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)

Thirty-four patients with advanced squamous cell carcinoma of the head and neck have been treated with sequential combination chemotherapy consisting of Cytoxan, methotrexate, oncovin, bleomycin and adriamycin, followed by Leucovorin (COMBAL). All patients had undergone extensive prior radiation and/or surgery. All the patients had recurrent cancer. Toxicity included two deaths from drug induced pancytophenia and one from sepsis. Treatment was well tolerated and could be given in the outpatient clinic. No bleomycin pulmonary or adriamycin cardiac toxicity was seen. Results include 4 patients who achieved complete remission, objective improvement in measurable lesions in 6 others, stabilization of disease for 1 to 3 mo. in 5, and progression of disease in 13. Survival has ranged from 1 to 19+ months with a median of 10.7 mo. for patients that were evaluated. We conclude that COMBAL produces objective evidence of improvement in approximately 45% of patients with far advanced, previously treated squamous cell carcinoma of the head and neck.
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PMID:Sequential combination chemotherapy for advanced squamous cell carcinoma of the head and neck. 9 40

We have treated sixty-two patients (21 with limited disease, 41 with extensive disease), on an outpatient-basis schedule of six drugs administered weekly for twelve weeks. Cyclophosphamide, 400 mg/m2, adriamycin, 20 mg/m2 and vincristine, 2 mg, full dose, were administered during weeks 1, 5 and 9; cisplatin, 50 mg/m2 and etoposide, 100 mg/m2 during weeks 2, 6 and 10; adriamycin and vincristine at the same doses during weeks 3, 7 and 11; methotrexate 30 mg/m2, during weeks 4, 8 and 12. After the first 28 patients vincristine was replaced by teniposide (VM-26) due to neurotoxicity. The overall response rate was 64.5% (complete remission 13 p., partial remission 27 p.). Toxicity grade 3-4, mainly nausea and vomiting or neutropenia, was recorded in 17 patients. Alopecia grade 1-2 was universal. One toxic death occurred from sepsis. The overall survival was 8 months (range 1-40), (95% CL: 53-77%); 8 months in limited disease (range 1-40), and 7 months in extensive disease (range 1-23). Time to treatment failure was 6 months (7 limited disease, 5 extensive disease). In conclusion, the results of this alternating schedule are poorer than those attained with standard, high-dose treatments, mainly in limited disease, but could be a less toxic option for patients with extensive disease.
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PMID:Alternating chemotherapy for small-cell lung cancer. A twelve-week schedule of six drugs. 131 40

Cyclophosphamide (CTX) 600 mg/m2, carboplatin 280 mg/m2, and cisplatin 50 mg/m2 were administered on day 1 every 4 weeks to 41 previously untreated ovarian cancer patients with residual disease greater than 2.0 cm after primary laparotomy. Of 22 patients with measurable disease treated with up to eight cycles of therapy, the overall clinical response rate was 73% (exact 95% confidence interval [CI], 50% to 89%), with 50% complete response (CR). Six of 11 clinical CR (cCR) patients underwent surgical restaging; three pathologic CRs (pCRs) and three pathologic partial responses (pPRs) with residual disease less than 2.0 cm were documented. Fourteen patients had nonmeasurable but assessable disease; the clinical response rate was 57% (Cl, 29% to 82%) with two (14%) CRs. Second-look surgery was performed in one of the two cCR patients; a pPR was documented. Five patients with nonassessable disease were stable during chemotherapy; two underwent surgery and had pCRs. The median time to treatment failure (TTF) was 14.8 months, and median survival for the 41 patients is 26.7 months. Overall, 37% of the patients had progression-free intervals of at least 2 years, and 27% have survival times in excess of 3 years. Hematologic toxicity was substantial but manageable, with 58% and 66% experiencing a granulocyte nadir less than 500/microL and a platelet nadir less than 50,000/microL, respectively. One treatment-associated fatality occurred as a result of leukopenic sepsis and renal failure in the setting of progressive disease and ureteral obstruction. Mild to moderate nausea and vomiting occurred in most patients, but none experienced severe ototoxicity or peripheral neuropathy. Over all courses, 73% of the projected dose intensity of CTX and carboplatin and 86% of cisplatin were delivered. Since granulocytopenia and thrombocytopenia were dose-limiting, the addition of colony-stimulating factors that support both myeloid and megakaryocyte precursors may permit further dose intensification.
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PMID:Cisplatin, carboplatin, and cyclophosphamide combination chemotherapy in advanced-stage ovarian carcinoma: an Eastern Cooperative Oncology Group pilot study. 191 29

