1/241. fibrinogen A alpha chain mutation (Arg554 Leu) associated with hereditary renal amyloidosis in a French family.A French family with hereditary renal amyloidosis (HRA) was studied. The disease presented in 7 of the 8 affected individuals with proteinuria or the nephrotic syndrome. The age of onset was in the fifth decade of life. There is currently no sign of extrarenal involvement in any affected individual. However, the nephropathy in this family is progressive and led to terminal renal failure in 4 patients. immunohistochemistry studies of glomerular amyloid deposits suggested that the amyloid protein was the fibrinogen A alpha chain. Direct dna sequencing revealed a G 4993 T transversion and subsequently Arg 554 Leu mutation in the fibrinogen A alpha chain. This is the first description of this fibrinogen A alpha chain mutation in europe. This family is of French descent and cannot be related to the previously reported Peruvian/Mexican and African-American kindreds.- - - - - - - - - - ranking = 1keywords = family, life (Clic here for more details about this article) |
2/241. A novel variant of transthyretin (Glu42Asp) associated with sporadic late-onset cardiac amyloidosis.A sixty-three year old French man presented with isolated late-onset amyloid cardiomyopathy proven by endomyocardial biopsy. There was no known family history of amyloidosis. immunohistochemistry of cardiac deposits suggested that amyloi fibrils were derived from transthyretin. dna sequencing revealed a point mutation in exon 2 of the transthyretin gene responsible for a novel amyloidogenic variant Asp42.- - - - - - - - - - ranking = 0.14282947595028keywords = family (Clic here for more details about this article) |
3/241. Fatal cardiac beta2-microglobulin amyloidosis in patients on long-term hemodialysis.We report two long-term hemodialysis patients who developed severe congestive heart failure attributable to cardiac heavy amyloid deposition. Both patients became hypotensive during dialysis sessions, gradually making it difficult to continue hemodialysis, and they died of congestive heart failure. At autopsy, left ventricle walls in each case contained diffuse extensive deposits of amyloid. The distribution of amyloid was not localized to vessel walls but was widely disseminated throughout the left ventricle walls and replaced myocardial muscle fibers. Immunohistochemical examination showed positive staining for anti-human beta2-microglobulin antibody. We conclude that cardiac dialysis-related amyloidosis should also be considered in long-term hemodialysis patients with congestive heart failure as a life-threatening complication.- - - - - - - - - - ranking = 0.00019366834805441keywords = life (Clic here for more details about this article) |
4/241. familial mediterranean fever. No role of mycobacterium tuberculosis in ten patients.BACKGROUND: Tuberculosis (TB) and familial mediterranean fever (FMF) are two common diseases in our region, turkey. Both share some properties in common: Both cause AA type amyloidosis and have association with some immunological abnormalities. Upon incidentally observing mycobacterium tuberculosis in bone marrow biopsies of three patients with FMF in a previous study, we intended to elucidate this association prospectively. MATERIAL AND methods: In this study, we examined prospectively 10 FMF patients, 5 male and 5 female, with a median duration of 31 years disease activity. All were under colchicine therapy. They had no sign of renal involvement. The bone marrow biopsies of these patients were examined for the presence of M. tuberculosis by polymerase chain reaction (PCR), BACTEC culture and pathological stains. Pathological examination was performed for the existence of granuloma and amyloid deposition by hematoxylin-eosin, Crystal Violet and congo red stains. RESULTS: The examination of all bone marrow specimens by the mentioned methods suggest that mycobacterium tuberculosis has no role in the ethiopathogenesis of FMF. Although the patients had a positive family history of 60% for tuberculosis and in 80% of them with positive tuberculin skin test. CONCLUSIONS: We concluded that although there seemed to be a kind of association between both diseases, this relationship is not via the direct existence of bacteria itself. Considering high family history and skin test positivity, one should look for the presence of autoimmune mechanisms under this suspicious relationship between tuberculosis and FMF. Also, this is the first study examined the state of amyloidosis in the bone marrow at an earlier stage of FMF without overt renal findings.- - - - - - - - - - ranking = 0.28565895190056keywords = family (Clic here for more details about this article) |
