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)

Prostaglandin E (PGE) has been hypothesized to be the endogenous metabolite that results in the immunosuppression seen in patients with tumor and trauma. This has resulted in multiple investigators proposing that administration of PGE inhibitors, such as aspirin and indomethacin, might improve immune function in such patients. We administered a long acting PGE analog, misoprostol, to nine normal healthy volunteers for five days and assayed immune function before and after therapy. The PGE analog improved lymphocyte blastogenesis and increased tumor necrosis factor production. The PGE analog also resulted in the volunteers having symptoms similar to those seen in patients with sepsis. The results of these studies indicate that elevated levels of PGE do not seem to result in impairment of immune function, but may be the endogenous metabolite responsible for the symptologic factors seen in infected patients.
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PMID:Effect of prostaglandin E on immune function in normal healthy volunteers. 141 90

Cyclosporin (CsA) is a potent modulator of multidrug resistance (MDR) and has been combined with etoposide (VP-16) to purge MDR leukemic cells from human bone marrow (BM) in vitro. We studied the feasibility of this approach in an in vivo model for autologous BM transplantation using the murine leukemia cell line P388 and its MDR variant P388/ADR. Colony-forming assays with 2-h drug exposure revealed a tumor selectivity of VP-16 for P388 cells compared to normal murine marrow granulocyte-macrophage colony-forming units (CFU-GM), whereas P388/ADR cells were resistant to VP-16. Simultaneous incubation with CsA restored sensitivity in these cells. Almost 4 logs of cell kill were achieved by treating P388/ADR cells with 60 microM VP-16 plus 2.5 microM CsA (combination A) or 40 microM VP-16 plus 10 microM CsA (combination B), whereas there was a 2.5-log reduction of CFU-GM at these doses. Even though the myelotoxicity of VP-16 was increased by the addition of CsA, this effect was nonspecific as shown by a similar chemosensitization in sensitive P388 as well as in P388/VP 2.5 cells, an atypical MDR variant lacking P-glycoprotein. In vivo experiments addressed the ability of BM treated with VP-16 and CsA to rescue lethally irradiated mice and to purge leukemic cells. In total, 1/14 lethally irradiated mice died due to sepsis within 10 days after receiving 15 x 10(6) BM cells treated ex vivo with combination A in contrast to 1/4 for combination B. All 16 surviving animals demonstrated long-term engraftment. When simulated remission marrow contaminated with 0.1% P388/ADR was purged with VP-16 (60 microM) or CsA (2.5 microM) alone, all mice died from leukemia before day 16 after transplantation (median 14.3 and 12.2 days). In contrast, nine of ten animals receiving similar marrow purged with combination A survived > 60 days without any evidence of disease (p < 0.01). We conclude that combining VP-16 and CsA was effective in purging MDR leukemia cells from transplanted BM in this murine model.
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PMID:Use of etoposide in combination with cyclosporin for purging multidrug-resistant leukemic cells from bone marrow in a mouse model. 146 39

The authors report their experience with transhiatal esophageal resection accumulated during the period between January 1978 and March 1990. Indications for the procedure included cancer of the gastric cardia (26.3%), cancer of the hypopharynx (3.8%), cancer of the esophagus (59.2%), and benign esophageal disease (9.8%). Esophageal substitution was performed using a tubulized stomach (63.6%), ileo-ceco-coloplasty (28.5%), left colon (7.6%), and jejunum (0.3%). The majority of patients with neoplastic disease were found to be in an advanced stage (67.3% of esophageal cancer patients and 69.7% of cancer of the cardia patients with stage III disease). The mean intra-operative volume of blood transfused varied between 533 and 1,220 ml. Sixteen patients required hospitalization in the intensive care unit. The mean length of post-operative hospitalization varied between 16.8 and 20.6 days. Operative complications included hemorrhage (0.3%) and tracheal injury (0.6%). Operative (30 day) mortality was 5.8%. Causes of death included respiratory insufficiency (35.2%), pulmonary sepsis (23.5%), abdominal sepsis (17.8%), and others (undefined, 23.5%). The 5 year survival was 48.5% for cancer of the gastric cardia, 57.1% for cancer of the hypopharynx and 11.8% for esophageal cancer.
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PMID:Esophageal resection by cervico-abdominal approach without thoracotomy. 147 91

