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At least 595 records · Page 33Linked to original sources
PubMed1995

A novel allelic variant of serum amyloid A, SAA1 gamma: genomic evidence, evolution, frequency, and implication as a risk factor for reactive systemic AA-amyloidosis.

Reactive systemic amyloidosis, also called AA-amyloidosis is a rare fatal complication of common chronic inflammatory diseases such as rheumatoid arthritis. It has been proposed that as yet undefined factors other than persistent elevation of serum level of the precursor protein, serum amyloid A (SAA), are also important for the development of AA-amyloidosis. In this work we show genomic evidence for a novel allelic variant of human SAA, SAA1 gamma, which we have recently identified at the protein level. The SAA1 gamma [Ala52(GCC), Ala57(GCG)] differed from SAA1 alpha [Val52(GTC), Ala57(GCG)] only at one base, indicating a single point mutation. On the other hand, SAA1 beta [Ala52(GCC), Val57(GTG)] had not only one, but additional differences in a nearby intron and this portion was identical to the SAA2 gene, suggesting a crossing-over between the SAA1 and SAA2 genes. Furthermore, we report that there was a significant difference in the observed numbers of SAA1 alleles between rheumatoid arthritis patients with AA-amyloidosis and the control population (chi 2(2) = 11.59, p = 0.003) with a higher frequency of gamma-allele in the AA-amyloid group (0.70 vs. 0.37). There was also a notable difference in the distribution of SAA1 genotypes (chi 5(2) = 14.63, p = 0.012) with an increased frequency of gamma/gamma-homozygotes in the AA-amyloid group (0.60 vs. 0.18). Thus our findings indicate that this novel allelic variant may be an important risk factor for the development of AA-amyloidosis.

Adult↗
PubMed1996

Dialysis-related amyloidosis: visceral involvement and protein constituents.

beta 2-M amyloidosis mainly concerns dialysis patients and typically presents with osteoarticular symptoms. In order to precise the incidence and gravity of visceral involvement, subcutaneous abdominal fat aspirates, skin and rectal biopsies, as well as echocardiograms were performed in 26 patients with severe beta 2-M amyloidosis. Visceral amyloidosis was confirmed in 58% and the numbers were even higher when including heart abnormalities suggestive of amyloidosis (81%). Clinical manifestations of visceral involvement were usually not severe and include odynophagia, gastrointestinal haemorrhage, intestinal obstruction, kidney stones, myocardial dysfunction and subcutaneous tumours. The removal and synthesis rates of beta 2-M were assessed during dialysis. Serum 131I-beta 2-M levels decreased by 5-10% with cuprophane and by 40-45% with polysulfone and polyacrylonitrile membranes. These reduction rates were higher than those found with unlabelled beta 2-M suggesting an increased synthesis or release during dialysis. The protein constituents of amyloid deposits were studied. Two different preparative methods to extract the proteins from amyloid deposits were used. TCA precipitation showed the presence of several proteins which were not observed with PBS homogenizing and resuspending in guanidine. The protein constituents of amyloid fibrils were studied by both, two dimensional gel electrophoresis (2D-gel) as well as protein sequencing after gel filtration. Similarly, the technical approach used for protein analysis greatly influenced the results. It was observed that 2D-gel displayed the presence of proteins which were missed by the gel filtration technique. Some of the proteins contained in amyloid deposits in addition to beta 2-M, were identified as globin chains, kappa and lambda light chains of immunoglobulins, and alpha 2 macroglobulin. A putative participation of these other protein constituents on the pathogenesis of beta 2-microglobulin amyloidosis is discussed.

Amyloidosis↗
PubMed1999

Hereditary renal amyloidosis associated with variant lysozyme in a large English family.

