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Sample records for amyloidosis

  1. Amyloidosis

    International Nuclear Information System (INIS)

    Glenner, G.G.; Osserman, E.F.

    1986-01-01

    The subjects covered in this Symposium range through almost every clinical medical specialty. From an average of one paper in each of the past three Symposiums, the explosive interest in cerebral amyloidosis has led to the presentation of 12 papers on this subject in the present volume. The genetically predisposed familial amyloidotic processes, such as the polyneuropathies and familial Mediterranean fever have also stimulated extensive and intriguing investigations which have revealed the striking effect of a single amino acid substitution in transforming a normal protein into a lethal ''amyloidogenic'' one. This Symposium clearly depicts the advances since the first amyloid fibril protein was definitively identified and defined 14 years ago. Since all amyloid fibril proteins so far described are variants of normal proteins, attention to gene abnormalities now becomes a significant focus as well as the pathogenic sequences which lead in these cases to twisted Β-pleated sheet (amyloid) fibril formation. Tentative concepts such as the ''amyloidogenic protein precursor of the fibril,'' ''proteolysis as one mechanism of fibril formation,'' ''Congo red birefringence as a marker for the twisted Β-pleated sheet protein'' are now substantiated by recurring confirmation. Even a prophylactic treatment for one of the amyloidotic conditions, familial Mediterranean fever, is now available. Predictably, as the pathogeneses of the amyloid diseases are individually deciphered, highly specific and directed therapies will evolve to treat their devastated victims

  2. [Cardiac amyloidosis].

    Science.gov (United States)

    Boussabah, Elhem; Zakhama, Lilia; Ksontini, Iméne; Ibn Elhadj, Zied; Boukhris, Besma; Naffeti, Sana; Thameur, Moez; Ben Youssef, Soraya

    2008-09-01

    PREREQUIS: Amyloidosis is a rare infiltrative disease characterized by multiple clinical features. Various organs are involved and the cardiovascular system is a common target of amyloidosis. Cardiac involvement may occur with or without clinical manifestations and is considered as a major prognostic factor. To analyze the clinical features of cardiac involvement, to review actual knowledgement concerning echocardiographic diagnostic and to evaluate recent advances in treatment of the disease. An electronic search of the relevant literature was carried out using Medline and Pubmed. Keys words used for the final search were amyloidosis, cardiopathy and echocardiography. We considered for analysis reviews, studies and articles between 1990 and 2007. Amyloidosis represents 5 to 10% of non ischemic cardiomyoparhies. Cardiac involvement is the first cause of restrictive cardiomyopathy witch must be evoked in front of every inexplained cardiopathy after the age of forty. The amyloid nature of cardiopathy is suggered if some manifestations were associated as a peripheric neuropathy, a carpal tunnel sydrome and proteinuria > 3g/day. Echocardiography shows dilated atria, a granular sparkling appearance of myocardium, diastolic dysfunction and thickened left ventricle contrasting with a low electric voltage. The proof of amyloidosis is brought by an extra-cardiac biopsy, the indications of endomyocardial biopsy are very limited. The identification of the amyloid nature of cardiopathy has an direct therapeutic implication: it indicates the use of digitalis, calcium channel blockers and beta-blockers. Today the treatment of amyloidosis remains very unsatisfactory especially in the cardiac involvement. An early diagnosis before the cardiac damage may facilitate therapy and improve prognosis.

  3. Amyloidosis and Kidney Disease

    Science.gov (United States)

    ... Solitary Kidney Your Kidneys & How They Work Amyloidosis & Kidney Disease What is amyloidosis? Amyloidosis is a rare disease ... Advancement & Transfer Meetings & Workshops Health Information Diabetes Digestive Diseases Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine ...

  4. AL Amyloidosis

    Directory of Open Access Journals (Sweden)

    Desport Estelle

    2012-08-01

    Full Text Available Abstract Definition of the disease AL amyloidosis results from extra-cellular deposition of fibril-forming monoclonal immunoglobulin (Ig light chains (LC (most commonly of lambda isotype usually secreted by a small plasma cell clone. Most patients have evidence of isolated monoclonal gammopathy or smoldering myeloma, and the occurrence of AL amyloidosis in patients with symptomatic multiple myeloma or other B-cell lymphoproliferative disorders is unusual. The key event in the development of AL amyloidosis is the change in the secondary or tertiary structure of an abnormal monoclonal LC, which results in instable conformation. This conformational change is responsible for abnormal folding of the LC, rich in β leaves, which assemble into monomers that stack together to form amyloid fibrils. Epidemiology AL amyloidosis is the most common type of systemic amyloidois in developed countries with an estimated incidence of 9 cases/million inhabitant/year. The average age of diagnosed patients is 65 years and less than 10% of patients are under 50. Clinical description The clinical presentation is protean, because of the wide number of tissues or organs that may be affected. The most common presenting symptoms are asthenia and dyspnoea, which are poorly specific and may account for delayed diagnosis. Renal manifestations are the most frequent, affecting two thirds of patients at presentation. They are characterized by heavy proteinuria, with nephrotic syndrome and impaired renal function in half of the patients. Heart involvement, which is present at diagnosis in more than 50% of patients, leading to restrictive cardiopathy, is the most serious complication and engages prognosis. Diagnostic methods The diagnosis relies on pathological examination of an involved site showing Congo red-positive amyloid deposits, with typical apple-green birefringence under polarized light, that stain positive with an anti-LC antibody by immunohistochemistry and

  5. Diagnostic studies in amyloidosis

    NARCIS (Netherlands)

    Hazenberg, Bouke Pier Cornelis

    2007-01-01

    In this thesis two diagnostic techniques are studied in amyloidosis. Systemic amyloidosis is characterized by deposition of amyloid fibrils (tiny fibres) throughout the body resulting in damage of vital organs. Amyloid can be detected in a tissue specimen stained with Congo red: red-stained amyloid

  6. [Amyloidosis in hemodialysis patients].

    Science.gov (United States)

    Bardin, T; Zingraff, J; Benoît, J; Kuntz, D; Drüeke, T

    1987-05-16

    Amyloidosis in long-term haemodialysis patients mainly involves the osteo-articular system. It is held responsible for carpal tunnel syndrome, chronic arthralgia and various types of arthropathy, chronic synovitis and tenosynovitis, haemarthrosis, subacute polyarthritis and destructive arthropathies of the limbs and spine. Radiologically, amyloidosis may appear as bone cavities, particularly visible in the hips and wrists. Its frequency increases with the duration of haemodialysis. Biochemically, amyloidosis consists of beta 2-microglobulin (beta 2-M). This protein accumulates in uraemic patients under dialysis and seems to play a major role in the pathogenesis of amyloid deposits. The accumulation is due to renal impairment, being maximum in anuric patients. However, the unsatisfactory clearance of beta 2-M by dialysis methods also contributes to its retention: the production and elimination of beta 2-M seems to vary according to the extrarenal clearing technique. These data suggest that improvements in clearing techniques will eventually prevent dialysis amyloidosis.

  7. Insulin-derived amyloidosis

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    Yashdeep Gupta

    2015-01-01

    Full Text Available Amyloidosis is the term for diseases caused by the extracellular deposition of insoluble polymeric protein fibrils in tissues and organs. Insulin-derived amyloidosis is a rare, yet significant complication of insulin therapy. Insulin-derived amyloidosis at injection site can cause poor glycemic control and increased insulin dose requirements because of the impairment in insulin absorption, which reverse on change of injection site and/or excision of the mass. This entity should be considered and assessed by histopathology and immunohistochemistry, in patients with firm/hard local site reactions, which do not regress after cessation of insulin injection at the affected site. Search strategy: PubMed was searched with terms "insulin amyloidosis". Full text of articles available in English was reviewed. Relevant cross references were also reviewed. Last search was made on October 15, 2014.

  8. Primary systemic amyloidosis

    Directory of Open Access Journals (Sweden)

    Tanasilović Srđan

    2007-01-01

    Full Text Available Background. Systemic amyloidosis is a rare disorder which usually occurs in aged persons and has a poor prognosis. Systemic amyloidosis can be primary, occasionally associated with multiple myeloma, or secondary, associated with another disease. Case report. We presented a 72-year-old male patient with periocular purpura ("racoon sign" and waxy papules, petechiae and ecchymoses on the neck and thoracic area. Purpuric macules were present also on the lips and tongue which was edematous (macroglossia. The skin lesions occurred two years earlier, the patient lost more than 15 kilograms of the body mass for less than a year. Immunoelectrophoresis of urine and serum demonstrated the presence of immunoglobulin light chains of the circulating monoclonal protein. Histopathological examination of skin lesions showed Congo red positive deposits in the derm. Cardiac evaluation revealed the signs of heart failure, and renal evaluation revealed nephrotic syndrome, with excessive protein lost. He was treated with oral melphalan and prednisolone, and died 7 days after starting the therapy due to heart failure. Conclusion. This patient considered as a rare case with systemic amyloidosis highlights the importance of histopathological and physical examination in any cases with periocular purpura, petechiae, ecchymoses and macroglossia.

  9. Pulmonary amyloidosis: computed tomography findings

    International Nuclear Information System (INIS)

    Marchiori, Edson; Ferreira, Angela; Crespo, Sheila Jandira Vianna

    2003-01-01

    We report the computed tomography findings of five patients with pathology proven pulmonary amyloidosis. Tracheobronchial amyloidosis with calcified nodules and plaques in the tracheal wall were seen in two patients. Two other patients had diffuse parenchymal disease with calcified lesions, one had reticular and nodular sub pleural opacities whereas the other had nodular interlobular septal thickening and a parenchymal consolidation. The latter presented the nodular type of the disease with multiple sharp nodules scattered throughout the lungs and interspersed calcifications. The computed tomography findings observed were not specific but strongly suggestive of amyloidosis. (author)

  10. Unique type of isolated cardiac valvular amyloidosis

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    Reehana Salma

    2006-10-01

    Full Text Available Abstract Background Amyloid deposition in heart is a common occurrence in systemic amyloidosis. But localised valvular amyloid deposits are very uncommon. It was only in 1922 that the cases of valvular amyloidosis were reported. Then in 1980, Goffin et al reported another type of valvular amyloidosis, which he called the dystrophic valvular amyloidosis. We report a case of aortic valve amyloidosis which is different from the yet described valvular amyloidosis. Case presentation A 72 years old gentleman underwent urgent aortic valve replacement. Intraoperatively, a lesion was found attached to the inferior surface of his bicuspid aortic valve. Histopathology examination of the valve revealed that the lesion contained amyloid deposits, identified as AL amyloidosis. The serum amyloid A protein (SAP scan was normal and showed no evidence of systemic amyloidosis. The ECG and echocardiogram were not consistent with cardiac amyloidosis. Conclusion Two major types of cardiac amyloidosis have been described in literature: primary-myelomatous type (occurs with systemic amyolidosis, and senile type(s. Recently, a localised cardiac dystrophic valvular amyloidosis has been described. In all previously reported cases, there was a strong association of localised valvular amyloidosis with calcific deposits. Ours is a unique case which differs from the previously reported cases of localised valvular amyloidosis. In this case, the lesion was not associated with any scar tissue. Also there was no calcific deposit found. This may well be a yet unknown type of isolated valvular amyloidosis.

  11. Demonstrations by osteo systemic amyloidosis

    International Nuclear Information System (INIS)

    Toro Gutierrez, Carlos Enrique; Quintana Duque, Mario Andres; Restrepo, Jose Felix; Rondon, Federico; Paez, Oscar; Iglesias Gamarra, Antonio

    2007-01-01

    Amyloidosis is a generic term that refers to extracellular tissue deposition of fibrils composed of low molecular weigh subunits of a variety of proteins. Amyloidosis classification depends on its etiology and subtype of protein involved. Systemic secondary amyloidosis (AA) is the most frequent subtype seen on rheumatology services because rheumatoid arthritis is currently the most frequent cause of AA, although its incidence has been declined because a better treatment of rheumatoid arthritis with disease-modifying anti-rheumatic, drugs (DMARD). In this review we provide a general overview of the pathogenesis, clinical manifestations, diagnosis, and treatment of the systemic amyloidosis, emphasizing on the rheumatic manifestations of these disorders. Besides, we present a photographic material obtained in the last 20 years in several rheumatologic centers in our country that it has a crucial role in the diagnosis and follow-up of this infrequent pathology

  12. Primary conjunctival amyloidosis

    Directory of Open Access Journals (Sweden)

    Chandana Chakraborti

    2014-01-01

    Full Text Available A 19-year-old previously healthy male presented with a 4 year history of painless drooping of right upper eyelid.On eversion of the right upper eyelid, a yellowish pink mass was seen in the tarsal region. Rest of the ocular examination was normal in both the eyes. Initial biopsy showed chronic inflammation. Subsequently, the entire mass was excised and histopathological examination showed the presence of amyloid in the subconjunctival stroma. At 3 months follow-up, similar lesion was detected in the right lower, left upper, and lower lid, which were treated with cryotherapy, with partial resolution. Patient has been followed up for more than 2 years without any complaints. To our knowledge, this is the first case report of an isolated primary conjunctival amyloidosis with involvement of both the upper and lower palpebral conjunctiva of either eye. It was treated successfully by excision and cryotherapy.

  13. [Hereditary transthyretin amyloidosis].

    Science.gov (United States)

    Hund, E

    2014-10-01

    Hereditary amyloidosis is an autosomal dominant fatal multisystem disease caused by extracellular deposition of misfolded proteins and, therefore represents a hereditary protein folding or deposition disease that leads to progressive organ damage and eventually death. In most instances mutations within the transthyretin gene are the underlying cause. The main manifestation is a rapidly progressing axonal sensorimotor and autonomic polyneuropathy (familial amyloid polyneuropathy, FAP). Cardiac involvement is frequent in FAP and additional manifestations include the gastrointestinal tract and the eyes. A second manifestation type is cardiomyopathy with little or no polyneuropathy (familial amyloid cardiomyopathy, FAC). For therapy, orthotopic liver transplantation has been established for 25 years. Recently, the oral agent tafamidis, a transthyretin stabilizer, was licensed for treatment of stage 1 polyneuropathy. Additional treatment options are currently being studied.

  14. Amyloidosis of the thyroid gland: ultrasonographic aspect

    International Nuclear Information System (INIS)

    Moya, M.I.; Vilas, I.; Menargues, M.A.; Hernandez, M.

    1998-01-01

    Subclinical amyloid infiltration of the thyroid gland is very common. However, amyloidosis rarely provokes thyroid symptoms. We describe a case of goiter due to secondary amyloidosis and review the characteristic ultrasound findings associated with this condition. (Author) 6 refs

  15. Localized Lymph Node Light Chain Amyloidosis

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    Binod Dhakal

    2015-01-01

    Full Text Available Immunoglobulin-derived light chain amyloidosis can occasionally be associated with localized disease. We present a patient with localized lymph node light chain amyloidosis without an underlying monoclonal protein or lymphoproliferative disorder and review the literature of lymph node amyloidosis discussing work-up and risk factors for systemic progression.

  16. Amiloidosis bucal Oral amyloidosis

    Directory of Open Access Journals (Sweden)

    Isabella Lima Arrais Ribeiro

    2012-03-01

    , confirmado con la coloración del espécimen con el reactivo rojo congo. Los depósitos de amiloide fueron encontrados en el tejido conjuntivo, que con la luz polarizada presentó birrefringencia. Tal hallazgo fue preocupante, ya que la amiloidosis afecta diversos tejidos, lo que puede provocar complicaciones sistémicas. Por esa razón la paciente fue orientada a buscar atención médica. Sin embargo, abandonó el tratamiento y falleció 6 meses después del diagnóstico de la enfermedad. Lesiones bucales aparentemente simples pueden revelar enfermedades raras y de difícil tratamiento. El diagnóstico preciso y la supervisión médica son fundamentales para la sobrevida del paciente.Amyloidosis is an uncommon complicated disease of a difficult diagnosis occurring due to the amyloid substance depot in the extracellular medium. Being diagnosed in the oral cavity, the patient must to be supervised to assess the potential systemic complications of disease. The aim of present paper was to present a case of oral amyloidosis in a female patient ages 72 presenting with traumatic fibroma. After performance of a biopsy and the histopathological examination, the diagnosis was the presence of amyloidosis, confirmed with the help of the sample using Congo red reactant. Amyloid depots were found in the conjunctive tissue which under the polarized light showed birefringence. This finding was worrying since the amyloidosis involves different tissues leading to systemic complications. Thus, the patient was oriented to search medical care; however she abandons treatment dying 6 months after diagnosis of the disease. The apparently single oral injuries may to reveal uncommon diseases and of difficult treatment. The precise treatment and the medical supervision are essential in the patient's survival.

  17. Light chain amyloidosis

    Directory of Open Access Journals (Sweden)

    Paolo Milani

    2018-03-01

    Full Text Available Light chain (AL amyloidosis is caused by a usually small plasma-cell clone that is able to produce the amyloidogenic lights chains. They are able to misfold and aggregate, deposit in tissues in the form of amyloid fibrils and lead to irreversible organ dysfunction and eventually death if treatment is late or ineffective. Cardiac damage is the most important prognostic determinant. The risk of dialysis is predicted by the severity of renal involvement, defined by the baseline proteinuria and glomerular filtration rate, and by response to therapy. The specific treatment is chemotherapy targeting the underlying plasma-cell clone. This needs be risk adapted, according to the severity of cardiac and/or multi-organ involvement. Autologous stem cell transplant (preceded by induction and/or followed by consolidation with bortezomib-based regimens can be considered for low-risk patients (~20%. Bortezomib combined with alkylators is used in the majority of intermediate-risk patients, and with possible dose escalation in high-risk subjects. Novel, powerful anti-plasma cell agents were investigated in the relapsed/refractory setting, and are being moved to upfront therapy in clinical trials. In addition, the use of novel approaches based on antibodies targeting the amyloid deposits or small molecules interfering with the amyloidogenic process gave promising results in preliminary studies. Some of them are under evaluation in controlled trials. These molecules will probably add powerful complements to standard chemotherapy. The understanding of the specific molecular mechanisms of cardiac damage and the characteristics of the amyloidogenic clone are unveiling novel potential treatment approaches, moving towards a cure for this dreadful disease.

  18. Amyloidosis in retinal neurodegenerative diseases

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    Ambra Masuzzo

    2016-08-01

    Full Text Available As a part of the Central Nervous System, the retina may reflect both physiological processes and abnormalities related to pathologies that affect the brain. Amyloidosis due to the accumulation of amyloid-beta was initially regarded as a specific and exclusive characteristic of neurodegenerative alterations seen in the brain of Alzheimer’s disease patients. More recently, it turned out that amyloidosis-related alterations, similar to those seen in the brain of Alzheimer’s patients, also occur in the retina. Remarkably, these alterations were identified not only in primary retinal pathologies, such as age-related macular degeneration and glaucoma, but also in the retinas of Alzheimer’s patients. In this review, we first briefly discuss the biogenesis of amyloid-beta, a peptide involved in amyloidosis. We then discuss some pathological aspects (synaptic dysfunction, mitochondrial failure, glial activation and vascular abnormalities related to the neurotoxic effects of amyloid-beta. We finally highlight the common features shared by Alzheimer’s disease, age-related macular degeneration and glaucoma in the context of amyloid-beta amyloidosis and further discuss why the retina, due to the transparency of the eye, can be considered as a window to the brain.

  19. Overview of systemic and localized amyloidosis

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    Saulius Girnius

    2013-10-01

    Full Text Available Amyloidosis is a family of protein misfolding disorders, in which insoluble fibrillar proteins deposit extracellularly and cause end organ damage. Depending on the precursor protein, clinical manifestations in amyloidosis vary significantly. In systemic amyloidosis, the heart, kidneys, and nerves are most commonly affected, resulting in congestive heart failure, arrhythmia, nephrotic syndrome, renal failure, and peripheral and autonomic neuropathies. In localized amyloidosis, amyloid deposits at the site of production, so only one organ is disrupted. Once amyloidosis is confirmed histologically, the precursor subtype must be identified using immunohistochemistry, immunofixation, electron microscopy, or laser microdissection and mass spectrometry. Treatment should not be initiated prior to the identification of the type of amyloidosis. Currently, treatment focuses on the suppression of the precursor protein: in AL amyloidosis, chemotherapy or autologous stem cell transplants suppress production of immunoglobulin light chains; in AA amyloidosis, anti-microbial and anti-inflammatory agents suppress amyloid A production; and in AF amyloidosis, a liver transplantation removes the source of mutant transthyretin protein production. Newer drugs are being developed to target amyloidosis at an epigenetic level or stabilize folding intermediates, but there are currently in development.http://dx.doi.org/10.7175/rhc.v4i4.662

  20. Subtle neuropsychiatric and neurocognitive changes in hereditary gelsolin amyloidosis (AGel amyloidosis)

    OpenAIRE

    Kantanen, Mari; Kiuru-Enari, Sari; Salonen, Oili; Kaipainen, Markku; Hokkanen, Laura

    2014-01-01

    Hereditary gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominant form of systemic amyloidosis caused by a c.640G>A or c.640G>T mutation in the gene coding for gelsolin. Principal clinical manifestations include corneal lattice dystrophy, cranial neuropathy and cutis laxa with vascular fragility. Signs of minor CNS involvement have also been observed, possibly related to cerebral amyloid angiopathy (CAA). To investigate further if AGel amyloidosis carries a risk for a specific neuro...

  1. Osteo-articular manifestations of amyloidosis.

    Science.gov (United States)

    M'bappé, Pauline; Grateau, Gilles

    2012-08-01

    Whether it is overload disease or mispleated proteins, amyloid is a great pretender. This is especially true for all of the osteo-articular manifestations of amyloid light chain (AL) amyloidosis, which may mimic rheumatoid arthritis, polymyalgia rheumatica, a myeloma or a bone tumour. To improve the prognosis, AL amyloidosis must be considered in front of atypical osteo-articular manifestations. Amyloidosis Ab2M of chronic haemodialysis (members' arthropathy and destructive spondylitis) is a specific entity that needs to be differentiated from other osteoarthropathies of chronic renal failure. It has become exceptional since the progress of haemodialysis. Finally transthyretin amyloidosis(ATTR) can be responsible for carpal tunnel syndrome(CTS) in its genetic and senile form. Although amyloidosis is rare, it represents one of the aetiologies of CSC, regardless of its type. In the specific context of haemodialysis, this poses no difficulty for the clinician. Yet AL amyloidosis must be considered more often, as must senile amyloidosis ATTR in the elderly. It seems obvious that the anatomo-pathologic analysis with specific staining with Congo red - see typing - should be systematically performed in the case of surgical neurolysis. Amyloidosis is defined by the extracellular deposit of proteins which share common tinctorial affinities, a fibril aspect under electron microscopy and spatial conformation called beta pleated. Once regarded as a mere overload disease, it is currently considered as a disease of misfolded proteins. Indeed, it is certain that abnormalities of spatial pattern play an essential role in the responsibility for the pathology of many proteins whose amyloid fibre is the final common way. They involve both changes in the conformation of proteins and other major in vivo interactions between amyloid protein and the extracellular matrix. In most cases, amyloidosis represents the bulk of histopathological lesions and its pathogenic role is certain. In

  2. Primary localised cutaneous amyloidosis - a systematic review

    DEFF Research Database (Denmark)

    Kaltoft, Britta; Schmidt, Grethe; Lauritzen, Anne Falensteen

    2013-01-01

    Amyloidosis is defined as extracellular deposits of heterogenic, misfolded proteins, amyloid fibrils, in various tissues. The aim of our study was to review the literature and to evaluate the risk of developing systemic amyloidosis (SA) and the risk of local recurrence of primary localised...

  3. Renal amyloidosis in a child with neutropenia

    Directory of Open Access Journals (Sweden)

    Hasan Otukesh

    2011-01-01

    Full Text Available Amyloidosis represents a heterogeneous group of disorders of protein metabolism and is characterized by deposition of fibrillar proteins in the intra- and extracellular spaces. Here, a case of generalized amyloidosis associated with neutropenia is presented. She had a medical history of multiple bacterial infections. At the age of 14 years, she developed nephrotic syndrome. An increase of antigenic stimulation during the intermittent bouts of acute infections would have been the main factor responsible for the development of secondary amyloidosis in this case. To the best of our knowledge, coexistence between neutropenic disorders and renal amyloidosis in children has not been reported till date. The purpose of this report is to present a case of secondary amyloidosis associated with neutropenia in pediatric age group, probably for the first time.

  4. Systemic AA amyloidosis: epidemiology, diagnosis, and management.

    Science.gov (United States)

    Real de Asúa, Diego; Costa, Ramón; Galván, Jose María; Filigheddu, María Teresa; Trujillo, Davinia; Cadiñanos, Julen

    2014-01-01

    The term "amyloidosis" encompasses the heterogeneous group of diseases caused by the extracellular deposition of autologous fibrillar proteins. The global incidence of amyloidosis is estimated at five to nine cases per million patient-years. While amyloid light-chain (AL) amyloidosis is more frequent in developed countries, amyloid A (AA) amyloidosis is more common in some European regions and in developing countries. The spectrum of AA amyloidosis has changed in recent decades owing to: an increase in the median age at diagnosis; a percent increase in the frequency of primary AL amyloidosis with respect to the AA type; and a substantial change in the epidemiology of the underlying diseases. Diagnosis of amyloidosis is based on clinical organ involvement and histological evidence of amyloid deposits. Among the many tinctorial characteristics of amyloid deposits, avidity for Congo red and metachromatic birefringence under unidirectional polarized light remain the gold standard. Once the initial diagnosis has been made, the amyloid subtype must be identified and systemic organ involvement evaluated. In this sense, the (123)I-labeled serum amyloid P component scintigraphy is a safe and noninvasive technique that has revolutionized the diagnosis and monitoring of treatment in systemic amyloidosis. It can successfully identify anatomical patterns of amyloid deposition throughout the body and enables not only an initial estimation of prognosis, but also the monitoring of the course of the disease and the response to treatment. Given the etiologic diversity of AA amyloidosis, common therapeutic strategies are scarce. All treatment options should be based upon a greater control of the underlying disease, adequate organ support, and treatment of symptoms. Nevertheless, novel therapeutic strategies targeting the formation of amyloid fibrils and amyloid deposition may generate new expectations for patients with AA amyloidosis.

  5. A Case of Familial Lichen Amyloidosis

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    Şeniz Ergin

    2008-12-01

    Full Text Available Familial lichen amyloidosis which is also referred to familial primary cutaneous amyloidosis is a rare clinical variant of cutaneous amyloidosis. Lichen amyloidosis is characterized by persistent, pruritic, small brown papules often located on anterior surfaces of legs which show tendency to form plaques. Amyloid deposits would be identified in papillary dermis in histopathological examination. In our clinic, a 42 year old woman with a widespread involvement describing that similar skin findings were present in her both daughters, elder brother and her nephew was evaluated with suspicion of lichen amyloidosis. In histopathological examination of the involved skin, because of determining amyloid deposits in papillary dermis the case was cited as lichen amyloidosis. Our case was searched for the accompanying diseases such as atopic dermatitis, chronic urticaria, lichen planus, multiple endocrine neoplasia and Kimura disease. The family history of our patient was consistent with autosomal dominant inheritance. Familial lichen amyloidosis has been reported as cases with autosomal dominant inheritance from Russia, Germany, United Kingdom and South America. The genetic researches over familial lichen amylodiosis are limited to the cases with multiple endocrine neoplasia. In this rarely reported cases, further genetical researches are necessary in order to determine the responsible gen locus. (Turkderm 2008; 42: 137-9

  6. An interesting case of renal amyloidosis

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    A Hajra

    2016-01-01

    Full Text Available In amyloidosis, there is an extracellular deposition of beta-sheet fibrils. Over 25 proteins have been demonstrated to form amyloid. One of them is Ig amyloid light (AL chains. We are presenting a 40-year-old female who presented with progressive kyphoscoliosis for last 2 years following a minor trauma and bilateral pedal edema for last 3 months. On further investigation, we found that she had a biclonal variety of MM with amyloidosis of kidney leading to massive proteinuria. Very few case reports are available where patient with biclonal variety of MM develop renal amyloidosis.

  7. AL Amyloidosis Complicated by Persistent Oral Bleeding

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    Luiz Antonio Liarte Marconcini

    2015-01-01

    Full Text Available A case of amyloid light chain (AL amyloidosis is presented here with uncontrolled bleeding after a nonsurgical dental procedure, most likely multifactorial in nature, and consequently treated with a multidisciplinary approach.

  8. Genetics Home Reference: primary localized cutaneous amyloidosis

    Science.gov (United States)

    ... are mildly itchy. Nodular amyloidosis is characterized by firm, raised bumps (nodules) that are pink, red, or ... 31: Cytokines, receptors, signal transduction and physiology. Cytokine Growth Factor Rev. 2015 Oct;26(5):545-58. ...

  9. Secondary Cutaneous Amyloidosis Associated with Mycosis Fungoides

    Science.gov (United States)

    2018-02-16

    and has been reported with PUVA use. To date, there are three reported cases of secondary localized cutaneous amyloidosis associated with mycosis...Secondary localized cutaneous amyloidosis is often not clinically apparent , but may be seen histologically. It is associated with several skin tumors...fungoides prior to any treatment. We present a case of a 39-year-old female who presented to the dermatology clinic for evaluation of facial acne

  10. Obesity is a significant susceptibility factor for idiopathic AA amyloidosis.

    Science.gov (United States)

    Blank, Norbert; Hegenbart, Ute; Dietrich, Sascha; Brune, Maik; Beimler, Jörg; Röcken, Christoph; Müller-Tidow, Carsten; Lorenz, Hanns-Martin; Schönland, Stefan O

    2018-01-24

    To investigate obesity as susceptibility factor in patients with idiopathic AA amyloidosis. Clinical, biochemical and genetic data were obtained from 146 patients with AA amyloidosis. Control groups comprised 40 patients with long-standing inflammatory diseases without AA amyloidosis and 56 controls without any inflammatory disease. Patients with AA amyloidosis had either familial Mediterranean fever (FMF) or long-standing rheumatic diseases as underlying inflammatory disease (n = 111, median age 46 years). However, in a significant proportion of patients with AA amyloidosis no primary disease was identified (idiopathic AA; n = 37, median age 60 years). Patients with idiopathic AA amyloidosis were more obese and older than patients with AA amyloidosis secondary to FMF or rheumatic diseases. Serum leptin levels correlated with the body mass index (BMI) in all types of AA amyloidosis. Elevated leptin levels of more than 30 µg/l were detected in 18% of FMF/rheumatic + AA amyloidosis and in 40% of patients with idiopathic AA amyloidosis (p = .018). Finally, the SAA1 polymorphism was confirmed as a susceptibility factor for AA amyloidosis irrespective of the type of the disease. Obesity, age and the SAA1 polymorphism are susceptibility factors for idiopathic AA amyloidosis. Recent advances in treatment of FMF and rheumatic disorders will decrease the incidence of AA amyloidosis due to these diseases. Idiopathic AA, however, might be an emerging problem in the ageing and increasingly obese population.

  11. Amyloidosis

    Science.gov (United States)

    ... in tissue. This condition is less common with modern dialysis techniques. Race. People of African descent appear ... logo are trademarks of Mayo Foundation for Medical Education and Research. © 1998-2018 Mayo Foundation for Medical ...

  12. Amyloidosis

    Science.gov (United States)

    ... to Content ASCO.org Conquer Cancer Foundation ASCO Journals Donate eNews Signup f Cancer.net on Facebook t Cancer.net on Twitter q Cancer.net on YouTube g Cancer.net on Google Menu Home Types of Cancer Navigating Cancer Care Coping With Cancer Research and Advocacy Survivorship Blog About ...

  13. Macular Amyloidosis and Epstein-Barr Virus

    Directory of Open Access Journals (Sweden)

    Yalda Nahidi

    2016-01-01

    Full Text Available Background. Amyloidosis is extracellular precipitation of eosinophilic hyaline material of self-origin with special staining features and fibrillar ultrastructure. Macular amyloidosis is limited to the skin, and several factors have been proposed for its pathogenesis. Detection of Epstein-Barr virus (EBV DNA in this lesion suggests that this virus can play a role in pathogenesis of this disease. Objective. EBV DNA detection was done on 30 skin samples with a diagnosis of macular amyloidosis and 31 healthy skin samples in the margin of removed melanocytic nevi by using PCR. Results. In patients positive for beta-globin gene in PCR, BLLF1 gene of EBV virus was positive in 23 patients (8 patients in case and 15 patients in the control group. There was no significant difference in presence of EBV DNA between macular amyloidosis (3.8% and control (23.8% groups (P=0.08. Conclusion. The findings of this study showed that EBV is not involved in pathogenesis of macular amyloidosis.

  14. [Osteoarticular amyloidosis caused by dialysis].

    Science.gov (United States)

    Orzincolo, C; Bedani, P L; Scutellari, P N; Cardona, P; Farinelli, A; Vita, G

    1988-01-01

    The accumulation of amyloid in the bone and joint system has recently been recognized as a peculiar disease in patients undergoing long-term hemodialysis (5 years at least), especially in those who use cuprophan membranes. The pathology of amyloidosis is characterized by deposits of amyloid (beta 2-microglobulin mainly) in the bone, in the synovia, and in pericapsular soft tissues. The skeleton of 46 long-term hemodialysis patients (19 males and 27 females) was studied by X-ray: bone and joint abnormalities due to amyloid deposition were observed in 45% of cases. The shoulder, hip, and wrist were the most frequently involved joints. Destructive spondyloarthropathy was present in 15% of cases. The radiographic patterns of AOD are generally divided into axial and peripheral lesions. In the appendicular skeleton abnormalities include: well-defined lytic areas (geodes), pathologic fractures, marginal erosions, and periarticular soft tissue swelling. Destructive spondyloarthropathy is frequently present in the cervical spine (85% of our cases), and is characterized by narrowing of the intervertebral space, marginal erosion, and subchondral bone sclerosis of the vertebral body.

  15. Autologous Stem Cell Transplant for AL Amyloidosis

    Directory of Open Access Journals (Sweden)

    Vivek Roy

    2012-01-01

    Full Text Available AL amyloidosis is caused by clonal plasma cells that produce immunoglobulin light chains which misfold and get deposited as amyloid fibrils. Therapy directed against the plasma cell clone leads to clinical benefit. Melphalan and corticosteroids have been the mainstay of treatment for a number of years and the recent availability of other effective agents (IMiDs and proteasome inhibitors has increased treatment options. Autologous stem cell transplant (ASCT has been used in the treatment of AL amyloidosis for many years. It is associated with high rates of hematologic response and improvement in organ function. However, transplant carries considerable risks. Careful patient selection is important to minimize transplant related morbidity and mortality and ensure optimal patient outcomes. As newer more affective therapies become available the role and timing of ASCT in the overall treatment strategy of AL amyloidosis will need to be continually reassessed.

  16. Incidence and survival in non-hereditary amyloidosis in Sweden

    Directory of Open Access Journals (Sweden)

    Hemminki Kari

    2012-11-01

    Full Text Available Abstract Background Amyloidosis is a heterogeneous disease caused by deposition of amyloid fibrils in organs and thereby interfering with physiological functions. Hardly any incidence data are available and most survival data are limited to specialist clinics. Methods Amyloidosis patients were identified from the Swedish Hospital Discharge and Outpatients Registers from years 2001 through 2008. Results The incidence of non-hereditary amyloidosis in 949 patients was 8.29 per million person-years and the diagnostic age with the highest incidence was over 65 years. Secondary systemic amyloidosis showed an incidence of 1 per million and a female excess and the largest number of subsequent rheumatoid arthritis deaths; the median survival was 4 years. However, as rheumatoid arthritis deaths also occurred in other diagnostic subtypes, the incidence of secondary systemic amyloidosis was likely to be about 2.0 per million. The median survival of patients with organ-limited amyloidosis was 6 years. Most myeloma deaths occurred in patients diagnosed with unspecified or ‘other’ amyloidosis. These subtypes probably accounted for most of immunoglobulin light chain (AL amyloidosis cases; the median survival time was 3 years. Conclusions The present diagnostic categorization cannot single out AL amyloidosis in the Swedish discharge data but, by extrapolation from myeloma cases, an incidence of 3.2 per million could be ascribed to AL amyloidosis. Similarly, based on rheumatoid arthritis death rates, an incidence of 2.0 could be ascribed to secondary systemic amyloidosis.

  17. Gastric Outlet Obstruction due to Gastrointestinal Amyloidosis.

    Science.gov (United States)

    Cohen, Jared A; An, Jong; Brown, Alexander W; Spearman, Darren; Paredes, Angelo

    2017-03-01

    A 64- year-old man with smoldering myeloma presented to the hospital for nausea, vomiting, and PO intolerance. Abdominal CT demonstrated massive gastric distention and collapsed proximal duodenum consistent with gastric outlet obstruction (GOO). Esophagogastroduodenoscopy demonstrated pyloric edema. Duodenal biopsies were consistent with AL amyloidosis. Given the concerns for bleeding risk and immediate need to start chemotherapy, surgery was deferred. Chemotherapy was initiated with a good clinical response. Our non-operative approach is novel, eliminates perioperative adverse events, allows for early initiation of chemotherapy, and can serve as a model for patients with GOO resulting from AL amyloidosis who are not surgical candidates.

  18. Reiter′s Sundrome With Secondary Amyloidosis

    Directory of Open Access Journals (Sweden)

    Sayal S.K

    2001-01-01

    Full Text Available A 35 year old male had arthropathy of large joints, psoriasiform skin lesions and circinate balanitis preceded by recurrent episodes of dysentery. He also developed feature of nephritic syndrome due to secondary amyloidosis as confirmed by renal and rectal biopsy.

  19. Primary Amyloidosis Presenting as Small Bowel Encapsulation

    Directory of Open Access Journals (Sweden)

    Jennifer Jones

    2004-01-01

    Full Text Available Amyloidosis is a pathological process which encompasses a spectrum of diseases that result from extracellular deposition of pathological fibrillar proteins. Clinical presentations vary depending on the organs involved. There is no documented case of amyloidosis presenting as small bowel encapsulation. A previously healthy 62-year-old man developed a small bowel obstruction in 1997. At surgery, a peculiar membrane encasing his entire small bowel was discovered. This appeared to have no vascularity and was removed without difficulty, exposing a grossly normal bowel. Histopathology revealed thick bands of collagen overlying the peritoneal surface, which was congo red positive and showed apple green birefringence. The findings were consistent with encapsulating peritonitis due to amyloidosis. There was no history or symptoms of any chronic inflammatory condition and he became symptom-free postoperatively. An abdominal fat pad biopsy failed to demonstrate amyloidosis. Endoscopic duodenal biopsies revealed classical primary amyloidosis. Quantitative immunoglobulins, lactate dehydrogenase, C3, C4 and beta-2 microglobulin were normal. Protein electrophoresis identified monoclonal paraprotein, immunoglobulin G lambda 3.7 g/L. Bone marrow biopsy and aspirate revealed only a mild plasmacytosis (5% to 10%. Echocardiogram and skeletal survey were normal. He had mild proteinuria. Complete blood count, C-reactive protein, calcium, albumin and total protein were normal. No specific therapy was instituted. In January of 1998 the patient remained asymptomatic with no gastrointestinal, cardiovascular or constitutional symptoms. He had developed nephrotic range proteinuria (3.95 g/24 h, microalbuminuria, hypoalbuminemia and a renal biopsy consistent with renal amyloidosis. In 1999 there was an increase in the monoclonal paraprotein (6.2 g/L. The remaining investigations were normal except for an echocardiogram which showed left ventricular hypertrophy but a normal

  20. Subtle neuropsychiatric and neurocognitive changes in hereditary gelsolin amyloidosis (AGel amyloidosis).

    Science.gov (United States)

    Kantanen, Mari; Kiuru-Enari, Sari; Salonen, Oili; Kaipainen, Markku; Hokkanen, Laura

    2014-01-01

    Hereditary gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominant form of systemic amyloidosis caused by a c.640G>A or c.640G>T mutation in the gene coding for gelsolin. Principal clinical manifestations include corneal lattice dystrophy, cranial neuropathy and cutis laxa with vascular fragility. Signs of minor CNS involvement have also been observed, possibly related to cerebral amyloid angiopathy (CAA). To investigate further if AGel amyloidosis carries a risk for a specific neuropsychological or psychiatric symptomatology we studied 35 AGel patients and 29 control subjects. Neuropsychological tests showed abnormalities in visuocontructional and -spatial performance in AGel patients, also some indication of problems in processing efficacy was found. At psychiatric evaluation the patient group showed more psychiatric symptomatology, mainly depression. In brain MRI, available in 16 patients and 14 controls, we found microhemorrhages or microcalcifications only in the patient group, although the number of findings was small. Our study shows that AGel amyloidosis can be associated with visuoconstructional problems and depression, but severe neuropsychiatric involvement is not characteristic. The gelsolin mutation may even induce cerebrovascular fragility, but further epidemiological and histopathological as well as longitudinal follow-up studies are needed to clarify gelsolin-related vascular pathology and its clinical consequences.

  1. Subtle neuropsychiatric and neurocognitive changes in hereditary gelsolin amyloidosis (AGel amyloidosis

    Directory of Open Access Journals (Sweden)

    Mari Kantanen

    2014-07-01

    Full Text Available Hereditary gelsolin amyloidosis (AGel amyloidosis is an autosomal dominant form of systemic amyloidosis caused by a c.640G>A or c.640G>T mutation in the gene coding for gelsolin. Principal clinical manifestations include corneal lattice dystrophy, cranial neuropathy and cutis laxa with vascular fragility. Signs of minor CNS involvement have also been observed, possibly related to cerebral amyloid angiopathy (CAA. To investigate further if AGel amyloidosis carries a risk for a specific neuropsychological or psychiatric symptomatology we studied 35 AGel patients and 29 control subjects. Neuropsychological tests showed abnormalities in visuocontructional and -spatial performance in AGel patients, also some indication of problems in processing efficacy was found. At psychiatric evaluation the patient group showed more psychiatric symptomatology, mainly depression. In brain MRI, available in 16 patients and 14 controls, we found microhemorrhages or microcalcifications only in the patient group, although the number of findings was small. Our study shows that AGel amyloidosis can be associated with visuoconstructional problems and depression, but severe neuropsychiatric involvement is not characteristic. The gelsolin mutation may even induce cerebrovascular fragility, but further epidemiological and histopathological as well as longitudinal follow-up studies are needed to clarify gelsolin-related vascular pathology and its clinical consequences.

  2. Laryngeal Amyloidosis Mimicking Glottic Cancer: A Case Report

    International Nuclear Information System (INIS)

    Lee, Sun Jin; Kim, Jee Young; Ahn, Kook Jin; Kim, Bum Soo; Park, Young Hak

    2010-01-01

    Amyloidosis is a slowly progressive, benign disease that is characterized by the extracellular deposition of fibrillar proteins in many different tissues and organs throughout the body. Primary amyloidosis can be subdivided into the systemic and localized forms. The localized form is less common than the systemic form and the larynx is the most frequently affected site. The importance of laryngeal amyloidosis lies in its possible confusion with glottic cancer because of the clinical feature. We report here on a case of laryngeal amyloidosis in a 47-year-old man who suffered from progressive dyspnea

  3. Laryngeal Amyloidosis Mimicking Glottic Cancer: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sun Jin; Kim, Jee Young; Ahn, Kook Jin; Kim, Bum Soo [The Catholic University of Korea, Seoul (Korea, Republic of); Park, Young Hak [St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

    2010-08-15

    Amyloidosis is a slowly progressive, benign disease that is characterized by the extracellular deposition of fibrillar proteins in many different tissues and organs throughout the body. Primary amyloidosis can be subdivided into the systemic and localized forms. The localized form is less common than the systemic form and the larynx is the most frequently affected site. The importance of laryngeal amyloidosis lies in its possible confusion with glottic cancer because of the clinical feature. We report here on a case of laryngeal amyloidosis in a 47-year-old man who suffered from progressive dyspnea.

  4. Isolated Tricuspid Regurgitation: Initial Manifestation of Cardiac Amyloidosis

    Directory of Open Access Journals (Sweden)

    Dong Woog Yoon

    2015-12-01

    Full Text Available Amyloid deposits in the heart are not exceptional in systemic amyloidosis. The clinical manifestations of cardiac amyloidosis may include restrictive cardiomyopathy, characterized by progressive diastolic and eventually systolic biventricular dysfunction; arrhythmia; and conduction defects. To the best of our knowledge, no previous cases of isolated tricuspid regurgitation as the initial manifestation of cardiac amyloidosis have been reported. We describe a rare case of cardiac amyloidosis that initially presented with severe tricuspid regurgitation in a 42-year-old woman who was successfully treated with tricuspid valve replacement. Unusual surgical findings prompted additional evaluation that established a diagnosis of plasma cell myeloma.

  5. Gastrointestinal amyloidosis - a differential diagnostic problem

    Energy Technology Data Exchange (ETDEWEB)

    Beyer, D.; Krug, B.; Stelzner, M.

    1986-11-01

    The diagnostic radiologist may have problems with the differential diagnosis of gastrointestinal amyloidosis combined with only uncharacteristic clinical symptoms. In the stomach upper gastrointestinal series show in most cases stenosing submucosal masses in the gastric antrum with diminished peristalsis and pliability. Sonography reveals a circular thickening of the gastric antrum wall. Only a synopsis of radiologic changes, the patient's history, laboratory tests and biopsies render a clue to the correct diagnosis. In the small bowel segmental or total intestinal dilatation with sonographically demonstrable thickening of the bowel wall and diminished motility, prolonged transit and eventually obstruction or paralytic ileus can be demonstrated. In patients with simultaneous plasmocytoma the radiologist has to take a gastrointestinal involvement by concurrent amyloidosis into account.

  6. Gastrointestinal amyloidosis - a differential diagnostic problem

    International Nuclear Information System (INIS)

    Beyer, D.; Krug, B.; Stelzner, M.; Koeln Univ.

    1986-01-01

    The diagnostic radiologist may have problems with the differential diagnosis of gastrointestinal amyloidosis combined with only uncharacteristic clinical symptoms. In the stomach upper gastrointestinal series show in most cases stenosing submucosal masses in the gastric antrum with diminished peristalsis and pliability. Sonography reveals a circular thickening of the gastric antrum wall. Only a synopsis of radiologic changes, the patient's history, laboratory tests and biopsies render a clue to the correct diagnosis. In the small bowel segmental or total intestinal dilatation with sonographically demonstrable thickening of the bowel wall and diminished motility, prolonged transit and eventually obstruction or paralytic ileus can be demonstrated. In patients with simultaneous plasmocytoma the radiologist has to take a gastrointestinal involvement by concurrent amyloidosis into account. (orig.) [de

  7. Medical image of the week: pulmonary amyloidosis

    Directory of Open Access Journals (Sweden)

    Rohant N

    2015-06-01

    Full Text Available A 61-year-old man with chronic obstructive pulmonary disease (COPD on oxygen and chronic steroids presented with a mechanical fall. Initial vital signs and laboratory studies were unremarkable. A chest radiograph performed in the emergency department to evaluate for fractures demonstrated innumerable, high-density pulmonary nodules most pronounced and confluent in the periphery and lung bases (Figure 1. Computed tomography of the chest demonstrated multiple pulmonary nodules and masses with course, eccentric calcifications (Figure 2. Further workup, including biopsies of the masses and full body imaging, revealed primary pulmonary amyloidosis limited to the lung parenchyma. Primary amyloidosis, a disorder of extracellular proteinaceous fibril deposition, is rarely seen affecting the lung parenchyma as the only site of disease as demonstrated here (1. The gentleman underwent autologous bone marrow transplant and did well for approximately 5 years before he developed a progressive cough, hemoptysis, and increased oxygen requirements. He is now being evaluated for lung transplant.

  8. Autologous Stem Cell Transplant for AL Amyloidosis

    OpenAIRE

    Roy, Vivek

    2012-01-01

    AL amyloidosis is caused by clonal plasma cells that produce immunoglobulin light chains which misfold and get deposited as amyloid fibrils. Therapy directed against the plasma cell clone leads to clinical benefit. Melphalan and corticosteroids have been the mainstay of treatment for a number of years and the recent availability of other effective agents (IMiDs and proteasome inhibitors) has increased treatment options. Autologous stem cell transplant (ASCT) has been used in the treatment of ...

  9. Leukocyte derived chemotaxin 2 (ALECT2 amyloidosis

    Directory of Open Access Journals (Sweden)

    Uday P Kulkarni

    2015-07-01

    Full Text Available We describe the first case from India of ALECT2 amyloidosis. An adult Punjabi male presented with progressive renal dysfunction and non-nephrotic range proteinuria. Serum protein electrophoresis and Immunofixation were normal, with mildly elevated serum free light chain ratio. Renal biopsy confirmed the presence of amyloid. Immunohistochemistry was negative for monoclonal light chains. Proteomic analysis confirmed the presence of ALECT2 amyloid. The present case highlights the need for confirmatory testing for typing of amyloid.

  10. Immunoglobulin D and cardiac amyloidosis: development and a case illustration.

    Science.gov (United States)

    Servonnet, Aurélie; Bouvier, François; Garcia Hejl, Carine; Sanmartin, Nancy; Renard, Christophe

    2016-06-01

    Amyloidosis results from extra-cellular deposition of proteins which interfere with tissue function. We report the case of a patient with pathological heart involvement which is caused by immunoglobulin D amyloidosis, and review current data on the amyloidois diagnosis and management.

  11. Renal amyloid A amyloidosis as a complication of hidradenitis suppurativa

    DEFF Research Database (Denmark)

    Schandorff, Kristine D; Miller, Iben M; Krustrup, Dorrit

    2016-01-01

    Rheumatic disease is the dominant cause of amyloid A (AA) amyloidosis, but other chronic inflammatory diseases may have similar consequences. Hidradenitis suppurativa (HS) is a relatively common, but little known skin disease characterized by chronic inflammation. Here we present a case of chroni...... HS leading to biopsy-verified severe renal AA amyloidosis and dialysis dependency....

  12. Idiopathic systemic AA-amyloidosis in a skunk (Mephitis mephitis).

    Science.gov (United States)

    Elhensheri, Mohamed; Linke, Reinhold P; Blankenburg, Anja; Beineke, Andreas

    2012-03-01

    This report describes a case of systemic amyloidosis in a captive striped skunk. At necropsy, bilateral alopecia, as well as reno-, hepato-, and splenomegaly were present. Congo red staining and immunohistochemistry revealed depositions of AA-amyloid in different organs. The lack of a predisposing disease is suggestive of idiopathic systemic AA-amyloidosis.

  13. Amyloidosis in Hodgkin's Disease | Falkson | South African Medical ...

    African Journals Online (AJOL)

    A patient with a 13-year history of Hodgkin's disease, who developed the terminal complication of amyloidosis manifesting in a nephrotic syndrome resulting in death, is reported. The incidence of this rare complication is reviewed from reports in the literature; to date only 53 unequivocal cases of amyloidosis, in association ...

  14. Dysautonomias in Amyloidosis: : Need for an interdisciplinary approach

    NARCIS (Netherlands)

    Hazenberg, B. P. C.

    2013-01-01

    Systemic amyloidosis is a life-threatening and frequently unrecognized cause of dysautonomia. Autonomic neuropathy is a common manifestation of AL amyloidosis (caused by deposition of an immunoglobulin free light chain produced by an underlying plasma cell clone) and of autosomal dominant hereditary

  15. The Prevalence and Management of Systemic Amyloidosis in Western Countries

    NARCIS (Netherlands)

    Nienhuis, Hans L A; Bijzet, Johan; Hazenberg, Bouke P C

    BACKGROUND: Amyloidosis has been a mystery for centuries, but research of the last decennia has clarified many of the secrets of this group of diseases. A protein-based classification of amyloidosis helps to understand problems that were part of the obsolete clinical classification in primary,

  16. [Value of aspiration biopsy of subcutaneous fat in amyloidosis].

    Science.gov (United States)

    Ponce, P; Carvalho, F; Coelho, A

    1986-01-01

    Fine-needle aspiration of subcutaneous fat (FNAF) was performed in 24 patients, 12 with previously diagnosed amyloidosis presenting with proteinuria or nephrotic syndrome, and 12 presenting a nephrotic syndrome without amyloidosis on renal biopsy. FNAF was positive in 10 of 12 patients with amyloidosis (sensitivity: 83%) and negative in 12 of 12 patients with non-amyloid nephrotic syndrome (specificity: 100%). Considering a 2.5 to 10% prevalence of amyloidosis in adult patients with proteinuria or nephrotic syndrome, a positive FNAF is diagnostic of amyloidosis, and a negative FNAF rules out the diagnosis with a probability of 98 to 99%. FNAF is a simple and safe method which can be useful in patients who cannot undergo a renal biopsy.

  17. 77 FR 6466 - Schedule for Rating Disabilities; AL Amyloidosis (Primary Amyloidosis)

    Science.gov (United States)

    2012-02-08

    ... DEPARTMENT OF VETERANS AFFAIRS 38 CFR Part 4 RIN 2900-AN75 Schedule for Rating Disabilities; AL... Department of Veterans Affairs (VA) is amending its Schedule for Rating Disabilities by updating the schedule of ratings for the hemic and lymphatic systems to include AL amyloidosis. This regulatory action is...

  18. 75 FR 65279 - Schedule for Rating Disabilities; AL Amyloidosis (Primary Amyloidosis)

    Science.gov (United States)

    2010-10-22

    ... DEPARTMENT OF VETERANS AFFAIRS 38 CFR Part 4 RIN 2900-AN75 Schedule for Rating Disabilities; AL... document proposes to amend the Department of Veterans Affairs (VA) Schedule for Rating Disabilities (rating schedule) by updating the schedule of ratings for the hemic and lymphatic systems to include AL amyloidosis...

  19. A Case of Amyloidosis Presenting as Chronic Cholecystitis, Misdiagnosed as Polymyalgia Rheumatica.

    Science.gov (United States)

    Um, Yoo Jin; Kim, Hyoun Ah; Jung, Jin Hee; Cho, Hundo; Kang, Joon Koo

    2016-07-25

    Amyloidosis is a rare disease defined by extracellular deposits of amorphous fibrillar proteins, derived from aggregations of misfolded proteins. Localization of amyloidosis in the gallbladder is uncommon; only eight cases have been reported. We describe a case of amyloidosis diagnosed by cholecystectomy, which possibly also affected the liver and kidney. The patient was misdiagnosed with polymyalgia rheumatica, but after a cholecystectomy to treat chronic cholecystitis, we ultimately diagnosed him with amyloidosis. We review amyloidosis with gallbladder involvement in the literature.

  20. Amiloidosis oral nodular Oral nodular amyloidosis

    Directory of Open Access Journals (Sweden)

    P. Martos Díaz

    2008-02-01

    Full Text Available Introducción. La amiloidosis constituye una entidad marcada por el depósito de amiloide en diferentes tejidos. En la cavidad oral se manifiesta habitualmente en forma de macroglosia, y más raramente, como nódulos dispuestos en la superficie. Caso clínico. Varón afecto de Mieloma Múltiple, que comienza con lesiones nodulares en labio inferior y lengua. A raíz de estas lesiones, mediante estudio histológico, es diagnosticado de Amiloidosis Sistémica. Discusión. Los nódulos amiloideos en la cavidad oral, constituyen una manifestación rara de la amiloidosis sistémica. Su aparición conlleva la necesidad de realizar un diagnostico diferencial con otras entidades y el diagnostico de certeza se obtiene mediante el análisis histológico.Introduction. Amyloidosis is a condition characterized by the deposit of amyloid in different tissues. In the oral cavity it is usually manifested as macroglossia and, more rarely, as nodules on the surface. Clinical case. A man had multiple myeloma that began with nodular lesions of the lower lip and tongue. As a result of these lesions, the patient was diagnosed of systemic amyloidosis by histological study. Discussion. Amyloid nodules in the oral cavity are a rare manifestation of systemic amyloidosis. Its appearance entails the necessity to make I diagnose differential with other organizations and I diagnose of certainty is obtained by means of the histological analysis.

  1. Skin deposits in hereditary cystatin C amyloidosis

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Blöndal, H; Gudmundsson, G

    1990-01-01

    Clinically normal skin from 47 individuals aged 9-70 years was investigated. Cystatin C amyloid deposits were found in various locations of the skin by light and/or electron microscopy, in all 12 patients with a clinical history of hereditary cystatin C amyloidosis (HCCA). Six asymptomatic...... individuals, who had the Alu 1 restriction fragment length polymorphism (RFLP) marker reported to cosegregate with the disease, also had cystatin C amyloid deposits in the skin. Three asymptomatic individuals (age 17-46) belonging to the HCCA families were without amyloid in the skin but had Alu 1 RFLP marker...

  2. New insights into systemic amyloidosis: primary amyloidosis associated with tubercular lymphadenitis

    Directory of Open Access Journals (Sweden)

    Shivraj Meena, Nirmal Ghati, Rita Sood, Naval Kishore Vikram

    2014-11-01

    Full Text Available Tuberculosis is generally followed by secondary amyloidosis. The association of primary systemic amyloidosis with tuberculosis is very rare. There is only one case thus far reported in literature. We report such a rare case of primary amyloidosis with tuberculous lymphadenopathy. A 45 year old woman presented at the medicine department of all India institute of medical sciences , New Delhi with on & off erythematous rashes over both eyes for 1 year; low grade fever, fatigue and significant weight loss for 4 months, dysphagia for solid food since 1 month. Main finding on examination were pallor, macroglossia, bilateral periorbital erythematous rashes (racoon eyes, hepatomegaly & cardiomegaly. She had raised serum alkaline phosphatase level. Chest x-ray revealed cardiomegaly. USG abdomen revealed multiple retroperitoneal mesenteric lymph nodes and hepatomegaly. USG guided FNAC from mesenteric lymph node showed acid fast bacillus. Histological examination of liver biopsy showed amyloid deposition on congo red stain. Patient was treated with DOTS category I ATT with Bortezomib and Dexamethasone based weekly chemotherapy.

  3. NUCLEAR IMAGING IN THE DIAGNOSIS OF CARDIAC AMYLOIDOSIS

    Directory of Open Access Journals (Sweden)

    V. B. Sergienko

    2018-01-01

    Full Text Available Histological analysis of endomyocardial tissue is still the gold standard for the diagnosis of cardiac amyloidosis but has its limitations. Accordingly, there is a need for noninvasive techniques to cardiac amyloidosis diagnostics. Echocardiography and magnetic resonance imaging can show characteristics which may not be very specific for cardiac amyloid. Recently, new opportunities of nuclear imaging in risk stratification and assessment of prognosis for patients with cardiac amyloidosis have appeared. During the last two decades different classes of radiopharmaceuticals have been developed based on compounds tropic to the components of amyloid infiltrates. In this paper we describe the current possibilities and perspectives of nuclear medicine techniques in patients with cardiac amyloidosis, including osteotropic and neurotropic scintigraphy, single-photon and positron emission tomography

  4. [Otolaryngological complaints in tongue amyloidosis: a case report].

    Science.gov (United States)

    Pons Rocher, F; Guallart Doménech, F; Mompó Romero, L; Artazkozl del Toro, J J; Serrano Badía, E; Dalmau Galofré, J; Faubel Serra, M

    1994-01-01

    We present a case of Amyloidosis of the oral cavity associated to multiple mieloma, with otolaryngological symptom. Review of structural characterization of the disease, its pathogenesis and clinical disorders when displayed in thyroid, oral cavity and upper respiratory tract.

  5. Cardiac amyloidosis detection with pyrophosphate-99mTc scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Souza, D.S.F.; Ichiki, W.A.; Coura Filho, G.B.; Izaki, M.; Giorgi, M.C.P.; Soares Junior, J; Meneghetti, J.C. [Universidade de Sao Paulo (FM/USP), SP (Brazil). Fac. de Medicina. Instituto do Coracao. Servico de Medicina Nuclear e Imagem Molecular

    2008-07-01

    Full text: Introduction: Amyloidosis is a rare disease, characterized by extracellular deposition of insoluble amyloid fibrils in organs and tissues. It may affect virtually any system, preferably heart, kidneys and liver. The cardiac involvement produces a spectrum of clinical features, usually with progressive dysfunction. Early diagnosis is important for institution of appropriate therapy. Case report: Male patient, 75 years old, with diagnosed congestive heart failure functional class III and Mobitz II second-degree atrial-ventricular block, was hospitalized for implantation of definitive cardiac pacemaker. Patient mentioned history of worsening effort dyspnoea over a one-month period, progressing to minimum effort, orthopnea, paroxysmal nocturnal dyspnoea and paroxysms of dry cough, and swelling of lower limbs. Echocardiography showed diffuse hypertrophy of left ventricle (LV), with systolic dysfunction due to diffuse hypokinesia and hyperrefringent aspect in the septum. It was questioned a cardiac infiltrating process. Cardiac amyloidosis was considered as a diagnostic hypothesis. The patient underwent a pyrophosphate-{sup 99m}Tc scintigraphy, which showed abnormal tracer uptake in the heart projection, with diffuse pattern on the left ventricle walls, compatible with the clinical suspicion cardiac amyloidosis, which was later confirmed by endomyocardial biopsy. Discussion: In this case report, the patient had clinical and other auxiliary examinations, such as electrocardiography and Doppler echocardiography, compatible with cardiac amyloidosis, which led to implementation with pyrophosphate-{sup 99m}Tc scintigraphy and later endomyocardial biopsy. Cardiac amyloidosis occurs in about half the cases of primary amyloidosis (AL) and is rare in secondary amyloidosis (AA). Its clinical presentation is polymorphic and it can be classified into four distinctive types: restrictive cardiomyopathy, systolic dysfunction, postural hypotension and conduction disorders

  6. Cardiac amyloidosis detection with pyrophosphate-99mTc scintigraphy

    International Nuclear Information System (INIS)

    Souza, D.S.F.; Ichiki, W.A.; Coura Filho, G.B.; Izaki, M.; Giorgi, M.C.P.; Soares Junior, J; Meneghetti, J.C.

    2008-01-01

    Full text: Introduction: Amyloidosis is a rare disease, characterized by extracellular deposition of insoluble amyloid fibrils in organs and tissues. It may affect virtually any system, preferably heart, kidneys and liver. The cardiac involvement produces a spectrum of clinical features, usually with progressive dysfunction. Early diagnosis is important for institution of appropriate therapy. Case report: Male patient, 75 years old, with diagnosed congestive heart failure functional class III and Mobitz II second-degree atrial-ventricular block, was hospitalized for implantation of definitive cardiac pacemaker. Patient mentioned history of worsening effort dyspnoea over a one-month period, progressing to minimum effort, orthopnea, paroxysmal nocturnal dyspnoea and paroxysms of dry cough, and swelling of lower limbs. Echocardiography showed diffuse hypertrophy of left ventricle (LV), with systolic dysfunction due to diffuse hypokinesia and hyperrefringent aspect in the septum. It was questioned a cardiac infiltrating process. Cardiac amyloidosis was considered as a diagnostic hypothesis. The patient underwent a pyrophosphate- 99m Tc scintigraphy, which showed abnormal tracer uptake in the heart projection, with diffuse pattern on the left ventricle walls, compatible with the clinical suspicion cardiac amyloidosis, which was later confirmed by endomyocardial biopsy. Discussion: In this case report, the patient had clinical and other auxiliary examinations, such as electrocardiography and Doppler echocardiography, compatible with cardiac amyloidosis, which led to implementation with pyrophosphate- 99m Tc scintigraphy and later endomyocardial biopsy. Cardiac amyloidosis occurs in about half the cases of primary amyloidosis (AL) and is rare in secondary amyloidosis (AA). Its clinical presentation is polymorphic and it can be classified into four distinctive types: restrictive cardiomyopathy, systolic dysfunction, postural hypotension and conduction disorders. Cardiac

  7. Solitary plasmacytoma of spine with amyloidosis

    Directory of Open Access Journals (Sweden)

    Cui-yun SUN

    2017-01-01

    Full Text Available Objective To report the diagnosis and treatment of one case of solitary plasmacytoma of spine with amyloidosis and investigate the clinicopathological features combined with literatures. Methods and Results The patient was a 46-year-old woman. She suffered from weakness of both lower limbs, unsteady gait and numbness of toes for 20 d. MRI examination revealed an irregular mass behind the spinal cord at T5-7 level and T6-7 vertebral body accessory. The enhanced MRI showed obvious heterogeneous enhancement. The border was clear and spinal dura mater was compressed to shift forward. During operation, T5-7 processus spinosus and vertebral laminae were eroded, and the cortex of bone showed "moth-eaten" erosion. The intraspinal and extradural lesion had rich blood supply, loose bone structure and intact spinal dura mater. Histologically, tumor cells were composed of intensive small cells, and focal plasmacytoid cells were seen. Flake pink staining substance was among them. Artificial cracks were common and multinuclear giant tumor cells were scatteredly distributed. Immunohistochemical analysis showed the cytoplasm of tumor cells were diffusely positive for CD138, CD38 and vimentin (Vim,scatteredly positive for leukocyte common antigen (LCA, and negative for immune globulin κ light chain(IgGκ and λ light chain (IgGλ, CD99, S-100 protein (S-100, pan cytokeratin (PCK, epithelial membrane antigen (EMA, HMB45 and CD34. The Ki-67 labeling index was 1.25%. Congo red staining showed the pink staining substance was brownish red. Hybridization in situ examination showed the DNA content of IgGκ was more than that of IgGλ. The final pathological diagnosis was solitary plasmacytoma of spine with amyloidosis. The patient was treated with postoperative chemotherapy, and there was no recurrence or metastasis during 18-month follow-up period. Conclusions Solitary plasmacytoma of spine with amyloidosis is a rare tumor. The imaging features can offer a few

  8. Dialysis-related amyloidosis: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Scarpioni R

    2016-12-01

    Full Text Available R Scarpioni, M Ricardi, V Albertazzi, S De Amicis, F Rastelli, L Zerbini Department of Nephrology and Dialysis, Azienda Unità Sanitaria Local (AUSL Hospital “Guglielmo da Saliceto”, Piacenza, Italy Abstract: Amyloidosis refers to the extracellular tissue deposition of fibrils composed of low-molecular-weight subunits of a variety of proteins. These deposits may result in a wide range of clinical manifestations depending upon their type, location, and the amount of deposition. Dialysis-related amyloidosis is a serious complication of long-term dialysis therapy and is characterized by the deposition of amyloid fibrils, principally composed of β2 microglobulins (β2M, in the osteoarticular structures and viscera. Most of the β2M is eliminated through glomerular filtration and subsequent reabsorption and catabolism by the proximal tubules. As a consequence, the serum levels of β2M are inversely related to the glomerular filtration rate; therefore, in end-stage renal disease patients, β2M levels increase up to 60-fold. Serum levels of β2M are also elevated in several pathological conditions such as chronic inflammation, liver disease, and above all, in renal dysfunction. Retention of amyloidogenic protein has been attributed to several factors including type of dialysis membrane, prolonged uremic state and/or decreased diuresis, advanced glycation end products, elevated levels of cytokines and dialysate. Dialysis treatment per se has been considered to be an inflammatory stimulus, inducing cytokine production (such as interleukin-1, tumor necrosis factor-α, interleukin-6 and complement activation. The released cytokines are thought to stimulate the synthesis and release of β2M by the macrophages and/or augment the expression of human leukocyte antigens (class I, increasing β2M expression. Residual renal function is probably the best determinant of β2M levels. Therefore, it has to be maintained as long as possible. In this article

  9. Therapeutic regional dermabrasion in papular lichen amyloidosis of shins

    OpenAIRE

    Savant S

    1995-01-01

    Therapeutic regional dermabrasion of shins is a useful surgical method for planing away the persistent pruritic lichenified hyperkeratotic eruptions of papular lichen amyloidosis. Nine patients (6 females and 3 males) of 35 to 52 years age having papular lichen amyloidosis on shins, refractory to various medical lines of treatment for 5-12 years duration were subjected to regional dermabrasion. Extensor surfaces (shins) of both lower extremities (18 sites) in all 9 cases were treated by multi...

  10. Characteristics of AA amyloidosis patients in San Francisco.

    Science.gov (United States)

    Lejmi, Hiba; Jen, Kuang-Yu; Olson, Jean L; James, Sam H; Sam, Ramin

    2016-04-01

    AA amyloidosis due to subcutaneous injection of drugs of abuse has been described in the USA, but all the existing literature is from more than 20 years ago. There is more recent literature from Europe. We have observed a high incidence of AA amyloidosis in the county hospital in San Francisco. Here, we describe 24 patients who had kidney biopsy-proven AA amyloidosis from our hospital from 1998 to 2013. All the patients were thought to have AA amyloidosis from skin popping of illicit drugs after having exhausted the intravenous route. These patients with biopsy-proven AA amyloidosis were analysed further. All patients were found to have hepatitis C infection, hypertension was not common, most had advanced kidney failure, and acidosis was common as was tubulointerstitial involvement on the kidney biopsy. Other organ involvement included hepatomegaly and splenomegaly in a number of patients; direct myocardial involvement was not seen, but pulmonary hypertension, history of deep vein thrombosis and pulmonary embolism were common. The prognosis of these patients was poor. The mortality rate approached 50% 1 year after biopsy, and most of the patient needed dialysis shortly after diagnosis. Cessation of drug use seemed beneficial but rarely achievable. AA amyloidosis from skin popping is common in San Francisco. Most patients with renal involvement end up on dialysis, and mortality rates are exceedingly high. © 2015 Asian Pacific Society of Nephrology.

  11. Iodine-123-labelled serum amyloid P component scintigraphy in amyloidosis

    International Nuclear Information System (INIS)

    Saile, R.; Deveaux, M.; Marchandise, X.; Duquesnoy, B.

    1993-01-01

    This study describes the results of scintigraphy with iodine-123-labelled serum amyloid P component (SAP) as a means of establishing the distribution of organ involvement in amyloidosis. The significance of 123 I-SAP scans obtained in 15 patients with biopsy-proven AA or AL amyloidosis is discussed. Biopsy-proven amyloidosis was typically confirmed by scintigraphy, though such confirmation was not obtained in the kidneys in six patients with histological proof of extensive renal amyloid deposition. This lack of uptake may have been due to the accumulation of a major part of the 123 I-SAP in the spleen and/or liver. Twenty-four hour whole-body retention of 123 I-SAP was higher in patients with amyloidosis than in controls. Twenty-four hour tracer accumulation of the radioactivity in the extravascular compartment was notably greater in patients than in controls and appeared to be a good diagnostic criterion. We conclude that 123 I-SAP scintigraphy may be helpful for the evaluation of organ involvement not only in patients with biopsy-proven amyloidosis but also when a biopsy cannot be performed or when a strong suspicion of amyloidosis exists in spite of repeated negative biopsises. (orig.)

  12. Long-term follow-up after surgery in localized laryngeal amyloidosis

    NARCIS (Netherlands)

    Hazenberg, Aldert J. C.; Hazenberg, Bouke P. C.; Dikkers, Frederik G.

    2016-01-01

    To study effectiveness of surgery and watchful waiting in localized laryngeal amyloidosis, retrospective case series. This retrospective study comprises all consecutive patients with localized laryngeal amyloidosis surgically treated in a tertiary hospital between 1994 and February 2016. Recurrence

  13. Long-term follow-up after surgery in localized laryngeal amyloidosis

    NARCIS (Netherlands)

    Hazenberg, Aldert J. C.; Hazenberg, Bouke P. C.; Dikkers, Frederik G.

    To study effectiveness of surgery and watchful waiting in localized laryngeal amyloidosis, retrospective case series. This retrospective study comprises all consecutive patients with localized laryngeal amyloidosis surgically treated in a tertiary hospital between 1994 and February 2016. Recurrence

  14. The Prevalence and Management of Systemic Amyloidosis in Western Countries.

    Science.gov (United States)

    Nienhuis, Hans L A; Bijzet, Johan; Hazenberg, Bouke P C

    2016-04-01

    Amyloidosis has been a mystery for centuries, but research of the last decennia has clarified many of the secrets of this group of diseases. A protein-based classification of amyloidosis helps to understand problems that were part of the obsolete clinical classification in primary, secondary, and familial amyloidosis. All types of amyloid are secondary to some underlying precursor-producing process: each type is caused by a misfolded soluble precursor protein that becomes deposited as insoluble amyloid fibrils. The incidence of amyloidosis is not well documented, but probably falls between 5 and 13 per million per year. Prevalence data are scarce, but one UK study indicates about 20 per million inhabitants. Amyloidosis can be localized (amyloid deposited in the organ or tissue of precursor production) or systemic (amyloid at one or more sites distant from the site of precursor production). The major systemic types of amyloidosis are AL (associated with a light chain-producing plasma cell dyscrasia), AA (associated with longstanding inflammation), wild-type ATTR (associated with normal transthyretin and old age), and hereditary ATTR (associated with a transthyretin mutation) amyloidosis. Imaging techniques, such as cardiac ultrasound, magnetic resonance imaging, bone scintigraphy, and serum amyloid P component scintigraphy, are useful both for diagnosing amyloidosis and for assessing disease severity. Serologic markers are useful for detecting organ disease and disease monitoring during follow-up. Current treatment modalities are directed against the ongoing supply of precursor proteins and thereby aim to stop further accumulation of amyloid. Novel treatment modalities, such as interference with amyloid formation and even removal of amyloid, are being studied. A well-thought and planned monitoring during follow-up helps to assess the effect of treatment and to early detect possible progression of amyloidosis. Clinical management comprises histologic proof of amyloid

  15. Breast amyloidosis in a female patient with multiple myeloma: Ultrasonographic and mammographic findings

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Ah Rhm; Kim, Joon Mee; Nam, Se Jin [Inha University Hospital, Incheon (Korea, Republic of)

    2017-05-15

    Amyloidosis is a rare disease characterized by pathological protein deposits in organs or tissues. Breast involvement by amyloidosis is rare. We report a female patient with amyloidosis in the breast, with underlying multiple myeloma, which presents as a focal asymmetry on a screening mammogram and a low suspicious mass lesion by ultrasonography.

  16. Hereditary Fibrinogen Aα-Chain Amyloidosis in Asia: Clinical and Molecular Characteristics.

    Science.gov (United States)

    Yazaki, Masahide; Yoshinaga, Tsuneaki; Sekijima, Yoshiki; Kametani, Fuyuki; Okumura, Nobuo

    2018-01-22

    Hereditary fibrinogen Aα-chain amyloidosis (Aα-chain amyloidosis) is a type of autosomal dominant systemic amyloidosis caused by mutations in fibrinogen A α -chain gene ( FGA ). Patients with Aα-chain amyloidosis have been mainly reported in Western countries but have been rarely reported in Asia, with only five patients with Aα-chain amyloidosis being reported in Korea, China, and Japan. Clinically, the most prominent manifestation in Asian patients with Aα-chain amyloidosis is progressive nephropathy caused by excessive amyloid deposition in the glomeruli, which is similar to that observed in patients with Aα-chain amyloidosis in Western countries. In molecular features in Asian Aα-chain amyloidosis, the most common variant, E526V, was found in only one Chinese kindred, and other four kindred each had a different variant, which have not been identified in other countries. These variants are located in the C-terminal region (amino acid residues 517-555) of mature Aα-chain, which was similar to that observed in patients with Aα-chain amyloidosis in other countries. The precise number of Asian patients with Aα-chain amyloidosis is unclear. However, patients with Aα-chain amyloidosis do exist in Asian countries, and the majority of these patients may be diagnosed with other types of systemic amyloidosis.

