Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied clinical effect of a combination therapy with cefozopran (CZOP) and tobramycin (TOB) for infections in 80 patients with hematologic diseases in 15 institutes. Combined doses with CZOP 2 g and TOB 60-90 mg twice a day had been given intravenously. Of the 80 patients, 61 patients (42 with acute leukemia, 10 with malignant lymphoma, 3 with aplastic anemia, 2 with chronic myeloid leukemia, 2 with multiple myeloma, and 2 with myelodysplastic syndrome) were evaluable. Those consisted of 6 patients with septicemia, 49 with suspected septicemia, 3 with pneumonia, and 3 with other infections. Clinical efficacy by the treatment was excellent in 24, good in 17, fair in 9, and poor in 11 patients, and the overall efficacy rate including excellent and good was 67.2%. Microbiologically, 5 of the 6 patients with septicemia (1 coagulase negative Staphylococcus, 2 S. pneumoniae, 1 S. oralis, and 1 E. coli) were responded. The efficacy rate in patients with severe granulocytopenia showing 100/microliter or lesser neutrophil counts during the drug administration was 57.1% (12/21). Side effects and abnormal changes of clinical laboratory findings were observed in 5 patients, and 16 patients, respectively, but most of them were mild. The findings above suggested that the combination therapy with CZOP and TOB is useful as an empiric therapy for severe infections in patients with hematologic diseases.
 ...
PMID:[Clinical effects of combination therapy with cefozopran and tobramycin for severe infections in patients with hematologic diseases]. 1022 Nov 80

Polyagglutination, although an uncommon phenomenon in transfusion medicine, is becoming increasingly recognized as a potential pitfall in correct ABO typing and can hinder the rapid allocation of accurately crossmatched blood products. Polyagglutination refers to erythrocytes which demonstrate agglutination with the majority of adult sera upon initial ABO crossmatch testing. Most types of polyagglutination involve alteration of red cell surface antigens through microbial enzymatic activity in patients with sepsis, and subsequent interaction of these newly exposed 'cryptantigens' with naturally occuring IgM antibody which is present in most adult sera. Less common variants include essential inborn variations in red cell development, and have been associated with myelodysplastic syndromes, congenital anemias, and various leukemias; it has been suggested that patients shown to possess these types of polyagglutination may benefit from increased hematologic surveillance. Recognition of polyagglutination in these settings is important to allow successful resolution of ABO typing discrepancies and permit efficient administration of appropriate blood products to these patients, who are often quite ill. The classification and method of laboratory recognition of polyagglutination is reviewed.
 ...
PMID:The classification, recognition and significance of polyagglutination in transfusion medicine. 1022 7

