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Localized AL amyloidosis of the colon: an unrecognized entity.

Virtually all patients who present with rectal bleeding and amyloid of the colon have evidence of systemic amyloidosis and require therapy. The small subset of patients with amyloidosis localized to the colon must be recognized and treatment avoided. We queried our file for patients who had amyloidosis of the colon but no evidence of systemic amyloidosis during long-term follow-up. We identified 3 patients who presented with rectal bleeding and who, on investigation, had primary amyloidosis of the colon but no evidence of systemic amyloidosis during a follow-up of 4.5 to 20 years. These patients had no evidence of a plasma cell dyscrasia and received no chemotherapy to prevent deposition of amyloid. It is important to recognize this rare subset and avoid treatment with alkylating agents or high-dose therapy followed by autologous stem cell transplantation. Alkylating agent therapy may be associated with myelodysplasia or acute leukemia. In addition, the cost, inconvenience, and morbidity of therapy are avoided by observation. Patients who present with rectal bleeding and a subsequent diagnosis of amyloidosis of the colon likely will be subjected to chemotherapy or transplantation. Such patients must be recognized and treatment avoided if there is no evidence of systemic amyloidosis because they remain stable for many years.

Adult↗

Tracheobronchial amyloidosis.

OBJECTIVE: To evaluate the presentation and clinical course of patients with tracheobronchial amyloidosis. PATIENTS AND METHODS: We retrospectively reviewed the records of all patients with biopsy-proven tracheobronchial amyloidosis who were evaluated at the Mayo Clinic in Rochester, Minn, between 1973 and 1999. All relevant information, such as clinical, historical, demographic, laboratory, and histological data, was examined. RESULTS: Tracheobronchial amyloidosis was diagnosed in 17 patients (9 women and 8 men), with a mean age of 56.6 years. The most common symptoms at presentation were dyspnea, cough, hemoptysis, and hoarseness. None of the 14 patients who underwent investigation for systemic amyloidosis had any evidence of disease outside the tracheobronchial system except for a man in whom multiple myeloma had been diagnosed 3 years before the development of respiratory disease. Treatment of tracheobronchial amyloidosis consisted of laser or forceps resection, external radiation, systemic therapy, or observation. Two patients died of complications directly related to their disease. CONCLUSIONS: Patients presenting with tracheobronchial amyloidosis have symptoms similar to those caused by various airway disorders. Tracheobronchial amyloidosis is not typically associated with systemic amyloidosis or pulmonary parenchymal involvement. It often recurs and despite repeated attempts with bronchoscopic techniques, airway compromise remains a major problem.

Adult↗

[Left ventricular filling disturbances in cardiac amyloidosis: a study of atrial sound and diastolic inflow velocities].

Cardiac amyloidosis is characterized by left ventricular filling disturbances in a relatively early stage. To investigate such disturbances more precisely, we studied atrial sound and left ventricular inflow velocity patterns. Twelve cases diagnosed as cardiac amyloidosis according to the clinical criteria including rectal biopsies and serum amyloid proteins or at autopsy were reviewed and analyzed. Their mean age was 60.9 +/- 12.5 years. Twelve age-matched cases with hypertrophic cardiomyopathy (HCM) served as the controls. We measured the amplitude of atrial sound by low-frequency phonocardiograms and the ratio of the heights of the A wave of apexcardiograms (ACG) to the total amplitude of the ACG. The mitral inflow velocity patterns were recorded using pulsed Doppler echocardiography. The rapid filling wave (R), atrial filling wave (A) and the ratio of A to R (A/R) were measured. In the amyloidosis group, atrial sound moderately increased in 2 cases, it was faint in 9 and not manifest in the remaining one. The A wave in the amyloidosis group was significantly smaller than that in the HCM group (p < 0.001) (12.4 +/- 3.9 vs 22.4 +/- 5.6%). In the left ventricular inflow velocity patterns, the R in amyloidosis was smaller than that in HCM (41.7 +/- 16.0 vs 56.4 +/- 12.1 cm/sec) (p < 0.02). The A in amyloidosis was also smaller than that in HCM (40.5 +/- 13.4 vs 58.1 +/- 13.0 cm/sec) (p < 0.006). The A/R was 1.0 +/- 0.34 in amyloidosis and 1.1 +/- 0.32 in HCM (N.S.). Both A and R were significantly less in amyloidosis than those in HCM.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The pattern of amyloidosis in Malaysia.