  17. Diagnostic performance of amyloid A protein quantification in fat tissue of patients with clinical AA amyloidosis

    NARCIS (Netherlands)

    Hazenberg, Bouke P. C.; Bijzet, Johannes; Limburg, Pieter C.; Skinner, Martha; Hawkins, Philip N.; Butrimiene, Irena; Livneh, Avi; Lesnyak, Olga; Nasonov, Evgeney L.; Filipowicz-Sosnowska, Anna; Guel, Ahmet; Merlini, Giampaolo; Wiland, Piotr; Oezdogan, Huri; Gorevic, Peter D.; Ben Maiz, Hedi; Benson, Merrill D.; Direskeneli, Haner; Kaarela, Kalevi; Garceau, Denis; Hauck, Wendy; van Rijswijk, Martin

    Objective. Amyloid A protein quantification in fat tissue is a new immunochemical method for detecting AA amyloidosis, a rare but serious disease. The objective was to assess diagnostic performance in clinical AA amyloidosis. Methods. Abdominal subcutaneous fat tissue of patients with AA amyloidosis

  18. Localized gastrointestinal amyloidosis presenting with protein-losing enteropathy and massive hemorrhage

    Directory of Open Access Journals (Sweden)

    Bárbara Corrêa

    Full Text Available Amyloidosis of the gastrointestinal tract is usually a systemic disease. Localized gastrointestinal amyloidosis without evidence of extraintestinal involvement or an associated plasma cell dyscrasia is uncommon and does not usually cause death. We report a case of a patient with localized gastrointestinal amyloidosis who presented with protein-losing enteropathy and a fatal upper gastrointestinal bleed.

  19. Symptomatic Primary (AL Amyloidosis of the Stomach and Duodenum

    Directory of Open Access Journals (Sweden)

    Reidar Fossmark

    2013-01-01

    Full Text Available Primary (AL amyloidosis of the gastrointestinal tract is relatively rare, and symptomatic amyloidosis of the stomach is even more seldom. We present the case of a patient who was referred to upper endoscopy because of weight loss, nausea, and vomiting. Large areas of intramucosal hemorrhages were seen, and biopsies resulted in profuse bleeding stopped with endoscopic clips. The biopsies showed amyloid depositions and further workup revealed that the patient also had cardiac and neuropathic involvements. The patient started treatment with dexamethasone, melphalan and bortezomib. After treatment was started the nausea and epigastric discomfort improved, and a reduction in the biochemical markers troponin T, NT-proBNP, and M-component was observed. Gastric amyloidosis is rarely seen at upper endoscopy in patients without a previously established diagnosis, but the unusual endoscopic findings and bleeding tendency after biopsy should be kept in mind by gastroenterologists.

  20. Amyloidosis cutis dyschromica: A rare reticulate pigmentary dermatosis

    Directory of Open Access Journals (Sweden)

    Shyam Verma

    2015-01-01

    Full Text Available We are reporting a rare case of amyloidosis cutis dyschromica in a 41-year-old man. This is a rare form of primary cutaneous amyloidosis characterized by reticulate pigmentation with hypopigmented and hyperpigmented macules, onset in childhood, familial tendency in some, occasional mild itching and deposition of amyloid in the papillary dermis. Our case also had multiple bilaterally symmetrical hyperpigmented keratotic papules abutting the axillary vault resembling those seen in Dowling-Deogs disease. The other unusual feature in this patient was the strong family history of vitiligo, which we are unable to explain. We have also tried to explain the mechanism leading to the hyperpigmentation and hypopigmentation in amyloidosis cutis dyschromica.

  1. Clinical and histopathological study of primary cutaneous macular amyloidosis

    Directory of Open Access Journals (Sweden)

    Fatima Razvi

    2013-02-01

    Full Text Available Primary cutaneous amyloidosis often presents with pigmentary dystonias of the skin in the form of asymptomatic reticulate hyper-pigmentation or pruritic lichenoid papular lesions. The aim of this study was to evaluate the incidence of primary cutaneous macular amyloidosis and also to find out the possible etiological agents, to correlate their clinical disease with histopathological positivity for amyloid deposition, and to find out the percentage of positive cas-es by special stains. A total of 24 patients attending dermatology out-patient clinic of Princess Esra Hospital, Hyderabad over a pe-riod of 1 year presenting with hyperpigmented skin lesions and clinically diagnosed as macular amyloidosis were taken up for this study.

  2. Stabilisation of Laryngeal AL Amyloidosis with Long Term Curcumin Therapy

    Directory of Open Access Journals (Sweden)

    Terry Golombick

    2015-01-01

    Full Text Available Multiple myeloma (MM, smoldering myeloma (SMM, and monoclonal gammopathy of undetermined significance (MGUS represent a spectrum of plasma cell dyscrasias (PCDs. Immunoglobulin light chain amyloidosis (AL falls within the spectrum of these diseases and has a mortality rate of more than 80% within 2 years of diagnosis. Curcumin, derived from turmeric, has been shown to have a clinical benefit in some patients with PCDs. In addition to a clinical benefit in these patients, curcumin has been found to have a strong affinity for fibrillar amyloid proteins. We thus administered curcumin to a patient with laryngeal amyloidosis and smoldering myeloma and found that the patient has shown a lack of progression of his disease for a period of five years. This is in keeping with our previous findings of clinical benefits of curcumin in patients with plasma cell dyscrasias. We recommend further evaluation of curcumin in patients with primary AL amyloidosis.

  3. [AA amyloidosis: a little-known complication of chronic leg ulcer].

    Science.gov (United States)

    Waton, J; Fays-Michel, S; Chandeclerc, M L; Corby, S; Cuny, J F; Barbaud, A; Schmutz, J-L

    2008-02-01

    AA amyloidosis, secondary to inflammatory chronic diseases like rheumatoid arthritis, is often complicated by renal failure. Chronic inflammatory dermatoses constitute rare causes of AA amyloidosis. We describe two cases of AA amyloidosis discovered after renal failure in patients presenting leg ulcers for several years. AL amyloidosis was suspected in both cases because of a history of monoclonal gammopathy in one patient and of plasmocytoma in the other. The diagnosis of AA amyloidosis was confirmed on renal histology through the detection of AA antibodies in amyloid deposits. No extrarenal amyloidosis was seen in either patient and there were no inflammatory diseases other than chronic leg ulcers. AA amyloidosis is caused by serum amyloid protein A (SAA), a reactive inflammatory protein. AA amyloidosis is thus caused by chronic inflammatory diseases, but only rarely by cutaneous inflammatory diseases. To our knowledge, the literature contains only seven other published cases of AA amyloidosis secondary to chronic leg ulcers. A review of the literature does not indicate whether cure of ulcers has any effect on the accompanying renal failure. We imagine that AA amyloidosis secondary to leg ulcer is in fact under-diagnosed. However, since the first specific treatment for AA amyloidosis is currently being evaluated by the Food and Drug Administration, it is essential that this serious complication of chronic leg ulcers be widely recognised.

  4. [Hepatic amyloidosis as cause of severe intrahepatic cholestasis].

    Science.gov (United States)

    Gavilán, J C; Bermúdez, F J; Márquez, A; Sánchez-Carrillo, J J; González-Santos, P

    2003-01-01

    The liver is frequently involved by amyloidosis, but hyperbilirubinemia and liver failure are uncommon features. A mild elevation of the serum alkaline phosphatase value and, less frequently, hepatomegaly are the most common findings. Usually the patients have no symptoms related with the liver involvement; the clinical manifestation and the long term prognosis depends on the renal and cardiac disease. We report an unusual clinical presentation of primary amyloidosis in a previously asymptomatic 65 years old woman who was admitted to the hospital because of ictericia and ascitis mimicking a drug induced acute hepatic failure.

  5. Thermal Stability Threshold for Amyloid Formation in Light Chain Amyloidosis

    Directory of Open Access Journals (Sweden)

    Tanya L. Poshusta

    2013-11-01

    Full Text Available Light chain (AL amyloidosis is a devastating disease characterized by amyloid deposits formed by immunoglobulin light chains. Current available treatments involve conventional chemotherapy and autologous stem cell transplant. We have recently concluded a phase III trial comparing these two treatments. AL amyloidosis patients who achieve hematological complete response (CR do not necessarily achieve organ response regardless of the treatment they received. In order to investigate the possible correlation between amyloid formation kinetics and organ response, we selected AL amyloidosis patients from the trial with kidney involvement and CR after treatment. Six patients were selected and their monoclonal immunoglobulin light chains were characterized. The proteins showed differences in their stability and their kinetics of amyloid formation. A correlation was detected at pH 7.4, showing that less stable proteins are more likely to form amyloid fibrils. AL-T03 is too unstable to form amyloid fibrils at pH 7.4. This protein was found in the only patient in the study that had organ response, suggesting that partially folded species are required for amyloid formation to occur in AL amyloidosis.

  6. Frictional amyloidosis in Oman - A study of ten cases

    Directory of Open Access Journals (Sweden)

    Mysore Venkataram

    2002-01-01

    Full Text Available Macular amyloidosis is an important cause for cutaneous pigmentation, the aetiology of which is poorly understood. Friction has recently been implicated the causation of early lesions, referred to as frictional amyloidosis. Confirmation of diagnosis by the detect on of amyloid using histochemical stains is inconsistent. Ten patients with pigmentation suggestive of macular amyloidosis were studied with detailed history, clinical examination, biopsy for histochemistry and electron microscopy. Nine out of ten patients had a history of prolonged friction with various objects such as bath sponges, brushes, towels, plant sticks and leaves. Amyloid was demonstrated by histochemical staining in only six out of ten cases. In the remaining four cases, amyloid was detected by electron microscopy. These consisted of aggregates of non-branching, extracellular, intertwining fibres measuring between 200-500 nm in length and between 20-25 nm in diameter. The study confirms the role of friction in the causation of this condition. Histochemical stains are not always successful in the detection of amyloid and electron microscopy is helpful for confirming its presence. The term frictional amyloidosis aptly describes the condition.

  7. Laryngeal Presentation of Systemic Apolipoprotein A-I-Derived Amyloidosis

    NARCIS (Netherlands)

    Hazenberg, Aldert J. C.; Dikkers, Frederik G.; Hawkins, Philip N.; Bijzet, Johan; Rowczenio, Dorota; Gilbertson, Janet; Posthumus, Marcel D.; Leijsma, Martha K.; Hazenberg, Bouke P. C.

    Objective: To study the clinical and pathological characteristics of two patients with laryngeal apolipoprotein A-I (apoA-I)-derived (AApoAI) amyloidosis with the apolipoprotein A-I variants Leu174Ser and Leu178Pro, respectively. The latter variant has not been associated with amyloid before. Study

  8. Systemic AA amyloidosis in the red fox (Vulpes vulpes).

    Science.gov (United States)

    Rising, Anna; Cederlund, Ella; Palmberg, Carina; Uhlhorn, Henrik; Gaunitz, Stefan; Nordling, Kerstin; Ågren, Erik; Ihse, Elisabet; Westermark, Gunilla T; Tjernberg, Lars; Jörnvall, Hans; Johansson, Jan; Westermark, Per

    2017-11-01

    Amyloid A (AA) amyloidosis occurs spontaneously in many mammals and birds, but the prevalence varies considerably among different species, and even among subgroups of the same species. The Blue fox and the Gray fox seem to be resistant to the development of AA amyloidosis, while Island foxes have a high prevalence of the disease. Herein, we report on the identification of AA amyloidosis in the Red fox (Vulpes vulpes). Edman degradation and tandem MS analysis of proteolyzed amyloid protein revealed that the amyloid partly was composed of full-length SAA. Its amino acid sequence was determined and found to consist of 111 amino acid residues. Based on inter-species sequence comparisons we found four residue exchanges (Ser31, Lys63, Leu71, Lys72) between the Red and Blue fox SAAs. Lys63 seems unique to the Red fox SAA. We found no obvious explanation to how these exchanges might correlate with the reported differences in SAA amyloidogenicity. Furthermore, in contrast to fibrils from many other mammalian species, the isolated amyloid fibrils from Red fox did not seed AA amyloidosis in a mouse model. © 2017 The Protein Society.

  9. Secondary amyloidosis in a bull with Chediak-Higashi syndrome.

    Science.gov (United States)

    Burns, G L; Meyers, K M; Prieur, D J

    1984-01-01

    A ten year old Hereford bull with Chediak-Higashi syndrome was examined at necropsy after a lifelong history of recurrent bacterial infections. Amyloidosis, which has not been previously reported in Chediak-Higashi, was identified in liver, spleen and kidney. Images Fig. 1. Fig. 2. PMID:6713250

  10. Secondary amyloidosis in a bull with Chediak-Higashi syndrome.

    OpenAIRE

    Burns, G L; Meyers, K M; Prieur, D J

    1984-01-01

    A ten year old Hereford bull with Chediak-Higashi syndrome was examined at necropsy after a lifelong history of recurrent bacterial infections. Amyloidosis, which has not been previously reported in Chediak-Higashi, was identified in liver, spleen and kidney.

  11. Renal Involvement in AA Amyloidosis: Clinical Outcomes and Survival

    Directory of Open Access Journals (Sweden)

    Murvet Yilmaz

    2013-03-01

    Full Text Available Background: The natural history of AA amyloidosis is typically progressive, leading to multiple organ failure and death. We analyzed the etiology as well as clinical and laboratory features of patients with biopsy-proven AA amyloidosis and evaluated the ultimate outcome. Methods: Seventy-three patients (24 female; mean age 41.85±15.89 years were analyzed retrospectively. Demographic, clinical and laboratory features were studied and the outcome was assessed. Results: Familial Mediterranean Fever and tuberculosis were the most frequent causes of amyloidosis. Mean serum creatinine and proteinuria at diagnosis were 4.65±4.89 mg/dl and 8.04±6.09 g/day, respectively; and stage I, II, III, IV and V renal disease were present in 19.2%, 13.7%, 16.4%, 11%, and 39.7% of the patients, respectively. ESRD developed in 16 patients during the follow-up period. All of the ESRD patients started a dialysis programme. Thirty patients (41% died during the follow-up period; median patient survival was 35.9±6.12 months. Old age, tuberculosis etiology, advanced renal disease and low serum albumin levels were associated with a worse prognosis. Serum albumin was a predictor of mortality in logistic regression analysis. Conclusion: The ultimate outcome of the patients with AA amyloidosis is poor, possibly due to the late referral to the nephrology clinics. Early referral may be helpful to improve prognosis.

  12. Churg-Strauss syndrome associated with AA amyloidosis: a case ...

    African Journals Online (AJOL)

    Churg Strauss syndrome is a rare systemic and pulmonary vasculitis exceptionally associated with AA amyloidosis. We report the case of a 65-year old woman with past medical history of asthma. She developed polyarthralgia, headache and purpura. A laboratory workout found hypereosinophilia (1150/μL), positive ...

  13. Spontaneous, Experimentally Induced, and Transmissible AA Amyloidosis in Japanese Quail ( Coturnix japonica).

    Science.gov (United States)

    Nakayama, Yumi; Kamiie, Junichi; Watanabe, Gen; Suzuki, Kazuhiko; Murakami, Tomoaki

    2017-11-01

    The authors describe a spontaneous case of amyloid A (AA) amyloidosis in an adult female Japanese quail ( Coturnix japonica). The bird developed AA amyloidosis secondary to chronic peritonitis caused by a Gram-negative bacillus infection. Mild amyloid deposition was also identified in the intestinal tract of apparently healthy adult individuals, suggesting that quail may develop intestinal amyloidosis with age. Based on these observations, it was hypothesized that quail can develop AA amyloidosis following inflammatory stimulation with lipopolysaccharide (LPS). Therefore, adult quail were repeatedly injected with LPS and the development of AA amyloidosis was confirmed. The amyloid deposition in this model increased when quail amyloid was intravenously injected as an amyloid-enhancing factor. The experiments were repeated with young quail, but amyloid deposits were not observed following LPS injections. However, AA amyloidosis did develop when quail amyloid was injected in addition to LPS. These results indicated that adult quail develop AA amyloidosis after inflammatory stimulation with LPS. Furthermore, quail AA amyloidosis was shown to have transmissibility regardless of age. Interestingly, the authors found that administration of chicken amyloid fibrils also induced AA amyloidosis in young quail. This is the first report of cross-species transmission of avian AA amyloidosis.

  14. Fecal transmission of AA amyloidosis in the cheetah contributes to high incidence of disease

    Science.gov (United States)

    Zhang, Beiru; Une, Yumi; Fu, Xiaoying; Yan, Jingmin; Ge, FengXia; Yao, Junjie; Sawashita, Jinko; Mori, Masayuki; Tomozawa, Hiroshi; Kametani, Fuyuki; Higuchi, Keiichi

    2008-01-01

    AA amyloidosis is one of the principal causes of morbidity and mortality in captive cheetahs (Acinonyx jubatus), which are in danger of extinction, but little is known about the underlying mechanisms. Given the transmissible characteristics of AA amyloidosis, transmission between captive cheetahs may be a possible mechanism involved in the high incidence of AA amyloidosis. In this study of animals with AA amyloidosis, we found that cheetah feces contained AA amyloid fibrils that were different from those of the liver with regard to molecular weight and shape and had greater transmissibility. The infectious activity of fecal AA amyloid fibrils was reduced or abolished by the protein denaturants 6 M guanidine·HCl and formic acid or by AA immunodepletion. Thus, we propose that feces are a vehicle of transmission that may accelerate AA amyloidosis in captive cheetah populations. These results provide a pathogenesis for AA amyloidosis and suggest possible measures for rescuing cheetahs from extinction. PMID:18474855

  15. Lysozyme amyloidosis – a case report and review of the literature

    OpenAIRE

    Pleyer, Christopher; Flesche, Jan; Saeed, Fahad

    2015-01-01

    Lysozyme amyloidosis is an exceedingly rare hereditary autosomal dominant amyloidosis, which is characterized by the precipitation of lysozyme protein within the body, leading to multi-organ dysfunction. Herein, we present the case of a U.S. family affected by lysozyme amyloidosis. In particular, we report pericardial disease involvement leading to recurrent pericardial effusion, which to our knowledge has not been described yet. To our knowledge, we have also for the first time identified th...

  16. Amyloidosis and crohn's disease Amiloidosis y enfermedad de Crohn

    Directory of Open Access Journals (Sweden)

    Antonio Guardiola-Arévalo

    2011-05-01

    Full Text Available Secondary amyloidosis is a rare but serious complication of inflammatory bowel disease that may influence the prognosis even more than the underlying disease. Due to a better knowledge of the association of secondary amyloidosis to inflammatory bowel disease, early diagnosis of this complication is becoming more frequent, but its treatment continues to pose a challenge. We report 4 cases of patients with Crohn's disease and amyloidosis diagnosed in the inflammatory bowel disease Units of Toledo and Ciudad Real, which represent 0.68% of the patients with Crohn's disease of our health areas. There have been not cases of amyloidosis in patients with ulcerative colitis. In our 4 patients the secondary amyloidosis was clearly related to Crohn's disease, which was often of fistulising type. The predominant clinical picture of amyloidosis was nephrotic syndrome. The patients responded to medical and surgical treatment of Crohn's disease and colchicine, which improved renal function in all cases except in one who required kidney transplantation.La amiloidosis sistémica adquirida es una complicación rara pero grave de la enfermedad inflamatoria intestinal crónica, pudiendo condicionar el pronóstico más que la propia enfermedad de base. Debido al mejor conocimiento de la asociación de amiloidosis secundaria a enfermedad inflamatoria intestinal, el diagnóstico temprano se hace cada vez con mayor frecuencia, pero su tratamiento continúa siendo un reto. Describimos 4 casos clínicos de pacientes con enfermedad de Crohn (EC y amiloidosis diagnosticados en las Unidades de EIIC de Toledo y Ciudad Real, lo que representa el 0,68% de los caso de EC de nuestras áreas sanitarias. No se ha descrito ningún caso de amiloidosis en pacientes con colitis ulcerosa. En los 4 pacientes la AA estaba claramente relacionada con la EC, y predominaron las formas estenosantes-perforantes. El cuadro clínico de presentación de la amiloidosis en la mayoría de los casos

  17. Familial amyloidosis cutis dyschromica in three siblings: report from Indonesia

    Directory of Open Access Journals (Sweden)

    Melyawati Hermawan

    2014-11-01

    Full Text Available Amyloidosis cutis dyschromica (ACD is an extremely rare type of primary cutaneous amyloidosis. To date there are fewer than 40 published cases worldwide; some were reported affecting several family members. Its resemblance to other common pigmentation disorders makes it rarely recognized at first sight. Our patient, the 12-year-old firstborn son of non-consanguineous parents presented with generalized mottled pigmentation starting from lower extremities. His siblings suffered from similar condition. The clue for diagnosis is the amyloid deposition in the papillary dermis. The etiology of ACD is still unknown, but genetic factors and ultraviolet radiation are implicated. It is proposed that disturbance of keratinocyte repair following ultraviolet radiation results in amyloid deposition. The treatment remains a challenge. Oral acitretin treatment, thought to repair keratinization defect, gave a slight improvement in our case. Our is the first case of ACD reported in Indonesia.

  18. Bilateral uveal effusion associated with scleral thickening due to amyloidosis.

    Science.gov (United States)

    Liew, S C; McCluskey, P J; Parker, G; Taylor, R F

    2000-09-01

    A 45-year-old man with primary systemic amyloidosis was found to have bilateral uveal effusions secondary to thickened sclera according to magnetic resonance imaging of the orbits. The patient was treated with bilateral sclerectomies and vortex vein decompression, and had an excellent outcome. Light microscopy of excised sclera revealed severe infiltration of the tissue by amyloid. To our knowledge, this is the first report of amyloid infiltration of the sclera leading to uveal effusion. Arch Ophthalmol. 2000;118:1293-1295

  19. Rheumatic polymyalgia like presentation of multiple myeloma and amyloidosis

    International Nuclear Information System (INIS)

    Medina, Yimy F; Martinez, Jose Bernardo; Restrepo, Jose Felix; Rondon, Federico; Iglesias Gamarra, Antonio

    2005-01-01

    Polymyalgia rheumatica is a disorder with defined clinical characteristics and may be the initial expression or to be associated to other diseases. Although it is not associated to neoplastic diseases, may be their initial manifestation. We report a patient who presented the initial complaining of polymyalgia rheumatica as a manifestation of another illness, amyloidosis associated to multiple myeloma. We also discuss the clinical characteristics of these entities and revised the available literature with regard to this association

  20. MRI of pathology-proven peripheral nerve amyloidosis

    Energy Technology Data Exchange (ETDEWEB)

    McKenzie, Gavin A.; Broski, Stephen M.; Howe, Benjamin M.; Spinner, Robert J.; Amrami, Kimberly K.; Dispenzieri, Angela; Ringler, Michael D. [Mayo Clinic, Department of Musculoskeletal Radiology, Rochester, MN (United States)

    2017-01-15

    To highlight the MRI characteristics of pathologically proven amyloidosis involving the peripheral nervous system (PNS) and determine the utility of MRI in directing targeted biopsy for aiding diagnosis. A retrospective study was performed for patients with pathologically proven PNS amyloidosis who also underwent MRI of the biopsied or excised nerve. MRI signal characteristics, nerve morphology, associated muscular denervation changes, and the presence of multifocal involvement were detailed. Pathology reports were reviewed to determine subtypes of amyloid. Charts were reviewed to gather patient demographics, neurological symptoms and radiologist interpretation. Four men and three women with a mean age of 62 ± 11 years (range 46-76) were identified. All patients had abnormal findings on EMG with mixed sensorimotor neuropathy. All lesions demonstrated diffuse multifocal neural involvement with T1 hypointensity, T2 hyperintensity, and variable enhancement on MRI. One lesion exhibited superimposed T2 hypointensity. Six of seven patients demonstrated associated muscular denervation changes. Peripheral nerve amyloidosis is rare, and the diagnosis is difficult because of insidious symptom onset, mixed sensorimotor neurologic deficits, and the potential for a wide variety of nerves affected. On MRI, peripheral nerve involvement is most commonly characterized by T1 hypointensity, T2 hyperintensity, variable enhancement, maintenance of the fascicular architecture with fusiform enlargement, multifocal involvement and muscular denervation changes. While this appearance mimics other inflammatory neuropathies, MRI can readily detect neural changes and direct-targeted biopsy, thus facilitating early diagnosis and appropriate management. (orig.)

  1. Uninvolved immunoglobulins predicting hematological response in newly diagnosed AL amyloidosis.

    Science.gov (United States)

    Muchtar, Eli; Magen, Hila; Itchaki, Gilad; Cohen, Amos; Rosenfeld, Ra'ama; Shochat, Tzippy; Kornowski, Ran; Iakobishvili, Zaza; Raanani, Pia

    2016-02-01

    Immunoparesis serves as a marker for elevated risk for progression in plasma cell proliferative disorders. However, the impact of immunoparesis in AL amyloidosis has not been addressed. Immunoparesis was defined qualitatively as any decrease below the low reference levels of the uninvolved immunoglobulins and quantitatively, as the relative difference between the uninvolved immunoglobulins and the lower reference values. Forty-one newly diagnosed AL amyloidosis patients were included. Sixty-six percent of patients had a suppression of the uninvolved immunoglobulins. The median relative difference of the uninvolved immunoglobulins was 18% above the low reference levels [range (-71%)-210%]. Ninety percent of the patients were treated with novel agents-based regimens, mostly bortezomib-containing regimens. Nineteen percent of the patients did not attain response to first line treatment. Patients with relative difference of uninvolved immunoglobulins below -25% of the low reference levels were less likely to respond to first line treatment compared to patients with a relative difference of -25% and above [odds ratio for no response vs. partial response and better 30 [(95% CI 4.1-222.2), P=0.0004]. Patients who failed first line treatment were successfully salvaged with lenalidomide-based treatment. Immunoparesis, if assessed quantitatively, may serve as a predictor of response in AL amyloidosis patients treated with bortezomib-containing regimens. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Amyloidosis in association with spontaneous feline immunodeficiency virus infection.

    Science.gov (United States)

    Asproni, Pietro; Abramo, Francesca; Millanta, Francesca; Lorenzi, Davide; Poli, Alessandro

    2013-04-01

    Tissues from 34 naturally feline immunodeficiency virus (FIV)-infected cats, 13 asymptomatic cats and 21 cats with signs of feline acquired immunodeficiency syndrome (F-AIDS), and 35 FIV-seronegative subjects were examined to determine the presence of amyloid deposits. Twenty experimentally FIV-infected cats and five specific pathogen-free (SPF) control cats were also included in the study. Paraffin-embedded sections from kidney and other organs were submitted to histological and histochemical analysis. Amyloid deposits were identified by a modified Congo red stain and confirmed by electron microscopy to demonstrate the presence of amyloid fibrils in amyloid positive glomeruli. In all positive cases, secondary amyloidosis was identified with potassium permanganate pretreatment and amyloid type was further characterised by immunohistochemistry using primary antibodies against human AA and feline AL amyloids. Amyloid deposits were present in different tissues of 12/34 (35%) naturally FIV-infected cats (seven presenting F-AIDS and five in asymptomatic phase) and in 1/30 FIV-seronegative cats. All the experimentally FIV-infected and SPF subjects showed no amyloid deposits. Amyloidosis has been reported in human lentiviral infections, and the data reported here demonstrate the need, in naturally FIV-infected cats, to consider the presence of amyloidosis in differential diagnosis of hepatic and renal disorders to better assess the prognosis of the disease.

  3. Serum amyloid A protein in amyloidosis, rheumatic, and neoplastic diseases

    International Nuclear Information System (INIS)

    Benson, M.D.; Cohen, A.S.

    1979-01-01

    Serum levels of amyloid protein A (SAA) have been shown to be elevated in different types of amyloidosis and in rheumatic diseases by radioimmunoassay using 125 iodine labeled AA and anti-AA. SAA levels were elevated in both primary and secondary amyloidosis, but there were highly significant differences between these levels. In heredofamilial amyloid, SAA levels were within normal limits. While the mean SAA level was elevated in persons over 70 years, the fact that some persons in this age group had normal levels suggested that marked elevation after age 70 may be due to occult inflammatory or neoplastic disease. High SAA levels in patients with rheumatoid arthritis correlated, in most cases, with physician evaluation of disease activity and Westergren ESR. SAA levels in patients with systemic lupus erythematosus were lower than those in patients with rheumatoid arthritis, and most patients with degenerative joint disease had normal levels. Very high levels of SAA were found in patients with neoplastic diseases. Patients with carcinoma of the lung and bowel had much higher levels than patients with carcinoma of the breast. Determination of SAA levels may be of value in evaluating different forms of systemic amyloidosis, assessing the activity of rheumatic disease, and screening for occult inflammatory or neoplastic disease

  4. Amyloid Load in Fat Tissue Reflects Disease Severity and Predicts Survival in Amyloidosis

    NARCIS (Netherlands)

    Van Gameren, Ingrid I.; Hazenberg, Bouke P. C.; Bijzet, Johan; Haagsma, Elizabeth B.; Vellenga, Edo; Posthumus, Marcel D.; Jager, Pieter L.; Van Rijswijk, Martin H.

    Objective. The severity of systemic amyloidosis is thought to be related to the extent of amyloid deposition. We studied whether amyloid load in fat tissue reflects disease severity and predicts survival. Methods. We studied all consecutive patients with systemic amyloidosis seen between January

  5. Primary idiopathic systemic amyloidosis – rare classical cases with fatal outcome

    Directory of Open Access Journals (Sweden)

    Shivakumar Patil

    2016-07-01

    Full Text Available Primary systemic amyloidosis is a rare condition. We report two cases of primary systemic amyloidosis. Both the cases were without any hematological abnormality. Cutaneous features were the predominant presenting symptoms in these patients. The patients presented with typical waxy lesions on face and macroglossia. Diagnosis was confirmed by histopathology with haematoxylin and eosin staining and Congo red staining

  6. The Hidden Cost of Untreated Paragangliomas of the Head and Neck: Systemic Reactive (AA Amyloidosis

    Directory of Open Access Journals (Sweden)

    Erkan Dervisoglu

    2015-01-01

    Full Text Available We report a case of a 51-year-old man who was diagnosed with systemic reactive (AA amyloidosis in association with untreated glomus jugulare and glomus caroticum tumors. He refused radiotherapy and renal replacement therapy. Paragangliomas, although rare, should be considered one of the tumors that can result in AA amyloidosis.

  7. Lichen amyloidosis induced on the upper back by long-term friction with a nylon towel.

    Science.gov (United States)

    Yoshida, Aki; Takahashi, Kazuhiro; Tagami, Hachiro; Akasaka, Toshihide

    2009-01-01

    Primary localized cutaneous amyloidosis can take several clinical forms. In Asia, macular amyloidosis caused by prolonged friction from a rough nylon towel or brush is common, and macular amyloidosis and lichen amyloidosis occasionally occur together, as so-called biphasic amyloidosis. We report herein the case of an 83-year-old Japanese man with lichen amyloidosis caused by prolonged nylon towel friction. This patient presented with unique symmetrical papular lesions on the upper back and shoulders. Lesions comprised slightly shiny, brownish, fine uniform papules approximately 0.5 mm in diameter, showing a partially linear, annular or rippled arrangement. Although this case was caused by prolonged nylon towel friction, no coexisting macular lesions could be found. To the best of our knowledge, this represents the first case of lichen amyloidosis induced by nylon towel friction in the absence of the macular amyloidosis that is usually observed in such cases. We instructed the patient to stop the habit of nylon towel rubbing and prescribed a topical steroid ointment and cepharanthine. After 6 months of treatment, papular lesions became clearly flatter.

  8. [Oral amyloidosis. Concept, histopathology, clinical manifestations and treatment. Presentation of a clinical case].

    Science.gov (United States)

    Bermejo Fenoll, A; Sánchez Pérez, A; Orts Feliciano, R

    1991-05-01

    The definition and current classification of amyloidosis as well as the incidence, etiopathogenesis, pathology, clinical manifestations, specific diagnosis and prognosis and treatment of the disease are reviewed. A case of amyloidosis of the oral cavity without systemic involvement is reported. A 77 year-old woman suffered from multiple tumor masses in the mouth and presented with symptoms of impaired speech and ingestion.

  9. Optimization of Serum Immunoglobulin Free Light Chain Analysis for Subclassification of Cardiac Amyloidosis.

    Science.gov (United States)

    Halushka, Marc K; Eng, George; Collins, A Bernard; Judge, Daniel P; Semigran, Marc J; Stone, James R

    2015-06-01

    Accurate and rapid classification of cardiac amyloidosis is important for patient management. We have optimized the use of serum free light chain kappa and lambda values to differentiate immunoglobulin light chain amyloid (AL) amyloidosis from transthyretin amyloid and amyloid A using 85 cases of tissue-proven cardiac amyloidosis, in which there was direct classification of amyloidosis by mass spectrometry or immunofluorescence. The serum free light chain kappa/lambda ratios were non-overlapping for the three major groups: AL-lambda (0.01-0.41, n = 30), non-AL (0.52-2.7, n = 43), and AL-kappa (6.7-967, n = 12). A kappa/lambda ratio value between 0.5 and 5.0 had 100 % sensitivity and 100 % specificity for distinguishing AL amyloidosis from non-AL amyloidosis. This optimized range for serum light chain kappa/lambda ratio provides extremely robust classification of cardiac amyloidosis. Cases of cardiac amyloidosis in which the serum kappa/lambda free light chain ratio falls close to these new cutoff values may benefit most from direct amyloid subtyping.

  10. Renal amyloidosis: a synopsis of its clinical presentation, diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Elena V. Zakharova

    2015-04-01

    Full Text Available Amyloidosis is a heterogeneous group of hereditary and acquired diseases in which normally soluble plasma proteins are deposited in the extracellular and/or intracellular space in abnormal, insoluble, fibrillar form. Renal damage is one of the most common features of systemic amyloidosis, and the presentation is most commonly due to the consequences of renal involvement, with proteinuria and progressive renal decline. Progression to end-stage renal failure is common. Early diagnosis of systemic amyloidosis is difficult. Renal amyloidosis typically presents with nephrotic syndrome and/or renal failure. Treatment of AL amyloidosis aims to reduce production of the monoclonal immunoglobulin precursor via chemotherapy. Current options for treatment include melphalan+dexamethasone or cyclophosphamide-bortezomib-dexamethasone regimens, or in selected patients, high-dose melphalan with autologous stem cell transplantation. The focus of current research is on pharmacological therapy to solubilize amyloid fibrils and increase tissue catabolism of amyloid deposits.

  11. What is the role of giant cells in AL-amyloidosis?

    DEFF Research Database (Denmark)

    Olsen, K E; Sletten, K; Sandgren, O

    1999-01-01

    . In this work it is shown that that there is a difference between localized and systemic amyloidosis in respect to accompanying giant cells which constantly are found associated with amyloid deposits in localized AL-amyloidosis. In addition, giant cells were found together with amyloid deposits in lymph nodes...... of some cases of systemic AL-amyloidosis. Based on these findings and electron microscopic studies, it is discussed whether the giant cells actively participate in amyloid fibril formation by uptake and modification of the precursor protein or the giant cells are part of a foreign body reaction. Included......AL-amyloidosis is one of the most common amyloidoses and can be found in a localized and a systemic form. The precursor protein is an immunoglobulin light chain which as AL-protein in both localized and systemic AL-amyloidosis shows the same pattern of fragmentation and changes of primary structure...

  12. Lichen amyloidosis successfully treated with fractional ablative laser CO2: A new alternative therapeutic.

    Science.gov (United States)

    Korbi, Mouna; Akkari, Hayet; Soua, Yosra; Mohamed, Mariem; Youssef, Monia; Belhajdali, Hichem; Zili, Jameledine

    2018-02-05

    Lichen amyloidosis is a primary localized cutaneous amyloidosis. Different types of treatment have been used without complete resolution. Herein, we report a case of patient suffering from lichen amyloidosis successfully treated with fractional ablative laser CO 2 . He was a 59-year-old man diagnosed lichen amyloidosis localized on the legs 10 years ago. He was treated with topical corticosteroids without any improvement. Then, we started treating the affected area with CO 2 laser (limmer*) at a setting of 5-8 J/cm 2 and 8 mm laser spot size. A considerable improvement was noticed after the first session. A total healing was reported after four sessions. To the best of our knowledge, only 11 reported cases of lichen amyloidosis have been successfully treated with laser CO 2 . However, our clinical finding seems to be one of the best reported results.

  13. [Pathological and clinical correlations in renal AA amyloidosis: A Moroccan series of 30 cases].

    Science.gov (United States)

    Bziz, Asmae; Rouas, Lamia; Lamalmi, Najat; Malihy, Abderrahmane; Cherradi, Nadia; Ouzeddoun, Naima; Bayahia, Rabia; Flayou, Kaoutar; Chala, Sanae; Bouclouze, Aziz; Benomar, Ali; Abouqal, Redouan; Alhamany, Zaitouna

    2015-12-01

    Study of histological and clinical correlations of 30 cases of renal amyloidosis AA diagnosed between November 2010 and December 2012. The main causes associated with amyloidosis AA were represented by chronic infectious diseases (60%). Nephrotic syndrome and renal failure were observed in 94% and 73% respectively. The distribution of amyloid deposits: 90% of patients had a glomerular form and 10% had a vascular form. Inflammatory reaction associated with AA renal amyloidosis was present in 50% of cases. This inflammation was observed near amyloid deposits associated with a deposition of immunoglobulin chains and/or complement factors. Our study confirms the predominance of AA amyloidosis complicating chronic infectious diseases, especially tuberculosis. Our data point out a relationship between the morphology of renal AA amyloidosis, its clinical presentation and prognosis. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  14. Changing epidemiology of AA amyloidosis: clinical observations over 25 years at a single national referral centre.

    Science.gov (United States)

    Lane, Thirusha; Pinney, Jennifer H; Gilbertson, Janet A; Hutt, David F; Rowczenio, Dorota M; Mahmood, Shameem; Sachchithanantham, Sajitha; Fontana, Marianna; Youngstein, Taryn; Quarta, Candida C; Wechalekar, Ashutosh D; Gillmore, Julian D; Hawkins, Philip N; Lachmann, Helen J

    2017-09-01

    Systemic AA amyloidosis is a serious complication of chronic inflammation; however, there are relatively few published data on its incidence. We investigated the changing epidemiology of AA amyloidosis over a 25-year period at a single national referral centre. We conducted a retrospective study of all patients diagnosed with AA amyloidosis who had attended the centre between 1990 and 2014 inclusive. Six hundred and twenty-five patients were studied in three cohorts: C1: 1990-1997; C2: 1998-2006; C3: 2007-2014. Mean age at presentation increased from 46 in C1 to 56 in C3 (p AA amyloidosis over a quarter of a century, reflecting advances in therapeutics and overall management of complex chronic disease in an ageing population. AA amyloidosis of uncertain aetiology presents an emerging major problem. Newer techniques such as next-generation sequencing may aid diagnosis and effective treatment, thereby improving overall survival.

  15. Renal amyloidosis secondary to childhood tuberculosis: A report of two cases

    Directory of Open Access Journals (Sweden)

    Krishnamurthy S

    2009-01-01

    Full Text Available Childhood renal amyloidosis is a rare entity and is mostly secondary in nature. We describe two cases of renal amyloidosis in association with childhood tuberculosis. The first case was a 10-year-old girl who presented with abdominal tuberculosis and nephrotic syndrome, while the second case was a 5-year-old boy who presented with disseminated tuberculosis and nephrotic syndrome. They were found to have amyloidosis on renal biopsy. The former was treated with anti-tubercular drugs, while the latter required anti-tubercular drugs and steroids. Both the cases showed clinical improvement with remission of nephrotic syndrome. Successful treatment of tuberculosis can result in remission of nephrotic syndrome due to secondary renal amyloidosis. It is important, especially in developing countries, to be aware that tuberculosis continues to be part of the differential diagnosis of amyloidosis in children.

  16. Recurrent syncope and cardiac arrest in a patient with systemic light chain amyloidosis treated with bortezomib

    Directory of Open Access Journals (Sweden)

    Navin Jaipaul

    2016-05-01

    Full Text Available About 10-15% of patients with multiple myeloma develop light chain (AL amyloidosis. AL amyloidosis is a systemic disease that may involve multiple organs, often including the heart. It may present clinically with bradyarrhythmia and syncope. The proteasome inhibitor bortezomib has been used with clinical efficacy in treating patients with AL amyloidosis but also implicated as a possible cause of cardiomyocyte injury. We report a case of a 48-year-old man with AL amyloidosis and increased frequency of syncope and cardiac arrest after starting bortezomib. The biologic and clinical plausibility of a heightened risk for cardiac arrest in patients with cardiac AL amyloidosis and history of syncope being treated with bortezomib is a possibility that is not well documented in the medical literature and warrants further investigation.

  17. Pancreatic Islet Cell Amyloidosis Manifesting as a Large Pancreas

    International Nuclear Information System (INIS)

    Onur, Mehmet Ruhi; Yalniz, Mehmet; Poyraz, Ahmet Kursad; Oezercan, Ibrahim Hanifi; Ozkan, Yusuf

    2012-01-01

    A 39-year-old female patient presented to our hospital with epigastric pain lasting for two months. Laboratory results showed impaired glucose tolerance. Ultrasonography of the patient showed a hypoechoic, diffusely enlarged pancreas. CT revealed a large pancreas, with multiple calcifications. On MRI, a diffusely enlarged pancreas was seen hypointense on both T1- and T2-weighted images with heterogeneous enhancement after gadolinium administration. A biopsy of the pancreas revealed primary amyloidosis of islet cells. Decreased signal on T1-weighted images without inflammation findings on CT and MRI were clues for the diagnosis.

  18. Upper Gastrointestinal Bleeding from Gastric Amyloidosis in a Patient with Smoldering Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Mihajlo Gjeorgjievski

    2015-01-01

    Full Text Available Amyloidosis is a common complication of patients with monoclonal gammopathy of undetermined significance (MGUS, smoldering multiple myeloma (SMM, and multiple myeloma (MM. This proteinaceous material can be deposited intercellularly in any organ system, including the gastrointestinal (GI tract. In the GI tract, amyloidosis affects the duodenum most commonly, followed by the stomach and colorectum. Gastric amyloidosis causes symptoms of nausea, vomiting, early satiety, abdominal pain, and GI bleeding. A case of upper GI bleeding from gastric amyloidosis is presented in a patient with SMM. Esophagogastroduodenoscopy (EGD revealed a gastric mass. Endoscopic biopsies revealed amyloid deposition in the lamina propria, consistent with gastric amyloidosis. Liquid chromatography tandem mass spectrometry performed on peptides extracted from Congo red-positive microdissected areas of paraffin-embedded stomach specimens revealed a peptide profile consistent with AL- (lambda- type amyloidosis. Based on this and multiple other case reports, we recommend that patients with GI bleeding and MGUS, SMM, or MM undergo EGD and pathologic examination of endoscopic biopsies of identified lesions using Congo red stains for amyloidosis for early diagnosis and treatment.

  19. Renal failure due to primary amyloidosis: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Ramon Andrade Bezerra de Mello

    Full Text Available CONTEXT: Primary amyloidosis, also known as AL amyloidosis, is commonly caused by clonal expansion of plasma cells in the bone marrow, thereby segregating light chains of clonal immunoglobulin that settle in tissues in the form of insoluble amyloid fibrils. The aim of this study was to report a case of primary amyloidosis with renal failure, diagnosed in Hospital São João, Porto, Portugal, focusing on the diagnostic difficulties and presenting a literature review. CASE REPORT: A 68-year-old Caucasian man was admitted to the Internal Medicine Department of the hospital with a condition of anasarca and nephrotic syndrome. After performing a renal biopsy that tested positive using Congo red and immunohistochemistry, lambda light chain amyloidosis was diagnosed. This evolved into terminal renal disease, which led to hemodialysis and several episodes of urinary and catheter infections. He was started on chemotherapy, consisting of bortezomib 0.7 mg/m² and dexamethasone 40 mg in six cycles. This led to clinical improvement, stabilization of the illness and good tolerance of the treatment. CONCLUSION: Amyloidosis is a rare entity that is difficult to diagnose. This is because of the unspecific early clinical manifestations of the disease. The hypothesis of amyloidosis is only considered when specific organ failure occurs. This case consisted of primary amyloidosis with involvement of the kidneys as an initial presentation of the disease and its difficulties were shown, going from the clinical approach to the final diagnosis.

  20. Upper Gastrointestinal Bleeding from Gastric Amyloidosis in a Patient with Smoldering Multiple Myeloma.

    Science.gov (United States)

    Gjeorgjievski, Mihajlo; Purohit, Treta; Amin, Mitual B; Kurtin, Paul J; Cappell, Mitchell S

    2015-01-01

    Amyloidosis is a common complication of patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM). This proteinaceous material can be deposited intercellularly in any organ system, including the gastrointestinal (GI) tract. In the GI tract, amyloidosis affects the duodenum most commonly, followed by the stomach and colorectum. Gastric amyloidosis causes symptoms of nausea, vomiting, early satiety, abdominal pain, and GI bleeding. A case of upper GI bleeding from gastric amyloidosis is presented in a patient with SMM. Esophagogastroduodenoscopy (EGD) revealed a gastric mass. Endoscopic biopsies revealed amyloid deposition in the lamina propria, consistent with gastric amyloidosis. Liquid chromatography tandem mass spectrometry performed on peptides extracted from Congo red-positive microdissected areas of paraffin-embedded stomach specimens revealed a peptide profile consistent with AL- (lambda-) type amyloidosis. Based on this and multiple other case reports, we recommend that patients with GI bleeding and MGUS, SMM, or MM undergo EGD and pathologic examination of endoscopic biopsies of identified lesions using Congo red stains for amyloidosis for early diagnosis and treatment.

  1. Experimental transmission of systemic AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice

    Science.gov (United States)

    Maeda, Mayuko; Murakami, Tomoaki; Muhammad, Naeem; Inoshima, Yasuo; Ishiguro, Naotaka

    2016-01-01

    AA amyloidosis is a protein misfolding disease characterized by extracellular deposition of amyloid A (AA) fibrils. AA amyloidosis has been identified in food animals, and it has been postulated that AA amyloidosis may be transmissible to different animal species. Since the precursor protein of AA fibrils is serum amyloid A (SAA), which is an inflammatory acute phase protein, AA amyloidosis is considered to be associated with inflammatory diseases such as rheumatoid arthritis. Chronic diseases such as autoimmune disease and type 2 diabetes mellitus could be potential factors for AA amyloidosis. In this study, to examine the relationship between the induction of AA amyloidosis and chromic abnormalities such as autoimmune disease or type 2 diabetes mellitus, amyloid fibrils from mice, cattle, or chickens were experimentally injected into disease model mice. Wild-type mice were used as controls. The concentrations of SAA, IL-6, and IL-10 in autoimmune disease model mice were higher than those of control mice. However, induction of AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice was lower than that in control mice, and the amount of amyloid deposits in the spleens of both mouse models was lower than that of control mice according to Congo red staining and immunohistochemistry. These results suggest that factors other than SAA levels, such as an inflammatory or anti-inflammatory environment in the immune response, may be involved in amyloid deposition. PMID:27321428

  2. Amyloidosis involving the respiratory system: 5-year's experience of a multi-disciplinary group's activity.

    Science.gov (United States)

    Scala, Raffaele; Maccari, Uberto; Madioni, Chiara; Venezia, Duccio; La Magra, Lidia Calogera

    2015-01-01

    Amyloidosis may involve the respiratory system with different clinical-radiological-functional patterns which are not always easy to be recognized. A good level of knowledge of the disease, an active integration of the pulmonologist within a multidisciplinary setting and a high level of clinical suspicion are necessary for an early diagnosis of respiratory amyloidosis. The aim of this retrospective study was to evaluate the number and the patterns of amyloidosis involving the respiratory system. We searched the cases of amyloidosis among patients attending the multidisciplinary rare and diffuse lung disease outpatients' clinic of Pulmonology Unit of the Hospital of Arezzo from 2007 to 2012. Among the 298 patients evaluated during the study period, we identified three cases of amyloidosis with involvement of the respiratory system, associated or not with other extra-thoracic localizations, whose diagnosis was histo-pathologically confirmed after the pulmonologist, the radiologist, and the pathologist evaluation. Our experience of a multidisciplinary team confirms that intra-thoracic amyloidosis is an uncommon disorder, representing 1.0% of the cases of rare and diffuse lung diseases referred to our center. The diagnosis of the disease is not always easy and quick as the amyloidosis may involve different parts of the respiratory system (airways, pleura, parenchyma). It is therefore recommended to remind this orphan disease in the differential diagnosis of the wide clinical scenarios the pulmonologist may intercept in clinical practice.

  3. Is the presence of AA amyloidosis associated with impaired coronary flow reserve?

    Science.gov (United States)

    Bulut, Mustafa; Keles, Nursen; Caliskan, Zuhal; Kostek, Osman; Aksu, Feyza; Ozdil, Kamil; Akcakoyun, Mustafa; Demircioglu, Kenan; Yilmaz, Yusuf; Kanbay, Mehmet; Caliskan, Mustafa

    2016-08-01

    Systemic amyloid A protein (AA) amyloidosis may occur as a complication of many chronic inflammatory disorders. Patients receiving inadequate anti-inflammatory and immunosuppressive therapies have an increased risk of developing systemic AA amyloidosis. Inflammation plays a role in all stages and the thrombotic complications of atherosclerosis. In the absence of epicardial coronary stenosis, coronary flow reserve (CFR) reflects coronary microvascular dysfunction. In the present study, we hypothesized that amyloid advanced subclinical inflammation in chronic inflammatory diseases (CID) patients may further affect coronary microcirculation. Thirty-two patients with biopsy-diagnosed renal AA, 73 patients with non-amyloid CID, and a group of healthy volunteers were included in the study. The measurements of coronary flow velocity were performed by a single investigator with expertise in transthoracic Doppler harmonic echocardiography (TTDE). The AA amyloidosis subgroup had significantly lower CFR values than other non-amyloid CID patients and the control individuals (1.8 (1.5-2.1) vs. 2.1 (2.0-2.4) and 3.0 (2.8-3.2), p AA amyloidosis and elevated hs - CRP independently predict impairment of the CFR (p AA amyloidosis is related to decreased CFR values and the presence of AA amyloidosis and elevated hs - CRP independently predict impairment of the CFR. Therefore, patients with AA amyloidosis may have an increased risk of developing coronary artery diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Experimental transmission of systemic AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice.

    Science.gov (United States)

    Maeda, Mayuko; Murakami, Tomoaki; Muhammad, Naeem; Inoshima, Yasuo; Ishiguro, Naotaka

    2016-11-01

    AA amyloidosis is a protein misfolding disease characterized by extracellular deposition of amyloid A (AA) fibrils. AA amyloidosis has been identified in food animals, and it has been postulated that AA amyloidosis may be transmissible to different animal species. Since the precursor protein of AA fibrils is serum amyloid A (SAA), which is an inflammatory acute phase protein, AA amyloidosis is considered to be associated with inflammatory diseases such as rheumatoid arthritis. Chronic diseases such as autoimmune disease and type 2 diabetes mellitus could be potential factors for AA amyloidosis. In this study, to examine the relationship between the induction of AA amyloidosis and chromic abnormalities such as autoimmune disease or type 2 diabetes mellitus, amyloid fibrils from mice, cattle, or chickens were experimentally injected into disease model mice. Wild-type mice were used as controls. The concentrations of SAA, IL-6, and IL-10 in autoimmune disease model mice were higher than those of control mice. However, induction of AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice was lower than that in control mice, and the amount of amyloid deposits in the spleens of both mouse models was lower than that of control mice according to Congo red staining and immunohistochemistry. These results suggest that factors other than SAA levels, such as an inflammatory or anti-inflammatory environment in the immune response, may be involved in amyloid deposition.

  5. Intensity-modulated radiotherapy for localized nasopharyngeal amyloidosis. Case report and literature review

    International Nuclear Information System (INIS)

    Luo, Ming; Peng, Gang; Shi, Liangliang; Li, Zhenyu; Fei, Shijiang; Ding, Qian; Cheng, Jing; Ming, Xing

    2016-01-01

    Primary localized amyloidosis is characterized by the deposition of amyloid proteins restricted to one organ, without systemic involvement. Primary nasopharyngeal amyloidosis is an exceedingly rare condition, for which the standard treatment remains unknown. Because of its challenging anatomical position, surgery alone hardly results in complete resection of the localized amyloidosis. Therefore, an interdisciplinary planning board to design optimal treatment is of particular importance. A 39-year-old man presented with a several-week history of nasal obstruction and epistaxis. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of a retro-odontoid nonenhancing soft tissue mass. The endoscopic biopsy demonstrated that the mass was amyloid in nature. An extensive systemic workup revealed an absence of inflammatory process, systemic amyloidosis, or plasma cell dyscrasia. The patient was treated with a combination of surgery and radiotherapy, showing no evidence of recurrence or progression at his 1-year follow-up. Primary solitary amyloidosis is a rare form of amyloidosis. To the best of our knowledge, this is the first report of a nasopharyngeal amyloidosis case treated with excision and radiation leading to complete remission. Because of the difficulty for surgeons to achieve radical resection with such lesions, radiotherapy proved to be an excellent adjuvant treatment in this case. (orig.) [de

  6. Magnetic resonance imaging with liver-specific contrast agent in primary amyloidosis and intrahepatic cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, J.M.; Santoni-Rugiu, E.; Chabanova, E.; Logager, V.; Hansen, A.B.; Thomsen, H.S. [Depts. of Radiology and Pathology, Copenhagen Univ. Hospital, Herlev (Denmark)

    2007-02-15

    Magnetic resonance imaging (MRI) findings in hepatic amyloidosis are not well defined. Here, we report on a patient with renal failure caused by primary amyloidosis (AL type) who developed jaundice. Ultrasound and computed tomography were normal except for some ascites. MRI with oral manganese-containing contrast agent revealed several focal areas without contrast uptake in the hepatocytes and no bile secretion after 8 hours. No extrahepatic bile obstructions were found. Liver biopsy showed severe intraportal, vascular, and parenchymal amyloidosis causing severe cholestasis and atrophy of hepatocytes.

  7. Cases of a Borderline Pathology That Can Mimic Bladder Cancer: Primary Amyloidosis of Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Cemal Selçuk İşoğlu

    2015-06-01

    Full Text Available Amyloidosis is a disease characterised by accumulation of a fibrillar protein called amyloid in the extracellular space. The kidneys, ureters and the bladder can be affected in the urinary tract. However, primary amyloidosis of bladder is a rare entity. Macroscopic hematuria could be the first and only symptom of primary amyloidosis of the bladder; therefore, it has similar findings with urinary tract malignancies. Histopathological evaluation is mandatory for the diagnosis. Follow-up should always include cystoscopic evaluation as recurrence is expected in the natural course.

  8. Pulmonary amyloidosis: computed tomography findings; Amiloidose pulmonar: aspectos na tomografia computadorizada

    Energy Technology Data Exchange (ETDEWEB)

    Marchiori, Edson [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Disciplina de Radiologia)). E-mail: edmarchiori@zipmail.com.br Souza Junior, Arthur Soares (Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil); Ferreira, Angela [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Disciplina de Pneumologia; Azevedo, Karla Confessor [Santa Casa de Misericordia do Rio de Janeiro, RJ (Brazil). Servico de Radiologia; Fialho, Suzane Mansur [Clinica Radiologica Emilio Amorim, Rio de Janeiro, RJ (Brazil); Crespo, Sheila Jandira Vianna [Instituto Nacional do Cancer INCa, Rio de Janeiro, RJ (Brazil)

    2003-04-01

    We report the computed tomography findings of five patients with pathology proven pulmonary amyloidosis. Tracheobronchial amyloidosis with calcified nodules and plaques in the tracheal wall were seen in two patients. Two other patients had diffuse parenchymal disease with calcified lesions, one had reticular and nodular sub pleural opacities whereas the other had nodular interlobular septal thickening and a parenchymal consolidation. The latter presented the nodular type of the disease with multiple sharp nodules scattered throughout the lungs and interspersed calcifications. The computed tomography findings observed were not specific but strongly suggestive of amyloidosis. (author)

  9. Renal AA amyloidosis in a patient with hereditary complete complement C4 deficiency

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    Imed Helal

    2011-01-01

    Full Text Available Hereditary complete C4 deficiency has until now been reported in 30 cases only. A disturbed clearance of immune- complexes probably predisposes these individuals to systemic lupus erythematosus, other immune- complex diseases and recurrent microbial infections. We present here a 20- year- old female with hereditary complete C4 deficiency. Renal biopsy demonstrated renal AA amyloidosis. This unique case further substantiates that deficiency of classical pathway components predisposes to the development of recurrent microbial infections and that the patients may develop AA amyloidosis. Furthermore, in clinical practice, the nephrotic syndrome occurring in a patient with hereditary complete complement C4 deficiency should lead to the suspicion of renal AA amyloidosis.

  10. Age-dependent cognitive dysfunction in untreated hereditary transthyretin amyloidosis.

    Science.gov (United States)

    Martins da Silva, Ana; Cavaco, Sara; Fernandes, Joana; Samões, Raquel; Alves, Cristina; Cardoso, Márcio; Kelly, Jeffery W; Monteiro, Cecília; Coelho, Teresa

    2018-02-01

    Central nervous system (CNS) involvement in hereditary transthyretin (TTR) amyloidosis has been described in patients whose disease course was modified by liver transplant. However, cognitive dysfunction has yet to be investigated in those patients. Moreover, CNS involvement in untreated patients or asymptomatic mutation carriers remains to be studied. A series of 340 carriers of the TTRVal30Met mutation (180 symptomatic and 160 asymptomatic) underwent a neuropsychological assessment, which included the Dementia Rating Scale-2 (DRS-2), auditory verbal learning test, semantic fluency, phonemic fluency, and trail making test. Cognitive deficits were identified at the individual level, after adjusting the neuropsychological test scores for demographic characteristics (sex, age, and education), based on large national normative data. The presence of cognitive dysfunction was determined by deficit in DRS-2 and/or multiple cognitive domains. Participants were also screened for depression based on a self-report questionnaire. The frequency of cognitive dysfunction was higher (p = 0.003) in symptomatic (9%) than in asymptomatic (2%) carriers. Among older carriers (≥ 50 years), the frequency of cognitive dysfunction was higher (p hereditary TTR amyloidosis patients with peripheral polyneuropathy, even in the early stages of the disease.

  11. Light chain (AL amyloidosis: update on diagnosis and management

    Directory of Open Access Journals (Sweden)

    Rosenzweig Michael

    2011-11-01

    Full Text Available Abstract Light chain (AL amyloidosis is a plasma cell dyscrasia characterized by the pathologic production of fibrillar proteins comprised of monoclonal light chains which deposit in tissues and cause organ dysfunction. The diagnosis can be challenging, requiring a biopsy and often specialized testing to confirm the subtype of systemic disease. The goal of treatment is eradication of the monoclonal plasma cell population and suppression of the pathologic light chains which can result in organ improvement and extend patient survival. Standard treatment approaches include high dose melphalan (HDM followed by autologous hematopoietic stem cell transplantation (SCT or oral melphalan with dexamethasone (MDex. The use of novel agents (thalidomide, lenalidomide and bortezomib alone and in combination with steroids and alkylating agents has shown efficacy and continues to be explored. A risk adapted approach to SCT followed by novel agents as consolidation reduces treatment related mortality with promising outcomes. Immunotherapeutic approaches targeting pathologic plasma cells and amyloid precursor proteins or fibrils are being developed. Referral of patients to specialized centers focusing on AL amyloidosis and conducting clinical trials is essential to improving patient outcomes.

  12. Therapeutic regional dermabrasion in papular lichen amyloidosis of shins

    Directory of Open Access Journals (Sweden)

    Savant S

    1995-01-01

    Full Text Available Therapeutic regional dermabrasion of shins is a useful surgical method for planing away the persistent pruritic lichenified hyperkeratotic eruptions of papular lichen amyloidosis. Nine patients (6 females and 3 males of 35 to 52 years age having papular lichen amyloidosis on shins, refractory to various medical lines of treatment for 5-12 years duration were subjected to regional dermabrasion. Extensor surfaces (shins of both lower extremities (18 sites in all 9 cases were treated by multiple sittings of spot dermabrasion. All 18 sites healed with superficial scarring and complete response (100% with total clearance of lesions was observed in all 18 sites. Pruritus stopped in all the 18 dermabraded sites immediately. No local recurrence has been observed in any sites over a minimum follow up peroid of 1½ years. Apart from superficial scarring occurring at all 18 sites the other side effect observed was varying degree of hypopigmentation in 10 out of the 18 sites dermabraded. Complication in the form of parchment like deep atrophic scarring with persistant hypopigmentation, erythema and at places depigmentation were obseved at 2 sites which were dermabraded deeply. Similar complications with delayed wound healing were observed at the 3rd site as sequel to secondary bacterial infection following spot dermabrasion

  13. Therapeutic regional dermabrasion in papular lichen amyloidosis of shins.

    Science.gov (United States)

    Savant, S S

    1995-01-01

    Therapeutic regional dermabrasion of shins is a useful surgical method for planing away the persistent pruritic lichenified hyperkeratotic eruptions of papular lichen amyloidosis. Nine patients (6 females and 3 males) of 35 to 52 years age having papular lichen amyloidosis on shins, refractory to various medical lines of treatment for 5-12 years duration were subjected to regional dermabrasion. Extensor surfaces (shins) of both lower extremities (18 sites) in all 9 cases were treated by multiple sittings of spot dermabrasion. All 18 sites healed with superficial scarring and complete response (100%) with total clearance of lesions was observed in all 18 sites. Pruritus stopped in all the 18 dermabraded sites immediately. No local recurrence has been observed in any sites over a minimum follow up peroid of 1½ years. Apart from superficial scarring occurring at all 18 sites the other side effect observed was varying degree of hypopigmentation in 10 out of the 18 sites dermabraded. Complication in the form of parchment like deep atrophic scarring with persistant hypopigmentation, erythema and at places depigmentation were obseved at 2 sites which were dermabraded deeply. Similar complications with delayed wound healing were observed at the 3rd site as sequel to secondary bacterial infection following spot dermabrasion.

  14. Localized amyloidosis of the stomach mimicking a superficial gastric cancer.

    Science.gov (United States)

    Kagawa, Miwako; Fujino, Yasuteru; Muguruma, Naoki; Murayama, Noriaki; Okamoto, Koichi; Kitamura, Shinji; Kimura, Tetsuo; Kishi, Kazuhiro; Miyamoto, Hiroshi; Uehara, Hisanori; Takayama, Tetsuji

    2016-06-01

    A 73-year-old man was referred to our hospital for further examination of a depressed lesion in the stomach found by cancer screening gastroscopy. A barium upper gastrointestinal series showed an area of irregular mucosa measuring 15 mm on the anterior wall of the gastric body. Esophagogastroduodenoscopy revealed a 15 mm depressed lesion on the anterior wall of the lower gastric body. We suspected an undifferentiated adenocarcinoma from the appearance and took some biopsies. However, histology of the specimens revealed amyloidal deposits in the submucosal layer without malignant findings. Congo red staining was positive for amyloidal protein and green birefringence was observed under polarized light microscopy. Congo red staining with prior potassium permanganate incubation confirmed the light chain (AL) amyloid type. There were no amyloid deposits in the colon or duodenum. Computed tomography of the chest, abdomen, and pelvis showed no remarkable findings. Thus, this case was diagnosed as a localized gastric amyloidosis characterized by AL type amyloid deposition in the mucosal or submucosal layer. As the clinical outcome of gastric AL amyloidosis seems favorable, this case is scheduled for periodic examination to recognize potential disease progression and has been stable for 2 years.

  15. Diagnostic performance of transthyretin measurement in fat tissue of patients with ATTR amyloidosis

    NARCIS (Netherlands)

    Hazenberg, B.P.C.; Van Schijndel, B.; Bijzet, J.; Limburg, P.C.; Bos, R.; Haagsma, E.B.

    2010-01-01

    Background: The diagnostic performance was studied of a transthyretin (TTR) ELISA for detection and characterisation of transthyretin-derived (ATTR) amyloid in abdominal subcutaneous fat tissue. Methods: Fat tissue specimens were analysed of 38 consecutive patients with hereditary ATTR amyloidosis,

  16. Ventricular fibrillation after bortezomib therapy in a patient with systemic amyloidosis

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    Satoshi Yamasaki

    2013-09-01

    Full Text Available A 64-year-old female was diagnosed with systemic amyloidosis associated with multiple myeloma. Bortezomib and dexamethasone-therapy was initiated; however, she developed lethal ventricular fibrillation (VF and cardiac arrest after 84 hours of therapy. Cardiopulmonary resuscitation using direct current shocks with epinephrine and amiodarone was initiated but failed to receive cardiac function. Although her arterial pulsations recovered immediately after the injection of vasopressin, she died of heart failure 8 hours after the onset of VF. Cardiac amyloidosis was verified by autopsy. Although the direct association of bortezomib with lethal VF remained to be clarified in our patient, the current report emphasizes on bortezomib as a substantial risk factor for cardiomyocyte damage. The potential risk of lethal events associated with cardiac amyloidosis should be carefully considered during bortezomib treatment for patients with AL amyloidosis.

  17. Macroglossia due to Systemic Amyloidosis: Is There a Role for Radiotherapy

    Directory of Open Access Journals (Sweden)

    Isabelle Thibault

    2011-08-01

    Full Text Available Background: Macroglossia due to amyloid depositions can cause cosmetic problems and functional disability, and can lead to life-threatening airway obstruction. Management of macroglossia in systemic amyloidosis is controversial, and the role of surgery is unclear. Case Description: We present a case of a 66-year-old woman affected by macroglossia due to light chain amyloidosis who presented with eating and breathing difficulties. Because of prior successful results of radiotherapy for localized amyloid disease, our patient was treated with external beam radiation therapy (20 Gy in 10 fractions. The treatment was well tolerated by the patient. However, her systemic amyloidosis progressed, with a subclinical increase in tongue width. Conclusions: This is the first reported use of radiotherapy for amyloidosis of the tongue. There was no evidence of benefit using a total dose of 20 Gy. This therapeutic modality is not recommended for the routine management of macroglossia.

  18. Direct tissue evaluation via immunofluorescence: in the diagnosis of hereditary transthyretin cardiac amyloidosis.

    Science.gov (United States)

    Fradley, Michael G; Thakuria, Joseph V; Collins, A Bernard; Moore, Stephanie A; Stone, James R

    2012-01-01

    Multiple precursor proteins have been shown to cause cardiac amyloidosis. The most common forms are due either to immunoglobulin light chains or to transthyretin proteins (either wild-type or mutant forms). Correct subclassification of the amyloid is paramount because treatment differs in accordance with the type of amyloidosis. Indirect diagnostic methods, including serologic analysis, can lead to misdiagnosis. Definitive diagnosis often requires analysis of amyloid in the tissue. We present a case of a woman who was diagnosed with hereditary transthyretin cardiac amyloidosis by means of immunofluorescence and genetic analysis. This case highlights the importance-in the diagnostic algorithm of cardiac amyloidosis-of direct evaluation of the tissue with immunofluorescence and of genetic testing.

  19. Anakinra induces complete remission of nephrotic syndrome in a patient with familial mediterranean fever and amyloidosis.

    Science.gov (United States)

    Sevillano, Ángel M; Hernandez, Eduardo; Gonzalez, Esther; Mateo, Isabel; Gutierrez, Eduardo; Morales, Enrique; Praga, Manuel

    2016-01-01

    Renal amyloidosis is one of the most severe complications of familial Mediterranean fever (FMF). Colchicine has reduced the incidence of this complication, which now only appears in untreated, under-treated and resistant patients, but it is usually ineffective in patients with advanced amyloidosis. Here we report a patient with FMF and biopsy-proven amyloidosis who presented with nephrotic syndrome despite colchicine treatment. Anakinra (an interleukin-1β inhibitor) was started and a dramatic complete remission of nephrotic syndrome was observed in the following months. Anakinra can be an effective treatment for FMF patients with severe secondary amyloidosis. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  20. Cardiac Involvement is Underdiagnosed in Patients with Biopsy-Proven Systemic AL Amyloidosis

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    Haoyi Zheng

    2016-01-01

    Diagnosis of cardiac amyloidosis based on presence of heart failure symptoms led to underdiagnosis of cardiac involvement defined by the NCCN criteria. Guideline recommended assessment of cardiac involvement and cardiac response to treatment was not routinely implemented in our cohort.

  1. Long-term TNF-alpha blockade in patients with amyloid A amyloidosis complicating rheumatic diseases.

    Science.gov (United States)

    Fernández-Nebro, Antonio; Olivé, Alejandro; Castro, María Carmen; Varela, Angela Herranz; Riera, Elena; Irigoyen, Maria V; García de Yébenes, María Jesús; García-Vicuña, Rosario

    2010-05-01

    To evaluate the effectiveness and safety of anti-tumor necrosis factor therapy in patients with amyloid A amyloidosis. Multicenter, controlled, dynamic prospective cohort study of 36 patients with amyloid A amyloidosis (94% kidney involvement) treated with anti-tumor necrosis factor agents (drug exposure of 102.97 patient-years). As an external control group, 35 propensity score-matched non-amyloid patients were chosen from the Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología registry. The end points were kidney response and progression, anti-tumor necrosis factor continuation rate, patient survival, and adverse events. At the end of follow-up, a kidney response was observed in 12 of 22 patients (54.5%) and a kidney progression was observed in 6 of 36 patients (17%). The kidney amyloidosis remained stable in 16 of 36 patients (44%). The level of acute phase reactants diminished but did not reach the normal level. The continuation rates of anti-tumor necrosis factor drugs among patients with amyloid A amyloidosis after 1, 2, 3, and 4 or more years were 80%, 80%, 61%, and 52%, respectively, comparable to controls. The 5-year cumulative survival of amyloid A amyloidosis cases was 90.6%, and the 10-year survival was 78.5%. In a multivariate Cox regression analysis, the duration of amyloidosis and the level of proteinuria at the onset of anti-tumor necrosis factor treatment were independent predictors of treatment failure, whereas the level of proteinuria was the only factor that predicts mortality. Most adverse events were similar in both groups, although the number of infections was 3 times higher in amyloid A amyloidosis cases. Anti-tumor necrosis factor drugs are effective in treating amyloid A amyloidosis, although they might increase the risk of infection. Copyright 2010 Elsevier Inc. All rights reserved.

  2. Cardiac amyloidosis induces up-regulation of Deleted in Malignant Brain Tumors 1 (DMBT1)

    DEFF Research Database (Denmark)

    Müller, Hanna; Renner, Marcus; Bergmann, Frank

    2013-01-01

    Amyloidosis is a life-threatening protein misfolding disease and affects cardiac tissue, leading to heart failure, myocardial ischemia and arrhythmia. Amyloid deposits result in oxidative stress, inflammation and apoptosis. The purpose of this study was to examine the role of innate defense compo...... components, i.e., Deleted in Malignant Brain Tumors 1 (DMBT1) and the complement system, in different types of cardiac amyloidosis....

  3. Focal Amyloidosis of the Orbit Presenting as a Mass: MRI and CT Features

    International Nuclear Information System (INIS)

    Yerli, Hasan; Aydin, Erdinc; Avci, Suat; Haberal, Nihan; Oto, Sibel

    2011-01-01

    Focal orbital amyloidosis is a rare entity and little is known about its magnetic resonance imaging (MRI) features. In this case report, imaging features of a case of focal orbital amyloidosis presenting as a mass have been documented together with its histopathological findings. On MRI, a well-defined mass was seen as isointense with rectus muscle on T1-weighted images and heterogeneously hypointense on T2-weighted images. Punctuate calcifications were observed on the computerized tomography (CT) examination

  4. Abdominal fat pad excisional biopsy for the diagnosis and typing of systemic amyloidosis.

    Science.gov (United States)

    Garcia, Yessica; Collins, A Bernard; Stone, James R

    2018-02-01

    In the past, the diagnosis and typing of amyloidosis often required an invasive biopsy of an internal organ, such as the heart or kidneys. Abdominal fat pad excisional biopsy (FPEB) offers a less invasive approach, but the sensitivity of this technique has been unclear. To determine the sensitivity of FPEB for immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, we performed a retrospective clinicopathologic analysis of 97 patients who had undergone FPEB, of which 16 were positive for amyloid. The most significant pretest feature predicting a positive FPEB was a serum free light chain κ/λ ratio less than .5, and in this group of patients the probability of a positive biopsy was dependent on the size of the biopsy (P=.004). In FPEBs, the amyloid was present in multiple distinct patterns: pericellular, septal, medium-sized vessel, small vessel, and nodular. For patients with AL amyloidosis for which direct typing was attempted using the FPEB tissue, the amyloid was successfully typed in the FPEB in 90% of cases. The overall sensitivity of FPEB was 79% for AL amyloidosis and 12% for ATTR amyloidosis (P=.0003). In patients with AL amyloidosis, the sensitivity of FPEB was dependent on biopsy size, with small biopsies (≤700 mm 3 ) having a sensitivity of ~50%, and large biopsies (>700 mm 3 ) having a sensitivity of ~100%. This study demonstrates that FPEB has high sensitivity for AL amyloidosis, and can be routinely used to type the amyloid. However, FPEB has low sensitivity for ATTR amyloidosis in our patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Purpuric halo around hemangioma as a clue for primary systemic amyloidosis: Case report and review of literature

    Directory of Open Access Journals (Sweden)

    Yin-Shuo Chang

    2018-03-01

    Full Text Available Mucocutaneous lesion appears in up to 40% of patients with primary systemic amyloidosis (AL amyloidosis. The cutaneous signs may be co-expressed with other organ involvement or even solely presented as the first clue. We reported a case of systemic AL amyloidosis who was initially presented as a solitary hemangioma with a purpuric halo. Excisional biopsy revealed a hemangioma with amyloid deposited in thickened vascular walls. Systemic AL amyloidosis was diagnosed after thorough survey. The stage of disease at the time of initial treatment is the greatest prognostic factor. To our knowledge, this is the first case of systemic AL amyloidosis initially presented as a purpuric halo around hemangioma in Taiwan. This target-like lesion should be linked to systemic AL amyloidosis and early diagnosis is extraordinary important.

  6. Prognostic value of depressed midwall systolic function in cardiac light-chain amyloidosis.

    Science.gov (United States)

    Perlini, Stefano; Salinaro, Francesco; Musca, Francesco; Mussinelli, Roberta; Boldrini, Michele; Raimondi, Ambra; Milani, Paolo; Foli, Andrea; Cappelli, Francesco; Perfetto, Federico; Palladini, Giovanni; Rapezzi, Claudio; Merlini, Giampaolo

    2014-05-01

    Cardiac amyloidosis represents an archetypal form of restrictive heart disease, characterized by profound diastolic dysfunction. As ejection fraction is preserved until the late stage of the disease, the majority of patients do fulfill the definition of diastolic heart failure, that is, heart failure with preserved ejection fraction (HFpEF). In another clinical model of HFpEF, that is, pressure-overload hypertrophy, depressed midwall fractional shortening (mFS) has been shown to be a powerful prognostic factor. To assess the potential prognostic role of mFS in cardiac light-chain amyloidosis with preserved ejection fraction, we enrolled 221 consecutive untreated patients, in whom a first diagnosis of cardiac light-chain amyloidosis was concluded between 2008 and 2010. HFpEF was present in 181 patients. Patients in whom cardiac involvement was excluded served as controls (n = 121). Prognosis was assessed after a median follow-up of 561 days. When compared with light-chain amyloidosis patients without myocardial involvement, cardiac light-chain amyloidosis was characterized by increased wall thickness (P model. In cardiac light-chain amyloidosis with normal ejection fraction, depressed circumferential mFS, a marker of myocardial contractile dysfunction, is a powerful predictor of survival.

