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Gut Feb 1991Hepatic venous catheterisation and transvenous liver biopsy were performed in five patients with hepatic amyloidosis. In three patients, hepatic venous pressures were... (Review)
Review
Hepatic venous catheterisation and transvenous liver biopsy were performed in five patients with hepatic amyloidosis. In three patients, hepatic venous pressures were normal and histological examination of the liver biopsy specimen showed discrete and sparse perisinusoidal amyloid deposits. In the other two, however, the gradient between wedged and free hepatic venous pressures was increased (12 and 16 mmHg; normal 1-4 mmHg) and amyloid deposits were abundant and diffuse in the Disse's space. This study shows that portal hypertension in patients with hepatic amyloidosis is of the sinusoidal type and is related to the reduction of vascular space of hepatic sinusoids by massive perisinusoidal amyloid deposits. Furthermore, portal hypertension is associated with a poor prognosis in patients with hepatic amyloidosis.
Topics: Aged; Amyloidosis; Female; Humans; Hypertension, Portal; Liver Diseases; Male; Middle Aged
PubMed: 1864548
DOI: 10.1136/gut.32.2.227 -
Journal of Biochemistry May 2024Amyloidosis is characterized by the abnormal accumulation of amyloid proteins. The causative proteins aggregate from monomers to oligomers and fibrils, among which some... (Review)
Review
Amyloidosis is characterized by the abnormal accumulation of amyloid proteins. The causative proteins aggregate from monomers to oligomers and fibrils, among which some intermediate oligomers are considered as major toxins. Cytotoxic oligomers are generated not only by aggregation but also via fibril disaggregation. However, little is known about the structural characteristics and generation conditions of cytotoxic oligomers produced during disaggregation. Herein, we summarized the structural commonalities of cytotoxic oligomers formed under various disaggregation conditions, including the addition of heat shock proteins or small compounds. In vitro experimental data demonstrated the presence of high-molecular-weight oligomers (protofibrils or protofilaments) that exhibited a fibrous morphology and β-sheet structure. Molecular dynamics simulations indicated that the distorted β-sheet structure contributed to their metastability. The tendency of these cytotoxic oligomers to appear under mild disaggregation conditions, implied formation during the early stages of disaggregation. This review will aid researchers in exploring the characteristics of highly cytotoxic oligomers and developing drugs that target amyloid aggregates.
Topics: Humans; Amyloid; Molecular Dynamics Simulation; Protein Aggregates; Amyloidosis; Protein Aggregation, Pathological
PubMed: 38430131
DOI: 10.1093/jb/mvae023 -
Journal of Investigative Medicine High... 2024Gastrointestinal amyloidosis is a rare condition commonly found in the setting of systemic AL amyloidosis. Amyloid can deposit throughout the gastrointestinal tract and... (Review)
Review
Gastrointestinal amyloidosis is a rare condition commonly found in the setting of systemic AL amyloidosis. Amyloid can deposit throughout the gastrointestinal tract and the resulting symptoms vary depending on the site of deposition. Gastrointestinal (GI) manifestations can range from weight loss or abdominal pain, to more serious complications like gastrointestinal bleeding, malabsorption, dysmotility, and obstruction. This case describes a patient with known history of IgG lambda AL amyloidosis, presenting with epigastric pain and unintentional weight loss found to have gastroduodenal amyloidosis. The definitive diagnosis of GI amyloidosis requires endoscopic biopsy with Congo red staining and visualization under polarized light microscopy. There are currently no specific guidelines for the management of GI amyloidosis. Generally, the goal is to treat the underlying cause of the amyloidosis along with symptom management. Our patient is being treated with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) and started on hemodialysis due to progression of renal disease.
Topics: Humans; Abdominal Pain; Amyloidosis; Biopsy; Gastrointestinal Hemorrhage; Immunoglobulin Light-chain Amyloidosis; Weight Loss
PubMed: 38462925
DOI: 10.1177/23247096241237759 -
Orphanet Journal of Rare Diseases Dec 2022Systemic amyloidosis is caused by the deposition of misfolded protein aggregates in tissues, leading to progressive organ dysfunction and death. Epidemiological studies...
BACKGROUND
Systemic amyloidosis is caused by the deposition of misfolded protein aggregates in tissues, leading to progressive organ dysfunction and death. Epidemiological studies originate predominantly from high-income countries, with few data from Latin America. Due to the non-specific clinical manifestations, diagnosing amyloidosis is often challenging and patients experience a long journey and delay in diagnosis. This study aimed to assess clinical and laboratory characteristics, the diagnostic journey, and outcomes of patients with biopsy-proven systemic amyloidosis diagnosed between 2009 and 2020 at a university referral center in a middle-income Latin American country. Patients´ medical records were retrospectively reviewed.
