52 research outputs found
Clinical practice guidelines for the management of atypical haemolytic uraemic syndrome in the United Kingdom
No full textAtypical haemolytic uraemic syndrome (aHUS) is associated with a poor prognosis with regard to survival at presentation, recovery of renal function and transplantation. It is now established that aHUS is a disease of complement dysregulation with mutations in the genes encoding both complement regulators and activators, and autoantibodies against the complement regulator factor H. Identification of the underlying molecular abnormality in an individual patient can now help to guide their future management. In these guidelines we make recommendations for the investigation and management of aHUS patients both at presentation and in the long-term. We particularly address the role of renal transplantation alone and combined liver-kidney transplantation
Haemolytic Uraemic Syndrome
No full textAtypical haemolytic uraemic syndrome (aHUS) is a disease characterized by complement overactivation in which inherited defects in complement genes and acquired autoantibodies against complement regulatory proteins have been described. Identification of the underlying defect can both predict disease outcome and guide treatment. The ability to remove inhibitory autoantibodies and hyper-active complement components in addition to its ability to replace defective complement regulators means that plasma exchange is currently first-line therapy. In those with factor H and factor I mutations who do progress to end-stage renal failure, renal transplantation usually fails due to recurrent HUS. In this situation, combined liver-kidney transplantation has been suggested to correct the underlying genetic defect. Newer agents, such as the complement inhibitor eculizumab, may herald a new era in the treatment of aHUS.</jats:p
Distribution and determinants of circulating complement factor H concentration determined by a high-throughput immunonephelometric assay
No full textBACKGROUND:
Research on complement factor H (fH) in human disease is hampered by lack of an assay suitable for use in large-scale epidemiological studies. We describe the development and validation of a high throughput nephelometric assay for fH.
METHODS:
Reagents from a commercial radial immunodiffusion (RID) assay (The Binding Site) were adapted for use on the Siemens BNII high throughput nephelometric instrument. The assay was calibrated with a highly purified human fH preparation with rigorously determined concentration, and assay performance was comprehensively evaluated using samples from healthy human volunteers, with the commercial RID assay as a comparator. The distribution and determinants of circulating fH concentration in humans were then investigated in a large representative population sample.
RESULTS:
The nephelometric assay had recovery close to 100%, was reproducible with intra- and inter-assay CV's of 11% and 5-15% respectively, and had a wider operating range than the RID assay. fH values were unaffected after multiple freeze-thaw cycles demonstrating that it is evidently a stable analyte for immunoassay. fH concentration was unaltered by an acute inflammatory stimulus. The population study showed that plasma fH concentration is associated with circulating lipids and indices of body fat.
CONCLUSION:
We present the first high throughput assay for circulating fH; the assay is accurate and reliable with reproducible measures from stored samples. It has established the distribution of fH values at a population level and demonstrated important associations with circulating lipids and indices of body fat, thus providing an important reference for future clinical and epidemiological investigations
Atypical Hemolytic Uremic Syndrome
No full textHemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. The atypical form of HUS is a disease characterized by complement overactivation. Inherited defects in complement genes and acquired autoantibodies against complement regulatory proteins have been described. Incomplete penetrance of mutations in all predisposing genes is reported, suggesting that a precipitating event or trigger is required to unmask the complement regulatory deficiency. The underlying genetic defect predicts the prognosis both in native kidneys and after renal transplantation. The successful trials of the complement inhibitor eculizumab in the treatment of atypical HUS will revolutionize disease managemen
The instant expert: plastics, processing and properties
