Aplastic anemia and paroxysmal nocturnal hemoglobinuria: search for a pathogenetic link

The association of paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia (AA) raises the yet unresolved questions as to whether these two disorders are different forms of the same disease. We compared two groups of patients with respect to cytogenetic features, glycosylphosphatidylinositol (GPI)-linked protein expression, protein C/protein S/thrombomodulin/antithrombin III activity, and PIG-A gene expression. The first group consisted of eight patients with PNH (defined as positive Ham and sucrose tests at diagnosis), and the second, 37 patients with AA. Twelve patients with AA later developed a PNH clone. Monoclonal antibodies used to study GPI-linked protein expression (CD14 [on monocytes], CD16 [on neutrophils], CD48 [on lymphocytes and monocytes], CD67 [on neutrophils and eosinophils], and, more recently, CD55, CD58, and CD59 [on erythrocytes]) were also tested on a cohort of 20 normal subjects and five patients with constitutional AA. Ham and sucrose tests were performed on the same day as flow- cytometric analysis. Six of 12 patients with AA, who secondarily developed a PNH clone, had clinical symptoms, while all eight patients with PNH had pancytopenia and/or thrombosis and/or hemolytic anemia. Cytogenetic features were normal in all but two patients. Proteins C and S, thrombomodulin, and antithrombin III levels were within the normal range in patients with PNH and in those with AA (with or without a PNH clone). In patients with PNH, CD16 and CD67 expression were deficient in 78% to 98% of the cells and CD14 in 76% to 100%. By comparison, a GPI-linked defect was detected in 13 patients with AA, affecting a mean of 32% and 33% of CD16/CD67 and CD14 cell populations, respectively. Two of three tested patients with PNH and 1 of 12 patients with AA had a defect in the CD48 lymphocyte population. In a follow-up study of our patient cohort, we used the GPI-linked molecules on granulocytes and monocytes investigated earlier and added the study of CD55, CD58, and CD59 on erythrocytes. Two patients with PNH and 14 with AA were studied for 6 to 13 months after the initial study. Among patients with AA, four in whom no GPI-anchoring defect was detected in the first study had no defect in follow-up studies of all blood-cell subsets (including erythrocytes). Analysis of granulocytes, monocytes, and erythrocytes was performed in 7 of 13 AA patients in whom affected monocytes and granulocytes were previously detected. A GPI-anchoring defect was detected on erythrocytes in five of six.(ABSTRACT TRUNCATED AT 400 WORDS)     

Living with severe osteoarthritis while awaiting hip and knee joint replacement surgery

Objectives: To explore the lived experiences of patients with severe osteoarthritis (OA) of the hip or knee joint while awaiting joint replacement surgery. Methods: An exploratory qualitative approach using phenomenology was adopted for the purpose of the study. Unstructured interviews were carried out on a sample of six patients who had been referred to the National Health Service waiting list for a primary hip or knee replacement. The participants were invited to share their experiences and concerns relating to how they were coping with end‐stage OA of their hip or knee joint. Interviews were digitally recorded and transcribed verbatim. Narrative data were analysed using Giorgi's (1985) procedural steps to reveal themes which recurred in the participants' stories. Results: Six themes emerged from the data, central to the experience of living with severe OA. They were: coping and living with pain; not being able to walk; coping with everyday activities; body image; advice and support available; and the effect of their disease upon family, friends and helpers. There were also a number of sub‐themes associated with each major theme. Conclusions: This study suggests that there is an absence of generic support, guidance and information relating to the management of symptoms of OA for individuals awaiting hip and knee replacement surgery. Patients awaiting hip and knee joint replacement surgery often have difficulty in managing their symptoms. Support in general appears to be dependent on the availability of resources in the primary care setting. Potential patients who are fortunate to know or meet someone who has undergone a similar procedure learn from the experience of exchanging information between themselves, along with coping strategies in the management of their symptoms. Copyright © 2008 John Wiley & Sons, Ltd.     

VASCULAR DIALYSIS ACCESS FLOW MEASUREMENT: EARLY INTERVENTION THROUGH EARLY DETECTION

Aim: The aim of the project is to determine the effectiveness of using online access flow measurement, thermodilution method (Fresenius BTM?), in detecting and predicting thrombosis or stenosis of the haemodialysis fistula, so that early intervention could be instituted. Methodology: All haemodialysis patients with permanent vascular dialysis access, either arteriovenous fistula (AVF) or arteriovenous fistula graft (AVG), in a large tertiary referral Dialysis Service in Australia were included in this prospective observational quality project, conducted over 12 months. Results: Out of 165 patients studied, 36 patients were found to have poor dialysis access flow, defined as AVF—flow of <200 ml/min or a decrease of 25% from last measurement or AVG—flow of <600 ml/min or a decrease of 25% from last measurement. Doppler ultrasounds were performed, and confirmed findings of significant stenosis, either on the arterial or venous sites, as indicated by poor dialysis access flow results. Conclusion: Thermodilution technique is a reliable and effective method of detecting poor dialysis access flow for patients with permanent vascular access, comparable with other techniques.     