Congo red screening of routine biopsies at the University Hospital Kuala Lumpur revealed the following categories of amyloidosis: systemic AL (5.9%); systemic AA (3.2%); isolated atrial (14%); primary localized cutaneous (7.5%); other primary localized deposits (3.2%); localized intratumour (58%); and dystrophic (8.6%). Unlike in the West, AA amyloidosis in this population was usually secondary to leprosy or tuberculosis. Liver involvement in AL amyloidosis was shown to exhibit a sinusoidal pattern and differed from the vascular pattern of AA amyloidosis. Within the category of AA amyloidosis, there were two patterns of renal involvement--glomerular and vascular, with the glomerular pattern carrying a more ominous clinical picture. Notable among the localized amyloidoses were isolated atrial amyloidosis complicating chronic rheumatic heart disease, intratumour amyloidosis within nasopharyngeal carcinomas and dystrophic amyloidosis which occurred in fibrotic tissues.

Adolescent↗

Study of a restriction fragment length polymorphism for serum amyloid P gene in rheumatoid arthritis with amyloidosis.

Amyloidosis is a severe complication of rheumatoid arthritis (RA). A restriction fragment length polymorphism (RFLP) using MspI for the serum amyloid P gene was recently found to be associated with amyloidosis in juvenile arthritis. The aim of our study was to determine whether this RFLP could serve as a genetic marker for the development of secondary amyloidosis in RA. The prevalence of this marker was determined in 4 groups of patients: patients with amyloidosis secondary to RA; with amyloidosis secondary to various diseases excluding RA; with RA but without amyloidosis; adult controls without any known disease related to reactive amyloidosis. No significant differences were seen between these 4 groups with relation to this polymorphism, so that it cannot serve as a genetic marker for amyloidosis complicating RA in our population.

Amyloidosis↗

[An AA-amyloidosis course in patients with rheumatoid arthritis].

AIM: To characterize renal amyloidosis in patients with rheumatoid arthritis and stages of amyloid nephropathy. MATERIAL AND METHODS: The trial covered 30 patients (6 males and 24 females) with documented rheumatoid arthritis (RA) complicated with secondary AA-amyloidosis. Amyloidosis diagnosis was confirmed in all the patients morphologically, the samples were studied with the peroxidase immunohistochemical method using specific monoclonal antibodies to SAA. Clinical manifestations of RA were assessed by the disease activity, functional impairment of the joints, x-ray alterations, extraarticular signs of RA, etc. All the patients were examined clinically, total blood count and biochemical tests were made. RESULTS: In 23 (77%) of 30 examinees with RA, proteinuria as the first clinical symptom of AA-amyloidosis emerged with the first 15 years of RA. RA of the second-third degree of activity were diagnosed in 25 (83%) patients, 21 (70%) patients had apparent destructive changes in the joints (x-ray stage III-IV). Severe functional insufficiency of the joints was observed in 25 (83%) patients, deformation of the joints - in 27 (90%) patients. Clinically, renal amyloidosis was characterized by change of stages - from moderate proteinuria to nephrotic syndrome and renal failure. Prognosis of amyloid nephropathy in RA depends on duration of the proteinuric stage: if this stage is short (3 years maximum), the prognosis is worse than in its long duration. CONCLUSION: RA ranks first among causes of secondary AA-amyloidosis. Development of AA-amyloidosis in RA patients is most probable in the first 15 years of the course of the articular process. Amyloidosis is more frequent in patients with severe clinical manifestations of RA.

