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1.
Int Nurs Rev ; 67(3): 420-426, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32700371

RESUMO

BACKGROUND: Job satisfaction is important for increasing nurse retention rates. However, there is little research examining whether there is an association between nationality and job satisfaction among nurses. AIM: To examine whether there is an association between nationality and nurse job satisfaction. METHODS/DESIGN: A cross-sectional survey design was utilized, and 743 nurses from three major government hospitals in Saudi Arabia participated in the survey. Job satisfaction was measured using McCloskey/Mueller Satisfaction Scale. Data were collected between May 2014 and February 2015. RESULTS: Compared with Saudi nurses, expatriate nurses had overall lower job satisfaction after controlling for other predictors. While expatriates were less satisfied than Saudi nurses about extrinsic rewards and family-work balance, however, Saudi nurses were less satisfied than expatriate nurses about their professional opportunities, praise and recognition, and co-worker relationships. CONCLUSION: For some subscales, Saudi nurses were more satisfied than expatriate nurses, while for other subscales, the opposite was true. Nationality should be included in job satisfaction studies in countries with migrant workforces, as nationality-based differences may have been present but masked in earlier international studies by aggregating satisfaction across national groups. IMPLICATIONS FOR NURSING & HEALTH POLICY: Policy makers in Saudi Arabia and other countries with migrant nursing workforces should have effective induction programmes that help newly employed nurses - migrant and local - clearly understand their jobs, roles and responsibilities. Policy makers must have sufficient evidence to modify the reward system to ensure fairness and equality for all.


Assuntos
Diversidade Cultural , Etnicidade/psicologia , Satisfação no Emprego , Recursos Humanos de Enfermagem Hospitalar/psicologia , Adulto , Estudos Transversais , Etnicidade/estatística & dados numéricos , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricos , Arábia Saudita , Inquéritos e Questionários
2.
Ann Oncol ; 26(1): 185-192, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25361995

RESUMO

BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0 cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011). CONCLUSIONS: The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome. CLINICAL TRIAL NUMBERS: NCT00510926, NCT00514488, NCT00769327, NCT00481052.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Esplenomegalia/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Tirosina Quinases/antagonistas & inibidores , Baço/patologia , Adulto Jovem
3.
J R Army Med Corps ; 161 Suppl 1: i26-i33, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26419524

RESUMO

INTRODUCTION: Little empirical evidence exists to identify the impact that a partner's absence or presence has on the mother's decision-making and her consequential help-seeking behaviour when her child is unwell. METHODS: This study used a qualitative design in three phases using focus groups and interviews to explore Army mothers' help-seeking behaviour as a lone parent when their child was unwell during the out-of-hours period. Thirty-one parents from a British Army garrison were interviewed. RESULTS: The findings demonstrated that Army life created a combination of stressors for Army mothers, which altered their help-seeking behaviour when their child was unwell. When their partner was available, mothers contacted health services as a last resort, once all other avenues had been exhausted. However, in contrast, in their partners' absence, they were contacted as a first resort. CONCLUSION: An algorithm was generated from the findings, which illustrates the importance of ascertaining whether the mother is alone at the time of the consultation. Increased emotional vulnerability intensified the need for reassurance and affected a mother's decision-making ability. Primary healthcare staff should ascertain whether mothers are currently lone parents at an early stage of their assessment, as this may influence the entire consultation.


Assuntos
Tomada de Decisões , Militares/psicologia , Mães/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Pais Solteiros/psicologia , Estresse Psicológico/psicologia , Adaptação Psicológica , Adulto , Plantão Médico , Criança , Pré-Escolar , Feminino , Grupos Focais , Humanos , Lactente , Pesquisa Qualitativa , Reino Unido
4.
Vet Res Commun ; 48(3): 1941-1947, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38499909

RESUMO

The aim of this study was to molecularly investigate the presence of antimicrobial resistance genes (ARGs) in organ samples from 11 Apennine wolves (Canis lupus italicus) collected in Central Italy. Samples from lung, liver, spleen, kidney, tongue and intestine were investigated by PCRs targeting the following genes: tet(A), tet(B), tet(C), tet(D), tet(E), tet(G), tet(K), tet(L), tet(M), tet(O), tetA(P), tet(Q), tet(S), tet(X), sul1, sul2, sul3, blaCTX-M, blaSHV, blaTEM and mcr-1. A PCR positivity was highlighted for 13 out of the 21 tested genes; no positive results were obtained for tet(C), tet(D), tet(E), tet(G), sul3, blaCTX, blaSHV and mcr-1 genes. All 11 animals sampled showed positivity for one or more resistance genes. The results confirm the potential role of the wolf as an indicator and/or vector of antimicrobial-resistant bacteria or ARGs.