BACKGROUND: Two kindreds with hereditary systemic amyloidosis caused by the first two mutations to be described in the human lysozyme gene were discovered recently and study of the variant lysozyme has been powerfully informative about mechanisms of amyloid fibrillogenesis. However, the clinical manifestations in these families, additional members of which have lately been identified, have not previously been reported in detail. METHODS: The proband presented with proteinuria aged 50 and a family history of amyloidosis, and underwent renal biopsy, whole-body serum amyloid P component (SAP) scintigraphy, and sequencing of the lysozyme gene. Her family history and the phenotype of hereditary lysozyme amyloidosis were thoroughly documented and compared with the presentation and natural history of all other known patients with this condition. RESULTS: The proband belonged to an extended English family other members of which were known to have hereditary lysozyme amyloidosis. Those with amyloid in previous generations presented with renal involvement, frequently developed complications due to gastrointestinal amyloid, and died before age 60. All amyloid deposits were composed of lysozyme and complete concordance was established between amyloid and heterozygosity for a point mutation in the lysozyme gene, encoding the previously reported Asp67His substitution in the mature protein. CONCLUSION: The phenotype, reported for the first time in this extended kindred, contrasts with that of an apparently unrelated family carrying the same mutation who presented with spontaneous hepatic haemorrhage and rupture, and with the manifestations in a family with the lysozyme Ile56Thr variant who presented with dermal petechiae before proceeding to fatal visceral amyloidosis. A remarkably wide spectrum of disease can be caused by the same amyloid fibril protein, although renal involvement predominates in all cases except those dying of hepatic rupture.

Amyloidosis↗
PubMed2002

A retrospective analysis for aetiology and clinical findings of 287 secondary amyloidosis cases in Turkey.

BACKGROUND: Secondary amyloidosis is the most frequent of the various types of systemic amyloidosis, the epidemiology of which is not yet fully known. The aim of our study was to evaluate retrospectively the collective data for the aetiological distribution, clinical findings and approaches to the management of secondary amyloidosis in Turkey. METHODS: Data from a simple questionnaire addressing aetiology, and demographic and clinical characteristics of patients with biopsy-proven secondary amyloidosis was retrospectively analysed. Eleven nephrology clinics contributed data for this study. RESULTS: The 11 contributing centres provided a total of 287 cases (102 female, 185 male). The aetiological distribution was as follows: familial Mediterranean fever (FMF) 64%, tuberculosis 10%, bronchiectasis and chronic obstructive lung disease 6%, rheumatoid arthritis 4%, spondylarthropathy 3%, chronic osteomyelitis 2%, miscellaneous 4%, unknown 7%. Oedema accompanied by proteinuria was present in 88% of the cases, hepatomegaly in 17%, and splenomegaly in 11%. The mean systolic and diastolic blood pressures were 115+/-26 and 73+/-15 mmHg respectively. The family history was positive in 16%; 73% of the cases were on colchicine treatment when the questionnaire was administered. Thirty-eight per cent of the cases had progressed to ESRD and were on renal replacement therapy. CONCLUSIONS: FMF is the leading cause of secondary amyloidosis in Turkey, followed by tuberculosis. Oedema accompanied by proteinuria is the most prominent presenting finding, and hypotension seems to be common among these patients.

Adolescent↗
PubMed2002

Mutational spectrum in the MEFV and TNFRSF1A genes in patients suffering from AA amyloidosis and recurrent inflammatory attacks.

BACKGROUND: Among hereditary fevers characterized by recurrent attacks of fever and organ localized inflammation, familial Mediterranean fever (FMF), and tumour necrosis factor receptor superfamily 1A (TNFRSF1A) receptor associated periodic syndrome (TRAPS) are diseases with identified genes that can be associated with renal amyloidosis of the AA type. In this study we have characterized FMF and TRAPS genotypes in 38 unrelated patients suffering from amyloidosis AA and recurrent inflammatory attacks. METHODS: Mutations of the MEFV and TNFRSF1A genes, responsible respectively for FMF and TRAPS, were searched for by amplifying, using polymerase chain reaction (PCR), genomic DNA, and direct sequencing. RESULTS: Twenty-seven patients (71%) carried mutations in MEFV (22 patients with two mutations, two patients with a single mutation) or TNFRSF1A genes (three patients). Patients with MEFV mutations belonged to the classical at-risk ethnic group for FMF: Sephardic Jews, Turks, Armenians, and Arabs from the Maghreb. The main genotype encountered was M694V/M694V (19/22), one Turkish patient was M680I/M680I, and two Arab patients from the Maghreb were M694I/M694I. We found three Caucasian patients with the C55S, C70Y, R92Q mutations in the TNFRSF1A gene. CONCLUSIONS: In this series we observed that FMF is the main cause of AA amyloidosis in Sephardic Jews and Turks. MEFV and TNFRSF1A mutations were found in only 6 of 14 Arab patients from the Maghreb. We found three families (one Caucasian and two from Maghreb) with AA amyloidosis without MEFV or TNFRSF1A mutations, suggesting that other genetic cause(s) exist(s). The characterization of mutations in MEFV and TNFRSF1A is important for the therapeutic behaviour of AA amyloidosis associated with inherited recurrent fever.

