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)

Based on in vitro evidence of time-dependent synergistic kill of HL-60 leukemia cells exposed to Ara-C and mitoxantrone, 44 patients with relapsed or refractory AML and 3 with blastic CML were treated with a timed sequence of both drugs. There were 25 females and 22 males, with a median age of 53 (range 21-75). Of 31 patients with relapsed AML, 24 had one prior remission, 6 had two and 1 had three. Of these, 15 had failed a second reinduction attempt. Thirteen patients were primarily refractory to induction with Ara-C plus daunorubicin. Each dose of Ara-C, 500 mg/m2, was followed after 6 hr by mitoxantrone, 5 mg/m2, and the sequence was repeated four to six times (44-68 hr) in different cohorts of patients. All but two patients (one with blastic CML and one in relapse and refractory) are evaluable for response and toxicity. Of 16 patients in relapse without prior reinduction 7 achieved CR and 3 PR (62% response rate); there were 3 CR in the 14 patients who were in relapse and refractory (21% response rate) and 4 CR and 1 PR (35% response rate) in the 14 patients with primary anthracycline resistance. Five of seven patients previously exposed to mitoxantrone achieved CR. Response lasted from 2 to 42 months, with two patients alive and in continuing remission at 34 and 42 months. Average marrow recovery was seen after 25 days and time to remission was 30 days. Six patients died in induction (four from sepsis and two from the tumor lysis syndrome) and 21 had progressive disease. Chemotherapy was well tolerated with minor nausea and vomiting in 13 patients, moderate in 20, and severe in 2. Most patients did not have evidence of drug-induced mucositis: it was minor in 9 and moderate in 2. Renal dysfunction was attributable to the use of nephrotoxic antibiotics. Hepatic dysfunction was reversible and was minor in 10 patients, moderate in 13, and severe in 3. Sequential, timed administration of intermediate-dose Ara-C and mitoxantrone is an active and well-tolerated antileukemic regimen.
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PMID:Sequential intermediate-dose cytosine arabinoside and mitoxantrone for patients with relapsed and refractory acute myelocytic leukemia. 220 4

The retrospective study of acute renal failure (ARF) in patients with hematologic neoplasms was carried out. ARF occurred in 32 (6.1%) of 526 patients with hematologic neoplasms. Twenty-one (66%) patients recovered from ARF, but only 7 (22%) survived and were discharged from the hospital and 25 (78%) died of ARF or other complications. In 17 patients with leukemia or malignant histiocytosis, sepsis and/or disseminated intravascular coagulation were the most common causes of ARF, and all 17 patients died. In 11 patients with multiple myeloma, ARF was always attributable to the underlying disease, and the clinical course improved with the initiation of blood purification therapy (hemodialysis, plasma exchange) and chemotherapy. Five patients in blast crisis of chronic myelogenous leukemia or non-Hodgkin's lymphoma developed ARF as a result of tumor lysis syndrome. In this group, renal function improved with hemodialysis but only 2 patients survived. Patients with oliguria had worse outcomes than those without oliguria. Survival appeared to depend not on renal function but on the underlying disease, the cause of ARF, and other complications. These findings suggest that, in patients with hematologic neoplasms complicated by ARF, early initiation of blood purification therapy will improve the prognosis.
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PMID:[Acute renal failure in patients with hematologic neoplasms]. 238 Oct 56

Among patients suffering from nonseminomatous germ-cell tumor, with a poor prognosis, a subset underwent respiratory failure and died very early in the course of their treatment. Between 1982 and 1989, 11 out of 56 such patients (20%) died within the first 5 weeks of chemotherapy. The clinical, radiological, biological and infectious characteristics of these patients were analyzed. Nine patients had extensive pulmonary metastases and the 2 others presented a bulky mediastinal mass with pleural effusion. All patients experienced acute respiratory distress during chemotherapy and underwent mechanical ventilation. All patients were febrile, and septicemia was documented in 7 cases. WHO grade 4 and grade 1-2 renal toxicities occurred in 3 and 4 patients respectively. There was no tumor lysis syndrome. All patients died within 35 days from the start of therapy; 4 were autopsied. These 11 patients represent a clinical entity, having what we called super-high-risk germ cell tumors. Early death is related to pulmonary distress within the first 5 weeks of therapy. The origin of the pulmonary distress is multifactorial: bulky disease of the chest, infection, and interstitial fibrosis. Immediate full-dose standard chemotherapy in association with intensive supportive care is recommended in the management of these patients.
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PMID:Super-high-risk germ-cell tumors: a clinical entity. Report of eleven cases. 808 45

