Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten patients with AML refractory to anthracyclines and cytosine arabinoside were treated with vincristine 1.4 mg/m2 and methotrexate (MTX) 2.5 gm/m2 by intravenous (IV) bolus on day 1 [citrovorum factor (CF) rescue began 24 h later], BCNU 80 mg/m2, and cyclophosphamide 900 mg/m2 IV 36 h after MTX and MGBG 300 mg/m2 IV over 1-2 h on days 3, 4, and 5. Bone marrow aplasia was achieved in all patients by day 12. Five patients (50%) achieved complete remission (CR). Two patients died of sepsis during induction. The median duration of remission was 24 weeks (range 8-38). Maintenance therapy was employed in three patients (high-dose MTX-CF in 2 and MGBG plus BCNU in 1), but did not appear to significantly increase the duration of remission. Nausea and vomiting occurred in eight patients. Five patients developed moderate stomatitis and one developed a moderately severe cutaneous reaction. This pilot experience demonstrates that patients with refractory AML can achieve CR after aggressive treatment with so-called second-line drugs. and may indicate that collateral sensitivity to MTX exists in cells which have become resistant to anthracyclines, a situation we previously described in an experimental cell line.
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PMID:Treatment of patients with refractory myelogenous leukemia with BCOMM[1,3-bis-chloro(2-chloroethyl)-1-nitrosourea (BCNU), oncovin (vincristine), cyclophosphamide, high-dose methotrexate and methyl-glyoxal bis-guanylhydrazone (MGBG)]. 695 16

Twenty-four patients with advanced malignancy received 30 courses of VP-16-213 delivered by a protracted infusion for a minimum of 5 days or 120 hours in a phase I study to determine the maximum tolerated dose. Toxic effects included fluid overload (due to the necessary use of normal saline as the drug delivery vehicle), stomatitis, and marrow suppression with leukopenia and thrombocytopenia. Except for the stomatitis, gastrointestinal effects were virtually absent. The dose-limiting toxic effect was marrow suppression observed at a dose of 60 mg/m2/day X 5 days (300 mg/m2/course). Six of seven patients treated at this dose developed marrow suppression: 50% (three of six patients) had life-threatening leukopenia associated with fever only (one patient), sepsis (one), and septic death (one).
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PMID:Phase I study of VP-16-213 (Etoposide) administered as a continuous 5-day infusion. 727 24

A similar sequence to a mouse immunodominant CTL peptide (SYVLQGN, single-letter amino acid code, conserved amino acids underlined) identified in the nucleoproteins of several strains of vesicular stomatitis virus (VSV) (37) was found in the nucleoproteins of viral hemorrhagic septicemia virus (VHSV) of salmonid fish (GYVYQGL in VHSV 07.71 and GYVYQGS in VHSV Makah) and not in the nucleoproteins of other rhabdoviruses. The in vivo immunization of fingerling salmonid fish (rainbow trout Onchorynchus mykiss, W) with this VHSV peptide and their subsequent challenge with VHSV resulted in the enhancement rather than in the reduction of fingerling trout mortality. Possible implications for the development of subunit vaccines against VHSV are discussed.
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PMID:Enhancement of fish mortality by rhabdovirus infection after immunization with a viral nucleoprotein peptide. 751 69

We retrospectively reviewed the regimen-related toxicity associated with busulphan (1 mg/kg orally QID days -7 to -4) and cyclophosphamide (60 mg/kg IV days -3 and -2) (Bu/Cy) chemotherapy in 69 consecutive patients who underwent autologous bone marrow transplantation (ABMT). Twenty-four patients received bone marrow (BM) alone, 22 received BM plus post-transplant granulocyte-colony stimulating factor (G-CSF) and 23 received peripheral blood progenitor cells (PBPC) +/- BM plus post-transplant G-CSF. Toxicity was scored using the criteria of Bearman. Grade II and III toxicities included mucosa (38%), liver (8%), central nervous system (5%), kidney (5%), heart (3%), pericardium (2%), bladder (2%) and lung (2%). There were five treatment related deaths (7%) from pneumonitis (2) and veno-occlusive disease, pulmonary hemorrhage and sepsis (1 each). Post-transplant G-CSF (+/- PBPC) resulted in a trend (p = 0.07) towards a reduction in post-transplant stomatitis, but did not impact on the already low incidence of other organ toxicities. As Bu/Cy for ABMT is associated with minimal non-hemopoietic toxicity, the addition of other cytotoxic agents is justified in an attempt to augment the anti-tumour effect of this conditioning regimen.
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PMID:High dose busulphan/cyclophosphamide for autologous bone marrow transplantation is associated with minimal non-hemopoietic toxicity. 752 88