Amino Acid Sequence↗
PubMed2003

Current therapeutic possibilities in primary and secondary amyloidosis and our experience with 31 patients.

Primary (AL) and secondary (AA) amyloidosis are systemic diseases characterized by a process of amyloid deposition in many organs with unsatisfactory survival of patients. Apart from surgical intervention in those patients with bronchiectasias or osteomyelitis, the possibilities of influencing the development of AA amyloidosis are limited. The milestone therapy in patients with rheumatic diseases includes early treatment with DMARDs (disease-modifying antirheumatic drugs). A new promising therapeutic alternative is represented by anti-tumour necrosis factor-alpha (TNF-alpha) drugs such as infliximab and etanercept. The last class of agents used in the treatment of AA interferes with fibril formation: iododoxorubicin and low molecular weight sulfates (fibrilex). In the group of patients with AL, in addition to the standard combination of melphalan and prednisone, other therapeutic approaches such as ASCT (autologous stem cell transplantation) and new drugs with different mechanisms of action have been added recently. For the future, we can expect the development of immunotherapy (both active vaccination and passive immunization). In our department, we have treated 17 patients with AL and 14 patients with AA amyloidosis since 1995. We used various treatment regimens in both groups of patients. The treatment stabilized the disease or achieved partial remission in only 36% of patients with AA amyloidosis despite the use of intensive therapeutic modalities, while in the AL group a response was achieved in 82% of patients. ASCT improves patients survival in AL amyloidosis, but strict selection criteria are necessary (less than two affected organs and no signs of myocardial dysfunction).

Adult↗
PubMed1997

'Localized amyloidosis': 123I-labelled SAP component scintigraphy and labial salivary gland biopsy.

In apparently localized amyloidosis, there is no appropriate test to determine whether systemic deposits exist. We studied the value of serum amyloid P component (SAP) scintigraphy and labial salivary gland (LSG) biopsy on patients with apparently localized amyloidosis in 12 patients who had neither clinical nor biological evidence of systemic amyloidosis. All patients had an LSG biopsy and echocardiography. Iodine-123-labelled serum amyloid P component (123I-SAP) scintigraphy was performed in all patients. Whole-body scintigraphy was done, and tissue retention was evaluated at 24 h and 48 h. Of these 12 patients, three had amyloidosis in their LSG and had abnormal 123I-SAP scintigraphy; these three had a secondary clinical history of systemic amyloidosis. Three other patients had abnormal 123I-SAP scintigraphy without detectable systemic amyloid deposits, but one had a previous history of bilateral carpal tunnel syndrome treated with infiltration. 123I-SAP scintigraphy in association with LSG biopsy may be helpful in determining the localized or systemic character of amyloid disease.

Adult↗
PubMed2000

Familial Mediterranean fever and systemic amyloidosis in untreated Turkish patients.

We compared the frequencies of seven MEFV mutations (M694V, M680I, V726A, M694I, K695R, R761H, E148Q) and the clinical findings in 20 Turkish FMF patients who had not developed amyloidosis by the age of 40 years in the absence of colchicine therapy, with those in 27 Turkish amyloidosis patients. No mutation frequency, including that of M694V, was different between the two groups. Family history of amyloidosis and parental consanguinity were noted to be higher in the amyloidosis group. The seven mutations do not appear to be sufficient to explain the development of amyloidosis in Turkish FMF patients. Other genetic factors may be important for this association.

