Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a case of idiopathic crescentic glomerulonephritis with pulmonary hemorrhage associated with anti-myeloperoxidase antibodies (anti-MPO ab). A 74 year-old female was admitted to our hospital because of rapidly progressive glomerulonephritic syndrome and dyspnea with bloody sputum. On admission anti-MPO ab, one of anti-neutrophil cytoplasmic antibodies, were detected but anti-GBM antibodies and immune complexes were not detected. Renal biopsy showed crescentic glomerulonephritis and lung biopsy showed massive alveolar hemorrhage. Both tissue had pauci-immune deposit by immunofluorescence microscopy. Hemodialysis and steroid administration were started. Pulmonary hemorrhage was improved remarkably, but renal failure progressed rapidly to end stage kidney, then hemodialysis was continued. Although subsequent 3 years uneventful maintenance hemodialysis had been performed, she admitted to our hospital again because of progressive dyspnea with hemoptysis after upper respiratory tract infection. On admission anti-MPO ab were detected again and steroid administration was started. Pulmonary hemorrhage was improved with decreased anti-MPO ab titer. While tapering the dosis of steroid, anti-MPO ab again increased and pulmonary hemorrhage recurred. Although pulse methylprednisolone therapy and plasma exchange were performed, respiratory failure progressed rapidly and she died of sepsis. Postmortem examination showed no evidence of systemic vasculitis. In this case, titer of anti-MPO ab was associated with not only idiopathic crescentic glomerulonephritis but also with pulmonary hemorrhage. We tried to detect enzymatically active MPO in serum. Titer of serum MPO was also associated with disease activity and anti-MPO ab. It is suggested that both anti-MPO ab and serum MPO are closely related to the pathogenesis of idiopathic crescentic glomerulonephritis and pulmonary hemorrhage.
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PMID:[A case of anti-myeloperoxidase antibodies-associated idiopathic crescentic glomerulonephritis with pulmonary hemorrhage]. 166 75

Patients with malignant astrocytoma continue to respond poorly to chemotherapy and have a dismal prognosis. Cyclophosphamide (CTX) and etoposide demonstrate activity against malignant astrocytoma at standard dosages, with bone marrow suppression as the limiting toxicity. In order to allow dose intensification, minimize leukopenia, and improve efficacy granulocyte colony-stimulating factor (G-CSF) was used in combination with CTX and etoposide. The protocol consisted of CTX (2 mg/m2/d, days 1, 2), etoposide (200-300 mg/m2/d, days 1-3), and G-CSF (5-10 micrograms/d subcutaneously, days 4-18), every 4 weeks. Nine evaluable patients (7 glioblastoma multiforme, 2 anaplastic astrocytoma) were treated, ranging in age from 26-67 (mean 41). One of 9 patients responded (11%) with a partial response (13+ months), 3 had stable disease (33%; 8, 5, 2.5 months), and 5 had progressive disease (3, 2.5, 2, 1.5, 1 months). The median time to progression for responders was 6.5 months, while overall it was 2.5 months. Overall median survival was only 7.0 months. Toxicity was frequent and severe, typically delaying treatment cycles. The most common complications were severe myeolosuppression (9), sepsis (8), rash (6), urinary infection (5), and anorexia (5). Treatment delays caused by infections and other complications occurred often, abrogating the intended dose intensification. The received dose intensity (DI) for CTX was 400-425 mg/m2/week (relative DI 0.41), while for etoposide it was 75 mg/m2/week (relative DI 0.42). In summary, as used in this protocol, dose intensive chemotherapy with CTX, etoposide, and G-CSF does not improve efficacy over standard regimens and results in excessive toxicity.
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PMID:Attempted dose intensified cyclophosphamide, etoposide, and granulocyte colony-stimulating factor for treatment of malignant astrocytoma. 759 59

Anti-glomerular basement membrane antibody mediated disease (anti-GBM disease) is an uncommon cause of renal failure. Presentation is usually dramatic, with renal failure and alveolar hemorrhage leading to an early diagnosis. In contrast, we here describe 3 cases which presented with atypical features, and where diagnosis was delayed due to the presence of other factors which were initially felt sufficient to explain the clinical status. No patient recovered renal function, and one died from sepsis. We also present data on 15 patients presenting to Guy's Hospital over the past 10 years with anti-GBM disease and creatinine > 500 mumol/l. The median delay from presentation to diagnosis was 7 days, range 1-81 days. Two patients died, and only one recovered renal function. We speculate that earlier referral and renal biopsy might have improved outcome in these patients, and recommend a policy of early biopsy in all cases of acute renal failure with atypical feature, delay in recovery, or where a clearcut cause is not established.
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PMID:Unusual presentations of anti-glomerular basement membrane antibody mediated disease are associated with delayed diagnosis and poor outcome. 857 27