Adult↗

Classification of amyloidosis by the detection of clonal excess of plasma cells in the bone marrow.

In 28 cases of amyloidosis, bone marrow was examined to determine whether detection of clonal excess of plasma cells could be used to distinguish immunoglobulin-derived amyloidosis from other forms of amyloidosis. Patients were selected from a group of 315 cases of biopsy-proved amyloidosis in which bone marrow aspiration and biopsy had been done. There was no detectable monoclonal immunoglobulin in the serum or in the urine in 28 patients. Of 13 patients with immunoglobulin-derived amyloidosis, a clonal excess of plasma cells in the bone marrow could be detected in 11 (sensitivity, 85%), even though no immunoglobulin could be found circulating in the serum or urine after immunofixation with two light chain antisera of different sources. The 15 remaining patients had other forms of amyloidosis; 14 had polyclonal populations of plasma cells in the bone marrow (specificity, 93%). The positive predictive value of clonal excess was 92% and its negative predictive value was 88%. We conclude that, in the subset of patients with amyloidosis who do not have a circulating M component in the serum or urine detection of a clonal excess of plasma cells is useful in characterizing the type of amyloidosis. Correct classification is important for appropriate assessment of prognosis and therapy for the group of patients.

Adult↗

[The incidence and possibility of detecting various forms of senile amyloidosis (based on autopsy data from the clinics of the I. M. Sechenov 1st Moscow Medical Institute from 1955 to 1987)].

It is shown that senile amyloidosis can not be detected without use of special stain (Congo red, thyophlavin T): not a single case was found when 17445 pathology records were reexamined for 30-year period. Special staining methods allow detection of senile amyloidosis in 6.8% of cases. Local forms of senile amyloidosis (isolated auricula amyloidosis, aortal amyloidosis, cerebral amyloidosis, amyloidosis of the pancreatic insular apparatus or that of seminal vesicles) constitute 85.4%, generalized and multiorgan forms--14.6%. Every form of the senile amyloidosis has its own features with regard to the incidence, age, sex and age peak.

Adult↗

[Amyloidosis in Crohn disease. Case reports and review of the literature].

A review of the literature on Crohn's disease with secondary amyloidosis and four own case reports are presented. At least 1% of patients with Crohn's disease develop amyloidosis. The extent of the inflammatory bowel disease seems to have an influence on the occurrence of amyloidosis. The survival time of 40 out of 72 patients was 2.1 years after the onset of diagnosis. The complications induced by the amyloidosis determine the fate of the patients. Therefore the periodical protein determination in urine and the Congo-red-colouring of rectal mucosa after rectoscopy are justified. After the diagnosis of amyloidosis in patients with Crohn's disease the inflammation should be treated consequently, according to the principles of the treatment of the underlying disease. But the resection of the inflammatory bowel should be avoided if the renal function is still sufficient, because frequently there occurs a postoperative renal failure. In the case of renal amyloidosis with a creatinin-clearance of more than 10 ml/min, a therapeutic attempt should be made with 1.0 to 1.5 mg/day of colchicin or 10 g/day dimethylsulphoxid (DMSO) for at least six months. During existing renal failure the proceeding of amyloidosis in other organs is to be expected. The secondary amyloidosis disposes the fate of the patients.

Adult↗

Amyloidosis at Groote Schuur Hospital, Cape Town.

The records of 52 patients with amyloidosis admitted to Groote Schuur Hospital, Cape Town, between January 1969 and August 1982 were analysed. The male: female ratio was 1,3:1 and the mean age was 49,3 years. Forty-eight per cent of the patients had secondary amyloidosis, 21% had primary amyloidosis, 11,5% had localized amyloidosis and 11,5% had amyloidosis associated with multiple myeloma. Tuberculosis, chronic pulmonary sepsis and other chronic infections were present in 88% and rheumatoid arthritis in 16% of the patients with secondary amyloidosis. The commonest features at diagnosis were proteinuria (70%), oedema (52%) and hepatomegaly (39%). The diagnosis of amyloidosis was established by renal, liver and rectal biopsy (either singly or in combination) in 82% of cases. The prevalence of amyloidosis at autopsy was 0,28%.

