescent , Male , Female , Humans , Body Image , Diet
8.
Leukemia ; 17(2): 437-41, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12592344

ABSTRACT

The objective of our study was to determine the effect of adding r-metHuSCF to Filgrastim and cyclophosphamide for mobilization of peripheral blood progenitor cells (PBPC), on collection of CD34(+) cells and engraftment after autologous stem cell transplant. Twenty-three patients with previously treated stage II-IV breast cancer received cyclophosphamide (3 g/m(2)), Filgrastim 5 microg/kg daily and r-metHuSCF 20 microg/kg daily. Two PBPC collections were performed on consecutive days starting the day the WBC count was above 7.5 x 10(3)/microl. Collection was performed between days +9 and +12 and the median number of CD34(+) cells collected was 9.9 x 10(6)/kg (1.1-53.1) and 6.6 x 10(6)/kg (1.4-33.8) for the first and second apheresis, respectively. Despite being previously treated patients, the target CD34(+) cell dose required for SCT was obtained in all patients. SCT was associated with rapid neutrophil and platelet engraftment and a highly significant correlation was observed between the number of CD34(+) cells infused and engraftment. Treatment with SCF plus filgrastim was well tolerated, with mild to moderate local skin rash being the most frequently reported adverse event. In conclusion, addition of r-metHuSCF induces mobilization of a large number of CD34(+) cells which results in shortening of time to engraftment and hospitalization.


Subject(s)
Breast Neoplasms/therapy , Cyclophosphamide/therapeutic use , Granulocyte Colony-Stimulating Factor/therapeutic use , Hematopoietic Stem Cell Mobilization/methods , Hematopoietic Stem Cells/pathology , Stem Cell Factor/analogs & derivatives , Stem Cell Factor/therapeutic use , Stem Cell Transplantation/methods , Adult , Aged , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Female , Filgrastim , Hematopoietic Stem Cells/drug effects , Humans , Lymphatic Metastasis , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Recombinant Proteins/therapeutic use , Stem Cell Transplantation/adverse effects , Transplantation, Autologous , Treatment Outcome
9.
Br J Haematol ; 115(1): 213-21, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11722435

ABSTRACT

We have investigated the influence of ex vivo expansion of human CD34(+) cord blood cells on the expression and function of adhesion molecules involved in the homing and engraftment of haematopoietic progenitors. Ex vivo expansion of umbilical cord blood CD34(+) cells for 6 d in the presence of interleukin 3 (IL-3), IL-6 and stem cell factor (SCF) or IL-11, SCF and Flt-3L resulted in increased expression of alpha 4, alpha 5, beta 1, alpha M and beta 2 integrins. However, a significant decrease in the adhesion of progenitor cells to fibronectin was observed after the ex vivo culture (adhesion of granulocyte-macrophage colony-forming units (CFU-GM) was 22 +/- 4% in fresh cells versus 5 +/- 2% and 2 +/- 2% in each combination of cytokines). Incubation with the beta 1 integrin-activating antibody TS2/16 restored adhesion to fibronectin. Transplantation of ex vivo expanded umbilical cord blood CD34(+) cells was associated with an early delayed engraftment in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Incubation of cells with the monoclonal antibody TS2/16 before transplantation almost completely abrogated NOD/SCID repopulating ability of both fresh and expanded CD34(+) cells. The seeding efficiency of fresh and expanded CD34(+) cells was similar, but markedly reduced after incubation with the TS2/16 monoclonal antibody. Our results show that functional activation of beta 1 integrins could overcome the decreased very late antigen (VLA)-4- and VLA-5-mediated adhesion observed after ex vivo expansion of haematopoietic progenitors. However, in vivo, these effects induced an almost complete abrogation of the homing and repopulating ability of CD34(+) UCB cells.


Subject(s)
Antigens, CD34 , Integrins/metabolism , Leukocytes, Mononuclear/physiology , Animals , Cell Division , Cells, Cultured , Fetal Blood/immunology , Fetal Blood/metabolism , Fibronectins/metabolism , Flow Cytometry/methods , Humans , Integrin alpha4beta1 , Leukocytes, Mononuclear/transplantation , Mice , Mice, Inbred NOD , Mice, SCID , Receptors, Fibronectin/metabolism , Receptors, Lymphocyte Homing/metabolism
10.
Clín. salud ; 12(3): 391-404, sept. 2001. tab, graf
Article in Es | IBECS | ID: ibc-8237