Assuntos
Lobos , Animais , Itália , Lobos/microbiologia , Lobos/genética , Farmacorresistência Bacteriana/genética , Antibacterianos/farmacologia , Animais Selvagens , Reação em Cadeia da Polimerase/veterinária , Genes Bacterianos
5.
Nat Genet ; 25(1): 14-5, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10802645

RESUMO

Haemochromatosis is a common recessive disorder characterized by progressive iron overload, which may lead to severe clinical complications. Most patients are homozygous for the C282Y mutation in HFE on 6p (refs 1-5). A locus for juvenile haemochromatosis (HFE2) maps to 1q (ref. 7). Here we report a new locus (HFE3) on 7q22 and show that a homozygous nonsense mutation in the gene encoding transferrin receptor-2 (TFR2) is found in people with haemochromatosis that maps to HFE3.


Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 7/genética , Hemocromatose/genética , Mutação/genética , Receptores da Transferrina/genética , Animais , Códon sem Sentido/genética , Feminino , Humanos , Masculino , Camundongos , Linhagem
6.
Vet Res Commun ; 47(4): 2351-2355, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37436553

RESUMO

In recent years an increasing interest has been focused on the contribution of wildlife in ecology and evolution of the antimicrobial resistance (AMR). The aim of this study was to molecularly investigate the presence of antimicrobial resistance genes (ARGs) in organ samples from a golden jackal (Canis aureus) found dead in the Marche region (Central Italy). Samples from lung, liver, spleen, kidney, and intestine were investigated by PCRs targeting the following genes: tet(A), tet(B), tet(C), tet(D), tet(E), tet(G), tet(K), tet(L), tet(M), tet(O), tet(S), tet(P), tet(Q), tet(X), sul1, sul2, sul3, blaCTX-M, blaSHV, blaTEM, and mcr-1 to mcr-10. One or more ARGs were detected in all organs tested, except the spleen. Specifically, the lung and liver were positive for tet(M) and tet(P), the kidney for mcr-1 and the intestine for tet(A), tet(L), tet(M), tet(O), tet(P), sul3 and blaTEM-1. These results, according to the opportunistic foraging strategy of the jackal, confirm its potential role as a good bioindicator of AMR environmental contamination.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Animais , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Chacais , Itália
7.
J Sports Med Phys Fitness ; 52(3): 229-36, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22648460

RESUMO

AIM: The aim of this study, based on the interaction between two aerobic and anaerobic metabolisms with a parallel production of both aerobic and anaerobic ATP, was to develop a high intensity training programme and increase the aerobic contribution. We examined the applicability of a 16-week training programme with an ergospirometer treadmill and field tests on eight water polo players. METHODS: Tests/retests of repeated exercises to 90V (90% of maximum personal speed over 100 m freestyle) and Speed Endurance Training (SET) after eight weeks were developed. A one-way blocked ANOVA with random blocks was used and each player represented a particular block with two before-after treatments with the aim of reducing error by subtracting both the variance due to the difference between the treatments and that due to the difference between the blocks. RESULTS: A reduction (15.2%) in blood lactate was observed in response to the same absolute workload (before-after). Furthermore the anaerobic contribution to VO2max (ESCAna, Estimated Anaerobic Contribution) after eight weeks of training at 90maxV and the anaerobic contribution to VO2max (ESCAna) after speed endurance training (SET) were very significant (P<0.004) with a reduction in the anaerobic contribution of 16%. The results of the field tests show that there was a very significant reduction (P<0.001) in lactate between 90maxV and maximal aerobic power velocity (MAPv) of 24%. CONCLUSION: With 90maxV and SET, space was gained towards those velocities, which had previously required a considerable anaerobic contribution. In this way match speed was increased.