Continuous hemofiltration (CH) is being used in increasing numbers of pediatric intensive care unit patients. Experience with 114 CH treatments in 98 critically ill children from March 1988 to March 1993 is presented in this study. Ages ranged from 1 day to 23 yr (mean +/- SE = 7.1 +/- 0.7 yr), and 54% of patients were male. Seventeen percent of all treatments were performed in neonates under 1 month of age. The most common primary diagnoses were sepsis and adult respiratory distress syndrome (11 patients each), liver transplantation and hypoplastic left heart syndrome (10 patients each), and hemolytic uremic syndrome (9 patients). The most frequent indications for CH were fluid overload and acute renal failure (42% each). Choices for CH included: continuous arteriovenous hemofiltration (CAVH, 50%), continuous arteriovenous hemodiafiltration (CAVH, 23%), continuous venovenous hemofiltration (CVVH, 18%), and continuous venovenous hemodiafiltration (CVVH-D, 9%). Choices for anticoagulation included: none (47%), regional (49%), and systemic (4%). Treatment duration ranged from 1 to 25 days (mean = 5.3 +/- 0.4 days). Mean filter life span for 363 filters was 0.94 +/- 0.1 filters/patient per day. Despite an overall survival rate of 43%, survival to discharge varied greatly (0 to 100%) among the 24 diagnostic groups: tumor lysis syndrome and systemic lupus erythematosus (3/3 patients each, 100%), hemolytic uremic syndrome (8/9 patients, 89%). This compares with: bone marrow transplantation (0/6 patients, 0%), hypoplastic left heart syndrome (2/10 patients, 20%), and leukemia (1/4 patients, 25%). Survival to hospital discharge was better in patients who did not receive pressors (P < 0.005) and in patients treated with combined ultrafiltration and dialysis (CAVH-D, CVVH-D) compared with ultrafiltration alone (CAVH, CVVH) (P < 0.005), but was not notably affected by patient age, sex, use of anticoagulation, filter life span, blood pump-assisted versus spontaneous CH, or duration of therapy. Filter life span was not affected by use of anticoagulation, but was remarkably longer in patients with arteriovenous versus venovenous CH (P < 0.004). It was concluded that: (1) empirical anticoagulation of patients treated with CH is not necessary; (2) children with a minority of underlying diseases and those requiring pressor support at initiation of CH appear to have relatively poor survival rates despite the technically effective use of CH; and (3) the addition of countercurrent dialysis to routine CH may enhance patient survival to hospital discharge.
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PMID:Determinants of survival in pediatric continuous hemofiltration. 858 15

Acute renal failure (ARF) is one of the most frequent and potentially life threatening complications following bone marrow transplantation (BMT). Several renal syndromes that occur are either unique or occur with a disproportionate frequency post-BMT. Clinically ARF can be classified according to the time of onset post-BMT. Immediate ARF syndromes include tumor lysis syndrome and marrow-infusion associated toxicity, which usually occur within 5 days post-BMT. Hepatorenal-like syndrome secondary to venoocclusive disease occur within one month and is the most common cause of early ARF syndrome. The late renal syndromes, more than 4 weeks post-BMT, include BMT-associated nephropathy, which may be acute or chronic, and cyclosporin nephrotoxicity. Other non-specific causes of ARF such as sepsis, hypotension, volume depletion, nephrotoxic agents and obstructive uropathy can also occur at any time period. Frequently ARF is multifactorial in these patients with complicated clinical course. Therapeutic approach depend on the underlying etiology. Supportive treatment such as optimization of volume status and dialysis when indicated are important steps as specific therapy is rarely available. Therefore, efforts should be targeted to the prevention of ARF. This includes prophylaxis for tumor lysis syndrome and marrow infusion toxicity by hydration and alkaline diuresis, avoiding nephrotoxic agents, early recognition and treatment of infection and correction of volume depletion.
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PMID:Acute renal failure following bone marrow transplantation. 960 30