To compare the antileukemic efficacy of idarubicin and mitoxantrone in elderly patients with acute myeloid leukemia (AML) and to evaluate the feasibility of autologous transplantation using PBSC after consolidation in those with a good performance status, 160 patients (median age 69 years), with AML at diagnosis, 118 of them with de novo AML and 42 with AML secondary to myelodysplastic syndrome or toxic exposure (sAML), received induction treatment with idarubicin, 8 mg/m2/day or mitoxantrone, 7 mg/m2/day, on days 1, 3, and 5, both combined with VP-16, 100 mg/m2/day on days 1 to 3 and cytarabine (araC), 100 mg/m2/day, on days 1 to 7. G-CSF, 5 microg/kg/day, was administered after chemotherapy in patients aged more than 70 years. Patients in complete remission (CR) received one course of consolidation using the same schedule as for induction except the araC administration was shortened to 5 days. Some patients younger than 70 years were then scheduled for autologous stem cell harvest on days 5 to 7 of G-CSF, 5 microg/kg/day, initiated after hematopoietic recovery from consolidation. Autologous transplantation was performed following an additional chemotherapy conditioning. Ninety-five patients (59%) achieved CR, without significant difference between the idarubicin (56% CR) and mitoxantrone (63% CR) group. There was also no significant difference in CR rate between de novo AML (63%) and secondary AML (55%) (P = 0.12). Patients aged < 70 years had 67% CR, while patients aged > or = 70 years had 49% (P = 0.02). There was no significant difference in the duration of aplasia between the two arms. Median time to neutrophil recovery was 22 days in patients who received G-CSF following induction and 27 days in patients who did not (P = 0.006). Severe extrahematologic toxicities of induction did not differ between the two arms and included sepsis (39%), diarrhea (13%), hyperbilirubinemia (8%), hemorrhage (6%) and vomiting (6%). Overall, 14 patients (9%), died from toxicity of induction. First consolidation was administered in 74 patients of whom seven (9%) died from toxicity. Nineteen patients have received transplantation. Median time to recovery of neutrophils > 0.5 x 10(9)/l was 13 days and of platelets > 50 x 10(9)/l 43 days following consolidation. There were two toxic deaths. Median disease-free survival and survival from time of achieving CR of non transplanted patients are 6 and 7 months respectively without difference between the two arms. Fourteen transplanted patients relapsed at a median of 5 months post-transplant. We conclude that this regimen is well tolerated and has a good efficacy to induce CR, without a significant difference in efficacy and toxicity between idarubicin and mitoxantrone. Intensive postinduction, including transplantation, is feasible; however, this procedure did not seem to prevent early relapse in the majority of patients. Neither the high rate of CR nor consolidation nor transplant procedure in a selected group of patients did translate into improved DFS and/or survival.
 ...
PMID:Multicenter randomized phase II trial of idarubicin vs mitoxantrone, combined with VP-16 and cytarabine for induction/consolidation therapy, followed by a feasibility study of autologous peripheral blood stem cell transplantation in elderly patients with acute myeloid leukemia. 1036 Mar 70

Topotecan is a topoisomerase I inhibitor with significant activity in patients with myelodysplastic syndrome and chronic myelomonocytic leukemia. Pre-clinical data suggest a synergistic activity with DNA damaging agents such as cyclophosphamide, where topotecan might prevent the repair of cyclophosphamide-induced DNA damage. We thus designed a combination including cyclophosphamide 500 mg/m2 every 12 hours given on days 1 to 3; topotecan 1.25 mg/m2/day by continuous infusion on days 2 to 6, and cytosine arabinoside (ara-C) 2 g/m2 over 4 hours daily for 5 days on days 2 to 6 (CAT). Sixty six (63 evaluable) patients were treated. Fifty two patients had refractory (n=12) or relapsed (n=40) acute myelogenous leukemia (AML), and eleven had acute lymphocytic leukemia (ALL) (refractory n=3, relapsed n=8); their median age was 57 years (range, 18 to 79 years). Eleven patients (17%) achieved a complete remission (CR), and two patients (3%) had a hematologic improvement (HI; met all criteria for CR except for platelets < 100x10(9)/L), for an overall response rate of 20%. Responses occurred in 12 of 52 AML patients (23%), including 10 CR (19%) and 2 HI (4%), and in 1 of 11 patients with ALL (9%). Myelosuppression was universal; there were 23 episodes of pneumonia or sepsis and 18 episodes of fever of unknown origin complicating 74 courses of CAT. Non-hematologic toxicity was mostly gastrointestinal, including nausea, vomiting, diarrhea and mucositis, but was severe in only 8%. In summary, the CAT regimen is well tolerated and has significant anti-leukemia activity which warrants further investigation.
 ...
PMID:Cyclophosphamide, ara-C and topotecan (CAT) for patients with refractory or relapsed acute leukemia. 1078 92

A family is described in which three members, the propositus, his brother, and son, developed a myelodysplastic syndrome (MDS) at the ages of 52, 35, and 25, respectively. A fourth member, the paternal uncle of the propositus, was diagnosed with chronic lymphocytic leukemia. Two of the three affected Individuals had megaloblastoid marrows with recognizable bone marrow cytogenetic abnormalities and progressive, nonleukemic bone marrow failure. The propositus was unresponsive to G-CSF and eventually died of sepsis. The second affected family member died of bone marrow transplant complications. The third affected family member underwent bone marrow transplantation and is showing signs of graft survival despite minor complications. The affected members of this pedigree appear to represent a continuum in severity of disease and, therefore, pathogenesis. The pattern of inheritance and clinical progression of the disease suggest a genetic defect which may predispose individuals to the development of MDS.
 ...
PMID:Familial myelodysplastic syndrome with early age of onset. 1081 88

