RESUMEN
We report the chromosomal findings in a 4-year-old female with precursor B-cell acute lymphoblastic leukemia (ALL). The diagnostic karyotype showed an isochromosome 7q, i(7)(q10), as well as questionable rearrangements on 9p and 11q. Fluorescence in situ hybridization (FISH) studies on both interphase and metaphase cells using the MLL "break-apart" and the centromeric chromosome 4 probes were instrumental in the characterization of an MLL gene rearrangement, which was cryptic by conventional cytogenetic analysis. Specifically, the FISH pattern was consistent with an insertion of the 5' region of the MLL gene into chromosome 4 at band q21, most likely a variant t(4;11)(q21;q23). This is the second case of FISH detection of an ins(4;11) in ALL. Our case exemplifies the importance of FISH in the further characterization of precursor B-cell ALL cases without any apparent prognostically significant chromosomal abnormalities.
Asunto(s)
Linfoma de Burkitt/genética , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 4 , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocación Genética , Linfoma de Burkitt/patología , Preescolar , Bandeo Cromosómico , Femenino , N-Metiltransferasa de Histona-Lisina , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Mutagénesis Insercional , Proteína de la Leucemia Mieloide-Linfoide/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologíaRESUMEN
Sodium phenylbutyrate (PB) is an aromatic fatty acid with cytostatic and differentiating activity against malignant myeloid cells (ID(50), 1-2 mM). Higher doses induce apoptosis. Patients with myelodysplasia (n = 11) and acute myeloid leukemia (n = 16) were treated with PB as a 7-day continuous infusion repeated every 28 days in a Phase I dose escalation study. The maximum tolerated dose was 375 mg/kg/day; higher doses led to dose-limiting reversible neurocortical toxicity. At the maximum tolerated dose, PB was extremely well tolerated, with no significant toxicities; median steady-state plasma concentration at this dose was 0.29 +/- 0.16 mM. Although no patients achieved complete or partial remission, four patients achieved hematological improvement (neutrophils in three, platelet transfusion-independence in one). Other patients developed transient increases in neutrophils or platelets and decrements in circulating blasts. Monitoring of the percentage of clonal cells using centromere fluorescence in situ hybridization over the course of PB administration showed that hematopoiesis remained clonal. Hematological response was often associated with increases in both colony-forming units-granulocyte-macrophage and leukemic colony-forming units. PB administration was also associated with increases in fetal erythrocytes. These data document the safety of continuous infusion PB and provide preliminary evidence of clinical activity in patients with myeloid malignancies.
Asunto(s)
Leucemia Mieloide/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológico , Fenilbutiratos/uso terapéutico , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Alopecia/inducido químicamente , Antígenos CD34/análisis , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Células Clonales , Diarrea/inducido químicamente , Relación Dosis-Respuesta a Droga , Hemoglobina Fetal/efectos de los fármacos , Hemoglobina Fetal/metabolismo , Citometría de Flujo , Hemorragia/inducido químicamente , Humanos , Persona de Mediana Edad , Mucosa Bucal/efectos de los fármacos , Mucosa Bucal/patología , Síndromes Mielodisplásicos/inmunología , Náusea/inducido químicamente , Fenilbutiratos/efectos adversos , Fenilbutiratos/farmacocinética , Estomatitis/inducido químicamente , Resultado del Tratamiento , Vómitos/inducido químicamenteRESUMEN
AIM: The purpose of this paper is to present a concept analysis of intentional action. BACKGROUND: Intentional action is a relevant concept for nurses because health behaviour involves action by the client of care. In addition, nurses take action when they assist their clients. Intentional action is a type of action distinguished by the presence of specific developmental skills and by intent or purpose. DESIGN: This concept analysis reflects a comprehensive review of the action literature. FINDINGS: This review revealed two views of intentional action: as social behaviour and as self-regulated behaviour influenced by external and internal factors. Based on these findings, the antecedents and consequences of this type of action are identified and the process of action is described. CONCLUSIONS: The concept model illustrates the relationship of intentional action with external and internal factors and demonstrates its continuous nature. Areas for further inquiry include exploration of the effect of factors such as self-efficacy, motivation, self-esteem, managed care and reduced health care resources on intention and subsequent action; as well as the efficacy of nursing interventions designed to influence health behaviour such as health promotion education and treatment counselling.
Asunto(s)
Actitud del Personal de Salud , Modelos de Enfermería , Motivación , Relaciones Enfermero-Paciente , Atención de Enfermería/psicología , Proceso de Enfermería , Teoría de Enfermería , Consejo , Objetivos , Conductas Relacionadas con la Salud , Humanos , Control Interno-Externo , Atención de Enfermería/métodos , Investigación en Evaluación de Enfermería , Planificación de Atención al Paciente , Educación del Paciente como Asunto , Competencia Profesional/normas , Autoeficacia , Conducta SocialRESUMEN
As the 21st century approaches, one very important issue for nursing is the increased prevalence of chronic conditions such as arthritis. Self-management is one way that individuals can cope with the uncertainty and many changes chronic illness brings. The purpose of this article is to describe a nursing model that addresses the need for enhanced self-management skills and the rehabilitation nurse's role in this process. The model is based on the concept of intentional action and uses Orem's (1995) self-care deficit nursing theory as its conceptual structure. The expected outcomes of care for clients are effective self-management skills and subsequently improved health status and quality of life. The model will be useful in the design of rehabilitation nursing research as well as in the planning of care for individuals with chronic illness.
