Measurement of imatinib uptake by flow cytometry.

One of the essential parameters of targeted therapy efficiency in cancer treatment is the amount of drug reaching the therapeutic target area. Imatinib (IM) was the first specifically targeted drug to be developed and has revolutionized the treatment of patients with chronic myeloid leukemia (CML). To evaluate cellular uptake of IM, we developed a method based on the chemical structure of the molecule and using the natural UV fluorescence that we quantified by flow cytometry. In two CML cell lines, we obtained a satisfactory relationship between intracellular IM (ICIM) levels and media concentrations, and we found a strong correlation between ICIM at 1 h and IM efficacy at 24 h, demonstrating that ICIM at 1 h might be a relevant predictive parameter of cell sensitivity. Our method was more sensitive than the standard physicochemical method. We applied our method to primary cells and found cell morphology-dependent IM accumulation. Moreover, in CML cells from patients at diagnosis, IM accumulation was heterogeneous. In all cases, ICIM at the single-cell level was much higher than in culture media arguing in favor of a predominantly active uptake process. We developed a simple method directly applicable to primary cells that has shown two major advantages: only a small number of cells are required, and cell subsets can be identified according to morphological criteria and/or the presence of particular antigenic sites. This method provides a new tool to assess CML cell sensitivity to IM, and ICIM levels in native CML cells could be used to monitor therapeutic response.

Effects of imiglucerase treatment on traumatic fracture and bone and blood abnormalities in a patient with previously untreated type 1 gaucher disease.

OBJECTIVE: This letter reports on the effect of enzyme replacement therapy with imiglucerase on bone healing and bone and blood abnormalities in a woman with previously untreated type 1 Gaucher disease (GD). METHODS: The 49-year-old patient had been diagnosed with GD at the age of 28 years and had previously undergone splenectomy. She presented with pseudarthrosis 14 months after sustaining a traumatic fracture of the tibia and fibula. Therapy was begun with imiglucerase 60 U/kg q2wk. The effects of treatment on bone healing were monitored radiographically, and effects on blood and bone marrow biology were monitored by hemograms, myelograms, and hematopoietic and mesenchymal clonogenic assays. RESULTS: Objective bone healing was observed starting in the third month of imiglucerase treatment. Blood abnormalities normalized and bone marrow parameters improved over the first 9 months, including a decrease in Gaucher cells, an increase in bone marrow CD34+ cell cloning efficiency, and the appearance of mesenchymal progenitors. CONCLUSION: This research letter reports the results of hematologic and bone evaluations during enzyme replacement therapy with imiglucerase in a woman with previously untreated type 1 GD who presented with a traumatic fracture.

O transporte inter-hospitalar do doente crítico: documentação e continuidade de cuidados / The inter-hospital transport of the critically ill patient: documentation and continuity of care

O transporte inter-hospitalar do doente crítico é um procedimento frequente face à necessidade de meios complementares de diagnóstico e terapêutica com elevado nível de diferenciação. Embora represente um risco adicional para o doente, o planeamento adequado é fundamental para a diminuição da ocorrência de complicações. Partindo de uma experiência profissional enquanto enfermeira envolvida no processo de transporte inter-hospitalar do doente crítico e de uma avaliação e reflexão enquanto estudante de mestrado em estágio num serviço de urgência, decidiuse por estudar a documentação dos cuidados de enfermagem durante o transporte inter-hospitalar do doente crítico, como garantia da continuidade dos cuidados. Optou-se pela metodologia de projeto, partindo de um diagnóstico de situação realizado através de um questionário para identificação de incidentes/ocorrências clínicos e técnicos mais frequentes durante o processo de transporte. Participaram no projeto de intervenção em serviço 64 enfermeiros do Serviço de Urgência e da Unidade de Cuidados Intermédios Polivalente de um Hospital da Região Norte (N=64). Os dados obtidos foram sujeitos a análise descritiva, sendo posteriormente apresentados aos enfermeiros-chefes e à equipa de enfermagem. De forma genérica, pode dizer-se que os incidentes/ocorrências clínicos mais reportados foram o aumento/diminuição da tensão arterial, a alteração do traçado eletrocardiográfico e a diminuição da saturação periférica de oxigénio, destacando-se a trepidação, a limitação do espaço para aceder ao doente e aos equipamentos e o desconhecimento dos materiais e dos equipamentos de transporte como os incidentes/ocorrências técnicos mais frequentes. Com base nestes dados, foi elaborado um documento que permite ao enfermeiro, envolvido no transporte do doente crítico, documentar o processo de tomada de decisão e garantir a continuidade de cuidados. Salienta-se, ainda, que a criação de uma equipa de transporte especializada, meios de transporte mais adequados, bem como a necessidade de documentação e registos, de melhoria no planeamento e formação na área, foram sugestões apresentadas pelos enfermeiros como importantes e necessárias para a melhoria do transporte inter-hospitalar do doente crítico. A possibilidade de registo das intervenções de enfermagem, aliadas às sugestões que os enfermeiros apresentaram, podem ser um contributo para a melhoria dos cuidados de enfermagem prestados ao doente crítico durante o transporte inter-hospitalar.

The interhospital transportation of the critical patient is a frequent procedure due to the need for complementary diagnostic and therapeutic means with a high level of differentiation. Although it poses an additional risk to the patient, adequate planning is critical to reducing the occurrence of complications. Starting from a professional experience as a nurse involved in the interhospital transportation process of the critically ill patient and an evaluation and reflection as a master's student in an emergency department, it was decided to study the documentation of nursing care during interhospital transportation of the critical patient, as a guarantee of continuity of care. We chose the project methodology, based on a situation diagnosis performed through a questionnaire to identify the most frequent clinical and technical incidents/occurrences during the transportation process. Sixty-four nurses from the Emergency Department and the Polyvalent Intermediate Care Unit of a Hospital in the Northern Region (N=64) participated in the project. The data were subjected to descriptive analysis and later presented to the head nurses and the nursing team. Generally, the most reported clinical incidents/occurrences were increased/decreased blood pressure, altered electrocardiographic tracing and decreased peripheral oxygen saturation, especially the vibration, limiting the access space and equipment and the lack of knowledge of materials and transportation equipment such as the most frequent technical incidents/occurrences. Based on these data, a document was developed that allows the nurse, involved in the transportation of the critical patient, to document the decision-making process and ensure continuity of care. It should also be noted that the creation of a specialized transport team, more adequate means of transport, and the need for documentation and records to improve planning and training in the area were suggestions presented by nurses as important and necessary for the improvement interhospital transport of the critical patient. The possibility of registration of nursing interventions combined with the suggestions that the nurses presented may be a contribution to the improvement of the nursing care provided to the critical patient in the interhospital transport.