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)

To augment the antitumor effect of high-dose melphalan and determine pharmacokinetics we conducted a phase I trial of escalating doses of high-dose IV melphalan with the chemosensitizer misonidazole for patients with advanced colorectal carcinoma. Fourteen patients with modified Dukes D adenocarcinoma of the colorectum were treated with a single course of melphalan (40-60 mg/m2 i.v. bolus q.d. X 3 days) and misonidazole (1-3 g/m2 p.o. q.d. X 3 days) followed by autologous bone marrow transplantation. Toxicity consisted of severe myelosuppression, moderate nausea and vomiting, and mild mucositis and diarrhea. One patient developed unexplained renal tubular acidosis, and a diffuse encephalopathy occurred in another patient. Three patients died within the first 30 days after the start of treatment, two due to tumor progression and one due to sepsis and disseminated intravascular coagulation-induced intracerebral hemorrhage. Six of 14 patients achieved a partial response, and the median response duration was 4 months (range 3-10 months). Analysis of misonidazole serum concentrations showed similar pharmacokinetics to those previously reported, suggesting no significant drug interaction with intravenous melphalan. Mean peak serum concentrations ranged from 81.8 micrograms/ml to 115.2 micrograms/ml at the second and third misonidazole dose levels, which approximate those known to provide effective chemosensitization with melphalan in animal models. In this phase I study, we showed that maximally tolerated doses of intravenous melphalan can safely be combined with oral misonidazole. In view of the large volumes of oral misonidazole required at the highest dose level, subsequent studies to determine the maximally tolerated dose of misonidazole should employ the intravenous form.
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PMID:High-dose melphalan, misonidazole, and autologous bone marrow transplantation for the treatment of metastatic colorectal carcinoma. A phase I study. 265 May 27

Eikenella corrodens was isolated from a posttraumatic liver abscess in a man with previous hemicolectomy for sigmoid adenocarcinoma. Escherichia coli was the initial isolate, but sepsis persisted after its eradication by cefuroxime and metronidazole. A second specimen yielded E. corrodens which responded promptly to combined ampicillin and netilmicin. The patient died of disseminated cancer 6 months later.
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PMID:Isolation of Eikenella corrodens from a liver abscess. Case report. 266 90

Three distal pancreatectomies with preservation of the spleen are described. The indications were infiltration of the pancreatic tail by a gastric adenocarcinoma in the first patient; acute and chronic inflammation of the pancreas in the second and third. This type of operation takes very little longer than classic distal pancreatectomy with splenectomy, does not increase the incidence of postoperative complications and above all prevents the onset of sometimes lethal sepsis especially in young patients.
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PMID:[Distal pancreatectomy with conservation of the spleen. Apropos of 3 consecutive cases]. 277 Nov 6

Between 1980 and 1985, 24 patients with primary adenocarcinoma of the bile duct were treated with various combinations of surgery, biliary intubation, external irradiation, and transcatheter brachytherapy. Seventy-five percent of tumors were in the proximal bile ducts. Ten patients received no or only palliative radiation, Group 1, whereas 14 patients received definitive courses of radiation (4 by external beam irradiation, 2 by transcatheter irradiation, and 8 by both modalities), Group 2. Survival in Group 1 and Group 2 was significantly different (p less than 0.005) with median survivals of 2.0 and 12.8 months, respectively. This result may be in part due to differences in treatment and in part due to selection bias because the series is small, uncontrolled, and retrospective. Median survival of the 8 patients treated with combined modalities was 13.2 months (range 7.4-30.3) with 4 patients alive 8.7 to 16.2 months, 3 without cholangiographic evidence of disease. Complications of therapy were common, including bacterial sepsis (58%), cholangitis (38%), gastrointestinal bleeding (46%), intra or extrahepatic abscesses (33%), and recurrent biliary obstruction (25%). Cholangitis, hemorrhage, abscesses, and ulcers appeared more frequently in definitively treated patients, whereas recurrent biliary obstruction was absent in this group and frequent in Group 1. Differences in complication rates between groups were not statistically significant. Early diagnosis and management usually reversed a downhill clinical course in patients with abscess and hemorrhage. Both surgical and percutaneous techniques of biliary decompression, the usual initial form of therapy in bile duct cancer, are associated with frequent and serious complications. Although many of our complications may have derived from biliary decompression, it is possible that definitive treatment may have increased the frequency of serious complications.
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PMID:Definitive radiation therapy in bile duct carcinoma. 284 89

A previously unreported complication of low anterior resection of the rectum, seminal vesicle-rectal fistula, was encountered one month after surgery in an elderly patient with adenocarcinoma of the midrectum. Antibiotic-induced colitis in the immediate postoperative period led to anastomotic leakage with abscess formation and ensuing fistulization to the surgically denuded right seminal vesicle. Pneumaturia, bacteriuria, and right testicular pain were treated by cutaneous vasostomy and antimicrobial therapy. Despite recurrent low-grade urinary sepsis controlled by alternating courses of various antimicrobials, and radiation therapy for local tumor recurrence, the patient remained reasonably healthy until his death two years later due to stroke associated with cerebral metastases.
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PMID:Seminal vesicle-rectal fistula. Report of a case. 291 Jun 63

The case of a 49 year old male patient who presented with perianal mucinous adenocarcinoma is presented. This is a rare anal tumour with a low grade, well-differentiated histological pattern. Its pathogenesis remains obscure, although a long antecedent history of fistula in ano and associated perianal sepsis is characteristic. The exact etiological relationship with anal fistula is not clearly established. The upper rectum is usually spared. Perianal Paget's disease is often seen in association with the tumour. Metastases occur late and spread is usually to the inguinal group of lymph nodes. Clinical diagnosis is often delayed and difficult. Treatment is abdominoperineal resection with block dissection of the inguinal lymph nodes if the glands are involved.
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PMID:Perianal mucinous adenocarcinoma: a clue to its pathogenesis. 301 49

