Patient narratives: the potential for "patient-centred" interprofessional learning?

The central theme of the paper is concerned with the educational potential that patient narratives may hold for improving patient-centred interprofessional care. It follows the processes of a research project that was required to provide an educational intervention in a multiprofessionally-staffed stroke rehabilitation ward. It discusses the evolution of the project, focusing on the ways in which patient narratives were constructed, the purposes they served, and the responses of professionals to the narratives in subsequent workshops. Along the way, the paper reflects on the responses of patients that problematise the notion of "patient-centred" care. Together with the responses of professionals to the narratives, the paper raises questions about the obstacles to and possibilities for such care.     

Chitotriosidase activity in pleural effusions

Chitotriosidase (ChT) is mainly secreted by monocyte-derived macrophages, and is considered a useful marker of macrophage activation. Macrophages represent the first line of defence against Mycobacterium tuberculosis, and consequently the study of ChT activity in pleural effusions (PE) would be of clinical value in the laboratory characterization of tuberculous pleurisy. ChT and adenosine deaminase (ADA) activities were determined in 12 tuberculous PE, 26 non-tuberculous lymphocytic PE and 25 neutrophilic PE. The enzyme heterogeneity study for ChT was made by thermal inactivation at 60 degrees C according to Wajner et al. (Clin Biochem 2004;37:893). ChT activity was significantly higher in the group of tuberculous PE than in the non-tuberculous lymphocytic PE group (p < 0.01), although no significant difference was found with respect to neutrophilic PE. The correlation between ChT and ADA was statistically significant, although in the partial correlation keeping the protein concentration constant, statistical significance was only achieved in tuberculous and non-tuberculous lymphocytic PE (r = 0.358, p < 0.05). In lymphocytic PE, a ChT activity greater than 40 mmol/h/mL has a sensitivity of 92%, specificity of 72%, and efficiency of 78% for the biochemical characterization of tuberculous pleurisy. Residual activities obtained for ChT by heat inactivation did not make it possible to differentiate the enzyme isoforms in PE presumably secreted by macrophages and polymorphonuclear leukocytes.     

Inflammatory clearance of apoptotic cells after UVB challenge

In the human body, every day billions of apoptotic cells are produced. Removal of these cells is necessary, to prevent the release of intracellular toxic constituents, and occurs very effectively via phagocytosis by (semi)-professional phagocytes. This elimination process occurs rapidly and without inflammation. In systemic lupus erythematosus (SLE) a disturbed elimination of apoptotic cells has been implicated in the induction and reactivation of the disease. Accumulation of apoptotic cells may result in autoantibody formation. A delayed, pro-inflammatory clearance is also thought to play a crucial role in the development of inflammatory lesions once the disease has manifested. One of the hallmarks of patients with SLE is the development of cutaneous lesions upon exposure to sunlight. In this review, we will focus on apoptotic cells, their elimination, and the consequences of a disturbed elimination of apoptotic cells on the development of UVB induced inflammatory skin lesions.     

Bruton's tyrosine kinase and phospholipase Cgamma2 mediate chemokine-controlled B cell migration and homing

Control of integrin-mediated adhesion and migration by chemokines plays a critical role in B cell development, differentiation, and function; however, the underlying signaling mechanisms are poorly defined. Here we show that the chemokine SDF-1 induced activation of Bruton's tyrosine kinase (Btk) and that integrin-mediated adhesion and migration in response to SDF-1 or CXCL13, as well as in vivo homing to lymphoid organs, was impaired in Btk-deficient (pre-)B cells. Furthermore, SDF-1 induced tyrosine phosphorylation of Phospholipase Cgamma2 (PLCgamma2), which, unlike activation of the migration regulatory GTPases Rac or Rap1, was mediated by Btk. PLCgamma2-deficient B cells also exhibited impaired SDF-1-controlled migration. These results reveal that Btk and PLCgamma2 mediate chemokine-controlled migration, thereby providing insights into the control of B cell homeostasis, trafficking, and function, as well as into the pathogenesis of the immunodeficiency disease X-linked agammaglobulinemia (XLA).     

