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)

We report on preliminary experience with a modified M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) regimen in which adriamycin was replaced by the less toxic 4-epirubicin at equal doses (M-VEC). This study includes 58 patients suffering from advanced bladder cancer, with a minimum observation time of 12 months; each patient received at least two courses of M-VEC (mean follow-up 22 months, average 3.9 cycles). Most (22; 37.9%) of the tumors were T3-4 NO MO; 20 (34.4%) were T3-4 N1-2 MO; and 16 (27.7%) were T3-4 NO-2 M1. Microscopically, 52 (89.6%) were pure transitional cell carcinoma, 5 were (8.6%) squamous cell/carcinomatous transformation; 1 (1.8%) sarcoma was found. Chemotherapy was given as palliative treatment in 34 (58.6%) patients, as neo-adjuvant therapy in 19 (32.8%) cases and as adjuvant therapy in 5 (8.6%) patients. The overall response rate was 72.3% (CR = 51.7%), with a mean duration of response of 18+ months. The disease-free survival so far amounts to 24/58 (41.4%). Squamous cell carcinoma does not respond to M-VEC. Locally advanced bladder cancer (T3-4 NO-2 MO) responds significantly better than metastatic (M1) disease (78.5% vs 56.2%), resulting in an increased survival rate (57% versus 12.5%) after 22 months. The toxicity of M-VEC is considerably lower than has been reported for other regimens (M-VAC, CMV, CM). The toxic effects included mucositis (3%), nadir sepsis (2.4%) and drug-related death (2.4%).
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PMID:[Polychemotherapy using the M-VEC protocol (methotrexate, vinblastine, epirubicin, cisplatin) in advanced urinary bladder cancer--effectiveness and toxicity]. 292 97

Treatment results remain very poor for some clinical and histopathologic subsets of patients with aggressive non-Hodgkin's lymphoma. We treated 21 such patients with a high-dose combination chemotherapy regimen [Mega-COMLA (cyclophosphamide, cytarabine, vincristine, and methotrexate followed by leucovorin and prednisone) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)] in an attempt to improve disease-free survival. Neoplasms were classified using the Lukes-Collins system. Eight patients had T-cell lymphomas (convoluted lymphocytic lymphoma, four patients; T-cell lymphoma/leukemia, one; and peripheral T-cell lymphoma, three), eight had B-cell lymphomas (immunoblastic sarcoma, five patients; small noncleaved follicular center cell, one; and large noncleaved follicular center cell, two), and five had nontypable large noncleaved cell lymphomas. All patients were previously untreated; 18 of 21 patients had clinical stage III or IV disease. Following induction therapy (4-8 weeks' duration), 16 patients (76%) achieved complete remission, while three had partial remission. Two patients died of sepsis during induction therapy. Eleven of 16 complete responders (69%) remain in complete remission after a median follow-up of 35 months. The actuarial 3-year survival rate is 51% for the entire group. Myelosuppression with this regimen was severe and prolonged, with a median duration of neutropenia (less than 500 cells/microliter) of 14 days. Seven patients (33%) developed severe neuropathy following induction treatment. High-dose induction therapy with this regimen resulted in a high complete remission rate with manageable toxicity. Survival results are encouraging when compared retrospectively to our patients with similar poor-prognosis histologies treated with standard combination chemotherapy. However, the value of this intensive therapy, relative to newer ("third-generation") regimens, can only be established by prospective randomized studies.
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PMID:Effects of Mega-COMLA (cyclophosphamide, cytarabine, vincristine, and methotrexate followed by leucovorin and prednisone) plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in the treatment of lymphoid neoplasms with very poor prognosis. 301 6

The regimen of doxorubicin (DOX), ifosfamide (IFF), and dacarbazine (DTIC) (AID) for previously untreated inoperable or metastatic sarcoma has acceptable toxicity with significant activity. Twenty patients received 79 courses of DOX (60-75 mg/m2) with or without DTIC (900 mg/m2) by continuous infusion over 72 hours with escalating doses of IFF and mesna uroprotection. Nineteen patients were evaluable for toxicity. Myelosuppression was dose-limiting. The maximum tolerated dose was DOX at 60 mg/m2, DTIC at 900 mg/m2, and IFF at 7500 mg/m2 per course. Of the 79 courses analyzed, 33 (42%) resulted in wbc counts less than 1000/microliter; 14 (18%) were complicated by fever and neutropenia, and three by sepsis. There were no toxic deaths. Relative platelet sparing was observed and nadirs were brief. In contrast to bolus-dose DTIC divided over 5 days, DTIC by continuous infusion did not add significantly to gastrointestinal toxicity. Nausea and vomiting was well controlled by antiemetics. Mucositis occurred sporadically. Unlike our phase II study of IFF alone, no CNS or renal toxicity was observed. No cardiac toxicity was encountered, although only four patients have received greater than 450 mg/m2 of cumulative DOX. One episode of DOX extravasation occurred despite a long iv line that extended to the axilla. No serious tissue damage was observed, perhaps due to the dilute solutions of DOX used. Partial responses were seen in eight of 18 evaluable patients (44%) and in six of 11 patients at or near the phase II level. Two additional patients with minimal response have continued tumor regression. The median number of courses before partial response was four (range, one to five). The median duration of response has not been reached (3+ to 10+ months). An inoperable primary has been rendered surgically resectable in one patient. Activity in previously untreated sarcomas should be further evaluated in a randomized phase III study against a standard DOX-containing combination.
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PMID:Doxorubicin, ifosfamide, and dacarbazine (AID) with mesna uroprotection for advanced untreated sarcoma: a phase I study. 308 17

