Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nodular regenerative hyperplasia was found in nine patients who had hematological disease including polycythemia vera, agnogenic myeloid metaplasia, primary thrombocythemia, rheumatoid arthritis with thrombocytosis, multiple myeloma, and erythrocytosis associated with polycystic renal disease. Portal hypertension was suspected in three and features of hypersplenism were present in four. 2. Nodular regenerative hyperplasia occurred in livers which had widespread obliteration of portal vein radicals (obliterative portal venopathy). Morphometric analysis indicated that the portal vein lesions were predominately located in veins up to 0.2 mm in diameter and were significantly more frequent than similar lesions occurring in elderly persons. 3. The following pathogenesis of nodular regenerative hyperplasia is proposed: Thrombi, perhaps largely composed of platelet aggregates formed in the portal venous circulation or spleen, embolize to the liver and results in obliterative vascular lesions. Atrophy and regenerative nodule formation occur in response to the interruption of the portal blood supply.
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PMID:Nodular regenerative hyperplasia of the liver in hematologic disorders: a possible response to obliterative portal venopathy. A morphometric study of nine cases with an hypothesis on the pathogenesis. 743 53

Gaucher-like cells have occasionally been described in various haematological malignancies including Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma (MM) and chronic myelogenous leukaemia (CML). A special type of this phenomenon is crystal-storing histocytosis or the so-called pseudo-pseudo Gaucher cells (PPGC) in which crystalline protein storage in macrophages is induced by paraproteinemia. Here we describe a 54-year-old man with an initial suspicion of Gaucher disease and monoclonal IgA gammopathy in whom a correct diagnosis of lymphoplasmacytic lymphoma (LPL) with massive infiltration of bone marrow and spleen by PPGC was confirmed by immunological, ultrastructural and molecular characterisation. The activity of leukocyte beta-glucocerebrosidase was only slightly elevated (7.3 nmol/mg protein/1 h) which ruled out the diagnosis of classic Gaucher's disease. The patient received two courses of CHOP without improvement and anti-CD20 monoclonal antibody (rituximab) with only temporary stabilisation. Subsequently, he underwent splenectomy because of prolonged severe pancytopenia and a suspicion of hypersplenism. After splenectomy significant haematological improvement was observed. Following anti-CD20 therapy, changes in immunoprofile and morphology of tumour cells were evident. Before treatment the population of LPL was more divergent, with expression of LCA, CD20, CD38 and CD138. However, after the treatment, there were more mature plasma cells which no longer expressed CD20 antigen-this picture was more consistent with the diagnosis of plasma cell myeloma. Similarly, in the spleen there were no CD-20-positive cells evident. Finally, the patient received two courses of VAD vincristine, doxorubicin, dexamethasone) with further haematological improvement but complete response was not achieved.
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PMID:Lymphoplasmacytic lymphoma with monoclonal gammopathy-related pseudo-Gaucher cell infiltration in bone marrow and spleen--diagnostic and therapeutic dilemmas. 1261 22

Type II cryoglobulinemia (CG) is a heterogeneous, generally indolent disorder caused by a monoclonal antibody with activity against polyclonal antibodies and is commonly associated with hepatitis C, lymphoproliferative disorders (LPDs), or autoimmune diseases. It can lead to substantial morbidity, including renal failure, cutaneous ulcers, or neuropathy. Medical records were reviewed for 8 patients with previously treated symptomatic CG who were part of a prospectively held dysproteinemia database. Patients subsequently received 14 total courses of rituximab treatment (standard infusion, 375 mg/m2 for 4 or 8 doses) between February 1999 and March 2005. One patient had essential CG, and 1 had Gaucher disease with hypersplenism. Six patients had an LPD, and 4 of them had concomitant disorders (2 with hepatitis C and 2 with Sjogren syndrome). Treatment indications included purpura, LPD, cutaneous ulcers, and renal failure. Clinical improvement was evaluated by improved cryocrit, total complement, C4, and rheumatoid factor. Six patients had some clinical improvement. Cutaneous manifestations were the most responsive; renal disease and lymphoma were more refractory. Laboratory values showed improvement after 7 of 12 available treatment courses. No adverse reactions were noted. Overall, rituximab appears to be a safe and effective therapy.
Clin Lymphoma Myeloma 2006 Sep
PMID:Response to rituximab in patients with type II cryoglobulinemia. 1702 26

