Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a patient treated for IgA kappa myeloma, bone marrow relapse and a sharp drop in the serum IgA level paralleled tissue deposition of non-amyloid material reactive with anti-kappa anti-alpha sera in immunofluorescence studies of kidney and liver biopsies. Clinical manifestations were progressive renal failure with nephrotic syndrome, with both tubular and glomerular lesions (including nodular glomerulosclerosis), hepatomegaly, cardiac and neurological symptoms. Biosynthesis experiments showed the production of alpha chains diminished in length by about one domain which were rapidly degraded predominantly after secretion and of two species of light chains; normal-sized light chains which assembled with alpha chains and abnormally short ones which were secreted as free light chains. The apparent molecular weight of the light chains was larger in secretions than in cytoplasmic extracts, suggesting their glycosylation. These results suggest a causal relationship between tissue deposition and production of abnormal immunoglobulins by a variant clone, the emergence of which was possibly induced by Melphalan therapy.
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PMID:Synthesis of abnormal heavy and light chains in multiple myeloma with visceral deposition of monoclonal immunoglobulin. 678 55

Patients with unexplained heart failure, hepatomegaly, nephrotic syndrome, or peripheral neuropathy should be evaluated for primary systemic (amyloid light-chain, or AL) amyloidosis by first seeking evidence of a clonal plasma cell disorder with serum and urine immunofixation studies, as well as a bone marrow biopsy. Immunostaining of the marrow biopsy for lambda and kappa isotypes will usually demonstrate a dominant clonal population of plasma cells if immunofixation studies are negative (less than 10% of cases). Tissue diagnosis of amyloidosis should be sought by biopsy of the abdominal fat or an involved organ. In addition, patients with stable myeloma or monoclonal gammopathy of undetermined significance who develop such conditions or become progressively ill should be evaluated for amyloidosis. We recommend that newly diagnosed patients with AL amyloidosis, who meet criteria for autologous hematopoietic cell transplantation, be considered for high-dose melphalan with stem cell support. Criteria usually include adequate cardiac, pulmonary, and hepatic function. AL amyloidosis patients treated with autologous transplantation frequently achieve durable complete remissions of the plasma cell disease and marked improvement in amyloid-related organ dysfunction. AL amyloidosis patients with dominant cardiac amyloid, who are without symptomatic pleural effusions and have no history of cardiac syncope or symptomatic arrhythmias, may be considered for autologous transplantation but are at increased risk of peritransplant mortality. Autologous transplantation should not routinely be offered to patients with dominant cardiac amyloid with recurrent effusions or histories of syncope or arrhythmias or to patients older than 50 years of age with more than two major organ systems involved (eg, heart, kidneys, liver, and peripheral nerves). We recommend that AL patients with isolated advanced cardiac or hepatic amyloidosis be considered for solid organ replacement followed by autologous transplantation. Otherwise, AL patients who are elderly or ineligible for autologous transplantation may be treated with oral melphalan (Alkeran, GlaxoWellcome, Middlesex, UK) and prednisone; however, because the response rate is only about 25% and the prognosis poor, such patients might also be enrolled on clinical trials of emerging therapies.
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PMID:Primary systemic amyloidosis. 1205 64