An attempt has been made in this article to summarize the state-of-the-art clinical experience with the use of anti-TNF therapies in four diseased states with special emphasis on myelodysplastic syndromes. Given the central role of TNF-alpha in initiating and perpetuating the chronic damage produced in the diseased organs by controlling a cascade of pro-inflammatory cytokines, as well as its acute role in sepsis, theoretically speaking, neutralization of this peptide was a natural therapeutic choice. Results of the initial clinical trials appear encouraging and sometimes dramatic in their efficacy. The mechanism of response however, is interesting in that even when TNF-alpha is directly targeted by a monoclonal antibody, the resulting benefits can frequently not be attributed to TNF suppression alone. Rather, it appears that a more general effect on the T-lymphocytes is also contributing to the responses being seen. This raises the new possibility of combining anti-cytokine and anti-T-cell strategies to treat at least the more chronic diseases such as Crohn's disease and myelodysplastic syndromes. Continued clinical trials testing these strategies are clearly warranted.
 ...
PMID:Anti-TNF therapies in rheumatoid arthritis, Crohn's disease, sepsis, and myelodysplastic syndromes. 1089 88

In this prospective, multicenter, phase 2 study, multiple myeloma (MM) patients with primary resistant disease or recurrent chemosensitive disease, in chemoresistant relapse, or in second or subsequent remission were treated with high-dose chemoradiotherapy followed by autologous peripheral blood stem cell (PBSC) rescue. PBSCs were collected using granulocyte-macrophage colony-stimulating factor (GM-CSF) 5 microg/kg per day subcutaneously for 3 days. Patients underwent high-dose chemoradiotherapy consisting of melphalan (140 mg/m2 x 1 day), cyclophosphamide (60 mg/kg per day x 2 days), methylprednisolone (2 g/d x 7 days), and total body radiation (150 cGy bid x 3 days) followed by peripheral blood stem cell reinfusion (> or = 1.2 x 10(9) mononucleated cells per kg) and GM-CSF support (5 microg/kg per day) and were evaluated for response, survival, and toxicity. Thirty-six patients, median age 53.4 years, completed the study. The mean pretransplantation cumulative melphalan dose was 464 +/- 72 mg. Excluding the 3 patients (8.3%) who failed to engraft, the median times to engraftment and platelet recovery were 10 days (range, 8-39 days) and 17 days (range, 7-67 days), respectively. Four patients (11.1%) died of complications related to the regimen (main causes of death, sepsis and acute respiratory distress syndrome) within the first 100 days. Twenty-two patients (61.1%) achieved complete response (CR), 8 (22.2%) partial response, and 2 (5.5%) no response. Two patients developed myelodysplastic syndrome after achieving CR. For all 36 patients, the probability of overall survival at 5 years was 27.3%. Median survival was 31 months (range, 0.3-81 months) in all patients and 42 months (range, 3.4-81 months) in those with CR. The probabilities of overall and disease-free survival at 5 years for the 22 patients who achieved CR were 43.6% and 15.7%, respectively. This high-dose chemotherapy regimen coupled with PBSC rescue is associated with a high CR rate and is capable of inducing long-term survival in a subset of heavily pretreated patients with primary resistant or recurrent MM.
 ...
PMID:Treatment of primary resistant or relapsed multiple myeloma with high-dose chemoradiotherapy, hematopoietic stem cell rescue, and granulocyte-macrophage colony-stimulating factor. 1097 14