  7. Ursodeoxycholic acid for treatment of cholestasis in patients with hepatic amyloidosis

    Directory of Open Access Journals (Sweden)

    Faust Dominik

    2009-01-01

    Full Text Available Background. Amyloidosis represents a group of different diseases characterized by extracellular accumulation of pathologic fibrillar proteins in various tissues and organs. Severe amyloid deposition in the liver parenchyma has extrahepatic involvement predominantly in the kidney or heart. We evaluated the effect of ursodeoxycholic acid, in four patients with severe hepatic amyloidosis of different etiologies, who presented with increased alkaline phosphatase and γ-glutamyl transferase. Case report. The study included four patients who presented with amyloidosis-associated intrahepatic cholestasis. Three of them had renal amyloidosis which developed 1-3 years before cholestasis occurred, the remaining one having intrahepatic cholestasis as the primary sign of the disease. Amyloidosis was identified from liver biopsies in all patients by its specific binding to Congo red and green birefringence in polarized light. The biochemical nature and the class of amyloid deposits were identified immunohistochemically. In addition to their regular treatment, the patients received 750 mg ursodeoxycholic acid per day. After 2-4 weeks all patients had a significant decrease of serum alkaline phosphatase and γ-glutamyl transferase, and their general status significantly improved. Conclusion. Treatment with ursodeoxycholic acid may be beneficial in patients with hepatic amyloidosis, and do extend indications for the use of ursodeoxycholic acid in amyloidotic cholestatic liver disease.

  8. Anxiety and depression among amyloid light-chain cardiac amyloidosis patients: The role of life satisfaction.

    Science.gov (United States)

    Smorti, Martina; Guarnieri, Silvia; Bergesio, Franco; Perfetto, Federico; Cappelli, Francesco

    2016-06-01

    The present study aimed to provide a contribution to the study of a rare disease, amyloid light-chain (AL) cardiac amyloidosis, which is the most common type of systemic amyloidosis. In AL amyloidosis prognosis is determined by cardiac involvement. Although the association between psychological distress (e.g. anxiety and depression) and AL cardiac amyloidosis is documented, very little is known about the psychosocial variables that may mediate the association. The aim of the study is therefore to examine the potential mediating role of life satisfaction in the relationship between cardiac symptom severity (independent variable) and anxious and depressive symptoms (dependent variables) in AL patients. Forty-three AL amyloidosis patients (57.1% males) with cardiac amyloidosis were administered the Satisfaction with Life Scale, the State-Trait Anxiety Inventory and the Centre for Epidemiological Study-Depression Scale. Clinical variables such as months since cardiac symptom onset and cardiac symptom severity were collected. Findings showed significant relationships between symptom severity and psychological disorders (e.g. anxiety and depression) and these were mediated by life satisfaction. Overall, findings highlight the importance of subjective well-being (e.g. life satisfaction) to reduce anxious and depressive symptoms and to improve general health in AL patients. © The European Society of Cardiology 2015.

  9. Accurate analysis and visualization of cardiac (11)C-PIB uptake in amyloidosis with semiautomatic software.

    Science.gov (United States)

    Kero, Tanja; Lindsjö, Lars; Sörensen, Jens; Lubberink, Mark

    2016-08-01

    (11)C-PIB PET is a promising non-invasive diagnostic tool for cardiac amyloidosis. Semiautomatic analysis of PET data is now available but it is not known how accurate these methods are for amyloid imaging. The aim of this study was to evaluate the feasibility of one semiautomatic software tool for analysis and visualization of (11)C-PIB left ventricular retention index (RI) in cardiac amyloidosis. Patients with systemic amyloidosis and cardiac involvement (n = 10) and healthy controls (n = 5) were investigated with dynamic (11)C-PIB PET. Two observers analyzed the PET studies with semiautomatic software to calculate the left ventricular RI of (11)C-PIB and to create parametric images. The mean RI at 15-25 min from the semiautomatic analysis was compared with RI based on manual analysis and showed comparable values (0.056 vs 0.054 min(-1) for amyloidosis patients and 0.024 vs 0.025 min(-1) in healthy controls; P = .78) and the correlation was excellent (r = 0.98). Inter-reader reproducibility also was excellent (intraclass correlation coefficient, ICC > 0.98). Parametric polarmaps and histograms made visual separation of amyloidosis patients and healthy controls fast and simple. Accurate semiautomatic analysis of cardiac (11)C-PIB RI in amyloidosis patients is feasible. Parametric polarmaps and histograms make visual interpretation fast and simple.

  10. Plasmacytoma with amyloidosis masquerding as tuberculosis on cytology

    Directory of Open Access Journals (Sweden)

    Sharma Neelam

    2009-01-01

    Full Text Available Amyloid material on lymph node cytology smears can mimic caseous necrosis. We report one such case where a 50-year-old lady presented with a nasal mass and cervical lymphadenopathy. Fine needle aspiration cytology smears of the cervical lymph node were interpreted as tuberculous lymphadenitis based on the presence of an occasional epithelioid cell and caseous material. The patient did not respond to antituberculous therapy and was revaluated. Repeat aspiration from the lymph node showed numerous plasma cells and myeloma cells in addition to the amorphous material which was confirmed to be amyloid on staining with congo red. A diagnosis of plasmacytoma with amyloidosis was rendered. Imprint smears from nasal mass, detailed hematology workup and subsequent histology confirmed the diagnosis.

  11. Systemic AL amyloidosis with unusual cutaneous presentation unmasked by carotenoderma

    Czech Academy of Sciences Publication Activity Database

    Hůlková, H.; Vlášková, H.; Elleder, M.; Svojanovský, J.; Ševela, K.; Krusová, D.; Hanuš, J.; Souček, M.; Vězda, P.; Márová, I.; Feit, J.; Zambo, I.; Kovačevicova, M.; Kostrouchová, V.; Kostrouch, Z.; Novák, Petr

    2014-01-01

    Roč. 21, č. 5 (2014), s. 57-61 ISSN 1350-6129 R&D Projects: GA MŠk ED1.1.00/02.0109; GA MŠk(CZ) EE2.3.20.0055; GA MŠk LO1211; GA MŠk EE2.3.30.0003 Grant - others:Masaryk University, Brno(CZ) MUNI/A/1012/2009; GA MŠk(CZ) Prvouk-P27/LF1/1; Karlova Universita(CZ) UNCE 20422; Universita Karlova(CZ) UNCE 204011; Universita Karlova(CZ) PRVOUK-P24/LF1/3 Institutional support: RVO:61388971 Keywords : alzheimer * gene * amyloidosis Subject RIV: EC - Immunology Impact factor: 2.010, year: 2014

  12. Pathology of AA amyloidosis in domestic sheep and goats.

    Science.gov (United States)

    Ménsua, C; Carrasco, L; Bautista, M J; Biescas, E; Fernández, A; Murphy, C L; Weiss, D T; Solomon, A; Luján, L

    2003-01-01

    We describe the main pathologic changes in small ruminants affected by AA amyloidosis, together with the partial sequence of the protein involved. Twenty-one sheep and one goat were selected for presenting macroscopic kidney lesions compatible with systemic amyloidosis. Available tissue samples were studied by histologic, immunopathologic, and ultrastructural means. Renal lesions were characterized grossly by pale cortical surfaces with scattered, miliary, whitish-yellow foci and on cut cortical surfaces by straight, whitish-yellow striations. Gangrenous pneumonia was observed in 16 out of 21 affected sheep (76.2%), although other chronic inflammations were also observed. Amyloid was detected in all grossly affected kidneys using Congo red staining, lesions being most remarkable in glomeruli, affecting 95.5% of animals studied. Congophilic deposits were also observed in intertubular interstitium (68.2%) and medulla (57.1%). All amyloid-affected animals presented proximal convoluted tubule lesions, mostly characterized by an increase in diameter and by hyaline granular degeneration that were responsible for the macroscopic appearance of the kidney. Histologically, amyloid was also seen in blood vessels, spleen, liver, lymph nodes, gastrointestinal tract, and adrenal glands. All amyloid deposits demonstrated greenish-yellow birefringence with polarized light, and the antisera prepared against goat amyloid extracts specifically reacted with birefringent congophilic deposits of both sheep and goats. Ultrastructurally, these deposits were formed by masses of straight, nonbranching fibrils located predominantly in the basement membranes of glomerular capillaries and in the mesangium. Partial sequence of the protein in sheep and goats indicated a high degree of homology with the previously reported sequence of sheep Serum Amyloid A.

  13. Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics.

    Science.gov (United States)

    Vrana, Julie A; Theis, Jason D; Dasari, Surendra; Mereuta, Oana M; Dispenzieri, Angela; Zeldenrust, Steven R; Gertz, Morie A; Kurtin, Paul J; Grogg, Karen L; Dogan, Ahmet

    2014-07-01

    Examination of abdominal subcutaneous fat aspirates is a practical, sensitive and specific method for the diagnosis of systemic amyloidosis. Here we describe the development and implementation of a clinical assay using mass spectrometry-based proteomics to type amyloidosis in subcutaneous fat aspirates. First, we validated the assay comparing amyloid-positive (n=43) and -negative (n=26) subcutaneous fat aspirates. The assay classified amyloidosis with 88% sensitivity and 96% specificity. We then implemented the assay as a clinical test, and analyzed 366 amyloid-positive subcutaneous fat aspirates in a 4-year period as part of routine clinical care. The assay had a sensitivity of 90%, and diverse amyloid types, including immunoglobulin light chain (74%), transthyretin (13%), serum amyloid A (%1), gelsolin (1%), and lysozyme (1%), were identified. Using bioinformatics, we identified a universal amyloid proteome signature, which has high sensitivity and specificity for amyloidosis similar to that of Congo red staining. We curated proteome databases which included variant proteins associated with systemic amyloidosis, and identified clonotypic immunoglobulin variable gene usage in immunoglobulin light chain amyloidosis, and the variant peptides in hereditary transthyretin amyloidosis. In conclusion, mass spectrometry-based proteomic analysis of subcutaneous fat aspirates offers a powerful tool for the diagnosis and typing of systemic amyloidosis. The assay reveals the underlying pathogenesis by identifying variable gene usage in immunoglobulin light chains and the variant peptides in hereditary amyloidosis. Copyright© Ferrata Storti Foundation.

  14. Localized gastric amyloidosis differentiated histologically from scirrhous gastric cancer using endoscopic mucosal resection: a case report

    Directory of Open Access Journals (Sweden)

    Kamata Tsugumasa

    2012-08-01

    Full Text Available Abstract Introduction Amyloidosis most often manifests as a systemic involvement of multiple tissues and organs, and an amyloidal deposit confined to the stomach is extremely rare. It is sometimes difficult to provide a definitive diagnosis of localized gastric amyloidosis by biopsy specimen and diagnosis of amyloidosis in some cases has been finalized only after surgical resection of the stomach. Case presentation A 76-year-old Japanese woman with epigastric discomfort underwent an esophagogastroduodenoscopy procedure. The esophagogastroduodenoscopy revealed gastric wall thickening, suggesting scirrhous gastric carcinoma, at the greater curvature from the upper to the lower part of the gastric corpus. A biopsy specimen revealed amyloid deposits in the submucosal layer with no malignant findings. We resected a representative portion of the lesion by endoscopic mucosal resection using the strip biopsy method to obtain sufficient tissue specimens, and then conducted a detailed histological evaluation of the samples. The resected specimens revealed deposition of amyloidal materials in the gastric mucosa and submucosa without any malignant findings. Congo red staining results were positive for amyloidal protein and exhibited green birefringence under polarized light. Congo red staining with prior potassium permanganate incubation confirmed the light chain (AL amyloid protein type. Based on these results, gastric malignancy, systemic amyloidosis and amyloid deposits induced by inflammatory disease were excluded and this lesion was consequently diagnosed as localized gastric amyloidosis. Our patient was an older woman and there were no findings relative to an increase in gastrointestinal symptoms or anemia, so no further treatment was performed. She continued to be in good condition without any finding of disease progression six years after verification of our diagnosis. Conclusions We report an unusual case of primary amyloidosis of the stomach

  15. Renal Amyloidosis Associated With 5 Novel Variants in the Fibrinogen A Alpha Chain Protein.

    Science.gov (United States)

    Rowczenio, Dorota; Stensland, Maria; de Souza, Gustavo A; Strøm, Erik H; Gilbertson, Janet A; Taylor, Graham; Rendell, Nigel; Minogue, Shane; Efebera, Yvonne A; Lachmann, Helen J; Wechalekar, Ashutosh D; Hawkins, Philip N; Heimdal, Ketil R; Selvig, Kristian; Lægreid, Inger K; Demoulin, Nathalie; Aydin, Selda; Gillmore, Julian D; Wien, Tale N

    2017-05-01

    Fibrinogen A alpha chain amyloidosis is an autosomal dominant disease associated with mutations in the fibrinogen A alpha chain ( FGA ) gene, and it is the most common cause of hereditary renal amyloidosis in the UK. Patients typically present with kidney impairment and progress to end-stage renal disease over a median time of 4.6 years. Six patients presented with proteinuria, hypertension, and/or lower limb edema and underwent detailed clinical and laboratory investigations. A novel FGA gene mutation was identified in each case: 2 frameshift mutations F521Sfs*27 and G519Efs*30 and 4 single base substitutions G555F, E526K, E524K, R554H. In 5 subjects, extensive amyloid deposits were found solely within the glomeruli, which stained specifically with antibodies to fibrinogen A alpha chain, and in one of these cases, we found coexistent fibrinogen A alpha chain amyloidosis and anti-glomerular basement membrane antibody disease. One patient was diagnosed with light-chain amyloidosis after a bone marrow examination revealed a small clonal plasma cell population, and laser microdissection of the amyloid deposits followed by liquid chromatography and tandem mass spectrometry identified kappa light chain as the fibril protein. We report 6 novel mutations in the FGA gene: 5 were associated with renal fibrinogen A alpha chain amyloidosis and 1 was found to be incidental to light-chain amyloid deposits discovered in a patient with a plasma cell dyscrasia. Clinical awareness and suspicion of hereditary amyloidosis corroborated by genetic analysis and adequate typing using combined immunohistochemistry and laser microdissection and mass spectrometry is valuable to avoid misdiagnosis, especially when a family history of amyloidosis is absent.

  16. Long-term prognosis of AL and AA renal amyloidosis: a Japanese single-center experience.

    Science.gov (United States)

    Ozawa, Masatoyo; Komatsuda, Atsushi; Ohtani, Hiroshi; Nara, Mizuho; Sato, Ryuta; Togashi, Masaru; Takahashi, Naoto; Wakui, Hideki

    2017-04-01

    Few studies have been conducted on the long-term prognosis of patients with amyloid light chain (AL) and amyloid A (AA) renal amyloidosis in the same cohort. We retrospectively examined 68 patients with biopsy-proven renal amyloidosis (38 AL and 30 AA). Clinicopathological findings at the diagnosis and follow-up data were evaluated in each patient. We analyzed the relationship between clinicopathological parameters and survival data. Significant differences were observed in several clinicopathological features, such as proteinuria levels, between the AL and AA groups. Among all patients, 84.2 % of the AL group and 93.3 % of the AA group received treatments for the underlying diseases of amyloidosis. During the follow-up period (median 18 months in AL and 61 months in AA), 36.8 % of the AL group and 36.7 % of the AA group developed end-stage renal failure requiring dialysis, while 71.1 % of the AL group and 56.7 % of the AA group died. Patient and renal survivals were significantly longer in the AA group than in the AL group. eGFR of >60 mL/min/1.73 m 2 at biopsy and an early histological stage of glomerular amyloid deposition were identified as low-risk factors. A multivariate analysis showed that cardiac amyloidosis and steroid therapy significantly influenced patient and renal survivals. Our results showed that heart involvement was the major predictor of poor outcomes in renal amyloidosis, and that the prognosis of AA renal amyloidosis was markedly better than that in previously reported cohorts. Therapeutic advances in inflammatory diseases are expected to improve the prognosis of AA amyloidosis.

  17. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL) : A consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis

    NARCIS (Netherlands)

    Gertz, MA; Comenzo, R; Falk, RH; Fermand, JP; Hazenberg, BP; Hawkins, PN; Merlini, G; Moreau, P; Ronco, P; Sanchorawala, [No Value; Sezer, O; Solomon, A; Grateau, G

    We undertook this study to develop uniformly accepted criteria for the definition of organ involvement and response for patients on treatment protocols for immunoglobulin light-chain amyloidosis (AL). A consensus panel was convened comprising 13 specialists actively involved in the treatment of

  18. Diagnostic performance and prognostic value of extravascular retention of I-123-labeled serum amyloid P component in systemic amyloidosis

    NARCIS (Netherlands)

    Hazenberg, Bouke P. C.; van Rijswijk, Martin H.; Lub-de Hooge, Marjolijn N.; Vellenga, Edo; Haagsma, Elizabeth B.; Posthumus, Marcel D.; Jager, Pieter L.

    Serum amyloid P component (SAP) binds to amyloid.I-123-SAP scintigraphy is used to evaluate the extent and distribution of amyloid in systemic amyloidosis and has great clinical value in the detection of systemic amyloidosis. The aim of the study was to assess during scintigraphy the diagnostic

  19. IgG,kappa monoclonal gammopathy of unknown significance with AL amyloidosis simulating giant cell arteritis

    Directory of Open Access Journals (Sweden)

    Pompilian Valer Mihai

    2017-09-01

    Full Text Available Monoclonal gammopathies complicated by AL amyloidosis can mimic giant cell arteritis (GCA. We hereby present the case of a 63 year old woman in whom symptoms consistent with GCA were the first manifestations of a monoclonal gammopathy of unknown significance (MGUS associated with amyloidosis. A 63 year old woman was admitted for temporal headache, maseterine claudication, neck and shoulder stiffness. She was recently diagnosed with carpal tunnel syndrome. On physical examination she had prominent temporal arteries, macroglosia and orthostatic hypotension. Muscular strength was normal. She had high ESR and CRP; in this clinical context, GCA was suspected. A gamma spike on serum protein electrophoresis raised the suspicion of monoclonal gammopathy (MG. Immunoelectrophoresis revealed monoclonal bands for IgG and kappa chains. Massive deposits of amyloid and no inflammation were found on temporal artery biopsy. Multiple myeloma and lymphoma were ruled out. A diagnosis of AL amyloidosis complicating MGUS was formulated. She did well on therapy with bortezomib, cyclophosphamide and dexamethasone. Cases published in medical literature reveal amyloidosis mimicking GCA in the setting of established MGUS. As far as we know, this is the first case of MGUS with IgG and kappa chains in which a GCA-like picture induced by amyloidosis was present from the very onset.

  20. 18F-fluorodeoxyglucose positron emission tomography might be useful for diagnosis of hepatic amyloidosis

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    Tawada A

    2014-06-01

    Full Text Available Akinobu Tawada,1 Tatsuo Kanda,1 Takashi Oide,2 Toshio Tsuyuguchi,1 Fumio Imazeki,1,3 Yukio Nakatani,2 Osamu Yokosuka11Department of Gastroenterology, 2Department of Diagnostic Pathology, Chiba University Hospital, Chuo-ku, Chiba, Japan; 3Safety and Health Organization, Chiba University, Inage-ku, Chiba, JapanAbstract: We report on a woman with hepatic involvement of primary systemic (immunoglobulin light chain, AL amyloidosis. Her diagnosis was confirmed by liver biopsy. Clinical symptoms of hepatic amyloidosis are generally mild at its first stage, with most frequent findings being hepatomegaly and alkaline phosphatase elevation. Recent advances in the understanding of the pathophysiology of systemic amyloidosis have made several treatments available. However, its prognosis is occasionally poor. Because liver biopsy is not always safe, other modalities for the diagnosis are needed. Of interest was that fluorodeoxyglucose (FDG uptake into the liver was observed, compared with that into the spleen, in this patient, indicating that FDG positron emission tomography and computed tomography might be useful for the diagnosis of hepatic amyloidosis with mild liver dysfunction.Keywords: amyloidosis, diagnosis, hepatic involvement, FDG PET

  1. Isolated Light Chain Amyloidosis Involving the Parotid Gland: A Case Report.

    Science.gov (United States)

    Gareb, Barzi; Perry, Michael; Tadrous, Paul Joseph

    2018-03-08

    Amyloidosis in the parotid gland is rare and is usually associated with systemic amyloidosis. Localized amyloidosis in the parotid gland is extremely rare. We present a case of localized light chain amyloidosis of the parotid gland without systemic involvement. A 70-year-old woman presented with an asymptomatic swelling of the right parotid region. The findings of a physical examination, hematologic and biochemical investigations, imaging, and cytology were inconclusive. The patient underwent an extracapsular dissection of the right parotid gland. Histologic analysis showed that the tissue of the right parotid gland mostly consisted of amyloid deposition. The amyloid stained with antibodies to lambda light chains. Additional investigations showed no systemic involvement. The patient is asymptomatic 5 months after surgery. Clinicians should be aware of the possibility of localized amyloid light chain amyloidosis in the parotid gland, especially if magnetic resonance imaging, computed tomography imaging, and ultrasound findings are inconclusive, and they should recognize, evaluate, and treat it accordingly. Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. All rights reserved.

  2. Increased Prognostic Value of Query Amyloid Late Enhancement Score in Light-Chain Cardiac Amyloidosis.

    Science.gov (United States)

    Wan, Ke; Sun, Jiayu; Han, Yuchi; Liu, Hong; Yang, Dan; Li, Weihao; Wang, Jie; Cheng, Wei; Zhang, Qing; Zeng, Zhi; Chen, Yucheng

    2018-02-23

    Late gadolinium enhancement (LGE) pattern is a powerful imaging biomarker for prognosis of cardiac amyloidosis. It is unknown if the query amyloid late enhancement (QALE) score in light-chain (AL) amyloidosis could provide increased prognostic value compared with LGE pattern.Methods and Results:Seventy-eight consecutive patients with AL amyloidosis underwent contrast-enhanced cardiovascular magnetic resonance imaging. Patients with cardiac involvement were grouped by LGE pattern and analyzed using QALE score. Receiver operating characteristic curve was used to identify the optimal cut-off for QALE score in predicting all-cause mortality. Survival of these patients was analyzed with the Kaplan-Meier method and multivariate Cox regression. During a median follow-up of 34 months, 53 of 78 patients died. The optimal cut-off for QALE score to predict mortality at 12-month follow-up was 9.0. On multivariate Cox analysis, QALE score ≥9 (HR, 5.997; 95% CI: 2.665-13.497; Pvalue in AL cardiac amyloidosis. QALE score ≥9 has added value to differentiate prognosis in AL amyloidosis patients with a subendocardial LGE pattern.

  3. [Amyloidosis associated with chronic granulomatous disease in a patient with a renal transplant and recurrent urinary tract infections].

    Science.gov (United States)

    Peces, R; Ablanedo, P; Seco, M

    2002-01-01

    Chronic granulomatous disease is a group of syndromes which share a defect in a component of the phagocyte NADPH-oxidase complex. Without this enzyme activity, phagocytic cells cannot produce superoxide, peroxide, and other potent microbicidal radicals, and are less able to kill ingested pathogens. The clinical picture is characterised by recurrent life-threatening bacterial and fungal infections and abnormal tissue granuloma formation. On the other hand, amyloidosis is a systemic disease with renal involvement occurring in the majority of cases. Recurrent amyloidosis is a rare but well documented event in renal transplant recipients. However, graft loss secondary to amyloidosis has been noted infrequently. In addition, de novo amyloidosis has not been previously associated with graft loss. We report here a renal transplant recipient with chronic granulomatous disease and history of recurrent urinary tract infections, who developed nephrotic syndrome and progressive renal insufficiency secondary to de novo AA amyloidosis leading to graft loss 66 months after transplantation.

  4. Nanolayers for early diagnostics of proteins involved in degenerative amyloidosis

    Directory of Open Access Journals (Sweden)

    Martina M.R.

    2013-08-01

    Full Text Available FK-506 binding protein (FKBP12 is a protein of the family of immunophilins, involved in many neurodegenerative diseases such as Alzheimer’s syndrome where FKBP12 is known to be over-expressed in early stages of the disease. We designed and built Langmuir-Blodgett nanostructures incorporating ligands with high affinity for FKBP12: Tacrolimus (FK506 and Rifaximin as candidate nanosensors to detect low FKBP12 concentration in the initial phase of the amyloidosis. The binding process of the different ligands has been studied by means of photophysical measurements investigating the fluorescence quenching of the tryptophan residue in the binding pocket of FKBP12 by addition of the ligand in solution. Immobilization of the ligands was achieved adopting biomimetic strategy: phospholipid Langmuir-Blodgett films are proposed as nanoscaffolds for ligand inclusion. Several phospholipid nanoarchitectures differing in lipid composition, fluidity, number of layers and method of production (incubation versus co-spreading were screened. The results have shown that both FK506 and Rifaximin ligands penetrate the lipid matrix either as monomers or as aggregates depending on their initial concentration. More importantly, the experiments demonstrated that the ligands in the LB scaffolds efficiently quench FKBP12 fluorescence in solution as a consequence of ligand binding to the protein.

  5. Protein/Peptide Aggregation and Amyloidosis on Biointerfaces

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    Qi Lu

    2016-08-01

    Full Text Available Recently, studies of protein/peptide aggregation, particularly the amyloidosis, have attracted considerable attention in discussions of the pathological mechanisms of most neurodegenerative diseases. The protein/peptide aggregation processes often occur at the membrane–cytochylema interface in vivo and behave differently from those occurring in bulk solution, which raises great interest to investigate how the interfacial properties of artificial biomaterials impact on protein aggregation. From the perspective of bionics, current progress in this field has been obtained mainly from four aspects: (1 hydrophobic–hydrophilic interfaces; (2 charged surface; (3 chiral surface; and (4 biomolecule-related interfaces. The specific physical and chemical environment provided by these interfaces is reported to strongly affect the adsorption of proteins, transition of protein conformation, and diffusion of proteins on the biointerface, all of which are ultimately related to protein assembly. Meanwhile, these compelling results of in vitro experiments can greatly promote the development of early diagnostics and therapeutics for the relevant neurodegenerative diseases. This paper presents a brief review of these appealing studies, and particular interests are placed on weak interactions (i.e., hydrogen bonding and stereoselective interactions that are also non-negligible in driving amyloid aggregation at the interfaces. Moreover, this paper also proposes the future perspectives, including the great opportunities and challenges in this field as well.

  6. A case of intramural coronary amyloidosis associated with hemodialysis.

    Science.gov (United States)

    Ronny, Faisal M Huq; Kleinman, George; Kurtin, Paul James; Fallon, John Thomas

    2017-01-01

    Dialysis-related amyloidosis predominantly occurs in osteo-articular structures and dialysis-related amyloid (DRA) substances also deposit in extra-articular tissues. Clinical manifestations of DRA include odynophagia, gastrointestinal hemorrhage, intestinal obstruction, kidney stones, myocardial dysfunction, and subcutaneous tumors. The pathological characteristics of DRA in the heart of hemodialysis patients have rarely been reported. We report the case of a 73-year-old female with a history of cerebral palsy and end-stage renal disease status post two failed renal transplants who had been on hemodialysis for 30 years. The patient was admitted with the working diagnosis of pneumonia. An echocardiography showed markedly reduced biventricular function manifested by low blood pressure with systolic in the 70s and elevated pulmonary artery pressure of 45 mmHg, which did not respond to therapy. Following her demise, the autopsy revealed bilateral pulmonary edema and pleural effusions. There was cardiac amyloid deposition exclusively in the coronary arteries but not in the perimyocytic interstitium. Amyloids were also found in pulmonary and intrarenal arteries and the colon wall. Previous case reports showed that beta 2-microglobulin amyloid deposits in various visceral organs but less frequently in the atrial and/or the ventricular myocardium. In the present case, amyloids in the heart were present in the intramural coronary arteries causing myocardial ischemia and infarction, which was the immediate cause of death.

  7. Characteristics and Long-Term Outcome of Patients with Systemic Immunoglobulin Light-Chain Amyloidosis

    DEFF Research Database (Denmark)

    Nelson, Lærke Marie; Gustafsson, Finn; Gimsing, Peter

    2015-01-01

    Background/Aims: Immunoglobulin light-chain (AL) amyloidosis is a systemic disorder that causes progressive organ dysfunction. The optimal treatment strategy requires accurate patient stratification with an emphasis on the extent of cardiac involvement. Reports on its prognosis are sparse...... and predominantly originate from highly selected centers. We aimed to evaluate patient characteristics and outcomes in a cohort treated at a single center. Methods: This is a single-center retrospective study of 63 consecutive patients diagnosed with AL amyloidosis between January 2000 and December 2012. Patients...... were evaluated by treatment strategy and cardiac involvement. Results: The mean age at diagnosis was 61.4 years (±8.9), and 39 patients (62%) were male. Thirty-two (51%) patients presented with cardiac amyloid involvement (CA) and the remaining 31 (49%) had noncardiac amyloidosis (NCA). The median...

  8. Histochemical Differential Diagnosis and Polarization Optical Analysis of Amyloid and Amyloidosis

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    M. Bély

    2006-01-01

    Full Text Available Amyloidosis is characterized by extracellular deposition of protein fibrils of chemically heterogeneous composition. Early recognition and identification of amyloid deposits allows an early start of therapy, which may entail a better prognosis. Congo red staining according to Romhányi (1971 is a highly specific and sensitive method for early microscopic recognition of amyloidosis. The main and most important types of amyloidosis may be distinguished by classic histochemical methods of performate pretreatment according to Romhányi (1979, or by KMnO4 oxidation according to Wright (1977 followed by Congo red staining and viewed under polarized light. Differences in the speed of breakdown (disintegration of amyloid deposits according to Bély and Apáthy allow a more precise distinction of various types of amyloid.

  9. Bendamustine-Induced Nephrogenic Diabetes Insipidus in a Patient With AL Amyloidosis.

    Science.gov (United States)

    Uwumugambi, Nsabimana A; Sanchorawala, Vaishali; Shelton, Anthony C; Stern, Lauren; Gordon, Craig E

    2017-02-01

    Nephrogenic diabetes insipidus is a condition characterized by polyuria with dilute urine due to the inability of the principal cells of the renal collecting ducts to respond to antidiuretic hormone and concentrate urine. Nephrogenic diabetes insipidus can be drug induced, and several chemotherapeutic agents have been reported to cause it. Bendamustine is a traditional chemotherapeutic agent being studied for treatment for relapsed systemic AL amyloidosis. We report a case of a 59-year-old man with AL amyloidosis who developed partial nephrogenic diabetes insipidus after receiving bendamustine for treatment of AL amyloidosis. The nephrogenic diabetes insipidus responded well to sodium restriction, hydrochlorothiazide, and desmopressin treatment, allowing the patient to receive subsequent bendamustine cycles without polyuria. Nephrogenic diabetes insipidus resolved shortly after completion of bendamustine therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  10. A prospective study of nutritional status in immunoglobulin light chain amyloidosis.

    Science.gov (United States)

    Sattianayagam, Prayman T; Lane, Thirusha; Fox, Zoe; Petrie, Aviva; Gibbs, Simon D J; Pinney, Jennifer H; Risom, Signe S; Rowczenio, Dorota M; Wechalekar, Ashutosh D; Lachmann, Helen J; Gilbertson, Janet A; Hawkins, Philip N; Gillmore, Julian D

    2013-01-01

    Weight loss is common in systemic immunoglobulin light chain amyloidosis but there are limited data on the impact of nutritional status on outcome. Using the Patient-Generated Subjective Global Assessment (PG-SGA) score, we prospectively examined nutritional status in 110 consecutive newly-diagnosed, treatment-naïve patients with immunoglobulin light chain amyloidosis attending the UK National Amyloidosis Centre. At study entry, 72 of 110 (66%) patients had a PG-SGA score of 4 or over, indicating malnutrition requiring specialist nutritional intervention. Number of amyloidotic organs, elevated alkaline phosphatase, presence of autonomic neuropathy and advanced Mayo disease stage were independently associated with poor nutritional status (Pnutritional intervention could improve patient outcomes.

  11. Laser microdissection and mass spectrometry-based proteomics aids the diagnosis and typing of renal amyloidosis.

    Science.gov (United States)

    Sethi, Sanjeev; Vrana, Julie A; Theis, Jason D; Leung, Nelson; Sethi, Anjali; Nasr, Samih H; Fervenza, Fernando C; Cornell, Lynn D; Fidler, Mary E; Dogan, Ahmet

    2012-07-01

    Accurate diagnosis and typing of renal amyloidosis is critical for prognosis, genetic counseling, and treatment. Laser microdissection and mass spectrometry are emerging techniques for the analysis and diagnosis of many renal diseases. Here we present the results of laser microdissection and mass spectrometry performed on 127 cases of renal amyloidosis during 2008-2010. We found the following proteins in the amyloid deposits: immunoglobulin light and heavy chains, secondary reactive serum amyloid A protein, leukocyte cell-derived chemotaxin-2, fibrinogen-α chain, transthyretin, apolipoprotein A-I and A-IV, gelsolin, and β-2 microglobulin. Thus, laser microdissection of affected areas within the kidney followed by mass spectrometry provides a direct test of the composition of the deposit and forms a useful ancillary technique for the accurate diagnosis and typing of renal amyloidosis in a single procedure.

  12. MRI in cardiac sarcoidosis and amyloidosis; MRT bei kardialer Sarkoidose und Amyloidose

    Energy Technology Data Exchange (ETDEWEB)

    Bauner, K.U. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany); Wintersperger, B. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany); University of Toronto, Department of Medical Imaging, Toronto General Hospital, Toronto, ON (Canada)

    2013-01-15

    Sarcoidosis and amyloidosis are both multisystem disorders, which may involve the heart; however, isolated cardiac disease is rare. Diagnosis of cardiac sarcoidosis and amyloidosis is crucial because the patient prognosis is dependent on cardiac involvement and early treatment. Echocardiography is the first line imaging modality in the diagnostic work-up of both diseases, possibly giving hints towards the correct diagnosis. Besides myocardial biopsy and radionuclide studies cardiac magnetic resonance imaging (MRI) is routinely performed in patients suspect of having infiltrative cardiomyopathy. The T1 mapping procedure is currently being evaluated as a new technique for detection and quantification of global myocardial enhancement, as seen in cardiac amyloidosis. Sensitivities and specificities for detection of cardiac sarcoidosis and amyloidosis can be significantly improved by MRI, especially with late gadolinium enhancement (LGE) imaging. In cardiac sarcoidosis the use of LGE is outcome-related while in amyloidosis analysis of T1-mapping may be of prognostic value. If cardiac involvement in sarcoidosis or amyloidosis is suspected cardiac MRI including LGE should be performed for establishing the diagnosis. (orig.) [German] Die Sarkoidose und Amyloidose sind Multisystemerkrankungen, in deren Verlauf es zu einer kardialen Beteiligung kommen kann. Bildgebend wird als primaeres Verfahren die Echokardiographie eingesetzt. Zur weiteren Diagnostik wird neben der Biopsie und nuklearmedizinischen Verfahren v. a. die MRT herangezogen. Als neuere Technik zur Darstellung globaler diffuser Kontrastmittelanreicherungen, wie sie im Rahmen der Amyloidose vorkommen, wird z. Z. das T1-Mapping evaluiert. Durch den Einsatz der MRT, insbesondere des Late-Gadolinium-Enhancements (LGE), koennen die Sensitivitaet und Spezifitaet in der Diagnostik der kardialen Sarkoidose und Amyloidose entscheidend verbessert werden. Bei der Sarkoidose stellt das Vorhandensein eines LGE einen

  13. Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease.

    Science.gov (United States)

    Wang, Fen; Gordon, Brian A; Ryman, Davis C; Ma, Shengmei; Xiong, Chengjie; Hassenstab, Jason; Goate, Alison; Fagan, Anne M; Cairns, Nigel J; Marcus, Daniel S; McDade, Eric; Ringman, John M; Graff-Radford, Neill R; Ghetti, Bernardino; Farlow, Martin R; Sperling, Reisa; Salloway, Steve; Schofield, Peter R; Masters, Colin L; Martins, Ralph N; Rossor, Martin N; Jucker, Mathias; Danek, Adrian; Förster, Stefan; Lane, Christopher A S; Morris, John C; Benzinger, Tammie L S; Bateman, Randall J

    2015-09-01

    To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change over time (mean follow-up 2.32 years ± 0.92, range 0.89-4.19) after controlling for estimated years from expected symptom onset, APOE ε4 allelic status, and education. In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination. Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials. © 2015 American Academy of Neurology.

  14. Evaluation of 61 Secondary Amyloidosis Patients: A Single-Center Experience from Turkey

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    Can Huzmeli

    2016-09-01

    Full Text Available Aim: To evaluate demographic,clinical and laboratory characteristics, causes, MEFV gene mutations, and mortality rates of patients with secondary amyloidosis. Material and Method: 61 patients who had been diagnosed with secondary amyloidosis by renal and rectal biopsy between 2007 and 2013 in the nephrology clinic of Cumhuriyet University, Faculty of Medicine, were included in the study. Demographic characteristics, causes of secondary amyloidosis, MEFV gene mutations, end-stage renal failure (ESRF, renal transplantation, and mortality rates were examined retrospectively. Results: In etiological terms, Familial Mediterranean Fever (FMF occurrence was 62.2% (38, bronchiectasis and emphysema 9.8% (6, tuberculosis 4.9% (3, coexistence of FMF and ankylosing spondylitis 3.2% (2, coexistence of FMF and rheumatoid arthritis 1.6% (1, coexistence of FMF and systemic lupus erythematosus (SLE 1.6% (1, osteomyelitis 1.6% (1, septic arthritis 1.6% (1, Crohn%u2019s disease 1.6% (1, colon cancer 1.6% (1, coexistence of bronchiectasis and tuberculosis 1.6% (1, rheumatoid arthritis 1.6% (1, and idiopathic cases 6.5% (4. Proteinuria was determined at nephrotic level among 68% (32 of 47 patients who had secondary amyloidosis. MEFV gene mutation of 45 patients with secondary amyloidosis was assessed. Most patients had M694V gene mutation. Surprisingly, we detected heterozygous E148Q mutation in 3 cases. 12 cases died; of these, 9 had ESRF. Five cases with ESRF underwent renal transplantation. Discussion: We found FMF as the most common cause for secondary AA amyloidosis in this study. Further studies should be done with larger or multicenter cohorts.

  15. Significant association between renal function and area of amyloid deposition in kidney biopsy specimens in both AA amyloidosis associated with rheumatoid arthritis and AL amyloidosis.

    Science.gov (United States)

    Kuroda, Takeshi; Tanabe, Naohito; Hasegawa, Eriko; Wakamatsu, Ayako; Nozawa, Yukiko; Sato, Hiroe; Nakatsue, Takeshi; Wada, Yoko; Ito, Yumi; Imai, Naofumi; Ueno, Mitsuhiro; Nakano, Masaaki; Narita, Ichiei

    2017-06-01

    The kidney is a major target organ for systemic amyloidosis, which results in proteinuria and an elevated serum creatinine level. The clinical manifestations and precursor proteins of amyloid A (AA) and light-chain (AL) amyloidosis are different, and the renal damage due to amyloid deposition also seems to differ. The purpose of this study was to clarify haw the difference in clinical features between AA and AL amyloidosis are explained by the difference in the amount and distribution of amyloid deposition in the renal tissues. A total of 119 patients participated: 58 patients with an established diagnosis of AA amyloidosis (AA group) and 61 with AL amyloidosis (AL group). We retrospectively investigated the correlation between clinical data, pathological manifestations, and the area occupied by amyloid in renal biopsy specimens. In most of the renal specimens the percentage area occupied by amyloid was less than 10%. For statistical analyses, the percentage area of amyloid deposition was transformed to a common logarithmic value (Log 10 %amyloid). The results of sex-, age-, and Log 10 %amyloid-adjusted analyses showed that systolic blood pressure (SBP) was higher in the AA group. In terms of renal function parameters, serum creatinine, creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) indicated significant renal impairment in the AA group, whereas urinary protein indicated significant renal impairment in the AL group. Pathological examinations revealed amyloid was predominantly deposited at glomerular basement membrane (GBM) and easily transferred to the mesangial area in the AA group, and it was predominantly deposited at in the AL group. The degree of amyloid deposition in the glomerular capillary was significantly more severe in AL group. The frequency of amyloid deposits in extraglomerular mesangium was not significantly different between the two groups, but in AA group, the degree amyloid deposition was significantly more severe, and

  16. An Incidental Finding of AL-associated Amyloidosis Presenting as Gastric Ulcers

    Directory of Open Access Journals (Sweden)

    Nadia Huq

    2018-01-01

    Full Text Available Gastrointestinal tract amyloidosis has been reported in rare instances and related symptoms are usually nonspecific to the disease process. We present a patient who initially had melena on anticoagulation and endoscopy revealed a bleeding gastric ulcer. Hemostasis was achieved. The patient had a recurrence of symptoms despite being off anticoagulation months later and at that time repeat endoscopy showed multiple gastric ulcers with surrounding friable mucosa. Biopsy results were significant for light chain associated-amyloidosis. This case represents a rare cause of gastric ulcer.

  17. Endobronchial amyloidosis mimicking bronchial asthma: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Kang Hyun-Wook

    2016-01-01

    Full Text Available Among two tracheobronchial forms (local and diffuse and two parenchymal forms (nodular and alveolar septal that were reported in previous literature, localized endobronchial amyloidosis is an uncommon disease of unknown cause. Bronchial amyloid deposits can occur as focal nodules or multifocal infiltration of the submucosa. We report the case of a 47-year-old man who had complained of dyspnea and wheezing for 1 month and who had been treated for severe asthma at another hospital. Endobronchial amyloidosis was confirmed by histological examination of the bronchial biopsies.

  18. Amyloidosis involving the respiratory system: 5-year′s experience of a multi-disciplinary group′s activity

    Directory of Open Access Journals (Sweden)

    Raffaele Scala

    2015-01-01

    Full Text Available Amyloidosis may involve the respiratory system with different clinical-radiological-functional patterns which are not always easy to be recognized. A good level of knowledge of the disease, an active integration of the pulmonologist within a multidisciplinary setting and a high level of clinical suspicion are necessary for an early diagnosis of respiratory amyloidosis. The aim of this retrospective study was to evaluate the number and the patterns of amyloidosis involving the respiratory system. We searched the cases of amyloidosis among patients attending the multidisciplinary rare and diffuse lung disease outpatients′ clinic of Pulmonology Unit of the Hospital of Arezzo from 2007 to 2012. Among the 298 patients evaluated during the study period, we identified three cases of amyloidosis with involvement of the respiratory system, associated or not with other extra-thoracic localizations, whose diagnosis was histo-pathologically confirmed after the pulmonologist, the radiologist, and the pathologist evaluation. Our experience of a multidisciplinary team confirms that intra-thoracic amyloidosis is an uncommon disorder, representing 1.0% of the cases of rare and diffuse lung diseases referred to our center. The diagnosis of the disease is not always easy and quick as the amyloidosis may involve different parts of the respiratory system (airways, pleura, parenchyma. It is therefore recommended to remind this orphan disease in the differential diagnosis of the wide clinical scenarios the pulmonologist may intercept in clinical practice.

  19. Diagnostic performance of I-123-labeled serum amyloid P component scintigraphy in patients with amyloidosis

    NARCIS (Netherlands)

    Hazenberg, BPC; van Rijswijk, MH; Piers, DA; Lub-de Hooge, MN; Vellenga, E; Haagsma, EB; Hawkins, PN; Jager, PL

    Purpose: To assess the diagnostic accuracy and additional information provided by I-123-labeled serum amyloid P component ( SAP) scintigraphy in patients with systemic and localized amyloidosis. Subjects and Methods: I-123-labeled human SAP was injected intravenously into 20 controls and 189

  20. Intratubular amyloid in light chain cast nephropathy is a risk factor for systemic light chain amyloidosis.

    Science.gov (United States)

    Gibier, Jean-Baptiste; Gnemmi, Viviane; Glowacki, François; Boyle, Eileen M; Lopez, Benjamin; MacNamara, Evelyne; Hoffmann, Maxime; Azar, Raymond; Guincestre, Thomas; Bourdon, Franck; Copin, Marie-Christine; Buob, David

    2017-10-20

    Light chain cast nephropathy is the most common form of kidney disease in patients with multiple myeloma. Light chain casts may occasionally show amyloid staining properties, that is, green birefringence after Congo red staining. The frequency and clinical significance of this intratubular amyloid are poorly understood. Here, we retrospectively assessed the clinicopathological features of 60 patients with histologically proven light chain cast nephropathy with a specific emphasis on intratubular amyloid, especially, its association with extrarenal systemic light chain amyloidosis. We found intratubular amyloid in 17 cases (17/60, 28%) and it was more frequent in patients with λ light chain gammopathy (13/17 in the 'intratubular amyloid' group vs 19/43 in the 'no intratubular amyloid' group, P=0.02). Pathological examination of extrarenal specimens showed that intratubular amyloid was significantly associated with the occurrence of systemic light chain amyloidosis (5/13 in the 'intratubular amyloid' group vs 0/30 in the 'no intratubular amyloid' group, P=0.001). Our results indicate that first, intratubular amyloid is not a rare finding in kidney biopsies of patients with light chain cast nephropathy, and, second, it reflects an amyloidogenic capacity of light chains that can manifest as systemic light chain amyloidosis. Thus, intratubular amyloid should be systematically screened for in kidney biopsies from patients with light chain cast nephropathy and, if detected, should prompt a work-up for associated systemic light chain amyloidosis.Modern Pathology advance online publication, 20 October 2017; doi:10.1038/modpathol.2017.124.

  1. Evaluation of Tc-99m-MAMA-chrysamine G as an in vivo probe for amyloidosis

    NARCIS (Netherlands)

    Dezutter, NA; Jager, PL; de Groot, TJ; Dupont, PJ; Tooten, PCJ; Zekarias, B; Gruys, E; Verbruggen, AM

    To date, systemic amyloidosis is diagnosed histologically using Congo red staining or in vivo using iodine-123 labelled serum amyloid P component (I-123-SAP) scintigraphy. We developed Tc-99m-MAMA-CG, a Tc-99m-labelled derivative of the lipophilic Congo red analogue chrysamine G (CG), as a possible

  2. Amyloidosis: A story of how inframammary erosions eclipsed inconspicuous periorbital ecchymoses

    Directory of Open Access Journals (Sweden)

    Andrew Kelsey, MD

    2016-03-01

    Full Text Available Systemic amyloidosis is a rare disease that can be rapidly progressive due to widespread organ involvement. There are well-described renal, cardiac, pulmonary, neurological, and dermatologic findings. Here, we outline one patient’s experience with the condition from presentation to making the diagnosis. She presented with pathognomonic dermatologic findings including pinch purpura and ecchymoses found in the skin folds.

  3. Senile amyloidosis and neuron binding antibody in the aging Syrian hamster

    International Nuclear Information System (INIS)

    Blumenthal, H.T.; Musacchia, X.J.

    1985-01-01

    The effects of age, sex, and irradiation on the genesis of amyloidosis, neuron-binding antibody (NBA), and the concomitant appearance of these two phenomena were studied in a colony of Syrian hamsters. In nonirradiated controls amyloidosis increased in prevalence with age after 12 months, and prevalence was higher in females than in males. Irradiation had the effect of advancing the appearance of amyloidosis to the 7-12 months group but did not intensify the amyloidotic process. IgG binding to the nucleus or cytoplasm of neurons was rare, and, despite the fact that IgM and IgA binding to these structures was present in about one-third of the animals, there was neither an aging nor an irradiation effect. The only statistically significant findings with respect to the concomitant occurrence of amyloid and NBA were negative correlations between nuclear IgM and IgA binding and amyloidosis. Of the various species thus far studied, the hamster is the first in which there has been no aging effect in respect to NBA

  4. A prospective study of nutritional status in immunoglobulin light chain amyloidosis

    DEFF Research Database (Denmark)

    Sattianayagam, PT; Lane, T; Fox, Z

    2013-01-01

    Weight loss is common in systemic immunoglobulin light chain amyloidosis but there are limited data on the impact of nutritional status on outcome. Using the Patient-Generated Subjective Global Assessment (PG-SGA) score, we prospectively examined nutritional status in 110 consecutive newly-diagno...

  5. Microglia in diffuse plaques in hereditary cerebral hemorrhage with amyloidosis (Dutch). An immunohistochemical study

    NARCIS (Netherlands)

    Maat-Schieman, M. L.; Rozemuller, A. J.; van Duinen, S. G.; Haan, J.; Eikelenboom, P.; Roos, R. A.

    1994-01-01

    In hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D) beta/A4 amyloid deposition is found in meningocortical blood vessels and in diffuse plaques in the cerebral cortex. Diffuse plaques putatively represent early stages in the formation of senile plaques. Microglia are intimately

  6. Intensity-modulated radiotherapy for localized nasopharyngeal amyloidosis. Case report and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Ming [Hubei University of Medicine, Department of Clinical Oncology, Taihe Hospital, Shiyan, Hubei (China); Peng, Gang; Shi, Liangliang; Li, Zhenyu; Fei, Shijiang; Ding, Qian; Cheng, Jing [HuaZhong University of Science and Technology, Cancer Center, Union Hospital, Tongji Medical College, Wuhan (China); Ming, Xing [Hubei University of Medicine, Department of infection control and prevention, Taihe Hospital, Shiyan, Hubei (China)

    2016-12-15

    Primary localized amyloidosis is characterized by the deposition of amyloid proteins restricted to one organ, without systemic involvement. Primary nasopharyngeal amyloidosis is an exceedingly rare condition, for which the standard treatment remains unknown. Because of its challenging anatomical position, surgery alone hardly results in complete resection of the localized amyloidosis. Therefore, an interdisciplinary planning board to design optimal treatment is of particular importance. A 39-year-old man presented with a several-week history of nasal obstruction and epistaxis. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of a retro-odontoid nonenhancing soft tissue mass. The endoscopic biopsy demonstrated that the mass was amyloid in nature. An extensive systemic workup revealed an absence of inflammatory process, systemic amyloidosis, or plasma cell dyscrasia. The patient was treated with a combination of surgery and radiotherapy, showing no evidence of recurrence or progression at his 1-year follow-up. Primary solitary amyloidosis is a rare form of amyloidosis. To the best of our knowledge, this is the first report of a nasopharyngeal amyloidosis case treated with excision and radiation leading to complete remission. Because of the difficulty for surgeons to achieve radical resection with such lesions, radiotherapy proved to be an excellent adjuvant treatment in this case. (orig.) [German] Die primaere lokalisierte Amyloidose ist durch die Ablagerung von Amyloidproteinen gekennzeichnet, die sich auf ein Organ beschraenkt, also nicht systemisch ist. Eine primaere Amyloidose im Nasen-Rachen-Raum ist ausserordentlich selten, bisher gibt es keine Standardtherapie. Ihre anatomische Position bedeutet eine Herausforderung, nur selten resultiert eine chirurgische Intervention in einer vollstaendigen Resektion der lokalisierten Amyloidose. Daher ist die Beteiligung mehrerer Disziplinen fuer eine optimale Behandlung von besonderer

  7. Evaluation of systemic amyloidosis by scintigraphy with 123I-labeled serum amyloid P component

    International Nuclear Information System (INIS)

    Hawkins, P.N.; Lavender, J.P.; Pepys, M.B.

    1990-01-01

    In systemic amyloidosis the distribution and progression of disease have been difficult to monitor, because they can be demonstrated only by biopsy. Serum amyloid P component (SAP) is a normal circulating plasma protein that is deposited on amyloid fibrils because of its specific binding affinity for them. We investigated whether labeled SAP could be used to locate amyloid deposits. Purified human SAP labeled with iodine-123 was given intravenously to 50 patients with biopsy-proved systemic amyloidosis--25 with the AL (primary) type and 25 with the AA (secondary) type--and to 26 control patients with disease and 10 healthy subjects. Whole-body images and regional views were obtained after 24 hours and read in a blinded fashion. In the patients with amyloidosis the 123I-SAP was localized rapidly and specifically in amyloid deposits. The scintigraphic images obtained were characteristic and appeared to identify the extent of amyloid deposition in all 50 patients. There was no uptake of the 123I-SAP by the control patients and the healthy subjects. In all patients with AA amyloidosis the spleen was affected, whereas the scans showed uptake in the heart, skin, carpal region, and bone marrow only in patients with the AL type. Positive images were seen in six patients in whom biopsies had been negative or unsuccessful; in all six, amyloid was subsequently found on biopsy or at autopsy. Progressive amyloid deposition was observed in 9 of 11 patients studied serially. Scintigraphy after the injection of 123I-SAP can be used for diagnosing, locating, and monitoring the extent of systemic amyloidosis

  8. Atrophy rates in asymptomatic amyloidosis: implications for Alzheimer prevention trials.

    Directory of Open Access Journals (Sweden)

    K Abigail Andrews

    % absolute slowing of hippocampal atrophy rate in an 18-month treatment trial. We conclude that hippocampal atrophy may be a feasible outcome measure for secondary prevention studies in asymptomatic amyloidosis.

  9. {sup 18}F-FDG PET/CT in Primary AL Hepatic Amyloidosis Associated with Multiple Myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Son, Youn Mi; Bak, Cheol Hee [Seoul Medical Center, Seoul (Korea, Republic of); Choi, Joon Young; Cheon, Mi Ju; Kim, Young Eun; Lee, Kyung Han; Kim, Byung Tae [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2011-10-15

    We report here on a rare case of primary AL hepatic amyloidosis associated with multiple myeloma in a 64-year-old woman. The patient was referred for evaluating her progressive jaundice and right upper quadrant pain. {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET)/computed tomography (CT) showed diffusely and markedly increased {sup 18}F-FDG uptake in the liver. Although there have been several case studies showing positive {sup 18}F-FDG uptake in pulmonary amyloidosis, to the best of our knowledge, the {sup 18}F-FDG PET/CT findings of hepatic amyloidosis or primary hepatic amyloidosis associated with multiple myeloma have not been reported previously.

  10. [A review for recent advances in AA amyloid research and therapeutic approach to AA amyloidosis complicating rheumatoid arthritis].

    Science.gov (United States)

    Tamura, Hiroaki; Hasegawa, Kiminori

    2009-02-01

    AA amyloidosis is a life threatening clinical complication of chronic inflammatory diseases such as rheumatoid arthritis. It has been demonstrated biochemically that amyloidosis resulted from abnormal folding of proteins, which are deposited as insoluble fibrils in extracellular tissue, leading to the disruption of their normal function. In this regard, amyloidosis has been recognized as a conformation disorder. Interestingly, genetic polymorphisms of amyloid precursor protein (SAA) have been reported to associate with increased risk for AA amyloidosis. Also recent biochemical research revealed that SAA is synthesized under the influence of the proinflammatory cytokines, such as IL-6, TNF-alpha, IL-1. Additionally, it was suggested that amyloid deposits in extracellular tissue could reflect to the serum level of SAA in the reversible fashion, leading to the hypothesis that the control of the SAA synthesis could be beneficial to the treatment of amyloidosis. In this context, anti-cytokine therapies may be most effective. Especially the inhibition of IL-6 is critical to suppression of SAA production, so treatment with a humanized monoclonal antibody against human IL-6 receptor may not only ameliorate RA disease activity but also pave the way for the treatment of AA amyloidosis.

  11. Longitudinal study of experimental induction of AA amyloidosis in mice seeded with homologous and heterologous AA fibrils.

    Science.gov (United States)

    Muhammad, Naeem; Murakami, Tomoaki; Inoshima, Yasuo; Ishiguro, Naotaka

    2016-09-01

    To investigate pathogenesis and kinetics of experimentally induced murine AA amyloidosis seeded with homologous (murine) and heterologous (bovine) AA fibrils. Experimental AA amyloidosis was induced by administration of inflammatory stimulus and preformed AA fibrils to a total of 111 female C57/Black mice. In this longitudinal study, heterologous (bovine) as well as homologous (murine) AA fibrils were injected intraperitoneally to mice in various combinations. Re-stimulation was done at 120 or 300 days post first inoculation. To analyze the intensity of amyloid depositions in mice organs, immunohistochemical techniques and image J software were used. Assessment of cytokines level in sera was done using a Mouse Th1/Th2/Th17 Cytokine CBA Kit. Incidence and severity of AA amyloidosis were quite low in mice inoculated with heterologous bovine AA fibrils than homologous murine one. Homologous AA fibrils administration at first and second inoculation caused maximum amount of amyloid depositions and severe systemic form of amyloidosis. Increase in the level of pro-inflammatory cytokine IL-6 was observed after first inoculation, while second inoculation caused a further increase in the level of anti-inflammatory cytokine IL-10. AA amyloidosis can be induced by heterologous as well as homologous AA fibrils. Severity of AA amyloidosis induced with homologous AA fibrils is higher compared to heterologous AA fibrils.

  12. Positron emission tomography (PET) utilizing Pittsburgh compound B (PIB) for detection of amyloid heart deposits in hereditary transthyretin amyloidosis (ATTR).

    Science.gov (United States)

    Pilebro, Björn; Arvidsson, Sandra; Lindqvist, Per; Sundström, Torbjörn; Westermark, Per; Antoni, Gunnar; Suhr, Ole; Sörensen, Jens

    2018-02-01

    DPD scintigraphy has been advocated for imaging cardiac amyloid in ATTR amyloidosis. PET utilizing 11 C-Pittsburgh compound B (PIB) is the gold standard for imaging brain amyloid in Alzheimer's disease. PIB was recently shown to identify cardiac amyloidosis in both AL and ATTR amyloidosis. In the ATTR population, two types of amyloid fibrils exist, one containing fragmented and full-length TTR (type A) and the other only full-length TTR (type B). The aim of this study was to further evaluate PIB-PET in patients with hereditary ATTR amyloidosis. Ten patients with biopsy-proven V30M ATTR amyloidosis and discrete or no signs of cardiac involvement were included. Patients were grouped according to TTR-fragmentation. All underwent DPD scintigraphy, echocardiography, and PIB-PET. A left ventricular PIB-retention index (PIB-RI) was established and compared to five normal volunteers. PIB-RI was increased in all patients (P PIB-PET, in contrast to DPD scintigraphy, has the potential to specifically identify cardiac amyloid depositions irrespective of amyloid fibril composition. The heart appears to be a target organ for amyloid deposition in ATTR amyloidosis.

  13. {sup 123}I-Labelled metaiodobenzylguanidine for the evaluation of cardiac sympathetic denervation in early stage amyloidosis

    Energy Technology Data Exchange (ETDEWEB)

    Noordzij, Walter; Glaudemans, Andor W.J.M.; Rheenen, Ronald W.J. van; Dierckx, Rudi A.J.O.; Slart, Riemer H.J.A. [University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, PO Box 30.001, Groningen (Netherlands); Hazenberg, Bouke P.C. [University of Groningen, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen (Netherlands); Tio, Rene A. [University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen (Netherlands)

    2012-10-15

    Cardiac amyloidosis is a rare disorder, but it may lead to potentially life-threatening restrictive cardiomyopathy. Cardiac manifestations frequently occur in primary amyloidosis (AL) and familial amyloidosis (ATTR), but are uncommon in secondary amyloidosis (AA). Echocardiography is the method of choice for assessing cardiac amyloidosis. Amyloid deposits impair the function of sympathetic nerve endings. Disturbance of myocardial sympathetic innervations may play an important role in the remodelling process. {sup 123}I-MIBG can detect these innervation changes. Patients with biopsy-proven amyloidosis underwent general work-up, echocardiography and {sup 123}I-MIBG scintigraphy. Left ventricular internal dimensions and wall thickness were measured, and highly refractile cardiac echoes (sparkling) were analysed. Early (15 min) and late (4 h) heart-to-mediastinum ratio (HMR) and wash-out rate were determined after administration of MIBG. Included in the study were 61 patients (30 women and 31 men; mean age 62 years; 39 AL, 11 AA, 11 ATTR). Echocardiographic parameters were not significantly different between the groups. Sparkling was present in 72 % of ATTR patients, in 54 % of AL patients and in 45 % of AA patients. Mean late HMR in all patients was 2.3 {+-} 0.75, and the mean wash-out rate was 8.6 {+-} 14 % (the latter not significantly different between the patient groups). Late HMR was significantly lower in patients with echocardiographic signs of amyloidosis than in patients without (2.0 {+-} 0.70 versus 2.8 {+-} 0.58, p < 0.001). Wash-out rates were significantly higher in these patients (-3.3 {+-} 9.9 % vs. 17 {+-} 10 %, p < 0.001). In ATTR patients without echocardiographic signs of amyloidosis, HMR was lower than in patients with the other types (2.0 {+-} 0.59 vs. 2.9 {+-} 0.50, p = 0.007). MIBG HMR is lower and wash-out rate is higher in patients with echocardiographic signs of amyloidosis. Also, {sup 123}I-MIBG scintigraphy can detect cardiac denervation in

  14. Primary localized amyloidosis of the urinary tract frequently mimics neoplasia: a clinicopathologic analysis of 11 cases.

    Science.gov (United States)

    Zhou, Fang; Lee, Peng; Zhou, Ming; Melamed, Jonathan; Deng, Fang-Ming

    2014-01-01

    Localized urinary tract amyloidosis (UTA) is a rare disease that mimics neoplasia clinically, cystoscopically, and radiologically. We report eleven cases of isolated UTA from the urinary bladder (n=7) and upper urinary tract including the ureter (n=2) and renal pelvis (n=2). All cases clinically presented as mass lesions prior to histologic examination and clinically suggested a neoplastic process. The amyloid composition in most cases was mixed Kappa and Lambda light chains. All cases were cured after surgical excision except one case which was diagnosed as plasmacytosis/plasmacytoma six months later. Localized amyloidosis of the urinary tract usually has a benign clinical course and simple resection is recommended after systemic disease is ruled out.

  15. Can videolaryngoscopy be a first option in a patient with laryngeal amyloidosis?

    Science.gov (United States)

    España Fuente, L; Mella Pérez, G; Laserna Cocina, B; González González, J L

    2018-03-01

    Amyloidosis is a term that involves a group of diseases characterised by deposition of extracellular monoclonal light-chain fibrillar immunoglobulin aggregates in the body, including many organs, with the larynx among them. A case is presented of a 78 year-old man who was referred to our institution for strangulated umbilical hernia treatment. He suffered from progressive hoarseness and dysphagia for 5months. He had a history of primary laryngeal amyloidosis. Awake intubation was performed successful with the King Vision ® video-laryngoscopy. Sedation was achieved using a remifentanil infusion and midazolam. Haemorrhagic lesions are caused by deposition of amyloid in and around vessels, resulting in increased vascular fragility. Therefore, anaesthetists should take care in intubating the tracheas of these patients. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Renal and suprarenal insufficiency secondary to familial Mediterranean fever associated with amyloidosis: a case report

    Directory of Open Access Journals (Sweden)

    Sari Nagehan

    2011-08-01

    Full Text Available Abstract Introduction Familial Mediterranean fever is an autosomal recessive disease that predominantly affects people of the Mediterranean coast. One of the most frequent complications of the disease is amyloidosis. This clinical entity is known as secondary (also called AA amyloidosis. Case presentation In this report, we describe the case of a 33-year-old Turkish man with familial Mediterranean fever and chronic renal insufficiency. He was admitted to our clinic with symptoms of suprarenal insufficiency. The patient died three months later as a result of cardiac arrest. Conclusion Our aim is to make a contribution to the literature by reporting a case of combined insufficiency due to the accumulation of renal and adrenal amyloid in a patient with familial Mediterranean fever, which has very rarely been described in the literature. We hope that adrenal insufficiency, which becomes fatal if not diagnosed and treated rapidly, will come to mind as easily as chronic renal failure in clinical practice.

  17. Nasal mucosa: a new site for tissue biopsy to diagnose hereditary TTR amyloidosis.

    Science.gov (United States)

    Munar-Qués, Miguel; Solé, Manel; Martínez-Nadal, Jacinto; Murcia-Sáiz, Antonio; Mas-Degano, José Manuel

    2014-11-07

    We report 2 carriers of the TTRV30M mutation and its plasmatic biochemical marker with clinical symptoms compatible with hereditary TTR amyloidosis. Based on our previously reported casual finding of amyloid TTR in nasal mucosa (2008), we requested biopsy of this tissue to search for amyloid with Congo red staining and TTR immunohistochemical analysis. The histological diagnosis was achieved by retrospective analysis of surgical sinonasal biopsy in the first patient and prospective biopsy of inferior nasal concha in the second. Large interstitial deposits of ATTR were observed in both cases. We suggest nasal mucosa as a suitable site for tissue biopsy in patients with suspected hereditary TTR amyloidosis. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  18. [Osteo-articular amyloidosis caused by dialysis. Clinical and radiologic aspects].

    Science.gov (United States)

    Baldrati, L; Brunetti, L; Rocchi, A; Bonsanto, R; Docci, D; Turci, F

    1990-10-01

    Twenty-nine patients who had received chronic hemodialysis for more than 5 years provided the material for the present study. In 12 of them (41%) there were radiological findings of dialysis related amyloidosis, mainly destructive spondyloarthropathy of the cervical spine (n = 11) and geodes of the shoulder (n = 5). When compared with negative patients, these patients were significantly older (p less than 0.001 and had been dialyzed for longer periods of time (p less than 0.01). Moreover, in such patients there was an higher incidence of carpal tunnel syndrome (p less than 0.025) and shoulder pain (p less than 0.001). Our results confirm that osteoarticular amyloidosis is a frequent long-term complication of chronic hemodialysis and underline the correlation between clinical and radiological findings.

  19. Three cases of systemic amyloidosis successfully diagnosed by subcutaneous fat tissue biopsy of the hip

    Directory of Open Access Journals (Sweden)

    Arahata M

    2016-08-01

    Full Text Available Masahisa Arahata,1 Shigeru Shimadoi,1 Satosi Yamatani,1 Shin-ichi Hayashi,2 Shigeharu Miwa,2 Hidesaku Asakura,3 Shinji Nakao4 1Department of Internal Medicine, Nanto Municipal Hospital, Nanto, 2Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 3Department of Internal Medicine (III, 4Department of Cellular Transplantation Biology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan Abstract: Fine-needle aspiration biopsy of the abdominal fat pad is considered to be a minimally invasive procedure for diagnosing systemic amyloidosis. However, this procedure is sometimes difficult and can be dangerous for elderly patients whose abdominal fat layer is thin because of malnutrition. In such cases, alternative diagnostic methods are required. We report three elderly patients with heart failure complicated by malnutrition. In all cases, electrocardiogram showed low voltage in the limb leads and a pseudoinfarct pattern in the chest leads, and echocardiography showed left ventricular wall thickening with granular sparkling appearance. These patients were suspected of having amyloid cardiomyopathy but could not undergo myocardial biopsies because of their poor conditions. After failed attempts at biopsy of the abdominal fat pad or the other organs, subcutaneous fat tissue biopsy over the hip led to the diagnosis of systemic amyloidosis with cardiomyopathy. The resultant diagnosis guided us to choose the appropriate treatment for the patients. This article illustrates that subcutaneous fat tissue biopsy of the hip could be a useful procedure for diagnosing systemic amyloidosis in elderly patients, particularly when a fat tissue biopsy of the abdomen is associated with a high risk of complications because of malnutrition. Keywords: systemic amyloidosis, amyloid cardiomyopathy, fine-needle aspiration biopsy, subcutaneous fat tissue, hip

  20. Effects of Biologic Agents in Patients with Rheumatoid Arthritis and Amyloidosis Treated with Hemodialysis

    Science.gov (United States)

    Kuroda, Takeshi; Tanabe, Naohito; Nozawa, Yukiko; Sato, Hiroe; Nakatsue, Takeshi; Kobayashi, Daisuke; Wada, Yoko; Saeki, Takako; Nakano, Masaaki; Narita, Ichiei

    2016-01-01

    Objective Our objective was to examine the safety and effects of therapy with biologics on the prognosis of rheumatoid arthritis (RA) patients with reactive amyloid A (AA) amyloidosis on hemodialysis (HD). Methods Twenty-eight patients with an established diagnosis of reactive AA amyloidosis participated in the study. The survival was calculated from the date of HD initiation until the time of death, or up to end of June 2015 for the patients who were still alive. HD initiation was according to the program of HD initiation for systemic amyloidosis patients associated with RA. Results Ten patients had been treated with biologics before HD initiation for a mean of 28.2 months (biologic group), while 18 had not (non-biologic group). HD was initiated in patients with similar characteristics except for the tender joint count, swollen joint count, and disease activity score (DAS)28-C-reactive protein (CRP). History of biologics showed that etanercept was frequently used for 8 patients as the first biologic. There was no significant difference in the mortality rate according to a Kaplan-Meier analysis (p=0.939) and or associated risk of death in an age-adjusted Cox proportional hazards model (p=0.758) between both groups. Infections were significantly more frequent causes of death in the biologic group than in the non-biologic group (p=0.021). However, treatment with biologics improved the DAS28-CRP score (p=0.004). Conclusion Under the limited conditions of AA amyloidosis treated with HD, the use of biologics might affect infection and thus may not improve the prognosis. Strict infection control is necessary for the use of biologics with HD to improve the prognosis. PMID:27725536

  1. Secondary renal amyloidosis in a patient of pulmonary tuberculosis and common variable immunodeficiency

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    Balwani Manish R

    2015-04-01

    Full Text Available Common variable immunodeficiency (CVID usually manifests in the second or third decade of life with recurrent bacterial infections and hypoglobulinemia. Secondary renal amyloidosis with history of pulmonary tuberculosis is rare in CVID, although T cell dysfunction has been reported in few CVID patients. A 40-year-old male was admitted to our hospital with a 3-month history of recurrent respiratory infections and persistent pitting pedal edema. His past history revealed 3 to 5 episodes of recurrent respiratory tract infections and diarrhoea each year since last 20 years. He had been successfully treated for sputum positive pulmonary tuberculosis 8 years back. Laboratory studies disclosed high erythrocyte sedimentation rate (ESR, hypoalbuminemia and nephrotic range proteinuria. Serum immunoglobulin levels were low. CD4/CD8 ratio and CD3 level was normal. C3 and C4 complement levels were normal. Biopsy revealed amyloid A (AA positive secondary renal amyloidosis. Glomeruli showed variable widening of mesangial regions with deposition of periodic schiff stain (PAS pale positive of pink matrix showing apple green birefringence on Congo-red staining. Immunohistochemistry was AA stain positive. Immunofluorescence microscopy revealed no staining with anti-human IgG, IgM, IgA, C3, C1q, kappa and lambda light chains antisera. Patient was treated symptomatically for respiratory tract infection and was discharged with low dose angiotensin receptor blocker. An old treated tuberculosis and chronic inflammation due to recurrent respiratory tract infections were thought to be responsible for AA amyloidosis. Thus pulmonary tuberculosis should be considered in differential diagnosis of secondary causes of AA renal amyloidosis in patients of CVID especially in endemic settings.

  2. A case of localized amyloidosis of the eyelid misdiagnosed as recurrent chalazion

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    Hind Manaa Alkatan

    2017-07-01

    Full Text Available Localized amyloidosis of the eyelid is uncommon and is classically associated with systemic manifestations. We present an interesting case of a localized eyelid mass misdiagnosed as a recurrent chalazion presenting in an 85-year-old Saudi gentleman with no definite associate findings suggestive of an underlying systemic amyloid disease. Debulking surgery was subsequently performed. Proper diagnosis was reached based on the histopathologic examination of the excised tissue, which demonstrated the typical Congo red staining of the amyloid deposits.

  3. A case of localized amyloidosis of the eyelid misdiagnosed as recurrent chalazion.

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    Manaa Alkatan, Hind; Al-Mohizea, Asma; Alsuhaibani, Adel

    2017-01-01

    Localized amyloidosis of the eyelid is uncommon and is classically associated with systemic manifestations. We present an interesting case of a localized eyelid mass misdiagnosed as a recurrent chalazion presenting in an 85-year-old Saudi gentleman with no definite associate findings suggestive of an underlying systemic amyloid disease. Debulking surgery was subsequently performed. Proper diagnosis was reached based on the histopathologic examination of the excised tissue, which demonstrated the typical Congo red staining of the amyloid deposits.

  4. Impact of regional left ventricular function on outcome for patients with AL amyloidosis.

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    Dan Liu

    Full Text Available OBJECTIVES: The aim of this study was to explore the left ventricular (LV deformation changes and the potential impact of deformation on outcome in patients with proven light-chain (AL amyloidosis and LV hypertrophy. BACKGROUND: Cardiac involvement in AL amyloidosis patients is associated with poor outcome. Detecting regional cardiac function by advanced non-invasive techniques might be favorable for predicting outcome. METHODS: LV longitudinal, circumferential and radial peak systolic strains (Ssys were assessed by speckle tracking imaging (STI in 44 biopsy-proven systemic AL amyloidosis patients with LV hypertrophy (CA and in 30 normal controls. Patients were divided into compensated (n = 18 and decompensated (n = 26 group based on clinical assessment and followed-up for a median period of 345 days. RESULTS: Ejection fraction (EF was preserved while longitudinal Ssys (LSsys was significantly reduced in both compensated and decompensated groups. Survival was significantly reduced in decompensated group (35% vs. compensated 78%, P = 0.001. LSsys were similar in apical segments and significantly reduced in basal segments between two patient groups. LSsys at mid-segments were significantly reduced in all LV walls of decompensated group. Patients were further divided into 4 subgroups according to the presence or absence of reduced LSsys in no (normal, only basal (mild, basal and mid (intermediate and all segments of the septum (severe. This staging revealed continuously worse prognosis in proportion to increasing number of segments with reduced LSsys (mortality: normal 14%, mild 27%, intermediate 67%, and severe 64%. Mid-septum LSsys<11% suggested a 4.8-fold mortality risk than mid-septum LSsys≥11%. Multivariate regression analysis showed NYHA class and mid-septum LSsys were independent predictors for survival. CONCLUSIONS: Reduced deformation at mid-septum is associated with worse prognosis in systemic amyloidosis patients with LV

  5. Risk of transmission of systemic transthyretin amyloidosis after domino liver transplantation.

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    Lladó, Laura; Baliellas, Carme; Casasnovas, Carlos; Ferrer, Isidre; Fabregat, Joan; Ramos, Emilio; Castellote, Jose; Torras, Jaume; Xiol, Xavier; Rafecas, Antoni

    2010-12-01

    Recent reports of the transmission of systemic transthyretin (TTR) amyloidosis after domino liver transplantation (DLT) using grafts from patients with familial amyloid polyneuropathy (FAP) have raised concerns about the procedure. The aim of this study was to evaluate the transmission incidence of systemic TTR amyloidosis after DLT with a complete clinical, neurological, and pathological assessment. At our institution, DLT has been performed 31 times with livers from patients with FAP. Seventeen of the 19 patients still alive in 2008 agreed to enter the study. This cross-sectional study of this cohort of patients included clinical assessments, rectal biopsy, and electroneuromyography (as well as sural nerve biopsy when it was indicated). The mean follow-up at the time of the study was 62.6 ± 2.9 months. Clinically, 3 patients complained of weak dysesthesia. When a focused study was performed, 8 patients reported some kind of neurological and/or gastrointestinal disturbance. Six of the rectal biopsy samples showed amyloid deposits (TTR-positive). Electromyography (EMG) showed signs of mild sensorimotor neuropathy in 3 cases and moderate to severe sensorimotor neuropathy in 1 case. Only 2 of the 4 patients with EMG signs of polyneuropathy showed amyloid deposits in their rectal biopsy samples. Sural nerve biopsy revealed amyloid deposits (TTR-positive) in all 4 patients with EMG signs of polyneuropathy. Two patients with normal EMG findings had TTR-positive amyloid deposits in their sural nerve biopsy samples. In conclusion, de novo systemic amyloidosis after DLT may be more frequent and appear earlier than was initially thought. In our opinion, however, the graft shortage still justifies DLT in selected patients, despite the risk of de novo systemic amyloidosis. Sural nerve biopsy with EMG and clinical correlation is mandatory for confirming the disease. Indeed, other causes of neuropathy should be excluded. Copyright © 2010 American Association for the Study of

  6. Comparative study of Congo red fluorescence and immunohistochemistry in cutaneous amyloidosis.

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    Fernandez-Flores, A

    2010-01-01

    Detection of amyloid can be done by several techniques either histochemical or immunohistochemical. Among them, one of the less mentioned in texts of reference and in reports on amyloidosis, is the examination with ultraviolet light of the stain of Congo red. We intend to examine cases of amyloidosis stained with Congo red with ultraviolet light and to see if such method offers advantages with respect to Congo red only and to immunohistochemistry. We examined 12 cases of cutaneous amyloidosis Hematoxylin-Eosin, Congo red stains (with and without permanganate treatment), Thioflavin T and immunohistochemical stains. We also evaluated Congo red fluorescence (CRF). 66.66% were women and 33.34% were men. The traditional methods for the detection of amyloid (Congo red and Thioflavin T) were positive in 87.50% while immunohistochemistry was positive in 100% of the cases. In one case, immunohistochemistry detected Congo red negative deposits of amyloid. In another case, immunohistochemistry was strong while CRF was weak. CRF was always weak in all the cases in which it was seen. Immunohistochemistry is superior in the detection of cutaneous amyloid over the other techniques tested. CRF did not result, in our experience, to be so useful.