Assuntos
Desempenho Atlético/fisiologia , Educação Física e Treinamento/métodos , Resistência Física/fisiologia , Esportes , Limiar Anaeróbio/fisiologia , Análise de Variância , Teste de Esforço , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Aptidão Física/fisiologia , Água , Adulto Jovem
8.
Clin Nutr ; 41(12): 3055-3060, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-34049750

RESUMO

BACKGROUND & AIMS: After prolonged hospitalization, the assessment of nutritional status and the identification of adequate nutritional support is of paramount importance. In this observational study, we aimed at assessing the presence of a malnutrition condition in SARS-Cov2 patients after the acute phase and the effects of a multidisciplinary rehabilitation program on nutritional and functional status. METHODS: We recruited 48 patients (26 males/22 females) admitted to our Rehabilitation Unit after discharge from acute Covid Hospitals in northern Italy with negative swab for SARS-Cov2. We used the Global Leadership Initiative on Malnutrition (GLIM) criteria to identify patients with different degrees of malnutrition. Patients underwent a 3 to 4-week individual multidisciplinary rehabilitation program consisting of nutritional intervention (energy intake 27to30 kcal/die/kg and protein intake 1-1.3 g/die/kg), exercise for total body conditioning and progressive aerobic exercise with cycle- and arm-ergometer (45 min, 5 days/week). At admission and discharge from our Rehabilitation Unit, body composition and phase angle (PhA) (BIA101 Akern), muscle strength (handgrip, HG) and physical performance (Timed-Up-and-Go, TUG) were assessed. RESULTS: At admission in all patients the mean weight loss, as compared to the habitual weight, was -12.1 (7.6)%, mean BMI was 25.9 (7.9) kg/m2, mean Appendicular Skeletal Muscle Index (ASMI) was 6.6 (1.7) kg/m2 for males and 5.4 (1.4) kg/m2 for females, mean phase angle was 2.9 (0.9)°, mean muscle strength (HG) was 21.1 (7.8) kg for males and 16.4 (5.9) kg for females, mean TUG value was 23.7 (19.2) s. Based on GLIM criteria 29 patients (60% of the total) showed a malnutrition condition. 7 out of those 29 patients (24%) presented a mild/moderate grade and 22 patients (76%) a severe grade. After a rehabilitation program of an average duration of 25 days (range 13-46) ASMI increased, with statistically significant differences only in females (p = 0.001) and HG improved only in males (p = 0.0014). In all of the patients, body weight did not change, CRP/albumin (p < 0.05) and TUG (p < 0.001) were reduced and PhA increased (p < 0.01). CONCLUSIONS: We diagnosed a malnutrition condition in 60% of our post SARS-Cov2 patients. An individualized nutritional intervention with adequate energy and protein intake combined with tailored aerobic and strengthening exercise improved nutritional and functional status.


Assuntos
COVID-19 , Desnutrição , Masculino , Feminino , Humanos , Estado Nutricional , RNA Viral , Força da Mão , SARS-CoV-2 , Desnutrição/diagnóstico , Desnutrição/etiologia
9.
J Exp Med ; 155(2): 623-8, 1982 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-6977012

RESUMO

An infrequent (2-3%) B lymphocyte subpopulation was found in the normal human tonsil and lymph nodes that shows the phenotypic characteristics of B-chronic lymphocytic leukemia (B-CLL) (rosette formation with mouse erythrocytes, weak expression of membrane Ig, staining for HLA-DR, and OKT1 or Leu-1 detecting a T cell-associated p65 antigen). Preliminary evidence suggests that at least a subpopulation of these cells is found, in small proportions, within the germinal centers. These cells were not observed in the human bone marrow. B-CLL may involve this peripheral B lymphocyte subset.


