1,721,201 research outputs found
AA amyloidosis without systemic inflammation: when clinical evidence validates predictions of experimental medicine
No full textAmyloid A (AA) amyloidosis is a well-known consequence of chronic inflammatory diseases in which elevated plasma concentrations of serum amyloid A result in amyloid aggregation and organ damage. In this issue, Sikora et al. report, for the first time, an inherited form of AA amyloidosis occurring in the absence of systemic inflammation. This finding may provide novel insights into the pathogenesis of AA amyloidosis, allowing researchers to further dissect the role of inflammation from that of serum amyloid A
Seek and You Shall Find: Is Subclinical Amyloid More Common Than Expected?
No full texthttps://www.ncbi.nlm.nih.gov/pubmed/3039254
Expanding the spectrum of systemic amyloid diseases: a new hint from the kidney
No full texthttps://www.ncbi.nlm.nih.gov/pubmed/2752111
Hereditary amyloidosis
No full textOur experience with 465 patients with sporadic, biopsy-proven, systemic amyloidosis indicates that immunoelectron-microscopical typing of amyloid deposits improves diagnostic accuracy and optimizes DNA analysis.3
The diagnosis of AL amyloidosis must not be presumed, and no patient should receive chemotherapy for a monoclonal disorder if the diagnosis has not been verified.4 Monoclonality was documented by high-resolution immunofixation5 in 96 percent of 446 patients who ultimately received a diagnosis of primary amyloidosis and by immunoelectron microscopy in the remaining 4 percent.
Since the presence of a monoclonal protein supports, but does not prove, the diagnosis of AL amyloidosis, we used immunoelectron microscopy to type the amyloid deposits in 134 consecutive patients with sporadic systemic amyloidosis who presented with a monoclonal protein. The diagnosis of AL amyloidosis was established in 129 patients, all of whom had a clinical presentation consistent with the diagnosis. Among five patients with a questionable history or presentation, amyloid typing disclosed AL amyloid in two patients, transthyretin in two, and apolipoprotein A-I in one. We found that ultrastructural immunohistochemical analysis unambiguously characterized the amyloid deposits, by colocalizing the specific protein with the fibrils, in all 37 patients (8 percent) who had sporadic amyloidosis without a monoclonal protein. It allowed typing of κ and λ light-chain deposits in all instances, whereas traditional immunohistochemical analysis was positive in only 38 percent of patients.1 The variable penetrance of the genetic defects indicates the need for confirmation by tissue typing. It seems more cost effective to focus the DNA analysis on specific genes by first typing the amyloid deposits with the use of ultrastructural immunohistochemical techniques
Transthyretin-associated familial amyloid polyneuropathy - current and emerging therapies
No full textTransthyretin-associated familial amyloid polyneuropathy (TTR-FAP), the most common form of systemic hereditary amyloidosis worldwide, is a late-adult-onset autosomal dominant disease caused by mutations in the TTR gene, with peaks in prevalence in endemic areas. The clinical picture is dominated by a progressive length-dependent polyneuropathy with onset in the feet with loss of temperature and pain sensations, accompanied by life-threatening autonomic dysfunction and infiltrative cardiomyopathy, as well as ocular disturbances. Variable expressivity, in terms of age of onset and involvement of extra-neurological sites, can be due to different mutations, but is also observed among individuals with the same mutation in different countries. Therefore diagnosis of TTR-FAP is often a challenge and must rely on careful clinical assessment combined with a multidisciplinary approach. Elimination of the synthesis of mutated TTR, through liver transplantation, may arrest the progressive neuropathy but not the cardiac and ocular involvement. Novel drugs have recently been developed based on a better understanding of the molecular mechanisms of the disease. Drugs that prevent the misfolding and deposition of mutated TTR have entered clinical trials, and one of these, tafamidis meglumine, has been approved in Europe and is now clinically available. Other medicines are now in the pipeline aimed at suppressing the expression of the mutated TTR gene or at promoting amyloid fibril destructuration, favouring resorption of amyloid deposits. These recent advancements provide grounded hope of an imminent significant improvement in the care of this life-threatening multi-system disease. © TOUCHBRIEFINGS 2012
Amyloidosis in Heart Failure
No full textPurpose: Amyloidosis represents an increasingly recognized but still frequently missed cause of heart failure. In the light of many effective therapies for light chain (AL) amyloidosis and promising new treatment options for transthyretin (ATTR) amyloidosis, awareness among caregivers needs to be raised to screen for amyloidosis as an important and potentially treatable differential diagnosis. This review outlines the diversity of cardiac amyloidosis, its relation to heart failure, the diagnostic algorithm, and therapeutic considerations that should be applied depending on the underlying type of amyloidosis. Recent Findings: Non-biopsy diagnosis is feasible in ATTR amyloidosis in the absence of a monoclonal component resulting in higher detection rates of cardiac ATTR amyloidosis. Biomarker-guided staging systems have been updated to facilitate risk stratification according to currently available biomarkers independent of regional differences, but have not yet prospectively been tested. Novel therapies for hereditary and wild-type ATTR amyloidosis are increasingly available. The complex treatment options for AL amyloidosis are improving continuously, resulting in better survival and quality of life. Mortality in advanced cardiac amyloidosis remains high, underlining the importance of early diagnosis and treatment initiation. Summary: Cardiac amyloidosis is characterized by etiologic and clinical heterogeneity resulting in a frequently delayed diagnosis and an inappropriately high mortality risk. New treatment options for this hitherto partially untreatable condition have become and will become available, but raise challenges regarding their implementation. Referral to specialized centers providing access to extensive and targeted diagnostic investigations and treatment initiation may help to face these challenges
Autoinflammatory diseases in Dermatology: a peculiar case of familial mediterranean fever
No full textAnatomic and Clinical Clues to in vivo mechanisms of amyloidogenesis. in , (2005) vol. 1, pp.29-48.
No full textExpression, regulation and localisation of dystrophin isoforms in human foetal skeletal and cardiac muscle
No full textWe characterised the expression, localisation and developmental regulation of the three major dystrophin isoforms in human foetal skeletal and cardiac muscles and in the corresponding cultures. Gene expression studies in foetal cardiac muscle-tissue and cultures showed that the Muscle- and the Brain- but not the Purkinje-transcripts were always co-expressed. In skeletal muscle the Muscle-isoform was already present at 11.8 weeks while the Brain-isoform was detected only after 13 weeks. Myoblast cultures showed a similar sequence of isoform transcription. The Purkinje-isoform was never detected. Localisation studies showed that in cardiac muscle dystrophin was seen discontinuously at the sarcolemma from 8.5 weeks, and evenly expressed by 15 weeks. Cardiomyocyte cultures expressed desmin but not dystrophin after 7 days. Protein studies in foetal skeletal muscle suggested that dystrophin is expressed in the cytoplasm from 8.5 weeks and at the sarcolemma only after 10.5 weeks. Similar results were obtained in cultured myoblasts. This study shows that in cardiac muscle both the Muscle- and Brain-isoforms are transcribed in parallel from the very early stages of development, while in skeletal muscle transcription of the Muscle-isoform occurs first, followed by the Brain-isoform
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