  7. Amiloidosis secundaria en la enfermedad inflamatoria intestinal Secondary amyloidosis in Chrohn's disease

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    S. Seijo Ríos

    2008-12-01

    Full Text Available La amiloidosis es una entidad clínica que se produce a consecuencia del depósito a nivel extracelular de un material proteico amorfo, causando una desorganización de la arquitectura normal de múltiples órganos y tejidos y, por tanto, una alteración funcional de los mismos. La amiloidosis secundaria es una complicación infrecuente pero muy grave que aparece en el contexto de neoplasias, enfermedades infecciosas e inflamatorias de curso crónico, como es el caso de la enfermedad inflamatoria intestinal, principalmente enfermedad de Crohn, ensombreciendo el pronóstico de estos pacientes. A continuación presentamos dos casos clínicos correspondientes a dos pacientes con enfermedad de Crohn que desarrollaron amiloidosis secundaria.Amyloidosis is a clinical entity that results from the deposition of an extracellular protein material that causes disruption in the normal architecture of multiple organs and tissues, and impairs their function. Secondary amyloidosis is a rare but serious complication that may worsen the prognosis of patients with cancer, infection or chronic inflammatory disease, including inflammatory bowel disease, particularly Crohn's disease. We report two cases of Crohn's disease associated with secondary amyloidosis.

  8. Bilateral optic neuropathy and intraretinal deposits after pars plana vitrectomy in amyloidosis

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    Rossetti Alberto

    2015-01-01

    Full Text Available Pathological examination of material from a nonextensive pars plana vitrectomy (PPV in the right eye provided a diagnosis of nonfamilial amyloidosis in a 68-year-old woman, who presented with bilateral glass wool-like vitreous opacities. Genetic testing revealed a Tyr114Cys mutation in the transthyretin gene. Six months after PPV, perimetry showed intense constriction with a temporal island and central scotoma in the right eye. An extensive PPV was performed in the left eye. Spectral domain optical coherence tomography evidenced bilateral epimacular amyloid deposits and unreported reflective spots within the inner retina. One year later, visual acuity had decreased to 20/400 in the left eye, with mild vitreous opacity, pale cupped optic disc and inferior altitudinal field defect. Bilateral diurnal intraocular pressure, transiently increased after PPV, never exceeded 16 mmHg with medication. Our patient presented optic nerve blood supply impairment, due to amyloidosis, which caused optic atrophy. Epiretinal and intraretinal deposit detection could aid in diagnosing patients with suspected amyloidosis.

  9. Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease

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    van Duinen, S.G.; Castano, E.M.; Prelli, F.; Bots, G.T.A.B.; Luyendijk, W.; Frangione, B.

    1987-01-01

    Hereditary cerebral hemorrhage with amyloidosis in Dutch patients is an autosomal dominant form of vascular amyloidosis restricted to the leptomeninges and cerebral cortex. Clinically the disease is characterized by cerebral hemorrhages leading to an early death. Immunohistochemical studies of five patients revealed that the vascular amyloid deposits reacted intensely with an antiserum raised against a synthetic peptide homologous to the Alzheimer disease-related β-protein. Silver stain-positive, senile plaque-like structures were also labeled by the antiserum, yet these lesions lacked the dense amyloid cores present in typical plaques of Alzheimer disease. No neurofibrillary tangles were present. Amyloid fibrils were purified from the leptomeningeal vessels of one patient who clinically had no signs of dementia. The protein had a molecular weight of ∼ 4000 and its partial amino acid sequence to position 21 showed homology to the β-protein of Alzheimer disease and Down syndrome. These results suggest that hereditary cerebral hemorrhage with amyloidosis of Dutch origin is pathogenetically related to Alzheimer disease and support the concept that the initial amyloid deposition in this disorder occurs in the vessel walls before damaging the brain parenchyma. Thus, deposition of β-protein in brain tissue seems to be related to a spectrum of diseases involving vascular syndromes, progressive dementia, or both

  10. Reactive eccrine syringofibroadenomatosis secondary to primary cutaneous amyloidosis: a novel association.

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    Saggini, Andrea; Mully, Thaddeus

    2014-04-01

    We report the unprecedented case of reactive eccrine syringofibroadenoma (ESFA) secondary to primary cutaneous amyloidosis. A 62-year-old woman of Asian ethnicity presented with a pruritic rash on the back of long-standing duration. Physical examination revealed diffuse hyperpigmentation localized to the interscapular region; there were a multitude of hyperpigmented macules merged in a rippled pattern intermixed with scattered papules and cobblestone-like areas. A punch biopsy from a papule was taken. Histopathological examination revealed a network of epithelial strands and cords hanging from the epidermis and harboring foci of ductal differentiation. Eosinophilic collections of amorphous material were found between the epithelial strands, obscuring the superficial dermis. The microscopic picture was consistent with primary cutaneous amyloidosis associated with reactive ESFA. Results of histochemical and immunohistochemical staining confirmed the diagnosis. We speculate that pathogenetic mechanisms intrinsic to primary cutaneous amyloidosis, in addition to unknown genetic factors, resulted in clinical changes of lichen amyloidosus associated with an abnormal hyperplastic epithelial response with histopathological features of ESFA rather than the common epidermal change of acanthosis and hyperkeratosis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Living kidney transplantation between brothers with unrecognized renal amyloidosis as the first manifestation of familial Mediterranean fever: a case report.

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    Peces, Ramón; Afonso, Sara; Peces, Carlos; Nevado, Julián; Selgas, Rafael

    2017-08-31

    Familial Mediterranean fever is an autosomal recessive disease characterized by recurrent episodes of fever and polyserositis and by the onset of reactive amyloid-associated amyloidosis. Amyloidosis due to familial Mediterranean fever can lead to end-stage renal disease, culminating in kidney transplantation for some patients. In this study, we report the clinical outcome of two brothers with familial Mediterranean fever who were the inadvertent donor and recipient, respectively, of a kidney. Subsequently, they were diagnosed with renal amyloidosis secondary to familial Mediterranean fever and were successfully treated with anakinra and colchicine. Two brothers with familial Mediterranean fever and renal amyloidosis were the inadvertent donor and recipient, respectively, of a kidney. The recipient had presented recurrent acute febrile episodes of familial Mediterranean fever, developed nephrotic syndrome secondary to amyloidosis and needed bilateral nephrectomy and chronic dialysis. His elder brother, in apparent good health, donated his left kidney to his brother. Immediately after the kidney transplantation, both the donor and recipient presented massive proteinuria, impaired renal function and elevated serum amyloid A levels. Biopsies of the brothers' kidneys showed amyloidosis. Genetic studies thereafter revealed a homozygous variant for the MEFV gene (NM_000243.2.c.2082G > A; p.M694I) in both brothers. At this point, both the donor and recipient were treated with colchicine and anakinra, resulting in improved renal function, decreased proteinuria, undetectable serum amyloid A levels and stable renal function at 62 months of follow-up and no major adverse effects. In familial Mediterranean fever, analyses of the MEFV gene should be performed in potential live kidney donors from a direct family member (either between siblings or between parents and children). In addition, genetic studies are required when consanguinity is suspected between members involved in

  12. Atypical rapid progression of osteoarticular amyloidosis involving the hip in a patient on hemodialysis using polyacrylonitrile membranes

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    Lee, Kenneth S. [University of Wisconsin School of Medicine and Public Health, Department of Radiology, University of Wisconsin Hospital and Clinics, Madison, WI (United States); Holsbeeck, Marnix T. van [Wayne State School of Medicine, Department of Radiology, Henry Ford Hospital, Detroit, MI (United States); Abbud, Alexander [Wayne State School of Medicine, Department of Pathology, Henry Ford Hospital, Detroit, MI (United States)

    2010-01-15

    Amyloidosis related to dialysis is a well-known complication affecting many organ systems, in particular the musculoskeletal system. In 1985 Shirahama et al. (Biochem Biophys Res Commun 53:705-709, 1985) identified beta-2 microglobulin (MG) as the offending constituent by using protein purification techniques. Amyloidosis has been increasing in prevalence because of longer life spans and increased chronic medical conditions such as end-stage renal disease. When dialysis-related amyloidosis involves the musculoskeletal system, it affects the shoulder girdle, the so called shoulder pad sign, the wrist, hip, knee, and spine (Resnick, Diagnosis of bone and joint disorders, 4th edn., pp. 2054-2058 and 2176-2183, 2002). Other osteoarticular manifestations of amyloidosis include osteoporosis, lytic lesions, and pathologic fractures. It has been well documented that the prevalence of amyloid is dependent on duration of dialysis - over 90% in patients on dialysis for over 7 years (Jadoul, Nephrol Dial Transplant 13:61-64, 1998). However, a recent changeover to high-flux membranes used in hemofiltration has been reported to delay its onset (Campistol et al., Contrib Nephrol 125:76-85, 1999). We report on the radiographic, nuclear medicine, and computed tomography (CT) findings of osteoarticular amyloidosis involving the hip, and sequence its atypical rapid onset. The imaging, histopathological findings, and differential diagnosis are discussed. (orig.)

  13. Identification of a Unique Amyloid Sequence in AA Amyloidosis of a Pig Associated With Streptococcus Suis Infection.

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    Kamiie, J; Sugahara, G; Yoshimoto, S; Aihara, N; Mineshige, T; Uetsuka, K; Shirota, K

    2017-01-01

    Here we report a pig with amyloid A (AA) amyloidosis associated with Streptococcus suis infection and identification of a unique amyloid sequence in the amyloid deposits in the tissue. Tissues from the 180-day-old underdeveloped pig contained foci of necrosis and suppurative inflammation associated with S. suis infection. Congo red stain, immunohistochemistry, and electron microscopy revealed intense AA deposition in the spleen and renal glomeruli. Mass spectrometric analysis of amyloid material extracted from the spleen showed serum AA 2 (SAA2) peptide as well as a unique peptide sequence previously reported in a pig with AA amyloidosis. The common detection of the unique amyloid sequence in the current and past cases of AA amyloidosis in pigs suggests that this amyloid sequence might play a key role in the development of porcine AA amyloidosis. An in vitro fibrillation assay demonstrated that the unique AA peptide formed typically rigid, long amyloid fibrils (10 nm wide) and the N-terminus peptide of SAA2 formed zigzagged, short fibers (7 nm wide). Moreover, the SAA2 peptide formed long, rigid amyloid fibrils in the presence of sonicated amyloid fibrils formed by the unique AA peptide. These findings indicate that the N-terminus of SAA2 as well as the AA peptide mediate the development of AA amyloidosis in pigs via cross-seeding polymerization.

  14. Elevation of Plasmin-α2-plasmin Inhibitor Complex Predicts the Diagnosis of Systemic AL Amyloidosis in Patients with Monoclonal Protein.

    Science.gov (United States)

    Ishiguro, Kazuya; Hayashi, Toshiaki; Yokoyama, Yoshihiro; Aoki, Yuka; Onodera, Kei; Ikeda, Hiroshi; Ishida, Tadao; Nakase, Hiroshi

    2017-10-11

    Objective The complication of systemic immunoglobulin light chain (AL) amyloidosis in patients with monoclonal immunoglobulin affects the prognosis, but amyloid deposition in tissues is sometimes difficult to detect due to bleeding tendencies and preferential distributions. However, fibrinolysis is known to be exacerbated in patients with systemic AL amyloidosis specifically. We therefore explored new biomarkers for predicting a diagnosis of systemic AL amyloidosis focusing on coagulation and fibrinolysis markers. Methods We reviewed the clinical features and treatment outcomes of patients with serum monoclonal protein, including primary systemic AL amyloidosis and multiple myeloma (MM), treated at our hospital between January 2008 and December 2014. Results Among several biomarkers, only the serum level of plasmin-α2-plasmin inhibitor complex (PIC) in patients with systemic AL amyloidosis (n=26) at the diagnosis was significantly higher than in patients with MM without AL amyloidosis (n=26) (mean ± standard deviation, 3.69±2.82 μg/mL vs. 1.23±0.97 μg/mL, p<0.01). The cut-off for predicting a diagnosis of systemic AL amyloidosis in patients with serum monoclonal protein was 1.72 μg/mL with 84.6% sensitivity and 80.8% specificity. Hepatic involvement resulted in a significantly higher PIC level than no involvement in patients with systemic AL amyloidosis. The serum PIC level was also associated with the hematological response of systemic AL amyloidosis. Conclusion PIC is a useful biomarker for the diagnosis and management of patients with systemic AL amyloidosis.

  15. Acquired A amyloidosis from injection drug use presenting with atraumatic splenic rupture in a hospitalized patient: a case report

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    Hanks Douglas K

    2011-01-01

    Full Text Available Abstract Introduction Little is known about splenic rupture in patients who develop systemic acquired A amyloidosis. This is the first report of a case of atraumatic splenic rupture in a patient with acquired A amyloidosis from chronic injection drug use. Case presentation A 58-year-old Caucasian man with a long history of injection drug use, hospitalized for infective endocarditis, experienced atraumatic splenic rupture and underwent splenectomy. Histopathological and microbiological analyses of the splenic tissue were consistent with systemic acquired A amyloidosis, most likely from injection drug use, that led to splenic rupture without any recognized trauma or evidence of bacterial embolization to the spleen. Conclusion In patients with chronic inflammatory conditions, including the use of injection drugs, who experience acute onset of left upper quadrant pain, the diagnosis of atraumatic splenic rupture must be considered.

  16. Accumulation of Tc99m-DMSA-3 in the spleen in a case of multiple myeloma with associated amyloidosis

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    Barai Sukanta

    2005-01-01

    Full Text Available We describe a case of a 58-year-old male with longstanding hypertension and Type 2 diabetes mellitus who developed sudden onset renal impairment. The first clue to the possible presence of amyloidosis in this case was provided by the radionuclide renal cortical scan performed with trivalent dimercapto succinic acid (Tc99m-DMSA-3, which revealed intense tracer uptake in the spleen suggesting amyloid deposit. Further workup to ascertain the cause of amyloidosis led to the diagnosis of multiple myeloma. We conclude that in cases of extra-renal or splenic accumulation of Tc99m-DMSA-3, a diagnosis of amyloidosis should be considered, in an appropriate clinical setting.

  17. A multicenter report of biologic agents for the treatment of secondary amyloidosis in Turkish rheumatoid arthritis and ankylosing spondylitis patients.

    Science.gov (United States)

    Pamuk, Ömer Nuri; Kalyoncu, Umut; Aksu, Kenan; Omma, Ahmet; Pehlivan, Yavuz; Çağatay, Yonca; Küçükşahin, Orhan; Dönmez, Salim; Çetin, Gözde Yıldırım; Mercan, Rıdvan; Bayındır, Özün; Çefle, Ayşe; Yıldız, Fatih; Balkarlı, Ayşe; Kılıç, Levent; Çakır, Necati; Kısacık, Bünyamin; Öksüz, Mustafa Ferhat; Çobankara, Veli; Onat, Ahmet Mesut; Sayarlıoğlu, Mehmet; Öztürk, Mehmet Akif; Pamuk, Gülsüm Emel; Akkoç, Nurullah

    2016-07-01

    In this multicenter, retrospective study, we evaluated the efficacy and safety of biologic therapies, including anti-TNFs, in secondary (AA) amyloidosis patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In addition, the frequency of secondary amyloidosis in RA and AS patients in a single center was estimated. Fifty-one AS (39M, 12F, mean age: 46.7) and 30 RA patients (11M, 19F, mean age: 51.7) with AA amyloidosis from 16 different centers in Turkey were included. Clinical and demographical features of patients were obtained from medical charts. A composite response index (CRI) to biologic therapy-based on creatinine level, proteinuria and disease activity-was used to evaluate the efficacy of treatment. The mean annual incidence of AA amyloidosis in RA and AS patients was 0.23 and 0.42/1000 patients/year, respectively. The point prevalence in RA and AS groups was 4.59 and 7.58/1000, respectively. In RA group with AA amyloidosis, effective response was obtained in 52.2 % of patients according to CRI. RA patients with RF positivity and more initial disease activity tended to have higher response rates to therapy (p values, 0.069 and 0.056). After biologic therapy (median 17 months), two RA patients died and two developed tuberculosis. In AS group, 45.7 % of patients fulfilled the criteria of good response according to CRI. AS patients with higher CRP levels at the time of AA diagnosis and at the beginning of anti-TNF therapy had higher response rates (p values, 0.011 and 0.017). During follow-up after anti-TNF therapy (median 38 months), one patient died and tuberculosis developed in two patients. Biologic therapy seems to be effective in at least half of RA and AS patients with AA amyloidosis. Tuberculosis was the most important safety concern.

  18. Marginal zone B-cell lymphoma of MALT in small intestine associated with amyloidosis: a rare association.

    Science.gov (United States)

    Park, Sanghui; Cho, Hyun Yee; Ha, Seung Yeon; Chung, Dong Hae; Kim, Na Rae; An, Jung Suk

    2011-05-01

    A 62-yr-old man presented with a 5-yr history of intermittent abdominal distention and pain. These symptoms persisted for several months and subsided without treatment. A diagnosis of suspected small bowel lymphoma was made based on plain radiograph and computerized tomogram findings, and he was referred to our institution for further evaluation. Segmental resection of the small intestine was performed and the diagnosis of marginal zone B-cell lymphoma associated with amyloidosis was made. This is the first case of marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) in the small intestine associated with amyloidosis in Korea.

  19. Association of Cerebral Amyloidosis, Blood Pressure, and Neuronal Injury with Late-life Onset Depression

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    Min Soo Byun

    2016-10-01

    Full Text Available Previous literature suggests that Alzheimer’s disease (AD process may contribute to late-life onset depression (LLOD. Therefore, we investigated the association of LLOD with cerebral amyloidosis and neuronal injury, the two key brain changes in AD, along with vascular risks. Twenty nine non-demented individuals who first experienced major depressive disorder (MDD after age of 60 years were included as LLOD subjects, and 27 non-demented elderly individuals without lifetime experience of MDD were included as normal controls (NC. Comorbid mild cognitive impairment (MCI was diagnosed in 48% of LLOD subjects and in 0% of NC. LLOD, irrespective of comorbid MCI diagnosis, was associated with prominent prefrontal cortical atrophy. Compared to NC, LLOD subjects with comorbid MCI (LLODMCI showed increased cerebral 11C-Pittsburg compound B (PiB retention and plasma beta-amyloid 1-40 and 1-42 peptides, as measures of cerebral amyloidosis; and, such relationship was not observed in overall LLOD or LLOD without MCI (LLODwoMCI. LLOD subjects, particularly the LLODwoMCI, had higher systolic blood pressure (SBP than NC. When analyzed in the same multiple logistic regression model that included prefrontal gray matter (GM density, cerebral amyloidosis and SBP as independent variables, only prefrontal GM density showed a significant independent association with LLOD regardless of MCI comorbidity status. Our findings suggest AD process might be related to LLOD via prefrontal neuronal injury in the MCI stage, whereas vascular processes—SBP elevation, in particular—are associated with LLOD via prefrontal neuronal injury even in cognitively intact or less impaired individuals.

  20. Abrupt Onset of Refractory Heart Failure Associated With Light-Chain Amyloidosis in Hypertrophic Cardiomyopathy.

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    Tomberli, Benedetta; Cappelli, Francesco; Perfetto, Federico; Olivotto, Iacopo

    2017-01-01

    The natural history of hypertrophic cardiomyopathy (HCM) is complex and may include progressive heart failure and severe left ventricular dysfunction. When disease progression is abrupt, however, other coexisting diseases should be ruled out. This may be difficult in the case of amyloidosis, which classically mimics HCM. We present an example of severe clinical deterioration in a patient with HCM due to superimposed amyloid light-chain amyloidosis. A man in his 70s with a longstanding history of genetically confirmed HCM presented with rapid development of congestive heart failure over 6 months, in sharp contrast to a previously stable, asymptomatic clinical course. He was diagnosed as having the illness in his late 40s after a resuscitated cardiac arrest and regularly followed up on a yearly basis. His most recent electrocardiogram was profoundly changed from previous tracings, with marked and diffuse voltage reduction (QS in V1-V3) and inferolateral T-wave inversion. The echocardiogram showed an abrupt increase in the severity of left ventricular (LV) hypertrophy, with a concentric rather than asymmetric appearance, granular sparkling of the myocardium, biatrial enlargement, thickening of the mitral valve leaflets, and interatrial septum and mild pericardial effusion. Severe LV dysfunction with a restrictive LV filling pattern was evident, which is associated with LV outflow tract obstruction loss and right ventricle systolic impairment. Following hospital admission, multiple myeloma was diagnosed and confirmed by bone marrow biopsy and aspiration. Furthermore, abdominal fat aspiration showed amyloid deposition and confirmed the diagnosis of amyloid light-chain amyloidosis. Electrocardiograms, echocardiographic images, and videos presented in this report describe the abrupt and marked evolution of a sarcomeric to infiltrative cardiomyopathy, leading to an ominous outcome in which the patient died despite specific treatment. While progression to the end

  1. Methylene Blue Modulates β-Secretase, Reverses Cerebral Amyloidosis, and Improves Cognition in Transgenic Mice*

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    Mori, Takashi; Koyama, Naoki; Segawa, Tatsuya; Maeda, Masahiro; Maruyama, Nobuhiro; Kinoshita, Noriaki; Hou, Huayan; Tan, Jun; Town, Terrence

    2014-01-01

    Amyloid precursor protein (APP) proteolysis is required for production of amyloid-β (Aβ) peptides that comprise β-amyloid plaques in the brains of patients with Alzheimer disease (AD). Here, we tested whether the experimental agent methylene blue (MB), used for treatment of methemoglobinemia, might improve AD-like pathology and behavioral deficits. We orally administered MB to the aged transgenic PSAPP mouse model of cerebral amyloidosis and evaluated cognitive function and cerebral amyloid pathology. Beginning at 15 months of age, animals were gavaged with MB (3 mg/kg) or vehicle once daily for 3 months. MB treatment significantly prevented transgene-associated behavioral impairment, including hyperactivity, decreased object recognition, and defective spatial working and reference memory, but it did not alter nontransgenic mouse behavior. Moreover, brain parenchymal and cerebral vascular β-amyloid deposits as well as levels of various Aβ species, including oligomers, were mitigated in MB-treated PSAPP mice. These effects occurred with inhibition of amyloidogenic APP proteolysis. Specifically, β-carboxyl-terminal APP fragment and β-site APP cleaving enzyme 1 protein expression and activity were attenuated. Additionally, treatment of Chinese hamster ovary cells overexpressing human wild-type APP with MB significantly decreased Aβ production and amyloidogenic APP proteolysis. These results underscore the potential for oral MB treatment against AD-related cerebral amyloidosis by modulating the amyloidogenic pathway. PMID:25157105

  2. Experimental induction of chicken amyloid A amyloidosis in white layer chickens by inoculation with inactivated vaccines.

    Science.gov (United States)

    Habibi, Wazir Ahmad; Hirai, Takuya; Niazmand, Mohammad Hakim; Okumura, Naoko; Yamaguchi, Ryoji

    2017-10-01

    We investigated the amyloidogenic potential of inactivated vaccines and the localized production of serum amyloid A (SAA) at the injection site in white layer chickens. Hens in the treated group were injected intramuscularly three times with high doses of inactivated oil-emulsion Salmonella Enteritidis vaccine and multivalent viral and bacterial inactivated oil-emulsion vaccines at two-week intervals. Chickens in the control group did not receive any inoculum. In the treated group, emaciation and granulomas were present, while several chickens died between 4 and 6 weeks after the first injection. Hepatomegaly was seen at necropsy, and the liver parenchyma showed inconsistent discolouration with patchy green to yellowish-brown areas, or sometimes red-brown areas with haemorrhage. Amyloid deposition in the liver, spleen, duodenum, and at injection sites was demonstrated using haematoxylin and eosin staining, Congo red, and immunohistochemistry. The incidence of chicken amyloid A (AA) amyloidosis was 47% (28 of 60) in the treated group. In addition, RT-PCR was used to identify chicken SAA mRNA expression in the liver and at the injection sites. Furthermore, SAA mRNA was detected by in situ hybridization in fibroblasts at the injection sites, and also in hepatocytes. We believe that this is the first report of the experimental induction of systemic AA amyloidosis in white layer chickens following repeated inoculation with inactivated vaccines without the administration of amyloid fibrils or other amyloid-enhancing factors.

  3. Scintigraphic imaging and turnover studies with iodine-131 labelled serum amyloid P component in systemic amyloidosis

    International Nuclear Information System (INIS)

    Hawkins, P.N.; Pepys, M.B.; Aprile, C.; Capri, G.; Vigano, L.; Munzone, E.; Gianni, L.; Merlini, G.

    1998-01-01

    Radiolabelled serum amyloid P component (SAP) is a specific tracer for amyloid. Iodine-123 has ideal physical characteristics for scintigraphy but is expensive and not widely available. Here we report serial imaging and turnover studies in which we labelled SAP with iodine-131, a cheap alternative isotope which would be expected to yield poorer images but permit more prolonged turnover measurements. Imaging and plasma clearance and whole body retention (WBR) of tracer were studied for up to 7 days in ten patients with proven systemic AL amyloidosis and two patients in whom the diagnosis was suspected, after i.v. administration of about 37 MBq of 131 I-SAP. Normal blood pool images were obtained in the latter two subjects and amyloidosis was subsequently refuted histologically. WBR at 48 h was 65% of the injected dose (i.d.). Among the other ten patients, amyloid deposits were identified in the spleen in eight cases, liver in five and kidneys in four; other sites that gave positive results included bone, joints and soft tissues, and the myocardium in one case. Up to 95% of the tracer localised into amyloid within 6-h, and the values for WBR became progressively more discriminating during the study period, exceeding the normal reference value ( 131 I-SAP produced diagnostic scans in every patient in this series and, coupled with the detailed turnover information, is adequate for monitoring disease progress. (orig.)

  4. Nonfluent/Agrammatic PPA with In-Vivo Cortical Amyloidosis and Pick’s Disease Pathology

    Directory of Open Access Journals (Sweden)

    Francesca Caso

    2013-01-01

    Full Text Available The role of biomarkers in predicting pathological findings in the frontotemporal dementia (FTD clinical spectrum disorders is still being explored. We present comprehensive, prospective longitudinal data for a 66 year old, right-handed female who met current criteria for the nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA. She first presented with a 3-year history of progressive speech and language impairment mainly characterized by severe apraxia of speech. Neuropsychological and general motor functions remained relatively spared throughout the clinical course. Voxel-based morphometry (VBM showed selective cortical atrophy of the left posterior inferior frontal gyrus (IFG and underlying insula that worsened over time, extending along the left premotor strip. Five years after her first evaluation, she developed mild memory impairment and underwent PET-FDG and PiB scans that showed left frontal hypometabolism and cortical amyloidosis. Three years later (11 years from first symptom, post-mortem histopathological evaluation revealed Pick's disease, with severe degeneration of left IFG, mid-insula, and precentral gyrus. Alzheimer’s disease (AD (CERAD frequent/Braak Stage V was also detected. This patient demonstrates that biomarkers indicating brain amyloidosis should not be considered conclusive evidence that AD pathology accounts for a typical FTD clinical/anatomical syndrome.

  5. Amyloidosis, Inflammation, and Oxidative Stress in the Heart of an Alkaptonuric Patient

    Directory of Open Access Journals (Sweden)

    Lia Millucci

    2014-01-01

    Full Text Available Background. Alkaptonuria, a rare autosomal recessive metabolic disorder caused by deficiency in homogentisate 1,2-dioxygenase activity, leads to accumulation of oxidised homogentisic acid in cartilage and collagenous structures present in all organs and tissues, especially joints and heart, causing a pigmentation called ochronosis. A secondary amyloidosis is associated with AKU. Here we report a study of an aortic valve from an AKU patient. Results. Congo Red birefringence, Th-T fluorescence, and biochemical assays demonstrated the presence of SAA-amyloid deposits in AKU stenotic aortic valve. Light and electron microscopy assessed the colocalization of ochronotic pigment and SAA-amyloid, the presence of calcified areas in the valve. Immunofluorescence detected lipid peroxidation of the tissue and lymphocyte/macrophage infiltration causing inflammation. High SAA plasma levels and proinflammatory cytokines levels comparable to those from rheumatoid arthritis patients were found in AKU patient. Conclusions. SAA-amyloidosis was present in the aortic valve from an AKU patient and colocalized with ochronotic pigment as well as with tissue calcification, lipid oxidation, macrophages infiltration, cell death, and tissue degeneration. A local HGD expression in human cardiac tissue has also been ascertained suggesting a consequent local production of ochronotic pigment in AKU heart.

  6. Rapid intestinal transit as a primary cause of severe chronic diarrhea in patients with amyloidosis.

    Science.gov (United States)

    Guirl, Michael J; Högenauer, Christoph; Santa Ana, Carol A; Porter, Jack L; Little, Katherine H; Stone, Marvin J; Fordtran, John S

    2003-10-01

    The cause of severe diarrhea in patients with systemic amyloidosis is obscure. We therefore performed pathophysiological studies in three such patients in an effort to determine the mechanism of amyloid diarrhea. Epithelial cell absorption rate of electrolytes was measured during steady state GI perfusion of a saline-mannitol solution. GI transit time of PEG and absorption of radiolabeled bile acid were measured simultaneously while subjects ingested three meals per day. To obtain a diarrhea control group for transit time and bile acid absorption, normal subjects were studied when they had diarrhea caused by ingestion of Milk of Magnesia (MOM). Diarrhea could not be explained by malabsorption of ingested nutrients, bacterial overgrowth, bile acid malabsorption, or epithelial cell malabsorption of electrolytes. However, 25% of polyethylene glycol (PEG) ingested with a standard meal was recovered in stool in 45 min, which is 10 times faster than in normal subjects with equally severe diarrhea caused by ingestion of MOM. All of the patients had autonomic neuropathy that remained unrecognized for 15-36 months after onset of chronic diarrhea; it seems likely that this was the cause of rapid transit. Severe chronic diarrhea in three patients with systemic amyloidosis was mediated by extremely rapid transit of chyme and digestive secretions through the intestine.

  7. Systemic Amyloidosis and Cardiac Autonomic Neuropathy Associated with Waldenstrom’s Macroglobulinemia

    Directory of Open Access Journals (Sweden)

    Aasems Jacob

    2017-01-01

    Full Text Available A 73-year-old male with long-standing Waldenstrom’s macroglobulinemia complicated with systemic amyloidosis presented with a witnessed syncopal episode. He had complaints of orthostatic dizziness and palpitations for few months. Orthostatic hypotension and peripheral neuropathy were demonstrated on physical examination. EKG, 24-hour Holter monitoring, and 2D echocardiogram were unremarkable. MRI of the brain ruled out stroke. Patients with amyloidosis can develop cardiovascular disease through amyloid cardiomyopathy, small vessel disease, conduction defects, pericardial effusion, or autonomic denervation. After ruling out other life-threatening causes, Ewing’s battery of tests was done to rule out cardiac autonomic neuropathy. Two heart rate tests and one blood pressure test were abnormal which indicated severe cardiac autonomic neuropathy. Cardiac autonomic neuropathy can mask symptoms of acute coronary syndrome and hence early diagnosis using the simple bedside maneuver is beneficial. The test is also important for prognostication. Absence of augmentation of cardiac output from inadequate autonomic stimulation will lead to postural hypotension, exercise intolerance, and tachycardia. There may be no change in heart rate with Valsalva or deep breathing both of which increase parasympathetic tone. As the condition progresses, it may result in cardiac denervation which can result in silent myocardial infarction, syncope, and sudden death.

  8. Mechanism of Action and Clinical Application of Tafamidis in Hereditary Transthyretin Amyloidosis.

    Science.gov (United States)

    Coelho, Teresa; Merlini, Giampaolo; Bulawa, Christine E; Fleming, James A; Judge, Daniel P; Kelly, Jeffery W; Maurer, Mathew S; Planté-Bordeneuve, Violaine; Labaudinière, Richard; Mundayat, Rajiv; Riley, Steve; Lombardo, Ilise; Huertas, Pedro

    2016-06-01

    Transthyretin (TTR) transports the retinol-binding protein-vitamin A complex and is a minor transporter of thyroxine in blood. Its tetrameric structure undergoes rate-limiting dissociation and monomer misfolding, enabling TTR to aggregate or to become amyloidogenic. Mutations in the TTR gene generally destabilize the tetramer and/or accelerate tetramer dissociation, promoting amyloidogenesis. TTR-related amyloidoses are rare, fatal, protein-misfolding disorders, characterized by formation of soluble aggregates of variable structure and tissue deposition of amyloid. The TTR amyloidoses present with a spectrum of manifestations, encompassing progressive neuropathy and/or cardiomyopathy. Until recently, the only accepted treatment to halt progression of hereditary TTR amyloidosis was liver transplantation, which replaces the hepatic source of mutant TTR with the less amyloidogenic wild-type TTR. Tafamidis meglumine is a rationally designed, non-NSAID benzoxazole derivative that binds with high affinity and selectivity to TTR and kinetically stabilizes the tetramer, slowing monomer formation, misfolding, and amyloidogenesis. Tafamidis is the first pharmacotherapy approved to slow the progression of peripheral neurologic impairment in TTR familial amyloid polyneuropathy. Here we describe the mechanism of action of tafamidis and review the clinical data, demonstrating that tafamidis treatment slows neurologic deterioration and preserves nutritional status, as well as quality of life in patients with early-stage Val30Met amyloidosis.

  9. Histological regression of amyloid in AL amyloidosis is exclusively seen after normalization of serum free light chain

    NARCIS (Netherlands)

    van Gameren, Ingrid I.; van Rijswijk, Martin H.; Bijzet, Johan; Vellenga, Edo; Hazenberg, Bouke P.

    Background Histological regression of amyloid has not been studied systematically but is assessed by clinical parameters. We analyzed the change of amyloid deposition in fat tissue in patients with AL amyloidosis following chemotherapy and studied the relation with type of hematologic response.

  10. Atypical Presentation of Gelsolin Amyloidosis in a Man of African Descent with a Novel Mutation in the Gelsolin Gene.

    Science.gov (United States)

    Oregel, Karlos Z; Shouse, Geoffrey P; Oster, Cyrus; Martinez, Freddy; Wang, Jun; Rosenzweig, Michael; Deisch, Jeremy K; Chen, Chien-Shing; Nagaraj, Gayathri

    2018-03-30

    BACKGROUND Gelsolin amyloidosis is a very rare systemic disease presenting with a pathognomonic triad of corneal lattice dystrophy, cutis laxa, and polyneuropathy. The disease is mostly restricted to a Finnish population with known mutations (G654A, G654T) in exon 4 of the gelsolin gene. The mutations lead to errors in protein processing and folding, and ultimately leads to deposition of an amyloidogenic fragment in the extracellular space, causing the symptoms of disease. CASE REPORT We present a case of gelsolin amyloidosis in a male of African descent with an atypical clinical presentation including fevers, skin rash, polyneuropathy, and anemia. Gelsolin amyloidosis was diagnosed based on mass spectrometry of tissue samples. Importantly, a novel mutation in the gelsolin gene (C1375G) in exon 10 was found in this patient. His atypical presentation can possibly be attributed to the presence of a novel mutation in the gelsolin gene as the likely underlying cause of the syndrome. PCR primers were used to amplify the gelsolin gene from genomic DNA. Purified PCR products were then shipped to Eton Biosciences (San Diego, CA) for sequencing. CONCLUSIONS This study carries several important lessons relevant to the practice of medicine. First, the differential diagnosis for multisystem disease presentations should always include amyloidosis. Second, despite what has been uncovered about the molecular biology of disease, there is always more that can be discovered. Finally, further work to verify the link between this mutation and the clinical syndrome is still needed, as are effective treatments for this disease.

  11. Low serum levels of prohepcidin, but not hepcidin-25, are related to anemia in familial amyloidosis TTR V30M.

    NARCIS (Netherlands)

    Beirao, I.; Almeida, S.; Swinkels, D.W.; Costa, P.M.; Moreira, L.; Fonseca, I.; Freitas, C.; Cabrita, A.; Porto, G.

    2008-01-01

    Familial amyloidosis TTR V30M (FAP-I) usually presents as a sensorimotor and autonomic neuropathy. Anemia was first described in this disease more than 20 years ago and classified as an anemia of chronic disease. However, so far no studies have addressed the role of inflammatory proteins in this

  12. Tocilizumab in the treatment of twelve cases with aa amyloidosis secondary to familial mediterranean fever.

    Science.gov (United States)

    Ugurlu, Serdal; Hacioglu, Aysa; Adibnia, Yasaman; Hamuryudan, Vedat; Ozdogan, Huri

    2017-05-30

    There is no established treatment of AA amyloidosis, a long-term complication of various chronic inflammatory diseases associated with increased mortality, such as familial Mediterranian fever (FMF). Recently there are few reports pointing out that tocilizumab(TCZ), an anti IL-6 agent may be effective in AA amyloidosis resistant to conventional treatments. We report our data on the effect of TCZ in patients with FMF complicated with AA amyloidosis. FMF patients with histologically proven AA amyloidosis, treated with TCZ (8 mg/kg per month) were followed monthly and the changes in creatinine, creatinine clearance, the amount of 24-hour urinary protein, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were noted throughout the treatment period. Adverse effects of the treatment were closely monitored. TCZ was given to 12 patients (6 F, 6 M) who also continued to receive colchicine (1.9 ± 0.4 mg/day). Coexisting diseases were ankylosing spondylitis(4) and Crohn's disease(1). The mean age was 35.2 ± 10.0 years and the mean follow-up on TCZ was 17.5 ± 14.7 months. The renal functions remained stable (mean creatinine from 1.1 ± 0.9 mg/dl to 1.0 ± 0.6 mg/dl), while a significant decrease in acute phase response (the mean CRP from 18.1 ± 19.5 mg/L to 5.8 ± 7.1 mg/L and ESR from 48.7 ± 31.0 mm/h to 28.7 ± 28.3 mm/h) was observed and the mean 24-hour urinary protein excretion reduced from 6537.6 ± 6526.0 mg/dl to 4745.5 ± 5462.7 mg/dl. Two patients whose renal functions were impaired prior to TCZ therapy improved significantly on this regimen. No infusion reaction was observed. None of the patients experienced any FMF attack under TCZ treatment with the exception of 2, one of whom had less frequent attacks while the other had episodes of erysipelas-like erythema. CONCLUSıON: Tocilizumab improved the acute phase response and the renal function in this group of patients and was generally well

  13. Imaging findings and literature review of {sup 18}F-FDG PET/CT in primary systemic AL amyloidosis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joo Hee; Lee, Ga Yeon; Kim, Seok Jin; Kim, Ki Hyun; Jeon, Eun Seok; Lee, Kyung Han; Kim, Byung Tae; Choi, Joon Young [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2015-09-15

    Although several case reports and case series have described {sup 18}F-FDG PET/CT in amyloidosis, the value of {sup 18}F-FDG PET/CT for diagnosing amyloidosis has not been clarified. We investigated the imaging findings of {sup 18}F-FDG PET/CT in patients with primary systemic AL amyloidosis. Subjects were 15 patients (M:F = 12:3; age, 61.5 ± 7.4 years) with histologically confirmed primary systemic AL amyloidosis who underwent pretreatment {sup 18}F-FDG PET/CT to rule out the possibility of malignancy or for initial workup of alleged cancer. For involved organs, visual and semiquantitative analyses were performed on {sup 18}F-FDG PET/CT images. In total, 22 organs (10 hearts, 5 kidneys, 2 stomachs, 2 colons, 1 ileum, 1 pancreas, and 1 liver) were histologically confirmed to have primary systemic AL amyloidosis. F-FDG uptake was significantly increased in 15 of the 22 organs (68.2 %; 10 hearts, 2 kidneys, 1 colon, 1 ileum, and 1 liver; SUV{sub max} = 7.0 ± 3.2, range 2.1–14.1). However, in 11 of 15 PET-positive organs (78.6 %; 10 hearts and the ileum), it was difficult to differentiate pathological uptake from physiological uptake. Definitely abnormal {sup 18}F-FDG uptake was found in only 4 of the 22 organs (18.2 %; 2 kidneys, 1 colon, and the liver). {sup 18}F-FDG uptake was negative for pancreas and gastric lesions. Although {sup 18}F-FDG PET/CT showed high uptake in two-thirds of the organs involving primary systemic AL amyloidosis, its sensitivity appeared to be low to make differentiation of pathological uptake from physiological uptake. However, due to the small number of cases, further study for the role of {sup 18}F-FDG PET/CT in amyloidosis will be warranted.

  14. Three-dimensional Speckle Tracking Echocardiography in Light Chain Cardiac Amyloidosis: Examination of Left and Right Ventricular Myocardial Mechanics Parameters.

    Science.gov (United States)

    Urbano-Moral, Jose Angel; Gangadharamurthy, Dakshin; Comenzo, Raymond L; Pandian, Natesa G; Patel, Ayan R

    2015-08-01

    The study of myocardial mechanics has a potential role in the detection of cardiac involvement in patients with amyloidosis. This study aimed to characterize 3-dimensional-speckle tracking echocardiography-derived left and right ventricular myocardial mechanics in light chain amyloidosis and examine their relationship with brain natriuretic peptide. In patients with light chain amyloidosis, left ventricular longitudinal and circumferential strain (n=40), and right ventricular longitudinal strain and radial displacement (n=26) were obtained by 3-dimensional-speckle tracking echocardiography. Brain natriuretic peptide levels were determined. All myocardial mechanics measurements showed differences when compared by brain natriuretic peptide level tertiles. Left and right ventricular longitudinal strain were highly correlated (r=0.95, P<.001). Left ventricular longitudinal and circumferential strain were reduced in patients with cardiac involvement (-9±4 vs -16±2; P<.001, and -24±6 vs -29±4; P=.01, respectively), with the most prominent impairment at the basal segments. Right ventricular longitudinal strain and radial displacement were diminished in patients with cardiac involvement (-9±3 vs -17±3; P<.001, and 2.7±0.8 vs 3.8±0.3; P=.002). On multivariate analysis, left ventricular longitudinal strain was associated with the presence of cardiac involvement (odds ratio = 1.6; 95% confidence interval, 1.04 to 2.37; P=.03) independent of the presence of brain natriuretic peptide and troponin I criteria for cardiac amyloidosis. Three-dimensional-speckle tracking echocardiography-derived left and right ventricular myocardial mechanics are increasingly altered as brain natriuretic peptide increases in light chain amyloidosis. There appears to be a strong association between left ventricular longitudinal strain and cardiac involvement, beyond biomarkers such as brain natriuretic peptide and troponin I. Copyright © 2015 Sociedad Española de Cardiología. Published by

  15. Kinetic studies with iodine-123-labeled serum amyloid P component in patients with systemic AA and AL amyloidosis and assessment of clinical value

    NARCIS (Netherlands)

    Jager, PL; Hazenberg, BPC; Franssen, EJF; Limburg, PC; van Rijswijk, MH; Piers, DA

    In systemic amyloidosis, widespread amyloid deposition interferes with organ function, frequently with fatal consequences. Diagnosis rests on demonstrating amyloid deposits in the tissues, traditionally with histology although scintigraphic imaging with radiolabeled serum amyloid P component (SAP)

  16. CNS involvement in V30M transthyretin amyloidosis: clinical, neuropathological and biochemical findings.

    Science.gov (United States)

    Maia, Luís F; Magalhães, Rui; Freitas, Joel; Taipa, Ricardo; Pires, Manuel Melo; Osório, Hugo; Dias, Daniel; Pessegueiro, Helena; Correia, Manuel; Coelho, Teresa

    2015-02-01

    Since liver transplant (LT) was introduced to treat patients with familial amyloid polyneuropathy carrying the V30M mutation (ATTR-V30M), ocular and cardiac complications have developed. Long-term central nervous system (CNS) involvement was not investigated. Our goals were to: (1) identify and characterise focal neurological episodes (FNEs) due to CNS dysfunction in ATTR-V30M patients; (2) characterise neuropathological features and temporal profile of CNS transthyretin amyloidosis. We monitored the presence and type of FNEs in 87 consecutive ATTR-V30M and 35 non-ATTR LT patients. FNEs were investigated with CT scan, EEG and extensive neurovascular workup. MRI studies were not performed because all patients had cardiac pacemakers as part of the LT protocol. We characterised transthyretin amyloid deposition in the brains of seven ATTR-V30M patients, dead 3-13 years after polyneuropathy onset. FNEs occurred in 31% (27/87) of ATTR-V30M and in 5.7% (2/35) of the non-ATTR transplanted patients (OR=7.0, 95% CI 1.5 to 33.5). FNEs occurred on average 14.6 years after disease onset (95% CI 13.3 to 16.0) in ATTR-V30M patients, which is beyond the life expectancy of non-transplanted ATTR-V30M patients (10.9, 95% CI 10.5 to 11.3). ATTR-V30M patients with FNEs had longer disease duration (OR=1.24; 95% CI 1.07 to 1.43), renal dysfunction (OR=4.65; 95% CI 1.20 to 18.05) and were men (OR=3.57; 95% CI 1.02 to 12.30). CNS transthyretin amyloidosis was already present 3 years after polyneuropathy onset and progressed from the meninges and its vessels towards meningocortical vessels and the superficial brain parenchyma, as disease duration increased. Our findings indicate that CNS clinical involvement occurs in ATTR-V30M patients regardless of LT. Longer disease duration after LT can provide the necessary time for transthyretin amyloidosis to progress until it becomes clinically relevant. Highly sensitive imaging methods are needed to identify and monitor brain ATTR. Disease

  17. Regional differences in prognostic value of cardiac valve plane displacement in systemic light-chain amyloidosis.

    Science.gov (United States)

    Ochs, Marco M; Fritz, Thomas; Arenja, Nisha; Riffel, Johannes; Andre, Florian; Mereles, Derliz; Siepen, Fabian Aus dem; Hegenbart, Ute; Schönland, Stefan; Katus, Hugo A; Friedrich, Matthias G W; Buss, Sebastian J

    2017-11-09

    To compare the prognostic value of cardiac valve plane displacement (CVPD) on various locations in cardiac light chain (AL) amyloidosis. Consecutive patients with biopsy-proven cardiac involvement in AL amyloidosis who had undergone cardiovascular magnetic resonance (CMR) between 2005 and 2014 in our institution, were retrospectively identified and data analyzed. The primary combined endpoint was all-cause mortality or heart transplantation. Systolic CVPD were obtained from standard cine bSSFP in 2-, 3- and 4-chamber views at anterior aortic plane systolic excursion (AAPSE); anterior, anterolateral, inferolateral, inferior, inferoseptal mitral (MAPSE); and lateral tricuspid (TAPSE) annular segments. We identified 68 patients (58 ± 10 years; 59% male). Median follow-up period was 1.2 years (IQR, 0.3-4.1). Significant differences in CVPD between patients who reached a primary endpoint (n = 44) and transplant-free survivors were found only for AAPSE (6.1 mm (IQR, 4.6-9.4) vs. 8.8 mm (IQR, 6.9-10.4); p = 0.02) and MAPSE anterolateral (7.3 mm (IQR, 5.4-11.7) vs. 10.5 mm (IQR, 8.1-13.4); p = 0.03). AAPSE (χ 2  = 15.6; p = 0.0002) provided the best predictive value for transplant-free survival compared to all other valvular plane locations. A high-risk cutoff (AAPSE ≤ 7.6 mm) was calculated by ROC analysis to predict all-cause death or heart transplantation within 6 months from index examination (AUC = 0.80; CI: 0.68 to 0.89; p model of late gadolinium enhancement and global longitudinal strain (GLS) (∆χ 2  = 5.8, p = 0.02) as well as to a clinical model including Karnofsky index and NT-proBNP (∆χ 2  = 6.2, p = 0.01). In patients with cardiac involvement in AL amyloidosis, systolic CVPD obtained from standard long axis cine views appear to indicate outcome better, when obtained in the anterior aortic plane (AAPSE) and provide incremental prognostic value to LGE and strain measurements.

  18. [The prognostic value of baseline serum free light chain in cardiac amyloidosis].

    Science.gov (United States)

    Zhao, Lei; Tian, Zhuang; Fang, Quan

    2016-03-01

    To analyze the prognostic value of baseline serum free light chain (sFLC) in light-chain (AL) cardiac amyloidosis. Twenty-seven patients with AL cardiac amyloidosis were retrospectively reviewed from January 2014 to January 2015. sFLC was measured by immuoturbidimetric assay. Baseline characteristics, echocardiographic parameters and electrocardiogram data were analyzed. According to the median baseline dFLC (involved sFLC minus uninvolved sFLC), patients were categorized into either the low dFLC(≤ 307 mg/L) or the high dFLC group (>307 mg/L). More subjects in the high dFLC group with early/late diastolic mitral velocity ratio (E/A ratio) over 2 (71.4% vs 30.8%, P=0.035), and subjects in this group had a shorter median survival time than those in the low dFLC group (3 months vs 17 months, P=0.004). A similar phenomenon for median survival time was observed when the subjects were redivided either by a new cut-off value of 180 mg/L for dFLC (low dFLC group: 17 months; high dFLC group: 4 months, P=0.014) or a κ/λ ratio, in which subjects with κ type sFLC-ratio ≤ 19.6 and λ type sFLC-ratio>0.065 were in the low sFLC-ratio group (17 months) and those with κ type sFLC-ratio > 19.6 and λ type sFLC-ratio ≤ 0.065 were in the high sFLC-ratio group (4 months, P=0.023). In multivariate analysis, dFLC and New York Heart Association (NYHA)classification of cardiac function were two risk factors associated with all-cause mortality in patients, among which the hazard ratio for higher dFLC was 4.28 (95%CI 1.55-11.8, P=0.005). The level of sFLC could be a marker for the prognosis of AL cardiac amyloidosis.

  19. [Morphological and biochemical features of cerebral beta-amyloidosis in long-livers].

    Science.gov (United States)

    Kozyrev, K M; Siatkin, S P; Berezov, T T

    2002-01-01

    This is the first assessment of the pathogenetic values of some environmental factors in the occurrence and progression of cerebral beta-amyloidosis (Alzheimer's disease, senile dementia) in long-livers of different climatic areas of the Republic of North Ossetia-Alania. New isoenzyme serum assays for determining creatine kinase BB-isoenzyme and the transaminase activity in the spinal fluid are proposed, which may be used as potential markers in the biochemical diagnosis of Alzheimer's disease. They can both provide valuable information on the severity of morphological lesions of cerebral cells in Alzheimer's disease and serve as the basis for the differential diagnosis of different forms of dementia wherein dystrophic changes in CNS cells are absent or slightly pronounced.

  20. Nodular immunocyte-derived (AL) amyloidosis in the trachea of a dog.

    Science.gov (United States)

    Besancon, M Faulkner; Stacy, Brian A; Kyles, Andrew E; Moore, Peter F; Vernau, William; Smarick, Sean D; Rasor, Liberty A

    2004-04-15

    A 7-year-old castrated male Miniature Schnauzer was examined because of labored breathing and episodes of respiratory distress that progressed to collapse. On cervical radiographs, a focal soft tissue mass in the caudal cervical portion of the trachea was observed, and during tracheoscopy, a 1 x 1 cm, pedunculated, multinodular, pink, intraluminal mass extending from the dorsal tracheal membrane and obstructing approximately 80% of the tracheal lumen was seen. Tracheal resection and anastomosis was performed to remove the mass, and the dog recovered without complications. On histologic examination, the mass consisted of a large accumulation of homogeneous, faintly fibrillar eosinophilic material admixed with a predominantly plasma cell infiltrate; examination of sections stained with thioflavin T and Congo red stain confirmed that the eosinophilic material was amyloid. A diagnosis of nodular, immunocyte-derived (AL) amyloidosis was made. Seventeen months after surgery, the dog had a relapse of respiratory distress because of an extramedullary plasmacytoma involving the trachea.

  1. Cardiac Amyloidosis and its New Clinical Phenotype: Heart Failure with Preserved Ejection Fraction.

    Science.gov (United States)

    Mesquita, Evandro Tinoco; Jorge, Antonio José Lagoeiro; Souza, Celso Vale; Andrade, Thais Ribeiro de

    2017-07-01

    Heart failure with preserved ejection fraction (HFpEF) is now an emerging cardiovascular epidemic, being identified as the main phenotype observed in clinical practice. It is more associated with female gender, advanced age and comorbidities such as hypertension, diabetes, obesity and chronic kidney disease. Amyloidosis is a clinical disorder characterized by the deposition of aggregates of insoluble fibrils originating from proteins that exhibit anomalous folding. Recently, pictures of senile amyloidosis have been described in patients with HFpEF, demonstrating the need for clinical cardiologists to investigate this etiology in suspect cases. The clinical suspicion of amyloidosis should be increased in cases of HFPS where the cardio imaging methods are compatible with infiltrative cardiomyopathy. Advances in cardio imaging methods combined with the possibility of performing genetic tests and identification of the type of amyloid material allow the diagnosis to be made. The management of the diagnosed patients can be done in partnership with centers specialized in the study of amyloidosis, which, together with the new technologies, investigate the possibility of organ or bone marrow transplantation and also the involvement of patients in clinical studies that evaluate the action of the new emerging drugs. Resumo A insuficiência cardíaca com fração de ejeção preservada (ICFEP) é hoje uma epidemia cardiovascular emergente, sendo identificada como o principal fenótipo observado na prática clínica. Está mais associado ao sexo feminino, idade avançada e a comorbidades como hipertensão arterial, diabetes, obesidade e doença renal crônica. A amiloidose é uma desordem clínica caracterizada pelo depósito de agregados de fibrilas insolúveis originadas de proteínas que apresentam dobramento anômalo. Recentemente, têm sido descritos quadros de amiloidose senil em pacientes com ICFEP, demonstrando a necessidade de os cardiologistas clínicos investigarem

  2. Cellular processing of the amyloidogenic cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Merz, G S; Schwenk, V

    1999-01-01

    of an amyloidogenic mutation on the intracellular processing of its protein product. The protein, a mutant of the cysteine protease inhibitor cystatin C, is the amyloid precursor protein in Hereditary Cerebral Hemorrhage with Amyloidosis--Icelandic type (HCHWA-I). The amyloid fibers are composed of mutant cystatin C......An important gap in our understanding of the pathogenesis of the amyloidoses is the identification of the cellular events that lead from synthesis of an amyloid precursor protein to its conversion to the amyloid fiber subunit. We address this question by characterizing the effects...... (L68Q) that lacks the first 10 amino acids. We have previously shown that processing of wild-type cystatin C entails formation of a transient intracellular dimer that dissociates prior to secretion, such that extracellular cystatin C is monomeric. We report here that the cystatin C mutation engenders...

  3. Amyloid Cardiomyopathy in Hereditary Transthyretin V30M Amyloidosis - Impact of Sex and Amyloid Fibril Composition.

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    Sandra Arvidsson

    Full Text Available Transthyretin V30M (ATTR V30M amyloidosis is a phenotypically diverse disease with symptoms ranging from predominant neuropathy to exclusive cardiac manifestations. The aims of this study were to determine the dispersion of the two types of fibrils found in Swedish ATTR V30M patients -Type A consisting of a mixture of truncated and full length ATTR fibrils and type B fibrils consisting of full length fibrils, and to estimate the severity of cardiac dysfunction in relation to fibril composition and sex.Echocardiographic data were analysed in 107 Swedish ATTR V30M patients with their fibril composition determined as either type A or type B. Measurements of left ventricular (LV dimensions and evaluation of systolic and diastolic function including speckle tracking derived strain were performed. Patients were grouped according to fibril type and sex. Multivariate linear regression was utilised to determine factors of significant impact on LV thickness.There was no significant difference in proportions of the two types of fibrils between men and women. In patients with type A fibrils, women had significantly lower median septal (p = 0.007 and posterior wall thicknesses (p = 0.010, lower median LV mass indexed to height (p = 0.008, and higher septal strain (p = 0.037, as compared to males. These differences were not apparent in patients with type B fibrils. Multiple linear regression analysis revealed that fibril type, sex and age all had significant impact on LV septal thickness.This study demonstrates a clear difference between sexes in the severity of amyloid heart disease in ATTR V30M amyloidosis patients. Even though type A fibrils were associated with more advanced amyloid heart disease compared to type B, women with type A fibrils generally developed less cardiac infiltration than men. The differences may explain the better outcome for liver transplanted late-onset female patients compared to males.

  4. Bortezomib with or without dexamethasone in primary systemic (light chain) amyloidosis.

    Science.gov (United States)

    Kastritis, Efstathios; Wechalekar, Ashutosh D; Dimopoulos, Meletios A; Merlini, Giampaolo; Hawkins, Philip N; Perfetti, Vittorio; Gillmore, Julian D; Palladini, Giovanni

    2010-02-20

    PURPOSE To assess the efficacy and tolerability of bortezomib with or without dexamethasone and to define prognostic factors for patients with primary systemic light chain (AL) amyloidosis treated with bortezomib or both. PATIENTS AND METHODS Ninety-four patients from three centers were analyzed: 19% received the combination as first-line treatment, 81% had a median of two previous therapies, and 69% had refractory disease, while most patients had symptomatic heart involvement or elevated serum N-terminal pro-brain natriuretic peptide (NT-proBNP). Results A hematologic response was achieved in 71% within a median of 52 days, including 25% complete responses (CRs). Previously untreated patients had a 47% CR rate. Age 65 years or younger (P = .043) and twice weekly administration of bortezomib (P = .041) were associated with higher response rates. A cardiac response was documented in 29% of patients, in most as sustained improvement of functional class and less often as a decrease in wall thickness. Hematologic responses were associated with a cardiac response and NT-proBNP reduction. After a median follow-up of 12 months, 29% of patients had organ progression and 27% had hematologic progression. Median survival has not been reached and the 1-year survival rate is 76%. Baseline NT-proBNP was independently associated with survival (P = .001), while in a landmark analysis, survival was associated with NT-proBNP reduction of > or = 30% (P = .006) and achievement of hematologic response (P = .001). Toxicity was manageable and mostly consisted of neuropathy, orthostasis, peripheral edema, and constipation or diarrhea. CONCLUSION Bortezomib with or without dexamethasone is active in AL amyloidosis and induces rapid responses and high rates of hematologic and organ responses. Serial measurement of cardiac biomarkers is a powerful predictor of outcome.

  5. Potentiation of fluindione or warfarin by dexamethasone in multiple myeloma and AL amyloidosis.

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    Sellam, Jérémie; Costedoat-Chalumeau, Nathalie; Amoura, Zahir; Aymard, Guy; Choquet, Sylvain; Trad, Salim; Vignes, Bénédicte Lebrun; Hulot, Jean-Sébastien; Berenbaum, Francis; Lechat, Philippe; Cacoub, Patrice; Ankri, Annick; Mariette, Xavier; Leblond, Véronique; Piette, Jean-Charles

    2007-10-01

    Patients with primary systemic (AL) amyloidosis or multiple myeloma are frequently treated with cyclic dexamethasone (DXM) courses and often require oral anticoagulants. We previously reported a strong potentiation of oral anticoagulants with intravenous methylprednisolone and observed a similar potentiation with DXM in 3 patients, which led us to prospectively investigate the interaction between DXM and oral anticoagulants. Nine patients with multiple myeloma (n=6) or AL amyloidosis (n=3), including 6 prospective patients, taking fluindione (n=8) or warfarin (n=1), were studied for a total of 10 cycles. DXM (40 mg/day for 4 days every 28 days) was administered alone (n=4) or with melphalan (n=5). One patient was studied for 2 consecutive cycles after a moderate increase in the international normalized ratio (INR) during the first course of DXM. International normalized ratio (INR) was measured serially during DXM administration. Plasma oral anticoagulant concentrations were measured for 5 cycles. The mean INR increased from 2.75 (range: 1.80-3.6) at baseline to 5.22 (3.09-7.07) after DXM. Oral anticoagulants were transiently stopped during 8 cycles and 1 mg oral vitamin K was given during 2. No serious bleeding was observed. Plasma oral anticoagulant concentrations increased after DXM administration. In controls receiving DXM without oral anticoagulants, DXM alone did not increase prothrombin time. High dose DXM can potentiate oral anticoagulants and elevate INR substantially. INR should therefore be monitored repeatedly during concomitant administration of these 2 drugs to allow individual adaptation of oral anticoagulant doses.

  6. Globular hepatic amyloid is highly sensitive and specific for LECT2 amyloidosis.

    Science.gov (United States)

    Chandan, Vishal S; Shah, Sejal S; Lam-Himlin, Dora M; Petris, Giovanni De; Mereuta, Oana M; Dogan, Ahmet; Torbenson, Michael S; Wu, Tsung-Teh

    2015-04-01

    Globular hepatic amyloid (GHA) is rare, and its clinical significance remains unclear. Recently, leukocyte chemotactic factor-associated amyloidosis (ALECT2) has been reported to involve the liver, showing a globular pattern. We reviewed 70 consecutive cases of hepatic amyloidosis to determine the prevalence and morphology of hepatic amyloid subtypes, especially ALECT2 and its association with GHA. Each case was reviewed for amyloid subtype (immunohistochemistry and/or mass spectrometry), its pattern (linear or globular), and distribution (vascular, perisinusoidal, or stromal). In addition, 24 cases of confirmed hepatic ALECT2 on mass spectrometry from our consultation files were also reviewed. LECT2 immunostaining was performed in 49 cases. Of the 70 cases, immunoglobulin light chain (AL) type was most common with 41 cases (59%), followed by transthyretin (ATTR) 15 cases (22%), 3 cases each of fibrinogen A (AFib) (4%), serum amyloid A (AA) (4%), and ALECT2 (4%), 2 cases of apolipoproteins (AApoA1) (3%), and 3 cases (4%) were unclassified. Three of our 70 cases (4%), with ALECT2, and all 24 cases (100%) of mass spectrometry-confirmed hepatic ALECT2 showed only GHA deposits in the hepatic sinusoids and portal tracts. Three (4%) other cases of AL type showed a focal globular pattern admixed with prominent linear amyloid. None of the other amyloid subtypes showed GHA. LECT2 immunostain was positive in all 27 cases (100%) of ALECT2 and negative in the other 22 non-ALECT2 cases (100%) (14 AL, 5 ATTR, 1 AA, 1 AFib, 1 AApoA1). Pure GHA is uncommon (4%) but is highly specific for ALECT2, and LECT2 immunostain is helpful in confirming this amyloid type.

  7. Light chain amyloidosis: Experience in a tertiary hospital: 2005-2013.

    Science.gov (United States)

    Krsnik, I; Cabero, M; Morillo, D; Segovia, J; García-Pavía, P; Gómez-Bueno, M; Salas, C

    2015-01-01

    AL amyloidosis is a rare condition whose management is undergoing changes due to recent advances in diagnosis and treatment. We describe a contemporary series of patients with AL amyloidosis to analyze the features that enable early diagnosis and optimal management. We recruited for analysis 32 patients (19 women; mean age, 63 years) treated consecutively at our center. Eighty-four percent of the patients presented with asthenia, dyspnea or edema, with a previous duration of symptoms of 8 months (median). Cardiac (21/32) and renal impairment were the most common type (11/32). All of the patients, except one, had a monoclonal component in serum/urine or abnormal values for free light chains (78%, λ). The bone marrow (BM) showed clonal plasmacytosis in 29 cases. All of the cardiac biopsies and 50% of the BM biopsies showed amyloid deposits. The results of the echocardiogram and/or cardiac resonance were abnormal in 27/30 cases. The median NT-proBNP value at diagnosis was 5200 ng/ml. Thirteen patients died due to heart failure, 2 due to rejection after heart transplantation, 2 due to pneumonia and 1 after a stroke. Ten patients did not undergo treatment, 12 were treated with bortezomib and 5 were treated with alkylating agents. Five patients underwent heart transplantation and 4 underwent autologous bone marrow transplantation. Fourteen patients achieved a complete hematologic response and 10 achieved organ response. The median survival was 17 months. Cardiac involvement is the major determinant of prognosis. Yield of involved organ biopsy is high (100% heart biopsies). Antineoplastic treatment with bortezomib and/or autologous bone marrow transplantation achieves hematological responses with improvements in organ impairment. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  8. Cardiac Amyloidosis

    Science.gov (United States)

    ... L. Kruger , Rodney H. Falk Download PDF https://doi.org/10.1161/CIRCULATIONAHA.111.069195 Circulation. 2012; 126: ... e178-e182 , originally published September 17, 2012 https://doi.org/10.1161/CIRCULATIONAHA.111.069195 Citation Manager Formats ...

  9. Cardiac amyloidosis

    Science.gov (United States)

    ... heart signals Prednisone, an anti-inflammatory medicine A heart transplant may be considered for people with some types ... accountability. A.D.A.M. is among the first to achieve this important distinction for online health ...

  10. Peripherally applied synthetic peptide isoAsp7-Aβ(1-42) triggers cerebral β-amyloidosis.

    Science.gov (United States)

    Kozin, S A; Cheglakov, I B; Ovsepyan, A A; Telegin, G B; Tsvetkov, P O; Lisitsa, A V; Makarov, A A

    2013-10-01

    Intracerebral and intraperitoneal inoculation with β-amyloid-rich brain extracts originating from patients with Alzheimer's disease as well as intracerebral injection of aggregates composed of synthetic Aβ can induce cerebral β-amyloidosis, and associated cognitive dysfunctions in susceptible animal hosts. We have found that repetitive intravenous administration of 100 μg of synthetic peptide corresponding to isoAsp7-containing Aβ(1-42), an abundant age-dependent Aβ isoform present both in the pathological brain and in synthetic Aβ preparations, robustly accelerates formation of classic dense-core congophilic amyloid plaques in the brain of β-amyloid precursor protein transgenic mice. Our findings indicate this peptide as an inductive agent of cerebral β-amyloidosis in vivo.

  11. CRYPTOCOCCUS NEOFORMANS VAR. GRUBII-ASSOCIATED RENAL AMYLOIDOSIS CAUSING PROTEIN-LOSING NEPHROPATHY IN A RED KANGAROO (MACROPUS RUFUS).

    Science.gov (United States)

    Thurber, Mary Irene; Gjeltema, Jenessa; Sheley, Matthew; Wack, Ray F

    2017-09-01

    A 10-year-old male castrated red kangaroo (Macropus rufus) presented with mandibular swelling. Examination findings included pitting edema with no dental disease evident on examination or radiographs. The results of blood work were moderate azotemia, hypoalbuminemia, and severely elevated urine protein:creatinine ratio (9.9). Radiographs showed an interstitial pattern of the caudal right lung, and an abdominal ultrasound demonstrated scant effusion. Symptomatic and empirical therapy with antibiotics, anti-inflammatory drugs, and an angiotensin-converting enzyme (ACE) inhibitor did not resolve clinical signs. Due to poor prognosis and declining quality of life, euthanasia was elected. Necropsy revealed chronic granulomatous pneumonia of the caudal right lung lobe with intralesional Cryptococcus, identified as C. neoformans var. grubii by DNA sequencing. Severe bilateral glomerular and tubulointerstitial amyloidosis induced protein-losing nephropathy, leading to tri-cavitary effusion, subcutaneous edema, and cachexia. The authors speculate that renal amyloidosis was associated with chronic cryptococcal pneumonia in this red kangaroo.

  12. Utility of abdominal skin plus subcutaneous fat and rectal mucosal biopsy in the diagnosis of AL amyloidosis with renal involvement.

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    Ting Li

    Full Text Available Skin fat biopsy of the abdominal wall is a simple and safe method for detecting amyloidosis, and rectal mucosal biopsy is also frequently used for screening for the disease; however, the sensitivity of these approaches has not been fully studied. The aim of this study was to evaluate the efficacy of skin fat biopsy combined with rectal mucosal biopsy as a screening procedure for the diagnosis of systemic immunoglobulin light-chain (AL amyloidosis.We retrospectively analyzed 224 AL amyloidosis patients confirmed by renal biopsy, including a test group of 165 patients and validation group of 59 patients. Surgical skin fat biopsy from the abdominal wall and rectal mucosal biopsy under endoscopy was performed to obtain specimens. Congo red staining and immunofluorescence staining with antibodies against light chains were performed to type the disease. Pathology reports were reviewed to assess the diagnostic sensitivity of skin fat biopsy and rectal mucosal biopsy. Diagnostic specificity was not examined in the present study, because no healthy volunteers and only few patients with other diseases had performed immunofluorescence staining on skin fat and rectal specimens.Of the 165 patients in the test group, Congo red staining of skin fat and rectal mucosal specimens was associated with a sensitivity of 89.3% and 94.8%, respectively. The sensitivity increased to 98.9% by combining both biopsy methods. Immunofluorescence stains were positive in 81.1% of patients undergoing skin fat biopsy and 84.7% of patients undergoing rectal mucosal biopsy. Immunofluorescence stains yielded positive results in 86.7% of cases combining skin fat biopsy with rectal mucosal biopsy. The diagnostic results also performed well in the validation group.Surgical skin biopsy including the subcutaneous fat pad can be performed safely at the bedside and is useful for diagnosing AL amyloidosis. Combining skin fat biopsy with rectal mucosal biopsy may identify amyloid deposits in

  13. Detection of AA76, a Common Form of Amyloid A Protein, as a Way of Diagnosing AA Amyloidosis.

    Science.gov (United States)

    Sato, Junji; Okuda, Yasuaki; Kuroda, Takeshi; Yamada, Toshiyuki

    2016-01-01

    Reactive amyloid deposits consist of amyloid A (AA) proteins, the degradation products of serum amyloid A (SAA). Since the most common species of AA is the amino terminal portion produced by cleavage between residues 76 and 77 of SAA (AA76), the presence of AA76 in tissues could be a consequence of AA amyloid deposition. This study assessed the diagnostic significance of the detection of AA76 for AA amyloidosis using two different approaches. Biopsy specimens (n=130 from 54 subjects) from gastroduodenal mucosa or abdominal fat (n=9 from 9 subjects) of patients who had already been diagnosed with or were suspected of having AA amyloidosis were used. Fixed mucosal sections were subjected to immunohistochemistry using a newly developed antibody recognizing the carboxyl terminal end of AA76 (anti-AA76). The non-fixed materials from gastroduodenal mucosa or abdominal fat were subjected to immunoblotting for detection of the size of AA76. Among the gastroduodenal specimens (n=115) from already diagnosed patients, the positive rates of Congo red staining, immunohistochemistry using anti-AA76, and immunoblotting were 68.4%, 73.0%, and 92.2%, respectively. The anti-AA76 did not stain the supposed SAA in the blood or leakage, which was stained by anti-SAA antibody. AA76 was not detected either by immunohistochemistry or by immunoblot in the materials from patients in whom AA amyloidosis had been ruled out. In the abdominal fat, the immunoblot detected AA76 in 8 materials from 8 already diagnosed patients and did not in 1 patient whose gastroduodenal mucosa was negative. In conclusion, the detection of AA76 may alter the ability to diagnose AA amyloidosis. In immunohistochemistry for fixed specimens, the new anti-AA76 antibody can improve the specificity. Immunoblot for non-fixed materials, which can considerably improve the sensitivity, should be beneficial for small materials like abdominal fat. © 2016 by the Association of Clinical Scientists, Inc.

  14. Visualization of multiple organ amyloid involvement in systemic amyloidosis using11C-PiB PET imaging.

    Science.gov (United States)

    Ezawa, Naoki; Katoh, Nagaaki; Oguchi, Kazuhiro; Yoshinaga, Tsuneaki; Yazaki, Masahide; Sekijima, Yoshiki

    2018-03-01

    To investigate the utility of Pittsburgh compound B (PiB) positron emission tomography (PET) imaging for evaluating whole-body amyloid involvement in patients with systemic amyloidosis. Whole-body 11 C-PiB PET was performed in seven patients with systemic immunoglobulin light-chain (AL) amyloidosis, seven patients with hereditary transthyretin (ATTRm) amyloidosis, one asymptomatic TTR mutation carrier and three healthy controls. The correlations between clinical organ involvement, radiological 11 C-PiB uptake and histopathological findings were analysed for each organ. Organ involvement on 11 C-PiB PET imaging showed good correlations with the clinical findings for the heart and stomach. Abnormal tracer uptake was also observed in the spleen, lachrymal gland, submandibular gland, sublingual gland, lymph node, brain, scalp, extraocular muscles, nasal mucosa, pharynx, tongue and nuchal muscles, most of which were asymptomatic. Physiological tracer uptake was universally observed in the urinary tract (kidney, renal pelvis, ureter and bladder) and enterohepatic circulatory system (liver, gallbladder, bile duct and small intestine) in all participants. Most of the patients and one healthy control subject showed asymptomatic tracer uptake in the lung and parotid gland. The peripheral nervous system did not show any tracer uptake even in patients with apparent peripheral neuropathy. Histological amyloid deposition was confirmed in biopsied myocardium and gastric mucosa where abnormal 11 C-PiB retention was observed. 11 C-PiB PET imaging can be used clinically in the systemic evaluation of amyloid distribution in patients with AL and ATTRm amyloidosis. Quantitative analysis of 11 C-PiB PET images may be useful in therapy evaluation and will reveal whether amyloid clearance is correlated with clinical response.

  15. Auto-SCT improves survival in systemic light chain amyloidosis: a retrospective analysis with 14-year follow-up.

    Science.gov (United States)

    Parmar, S; Kongtim, P; Champlin, R; Dinh, Y; Elgharably, Y; Wang, M; Bashir, Q; Shah, J J; Shah, N; Popat, U; Giralt, S A; Orlowski, R Z; Qazilbash, M H

    2014-08-01

    Optimal treatment approach continues to remain a challenge for systemic light chain amyloidosis (AL). So far, Auto-SCT is the only modality associated with long-term survival. However, failure to show survival benefit in randomized study raises questions regarding its efficacy. We present a comparative outcome analysis of Auto-SCT to conventional therapies (CTR) in AL patients treated over a 14-year period at our institution. Out of the 145 AL amyloidosis patients, Auto-SCT was performed in 80 patients with 1-year non-relapse mortality rate of 12.5%. Novel agents were used as part of induction therapy in 56% of transplant recipients vs 46% of CTR patients. Hematological and organ responses were seen in 74.6% and 39% in the Auto-SCT arm vs 53% and 12% in the CTR arm, respectively. The projected 5-year survival for Auto-SCT vs CTR was 63% vs 38%, respectively. Landmark analysis of patients alive at 1-year after diagnosis showed improved 5-year OS of 72% with Auto-SCT vs 65% in the CTR arm. In the multivariate analysis, age SCT were associated with improved survival. In conclusion, Auto-SCT is associated with long-term survival for patients with AL amyloidosis.