Preoperative embolisation of renal carcinomas has several pros and cons for the patient. The negative aspects can be summarized as 'post-infarction' syndrome'. Radiologically, intrarenal gas formation is always evident. As sterile breakdown products of tumor cell necrosis these have to be interpreted as regular postinterventional findings and not as indicators for infection or even sepsis. Tumor embolisation as a means to reduce surgical difficulties in large hypervascularized renal carcinomas and also as a palliative measure in marked macrohematuria and/or tumor-induced flank pain is thus very conceivable. The best time for the tumor-nephrectomy is the day of embolisation or the first postinterventional day. This makes the nephrectomy easier and prevents the postinfarction syndrome for the patient.
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PMID:Gas formation after renal artery embolisation: genesis and clinical relevance. 147 62

We present a retrospective study of 68 esophageal cancer patients treated with surgery between 1975 and 1991. Results showed a resectability of 73.5% with the most frequent surgical approach being a Lewis esophagectomy. The mean hospitalization time was 24.7 days with a postoperative mortality of 7.3%. Other complications included anastomotic leakage, wound infection, sepsis and pulmonary disorders. Over-all survival at 3 years was 17.3%, reaching 24% in resected patients. Survival according to lymph node involvement was 13.4% for lymph node positive patients and 34.5% for node negative patients. According to histopathologic stage, survival rates were 34.6% and 8.59% for early and advanced tumor respectively, the difference being statistically significant using the Mantel-Haenszel test.
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PMID:[Cancer of the esophagus (II): the results of surgery, anatomicopathological study and patient survival]. 149 56

Children with malignant disease have an increased risk for bacterial infections. We investigated a possible correlation between septic episodes and decreased IgG subclass levels in 63 patients. At diagnosis 13 of 50 children showed decreased IgG subclass levels: 10x IgG4, 2x IgG1, and 1x IgG3 + IgG4 were reduced. Bone marrow infiltration by tumor cells did not increase the frequency of subclass reductions (4/25 with, 9/25 without bone marrow infiltration). The time course of subclass levels was followed during 37 febrile episodes (mainly fever of unknown origin, septicemia, pneumonia) of 23 children under cytostatic therapy. 6 patients showed transient low IgG subclasses: 2x IgG4, 1x IgG1, 1x IgG3, 1x IgG2 + IgG4, and 1x IgG1 + IgG3 + IgG4. Children with decreased IgG subclass levels appeared to occur more independently of leucopenia. In general, febrile episodes in children with subclass decreases did not last a longer period and did not occur more frequently than in children without IgG subclass deficiencies. In conclusion, the determination of IgG subclasses in cancer children at diagnosis or during chemotherapy did not add substantial information of prognostic or therapeutic relevance.
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PMID:[The IgG subclass level in children and adolescents with malignant diseases]. 151 65

A 43-yr-old woman developed carcinoma of the ampulla of Vater 20 yr after being successfully treated for Hodgkin's disease with radiotherapy and chemotherapy. Conditions related to the chronic effect of radiation, such as narrowing and fibrosis of abdominal tissue, hampered her diagnosis and treatment. After a total pancreatectomy to remove the carcinoma, the patient recovered. However, 15 months later, she developed severe digestive disturbances, adrenal insufficiency, pulmonary emboli, and vasculitis. She died the next month of sepsis and adult respiratory distress syndrome. Although her complications probably were related to residual effects from therapy and surgery, she had no clinical evidence of tumor recurrence.
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PMID:Carcinoma of the ampulla of vater after curative treatment for Hodgkin's disease. 153 76

