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)

Gamma-Glutamyltransferase activity was studied in a man presenting with recurrent septicemia owing to pyonephrosis and renal carcinoma. Increased activity in the urine was ascribable to administration of the aminoglycoside antibiotic, tobramycin. That the renal carcinoma did not contribute to the increased values was confirmed by homogenization and enzyme histochemistry of the tumor. Although the activity of this enzyme in serum was greater than normal, this persisted postoperatively, and thus was not related to the renal carcinoma.
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PMID:Effect of tobramycin on urinary gamma-glutamyltransferase activity: Studies in a case of renal carcinoma. 0 98

According to cell cycle synchrony principles, bleomycin was infused for 48 hours, followed by a dose of either methotrexate or hydroxyurea after a 24-hour rest, in 36 adult patients with disseminated carcinoma. In this preliminary study, a 59% response rate was noted among patients with epidermoid carcinoma of the head and neck. Four of four patients with transitional cell carcinoma of bladder and one patient with hypernephroma also responded. No responses were noted among five patients with epidermoid carcinoma of the lung. The length of response ranged from 1 to 8 months (median, 2 months). Seventy-seven percent of the responders had extensive prior radiotherapy. The first patient treated had fatal sepsis with leukopenia, which prompted a widening of the treatment interval. Subsequently, toxicity was mainly mild or absent, the moderate or severe toxicity was primarily neutropenia, which was reversible. The use of low-dose bleomycin infusion is safe and may play a role in cancer therapy in combination with other agents specific for certain tumors. The length of infusion should be determined by the cell cycle of the tumor, if its potential synchronizing capabilities are to be exploited.
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PMID:Intravenous bleomycin infusion as a potential syncronizing agent in human disseminated malignancies: a preliminary report. 6 5

Cyclophospamide was given in two dose schedules to 25 patients with a variety of nonlymphoid solid tumors. Eleven patients were given 18 courses of cyclophosphamide at a total dose of 60 mg/kg. Sixteen patients received 26 courses at a total dose of 100 mg/kg. Two patients were treated with both regimens. Partial responses were achieved in two patients treated with 60-mg/kg dose of cyclophosphamide. One of these patients had osteogenic sarcoma and the other had renal carcinoma. The higher dose also produced two partial responses, one in a patient with anaplastic carcinom a of the lung and the other in a patient with anaplastic carcinoma of the lung and the other in a patient with embryonal testicular carcinoma. Mean leukocyte counts fell to a nadir of 1400 cells/mm after 60 mg/kg while they dropped to below 1000 cells/mm for 5 days after 100 mg/kg of cyclophosphamide. Mean platelet counts remained above 150,000 platelets/mm after both cyclophosphamide schedules. In fective complications were documented aftter three of the 18 courses at 60 mg/kg and after ten of the 26 courses at 100 mg5kg. In the latter group, there were three episodes of bacteremia, including one death from pseudomonas sepsis. Nonhematologic toxicity noted with the 100-mg/kg dose of cyclophosphamide included rare instances of electrocardiogram changes and serum enzyme alterations compatible with myocardial toxicity. The intensive cyclophosphamide therapy did not appear to result in an increased antitumor response in malignancies usually considered to be refractory to alkylating agents.
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PMID:Intensive cyclophosphamide (NSC-26271) therapy for solid tumors. 109

Twenty-six patients with advanced renal cell carcinoma were treated with suramin administered by continuous infusion, with dosing determined by a nomogram. One patient achieved a partial response and five patients achieved a minor response or had stable disease for > 3 months. Toxicities included an immune-mediated thrombocytopenia in one patient and Staphylococcus sepsis that was not associated with neutropenia in five patients. Pharmacokinetic parameters were determined by the ADAPT II MAP-Bayesian parameter estimation program. Patient data were fit using a two-compartment open model and first-order rate elimination. This showed a wide interpatient variation in time to target level (median, 13.8 days), volume of distribution (median, 15.2 liters/m2), and t1/2-beta (median, 20.6 days). The patients who achieved a partial response, minor response, or stable disease had a slower elimination rate of suramin, compared to patients with progressive disease. Tumor specimens were obtained prior to therapy and were analyzed for the production of five different growth factor-specific RNA transcripts. These included transforming growth factor alpha, acidic fibroblast growth factor, basic fibroblast growth factor, and platelet-derived growth factor types A and B. No difference in the pattern of growth factor expression was seen in tumors of responding and nonresponding patients. Suramin does not have significant antitumor activity in renal cell carcinoma. The wide variability in pharmacokinetics suggests that individual dosing should be used in future trials of suramin for treatment for other malignancies. Pertinent corollary studies of tumor biology and clinical pharmacology should be included whenever possible in clinical trials in patients with renal cell carcinoma.
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PMID:Phase II trial of suramin in patients with advanced renal cell carcinoma: treatment results, pharmacokinetics, and tumor growth factor expression. 139 2