5/241. Hereditary cardiac amyloidosis associated with the transthyretin Ile122 mutation in a white man.An 83 year old white man with atrial fibrillation was admitted to hospital after a cerebral infarct. echocardiography was characteristic of cardiac amyloid deposition and subsequent tests confirmed amyloidosis of transthyretin (TTR) type, in association with the Ile122 mutation of the TTR gene; this has only been reported previously in african americans in whom it occurs with an allele frequency of 2%. Haplotype analysis did not suggest a different founder than for the African Ile122 mutation. Cardiac amyloidosis should be considered among elderly patients presenting with cardiac failure and/or arrhythmia, particularly if they are resistant to conventional treatment; if confirmed, it should be followed by precise characterisation of amyloid fibril type. The prevalence of autosomal dominant cardiac TTR amyloidosis in elderly white people is unknown but early diagnosis and supportive treatment may prevent complications among affected family members.- - - - - - - - - - ranking = 0.15900840986745keywords = family, family member, member (Clic here for more details about this article) |
6/241. Acute leukemia following prolonged cytotoxic agent therapy.1. Nine patients in whom acute non-lymphoblastic leukemia (ANLL) developed following prolonged alkylating agent therapy are described. Five of the patients received no radiotherapy. The conditions treated were: Hodgkin's disease (four patients), primary amyloidosis, primary macroglobulinemia, malignant lymphoma, multiple myeloma, and carcinoma of the tonsil. 2. Prior to the advent of chemotherapy, this complication was not observed in large series of patients with lymphoproliferative disorders and multiple myeloma. However, the medical literature now contains at least 125 other detailed reports of ANLL developing after prolonged cytotoxic agent therapy. 3. multiple myeloma and Hodgkin's disease, both of which commonly have good responses to chemotherapy, predominate as the underlying diseases. However, 35% of the case reports involve patients with other illnesses, including 12 patients who did not have neoplasms. 4. More than half of the patients developing ANLL have received chemotherapy alone without radiotherapy. 5. At least half of the patients developing ANLL experienced long periods of significant cytopenia during therapy, often with documentation of bone marrow dysplasia. 6. The wide variety of drugs associated with this complication suggests that any cytotoxic agent may be leukemogenic. However, alkylating agents overwhelmingly predominate as the class of compounds which are most often associated with terminal ANLL. 7. The vast majority of patients reported in the literature with ANLL complicating underlying malignancies have received cytotoxic drugs for prolonged periods (median 3 1/2 years) and leukemia developed most commonly 3 to 5 years after the diagnosis of the underlying disease. Most of these patients benefited from therapy and survived longer (median 5 years) than historical control of untreated patients. 8. The leukemogenic potential in man of prolonged cytotoxic agents therapy, especially with alkylating agents, seems to be well established. This evidence admonishes against the prolonged use of these drugs in non-fatal disorders. 9. More accurate assessment of risk: benefit ratios awaits the results of prospective controlled studies. The results of these studies could also lead to significant modifications in recommendations for long-term maintenance therapy with cytotoxic agents.- - - - - - - - - - ranking = 0.00019366834805441keywords = life (Clic here for more details about this article) |
7/241. Transthyretin amyloidosis and superficial siderosis of the CNS.OBJECTIVE: To describe a previously unreported clinical and radiologic presentation of hereditary transthyretin (TTR)-related amyloidosis. BACKGROUND: Unexplained cerebellar ataxia, pyramidal syndrome, and hearing loss are observed in some patients with TTR-related amyloidoses. methods: We performed clinical, radiologic, and pathologic examinations of three family members with TTR-related (Ala36Pro) amyloidosis. RESULTS: The patient was a 69-year-old woman with vitreal amyloid deposits, progressive sensorineural deafness, cerebellar ataxia, pyramidal syndrome, and recurrent transient neurologic symptoms. Cranial MRI showed