A prospective neoadjuvant trial utilizing chemotherapy (CTX) and radiotherapy (XRT) prior to pancreatectomy was established to determine the feasibility of resection after aggressive pretreatment and its effect on survival. Fifteen patients with pancreatic cancer (14 head, 1 body) and 1 patient with duodenal cancer, (with paraaortic adenopathy), were subjected to combination treatment with infusional 5-FU, bolus injection of mitomycin-C, and XRT (4 patients were treated off the protocol). Patients were restaged 3 wk after XRT, and those deemed resectable underwent a pancreatic resection. Three patients did not undergo exploration after the neoadjuvant therapy, although two of these were deemed resectable by CT scan. The remaining 13 patients underwent exploration and 10 underwent resection. Three did not undergo resection because of extrapancreatic disease, although their primary tumors were resectable. One patient had no residual tumor in the specimen. The others had residual tumor with evidence of necrosis and hyalinization, but all margins were free of tumor. There were two perioperative deaths from sepsis. Of the remaining patients who underwent resection, one died of a myocardial infarction at 9 mo. One patient died with recurrent disease at 19 mo. The remaining patients are alive 40, 32, 11, 11, 10, and 4 mo since diagnosis and are currently free of disease. Aggressive neoadjuvant chemoradiotherapy can be performed safely, allows successful resection, and may yield long-term survival or curve.
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PMID:Increased resectability of locally advanced pancreatic and periampullary carcinoma with neoadjuvant chemoradiotherapy. 208 23

Thirty-one patients affected by advanced ALL entered this study. Twenty (1 in I CR, 9 in II CR, 6 in III CR and 4 extramedullary relapses) were treated with the BMVC conditioning regimen. Eleven (9 in II CR, 2 in III CR) received the Busulfan plus Cytoxan conditioning regimen. Asta-Z 7654-purged marrow was reinfused at day 0. Both protocols were well tolerated. Two patients treated with the BMVC regimen died in aplasia from sepsis; 1 patient died in CR 5 months after transplantation, 13 relapsed after a median time of 4 months (range 1-31). Four patients are in CCR with a median follow-up of 16 months (range 11-24). In the BU + CY treated group no toxic deaths were observed. Four patients relapsed after a median of 3 months (range 2-7) and 7 are in CCR with a median follow-up of 5 months (range 2-28).
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PMID:Results of two different conditioning regimens followed by ABMT in refractory acute lymphoblastic leukemia. 249 86

High dose chemo-radiotherapy followed by autologous bone marrow transplantation (ABMT) is known to be an effective treatment in stage IV neuroblastoma (NB). Since October '84, 19 children with NB (12 relapsed or resistant: Group A; 7 in first CR: Group B) received ablative therapy (AT) consisting of VCR (4 mg/mg), L-PAM (140 mg/mg) and fractionated TBI (1000 Rads). Induction strategy at diagnosis or at relapse included high dose Peptichemio, 2-3 cycles of Vincristine-Cyclophosphamide--high dose Platinum and surgery. Bone marrow was harvested after 2 evaluation proved negative by cytomorphology, histology and immunofluorescence. Mononuclear cells (median 6.7 x 10(7)/kg) were cryopreserved and reinfused without purging. At the time of AT in Group A8 children were in CR, 4 had minimal diseases; in Group B 6 were in CR and one in PR. One toxicity-related death occurred on day 7 in a child in first CR; median duration of granulocytopenia 0.5 x 10(9)/l and thrombocytopenia less than 50 x 10(9)/l were 20 days (R: 9-40) and 27 days (R: 11-51) respectively. Persistent immune thrombocytopenia occurred in 4 children. Fever higher tha 38 degrees C developed in all patients: sepsis was documented in 6 patients. Extramedullary toxicity was moderate: GI tract was the most affected. Two out of 5 children who received AT having residual disease achieved CR; relapse or progression of disease occurred in all these patients. Four out of 8 children in second or subsequent CR and 4 out of 5 in first CR are alive and well at 3-12 months (median 7).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Total body irradiation, vincristine in continuous infusion and high-dose melphalan with transplant of autologous bone marrow in the treatment of neuroblastoma]. 330 21

