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)

Patients with ARF and haematological malignancy (excluding myeloma), presenting to a single unit over 10 years were analyzed to see if patients likely to benefit from intensive renal supportive therapy could be identified. 31 episodes of ARF were identified in 29 patients (mean age 51 +/- 2.9 yr): 19 were associated with acute leukaemia (13 AML, 6 ALL); 10 with lymphoma. Acute tubular necrosis (ATN) was identified as the cause of ARF in 26 cases, with sepsis (96%) and exposure to nephrotoxic drugs (88%), especially aminoglycosides, being the commonest precipitating factors. Toxic levels of the latter were commonly documented. Patient survival was 45%. Requirement for mechanical ventilation resulted in a universally fatal outcome; age greater than 55 yr and the presence of CNS symptoms or signs were also significantly associated with a poor outcome. Non-ATN causes (urate nephropathy or obstruction) carried a better prognosis. However, only 4 patients (14%) lived for more than 6 months following ARF. Thus, although a subgroup of patients more likely to benefit from treatment can be identified, the overall prognosis is poor and limited by that of the underlying disease. The potential benefit of avoiding nephrotoxic drugs, especially aminoglycosides, in these patients is highlighted by this study.
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PMID:Acute renal failure associated with haematological malignancies: a review of 10 years experience. 188 80

The INK4A/ARF locus yields two tumor suppressors, p16INK4A and p14ARF, and is frequently deleted in human tumors. We studied their mRNA expressions in 41 hematopoietic cell lines and in 137 patients with hematological malignancies; we used a quantitative reverse transcription-PCR assay. Normal peripheral bloods, bone marrow and lymph nodes expressed little or undetectable p16INK4A and p14ARF mRNAs, which were readily detected in 12 and 17 of 41 cell lines, respectively. Patients with hematological malignancies frequently lacked p16INK4A expression (60/137) and lost p14ARF expression less frequently (19/137, 13.9%). Almost all patients without p14ARF expression lacked p16INK4A expression, which may correspond to deletions of the INK4A/ARF locus. Undetectable p16INK4A expression with p14ARF expression in 41 patients may correspond to p16INK4A promoter methylation or to normal expression status of the p16INK4A gene. All patients with follicular lymphoma (FL), myeloma or acute myeloid leukemia (AML) expressed p14ARF while nine of 23 patients with diffuse large B cell lymphoma (DLBCL) lost p14ARF expression. Patients with ALL, AML or blast crisis of chronic myelogenous leukemia expressed abundant p16INK4A mRNAs more frequently than patients with other diseases (12/33 vs 6/104, P < 0.01). Patients with FL and high p14ARF expression had a significantly shorter survival time while survival for patients with DLBCL and increased p14ARF expression tended to be longer. These observations indicate that p16INK4A and p14ARF expression is differentially affected among hemato- logical malignancies and that not only inactivation but also increased expression may have clinical significance.
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PMID:Expression of p16INK4A and p14ARF in hematological malignancies. 1055 50

Three hundred fifteen (315) elderly (> or = 60 years) patients with clinical renal diseases were evaluated for the evidence of glomerular diseases between November 1998 to June 2002. Glomerular diseases (GN) were observed in 20.6% (65/315) of the elderly patients. The age of the patients (male 56; female 9) ranged between 60-90 (mean 64.17 +/- 3.83) years. The clinical presentation of GN included: nephrotic syndrome 40 (61.5%), acute nephritic syndrome 19 (29.2%), rapidly progressive GN 4 (6.15%) and asymptomatic urinary abnormality 2 (3.0%). Overall, primary and secondary glomerular disease were seen in 47 (72.3%) and 18 (27.6%) elderly patients respectively. Idiopathic membranous nephropathy was the most common GN responsible for nephrotic syndrome in 11 (27.5%) of elderly patients. Diabetic Nephropathy related to type 2 diabetes mellitus was the second common cause 9 (22.5%) of nephrotic syndrome. Amyloidosis was noted in 6 (15%) patients. Nephrotic syndrome was related to leprosy in one patient. Amyloidosis occurred in association with multiple myeloma in 5 and carcinoma colon in 1 patient. Thus, primary and secondary GN were responsible for nephrotic syndrome in 60% and 40% of cases respectively. Endocapillary proliferative GN of post infectious etiology was the most prevalent (82.6%) form of acute GN in our elderly patients. Hypertension occurred in 78.2% of cases and edema in 69.5%. Pulmonary congestion (52.2%) and ARF (73.9%) were the dominant presenting feature of acute GN and 39% of patients required dialytic support. Glomerular crescents were seen in 4 (17.4%) patients with acute glomerulonephritis. Pauci-immune crescentic GN which is the commonest type of acute GN in the elderly in western countries was not observed in this study. Renal biopsy revealed mesangiocapillary GN (1) and mesangioproliferative GN (1) in two patients with asymptomatic urinary abnormalities. Thus, overall spectrum of glomerular disease in the Indian elderly population is similar to that of developed countries except in two ways: (1) post infectious endocapillary proliferative-GN was the commonest type of acute GN (2) rarity or absence of pauci-immune crescentic glomerulonephritis.
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PMID:Glomerular diseases in the elderly in India. 1507 10