Adult↗

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

UNLABELLED: 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) has lately been developed as a specific noninvasive alternative. We report a detailed analysis of the abnormal turnover of SAP in patients with systemic amyloidosis and an assessment of its clinical value. METHODS: Iodine-123-labeled human SAP (200 MBq) SAP was injected intravenously into 49 patients with histologically proven systemic AA- or AL- amyloidosis and in 7 control subjects. Plasma clearance and whole-body retention of labeled SAP were analyzed over 48 hr using plasma sampling, whole-body gamma camera imaging and measurement of radioactivity in the urine. The rate of SAP synthesis and interstitial exchange were determined, and the size of the amyloid compartment was compared with clinical estimates of whole-body amyloid load and patient survival. RESULTS: All plasma time-activity curves were biphasic. In comparison with control subjects, patients with amyloidosis showed significantly faster plasma disappearance [4-hr value: AA 48% +/- 18%, AL 45% +/- 15% versus 65% +/- 8% (p < 0.05)], higher total-body retention 48 hr p.i. [AA 74% +/- 14%, AL 73% +/- 17% versus 46% +/- 15% (p < 0.01)] and especially higher extravascular retention 48 hr p.i. [AA 59% +/- 16%, AL 58% +/- 19% versus 30% +/- 14% (p < 0.01)]. Extravascular retention correlated with clinical estimation of the amyloid load. If extravascular retention values in patients with AL amyloidosis were over 60%, survival was decreased (median 4 versus 23 mo, p < 0.001). Markedly increased interstitial exchange rates were present in amyloidosis (AA 64 +/- 61, AL 50 +/- 37 versus 18 +/- 8 mg/hr), whereas the SAP synthesis rate did not differ from the control values (AA 5.0 +/- 3.0, AL 5.5 +/- 3.2 versus 4.5 +/- 1.4 mg/hr). CONCLUSION: The presence of systemic amyloidosis is characterized by accelerated initial clearance of 123I-SAP from the plasma and increased interstitial exchange rate and extravascular retention. These findings reflect reversible binding of radiolabeled SAP to amyloid deposits and provide clinically useful information for diagnosis, monitoring of therapy and prognosis in patients with systemic amyloidosis.

Adult↗

[Participation of apoptosis in renal amyloidosis].

Renal amyloidosis shows symptoms of renal dysfunction due to the deposition of amyloid protein in the kidney. Recently, it was reported that apoptosis plays an important role in the pathogenesis of type-2 diabetes mellitus and Alzheimer's disease of which amyloid deposition is seen in the tissue. We investigated whether or not apoptosis and related factors are observed in renal amyloidosis. In situ nick end labeling (TUNEL) was performed in seven autopsied renal tissues with primary and secondary amyloidosis and 10 autopsied renal tissues without renal disease as the control. The number of TUNEL-positive cells was significantly increased in both the glomeruli and tubulus of the kidney with amyloidosis than in the control. Electron microscopic analysis was performed on one biopsied renal tissue with amyloidosis and six biopsied renal tissues with minor abnormalities as the control. Typical apoptotic cells were observed only in the former. Bax product, an inducer of apoptosis, and Bcl-2 protein, an inhibitor of apoptosis, were examined immunohistochemically in the seven autopsied renal tissues with amyloidosis and 10 autopsied control tissues. Bax was overexpressed in the tubulus and glomeruli of subjects with renal amyloidosis, compared to the normal controls. However, Bcl-2 protein was not detected in the glomeruli in any of the subjects examined. These results indicate that apoptotic cells are increased in number in renal amyloidosis and Bax overexpression may play an important role in this increase.

Aged↗

Liver transplantation for hereditary transthyretin amyloidosis.