A phase III randomised study, comparing treatment with fluorouracil, epidoxorubicin and methotrexate (FEMTX) with the best supportive care, was conducted in patients with unresectable or metastatic gastric cancer. During the period from July 1986 to June 1992, 41 patients were randomised to receive FEMTX or best supportive care. MTX was given in a dose of 1500 mg m-2 intravenously (i.v.) followed after 1 h by 5-FU 1500 mg m-2 i.v. on day 1; leucovorin rescue was started after 24 h (30 mg orally every 6 h for 48 h) and epidoxorubicin 60 mg m-2 i.v. was administered on day 15. In addition both groups received tablets containing vitamins A and E. Response rates for FEMTX were as follows: complete response (CR), 19% (4/21); partial response (PR), 10% (2/21); no change (NC), 33% (7/21); and progressive disease (PD), 24% (5/21). Response rates in the control group were: NC, 20% (4/20); and PD, 80% (16/20). Increased pain was observed in one patient in the treated group and in 11 patients in the control group within the first 2 months. WHO grade III/IV toxicity in the chemotherapy group was as follows: nausea/vomiting 40%, diarrhoea 10%, stomatitis 15%, leucopenia 50% and thrombocytopenia 10%. One possible treatment-related death was due to sepsis. The median time to progression in the FEMTX group was 5.4 months [95% confidence interval (CI) 3.1-11.7 months], but only 1.7 months in the control group (95% CI 1.2-2.7 months) (P = 0.0013). Similarly, the FEMTX group displayed significantly (P = 0.0006) prolonged survival compared with the control group, i.e. median survival 12.3 months (95% CI 7.1-15.6 months) vs 3.1 months (95% CI 1.6-4.6 months). In conclusion, FEMTX combined with vitamin A and E is a fairly well-tolerated treatment, giving a response rate of 29% in patients with advanced gastric cancer, and also prolonging patients' survival. It can be used as a reference treatment in testing new investigational combinations.
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PMID:Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. 753 17

Sixteen adult patients with relapsed (7 patients) or refractory (9 patients) acute leukemia received mitoxantrone (10 mg/m2 per day for 3 days) and etoposide (200 mg/m2 per day for 3 days) with escalating dose of cyclosporin A (CsA) from a loading dose of 2 mg to 6.5 mg/kg per 2 h followed by 3 days continuous infusion of 5-15 mg/kg per day. The major toxicities were stomatitis and prolonged aplasia, occurring for 15 mg/kg per day of CsA. Transient conjugated hyperbilirubinemia occurred in all patients, and was CsA dose-dependent (r = 0.7). Adequate serum levels of CsA (> 1 microgram/ml) were obtained in 3/6 patients treated with 10 mg/kg per day and 4/4 patients with 15 mg/kg per day. The pharmacokinetic of mitoxantrone showed an unusual increase of carboxylic metabolites, parallel to CsA levels. We observed six responses (two complete and four partial remissions), and eight resistances. Two patients died at days 3 and 8 from sepsis. Before treatment, 7/16 patients tested for P-gp with C219 were positive (> 10% positive cells). 3/6 responders were P-gp-positive. At time of leukemic regrowth, cells expressing P-gp before therapy reverted to P-gp-negative cells.
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PMID:Cyclosporin A as a modifier agent in the salvage treatment of acute leukemia (AL). 809 34

Preparative regimens containing busulfan (BU) followed by allogeneic bone marrow transplantation (BMT) were used in 27 consecutive patients with myelodysplastic syndromes (MDS). The median age was 33 years (range, 4 to 54). Ten were female and 17 male. Sixteen patients had primary MDS, 11 other patients had antecedent hematologic diseases or developed MDS after cytotoxic and/or radiation therapy. Six patients had leukemic transformation and received antileukemic therapy before BMT. Pre-BMT cytogenetic studies showed complex chromosomal abnormalities in 13 patients, a simple abnormality in 5 patients, and normal chromosome in 8 patients. Three BU-based preparative regimens were used: 1 patient received BU 4 mg/kg orally (PO) daily for 4 days and cyclophosphamide (CY) 50 mg/kg intravenously (IV) daily for 4 days (BUCY-4); 24 patients received BU 4 mg/kg PO daily for 4 days, cytosine arabinoside (ara-C) 2 g/m2 IV every 12 hours for 4 doses, and CY 60 mg/kg IV daily for 2 days (BAC); and 2 patients with preceding Fanconi anemia received BU 2 mg/kg PO daily for 4 days followed by total lymphoid irradiation of 5 Gy. Seventeen of 27 patients are alive with no evidence of disease. Ten patients have died: 2 from hepatic veno-occlusive disease, 3 from sepsis, 1 from a cerebral bleed, 1 from a massive gastrointestinal (GI) bleed associated with acute graft-versus-host disease, 1 from hemolytic uremic syndrome with adult respiratory distress syndrome, 1 from bronchiolitis obliterans, and the only patient who did not engraft died from acute myeloid leukemia. Regimen-related toxicities (RRT) include GI tract (diarrhea, 14; stomatitis, 11), liver (9), cardiac (1), and skin (5). Patients who received a genotypically matched marrow graft had a significantly better disease-free survival (DFS) than patients who received a nongenotypic marrow graft (P = .02). The Kaplan-Meier analysis projects an overall DFS of 56% +/- 13% and 78% +/- 10% for patients who received a genotypically matched marrow graft. With the exception of a child who did not engraft, there was no relapse of MDS or leukemia. Excellent DFS, acceptable RRT, and the ease of administration are advantages of this regimen.
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PMID:Busulfan-based regimens and allogeneic bone marrow transplantation in patients with myelodysplastic syndromes. 847 79

