Differential diagnosis of suspected multiple sclerosis: a consensus approach

BACKGROUND AND OBJECTIVES: Diagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis. METHODS: Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases. RESULTS: We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of "clinically isolated syndromes" (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system. CONCLUSIONS: Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision

Cell filtration-laser scanning cytometry for the characterisation of circulating breast cancer cells.

Background Epithelial cells may be detected in the circulation of the majority of patients with metastatic breast cancer. Quantification of such presumptive cancer cells might allow for the monitoring of patients with early or late stage disease as an early index of relapse. Additionally, biomarker analysis may allow a more rational approach to therapeutics. We have developed a new method for the detection and characterisation of these cells.Methods Blood was filtered through polycarbonate membranes containing cylindrical pores, 8 microm in diameter. All the red cells and a large majority of the white blood cells passed through the filter while the larger epithelial cells were trapped. Cells on the membrane were fixed in ethanol, stained with propidium iodide and anti-pan-cytokeratin-FITC (to identify epithelial cells). The filters were then examined by laser scanning cytometry (LSC), which allowed enumeration and localisation of cells.Results With normal blood spiked with cells from breast carcinoma cell lines, 99.9% of the leukocytes passed through the membrane, while close to 100% of the epithelial cells were trapped, with a detection limit of less than one epithelial cell/ml of blood. All of 20 samples from patients with widespread metastatic disease contained cytokeratin-positive cells with the morphological characteristics of carcinoma cells, the number of cells ranging from 0.2 to 5.7/ml of blood.Conclusions Cell filtration-LSC is a viable technique for detecting and studying breast carcinoma cells in peripheral blood

The transformation competence perspective

Reflections on a number of participative projects have led to the conclusion that, when planning and conducting OR interventions, particular attention should be paid to the transformation to be attempted and to the competence of those who will be involved. The transformation required by a consulting project sets the scope of the ambition that is to be met by the craft skills and expertise of people, supported if appropriate by pre-defined methods. Competence refers to the skills, time and the ability to act of those involved in the intervention. In designing an intervention, activities have to be planned in the light of the transformation required, the competences of those involved and the pre-defined methods available. Pre-defined methods are characterized in terms of their transformation potential, the transformation that can be achieved by using the method in a specific context. The paper elaborates the proposed transformation competence perspective drawing on personal practical experience; its aim is to articulate an approach to the design of participative consulting interventions and compare it with alternatives