Adult↗
PubMed2001

Renal type AA amyloidosis associated with rheumatoid arthritis: a cohort study showing improved survival on treatment with pulse cyclophosphamide.

OBJECTIVE: To determine the incidence of renal AA amyloidosis and its association with rheumatoid arthritis (RA) in a cohort of all renal biopsies at one referral hospital and to measure the effect of a monthly pulse of cyclophosphamide on renal function and survival in these RA patients. METHOD: All renal biopsies with proven AA amyloidosis from a single pathology unit linked to a major nephrology referral unit in a university hospital were selected retrospectively and RA patients were identified. We studied 6931 renal biopsies. The effect of treatment with and without pulse cyclophosphamide on renal function and survival was studied in these patients. RESULTS: From March 1977 to February 1999, the incidence of AA amyloidosis was 2.4 cases/yr. The incidence and prevalence of the association of AA amyloidosis with RA were 0.68 cases/yr and 0.22% (15/6931) respectively. RA patients treated with cyclophosphamide (n=6) had a lower rate of renal function loss (P=0.013) and a higher median survival (P=0.026) than untreated patients (n=9). During the follow-up period, two out of six treated patients (33%) and all nine untreated patients (100%) died. CONCLUSIONS: AA amyloidosis is a rare complication of RA and complicates the evaluation of treatment. This retrospective study suggests that treatment with cyclophosphamide is able to reduce the incidence of end-stage renal failure and to increase survival. Prospective studies are needed to clarify this issue.

Adult↗
PubMed2003

Cytostatic therapy for AA amyloidosis complicating psoriatic spondyloarthropathy.

Psoriatic spondyloarthropathy (PSA) can occasionally be complicated by AA amyloid, and renal amyloidosis should be suspected in patients with PSA who have unexplained proteinuria. The diagnosis of amyloidosis can be made either histologically or by radiolabelled serum amyloid P component (SAP) scintigraphy. Prognosis is determined by the extent of organ involvement and associated impairment of function, and by the degree of response of the underlying disease to anti-inflammatory therapy. A review of the literature identified less than a dozen cases of AA amyloidosis complicating PSA, and the outcome in most cases was poor. We report here the favourable clinical course of a middle-aged Caucasian male patient with severe PSA who developed renal AA amyloidosis, in whom treatment with oral chlorambucil led to stabilization of the amyloid deposits and resolution of the associated nephrotic syndrome. We review the diagnosis and treatment of AA amyloidosis, including the management of patients with underlying inflammatory spondyloarthropathies, and propose the possible role of a therapeutic trial of anti-tumour necrosis factor alpha in patients with amyloid complicating inflammatory rheumatic diseases.

Amyloidosis↗
PubMed2003

Acute secondary gastrointestinal amyloidosis in a patient with rheumatoid arthritis.

Secondary amyloidosis is well recognized as a severe complication in the late stages of rheumatoid arthritis (RA). However, there have been few reported cases of secondary amyloidosis developing early during the course of RA. We here report the case of a 35-year-old woman, in whom RA who had been diagnosed 1 year before, with intractable watery diarrhea as a symptom of RA-induced secondary intestinal amyloidosis. Combination treatment with intravenous hyperalimentation, corticosteroids, and methotrexate (MTX) resulted in a dramatic improvement of her symptoms and objective findings of serological abnormalities. Subsequent administration of corticosteroids and MTX resulted in long-term survival without recurrence. This case indicates that we should be alert for the development of secondary amyloidosis, even in patients with a short history of RA, when the disease is active. Furthermore, combination therapy with intravenous hyperalimentation and strong immunosuppressive agents seems to be very efficacious in the treatment of RA-associated secondary intestinal amyloidosis.

Acute Disease↗
PubMedDate not supplied

Localized amyloidosis of the respiratory system: CT features.