The metabolic responses associated with the tumor-bearing state, as compared to states of sepsis and prolonged starvation, were examined. Tumor-bearing rats manifested significant elevation of triglycerides, significant reduction of glucose and insulin levels, significantly increased plasma skeletal muscle proteolysis-inducing activity, and an unchanged hepatic protein synthetic activity compared to control rats. Prolonged starvation produced an adaptation characterized by significant hypoglycemia and hypoinsulinemia, reduced hepatic protein synthesis, and increased peripheral protolysis compared to controls. Septic animals had glucose, insulin, and lipid levels similar to control animals but had increased hepatic protein synthesis. Each state manifested its own unique metabolic response compared to controls. It appears that the metabolic consequences of cancer in this sarcoma rat model is different than septic and prolonged starvation states.
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PMID:Tumor-associated metabolism in the rat is a unique physiologic entity. 388 27

A surgical technique for removal of the adductor muscle group invaded by primary soft tissue sarcoma is described. A review of the clinical histories of 14 patients showed that the major complication of this procedure was prolonged suction catheter drainage of lymph, followed by sepsis along the drain tracts. No rationale for removal of the inguinal lymphatics in the absence of direct involvement by tumor or palpable lymphatic metastasis was found in the literature. We conclude that in primary soft tissue sarcoma of the adductor muscle group, clinically uninvolved superficial inguinal lymphatics should be carefully preserved. The limited benefits from removal of these lymph nodes does not merit the marked increase in operative morbidity. A surgical technique for adductor muscle group excision is presented that allows the best principles of sarcoma surgery to be practiced and that carries on acceptable operative morbidity rate.
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PMID:Adductor muscle group excision. 628 31

Five cases of bladder sarcoma were treated at our Department between January, 1972 and December, 1981. These cases accounted for only 1.5% of the bladder tumors (335 cases) diagnosed during the same period. The patients ranged from 11 months to 67 years old. There were 2 males and 3 females. Rhabdomyosarcoma was seen in 2 cases, leiomyosarcoma in 2 cases and spindle cell sarcoma in 1 case. Treatment consisted of total cystectomy and urinary diversion followed by chemotherapy or radiotherapy in 3 cases and partial cystectomy followed by chemotherapy and/or radiotherapy in 2 cases. Two patients died during adjuvant chemotherapy. One patient, an 11-month-old boy died of septicemia facilitated by bone marrow suppression 1 month postoperatively. The other patient died of gastrointestinal bleeding 2 months postoperatively. Another case died of local recurrence at 1 year postoperatively. One woman has been free of disease for 5 1/2 years and the remaining case was lost to follow up. Aggressive multidisciplinary treatment consisting of surgery, radiotherapy and cyclic combination chemotherapy is discussed, and 203 cases of bladder sarcoma reported in the Japanese literature are reviewed.
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PMID:[Treatment of five cases of bladder sarcoma]. 651 99

Thirty patients with advanced head and neck cancer of diverse histologies received the combination of cis-diamminedichloroplatinum (CDDP) (100 mg/m2) and 5-fluorouracil (5-FU) (1,000 mg/m2/24 hours X 4 days) at 3-4 week intervals. Among all study participants, the median time to progression was 3.9 months and the median survival was 7.2 months. Among 20 patients with squamous cell carcinoma, we observed five objective regressions (25%). None of the responders had prior chemotherapy; four had extensive prior radiation therapy. Among 10 patients with non-squamous cell carcinoma neoplasms, we detected three objective responses (30%). Histopathology of the responding patients included poorly differentiated sarcoma, anaplastic carcinoma, and malignant mixed parotid tumor. Significant gastrointestinal toxicities included moderate-to-severe nausea (60%), vomiting (43%), and stomatitis (57%). Leukopenia (less than 4,000 cells/mm3) and thrombocytopenia (less than 130,000 cells/mm3) affected 78% and 41% of patients, respectively, without sepsis or hemorrhage.
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PMID:A phase II study of cis-diamminedichloroplatinum and 5-fluorouracil in advanced upper aerodigestive neoplasms. 654 Jul 63

