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)

Forty-two patients with advanced malignancy judged unlikely to respond to standard treatment received high-dose combination chemotherapy with cyclophosphamide, etoposide, and cisplatin in a phase I trial. Twenty-two of these patients who had at least a partial response (PR) to the first cycle of therapy received a second cycle, and eight patients received three or more cycles of therapy. Bone marrow replacement was not used. The maximum-tolerated doses (MTDs) were cyclophosphamide 2.5 g/m2 on days 1 and 2; etoposide 500 mg/m2 on days 1, 2, and 3; and cisplatin 50 mg/m2 on days 1, 2, and 3. Hematologic toxicity was not dose-limiting by study design. Recovery to an absolute granulocyte count above 100/microL occurred at a median of 9 days from onset (range, 3 to 23 days) at the MTD. Recovery was delayed after the third cycle. Only one patient on his third cycle failed to recover peripheral blood counts and died of sepsis an day 43. Hematologic toxicity was not dose-dependent. Nonhematologic toxicities included emesis, fatigue, alopecia, diarrhea, and anorexia and were generally well tolerated. The dose-limiting toxicities were fatal pulmonary or cardiac toxicities in five of nine patients treated at the highest dose level. Patients likely to do well can be selected by tumor type, response to prior therapy, and performance status. Nine of 36 assessable patients had a complete response (CR) and 13 a PR for a response rate of 61%. Five patients (12%) remain alive and free of disease at 15 to 32 months. Repeated cycles of dose-intensive combination therapy can produce long-term disease-free remissions in patients with refractory tumor types. The toxicity of the regimen is acceptable if patients are carefully selected.
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PMID:Phase I study of repeated cycles of high-dose cyclophosphamide, etoposide, and cisplatin administered without bone marrow transplantation. 199 24

We conducted a prospective, randomized trial to study the efficacy and tolerance of long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B. Ten patients were randomly assigned to a 6-month interferon regimen, and 10 patients were assigned to a 3-week interferon trial. Eleven patients (five assigned to long-term treatment and six to short-term treatment) did not complete interferon therapy: eight had either severe thrombocytopenia or neutropenia; one had pronounced fatigue in relationship to administration of interferon; one had spontaneous bacterial peritonitis and sepsis and died; and one had a massive fatal variceal hemorrhage during interferon therapy. Most of the serious hematologic complications occurred in patients with cirrhosis and hypersplenism. In one patient, seroconversion to hepatitis B virus DNA negativity occurred before the onset of treatment. Four of the five patients able to complete the 6-month interferon regimen and only one of four patients able to complete the 3-week trial had seroconversion to hepatitis B virus DNA negativity. Thus, we conclude that the therapeutic response was better among patients who were able to complete a 6-month interferon trial. In patients with cirrhosis and hypersplenism, development of either severe thrombocytopenia or leukopenia associated with interferon therapy precluded completion of treatment.
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PMID:Long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B: a prospective, randomized treatment trial. 221 80

Based on the report of some activity of combination therapy with dacarbazine (DTIC) and interferon alpha-2a (rIFN alpha-2a) in disseminated melanoma, we conducted a phase II study to determine the feasibility and efficacy in a large series of patients. DTIC was administered in 79 patients at the dose of 800 mg/m2 every 3 weeks and rIFN alpha-2a was given daily at the dose of 9 X 10(6) IU for the first 10 weeks and three times a week thereafter. Among the 75 evaluable patients, 25% achieved an objective response, with 8% complete and 17% partial remissions. The regression occurred within a mean time of 1.9 +/- 1.03 months from starting therapy and the mean duration of response was 8.2 +/- 4.2 months. The major side effects were vomiting, anorexia, fever, fatigue, and myalgia. There was one death related to sepsis after myelosuppression. In the other patients bone marrow and liver toxicities were not remarkable. Our data reveal that a combination regimen of rIFN alpha-2a with a cytotoxic agent has some therapeutic activity in the management of advanced malignant melanoma.
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PMID:Phase II study of interferon alpha-2a and dacarbazine in advanced melanoma. 222 Jun 60