The clinical and immune modulatory effects of interleukin-2 (IL-2) and interferon (INF) alfa-2a were examined in a phase II study in patients with metastatic renal cell carcinoma (six patients) and melanoma (eight patients). Treatment consisted in IL-2 3 MU/m2 continuous infusion days 1-4 and INF alfa-2a 6 MU/m2 subcutaneously day 1 and 4, both given on alternate weeks. Tumour response was assessed after four cycles of treatment or earlier, if necessary. Patients with stable disease or response were to be continued for another nine cycles or up to disease progression. The 14 patients received a total of 60 cycles of treatment. Major toxicities (WHO Grade III/IV) were fever, capillary leak syndrome with hypotension, nausea and vomiting, erythema with pruritus, leuco- and thrombopenia and sepsis with staphylococcus aureus. Five of 14 patients (36%) developed a self limiting autoimmune thyroiditis with HLA-DR expression on thyrocytes. Long term treatment toxicity was moderate with an average weight loss of 5% and an average fall in Karnofsky index of 10% compared to baseline. No responses were seen in renal cell carcinoma, two patients with melanoma had a partial and two a minor response with a duration of 1-7 months. Serial measurements of immune modulatory parameters showed a functional response to treatment with an increase of NK- and LAK-activity during the first two cycles, followed by a plateau and decrease during the third and fourth cycles. These findings were paralleled by a successive decline in treatment induced INF gamma response. These findings suggest, that alternative weekly treatment with IL-2 and INF alfa-2a results in an exhaustion of lytic capacity of NK- and LAK-cells and an attenuation of secondary cytokine release.
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PMID:Clinical and immune modulatory effects of alternative weekly interleukin-2 and interferon alfa-2a in patients with advanced renal cell carcinoma and melanoma. 199 8

The hearts of eight patients aged 22 to 67 years (mean, 41 years) who died during or within 4 days of interleukin-2 (IL-2) based immunotherapy for treatment of renal cell carcinoma or melanoma were studied at necropsy. Death resulted from combined cardiorespiratory failure in two patients, sepsis in four patients, acute myocardial infarction in one patient, and myocarditis in one patient. Transmural left ventricular necrosis was present in one of the two patients with significant atherosclerotic coronary artery narrowing. Noninfectious myocarditis was present in five patients: the inflammatory infiltrate was lymphocytic in four and composed of a mixture of eosinophils and lymphocytes in one. Although treatment-related deaths associated with high-dose IL-2 therapy are uncommon (1.5% in 652 consecutive patients), the potential for significant myocardial ischemia or myocarditis exists, and careful monitoring for arrhythmias or myocardial failure is warranted.
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PMID:Myocarditis or acute myocardial infarction associated with interleukin-2 therapy for cancer. 220 2

The use of interleukin-2 (IL-2), either alone or in combination with lymphokine-activated killer cells, tumor infiltrating lymphocytes, or other immunotherapeutic agents has added a new list of alternatives to conventional antineoplastic regimens. Little information is available about the pathologic changes occurring in patients treated with these agents. In this study, we reviewed the necropsy materials from 19 patients, 12 men and 7 women, with a variety of malignancies including melanoma, renal cell carcinoma, gastrointestinal and pulmonary adenocarcinoma, and metastatic gastrinoma, who died after receiving IL-2-based immunotherapy. Death occurred at intervals ranging from less than 1 hour to 143 days following the last dose of therapy. All patients dying at or less than 43 days following cessation of therapy had lymphoid infiltrates of varying intensity in residual tumor. At necropsy, the major cause of death unrelated to the presence of metastatic tumor was bacterial sepsis. In addition, we found evidence of significant cardiac and pulmonary toxicity: two patients with acute myocardial infarction, one with and one without significant coronary artery disease, two cases of unexplained lymphocytic myocarditis, and one case of fatal pulmonary capillary plugging following an infusion of lymphokine-activated killer cells. Thus, not unlike other forms of therapy for cancer, IL-2-based immunotherapy does not appear to be without significant toxicity.
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PMID:Pathologic findings associated with interleukin-2-based immunotherapy for cancer: a postmortem study of 19 patients. 233 30