Assuntos
Linfócitos B/imunologia , Leucemia Linfoide/imunologia , Animais , Anticorpos Monoclonais/imunologia , Linfócitos B/classificação , Galinhas , Cabras , Humanos , Camundongos , Camundongos Endogâmicos , Fenótipo , Receptores de Antígenos de Linfócitos B/imunologia , Formação de Roseta
10.
Neotrop Entomol ; 49(2): 213-226, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31916201

RESUMO

Ground beetles (Coleoptera: Carabidae) are among the early colonisers of recently deglaciated terrains. While patterns of carabid colonisation along forelands of retreating glaciers have been thoroughly investigated in temperate climates, information remains scarce in tropical mountains. This study aimed to describe for the first time the carabid beetle species assemblages along the chronosequence of two tropical Andean glaciers (Antisana and Carihuairazo, Ecuador). Shannon index, taxonomic distinctness and species assemblage composition did not reveal deterministic and directional patterns. Only the principal coordinate analysis performed on the Antisana dataset showed that some species had a clear preference for terrains deglaciated for more than 200 years. Our results showed that equatorial glacier forelands are colonised by pioneer species that persist from the recently deglaciated terrains (less than 25 years) to terrains deglaciated since more than 200 years. This pattern fits the 'addition and persistence model' of high-latitude glacier forelands, rather than the 'species replacement model' of the Alps. The pioneer species observed are high-altitude specialists adapted to constantly cold environments, but not specifically ice-related. In the current context of climate warming, pioneer and cold-adapted species living near the glaciers of equatorial mountains are therefore only threatened by the 'summit trap' risk, unlike in temperate regions, as they are not strictly linked to the glacier microclimate.


Assuntos
Distribuição Animal , Besouros/classificação , Camada de Gelo , Animais , Clima , Equador
11.
Photodiagnosis Photodyn Ther ; 26: 284-286, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30991109

RESUMO

P. aeruginosa is a gram-negative bacterium present in nosocomial infections with high morbidity and mortality. This microorganism is frequently resistant to antibiotics, leading to clinical complications. In the present report, we described a clinical case of a patient with severe oral lesions caused by P. aeruginosa, which was refractory to antibiotics treatment and presented positive clinical outcomes after some sessions of antimicrobial photodynamic inactivation (API) mediated by methylene blue dye. We discuss the potential of API for P. aeruginosa refractory infections and possible resistance mechanisms of this microorganism to different API protocols.


Assuntos
Azul de Metileno/uso terapêutico , Doenças da Boca/tratamento farmacológico , Doenças da Boca/microbiologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Adulto , Anti-Infecciosos/uso terapêutico , Feminino , Humanos , Pseudomonas aeruginosa
13.
Bone Marrow Transplant ; 40(4): 349-54, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17589537

RESUMO

We assessed the outcome of 170 patients with AML in first complete remission, aged 1-47 years (median 29), who had undergone an allogeneic BMT before or after 1990 (n=80 and n=90, respectively); all patients were prepared with cyclophosphamide and TBI; the median follow-up for surviving patients was 13 years. The donor was an HLA-identical sibling in 164 patients. Transplant-related mortality (TRM) was 30% before and 7% after 1990 (P<0.001); relapse-related death (RRD) was 26 and 11% (P=0.002); and actuarial 10-year survival was 42 and 79% (P<0.00001). Patients transplanted after 1990 were older, had a shorter interval diagnosis-BMT, had less FAB-M3 cases, received a higher dose of TBI, a higher marrow cell dose and combined (cyclosporine+methotrexate) GVHD prophylaxis. Patients relapsing after transplant had an actuarial survival of 0 vs 31% if grafted before or after 1990 (P=0.01), and their median follow-up exceeds 10 years. In conclusion, the overall survival of first remission AML undergoing an allogeneic BMT has almost doubled in the past two decades, despite older age and fewer M3 cases. Improvement has come not only from changes in transplant procedures, but also from effective rescue of patients relapsing after transplant.