Prolonged hypoxia concomitant with serum deprivation induces massive human mesenchymal stem cell death

Mesenchymal stem cells (MSCs) have been proposed for the repair of damaged tissue including bone, cartilage, and heart tissue. Upon in vivo transplantation, the MSCs encounter an ischemic microenvironment characterized by reduced oxygen (O2) tension and nutrient deprivation that may jeopardize viability of the tissue construct. The aim of this study was to assess the effects of serum deprivation and hypoxia on the MSC survival rates in vitro. As expanded MSCs are transferred from plastic to a scaffold in most tissue engineering approaches, possibly inducing loss of survival signals from matrix attachments, the effects of a scaffold shift on the MSC survival rates were also assessed. Human MSCs were exposed for 48 hours to (i) a scaffold substrate shift, (ii) serum deprivation, and (iii) O2 deprivation. MSCs were also exposed to prolonged (up to 120 hours) hypoxia associated with serum deprivation. Cell death was assessed by Live/Dead staining and image analysis. The MSC death rates were not affected by the shift to scaffold or 48-hour hypoxia, but increased with fetal bovine serum (FBS) starvation, suggesting that between the two components of ischemia, nutrient deprivation is the stronger factor. Long-term hypoxia combined with serum deprivation resulted in the complete death of MSCs (99 +/- 1%), but this rate was reduced by half when MSCs were exposed to hypoxia in the presence of 10% FBS (51 +/- 31%). These results show that MSCs are sensitive to the concurrent serum and O2 deprivation to which they are exposed when transplanted in vivo, and call for the development of new transplantation methods.     

High-resolution copy number analysis of paraffin-embedded archival tissue using SNP BeadArrays

High-density SNP microarrays provide insight into the genomic events that occur in diseases like cancer through their capability to measure both LOH and genomic copy numbers. Where currently available methods are restricted to the use of fresh frozen tissue, we now describe the design and validation of copy number measurements using the Illumina BeadArray platform and the application of this technique to formalin-fixed, paraffin-embedded (FFPE) tissue. In fresh frozen tissue from a set of colorectal tumors with numerous chromosomal aberrations, our method measures copy number patterns that are comparable to values from established platforms, like Affymetrix GeneChip and BAC array-CGH. Moreover, paired comparisons of fresh frozen and FFPE tissues showed nearly identical patterns of genomic change. We conclude that this method enables the use of paraffin-embedded material for research into both LOH and numerical chromosomal abnormalities. These findings make the large pathological archives available for genomic analysis, which could be especially relevant for hereditary disease where fresh material from affected relatives is rarely available.     

Estimating HIV incidence in voluntary counseling and testing clients in Uganda (1992-2003)

OBJECTIVES: To estimate HIV incidence from first-time testers among voluntary counseling and testing (VCT) clients in Uganda. METHODS: Data on 203,000 VCT clients tested from 1992 through 2003 were adjusted for temporal changes in the testing population. Differential mortality rates by HIV status were used to derive expected prevalence at future times from baseline prevalence within 5-year birth cohorts. Incidence was computed as the proportion of HIV-uninfected persons who seroconverted divided by the proportion negative at baseline. RESULTS: Annual HIV incidence per 100 uninfected persons increased from 0.9 (95% confidence interval [CI]: 0.8 to 1.1) in 1993 to 2.3 (95% CI: 2.2 to 2.5) in 2003 (chi test for trend, P < 0.001). Prevalence decreased from 23% to 13% in 1999 to 2000 and increased to 15% in 2003. Women had a higher incidence. Peak incidence shifted to older age groups over time. CONCLUSIONS: Estimating incidence from routine data presents a practical way of tracking HIV incidence and is a useful tool in targeting and evaluating the impact of prevention programs. Our analysis reveals a new phase of the HIV epidemic in Uganda: decreasing prevalence and increasing incidence, especially among middle-aged persons. These findings support the need for intensified prevention interventions among middle-aged persons in Uganda.     

A novel missense mutation in the NDP gene in a child with Norrie disease and severe neurological involvement including infantile spasms

Norrie disease (ND) is a rare X-linked recessive disorder characterized by congenital blindness and in some cases, mental retardation and deafness. Other neurological complications, particularly epilepsy, are rare. We report on a novel mutation identified in a patient with ND and profound mental retardation. The patient was diagnosed at the age of 6 months due to congenital blindness. At the age of 8 months he developed infantile spasms, which were diagnosed at 11 months as his EEG demonstrated hypsarrhythmia. Mutation analysis of the ND gene (NDP) of the affected child and his mother revealed a novel missense mutation at position c.134T > A resulting in amino acid change at codon V45E. To the best of our knowledge, such severe neurological involvement has not been previously reported in ND patients. The severity of the phenotype may suggest the functional importance of this site of the NDP gene.