Transthyretin (TTR) amyloidosis is the most common form of hereditary amyloidosis. It is a systemic amyloidosis caused by an amyloidogenic variant TTR (ATTR), of which the methionine for valine at position 30 (ATTR Val30Met) gives rise to a fatal neuropathic amyloidosis. Because more than 95% of TTR is produced by the liver, a liver transplantation should abolish the liver's production of amyloidogenic mutant TTR and thereby halt amyloid formation. The first liver transplantation for hereditary TTR amyloidosis was performed in Sweden in 1990 on a patient with ATTR Val30Met amyloidosis, and the result was encouraging. Today, liver transplantation for TTR amyloidosis is an established treatment. However, the disease is rarely seen except in a few endemic areas; therefore, most transplantation centers only receive a few cases. Because the disease phenotype varies with different TTR mutations and variability is even encountered for the same mutation, an evaluation of patients for transplantation must include an investigation of all organs that may be affected by the disease and may impact on the morbidity and mortality of the procedure. The aim of this review is to present the results of liver transplantation for TTR amyloidosis and give recommendations for patient evaluation and selection based on the literature and our experience with the disease.

Amyloid Neuropathies↗

Cardiac amyloidosis: heterogenous pathogenic backgrounds.

Cardiac amyloidosis is a fatal disorder which develops on the basis of the different pathologic conditions in systemic amyloidosis: the most common underlying disease is immunoglobulin light chain-derived primary amyloidosis and the next is transthyretin-related hereditary amyloidosis; the latter disorder, typically represented by familial amyloid polyneuropathy, was long regarded as an endemic disease. However, this disorder has now been shown to involve a highly variable clinical picture due to a large number of transthyretin gene mutations, and many patients with diverse ancestors suffer from severe cardiac amyloidosis. Additionally, senile systemic amyloidosis is now noted as a cause of cardiac dysfunction in elderly individuals. Echocardiogram and myocardial technetium-99m-pyrophosphate scintigraphy can provide characteristic findings. Immunohistochemistry on tissue amyloid, biochemical analysis of serum and urine proteins, and DNA sequencing are usually employed to determine the disease-related amyloid fibril protein. Although systemic amyloidosis has become treatable, the prognosis of each patient who received up-to-date and effective, but nevertheless stressful, therapy depends on the severity of cardiac involvement by amyloid deposition.

Amyloidosis↗

The inheritance of spontaneous amyloidosis development in mice: a model for hereditary threshold metabolic disorders.

To study the inheritance of spontaneous amyloidosis development in mice, we crossed the LLC strain (with a high incidence) with the A/J strain (with a low incidence) and with the HLC strain (with a zero incidence of amyloidosis). We produced the F1 and a backcross generation to each parental strain in each cross. Examination of the spleen, liver, and kidneys of each mouse for the presence of amyloid was made between age 15 and 18 months. The data fit neither a dominant nor a recessive single gene hypothesis for the development of amyloidosis. In consideration of amyloidosis as a hereditary threshold character, we developed an additive gene model. Subsequently, a test for fitness of the observed percentages to the expected percentages in the backcross generations was made according to this model. The observed percentages of amyloidosis in the spleens, livers, and individual mice agreed with the expected percentages in the LLC X A/J crosses but not in the LLC X HLC crosses. Therefore, we conclude that for the development of amyloidosis, a difference exists at one locus between LLC and A/J and at more than one locus between LLC and HLC. The probability of development of amyloidosis in an individual depends on the effects of the genes at these loci. For hereditary metabolic disorders that cannot be explained by either a single dominant or recessive gene hypothesis, this genetic model may be useful to test whether the development of the disease is due to additive effects of genes.

Amyloidosis↗

Serum amyloid P component scintigraphy and turnover studies for diagnosis and quantitative monitoring of AA amyloidosis in juvenile rheumatoid arthritis.