ABSTRACT

La tecnología de la Realidad Virtual (RV) está teniendo un gran impacto en diferentes ámbitos de la salud, especialmente en el de los tratamientos psicológicos. Este trabajo se centra en su utilidad para el tratamiento de la fobia a volar. Las intervenciones psicológicas para este problema basadas en la terapia de la exposición han demostrado ser eficaces, pero dada la naturaleza de este trastorno tienen importantes limitaciones, pues resultan caras en términos de tiempo, dinero y esfuerzos. La RV ayuda a superar estas dificultades, ya que permite recrear diferentes ambientes en los que la persona puede interactuar con sus miedos mientras está en un medio seguro y protegido (la consulta del terapeuta). El presente trabajo tiene dos objetivos: mostrar los escenarios virtuales que nuestro equipo ha diseñado para el tratamiento del miedo a volar mediante RV y presentar los resultados de un estudio de caso que apoyan su eficacia (AU)


Subject(s)
Humans , Phobic Disorders/therapy , User-Computer Interface
11.
Bone Marrow Transplant ; 27(3): 287-93, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11277176

ABSTRACT

The aim of this study was to determine whether the detection of CTC in the apheresis product contribute significantly to treatment failure of patients with high-risk breast carcinoma treated with high-dose chemotherapy (HDC) and stem cell transplantation (SCT). Patients were with stage II and III adenocarcinoma of the breast with > or = 10 axillary lymph nodes affected after primary surgery (> or = 10 N+) who had received HDC with SCT. We analyzed retrospectively the presence of CTC as assessed by immunocytochemistry (ICC) in the apheresis products obtained after standard adjuvant chemotherapy. We compared the clinical outcome of patients who received HDC and SCT with or without CTC-positive apheresis. One hundred and twenty-seven apheresis products samples were obtained from 51 patients. Fourteen (27.4%) of these samples were CTC positive. After a median follow-up of 4.6 years, 20 patients have relapsed, 14 died from progression of their disease and 30 patients remain alive and free of progression. For the whole group of patients the 5 year probabilities of DFS and OS were 60% (IC 95%, 47-75%) and 71% (IC 95%, 55-83%), respectively. However, the 5 year probabilities of DFS were 23% (IC 95%, 0-46) and 75% (IC 95%, 60-89) for patients with CTC positive and negative, respectively. The 5 year probabilities of OS were 42% (IC 95%, 15-68) and 83% (IC 95%, 70-95) for patients with CTC positive and negative, respectively. Both univariate and multivariate analysis showed that the presence of CTC in the apheresis product was the only prognostic factor associated with a higher incidence of clinically overt disease relapse (P = 0.002) and shorter survival (P = 0.003). The presence of cytokeratin-positive metastatic cells in the apheresis product increases the risk of relapse after HDC and SCT in patients with stage II and III adenocarcinoma of the breast with > or = 10 N+.


Subject(s)
Blood Component Removal/standards , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/standards , Neoplastic Stem Cells/pathology , Adult , Analysis of Variance , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Blood Component Removal/mortality , Breast Neoplasms/chemistry , Cell Separation , Combined Modality Therapy , Female , Humans , Immunohistochemistry/methods , Middle Aged , Prognosis , Recurrence , Retrospective Studies , Risk Factors , Survival Rate , Treatment Failure
12.
Transfusion ; 41(2): 201-5, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11239223

ABSTRACT

BACKGROUND: Data on the administration of rHuG-CSF to normal donors <18 years old are very limited. STUDY DESIGN AND METHODS: The results of rHuG-CSF administration to 61 donors <18 years old (Group A) were retrospectively evaluated and compared with results from 353 donors > or = 18 years old (Group B) who are included in the Spanish National Donor Registry. The mean age (range) in Group A and B was 14 (1-17) and 38 (18-71) years, respectively (p<0.001). The mean dose of rHuG-CSF was 10 microg per kg per day (range, 9-16) during a mean of 5 days (range, 4-6). Central venous access was placed more frequently in younger donors (25% vs. 6%; p<0.001). RESULTS: The mean number of CD34+ cells collected was 7.6 and 6.9 x 10(6) per kg of donor's body weight in Group A and B, respectively. Fifty-six percent of Group A donors needed only one apheresis to achieve > or = 4 x 10(6) CD34+ cells per kg versus 39 percent of Group B donors (p = 0.01). Side effects were more common in Group B (71% vs. 41%; p<0.001). CONCLUSION: The administration of rHuG-CSF to donors <18 years old leads to CD34+ cell mobilization in a pattern similar to that observed in adults. Greater age was associated with a more frequent requirement for more than one apheresis to achieve a similar number of CD34+ cells.