Interleukin-2 (IL-2) is secreted during the immune response to trauma, sepsis, and transplant rejection. Its role in the development of the metabolic abnormalities observed in these circumstances is not well defined. We studied the clinical, hormonal, and metabolic response to a 5-day IL-2 infusion (3 x 10(6) U/m2/day) of nine patients with metastatic renal carcinoma. IL-2 induced systemic manifestations after a latent period of 4 h (fever, tachycardia) or 8 h (hypotension). These manifestations persisted until the end of the infusion. Insulin levels were not modified. Among the stress hormones, cortisol increased at the onset of fever and tachycardia, whereas the rise in catecholamines occurred later (24 h) and appeared more as a response to the development of hypotension. The only metabolic effects observed were a late (third day) rise of lactate and a late and transient (third to fourth day) decrease of glycerol and nonesterified fatty acids. These metabolic modifications were temporally related to the development of hypotension and result more likely from low tissue perfusion rather than from a direct or hormone-mediated effect of IL-2.
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PMID:Hormonal and metabolic effects of chronic interleukin-2 infusion in cancer patients. 234 64

Renal autotransplantation with/without extra-corporeal surgery was performed in 53 patients between September, 1975 and december, 1987. Original disease was obstructive disease of the upper urinary tract in 25 patients, renovascular hypertension and renal vascular disease in 13, renal calculous disease in 12 and renal cell carcinoma in 3. Ten of the 53 patients had solitary kidneys. Three patients died on 14, 21 and 49 postoperative days of massive bleeding with disseminated intravascular coagulopathy caused by the rupture of transplant arterial anastomosis (1 patient with urinary obstructive disease) and sepsis caused by wound infection (2 patients with renal calculous disease). Two kidneys were removed on operative day and 8 postoperative days due to arterial thrombosis in 2 patients with aneurysm of intrarenal artery. The deterioration of renal function was observed in previously damaged kidneys of two patients with extensively damaged ureter. No other severe complications were observed. In 23 of 24 patients with the obstructive disease of the upper urinary tract, disappearance or improvement of the obstructive change was observed after surgery. All 5 patients with renovascular hypertension showed normo-tension without administration of antihypertensive drugs after surgery. In 3 of 5 patients with an aneurysm of the intrarenal artery, the aneurysm was removed and reconstruction of the artery was performed successfully. Two patients with arterio-venous fistula and one patient with nut cracker syndrome had no severe hematuria with bladder tamponade after surgery. Ten of 12 patients with renal calculous disease were treated successfully without residual calculi by this procedure. Three patients who had solitary kidney with renal cell carcinoma were treated successfully by this procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Renal autotransplantation and extra-corporeal surgery]. 265 70

Autopsy findings were reviewed in 43 patients clinically diagnosed in the last 12 years as having urogenital malignant tumors. Clinical diagnoses were 14 bladder carcinoma, 11 prostatic carcinoma, 6 renal cell carcinoma, 5 renal pelvic carcinoma, and 7 other malignant tumors. Autopsy showed that 31 cases died due to carcinoma and 12 because of other causes. The most common ultimate causes of death were DIC and infection, especially pneumonia and sepsis. Autopsy showed 36 of the 43 cases (83.7%) with metastasis. Clinical diagnosis showed 34 cases of metastasis, but the number of metastasized organs and lymph-nodes was much lower than in subsequent autopsy findings. Autopsy proved 5 cases of clinical misdiagnosis (11.6%) and 4 of undiagnosed malignant tumors (9.3%). In 15 cases (32.6%) the ultimate cause of death as revealed by autopsy had not been clinically diagnosed. Five cases diagnosed as having died due to cancer in fact were found to have died due to other causes. Recent diagnostic techniques are greatly advanced, yet many findings are still revealed for the first time by autopsy. Autopsy continues to be a very important final arbiter of progress and the effect of malignant tumors, and serves to remind us of the ongoing need for constant vigilance and improvement of clinical diagnostic techniques.
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PMID:[Review of 43 autopsy cases of urogenital malignant tumors]. 273 88


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