Mechanisms of T cell-induced glomerular injury in anti-glomeruler basement membrane (GBM) glomerulonephritis in rats

The effector mechanisms of T cell-dependent acute glomerular injury were studied in autologous phase anti-GBM glomerulonephritis (GN) in rats. Acute proliferative GN was induced in sensitized rats by a subnephritogenic dose of sheep anti-rat GBM antibody. Injury was manifested by proteinuria and glomerular leucocyte infiltration composed predominantly of macrophages but also CD4⁺ and CD8⁺ T cells. T cell depletion, using an anti-CD5 MoAb, demonstrated that glomerular leucocyte infiltration and proteinuria were T cell-dependent. Inhibition of T helper cell function using an anti-CD4 MoAb prevented proteinuria and glomerular macrophage and CD4⁺ T cell influx, but not accumulation of CD8⁺ T cells. Depletion of CD8⁺ T cells also prevented proteinuria and the influx of macrophages and CD8⁺ T cells, but not accumulation of CD4⁺ T cells. Macrophage depletion, using micro-encapsulated clodronate, prevented proteinuria and glomerular macrophage infiltration, but not the accumulation of CD4⁺ or CD8⁺ T cells, indicating that macrophages are the common cellular effectors for both CD4 and CD8 T cell-dependent injury. Evidence for cytotoxic mechanisms of injury (increased numbers of apoptotic cells or accumulation of natural killer (NK) cells in glomeruli) could not be demonstrated. These data suggest that acute glomerular injury in anti-GBM GN is the result of macrophage recruitment, which is dependent on both CD4 and CD8 T cells, and that direct T cell-mediated injury (cellular cytotoxicity) is not involved.     

Nursing home residents' perceptions of relocation

Summary

• ? The lived experience of relocating to a nursing home is explored from the perspective of 19 residents of Australian nursing homes.
• ? The interpretative research methodology is informed by hermeneutic phenomenology.
• ? In-depth interviews were conducted with 19 nursing home residents living in nursing homes in NSW. Interviews were audiotaped, transcribed and analysed to identify emergent themes.
• ? The themes are described and interpreted to provide an understanding of the relocation experience.

     

Stimulation of PAI-1 in rabbit anti-GBM glomerulonephritis

It has previously been shown in human disease and animal models of glomerulonephritis (GN) that fibrin deposition is associated with a net reduction of glomerular fibrinolytic activity as a result of reduced expression of plasminogen activators and increased expression of plasminogen activator inhibitor type 1 (PAI-1). Conditioned media (CM) prepared from cultured glomeruli of normal rabbits and rabbits 24 (Day 1) and 96 (Day 4) h after induction of anti-GBM GN were compared for their effects on the synthesis of fibrinolytic molecules in human endothelial cells (EC). Only CM from Day 4 GN rabbits showed PAI-1 protein stimulatory activity of up to 148% ( P <0.05; n =3) above that of untreated EC. This was also seen at the mRNA level. Glomerulonephritis Day 4 CM showed significantly higher amounts of tumour necrosis factor (TNF) and thrombin and transforming growth factor-β (TGF-β) bioactivity in comparison to glomerular CM from normal rabbits. After high performance liquid chromatography (HPLC) of Day 4 GN CM, PAI-1 stimulatory activity was found to correlate with the presence of interleukin 1 (IL-1), TNF and TGF-β. These results suggest a correlation between severity of anti-GBM GN in a rabbit model, increased PAI-1 synthesis and increased expression of TNF and TGF-β. This may potentiate glomerular fibrin and extracellular matrix deposition in anti-GBM GN, leading to glomerular crescent formation and eventual renal failure.     

Psychological and social recovery of children disfigured by physical trauma: elements of treatment supported by empirical data

Survivors of physically disfiguring trauma experience a series of assaults on the mind as well as on the body that present extraordinary challenges to human resilience. The 'trauma' for the survivor is complex. The injurious event itself is traumatic; additional traumas can also occur from painful and frightening medical treatments. The physical changes in the survivor's body are permanent reminders of the fear, horror, sadness and pain experienced. The reactions (real and imagined) of others to their disfigured bodies present survivors with the additional and ongoing trauma of feeling rejected, isolated, unworthy and humiliated.     