Subject(s)
Aging/physiology , Granulocyte Colony-Stimulating Factor/pharmacology , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cells/drug effects , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Recombinant Proteins
13.
Leukemia ; 15(3): 430-9, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11237067

ABSTRACT

Administration of stem cell factor (SCF) has been proven to enhance cytokine-induced mobilization of CD34+ hematopoietic progenitor cells (HPC) into the peripheral blood (PB). The aim of the present study was to explore in a homogeneous group of 22 uniformly treated breast cancer patients: (1) the kinetics of mobilization into PB of both CD34+ and CD34- cell subsets, including dendritic cells, in sequential samples obtained from day +7 up to day +12 after mobilization; and (2) the composition of the CD34+ and CD34- cell subsets present in the two leukapheresis products obtained for each patient. The following CD34+ and CD34- subsets were analyzed: early CD34+ HPC, erythroid-, myeloid- and B-lymphoid-committed CD34+ precursor cells, mature T, B and NK cells, monocytes, neutrophils, eosinophils, basophils, and dendritic cells (DC) including three subsets of lin-/HLADR+DC (CD16+, CD33high and CD123high). Our results show that the absolute number of PB CD34+ HPC progressively increases from day +7 onwards. As far as the CD34- PB leukocyte subsets are concerned, monocytes (CD14+) displayed the earliest recovery after mobilization predicting neutrophil recovery 1 day in advance. The number of CD34+ HPC collected in a single leukapheresis product was always > or = 1.4 x 10(6) cells/kg body weight. No significant changes were observed between the two leukapheresis sessions either as regards their composition in CD34+ HPC subsets or their CD34- leukocyte populations except for a higher ratio of both CD34+ erythroid/CD34+ myeloid HPC (0.35 +/- 0.13 vs 0.30 +/- 0.13; P = 0.04) and neutrophils/monocytes (1.58 +/- 2.1 vs 0.69 +/- 0.27; P = 0.009) found for the first leukapheresis. Interestingly, the overall number of dendritic cells (DC) was higher in the second leukapheresis (1.06 +/- 0.56 vs 1.9 +/- 0.46; P = 0.02) due to a selective increase of the CD16+ antigen-presenting cells. In summary, our results show that the combination of cyclophosphamide, G-CSF and SCF is highly effective for stem cell mobilization, with differences observed in the mobilization kinetics of the different hematopoietic cell subsets analyzed.


Subject(s)
Antigens, CD34/blood , Breast Neoplasms/immunology , Cyclophosphamide/administration & dosage , Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cell Mobilization , Stem Cell Factor/administration & dosage , Adolescent , Adult , Aged , Breast Neoplasms/drug therapy , Female , Humans , Immunophenotyping , Leukapheresis , Middle Aged , Recombinant Proteins
14.
Bone Marrow Transplant ; 25(11): 1203-8, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10849534

ABSTRACT

We determined prospectively the incidence of chromosomal abnormalities in patients with high-risk breast cancer (HRBC) after high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT), and correlated the cytogenetic abnormalities with the development of post-transplant myelodysplastic syndrome or acute myeloid leukemia (MDS/AML). From 1990 to 1999, 229 women with HRBC underwent ASCT. Cytogenetic analysis of bone marrow (BM) cells was performed 12-59 months after ASCT in 60 consecutive women uniformly treated with six courses of FAC/FEC followed by HDCT and ASCT. With a median follow-up of 36 months after ASCT, there were no cases of MDS/AML among the 229 patients. In the selected cohort of 60 patients, three (5%) showed clonal chromosomal abnormalities (two single trisomy X and one t(1;6)), whereas two additional patients showed non-clonal reciprocal translocations. Two of the patients with clonal aberrations had blood cytopenias as well as subtle dysplastic pictures in BM which were not classifiable as MDS according to the FAB criteria. Similar dysplastic features were also observed in four patients with normal karyotypes. All cytogenetic aberrations were transient and disappeared, except a +X detected by FISH in a residual cell population in one of the patients. Retrospective cytogenetic and FISH studies of samples obtained after six cycles of FAC/FEC and before transplant demonstrated no chromosomal abnormalities in any of the five patients with post-ASCT karyotypic changes. Early changes in karyotype detected in breast cancer patients following ASCT are transient and do not correlate with or predict development of MDS/AML. As these aberrations were not present before ASCT, they may be related to the HDCT regimen or transplant procedure rather than to the prior adjuvant therapy. Our results suggest that ASCT may be less likely to cause MDS or AML in breast cancer patients as compared to other malignancies. Bone Marrow Transplantation (2000) 25, 1203-1208.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/genetics , Breast Neoplasms/therapy , Chromosome Aberrations , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia/etiology , Myelodysplastic Syndromes/etiology , Neoplasms, Second Primary/etiology , Adult , Bone Marrow/pathology , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Middle Aged , Neoplasm Staging , Postmenopause , Predictive Value of Tests , Premenopause , Transplantation, Autologous
15.
J Exp Med ; 191(6): 977-84, 2000 Mar 20.
Article in English | MEDLINE | ID: mdl-10727459