We describe a 65-year old woman who developed a t(8;16)(p11;p13) positive acute myeloid leukemia (AML)-M4 without a prior myelodysplasia thirty-six months after a low-grade non-Hodgkin's lymphoma treated with alkylating agents (chlorambucil and cyclophosphamide) and fludarabine, a purine analog with a significant activity in lymphoproliferative disorders. The t(8;16)(p11;p13) is present in 0.4% of AML of M4-M5 cytotype. In the present case it was identified by conventional cytogenetics; involvement of the MOZ and CBP genes was demonstrated by fluorescence in situ hybridization, but not by reverse transcription polymerase chain reaction. The patient died of sepsis after the first course of induction chemotherapy. This is the first t(8;16) AML-M4 arising after fludarabine treatment of which the leukemogenic role in our case is very difficult to ascertain. Most t(8;16) t-AML cases had received anthracyclines with or without cyclophosphamide; none was ever administered chlorambucil. Our patient was never given anthracyclines and the cumulative doses of chlorambucil and cyclophosphamide employed were low.
 ...
PMID:Translocation (8;16) in a patient with acute myelomonocytic leukemia, occurring after treatment with fludarabine for a low-grade non-Hodgkin's lymphoma. 1102 2

Cefozopran (CZOP) and amikacin (AMK) were used concomitantly to treat infections complicated by hematological diseases. A total of 103 subjects were evaluated, and the all over efficacy rate was 69.9%. Acute leukemia was found in the largest number of patient, 57, followed by 29 cases of malignant lymphoma and 7 cases of myelodysplastic syndrome. By type of infection, patients having unknown origin were the largest in number, being 66, and the efficacy rate was 71.2%. The efficacy rates for sepsis, pneumonia and upper respiratory infection were 42.9% (7 cases), 71.4% (14 cases) and 90% (10 cases) respectively. The efficacy rates by neutrophil counts before administration of CZOP and AMK and at 1 week after administration were both 53.3% in the group of less than 100/microliter, both 60% in the group of less than 500/microliter. The efficacy rate by neutrophil counts at 1 week after administration was 58.6% in the group of less than 100/microliter. The efficacy rate was 75.4% in the group of granulocyte colony stimulating factor (G-CSF) concomitant usage, and 61.9% in the group of non-concomitant usage group. The efficacy rates by serum albumin levels before administration of CZOP and AMK and at 1 week after administration were both 92.9% in the group of over than 4 g/dl, both 50% in the group of less than 3 g/dl. Concomitant treatment with CZOP and AMK exhibited a high level of safety and efficacy rates in infections complicated by hematological diseases.
 ...
PMID:[Clinical effects of combination therapy with cefozopran and amikacin for infections in patients with hematological disorders]. 1133 82

Thrombocytopenia is generally of central origin in MDS, but can be due to peripheral platelet destruction in some cases. We studied platelet lifespan in 61 MDS cases with platelets < 70,000/mm3 and marrow blasts < 10%. Nine of them (15%) had a major platelet lifespan reduction (< 3.5 days), and were considered for splenectomy. Three of them were not splenectomized due to rapid death, patient refusal and older age plus liver predominance of platelet sequestration, respectively. The remaining six patients (two females and four males, median age 50 years, range 32 to 65) were splenectomized 3 to 21 months after diagnosis. Before splenectomy, five of them had RA and one had CMML. Platelets counts ranged from 5000 to 30,000/mm3 and did not durably respond to other treatments. Three of the patients has a relapse of platelet counts, concomitantly required platelet transfusion due to recurrent blending, whereas three had anemia (two required erythrocyte transfusion) and four had neutropenia. Three months after surgery, platelet counts ranged from 55,000 to 160,000/mm3 (> 100,000/mm3 in four cases), no patient required platelet or erythrocyte transfusion, but there was no effect on neutrophil counts. Three patients had a relapse of platelet counts, concomitant with progression to AML in two of them, whereas the third relapsing case achieved normal platelet counts with further danazol. One patient died with normal platelet counts 12 months after splenectomy (from sepsis, probably related to neutropenia rather than splenectomy). Two patients remained with normal platelet counts 10 and 52 months after surgery. Our findings suggest that the mechanism of thrombocytopenia should be studied more often in 'low risk' MDS (i.e. with low bone marrow blast counts) with thrombocytopenia, as about 15% of them appear to have peripheral platelet destruction. Some of those patients may benefit from splenectomy.
 ...
PMID:Role of splenectomy in the treatment of myelodysplastic syndromes with peripheral thrombocytopenia: a report on six cases. 1141 82


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>