From 1/1/80 to 5/31/90 111 patients underwent a colostomy on a gynecologic oncology service. Six patients developed 7 (6.3%) early colostomy-related complications, including sepsis (1), stomal retraction (1), ostomy wound infection (3), and partial stomal obstruction (2). The sepsis was felt to be related to spillage of stool upon maturing the colostomy, and this patient expired on Postoperative Day 63. There were no other mortalities attributed to the colostomies. Fourteen patients developed 17 (15.3%) delayed colostomy-related complications, including parastomal hernia (5), stomal retraction (1), stomal prolapse (3), tumor replacement (2), and site-choice problems (6). These results compare favorably with those in the literature and support the continued role of the gynecologic oncologist in gynecologic cancer-related gastrointestinal surgery.
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PMID:Complications of colostomy performed on gynecologic cancer patients. 154 34

The differential diagnosis of the swollen lower extremity in the patient with spinal cord injury includes deep venous thrombosis, fracture, cellulitis, joint sepsis, heterotopic ossification, hematoma formation, and neoplasm. A patient with an asymmetrically swollen limb who was found to have concurrent ipsilateral acute deep venous thrombosis and active heterotopic ossification is described. The diagnostic workup included various laboratory and radiologic studies. Therapy included anticoagulation with heparin and warfarin. To treat the heterotopic ossification, indomethacin, etidronate, and graded range of motion were used. We learned from this patient and several similar cases that acute deep-venous thrombosis and active heterotopic ossification may occur concurrently, and therapeutic anticoagulation did not lead to bleeding within or around the area of active heterotopic ossification. The possibility of a relationship between heterotopic ossification and deep venous thrombosis is presently being studied at our institution.
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PMID:Deep venous thrombosis associated with heterotopic ossification. 154 36

We conducted a phase I/II trial of 5-fluorouracil (5-FU)/folinic acid (FA) and alpha-2b interferon (IFN) in 43 previously untreated patients with measurable metastatic colorectal cancer. Patients had disease progression prior to therapy consistent of 5-FU 500 mg/m2 (level A) or 600 mg/m2 (level B) as starting dose administered as a 2-hour infusion, FA 200 mg/m2, and alpha-2b IFN 5MU/m2 subcutaneously. All drugs were given on days 1 to 5 and cycles were repeated after 3 to 4 weeks. The aim of the study was to define the maximal tolerable dose (MTD) of 5-FU for this schedule. In the absence of toxicity above MTD, defined as diarrhea and mucositis of World Health Organization grade 2 and leukopenia of World Health Organization, grade 3 5-FU was increased in increments of 100 mg/m2 for further cycles. Twenty-four patients were started on level A; 18 were started on level B. Forty-two patients were evaluable for toxicity, 32 for response. Three of 32 patients achieved a partial response; in 22 of 32 patients, tumor stabilization occurred. Forty percent of patients started on level A developed grade 2 diarrhea; 28% of patients developed grade 2 or 3 mucositis. Of 18 patients on level B, two patients experienced grade 4 mucositis (11%) and grade 3 or 4 diarrhea (11%). One drug-related death in the presence of sepsis occurred. Due to 11% of patients with grade 4 toxicity when started on 600 mg/m2 5-FU and 40% of patients with grade 2 diarrhea when started on level A, MTD as starting dose for 5-FU is 500 mg/m2 as a 2-hour infusion when used in combination with FA and IFN on a day 1 to 5 active schedule. We observed a wide range of 5-FU dose tolerated by individual patients. While some patients experienced severe, mainly gastrointestinal, toxicity on lower levels of 5-FU, others tolerated much higher 5-FU doses (11 patients, 700 mg/m2; 5 patients, 800 mg/m2; and one patient, 900 mg/m2). Our data suggest that double modulation of 5-FU by FA and IFN may not be superior to modulation of 5-FU with either drug alone.
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PMID:Interferon alpha-2b, 5-fluorouracil, and folinic acid combination therapy in advanced colorectal cancer: preliminary results of a phase I/II trial. 155 46


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