Emergency hemipelvectomy (HP) is a rare procedure. Only three incidents have been previously reported. This paper describes six additional cases, analyzes our results, and sets forth criteria for patient selection. There were five men and one woman. The median age was 38.5 years. Primary underlying diseases were sarcoma (three cases), peripheral vascular disease (one), deep vein thrombosis (one), and drug abuse (one). Life-threatening peripelvic sepsis and hemorrhage were indications for emergency HP. All six patients had multiple procedures prior to definitive HP. Four classical and two modified HPs were performed. The mean operative time was 3.5 hours, the mean blood loss 2292 ml. There were no intraoperative complications. The median duration of hospitalization was 56 days. Five of six patients were saved. Life-threatening peripelvic sepsis or hemorrhage associated with tumor recurrence, radiation, or failed vascular reconstruction is an indication for emergency HP. Neither age nor physical condition should be a deterrent. The patient should not be allowed to advance to a premorbid state before HP is considered, although concomitant intra-abdominal disease is a contraindication. HP is recommended in lieu of hip disarticulation. We anticipate that the need for emergency HP will increase as limb salvage procedures for extremity sarcomas and dysvascular disease become more frequent.
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PMID:Emergency hemipelvectomy in the control of life-threatening complications. 685 96

Inappropriate hepatic lipogenesis, hypertriglyceridaemia, decreased fatty acid oxidation and muscle protein wasting are common in patients with sepsis, cancer or AIDS. Given carnitine's role in the oxidation of fatty acids (FAs), we anticipated that carnitine might promote FA oxidation, thus ameliorating metabolic disturbances in lipopolysaccharide (LPS)- and methylcholanthrene-induced sarcoma models of wasting in rats. In the LPS model, rats were injected with LPS (24 mg kg-1 i.p.), and treated with carnitine (100 mg kg-1 i.p.) at -16, -8, 0 and 8 h post LPS. Rat health was observed, and plasma inflammatory cytokines and triglycerides (TG) were measured before and 3 h post LPS. In the sarcoma model, rats were implanted subcutaneously with tumour, and treated continuously with carnitine (200 mg kg-1 day-1 i.p.) via implanted osmotic pumps. Tumour burden, TG and cytokines were measured weekly for 4 weeks. Carnitine treatment significantly lowered the tumour-induced rise in TG (% rise) in the sarcoma model (700 +/- 204 vs 251 +/- 51, P < 0.03) in control and carnitine groups respectively. Levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) (pg ml-1) were also lowered by carnitine in both LPS (IL-1 beta: 536 +/- 65 vs 378 +/- 44: IL-6: 271 +/- 29 vs 222 +/- 32; TNF-alpha: 618 +/- 86 vs 367 +/- 54, P < or = 0.02) and sarcoma models (IL-1 beta: 423 +/- 33 vs 221 +/- 60; IL-6: 222 +/- 18 vs 139 +/- 38; TNF-alpha: 617 +/- 69 vs 280 +/- 77, P < or = 0.05) for control and carnitine groups respectively. We conclude that carnitine has a therapeutic effect on morbidity and lipid metabolism in these disease models, and that these effects could be the result of down-regulation of cytokine production and/or increased clearance of cytokines.
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PMID:Effects of L-carnitine on serum triglyceride and cytokine levels in rat models of cachexia and septic shock. 757 64

A total of 46 consecutive patients were entered into this study to assess the efficacy and toxicity of an epirubicin/ifosfamide combination in treating locally advanced and/or metastatic adult sarcomas (38 soft-tissue sarcomas and 7 bone sarcomas in 45 evaluable patients). Epirubicin was given at escalating doses (from 50 to 100 mg/m2) as an intravenous (i.v.) bolus on day 1, and ifosfamide was given i.v. at 1.2 g/m2 daily on days 1-5. Cycles were repeated every 4 weeks. The overall response rate was 38% (17 of 45 patients), reaching 42% (16 of 38) in the soft-tissue sarcoma group and 44% (17 of 39) in patients who had not been treated previously. In all, 4 complete responses (CRs, 9%) and 13 partial responses (PRs, 29%) were obtained. Most responses (about 68%) were reached within the first 2 cycles. The high-dose intensity of epirubicin (P < 0.04), the histologic type (P < 0.03), the presence of metastatic lesions only (P < 0.01), and the lack of previous treatment (P < 0.04) were found to be positively correlated with the probability of response. The median duration of response was 8 months. The median survival period was 10 months for all evaluable patients and 21 months for those achieving CRs and PRs (P < 0.01). The tumor grade, performance status, and extent of disease at entry into the study correlated with survival. The treatment was well tolerated; no case of sepsis occurred, and neither acute nor cumulative cardiotoxicity was observed. Epirubicin in combination with ifosfamide is therefore effective in advanced and/or metastatic disease with acceptable toxicity. The activity of this combination as compared with that of either of the two drugs given alone at optimal doses needs to be evaluated in prospective randomized trials.
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PMID:Ifosfamide plus epirubicin at escalating doses in the treatment of locally advanced and/or metastatic sarcomas. 845 3


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