Review article: Luminex technology for HLA antibody detection in organ transplantation

Since its inception in the early 1960s, the serologically based complement-dependent cytotoxicity (CDC) assay has been the cornerstone technique for the detection of human leucocyte antigen (HLA) antibodies, not only in pre-transplant renal patients, but also in other forms of organ transplantation. Recently, solid phase assays have been developed and introduced for this purpose, and in particular the Flow-based bead assays such as the Luminex system. This latter assay has proved to be far more sensitive than the CDC assay and has revealed pre-sensitization in potential transplant recipients not detected by other methods of HLA antibody detection. However, the clinical implications of this increased sensitivity have not been convincingly demonstrated until recently. This technology for HLA antibody detection permits the evaluation of the clinical importance of antibodies directed at, for example, HLA-DPB1 and HLA-DQA1, which has not been possible to date. There are Luminex issues, however, requiring resolution such as the ability to distinguish between complement fixing and non-complement fixing antibodies and determination of their relative clinical significance. Luminex technology will permit a re-evaluation of the role of HLA antibodies in both early and late antibody-mediated rejection.     

Improved maintenance of remission in ulcerative colitis by balsalazide 4 g/day compared with 2 g/day

The efficacy of two doses of balsalazide for the maintenance of remission in patients with ulcerative colitis was compared in a double-blind multicentre trial. Sixty-five patients received a 2 g daily dose, and 68 a 4 g dose. The patient groups were similar at entry for sex, age, and disease distribution. Clinical assessment was carried out at 3-monthly intervals, with sigmoidoscopy, rectal biopsy, and blood tests on entry and at 26 and 52 weeks. Clinical relapse over twelve months was significantly less common on the 4 g dose (36%), than on the 2 g dose (55%), P less than 0.01. There were eight withdrawals on 2 g daily and 13 on 4 g daily, six and nine respectively being mainly due to gastrointestinal intolerance. It is concluded that balsalazide is a well-tolerated drug, and is effective for the maintenance of remission in patients with ulcerative colitis, the optimal dose being greater than 2 g daily.     

WEGENER'S GRANULOMATOSIS: CLINICAL FEATURES AND OUTCOME IN SEVENTEEN PATIENTS

Seventeen patients with Wegener's granulomatosis are reviewed. Eleven males and six females, with a mean age of 46.9± 4.5 years, were followed for 35.7 ± 9.0 months. Mean duration from time of onset of symptoms to diagnosis was 8.5 ±3.1 months. Constitutional symptoms (100%), lower respiratory tract involvement (93%), renal involvement (87%), and upper respiratory tract involvement (80%) were the most frequent clinical manifestations. Arthritis (60%), dermal vasculitis (60%), and inflammatory ocular disease (40%) were also common. Elevated ESR (94%), anemia (70%), and lymphopenia (77%) were frequent laboratory findings prior to treatment. Five patients had renal failure at presentation and two patients progressed from no renal involvement at presentation to renal failure at diagnosis, while five patients progressed from renal involvement without impairment at diagnosis to end-stage renal failure. Seven patients died; six of these deaths were related to active Wegener's granulomatosis. The patients with a severe systemic vasculitis, and renal involvement had a poor outcome while predominant respiratory disease had a good prognosis.     

"LONG-TERM" SURVIVAL IN LIGHT-CHAIN MYELOMA WITH DIALYSIS THERAPY ALONE

We report a case of a 59 year old woman who presented in end-stage renal failure with lambda (A) light-chain myeloma (LLCM). Despite a large tumour burden, and refusal to accept cytotoxic chemotherapy, she was commenced on continuous ambulatory peritoneal dialysis (CAPO). With dialysis therapy alone she has shown considerable hematological improvement and remains well 18 months after diagnosis. The extremely poor prognosis attributed to light-chain myeloma is largely due to death from uremia. As the natural history of this disease in patients offered dialysis therapy is unknown, dialysis should not automatically be withheld from patients with LLCM.