A polyethylene glycol conjugate of L-asparaginase (PEGLA) was administered to 21 patients with refractory non-Hodgkin's lymphoma. The dose given was 2,000 mu/m2 intramuscularly every 2 weeks. Eligibility required at least one prior trial of chemotherapy and ambulatory performance status. At entry, all patients had measurable lesions and documented disease progression. The median age of the patients was 61 years; 18 (86%) were ambulatory with minimal symptoms, 12 patients (57%) had 3 or more prior regimens, and 13 (62%) had stage IV disease. Histologic subtype was low grade in 11 patients (52%), intermediate in 7 (33%), high grade in 2 (10%) and unclassifiable in one (5%). There were two partial responses (11%) noted (95% confidence interval of response of 1-30%). Eleven patients (52%) were removed from study due to disease progression. Nine patients (43%), required removal for toxicity (7 for protracted nausea and vomiting and 2 for confusion). One patient died of sepsis while on study but this was not considered drug related. Almost one third of patients complained of fatigue or loss of appetite. Nausea and vomiting occurred in approximately half the patients and was moderate to severe in 9. Diarrhea and abdominal pain were also noted in one-third of those treated. Changes in the partial thromboplastin time and fibrinogen were noted in most patients but resulted in no bleeding complications. In this trial, PEGLA displayed modest activity in a heterogenous group of patients with progressive non-Hodgkin's lymphoma.
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PMID:A phase II trial of PEG-L-asparaginase in the treatment of non-Hodgkins lymphoma. 234 67

A 46-year-old man was admitted to our hospital on Mar. 16, 1988 with the chief complaint of productive cough. The chest roentgenogram and tomogram showed a tumorous shadow in the right upper lobe, accompanied with stenosis of the trachea and the right main bronchus. Bronchofiberscopic examination confirmed a nodular tumor protruding into the lower part of the trachea from the right lateral wall and nearly complete obstruction of the right main bronchus. Pathological specimen obtained by transbronchial biopsy revealed "low differentiated adenocarcinoma". It was highly suspected that the primary lung cancer had directly invaded the trachea and the right main bronchus. His symptoms and roentgenological findings remarkably improved after radiation therapy. He was discharged on May 12. On Sep. 14, he was admitted to our hospital again because of hoarseness, general fatigue and increasing dyspnea. The chest CT demonstrated severe stenosis of the trachea, which was treated with another radiation therapy. Although his symptoms diminished, he had a sudden onset of high fever on Oct. 15. Immediately a blood culture and transtracheal aspiration (TTA) were performed. Gram-negative bacilli were isolated from the blood culture four days later. The administration of fosfomycin and tobramycin was started. However he died because of massive hemoptysis on Oct. 23. Several days after the death, an isolated strain was identified as Capnocytophaga ochracea by the biochemical characteristics. Culture of sputum obtained by TTA was negative for Capnocytophaga ochracea. Septicemia due to Capnocytophaga spp. is very rare and only one case (due to Capnocytophaga sputigena) has been reported until now in Japan. Our patient is thought to be the first case of septicemia due to Capnocytophaga ochracea in Japan.
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PMID:[A case of septicemia due to Capnocytophaga ochracea beginning post radiation therapy for lung cancer]. 235 15

Recombinant interferon alfa-2a (rIFN alpha-2a) synergistically augments the cytotoxic effects of the antimetabolite fluorouracil (5-FU) against two human colon cancer cell lines. A pilot clinical trial was initiated to determine whether this same combination of agents would show clinical utility greater than that expected with 5-FU alone in patients with advanced colorectal carcinoma. 5-FU was administered at 750 mg/m2/d for 5 days as a continuous intravenous infusion followed by weekly bolus therapy. rIFN alpha-2a was administered at 9 million units subcutaneously three times per week starting on day 1. Doses of 5-FU were modified for mucosal toxicities and myelo-suppression, and doses of rIFN alpha-2a were modified for fatigue and neurologic toxicities. Thirty-two previously untreated patients with advanced colorectal carcinoma were entered into a clinical trial. With the exception of one patient with a destructive lesion of the sacrum, all patients had metastases to visceral organs, abdominal wall, or pelvis. Twenty patients (63%) achieved a partial response, seven remained stable, and five had progressive disease. Mucosal toxicities limited delivery of full projected dose. Two patients died following episodes of watery diarrhea progressing to sepsis. A third died suddenly, secondary to an interstitial pneumonitis. The remainder of the toxicities were managed with dose reductions. At the median follow-up of 8 months, 23 of 32 patients remain alive. Nine are alive at 16 to 30+ months. The early results of this single-institution study are promising, but will require confirmation in a multi-institutional setting currently being conducted by the Eastern Cooperative Oncology Group.
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PMID:Clinical update on the role of fluorouracil and recombinant interferon alfa-2a in the treatment of colorectal carcinoma. 240 91