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine that has been identified in acute and chronic inflammatory conditions such as rheumatoid arthritis, sepsis, and renal allograft rejection. We investigated the glomerular expression of LIF at 30 minutes, and 3, 6, 9, 15 and 24 hours after administration of anti-GBM Ab (N = 3) by the RNase protection assay. Control rats received rabbit sera and were sacrificed at 30 minutes, and 6 and 24 hours. LIF mRNA relative to GAPDH mRNA was detected at low levels within the glomeruli of occasional control rats. However with the induction of anti-GBM Ab GN, there was a marked increase in LIF steady-state mRNA beginning at three hours which persisted through 24 hour. LIF mRNA was also detected in cultured mesangial cells stimulated with IL-1 beta, identifying this cell type as a potential glomerular source for this cytokine. To investigate the in vivo effect of LIF, Lewis rats were continuously infused with recombinant (r) human (h) LIF (approximately 0.5 ng/hr) or saline vehicle i.p. with ALZA osmotic pumps beginning at t = -24 hours (N = 8). All rats were injected with anti-GBM Ab intravenously at t = 0 (N = 16). LIF infusion decreased 24-hour urinary protein excretion by 85% (17 +/- 15 vs. 114 +/- 37 mg/day, P = 0.0001) and was associated with a 60% decrease in glomerular macrophage infiltration (0.8 +/- 0.2 vs. 2.0 +/- 0.6 ED-1 cells/glom, P = 0.0001). The administration of rhLIF did not affect the binding of the anti-GBM Ab to glomeruli. The beneficial effects of LIF were associated with a decrease in glomerular MCP-1 (56%), IL-1 (41%) and TNF (17%) steady state mRNA expression. The latter was associated with a 29% decrease in TNF-alpha protein expression within the glomerular lysate of nephritic rats administered LIF when compared with control rats. These data demonstrate a potential role for LIF in the therapy of anti-GBM Ab GN.
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PMID:Leukemia inhibitory factor ameliorates experimental anti-GBM Ab glomerulonephritis. 894 75

Between December 1996 and September 1998, 13 patients with advanced recurrent malignant brain tumors (9 with glioblastoma multiforme, 1 with gliosarcoma, and 3 with anaplastic astrocytoma) were treated with a single intratumoral injection of 2 x 10(9), 2 x 10(10), 2 x 10(11), or 2 x 10(12) vector particles (VP) of a replication-defective adenoviral vector bearing the herpes simplex virus thymidine kinase gene driven by the Rous sarcoma virus promoter (Adv.RSVtk), followed by ganciclovir (GCV) treatment. The VP to infectious unit ratio was 20:1. Our primary objective was to determine the safety of this treatment. Injection of Adv.RSVtk in doses <==2 x 10(11) VP, followed by GCV, was safely tolerated. Patients treated with the highest dose, 2 x 10(12) VP, exhibited central nervous system toxicity with confusion, hyponatremia, and seizures. One patient is living and stable 29.2 months after treatment. Two patients survived >25 months before succumbing to tumor progression. Ten patients died within 10 months of treatment, 9 from tumor progression and 1 with sepsis and endocarditis. Neuropathologic examination of postmortem tissue demonstrated cavitation at the injection site, intratumoral foci of coagulative necrosis, and variable infiltration of the residual tumor with macrophages and lymphocytes.
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PMID:Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir administration in patients with current malignant brain tumors. 1093 31

In summary, use of plasmapheresis has changed in recent years given advances in medical technology that have allowed a wider clinical application in the critical care setting. Membrane filtration technology has provided an alternative to centrifugation that can be easily applied in intensive care units. Use of plasmapheresis has also changed in recent years reflecting the availability of evidence largely obtained from controlled prospective studies. However, the clinical efficacy of plasmapheresis for many acute renal conditions is still controversial. Plasmapheresis appears to be a useful adjunct to conventional therapy in the treatment of anti-GBM nephritis, severe dialysis-dependent forms of pauciimmune RPGN, cryoglobulinemia, and HUS-TTP. Reported data also suggest a possible benefit of plasmapheresis in patients with myeloma cast nephropathy, sepsis, and poisoning/overdose, but the case for plasmapheresis in these disorders is largely unproven and the reported evidence insufficient to recommend its use outside research settings. In contrast, data from controlled trials do not support a role for plasmapheresis in immune complex-mediated RPGN, such as lupus nephritis, and acute allograft rejection. The more widespread application of prospective, randomized, controlled clinical trials should help to better define the value of plasmapheresis for treatment of acute renal diseases.
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PMID:Plasmapheresis. Technical aspects and indications. 1205 39