symmetric thin rims of low signal intensity in T2- and T2*-weighted images in the cortex of the sylvian fissures, of the cerebellar hemispheres and vermis, and in the quadrigeminal plate consistent with superficial siderosis of the CNS. Her older daughter had vitreal amyloid deposits, acute brown-sequard syndrome at C4, acute sensorineural deafness, and recurrent transient neurologic symptoms. Cranial MRI at age 48 revealed a rim of low signal intensity in T2- and T2*-weighted images in the superior vermis folia and the right sylvian cortex. In addition, two small hemosiderin deposits were seen in the left parietal cortex. Lumbar puncture yielded colorless CSF with increased ferritin content and was followed by fourth ventricle hemorrhage. Cranial MRI 11 months later showed progression of brain hemosiderin deposits. The younger daughter had vitreal deposits, sensorimotor polyneuropathy, and acute sensorineural hearing but no evidence of siderosis on cranial MRI. She died at age 43 years of posterior fossa subarachnoid hemorrhage, and the neuropathologic examination showed amyloid deposition in the leptomeningeal spaces and vessels. CONCLUSION: Transthyretin-related amyloidosis may cause superficial siderosis of the CNS through subarachnoid bleeding related to meningovascular amyloid deposition.- - - - - - - - - - ranking = 0.15900840986745keywords = family, family member, member (Clic here for more details about this article) |
8/241. 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.- - - - - - - - - - ranking = 1.2911395263919keywords = family, member (Clic here for more details about this article) |
9/241. Secondary amyloidosis associated with giant cell arteritis/polymyalgia rheumatica.Although giant cell arteritis (GCA) is characterized by chronic inflammation, secondary (AA) amyloidosis appears to be an exceptionally rare complication of this disorder. We describe an 84-year-old man with biopsy proven GCA and polymyalgia rheumatica (PMR) who was found at autopsy to have AA amyloid deposition in numerous organs, 9 years after his diagnosis of GCA. Persistent musculoskeletal symptoms, attributed to refractory PMR during the patient's life, were likely due to AA amyloidosis. This unrecognized complication of GCA/PMR confounded his therapy, leading to excessive treatment with corticosteroids and methotrexate. This case shows that the occurrence of AA amyloidosis should be considered in patients with "refractory PMR" developing after a period of treatment, and that autopsies play a vital role in enigmatic cases.- - - - - - - - - - ranking = 0.00019366834805441keywords = life (Clic here for more details about this article) |
10/241. pH-dependent fibrillogenesis of a VkappaIII bence jones protein.Disorders of immunoglobulin (Ig) synthesis that occur in malignant plasma-cell proliferation may result in either granular (LCDD) or fibrillar (AL) tissue deposition of light-chain monoclonal components. The structural features that govern the transition from soluble polypeptides to either fibrillar or granular conformational states remain undefined. Among the many factors presumed to play a role in these transitions the net charge of the molecule has been associated with folding conformation changes. The majority of the proteins involved in AL amyloidosis show acidic isoelectric points (pI 3.8-5.2), whereas most L chains with basic pIs deposit in granular patterns. In our studies a 12 kD VkappaIII fragment was purified as the main component of the fibrils isolated from myocardium and adipose tissue of the pericardium obtained post-mortem from an individual with systemic AL amyloidosis. An apparently identical 12 kD VL fragment with the same N-terminal sequence constituted the BJ protein present in the urine. This urinary protein exhibited strikingly cathodic electrophoretic mobility on agarose gels and lacked retention by anionic exchange chromatography matrices, indicative of a highly basic pI (>10). When it was subjected to in vitro fibril-formation experiments, the BJ protein adopted a fibrillar conformation only at acidic pHs, remaining aggregated but not fibrillar at physiological pH. The data indicate that a specific tissue deposition pattern involves not only structural properties of the protein but rather more complex mechanisms in which acidic micro-environments may contribute to the stabilization of amyloidogenic conformations.- - - - - - - - - - ranking = 0.00019366834805441keywords = life (Clic here for more details about this article) |
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