Assuntos
Transplante de Medula Óssea/métodos , Leucemia Mieloide Aguda/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Transplante de Medula Óssea/mortalidade , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/terapia , Humanos , Lactente , Itália/epidemiologia , Masculino , Recidiva Local de Neoplasia/terapia , Indução de Remissão/métodos , Risco , Análise de Sobrevida , Transplante Homólogo
14.
Biochem Pharmacol ; 144: 52-62, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28782526

RESUMO

Trabectedin and its analogue lurbinectedin are effective drugs used in the treatment of ovarian cancer. Since the presence of ascites is a frequent event in advanced ovarian cancer we asked the question whether ascites could modify the activity of these compounds against ovarian cancer cells. The cytotoxicity induced by trabectedin or lurbinectedin against A2780, OVCAR-5 cell lines or primary culture of human ovarian cancer cells was compared by performing treatment in regular medium or in ascites taken from either nude mice or ovarian cancer patients. Ascites completely abolished the activity of lurbinectedin at up to 10nM (in regular medium corresponds to the IC90), strongly reduced that of trabectedin, inhibited the cellular uptake of lurbinectedin and, to a lesser extent, that of trabectedin. Since α1-acid glycoprotein (AGP) is present in ascites at relatively high concentrations, we tested if the binding of the drugs to this protein could be responsible for the reduction of their activity. Adding AGP to the medium at concentration range of those found in ascites, we reproduced the anticytotoxic effect of ascites. Erythromycin partially restored the activity of the drugs, presumably by displacing them from AGP. Equilibrium dialysis experiments showed that both drugs bind AGP, but the affinity of binding of lurbinectedin was much greater than that of trabectedin. KD values are 8±1.7 and 87±14nM for lurbinectedin and trabectedin, respectively. The studies intimate the possibility that AGP present in ascites might reduce the activity of lurbinectedin and to a lesser extent of trabectedin against ovarian cancer cells present in ascites. AGP plasma levels could influence the distribution of these drugs and thus they should be monitored in patients receiving these compounds.


Assuntos
Ascite/metabolismo , Carbolinas/metabolismo , Dioxóis/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/metabolismo , Orosomucoide/metabolismo , Neoplasias Ovarianas/metabolismo , Tetra-Hidroisoquinolinas/metabolismo , Animais , Antineoplásicos Alquilantes/metabolismo , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Carbolinas/farmacologia , Carbolinas/uso terapêutico , Linhagem Celular Tumoral , Dioxóis/farmacologia , Dioxóis/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Camundongos , Camundongos Nus , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Ligação Proteica/fisiologia , Tetra-Hidroisoquinolinas/farmacologia , Tetra-Hidroisoquinolinas/uso terapêutico , Trabectedina , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
15.
Eur J Med Chem ; 41(9): 1025-40, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16737760

RESUMO

On the basis of the affinities at the alpha1a-, alpha1b- and alpha1d-adrenoceptors and the 5-HT1A receptor of a previous series of sixteen 2-[(2-phenoxyethyl)aminomethyl]-1,4-benzodioxanes ortho monosubstituted at the phenoxy moiety, a number of ortho disubstituted analogues were designed, synthesized in both the enantiomeric forms and tested in binding assays on the same receptors. The affinity values of the new compounds 1-11 were compared with those of the enantiomers of the 2,6-dimethoxyphenoxy analogue, the well-known alpha1 antagonist WB4101, and of the ortho monosubstituted derivatives, suggesting some distinctive aspects of the interaction of the phenoxy moiety, in particular with the alpha1a-AR and the 5-HT1A receptor, of the monosubstituted and the disubstituted compounds. A classical quantitative structure-activity relationship (Hansch) analysis was applied to the whole set of the S enantiomers of the ortho mono- and disubstituted WB4101 analogues (26 compounds), finding a very good correlation for the alpha1a affinity. For this latter, a significant parabolic relationship was also found with the volume of the two ortho substituents. Diametrically opposite, the same relationships for the 5-HT1A exhibit low or insignificant correlation coefficients.


Assuntos
Antagonistas Adrenérgicos/química , Antagonistas Adrenérgicos/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 1 , Dioxanos/antagonistas & inibidores , Dioxanos/farmacologia , Metilaminas/antagonistas & inibidores , Metilaminas/farmacologia , Relação Quantitativa Estrutura-Atividade , Animais , Células CHO , Cricetinae , Humanos , Estrutura Molecular , Estereoisomerismo
16.
J Exp Clin Cancer Res ; 25(3): 321-4, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17167971