This study among elderly renal Egyptian patients (n=220) with only 20 of them were subjected to renal biopsy. Results showed: diabetic nephropathy in 28.2%, hypertensive nephrosclerosis 25.5%, UTI, cystitis and pyelonephritis in 6.8%, renal stones in 5.9%, obstructive uropathy in 7.6%, simple cysts in 4.5%, CRF of unknown origin in 13.1%, and others in 26.4%. DM and HTN were S related to kidney function tests and increase in elderly. Other cardiovascular risk factors and smoking are reported by previous workers to be HS related to renal diseases. Age was significantly related to GFR, BUN and Cr. but sex difference was not significantly related to renal diseases. Multiple myeloma, lupus nephritis, vasculitis and hepatitis B were all recorded in few numbers of elderly Egyptians. HCV was more common and more likely to cause renal diseases. Abdomino-pelvic ultrasound was confirmatory to clinical renal diseases diagnosis. Among patients (n=20) biopsies showed focal necrotizing GN in 20%, membranous nephropathy in 50% and renal amyloidosis in 30%. CTIN was associated in some cases due to NSAID intake. Analgesic nephropathy was a common problem that might lead to ARF in some cases especially in the elderly. Ultrasound results among the biopsy group were confirmatory to clinical diagnosis.
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PMID:Pattern of renal diseases among elderly Egyptians patients with acute or chronic renal diseases in Ain Shams University and Nasser Institute Hospitals, Cairo, Egypt. 1633 99

A 55-year old woman with multiple myeloma was treated with hematopoietic stem cell transplantation (HSCT). She developed cutaneous and hepatic graft-vs-host disease (GVHD). Sixty-five days after HSCT, acute respiratory failure occurred. A thoracic computed tomography scan showed bilateral patchy infiltrates. Bronchoalveolar lavage revealed 40% eosinophils on differential cell count with no infectious pathogens. These findings were in favor of acute eosinophilic pneumonia. High-dose steroid treatment was started, which had a rapid and lasting favorable course. After HSCT, clinicians should be aware that acute eosinophilic pneumonia mimics infectious pneumonitis and can be associated with GVHD.
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PMID:Acute eosinophilic pneumonia after allogeneic hematopoietic stem cell transplantation. 1638 62

Gene-expression profiling has been used to define 3 molecular subtypes of diffuse large B-cell lymphoma (DLBCL), termed germinal center B-cell-like (GCB) DLBCL, activated B-cell-like (ABC) DLBCL, and primary mediastinal B-cell lymphoma (PMBL). To investigate whether these DLBCL subtypes arise by distinct pathogenetic mechanisms, we analyzed 203 DLBCL biopsy samples by high-resolution, genome-wide copy number analysis coupled with gene-expression profiling. Of 272 recurrent chromosomal aberrations that were associated with gene-expression alterations, 30 were used differentially by the DLBCL subtypes (P < 0.006). An amplicon on chromosome 19 was detected in 26% of ABC DLBCLs but in only 3% of GCB DLBCLs and PMBLs. A highly up-regulated gene in this amplicon was SPIB, which encodes an ETS family transcription factor. Knockdown of SPIB by RNA interference was toxic to ABC DLBCL cell lines but not to GCB DLBCL, PMBL, or myeloma cell lines, strongly implicating SPIB as an oncogene involved in the pathogenesis of ABC DLBCL. Deletion of the INK4a/ARF tumor suppressor locus and trisomy 3 also occurred almost exclusively in ABC DLBCLs and was associated with inferior outcome within this subtype. FOXP1 emerged as a potential oncogene in ABC DLBCL that was up-regulated by trisomy 3 and by more focal high-level amplifications. In GCB DLBCL, amplification of the oncogenic mir-17-92 microRNA cluster and deletion of the tumor suppressor PTEN were recurrent, but these events did not occur in ABC DLBCL. Together, these data provide genetic evidence that the DLBCL subtypes are distinct diseases that use different oncogenic pathways.
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PMID:Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. 1876 95

Asymptomatic infection due to Strongyloides stercoralis may result in potentially fatal disease in immunodepressed patients. A case of Strongyloides stercoralis hyperinfection discovered at autopsy in a 55-year-old man who had been undergoing treatment for multiple myeloma is reported, emphasizing the clinical and pathological findings. One day earlier, he presented severe headache, abdominal pain and oliguria, from which he developed acute respiratory failure and septic shock. Because of difficulty in reaching this diagnosis, empirical treatment before starting immunosuppressive therapy may be the best strategy for preventing hyperinfection by this worm.
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PMID:[Strongyloides stercoralis hyperinfection: autopsy case report]. 1885 18