  16. Safety and efficacy of high-dose melphalan and auto-SCT in patients with AL amyloidosis and cardiac involvement.

    Science.gov (United States)

    Girnius, S; Seldin, D C; Meier-Ewert, H K; Sloan, J M; Quillen, K; Ruberg, F L; Berk, J L; Doros, G; Sanchorawala, V

    2014-03-01

    In Ig light chain (AL) amyloidosis, cardiac involvement is associated with worse prognosis and increased treatment-related complications. In this retrospective cohort study, we assessed survival, hematologic and cardiac responses to high-dose melphalan and auto-SCT (HDM/SCT) in patients with AL amyloidosis and cardiac involvement, stratified by cardiac biomarkers brain natriuretic peptide and Troponin I, analogous to the Mayo cardiac staging. Forty-seven patients underwent HDM/SCT based upon functional measures; six patients had modified cardiac stage I disease, seventeen had modified cardiac stage II disease and twenty-four had modified cardiac stage III disease. Treatment-related mortality was 4% for all patients and 8% for patients with stage III disease. Three-year survival was 88% and EFS was 47%; these did not differ by stage. By intention-to-treat analysis, 27% of patients achieved a hematologic complete response and 32% a very good partial response, of whom 70 and 45%, respectively, have not required additional therapy at 36 months. Cardiac response was achieved in 53% of patients. We conclude that with appropriate patient selection and a risk-adapted treatment approach, HDM/SCT is safe and effective in patients with AL amyloidosis and cardiac involvement.

  17. Mice with alopecia, osteoporosis, and systemic amyloidosis due to mutation in Zdhhc13, a gene coding for palmitoyl acyltransferase.

    Directory of Open Access Journals (Sweden)

    Amir N Saleem

    2010-06-01

    Full Text Available Protein palmitoylation has emerged as an important mechanism for regulating protein trafficking, stability, and protein-protein interactions; however, its relevance to disease processes is not clear. Using a genome-wide, phenotype driven N-ethyl-N-nitrosourea-mediated mutagenesis screen, we identified mice with failure to thrive, shortened life span, skin and hair abnormalities including alopecia, severe osteoporosis, and systemic amyloidosis (both AA and AL amyloids depositions. Whole-genome homozygosity mapping with 295 SNP markers and fine mapping with an additional 50 SNPs localized the disease gene to chromosome 7 between 53.9 and 56.3 Mb. A nonsense mutation (c.1273A>T was located in exon 12 of the Zdhhc13 gene (Zinc finger, DHHC domain containing 13, a gene coding for palmitoyl transferase. The mutation predicted a truncated protein (R425X, and real-time PCR showed markedly reduced Zdhhc13 mRNA. A second gene trap allele of Zdhhc13 has the same phenotypes, suggesting that this is a loss of function allele. This is the first report that palmitoyl transferase deficiency causes a severe phenotype, and it establishes a direct link between protein palmitoylation and regulation of diverse physiologic functions where its absence can result in profound disease pathology. This mouse model can be used to investigate mechanisms where improper palmitoylation leads to disease processes and to understand molecular mechanisms underlying human alopecia, osteoporosis, and amyloidosis and many other neurodegenerative diseases caused by protein misfolding and amyloidosis.

  18. Fibrils from designed non-amyloid-related synthetic peptides induce AA-amyloidosis during inflammation in an animal model.

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    Per Westermark

    Full Text Available BACKGROUND: Mouse AA-amyloidosis is a transmissible disease by a prion-like mechanism where amyloid fibrils act by seeding. Synthetic peptides with no amyloid relationship can assemble into amyloid-like fibrils and these may have seeding capacity for amyloid proteins. PRINCIPAL FINDINGS: Several synthetic peptides, designed for nanotechnology, have been examined for their ability to produce fibrils with Congo red affinity and concomitant green birefringence, affinity for thioflavin S and to accelerate AA-amyloidosis in mice. It is shown that some amphiphilic fibril-forming peptides not only produced Congo red birefringence and showed affinity for thioflavin S, but they also shortened the lag phase for systemic AA-amyloidosis in mice when they were given intravenously at the time of inflammatory induction with silver nitride. Peptides, not forming amyloid-like fibrils, did not have such properties. CONCLUSIONS: These observations should caution researchers and those who work with synthetic peptides and their derivatives to be aware of the potential health concerns.

  19. The hormonal and radiological evaluation of adrenal glands, and the determination of the usefulness of low dose ACTH test in patients with renal amyloidosis.

    Science.gov (United States)

    Gündüz, Z; Keleştimur, F; Durak, A C; Utaş, C; Büyükberber, M; Düşünsel, R; Kurtoğlu, S; Poyrazoglu, M H

    2001-03-01

    Amyloidosis is a multisystem disease which may cause organ loss. Renal involvement is the most common clinical problem in amyloidosis, however involvement of endocrin organs is possible. In this study to assess adrenocortical function and to evaluate the usefulness of low dose ACTH test in patients with renal amyloidosis, we determined cortisol, 17-hydroxyprogesteron (17-OHP) and 11-deoxycortisol (11-DOC) responses to both 1 microg and 250 microg Synacthen. We also determined the size of adrenal glands radiologically by using computerized tomography. Twenty one patients with renal amyloidosis and 16 healthy subjects for hormonal evaluation, and 20 patients with renal amyloidosis and 22 healthy subjects for radiologic evaluation were included in the study. In four patients (19%) peak serum cortisol levels following stimulation with the low dose of Synacthen were less than 20 microg/dL (550 nmol/L). Two of them had also subnormal cortisol response to the 250 microg Synacthen stimulation test. Basal and stimulated levels of 11-DOC were lower than those of control values (p=0.000 and p<0.01 respectively). The mean 11-DOC responses to stimulation with 1 microg Synacthen were also significantly lower than the values obtained after the simulation with 250 microg Synacthen (p<0.01 and p=0.000). Cortisol responses to the stimulation with 250 microg Synacthen were also lower than the control responses (p<0.05). 17-OHP responses were similar to the control values in both tests. In the radiological evaluation the mean maximum width of right adrenal glands and the mean anterior and maximum width of left adrenal glands were significantly greater in the patient group (p<0.01). In conclusion, adrenal involvement and adrenal insufficiency is common in amyloidosis. Low 11-DOC levels in amyloidosis is a new finding and further detailed studies is required to explain its cause.

  20. Macroglossia decorrente de amiloidose sistêmica: relato de caso e revisão de literatura Macroglosia due to sistemic amyloidosis: case report and literature review

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    Sandra Doria Xavier

    2004-10-01

    Full Text Available Amiloidose é caracterizada por deposição extracelular anormal de amilóide em diferentes tecidos e órgãos, geralmente associada com disfunção do tecido ou órgão envolvido, cuja causa não é ainda conhecida. Pode ser dividida em amiloidose sistêmica e localizada. A forma sistêmica é dividida em: (1 primária; (2 amiloidose associada ao mieloma múltiplo; (3 secundária; (4 amiloidose heredofamiliar. Há uma considerável diferença de sobrevida entre os pacientes com forma localizada e sistêmica de amiloidose, e também com mieloma múltiplo. Não há tratamento satisfatório para amiloidose sistêmica. O presente estudo relata um caso de amiloidose sistêmica primária, com revisão de literatura. O diagnóstico de amiloidose foi conseguido com biópsia de língua e o envolvimento sistêmico confirmado através de aspirado de gordura abdominal. Apesar de a amiloidose não ser a principal hipótese diagnóstica que deva ser aventada quando nos deparamos com um paciente com macroglossia, esta doença não pode ser esquecida, uma vez que o suporte clínico é essencial para o controle das doenças que podem estar associadas, como falência renal, cardíaca e o mieloma múltiplo.Amyloidosis is characterized by the abnormal, extracelular deposition of one of a family of unrelated proteins, amyloid, in different tissues or organs; it is usually associated with tissue or organ disfunction. The cause is not yet known. Amyloidosis can be divided in systemic or localized form. The sistemic form can be divided in: (1 primary; (2 amyloidosis associated with multiple myeloma; (3 secondary; (4 heredofamilial amyloidosis. There is a considerable difference in the survival of patients with localized and systemic amyloidosis, and also with or without multiple myeloma. Satisfactory treatment for systemic amyloidosis does not exist. The present study was undertaken in order to report a case of primary sistemic amyloidosis as well as literature review

  1. Familial amyloidotic polyneuropathy: current and emerging treatment options for transthyretin-mediated amyloidosis

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    Hund E

    2012-06-01

    removing the main source of mutant TTR. Recently, orally administered tafamidis meglumine has been approved by European authorities for treatment of FAP. The substance has been shown to stabilize the TTR tetramer, thereby improving the outcome of patients with TTR-FAP. Various other strategies have been studied in vitro to prevent TTR amyloidosis, including gene therapy, immunization, dissolution of TTR aggregates, and free radical scavengers, but none of them is ready for clinical use so far.Keywords: FAP, transthyretin, amyloidosis, treatment, therapy

  2. Scintigraphic imaging and turnover studies with iodine-131 labelled serum amyloid P component in systemic amyloidosis

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    Hawkins, P.N.; Pepys, M.B. [Immunological Medicine Unit, Department of Medicine, Royal Postgraduate Medical School, London (United Kingdom); Aprile, C. [Nuclear Medicine Service, Scientific Institute Fondazione Maugeri, Pavia (Italy); Capri, G.; Vigano, L.; Munzone, E.; Gianni, L. [Division of Medical Oncology, Istituto Nazionale Tumori, Milan (Italy); Merlini, G. [Biotechnology Research Laboratories, University Hospital S. Matteo, Pavia (Italy)

    1998-07-01

    Radiolabelled serum amyloid P component (SAP) is a specific tracer for amyloid. Iodine-123 has ideal physical characteristics for scintigraphy but is expensive and not widely available. Here we report serial imaging and turnover studies in which we labelled SAP with iodine-131, a cheap alternative isotope which would be expected to yield poorer images but permit more prolonged turnover measurements. Imaging and plasma clearance and whole body retention (WBR) of tracer were studied for up to 7 days in ten patients with proven systemic AL amyloidosis and two patients in whom the diagnosis was suspected, after i.v. administration of about 37 MBq of {sup 131}I-SAP. Normal blood pool images were obtained in the latter two subjects and amyloidosis was subsequently refuted histologically. WBR at 48 h was <60% and 6-h plasma activity was >65% of the injected dose (i.d.). Among the other ten patients, amyloid deposits were identified in the spleen in eight cases, liver in five and kidneys in four; other sites that gave positive results included bone, joints and soft tissues, and the myocardium in one case. Up to 95% of the tracer localised into amyloid within 6-h, and the values for WBR became progressively more discriminating during the study period, exceeding the normal reference value (<25%) in all cases by day 7. The optimal imaging time was found to be between 24 and 48 h. The duration of the study enabled us to measure the tracer elimination half-life which was increased in all cases by up to tenfold. Follow-up studies performed after 2-24 months in four patients who were treated with iododoxorubicin showed regression of amyloid in one patient and a small increase in one case; in the other two patients the imaging and turnover studies were identical to baseline. Despite its unfavourable imaging characteristics, {sup 131}I-SAP produced diagnostic scans in every patient in this series and, coupled with the detailed turnover information, is adequate for monitoring

  3. Amiloidose na cavidade bucal: aspectos clínicos, histopatológicos e ultra-estruturais Amyloidosis in the oral cavity: clinical, histopathological and ultrastructural features

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    Paulo Rogério de Faria

    2003-06-01

    Full Text Available Amiloidose refere-se à deposição extracelular e progressiva de proteínas fibrilares patogênicas com características microscópicas e ultra-estruturais similares. A amiloidose pode ser sistêmica ou localizada. Descrevemos três pacientes que desenvolveram amiloidose intra-oral, sendo que dois casos manifestaram amiloidose localizada e o outro caso apresentou amiloidose sistêmica com acometimento de língua. Nos três casos, o exame histopatológico evidenciou depósitos de amilóide, os quais foram confirmados pela coloração de vermelho-congo. A ultra-estrutura mostrou material fibrilar compatível com amilóide. Apesar de infreqüente, a cavidade bucal pode ser um importante local de acometimento de amiloidose.Amyloidosis refers to extracellular and progressive deposition of the fibrilar protein with similar microscopic and ultrastructural features. Amyloid deposits can occur in the localized (one organ or systemic form (several organs. We report three patients which developed intraoral amyloidosis. Two of them were clinical cases which showed localized amyloidosis and another, an autopsied patient with systemic amyloidosis involving the tongue. In these three cases, the histopathologic study displayed amyloid deposits, which were confirmed with stain Congo red and apple-green birefringence under polarized light. Ultrastructural features presented fibrilar material compatible with amyloid. Although uncommon, oral cavity can be involved by amyloidosis.

  4. Significance of11C-PIB PET/CT in cardiac amyloidosis compared with99mTc-aprotinin scintigraphy: A pilot study.

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    Minamimoto, Ryogo; Awaya, Toru; Iwama, Kentaro; Hotta, Masatoshi; Nakajima, Kazuhiko; Hirai, Risen; Okazaki, Osamu; Hiroi, Yukio

    2018-03-27

    This study was to investigate the significance of 11 C-Pittsburgh B (PIB) PET/CT in patients with suspected cardiac amyloidosis compared with 99m Tc-aprotinin scintigraphy. Thirteen consecutive patients with suspected cardiac amyloidosis were considered for enrolment in this prospective pilot study. Participants were scheduled to undergo a series of 11 C-PIB PET/CT and 99m Tc-aprotinin within a 2-month period. Finally, we evaluated nine cases who underwent both imaging modalities, and compared imaging results with clinical and pathological results and prognosis. Six of the 9 patients who underwent both imaging modalities were diagnosed with amyloidosis, of whom 3 patients were diagnosed with cardiac amyloidosis from endomyocardial biopsy. These 3 patients with positive 11 C-PIB uptake at the left ventricle wall showed worsening of cardiac function progressing in the short term or death caused by acute exacerbation of chronic heart failure. Six of 8 patients with positive uptake on 99m Tc-aprotinin presented with amyloid deposition in the left ventricle wall, but symptoms remained stable if results of 11 C-PIB were not positive. In a small sample of subjects, the present study showed that 11 C-PIB accumulation in myocardium indicated cardiac amyloidosis with poor prognosis. Uptake of 11 C-PIB may be related to progressive amyloid deposition to the heart and can predict patient prognosis.

  5. A Novel Missense Mutation in Oncostatin M Receptor Beta Causing Primary Localized Cutaneous Amyloidosis

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    Marjan Saeedi

    2014-01-01

    Full Text Available Primary localized cutaneous amyloidosis (PLCA is a chronic skin disorder, caused by amyloid material deposition in the upper dermis. Autosomal dominant PLCA has been mapped earlier to pathogenic missense mutations in the OSMR gene, which encodes the oncostatin M receptor ß subunit (OSMRß. OSMRß is interleukin-6 family cytokine receptors and possesses two ligands, oncostatin M and interleukin-31, which both have biologic roles in inflammation and keratinocyte cell proliferation, differentiation, and apoptosis. Here, we identified a new OSMR mutation in a Kurdish family for the first time. Blood samples were taken from all the affected individuals in the family. DNA extraction was performed using salting out technique. Primers were designed for intron flanking individual exons of OSMR gene which were subjected to direct sequencing after PCR amplification for each sample. Sequencing showed a C/T substitution at position 613 in the proband. This mutation results in an L613S (leucine 613 to serine amino acid change. The identified mutation was observed in all affected family members but not in 100 ethnically matched healthy controls. Elucidating the molecular basis of familial PLCA provides new insight into mechanisms of itch in human skin and may lead to new therapeutic targets for pruritus.

  6. A novel missense mutation in oncostatin M receptor beta causing primary localized cutaneous amyloidosis.

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    Saeedi, Marjan; Ebrahim-Habibi, Azadeh; Haghighi, Alireza; Zarrabi, Fariba; Amoli, Mahsa M; Robati, Reza M

    2014-01-01

    Primary localized cutaneous amyloidosis (PLCA) is a chronic skin disorder, caused by amyloid material deposition in the upper dermis. Autosomal dominant PLCA has been mapped earlier to pathogenic missense mutations in the OSMR gene, which encodes the oncostatin M receptor ß subunit (OSMRß). OSMRß is interleukin-6 family cytokine receptors and possesses two ligands, oncostatin M and interleukin-31, which both have biologic roles in inflammation and keratinocyte cell proliferation, differentiation, and apoptosis. Here, we identified a new OSMR mutation in a Kurdish family for the first time. Blood samples were taken from all the affected individuals in the family. DNA extraction was performed using salting out technique. Primers were designed for intron flanking individual exons of OSMR gene which were subjected to direct sequencing after PCR amplification for each sample. Sequencing showed a C/T substitution at position 613 in the proband. This mutation results in an L613S (leucine 613 to serine) amino acid change. The identified mutation was observed in all affected family members but not in 100 ethnically matched healthy controls. Elucidating the molecular basis of familial PLCA provides new insight into mechanisms of itch in human skin and may lead to new therapeutic targets for pruritus.

  7. Insulin deficiency exacerbates cerebral amyloidosis and behavioral deficits in an Alzheimer transgenic mouse model

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    Teng Wei-Ping

    2010-11-01

    Full Text Available Abstract Background Although increasing evidence has indicated that brain insulin dysfunction is a risk factor for Alzheimer disease (AD, the underlying mechanisms by which insulin deficiency may impact the development of AD are still obscure. Using a streptozotocin (STZ-induced insulin deficient diabetic AD transgenic mouse model, we evaluated the effect of insulin deficiency on AD-like behavior and neuropathology. Results Our data showed that administration of STZ increased the level of blood glucose and reduced the level of serum insulin, and further decreased the phosphorylation levels of insulin receptors, and increased the activities of glycogen synthase kinase-3α/β and c-Jun N-terminal kinase in the APP/PS1 mouse brain. We further showed that STZ treatment promoted the processing of amyloid-β (Aβ precursor protein resulting in increased Aβ generation, neuritic plaque formation, and spatial memory deficits in transgenic mice. Conclusions Our present data indicate that there is a close link between insulin deficient diabetes and cerebral amyloidosis in the pathogenesis of AD.

  8. Quantification of Number of CD38 Sites on Bone Marrow Plasma Cells in Patients with Light Chain Amyloidosis and Smoldering Multiple Myeloma.

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    Kriegsmann, Katharina; Dittrich, Tobias; Neuber, Brigitte; Awwad, Mohamed H S; Hegenbart, Ute; Goldschmidt, Hartmut; Hillengass, Jens; Hose, Dirk; Seckinger, Anja; Müller-Tidow, Carsten; Ho, Anthony D; Schönland, Stefan; Hundemer, Michael

    2018-03-25

    Recent approaches in multiple myeloma (MM) treatment have targeted CD38. As antigen expression levels on plasma cells (PCs) were demonstrated to affect response to monoclonal antibody (mAb) treatment, a precise characterization of PC phenotype is warranted. Anti-CD38 mAb (isatuximab) was tested for antibody-dependent cellular cytotoxicity (ADCC) in MM cell lines. Quantification of the number of sites (NOS) of CD38 on bone marrow PCs and other immune cells obtained from light chain (AL) amyloidosis (n=46) and smoldering multiple myeloma (SMM) patients (n=19) was performed with two different quantitative flow cytometry (QFCM) applications. ADCC activity of isatuximab was observed in cell lines with >100 x10 3 CD38-NOS only. The average PC CD38-NOS was 153 ±53 x10 3 in AL amyloidosis and 138.7 ±53 x10 3 in SMM patients. Eight (17%) AL amyloidosis and 4 (21%) SMM patients showed a PC CD38-NOS level <100 x10 3 . In 4 AL amyloidosis and 2 SMM patients <10% of PCs had a CD38-NOS ≥100 x10 3 . The CD38-NOS identified on bone marrow lymphocytes, monocytes and granulocytes was 2 log units below the CD38-NOS on PCs (P<0.001). No significant differences in CD38-NOS expression levels on any of the analyzed PC subpopulations in AL amyloidosis and SMM patients were identified. Levels of CD38 expression affect the isatuximab-mediated ADCC in vitro. As PCs of patients with AL amyloidosis and SMM do not homogenously express high CD38 our data provide a rationale for assessment of CD38-NOS in patients with PC disorders prior to anti-CD38 treatment. This article is protected by copyright. All rights reserved. © 2018 International Clinical Cytometry Society.

  9. Experimental transmission of AA amyloidosis by injecting the AA amyloid protein into interleukin-1 receptor antagonist knockout (IL-1raKO) mice.

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    Watanabe, K; Uchida, K; Chambers, J K; Tei, M; Shoji, A; Ushio, N; Nakayama, H

    2015-05-01

    The incidence of AA amyloidosis is high in humans with rheumatoid arthritis and several animal species, including cats and cattle with prolonged inflammation. AA amyloidosis can be experimentally induced in mice using severe inflammatory stimuli and a coinjection of AA amyloid; however, difficulties have been associated with transmitting AA amyloidosis to a different animal species, and this has been attributed to the "species barrier." The interleukin-1 receptor antagonist knockout (IL-1raKO) mouse, a rodent model of human rheumatoid arthritis, has been used in the transmission of AA amyloid. When IL-1raKO and BALB/c mice were intraperitoneally injected with mouse AA amyloid together with a subcutaneous pretreatment of 2% AgNO3, all mice from both strains that were injected with crude or purified murine AA amyloid developed AA amyloidosis. However, the amyloid index, which was determined by the intensity of AA amyloid deposition, was significantly higher in IL-1raKO mice than in BALB/c mice. When IL-1raKO and BALB/c mice were injected with crude or purified bovine AA amyloid together with the pretreatment, 83% (5/6 cases) and 38% (3/8 cases) of IL-1raKO mice and 17% (1/6 cases) and 0% (0/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. Similarly, when IL-1raKO and BALB/c mice were injected with crude or purified feline AA amyloid, 33% (2/6 cases) and 88% (7/8 cases) of IL-1raKO mice and 0% (0/6 cases) and 29% (2/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. These results indicated that IL-1raKO mice are a useful animal model for investigating AA amyloidogenesis. © The Author(s) 2014.

  10. Exercise-Stress Echocardiography Reveals Systolic Anterior Motion of the Mitral Valve as a Cause of Syncopes in a Cardiac Amyloidosis Patient.

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    Clemmensen, Tor Skibsted; Mølgaard, Henning; Andersen, Niels Frost; Baerentzen, Steen; Poulsen, Steen Hvitfeldt

    2016-01-01

    Patients with cardiac amyloidosis are at increased AV-block and syncope risk. Therefore, a prophylactic pacemaker is often implanted. However, this case illustrates that other mechanisms should be ruled out prior to pacemaker implantation. The patient studied had mitral valve thickening without increased left ventricular outflow track (LVOT) velocity. However, bicycle exercise-stress test with simultaneous echocardiography revealed a stepwise decrease in blood pressure, a substantial increase in the LVOT velocity, and severe systolic anterior motion of the mitral valve. The patients' symptoms were likely explained by these findings. Therefore, a comprehensive clinical evaluation is warranted prior to pacemaker implantation in cardiac amyloidosis patients.

  11. Exercise-Stress Echocardiography Reveals Systolic Anterior Motion of the Mitral Valve as a Cause of Syncopes in a Cardiac Amyloidosis Patient

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    Tor Skibsted Clemmensen

    2016-01-01

    Full Text Available Patients with cardiac amyloidosis are at increased AV-block and syncope risk. Therefore, a prophylactic pacemaker is often implanted. However, this case illustrates that other mechanisms should be ruled out prior to pacemaker implantation. The patient studied had mitral valve thickening without increased left ventricular outflow track (LVOT velocity. However, bicycle exercise-stress test with simultaneous echocardiography revealed a stepwise decrease in blood pressure, a substantial increase in the LVOT velocity, and severe systolic anterior motion of the mitral valve. The patients’ symptoms were likely explained by these findings. Therefore, a comprehensive clinical evaluation is warranted prior to pacemaker implantation in cardiac amyloidosis patients.

  12. Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death.

    Science.gov (United States)

    Muchtar, Eli; Gertz, Morie A; Kumar, Shaji K; Lacy, Martha Q; Dingli, David; Buadi, Francis K; Grogan, Martha; Hayman, Suzanne R; Kapoor, Prashant; Leung, Nelson; Fonder, Amie; Hobbs, Miriam; Hwa, Yi Lisa; Gonsalves, Wilson; Warsame, Rahma; Kourelis, Taxiarchis V; Russell, Stephen; Lust, John A; Lin, Yi; Go, Ronald S; Zeldenrust, Steven; Kyle, Robert A; Rajkumar, S Vincent; Dispenzieri, Angela

    2017-04-13

    In light of major advances in immunoglobulin light chain (AL) amyloidosis, we evaluated the trends in presentation, management, and outcome among 1551 newly diagnosed AL amyloidosis patients seen in our institution from 2000 to 2014. As compared with the 2 intervals 2000-2004 and 2005-2009, patients diagnosed in 2010-2014 were less likely to have >2 involved organs. Utilization of autologous stem cell transplant (ASCT) was similar across all periods, about one-third of patients, but there was an increase in the use of pre-ASCT bortezomib induction and of unattenuated melphalan conditioning in 2010-2014 compared with earlier periods. Non-ASCT first-line regimen changed with 65% of patients in 2010-2014 received bortezomib-based therapy, 79% of patients in 2005-2009 received melphalan-dexamethasone, and 64% of patients in 2000-2004 received melphalan-prednisone. The rate of better than very good partial response (VGPR) was higher in more recent periods (66% vs 58% vs 51%; P = .001), a change largely driven by improved VGPR rates in the non-ASCT population. Overall survival (OS) has improved, with inflection points for improvement differing for the ASCT and non-ASCT groups. In the ASCT population, the greatest gains were after 2010 (4-year OS, 91% compared with 73% and 65%). In the non-ASCT group, greatest gains were after 2005 (4-year OS, 38%, 32%, and 16%). Fewer patients died within 6 months of diagnosis in the 2 later periods (24% vs 25% vs 37%; P < .001). Overall, outcomes among patients with AL amyloidosis have improved with earlier diagnosis, higher rates of VGPR, lower early mortality, and improved OS. © 2017 by The American Society of Hematology.

  13. Isolated primary amyloidosis of the inferior rectus muscle mimicking Graves' orbitopathy.

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    Monteiro, Mário Luiz Ribeiro; Gonçalves, Allan Christian Pieroni; Bezerra, Alanna Mara Pinheiro Sobreira

    2016-01-01

    The diagnosis of Graves' orbitopathy is usually straightforward. However, orbital diseases that mimick some clinical signs of Graves' orbitopathy may cause diagnostic confusion, particularly when associated to some form of thyroid dysfunction. This report describes the rare occurrence of localized inferior rectus muscle amyloidosis in a patient with autoimmune hypothyroidism, who was misdiagnosed as Graves' orbitopathy. A 48-year-old man complained of painless progressive proptosis on the left side and intermittent vertical diplopia for 6 months. The diagnosis of Graves' orbitopathy was entertained after magnetic resonance imaging revealing a markedly enlarged, tendon-sparing inferior rectus enlargement on the left side, and an autoimmune hypothyroidism was disclosed on systemic medical workup. After no clinical improvement with treatment, the patient was referred to an ophthalmologist and further investigation was performed. The presence of calcification in the inferior rectus muscle on computed tomography, associated with the clinical findings led to a diagnostic biopsy, which revealed amyloid deposition. This report emphasizes that a careful evaluation of atypical forms of Graves' orbitopathy may be crucial and should include, yet with rare occurrence, amyloidosis in its differential diagnosis. RESUMO O diagnóstico de orbitopatia de Graves usualmente é fácil de ser estabelecido. No entanto, doenças da órbita que simulam alguns sinais clínicos da orbitopatia de Graves podem levar à confusão diagnóstica, particularmente quando associada à alguma forma de disfunção tireoidiana. Relatamos a ocorrência rara de amiloidose localizada no músculo reto inferior em paciente com hipotireoidismo autoimune, que recebeu inicialmente o diagnóstico errôneo de orbitopatia de Graves. Paciente masculino, 48 anos, com queixa de proptose progressiva e indolor do lado esquerdo e diplopia vertical intermitente há 6 meses. O diagnóstico de orbitopatia de Graves foi

  14. Noninvasive detection of cardiac amyloidosis using delayed enhanced MDCT: a pilot study

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    Deux, Jean-Francois [University Paris Est Creteil, Assistance Publique-Hopitaux de Paris, Cardiac MR Unit, Radiology Department, Henri Mondor Hospital, Creteil (France); University Paris Est Creteil, Assistance Publique-Hopitaux de Paris, CNRS EAC 4396, Centre de Recherches Chirurgicales, Henri Mondor Hospital, Creteil (France); Reseau Amylose Mondorien, Henri Mondor Hospital, Creteil (France); Mihalache, Cristian-Ionut; Legou, Francois; Luciani, Alain; Kobeiter, Hicham; Rahmouni, Alain [University Paris Est Creteil, Assistance Publique-Hopitaux de Paris, Cardiac MR Unit, Radiology Department, Henri Mondor Hospital, Creteil (France); Damy, Thibaud [Reseau Amylose Mondorien, Henri Mondor Hospital, Creteil (France); University Paris Est Creteil, Assistance Publique-Hopitaux de Paris, Cardiology Department, Henri Mondor Hospital, Creteil (France); Mayer, Julie [University Paris Est Creteil, Assistance Publique-Hopitaux de Paris, Cardiac MR Unit, Radiology Department, Henri Mondor Hospital, Creteil (France); Reseau Amylose Mondorien, Henri Mondor Hospital, Creteil (France); Rappeneau, Stephane [Reseau Amylose Mondorien, Henri Mondor Hospital, Creteil (France); Plante-Bordeneuve, Violaine [Reseau Amylose Mondorien, Henri Mondor Hospital, Creteil (France); University Paris Est Creteil, Assistance Publique-Hopitaux de Paris, Department of Neurophysiology of Neurology, Henri Mondor Hospital, Creteil (France)

    2015-08-15

    To evaluate myocardial enhancement of patients with cardiac amyloidosis (CA) using computed tomography (CT). Thirteen patients with CA and 11 control patients were examined with first-pass and delayed CT acquisition. A qualitative and quantitative analysis of images was performed. Myocardial attenuation, myocardial signal-to-noise ratio (SNR{sub myoc}), blood pool SNR (SNR{sub blood}), contrast-to-noise ratio between blood pool and myocardium (CNR{sub blood-myoc}) and relative attenuation index (RAI) defined as variation of myocardial attenuation between delayed and first-pass acquisitions were calculated. Two false negative cases (15 %) and three false positive cases (27 %) were detected on qualitative analysis. SNR{sub myoc} of patients with CA was significantly (p < 0.05) lower on first-pass (4.08 ± 1.9) and higher on delayed acquisition (7.10 ± 2.7) than control patients (6.1 ± 2.2 and 5.03 ± 1.8, respectively). Myocardial attenuation was higher in CA (121 ± 39 HU) than control patients (81 ± 17 HU) on delayed acquisition. CNR{sub blood-myoc} was significantly (p < 0.05) lower in CA (1.51 ± 0.7) than control patients (2.85 ± 1.2) on delayed acquisition. The RAI was significantly (p < 0.05) higher in CA (0.12 ± 0.25) than in control patients (-0.56 ± 0.21). Dual phase MDCT can detect abnormal myocardial enhancement in patients with CA. (orig.)

  15. Microglia in diffuse plaques in hereditary cerebral hemorrhage with amyloidosis (Dutch). An immunohistochemical study.

    Science.gov (United States)

    Maat-Schieman, M L; Rozemuller, A J; van Duinen, S G; Haan, J; Eikelenboom, P; Roos, R A

    1994-09-01

    In hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D) beta/A4 amyloid deposition is found in meningocortical blood vessels and in diffuse plaques in the cerebral cortex. Diffuse plaques putatively represent early stages in the formation of senile plaques. Microglia are intimately associated with congophilic plaques in Alzheimer's disease (AD), but microglial involvement in diffuse plaque formation is controversial. Therefore, we studied the relationship between microglia and diffuse plaques in the cerebral cortex of four patients with HCHWA-D using a panel of macrophage/microglia markers (mAbs LCA, LeuM5, LeuM3, LN3, KP1, OKIa, CLB54, Mac1, Ki-M6, AMC30 and the lectin RCA-1). Eight AD patients, one demented Down's syndrome (DS) patient and four non-demented controls were included for comparison. In controls and HCHWA-D patients ramified or "resting" microglia formed a reticular array in cortical gray and subcortical white matter. Microglial cells in or near HCHWA-D diffuse plaques retained their normal regular spacing and ramified morphology. In AD/DS gray matter more microglial cells were stained than in controls and HCHWA-D patients. Intensely immunoreactive microglia with enlarged cell bodies and short, thick processes clustered in congophilic plaques. In contrast to the resting microglia, these "activated microglia" strongly expressed class II major histocompatibility complex antigen, HLA-DR, and were AMC30-immunoreactive. These findings support the view that microglia play a role in the formation of congophilic plaques but do not initiate diffuse plaque formation. Another finding in this study is the presence of strong monocyte/macrophage marker immunoreactivity in the wall of cortical congophilic blood vessels in HCHWA-D.

  16. Neuropathy and efficacy of once weekly subcutaneous bortezomib in multiple myeloma and light chain (AL amyloidosis.

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    Surbhi Sidana

    Full Text Available Randomized studies have shown that bortezomib (BTZ can be given weekly via intravenous (IV route or twice weekly via subcutaneous (SC route with lower neuropathy risk and no loss of anti-myeloma efficacy compared to original standard IV twice weekly schedule. Weekly SC should therefore yield the best therapeutic index and is widely used but has not been compared to established administration schedules in the context of a clinical trial.Comprehensive electronic medical record review was done for disease control and neuropathy symptoms of 344 consecutive patients who received their first BTZ-containing regimen for myeloma or AL amyloidosis before or after we changed to SC weekly in December 2010. Univariate and multivariable analyses were carried out that adjusted for age, underlying disease, concurrently used anticancer agents, underlying conditions predisposing to neuropathy, and number of prior regimens compared SC weekly to other schedules.Fifty-three patients received BTZ SC weekly, 17 SC twice weekly, 127 IV weekly and 147 IV twice weekly. Risk for neuropathy of any grade was higher with other schedules compared to SC weekly (44.3% vs. 26.9%, p = 0.001 while response rate was similar (72.1% vs. 76.6%, respectively, p = 0.15. Multivariable analyses upheld higher neuropathy risk (Odds ratio 2.45, 95% CI 1.26-4.76, p = 0.008 while the likelihood of not achieving a response (= partial response or better was comparable (Odds ratio 1.25, 95% CI 0.58-2.71, p = 0.56 for other schedules compared to SC weekly, respectively. Lower neuropathy risk translated into longer treatment duration when BTZ was started SC weekly (p = 0.001.Weekly SC BTZ has activity comparable to other schedules and causes low rates of neuropathy.

  17. Diagnosis and typing of systemic amyloidosis: The role of abdominal fat pad fine needle aspiration biopsy.

    Science.gov (United States)

    Halloush, Ruba A; Lavrovskaya, Elena; Mody, Dina R; Lager, Donna; Truong, Luan

    2010-01-15

    Systemic amyloidosis (SA) has a broad nonspecific clinical presentation. Its diagnosis depends on identifying amyloid in tissues. Abdominal fat pad fine needle aspiration (FPFNA) has been suggested as a sensitive and specific test for diagnosing SA. Thirty-nine FPFNA from 38 patients (16 women and 20 men, age range 40-88 years) during a 15-year period were reviewed. Smears and cell blocks were stained with Congo red (CR). A panel of antibodies (serum amyloid protein, serum amyloid A, albumin, transthyretin, kappa light chain and lambda light chain) was used on six cell blocks from five patients. The FNA findings were correlated with clinical and histological follow-up. FPFNAs were positive, confirmed by CR in 5/39 (13%), suspicious in 1/39 (3%), negative in 28/39 (72%), and insufficient for diagnosis in 5/39 (13%) of cases. In all the positive cases, SA was confirmed within 2-16 weeks. Among the 28 negative cases, SA was diagnosed in 21, the rest were lost to follow-up. Among the insufficient cases, SA was diagnosed in four and one was lost to follow-up. Specificity was 100%, whereas sensitivity was 19%. SA typing using cell block sections was successful in three, un-interpretable in one, and negative in two cases. FPFNA for SA is not as good as previously reported. This may be due to different practice setting, level of experience, diagnostic technique, or absence of abdominal soft tissue involvement. A negative result of FPFNA does not exclude SA. Immune phenotyping of amyloid is possible on cell block.

  18. Diagnosis and typing of systemic amyloidosis: The role of abdominal fat pad fine needle aspiration biopsy

    Directory of Open Access Journals (Sweden)

    Halloush Ruba

    2009-01-01

    Full Text Available Introduction: Systemic amyloidosis (SA has a broad nonspecific clinical presentation. Its diagnosis depends on identifying amyloid in tissues. Abdominal fat pad fine needle aspiration (FPFNA has been suggested as a sensitive and specific test for diagnosing SA. Materials and Methods: Thirty-nine FPFNA from 38 patients (16 women and 20 men, age range 40-88 years during a 15-year period were reviewed. Smears and cell blocks were stained with Congo red (CR. A panel of antibodies (serum amyloid protein, serum amyloid A, albumin, transthyretin, kappa light chain and lambda light chain was used on six cell blocks from five patients. The FNA findings were correlated with clinical and histological follow-up. Results: FPFNAs were positive, confirmed by CR in 5/39 (13%, suspicious in 1/39 (3%, negative in 28/39 (72%, and insufficient for diagnosis in 5/39 (13% of cases. In all the positive cases, SA was confirmed within 2-16 weeks. Among the 28 negative cases, SA was diagnosed in 21, the rest were lost to follow-up. Among the insufficient cases, SA was diagnosed in four and one was lost to follow-up. Specificity was 100%, whereas sensitivity was 19%. SA typing using cell block sections was successful in three, un-interpretable in one, and negative in two cases. Conclusion: FPFNA for SA is not as good as previously reported. This may be due to different practice setting, level of experience, diagnostic technique, or absence of abdominal soft tissue involvement. A negative result of FPFNA does not exclude SA. Immune phenotyping of amyloid is possible on cell block.

  19. Amyloid detection in the transverse carpal ligament of patients with hereditary ATTR V30M amyloidosis and carpal tunnel syndrome.

    Science.gov (United States)

    Samões, Raquel; Taipa, Ricardo; Valdrez, Kátia; Gonçalves, Isabel; Melo Pires, Manuel; Martins da Silva, Ana; Coelho, Teresa

    2017-06-01

    Carpal tunnel syndrome (CTS) is a nonspecific manifestation of hereditary ATTR amyloidosis (ATTRm). Amyloid deposition of wild-type TTR (WT-ATTR) has been found in transverse carpal ligament (TCL) in idiopathic CTS. We retrospectively studied a group of patients with ATTRm and CTS submitted to carpal tunnel release surgery (CTRS). From the nerve conduction studies performed in our Clinical Unit dedicated to hereditary amyloidosis between July 2009 and October 2013, we selected patients who fulfilled neurophysiological criteria for CTS, had been submitted to CTRS and whose TCL was available for pathology. Clinical registries were reviewed and amyloid detection in the ligaments was performed using Congo-red staining. We included 16 patients: three males (18.8%), mean age = 46.1 years old, all with V30M mutation. At the time of surgery, four patients were considered asymptomatic and 12 symptomatic carriers, five of them late-onset ATTRm (onset age >50 years old). In all but one patient, the CTS preceded the polyneuropathy. Amyloid detection in the TCL was positive in 14 patients (87.5%). In most patients, CTS preceded or was contemporary to the polyneuropathy and amyloid detection in TCL was positive. The detection of amyloid in TCL may add specificity to CTS as an early manifestation of the disease but more studies are needed.

  20. Acceleration of Amyloidosis by Inflammation in the Amyloid-Beta Marmoset Monkey Model of Alzheimer’s Disease

    Science.gov (United States)

    Philippens, Ingrid H.; Ormel, Paul R.; Baarends, Guus; Johansson, Maja; Remarque, Ed J.; Doverskog, Magnus

    2016-01-01

    Background: The immune system is increasingly mentioned as a potential target for Alzheimer’s disease (AD) treatment. Objective: In the present pilot study, the effect of (neuro)inflammation on amyloidopathy was investigated in the marmoset monkey, which has potential as an AD animal model due to its natural cerebral amyloidosis similar to humans. Methods: Six adult/aged marmosets (Callithrix jacchus) were intracranial injected with amyloid-beta (Aβ) fibrils at three cortical locations in the right hemisphere. Additionally, in half of the monkeys, lipopolysaccharide (LPS) was co-injected with the Aβ fibrils and injected in the other hemisphere without Aβ fibrils. The other three monkeys received phosphate buffered saline instead of LPS, as a control for the inflammatory state. The effect of inflammation on amyloidopathy was also investigated in an additional monkey that suffered from chronic inflammatory wasting syndrome. Mirror histology sections were analyzed to assess amyloidopathy and immune reaction, and peripheral blood for AD biomarker expression. Results: All LPS-injected monkeys showed an early AD immune blood cell expression profile on CD95 and CD45RA. Two out of three monkeys injected with Aβ and LPS and the additional monkey, suffering from chronic inflammation, developed plaques. None of the controls, injected with Aβ only, developed any plaques. Conclusion: This study shows the importance of immune modulation on the susceptibility for amyloidosis, a hallmark of AD, which offers new perspectives for disease modifying approaches in AD. PMID:27662314

  1. Acceleration of Amyloidosis by Inflammation in the Amyloid-Beta Marmoset Monkey Model of Alzheimer's Disease.

    Science.gov (United States)

    Philippens, Ingrid H; Ormel, Paul R; Baarends, Guus; Johansson, Maja; Remarque, Ed J; Doverskog, Magnus

    2017-01-01

    The immune system is increasingly mentioned as a potential target for Alzheimer's disease (AD) treatment. In the present pilot study, the effect of (neuro)inflammation on amyloidopathy was investigated in the marmoset monkey, which has potential as an AD animal model due to its natural cerebral amyloidosis similar to humans. Six adult/aged marmosets (Callithrix jacchus) were intracranial injected with amyloid-beta (Aβ) fibrils at three cortical locations in the right hemisphere. Additionally, in half of the monkeys, lipopolysaccharide (LPS) was co-injected with the Aβ fibrils and injected in the other hemisphere without Aβ fibrils. The other three monkeys received phosphate buffered saline instead of LPS, as a control for the inflammatory state. The effect of inflammation on amyloidopathy was also investigated in an additional monkey that suffered from chronic inflammatory wasting syndrome. Mirror histology sections were analyzed to assess amyloidopathy and immune reaction, and peripheral blood for AD biomarker expression. All LPS-injected monkeys showed an early AD immune blood cell expression profile on CD95 and CD45RA. Two out of three monkeys injected with Aβ and LPS and the additional monkey, suffering from chronic inflammation, developed plaques. None of the controls, injected with Aβ only, developed any plaques. This study shows the importance of immune modulation on the susceptibility for amyloidosis, a hallmark of AD, which offers new perspectives for disease modifying approaches in AD.

  2. Amiloidose-mieloma múltiplo apresentando-se como pseudomiopatia Multiple myeloma-amyloidosis presenting as pseudomyopathy

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    Mário Sérgio F Santos

    2011-12-01

    Full Text Available Amiloidose é uma designação genérica para se referir à deposição de fibrilas amiloides nos tecidos corporais. Ela apresenta-se, frequentemente, após os 40 anos de idade, com envolvimento localizado ou sistêmico, associada a mieloma múltiplo ou a doenças inflamatórias crônicas, podendo mimetizar diferentes síndromes reumatológicas. Relata-se o caso de uma paciente com amiloidose associada a mieloma múltiplo cuja apresentação inicial simulava miopatia.Amyloidosis is a generic term that refers to the deposition of amyloid fibrils in bodily tissues. Its onset is usually after 40 years of age, with localized or systemic involvement associated with multiple myeloma or chronic inflammatory diseases, and can mimic various rheumatic syndromes. We report the case of a patient with amyloidosis associated with multiple myeloma, showing clinical characteristics of pseudomyopathy

  3. The specific case: cardiac amyloidosis as differential diagnosis in case of restricted cardiac pump function; Der besondere Fall. Amyloidose des Herzens als Differenzialdiagnose bei eingeschraenkter kardialer Pumpfunktion

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    D' Errico, L. [Universitaetsspital Basel (Switzerland). Klinik fuer Radiologie und Nuklearmedizin; Zellweger, M.; Niemann, T.

    2014-03-15

    The NMR imaging data in combination with clinical characterization and echocardiography are consistent with the diagnosis of a cardiac amyloidosis. The article describes disease pattern and diagnosis based on contrast agent accumulation and diastolic functional disturbances. CT was performed to exclude pulmonary embolism.

  4. Development of Renal Failure without Proteinuria in a Patient with Monoclonal Gammopathy of Undetermined Significance: An Unusual Presentation of AL Kappa Amyloidosis

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    Yijuan Sun

    2012-01-01

    Full Text Available AL amyloidosis complicating monoclonal gammopathy of undetermined significance (MGUS has usually a predominant glomerular deposition of lambda light chain. Heavy proteinuria is one of its cardinal manifestations. A 78-year-old man with a 9-year history of IgG kappa light-chain-MGUS and normal urine protein excretion developed severe renal failure. Serum levels of kappa light chain and serum IgG had been stable while proteinuria was absent throughout the nine-year period. For the first eight years, he had stable stage III chronic kidney disease attributed to bladder outlet obstruction secondary to prostatic malignancy. In the last year, he developed progressive serum creatinine elevation, without any increase in the serum or urine levels of paraproteins or any sign of malignancy. Renal ultrasound and furosemide renogram showed no evidence of urinary obstruction. Renal biopsy revealed AL amyloidosis, with reactivity exclusive for kappa light chains, affecting predominantly the vessels and the interstitium. Glomerular involvement was minimal. Melphalan and prednisone were initiated. However, renal function continues deteriorating. Deposition of AL kappa amyloidosis developing during the course of MGUS predominantly in the wall of the renal vessels and the renal interstitium, while the involvement of the glomeruli is minimal, leads to progressive renal failure and absence of proteinuria. Renal biopsy is required to detect both the presence and the sites of deposition of renal AL kappa light chain amyloidosis.

  5. Longitudinal left ventricular function for prediction of survival in systemic light-chain amyloidosis: incremental value compared with clinical and biochemical markers.

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    Buss, Sebastian J; Emami, Mostafa; Mereles, Derliz; Korosoglou, Grigorios; Kristen, Arnt V; Voss, Andreas; Schellberg, Dieter; Zugck, Christian; Galuschky, Christian; Giannitsis, Evangelos; Hegenbart, Ute; Ho, Anthony D; Katus, Hugo A; Schonland, Stefan O; Hardt, Stefan E

    2012-09-18

    The aim of the study was to determine whether longitudinal left ventricular (LV) function provides prognostic information in a large cohort of patients with systemic light-chain (AL) amyloidosis. AL amyloidosis is associated with a high incidence of cardiovascular events. Reduced myocardial longitudinal function is one of the hallmarks of myocardial involvement in this rare disease. Two hundred six consecutive patients with biopsy-proven AL amyloidosis were investigated in this prospective observational study. Echocardiographic imaging parameters, mean tissue Doppler-derived longitudinal strain (LS), and two-dimensional global longitudinal strain (2D-GLS) of the LV, cardiac serological biomarkers, and comprehensive clinical disease characteristics were assessed. The primary endpoint was all-cause mortality or heart transplantation. After a median follow-up of 1207 days, LS and 2D-GLS were significant predictors of survival in AL amyloidosis. The cutoff values discriminating survivors from nonsurvivors were -10.65% for LS and -11.78% for 2D-GLS. In a multivariable echocardiographic Cox model, only diastolic dysfunction and 2D-GLS remained as independent predictors of survival. In comprehensive clinical models, 2D-GLS (p chains (p value compared with that derived from pathologic free light chains or cTnT in patients evaluated before firstline chemotherapy (n = 113; p < 0.0001), and remained the only independent predictor besides the Karnofsky index in subjects with preserved LV ejection fraction (≥50%; n = 127; p < 0.01). LS and 2D-GLS both offered significant incremental information (p < 0.001) for the assessment of outcome compared with clinical variables (age, Karnofsky index, and New York Heart Association functional class) and serological biomarkers. In the largest serial investigation reported so far, reduced LV longitudinal function served as an independent predictor of survival in AL amyloidosis and offered incremental information beyond standard clinical

  6. The value of the levels of acute phase reactants for the prediction of familial Mediterranean fever associated amyloidosis: a case control study.

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    Yalçinkaya, F; Cakar, N; Acar, B; Tutar, E; Güriz, H; Elhan, A H; Oztürk, S; Kansu, A; Ince, E; Atalay, S; Girgin, N; Doğru, U; Aysev, D; Ekim, M

    2007-04-01

    In order to determine the role of levels of acute phase proteins (APPs) for the development of amyloidosis in familial Mediterranean fever (FMF) patients, the levels of serum amyloid A (SAA), C reactive protein (CRP), fibrinogen and erythrocyte sedimentation rate were measured in paired sera of 36 FMF patients during and in between acute attacks, 39 of their healthy parents (obligate heterozgotes), and 15 patients with FMF associated amyloidosis. To compare the levels of APPs, 39 patients with chronic infections or inflammatory diseases who may develop secondary amyloidosis, 20 patients with acute infections who are known to have elevated acute phase response but will never develop amyloidosis and 19 healthy controls were included. The median levels of all APPs are increased in the patients with FMF during attacks and a significant decrease was observed after the attack was over. The level of SAA was above reference range in all FMF patients during the attack free period and the level of at least one other APP was also above normal in 64% of the patients. Both CRP and SAA levels were found to be higher in obligate heterozygotes compared to controls. The levels of SAA in patients with FMF during the attack-free period, obligate heterozygotes and patients with FMF-amyloidosis were found to be similar. The levels in each group were found to be higher than SAA levels found in healthy controls yet lower than the levels measured in the patients with acute infections and patients with chronic inflammation or chronic infections. In conclusion, our results show that SAA level reflects subclinical inflammation with high sensitivity but its value for the prediction of amyloid formation process seems to be low.

  7. Cardiac Dysautonomia Predicts Long-Term Survival in Hereditary Transthyretin Amyloidosis After Liver Transplantation.

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    Algalarrondo, Vincent; Antonini, Teresa; Théaudin, Marie; Chemla, Denis; Benmalek, Anouar; Lacroix, Catherine; Castaing, Denis; Cauquil, Cécile; Dinanian, Sylvie; Eliahou, Ludivine; Samuel, Didier; Adams, David; Le Guludec, Dominique; Slama, Michel S; Rouzet, François

    2016-12-01

    This study sought to compare techniques evaluating cardiac dysautonomia and predicting the risk of death of patients with hereditary transthyretin amyloidosis (mATTR) after liver transplantation (LT). mATTR is a multisystemic disease involving mainly the heart and the peripheral nervous system. LT is the reference treatment, and pre-operative detection of high-risk patients is critical. Cardiovascular dysautonomia is commonly encountered in ATTR and may affect patient outcome, although it is not known yet which technique should be used in the field to evaluate it. In a series of 215 consecutive mATTR patients who underwent LT, cardiac dysautonomia was assessed by a dedicated clinical score, time-domain heart rate variability, 123 -meta-iodobenzylguanidine heart/mediastinum ( 123 -MIBG H/M) ratio on scintigraphy, and heart rate response to atropine (HRRA). Patient median age was 43 years, 62% were male and 69% carried the Val30Met mutation. Cardiac dysautonomia was documented by at least 1 technique for all patients but 6 (97%). In univariate analysis, clinical score, 123 -MIBG H/M ratio and HRRA were associated with mortality but not heart rate variability. The 123 -MIBG H/M ratio and HRRA had greater area under the curve (AUC) of receiver-operating characteristic curves than clinical score and heart rate variability (AUC: 0.787, 0.748, 0.656, and 0.523, respectively). Multivariate score models were then built using the following variables: New York Heart Association functional class, interventricular septum thickness, and either 123- MIBG H/M ratio (S MIBG ) or HRRA (S atropine ). AUC of S MIBG and S atropine were greater than AUC of univariate models, although nonsignificantly (AUC: 0.798 and 0.799, respectively). Predictive powers of S MIBG , S atropine , and a reference clinical model (AUC: 0.785) were similar. Evaluation of cardiac dysautonomia is a valuable addition for predicting survival of mATTR patients following LT. Among the different techniques that

  8. Intraventricular dyssynchrony in light chain amyloidosis: a new mechanism of systolic dysfunction assessed by 3-dimensional echocardiography

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    Truran Seth

    2008-08-01

    Full Text Available Abstract Background Light chain amyloidosis (AL is a rare but often fatal disease due to intractable heart failure. Amyloid deposition leads to diastolic dysfunction and often preserved ejection fraction. We hypothesize that AL is associated with regional systolic dyssynchrony. The aim is to compare left ventricular (LV regional synchrony in AL subjects versus healthy controls using 16-segment dyssynchrony index measured from 3-dimension-al (3D echocardiography. Methods Cardiac 3D echocardiography full volumes were acquired in 10 biopsy-proven AL subjects (60 ± 3 years, 5 females and 10 healthy controls (52 ± 1 years, 5 females. The LV was subdivided into 16 segments and the time from end-diastole to the minimal systolic volume for each of the 16 segments was expressed as a percent of the cycle length. The standard deviations of these times provided a 16-segment dyssynchrony index (16-SD%. 16-SD% was compared between healthy and AL subjects. Results Left ventricular ejection fraction was comparable (control vs. AL: 62.4 ± 0.6 vs. 58.6 ± 2.8%, p = NS. 16-SD% was significantly higher in AL versus healthy subjects (5.93 ± 4.4 vs. 1.67 ± 0.87%, p = 0.003. 16-SD% correlated with left ventricular mass index (R 0.45, p = 0.04 but not to left ventricular ejection fraction. Conclusion Light chain amyloidosis is associated with left ventricular regional systolic dyssynchrony. Regional dyssynchrony may be an unrecognized mechanism of heart failure in AL subjects.

  9. Significant association between renal function and amyloid-positive area in renal biopsy specimens in AL amyloidosis

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    Kuroda Takeshi

    2012-09-01

    Full Text Available Abstract Background The kidney is a major target organ for systemic amyloidosis that often affects the kidney including proteinura, and elevated serum creatinine (Cr. The correlation between amount of amyloid deposits and clinical parameters is not known. The aim of this study was to clarify correlation the amyloid area in all renal biopsy specimen and clinical parameters. Methods Fifty-eight patients with an established diagnosis of AL amyloidosis participated in the study. All patients showed amyloid deposits in renal biopsies. We retrospectively investigated the correlation between clinical data and amyloid occupied area in whole renal biopsy specimens. Results The area occupied by amyloid was less than 10% in 57 of the 58 patients, and was under 2% in 40. For statistical analyses, %amyloid-positive areas were transformed to common logarithmic values (Log10%amyloid. Cr showed significant correlation with Log10%amyloid and estimated glomerular filtration rate (eGFR showed the significant negative correlation. Patient age, cleatinine clearance (Ccr, blood urea nitorogen, and urinary protein was not significantly correlated with Log10%amyloid. The correlation with other clinical factors such as sex, and serum concentrations of total protein, albumin, immunoglobulins, compliments was evaluated. None of these factors significantly correlated with Log10%amyloid. According to sex- and age- adjusted multiple linear regression analysis, Log10%amyloid had significant positive association with Cr and significant negative association with eGFR. Conclusion There is significant association between amyloid-positive area in renal tissue and renal function, especially Cr and eGFR. The level of Cr and eGFR may be a marker of amount of amyloid in renal tissue.

  10. Amiloidose manifestando-se com pseudo-hipertrofia muscular Amyloidosis presenting as muscle pseudohypertrophy

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    Rodrigo Bortoli

    2007-12-01

    Full Text Available Amiloidose tipo AL é uma doença rara causada pela deposição extracelular de fragmentos de cadeias leves monoclonais em órgãos e tecidos. Pode apresentar-se com uma ampla variedade de sinais e sintomas, e o acometimento cutâneo-muscular, simulando pseudo-hipertrofia muscular, é um achado muito raro. São descritos dois casos que apresentaram tal manifestação. CASO 1 - Mulher, 61 anos, há quatro meses com história de mialgia e aumento da massa muscular nas cinturas pélvica, escapular e região cervical. Não havia alterações significativas ao exame físico, exceto aparente hipertrofia muscular difusa e discreta macroglossia. CASO 2 - Homem, 51 anos, há dois anos com cansaço e espessamento cutâneo progressivo do dorso, pescoço e braços. Em outros serviços levantou suspeitas diagnósticas de esclerodermia ou de escleredema de Buschke; desde fevereiro de 2007 passou a ser acompanhado nesse serviço e referia, havia cerca de um ano, disfagia para sólidos, disartria e dificuldade para movimentar a língua. Chamava atenção em seu exame o porte físico atlético com musculatura torácica proeminente, porém referia não fazer exercícios físicos. Em ambos os casos, a biópsia cutânea foi realizada com identificação do depósito amilóide por meio da coloração de vermelho congo.AL amyloidosis is a rare disease secondary to extracellular deposition of light chains fragments in organs and tissues. It can cause a wide variety of signs and symptoms, being the muscular pseudohypertrophy form a very rare finding. CASE 1 - a 61-year-old female had a history of myalgia and increase of muscular mass on pelvic and scapular girdle and cervical region. Besides the generalized muscular hypertrophy and discrete macroglossia, the rest of physical examination was normal. CASE 2 - a 51-year-old male complained of tiredness and progressive cutaneous thickening on his thorax, neck and arms for the last two years. Initially, he was misdiagnosed

  11. Reduced trans-mitral A-wave velocity predicts the presence of wild-type transthyretin amyloidosis in elderly patients with left ventricular hypertrophy.

    Science.gov (United States)

    Yamamura, Satoru; Izumiya, Yasuhiro; Ishida, Toshifumi; Onoue, Yoshiro; Kimura, Yuichi; Hanatani, Shinsuke; Araki, Satoshi; Fujisue, Koichiro; Sueta, Daisuke; Kanazawa, Hisanori; Takashio, Seiji; Usuku, Hiroki; Sugamura, Koichi; Sakamoto, Kenji; Yamamoto, Eiichiro; Yamamuro, Megumi; Yasuda, Hisayo; Kojima, Sunao; Kaikita, Koichi; Hokimoto, Seiji; Ogawa, Hisao; Tsujita, Kenichi

    2017-06-01

    Wild-type transthyretin amyloidosis (ATTRwt) is often overlooked in elderly patients with left ventricular hypertrophy (LVH). Impaired atrial function, in addition to ventricular diastolic dysfunction, is one of the hallmarks of cardiac amyloidosis. Here, we assessed the hypothesis that atrial function evaluated by A-velocity in pulse Doppler echocardiography is useful to differentiate ATTRwt in elderly patients with LVH. We analyzed 133 consecutive patients who underwent tissue biopsy to rule out infiltrative cardiomyopathy in our institute. We excluded patients younger than 50 years, without LVH (LV thickness was less than 12 mm), with other types of cardiac amyloidosis and patients with chronic atrial fibrillation, and analyzed remaining 51 patients (ATTRwt: 16, non-ATTRwt: 35). ATTRwt patients were significantly older and had advanced heart failure compared with non-ATTRwt group. In echocardiography, E/A, E/e', and relative wall thickness was significantly higher in ATTRwt group than non-ATTRwt group. A-velocity was significantly decreased in ATTRWT group compared with non-ATTRwt group (40.8 ± 20.8 vs. 78.7 ± 28.2 cm/s, p = 0.0001). Multivariate logistic analysis using eight forced inclusion models identified trans-mitral Doppler A-wave velocity was more significant factor of cardiac amyloidosis in ATTRwt. In receiver operating characteristic (ROC) analysis, the area under the curve (AUC) for A-wave velocity in discrimination between ATTRwt and non-ATTRwt were 0.86 (CI 0.76-0.96, p reduced A-velocity predicts the presence of ATTRwt in elderly patients with LVH in sinus rhythm.

  12. Prognostic and Added Value of Two-Dimensional Global Longitudinal Strain for Prediction of Survival in Patients with Light Chain Amyloidosis Undergoing Autologous Hematopoietic Cell Transplantation.

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    Pun, Shawn C; Landau, Heather J; Riedel, Elyn R; Jordan, Jonathan; Yu, Anthony F; Hassoun, Hani; Chen, Carol L; Steingart, Richard M; Liu, Jennifer E

    2018-01-01

    Autologous hematopoietic cell transplantation (HCT) is a first-line therapy for prolonging survival in patients with light-chain (AL) amyloidosis. Cardiac involvement is the most important determinant of survival. However, patients with advanced cardiac involvement have often been excluded from HCT because of high risk for transplantation-related mortality and poor overall survival. Whether baseline left ventricular global longitudinal strain (GLS) can provide additional risk stratification and predict survival after HCT in this high-risk population remains unclear. The aim of this study was to evaluate the prognostic implication of baseline GLS and the added value of GLS beyond circulating cardiac biomarkers for risk stratification in patients with AL amyloidosis undergoing HCT. Eighty-two patients with newly diagnosed AL amyloidosis who underwent upfront HCT between January 2007 and April 2014 were included in the study. Clinical, echocardiographic, and serum cardiac biomarker data were collected at baseline and 12 months following HCT. GLS measurements were performed using a vendor-independent offline system. The median follow-up time for survivors was 58 months. Sixty-four percent of patients were in biomarker-based Mayo stage II or III. GLS, brain natriuretic peptide, troponin, and mitral E/A ratio were identified as the strongest predictors of survival (P value that best discriminated survivors from nonsurvivors, and the application of this cutoff value provided further mortality risk stratification within each Mayo stage. GLS is a strong predictor of survival in patients with AL amyloidosis undergoing HCT, potentially providing incremental value over serum cardiac biomarkers for risk stratification. GLS should be considered as a standard parameter along with serum cardiac biomarkers when evaluating eligibility for HCT or other investigational therapies. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

  13. Combination of lenalidomide and low-dose dexamethasone therapy promotes the anticoagulant activity of warfarin in patients with immunoglobulin light-chain amyloidosis.

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    Kitazawa, Fumiaki; Fuchida, Shin-Ichi; Ise, Fumitaka; Kado, Yoko; Ueda, Kumi; Kokufu, Takatoshi; Okano, Akira; Hatsuse, Mayumi; Murakami, Satoshi; Nakayama, Yuko; Takara, Kohji; Shimazaki, Chihiro

    2017-07-01

    The present study aimed to evaluate the drug interactions between warfarin and combination chemotherapy with lenalidomide and low-dose dexamethasone in immunoglobulin light-chain (AL) amyloidosis patients with unstable international normalized ratios (INR). The changes to INR values over time in 3 AL amyloidosis patients treated with warfarin and a combination of lenalidomide and low-dose dexamethasone between March 2011 and February 2015 were analyzed retrospectively. The mean INR value was 1.52 prior to the combination chemotherapy, and the value increased 1.7-fold during treatment. The median time to reach maximum values was 17 days. Horn's drug Interaction Probability Scale indicated a possible interaction between lenalidomide and warfarin. These patients exhibited no marked alterations in hepatic function or serum albumin concentrations prior to and following combination chemotherapy and no additional administration of CYP2C9 inhibitors or vitamin K supplements was conducted. In addition, no patient experienced chemotherapy-induced nausea or appetite loss. These findings suggest that the total clearance or protein binding of warfarin remained unchanged. Therefore, the combination of warfarin and lenalidomide may cause a pharmacodynamic interaction, more likely by inhibiting the production of interleukin-6. In conclusion, clinically important interactions between warfarin and lenalidomide and low-dose dexamethasone therapy were observed in AL amyloidosis patients, where INR values signi ficantly increased. Therefore, close and regular monitoring of patients during the course of treatment is important, and the dose of warfarin should be reduced if required.

  14. Mieloma múltiple y arteritis de células gigantes sin amiloidosis Simultaneous multiple myeloma and giant cell arteritis without systemic amyloidosis

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    Bárbara C. Finn

    2006-12-01

    Full Text Available La amiloidosis sistémica primaria y el mieloma múltiple con amiloidosis primaria se han presentado con características clínicas e histopatológicas que simulan una arteritis de células gigantes. Hasta el momento la asociación se basaba en el rol antigénico del depósito de amiloide sobre las arterias, desencadenando la respuesta inmune que finaliza con una arteritis. Presentamos el primer caso en la literatura de un paciente con mieloma múltiple y arteritis de células gigantes sin amiloidosis sistémica, sugiriendo una relación patogénica entre estas dos entidades. En el caso de nuestro paciente se descartó la presencia de amiloide en la pared arterial, por lo que proponemos que el estímulo para el desarrollo de la arteritis podría ser una excesiva producción de interleuquina 6 fabricada por las células mielomatosas.Primary systemic amyloidosis with clinical and histopathologic features of giant cell arteritis has already been described. The association of multiple myeloma (with primary amyloidosis and giant cell arteritis is also known. We present the first case in the literature of a patient with multiple myeloma and giant cell arteritis without systemic amyloidosis, suggesting a pathogenic relationship between the two diseases.

  15. Dialysis-related amyloidosis of the hip joints in long-term hemodialysis patients. MRI findings of hip joints in twelve female hemodialysis patients

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    Suzuki, Hitoe; Shibuya, Asuka; Ando, Minoru; Akiba, Takashi; Nitta, Kosaku

    2007-01-01

    We report a female with amyloid arthropathy of the hip joints. She was a 67-year-old woman who had been treated by hemodialysis for 22 years. She had demonstrated a 5-month history of continuous low-grade fever and pain in her left hip and she was finally unable to walk by herself. Findings on X-ray films and MRI of the hip joints suggested avascular necrosis in both femur heads. To palliate symptoms, bipolar surgery on the left hip joint was performed. Pathological examination of bone tissue specimen demonstrated that there was some , β 2 -microglobulin (β 2 -MG)-related amyloid accumulation in the femur head. Based on this clinical experience, we performed MRI screening for amyloid lesions of the hip joints in another 11 asymptomatic female patients undergoing hemodialysis for 20 years or more. Cystic lesions of the hip joints were observed in 8 patients, amyloid arthropathy in 2 patients, and fluid trapped in the joint in 1 patient. Patients with amyloidosis had significantly lower serum β 2 -MG levels than patients without amyloidosis (28.6 mg/L versus 41.4 mg/L; p=0.0339). Our findings show that dialysis-related amyloidosis of the hip joints is one of the potential and significant problems in female patients on long-term hemodialysis therapy. It may be important to screen for this pathological condition in long-term hemodialysis patients. (author)

  16. Translocations of 14q32 and deletions of 13q14 are common chromosomal abnormalities in systemic amyloidosis.

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    Harrison, Christine J; Mazzullo, Helen; Ross, Fiona M; Cheung, Kan L; Gerrard, Gareth; Harewood, Louise; Mehta, Atul; Lachmann, Helen J; Hawkins, Philip N; Orchard, Kim H

    2002-05-01

    Systemic monoclonal immunoglobulin light chain amyloidosis (AL) is associated with clonal plasma cell dyscrasias that are often subtle and non-proliferating. AL shares numerical chromosomal changes with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). Illegitimate translocations involving the immunoglobulin heavy chain gene (IGH) at 14q32 and deletions of the long arm of chromosome 13, [del(13q)], commonly occur in MM, MGUS and plasma cell leukaemia. In AL IGH rearrangements have been identified but, to date, there are no reports of del(13q). In this study of 32 patients with AL, 24 with systemic and eight with localized disease, translocations involving IGH and del(13q) were found using dual-colour interphase fluorescence in situ hybridization (FISH). IGH translocations were observed in 11 patients (37% overall and in 46% with systemic disease), of which nine had the IGH/CCND1 fusion from t(11;14)(q13;q32). Two showed IGH translocations other than the t(11;14) or t(4;14)(p16;q32). In one of these patients a breakpoint within the constant region of IGH between Calpha1 and Calpha2 was indicated. In the second a deletion covering Calpha1 and Calpha2 accompanied the translocation. Ten patients (27% overall and 33% of those with systemic disease) showed del(13q). The gain or loss of IGH and CCND1 signals provided evidence of numerical chromosomal changes in three patients.

  17. Myocardial deformation imaging and rare cardiomyopathies with hypertrophic phenotype: a review focused on Fabry disease, Friedreich ataxia and amyloidosis

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    Bahaa Fadel

    2013-06-01

    Full Text Available Tissue Doppler and deformation imaging, including Doppler-derived strain and speckle tracking, have significantly improved our understanding of cardiac mechanics in both physiological and pathological states. The various modes of left ventricular deformation (longitudinal, circumferential, radial and twist leading to systolic contraction can nowadays be quantified. One of the best applications of deformation imaging is in the area of hypertrophic cardiomyopathies. Deformation imaging allows the evaluation of global and regional myocardial performance and the noninvasive characterization of abnormal intramural myocardial mechanics. In this review, we discuss the role of myocardial deformation imaging derived by echocardiography in the assessment of rare hypertrophic phenotype including Fabry disease, Friedreich ataxia and amyloidosis. Deformation imaging allows for early identification of myocardial dysfunction in many hypertrophic disorders, at an earlier stage than that provided by standard imaging or echocardiographic techniques. This allows for the implementation of appropriate therapy before significant disease progression has occurred and prior to the development of advanced myocardial fibrosis. Thus therapy would likely be more effective and may potentially lead to improvement in patient outcome. Additionally strain imaging allows to better monitoring the efficacy of therapy by assessing the progression and regression of myocardial involvement. Finally, findings on strain imaging carry important prognostic information in many hypertrophic disorders.

  18. Amyloidosis, synucleinopathy, and prion encephalopathy in a neuropathic lysosomal storage disease: the CNS-biomarker potential of peripheral blood.

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    Bartholomew J Naughton

    Full Text Available Mucopolysaccharidosis (MPS IIIB is a devastating neuropathic lysosomal storage disease with complex pathology. This study identifies molecular signatures in peripheral blood that may be relevant to MPS IIIB pathogenesis using a mouse model. Genome-wide gene expression microarrays on pooled RNAs showed dysregulation of 2,802 transcripts in blood from MPS IIIB mice, reflecting pathological complexity of MPS IIIB, encompassing virtually all previously reported and as yet unexplored disease aspects. Importantly, many of the dysregulated genes are reported to be tissue-specific. Further analyses of multiple genes linked to major pathways of neurodegeneration demonstrated a strong brain-blood correlation in amyloidosis and synucleinopathy in MPS IIIB. We also detected prion protein (Prnp deposition in the CNS and Prnp dysregulation in the blood in MPS IIIB mice, suggesting the involvement of Prnp aggregation in neuropathology. Systemic delivery of trans-BBB-neurotropic rAAV9-hNAGLU vector mediated not only efficient restoration of functional α-N-acetylglucosaminidase and clearance of lysosomal storage pathology in the central nervous system (CNS and periphery, but also the correction of impaired neurodegenerative molecular pathways in the brain and blood. Our data suggest that molecular changes in blood may reflect pathological status in the CNS and provide a useful tool for identifying potential CNS-specific biomarkers for MPS IIIB and possibly other neurological diseases.

  19. Depletion of spleen macrophages delays AA amyloid development: a study performed in the rapid mouse model of AA amyloidosis.

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    Katarzyna Lundmark

    Full Text Available AA amyloidosis is a systemic disease that develops secondary to chronic inflammatory diseases Macrophages are often found in the vicinity of amyloid deposits and considered to play a role in both formation and degradation of amyloid fibrils. In spleen reside at least three types of macrophages, red pulp macrophages (RPM, marginal zone macrophages (MZM, metallophilic marginal zone macrophages (MMZM. MMZM and MZM are located in the marginal zone and express a unique collection of scavenger receptors that are involved in the uptake of blood-born particles. The murine AA amyloid model that resembles the human form of the disease has been used to study amyloid effects on different macrophage populations. Amyloid was induced by intravenous injection of amyloid enhancing factor and subcutaneous injections of silver nitrate and macrophages were identified with specific antibodies. We show that MZMs are highly sensitive to amyloid and decrease in number progressively with increasing amyloid load. Total area of MMZMs is unaffected by amyloid but cells are activated and migrate into the white pulp. In a group of mice spleen macrophages were depleted by an intravenous injection of clodronate filled liposomes. Subsequent injections of AEF and silver nitrate showed a sustained amyloid development. RPMs that constitute the majority of macrophages in spleen, appear insensitive to amyloid and do not participate in amyloid formation.

  20. Serum immunoglobulin free light-chain measurement in primary amyloidosis: prognostic value and correlations with clinical features.

    Science.gov (United States)

    Kumar, Shaji; Dispenzieri, Angela; Katzmann, Jerry A; Larson, Dirk R; Colby, Colin L; Lacy, Martha Q; Hayman, Suzanne R; Buadi, Francis K; Leung, Nelson; Zeldenrust, Steve R; Ramirez-Alvarado, Marina; Clark, Raynell J; Kyle, Robert A; Rajkumar, S Vincent; Gertz, Morie A

    2010-12-09

    Immunoglobulin free light chains (FLCs) are the precursors of amyloid fibrils in primary amyloidosis (AL). We studied the relationship between FLC levels and clinical features in 730 patients with newly diagnosed AL. The plasma cell clone was λ in 72% patients, and κ in 28% patients. κ-AL had more GI tract and liver involvement, where as renal involvement was more with λ-AL. While the overall survival (OS) was similar for κ and λ-AL, the median OS for those without an identifiable serum heavy chain was significantly shorter (12.6 vs 29.9 months; P = .02). The OS was shorter among those with a higher dFLC (involved FLC-uninvolved FLC; κ > 29.4 mg/dL or λ > 18.2 mg/dL using median for cutoff); 10.9 vs 37.1 months; P analysis, dFLC was independent of other prognostic factors. The type of light chain impacts the spectrum of organ involvement and the FLC burden correlates with survival in AL.

  1. The E3 ubiquitin ligase Idol controls brain LDL receptor expression, ApoE clearance, and Aβ amyloidosis.

    Science.gov (United States)

    Choi, Jinkuk; Gao, Jie; Kim, Jaekwang; Hong, Cynthia; Kim, Jungsu; Tontonoz, Peter

    2015-11-18

    Apolipoprotein E (ApoE) is an important modifier of Alzheimer's disease (AD) pathogenesis, and its abundance has been linked to the clearance of β-amyloid (Aβ) in the brain. The pathways that control the clearance of ApoE in the brain are incompletely understood. We report that Idol, an E3 ubiquitin ligase that targets the low-density lipoprotein receptor (LDLR) for degradation, is a critical determinant of brain ApoE metabolism and Aβ plaque biogenesis. Previous work has shown that Idol contributes minimally to the regulation of hepatic LDLR expression in mice. By contrast, we demonstrate that Idol is a primary physiological regulator of LDLR protein in the brain, controlling the clearance of both ApoE-containing high-density lipoprotein (HDL) particles and Aβ. We studied the consequences of loss of Idol expression in a transgenic mouse model of Aβ amyloidosis. Idol deficiency increased brain LDLR, decreased ApoE, decreased soluble and insoluble Aβ, reduced amyloid plaque burden, and ameliorated neuroinflammation. These findings identify Idol as a gatekeeper of LDLR-dependent ApoE and Aβ clearance in the brain and a potential enzyme target for therapeutic intervention in AD. Copyright © 2015, American Association for the Advancement of Science.