One-Year Prospective Evaluation of the Early Loading of Unsplinted Conical Brånemark Fixtures with Mandibular Overdentures Immediately following Surgery

Background: Prospective evaluation of the early loading of unsplinted Branemark implants with mandibular over‐dentures opposing conventional dentures is not evident in the implant‐related literature. Purpose: To clinically evaluate progressive and early loading of 20 unsplinted conical Brånemark implants in edentulous mandibles with overdentures. Materials and Methods: Ten edentulous patients all had two conical Brånemark implants placed in the anterior mandible with mandatory primary stability with bicortical anchorage. Ball abutment connection was performed simultaneously. Previously constructed conventional mandibular dentures were temporarily relined with tissue conditioner postoperatively and worn with moderation for the first 2 weeks to allow progressive loading. Early loading of the implants followed after 2 weeks, with inclusion of the respective matrices in the mandibular dentures, using a definitive reline procedure. Results: All patients successfully functioned with their mandibular implant overdentures from 2 to 52 weeks postoperatively. Mean marginal bone loss was within established criteria for success:0.22 mm (SD = 0.48 mm) mesially and 0.30 mm (SD = 0.39 mm) distally on the conical implants. Mobility tests using the Periotest instrument became more negative, although not at statistically significant levels. Difficulties in the management of the peri‐implant mucosa between surgery and loading at 2 weeks were observed in 40% of the patients. Conclusions: These preliminary 1‐year results show that successful early loading of unsplinted conical Brånemark implants with mandibular overdentures is possible.     

A novel 37-Kd adhesive membrane protein from cloned murine bone marrow stromal cells and cloned murine hematopoietic progenitor cells

The adhesion of hematopoietic progenitor cells to bone marrow stromal cells is critical to hematopoiesis and involves multiple effector molecules. Stromal cell molecules that participate in this interaction were sought by analyzing the detergent-soluble membrane proteins of GBI/6 stromal cells that could be adsorbed by intact FDCP-1 progenitor cells. A single-chain protein from GBI/6 cells having an apparent molecular weight of 37 Kd was selectively adsorbed by FDCP-1 cells. This protein, designated p37, could be surface-radiolabeled and thus appeared to be exposed on the cell membrane. An apparently identical 37- Kd protein was expressed by three stromal cell lines, by Swiss 3T3 fibroblastic cells, and by FDCP-1 and FDCP-2 progenitor cells. p37 was selectively adsorbed from membrane lysates by a variety of murine hematopoietic cells, including erythrocytes, but not by human erythrocytes. Binding of p37 to cells was calcium-dependent, and was not affected by inhibitors of the hematopoietic homing receptor or the cell-binding or heparin-binding functions of fibronectin. It is proposed that p37 may be a novel adhesive molecule expressed on the surface of a variety of hematopoietic cells that could participate in both homotypic and heterotypic interactions of stromal and progenitor cells.     

Liver-derived fetal hematopoietic stem cells selectively and preferentially home to the fetal bone marrow

In the course of ontogeny, the homing site for the hematopoietic stem cells (HSC) moves with certain predictability from the yolk sac to the liver/spleen and then to the marrow. The pattern of this migration has thus far been established mostly on a morphologic basis. To delineate further the course of this migration and to gain insight into its possible mechanism, we used in utero transplantation of allogeneic or xenogeneic HSC in preimmune sheep fetuses. Sex chromosome, type of hemoglobin, and species-specific surface markers were used to follow the path of transplanted cells in the fetus. Before the development of the bone marrow, transplanted HSC (liver- or marrow-derived) homed exclusively to the liver/spleen. With the development of marrow, around day 60 of gestation (term, 145 days), homing occurred also in the nascent marrow and by day 80 transplanted cells homed exclusively to the marrow. This suggests that there may be a hierarchy in homing sites, with those of the marrow having higher affinity than those of liver/spleen. Interestingly, despite a change in homing that was followed by the expansion of the marrow compartment of HSC (ie, HSC proliferation), these cells did not participate actively in blood cell formation during most of the prenatal period. Liver remained the major hematopoietic organ throughout the gestation. It was only during the perinatal period that this organ assumed the function of hematopoiesis from the liver. This lack of expression of HSC in fetal marrow can possibly be attributable to the immaturity of marrow stroma required for differentiation and maturation of progenitors and the orderly egress of mature cells into the blood stream. The availability of this model allows us to begin studies in the molecular mechanism of stem cell homing in vivo during ontogeny.     

‘Levels’ of attainment in nursing practice: reality or illusion?

In earlier research based on an analysis of course documentation, it had been found that there was little consensus among nurse educators concerning the parameters which distinguish levels of practice skills, particularly those which differentiate diploma and degree qualifications in the United Kingdom. This result was confirmed and strengthened in the current study. Lecturers in nursing, when presented with a sorting task using 40 statements derived from course documentation selected from the earlier study, were unable to distinguish statements describing diploma level from those describing degree level practice. Possible reasons for the difficulty are discussed. It is concluded that the attempt to represent practice skill in a hierarchy of assessment for degree or diploma qualifications is premature since the parameters of practice remain unreliably specified.     

Students' expectations of postregistration degree programmes

The needs of postregistration students pursuing degree-linked clinical courses have received little attention and there are few insights concerning their aspirations when they enrol on such courses. Thus the aim of this study was to explore postregistration students' perceptions of the specific needs of their patient/client group and to examine how they envisaged the course on which they had just enrolled might help them to meet these needs in addition to their own requirements for professional and personal development. Data were collected by group interview from 62 students enrolling on eight different postregistration courses, all employed in an acute hospital trust. The results were analysed inductively. They indicated that students had internalized the state of the healthcare market and were keenly aware of the need to fulfil the expectations of employers and the public, while fulfilling their own needs for education and pursuing their own professional and career trajectories. They appeared ambitious and yet appeared to demonstrate empathy for patients and their families and felt a tremendous desire to provide care of a high quality through the optimal development of technical expertise. Students' emphasis on the importance of keeping abreast of technological developments should not be lightly dismissed considering its prominent position within the acute areas where they were employed, especially as it did not replace their desire to promote the caring aspects of their work.