How to involve hard to reach groups: a consumer-led project with lay carers of people with advanced HIV infection

The identification and provision of support to lay carers is crucial if Health Authorities are to meet the identified health care needs of their populations. This paper outlines in Part One the process for recruiting a defined but potentially hard to reach group, namely lay carers of people with advanced HIV infection, into a project designed as part of an ongoing development in HIV/AIDS education, the specific difficulties encountered, and how these were overcome. Part Two describes how to make a video, highlighting the involvement of carers in all stages of the research and development of a health education video-based resource package. Crucial to overcoming many of the difficulties and in winning the confidence and trust of the carers was the overview throughout of a committed multi-disciplinary Steering Group, the emphasis on confidentiality, the support of colleagues in the six UK centres, and the sensitivity and skills of the university research and production facilitators. This process ensured that the carers as consumers were involved in a continuing and active dialogue through the project.     

Evaluation of distance-weighted SPECT reconstruction for skeletal scintigraphy

In 15 patients who had undergone skeletal scintigraphy for evaluation of low back pain, single-photon emission computed tomography (SPECT) reconstruction techniques of distance-weighted filtered backprojection (new method) and non-distance-weighted filtered backprojection (standard method) were compared. Mid-spine sagittal views differing only by reconstruction methods were evaluated by trained observers and by a quantitative profile technique. When asked to compare image quality, the observers demonstrated a clear preference for images reconstructed by the new method. Profile quantitation showed significantly greater contrast in more superficial structures with the new method.     

Long-term interleukin-6 administration stimulates sustained thrombopoiesis and acute-phase protein synthesis in a small primate-- the marmoset

Interleukin-6 (IL-6) has been ascribed significant roles in both hematopoiesis and the immune response, although its contribution to host defence as a whole is poorly understood. Because short-term IL-6 treatment was previously shown to stimulate megakaryocytopoiesis, we investigated the effect of long-term administration of IL-6 on megakaryocytopoiesis and other systemic parameters in nonhuman primates. We chose a small primate, the marmoset (Callithrix jacchus), which enabled long-term administration at high doses. Recombinant human IL-6 (rhIL-6) administered at doses of up to 1,000 micrograms/kg/d over 4 and 9 weeks caused a sustained twofold to threefold increase of thrombocyte counts, peaking at 4 weeks. Thrombocyte counts declined thereafter, despite continuing IL-6 administration. The number of bone marrow megakaryocytes at 4 and 9 weeks was not increased compared with controls, but the ploidy grade was augmented, suggesting that IL-6 effects are restricted to mature megakaryocytes in vivo. An acute-phase protein response was observed within 24 hours after the first IL-6 administration and reached a maximum after 1 week of IL-6 administration at 25 micrograms/kg. Serum C-reactive protein, haptoglobin, and ceruloplasmin were increased, whereas albumin and transferrin levels declined. The acute-phase protein response was not associated with any morphologic evidence of hepatocellular damage. The increased levels of Ig and soluble IL-2 receptor in the serum levels reflected systemic immunostimulation. There was no evidence of renal mesangioproliferative pathology. Antibodies against rhIL-6 developed within 2 weeks, continuously increasing during the course of the study. High titers of neutralizing antibodies appeared concomitantly with the decrease in platelet counts and decline in acute-phase proteins. Therefore, despite the pleiotropic effects of IL-6 observed in vitro, long-term administration of IL-6 caused a selective and sustained stimulation of thrombopoiesis in marmosets that was only ablated by the appearance of neutralizing antibodies, and high doses were well tolerated in marmosets. A long-term targeting of IL-6 to cells of the megakaryocytic lineage, without evoking general toxicity, confirms the potential therapeutic usefulness of rhIL-6 for the chronic treatment of thrombocytopenic patients.     

The enhancement of siPLK1 penetration across BBB and its anti glioblastoma activity in vivo by magnet and transferrin co-modified nanoparticle

In order to enhance the penetration of small interference RNA against the polo-like kinase I (siPLK1) across BBB to treat glioblastoma (GBM), transferrin (Tf) modified magnetic nanoparticle (Tf-PEG-PLL/MNP@siPLK1) was prepared. The in vitro experiments indicated that Tf-PEG-PLL/MNP@siPLK1 enhanced the cellular uptake of siPLK1, which resulted in an increase of gene silencing effect and cytotoxicity of Tf-PEG-PLL/MNP@siPLK1 on U87 cells. Besides, Tf-PEG-PLL/MNP@siPLK1 significantly inhibited the growth of U87 glioblastoma spheroids and markedly increased the BBB penetration efficiency of siPLK1 with the application of external magnetic field in in-vitro BBB model. The in vivo experiments indicated that siPLK1 selectively accumulated in the brain tissue, and markedly reduced tumor volume and prolonged the survival time of GBM-bearing mice after Tf-PEG-PLL/MNP@siPLK1 was injected to GBM-bearing mice via tail vein. The above data indicated that magnet and transferrin co-modified nanoparticle enhanced siPLK1 penetration across BBB and increased its anti GBM activity in vivo.     

Desmoplastic Fibroblastoma: A Light and Ultrastructural Description of Two Cases

The authors report 2 cases of collagenous fibroma in which ultrastructural analysis revealed the presence of fibronexus junctions, markers of myofibroblastic differentiation, never described in this rare lesion before. The tumors occurred in the trapezius muscle and in the right arms of a 41-year-old and a 25-year-old man. They were both intramuscular and showed sharp edges. Grossly, the excised masses were whitish and firm. Microscopically, they were both composed of stellate or spindle-shaped cells separated by a collagenous hypovascular and focally myxoid stroma. Mitotic figures and necrotic areas were not identified. Immunohistochemistry showed positivity for vimentin and focal positivity for smooth and human muscle actin, and flow cytometry showed the tumoral cells to be diploid.     

Prevalence of Sarcopenia and Its Impact on Postoperative Outcome in Patients With Crohn's Disease Undergoing Bowel Resection

Background: Sarcopenia has been proposed to be a prognostic factor of outcomes for various diseases but has not been applied to Crohn's disease (CD). We aimed to assess the impact of sarcopenia on postoperative outcomes after bowel resection in patients with CD. Materials and Methods: Abdominal computed tomography images within 30 days before bowel resection in 114 patients with CD between May 2011 and March 2014 were assessed for sarcopenia as well as visceral fat areas and subcutaneous fat areas. The impact of sarcopenia on postoperative outcomes was evaluated using univariate and multivariate analyses. Results: Of 114 patients, 70 (61.4%) had sarcopenia. Patients with sarcopenia had a lower body mass index, lower preoperative levels of serum albumin, and more major complications (15.7% vs 2.3%, P = .027) compared with patients without sarcopenia. Moreover, predictors of major postoperative complications were sarcopenia (odds ratio [OR], 9.24; P = .04) and a decreased skeletal muscle index (1.11; P = .023). Preoperative enteral nutrition (OR, 0.13; P = .004) and preoperative serum albumin level >35 g/L (0.19; P = .017) were protective factors in multivariate analyses. Conclusion: The prevalence of sarcopenia is high in patients with CD requiring bowel resection. It significantly increases the risk of major postoperative complications and has clinical implications with respect to nutrition management before surgery for CD.