While there is clear support for the use of continuous renal replacement therapy (CRRT) in critically ill acute renal failure patients, there are other illnesses without renal involvement where CRRT might be of value. These include sepsis and other inflammatory syndromes such as acute respiratory distress syndrome (ARDS) and cardiopulmonary bypass where removal of inflammatory mediators by hemofiltration is hypothesized to improve outcome. Adsorption appears to be the predominant mechanism of mediator elimination. However, the observed hemodynamic improvement can, at least partially, be attributed to a reduction of body temperature or to fluid removal, and the evidence for a clinically important removal of proinflammatory cytokines remains limited. Continuous and therefore smooth fluid removal may improve organ function in ARDS, after surgery with cardiopulmonary bypass, and in patients with refractory congestive heart failure. Continuous removal of endogenous toxins, eventually combined with intermittent hemodialysis, is probably beneficial in inborn errors of metabolism, severe lactic acidosis, or tumor lysis syndrome.
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PMID:Non-renal indications for continuous renal replacement therapy. 1056 Aug 14

Patients with chronic lymphocytic leukemia (CLL) who fail fludarabine (Fluda) therapy have a poor response to subsequent salvage regimens and a poor prognosis. This study was undertaken to determine the efficacy and toxicity of a cis-platinum, (cis-p)fluda and arabinosyl cytosine (ara-C) combination in patients who were refractory to fluda or had relapsed following prior fluda therapy for CLL. Forty-one patients who had progressive CLL were treated on study. Eleven patients (27%) were sensitive to fluda and thirty (73%) refractory prior to study entry. Therapy consisted of cis-p 100 mg/m2 continuous intravenous (i.v.) infusion over 4 days, fluda 30 mg/m2 i.v. over 15 minutes on Days 3 and 4 either given alone (PF) or with ara-C 500 mg/m2 i.v. over 1 hour on Day 4 (PFA). The median number of PF or PFA courses received was two. No patient achieved a complete response. Eight patients (19%) achieved a partial response (PR), 28 were taken off study with progressive or refractory disease and 5 had induction deaths. The overall median survival was 6 months, 15 months in responding patients, and 4 months in non-responding patients. Rai stage I-II patients had a median survival of 7 months and stage III-IV patients had a median survival of 3 months. Major toxicities (myelosuppression, sepsis, renal failure and tumor lysis syndrome) were frequent. In conclusion, it can be said that the PF and PFA regimens have equivalent modest activity in patients with progressive CLL following prior fluda therapy, predominantly among patients whose disease was sensitive to fluda at last prior exposure. Ara-C did not add to the activity of the cis-p/fluda combination in this study group.
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PMID:Sequential cis-platinum and fludarabine with or without arabinosyl cytosine in patients failing prior fludarabine therapy for chronic lymphocytic leukemia: a phase II study. 1061 50

Fourteen children, newborn to 17 years of age, underwent continuous veno-venous hemofiltration with dialysis (CVVHD), using a new FDA-approved bicarbonate-based calcium-free dialysis solution (Normocarb) in combination with citrate anticoagulation. Dialysis prescription included use of the PRISMA system (Gambro, Lakewood, Colo., USA), with ACD-A (Baxter, Deerfield, Ill., USA) for anticoagulation and Normocarb (Dialysis Solution, Richmond Hills, Ontario, Canada) for dialysate. Diagnosis included 11 children with sepsis and 3 children with tumor lysis syndrome. Mean weight was 31.6+/-4.7 kg (range 3.7-62 kg) and average length of therapy was 11.4+/-3.7 days (range 6 h to 67 days). Length of circuit patency was 71.3+/-7.2 h (range 6 h to 127 h), which was influenced in part by a decision to change circuits at 72 h as per manufacturer's recommendation. No bleeding occurred. This protocol utilizes industry-manufactured CVVHD machinery with both thermic and ultrafiltration control, with an effective anticoagulation protocol, and industry-produced bicarbonate dialysate. The use of industry machinery and solutions allows for consistent industrial quality assurance standards. This potentially may decrease the cost of therapy and minimize the risk of pharmacy errors that can occur with pharmacy-made dialysis solutions.
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PMID:Pediatric hemofiltration: Normocarb dialysate solution with citrate anticoagulation. 1195 49