Twenty selected patients with advanced malignant tumour (11 women and 9 men; mean age 52.8 [17-83] years) were on home parenteral nutrition because of ileus and (or) shortintestine syndrome. Mean survival time after onset of total parenteral nutrition in hospital was 107 (23-467) days. Mean treatment period at home was 81 (13-376) days, in hospital 26 (3-91) days. The patients with the shortest survival time all had metastasizing gastric carcinoma. The most common complaint was physical fatigue. In one patient there was a treatment-related complication (catheter sepsis). The results document that total parenteral home nutrition of carefully selected patients with advanced malignant tumour makes it possible for the remaining period of life to be spent, in acceptable conditions, at home rather than in hospital.
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PMID:[Home parenteral feeding in advanced tumor diseases]. 250 97

Neurological symptoms including lethargy, obtundation, and confusion are early and common findings in patients with sepsis. The etiology of the mental status changes that occur during severe infection is not known. We investigated the effects of sepsis on the levels of high-energy phosphates to determine whether decreased energy metabolism was a factor in the depressed neurological state. The time course of changes in brain pH and brain high-energy phosphate metabolites during an Escherichia coli infusion was determined from sequential phosphorus-31 nuclear magnetic resonance (31P-NMR) spectra of ketamine-xylazine-anesthetized rats. A second group of rats received 0.9% saline infusion and served as a control group. Despite severe obtundation and near loss of righting reflex, the rats in the septic group had no significant differences in the brain pH, the ratio of phosphocreatine (PCr) to beta-adenosine 5'-triphosphate (beta-ATP), or in the ratio of PCr to Pi. The only significant decrease in brain high-energy phosphates or pH occurred terminally in the septic rat group and corresponded with a rapidly falling arterial blood pressure. We conclude that the severe neurological depression that is characteristic of sepsis is not due to decreased levels of brain high-energy phosphates or brain acidosis.
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PMID:An in vivo examination of rat brain during sepsis with 31P-NMR spectroscopy. 261 Feb 45

Capsule-deficient Cryptococcus neoformans (CN-CD) infection is very rare. The authors recently experienced the case of CN-CD infection with the complication of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in a 83 year old woman. She was admitted to our hospital with the complaints of fever and general fatigue on June 10, 1987. At the time of admission, there were no abnormal findings except a mildly lowered consciousness level on physical examination, there were no abnormal neurological finding nor meningeal signs. Laboratory data revealed a mild leukocytosis and hyponatremia. Chest X-P showed a few small nodular shadows scattered in both lungs. Antibiotics therapy was of no help and hyponatremia became worse. Then with the suspicion of SIADH, Demeclocycline was administered and limitation of water intake was decreased and hyponatremia improvement was used. Yeast-like fungi was detected in the venous blood culture and in the cerebrospinal fluid (cell count: 252/3) CN-CD by India-ink preparation and bacteriological nature were determined. We made a diagnosis of sepsis and meningitis by CN-CD accompanied with SIADH. In spite of Miconazole administration intravenously and intrathecally, she died 2 months after admission. The minimal inhibitory concentration (micrograms/ml) of antibiotics against the isolated CN-CD was as follows: Amphotericin B: 0.78, 5-PC: 1.56, Miconazole less than or equal to 0.05, Nystatin: 25, Ketoconazole: 0.78.
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PMID:[A case of sepsis and meningitis due to capsule-deficient Cryptococcus neoformans with SIADH]. 269 39

We reported a case of halothane-induced fulminant hepatitis with acute renal failure which developed 6 days after reexposure to halothane. The patient was a 58-year-old female. She had a history of liver dysfunction after exposure to halothane 6 years previously. She had surgical treatment of clubfoot under halothane anesthesia in other hospital. Preoperative physical examination and laboratory data were normal. On the 6th post-operative day she abruptly developed high fever and general fatigue. Next day, she was transferred to our hospital. At admission, fulminant hepatitis complicated with acute renal failure was diagnosed with severe liver and renal damage. She was immediately treated with plasma exchange, glucose-insulin therapy, and hemodialysis. Serum transaminase level returned to normal value within a week. However, despite repeated hemodialysis, renal function did not improve, and she died of P. aeruginosa sepsis on 28th day after the operation. It may be suggested that in this patient hypersensitivity to halothane has persisted during the six years.
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PMID:[A case of fulminant hepatitis after reexposure to halothane six years later]. 281 Jul 19


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