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

Cyclophosphamide-induced neutropenia exacerbates septic shock and multiple organ injury in conscious rats during Escherichia coli (EC) bacteremia despite antibiotics and fluid administration. We hypothesized that such shock and inflammatory organ injury would be mitigated by rBPI23's microbicidal activity and/or binding of EC endotoxins. Four days after 100 mg cyclophosphamide/kg, catheterized rats with < 300 PMNs/microL were pretreated with rBPI23 or the irrelevant 22 kDa protein thaumatin [3.3-6.6 mg/kg, i.v. in 0.9% NaCl (NS)] 5 min before graded i.v. infection with 5 x 10(9) or 1 x 10(10) cfu of EC serotype 055:B5 ending at t = 0. Posttreatment with each protein continued (3.3-6.6 mg/kg in 1 mL NS/h) through 8 h, in addition to penicillin plus amikacin sulfate at t = 1.5 and 8 h. Arterial samples were obtained before pretreatment and at t = 1.5, 4.5, 8, and 24 h when animals were necropsied. One of eight thaumatin + 5 x 10(9) EC rats and none of six thaumatin + 10(10) EC rats survived 24 h. In contrast, rBPI23 significantly reduced mortality after either inoculum, improved bacterial clearance, and led to renormalization of early EC-induced hypotension, hypothermia, tachypnea, hyperoxemia, and hypocarbia. Compared with thaumatin, however, rBPI23 did not reduce circulating endotoxin or bioactive and antigenic tumor necrosis factor-alpha. Sepsis-induced severe neutropenia (< 50 PMNs/microL) evident in all EC rats by t = 1.5 h was reversed with rBPI23 by t = 8 h, but thrombocytopenia (< 5 x 10(4) platelets/microL) evident in all groups by t = 4.5 h was not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The recombinant 23-kDa N-terminal fragment of bactericidal/permeability-increasing protein (rBPI23) decreases Escherichia coli-induced mortality and organ injury during immunosuppression-related neutropenia. 856 60

To evaluate the role of tumour necrosis factor (TNF) in gut-derived sepsis, mice were given Pseudomomas aeruginosa strain D4 by bacterial suspension in their drinking water during which time ampicillin (200 mg/kg) was given to disrupt the normal indigenous bacterial flora. Cyclophosphamide was additionally administered to induce bacterial translocation of the P. aeruginosa that had colonized the gastrointestinal tract, and thereby to cause gut-derived sepsis. In this model, TNF-alpha was detected in serum from the next day after the second cyclophosphamide administration, increasing to level of 3 ng/ml in lethal conditions. Average serum TNF-alpha level was significantly higher in mice with bacteraemia than in those without bacteraemia. Treatment with 0.8 microg/kg of recombinant human TNF-alpha (rhTNF-alpha) did not affect the mortality, whereas administration of either 4 and 20 microg/kg of rhTNF-alpha significantly increased the mortality rate in comparison with saline-treated mice. Bacterial counts in liver and blood were significantly higher in 20 microg/kg of rhTNF-alpha treated mice than in saline-treated mice. Treatment with murine anti-TNF-alpha monoclonal antibody significantly reduced the mortality from septic infection. We conclude that TNF-alpha may facilitate bacterial translocation and causes deterioration of gut-derived sepsis due to P. aeruginosa in mice.
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PMID:Adverse effects of tumour necrosis factor in cyclophosphamide-treated mice subjected to gut-derived Pseudomonas aeruginosa sepsis. 934 9

Acute lung injury and the acute respiratory distress syndrome (ARDS) are significant causes of morbidity and mortality following sepsis and hemorrhage. Increased IL-1beta production in the lung is important in the development of acute inflammatory lung injury. Although neutrophils are an important component of the inflammatory response that characterizes acute lung injury, there is little information to suggest that they are capable of initiating cytokine-mediated immune responses in the lung. To explore the role of neutrophils in the early stages of acute lung injury, we examined IL-1beta production by mouse lung neutrophils after hemorrhage and endotoxemia. There was a significant increase in IL-1beta expression among intraparenchymal pulmonary neutrophil/mononuclear cells (IPNMC) 1 h after hemorrhage or endotoxemia. IL-1beta was detected only in a neutrophil-rich fraction of the IPNMC, but not in T and B lymphocytes positively selected from the IPNMC. Cyclophosphamide (CTX)-treated neutropenic mice expressed significantly less IL-1beta in IPNMC after hemorrhage or endotoxemia compared with CTX-untreated controls. Immunohistochemical analysis of lung sections from mice after hemorrhage or endotoxemia revealed IL-1beta expression in infiltrating neutrophils. These data indicate that IL-1beta-producing neutrophils traffic to the lungs rapidly in response to hemorrhage or endotoxemia and support the concept that proinflammatory cytokine production by lung neutrophils may contribute to the development of lung injury after blood loss and sepsis.
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PMID:Neutrophils are major contributors to intraparenchymal lung IL-1 beta expression after hemorrhage and endotoxemia. 955 41


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