ABSTRACT

Bcr-Abl-expressing leukemic cells are highly resistant to apoptosis induced by chemotherapeutic drugs. Although a number of signaling molecules have been shown to be activated by the Bcr-Abl kinase, the antiapoptotic pathway triggered by this oncogene has not been elucidated. Here, we show that the interleukin 3-independent expression of the antiapoptotic protein, Bcl-xL, is induced by Bcr-Abl through activation of signal transducer and activator of transcription (Stat)5. Inhibition of the Bcr-Abl kinase activity in Bcr-Abl-expressing cell lines and CD34(+) cells from chronic myelogenous leukemia (CML) patients induces apoptosis by suppressing the capacity of Stat5 to interact with the bcl-x promoter. Interestingly, after inhibition of the Bcr-Abl kinase, the expression of Bcl-xL is downregulated more rapidly in chronic phase than in blast crisis CML cells, suggesting an involvement of this protein in disease progression. Overall, we describe a novel antiapoptotic pathway triggered by Bcr-Abl that may contribute to the resistance of CML cells to undergo apoptosis.


Subject(s)
Apoptosis , DNA-Binding Proteins/antagonists & inhibitors , Fusion Proteins, bcr-abl/antagonists & inhibitors , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/enzymology , Milk Proteins , Protein-Tyrosine Kinases/antagonists & inhibitors , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , Signal Transduction , Trans-Activators/antagonists & inhibitors , Apoptosis/genetics , Blast Crisis/enzymology , Blast Crisis/metabolism , Blast Crisis/pathology , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/physiology , Down-Regulation , Fusion Proteins, bcr-abl/genetics , Fusion Proteins, bcr-abl/metabolism , Fusion Proteins, bcr-abl/physiology , Humans , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Leukemia, Myeloid, Chronic-Phase/enzymology , Leukemia, Myeloid, Chronic-Phase/metabolism , Leukemia, Myeloid, Chronic-Phase/pathology , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins c-bcl-2/biosynthesis , STAT5 Transcription Factor , Signal Transduction/genetics , Trans-Activators/genetics , Trans-Activators/metabolism , Trans-Activators/physiology , Transfection , Up-Regulation , bcl-X Protein
16.
Bone Marrow Transplant ; 23(11): 1101-7, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10382948

ABSTRACT

We have determined the effect of delayed addition of G-CSF after chemotherapy on PBPC mobilization in a group of 30 patients with high risk breast cancer (HRBC) undergoing standard chemotherapy followed by high-dose chemotherapy (HDCT) and autologous SCT. Patients received FAC chemotherapy every 21 days followed by G-CSF at doses of 5 microg/kg/day starting on day +15 (groups 1 and 2) or +8 (group 3) after chemotherapy. PBPC collections were performed daily starting after 4 doses of G-CSF and continued until more than 2.5 x 10(6) CD34+ cells had been collected. In group 1, steady-state BM progenitors were also harvested and used for SCT. Groups 2 and 3 received PBPC only. The median number of collections was three in each group. Significantly more PB CD34+ cells were collected in patients receiving G-CSF starting on day 8 vs day 15 (9.43 x 10(6)/kg and 6.2 x 10(6)/kg, respectively) (P < 0.05). After conditioning chemotherapy all harvested cells including BM and PBPC were reinfused. Neutrophil and platelet engraftment was significantly faster in patients transplanted with day 8 G-CSF-mobilized PBPC (P < 0.05) and was associated with lower transplant related morbidity as reflected by days of fever, antibiotics or hospitalization (P < 0.05). Both schedules of mobilization provided successful long-term engraftment with 1 year post-transplant counts above 80% of pretransplant values. In conclusion, we demonstrate that delayed addition of G-CSF results in successful mobilization and collection of PBPC with significant advantage of day 8 G-CSF vs day 15. PBPC collections can be scheduled on a fixed day instead of being guided by the PB counts which provides a practical advantage. Transplantation of such progenitors results in rapid short-term and long-term trilineage engraftment.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/therapy , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cell Transplantation , Adolescent , Adult , Female , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Middle Aged , Risk , Transplantation, Autologous
17.
Cancer Genet Cytogenet ; 110(2): 111-4, 1999 Apr 15.
Article in English | MEDLINE | ID: mdl-10214358

