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)

Pharmacokinetic and clinical studies on cefotetan (CTT), a new cephamycin antibiotic, were carried out and the following results were obtained. Pharmacokinetic study Two patients, 7 years and 10 months of age (22 kg of body weight) and 9 years of age (28 kg of body weight), were administered 20 mg/kg of CTT by 30 minutes intravenous drip infusion. Serum levels of CTT were 148 micrograms/ml and 92 micrograms/ml immediately after the end of drip, 118 micrograms/ml and 63 micrograms/ml at 1 hour after the drip infusion. 76 micrograms/ml and 39 micrograms/ml at 2 hours after, 34 micrograms/ml and 18.2 micrograms/ml at 4 hours after and 18 micrograms/ml and 8.2 micrograms/ml at 6 hours after. Serum half-lives calculated were 1.92 hours and 1.78 hours respectively. Clinical study CTT was administered to a total of 14 patients, 3 with pneumonia, 2 with acute pyelonephritis, 2 with acute enteritis, each one with acute tonsillitis, acute bronchitis, acute bronchiolitis, sepsis, acute lymphadenitis, stomatitis and measles. Because that stomatitis and measles, however, were not indications of CTT, 2 cases with those diseases were excluded. CTT was administered at daily dose of 40 to 73 mg/kg in 2 to 4 portions for 3 to 5.5 days by intravenous drip infusion. Marked response was seen in 2 cases, moderate response in 9 and no response in 1, thus effectiveness rate was 91.7%. Neither side effects nor abnormal clinical laboratory findings were observed.
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PMID:[Clinical evaluation of cefotetan in pediatrics]. 658 29

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

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

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

A Phase II trial of edatrexate in patients with recurrent cervical carcinoma was conducted by the Gynecologic Oncology Group (GOG). Twenty patients were treated with edatrexate at a dose of 80 mg/m2 i.v. weekly for 5 consecutive weeks per cycle. Four patients received an inadequate trial and were inevaluable for response. Among the 16 patients evaluable for response, there were no objective responses: 50% had stable disease, 50% had progressive disease. All 20 patients were evaluable for toxicity, predominantly stomatitis and bone marrow suppression were substantial. Grades 3-4 bone marrow toxicity were observed in eight of 20 (40%) patients, and there were two deaths due to neutropenic sepsis. Fanconi's syndrome, possibly treatment related, was seen in two patients. Edatrexate administered in this dose and schedule has no demonstrated activity and has severe toxicity in patients with previously-treated advanced cervical cancer.
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PMID:A phase II trial of edatrexate in previously treated squamous cell cervical cancer: a Gynecologic Oncology Group study. 902 Feb 94


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