  2. Time-resolved studies define the nature of toxic IAPP intermediates, providing insight for anti-amyloidosis therapeutics

    Science.gov (United States)

    Abedini, Andisheh; Plesner, Annette; Cao, Ping; Ridgway, Zachary; Zhang, Jinghua; Tu, Ling-Hsien; Middleton, Chris T; Chao, Brian; Sartori, Daniel J; Meng, Fanling; Wang, Hui; Wong, Amy G; Zanni, Martin T; Verchere, C Bruce; Raleigh, Daniel P; Schmidt, Ann Marie

    2016-01-01

    Islet amyloidosis by IAPP contributes to pancreatic β-cell death in diabetes, but the nature of toxic IAPP species remains elusive. Using concurrent time-resolved biophysical and biological measurements, we define the toxic species produced during IAPP amyloid formation and link their properties to induction of rat INS-1 β-cell and murine islet toxicity. These globally flexible, low order oligomers upregulate pro-inflammatory markers and induce reactive oxygen species. They do not bind 1-anilnonaphthalene-8-sulphonic acid and lack extensive β-sheet structure. Aromatic interactions modulate, but are not required for toxicity. Not all IAPP oligomers are toxic; toxicity depends on their partially structured conformational states. Some anti-amyloid agents paradoxically prolong cytotoxicity by prolonging the lifetime of the toxic species. The data highlight the distinguishing properties of toxic IAPP oligomers and the common features that they share with toxic species reported for other amyloidogenic polypeptides, providing information for rational drug design to treat IAPP induced β-cell death. DOI: http://dx.doi.org/10.7554/eLife.12977.001 PMID:27213520

  3. Detection of amyloid in abdominal fat pad aspirates in early amyloidosis: Role of electron microscopy and Congo red stained cell block sections

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    Sumana Devata

    2011-01-01

    Full Text Available Background: Fine-needle aspiration biopsy (FNA of the abdominal fat pad is a minimally invasive procedure to demonstrate tissue deposits of amyloid. However, protocols to evaluate amyloid in fat pad aspirates are not standardized, especially for detecting scant amyloid in early disease. Materials and Methods: We studied abdominal fat pad aspirates from 33 randomly selected patients in whom subsequent tissue biopsy, autopsy, and/or medical history for confirmation of amyloidosis (AL were also available. All these cases were suspected to have early AL, but had negative results on abdominal fat pad aspirates evaluated by polarizing microscopy of Congo Red stained sections (CRPM. The results with CRPM between four reviewers were compared in 12 cases for studying inter observer reproducibility. 24 cases were also evaluated by ultrastructural study with electron microscopy (EM. Results: Nine of thirty-three (27% cases reported negative by polarizing microscopy had amyloidosis. Reanalysis of 12 mixed positive-negative cases, showed considerable inter-observer variability with frequent lack of agreement between four observers by CRPM alone (Cohen′s Kappa index of 0.1, 95% CI -0.1 to 0.36. EM showed amyloid in the walls of small blood vessels in fibroadipose tissue in four out of nine cases (44% with amyloidosis. Conclusion: In addition to poor inter-observer reproducibility, CRPM alone in cases with scant amyloid led to frequent false negative results (9 out of 9, 100%. For improved detection of AL, routine ultrastructural evaluation with EM of fat pad aspirates by evaluating at least 15 small blood vessels in the aspirated fibroadipose tissue is recommended. Given the high false negative rate for CRPM alone in early disease, routine reflex evaluation with EM is highly recommended to avert the invasive option of biopsying various organs in cases with high clinical suspicion for AL.

  4. Early Impairment of Cardiac Function and Asynchronization of Systemic Amyloidosis with Preserved Ejection Fraction Using Two-Dimensional Speckle Tracking Echocardiography.

    Science.gov (United States)

    Huang, He; Jing, Xian-chao; Hu, Zhang-xue; Chen, Xi; Liu, Xiao-qin

    2015-12-01

    To observe the ventricular global and regional function of the patients with systemic amyloidosis using two-dimensional speckle tracking echocardiography. The study enrolled 31 consecutive biopsy-proved patients with systemic amyloidosis who underwent echocardiographic examination and EF ≥ 55% and 37 age- and gender-matched healthy controls. We compared systolic strain and strain rate, diastolic strain rate, time to peak strain, peak delay time in longitudinal, radial, circumferential directions in 16 left ventricular segments. The global peak systolic longitudinal and radial strain of left ventricle, peak systolic longitudinal strain and strain rate, diastolic strain rate of right ventricular free wall were also compared. (1) Global peak systolic longitudinal strain (GPSLS), peak systolic longitudinal strain (PSLS) and strain rate (PSLSR), peak early diastolic longitudinal strain rate (PELSR) in 16 segments were decreased in case (P < 0.05). (2) Peak systolic radial strain and strain rate of inferoseptum and inferolateral at the level of papillary muscle were lower (P < 0.05), and peak early diastolic radial strain rate (PERSR) was reduced (P < 0.05). (3) Peak early diastolic circumferential strain rate was lower (P < 0.05). (4) Time to peak systolic longitudinal, radial, circumferential strain was longer, and peak delay time at the same level retarded (P < 0.05). (5) Into right ventricular wall, PSLS and PSLSR at mid-segment, and PSLSR, PELSR, peak atrial systolic longitudinal strain rate (PALSR) at basal were reduced (P < 0.05). (6) Inverse correlation between interventricular septum (IVS) thickness and GPSLS and GPSRS was found (P < 0.05). Systolic and diastolic dysfunction existed in systemic amyloidosis with preserved EF. Mechanical contraction disorder may be one reason for systolic dysfunction. GPLSR and GPRSR were negatively related to IVS thickness. © 2015, Wiley Periodicals, Inc.

  5. Prognosis of Light Chain Amyloidosis With Preserved LVEF: Added Value of 2D Speckle-Tracking Echocardiography to the Current Prognostic Staging System.

    Science.gov (United States)

    Barros-Gomes, Sergio; Williams, Brittney; Nhola, Lara F; Grogan, Martha; Maalouf, Joseph F; Dispenzieri, Angela; Pellikka, Patricia A; Villarraga, Hector R

    2017-04-01

    This study evaluated whether 2-dimensional speckle-tracking echocardiography (2D-STE) has incremental value for prognosis over traditional clinical, echocardiographic, and serological markers-with main focus on the current prognostic staging system-in light-chain (AL) amyloidosis patients with preserved left ventricular ejection fraction. Cardiac amyloidosis (CA) is the major determinant of outcome in AL amyloidosis. The current prognostic staging system is based primarily on serum levels of cardiac troponin T (cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and free light chain differential (FLC-diff). Consecutive patients with biopsy-proven AL amyloidosis and left ventricular ejection fraction ≥55% were divided into group 1 with CA (n = 63) and group 2 without CA (n = 87). Global longitudinal strain (GLS) by 2D-STE was performed with Vivid E9 (GE Healthcare Co., Milwaukee, Wisconsin) and syngo Velocity Vector Imaging (VVI) software (Siemens Medical Solutions USA, Inc., Malvern, Pennsylvania) (GLS GE and GLS VVI , respectively). Thirty-two deaths (51%) occurred in group 1 and 13 (15%) in group 2 (p ≤ 0.001). Group 1 had thicker walls, lower early diastolic tissue Doppler velocity at septal mitral annulus, and greater left ventricular mass, left atrial volume, glomerular filtration rate, FLC-diff, cTnT, and NT-proBNP (p value over cTnT, NT-proBNP, and FLC-diff. For survival analysis limited to group 2 (non-CA), GLS GE and GLS VVI both predicted all-cause mortality (GLS GE HR: 1.23; 95% CI: 1.03 to 1.47 [p = 0.02]; GLS VVI HR: 1.22; 95% CI: 1.01 to 1.49 [p = 0.04], respectively). 2D-STE predicted outcome and provided incremental prognostic information over the current prognostic staging system, especially in the group without CA. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  6. Differentiation of light-chain cardiac amyloidosis from hypertrophic cardiomyopathy using myocardial mechanical parameters by velocity vector imaging echocardiography.

    Science.gov (United States)

    Zhang, Lu; Zhou, Xiao; Wang, Jing; Mu, Yang; Liu, Bohan; Lv, Wenqing; Wang, Ye; Liu, Hongwei; Liu, Hongbin; Zhi, Guang

    2017-04-01

    We aimed to evaluate the diagnostic efficacy of layered velocity vector imaging (VVI)-derived left ventricular (LV) mechanical parameters in the differential diagnosis of primary light-chain cardiac amyloidosis (AL-CA) and hypertrophic cardiomyopathy (HCM). We recruited 35 subjects with histologically-diagnosed AL-CA, 35 subjects with HCM, and 30 age-matched healthy controls. We used conventional echocardiography and electrocardiogram to evaluate general heart function and electrophysiology properties. Furthermore, we applied two-dimensional VVI echocardiography to assess the layered mechanical parameters during systole, including endocardial and epicardial longitudinal strain (ENDO and EPI LSsys), circumferential strain (CSsys), radial strain (RSsys), rotation (ROT) and twist (TWI), in different LV walls and levels. Two groups of patients had similarly elevated LV wall thickness and mild diastolic dysfunction, but normal ejection fraction. ENDO LSsys of three circular LV levels and six LV walls was markedly decreased in AL-CA patients, with the most prominent reduction in the basal level. The reduction of ENDO and EPI LSsys in HCM subjects was less profound, and was restricted to certain LV wall and levels. AL-CA patients had significantly reduced RSsys in the LV basal level compared with control or HCM patients. Two groups of patients exhibited similar reduction in layered regional CSsys, ROT and TWI. ROC analysis revealed that the sensitivity and specificity of basal ENDO LSsys for predicting AL-CA was 86 and 89%. Assessment of layered LSsys of LV walls and levels by VVI appeared to provide a more sensitive and specific diagnostic index for the differential diagnosis of AL-CA from HCM than conventional echocardiography. Future studies are warranted to evaluate its diagnostic efficacy for AL-CA diagnosis in the large population.

  7. Discrete Pools of Oligomeric Amyloid-β Track with Spatial Learning Deficits in a Mouse Model of Alzheimer Amyloidosis.

    Science.gov (United States)

    Chiang, Angie C A; Fowler, Stephanie W; Reddy, Rohit; Pletnikova, Olga; Troncoso, Juan C; Sherman, Mathew A; Lesne, Sylvain E; Jankowsky, Joanna L

    2018-03-01

    Despite increasing appreciation that oligomeric amyloid-β (Aβ) may contribute to cognitive decline of Alzheimer disease, defining the most critical forms has been thwarted by the changeable nature of these aggregates and the varying methods used for detection. Herein, using a broad approach, we quantified Aβ oligomers during the evolution of cognitive deficits in an aggressive model of Aβ amyloidosis. Amyloid precursor protein/tetracycline transactivator mice underwent behavioral testing at 3, 6, 9, and 12 months of age to evaluate spatial learning and memory, followed by histologic assessment of amyloid burden and biochemical characterization of oligomeric Aβ species. Transgenic mice displayed progressive impairments in acquisition and immediate recall of the trained platform location. Biochemical analysis of cortical extracts from behaviorally tested mice revealed distinct age-dependent patterns of accumulation in multiple oligomeric species. Dot blot analysis demonstrated that nonfibrillar Aβ oligomers were highly soluble and extracted into a fraction enriched for extracellular proteins, whereas prefibrillar species required high-detergent conditions to retrieve, consistent with membrane localization. Low-detergent extracts tested by 82E1 enzyme-linked immunosorbent assay confirmed the presence of bona fide Aβ oligomers, whereas immunoprecipitation-Western blotting using high-detergent extracts revealed a variety of SDS-stable low-n species. These findings show that different Aβ oligomers vary in solubility, consistent with distinct localization, and identify nonfibrillar Aβ oligomer-positive aggregates as tracking most closely with cognitive decline in this model. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  8. Characterization of the response of primary cells relevant to dialysis-related amyloidosis to β2-microglobulin monomer and fibrils.

    Directory of Open Access Journals (Sweden)

    Morwenna Y Porter

    Full Text Available The formation of insoluble amyloid fibrils is associated with an array of devastating human diseases. Dialysis-related amyloidosis (DRA is a severe complication of hemodialysis that results in the progressive destruction of the bones and joints. Elevated concentrations of β(2-microglobulin (β(2m in the serum of subjects on hemodialysis promote the formation of amyloid fibrils in the osteoarticular tissues, but the cellular basis for the destruction of these tissues in DRA is poorly understood. In this study we performed a systematic analysis of the interaction of monomeric and fibrillar β(2m with primary human cells of the types present in the synovial joints of subjects with DRA. Building upon observations that macrophages infiltrate β(2m amyloid deposits in vivo we demonstrate that monocytes, the precursors of macrophages, cannot degrade β(2m fibrils, and that both monomeric β(2m and fibrillar β(2m are cytotoxic to these cells. β(2m fibrils also impair the formation of bone resorbing osteoclasts from monocytes and reduce the viability of osteoblasts, the cell type that produces bone. As a consequence, we predict that β(2m amyloid will disrupt the remodelling of the bone, which is critical for the maintenance of this tissue. Moreover, we show that β(2m fibrils reduce the viability of chondrocytes, rationalizing the loss of cartilage in DRA. Together, our observations demonstrate that β(2m cytotoxicity has multiple cellular targets in the osteoarticular tissues and is likely to be a key factor in the bone and joint destruction characteristic of DRA.

  9. Prognostic value of left atrial function in systemic light-chain amyloidosis: a cardiac magnetic resonance study.

    Science.gov (United States)

    Mohty, Dania; Boulogne, Cyrille; Magne, Julien; Varroud-Vial, Nicolas; Martin, Sylvain; Ettaif, Hind; Fadel, Bahaa M; Bridoux, Frank; Aboyans, Victor; Damy, Thibaud; Jaccard, Arnaud

    2016-09-01

    Cardiac involvement in systemic light-chain amyloidosis (AL) imparts an adverse impact on outcome. The left atrium (LA), by virtue of its anatomical location and muscular wall, is commonly affected by the amyloid process. Although LA infiltration by amyloid fibrils leads to a reduction in its pump function, the infiltration of the left ventricular (LV) myocardium results in diastolic dysfunction with subsequent increase in filling pressures and LA enlargement. Even though left atrial volume (LAV) is an independent prognostic marker in many cardiomyopathies, its value in amyloid heart disease remains to be determined. In addition, few data are available as to the prognostic value of LA function in systemic AL. Using cardiac magnetic resonance (CMR), the current study aims to assess the prognostic significance of the maximal LAV and total LA emptying fraction (LAEF) in patients with AL. Fifty-four consecutive patients (age 66 ± 10 years, 59% males) with confirmed systemic AL and mean LV ejection fraction of 60 ± 12% underwent CMR. As compared with patients with no or minimal cardiac involvement (Mayo Clinic [MC] stage I), those at moderate and high risk (MC stages II and III) had significantly larger indexed maximal LAV (36 ± 15 vs. 46 ± 13 vs. 52 ± 19 mL/m(2), P = 0.03) and indexed minimal LAV (20 ± 6 vs. 34 ± 11 vs. 44 ± 17 mL/m(2), P 16% (37 ± 11 vs. 94 ± 4%, P = 0.001). In multivariate analysis, lower LAEF remained independently associated with a higher risk of 2-year mortality (HR = 1.08 per 1% decrease, 95% CI: 1.02-1.15, P = 0.003). In patients with systemic AL, LAEF as assessed by CMR is associated with NYHA functional class, MC stage, myocardial LGE and 2-year mortality. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  10. Modified high-dose melphalan and autologous SCT for AL amyloidosis or high-risk myeloma: analysis of SWOG trial S0115.

    Science.gov (United States)

    Sanchorawala, V; Hoering, A; Seldin, D C; Finn, K T; Fennessey, S A; Sexton, R; Mattar, B; Safah, H F; Holmberg, L A; Dean, R M; Orlowski, R Z; Barlogie, B

    2013-11-01

    We designed a trial using two sequential cycles of modified high-dose melphalan at 100 mg/m(2) and autologous SCT (mHDM/SCT) in AL amyloidosis (light-chain amyloidosis, AL), AL with myeloma (ALM) and host-based high-risk myeloma (hM) patients through SWOG-0115. The primary objective was to evaluate OS. From 2004 to 2010, 93 eligible patients were enrolled at 17 centers in the United States (59 with AL, 9 with ALM and 25 with hM). The median OS for patients with AL and ALM was 68 months and 47 months, respectively, and has not been reached for patients with hM. The median PFS for patients with AL and ALM was 38 months and 16 months, respectively, and has not been reached for patients with hM. The treatment-related mortality (TRM) was 12% (11/93) and was observed only in patients with AL after SCT. Grade 3 and higher non-hematologic adverse events were experienced by 81%, 67% and 57% of patients with AL, ALM and hM, respectively, during the first and second HDM/SCT. This experience demonstrates that with careful selection of patients and use of mHDM for SCT in patients with AL, ALM and hM, even in the setting of a multicenter study, OS can be improved with acceptable TRM and morbidity.

  11. Long-term event-free and overall survival after risk-adapted melphalan and SCT for systemic light chain amyloidosis.

    Science.gov (United States)

    Landau, H; Smith, M; Landry, C; Chou, J F; Devlin, S M; Hassoun, H; Bello, C; Giralt, S; Comenzo, R L

    2017-01-01

    Stem cell transplantation (SCT), an effective therapy for amyloid light chain (AL) amyloidosis patients, is associated with low treatment-related mortality (TRM) with appropriate patient selection and risk-adapted dosing of melphalan (RA-SCT). Consolidation after SCT increases hematologic complete response (CR) rates and may improve overall survival (OS) for patients with SCT with or without consolidation. Melphalan was administered at 100 (14%), 140 (52%) and 200 (34%) mg/m 2 . The TRM rate at 100 days was 5%. RA-SCT resulted in CR in 24% (3 months) and 48% (12 months) of patients. The CR rate was particularly high (62%) in patients offered bortezomib consolidation. With a median follow-up among survivors of 7.7 years, median event-free survival (EFS) with RA-SCT was 4.04 years (95% confidence interval (CI): 3.41-5.01 years); median OS was 10.4 years (95% CI: 7.3-not achieved). Patients with CR at 12 months after SCT had significantly longer EFS (P=0.01) and OS (P=0.04). In a multivariate analysis, melphalan dose had no impact on EFS (P=0.26) or OS (P=0.11). For selected patients, RA-SCT was safe and was associated with extended long-term survival. With the availability of novel agents for consolidation, RA-SCT remains a very effective and important backbone treatment for AL amyloidosis.

  12. Severe Left Ventricular Hypertrophy, Small Pericardial Effusion, and Diffuse Late Gadolinium Enhancement by Cardiac Magnetic Resonance Suspecting Cardiac Amyloidosis: Endomyocardial Biopsy Reveals an Unexpected Diagnosis

    Directory of Open Access Journals (Sweden)

    Nina P. Hofmann

    2016-01-01

    Full Text Available Left ventricular (LV hypertrophy can be related to a multitude of cardiac disorders, such as hypertrophic cardiomyopathy (HCM, cardiac amyloidosis, and hypertensive heart disease. Although the presence of LV hypertrophy is generally associated with poorer cardiac outcomes, the early differentiation between these pathologies is crucial due to the presence of specific treatment options. The diagnostic process with LV hypertrophy requires the integration of clinical evaluation, electrocardiography (ECG, echocardiography, biochemical markers, and if required CMR and endomyocardial biopsy in order to reach the correct diagnosis. Here, we present a case of a patient with severe LV hypertrophy (septal wall thickness of 23 mm, LV mass of 264 g, and LV mass index of 147 g/m2, severely impaired longitudinal function, and preserved radial contractility (ejection fraction = 55%, accompanied by small pericardial effusion and diffuse late gadolinium enhancement (LGE by cardiac magnetic resonance (CMR. Due to the imaging findings, an infiltrative cardiomyopathy, such as cardiac amyloidosis, was suspected. However, amyloid accumulation was excluded by endomyocardial biopsy, which revealed the presence of diffuse myocardial fibrosis in an advanced hypertensive heart disease.

  13. Circulating free light chain measurement in the diagnosis, prognostic assessment and evaluation of response of AL amyloidosis: comparison of Freelite and N latex FLC assays.

    Science.gov (United States)

    Palladini, Giovanni; Jaccard, Arnaud; Milani, Paolo; Lavergne, David; Foli, Andrea; Bender, Sebastien; Lavatelli, Francesca; Bosoni, Tiziana; Valentini, Veronica; Pirolini, Laura; Ferraro, Giovanni; Basset, Marco; Russo, Francesca; Nuvolone, Mario; Albertini, Riccardo; Cogne, Michel; Merlini, Giampaolo

    2017-10-26

    The measurement of circulating free light chain (FLC) is essential in the diagnosis, prognostic stratification and evaluation of response to therapy in light chain (AL) amyloidosis. For more than 10 years, this has been done with an immunonephelometric assay based on polyclonal antibodies (Freelite), and cutoffs for staging and response assessment have been validated with this method. Recently, a new assay based on monoclonal antibodies (N latex FLC) has been marketed in Europe. We evaluated and compared the clinical performance of the two assays in 426 patients with newly diagnosed AL amyloidosis. We found suboptimal agreement between the two methods, with differences between values obtained with the Freelite and N latex FLC assays increasing with the concentration of clonal FLC. The diagnostic sensitivity of the Freelite (82%) and N latex FLC (84%) assays was similar, and both improved to 98% in combination with serum and urine immunofixation. The concentration of FLC measured with both methods had prognostic significance. Less pronounced decreases in FLC best predicted improved survival with the N latex FLC assay (33% vs. 50%), and there was poor concordance (84%) in discrimination of responders. The two assays have similar diagnostic and prognostic performance. However, they are not interchangeable, and follow-up should be done with either one. New response criteria are needed for the N latex FLC assay.

  14. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis.

    Science.gov (United States)

    van der Heijden, Roel A; Bijzet, Johan; Meijers, Wouter C; Yakala, Gopala K; Kleemann, Robert; Nguyen, Tri Q; de Boer, Rudolf A; Schalkwijk, Casper G; Hazenberg, Bouke P C; Tietge, Uwe J F; Heeringa, Peter

    2015-11-13

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features in the kidney, were fed low (10% lard) or high-fat diets (45% lard) for 24, 40 and 52 weeks. HFD-feeding induced overt adiposity, altered lipid and insulin homeostasis, increased systemic LGI and adipokine release. HFD-feeding also caused renal upregulation of pro-inflammatory genes, infiltrating macrophages, collagen I protein, increased urinary albumin and NGAL levels. HFD-feeding severely aggravated age-dependent structural changes in the kidney. Remarkably, enhanced amyloid deposition rather than sclerosis was observed. The degree of amyloidosis correlated significantly with body weight. Amyloid deposits stained positive for serum amyloid A (SAA) whose plasma levels were chronically elevated in HFD mice. Our data indicate obesity-induced chronic inflammation as a risk factor for the acceleration of age-dependent renal amyloidosis and functional impairment in mice, and suggest that obesity-enhanced chronic secretion of SAA may be the driving factor behind this process.

  15. Huntington's disease induced cardiac amyloidosis is reversed by modulating protein folding and oxidative stress pathways in the Drosophila heart.

    Science.gov (United States)

    Melkani, Girish C; Trujillo, Adriana S; Ramos, Raul; Bodmer, Rolf; Bernstein, Sanford I; Ocorr, Karen

    2013-01-01

    Amyloid-like inclusions have been associated with Huntington's disease (HD), which is caused by expanded polyglutamine repeats in the Huntingtin protein. HD patients exhibit a high incidence of cardiovascular events, presumably as a result of accumulation of toxic amyloid-like inclusions. We have generated a Drosophila model of cardiac amyloidosis that exhibits accumulation of PolyQ aggregates and oxidative stress in myocardial cells, upon heart-specific expression of Huntingtin protein fragments (Htt-PolyQ) with disease-causing poly-glutamine repeats (PolyQ-46, PolyQ-72, and PolyQ-102). Cardiac expression of GFP-tagged Htt-PolyQs resulted in PolyQ length-dependent functional defects that included increased incidence of arrhythmias and extreme cardiac dilation, accompanied by a significant decrease in contractility. Structural and ultrastructural analysis of the myocardial cells revealed reduced myofibrillar content, myofibrillar disorganization, mitochondrial defects and the presence of PolyQ-GFP positive aggregates. Cardiac-specific expression of disease causing Poly-Q also shortens lifespan of flies dramatically. To further confirm the involvement of oxidative stress or protein unfolding and to understand the mechanism of PolyQ induced cardiomyopathy, we co-expressed expanded PolyQ-72 with the antioxidant superoxide dismutase (SOD) or the myosin chaperone UNC-45. Co-expression of SOD suppressed PolyQ-72 induced mitochondrial defects and partially suppressed aggregation as well as myofibrillar disorganization. However, co-expression of UNC-45 dramatically suppressed PolyQ-72 induced aggregation and partially suppressed myofibrillar disorganization. Moreover, co-expression of both UNC-45 and SOD more efficiently suppressed GFP-positive aggregates, myofibrillar disorganization and physiological cardiac defects induced by PolyQ-72 than did either treatment alone. Our results demonstrate that mutant-PolyQ induces aggregates, disrupts the sarcomeric organization of

  16. Amiloidose renal em cão Shar-Pei: Relato de Caso Renal amyloidosis in a Shar-Pei dog: A case report

    Directory of Open Access Journals (Sweden)

    J.L. Reis Jr.

    2001-08-01

    Full Text Available O presente relato descreve os achados clínicos e anatomopatológicos de um caso de amiloidose renal em um cão macho de nove anos da raça Shar-Pei. O animal apresentava quadro clínico de esporotricose e de insuficiência renal e exames positivos para erlichiose e leishmaniose. No dia anterior ao óbito, o cão apresentou apatia, desidratação e anúria. À necropsia foram observados inúmeros pontos milimétricos esbranquiçados localizados no córtex renal e hepatização do lobo diafragmático esquerdo. O achado histológico mais importante foi deposição de material eosinofílico, amorfo e acelular localizado nos tufos glomerulares que se corou positivamente pelo vermelho congo (amilóide. Observaram-se nefrite supurada multifocal, espessamento da cápsula de Bowman e broncopneumonia supurada crônica, com fibrose intensa. A origem da amiloidose, no presente caso, poderia ser hereditária, assemelhando-se à amiloidose familiar descrita em cães da raça Shar-Pei, ou ser devida à inflamação supurada crônica e/ou leishmaniose.The clinical and pathological findings of a case of renal amyloidosis in a nine-year-old male Shar-Pei dog were described. Clinically, there were signs of sporotrichosis and renal insufficiency, besides being positive to leishmaniasis and ehrlichiosis. On the day before death, the animal became apathetic, dehydrated and anuric. On gross examination, there were several whitish millimetric spots seen widespread in both renal cortices and consolidation of the left diaphragmatic pulmonary lobe. The most important microscopic finding was a deposition of amorphous acellular material on the glomerular tufts which stained positively by congo red stain. Other changes were multifocal suppurative nephritis, thickening of the Bowman capsule and chronic suppurative bronchopneumonia. The origin of the amyloidosis in this case could be hereditary, being similar to familiar amyloidosis described in Shar-Pei breed, or due to

  17. Psychopathological dimensions in subjects with hereditary ATTR V30M amyloidosis and their relation with life events due to the disease.

    Science.gov (United States)

    Lopes, Alice; Fonseca, Isabel; Sousa, Alexandra; Rodrigues, Carla; Branco, Margarida; Coelho, Teresa; Sequeiros, Jorge; Freitas, Paula

    2018-03-01

    Chronic physical illness has been associated with emotional distress. Chronic diseases may change usual family patterns with economic, social and family losses. Hereditary ATTR V30M amyloidosis is a rare, fatal inherited systemic amyloidosis, with chronic evolution and beginning in adulthood. To evaluate psychopathological dimensions and how they correlated with disease-related life events, 209 symptomatic and asymptomatic carriers, participated in the study. Sociodemographic and Family and Personal History Disease questionnaires and brief symptom inventory (BSI) were applied. BSI indices, global severity index (GSI), positive symptom index (PSI) and positive symptom total (PST) scored higher than general population. Independent predictors for GSI >0.83 were female sex (OR = 3.46, p = .005) and being symptomatic carriers (OR = 3.03, p = .039). Independent predictors of a PST >26.99 were female sex (OR = 3.74, p = .012) symptomatic carrier (OR = 5.32, p = .025), age between 15 and 24 years at affected parent's death (OR = 5.26, p = .04). Independent predictors of a PSI >1.56 were being asymptomatic carrier (OR = 6.3, p = .036); to have children (OR = 3.19, p = .043) and have ≤14 years at parent's disease onset (OR = 6.39, p = .05). Results point to an important vulnerability of this population for psychological distress and psychiatric disease. Early life events related to disease, being sick and sex are associated with psychopathological distress.

  18. Effect of heating on the stability of amyloid A (AA) fibrils and the intra- and cross-species transmission of AA amyloidosis.

    Science.gov (United States)

    Ogawa, Saki; Murakami, Tomoaki; Inoshima, Yasuo; Ishiguro, Naotaka

    2015-01-01

    Amyloid A (AA) amyloidosis is a protein misfolding disease characterized by extracellular deposition of AA fibrils. AA fibrils are found in several tissues from food animals with AA amyloidosis. For hygienic purposes, heating is widely used to inactivate microbes in food, but it is uncertain whether heating is sufficient to inactivate AA fibrils and prevent intra- or cross-species transmission. We examined the effect of heating (at 60 °C or 100 °C) and autoclaving (at 121 °C or 135 °C) on murine and bovine AA fibrils using Western blot analysis, transmission electron microscopy (TEM), and mouse model transmission experiments. TEM revealed that a mixture of AA fibrils and amorphous aggregates appeared after heating at 100 °C, whereas autoclaving at 135 °C produced large amorphous aggregates. AA fibrils retained antigen specificity in Western blot analysis when heated at 100 °C or autoclaved at 121 °C, but not when autoclaved at 135 °C. Transmissible pathogenicity of murine and bovine AA fibrils subjected to heating (at 60 °C or 100 °C) was significantly stimulated and resulted in amyloid deposition in mice. Autoclaving of murine AA fibrils at 121 °C or 135 °C significantly decreased amyloid deposition. Moreover, amyloid deposition in mice injected with murine AA fibrils was more severe than that in mice injected with bovine AA fibrils. Bovine AA fibrils autoclaved at 121 °C or 135 °C did not induce amyloid deposition in mice. These results suggest that AA fibrils are relatively heat stable and that similar to prions, autoclaving at 135 °C is required to destroy the pathogenicity of AA fibrils. These findings may contribute to the prevention of AA fibril transmission through food materials to different animals and especially to humans.

  19. Amiloidose e insuficiência renal crônica terminal associada à hanseníase Amyloidosis and end-stage renal disease associated with leprosy

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    Geraldo Bezerra da Silva Júnior

    2010-08-01

    Full Text Available O envolvimento renal na hanseníase é diverso, incluindo glomerulonefrites, amiloidose e nefrite túbulo-intersticial. Um homem de 58 anos foi admitido com edema de membros inferiores e dispnéia. Na admissão, havia retenção de escórias nitrogenadas, anemia, hipercalemia e acidose metabólica, com necessidade de hemodiálise. Referia história de hanseníase virchoviana. Foi realizada biopsia renal, compatível com amiloidose. O paciente evoluiu estável, sem recuperação da função renal, permanecendo em tratamento hemodialítico. A hanseníase deve ser investigada em todo paciente com perda de função renal, sobretudo naqueles que apresentam lesões cutâneas ou outras manifestações sugestivas de hanseníase.Renal involvement in leprosy includes glomerulonephritis, amyloidosis and tubulointerstitial nephritis. A 58-year-old man was admitted with complaints of lower limb edema and dyspnea. At admission, nitrogen retention, anemia, hyperkalemia and metabolic acidosis were observed, requiring hemodialysis. The patient had a history of lepromatous leprosy. A renal biopsy was performed that was compatible with amyloidosis. The patient had a stable outcome, but without renal function recovery and remained on regular hemodialysis. Leprosy should be investigated in every patient with renal function loss, particularly in those with cutaneous lesions or other manifestations suggestive of leprosy.

  20. Macular amyloidosis and hypothyroidism

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    Chopra Adarsh

    1999-01-01

    Full Text Available A 53 year old woman presented with extensive pruritic hyperpigmented macules in interscapular area and extremities of four years duration.She was an established case of hypothyroidism on treatment for last four years.

  1. Amiloidosis bucal Oral amyloidosis

    OpenAIRE

    Isabella Lima Arrais Ribeiro; Vilson Lacerda Brasileiro Junior; Olavo Hoston Gonçalves Pereira; Marize Raquel Diniz da Rosa; Hálamo José Moura de Lira

    2012-01-01

    A amiloidose é uma doença complexa rara de difícil diagnóstico que ocorre devido à deposição de substância amilóide no meio extracelular. Ao ser diagnosticado na cavidade bucal, deve-se monitorar o paciente a fim de avaliar possíveis complicações sistêmicas da doença. Diante disso, o objetivo do presente estudo é relatar um caso de amiloidose oral em uma paciente do gênero feminino de 72 anos de idade. Baseado nos sinais clínicos observados, a hipótese diagnóstica foi de fibroma traumático. A...

  2. Secondary systemic amyloidosis

    Science.gov (United States)

    ... cell leukemia -- a type of blood cancer Hodgkin disease -- cancer of the lymph tissue Juvenile chronic arthritis -- arthritis that affects children Kidney dialysis Multiple myeloma -- a type of blood cancer ...

  3. Osteoarthropathy in dialysis amyloidosis

    International Nuclear Information System (INIS)

    Baldrati, L.; Feletti, C.; Capponcini, C.; Docci, D.; Rocchi, A.; Balbi, B.; Bonsanto, R.; Mughetti, M.; Pasini, A.

    1991-01-01

    Many long-term (>60 months) hemodialysis patients develop a severe osteoarticular disease, called 'dialysis arthropathy', which is characterized by the deposition in bone and synovia of a new type of amyloid made mainly of β 2 -microglobulin. In the present study, 31 patients (17 males, 14 females; age 54.1±13 years) undergoing chronic hemodialysis arthropathy by means of clinics and of radiological investigations (conventional radiography and computed tomography). Sixteen patients (51.6%) had radiographic evidence of dialysis arthropathy: geodes (shoulders, 12 cases; wrists, 11; hips, 2; knees, 2) and/or destructive arthropathies (cervical spine, 13 cases; dorsolumbar spine, 2; hands, 2; hips, 1). Within 24 months, these lesions were found to progress slowly in the majoriry of cases. In the diagnostic process, CT should be employed in the study of spine, shoulders and hips when the lesions have not been sufficiently demonstrated by conventional radiography in the presence of evident clinical signs. Patients with dialysis arthropathy had undergone dialysis for longer periods than those without it (p<0.005) and showed a significantly higher incidence of both carpal tunnel syndrome (p<0.0005) and shoulder pain (p<0.005). Our findings confirm the high incidence and clinical importance of dialysis arthropathy in long-term hemodialysis patients end the value of diagnostic imaging in screening such patients for those lesions

  4. Amiloidose pulmonar: relato de caso de achado radiológico da apresentação nodular em grande fumante Pulmonary amyloidosis: radiographic finding of nodular opacities in a heavy smoker

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    Jorge Montessi

    2007-06-01

    Full Text Available A amiloidose pulmonar é uma doença rara, caracterizada pelo depósito extracelular de proteínas fibrilares no pulmão. Amiloidose é um termo genérico para grupos heterogêneos de doenças, incluindo doença de Alzheimer e diabetes mellitus tipo II. Apresenta-se no aparelho respiratório sob as formas traqueobrônquica, nodular pulmonar e septal alveolar (parenquimatosa difusa. Relata-se o caso de uma mulher, tabagista (20 anos/maço, portadora de amiloidose nodular pulmonar, diagnosticada através de exames pré-operatórios à realização de colecistectomia videolaparoscópica.Pulmonary amyloidosis is a rare disease, characterized by extracellular deposition of fibrillary protein in the lungs. Amyloidosis is a generic term for a heterogeneous group of diseases, including Alzheimer's disease and type 2 diabetes mellitus. In the respiratory system, it appears in various forms: tracheobronchial; nodular pulmonary; and alveolar septal (diffuse parenchymal. We present the case of a woman who was a 20 pack-year smoker and had nodular pulmonary amyloidosis, as diagnosed through tests performed prior to laparoscopic cholecystectomy.

  5. The prognostic value of T1 mapping and late gadolinium enhancement cardiovascular magnetic resonance imaging in patients with light chain amyloidosis.

    Science.gov (United States)

    Lin, Lu; Li, Xiao; Feng, Jun; Shen, Kai-Ni; Tian, Zhuang; Sun, Jian; Mao, Yue-Ying; Cao, Jian; Jin, Zheng-Yu; Li, Jian; Selvanayagam, Joseph B; Wang, Yi-Ning

    2018-01-03

    Cardiac impairment is associated with high morbidity and mortality in immunoglobulin light chain (AL) type amyloidosis, for which early identification and risk stratification is vital. For myocardial tissue characterization, late gadolinium enhancement (LGE) is a classic and most commonly performed cardiovascular magnetic resonance (CMR) parameter. T1 mapping with native T1 and extracellular volume (ECV) are recently developed quantitative parameters. We aimed to investigate the prognostic value of native T1, ECV and LGE in patients with AL amyloidosis. Eighty-two patients (55.5 ± 8.5 years; 52 M) and 20 healthy subjects (53.2 ± 11.7 years; 10 M) were prospectively recruited. All subjects underwent CMR with LGE imaging and T1 mapping using a Modified Look-Locker Inversion-recovery (MOLLI) sequence on a 3 T scanner. Native T1 and ECV were measured semi-automatically using a dedicated CMR software. The left ventricular (LV) LGE pattern was classified as none, patchy, and global groups. Global LGE was considered when there was diffuse, transmural LGE in more than half of the short axis images. Follow-up was performed for all-cause mortality using Cox proportional hazards regression analysis and Kaplan-Meier survival curves. The patients demonstrated an increase in native T1 (1438 ± 120 ms vs. 1283 ± 46 ms, P = 0.001) and ECV (43.9 ± 10.9% vs. 27.0 ± 1.7%, P = 0.001) compared to healthy controls. Native T1, ECV and LGE showed significant correlation with Mayo Stage, and ECV and LGE showed significant correlation with echocardiographic E/E' and LV ejection fraction. During the follow-up for a median time of 8 months, 21 deaths occurred. ECV ≥ 44.0% (hazard ratio [HR] 7.249, 95% confidence interval (CI) 1.751-13.179, P = 0.002) and global LGE (HR 4.804, 95% CI 1.971-12.926, P = 0.001) were independently prognostic for mortality over other clinical and imaging parameters. In subgroups with the same LGE pattern

  6. Mutations in specific structural regions of immunoglobulin light chains are associated with free light chain levels in patients with AL amyloidosis.

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    Tanya L Poshusta

    Full Text Available BACKGROUND: The amyloidoses are protein misfolding diseases characterized by the deposition of amyloid that leads to cell death and tissue degeneration. In immunoglobulin light chain amyloidosis (AL, each patient has a unique monoclonal immunoglobulin light chain (LC that forms amyloid deposits. Somatic mutations in AL LCs make these proteins less thermodynamically stable than their non-amyloidogenic counterparts, leading to misfolding and ultimately the formation of amyloid fibrils. We hypothesize that location rather than number of non-conservative mutations determines the amyloidogenicity of light chains. METHODOLOGY/PRINCIPAL FINDINGS: We performed sequence alignments on the variable domain of 50 kappa and 91 lambda AL light chains and calculated the number of non-conservative mutations over total number of patients for each secondary structure element in order to identify regions that accumulate non-conservative mutations. Among patients with AL, the levels of circulating immunoglobulin free light chain varies greatly, but even patients with very low levels can have very advanced amyloid deposition. CONCLUSIONS: Our results show that in specific secondary structure elements, there are significant differences in the number of non-conservative mutations between normal and AL sequences. AL sequences from patients with different levels of secreted light chain have distinct differences in the location of non-conservative mutations, suggesting that for patients with very low levels of light chains and advanced amyloid deposition, the location of non-conservative mutations rather than the amount of free light chain in circulation may determine the amyloidogenic propensity of light chains.

  7. A complex case of renal amyloidosis with a rare co-occurrence of 2 mutations in separate hereditary periodic fever syndrome-related genes.

    Science.gov (United States)

    Cigni, Alessandro; Ledda, Franca; Satta, Andrea E

    2006-01-01

    A 41 year-old male was admitted because of nephrotic syndrome associated with renal impairment and arterial hypertension. Renal biopsy showed a complete subverting of renal architecture with eosinophilic, amorphous deposits which stained positive for Congo red and were positive for antibodies against AA-amyloid. Abdominal fat pad aspirate confirmed the diagnosis of AA amyloidosis. Despite high values of serum amyloid A (SAA), surprisingly medical history, physical examination and all tests failed to identify any underlying inflammatory disease, even asymptomatic, at presentation and during the whole follow-up period. The patient carried a mutation (Glu148Gln) in the MEFV gene, and a mutation (Arg92Gln) in the TNFRSF1A gene, both in heterozygosity. The patient has never complained of the typical features of the Familial Mediterranean fever or of the TNF receptor-associated periodic syndrome. The patient's father carried the same mutations. His father's medical history was unremarkable; renal tests, acute-phase reactants and SAA were normal. During a trial with colchicine (while the patient was also taking atorvastatin) SAA decreased, renal function continued to deteriorate and proteinuria remained high; no cardiac involvement was detected. Six months later our patient developed rhabdomyolysis, thus accelerating the decline of renal function and requiring the start of dialysis.

  8. Identification of S-sulfonation and S-thiolation of a novel transthyretin Phe33Cys variant from a patient diagnosed with familial transthyretin amyloidosis.

    Science.gov (United States)

    Lim, Amareth; Prokaeva, Tatiana; McComb, Mark E; Connors, Lawreen H; Skinner, Martha; Costello, Catherine E

    2003-08-01

    Familial transthyretin amyloidosis (ATTR) is an autosomal dominant disorder associated with a variant form of the plasma carrier protein transthyretin (TTR). Amyloid fibrils consisting of variant TTR, wild-type TTR, and TTR fragments deposit in tissues and organs. The diagnosis of ATTR relies on the identification of pathologic TTR variants in plasma of symptomatic individuals who have biopsy proven amyloid disease. Previously, we have developed a mass spectrometry-based approach, in combination with direct DNA sequence analysis, to fully identify TTR variants. Our methodology uses immunoprecipitation to isolate TTR from serum, and electrospray ionization and matrix-assisted laser desorption/ionization mass spectrometry (MS) peptide mapping to identify TTR variants and posttranslational modifications. Unambiguous identification of the amino acid substitution is performed using tandem MS (MS/MS) analysis and confirmed by direct DNA sequence analysis. The MS and MS/MS analyses also yield information about posttranslational modifications. Using this approach, we have recently identified a novel pathologic TTR variant. This variant has an amino acid substitution (Phe --> Cys) at position 33. In addition, like the Cys10 present in the wild type and in this variant, the Cys33 residue was both S-sulfonated and S-thiolated (conjugated to cysteine, cysteinylglycine, and glutathione). These adducts may play a role in the TTR fibrillogenesis.

  9. The Successful Diagnosis and Typing of Systemic Amyloidosis Using A Microwave-Assisted Filter-Aided Fast Sample Preparation Method and LC/MS/MS Analysis.

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    Weiyi Sun

    Full Text Available Laser microdissection followed by mass spectrometry has been successfully used for amyloid typing. However, sample contamination can interfere with proteomic analysis, and overnight digestion limits the analytical throughput. Moreover, current quantitative analysis methods are based on the spectrum count, which ignores differences in protein length and may lead to misdiagnoses. Here, we developed a microwave-assisted filter-aided sample preparation (maFASP method that can efficiently remove contaminants with a 10-kDa cutoff ultrafiltration unit and can accelerate the digestion process with the assistance of a microwave. Additionally, two parameters (P- and D-scores based on the exponentially modified protein abundance index were developed to define the existence of amyloid deposits and those causative proteins with the greatest abundance. Using our protocol, twenty cases of systemic amyloidosis that were well-typed according to clinical diagnostic standards (training group and another twenty-four cases without subtype diagnoses (validation group were analyzed. Using this approach, sample preparation could be completed within four hours. We successfully subtyped 100% of the cases in the training group, and the diagnostic success rate in the validation group was 91.7%. This maFASP-aided proteomic protocol represents an efficient approach for amyloid diagnosis and subtyping, particularly for serum-contaminated samples.

  10. The Successful Diagnosis and Typing of Systemic Amyloidosis Using A Microwave-Assisted Filter-Aided Fast Sample Preparation Method and LC/MS/MS Analysis.

    Science.gov (United States)

    Sun, Weiyi; Sun, Jian; Zou, Lili; Shen, Kaini; Zhong, Dingrong; Zhou, Daobin; Sun, Wei; Li, Jian

    2015-01-01

    Laser microdissection followed by mass spectrometry has been successfully used for amyloid typing. However, sample contamination can interfere with proteomic analysis, and overnight digestion limits the analytical throughput. Moreover, current quantitative analysis methods are based on the spectrum count, which ignores differences in protein length and may lead to misdiagnoses. Here, we developed a microwave-assisted filter-aided sample preparation (maFASP) method that can efficiently remove contaminants with a 10-kDa cutoff ultrafiltration unit and can accelerate the digestion process with the assistance of a microwave. Additionally, two parameters (P- and D-scores) based on the exponentially modified protein abundance index were developed to define the existence of amyloid deposits and those causative proteins with the greatest abundance. Using our protocol, twenty cases of systemic amyloidosis that were well-typed according to clinical diagnostic standards (training group) and another twenty-four cases without subtype diagnoses (validation group) were analyzed. Using this approach, sample preparation could be completed within four hours. We successfully subtyped 100% of the cases in the training group, and the diagnostic success rate in the validation group was 91.7%. This maFASP-aided proteomic protocol represents an efficient approach for amyloid diagnosis and subtyping, particularly for serum-contaminated samples.

  11. Novel recurrent chromosomal aberrations detected in clonal plasma cells of light chain amyloidosis patients show potential adverse prognostic effect: first results from a genome-wide copy number array analysis.

    Science.gov (United States)

    Granzow, Martin; Hegenbart, Ute; Hinderhofer, Katrin; Hose, Dirk; Seckinger, Anja; Bochtler, Tilmann; Hemminki, Kari; Goldschmidt, Hartmut; Schönland, Stefan O; Jauch, Anna

    2017-07-01

    Immunoglobulin light chain (AL) amyloidosis is a rare plasma cell dyscrasia characterized by the deposition of abnormal amyloid fibrils in multiple organs, thus impairing their function. In the largest cohort studied up to now of 118 CD138-purified plasma cell samples from previously untreated immunoglobulin light chain amyloidosis patients, we assessed in parallel copy number alterations using high-density copy number arrays and interphase fluorescence in situ hybridization (iFISH). We used fluorescence in situ hybridization probes for the IgH translocations t(11;14), t(4;14), and t(14;16) or any other IgH rearrangement as well as numerical aberrations of the chromosome loci 1q21, 8p21, 5p15/5q35, 11q22.3 or 11q23, 13q14, 15q22, 17p13, and 19q13. Recurrent gains included chromosomes 1q (36%), 9 (24%), 11q (24%), as well as 19 (15%). Recurrent losses affected chromosome 13 (29% monosomy) and partial losses of 14q (19%), 16q (14%) and 13q (12%), respectively. In 88% of patients with translocation t(11;14), the hallmark chromosomal aberration in AL amyloidosis, a concomitant gain of 11q22.3/11q23 detected by iFISH was part of the unbalanced translocation der(14)t(11;14)(q13;q32) with the breakpoint in the CCND1/MYEOV gene region. Partial loss of chromosome regions 14q and 16q were significantly associated to gain 1q. Gain 1q21 detected by iFISH almost always resulted from a gain of the long arm of chromosome 1 and not from trisomy 1, whereas deletions on chromosome 1p were rarely found. Overall and event-free survival analysis found a potential adverse prognostic effect of concomitant gain 1q and deletion 14q as well as of deletion 1p. In conclusion, in the first whole genome report of clonal plasma cells in AL amyloidosis, novel aberrations and hitherto unknown potential adverse prognostic effects were uncovered. Copyright© 2017 Ferrata Storti Foundation.

  12. Renal medullary AA amyloidosis, hepatocyte dissociation and multinucleated hepatocytes in a 14-year-old free-ranging lioness (Panthera leo

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    J.H. Williams

    2005-06-01

    Full Text Available A 14-year-old lioness, originating from Etosha in Namibia, and a member of a pride in Pilanesberg National Park since translocation in 1994, was euthanased due to fight-related vertebral fracture and spinal injury, incurred approximately 6-8 weeks previously. Blood specimens collected at the time of death showed mild anaemia and a leukogram reflecting stress and chronic infection. Necropsy conducted within 2 hours of death was on a dehydrated, emaciated animal with hindquarter wasting and chronic traumatic friction injuries from dragging her hindlegs. There was cellulitis in the region of bite-wounds adjacent to the thoraco-lumbar vertebral fracture, at which site there was spinal cord compression, and there was marked intestinal helminthiasis. The outer renal medullae appeared pale and waxy and the liver was macroscopically unremarkable. Histopathology and electron microscopy of the kidneys revealed multifocal to coalescing deposits of proximal medullary interstitial amyloid, which fluoresced strongly with thioflavine T, and was sensitive to potassium permanganate treatment prior to Congo Red staining, thus indicating inflammatory (AA origin. There was diffuse hepatocyte dissociation, as well as numerous binucleated and scattered multinucleated (up to 8 nuclei/cell hepatocytes, with swollen hepatocyte mitochondria, in liver examined light microscopically. Ultrastructurally, the mono-, bi- and multinucleated hepatocytes contained multifocal irregular membrane-bound accumulations of finely-granular, amorphous material both intra-cytoplasmically and intra-nuclearly, as well as evidence of irreversible mitochondrial injury. The incidence and relevance in cats and other species of amyloidosis, particularly with renal medullary distribution, as well as of hepatocyte dissociation and multinucleation, as reported in selected literature, is briefly overviewed and their occurrence in this lioness is discussed.

  13. Role of Endoplasmic Reticulum Stress in Learning and Memory Impairment and Alzheimer's Disease-Like Neuropathology in the PS19 and APPSwe Mouse Models of Tauopathy and Amyloidosis.

    Science.gov (United States)

    Briggs, Denise Isabelle; Defensor, Erwin; Memar Ardestani, Pooneh; Yi, Bitna; Halpain, Michelle; Seabrook, Guy; Shamloo, Mehrdad

    2017-01-01

    Emerging evidence suggests that endoplasmic reticulum (ER) stress may be involved in the pathogenesis of Alzheimer's disease (AD). Recently, pharmacological modulation of the eukaryotic translation initiation factor-2 (eIF2α) pathway was achieved using an integrated stress response inhibitor (ISRIB). While members of this signaling cascade have been suggested as potential therapeutic targets for neurodegeneration, the biological significance of this pathway has not been comprehensively assessed in animal models of AD. The present study investigated the ER stress pathway and its long-term modulation utilizing in vitro and in vivo experimental models of tauopathy (MAPT P301S)PS19 and amyloidosis (APP Swe ). We report that thapsigargin induces activating transcription factor-4 (ATF4) in primary cortical neurons (PCNs) derived from rat and APP Swe nontransgenic (nTg) and transgenic (Tg) mice. ISRIB mitigated the induction of ATF4 in PCNs generated from wild-type (WT) but not APP Swe mice despite partially restoring thapsigargin-induced translational repression in nTg PCNs. In vivo , C57BL/6J and PS19 mice received prolonged, once-daily administration of ISRIB. While the compound was well tolerated by PS19 and C57BL/6J mice, APP Swe mice treated per this schedule displayed significant mortality. Thus, the dose was reduced and administered only on behavioral test days. ISRIB did not improve learning and memory function in APP Swe Tg mice. While ISRIB did not reduce tau-related neuropathology in PS19 Tg mice, no evidence of ER stress-related dysfunction was observed in either of these Tg models. Taken together, the significance of ER stress and the relevance of these models to the etiology of AD require further investigation.

  14. Renal medullary AA amyloidosis, hepatocyte dissociation and multinucleated hepatocytes in a 14-year-old free-ranging lioness (Panthera leo).

    Science.gov (United States)

    Williams, J H; Van Wilpe, E; Momberg, M

    2005-06-01

    A 14-year-old lioness, originating from Etosha in Namibia, and a member of a pride in Pilanesberg National Park since translocation in 1994, was euthanased due to fight-related vertebral fracture and spinal injury, incurred approximately 6-8 weeks previously. Blood specimens collected at the time of death showed mild anaemia and a leukogram reflecting stress and chronic infection. Necropsy conducted within 2 hours of death was on a dehydrated, emaciated animal with hindquarter wasting and chronic traumatic friction injuries from dragging her hindlegs. There was cellulitis in the region of bite-wounds adjacent to the thoraco-lumbar vertebral fracture, at which site there was spinal cord compression, and there was marked intestinal helminthiasis. The outer renal medullae appeared pale and waxy and the liver was macroscopically unremarkable. Histopathology and electron microscopy of the kidneys revealed multifocal to coalescing deposits of proximal medullary interstitial amyloid, which fluoresced strongly with thioflavine T, and was sensitive to potassium permanganate treatment prior to Congo Red staining, thus indicating inflammatory (AA) origin. There was diffuse hepatocyte dissociation, as well as numerous binucleated and scattered multinucleated (up to 8 nuclei/cell) hepatocytes, with swollen hepatocyte mitochondria, in liver examined light microscopically. Ultrastructurally, the mono-, bi- and multinucleated hepatocytes contained multifocal irregular membrane-bound accumulations of finely-granular, amorphous material both intra-cytoplasmically and intra-nuclearly, as well as evidence of irreversible mitochondrial injury. The incidence and relevance in cats and other species of amyloidosis, particularly with renal medullary distribution, as well as of hepatocyte dissociation and multinucleation, as reported in selected literature, is briefly overviewed and their occurrence in this lioness is discussed.

  15. Macroglossia como primeira manifestação clínica da amiloidose primária Macroglossia as initial clinical manifestation of primary amyloidosis

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    Carla de Oliveira Alambert

    2007-02-01

    Full Text Available A amiloidose é uma doença rara causada pelo depósito patológico de substância amilóide no meio extracelular. Relatamos o caso de um paciente de 50 anos de idade, masculino, com história de edema de lábios e língua associado à equimose periorbitária bilateral há 6 meses. Ao exame físico, observamos importante macroglossia. Foram realizados exames complementares, e o diagnóstico foi confirmado pela análise histopatológica da biópsia de língua. O paciente recebeu tratamento com prednisona e melfalan com resposta insatisfatória. Evoluiu com insuficiência cardíaca congestiva e infecções urinárias e respiratórias de repetição. Após 7 meses do diagnóstico, o paciente foi internado com infecção pulmonar complicada com sepse e evoluiu a óbito.Amyloidosis is a rare disease caused by pathological deposit of an amyloid extracellular proteinaceus material. We report a case of a 50-year-old man with history of lips and tongue swelling associated to periorbital ecchimosys for 6 months. At the physical examination an important macroglossia was observed. Complementary tests were accomplished, and the pathological examination of the tongue biopsy confirmed the diagnosis. The patient was treated with prednisone and melphalan with an unsatisfactory response. Along the follow up the patient developed heart failure, and died 7 months after diagnosis of pulmonary infection and sepsis.

  16. Primary systemic amyloidosis associated with multiple myeloma Amiloidose sistêmica primária associada ao mieloma múltiplo

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    Ederson Valei Lopes de Oliveira

    2012-02-01

    Full Text Available This case report is about a 48-year-old female patient with systemic amyloidosis and multiple myeloma simultaneously. Amyloid cutaneous infiltrative lesions like papules, nodules, or plaques with a serous-hemorrhagic aspect were found in the eyelids, neck and retroauricular region, among others. She had presented intermittent papular lesions on the upper eyelids one year before, which worsened following local trauma. A local skin biopsy showed amorphous and eosinophilic substance in the dermis. Congo red staining confirmed the amyloid deposits. Abnormal exams: proteinuria (570mg/24h, Bence-Jones proteinuria and clonal plasma cells (70% found in myelogram. Following the diagnosis of multiple myeloma based on amyloid skin lesions, the patient was referred to the Hematology service and died 5 months after the diagnosis.Relatamos um caso de uma paciente de 48 anos com amiloidose sistêmica associada a mieloma múltiplo. Lesões infiltrativas cutâneas como pápulas, nódulos ou placas com aspecto sero-hemorrágico podem ser localizados nas pálpebras, pescoço, região retroauricular dentre outras. No presente caso, as pálpebras foram acometidas por pápulas, há 1 ano, de caráter intermitente e piora após trauma local. Biópsia local evidenciou material amorfo e eosinofílico na derme. A coloração vermelho do Congo confirmou presença de substância amiloide. Exames anormais: proteinúria de 570mg/24 horas, proteinúria de Bence-Jones positiva e mielograma com 70% de plasmócitos atípicos. Assim, realizou-se o diagnóstico de mieloma múltiplo a partir de manifestações cutâneas de amiloidose. Paciente encaminhada ao serviço de hematologia e foi a óbito em 5 meses.

  17. Cognitive and neuroimaging features and brain β-amyloidosis in individuals at risk of Alzheimer's disease (INSIGHT-preAD): a longitudinal observational study.

    Science.gov (United States)

    Dubois, Bruno; Epelbaum, Stephane; Nyasse, Francis; Bakardjian, Hovagim; Gagliardi, Geoffroy; Uspenskaya, Olga; Houot, Marion; Lista, Simone; Cacciamani, Federica; Potier, Marie-Claude; Bertrand, Anne; Lamari, Foudil; Benali, Habib; Mangin, Jean-François; Colliot, Olivier; Genthon, Remy; Habert, Marie-Odile; Hampel, Harald

    2018-04-01

    Improved understanding is needed of risk factors and markers of disease progression in preclinical Alzheimer's disease. We assessed associations between brain β-amyloidosis and various cognitive and neuroimaging parameters with progression of cognitive decline in individuals with preclinical Alzheimer's disease. The INSIGHT-preAD is an ongoing single-centre observational study at the Salpêtrière Hospital, Paris, France. Eligible participants were age 70-85 years with subjective memory complaints but unimpaired cognition and memory (Mini-Mental State Examination [MMSE] score ≥27, Clinical Dementia Rating score 0, and Free and Cued Selective Reminding Test [FCSRT] total recall score ≥41). We stratified participants by brain amyloid β deposition on 18 F-florbetapir PET (positive or negative) at baseline. All patients underwent baseline assessments of demographic, cognitive, and psychobehavioural, characteristics, APOE ε4 allele carrier status, brain structure and function on MRI, brain glucose-metabolism on 18 F-fluorodeoxyglucose ( 18 F-FDG) PET, and event-related potentials on electroencephalograms (EEGs). Actigraphy and CSF investigations were optional. Participants were followed up with clinical, cognitive, and psychobehavioural assessments every 6 months, neuropsychological assessments, EEG, and actigraphy every 12 months, and MRI, and 18 F-FDG and 18 F-florbetapir PET every 24 months. We assessed associations of amyloid β deposition status with test outcomes at baseline and 24 months, and with clinical status at 30 months. Progression to prodromal Alzheimer's disease was defined as an amnestic syndrome of the hippocampal type. From May 25, 2013, to Jan 20, 2015, we enrolled 318 participants with a mean age of 76·0 years (SD 3·5). The mean baseline MMSE score was 28·67 (SD 0·96), and the mean level of education was high (score >6 [SD 2] on a scale of 1-8, where 1=infant school and 8=higher education). 88 (28%) of 318 participants showed amyloid

  18. Genetics Home Reference: transthyretin amyloidosis

    Science.gov (United States)

    ... the brain, an accumulation of fluid in the brain (hydrocephalus), difficulty coordinating movements (ataxia), muscle stiffness and weakness (spastic paralysis), seizures, and loss of intellectual function (dementia). Eye ...

  19. Amyloidosis Associated with Neoplastic Diseases

    African Journals Online (AJOL)

    1974-09-21

    Sep 21, 1974 ... was admitted to hospital because of severe congestive heart failure. On examination her blood pressure was found to be. 95/50 mmHg, the skin dry and of parchment-like con- sistency, the face swollen and the tongue enlarged, and the neck veins were engorged. The chest was emphysematous and rales ...

  20. AL Amyloidosis and Agent Orange

    Science.gov (United States)

    ... the Media Room Public Affairs News Releases Speeches Videos Publications National Observances Veterans Day Memorial Day Celebrating America's Freedoms Special Events Adaptive Sports Program Creative Arts Festival Golden Age Games Summer Sports Clinic Training - Exposure - Experience (TEE) Tournament ...

  1. Axoval neuropathy as initial manifestation of primary amyloidosis: report of a case submitted to bone marrow transplantation Neuropatia axonal como manifestação inicial de amiloidose primária: relato de caso submetido a transplante de medula óssea

    Directory of Open Access Journals (Sweden)

    Orlando G. Povoas Barsottini

    2004-09-01

    Full Text Available Amyloidosis is a syndrome characterized by deposition of a highly insoluble protein material in the extracellular space that may affect several organs. It may be generalized and idiopathic (primary amyloidosis. We describe the case of a 48 years-old woman with axonal neuropathy associated with proteinuria, whose final investigation resulted in diagnosis of primary amyloidosis (AL. She was submitted to autologous bone marrow transplantation. We discuss some aspects related to diagnosis of neuropathy and current treatment of AL.A amiloidose é uma síndrome caracterizada pela deposição no meio extracelular de material protéico altamente insolúvel e que pode afetar vários órgãos. Pode ocorrer como doença generalizada e pode ser idiopática (amiloidose primária. Descrevemos o caso de mulher de 48 anos com neuropatia axonal associada a proteinúria na qual a investigação final resultou no diagnóstico de amiloidose primária (AL. Foi submetida a transplante autólogo de medula óssea sem complicações. Discutiremos aspectos relacionados ao diagnóstico da neuropatia e do tratamento atual da AL.

  2. Understanding the Disease Course and Therapeutic Benefit of Tafamidis Across Real-World Studies of Hereditary Transthyretin Amyloidosis with Polyneuropathy: A Proof of Concept for Integrative Data Analytic Approaches.

    Science.gov (United States)

    Serrano, Daniel; Atzinger, Christopher B; Botteman, Marc F

    2018-04-02

    Hereditary transthyretin (TTR) amyloidosis with polyneuropathy (hATTR-PN) is a rare, autosomal dominant amyloidosis characterized primarily by progressive ascending sensorimotor neuropathy often associated with  autonomic involvement. hATTR-PN is caused by a mutation in the TTR gene leading to protein misfolding and amyloid accumulation in peripheral nerves and vital organs. The latest global prevalence estimates point to 10,000 cases worldwide, with an upper end of about 40,000. Tafamidis has been approved in over 40 countries for delaying neurologic disease progression in early-stage hATTR-PN. Multiple observational studies have examined clinical outcomes in hATTR-PN patients treated with tafamidis in the routine clinical setting. Integrative data analysis (IDA) is a technique for optimally constructing synthetic treatment and control cohorts from multiple independent studies, which allows meta-analysis of patient-level data. Herein, we provide a proof of concept for the application of IDA to real-world and natural history hATTR-PN data. IDA permits increased understanding of outcomes in tafamidis-treated and untreated persons with hATTR-PN by optimally pooling all available information. Summary statistics corresponding to the Neuropathy Impairment Score-Lower Limb (NIS-LL) from five published studies were pooled, converted to change from baseline means and variances, and analyzed using IDA. IDA-based synthetic cohorts were generated by averaging across studies stratified on treatment versus control cohort. Trends in change from baseline in each study and the corresponding synthetic cohorts were plotted. Patient-level data were simulated from the synthetic cohort trends in a Monte Carlo simulation to highlight the ability to contrast synthetic cohort trends using the mixed model for repeated measures (MMRM). The average sample size among the five studies was 71 (37-128) patients. The average NIS-LL trends indicated that tafamidis-treated patients experienced

  3. Asymptomatic immunoglobulin light chain amyloidosis (AL) at the time of diagnostic bone marrow biopsy in newly diagnosed patients with multiple myeloma and smoldering myeloma. A series of 144 cases and a review of the literature.

    Science.gov (United States)

    Siragusa, Sergio; Morice, William; Gertz, Morie A; Kyle, Robert A; Greipp, Philip R; Lust, John A; Witzig, Thomas E; Lacy, Martha Q; Zeldenrust, Steven R; Rajkumar, S Vincent; Russell, Stephen J; Hayman, Suzanne R; Buadi, Francis; Kumar, Shaji K; Dingli, David; Dispenzieri, Angela

    2011-01-01

    The rate of asymptomatic amyloidosis (AL) among patients with newly diagnosed multiple myeloma (MM) or smoldering multiple myeloma (SMM) is unknown. We evaluated number and clinical significance of asymptomatic AL in consecutive MM and SMM patients, not having recognition of symptomatic AL at the time of their diagnostic bone marrow biopsy. Bone marrow biopsies were stained with Congo red and considered diagnostic for AL in case of positive Congo red staining with apple-green birefringence. Biopsies from 144 patients were evaluated: 77 had a diagnosis of MM and 67 of SMM. The median age was 59 (range 26-84) years; the median follow-up was 76 months (range 0-216). Immunoglobulin isotypes were 96/144 (67%), IgG; 23/144 (16%), IgA; 12/144 (8%), light chain only; 1/77 (1%), IgD; and biclonal or indeterminate, 12/144 (8%). Fifty-eight percent (84/144) were κ restricted. The presence of amyloid was found in two cases (1%, 95% CI -0.6 to 3.2), one in MM, and one in SMM group, and none had or developed signs or symptoms suggestive of organ involvement by amyloid. Among the 142 other patients without amyloid deposition in their index bone marrow, one (0.7%, 95% CI -0.6 to 2.0) developed symptomatic AL after 119 months.

  4. Value of tissue Doppler-derived Tei index and two-dimensional speckle tracking imaging derived longitudinal strain on predicting outcome of patients with light-chain cardiac amyloidosis.

    Science.gov (United States)

    Liu, Dan; Hu, Kai; Herrmann, Sebastian; Cikes, Maja; Ertl, Georg; Weidemann, Frank; Störk, Stefan; Nordbeck, Peter

    2017-06-01

    Prognosis of patients with light-chain cardiac amyloidosis (AL-CA) is poor. Speckle tracking imaging (STI) derived longitudinal deformation parameters and Doppler-derived left ventricular (LV) Tei index are valuable predictors of outcome in patients with AL-CA. We estimated the prognostic utility of Tei index and deformation parameters in 58 comprehensively phenotyped patients with AL-CA after a median follow-up of 365 days (quartiles 121, 365 days). The primary end point was all-cause mortality. 19 (33%) patients died during follow-up. Tei index (0.89 ± 0.29 vs. 0.61 ± 0.16, p < 0.001) and E to global early diastolic strain rate ratio (E/GLSR dias ) were higher while global longitudinal systolic strain (GLS sys ) was lower in non-survivors than in survivors (all p < 0.05). Tei index, NYHA functional class, GLS sys and E/GLSR dias were independent predictors of all-cause mortality risk, and Tei index ≥0.9 (HR 7.01, 95% CI 2.43-20.21, p < 0.001) was the best predictor of poor outcome. Combining Tei index and GLS sys yielded the best results on predicting death within 1 year (100% with Tei index ≥0.9 and GLS sys ≤13%) or survival (95% with Tei index ≤0.9 and GLS sys ≥13%). We conclude that 1-year mortality risk in AL-CA patients can be reliably predicted using Tei index or deformation parameters, with combined analysis offering best performance.

  5. Dementia in hereditary cystatin C amyloidosis

    DEFF Research Database (Denmark)

    Blöndal, H; Guomundsson, G; Benedikz, Eirikur

    1989-01-01

    Nineteen cases with verified Hereditary Cystatin C Amyloid Angiopathy are presented. All of the cases had one or more cerebrovascular insults starting at the age of 20-41 years and survived from 10 days to 23 years after the first insult. Progressive dementia was a prominent clinical feature...... in seventeen cases of whom two presented with dementia. At the last examination the majority had severe dementia and severely abnormal EEG. Anti-cystatin C positive amyloid vascular and perivascular infiltrates were found. The resulting damage to the microvasculature of the brain and secondary hemorrhages...... and infarctions were considered to be an adequate explanation for the dementia in these cases. Skin biopsies can now probably be used to demonstrate cystatin C positive amyloid deposits conclusively in the tissues of these patients....

  6. Primary (AL) amyloidosis with gastrointestinal involvement

    DEFF Research Database (Denmark)

    Madsen, Lone Galmstrup; Gimsing, Peter; Schiødt, Frank V

    2009-01-01

    ). Steatorrhea (2 mild, 1 moderate, 1 severe) was found in 4 of 7 patients examined. At presentation, 9 patients had hypoalbuminemia and 6 patients had anemia. Three patients were treated with home parenteral nutrition. Five patients received conventional chemotherapy (oral melphalan and prednisone) and 5...

  7. Diffuse Pigmentation of Back and Arms: Macular Amyloidosis or Other?

    Directory of Open Access Journals (Sweden)

    Masood Asgrai

    2013-05-01

    Full Text Available The study was undertaken to answer the question that how many patients with pigmentation of back and arms actually have amyloid deposits in pathology. 44 patients presenting with diffuse pigmentation of back and arms (DPOBA were selected. Skin biopsies were performed in all cases from the affected sites. On all formalin fixed and paraffin embedded specimens, the following histochemical stains were performed: Haematoxylin and eosin (H&E, Congo red and immunohistochemical staining using anti-cytokeratin monoclonal antibody. In 9 of 44 cases (20%, amyloid deposits were found. In the remaining 35 cases (80%, H&E, Congo red and immunohistochemical staining failed to show any amyloid deposition. We were unable to find amyloid deposition in most of the patients presented with DPOBA. It seems that the signs may be attributable other disorders with similar clinical but different pathophysiologic aspects

  8. Acceleration of hippocampal atrophy rates in asymptomatic amyloidosis.

    Science.gov (United States)

    Andrews, K Abigail; Frost, Chris; Modat, Marc; Cardoso, M Jorge; Rowe, Chris C; Villemagne, Victor; Fox, Nick C; Ourselin, Sebastien; Schott, Jonathan M

    2016-03-01

    Increased rates of brain atrophy measured from serial magnetic resonance imaging precede symptom onset in Alzheimer's disease and may be useful outcome measures for prodromal clinical trials. Appropriate trial design requires a detailed understanding of the relationships between β-amyloid load and accumulation, and rate of brain change at this stage of the disease. Fifty-two healthy individuals (72.3 ± 6.9 years) from Australian Imaging, Biomarkers and Lifestyle Study of Aging had serial (0, 18 m, 36 m) magnetic resonance imaging, (0, 18 m) Pittsburgh compound B positron emission tomography, and clinical assessments. We calculated rates of whole brain and hippocampal atrophy, ventricular enlargement, amyloid accumulation, and cognitive decline. Over 3 years, rates of whole brain atrophy (p atrophy (p = 0.001, p = 0.023), and ventricular expansion (p atrophy rates were also independently associated with β-amyloid accumulation over the first 18 months (p = 0.003). Acceleration of left hippocampal atrophy rate was associated with baseline β-amyloid load across the cohort (p atrophy are associated with both baseline β-amyloid load and accumulation, and that there is presymptomatic, amyloid-mediated acceleration of hippocampal atrophy. Clinical trials using rate of hippocampal atrophy as an outcome measure should not assume linear decline in the presymptomatic phase. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. [Radiologic and clinical aspects of osteoarticular amyloidosis caused by dialysis].

    Science.gov (United States)

    Baldrati, L; Rocchi, A; Balbi, B; Bonsanto, R; Mughetti, M; Pasini, A; Feletti, C; Capponcini, C; Docci, D

    1991-06-01

    Many long-term (greater than 60 months) hemodialysis patients develop a severe osteoarticular disease, called "dialysis arthropathy", which is characterized by the deposition in bone and synovia of a new type of amyloid made mainly of beta 2-microglobulin. In the present study, 31 patients (17 males, 14 females; age 54.1 +/- 13 years), undergoing chronic hemodialysis for 60-125 months, were examined for dialysis arthropathy by means of clinics and of radiological investigations (conventional radiography and computed tomography). Sixteen patients (51.6%) had radiographic evidence of dialysis arthropathy: geodes (shoulders, 12 cases; wrists, 11; hips, 2; knees, 2) and/or destructive arthropathies (cervical spine, 13 cases, dorsolumbar spine, 2; hands, 2; hips, 1). Within 24 months, these lesions were found to progress slowly in the majority of cases. In the diagnostic process, CT should be employed in the study of spine, shoulders and hips when the lesions have not been sufficiently demonstrated by conventional radiography in the presence of evident clinical signs. Patients with dialysis arthropathy had undergone dialysis for longer periods than those without it (p less than 0.005) and showed a significantly higher incidence of both carpal tunnel syndrome (p less than 0.0005) and shoulder pain (p less than 0.005). Our findings confirm the high incidence and clinical importance of dialysis arthropathy in long-term hemodialysis patients and the value of diagnostic imaging in screening such patients for those lesions.

  10. A new amyloidosis caused by fibrillar aggregates of mutated corneodesmosin

    DEFF Research Database (Denmark)

    Caubet, Cécile; Bousset, Luc; Clemmensen, Ole

    2010-01-01

    Heterozygous nonsense mutations in the CDSN gene encoding corneodesmosin (CDSN), an adhesive protein expressed in cornified epithelia and hair follicles, cause hypotrichosis simplex of the scalp (HSS), a nonsyndromic form of alopecia. Truncated mutants of CDSN ((mut)CDSN), which bear the N...

  11. ENDEAVOUR: Phase 3 Multicenter Study of Revusiran (ALN-TTRSC) in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)

    Science.gov (United States)

    2017-12-08

    Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC); Amyloidosis, Hereditary; Amyloid Neuropathies, Familial; Amyloid Neuropathies; Amyloidosis, Hereditary, Transthyretin-Related; Familial Transthyretin Cardiac Amyloidosis

  12. An evaluation of Congo red fluorescence for the diagnosis of amyloidosis.

    Science.gov (United States)

    Clement, Cecilia G; Truong, Luan D

    2014-08-01

    Congo red stain apple-green birefringence under polarized light is the most popular method for detecting amyloid; however, it has limitations. The goal of this study was to evaluate if examination of Congo red stain by fluorescent microscopy (FM) significantly enhances the diagnostic yield. Congo red-stained tissue sections were retrospectively and prospectively examined by light microscopy (LM) with and without polarizer and by FM using the Texas red filter and results by each method compared. Congo red-stained amyloid recognized by LM was unequivocally and easily identified by FM in each of 48 cases. In 22 of them, FM either confirmed the presence of a small amount of amyloid or lead to a definitive diagnosis, which was otherwise missed. Eight cases with Congo red-negative by LM were also negative by FM. In 8 cases with a false-positive Congo red stain, FM still detected the signal in 5, but it was absent in 3 cases. In conclusion, Congo red fluorescence improves the diagnostic yield of LM for both positive and negative cases. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Colchicine therapy in amyloidosis related with plasmacytic castleman disease presenting with nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Saime Paydas

    2015-01-01

    Full Text Available Castleman disease (CD is a neoplasm that presents with single or multiple lymphadenopathy. The disease is characterized by fever, weight loss, anemia, polyclonal hyperglobulinemia, splenomegaly, thrombocytosis and peripheral lymphadenopathy. In this paper, we report a young man with plasmacytic type CD and amyloid A (AA deposition who presented with intra-abdominal mass and nephrotic syndrome. He was successfully treated with colchicine following surgery.