Sixty patients with inoperable non-small-cell lung cancer (NSCLC) were entered into a phase II study that tested the combination of cisplatin (80 mg/m2, day, etoposide intravenously (IV) (100 mg, days 1 and etoposide orally (200 mg/m2, days 3 and 5). The regimen was repeated every 28 days for six courses, after which patients were allowed to receive additional treatment at the discretion of their physician. Overall objective response rate in 51 evaluable patients was 69% (95% confidence interval: range, 56% to 81%), with 16% sustaining complete remission (CR), 53% partial remission (PR), 17% stable disease (SD), and 14% progressive disease (PD). CR was pathologically confirmed by bronchoscopy and biopsy. One patient with a clinical PR underwent surgery and was shown to have a pathologic CR. Median survival of all evaluable patients was 52 weeks, greater than 75 weeks for CR patients, 52 weeks for PR patients, 42 weeks for SD patients, and 13 weeks for PD patients. Eleven patients (21.5%) developed CNS metastases, which resulted in the deaths of ten. Survival was significantly correlated with extent of disease, performance status, and albumin level, but not with histology or weight loss. Tumor response was significantly correlated only with histology (squamous-cell and large-cell undifferentiated carcinoma greater than adenocarcinoma). Side effects were nausea, vomiting, anorexia, alopecia, bone marrow suppression, and nephrotoxicity. One patient died from leukopenia and sepsis. Pharmacokinetic studies in ten patients showed the continuous presence of etoposide in plasma for six days at a level of at least 220 to 480 ng/mL. In order to investigate whether this very effective combination of cisplatin and etoposide can prolong survival in NSCLC, it will be tested as preoperative chemotherapy in a randomized trial in operable patients with T1N1 and T2N0-1 disease.
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PMID:A multicenter phase II trial of cisplatin and oral etoposide (VP-16) in inoperable non-small-cell lung cancer. 302 Jul 7

Tumor necrosis factor (TNF), a macrophage secretory protein produced by peripheral blood monocytes from patients with cancer, has been shown to possess cytotoxicity toward tumor cells in vitro. TNF in the blood of individuals with cancer is usually not detectable except with extremely sensitive radioimmunoassay or enzyme-linked immunosorbent assay (ELISA) methods. We have encountered two patients with the rare syndrome of extensive bone marrow necrosis in association with cancer. The first patient presented with marrow failure secondary to necrosis and was found to have adenocarcinoma in thoracic lymph nodes, lung, and marrow lymphatics at autopsy. Plasma tested at two dilutions (1:200 and 1:2,000) contained TNF at a concentration of 8.3 ng/ml, or 80 U/ml by a cytotoxicity assay using LM cells. The presence of TNF was confirmed with immunoblotting. The second patient had a poorly differentiated lymphoid tumor involving bone marrow, pancytopenia, and marrow necrosis. The plasma cytotoxicity assay indicated the presence of 0.7 ng/ml or 7 U/ml TNF. TNF was not detectable in plasma from six other patients with untreated cancer involving bone or bone marrow using either of our methods. The levels of TNF in the two patients with marrow necrosis were greater than those previously measured by others in patients with cancer but were comparable to those noted in patients with lethal sepsis. Since large doses of TNF have been shown to cause organ necrosis in animals, the data presented here are consistent with TNF involvement in mediating the observed marrow necrosis in our patients.
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PMID:Extensive bone marrow necrosis in patients with cancer and tumor necrosis factor activity in plasma. 318 18

In order to find an effective and suitable chemotherapy regimen for preoperative treatment of esophageal cancer, patients with inoperable or metastatic disease were treated with a combination of etoposide and cisplatin. Of 27 evaluable patients, 13 had squamous cell carcinoma, 13 adenocarcinoma, and 1 muco-epidermoid carcinoma. No complete responses were noted. Nine of 13 patients with squamous cell carcinoma and only one of 13 with adenocarcinoma showed a partial response. Nine of 10 responders achieved a partial response after 2 courses, one after 4 courses. There was one toxic death, due to sepsis during leukopenia. Other toxicities were alopecia, nausea and vomiting, nephrotoxicity, thrombocytopenia and leukopenia.
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PMID:Etoposide and cisplatin in advanced esophageal cancer. A preliminary report. 323 66

Between 1966 and 1980, 68 patients were identified who had a splenectomy before or concurrent with resection of a colorectal adenocarcinoma. Control subjects with concurrent disease were then matched with each study patient for age, sex, stage of disease, and date of operation. Follow-up was complete. Between splenectomy patients and control subjects, there was no difference in the site of primary disease (rectum versus colon), the number of patients receiving adjuvant therapy, the technique of resection (cure versus palliation), or the extent of regional disease. Overwhelming sepsis occurred in only one splenectomy patient. Splenectomy was associated with a significant decrease in survival at 5 years in patients with regional (stage C) disease but not in patients with localized (stage B) disease. More splenectomy patients received blood transfusions than control subjects, but an independent effect on survival could not be demonstrated. The mechanism responsible for this adverse impact of splenectomy is undefined. However, splenectomy should be considered a possible factor in the survival of patients operated on for regional colorectal cancer.
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PMID:Influence of splenectomy on survival rate of patients with colorectal cancer. 334 31


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