OBJECTIVE: To evaluate aspects of the natural history of AA amyloidosis complicating juvenile rheumatoid arthritis (JRA), and its response to therapy with chlorambucil. METHODS: Scintigraphy and 7-day turnover studies were performed in JRA patients with histologically proven (n = 35) or clinically suspected (n = 30) AA amyloidosis, following intravenous injection of 123I and 125I-labeled serum amyloid P component (SAP). Prospective monitoring studies were performed over 2-3 years in 20 patients with amyloidosis. All but 2 amyloidosis patients were treated with chlorambucil. RESULTS: Positive scanning results were obtained in all patients in whom imaging was performed within 12 years of positive biopsy findings of amyloid and in 5 patients with clinically suspected amyloidosis. Negative scanning results with normal SAP metabolism, indicating regression of amyloid, were obtained in 4 patients whose amyloidosis had been in full clinical remission for more than 12 years. Prospective monitoring studies in patients whose JRA-associated inflammatory activity was in remission demonstrated regression of amyloid in 8 patients and no substantial changes in 8 others; however, in 4 further patients with active inflammation, there was accumulation of amyloid. There was a very poor correlation between the amount of amyloid present at a particular site and the resultant organ dysfunction. CONCLUSION: Radiolabeled SAP scintigraphy and turnover studies are useful complementary tools in the diagnosis, screening, and quantitative monitoring of type AA amyloidosis in JRA. The amyloid deposits may progress and/or regress at different rates in different anatomic sites over short periods.

Adolescent↗

Hepatic amyloidosis: clinical appraisal in 77 patients.

The purpose of this study was to assess prognostic factors and survival in patients with liver involvement in immunoglobulin light-chain amyloidosis. Comparisons were made with other patients with immunoglobulin light-chain amyloidosis who did not have liver involvement. A total of 77 consecutively seen patients were evaluated: 19 had hepatic amyloidosis and 58 had amyloidosis without liver involvement. Eighteen of 19 patients with liver amyloidosis could be histologically diagnosed without needle biopsy of the liver. All but 2 had a detectable free light chain in the serum or urine, distinguishing this from other infiltrative liver processes. Patients with liver amyloid had significantly higher alkaline phosphatase levels and C-reactive protein levels compared with patients without hepatic amyloid. The majority of patients had extrahepatic involvement predominantly in the kidney (47%) or heart (42%). The presence of hyposplenism was not a good screening test for the presence of hepatic amyloid. Seven of 19 patients responded to chemotherapy with objective regressions of the clinical manifestations of renal, hepatic, or cardiac involvement. We conclude that the survival of patients with liver involvement in amyloidosis is no different than other patients with amyloidosis. This results from the high proportion of patients having associated renal or cardiac involvement. Most patients can be diagnosed without a liver biopsy when a monoclonal protein is found in the serum or urine. Serum albumin and C-reactive protein levels appear to distinguish patients with liver involvement from those without.

Adult↗

Casein-induced murine amyloidosis: amyloid and immunoglobulin production and proliferative capacity of splenocytes.

We have examined some aspects of lymphocyte and macrophage function in experimental murine amyloidosis. Casein-induced murine amyloidosis is a good model for studying secondary human amyloidosis while myeloma-associated murine amyloidosis is a poor model for human myeloma-associated amyloidosis. The amyloid of casein-induced and myeloma-associated murine amyloidosis cross-reacted immunologically. Neither form of amyloidosis was associated with L chain fragments or excess L chain production. Cellular immunologic reactivity of casein-induced amyloidotic mice, as assessed by lymphocyte transformation with mitogens, was abnormal using spleen lymphocytes but completely normal when thymus and peripheral blood lymphocytes were examined. The depressed activity could be attributed to splenic amyloid deposits. Intracellular amyloid was detected in the spleens of casein-injected mice prior to extracellular amyloid deposits. Amyloid containing cells could also be cultured from the spleen in a much higher proportion than that found in vivo. These cells may represent a subpopulation committed to amyloid synthesis.

Amyloid↗