  14. The genetic heterogeneity of hereditary transthyretin amyloidosis in a sample of the Brazilian population.

    Science.gov (United States)

    Lavigne-Moreira, Carolina; Marques, Vanessa Daccach; Magno Gonçalves, Marcus V; Fernandes de Oliveira, Mauricio; Tomaselli, Pedro J; Nunez, José; Moreira do Nascimento, Osvaldo J; Barreira, Amilton Antunes; Marques, Wilson

    2018-03-09

    To present the genetic heterogeneity of a sample of the Brazilian population with TTR mutations. This cohort study was descriptive and retrospective, and enrolled patients with peripheral neuropathy of unknown cause that were found to have a mutation in the TTR gene during the process of etiological investigation, between July 1997 to January 2016. Over the study period, 129 point mutations were identified in 448 tested patients, of whom 128 were of Brazilian origin. The TTR Val30Met mutation was identified in 116 patients (90,6%); while seven (4,7%) patients had a pathogenic non-TTR mutation and seven (4,7%) carried non-pathogenic mutations (4.7%). The four non-TTRMet30 pathogenic mutations were TTR Aps38Tyr; TTR Ile107Val; TTR Val71Ala; and TTR Val122Ile. In the non-pathogenic group, we only found two mutations, including TTR Gly6Ser and TTR Thr119Thr. Our study depicts a scenario of greater genetic heterogeneity among Brazilian hATTR patients with FAP. We expect that this number will grow fast over a short period of time, due to increasing availability of genetic tests, increasing knowledge of the disease and the multivariate origin of our population. This article is protected by copyright. All rights reserved.

  15. Cellular processing of the amyloidogenic cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Merz, G S; Schwenk, V

    1999-01-01

    An important gap in our understanding of the pathogenesis of the amyloidoses is the identification of the cellular events that lead from synthesis of an amyloid precursor protein to its conversion to the amyloid fiber subunit. We address this question by characterizing the effects of an amyloidog......An important gap in our understanding of the pathogenesis of the amyloidoses is the identification of the cellular events that lead from synthesis of an amyloid precursor protein to its conversion to the amyloid fiber subunit. We address this question by characterizing the effects...

  16. Kidney Involvement in Systemic Calcitonin Amyloidosis Associated With Medullary Thyroid Carcinoma

    NARCIS (Netherlands)

    Koopman, Timco; Niedlich-den Herder, Cindy; Stegeman, Coen A.; Links, Thera P.; Bijzet, Johan; Hazenberg, Bouke P. C.; Diepstra, Arjan

    A 52-year-old woman with widely disseminated medullary thyroid carcinoma developed nephrotic syndrome and slowly decreasing kidney function. A kidney biopsy was performed to differentiate between malignancy-associated membranous glomerulopathy and tyrosine kinase inhibitor-induced focal segmental

  17. Type I primary neuropathic amyloidosis (Andrade, Portuguese: a clinical and laboratory study of 21 cases

    Directory of Open Access Journals (Sweden)

    Eduardo M. Azevedo

    1975-06-01

    Full Text Available The authors present a review of 21 cases with the diagnosis of type I amyloid neuropathy based on epidemiological data, clinical evolution and histopathological findings. They call attention to the possibility of cranial nerves involvement (hyposmia, diplopia, masseterian hypotrophy, peripheral facial paralysis, hypoacusis, dysphonia, laryngeal paralysis, dysphagia, and trapezium muscle hypotrophy, to the severeness of the digestive symptoms, to the precocity of the autonomic disorders, and to the rather high incidence (6 cases of heart involvement. The electromyography showed anterior horn involvement in 3 cases. The electrocardiography showed repolarization disorders in 11 cases, left ventricular overload in 6 cases and atrioventricular block in 5 cases. The serum proteins electrophoresis showed frequent abnormalities, but no typical curve could be obtained. The barium-contrasted X-rays of the gastrointestinal tract showed no anatomical lesions, but functional abnormalities (hypo or hypermotility were found in 14 examinations. The Schilling test showed impairment of vitamin B12 absorption in 50% of the cases. However, with the concomitant administration of intrinsic factor (3 cases there was improvement of its absorption. This proves that the gastric mucosa plays an important role in the disease malabsorption. The test with labeled-triolein showed slow absorption in 2 cases and steatorrhea in 3 (6 tests. For the confirmation of the amyloid deposits, the best histopathological procedure was nerve biopsy. In men, when the nerve biopsy was negative, testicular biopsy has shown to be a good option.

  18. Recommendations for presymptomatic genetic testing and management of individuals at risk for hereditary transthyretin amyloidosis

    NARCIS (Netherlands)

    Obici, Laura; Kuks, Jan B.; Buades, Juan; Adams, David; Suhr, Ole B.; Coelho, Teresa; Kyriakides, Theodore

    Purpose of review These recommendations highlight recent experience in genetic counselling for the severe autosomal-dominant, late-onset transthyretin familial amyloid polyneuropathy (TTR-FAP) disease, and present a structured approach towards identification and monitoring of asymptomatic carriers

  19. Multiple factors contribute to the peripheral induction of cerebral beta-amyloidosis

    NARCIS (Netherlands)

    Eisele, Y.S.; Fritschi, S.K.; Hamaguchi, T.; Obermuller, U.; Fuger, P.; Skodras, A.; Schafer, C.; Odenthal, J.; Heikenwalder, M.; Staufenbiel, M.; Jucker, M.

    2014-01-01

    Deposition of aggregated amyloid-beta (Abeta) peptide in brain is an early event and hallmark pathology of Alzheimer's disease and cerebral Abeta angiopathy. Experimental evidence supports the concept that Abeta multimers can act as seeds and structurally corrupt other Abeta peptides by a

  20. Primary cutaneous amyloidosis involving the external ears along with the classical sites

    Directory of Open Access Journals (Sweden)

    Khaitan Binod

    2001-01-01

    Full Text Available A 26- year- old woman had multiple itchy persistent gradually progressive papular lesions on the forearms and shins for 10 and 4 years respectively. She also noticed similar lesions on both the ears for 4 years. There were no systemic symptoms. Cutaneous examination revealed multiple 2-3 mm discrete firm hyperpigmented papules on the extensors of forearms, shins and earlobes. Skin biopsy from all sites demonstrated deposits of amyloid in the papillary dermis. The patient was treated with cyclophosphamide 50 mg daily orally. There was more than 50% improvement in her lesions.

  1. Cathepsin B Improves ß-Amyloidosis and Learning and Memory in Models of Alzheimer's Disease.

    Science.gov (United States)

    Embury, Christine M; Dyavarshetty, Bhagyalaxmi; Lu, Yaman; Wiederin, Jayme L; Ciborowski, Pawel; Gendelman, Howard E; Kiyota, Tomomi

    2017-06-01

    Amyloid-ß (Aß) precursor protein (APP) metabolism engages neuronal endolysosomal pathways for Aß processing and secretion. In Alzheimer's disease (AD), dysregulation of APP leads to excess Aß and neuronal dysfunction; suggesting that neuronal APP/Aß trafficking can be targeted for therapeutic gain. Cathepsin B (CatB) is a lysosomal cysteine protease that can lower Aß levels. However, whether CatB-modulation of Aß improves learning and memory function deficits in AD is not known. To this end, progenitor neurons were infected with recombinant adenovirus expressing CatB and recovered cell lysates subjected to proteomic analyses. The results demonstrated Lamp1 deregulation and linkages between CatB and the neuronal phagosome network. Hippocampal injections of adeno-associated virus expressing CatB reduced Aß levels, increased Lamp1 and improved learning and memory. The findings were associated with the emergence of c-fos + cells. The results support the idea that CatB can speed Aß metabolism through lysosomal pathways and as such reduce AD-associated memory deficits.

  2. White matter hyperintensities and cerebral amyloidosis: necessary and sufficient for clinical expression of Alzheimer disease?

    Science.gov (United States)

    Provenzano, Frank A; Muraskin, Jordan; Tosto, Giuseppe; Narkhede, Atul; Wasserman, Ben T; Griffith, Erica Y; Guzman, Vanessa A; Meier, Irene B; Zimmerman, Molly E; Brickman, Adam M

    2013-04-01

    Current hypothetical models emphasize the importance of β-amyloid in Alzheimer disease (AD) pathogenesis, although amyloid alone is not sufficient to account for the dementia syndrome. The impact of small-vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging scans, may be a key factor that contributes independently to AD presentation. To determine the impact of WMHs and Pittsburgh Compound B (PIB) positron-emission tomography-derived amyloid positivity on the clinical expression of AD. Baseline PIB-positron-emission tomography values were downloaded from the Alzheimer's Disease Neuroimaging Initiative database. Total WMH volume was derived on accompanying structural magnetic resonance imaging data. We examined whether PIB positivity and total WMHs predicted diagnostic classification of patients with AD (n = 20) and control subjects (n = 21). A second analysis determined whether WMHs discriminated between those with and without the clinical diagnosis of AD among those who were classified as PIB positive (n = 28). A third analysis examined whether WMHs, in addition to PIB status, could be used to predict future risk for AD among subjects with mild cognitive impairment (n = 59). The Alzheimer's Disease Neuroimaging Initiative public database. The study involved data from 21 normal control subjects, 59 subjects with mild cognitive impairment, and 20 participants with clinically defined AD from the Alzheimer Disease's Neuroimaging Initiative database. Clinical AD diagnosis and WMH volume. Pittsburgh Compound B positivity and increased total WMH volume independently predicted AD diagnosis. Among PIB-positive subjects, those diagnosed as having AD had greater WMH volume than normal control subjects. Among subjects with mild cognitive impairment, both WMH and PIB status at baseline conferred risk for future diagnosis of AD. White matter hyperintensities contribute to the presentation of AD and, in the context of significant amyloid deposition, may provide a second hit necessary for the clinical manifestation of the disease. As risk factors for the development of WMHs are modifiable, these findings suggest intervention and prevention strategies for the clinical syndrome of AD.

  3. Primary extranodal marginal zone B-cell lymphoma with AL amyloidosis in cerebral parenchyma in an immunocompetent patient

    Directory of Open Access Journals (Sweden)

    Tadashi Terada, M.D., Ph.D.

    2015-09-01

    Full Text Available Herein reported is an extremely rare case of primary MALT lymphoma of cerebral parenchyma. A 79-year-old man presented with paresis. Imaging modalities identified a tumor measuring 3 cm in diameter in right cerebral parenchyma. An operation completely resected the tumor. Macroscopically, the tumor was well defined, but showed mild infiltrative features. Histologically, the tumor showed proliferation of small atypical lymphocytes separated by fibrous septae with AL amyloid depositions. No apparent plasma cell differentiation was seen. The tumor cells showed monotonous appearances with hyperchromatic nuclei but without nucleoli and nuclear indentations. Immunoblastic cells were scattered. Immunohistochemically, tumor cells were positive for vimentin, CD45, CD20, CD79α, bcl-2, CD3 (focal, CD45RO (focal, CD5 (focal, CD10, CD23, bcl-6, CD138, p53, and Ki-67 (labeling = 27%. The immunoblastic cells were positive for CD30. The lymphoid cells were negative for Epstein–Barr virus (EBV-related molecules of EBV latent membrane protein-1 (LMP-1 and EBV early RNAs (EBER. They were also negative for cytokeratins AE 1/3 and CAM5.2, cyclin D1, CD34, GFAP, α-smooth muscle actin, and S100 protein. Because of the heterogeneity of tumor cells and positive AL amyloid deposition, the author diagnosed it as primary MALT lymphoma. The patient is now free from tumors. Differential diagnosis was discussed.

  4. Effects of collagen-induced rheumatoid arthritis on amyloidosis and microvascular pathology in APP/PS1 mice

    Directory of Open Access Journals (Sweden)

    Moon Gyeong

    2011-10-01

    Full Text Available Abstract Background Evidence suggests that rheumatoid arthritis (RA may enhance or reduce the progression of Alzheimer's disease (AD. The present study was performed to directly explore the effects of collagen-induced rheumatoid arthritis (CIA on amyloid plaque formation, microglial activation, and microvascular pathology in the cortex and hippocampus of the double transgenic APP/PS1 mouse model for AD. Wild-type or APP/PS1 mice that received type II collagen (CII in complete Freund's adjuvant (CFA at 2 months of age revealed characteristics of RA, such as joint swelling, synovitis, and cartilage and bone degradation 4 months later. Joint pathology was accompanied by sustained induction of IL-1β and TNF-α in plasma over 4 weeks after administration of CII in CFA. Results CIA reduced levels of soluble and insoluble amyloid beta (Aβ peptides and amyloid plaque formation in the cortex and hippocampus of APP/PS1 mice, which correlated with increased blood brain barrier disruption, Iba-1-positive microglia, and CD45-positive microglia/macrophages. In contrast, CIA reduced vessel density and length with features of microvascular pathology, including vascular segments, thinner vessels, and atrophic string vessels. Conclusions The present findings suggest that RA may exert beneficial effects against Aβ burden and harmful effects on microvascular pathology in AD.

  5. Preclinical Validation of the Heparin-Reactive Peptide p5+14 as a Molecular Imaging Agent for Visceral Amyloidosis

    Directory of Open Access Journals (Sweden)

    Jonathan S. Wall

    2015-04-01

    Full Text Available Amyloid is a complex pathologic matrix comprised principally of paracrystalline protein fibrils and heparan sulfate proteoglycans. Systemic amyloid diseases are rare, thus, routine diagnosis is often challenging. The glycosaminoglycans ubiquitously present in amyloid deposits are biochemically and electrochemically distinct from those found in the healthy tissues due to the high degree of sulfation. We have exploited this unique property and evaluated heparin-reactive peptides, such as p5+14, as novel agents for specifically targeting and imaging amyloid. Herein, we demonstrate that radiolabeled p5+14 effectively bound murine AA amyloid in vivo by using molecular imaging. Biotinylated peptide also reacted with the major forms of human amyloid in tissue sections as evidenced immunohistochemically. Furthermore, we have demonstrated that the peptide also binds synthetic amyloid fibrils that lack glycosaminoglycans implying that the dense anionic motif present on heparin is mimicked by the amyloid protein fibril itself. These biochemical and functional data support the translation of radiolabeled peptide p5+14 for the clinical imaging of amyloid in patients.

  6. Acquired von Willebrand Syndrome associated to secondary IgM MGUS emerging after Autologous Stem Cell Transplantation for AL Amyloidosis

    Directory of Open Access Journals (Sweden)

    Victor H Jimenez-Zepeda

    2017-05-01

    Full Text Available Acquired von Willebrand syndrome (AVWS is a rare hemorrhagic disorder that occurs in patients with no prior personal or family history of bleeding. Here, we describe a case of AVWS occurring after autologous stem cell transplantation (ASCT. Interestingly, AVWS developed after bortezomib-based induction and conditioning regimens. Recent evidence suggests that the proximity of the bortezomib therapy to the collection of stem cells with consequent depletion of regulatory T cells after the conditioning regimen could explain some of the unusual autoimmune complications reported in patients receiving bortezomib prior to ASCT. In addition, this patient developed a secondary MGUS post-ASCT, which may have also contributed to the AVWS. To the best of our knowledge, this is the first case of post-ASCT AVWS reported. Prospective data is needed to better elucidate the mechanisms by which these unusual complications occur in patients receiving bortezomib prior to ASCT.

  7. State of Oral Mucosa as an Additional Symptom in the Course of Primary Amyloidosis and Multiple Myeloma Disease

    Directory of Open Access Journals (Sweden)

    Maciej R. Czerniuk

    2014-01-01

    Full Text Available Multiple myeloma (myeloma multiplex (MM is a malignant non-Hodgkin’s lymphoma derived from B cell. Its essence is a malignant clone of plasma cells synthesizing growth of monoclonal immunoglobulin, which infiltrate the bone marrow, destroy the bone structure, and prevent the proper production of blood cells components. The paper presents a case of 62-year-old patient who developed symptoms in addition to neurological and haematological changes in the oral mucosa in the course of multiple myeloma. The treatment resulted in partial improvement. The authors wish to draw attention not only to nonspecificity and rarity of changes in the mouth which can meet the dentist but also to the complexity of the multidisciplinary therapy patients diagnosed with MM.

  8. DHA supplemented in peptamen diet offers no advantage in pathways to amyloidosis: is it time to evaluate composite lipid diet?

    Directory of Open Access Journals (Sweden)

    Zareen Amtul

    Full Text Available Numerous reports have documented the beneficial effects of dietary docosahexaenoic acid (DHA on beta-amyloid production and Alzheimer's disease (AD. However, none of these studies have examined and compared DHA, in combination with other dietary nutrients, for its effects on plaque pathogenesis. Potential interactions of DHA with other dietary nutrients and fatty acids are conventionally ignored. Here we investigated DHA with two dietary regimes; peptamen (pep+DHA and low fat diet (low fat+DHA. Peptamen base liquid diet is a standard sole-source nutrition for patients with gastrointestinal dysfunction. Here we demonstrate that a robust AD transgenic mouse model shows an increased tendency to produce beta-amyloid peptides and amyloid plaques when fed a pep+DHA diet. The increase in beta-amyloid peptides was due to an elevated trend in the levels of beta-secretase amyloid precursor protein (APP cleaving enzyme (BACE, the proteolytic C-terminal fragment beta of APP and reduced levels of insulin degrading enzyme that endoproteolyse beta-amyloid. On the contrary, TgCRND8 mice on low fat+DHA diet (based on an approximately 18% reduction of fat intake ameliorate the production of abeta peptides and consequently amyloid plaques. Our work not only demonstrates that DHA when taken with peptamen may have a tendency to confer a detrimental affect on the amyloid plaque build up but also reinforces the importance of studying composite lipids or nutrients rather than single lipids or nutrients for their effects on pathways important to plaque development.

  9. Magnetization transfer contrast imaging detects early white matter changes in the APP/PS1 amyloidosis mouse model

    Directory of Open Access Journals (Sweden)

    Jelle Praet

    2016-01-01

    Full Text Available While no definitive cure for Alzheimer's disease exists yet, currently available treatments would benefit greatly from an earlier diagnosis. It has previously been shown that Magnetization transfer contrast (MTC imaging is able to detect amyloid β plaques in old APP/PS1 mice. In the current study we investigated if MTC is also able to visualize early amyloid β (Aβ induced pathological changes. In a cross-sectional study, a comparison was made between the MT ratio of wild type (WT and APP/PS1 mice at 2, 4, 6, 8 and 24 months of age. We observed an increased MT-ratio in the cortex of 24 month old APP/PS1 mice as compared to WT mice. However, when comparing the MT-ratio of the cortex of WT mice with the MT-ratio of the APP/PS1 mice at 2, 4, 6 or 8 months of age, no significant changes could be observed. In contrast to the cortex, we consistently observed a decreased MT-ratio in the splenium of 4, 6 and 8 month old APP/PS1 mice as compared to age-matched WT mice. Lastly, the decreased MT-ratio in the splenium of APP/PS1 mice correlated to the Aβ plaque deposition, astrogliosis and microgliosis. This MT-ratio decrease did however not correlate to the myelin content. Combined, our results suggest that MTC is able to visualize early Aβ-induced changes in the splenium but not the cortex of APP/PS1 mice.

  10. (99m)Tc-aprotinin - optimisation and validation of radiolabelling kits for routine preparation for diagnostic imaging of amyloidosis

    DEFF Research Database (Denmark)

    Denholt, Charlotte; Gillings, Nic

    2016-01-01

    Technetium-99m aprotinin was prepared from an optimised radiolabelling kit formulation containing aprotinin, alkaline buffer and stannous chloride (reducing agent) and radiolabelled using (99m) Tc-pertechnetate. The labelling was achieved within 25 min, with radiochemical purities of >98%....

  11. Activation of neuronal defense mechanisms in response to pathogenic factors triggering induction of amyloidosis in Alzheimer's disease.

    Science.gov (United States)

    Maltsev, Alexander V; Santockyte, Rasa; Bystryak, Simon; Galzitskaya, Oxana V

    2014-01-01

    We present a new model for etiology of Alzheimer's disease (AD) which postulates early involvement of specialized neuroprotective mechanisms in the pathology of AD. These neuroprotective mechanisms work in concert to regulate metabolic homeostasis in healthy neuronal cells, but contribute to the distinctive cytopathic phenotype of neuronal degeneration in AD. According to this model, two molecular/genetic hallmarks of AD, amyloid-β (Aβ) deposition and tau hyperphosphorylation, are associated with neuronal mechanisms for dissipating thermal energy associated with high levels of protein synthesis in highly temperature-sensitive neuronal cells. Development of effective methods of AD treatment will require a better understanding of how this neuronal defense system is activated in response to cytopathological triggers in sporadic AD. The cause and effect link between synthesis and processing of amyloid-β protein precursor (AβPP) and the AD terminal phenotype of neurofibrillary tangles and neuron loss involve the formation of Aβ peptides that accumulate as oligomers, cannot be controlled by neurons, and are toxic to the surrounding neuronal membranes. We analyze experimental and clinical studies that have investigated the correlation between phosphorylation of some transport proteins and increased synthesis of proteins in neurons. We also review the evidence related to the possibility that protein hyperphosphorylation may be a byproduct of energetic imbalances in AD cells associated with high levels of protein synthesis, and that activation of defense systems, through which energy-rich molecules are eliminated from the site of protein synthesis and are sequestered to the peripheral neuronal areas, may bring about some of the distinctive morphological features of AD.

  12. AJNT volume 5 issue 3 [Sep 2012].indd

    African Journals Online (AJOL)

    exclusion of other causes of secondary amyloidosis. The patient finally died due to heart failure and acute pulmonary edema. Conclusion: Long standing RHD can lead to secondary. AA amyloidosis. Keywords: AA Amyloidosis; Kidney Biopsy; Rheumatic. Heart Disease; Renal Amyloidosis. The authors declared no conflict ...

  13. Amyloidoses as seen by the Rheumatologist

    Directory of Open Access Journals (Sweden)

    J.Ch Gerster

    2011-09-01

    Full Text Available Amyloidosis is due to extracellular deposition in various organs and tissues of amorphous materials made of protein fibrils, whose thickness is 10 nm. Seventeen different amyloid fibrils are known (1. Amyloidosis can be localised or systemic. There are 4 systemic amyloidoses (2: Familial amyloidosis with mutated transthyretin. Primary, paraprotein associated, amyloidosis AL. Secondary AA amyloidosis in long- standing inflammation. β2-microglobulin...

  14. Complex interplay between brain function and structure during cerebral amyloidosis in APP transgenic mouse strains revealed by multi-parametric MRI comparison.

    Science.gov (United States)

    Grandjean, Joanes; Derungs, Rebecca; Kulic, Luka; Welt, Tobias; Henkelman, Mark; Nitsch, Roger M; Rudin, Markus

    2016-07-01

    Alzheimer's disease is a fatal neurodegenerative disorder affecting the aging population. Neuroimaging methods, in particular magnetic resonance imaging (MRI), have helped reveal alterations in the brain structure, metabolism, and function of patients and in groups at risk of developing AD, yet the nature of these alterations is poorly understood. Neuroimaging in mice is attractive for investigating mechanisms underlying functional and structural changes associated with AD pathology. Several preclinical murine models of AD have been generated based on transgenic insertion of human mutated APP genes. Depending on the specific mutations, mouse strains express different aspects of amyloid pathology, e.g. intracellular amyloid-β (Aβ) aggregates, parenchymal plaques, or cerebral amyloid angiopathy. We have applied multi-parametric MRI in three transgenic mouse lines to compare changes in brain function with resting-state fMRI and structure with diffusion tensor imaging and high resolution anatomical imaging. E22ΔAβ developing intracellular Aβ aggregates did not present functional or structural alterations compared to their wild-type littermates. PSAPP mice displaying parenchymal amyloid plaques displayed mild functional changes within the supplementary and barrel field cortices, and increased isocortical volume relative to controls. Extensive reduction in functional connectivity in the sensory-motor cortices and within the default mode network, as well as local volume increase in the midbrain relative to wild-type have been observed in ArcAβ mice bearing intracellular Aβ aggregates as well as parenchymal and vascular amyloid deposits. Patterns of functional and structural changes appear to be strain-specific and not directly related to amyloid deposition. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Complex interplay between brain function and structure during cerebral amyloidosis in APP transgenic mouse strains revealed by multi-parametric MRI comparison.

    OpenAIRE

    Grandjean J.; Derungs R.; Kulic L.; Welt T.; Henkerlmann M.; Nitsch R.M.; Rudin M.

    2016-01-01

    Alzheimer's disease is a fatal neurodegenerative disorder affecting the aging population. Neuroimaging methods in particular magnetic resonance imaging (MRI) have helped reveal alterations in the brain structure metabolism and function of patients and in groups at risk of developing AD yet the nature of these alterations is poorly understood. Neuroimaging in mice is attractive for investigating mechanisms underlying functional and structural changes associated with AD pathology. Several precl...

  16. Perinatal Choline Supplementation Reduces Amyloidosis and Increases Choline Acetyltransferase Expression in the Hippocampus of the APPswePS1dE9 Alzheimer's Disease Model Mice.

    Directory of Open Access Journals (Sweden)

    Tiffany J Mellott

    Full Text Available Prevention of Alzheimer's disease (AD is a major goal of biomedical sciences. In previous studies we showed that high intake of the essential nutrient, choline, during gestation prevented age-related memory decline in a rat model. In this study we investigated the effects of a similar treatment on AD-related phenotypes in a mouse model of AD. We crossed wild type (WT female mice with hemizygous APPswe/PS1dE9 (APP.PS1 AD model male mice and maintained the pregnant and lactating dams on a control AIN76A diet containing 1.1 g/kg of choline or a choline-supplemented (5 g/kg diet. After weaning all offspring consumed the control diet. As compared to APP.PS1 mice reared on the control diet, the hippocampus of the perinatally choline-supplemented APP.PS1 mice exhibited: 1 altered levels of amyloid precursor protein (APP metabolites-specifically elevated amounts of β-C-terminal fragment (β-CTF and reduced levels of solubilized amyloid Aβ40 and Aβ42 peptides; 2 reduced number and total area of amyloid plaques; 3 preserved levels of choline acetyltransferase protein (CHAT and insulin-like growth factor II (IGF2 and 4 absence of astrogliosis. The data suggest that dietary supplementation of choline during fetal development and early postnatal life may constitute a preventive strategy for AD.

  17. Exercise-Stress Echocardiography Reveals Systolic Anterior Motion of the Mitral Valve as a Cause of Syncopes in a Cardiac Amyloidosis Patient

    DEFF Research Database (Denmark)

    Clemmensen, Tor Skibsted; Mølgaard, Henning; Andersen, Niels Frost

    2016-01-01

    increased left ventricular outflow track (LVOT) velocity. However, bicycle exercise-stress test with simultaneous echocardiography revealed a stepwise decrease in blood pressure, a substantial increase in the LVOT velocity, and severe systolic anterior motion of the mitral valve. The patients' symptoms were...

  18. Enalapril Alone or Co-Administered with Losartan Rescues Cerebrovascular Dysfunction, but not Mnemonic Deficits or Amyloidosis in a Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Ongali, Brice; Nicolakakis, Nektaria; Tong, Xing-Kang; Aboulkassim, Tahar; Imboden, Hans; Hamel, Edith

    2016-01-01

    The co-administration of angiotensin converting enzyme inhibitors (ACEi) and angiotensin II (AngII) receptor blockers (ARB) that bind angiotensin type 1 receptors (AT1R) may protect from Alzheimer's disease (AD) better than each treatment taken alone. We tested the curative potential of the non brain-penetrant ACEi enalapril (3 mg/kg/day) administered for 3 months either alone or in combination with the brain penetrant ARB losartan (10 mg/kg/day) in aged (∼15 months) transgenic mice overexpressing a mutated form of the human amyloid-β protein precursor (AβPP, thereafter APP mice). We studied cerebrovascular function, protein levels of oxidative stress markers (superoxide dismutases SOD1, SOD2 and the NADPH oxidase subunit p67phox), amyloid-β (Aβ) pathology, astrogliosis, cholinergic innervation, AT1R and angiotensin IV receptor (AT4R) levels, together with cognitive performance. Both treatments normalized cerebrovascular reactivity and p67phox protein levels, but they did not reduce the cerebrovascular levels of SOD1. Combined treatment normalized cerebrovascular SOD2 levels, significantly attenuated astrogliosis, but did not reduce the increased levels of cerebrovascular AT1R. Yet, combined therapy enhanced thioflavin-S labeled Aβ plaque burden, a tendency not significant when Aβ1 - 42 plaque load was considered. None of the treatments rescued cognitive deficits, cortical AT4R or cholinergic innervation. We conclude that both treatments normalized cerebrovascular function by inhibiting the AngII-induced oxidative stress cascade, and that the positive effects of the combined therapy on astrogliosis were likely due to the ability of losartan to enter brain parenchyma. However, enalapril did not potentiate, and may even dampen, the reported cognitive benefits of losartan, raising caution when selecting the most appropriate antihypertensive therapy in AD patients.

  19. Aerobic Glycolysis in the Frontal Cortex Correlates with Memory Performance in Wild-Type Mice But Not the APP/PS1 Mouse Model of Cerebral Amyloidosis.

    Science.gov (United States)

    Harris, Richard A; Tindale, Lauren; Lone, Asad; Singh, Olivia; Macauley, Shannon L; Stanley, Molly; Holtzman, David M; Bartha, Robert; Cumming, Robert C

    2016-02-10

    Aerobic glycolysis and lactate production in the brain plays a key role in memory, yet the role of this metabolism in the cognitive decline associated with Alzheimer's disease (AD) remains poorly understood. Here we examined the relationship between cerebral lactate levels and memory performance in an APP/PS1 mouse model of AD, which progressively accumulates amyloid-β. In vivo (1)H-magnetic resonance spectroscopy revealed an age-dependent decline in lactate levels within the frontal cortex of control mice, whereas lactate levels remained unaltered in APP/PS1 mice from 3 to 12 months of age. Analysis of hippocampal interstitial fluid by in vivo microdialysis revealed a significant elevation in lactate levels in APP/PS1 mice relative to control mice at 12 months of age. An age-dependent decline in the levels of key aerobic glycolysis enzymes and a concomitant increase in lactate transporter expression was detected in control mice. Increased expression of lactate-producing enzymes correlated with improved memory in control mice. Interestingly, in APP/PS1 mice the opposite effect was detected. In these mice, increased expression of lactate producing enzymes correlated with poorer memory performance. Immunofluorescent staining revealed localization of the aerobic glycolysis enzymes pyruvate dehydrogenase kinase and lactate dehydrogenase A within cortical and hippocampal neurons in control mice, as well as within astrocytes surrounding amyloid plaques in APP/PS1 mice. These observations collectively indicate that production of lactate, via aerobic glycolysis, is beneficial for memory function during normal aging. However, elevated lactate levels in APP/PS1 mice indicate perturbed lactate processing, a factor that may contribute to cognitive decline in AD. Lactate has recently emerged as a key metabolite necessary for memory consolidation. Lactate is the end product of aerobic glycolysis, a unique form of metabolism that occurs within certain regions of the brain. Here we detected an age-dependent decline in the expression of aerobic glycolysis enzymes and a concomitant decrease in lactate levels within the frontal cortex of wild-type mice. Improved memory performance in wild-type mice correlated with elevated expression of aerobic glycolysis enzymes. Surprisingly, lactate levels remained elevated with age and increased aerobic glycolysis enzyme expression correlated with poorer memory performance in APP/PS1 mice. These findings suggest that while lactate production is beneficial for memory in the healthy aging brain, it might be detrimental in an Alzheimer's disease context. Copyright © 2016 the authors 0270-6474/16/361871-08$15.00/0.

  20. 12/15-Lipoxygenase Inhibition Reverses Cognitive Impairment, Brain Amyloidosis, and Tau Pathology by Stimulating Autophagy in Aged Triple Transgenic Mice.

    Science.gov (United States)

    Di Meco, Antonio; Li, Jian-Guo; Blass, Benjamin E; Abou-Gharbia, Magid; Lauretti, Elisabetta; Praticò, Domenico

    2017-01-15

    The 12/15-lipoxygenase (12/15-LO) enzyme is upregulated in the brains of patients with Alzheimer's disease (AD), and its expression levels influence the onset of the AD-like phenotype in mouse models. However, whether targeting this pathway after the neuropathology and behavioral impairments have been established remains to be investigated. Triple transgenic (3xTg) mice received either PD146176-a selective and specific pharmacological inhibitor of 12/15-LO-or placebo starting at 12 months of age for 12 weeks. They were then assessed for the effect of the treatment on neuropathologies and behavioral impairments. At the end of the study, mice in the control group showed a worsening of memory and learning abilities, whereas mice receiving PD146176 were undistinguishable from wild-type mice. The same group also had significantly lower amyloid beta levels and deposition, less tau neuropathology, increased synaptic integrity, and autophagy activation. Ex vivo and in vitro genetic and pharmacological studies found that the mechanism involved in these effects was the activation of neuronal autophagy. Our findings provide new insights into the disease-modifying action of 12/15-LO pharmacological inhibition and establish it as a viable therapeutic approach for patients with AD. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Dietary nucleosides and nucleotides do not affect tumor incidence but reduce amyloidosis incidence in B6C3F1 mice irradiated with californium-252.

    Science.gov (United States)

    Yokoyama, Hiroomi; Fujiwara, Hiroshi; Watanabe, Hiromitsu

    2004-04-01

    We investigated the effects of a dietary mixture of nucleosides and nucleotides (NS) on the systemic incidence rates of postirradiation carcinogenesis and non-neoplastic lesions in mice. Five-week-old male B6C3F1 mice were fed AIN-76B Purified Diet supplemented with NS for 1 wk and 13 mo before and after irradiation of neutron with californium-252 ((252)Cf); specifically NS was added to the AIN-76B Purified Diet (without nucleotide) to obtain a final concentration of 0%, 0.5%, or 2.5% NS. A commercial stock diet was also given to mice, and half of the mice were irradiated. Both irradiated and non-irradiated mice were used for reference controls. The incidence of liver tumors in each NS group was lower than that in the reference control group (P 252)Cf irradiation.

  2. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis

    NARCIS (Netherlands)

    van der Heijden, Roel A; Bijzet, Johan; Meijers, Wouter C; Yakala, Gopala K; Kleemann, Robert; Nguyen, Tri Q|info:eu-repo/dai/nl/304820482; de Boer, Rudolf A; Schalkwijk, Casper G; Hazenberg, Bouke P C; Tietge, Uwe J F; Heeringa, Peter

    2015-01-01

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal

  3. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis

    OpenAIRE

    Heijden, R.A. van der; Bijzet, J.; Meijers, W.C.; Yakala, G.K.; Kleemann, R.; Nguyen, T.Q.; Boer, R.A. de; Schalkwijk, C.G.; Hazenberg, B.P.C.; Tietge, U.J.F.; Heeringa, P.

    2015-01-01

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features i...

  4. Immunoelectrophoresis - blood

    Science.gov (United States)

    IEP - serum; Immunoglobulin electrophoresis - blood; Gamma globulin electrophoresis; Serum immunoglobulin electrophoresis; Amyloidosis - electrophoresis serum; Multiple myeloma - serum electrophoresis; Waldenström - serum electrophoresis

  5. Type I primary neuropathic amyloidosis (Andrade, Portuguese: a clinical and laboratory study of 21 cases Neuropatia amilóide primária tipo I (Andrade, Portuguesa: estudo clínico e laboratorial de 21 casos

    Directory of Open Access Journals (Sweden)

    Eduardo M. Azevedo

    1975-06-01

    Full Text Available The authors present a review of 21 cases with the diagnosis of type I amyloid neuropathy based on epidemiological data, clinical evolution and histopathological findings. They call attention to the possibility of cranial nerves involvement (hyposmia, diplopia, masseterian hypotrophy, peripheral facial paralysis, hypoacusis, dysphonia, laryngeal paralysis, dysphagia, and trapezium muscle hypotrophy, to the severeness of the digestive symptoms, to the precocity of the autonomic disorders, and to the rather high incidence (6 cases of heart involvement. The electromyography showed anterior horn involvement in 3 cases. The electrocardiography showed repolarization disorders in 11 cases, left ventricular overload in 6 cases and atrioventricular block in 5 cases. The serum proteins electrophoresis showed frequent abnormalities, but no typical curve could be obtained. The barium-contrasted X-rays of the gastrointestinal tract showed no anatomical lesions, but functional abnormalities (hypo or hypermotility were found in 14 examinations. The Schilling test showed impairment of vitamin B12 absorption in 50% of the cases. However, with the concomitant administration of intrinsic factor (3 cases there was improvement of its absorption. This proves that the gastric mucosa plays an important role in the disease malabsorption. The test with labeled-triolein showed slow absorption in 2 cases and steatorrhea in 3 (6 tests. For the confirmation of the amyloid deposits, the best histopathological procedure was nerve biopsy. In men, when the nerve biopsy was negative, testicular biopsy has shown to be a good option.Os autores apresentam uma revisão de 21 pacientes com diagnóstico de neuropatia amilóide tipo I, firmado sobre os dados epidemiológicos, a evolução clínica e os achados histopatológicos. Chamam a atenção para a possibilidade de comprometimento de vários nervos cranianos, para a gravidade do quadro digestivo, a precocidade dos distúrbios neurovegetativos e a incidência relativamente alta de sintomatologia cardíaca. Constituem contribuição para o melhor conhecimento da afecção, os estudos sobre a síndrome digestiva feitos através de exames radiológicos e dos testes de absorção de vitamina B12 e trioleína radioativas.

  6. Whole body amyloid deposition imaging by 123I-SAP scintigraphy

    NARCIS (Netherlands)

    van Rheenen, Ronald; Glaudemans, Andor; Hazenberg, Bouke

    2011-01-01

    Amyloidosis is the name of a group of diseases characterized by extracellular deposition of amyloid fibrils. Deposition of amyloid can be localized or systemic. The 123I-SAP-scan can be used to image extent and distribution of amyloid deposition in patients with systemic AA, AL and ATTR amyloidosis.

  7. Rheumatic Heart Disease Associated with Secondary Renal ...

    African Journals Online (AJOL)

    ... non-specific chronic inflammatory changes. The patient's secondary amyloidosis was presumed to be related to the long standing RHD after exclusion of other causes of secondary amyloidosis. The patient finally died due to heart failure and acute pulmonary edema. Conclusion: Long standing RHD can lead to secondary ...

  8. Variation of amino acid sequences of serum amyloid a (SAA) and immunohistochemical analysis of amyloid a (AA) in Japanese domestic cats.

    Science.gov (United States)

    Tei, Meina; Uchida, Kazuyuki; Chambers, James K; Watanabe, Ken-Ichi; Tamamoto, Takashi; Ohno, Koichi; Nakayama, Hiroyuki

    2018-02-02

    Amyloid A (AA) amyloidosis, a fatal systemic amyloid disease, occurs secondary to chronic inflammatory conditions in humans. Although persistently elevated serum amyloid A (SAA) levels are required for its pathogenesis, not all individuals with chronic inflammation necessarily develop AA amyloidosis. Furthermore, many diseases in cats are associated with the elevated production of SAA, whereas only a small number actually develop AA amyloidosis. We hypothesized that a genetic mutation in the SAA gene may strongly contribute to the pathogenesis of feline AA amyloidosis. In the present study, genomic DNA from four Japanese domestic cats (JDCs) with AA amyloidosis and from five without amyloidosis was analyzed using polymerase chain reaction (PCR) amplification and direct sequencing. We identified the novel variation combination of 45R-51A in the deduced amino acid sequences of four JDCs with amyloidosis and five without. However, there was no relationship between amino acid variations and the distribution of AA amyloid deposits, indicating that differences in SAA sequences do not contribute to the pathogenesis of AA amyloidosis. Immunohistochemical analysis using antisera against the three different parts of the feline SAA protein-i.e., the N-terminal, central, and C-terminal regions-revealed that feline AA contained the C-terminus, unlike human AA. These results indicate that the cleavage and degradation of the C-terminus are not essential for amyloid fibril formation in JDCs.

  9. Heavy and Light chain amyloidosois presenting as complete heart block: A rare presentation of a rare disease.

    Science.gov (United States)

    Priyamvada, P S; Morkhandikar, S; Srinivas, B H; Parameswaran, S

    2015-01-01

    Amyloidosis is an uncommon disease characterized by deposition of proteinaceous material in the extracellular matrix, which results from abnormal protein folding. Even though more than 25 precursor proteins are identified, majority of systemic amyloidosis results from deposition of abnormal immunoglobulin (Ig) light chains. In heavy chain amyloidosis (AH), deposits are derived from both heavy chain alone, whereas in heavy and light chain amyloidosis (AHL), the deposits are derived from Ig heavy chains and light chains. Both AH and AHL are extremely rare diseases. Here, we report an unusual presentation of IgG (lambda) AHL amyloidosis in the background of multiple myeloma, where the initial clinical presentation was complete heart block, which preceded the definitive diagnosis by 18 months.

  10. Heavy and Light chain amyloidosois presenting as complete heart block: A rare presentation of a rare disease

    Directory of Open Access Journals (Sweden)

    P S Priyamvada

    2015-01-01

    Full Text Available Amyloidosis is an uncommon disease characterized by deposition of proteinaceous material in the extracellular matrix, which results from abnormal protein folding. Even though more than 25 precursor proteins are identified, majority of systemic amyloidosis results from deposition of abnormal immunoglobulin (Ig light chains. In heavy chain amyloidosis (AH, deposits are derived from both heavy chain alone, whereas in heavy and light chain amyloidosis (AHL, the deposits are derived from Ig heavy chains and light chains. Both AH and AHL are extremely rare diseases. Here, we report an unusual presentation of IgG (lambda AHL amyloidosis in the background of multiple myeloma, where the initial clinical presentation was complete heart block, which preceded the definitive diagnosis by 18 months.

  11. [Clinical Laboratory Test Using Proteomics: The Usefulness of Proteomic Techniques for Amyloid Typing].

    Science.gov (United States)

    Tasaki, Masayoshi; Obayashi, Konen; Ando, Yukio

    2015-08-01

    Amyloidosis is a heterogeneous group of disorders characterized by the deposition of amyloid fibrils. To diagnose amyloidosis, it is important to detect amyloid deposits and identify the amyloid precursor protein in specimens, such as tissues and serum. Mass spectrometry is a powerful tool to measure the molecular weight and identify the protein. Recently, mass spectrometries such as liquid chromatography/tandem mass spectrometry and surface-enhanced laser desorption/ionization time of flight mass spectrometry, have made a contribution to amyloid typing. In the paper, we describe the usefulness of mass spectrometric analyses for the typing of amyloidosis.

  12. Sensitive and rapid assessment of amyloid by oligothiophene fluorescence in subcutaneous fat tissue

    NARCIS (Netherlands)

    Sjolander, Daniel; Bijzet, Johan; Hazenberg, Bouke P.; Nilsson, Peter R.; Hammarstrom, Per

    Systemic amyloidosis (SA) is often diagnosed late. Combining clinical and biochemical biomarkers is necessary for raising suspicion of disease. Fine needle aspiration (FNA) of subcutaneous fat enables SA detection by Congo red staining. The luminescent conjugated probe heptameric formic thiophene

  13. Amyloid Goiter Secondary to Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Bunyamin Aydin

    2016-01-01

    Full Text Available Diffuse amyloid goiter (AG is an entity characterized by the deposition of amyloid in the thyroid gland. AG may be associated with either primary or secondary amyloidosis. Secondary amyloidosis is rarely caused by inflammatory bowel diseases. Secondary amyloidosis is relatively more common in the patients with Crohn’s disease, whereas it is highly rare in patients with ulcerative colitis. Diffuse amyloid goiter caused by ulcerative colitis is also a rare condition. In the presence of amyloid in the thyroid gland, medullary thyroid cancer should be kept in mind in the differential diagnosis. Imaging techniques and biochemical tests are not very helpful in the diagnosis of secondary amyloid goiter and the definitive diagnosis is established based on the histopathologic analysis and histochemical staining techniques. In this report, we present a 35-year-old male patient with diffuse amyloid goiter caused by secondary amyloidosis associated with ulcerative colitis.

  14. How do Proteins Misfold and Aggregate?

    Indian Academy of Sciences (India)

    samrat

    Brain. Alzheimer's disease. Intrinsically disordered. Tau protein. Brain. Transmissible spongiform encephalopathy α-helical. Prion protein. Protein deposit. Disease. Type of structure. Amyloido- genic proteins. Skin & muscle. Injection-localized amyloidosis. Largely α - helical. Insulin. Brain. Parkinson's disease. Intrinsically.

  15. l'amylose laryngée à propos d'un cas laryngeal location of amylosis

    African Journals Online (AJOL)

    maxillofac. 1992 ; 93 : 54-57. 5-Vicente Villagomez, Felicitos Santos, Ramiro Santos and al. Amyloidosis: Uncommon cause of dysphonia. Head and Neck Surgery 2004, 13: 1275-276. 6- Quinquenel ML, Le Coza, Desrues B et ...

  16. Discordant results between biochemical and molecular transthyretin ...

    Indian Academy of Sciences (India)

    jgen/092/03/0599-0604. Keywords. transthyretin; discordant results; genetic testing; domino transplant; senile systemic amyloidosis. Author Affiliations. Honey V. Reddi1 Brittany C. Thomas1 Kurt S. Willkomm1 Matthew J. Ferber1 Kandelaria M.

  17. BONE MARROW TRANSPLANTATION

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. BONE MARROW TRANSPLANTATION. AUTOLOGOUS TRANSPLANTS: Oct 1986 - Dec 2007. Multiple Myeloma 90. NHL 39. Hodgkins lymphoma 19. AML 36. APML 9. ALL 2. Amyloidosis 2. Granulocytic Sarcoma 1.

  18. Disease: H01217 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ules (macular amyloidosis). PLCA is relatively common in South America and Asia, and some cases have an autosomal dominant family his...tory (familial PLCA, FPLCA). The genetic basis of FPLCA involves mutations in the O

  19. Disease: H01185 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01185 Cerebral amyloid angiopathy (CAA); Hereditary cerebral hemorrhage with amyl...ovani A, Tagliavini F ... TITLE ... Hereditary cerebral hemorrhage with amyloidosis associated with the E693K

  20. [Amyloid goiter].

    Science.gov (United States)

    Hrívó, A; Péter, I; Bánkúti, B; Péley, G; Baska, F; Besznyák, I

    1999-03-21

    Amyloid goitre is at an extremely rare occurrence. Authors review the origin of disease and its symptoms, diagnostic and therapeutic tools. The disease may be due to either primary or secondary systemic or local amyloidosis. Diagnosis may be made even before surgery on anamnestic data, on very rapid growth of thyroid glands, on diffuse appearance, on other symptoms of systemic amyloidosis, on findings of iconographic procedures and on detection of amyloid in aspirates. Final diagnosis is based on histology. Surgical therapy is aiming at avoidance of the existing and the threatening consequences of expanding mass. The outcome is independent from thyroid surgery, it is related to other manifestations of amyloidosis. Concerning with the present case the chronic superior vena cava syndrome and chylous pleural effusion as first described symptoms and asymptomatic hyperthyroxinaemia is emphasised. Neither other organ involvement, nor primary amyloidogenous molecula was found during the 18 months follow up, so patient has secondary and localised amyloidosis.

  1. Parotid Gland Biopsy, the Alternative Way to Diagnose Sjogren Syndrome

    NARCIS (Netherlands)

    Spijkervet, Fred. K.L.; Haacke, Erlin; Kroese, Frans G. M.; Bootsma, Hendrika; Vissink, Arjan

    Salivary gland biopsy is a technique broadly applied for the diagnosis of Sjogren syndrome (SS), lymphoma in SS, and connective tissue disorders (sarcoidosis, amyloidosis). In SS characteristic histology findings are found, including lymphocytic infiltration surrounding the excretory ducts in

  2. Amyloid arthropathy revealed by RS3PE syndrome.

    Science.gov (United States)

    Magy, N; Michel, F; Auge, B; Toussirot, E; Wendling, D

    2000-01-01

    Amyloid arthropathy is a form of primary AL amyloidosis with a monoclonal component in the blood and/or urine, and RS3PE syndrome is acute edematous polysynovitis in subjects older than 60 years. A 74-year-old man was diagnosed with both disorders. He was admitted for benign acute polyarthritis of the hands and feet and reported carpal tunnel symptoms predominating on the right. A synovial biopsy at the right wrist disclosed deposits that stained with Congo red even after potassium permanganate treatment (positive Wright's test). Articular AL amyloidosis was diagnosed. The symptoms resolved under glucocorticoid therapy alone, casting some doubt on their relationship with the amyloidosis. Roentgenograms showed geodes, a feature not present in RS3PE. Whether RS3PE may be among the possible presentations of articular amyloidosis is discussed.

  3. Diabetes Insipidus

    Science.gov (United States)

    ... Diabetes Inspidus Related Topics Section Navigation Kidney Disease Acquired Cystic Kidney Disease Amyloidosis & Kidney Disease Chronic Kidney ... nausea Severe dehydration can lead to seizures, permanent brain damage, and even death. Seek Immediate Care Usually, people ...

  4. Primary amyloid heart disease presenting as hypertrophic obstructive cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Weston, L.T.; Raybuck, B.D.; Robinowitz, M.; Brinker, J.A.; Oetgen, W.J.

    1986-01-01

    This report describes the unusual presentation of a patient with primary cardiac amyloidosis. Initial clinical symptoms and hemodynamic studies, including Technetium-99m-pyrophosphate scintigraphy, suggested hypertrophic obstructive cardiomyopathy, but endomyocardial biopsy revealed diffuse amyloid infiltration. Only two other cases of left ventricular outflow tract obstruction due to cardiac amyloidosis have been reported. The false-negative technetium-99m-pyrophosphate scintigram in this patient argues for the use of endomyocardial biopsy to aid in the diagnosis of left ventricular hypertrophy.

  5. Mécanisme d'association de deux protéines amyloïdogènes de l'héparane sulfate protéoglycane. Rôle du pH et de l'activité protéasique de la transthyrétine

    OpenAIRE

    Geneste, Ambre

    2014-01-01

    The analysis of the heparan sulfate proteoglycan (HSPG) association mechanism withamyloid proteins and the effect of physiological parameters (pH,…) on this mechanism allowa better understanding of the mechanisms leading to amyloidogenesis.Transthyretin (TTR), which circulates in both plasma and cerebrospinal fluid, is one of theproteins involved in amyloidosis. It leads to TTR amyloidosis and plays a role in Alzheimer’sdisease in sequestrating the beta-amyloid (Aβ) protein. Biochromatography...

  6. Genetic alterations of the BR12 Gene: familial British and Danish dementias

    DEFF Research Database (Denmark)

    Ghiso, J.; Rostagno, A.; Tomidokoro, Y.

    2006-01-01

    Classic arguments sustaining the importance of amyloid in the pathogenesis of dementia are usually centered on amyloid β (Aβ) and its role in neuronal loss characteristic of Alzheimer disease, the most common form of human cerebral amyloidosis. Two non-Aβ cerebral amyloidoses, familial British an...... membranes. These findings reaffirm the notion that non- Aβ amyloidosis constitute suitable alternative models to study the role of amyloid deposition in the mechanism of neuronal cell death....

  7. Cholinergic axon length reduced by 300 meters in the brain of an Alzheimer mouse model

    DEFF Research Database (Denmark)

    Nikolajsen, Gitte; Jensen, Morten Skovgaard; West, Mark J.

    2011-01-01

    Modern stereological techniques have been used to show that the total length of the cholinergic fibers in the cerebral cortex of the APPswe/PS1deltaE9 mouse is reduced by almost 300 meters at 18 months of age and has a nonlinear relationship to the amount of transgenetically-induced amyloidosis. ....... These data provide rigorous quantitative morphological evidence that Alzheimer's-like amyloidosis affects the axons of the cholinergic enervation of the cerebral cortex....

  8. In vivo visualization of amyloid deposits in the heart with 11C-PIB and PET

    DEFF Research Database (Denmark)

    Antoni, Gunnar; Lubberink, Mark; Estrada, Sergio

    2013-01-01

    UNLABELLED: Cardiac amyloidosis is a differential diagnosis in heart failure and is associated with high mortality. There is currently no noninvasive imaging test available for specific diagnosis. N-[methyl-(11)C]2-(4'-methylamino-phenyl)-6-hydroxybenzothiazole ((11)C-PIB) PET is used in the eval......UNLABELLED: Cardiac amyloidosis is a differential diagnosis in heart failure and is associated with high mortality. There is currently no noninvasive imaging test available for specific diagnosis. N-[methyl-(11)C]2-(4'-methylamino-phenyl)-6-hydroxybenzothiazole ((11)C-PIB) PET is used...... in the evaluation of brain amyloidosis. We evaluated the potential use of (11)C-PIB PET in systemic amyloidosis affecting the heart. METHODS: Patients (n = 10) diagnosed with systemic amyloidosis-including heart involvement of either monoclonal immunoglobulin light-chain (AL) or transthyretin (ATTR) type......-and healthy volunteers (n = 5) were investigated with PET/CT using (11)C-PIB to study cardiac amyloid deposits and with (11)C-acetate to measure myocardial blood flow to study the impact of global and regional perfusion on PIB retention. RESULTS: Myocardial (11)C-PIB uptake was visually evident in all...

  9. Association of Atrial Fibrillation with Morphological and Electrophysiological Changes of the Atrial Myocardium.

    Science.gov (United States)

    Matějková, Adéla; Šteiner, Ivo

    Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. For long time it was considered as pure functional disorder, but in recent years, there were identified atrial locations, which are involved in the initiation and maintenance of this arrhythmia. These structural changes, so called remodelation, start at electric level and later they affect contractility and morphology. In this study we attempted to find a possible relation between morphological (scarring, amyloidosis, left atrial (LA) enlargement) and electrophysiological (ECG features) changes in patients with AF. We examined grossly and histologically 100 hearts of necropsy patients - 54 with a history of AF and 46 without AF. Premortem ECGs were evaluated. The patients with AF had significantly heavier heart, larger LA, more severely scarred myocardium of the LA and atrial septum, and more severe amyloidosis in both atria. Severity of amyloidosis was higher in LAs vs. right atria (RAs). Distribution of both fibrosis and amyloidosis was irregular. The most affected area was in the LA anterior wall. Patients with a history of AF and with most severe amyloidosis have more often abnormally long P waves. Finding of long P wave may contribute to diagnosis of a hitherto undisclosed atrial fibrillation.

  10. Neuron and neuroblast numbers and cytogenesis in the dentate gyrus of aged APPswe/PS1dE9transgenic mice: Effect of long-term treatment with paroxetine.

    Science.gov (United States)

    Olesen, Louise Ørum; Sivasaravanaparan, Mithula; Severino, Maurizio; Babcock, Alicia A; Bouzinova, Elena V; West, Mark J; Wiborg, Ove; Finsen, Bente

    2017-08-01

    Altered neurogenesis may influence hippocampal functions such as learning and memory in Alzheimer's disease. Selective serotonin reuptake inhibitors enhance neurogenesis and have been reported to reduce cerebral amyloidosis in both humans and transgenic mice. We have used stereology to assess the longitudinal changes in the number of doublecortin-expressing neuroblasts and number of granular neurons in the dentate gyrus of APP swe /PS1 dE9 transgenic mice. Furthermore, we investigated the effect of long-term paroxetine treatment on the number of neuroblasts and granular neurons, hippocampal amyloidosis, and spontaneous alternation behaviour, a measure of spatial working memory, in transgenic mice. We observed no difference in granular neurons between transgenic and wild type mice up till 18months of age, and no differences with age in wild type mice. The number of neuroblasts and the performance in the spontaneous alternation task was reduced in aged transgenic mice. Paroxetine treatment from 9 to 18months of age reduced hippocampal amyloidosis without affecting the number of neuroblasts or granular neurons. These findings suggest that the amyloidosis affects the differentiation of neuroblasts and spatial working memory, independent of changes in total granular neurons. Furthermore, while long-term paroxetine treatment may be able to reduce hippocampal amyloidosis, it appears to have no effect on total number of granular neurons or spatial working memory. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. In vivo visualization of amyloid deposits in the heart with 11C-PIB and PET.

    Science.gov (United States)

    Antoni, Gunnar; Lubberink, Mark; Estrada, Sergio; Axelsson, Jan; Carlson, Kristina; Lindsjö, Lars; Kero, Tanja; Långström, Bengt; Granstam, Sven-Olof; Rosengren, Sara; Vedin, Ola; Wassberg, Cecilia; Wikström, Gerhard; Westermark, Per; Sörensen, Jens

    2013-02-01

    Cardiac amyloidosis is a differential diagnosis in heart failure and is associated with high mortality. There is currently no noninvasive imaging test available for specific diagnosis. N-[methyl-(11)C]2-(4'-methylamino-phenyl)-6-hydroxybenzothiazole ((11)C-PIB) PET is used in the evaluation of brain amyloidosis. We evaluated the potential use of (11)C-PIB PET in systemic amyloidosis affecting the heart. Patients (n = 10) diagnosed with systemic amyloidosis-including heart involvement of either monoclonal immunoglobulin light-chain (AL) or transthyretin (ATTR) type-and healthy volunteers (n = 5) were investigated with PET/CT using (11)C-PIB to study cardiac amyloid deposits and with (11)C-acetate to measure myocardial blood flow to study the impact of global and regional perfusion on PIB retention. Myocardial (11)C-PIB uptake was visually evident in all patients 15-25 min after injection and was not seen in any volunteer. A significant difference in (11)C-PIB retention in the heart between patients and healthy controls was found. The data indicate that myocardial amyloid deposits in patients diagnosed with systemic amyloidosis could be visualized with (11)C-PIB. No correlation between (11)C-PIB retention index and myocardial blood flow as measured with (11)C-acetate was found on the global level, whereas a positive correlation on the segmental level was seen in a single patient. (11)C-PIB and PET could be a method to study systemic amyloidosis of type AL and ATTR affecting the heart and should be investigated further both as a diagnostic tool and as a noninvasive method for treatment follow-up.

  12. Hereditär hjärnblödning. Demens vid cystatin C amyloidos

    DEFF Research Database (Denmark)

    Blöndal, H; Guomundsson, G; Benedikz, Eirikur

    1990-01-01

    Nineteen cases of hereditary cystatin C amyloidosis with cerebral haemorrhage are described. The first haemorrhage occurred between the ages of 20 and 41 years and the period of survival varied from 10 days to 23 years after the first insult. Progressive dementia was a striking clinical symptom...... in 17 of the patients and in two cases dementia was the first sign. At the last examination severe dementia and pronounced pathological EEG were established in the majority of the patients. Infiltration of amyloid substance positive for anti-cystatin C was found in the proximity of the blood vessels...... the name Hereditary Cystatin C Amyloidosis (HCCA)....

  13. [Pathological fractures of the femoral neck in hemodialyzed patients. Apropos of 26 cases].

    Science.gov (United States)

    Hardy, P; Benoit, J; Donneaud, B; Jehanno, P; Lortat-Jacob, A

    1994-01-01

    This study is based on a retrospective analysis of 26 pathological fractures of the femoral neck in 19 chronic haemodialysis patients. The purpose of this study is to analyze the epidemiological and etiological factors of these fractures in relation to osteo-arthropathy of the dialyzed patient, as well as the results of various treatments, both curative and preventive. 26 pathological fractures of the femoral neck appeared in 19 chronic haemodialysis patients, 11 men and 8 women, 6 patients presented bilateral fractures. The patient's average age at the time of the fracture was 61 years (27 to 82). The average duration of dialysis was 11 years with a minimum of 2 years and a maximum of 21 years. Hyper parathyroidism was found in 14 patients, aluminic intoxication in 6 and amyloidosis at the level of the coxo-femoral joint 18 times. Surgical treatment consisted of 6 osteosynthesis, 2 cephalic arthroplasties, 13 modular arthroplasties and 5 total hip arthroplasties. For each case, we studied the presence of necrosis of the femoral neck due to aluminic intoxication, osteoporosis due to hyperparathyroidism and also the presence of amyloidosis without aluminic intoxication. Cortisonic necrosis and porosis was found 4 times out of 26 cases, hyperparathyroidism once, aluminic osteomalacy 3 times and beta-2-microglobulin amyloid 18 times. Amyloidosis remains the most frequent etiological factor. All patients had been operated for median nerve compression in the carpal tunnel, usually 2.5 years before appearance of the pathological fracture. Non surgical treatment was used 5 times in undisplaced fractures without any sign of amyloidosis and was successful 3 times and unsuccessful twice necessitating a new operation by osteosynthesis. Out of 6 osteosynthesis performed for fractures either with little or no displacement we observed 4 failures, all of them in the cases with intra-osseous amyloidosis. Best results were obtained by arthroplasties. Modular arthroplasty has given

  14. Case series

    African Journals Online (AJOL)

    abp

    19 oct. 2017 ... Traitement des amyloses AL systémiques: à propos de 25 cas. Treatment of systemic AL amyloidosis: about 25 cases. Hicham Eddou1,&, Ali Zinebi1, Hicham El Maaroufi2, Mohammed Karim Moudden1, Kamal Doghmi2, Mohammed Mikdame2,. Mohammed El Baaj1. 1Service de Médecine Interne, Hôpital ...

  15. Distress in individuals facing predictive DNA testing for autosomal dominant late-onset disorders: Comparing questionnaire results with in-depth interviews

    NARCIS (Netherlands)

    Dudok-de Wit, A. C.; Tibben, A.; Duivenvoorden, H. J.; Niermeijer, M. F.; Passchier, J.; Trijsburg, R. W.; Lindhout, D.; Meijers-Heijboer, E. J.; Frets, P. G.; Lodder, L. N.; Zoetewij, M. W.; Klijn, J. G. M.; Brocker-Vriends, A.; van Haeringen, A.; Helderman, A. T. J. M.; Hilhorst-Hofstee, Y.; Kant, S.; Maat-Kievit, J. A.; Oosterwijk, J. C.; van der Smagt, J. J.; Vegter-van der Vlis, M.; Vries-van der Weerd, M. A. C. S.; Zoeteweij, M. W.; Bakker, E.; Devilee, P.; Losekoot, M.; Tops, C.; Cornelisse, C. J.; Vasen, H. F. A.

    1998-01-01

    In 50% risk carriers for Huntington disease (n = 41), hereditary cerebral hemorrhage with amyloidosis Dutch-type (n = 9) familial adenomatous polyposis coli (n = 45) and hereditary breast and ovarian cancer (n = 24), pretest intrusion and avoidance (Impact of Event Scale), anxiety and depression

  16. Distress in individuals facing predictive DNA testing for autosomal dominant late-onset disorders : Comparing questionnaire results with in-depth interviews

    NARCIS (Netherlands)

    DudokdeWit, AC; Tibben, A; Duivenvoorden, HJ; Niermeijer, MF; Passchier, J; Trijsburg, RW; Lindhout, D; Meijers-Heijboer, EJ; Frets, PG; Frets, PG; Lodder, LN; Zoetewij, MW; Klijn, JGM; Brocker-Vriends, A; van Haeringen, A; Helderman, ATJM; Hilhorst-Hofstee, Y; Kant, S; Maat-Kievit, JA; Oosterwijk, JC; van der Smagt, JJ; Vegter-van der Vlis, M; Vries-van der Weerd, MACS; Zoeteweij, MW; Bakker, E; Devilee, P; Losekoot, M; Tops, C; Cornelisse, CJ; Vasen, HFA

    1998-01-01

    In 50% risk carriers for Huntington disease (n = 41), hereditary cerebral hemorrhage with amyloidosis Dutch-type (n = 9) familial adenomatous polyposis coli (n = 45) and hereditary breast and ovarian cancer (n = 24), pretest intrusion and avoidance (Impact of Event Scale), anxiety and depression

  17. Native human serum amyloid P component is a single pentamer

    DEFF Research Database (Denmark)

    Sørensen, Inge Juul; Andersen, Ove; Nielsen, EH

    1995-01-01

    Serum amyloid P component (SAP) and C-reactive protein (CRP) are members of the pentraxin protein family. SAP is the precursor protein to amyloid P component present in all forms of amyloidosis. The prevailing notion is that SAP in circulation has the form of a double pentameric molecule (decamer...

  18. Detection of AA-type amyloid protein in labial salivary glands.

    Science.gov (United States)

    Sacsaquispe, Sonia-Julia; Antúnez-de Mayolo, Eleazar-Antonio; Vicetti, Rodolfo; Delgado, Wilson-Alejandro

    2011-03-01

    Among the diverse forms of amyloidosis, secondary type is the most frequent one. Diagnosis of amyloid deposition is based on the identification of the fibrillary protein amyloid by means of Congo Red (CR) or crystal violet (CV) stains, but these techniques do not differentiate between the different types of amyloid fibrils. The aim of this study was to identify by immunofluorescence (IF) AA amyloid a pathological fibrillar low-molecular-weight protein formed by cleavage of serum amyloid A (SAA) protein in labial salivary gland (LSG) biopsies from patients with secondary amyloidosis. 98 LSG were studied, 65 were from patients with secondary amyloidosis and 33 from subjects with chronic inflammatory diseases without evidence of this anomaly. All sections were stained with hematoxylin and eosin (H &E), CV, CR and IF using anti-AA antibodies. Positive and negative controls were used for all techniques. CV and CR demonstrated that the amyloid substance was found mainly distributed periductally (93.8%), followed by periacinar and perivascular locations (p <0.001); however, the IF demonstrated that amyloid AA substance predominates in the periacinar area (73.8%), followed by periductal and perivascular locations (p <0.001). IF has a sensitivity of 83%, 100% of specificity, 100% of predictive positive value and 75% of predictive negative value. The results of this study confirm the efficacy of the LSG biopsy as a highly reliable method for diagnosis of secondary amyloidosis.

  19. Allaying and alleviating amyloid agony and anxiety.

    Science.gov (United States)

    Gertz, Morie A

    2013-04-25

    In this issue of Blood, Wechalekar and colleagues demonstrate the importance of treating all patients with amyloidosis, no matter how severe their situation is, because clinically important responses are seen. They also identify the adverse prognostic impact of a systolic blood pressure of < 100 mm Hg.

  20. Cell milieu significantly affects the fate of AApoAI amyloidogenic variants: predestination or serendipity?

    Science.gov (United States)

    Gaglione, Rosa; Smaldone, Giovanni; Di Girolamo, Rocco; Piccoli, Renata; Pedone, Emilia; Arciello, Angela

    2018-03-01

    Specific apolipoprotein A-I variants are associated to severe hereditary amyloidoses. The organ distribution of AApoAI amyloidosis seems to depend on the position of the mutation, since mutations in residues from 1 to 75 are mainly associated to hepatic and renal amyloidosis, while mutations in residues from 173 to 178 are mostly responsible for cardiac, laryngeal, and cutaneous amyloidosis. Molecular bases of this tissue specificity are still poorly understood, but it is increasingly emerging that protein destabilization induced by amyloidogenic mutations is neither necessary nor sufficient for amyloidosis development. By using a multidisciplinary approach, including circular dichroism, dynamic light scattering, spectrofluorometric and atomic force microscopy analyses, the effect of target cells on the conformation and fibrillogenic pathway of the two AApoAI amyloidogenic variants AApoAI L75P and AApoAI L174S has been monitored. Our data show that specific cell milieus selectively affect conformation, aggregation propensity and fibrillogenesis of the two AApoAI amyloidogenic variants. An intriguing picture emerged indicating that defined cell contexts selectively induce fibrillogenesis of specific AApoAI variants. An innovative methodological approach, based on the use of whole intact cells to monitor the effects of cell context on AApoAI variants fibrillogenic pathway, has been set up. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Common MEFV mutations in Egyptian patients with familial ...

    African Journals Online (AJOL)

    Background: Familial Mediterranean fever (FMF) which is an autosomal recessive condition that primarily affect population of the Mediterranean basin. If undiagnosed effectively and treated with colchicine for life it may lead to serious consequences in terms of renal amyloidosis and renal failure. Objectives: We aim to check ...

  2. Inhibition of amyloid-beta-induced cell death in human brain pericytes in vitro.

    NARCIS (Netherlands)

    Rensink, A.A.M.; Verbeek, M.M.; Otte-Holler, I.; Donkelaar, H.J. ten; Waal, R.M.W. de; Kremer, H.P.H.

    2002-01-01

    Amyloid-beta protein (A beta) deposition in the cerebral vascular walls is one of the key features of Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). A beta(1-40) carrying the 'Dutch' mutation (HCHWA-D A beta(1-40)) induces pronounced degeneration of

  3. Author Details

    African Journals Online (AJOL)

    Falkson, G. Vol 79, No 1 (1991) - Articles Prognostic factors affecting the survival of patients with multiple myeloma A retrospective analysis of 86 patients. Abstract PDF · Vol 79, No 3 (1991) - Articles Metastatic breast cancer - age has a significant effect on survival. Abstract PDF · Vol 47, No 1 (1973) - Articles Amyloidosis in ...

  4. An integrated proteomics approach shows synaptic plasticity changes in an APP/PS1 Alzheimer's mouse model

    DEFF Research Database (Denmark)

    Kempf, Stefan J; Metaxas, Athanasios; Ibáñez-Vea, María

    2016-01-01

    The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosyl...

  5. Amyloid Fibril-Induced Structural and Spectral Modifications in the Thioflavin-T Optical Probe

    DEFF Research Database (Denmark)

    Murugan, N. Arul; Olsen, Jógvan Magnus Haugaard; Kongsted, Jacob

    2013-01-01

    Motivated by future possibilities to design target molecules for fibrils with diagnostic or therapeutic capability related to amyloidosis diseases, we investigate in this work the dielectric nature of amyloid fibril microenvironments in different binding sites using an optical probe, thioflavin-T...

  6. Multiple papular lesions in a patient with HIV and/or AIDS and ...

    African Journals Online (AJOL)

    Management: Microscopic examination of the biopsy material taken from the periocular lesion and then from perianal polyps revealed eosinophilic deposition, and stained positively by Congo red. Serum amyloid A level was negative. Antiretroviral therapy was continued. Conclusion: A rare form of amyloidosis in a patient ...

  7. Complement activation by the amyloid proteins A beta peptide and beta 2-microglobulin

    DEFF Research Database (Denmark)

    Nybo, Mads; Nielsen, E H; Svehag, S E

    1999-01-01

    component nor heparan sulfate did significantly alter the A beta-induced CA. The results indicate that not only fibrillar A beta but also oligomers of, in particular, beta 2M from patients with dialysis-associated amyloidosis are capable of inducing CA at supra-physiological concentrations....

  8. Insulin inhibits amyloid beta-induced cell death in cultured human brain pericytes

    NARCIS (Netherlands)

    Rensink, Annemieke A M; Otte-Höller, Irene; de Boer, Roelie; Bosch, Remko R; ten Donkelaar, Hans J; de Waal, Robert M W; Verbeek, Marcel M; Kremer, Berry

    Amyloid-beta (Abeta) deposition in the cerebral arterial and capillary walls is one of the characteristics of Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis-Dutch type. In vitro, Abeta1-40, carrying the "Dutch" mutation (DAbeta1-40), induced reproducible degeneration of

  9. Intestinal perforation caused by tuberculosis in a kidney transplant patient who was extensively evaluated for tuberculosis prior to transplant

    NARCIS (Netherlands)

    Rendering, H.; Zijlstra, J.G.; van Son, W.J.; De Maar, E.F.; Manson, W.L.; van der Werf, T.S.

    2006-01-01

    A 47-year-old man from Armenia presented at the emergency department with abdominal pain. He had had a kidney transplant 2 years earlier for renal failure caused by amyloidosis that was secondary to familial Mediterranean fever. He was also known to have chronic hepatitis B with persistent viraemia.

  10. Amyloid goitre following chronic osteomyelitis: case report and ...

    African Journals Online (AJOL)

    Amyloid goitre following chronic osteomyelitis: case report and review of literature. AZ Mohammed, ST Edino, O Ochicha. Abstract. Amyloid Goitre is a rare clinical entity associated with systemic amyloidosis. It poses a significant diagnostic and therapeutic challenge and may be confused with a neoplastic goiter. We present ...

  11. Amyloidogenic peptides for design of inhibitors of peptide aggregation and as templates for new bionanomaterials

    NARCIS (Netherlands)

    Elgersma, R.C.

    2008-01-01

    Misfolding of proteins from their soluble form into highly insoluble fibrillar deposits can lead to (non-)neurodegenerative disorders or systemic amyloidosis. This class of diseases (for which no therapy is available yet) is called amyloid diseases. Amyloid refers to the extracellular proteinaceous

  12. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management

    NARCIS (Netherlands)

    R. Kyle (Robert); B.G.M. Durie (Brian); S.V. Rajkumar (Vincent); O. Landgren; J. Bladé (Joan); G. Merlini; N. Kröger (Nicolaus); H. Einsele (Hermann); D. Vesole (David); M.A. Dimopoulos (Meletios); J.F. San Miguel (Jesús Fernando); H. Avet-Loiseau; R. Hajek (Roman); W. Chen (Wei); K.C. Anderson (Kenneth); H. Ludwig (Heinz); P. Sonneveld (Pieter); S. Pavlovsky; A. Palumbo (Antonio); P.G. Richardson; B. Barlogie (Bart); P. Greipp (Philip); R. Vescio (Robert); I. Turesson; J. Westin (Johan); M. Boccadoro (Mario)

    2010-01-01

    textabstractMonoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is

  13. Knee Pain in a Renal Transplant Patient

    Science.gov (United States)

    2017-04-26

    chronic kidney disease. They often develop soft tissue rheumatic syndromes , crystalline arthropathy, and metabolic bone disease. We describe a...birefringence under polarizing light, characteristic of amyloid. Discussion: Primary amyloidosis (AL) is the most common amyloid protein and may be...with rheumatologic manifestations including carpal tunnel syndrome , joint effusions, spondyloarthropathy, and cystic bone lesions. Fifty percent of

  14. Neuron and neuroblast numbers and cytogenesis in the dentate gyrus of aged APP(swe)/PS1(dE9) transgenic mice

    DEFF Research Database (Denmark)

    Olesen, Louise Orum; Sivasaravanaparan, Mithula; Severino, Maurizio

    2017-01-01

    the longitudinal changes in the number of doublecortin-expressing neuroblasts and number of granular neurons in the dentate gyrus of APPswe/PS1dE9 transgenic mice. Furthermore, we investigated the effect of long-term paroxetine treatment on the number of neuroblasts and granular neurons, hippocampal amyloidosis...

  15. Case report

    African Journals Online (AJOL)

    abp

    2012-06-11

    Jun 11, 2012 ... Abstract. Churg Strauss syndrome is a rare systemic and pulmonary vasculitis exceptionally associated with AA amyloidosis. We report the case of a 65-year old woman with past medical history of asthma. She developed polyarthralgia, headache and purpura. A laboratory workout found hypereosinophilia ...

  16. ABCC6 is unlikely to be a modifier gene for familial Mediterranean ...

    Indian Academy of Sciences (India)

    above on the Tel-Hashomer disease severity score (Pras et al. 1998), (ii) presence of renal amyloidosis diagnosed by persistent proteinuria and/or nephritic syndrome or chronic renal failure or (iii) absence of clinical amelioration despite colchicine administration. Group II patients (n = 56) were considered mildly affected ...

  17. Tracheobroncopathia Osteochondroplastica: Three Case Reports ...

    African Journals Online (AJOL)

    2017-05-16

    May 16, 2017 ... Generally chest radiography is normal, so thorax computed tomography can be remarkable in diagnosis of TO. Besides, final diagnosis can be established by viewing ossified nodules in trachea and bronchus through the fiberoptic bronchoscopy. Amyloidosis, tuberculosis, sarcoidosis, bronchial carcinoma,.