RESULTS
One hundred and forty-three patients were included. The median age at diagnosis was 60 years and 54% were male. Until the diagnosis, most of the patients (52%) were seen by at least 3 specialists, the main ones being: general practitioners (57%), nephrologists (45%), and cardiologists (38%). The most common manifestations were renal (54%) and cardiac (41%) disorders, and cachexia was seen in 36% of patients. In 72% of the cases, ≥ 2 biopsies were required until the final diagnosis. The median time from symptoms onset to diagnosis was 10.9 months, and most patients (75%) had ≥ 2 organs involved. The following subtypes were identified: AL (68%), ATTR (13%), AA (8%), AFib (4%), and inconclusive (7%). Median OS was 74.3 months in the non-AL subgroup and 18.5 months in AL. Among AL patients, those with advanced cardiac stage had the worst outcome [median OS 8.6 months versus 52.3 for stage III versus I-II, respectively (p < 0.001)]. AL subtype, cardiac involvement, and ECOG ≥ 2 were identified as independent risk factors for reduced survival.
CONCLUSIONS
Systemic amyloidosis is still an underdiagnosed condition and the delay in its recognition leads to poor outcomes. Medical education, better diagnostic tools, improvement in access to therapies, and establishment of referral centers may improve patient outcomes in middle-income countries.
Topics: Humans; Male; Female; Retrospective Studies; Amyloidosis; Immunoglobulin Light-chain Amyloidosis; Kidney; Biopsy
PubMed: 36471404
DOI: 10.1186/s13023-022-02584-3 -
Journal of Molecular Biology Oct 2018The term amyloid has historically been used to describe fibrillar aggregates formed as the result of protein misfolding and that are associated with a range of diseases... (Review)
Review
The term amyloid has historically been used to describe fibrillar aggregates formed as the result of protein misfolding and that are associated with a range of diseases broadly termed amyloidoses. The discovery of "functional amyloids" expanded the amyloid umbrella to encompass aggregates structurally similar to disease-associated amyloids but that engage in a variety of biologically useful tasks without incurring toxicity. The mechanisms by which functional amyloid systems ensure nontoxic assembly has provided insights into potential therapeutic strategies for treating amyloidoses. Some of the most-studied functional amyloids are ones produced by bacteria. Curli amyloids are extracellular fibers made by enteric bacteria that function to encase and protect bacterial communities during biofilm formation. Here we review recent studies highlighting microbial functional amyloid assembly systems that are tailored to enable the assembly of non-toxic amyloid aggregates.
Topics: Amyloid; Amyloidosis; Animals; Bacterial Proteins; Cell Survival; Humans; Protein Aggregates; Protein Aggregation, Pathological; Protein Folding; Protein Interaction Domains and Motifs; Protein Multimerization; Protein Stability; Structure-Activity Relationship
PubMed: 30017921
DOI: 10.1016/j.jmb.2018.07.007 -
Medicine Jan 2006Autosomal dominant hereditary amyloidosis represents not 1 disease but a group of diseases, each the result of mutations in a specific protein. The most common form is... (Review)
Review
Autosomal dominant hereditary amyloidosis represents not 1 disease but a group of diseases, each the result of mutations in a specific protein. The most common form is transthyretin amyloidosis, which has been recognized clinically for over 50 years as a familial polyneuropathy. Nonneuropathic amyloidoses (Ostertag type amyloidosis) include those due to abnormalities in lysozyme, fibrinogen Aalpha-chain, and apolipoprotein A-I and A-II. The role of lysozyme in amyloid-related human disorders was first described in 1993; to date, there have been only 9 publications describing this disorder, which is a nonneuropathic form of hereditary amyloidosis. Reported cases have involved 7 unrelated families. We describe here our own experience with 4 families suffering from lysozyme amyloidosis: the first had prominent renal manifestations with sicca syndrome, the second and third had prominent gastrointestinal symptoms, and the fourth had a dramatic bleeding event due to rupture of abdominal lymph nodes. To our knowledge, this last symptom has not been reported previously, but is reminiscent of the hepatic hemorrhage seen in a previously reported case of a patient with lysozyme amyloidosis. To characterize the manifestations of this disorder, we performed an exhaustive literature review.Although hereditary amyloidosis is thought to be a rare disease, it is probably not as rare as we think and may well be underdiagnosed. Moreover, some cases of lysozyme amyloidosis are probably confused with acquired monoclonal immunoglobulin light-chain (AL) amyloidosis, formerly known as primary amyloidosis, which is the most frequent type of amyloidosis. Because treatment for each type of amyloidosis is different, and because therapy directed at 1 type may worsen symptoms of the other types, it is important to determine precisely the nature of the amyloid protein. Thus, hereditary lysozyme amyloidosis should be considered in all patients with systemic amyloidosis, particularly in patients who present with renal, gastrointestinal, or bleeding complications without evidence of AL or AA (secondary) amyloidoses.