No full text"Plastics - they are everywhere." The first sentence of this book hints at the problem it seeks to address. The shear diversity of plastics materials has led to their use in products as varied as disposable packaging, life-saving medical devices, giant wind-turbine blades and tiny electronic components. Their prices and properties vary as widely, and they can be moulded, extruded, blown, formed, and shaped in many other ways. Traditionally made from petrochemicals, designers can now also choose from a range of natural materials. Performance will depend on chemical constitution, but also on the selection of processing aids and property modifiers which can be added to the basic material. For years, people have asked for a simple book to help them understand this complex subject. This is that book! Managers, sales personnel, industry newcomers, designers and end-users are all confronted with a bewildering range of technology and terminology by their colleagues, customers and suppliers. The Instant Expert: Plastics, Processing and Properties provides clear descriptions of the wide range of plastic materials, and explanations of the basic shaping and finishing processes. The author also talks about materials properties and testing, and provides some simple examples of why particular plastics are used in common or more challenging applications. Common abbreviations are explained. Readable from cover-to-cover, or easily referred to when questions arise, this book will be indispensible
Peak strain magnitudes and rates in the tibia exceed greatly those in the skull: An in vivo study in a human subject
No full textBone mass and architecture are the result of a genetically determined baseline structure, modified by the effect of internal hormonal/biochemical regulators and the effect of mechanical loading. Bone strain is thought to drive a feedback mechanism to regulate bone formation and resorption to maintain an optimal, but not excessive mass and organisation of material at each skeletal location. Because every site in the skeleton has different functions, we have measured bone strains induced by physiological and more unusual activities, at two different sites, the tibia and cranium of a young human male in vivo. During the most vigorous activities, tibial strains were shown to exceed 0.2%, when ground reaction exceeded 5 times body weight. However in the skull the highest strains recorded were during heading a heavy medicine/exercise ball where parietal strains were up to 0.0192%. Interestingly parietal strains during more physiological activities were much lower, often below 0.01%. Strains during biting were not dependent upon bite force, but could be induced by facial contortions of similar appearance without contact between the teeth. Rates of strain change in the two sites were also very different, where peak tibial strain rate exceeded rate in the parietal bone by more than 5 fold. These findings suggest that the skull and tibia are subject to quite different regulatory influences, as strains that would be normal in the human skull would be likely to lead to profound bone loss by disuse in the long bones
Atypical haemolytic uraemic syndrome
No full textThe haemolytic uraemic syndrome (HUS) is characterized by the triad of thrombocytopenia, microangiopathic haemolytic anaemia and acute renal failure. HUS may be classified as either diarrhoeal-associated or non-diarrhoeal/atypical (aHUS). aHUS has recently been shown to be a disease of complement dysregulation, with 50% of cases involving the complement regulatory genes, factor H (CFH), membrane cofactor protein (MCP; CD46), and factor I (IF). However, incomplete penetrance of mutations in each of these genes is reported. This suggests that a precipitating event or trigger is required to unmask the complement regulatory deficiency. The reported precipitating events predominantly cause endothelial injury. Discovery of these mutations has revealed important genotype-phenotype correlations. MCP-HUS has a better prognosis and a better outcome after transplantation than either CFH-HUS or IF-HUS. \ua9 The Author 2006
Plasma therapy in atypical haemolytic uremic syndrome: Lessons from a family with a factor H mutation
No full textWhilst randomised control trials are undoubtedly the best way to demonstrate whether plasma exchange or infusion alone is the best first-line treatment for patients with atypical haemolytic uremic syndrome (aHUS), individual case reports can provide valuable information. To that effect, we have had the unique opportunity to follow over a 10-year period three sisters with aHUS associated with a factor H mutation (CFH). Two of the sisters are monozygotic twins. A similar natural evolution and response to treatment would be expected for the three patients, as they all presented with the same at-risk polymorphisms for CFH and CD46 and no identifiable mutation in either CD46 or CFI. Our report of different modalities of treatment of the initial episode and of three transplantations and relapses in the transplant in two of them, strongly suggest that intensive plasma exchange, both acutely and prophylactically, can maintain the long-term function of both native kidneys and allografts. In our experience, the success of plasma therapy is dependent on the use of plasma exchange as opposed to plasma infusion alone, the prolongation of daily plasma exchange after normalisation of haematological parameters followed by prophylactic plasma exchange, the use of prophylactic plasma exchange prior to transplantation and the use of prophylactic plasma exchange at least once a week posttransplant with immediate intensification of treatment if there are any signs of recurrence. \ua9 The Author(s) 2008
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