  18. Tracheobroncopathia osteochondroplastica: Three case reports with ...

    African Journals Online (AJOL)

    Besides, final diagnosis can be established by viewing ossified nodules in trachea and bronchus through the fiberoptic bronchoscopy. Amyloidosis, tuberculosis, sarcoidosis, bronchial carcinoma, and tracheobronchial calcinosis must be remembered in differential diagnosis. Also ossifications in submucosa and proof of ...

  19. Terapeutika amyloidóz

    Czech Academy of Sciences Publication Activity Database

    Holubová, Monika; Hrubý, Martin

    2016-01-01

    Roč. 110, č. 12 (2016), s. 851-859 ISSN 0009-2770 R&D Projects: GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : amyloidosis * amyloid * Alzheimer's disease Subject RIV: CD - Macromolecular Chemistry Impact factor: 0.387, year: 2016 http://www.chemicke-listy.cz/common/article-vol_110-issue_12-page_851.html

  20. Abdominal wall fat pad biopsy

    Science.gov (United States)

    ... more difficult procedure. Normal Results The fat pad tissues are normal. What Abnormal Results Mean In the case of amyloidosis, abnormal results mean there is amyloid. This is a protein that collects in tissues and impairs organ and tissue function. Risks There ...

  1. Genetic microheterogeneity of human transthyretin detected by IEF

    NARCIS (Netherlands)

    Altland, Klaus; Benson, Merrill D.; Costello, Catherine E.; Ferlini, Alessandra; Hazenberg, Bouke R. C.; Hund, Ernst; Kristen, Arnt V.; Linke, Reinhold P.; Merlini, Giampaolo; Salvi, Fabrizio; Saraiva, Maria J.; Singer, Reinhard; Skinner, Martha; Winter, Pia

    Mutations of the human transthyretin (TTR) gene have attracted medical interest as a cause of amyloidosis. Recently, we have described in detail an electrophoretic procedure with PAGE followed by IEF in urea gradients for the study of the microheterogeneity of TTR monomers (Altland, K., Winter, P.,

  2. Antibodies to human serum amyloid P component eliminate visceral amyloid deposits.

    Science.gov (United States)

    Bodin, Karl; Ellmerich, Stephan; Kahan, Melvyn C; Tennent, Glenys A; Loesch, Andrzej; Gilbertson, Janet A; Hutchinson, Winston L; Mangione, Palma P; Gallimore, J Ruth; Millar, David J; Minogue, Shane; Dhillon, Amar P; Taylor, Graham W; Bradwell, Arthur R; Petrie, Aviva; Gillmore, Julian D; Bellotti, Vittorio; Botto, Marina; Hawkins, Philip N; Pepys, Mark B

    2010-11-04

    Accumulation of amyloid fibrils in the viscera and connective tissues causes systemic amyloidosis, which is responsible for about one in a thousand deaths in developed countries. Localized amyloid can also have serious consequences; for example, cerebral amyloid angiopathy is an important cause of haemorrhagic stroke. The clinical presentations of amyloidosis are extremely diverse and the diagnosis is rarely made before significant organ damage is present. There is therefore a major unmet need for therapy that safely promotes the clearance of established amyloid deposits. Over 20 different amyloid fibril proteins are responsible for different forms of clinically significant amyloidosis and treatments that substantially reduce the abundance of the respective amyloid fibril precursor proteins can arrest amyloid accumulation. Unfortunately, control of fibril-protein production is not possible in some forms of amyloidosis and in others it is often slow and hazardous. There is no therapy that directly targets amyloid deposits for enhanced clearance. However, all amyloid deposits contain the normal, non-fibrillar plasma glycoprotein, serum amyloid P component (SAP). Here we show that administration of anti-human-SAP antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects. Anti-SAP-antibody treatment is clinically feasible because circulating human SAP can be depleted in patients by the bis-d-proline compound CPHPC, thereby enabling injected anti-SAP antibodies to reach residual SAP in the amyloid deposits. The unprecedented capacity of this novel combined therapy to eliminate amyloid deposits should be applicable to all forms of systemic and local amyloidosis.

  3. A CLINICO-HISTOPATHOLOGICAL STUDY OF FRICTIONAL MELANOSIS

    Directory of Open Access Journals (Sweden)

    Keerthi Jampani

    2016-06-01

    Full Text Available OBJECTIVE The aim of the present study was to analyse different clinical patterns of frictional melanosis and to evaluate whether sun exposure is a causative or contributing factor for frictional melanosis. Furthermore, histopathology with haematoxylin and eosin along with special stains for amyloid like Congo red was done. METHODS 50 patients with clinical diagnosis of frictional melanosis participated in this study. INCLUSION CRITERIA Patients of all ages and both sexes with classical clinical features suggestive of frictional melanosis are included. EXCLUSION CRITERIA Patients having pigmentation over areas where the frictional melanosis presents classically but have been using chemicals, hair dyes and other agents which can cause photocontact dermatitis have been excluded from the study. A detailed history regarding duration of illness, progression and precipitating factors along with detailed clinical examination regarding the location of the lesions and type of lesions was done and patients were subjected to skin biopsy after obtaining a written consent. RESULTS Out of 50 cases, 39 (78% were confirmed with histopathology as frictional melanosis and 11(22% as macular amyloidosis. Among patients of frictional melanosis, 56.41% had only skin lesions. In macular amyloidosis 63.63% patients had itching along with skin lesions. In Frictional melanosis the most frequently involved site was extensor aspect of arm (78.48%. The most frequently involved site in macular amyloidosis was extensor aspect of forearm (93.34%. CONCLUSION In this study a total number of 50 patients with clinical presentation of frictional melanosis were analysed with female preponderance. Amyloid deposition is seen in those skin biopsy specimens taken from area of friction with sun exposure, which suggests that sun exposure could be one of the predisposing factors for macular amyloidosis. Thus, these findings confirm that frictional melanosis is a variant of macular

  4. Serum Amyloid A Protein Concentration in Blood is Influenced by Genetic Differences in the Cheetah (Acinonyx jubatus).

    Science.gov (United States)

    Franklin, Ashley D; Schmidt-Küntzel, Anne; Terio, Karen A; Marker, Laurie L; Crosier, Adrienne E

    2016-03-01

    Systemic amyloid A (AA) amyloidosis is a major cause of morbidity and mortality among captive cheetahs. The self-aggregating AA protein responsible for this disease is a byproduct of serum amyloid A (SAA) protein degradation. Transcriptional induction of the SAA1 gene is dependent on both C/EBPβ and NF-κB cis-acting elements within the promoter region. In cheetahs, 2 alleles exist for a single guanine nucleotide deletion in the putative NF-κB binding site. In this study, a novel genotyping assay was developed to screen for the alleles. The results show that the SAA1A (-97delG) allele is associated with decreased SAA protein concentrations in the serum of captive cheetahs (n = 58), suggesting genetic differences at this locus may be affecting AA amyloidosis prevalence. However, there was no significant difference in the frequency of the SAA1A (-97delG) allele between individuals confirmed AA amyloidosis positive versus AA amyloidosis negative at the time of necropsy (n = 48). Thus, even though there is evidence that having more copies of the SAA1A (-97delG) allele results in a potentially protective decrease in serum concentrations of SAA protein in captive cheetahs, genotype is not associated with this disease within the North American population. These results suggest that other factors are playing a more significant role in the pathogenesis of AA amyloidosis among captive cheetahs. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Amyloid myopathy: a diagnostic challenge

    Directory of Open Access Journals (Sweden)

    Heli Tuomaala

    2009-08-01

    Full Text Available Amyloid myopathy (AM is a rare manifestation of primary systemic amyloidosis (AL. Like inflammatory myopathies, it presents with proximal muscle weakness and an increased creatine kinase level. We describe a case of AL with severe, rapidly progressive myopathy as the initial symptom. The clinical manifestation and muscle biopsy were suggestive of inclusion body myositis. AM was not suspected until amyloidosis was seen in the gastric mucosal biopsy. The muscle biopsy was then re-examined more specifically, and Congo red staining eventually showed vascular and interstitial amyloid accumulation, which led to a diagnosis of AM. The present case illustrates the fact that the clinical picture of AM can mimic that of inclusion body myositis.

  6. Association between cortical thickness and CSF biomarkers in mild cognitive impairment and Alzheimer’s disease

    DEFF Research Database (Denmark)

    Mohades, Sara; Dubois, Jonathan; Parent, Maxime

    regional cortical thinning (CT) measured by Magnetic Resonance Imaging (MRI) and brain amyloidosis (measured by CSF Ab 1-42 concentrations), or tau hyperphosphorylation (tau 181; p-tau) in Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) patients. We test the hypothesis that the association...... between cortical thinning, amyloidosis or tau hyperphosphorylation depends on cortical regions and clinical stages of AD. Methods: T1-weighed MRIs and associated CSF markers from individuals with mild cognitive impairment (MCI; 16), Alzheimer Disease (AD; n¼7) and age-matched cognitively normal subjects...... analyses in the MCI group showed a positive correlation between CT and Ab 1-42 measures predominantly in the temporo-parietal regions, namely the precuneus (peak r¼0.67; p

  7. Familial Mediterranean Fever

    Directory of Open Access Journals (Sweden)

    Adem Kucuk

    2014-01-01

    Full Text Available Familial Mediterranean Fever is an autosomal recessive inherited disease with a course of autoinflammation, which is characterized by the episodes of fever and serositis. It affects the populations from Mediterranean basin. Genetic mutation of the disease is on MEFV gene located on short arm of Chromosome 16. The disease is diagnosed based on clinical evaluation. Amyloidosis is the most important complication. The only agent that decreases the development of amyloidosis and the frequency and severity of the episodes is colchicine, which has been used for about 40 years. In this review, we aimed to discuss especially the most recent advances about Familial Mediterranean Fever which is commonly seen in our population.

  8. Long-term outcome in patients treated with combined heart and liver transplantation for familial amyloidotic cardiomyopathy

    DEFF Research Database (Denmark)

    Nelson, Laerke M; Penninga, Luit; Sander, Kaare

    2013-01-01

    . All patients suffered from severe cardiomyopathy. RESULTS: Mean recipient age at transplantation was 48.3 ± 4.2 yr. Mean follow-up was 55 months. No peroperative mortality occured. Two patients died within the first year (infection, multi-organ failure) of transplantation. Cumulative survival at 4......BACKGROUND: The amyloidogenic transthyretin (ATTR) mutation Leu111Met causes a primarily cardiac amyloidosis: Familial amyloidotic cardiomyopathy (FAC). Combined heart-liver transplantation (CHLTx) is the preferred treatment for patients with heart failure due to familial amyloidosis......, but information on outcome of patients with Leu111Met mutation is limited. The aim of this study was to evaluate the long-term outcome of CHLTx in patients with FAC. METHODS AND MATERIALS: Between 1998 and 2009, CHLTx was performed in 7 FAC patients (four men). Six patients underwent simultaneous transplantation...

  9. [Cardiac tamponade as first manifestation in Mediterranean fever with autosomal dominant form].

    Science.gov (United States)

    Sánchez Ferrer, F; Martinez Villar, M; Fernández Bernal, A; Martín de Lara, I; Paya Elorza, I

    2015-01-01

    Familial Mediterranean fever (FMF) is a hereditary disease characterized by brief, recurring and self-limited episodes of fever and pain with inflammation, of one or several serous (peritoneum, pleura, pericardium, synovial or vaginal tunic of the testicle). Amyloidosis is its more important complication and the principal reason of death in the cases in which it appears. Diagnosis is based on the clinic and is confirmed by genetic tests. The treatment with Colchicine (0,02-0,03 mg/kg/day) prevents the recurrence of FMF attacks and the development of secondary (AA) amyloidosis. We report a case of a 13-year-old child in which FMF was diagnosed after several coincidental episodes with fever, pericarditis and cardiac tamponade. The genetic confirmation showed an autosomal dominant inheritance that is less frecuent than the recesive form, in this disease. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  10. Periorbital Ecchymosis (Raccoon Eye) and Orbital Hematoma following Endoscopic Retrograde Cholangiopancreatography.

    Science.gov (United States)

    Nasiri, Jafar; Zamani, Farhad

    2017-01-01

    Endoscopic retrograde cholangiopancreatography (ERCP) is a conventional technique for diagnosis and treatment of pancratobiliary diseases, which is associated with various complications, including pancreatitis, hemorrhage, cholangitis, perforation, and mortality. In our case, a 69-year-old woman with positive hepatobiliary symptoms underwent ERCP, at the end of which a rare complication (raccoon eye) occurred, which was hypothesized to be due to amyloidosis, but the patient refused to complete the diagnostic procedure and became symptom free after 3 weeks. Racoon eye or periorbital ecchymosis is caused by blood tracking into periorbital tissues, which is frequently observed after head trauma but is also observed in systemic diseases, such as amyloidosis, neuroblastoma, and surgical interventions. To the best of our knowledge, this is the first report of raccoon eye after ERCP; further reports will help to confirm that this complication should also be considered before performing ERCP and that complete diagnostic tests for the predisposing diseases prior to ERCP are necessary.

  11. Beta2-microglobulin.

    Science.gov (United States)

    Drüeke, Tilman B; Massy, Ziad A

    2009-01-01

    Among the uremic toxins in the "middle molecule" range, beta2-microglobulin (beta2-M) is certainly one of the most frequently studied compounds. Its serum level increases with the progression of chronic kidney disease, to reach very high concentrations in patients with end-stage kidney disease. It is the major protein component of dialysis-related amyloidosis, a dramatic complication which results from high extracellular concentration and posttranslational modification of beta2-M and a number of other promoters of amyloid fibril formation and deposition in osteo-articular tissues. Effective removal of beta2-M can be achieved with highly effective hemodialysis and hemodiafiltration techniques but predialysis session serum levels cannot be normalized. The prevalence and severity of beta2-M amyloidosis appear to have decreased in the last 20 years, although its occurrence may simply be delayed.

  12. [The disease of beta 2-amyloid deposition in the differential diagnosis of juxta-articular subchondral geode lesions].

    Science.gov (United States)

    Marri, C; Romagnoli, C; Solano, G; Caldeo, A; Emiliani, G

    1993-01-01

    Beta-2 amyloidosis deposition is a new type of amyloidosis recently observed in long-term hemodialysis patients. One of the major osteoarticular complications of this disease is the appearance of subchondral bone cysts. In this paper the radiologic features of such radiolucencies are described and the criteria are outlined of the differential diagnosis from the geodes found in other arthropathies or para-physiologic conditions. The importance of the status of the joint space is stressed: on the basis of its patterns, arthropathies may be grouped as follows: inhomogeneous space narrowing in degenerative arthritis; homogeneous space narrowing in inflammatory arthritis; normal or nearly normal joint space if there is no/not-prevalent involvement of articular cartilage.

  13. Differential recruitment efficacy of patient-derived amyloidogenic and myeloma light chain proteins by synthetic fibrils-A metric for predicting amyloid propensity.

    Directory of Open Access Journals (Sweden)

    Emily B Martin

    Full Text Available Monoclonal free light chain (LC proteins are present in the circulation of patients with immunoproliferative disorders such as light chain (AL amyloidosis and multiple myeloma (MM. Light chain-associated amyloid is a complex pathology composed of proteinaceous fibrils and extracellular matrix proteins found in all patients with AL and in ~10-30% of patients who presented with MM. Amyloid deposits systemically in multiple organs and tissues leading to dysfunction and ultimately death. The overall survival of patients with amyloidosis is worse than for those with early stage MM.We have developed a sensitive binding assay quantifying the recruitment of full length, patient-derived LC proteins by synthetic amyloid fibrils, as a method for studying their amyloidogenic potential. In a survey of eight urinary LC, both AL and MM-associated proteins were recruited by synthetic amyloid fibrils; however, AL-associated LC bound significantly more efficiently (p < 0.05 than did MM LCs. The LC proteins used in this study were isolated from urine and presumed to represent a surrogate of serum free light chains.The binding of LC to synthetic fibrils in this assay accurately differentiated LC with amyloidogenic propensity from MM LC that were not associated with clinical amyloid disease. Notably, the LC from a MM patient who subsequently developed amyloid behaved as an AL-associated protein in the assay, indicating the possibility for identifying MM patients at risk for developing amyloidosis based on the light chain recruitment efficacy. With this information, at risk patients can be monitored more closely for the development of amyloidosis, allowing timely administration of novel, amyloid-directed immunotherapies-this approach may improve the prognosis for these patients.

  14. Confocal Cornea Microscopy Detects Involvement of Corneal Nerve Fibers in a Patient with Light-Chain Amyloid Neuropathy Caused by Multiple Myeloma: A Case Report

    Directory of Open Access Journals (Sweden)

    Dietrich Sturm

    2016-06-01

    Full Text Available Changes in the subbasal corneal plexus detected by confocal cornea microscopy (CCM have been described for various types of neuropathy. An involvement of these nerves within light-chain (AL amyloid neuropathy (a rare cause of polyneuropathy has never been shown. Here, we report on a case of a patient suffering from neuropathy caused by AL amyloidosis and underlying multiple myeloma. Small-fiber damage was detected by CCM.

  15. What is the best acute phase reactant for familial Mediterranean fever follow-up and its role in the prediction of complications? A systematic review.

    Science.gov (United States)

    Erer, Burak; Demirkaya, Erkan; Ozen, Seza; Kallinich, Tilmann

    2016-04-01

    The most dreaded complication of familial Mediterranean fever (FMF) is amyloidosis; controversy exists as to what acute phase reactant (APR) should be monitored in these patients. To analyze the best acute phase reactant for FMF follow-up to help guide physicians to decide on what APR parameter to use, we also attempted to define the best APR in predicting the complications of FMF, specifically the development of amyloidosis. Systematic review based on a sensitive search to capture studies that: (1) included FMF patients; (2) measured serum amyloid A (SAA), CRP (C-reactive protein), proteinuria, or ESR (erythrocyte sedimentation rate); (3) amyloidosis were the outcome measure; (4) sensitivity, specificity, predictive value, and other performance parameters could be calculated; and (5) had a longitudinal design. Of 1905 captured items, 26 were selected for detailed review, of which only two finally met the criteria, and the quality was only moderate; the articles did not analyzed the performance by means of sensitivity and specificity to predict, or even detect, amyloidosis, and thus had to be calculated based on text. The 26 screened studies were very heterogeneous in designs, parameters measured, and results, despite being set from research questions similar to ours. They were mainly descriptive, and it was very difficult to interpret the true performance of the tests. The correlation between the various APR is low. The evidence supporting the monitoring of FMF with any APR over the others is limited. Well designed longitudinal studies with a mixture of outcomes should be undertaken. Until them, recommending an APR over other would be based on expert opinion and indirect evidence.

  16. Familial mediterranean fever: a fascinating model of inherited autoinflammatory disorder.

    Science.gov (United States)

    Portincasa, Piero; Scaccianoce, Giuseppe; Palasciano, Giuseppe

    2013-12-01

    Familial Mediterranean fever (FMF) is a rare inherited autosomal recessive autoinflammatory disorder characterized by recurrent and self-limited episodes of fever and painful serositis, lasting 1-3 days. FMF occurs almost exclusively among ethnic groups of the Mediterranean basin, although cases have also been found in Japan and Korean populations. Diagnosis is based on clinical features, response to colchicine and genetic analysis. Novel drugs are emerging, allowing better management of colchicine-resistant/colchicine-intolerant patients. This review aims to attract the attention of the readers on differential diagnosis and management of patients with FMF. The current state-of-the-art on FMF is outlined, with respect to epidemiological, genetic, pathophysiological and therapeutic characteristics, based on critical analysis of solid scientific literature. FMF is more frequent than it was thought before. The phenotypic expression of M694V is more severe than that of V726A. Patients with M694V/M694V homozygosity are exposed to a higher risk of developing renal amyloidosis, arthritis, dermatologic and oral lesions, higher fever and more frequent painful attacks. Life-long therapy with colchicine (1·0-2·4 mg/day) is effective and safe to prevent recurrent attacks and renal amyloidosis and to reverse proteinuria. In nonresponder patients, alternative novel approaches include interleukin-1 receptor antagonist anakinra and the interleukin-1 decoy receptor rilonacept. The prognosis of FMF is normal if AA amyloidosis is prevented. Colchicine remains the first-line therapy to treat pain and prevent amyloidosis. A follow-up should include clinical evaluation, therapeutic adjustments, measurement of serum amyloid A and proteinuria. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

  17. A Case of Immunotactoid Glomerulopathy with Rapid Progression to End-Stage Renal Disease

    Directory of Open Access Journals (Sweden)

    Shikha Jain

    2009-01-01

    Full Text Available Immunotactoid glomerulopathy (IGN is a rare immunoglobulin deposition disease. It is often mistaken for cryoglobulinemia or amyloidosis due to the similarities on biopsy findings. The disease progresses to end-stage renal disease (ESRD within 7 months to 10 years. This is the first case reported of a patient with a diagnosis of IGN who developed acute kidney injury (AKI and ESRD within 1 week of initial presentation.

  18. Familial amyloid polyneuropathy: elaboration of a therapeutic patient education programme, "EdAmyl".

    Science.gov (United States)

    Théaudin, Marie; Cauquil, Cécile; Antonini, Teresa; Algalarrondo, Vincent; Labeyrie, Céline; Aycaguer, Sophie; Clément, Mireille; Kubezyk, Marie; Nonnez, Géraldine; Morier, Agnès; Bourges, Catherine; Darras, Amandine; Mouzat, Laurence; Adams, David

    2014-12-01

    Transthyretin-related amyloidosis (ATTR) is an autosomal dominant disease affecting the peripheral and autonomic nervous system, heart, eyes and kidneys. It is the most disabling hereditary polyneuropathy in adults. The French National Reference centre for this disease was accredited in 2005 with 10 lines of action. One of them is to inform and educate patients about their disease to improve their care and reduce morbidities. We thus decided to elaborate a therapeutic patient education (TPE) programme, starting with patients' needs assessment. A qualitative research study was conducted with one-to-one semi-structured interviews of selected individuals. Recorded interviews were analysed to identify the skills that patients need to acquire. A TPE programme was elaborated on the basis of these findings. Seven patients, one asymptomatic carrier and two healthy spouses were interviewed. Analysis of the interviews showed that interviewees had a good knowledge of the disease and its symptoms but they had difficulties explaining the disease mechanism and did not have an adequate knowledge of the available treatment options, although they knew that liver transplant might halt progression of the disease. ATTR amyloidosis appeared to have a major negative impact on the patient's physical and mental well-being. Patients feared loss of autonomy and having to require assistance from their relatives and spouses. All interviewees were keen to participate in a TPE programme. Based on this needs assessment, we identified seven skills that patients need to acquire and several pedagogical goals to be achieved during the education programme. An interdisciplinary team then elaborated a complete TPE programme. Elaboration of a TPE programme for ATTR amyloidosis required to obtain useful information from the patients themselves, and their relatives, concerning their perception of their disease. This needs' assessment constituted the basis for designing the first TPE programme, to our

  19. Restrictive cardiomyopathy and pseudoxanthoma elasticum skin lesions.

    Science.gov (United States)

    Musumeci, Maria B; Semprini, Lorenzo; Casenghi, Matteo; Montesanti, Dalma; Mastromarino, Vittoria; Socciarelli, Fabio; Volpe, Massimo; Autore, Camillo

    2016-12-01

    : We report a rare case of a patient with AL amyloidosis and pseudoxanthoma elasticum skin lesions. An association between these two diseases has been previously described as amyloid elastosis in only six cases, but cardiac findings were not fully elucidated. The peculiarity of our case is that a severe cardiac involvement influenced the prognosis negatively. Furthermore, the electron microscopic examination did not show all the peculiar histopathological findings of amyloid elastosis, precluding a final diagnosis of this disease.

  20. Congenital and inherited renal disease of small animals.

    Science.gov (United States)

    Greco, D S

    2001-03-01

    Congenital renal diseases are present at birth and may be determined genetically; familial renal disorders occur in related animals with a higher frequency than would be expected by chance, and frequently are inherited. The most common familial disorders in cats and dogs include renal amyloidosis, renal dysplasia, polycystic kidneys, basement membrane disorders, and tubular dysfunction (Fanconi's syndrome). This article alerts the veterinarian to commonly observed congenital and hereditary conditions of the kidneys in small animals.

  1. The first step of hen egg white lysozyme fibrillation, irreversible partial unfolding, is a two-state transition

    OpenAIRE

    Xu, Ming; Shashilov, Victor A.; Ermolenkov, Vladimir V.; Fredriksen, Laura; Zagorevski, Dmitri; Lednev, Igor K.

    2007-01-01

    Amyloid fibril depositions are associated with many neurodegenerative diseases as well as amyloidosis. The detailed molecular mechanism of fibrillation is still far from complete understanding. In our previous study of in vitro fibrillation of hen egg white lysozyme, an irreversible partially unfolded intermediate was characterized. A similarity of unfolding kinetics found for the secondary and tertiary structure of lysozyme using deep UV resonance Raman (DUVRR) and tryptophan fluorescence sp...

  2. Kidney involvement in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    P. Lazzarini

    2011-09-01

    Full Text Available Rheumatoid Arthritis (RA is a widespread disease and its renal involvement, relatively common, is clinically significant because worsens course and mortality of the primary disease. There is still no agreement on the prevalence of renal disorders in RA: data analysis originates from different sources, as death certificates, autopsies, clinical and laboratory findings and kidney biopsies, each with its limitations. Histoimmunological studies on bioptical specimens of patients with RA and kidney damage, led to clarify prevalent pathologies. In order of frequency: glomerulonephritis and amyloidosis (60-65% and 20-30% respectively, followed by acute or chronic interstitial nephritis. Kidney injury during RA includes secondary renal amyloidosis, nephrotoxic effects of antirheumatic drugs and nephropathies as extra-articular manifestations (rheumatoid nephropathy. Amyloidosis affects survival, increases morbidity and is the main cause of end stage renal disease in patients with RA and nephropathy. Strong association between RA activity and amyloidosis needs the use of immunosuppressive and combined therapies, to prevent this complication and reduce risk of dialysis. Long-lasting and combined RA pharmacotherapy involves various renal side effects. In this review we describe NSAIDs and DMARDs (Disease-Modifying Antirheumatic Drugs nephrotoxicity, particularly by gold compounds, D-penicillamine, cyclosporine A and methotrexate. Rare cases of IgA glomerulonephritis during immunomodulating therapy with leflunomide and TNF blocking receptor (etanercept are reported; real clinical significance of this drug-related nephropathy will be established by development of RA treatment. In RA nephropathies, mesangial glomerulonephritis is the most frequent histological lesion (35-60 % out of biopsies from patients with urinary abnormalities and/or kidney impairment, followed by minimal change glomerulopathy (3-14% and p-ANCA positive necrotizing crescentic

  3. Wnt Signaling in Prostate Cancer Bone Metastases

    Science.gov (United States)

    2016-11-01

    of diacetyl (2,3- butanedione), an α-dicarbonyl flavoring which reacts with proteins . Cells process misfolded proteins by ubiquitination and... damage . DCXR may modify diacetyl toxicity. Impact: K63-ubiquitination in airway epithelium may be a mechanistically-based biomarker of protein damage ...1,2 1Dept. of Veterinary Preventive Medicine. 2Morris Animal Foundation Amyloidosis is a chronic, protein misfolding disorder that causes

  4. Calumenin interacts with serum amyloid P component

    DEFF Research Database (Denmark)

    Vorum, H; Jacobsen, Christian; Honoré, Bent

    2000-01-01

    with calumenin in the presence of Ca(2+). Amino acid sequencing identified this protein as serum amyloid P component (SAP). Furthermore, we verified and characterized the calumenin-SAP interaction by the surface plasmon resonance technique. The findings indicate that calumenin may participate...... in the immunological defense system and could be involved in the pathological process of amyloidosis that leads to formation of amyloid deposits seen in different types of tissues. Udgivelsesdato: 2000-Jan-14...

  5. Isaac Albeniz (1860-1909): Spanish musician who died of chronic renal disease.

    Science.gov (United States)

    García-Nieto, Víctor M; Peralta-Aros, Carolina

    2013-02-01

    Isaac Albéniz was a Spanish musician and pianist who was best known in France and England. One of his last works for piano, the suite Iberia, is well-known and identifies his country of origin. He died with terminal uraemia following longstanding chronic intestinal and kidney symptoms. Suggestions as to pathology include amyloidosis complicated by kidney stones and hypertension that sometimes manifested itself in the form of hypertensive crisis, accompanied by obesity.

  6. A specific nanobody prevents amyloidogenesis of D76N β2-microglobulin in vitro and modifies its tissue distribution in vivo

    Science.gov (United States)

    Raimondi, Sara; Porcari, Riccardo; Mangione, P. Patrizia; Verona, Guglielmo; Marcoux, Julien; Giorgetti, Sofia; Taylor, Graham W.; Ellmerich, Stephan; Ballico, Maurizio; Zanini, Stefano; Pardon, Els; Al-Shawi, Raya; Simons, J. Paul; Corazza, Alessandra; Fogolari, Federico; Leri, Manuela; Stefani, Massimo; Bucciantini, Monica; Gillmore, Julian D.; Hawkins, Philip N.; Valli, Maurizia; Stoppini, Monica; Robinson, Carol V.; Steyaert, Jan; Esposito, Gennaro; Bellotti, Vittorio

    2017-01-01

    Systemic amyloidosis is caused by misfolding and aggregation of globular proteins in vivo for which effective treatments are urgently needed. Inhibition of protein self-aggregation represents an attractive therapeutic strategy. Studies on the amyloidogenic variant of β2-microglobulin, D76N, causing hereditary systemic amyloidosis, have become particularly relevant since fibrils are formed in vitro in physiologically relevant conditions. Here we compare the potency of two previously described inhibitors of wild type β2-microglobulin fibrillogenesis, doxycycline and single domain antibodies (nanobodies). The β2-microglobulin -binding nanobody, Nb24, more potently inhibits D76N β2-microglobulin fibrillogenesis than doxycycline with complete abrogation of fibril formation. In β2-microglobulin knock out mice, the D76N β2-microglobulin/ Nb24 pre-formed complex, is cleared from the circulation at the same rate as the uncomplexed protein; however, the analysis of tissue distribution reveals that the interaction with the antibody reduces the concentration of the variant protein in the heart but does not modify the tissue distribution of wild type β2-microglobulin. These findings strongly support the potential therapeutic use of this antibody in the treatment of systemic amyloidosis. PMID:28429761

  7. SAP: structure, function, and its roles in immune-related diseases.

    Science.gov (United States)

    Xi, Dan; Luo, TianTian; Xiong, Haowei; Liu, Jichen; Lu, Hao; Li, Menghao; Hou, Yuqing; Guo, Zhigang

    2015-01-01

    Serum amyloid P component (SAP), also known as pentraxin-2, is a member of the pentraxin protein family with an established relationship to the immune response. In the last century, SAP has been used as a diagnostic marker in amyloidosis diagnosis and patient follow-up. SAP has been thought to have potential for treating and curing amyloidosis and fibrosis diseases. More recently, it has been shown that SAP may serve as both a diagnostic marker and a therapeutic target for many immune-related diseases, such as cardiovascular, pulmonary, nephritic, neurological and autoimmune diseases. In the cardiovascular system, SAP has been defined as the culprit in amyloidosis in the heart. SAP may also exert a protective role during the early stage of atherosclerosis and myocardial fibrosis. In noncardiovascular system diseases, SAP is being developed for the treatment of pulmonary fibrosis. In this review, we summarize SAP history, structure, and its roles in immune-related diseases in different systems with emphasis on the cardiovascular system. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Semantic verbal fluency pattern, dementia rating scores and adaptive behavior correlate with plasma Aβ42 concentrations in Down syndrome young adults

    Directory of Open Access Journals (Sweden)

    Laura eDel Hoyo

    2015-11-01

    Full Text Available Down syndrome is an intellectual disability disorder in which language and, specifically, verbal fluency are strongly impaired domains; nearly all adults show neuropathology of Alzheimer’s disease, including amyloid deposition by their fifth decade of life. In the general population, verbal fluency deficits are considered a strong Alzheimer’s disease predictor being the Semantic Verbal Fluency Task (SVFT a useful tool for enhancing early diagnostic. However, there is a lack of information about the association between the semantic verbal fluency pattern (SVFP and the biological amyloidosis markers in Down syndrome. In the current study, we used the SVFT in young adults with Down syndrome to characterize their SVFP, assessing total generated words, clustering, and switching. We then explored its association with early indicators of dementia, adaptive behavior and amyloidosis biomarkers, using the Dementia Questionnaire for Persons with Intellectual Disability (DMR, the Adaptive Behavior Assessment System-Second Edition (ABAS-II, and plasma levels of Aβ peptides (Aβ40 and Aβ42, as a potent biomarker of Alzheimer's disease. In Down syndrome, worse performance in SVFT and poorer communication skills were associated with higher plasma Aβ42 concentrations, a higher DMR score and impaired communication skills (ABAS–II. The total word production and switching ability in SVFT were good indicators of plasma Aβ42 concentration. In conclusion, we propose the SVFT as a good screening test for early detection of dementia and amyloidosis in young adults with Down syndrome.

  9. Amyloid and immune homeostasis.

    Science.gov (United States)

    Wang, Ying-Hui; Zhang, Yu-Gen

    2018-03-01

    Extracellular amyloid deposition defines a range of amyloidosis and amyloid-related disease. Addition to primary and secondary amyloidosis, amyloid-related disease can be observed in different tissue/organ that sharing the common pathogenesis based on the formation of amyloid deposition. Currently, both Alzheimer's disease and type 2 diabetes can be diagnosed with certainly only based on the autopsy results, by which amyloidosis of the associative tissue/organ is observed. Intriguingly, since it demonstrated that amyloid deposits trigger inflammatory reaction through the activation of cascaded immune response, wherein several lines of evidence implies a protective role of amyloid in preventing autoimmunity. Furthermore, attempts for preventing amyloid formation and/or removing amyloid deposits from the brain have caused meningoencephalitis and consequent deaths among the subjects. Hence, it is important to note that amyloid positively participates in maintaining immune homeostasis and contributes to irreversible inflammatory response. In this review, we will focus on the interactive relationship between amyloid and the immune system, discussing the potential functional roles of amyloid in immune tolerance and homeostasis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  10. A Case of Multiple Myeloma Diagnosed by Skin Lesions

    Directory of Open Access Journals (Sweden)

    Fatma Gülru Erdoğan

    2010-10-01

    Full Text Available Multiple myeloma, being a malignant proliferation of plasma cells in the bone marrow, has clinical spectrum varying from monoclonal gammopathy with unknown significance to plasma cell leukemia. The presenting symptoms have usually been bone pain, pathologic fractures or repeating infections. In patients with multiple myeloma, amyloid depositions may be seen in the skin. This form, defined as primary systemic amyloidosis, is characterized by light-chain amyloid fibril depositions. Our case applied with multiple, asymptomatic, yellowish papules localized on the face, trunk, oral and genital mucosa, gradually increasing during the last two years. He had no complaints, except for slight weight loss. In routine tests, the patient had no pathological laboratory findings, except high C-reactive protein levels. Further research revealed histopathologic and immunohistochemical findings consistent with amyloidosis. Upon these results, immunoglobulin G levels were measured and found high, and in protein electrophoresis, IgG monoclonal gammopathy was determined. The diagnosis of multiple myeloma is made by bone marrow biopsy. This patient is presented for being an asymptomatic case diagnosed by skin findings of amyloidosis.

  11. Lack of evidence for protein AA reactivity in amyloid deposits of lattice corneal dystrophy and amyloid corneal degeneration.

    Science.gov (United States)

    Gorevic, P D; Rodrigues, M M; Krachmer, J H; Green, C; Fujihara, S; Glenner, G G

    1984-08-15

    Amyloid fibrils occurring in primary and myeloma-associated (AL), secondary (AA), and certain neuropathic hereditary forms of systemic amyloidosis can be distinguished biochemically or immunohistologically as being composed of immunoglobulin light chain, protein AA, or prealbumin respectively. All types of systemic and several localized forms of amyloidosis contain amyloid P component (protein AP). We studied formalin-fixed tissue from eight cases of lattice corneal dystrophy by the immunoperoxidase method using antisera to proteins AA and AP, to normal serum prealbumin and prealbumin isolated from a case of hereditary amyloidosis, and to light-chain determinants; additional cases were examined by indirect immunofluorescence of fresh-frozen material. We found weak (1:10 dilution) staining with anti-AP, but no reactivity with other antisera. Congo red staining was resistant to pretreatment of sections with potassium permanganate, a characteristic of non-AA amyloid. Two-dimensional gels of solubilized proteins from frozen tissue from two cases of lattice corneal dystrophy resembled those obtained from normal human cornea. Western blots of two cases of polymorphous amyloid degeneration and solubilized protein from normal cornea did not react with radioactive iodine-labeled anti-AA or anti-AP with purified protein AP and unfixed protein AA amyloid tissue as controls. We were unable to corroborate the presence of protein AA in the amyloid deposits of lattice corneal dystrophy. Although staining with antiserum to protein AP was demonstrable, the molecular configuration of this protein in stromal deposits remains to be defined.

  12. In vitro binding of [³H]PIB to human amyloid deposits of different types.

    Science.gov (United States)

    Hellström-Lindahl, Ewa; Westermark, Per; Antoni, Gunnar; Estrada, Sergio

    2014-03-01

    Systemic amyloidosis is caused by extracellular deposition of insoluble fibrillar proteins arranged in β-pleated sheets. [(11)C]PIB has been used in PET studies to assess Aβ deposition in brain of patients with Alzheimer's disease (AD). The possibility to visualize other types of amyloid deposits with [(11)C]PIB would be of potential clinical importance in early diagnosis and for following therapeutic effects. In the present study, we evaluated in vitro binding of [(3)H]PIB to tissues containing transthyretin (ATTR), immunoglobulin light-chain (AL), amyloid protein A (AA) and Aβ amyloid. We found significantly higher binding of [(3)H]PIB in tissue from systemic amyloidoses than in control tissue, i.e. 4.7 times higher (p PIB showed the highest affinity to cortex of AD brain (IC50 = 3.84 nM), while IC50 values were much higher for ATTR, AA and AL type of amyloidosis and large variations in affinity were observed even within tissues having the same type of amyloidosis. Extraction with guanidine-HCl, which disrupts the β-sheet structure, decreased the protein levels and, concomitantly, the binding of [(3)H]PIB in all four types of amyloidoses.

  13. Semantic Verbal Fluency Pattern, Dementia Rating Scores and Adaptive Behavior Correlate With Plasma Aβ42 Concentrations in Down Syndrome Young Adults.

    Science.gov (United States)

    Hoyo, Laura Del; Xicota, Laura; Sánchez-Benavides, Gonzalo; Cuenca-Royo, Aida; de Sola, Susana; Langohr, Klaus; Fagundo, Ana B; Farré, Magí; Dierssen, Mara; de la Torre, Rafael

    2015-01-01

    Down syndrome (DS) is an intellectual disability (ID) disorder in which language and specifically, verbal fluency are strongly impaired domains; nearly all adults show neuropathology of Alzheimer's disease (AD), including amyloid deposition by their fifth decade of life. In the general population, verbal fluency deficits are considered a strong AD predictor being the semantic verbal fluency task (SVFT) a useful tool for enhancing early diagnostic. However, there is a lack of information about the association between the semantic verbal fluency pattern (SVFP) and the biological amyloidosis markers in DS. In the current study, we used the SVFT in young adults with DS to characterize their SVFP, assessing total generated words, clustering, and switching. We then explored its association with early indicators of dementia, adaptive behavior and amyloidosis biomarkers, using the Dementia Questionnaire for Persons with Intellectual Disability (DMR), the Adaptive Behavior Assessment System-Second Edition (ABAS-II), and plasma levels of Aβ peptides (Aβ40 and Aβ42), as a potent biomarker of AD. In DS, worse performance in SVFT and poorer communication skills were associated with higher plasma Aβ42 concentrations, a higher DMR score and impaired communication skills (ABAS-II). The total word production and switching ability in SVFT were good indicators of plasma Aβ42 concentration. In conclusion, we propose the SVFT as a good screening test for early detection of dementia and amyloidosis in young adults with DS.

  14. Wild-type hen egg white lysozyme aggregation in vitro can form self-seeding amyloid conformational variants.

    Science.gov (United States)

    Sivalingam, Vishwanath; Prasanna, Nalla Lakshmi; Sharma, Neetu; Prasad, Archana; Patel, Basant K

    2016-12-01

    Misfolded β-sheet-rich protein aggregates termed amyloid, deposit in vivo leading to debilitating diseases such as Alzheimer's, prion and renal amyloidosis diseases etc. Strikingly, amyloid can induce conversion of their natively folded monomers into similarly aggregated conformation via 'seeding'. The specificity of seeding is well documented in vivo for prions, where prion-variants arising from conformationally altered amyloids of the same protein, faithfully seed monomers into amyloid displaying the original variant's conformation. Thus far, amyloid variant formation is reported only for a few non-prion proteins like Alzheimer's Aβ42-peptide and β-2 microglobulin, however, their conformational cross-seeding capabilities are unexplored. While mutant human lysozyme causes renal amyloidosis, the hen egg white lysozyme (HEWL) has been extensively investigated in vitro as a model amyloid protein. Here we investigated if wild-type HEWL could form self-seeding amyloid variants to examine if variant formation is more wide-spread. We found that HEWL aggregates formed under quiescent versus agitated conditions, displayed different particle sizes, detergent stabilities & β-sheet content, and they only seeded monomeric HEWL under similar incubation conditions, but not under swapped incubation conditions thereby showing amyloid variant formation by HEWL analogous to prion variants. This may have implications to the amyloidosis caused by different mutants of human lysozyme. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. [Current aspects of the osteoarticular pathology of hemodialysis patients. Results and discussion of a rheumatological survey].

    Science.gov (United States)

    Foissac-Gegoux, P; Flipo, R M; Hardouin, P; Dumont, A; Duquesnoy, B; Lecomte-Houcke, M; Delcambre, B

    1986-01-01

    In a prospective study, 80 patients undergoing long-term hemodialysis, 30% more than ten years, were evaluated for joint function and radiographic abnormalities; 58 patients (72%) had clinical symptoms; non-specific arthralgia was the most frequent; 15 patients had inflammatory pain (shoulders 9, hands 3) and diminution of finger mobility (10). Radiological examinations showed 40 abnormal findings in 23 patients (28%): erosive arthropathies of fingers (4), and multiple geodes of the carpus (8), of the humeral head (7) or of the hip (9). We also detected spondylolisthesis (4), erosive arthropathy of cervical (6) or lumbar (2) spine. Pathological study of synovial biopsies was performed in 16 cases. Amyloidosis was found in 4 samples taken routinely. In 2 other cases the biopsy was done on the basis of lesions seen on x-rays: we found amyloidosis in the synovial membrane in both patients and in the bone in one. In 8 patients we found C3 deposits positive in immunofluorescence. These results underline the role of amyloidosis in the mechanism of some arthropathies in long-term hemodialysis patients.

  16. Peptide p5 binds both heparinase-sensitive glycosaminoglycans and fibrils in patient-derived AL amyloid extracts

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Emily B.; Williams, Angela [Department of Medicine, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37922 (United States); Heidel, Eric [Department of Surgery, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37922 (United States); Macy, Sallie [Department of Medicine, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37922 (United States); Kennel, Stephen J. [Department of Medicine, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37922 (United States); Department of Radiology, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37922 (United States); Wall, Jonathan S., E-mail: jwall@utmck.edu [Department of Medicine, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37922 (United States); Department of Radiology, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37922 (United States)

    2013-06-21

    Highlights: •Polybasic peptide p5 binds human light chain amyloid extracts. •The binding of p5 with amyloid involves both glycosaminoglycans and fibrils. •Heparinase treatment led to a correlation between p5 binding and fibril content. •p5 binding to AL amyloid requires electrostatic interactions. -- Abstract: In previously published work, we have described heparin-binding synthetic peptides that preferentially recognize amyloid deposits in a mouse model of reactive systemic (AA) amyloidosis and can be imaged by using positron and single photon emission tomographic imaging. We wanted to extend these findings to the most common form of visceral amyloidosis, namely light chain (AL); however, there are no robust experimental animal models of AL amyloidosis. To further define the binding of the lead peptide, p5, to AL amyloid, we characterized the reactivity in vitro of p5 with in situ and patient-derived AL amyloid extracts which contain both hypersulfated heparan sulfate proteoglycans as well as amyloid fibrils. Histochemical staining demonstrated that the peptide specifically localized with tissue-associated AL amyloid deposits. Although we anticipated that p5 would undergo electrostatic interactions with the amyloid-associated glycosaminoglycans expressing heparin-like side chains, no significant correlation between peptide binding and glycosaminoglycan content within amyloid extracts was observed. In contrast, following heparinase I treatment, although overall binding was reduced, a positive correlation between peptide binding and amyloid fibril content became evident. This interaction was further confirmed using synthetic light chain fibrils that contain no carbohydrates. These data suggest that p5 can bind to both the sulfated glycosaminoglycans and protein fibril components of AL amyloid. Understanding these complex electrostatic interactions will aid in the optimization of synthetic peptides for use as amyloid imaging agents and potentially as

  17. Concomitant detection of beta-amyloid peptides with N-terminal truncation and different C-terminal endings in cortical plaques from cases with Alzheimer's disease, senile monkeys and triple transgenic mice.

    Science.gov (United States)

    Härtig, Wolfgang; Goldhammer, Simone; Bauer, Ute; Wegner, Florian; Wirths, Oliver; Bayer, Thomas A; Grosche, Jens

    2010-09-01

    The disturbed metabolism of beta-amyloid peptides generated from amyloid precursor protein is widely considered as a main factor during the pathogenesis of Alzheimer's disease. A neuropathological hallmark in the brains from cases with Alzheimer's disease are senile plaques mainly composed of hardly soluble beta-amyloid peptides comprising up to 43 amino acids. Age-dependent cortical beta-amyloidosis was also shown in several transgenic mice and old individuals from various mammalian species, e.g., non-human primates. Beta-amyloid(1-42) is believed to be the main component in the core of senile plaques, whereas less hydrophobic beta-amyloid(1-40) predominantly occurs in the outer rim of plaques. Amino-terminally truncated pyroglutamyl-beta-amyloid(pE3-x) was recently found to be a beta-amyloid species of high relevance to the progression of the disease. While a few biochemical studies provided data on the co-occurrence of several beta-amyloid forms, their concomitant histochemical detection is still lacking. Here, we present a novel triple immunofluorescence labelling of amino- and differently carboxy-terminally truncated beta-amyloid peptides in cortical plaques from a case with Alzheimer's disease, senile macaques and baboons, and triple transgenic mice with age-dependent beta-amyloidosis and tau hyperphosphorylation. Additionally, beta-amyloid(pE3-x) and total beta-amyloid were concomitantly detected with beta-amyloid peptides ending with amino acid 40 or 42, respectively. Simultaneous staining of several beta-amyloid species reveals for instance vascular amyloid containing beta-amyloid(pE3-x) in Alzheimer's disease and monkeys, and may contribute to the further elucidation of beta-amyloidosis in neurodegenerative disorders and animal models. 2010 Elsevier B.V. All rights reserved.

  18. RAGE binds preamyloid IAPP intermediates and mediates pancreatic β cell proteotoxicity.

    Science.gov (United States)

    Abedini, Andisheh; Cao, Ping; Plesner, Annette; Zhang, Jinghua; He, Meilun; Derk, Julia; Patil, Sachi A; Rosario, Rosa; Lonier, Jacqueline; Song, Fei; Koh, Hyunwook; Li, Huilin; Raleigh, Daniel P; Schmidt, Ann Marie

    2018-02-01

    Islet amyloidosis is characterized by the aberrant accumulation of islet amyloid polypeptide (IAPP) in pancreatic islets, resulting in β cell toxicity, which exacerbates type 2 diabetes and islet transplant failure. It is not fully clear how IAPP induces cellular stress or how IAPP-induced toxicity can be prevented or treated. We recently defined the properties of toxic IAPP species. Here, we have identified a receptor-mediated mechanism of islet amyloidosis-induced proteotoxicity. In human diabetic pancreas and in cellular and mouse models of islet amyloidosis, increased expression of the receptor for advanced glycation endproducts (RAGE) correlated with human IAPP-induced (h-IAPP-induced) β cell and islet inflammation, toxicity, and apoptosis. RAGE selectively bound toxic intermediates, but not nontoxic forms of h-IAPP, including amyloid fibrils. The isolated extracellular ligand-binding domains of soluble RAGE (sRAGE) blocked both h-IAPP toxicity and amyloid formation. Inhibition of the interaction between h-IAPP and RAGE by sRAGE, RAGE-blocking antibodies, or genetic RAGE deletion protected pancreatic islets, β cells, and smooth muscle cells from h-IAPP-induced inflammation and metabolic dysfunction. sRAGE-treated h-IAPP Tg mice were protected from amyloid deposition, loss of β cell area, β cell inflammation, stress, apoptosis, and glucose intolerance. These findings establish RAGE as a mediator of IAPP-induced toxicity and suggest that targeting the IAPP/RAGE axis is a potential strategy to mitigate this source of β cell dysfunction in metabolic disease.

  19. Colon Biopsy Findings of Renal Transplant Patients.

    Science.gov (United States)

    Taştepe, Firdevs Zeynep; Özgün, Gonca; Özdemir, Binnaz Handan; Tepeoğlu, Merih; Haberal, Mehmet

    2016-11-01

    The purpose of this study was to evaluate colonic pathologies in renal transplant recipients. Patients with colon biopsies were selected from 1816 renal transplant recipients from January 1990 to December 2012 at Baskent University Hospital (Ankara, Turkey). Demographic and clinical findings with colon biopsies were examined. There were 84 patients who had colon biopsies after renal transplant. There were 57 male and 27 female patients (median age at renal transplant was 33 y). Chronic diarrhea was the most common clinical finding at the time of colon biopsy. The median interval from renal transplant to first colon biopsy was 48.1 ± 47.5 months. On microscopic evaluation, there were no pathologic changes in 17 patients. The remaining 67 patients had colitis (38 patients), polyps (17 patients), cytomegalovirus colitis (8 patients), and amyloidosis (4 patients). The mean interval between transplant and the diagnosis of colitis was 49.08 ± 42.6 months, amyloidosis was 47.5 ± 79.28 months, cytomegalovirus colitis was 5 ± 3.5 months, and polyps was 77.65 ± 58.8 months. There was a statistically significant difference between biopsy diagnosis and the time interval between transplant and colon biopsy (P colonic biopsies, 40 patients never had acute rejection episodes and 44 patients had at least 1 acute rejection episode. Seven of 8 patients with cytomegalovirus colitis, 19 of 38 with colitis, 3 of 4 with amyloidosis, and 5 of 17 with polyps had acute rejection episodes. In our report on colonic manifestations in renal transplant recipients, the most common colonic lesion was noninfectious colitis. Cytomegalovirus colitis is an important infection that affects immunosuppressed individuals, such as transplant recipients. Cytomegalovirus must be kept in mind, and thorough sectioning and immunohistochemical sta ining should be used if necessary in the presence of any clinical or histologic suspicion for infective colitis.

  20. The role of MEFV mutations in the concurrent disorders observed in patients with familial Mediterranean fever

    Science.gov (United States)

    Güncan, Sabri; Bilge, N. Şule Y.; Cansu, Döndü Üsküdar; Kaşifoğlu, Timuçin; Korkmaz, Cengiz

    2016-01-01

    Objective This study aimed to investigate the frequency in which familial Mediterranean fever (FMF) coexists with other diseases and determine whether Mediterranean fever (MEFV) gene mutations are involved in such coexistence. Material and Methods In total, 142 consecutive patients with FMF investigated for MEFV mutation were enrolled in this study [Female: 87; Male: 55, mean age 32±12 years (11–62)]. All the patients were questioned for the presence of concurrent disorders, and the medical records of these patients were revised retrospectively. A previous diagnosis of inflammatory disorder other than FMF was considered true if it met the relevant criteria. MEFV mutations were divided into 2 groups, namely M694V and its subgroup (homozygous or heterozygous) (Group I) and others (Group II). Compound heterozygosity for M694V mutation was included in Group II to form a homogeneous group for Group I. Group I and Group II were compared according to phenotypical features. The presence of MEFV mutation was investigated in exons 2, 3, 5, and 10 by the multiplex-PCR reverse hybridization method. Results Concomitant disorders were found in 17 of 73 patients with FMF (23%) in Group I and 5 of 56 patients (8.9%) in Group II (p=0.04). Concomitant disorders in Group I were as follows: 7 cases of amyloidosis, 2 cases of Behcet’s disease (BD), 4 cases of ankylosing spondylitis (AS), 1 case of antiphospholipid syndrome, 1 case of Henoch–Schonlein purpura (HSP), 1 case of combination of psoriatic arthritis, HSP, and membranoproliferative glomerulonephritis, and 1 case of AS and amyloidosis. In Group II, the following disorders were found: 1 case of amyloidosis, 1 case of BD, 1 case of AS, 1 case of ulcerative colitis, and 1 case of vitiligo. Conclusion The presence of M694V mutation may predispose patients with FMF to developing other inflammatory disorders. PMID:27733942

  1. Anti-TNFα therapy for chronic inflammatory disease in kidney transplant recipients: Clinical outcomes.

    Science.gov (United States)

    Garrouste, Cyril; Anglicheau, Dany; Kamar, Nassim; Bachelier, Claire; Rivalan, Joseph; Pereira, Bruno; Caillard, Sophie; Aniort, Julien; Gatault, Philippe; Soubrier, Martin; Sayegh, Johnny; Colosio, Charlotte; Buisson, Anthony; Thervet, Eric; Bouvier, Nicolas; Heng, Anne Elisabeth

    2016-10-01

    Anti-tumor necrosis factor-α (TNFα) therapy has improved the prognosis of many chronic inflammatory diseases. It appears to be well-tolerated by liver-transplant patients. However, their use and their safety in kidney-transplant patients have yet to be determined.In this retrospective study, we identified 16 adult kidney-transplant patients aged 46.5 years (34-51.8) who received anti-TNFα therapy from 7 kidney transplantation centers. The indications for this treatment included: chronic inflammatory bowel disease (n = 8), inflammatory arthritis (n = 5), AA amyloidosis (n = 1), psoriasis (n = 1), and microscopic polyangiitis (n = 1).Anti-TNFα therapies resulted in a clinical response in 13/16 patients (81%). Estimated glomerular filtration rates (MDRD-4) were similar on day 0 and at 24 months (M24) after anti-TNFα treatment had been initiated (41 [12-55] and 40 [21-53] mL/min/1.73 m, respectively). Two allograft losses were observed. The 1st case was due to antibody-mediated rejection (M18), while the 2nd was the result of AA amyloidosis recurrence (M20). There were several complications: 8 patients (50%) developed 23 serious infections (18 bacterial, 4 viral, and 1 fungal) and 4 developed cancer. Five patients died (infection n = 2, cardiac AA amyloidosis n = 1, intraalveolar hemorrhage following microscopic polyangiitis n = 1, and acute respiratory distress syndrome n = 1). On univariate analysis, recipient age associated with death (P = 0.009) and infection development (P = 0.06).Using anti-TNFα therapies, remission can be achieved in chronic inflammatory diseases in kidney-transplant patients. However, concommitant anti-TNFα and immunosuppresive therapies must be used with caution due to the high risk of infection, particularly after the age of 50.

  2. [Morphological and electrophysiological changes of the heart atria in necropsy patients with atrial fibrillation - a pilot study].

    Science.gov (United States)

    Matějková, Adéla; Steiner, Ivo

    2014-01-01

    Atrial fibrillation (AF), the most common supraventricular tachycardia, has a morphological base, so called remodelation of atrial myocardium, with its abnormal conduction pattern as a consequence. The remodelation regards electrical, contractile, and structural properties. In this pilot study we attempted to find relations between the myocardial morphological (scarring, amyloidosis, left atrial enlargement) and electrophysiological (ECG characteristics of the P-wave) changes in patients with AF. We examined 40 hearts of necropsy patients - 20 with a history of AF and 20 with no history of AF. Grossly, the heart weight and the size of the left atrium (LA) were evaluated. Histologically, 7 standard sites from the atria were examined. In each specimen, the degree of myocardial scarring and of deposition of isolated atrial amyloid (IAA) were assessed. We failed to show any significant difference in the P-wave pattern between patients with and without AF. Morphologically, however, there were several differences - the patients with AF had significantly heavier hearts, larger left atria, more severely scarred myocardium of the LA and the atrial septum, and more severe deposition of IAA in both atria in comparison to the control group of patients with sinus rhythm. The left atrial distribution of both fibrosis and amyloidosis was irregular. In patients with AF the former was most pronounced in the LA ceiling while the latter in the LA anterior wall. The entire series showed more marked amyloidosis in the left than in the right atrium. An interesting finding was the universal absence of IAA in the sinoatrial node. The knowledge of distribution of atrial myocardial structural changes could be utilized by pathologists in taking specimens for histology and also by cardiologists in targeting the radiofrequency ablation therapy.

  3. Importance of renal biopsy in patients aged 60 years and older: Experience from a tertiary care hospital

    Directory of Open Access Journals (Sweden)

    Pallav Gupta

    2018-01-01

    Full Text Available As the life expectancy is increasing, there is a rise in elderly population and consequent increase in the patients with renal disease. There is an inconsistency between clinical and histopathological diagnosis in elderly, and so renal biopsy is important in these patients to decide appropriate clinical management and prognosis. This study outlines the importance of renal biopsy in elderly and describes the clinical and pathologic spectrum of renal diseases in patient ≥60 years. All patients (age ≥60 years undergoing renal biopsies from January 2011 to December 2014 were included in this retrospective study. The clinical presentation and biochemical findings were recorded, and the patients were grouped based on their clinical presentation. Renal biopsies were also evaluated. The mean age of patients was 67.7 ± 6.4 years with a male:female ratio of 3:1. The most common clinical manifestation was nephrotic syndrome (37.4% followed by rapidly progressive renal failure (RPRF (20.6%. Amyloidosis and membranous nephropathy were two most common diagnoses in patients with nephrotic presentation whereas pauci-immune crescentic glomerulonephritis and cast nephropathy were common in patients presenting with RPRF. Clinical diagnosis differed from the histopathological diagnosis in 32% cases of nephrotic syndrome. There was good agreement between clinical diagnosis and histology in cases with RPRF. In 73% cases of elderly with (Type II diabetes suspected of having nondiabetic renal disease clinically, renal biopsy showed evidence of diabetic nephropathy. Renal biopsy is essential in the diagnosis of renal diseases even in elderly. Amyloidosis and membranous nephropathy are common causes of nephrotic syndrome in elderly. Renal biopsy is very useful in diagnosing cast nephropathy and amyloidosis as they are not suspected clinically. It is also helpful in elderly diabetics without retinopathy to differentiate between diabetic and nondiabetic kidney

  4. Killer Cell Immunoglobulin-Like Receptor (KIR) Genotype Distribution in Familial Mediterranean Fever (FMF) Patients.

    Science.gov (United States)

    Erken, Ertugrul; Goruroglu Ozturk, Ozlem; Kudas, Ozlem; Arslan Tas, Didem; Demirtas, Ahmet; Kibar, Filiz; Dinkci, Suzan; Erken, Eren

    2015-11-17

    BACKGROUND Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease predominantly affecting Mediterranean populations. The gene associated with FMF is the MEFV gene, which encodes for a protein called pyrin. Mutations of pyrin lead to uncontrolled attacks of inflammation, and subclinical inflammation continues during attack-free intervals. Killer cell immunoglobulin-like receptor (KIR) genes encode HLA class I receptors expressed by NK cells. The aim this study was to look for immunogenetic determinants in the pathogenesis of FMF and find out if KIR are related to susceptibility to disease or complications like renal amyloidosis. MATERIAL AND METHODS One hundred and five patients with FMF and 100 healthy individuals were involved in the study. Isolated DNA from peripheral blood was amplified by sequence specific PCR probes and analyzed by Luminex for KIR genotypes. Fisher Exact test was used to evaluate the variation of KIR gene distribution. RESULTS All patients and healthy controls expressed the framework genes. An activator KIR gene, KIR2DS2, was significantly more frequent in FMF patients (p=0.036). Renal amyloidosis and presence of arthritis were not associated with KIR genes and genotype. KIR3DL1 gene was more common in patients with high serum CRP (p=0.016). CONCLUSIONS According to our findings, we suggest that presence of KIR2DS2, which is an activator gene for NK cell functions, might be related to the autoinflammation in FMF. The potential effect of KIR genes on amyloidosis and other clinical features requires studies with larger sample sizes.

  5. Monoclonal Gammopathy of Undetermined Significance with Amyloid Deposition in the Lung and Non-Amyloid Eosinophilic Deposition in the Brain: A Case Report

    Directory of Open Access Journals (Sweden)

    Francois Abi-Fadel

    2010-01-01

    Full Text Available Background. Monoclonal gammopathy of undetermined significance (MGUS is rarely complicated by amyloidosis. Case. A 66-year-old white male presented to the emergency room (ER after an unwitnessed fall and change in mental status. Patient was awake and alert but not oriented. There was no focal deficit on neurological exam. Past medical history (PMH included hypertension, hypercholesterolemia, aortic valve replacement (nonmetallic, incomplete heart block controlled by a pacemaker and IgG- IgA type Monoclonal Gammopathy of Undetermined Significance. The MGUS was diagnosed 9 months ago on serum protein electrophoresis (SPEP as patient was referred to the outpatient clinic for hyperglobulinemia on routine blood work. In ER, a head-computed tomography (CT revealed multiple parenchymal hemorrhagic lesions suspicious for metastases. A CT chest, abdomen and pelvis revealed numerous ground-glass and solid nodules in the lungs. Lower extremity duplex and transesophageal echocardiogram were negative. Serial blood cultures and serologies for cryptococcus and histoplasmosis, antineutrophil cytoplasmic antibody (ANCA, antinuclear antibody (ANA, rheumatoid factor (RF, cryoglobulin, and antiglomerular basement membrane (anti-GBM antibodies were all negative. CT guided lung biopsy was positive for Thioflavin T amyloid deposits. Brain biopsy was positive for eosinophilic material (similar to the lungs but negative for Thioflavin T stain. The patient's clinical status continued to deteriorate with cold cyanotic fingers developing on day 12 and a health care acquired pneumonia, respiratory failure, and fungemia on day 18. On day 29, family withdrew life support and denied any autopsies. Conclusion. Described is an atypical course of MGUS complicated by amyloidosis of the lung and nonamyloid eosinophilic deposition in the brain. As MGUS might be complicated by diseases such as amyloidosis and multiple myeloma, a scheduled follow-up of these patients is always

  6. Extended analysis of AL-amyloid protein from abdominal wall subcutaneous fat biopsy

    DEFF Research Database (Denmark)

    Olsen, K E; Sletten, K; Westermark, Per

    1998-01-01

    In AL-amyloidosis the cause of amyloid fibril formation in beta-pleated sheets from the precursor protein immunoglobulin light chain is not established, but studies of AL-proteins indicate that amino acid substitutions are important in the pathogenesis. Amyloid material was extracted from...... a subcutaneous fat tissue biopsy and submitted to extended protein separation, typing and amino acid sequence analyses. The AL-protein belonged to the rare immunoglobulin light chain kappa, subtype kappa IV and contained unique amino acid substitutions, mostly in the highly preserved framework regions. The study...... shows that subcutaneous fat biopsies are useful sources of amyloid material for biochemical studies....

  7. NONSPECIFIC INFECTIONS OF THE BONE TISSUE

    Directory of Open Access Journals (Sweden)

    Zoran Golubovic

    2002-11-01

    Full Text Available Osteomyelitis represents an inflammation of the bone tissue caused by microorganisms. The cause of the inflammation can be bacteria, viruses and parasites. The bone infections are divided into specific and nonspecific. Regarding the course they take, they can be of acute or chronic form. Nonspecific bone infections are analyzed, namely, hematogenic and exogenous osteomyelitis. The most frequent complications of osteomyelitis are bone infection recidivism, pathological fractures, infection penetration into the joint, malign tissue alteration and amyloidosis as a consequence of the chronic infection.

  8. Urinary capillariosis in six dogs from Italy

    Directory of Open Access Journals (Sweden)

    A. Mariacher

    2016-06-01

    Full Text Available Canine urinary capillariosis is caused by the nematode Pearsonema plica. P. plica infection is seldomly detected in clinical practice mainly due to diagnostic limitations. This report describes six cases of urinary capillariosis in dogs from Italy. Recurrent cystitis was observed in one dog, whereas another patient was affected by glomerular amyloidosis. In the remaining animals, the infection was considered an incidental finding. Immature eggs of the parasite were observed with urine sediment examination in 3/6 patients. Increased awareness of the potential pathogenic role of P. plica. and clinical disease presentation could help identify infected animals.

  9. Familial Mediterranean fever: An updated review

    Science.gov (United States)

    Sarı, İsmail; Birlik, Merih; Kasifoğlu, Timuçin

    2014-01-01

    Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disorder characterised by acute attacks of fever and serosal inflammation. FMF primarily affects Jewish, Armenian, Turkish, and Arab populations. The disease is accompanied by a marked decrease in quality of life due to the effects of attacks and subclinical inflammation in the attack-free periods. Untreated or inadequately treated patients run the risk of amyloidosis, which is an important cause of morbidity and mortality. In this review, the current information available on FMF is summarised. PMID:27708867

  10. Notalgia Paraesthetica

    Directory of Open Access Journals (Sweden)

    Malakar Subrata

    1998-01-01

    Full Text Available Two cases of notalgia paraesthetica (NP are presented. Both the patients were female and above 30 years of age. Clinically the lesions closely simulated macular amyloidosis over interscapular region. However, history of associated pruritus, tingling, fornication and altered sensation over the patch pointed towards the diagnosis of NP, Histopathological examinations in both the cases revealed intraepidermal necrotic keratinocytes with desquamation remnants of necrotic keratinocytes in the stratum corneum. Congo red and crystal violet stains were negative for presence of amyloidal in thedermis. In both the patients, symptomatic improvement was observed after 3 weeks’ application of topical capsaicin.

  11. Amyloid goiter: two cases and a review of the Literature

    International Nuclear Information System (INIS)

    Yildiz, Levent; Kefeli, Mehmet; Kose, Behiye; Baris, Sancar

    2007-01-01

    Although involvement of the thyroid gland by amyloid is a relatively common phenomenon, clinically significant enlargement of the thyroid owing to amyloid deposition is an extremely rare occurrence. We describe two cases of amyloid goiter and review the relevant literature. The first case was systemic amylloidosis secondary to familial Mediterranean fever. The second case was a chronic renal failure patient who presented with an enlarged thyroid and upper airway obstructive symptoms. To date, true amyloid goiter secondary to amyloidosis associated with familial Mediterranean fever has only been reported in twelve patients. (author)

  12. Sciatic nerve tumor and tumor-like lesions - uncommon pathologies

    Energy Technology Data Exchange (ETDEWEB)

    Wadhwa, Vibhor; Thakkar, Rashmi S.; Carrino, John A.; Chhabra, Avneesh [Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Maragakis, Nicholas; Hoeke, Ahmet; Sumner, Charlotte J.; Lloyd, Thomas E. [Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD (United States); Belzberg, Allan J. [Johns Hopkins University School of Medicine, Department of Neurosurgery, Baltimore, MD (United States)

    2012-07-15

    Sciatic nerve mass-like enlargement caused by peripheral nerve sheath tumors or neurocutaneous syndromes such as neurofibromatosis or schwannomatosis has been widely reported. Other causes of enlargement, such as from perineuroma, fibromatosis, neurolymphoma, amyloidosis, endometriosis, intraneural ganglion cyst, Charcot-Marie-Tooth disease, and chronic inflammatory demyelinating polyneuropathy are relatively rare. High-resolution magnetic resonance imaging (MRI) is an excellent non-invasive tool for the evaluation of such lesions. In this article, the authors discuss normal anatomy of the sciatic nerve and MRI findings of the above-mentioned lesions. (orig.)

  13. CLINICOPATHOLOGIC CORRELATES OF FASCIOLIASIS IN TWO EASTERN GREY KANGAROOS (MACROPUS GIGANTEUS).

    Science.gov (United States)

    Portas, Timothy J; Taylor, David

    2015-12-01

    Infection with the introduced trematode Fasciola hepatica was associated with anemia, mild to moderate azotemia, hypoalbuminemia, and elevated liver enzymes and creatine kinase values in two free-ranging eastern grey kangaroos (Macropus giganteus). Both kangaroos were euthanized because of the severity of clinical signs associated with infection. Histopathologic changes included severe cholangiohepatitis, biliary hyperplasia, and fibrosis. Hepatic, splenic, and intestinal amyloidosis was present in one kangaroo and hepatic abscessation in the other; neither histologic change has been reported in macropodids with fascioliasis previously.

  14. Debilitation and mortality associated with besnoitiosis in four Virginia opossums (Didelphis virginiana).

    Science.gov (United States)

    Ellis, Angela E; Mackey, Elizabeth; Moore, Philip A; Divers, Stephen J; Hensel, Patrick; Carmichael, K Paige; Accola, Peter; Brown, Justin; Gottdenker, Nicole; Keel, M Kevin; Shock, Barbara C; Yabsley, Michael J

    2012-06-01

    Besnoitia spp. are coccidian parasites that infect a variety of wild and domestic mammals as well as some reptiles. Although infection with Besnoitia is common in Virginia opossums (Didelphis virginiana), clinical signs or death due to Besnoitia is rare. This manuscript describes four Virginia opossums that had severe clinical disease and inflammation associated with besnoitiosis. Clinical signs included trembling, incoordination, circling, blindness, poor body condition, and sudden death. Gross lesions included parasitic cysts in eyes, skin, and visceral organs. Histologically, cysts were often degenerate and associated with mild to marked inflammation, and amyloidosis was noted in one animal. Polymerase chain reaction and sequencing confirmed Besnoitia darlingi in three of the four opossums.

  15. MRI evaluation of amyloid myopathy

    International Nuclear Information System (INIS)

    Metzler, J.P.; Fleckenstein, J.L.; Veterans Affairs Medical Center, Dallas, TX; White, C.L. III; Veterans Affairs Medical Center, Dallas, TX; Haller, R.G.; Greenlee, R.G. Jr.; Veterans Affairs Medical Center, Dallas, TX; Frenkel, E.P.; Veterans Affairs Medical Center, Dallas, TX

    1992-01-01

    Amyloid myopathy is a rare complication of primary amyloidosis. The magnetic resonance imaging (MRI) features of two patients with amyloid myopathy were studied. Slight prolongation of muscle T1 and T2 relaxation times was evident but the striking abnormality was marked reticulation of the subcutaneous fat. The clinical findings of indurated extremities far exceeds the minimal signal intenisty alteration seen in the muscles. The MR appearance of amyloid myopathy differs from that of other neuromuscular conditions in the minimal changes found in muscle, but the striking abnormality seen in subcutaneous fat makes it distinct from many neuromuscular conditions. (orig.)

  16. Multiple Myeloma, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology.

    Science.gov (United States)

    Kumar, Shaji K; Callander, Natalie S; Alsina, Melissa; Atanackovic, Djordje; Biermann, J Sybil; Chandler, Jason C; Costello, Caitlin; Faiman, Matthew; Fung, Henry C; Gasparetto, Cristina; Godby, Kelly; Hofmeister, Craig; Holmberg, Leona; Holstein, Sarah; Huff, Carol Ann; Kassim, Adetola; Liedtke, Michaela; Martin, Thomas; Omel, James; Raje, Noopur; Reu, Frederic J; Singhal, Seema; Somlo, George; Stockerl-Goldstein, Keith; Treon, Steven P; Weber, Donna; Yahalom, Joachim; Shead, Dorothy A; Kumar, Rashmi

    2017-02-01

    Multiple myeloma (MM) is caused by the neoplastic proliferation of plasma cells. These neoplastic plasma cells proliferate and produce monoclonal immunoglobulin in the bone marrow causing skeletal damage, a hallmark of multiple myeloma. Other MM-related complications include hypercalcemia, renal insufficiency, anemia, and infections. The NCCN Multiple Myeloma Panel members have developed guidelines for the management of patients with various plasma cell dyscrasias, including solitary plasmacytoma, smoldering myeloma, multiple myeloma, systemic light chain amyloidosis, and Waldenström's macroglobulinemia. The recommendations specific to the diagnosis and treatment of patients with newly diagnosed MM are discussed in this article. Copyright © 2017 by the National Comprehensive Cancer Network.

  17. Effect of chronic irradiation combined with other damaging factors on some morphological systems of mice

    International Nuclear Information System (INIS)

    Ponomareva, T.V.; Merkushev, G.N.; Pil'shchuk, E.M.; Bikkulov, R.I.

    1978-01-01

    A model experiment on mice is carried out to study morphofunctional changes that occur in mammals chronically exposed to radiation in doses close to those in occupational exposures of a man. Mice have been exposed to gamma-radiation at dose rates of 6, 16, 40, 120, and 300 mr/day from the time of birth onward throughout lifetime. It is concluded that, where a chronic purulent infection is present, chronic irradiation at the above dose rates, with the exception of 6 mr/day, accelerates the onset of irreversible pathologic changes, in particular of amyloidosis, in immunocompetent organs

  18. More than simple hepatic cysts

    Directory of Open Access Journals (Sweden)

    Daniela Tabacelia

    2016-04-01

    Full Text Available Caroli diseaseis a rare congenital disorder that classically causes saccular dilatation of the bile ducts. The complications of Caroli include choledochal cysts with recurrent cholangitis, abscess formation, septicaemia, intrahepatic lithiasis and amyloidosis.We report a rare case of a young female with Caroli disease pointing out the intrahepatic lithiasis as a rare complication of the disease. Learning points Caroli disease is an uncommon condition that should be considered in the differential diagnosis of hepatic essential cysts. Clinically, it is characterized of recurrent episodes of fever and pain. The correct and early diagnostic is important because of the different complications and treatment unlike the essential hepatic cysts.

  19. B-Receptor Signaling in Cardiomyopathy

    Science.gov (United States)

    2015-11-16

    Carcinomas; Amyloidosis; Anal Cancer; Anemia; Cholangiocarcinoma of the Extrahepatic Bile Duct; Transitional Cell Carcinoma of Bladder; Bone Marrow Transplant Failure; Bone Cancer; Cancer of Brain and Nervous System; Breast Cancer; Carcinoma of the Large Intestine; Endocrine Cancer; Esophageal Cancer; Eye Cancer; Gall Bladder Cancer; Gastric (Stomach) Cancer; Gastrooesophageal Cancer; Gastrointestinal Stromal Tumor (GIST); Gynecologic Cancers; Head and Neck Cancers; Hepatobiliary Neoplasm; Kidney (Renal Cell) Cancer; Leukemia; Lung Cancer; Hodgkin Disease; Lymphoma, Non-Hodgkin; Mesothelioma; Multiple Myeloma; Myelodysplastic Syndromes (MDS); Neuroendocrine Tumors; Myeloproliferative Disorders; Pancreatic Cancer; Prostate Cancer; Skin Cancer; Soft Tissue Sarcoma; Testicular Cancer; Thymus Cancer; Thyroid Cancer

  20. Long-Term Health Effects of Repeated Exposure to Multiple Vaccines

    Science.gov (United States)

    2004-01-01

    Temporal arteritis 0 2 0 0.8 1.000 Amyloidosis 0 1 0 0.4 1.000 Guillain – Barre syndrome 0 1 0 0.4 1.000 Anemia of chronic disease 0 0 0 0 1.000 Aplastic...variety of investi- gational and licensed vaccines against the pathogens under study as adjuncts to environmental (i.e., physical barrier) pro- tection...yposensitization therapy in allergy clinics [4,5]. The magnitude (nearly three-fold) of the increased preva- ence of serum paraproteinemia among elderly individu