Two patients, a 58-year-old man and a 55-year-old woman, both under treatment for glioblastoma multiforme, were admitted with fever and neutropenia a few weeks after starting to take the oncolytic agent temozolomide. The man died of a cerebral haemorrhage against a background of severe thrombocytopenia and febrile neutropenia, and the woman died of neutropenic sepsis. Temozolomide is an oral alkylating agent that is considered to be a well-tolerated chemotherapeutic agent. It is important to be aware of the potentially life-threatening toxicity of every chemotherapeutic agent, including temozolomide. Therefore, temozolomide should be prescribed only by doctors with sufficient clinical experience with treatment by means of oncolytic agents, and with the recognition of the side effects and treatment of the complications of chemotherapy. In view of the multidisciplinary aspects of the treatment of patients with glioblastoma multiforme, treatment by a specialised team is preferable.
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PMID:[Temozolomide, an oral chemotherapeutic agent with potential severe toxicity]. 1732 84

Traditionally, patients who die with a malignancy have been excluded from donation. However, it has become a common practice to accept organs from donors that have low-grade tumors or tumors with low metastatic potential. The aim of this study was to analyze our experience with the use of liver grafts from donors with central nervous system (CNS) tumors. A retrospective review of 1173 liver transplants performed between 1992 and 2006 identified 42 donors diagnosed with a CNS tumor. Thirty-two tumors were malignant, and 10 tumors were benign. Forty-two liver transplant recipients received livers from these donors. All patients were followed until May 2007 with a mean follow-up of 29 +/- 17 months. Among 42 donors, there were 28 males and 14 females. The mean donor risk index was 1.78 +/- 0.39. Twenty (47.6%) of the CNS tumors were glioblastoma multiforme (astrocytoma grade IV), 11 (26.2%) were other astrocytomas, and 1 (2.4%) was an anaplastic ependymoma. Twenty (62.5%) neoplasms were grade IV tumors, 8 (25%) were grade II tumors, and 4 (12.5%) were grade III tumors. Over 80% of the patients had at least 1 kind of invasive procedure violating the blood-brain barrier. The rate of recurrence for the entire group was 2.4% (all CNS tumors). There were 7 (7.2%) deaths in all. The most common cause of death was sepsis (n = 3, 7.2%). There was no difference in survival between recipients of grafts from donors with CNS tumors and recipients of grafts from donors without CNS tumors (1 year: 82% versus 83.3%, P = not significant; 3 years: 77.4% versus 72%, P = not significant). In conclusion, in our experience, despite violation of the blood-brain barrier and high-grade CNS tumors, recurrence was uncommon. Grafts from these donors are often an overlooked source of high-quality organs from younger donors and can be appropriately used, particularly in patients who, despite low Model for End-Stage Liver Disease scores, carry a high risk of mortality.
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PMID:Liver grafts from donors with central nervous system tumors: a single-center perspective. 2058 88

We report a previously unrecognized complication of severe acute kidney injury (AKI) after the administration of pegfilgrastim with biopsy findings of mesangioproliferative glomerulonephritis (GN) and tubular necrosis. A 51-year-old white female with a history of breast cancer presented to the hospital with nausea, vomiting and dark urine 2 weeks after her third cycle of cyclophosphamide and docetaxel along with pegfilgrastim. She was found to have AKI with a serum creatinine (Cr) level of 6.9 mg/dl (baseline 0.7). At that time, her AKI was believed to be related to prior sepsis and/or daptomycin exposure that had occurred 5 weeks earlier. She was dialyzed for 6 weeks, after which her kidney function recovered to near baseline, but her urinalysis (UA) still showed 3.5 g protein/day and dysmorphic hematuria. Repeat blood cultures and serological workup (complement levels, hepatitis panel, ANA, ANCA and anti-GBM) were negative. She received her next cycle of chemotherapy with the same drugs. Two weeks later, she developed recurrent AKI with a Cr level of 6.7 mg/dl. A kidney biopsy showed mesangioproliferative GN, along with tubular epithelial damage and a rare electron-dense glomerular deposit. Pegfilgrastim was suspected as the inciting agent after exclusion of other causes. Her Cr improved to 1.4 mg/dl over the next 3 weeks, this time without dialysis. She had the next 2 cycles of chemotherapy without pegfilgrastim, with no further episodes of AKI. A literature review revealed a few cases of a possible association of filgrastim with mild self-limited acute GN. In conclusion, pegfilgrastim may cause GN with severe AKI. Milder cases may be missed and therefore routine monitoring of renal function and UA is important.
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PMID:Relapsing acute kidney injury associated with pegfilgrastim. 2332 57

A non-immunocompromised man developed acute Aspergillus pneumonia after spreading mouldy tree bark mulch. Despite normal renal function at presentation, he developed rapidly progressive glomerulonephritis with acute kidney injury due to anti-glomerular basement membrane antibodies (anti-GBM) 4 weeks later. He remained dialysis dependent and died of sepsis 10 months later. We hypothesise that he contracted invasive pulmonary Aspergillosis from heavy exposure to fungal spores, leading to epitope exposure in the alveoli with subsequent development of GBM auto-antibodies.
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PMID:Acute Aspergillus pneumonia associated with mouldy tree bark-chippings, complicated by anti-glomerular basement membrane disease causing permanent renal failure. 2443 35


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