Aberrant DNA methylation is considered an important epigenetic mechanism for gene inactivation. Monoclonal gammopathy of undetermined significance (MGUS) is believed to be a precursor of multiple myeloma (MM). We have analyzed methylation status of p15 INK4B , p16 INK4A , ARF, SOCS-1, p27 KIP1 , RASSF1A, and TP73 genes in bone marrow DNA samples from 21 MGUS and 44 MM patients, in order to determine the role of aberrant promoter methylation as one of the steps involved in the progression of MGUS to MM. Methylation specific polymerase chain reaction assay followed by DNA sequencing of the resulting product was performed. SOCS-1 gene methylation was significantly more frequent in MM (52%) than in MGUS (14%; p=0,006). Methylation frequencies of TP73, ARF, p15 INK4B , p16 INK4A , and RASSF1A were comparable in MGUS: 33%, 29%, 29%, 5%, and 0%, to that observed in MM: 45%, 29%, 32%, 7%, and 2%. All patients lacked methylation at p27 KIP1 gene. In both entities, a concurrent methylation of p15 INK4B and TP73 was observed. The mean methylation index of MGUS was lower (0.16) than that of MM (0.24; p<0.05). Correlations with clinicopathologic characteristics showed a higher mean age in MGUS patients with SOCS-1 methylated (p<0.001); meanwhile in MM, methylation of p15 INK4B was more frequent in males (p=0.009) and IgG isotype (p=0.038). Our findings suggest methylation of TP73, ARF, p15 INK4B , and p16 INK4A as early events in the pathogenesis and development of plasma cell disorders; meanwhile, SOCS-1 methylation would be an important step in the clonal evolution from MGUS to MM.
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PMID:DNA methylation analysis of tumor suppressor genes in monoclonal gammopathy of undetermined significance. 1972 27

Multiple myeloma (MM) is a plasma cell neoplasm that proceeds through a premalignant state of monoclonal gammopathy of unknown significance; however, the molecular events responsible for myelomagenesis remain uncharacterized. To identify cellular pathways deregulated in MM, we addressed that sumoylation is homologous to ubiquitination and results in the attachment of the ubiquitin-like protein Sumo onto target proteins. Sumoylation was markedly enhanced in MM patient lysates compared with normal plasma cells and expression profiling indicated a relative induction of sumoylation pathway genes. The Sumo-conjugating enzyme Ube2I, the Sumo-ligase PIAS1, and the Sumo-inducer ARF were elevated in MM patient samples and cell lines. Survival correlated with expression because 80% of patients with low UBE2I and PIAS1 were living 6 years after transplantation, whereas only 45% of patients with high expression survived 6 years. UBE2I encodes the sole Sumo-conjugating enzyme in mammalian cells and cells transfected with a dominant-negative sumoylation-deficient UBE2I mutant exhibited decreased survival after radiation exposure, impaired adhesion to bone marrow stroma cell and decreased bone marrow stroma cell-induced proliferation. UBE2I confers cells with multiple advantages to promote tumorigenesis and predicts decreased survival when combined with PIAS1. The sumoylation pathway is a novel therapeutic target with implications for existing proteasomal-based treatment strategies.
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PMID:The sumoylation pathway is dysregulated in multiple myeloma and is associated with adverse patient outcome. 1996 18

In cancer patients with acute respiratory failure (ARF), early adequate therapy is associated with better outcomes. We investigated the performance of the DIRECT approach, which uses criteria available at the bedside at admission to the intensive care unit (ICU), to identify causes of ARF in cancer patients. This cohort study included cancer patients with ARF of determined aetiology. Associations of aetiological groups with the selected criteria were evaluated using correspondence analysis. 424 cancer patients were included: 201 (47%) with bacterial pneumonia, 131 (31%) with opportunistic infections and 92 (22%) with noninfectious disorders. Mechanical ventilation (both invasive and noninvasive) was needed in 328 (77%) patients, treatment for shock in 217 (51%) patients and dialysis in 82 (19%) patients. 142 (34%) patients died in the ICU. Correspondence plots showed that bacterial pneumonia was associated with neutropenia, solid tumour, multiple myeloma, <3 days since symptom onset, shock, unilateral crackles and unilateral radiographic pattern. Opportunistic infections were associated with steroids, lymphoproliferative disorders and haematopoietic stem-cell transplantation, whereas noninfectious disorders were associated with acute leukaemia The selected criteria are strongly associated with causes of ARF in cancer patients and could be used to develop an algorithm for selecting first-line diagnostic investigations and empirical treatments.
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PMID:Clinical assessment for identifying causes of acute respiratory failure in cancer patients. 2390 47


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