PURPOSE: Amyloidosis includes a spectrum of diseases associated with an abnormal extracellular deposition of amyloid. The respiratory system is involved in approximately 50% of patients with amyloidosis. The purpose of this review is to present the CT findings of localized amyloidosis of the respiratory system. METHODS: We reviewed the CT findings of localized amyloidosis of the respiratory system from the previous reports and our experiences. RESULTS: Three patterns of involvement in respiratory system are presented: tracheobronchial nodular and diffuse parenchymal. CT demonstrates nodules, plaques, or diffuse thickening of the airways with calcification. Postobstructive collapse is associated in case of diffuse airway involvement. Parenchymal nodules have sharp and lobulated margins with peripheral or subpleural locations. High-resolution CT shows reticular opacities, interlobular septal thickening, and small, well-defined nodules of 2 to 4-mm in diameter predominantly in the subpleural regions. CONCLUSION: Amyloidosis of respiratory system has variable findings and CT scans clearly depict extent and distribution of the disease, its postobstructive pulmonary complication, and other associated findings such as calcification and lymphadenopathy.

Aged↗
PubMed2001

Amyloidosis-induced gastrointestinal bleeding in a patient with multiple myeloma.

We present a case of multiple myeloma (MM) complicated by recurrent amyloidosis-induced gastrointestinal bleeding. The patient presented with episodes of coffee-ground vomitus or massive hematochezia. No bleeding focus could be identified using endoscopy, a red blood cell scan, or angiography. Finally, a tissue biopsy taken at the irregular mucosa beside protruding vessels in the duodenum confirmed the diagnosis of gastrointestinal amyloidosis. As this case illustrates, the absence of systemic symptoms of amyloidosis and nonspecific endoscopic findings in gastrointestinal amyloidosis may make diagnosis difficult. Therefore, we recommend that a diagnosis of amyloidosis-induced gastrointestinal bleeding should be considered in patients with MM with an obscure hemorrhage.

Aged↗
PubMed1989

Amyloidosis in children with inflammatory bowel disease.

Reactive systemic or secondary amyloidosis occurs in 1-29% of adults with Crohn's disease, but only sporadic cases of amyloidosis have been recognized in children with inflammatory bowel disease. We therefore have studied operative specimens (ileal, ileocolonic, and colonic) from 46 children (30 with Crohn's disease and 16 with ulcerative colitis) to determine the frequency of amyloid deposits. Sections of bowel, skin, and lymph nodes (n = 940) were stained by Congo red and examined by light microscopy and by polarized light. Amyloid deposits were found in only one of 46 subjects, an 18-year-old girl who had had Crohn's disease for 6 years. Intestinal amyloid deposits, present 16 months before the clinical diagnosis of amyloidosis, were patchy and seen predominantly in the intestinal mucosa. We conclude that amyloidosis is rare in children requiring surgery for Crohn's disease and ulcerative colitis. Examination of Congo red-stained sections can detect even subclinical amyloidosis. The amyloid deposits in our patient, which were both patchy and consistently mucosal, suggest that multiple endoscopic biopsy samples, not necessarily containing submucosa, are sufficient for diagnosis.

Adolescent↗
PubMed2000

Surgical management of localized amyloidosis.

OBJECTIVE: To demonstrate the role of two-dimensional reconstruction images on computed tomography (CT) in the treatment planning for laryngeal amyloidosis. To discuss the treatment for isolated laryngeal amyloidosis and compare the role of endoscopic versus an open surgical approach to management. STUDY DESIGN: Retrospective review. METHODS: The medical records from 1984 to the present with the diagnosis of localized respiratory tract amyloidosis at Geisinger Medical Center were reviewed. RESULTS: Five previously unpublished cases of localized laryngeal amyloidosis were identified with the supraglottic region the major site of involvement. Hoarseness and airway compromise were the presenting symptoms. CT two-dimensional reconstruction imaging was used to evaluate two cases with extensive laryngeal involvement that required an external surgical approach to relieve symptoms. CONCLUSIONS: Localized laryngeal amyloidosis is a rare disease that requires surgical management when symptomatic. CT two-dimensional reconstruction can be helpful in detailing the extent of disease and planning surgery. A lateral external supraglottic approach has been found to be successful in treating patients with large supraglottic masses.