RESUMO

We carried out sequential molecular monitoring of different markers on two BCR-ABL positive ALL patients receiving a standard dose induction regimen, which was followed by a maintenance therapy that alternated imatinib and chemotherapy administration. Molecular study was performed at diagnosis, at the end of the induction phase, and then every three months during maintenance therapy. Each marrow sample underwent BCR-ABL analysis (p210 and p190 expression by RT-PCR and Real-time PCR) and monoclonal JH rearrangement analysis, while WT1 gene expression was detected by Real-time PCR. At diagnosis we detected high WT1 expression associated with the presence of both BCR-ABL transcripts and monoclonal JH rearrangement in both patients. Hematological remission, as well as a molecular status characterized by undetectable BCR-ABL expression, normal levels of WT1 expression, and persistence of monoclonal JH rearrangement, were achieved by both patients post-therapy. Follow up of patient 1 showed a progressive increase in WT-1 and in p-190 transcript, which was followed by cytogenetic and hematological relapse. We observed a progressive increase in the p210 transcript without a concomitant increase in WT-1 levels in patient 2. JH rearrangement was detected in all the samples analyzed. The molecular results may indicate the persistence of JH rearranged clonal cells with undetectable BCR-ABL. From a clinical point of view, our preliminary experience suggests that simultaneous analysis of BCR-ABL, JH and WT-1 expression may improve the study of MRD in Ph+ ALL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas de Fusão bcr-abl/genética , Rearranjo Gênico/genética , Cadeias J de Imunoglobulina/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Proteínas WT1/genética , Idoso , Benzamidas , Monitoramento de Medicamentos , Feminino , Humanos , Mesilato de Imatinib , Proteínas Tirosina Quinases/antagonistas & inibidores , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
Cancer Res ; 50(14): 4291-4, 1990 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-1694719

RESUMO

Selective elimination of multidrug resistance-positive cells (LoVo/Dx) was obtained by using the monoclonal antibody MRK 16, which recognizes a surface epitope of the Mr 170,000 glycoprotein, and a sheep anti-mouse immunoglobulin antibody, conjugated to the ribosome-inactivating protein saporin 6. The killing was greatly decreased or even abolished by adding the monoclonal antibody at a 100-fold concentration. Both the MRK 16 and anti-mouse saporin 6 conjugate did not show any killing activity when they were used separately. In cell suspensions composed of 90% normal bone marrow cells and 10% multidrug resistance-positive cells, the monoclonal antibody MRK 16 followed by the anti-mouse immunotoxin caused the elimination of 99% multidrug resistance-positive cells, as revealed by immunofluorescence and immunocytochemistry as well as by a clonal assay. Human normal hematopoietic precursors (granulomonocytic colony-forming units, erythroid burst-forming units, and multipotent granulomonocytic, erythroid, and megakaryocytic-forming units) were not affected by the MRK 16 plus immunotoxin treatment. This technique might be suitable for ex vivo bone purging in an appropriate clinical setting, such as autologous bone marrow transplantation.


Assuntos
Anticorpos Monoclonais , Antineoplásicos Fitogênicos/farmacologia , Células da Medula Óssea , Resistência a Medicamentos , Imunotoxinas/farmacologia , Glicoproteínas de Membrana/imunologia , N-Glicosil Hidrolases , Proteínas de Plantas/farmacologia , Medula Óssea/efeitos dos fármacos , Linhagem Celular , Neoplasias do Colo , Ensaio de Unidades Formadoras de Colônias , Doxorrubicina/farmacologia , Epitopos/análise , Humanos , Peso Molecular , Proteínas Inativadoras de Ribossomos Tipo 1 , Saporinas , Células Tumorais Cultivadas/citologia , Células Tumorais Cultivadas/efeitos dos fármacos , Ensaio Tumoral de Célula-Tronco
19.
J Clin Oncol ; 13(4): 840-6, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7707109