Topics: Adult; Aged; Amyloidosis; Female; Gastrointestinal Diseases; Hemorrhage; Humans; Kidney Diseases; Lymph Nodes; Male; Middle Aged; Muramidase; Rupture
PubMed: 16523055
DOI: 10.1097/01.md.0000200467.51816.6d -
Annals of Oncology : Official Journal... Jun 2008
Review
Topics: Amyloidosis; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Biomarkers; Dexamethasone; Dose-Response Relationship, Drug; Drug Therapy, Combination; Follow-Up Studies; Humans; Melphalan; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Remission Induction; Stem Cell Transplantation; Survival Analysis; Time Factors; Treatment Outcome
PubMed: 18519408
DOI: 10.1093/annonc/mdn200 -
Alimentary Pharmacology & Therapeutics Jun 2008Amyloidosis is one of the unusual diseases about which a physician may not think when it is affecting the patient. During the last three decades, there has been an... (Review)
Review
BACKGROUND
Amyloidosis is one of the unusual diseases about which a physician may not think when it is affecting the patient. During the last three decades, there has been an enormous progress in the understanding of the chemical nature, classification, pathogenesis, clinical features, diagnostic measures and therapy of this disorder.
AIM
To provide an updated review of amyloidosis affecting the gastrointestinal tract.
METHODS
Review of current medical literature.
RESULTS
Amyloid proteins (irrespective of the type) can deposit in various parts of the gastrointestinal tract and liver resulting in symptoms of abdominal pain, dysmotility, diarrhoea, gastrointestinal bleeding, hepatomegaly and even portal hypertension with its associated complications. Definitive diagnosis can only be made by histological examination of the affected organ. Disease modifying treatment with high-dose chemotherapy followed by autologous stem-cell transplantation has shown promise. Liver transplantation is an option for a select group of patients.
CONCLUSIONS
Suspicion of gastrointestinal amyloidosis in patients without known history of amyloidosis is difficult, but should be considered in those older than 30 years with unexplained diarrhoea, weight loss, autonomic dysfunction, malabsorption or proteinuria. While most gastrointestinal complications are managed symptomatically, causal therapy is reserved for a select few from various subtypes of this disorder.
Topics: Amyloidosis; Diagnosis, Differential; Gastrointestinal Agents; Gastrointestinal Diseases; Humans; Liver Transplantation; Steroids; Transplantation, Autologous
PubMed: 18363891
DOI: 10.1111/j.1365-2036.2008.03682.x -
JACC. Cardiovascular Imaging Dec 2009
Topics: Amyloidosis; Biopsy; Contrast Media; Echocardiography, Doppler; Electrocardiography; Heart Diseases; Humans; Magnetic Resonance Imaging; Myocardium; Predictive Value of Tests; Prognosis; Risk Assessment; Sensitivity and Specificity; Time Factors
PubMed: 20083071
DOI: 10.1016/j.jcmg.2009.10.001 -
Medicine Sep 2019Cardiac amyloidosis, considered for the last years to be a rare disease, is one of the determinants of HFpEF. The non-specific clinical presentation and the difficulties... (Review)
Review
RATIONALE
Cardiac amyloidosis, considered for the last years to be a rare disease, is one of the determinants of HFpEF. The non-specific clinical presentation and the difficulties related to endomyocardial biopsy have made cardiac amyloidosis an underdiagnosed clinical entity. Improvement of non-invasive diagnostic techniques and the development of new therapies increased clinical awareness for this form of restrictive cardiomyopathy. We here summarize echocardiography and Tc-HDP scintigraphy findings in 6 cases of cardiac amyloidosis and review the literature data of this progressive and fatal cardiomyopathy.
PATIENTS CONCERNS
The main clinical manifestations were fatigue, low exercise tolerance and edemas. The right heart failure symptoms usually dominated the clinical picture.
DIAGNOSES
All cases were evaluated by echocardiography; 3 cases were further examined by bone scintigraphy and 4 cases a peripheral biopsy was performed. Electrocardiography showed low-voltage QRS complexes and "pseudo-infarct" pattern in the precordial leads, contrary to the echocardiographic aspect, which revealed thickening of ventricle walls. Biatrial dilation and diastolic disfunction were observed. Impaired systolic function was detected in advanced stages of the disease. Tc-HDP scintigraphy revealed cardiac uptake of radiopharmaceutical and managed to confirm the diagnosis in 1 case of cardiac amyloidosis in which salivary gland biopsy was negative.
INTERVENTIONS
The treatment was based on managing fluid balance, with the mainstream therapy represented by diuretics. Neurohormonal agents, usually used in heart failure treatment were avoided, due to poor tolerance and worsening of disease course. The management of these 6 cases was challenging due to the refractory manifestation of congestive heart failure.
OUTCOMES
During follow-up, 4 of the 6 patients from the current study died in the first year after the final diagnosis was established.
LESSONS
Nuclear imaging of cardiac amyloidosis has a revolutionary development nowadays. Bone scintigraphy presents promising results for identifying patients at early stages of disease and to differentiate between cardiac amyloidosis types. Further studies are necessary for the standardization of imaging protocol and development of non-invasive diagnostic tools, especially in assessing the response to treatment and disease progression, for which little is known.
Topics: Adult; Aged; Aged, 80 and over; Amyloidosis; Diphosphonates; Echocardiography; Female; Heart; Heart Diseases; Humans; Male; Middle Aged; Myocardium; Organotechnetium Compounds; Radionuclide Imaging
PubMed: 31567998
DOI: 10.1097/MD.0000000000017256