ABSTRACT

The inv(16) and t(16;16) characterize a subgroup of acute myelomonocytic leukemia (AML) with distinct morphological features and a favorable prognosis. Both cytogenetic abnormalities result in a fusion of CBF beta at 16q22 and MYH11 gene at 16p13, whose detection by PCR and fluorescence in situ hybridization (FISH) is useful for diagnosis and monitoring of the disease. Variant translocations of inv(16)/t(16;16) are very rare and whether they are also associated with a favorable prognosis is unknown. We report a patient presenting with typical AML-M4Eo and a three-way translocation of inv(16) involving 16p13, 16q22, and 3q22. FISH studies on bone marrow (BM) chromosomes using CBFB and MYH11 DNA probes revealed a fusion of CBFB and MYH11 on 16q of the der(16), as well as a signal from MYH11 on 16p but not from CBFB; normal signals for both probes were present on the normal 16. Neither of these labeled probes was on the der(3), but the translocation between the der(3) and der(16) was confirmed by using a chromosome 16 painting probe. Molecular analysis of BM cells using RT-PCR identified a CBFB-MYH11 fusion transcript type D. After achieving complete remission, the patient relapsed. We conclude that FISH and PCR are feasible tools to distinguish cases with variant abnormalities of inv(16) from cases with other chromosome 16 abnormalities. Variant abnormalities of inv(16) may be not associated with favorable prognosis.


Subject(s)
Chromosome Inversion , Chromosomes, Human, Pair 16 , Leukemia, Myelomonocytic, Acute/genetics , Translocation, Genetic , Adult , Eosinophils/pathology , Female , Humans , In Situ Hybridization, Fluorescence , Male , Reverse Transcriptase Polymerase Chain Reaction
18.
Bone Marrow Transplant ; 22(1): 39-45, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9678794

ABSTRACT

Despite the wide use of G-CSF for mobilization of PBPC the best dose and schedule of G-CSF has not been definitively established. In this study we have compared three different schedules of G-CSF for mobilization of PBPC in normal donors including a single daily dose of 10 microg/kg/day for 5 days (21 donors) and doses of 6 (21 donors) or 8 microg/kg/12 h (6 donors) for 5 days. We demonstrate that G-CSF at doses of 6 and 8 microg/kg/12 h mobilizes significantly more CD34+ cells/ml of blood (83.3 +/- 6.7 and 121 +/- 6.9, respectively) than 10 microg/kg/day (71.6 +/- 6.5). Mobilization with 6 or 8 microg/kg/12 h of G-CSF was also associated with collection of significantly more CD34+ cells in comparison with 10 microg/kg/24 h (2.24 +/- 1.2 and 2.46 +/- 1.22 vs 1.15 +/- 0.8 CD34+ cells/kg of donor/blood volume). PBPC collection was associated with a significant decrease in platelet count which was not significantly different between the three groups. Ten days after the last PBPC collection platelet counts were within normal limits while there was a decrease in WBC and ANC. We conclude that G-CSF administered every 12 h at doses of 6 microg/kg provides better CD34+ cell yield than 10 microg/kg once a day in normal donors which may translate into a decrease in the number of aphereses required to obtain enough numbers of CD34+ cells for allogeneic PBPC transplant.


Subject(s)
Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cell Mobilization/methods , Hematopoietic Stem Cell Transplantation , Adolescent , Adult , Aged , Blood Cell Count/drug effects , Blood Component Removal/adverse effects , Child , Drug Administration Schedule , Female , Hematopoietic Stem Cell Mobilization/adverse effects , Humans , Male , Middle Aged , Transplantation, Homologous
20.
Vet Rec ; 140(14): 367-8, 1997 Apr 05.
Article in English | MEDLINE | ID: mdl-9133721

ABSTRACT

Sclerosing adenocarcinoma of the extrahepatic bile duct and pyometra were diagnosed in a 17-year-old entire female Siamese cat which had had anorexia, depression, acute icterus and abdominal distension for about a week. Clinical signs derived from he tumor were minimal and non-specific until the diffuse thickening of the bile duct obstructed bile flow and acute icterus resulted. Sclerosing adenocarcinoma of the extrahepatic bile duct is a human variant of bile duct carcinomas that has not, to the authors' knowledge, previously been described in the cat, but it appears to be as invasive as other feline hepatic tumours.


Subject(s)
Adenocarcinoma/veterinary , Bile Duct Neoplasms/veterinary , Bile Ducts, Extrahepatic/pathology , Cat Diseases/pathology , Adenocarcinoma/pathology , Animals , Bile Duct Neoplasms/pathology , Cats , Female
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