Adult↗
PubMed1988

Bone scan in systemic amyloidosis.

Thirty patients diagnosed as having systemic amyloidosis (six with primary amyloidosis and 24 with secondary amyloidosis) were given bone scans with 99Tcm-methylene diphosphonate in order to evaluate the skeletal and extra-osseous uptake and their clinical-scintigraphic correlation. Extra-osseous uptake appeared in nine instances, more frequently in primary (5/6) than in secondary (4/24) amyloidosis. Fourteen patients had clinical and echocardiographic suspicion of cardiac amyloidosis but only one showed cardiac uptake. Six patients had probable hepatic involvement but in only two cases was hepatic uptake seen. The extra-osseous uptake suggests the presence of amyloid deposits in the organs and soft tissues which take up the bone tracer. The absence of any uptake does not rule out amyloid infiltration.

Adult↗
PubMed2001

Clinical and biochemical outcome of hepatorenal transplantation for hereditary systemic amyloidosis associated with apolipoprotein AI Gly26Arg.

BACKGROUND: Treatment of systemic amyloidosis comprises measures to support failing organ function coupled with attempts to reduce the supply of the respective amyloid fibril precursor protein. Orthotopic hepatic transplantation is effective in familial amyloid polyneuropathy associated with variant transthyretin, because this protein is produced almost exclusively in the liver. Hepatic transplantation has not been performed in hereditary apolipoprotein AI (apoAI) amyloidosis, and the liver's contribution to plasma apoAI levels has not been determined in vivo. METHODS: A 57-year-old Irish man with hereditary systemic amyloidosis associated with apoAI Gly26Arg, which had led to end-stage renal failure and progressive liver dysfunction, underwent hepatorenal transplantation. His outcome was followed clinically and his amyloid deposits were monitored with serum amyloid P component scintigraphy. The proportion of variant apoAI in the plasma was estimated by quantitative isoelectric focusing before and after liver transplantation. RESULTS: Plasma levels of variant apoAI decreased by 50% after liver transplantation, and the patient was asymptomatic 2 years after surgery. Subclinical amyloid deposits that were present in his spleen and heart preoperatively have regressed and stabilized respectively. CONCLUSIONS: Orthotopic liver transplantation substantially reduces the supply of the amyloid fibril precursor protein in hereditary apoAI amyloidosis, and the excellent outcome in this patient probably reflects the balance between deposition and turnover of amyloid having been altered in favor of the latter. These findings support the use of liver transplantation in patients with hereditary apoAI amyloidosis who develop hepatic dysfunction.

Amino Acid Substitution↗
PubMed2007

Globular amyloid deposits isolated to the small bowel: a rare association with AL amyloidosis.

We describe a 55-year-old man with isolated duodenal and jejunal amyloidosis producing rare endoscopic and histologic findings. The patient had no specific gastrointestinal complaints but underwent esophagogastroduodenoscopy and colonoscopy because of progressive microcytic anemia. Endoscopy revealed multiple polyps, some filiform and measuring up to 3 cm in length, in the duodenum and proximal jejunum. Microscopically, the polyps resulted from amyloid deposition, predominantly within the submucosa, but also focally involving muscularis mucosae and lamina propria. The amyloid formed multiple globular submucosal deposits with a lamellated appearance reminiscent of corpora amylacea; linear amyloid deposition was also present in a perivascular distribution and within the overlying mucosa. Immunophenotyping confirmed AL amyloidosis with lambda immunoglobulin light chain restriction. There was no clinical evidence of visceral amyloidosis. The source of lambda light chain production was unclear as bone marrow biopsy and multiple gastrointestinal biopsies revealed normal numbers of polyclonal plasma cells. Further, immunoglobulin-free light chain assay was normal, as were serum and urine protein electrophoreses with immunofixation. This endoscopic presentation of isolated small bowel polyposis is an uncommon association with AL amyloidosis and to our knowledge this represents the first case of globular gastrointestinal amyloidosis resulting from AL amyloid.

Amyloid↗