Asunto(s)
Enfermedad Crónica/enfermería , Enfermedad Crónica/rehabilitación , Modelos de Enfermería , Enfermería en Rehabilitación/métodos , Actividades Cotidianas , Adaptación Psicológica , Adulto , Enfermedad Crónica/psicología , Femenino , Promoción de la Salud/métodos , Humanos , Esclerosis Múltiple/enfermería , Esclerosis Múltiple/psicología , Esclerosis Múltiple/rehabilitación , Investigación en Enfermería , Teoría de Enfermería , Planificación de Atención al Paciente , AutocuidadoRESUMEN
To further evaluate the activity of topotecan (TPT) in acute leukemia, TPT was administered (2.1 mg/m2/day for 5 days by continuous i.v. infusion) to adult patients with previously untreated acute lymphoblastic leukemia (ALL) with high-risk features (13 patients) or relapsed ALL (1 patient). Patients achieving a partial response or significant hematological improvement received a second course. All patients subsequently received standard treatment for ALL. Because complete response was achieved in only 1 of 14 patients, the study was terminated prematurely. An additional patient achieved minimal response, and a third patient normalized her hemogram despite ongoing leukemia in the marrow. Overall, six patients had significant hematological improvement (normalization of platelet and/or absolute neutrophil count). Two patients expired due to infections during induction chemotherapy. The primary nonhematological toxicities were mucositis and diarrhea. Exposure to TPT did not appear to influence the response to subsequent standard chemotherapy. The mean steady-state TPT plasma concentration, 16.1+/-1 nM, overlapped the range of LD90 values of primary human leukemia specimens. Cellular topo I content varied over a 3-fold range, encompassing levels found previously in relapsed patients. No relationship was found between topo I expression and markers of cellular proliferation or response to therapy. In contrast, low expression of the apoptosis inhibitor Bcl-2 was associated with response to TPT therapy. TPT has significant, albeit modest, single-agent activity against high-risk adult ALL. This study demonstrates the feasibility of evaluating promising new therapeutic agents in untreated patients with acute leukemia at high risk for failure with conventional therapy.
Asunto(s)
Antineoplásicos/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Topotecan/uso terapéutico , Adulto , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , ADN-Topoisomerasas de Tipo I/metabolismo , Femenino , Humanos , Recuento de Leucocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Factores de Riesgo , Inhibidores de Topoisomerasa I , Topotecan/efectos adversos , Topotecan/farmacocinética , Resultado del TratamientoRESUMEN
PURPOSE: The premise for this study was that topotecan (TPT) resistance in preclinical studies is associated with low level expression of the p-glycoprotein (Pgp) multi-drug transporter conferred by the multi-drug resistant (MDR) phenotype, which might be overcome in clinical practice by administering moderately (2.3-fold) higher doses of TPT that have shown to be feasible with granulocyte colony-stimulating factor (G-CSF) support. This phase II study evaluated the anti-tumor activity of TPT administered at its highest possible solid tumor dose with G-SCF in patients with fluoropyrimidine-refractory advanced colorectal carcinoma. The study also sought to identify pharmacodynamic (PD) determinants of both activity and toxicity. PATIENTS AND METHODS: TPT was administered as a 30-minute infusion daily for five days every three weeks at a dose of 3.5 mg/m2/day to patients with advance colorectal carcinoma who developed progressive disease either during treatment with fluoropyrimidine-based chemotherapy for advanced disease or within six months after receiving fluoropyrimidine-based adjuvant chemotherapy. This dose of TPT was previously determined to be the maximal tolerated dose (MTD) with G-CSF support in a phase I study involving solid tumor patients with similar risk factors for myelosuppression. Plasma sampling with performed during course 1 to characterize the pharmacokinetic (PK) and PD behavior of TPT. RESULTS: Seventeen patients who received 89 courses of TPT and G-CSF were evaluable for toxicity; 16 patients were evaluable for anti-tumor response. Toxicity, particularly myelosuppression, was substantial. At the 3.5 mg/m2/day dose level, absolute neutrophil counts (ANC) were less than 500/microliters for longer than 5 days in 17% of courses involving seven of seventeen (41%) patients. Severe neutropenia associated with fever occurred in 12.3% of courses; and platelet counts below 25,000/microliters were noted in 26.9% of courses. These toxicities resulted in dose reductions in seven of 17 (41%) patients. Nevertheless, 90% of the planned total dose of TPT was administered. No major responses were observed, though minor activity was noted in several patients. Both the median time to progression and the median survival time were short--2.5 and 4 months respectively. Although interindividual variability in the disposition of total TPT was observed, the lack of objective responses precluded PD assessments related to disease activity. Total TPT exposure was significantly higher than drug exposure achieved in similar patients at an identical dose in a previous phase I study of TPT and G-CSF, which may explain why more severe myelosuppressive effects occurred in the present study. There were no PD relationships evident between relevant PK parameters and the percent decrements in platelets and ANC's during course 1, although patients with severe toxic effects (ANC below 500/microliters for more than five days and/or platelets < 25,000/microliters) had higher drug exposure than patients with less severe toxicity (P < 0.018 and P = 0.09, respectively). CONCLUSIONS: Based on these results, the true response rate of TPT at its solid tumor MTD with G-CSF support is unlikely to approach 20%. Although a response rate of less than 20% might be viewed as significant in this disease setting and might be confirmed with sufficient statistical certainty by treating additional patients, the substantial toxicity, inconvenience, and cost associated with this high dose TPT/G-CSF regimen does not warrant the acceptance of a lower level of anti-tumor activity as a criterion for further development.