To evaluate the clinical benefit of the prophylactic use of urate oxidase in children with non-Hodgkin's lymphoma (NHL), we analyzed the incidence and complications of tumor lysis syndrome (TLS) in children with B-cell acute lymphoblastic leukemia (B-ALL) or stage III/IV Burkitt's lymphoma and a lactate dehydrogenase (LDH) level > or =500 U/l before and after the introduction of a protocol amendment to use urate oxidase for the prophylaxis of TLS. Data from 1791 children with NHL enrolled in the two subsequent multicenter studies NHL-BFM 90 and 95 were evaluated. The presence of the side effects TLS, anuria, sepsis, and other complications during the first 2 weeks after admission were registered. Until March 1996, no urate oxidase was used (period 1). From November 1997 all children with B-ALL or stage III and IV B-NHL and LDH > or =500 U/l should receive urate oxidase prophylactically (period 3). In between (period 2), urate oxidase was given in a minority of hospitals therapeutically. Initial chemotherapy was identical. Altogether, 78 children (4.4%) developed a TLS. Patients with B-ALL had the highest risk to develop a TLS (26.4%) followed by B-ALL/Burkitt's lymphoma and a LDH > or =500 U/l (14.9%). In period 1, 16.1% and 9.2% of the latter children developed a TLS or anuria, respectively, compared to 12.3% and 6.2% in period 3 ( p=NS). The incidence of sepsis remained unchanged (5.0% vs 4.6%). In children with B-ALL the differences in the incidence of TLS and anuria between period 3 and period 1 were more pronounced, reaching significance for anuria (15.4% vs 3.8%, p=0.03). Our results suggest that patients with the highest risk to develop a TLS might benefit from the prophylactic use of urate oxidase.
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PMID:Incidence of tumor lysis syndrome in children with advanced stage Burkitt's lymphoma/leukemia before and after introduction of prophylactic use of urate oxidase. 1263 48

One of the most important achievements in the contemporary intensive care management is introduction of continuous renal replacement therapy (CRRT). The most common indications for CRRT are acute renal failure complicated with heart failure, volume overload, hypercatabolism, acute or chronic liver failure, and/or brain swelling. Less common indications include systemic inflammatory response (SIRS), sepsis, multiorgan failure (MOF), adult respiratory distress syndrome, crush syndrome, tumor lysis syndrome, lactacidosis, and chronic heart failure. Methods of CRRT could be used during or after open heart operations, heart, lung or/and liver transplantation in adults and children. Modern approach to treatment of acute renal failure introduces dialysis early in the course of disease in order to avoid complications on other organs. Sepsis, SIRS and septic shock are still major therapeutic problems in intensive care units with a mortality rate over 50%. Numerous uncontrolled and several controlled clinical studies have demonstrated that CRRT could remove inflammatory substances including cytokines, activated components of the complement, and derivatives of the arachidonic acid. Hemodynamic stability and gas exchange in the lungs were significantly improved. These is due not only to removal of inflammatory substances but also to other nonspecific hemodynamic effects (control of body temperature, fluid and metabolic balance). Besides the convection, cytokines could be removed from the plasma with adsorption on the membrane of dialyzer or hemofilter. Prophylactic use of CCRT in patients with normal renal function, without disturbances in fluid excretion and with normal hemodynamics is still controversial, while the possible benefit is not higher than the risks of invasive therapeutic method, and there is no evidence that prophylactic CCRT could prevent development of acute renal failure in these patients. However, current knowledge of MOF pathophysiology justifies the use of CRRT in patients with signs of heart failure, disturbances in metabolic and fluid homeostasis and sepsis, and in patients with the risk of developing acute respiratory failure or MOF, despite the mild impairment of renal function according to laboratory results.
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PMID:[Indications for continuous renal function replacement therapy]. 1287 69


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