Gaucher disease is an inherited recessive autosomal metabolic defect due to a deficiency of the lysosomal enzyme beta-glucocerebrosidase. The enzyme substrate, glucocerebroside, accumulates in the body, predominantly in the liver, spleen, and bone marrow. Osteoarticular manifestations are often inaugural and contribute much of the morbidity and disability associated with Gaucher disease. There are three types of Gaucher disease. The most common is type 1, which can produce a broad range of presentations characterized by cytopenia and involvement of the spleen, liver, and bone marrow. Types 2 and 3 are rarest variants that manifest in infancy and cause neurologic damages. Patients with type 2 Gaucher disease usually die before 2years of age. beta-glucocerebrosidase assays and examination of bone marrow smears and biopsies ensure the diagnosis. Specific mutations in the beta-glucocerebrosidase gene are associated with specific clinical presentations: thus, the N370S mutation (heterozygous or homozygous) confers type 1 disease and the L444P mutation neurologic involvement and type 3 disease. Bone involvement is a feature in 70%-100% of cases. Abnormal bone remodeling, osteonecrosis and bony infarcts, osteopenia with fractures, and more rarely infections may occur. The other manifestations are dominated by cytopenia (thrombocytopenia, neutropenia, or anemia), hypersplenism, and liver enlargement. The risk of myeloma is increased. Parkinson-like syndromes were recently described in patients with type 1 disease. The enzyme chitotriosidase can be assayed to quantify the degree of macrophage activation. The chemokine CCL18 is another valuable marker but is not readily available in everyday practice. The treatment of Gaucher disease includes symptomatic drugs to relieve pain. Splenectomy is rarely necessary now that specific treatments are available. Enzyme replacement therapy (imiglucerase) has considerably improved the management of the highest risk patients. More recently, an enzyme inhibitor that decreases the production of the substrate (miglustat) was introduced. Chemical chaperone therapy and gene therapy hold promise for the future.
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PMID:Gaucher disease. 1799 73

Pancytopenia is defined by reduction of all the three formed elements of blood below the normal reference. It may be a manifestation of a wide variety of disorders, which primarily or secondarily affect the bone marrow. Haematological investigation forms the bedrock in the management of patients with pancytopenia and therefore needs detailed study. The total number of cases studied were 100 over a period of two years in the department of pathology, JSS Hospital, Mysore. Megaloblastic anaemia (33%) was the commonest cause of pancytopenia. Other causes were nutritional anaemia (16%), aplastic anaemia (14%), hypersplenism (10%), sepsis (9%) and leukaemia (5%). Less common causes were alcoholic liver disease, haemolytic anaemia, HIV, dengue, systemic lupus erythematosus, viral hepatitis, disseminated TB and multiple myeloma. Most of the patients were in the age group of 11-30 years with a male:female ratio of 1.6:1.Generalised weakness and fatigue (88%) were the commonest presenting complaints. Haemoglobin level varied from 1-10 g/dl with majorIty (70%) of them in the range of 5.1-10 g/dI. TLC was in the range of 500-4000 cells/cmm. Most (34%) of them had 3100-4000 cells/cmm. Platelet count was in the range of 4000-1,40,000 cells/cmm. Reticulocyte count varied from 0.1%-15% with majority (82%) of them ranging from 0.1%-2%. The bone marrow cellularity was hypocellular in 14%, hypercellular in 75%, and normocellular in 11% of the patients. Pancytopenia is a relatively common entity with inadequate attention in Indian subcontinent. A comprehensive clinical and haematological study of patients with pancytopenia will usually help in the identification of the underlying cause. However in view of wide array of aetiologies, pancytopenia continues to be a diagnostic challenge for haematologists.
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PMID:Bone marrow examination in pancytopenia. 2374 21