The binding of labeled phosphatidylserine (PS) to a collection of synthetic 15-mer peptides covering full-length glycoprotein G (G) of viral hemorrhagic septicemia virus (VHSV), a salmonid rhabdovirus, showed three dominant overlapping reactive peptides. This major PS-binding region was contained in a 28-mer peptide (p2; aa 82-109) with consecutive hydrophobic amino acid a-d heptad repeats (putative amphipathic alpha-helix) and 2 carboxy-terminal arginines. This 28-mer peptide showed a 10-fold higher apparent specific activity for PS binding than the 15-mer peptides. Binding to PS was also detected with virion-purified protein G but was not detected with other viral proteins. The highest apparent specific activity for PS binding was found with purified VHSV particles by both solid-phase and liquid assays. In contrast to the pH-independent PS binding to peptide p2, binding to virions was optimal at pH 5.6. PS binding to purified VHSV was greatly reduced by protease or detergent treatments that removed protein G, by treatment at pH 7.6, or by anti-p2 mouse antibodies at pH 5.6. The PS-binding region seems to be related to viral-host cell fusion since anti-p2 mouse antibodies inhibited VHSV-infected cell to cell fusion (fusion from within) and the pH profile of the VHSV-infected cell to cell fusion was similar to the pH profile of PS binding to VHSV. Comparative analysis showed that sequences similar to the major PS-binding domain of VHSV were also present in other fish rhabdoviruses and in rabies and vesicular stomatitis viruses.
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PMID:Pepscan mapping and fusion-related properties of the major phosphatidylserine-binding domain of the glycoprotein of viral hemorrhagic septicemia virus, a salmonid rhabdovirus. 861 7

Carcinomas of the exocrine pancreas respond poorly to most chemotherapy regimens. Recently continuous infusional 5-fluorouracil (200 mg m-(2)day-1) with 3 weekly cisplatin (60 mg m-2) and epirubicin (50 mg m-2) (the ECF regimen) has proven to be an active regimen in gastric and breast cancer and consequently worthy of further study in pancreatic cancer. Thirty-five patients were treated with the ECF regimen as above, of whom 29 were evaluable for response and 32 were evaluable for toxicity. The mean age was 59 years (range 37-75). Sixteen patients had locally advanced disease at presentation and 19 had metastases. Objective tumour responses were documented in five (17.3%) patients who achieved a partial response; in 18 (62%) patients there were no change and six (20.7%) patients progressed on therapy. Patients with either stable disease or partial response had a significantly improved overall survival (median = 253 days) compared with patients who progressed (median = 170 days; P = 0.01). Grade 3/4 (WHO) toxicity (all cycles) included alopecia in 18 (56%) patients, nausea/vomiting in eight (25%) stomatitis in three (9%) and diarrhoea in seven (22%) patients, with rhinorrhoea and excessive lacrimation in one patient each. Neutropenic sepsis occurred in 13 cycles in ten patients, and there was one toxic death due to sepsis. There were eight other episodes of non-neutropenic sepsis requiring hospital admission. Fourteen patients (40%) experienced complications with their Hickman lines, including thrombotic episodes (six patients) or their line falling out (five patients). ECF can prolong survival in patients with locally advanced or metastatic pancreatic cancer who demonstrate a response or stabilisation of their disease. However, this is associated with considerable toxicity.
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PMID:A phase II study of continuous-infusion 5-fluorouracil with cisplatin and epirubicin in inoperable pancreatic cancer. 863 Feb 89

Thirty-four patients with acute stomatogenic sepsis developing in grave ulcerative necrotic stomatitis (including that in Stevens-Johnson's and Lyell's syndromes) were examined. Homeostasis parameters were shifted in these patients. To facilitate timely diagnosis of acute stomatogenic sepsis, the authors offer a differential diagnostic table. Patients with grave forms of stomatitis are recommended to be referred for examination and treatment to specialized dentistry hospitals in order to early diagnose the disease and prevent the development of acute sepsis.
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PMID:[The clinico-laboratory characteristics and diagnosis of acute stomatogenic sepsis]. 875 38


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