RESUMO

PURPOSE: High-dose chemotherapy produces high complete remission (CR) rates and some survival advantage in patients with metastatic breast cancer (BC). A current issue is the possibility that these patients may have an even better prognosis with multiple high-dose treatments. In this study, we evaluated the feasibility of a four-step, high-dose sequential chemotherapy (HDSC) with double autologous hematopoietic progenitor-cell rescue. We also tested the hypothesis that peripheral-blood progenitor cells (PBPCs) harvested following a single recruitment with cyclophosphamide (CY) and granulocyte-macrophage colony-stimulating factor (GM-CSF) allow the safe administration of the whole HDSC with closely timed repeated courses of several non-cross-resistant agents. PATIENTS AND METHODS: The treatment plan included CY 7 g/m2, followed by GM-CSF 5 to 7 micrograms/kg/d administered by continuous intravenous (i.v.) infusion on days 2 to 14; PBPCs with or without bone marrow (BM) harvest; mitoxantrone (NOV) 60, 75, or 90 mg/m2 plus melphalan (L-PAM) 140 to 180 mg/m2 with hematopoietic rescue; methotrexate (MTX) 8 g/m2 plus vincristine (VCR) 1.4 mg/m2; and etoposide (VP-16) 1.5 g/m2 plus carboplatin (PP) 1.5 g/m2 with hematopoietic rescue. RESULTS: All 15 patients enrolled completed the entire treatment and there were no toxic deaths. Hematologic reconstitution was good at each step. The median number of days with an absolute neutrophil count (ANC) less than 100/microL and platelet count less than 20,000/microL were 8 and 3, respectively, after NOV plus L-PAM, and 7 and 4, respectively, after VP-16 plus PP. The main non-hematologic toxicity was mucositis, while organ toxicity was mild and reversible. CONCLUSION: This regimen is feasible, with acceptable toxicity. GM-CSF and PBPCs have a pivotal role, as they hasten hematologic reconstitution, abate toxicity, and allow rapid recycling.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/terapia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Estudos de Viabilidade , Feminino , Humanos , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Mitoxantrona/efeitos adversos , Metástase Neoplásica , Neutropenia/induzido quimicamente , Neutropenia/prevenção & controle , Indução de Remissão , Trombocitopenia/induzido quimicamente , Trombocitopenia/prevenção & controle , Vincristina/administração & dosagem , Vincristina/efeitos adversos
20.
J Clin Oncol ; 17(4): 1296, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10561192

RESUMO

PURPOSE: To compare the toxicity and effects on hematologic recovery and circulating progenitor cell mobilization of three cytokine regimens administered after high-dose cyclophosphamide (HD-CTX; 6 g/m(2)), given as the first step of a high-dose sequential chemotherapy. PATIENTS AND METHODS: Forty-eight patients with breast cancer or non-Hodgkin's lymphoma were randomized to receive granulocyte colony-stimulating factor (G-CSF) alone (arm 1), granulocyte-macrophage colony-stimulating factor (GM-CSF) alone (arm 2), or sequential interleukin-3 (IL-3) and GM-CSF (arm 3). Cytokines were administered as a single daily subcutaneous injection at a dose of 5 to 6 microg/kg/d. Progenitor cells were evaluated in peripheral blood as well as in apheretic product as both CD34(+) cells and granulocyte-macrophage colony-forming units (CFU-GM). RESULTS: Neutrophil recovery was faster in arm 1 as compared with arms 2 and 3 (P <.0001); no significant differences were observed between arms 2 and 3. In arm 3, a moderate acceleration of platelet recovery was observed, but it was statistically significant only as compared with arm 1 (P =.028). The peak of CD34(+) cells was hastened in a median of 2 days in arm 1 compared with arms 2 and 3 (P =.0002), whereas the median peak value of CD34(+) cells and CFU-GM was similar in the three patient groups. Administration of IL-3 and GM-CSF resulted in more significant toxicity requiring pharmacologic treatment in 90% of patients. CONCLUSION: The three cytokine regimens administered after HD-CTX are comparably effective in reducing hematologic toxicity and mobilizing the hematopoietic progenitor cells. G-CSF accelerates leukocyte recovery and progenitor mobilization. Although G-CSF-treated patients have somewhat slower platelet recovery, they definitely have fewer side effects.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Antineoplásicos Alquilantes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/sangue , Distribuição de Qui-Quadrado , Ciclofosfamida/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Humanos , Interleucina-3/administração & dosagem , Interleucina-3/efeitos adversos , Linfoma não Hodgkin/sangue , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Células-Tronco/efeitos dos fármacos , Resultado do Tratamento
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