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)

Adult acute myeloid leukaemia (AML) is uncommon, with an age-standardised incidence of approximately 3 per 100,000. Patients present (median age, > 60 years) with evidence of bone marrow failure, anaemia, leukopenia or thrombocytopenia and their sequelae, or AML is detected incidentally by a full blood count. Treatment for AML aims to eliminate leukaemia from bone marrow with intensive chemotherapy: age (over or under 60 years) and performance status determines whether standard or high-dose chemotherapy can be used, but fewer than half the patients with AML are under 60 years. Supportive therapy during initial induction chemotherapy is needed to control neutropenic sepsis and thrombocytopenic bleeding, and to ameliorate the side effects of chemotherapy. Standard induction chemotherapy produces complete remission in 56%-74% of patients; 20% are long term survivors; 10%-15% of patients die in the induction period. Allogeneic haemopoietic stem cell transplantation is recommended in patients under 50 years with an HLA- compatible sibling, with the best outcomes achieved in patients transplanted in first complete remission. It can also provide long term survival in patients who fail to achieve remission after induction therapy. The outcome of AML has improved, particularly for younger patients, but treatment outcomes for older patients and those with secondary leukaemia are still unsatisfactory. The mean overall survival of patients in randomised studies treated with standard therapy is still only 9-15 months.
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PMID:Adult acute myeloid leukaemia: update on treatment. 1002 73

We explored the combination of busulfan/cyclophosphamide/etoposide as conditioning regimen prior to bone marrow transplantation in 31 patients with acute myeloid leukemia (AML) in first complete remission. The preparative regimen consisted of 16 mg/kg busulfan, 30-60 mg/kg VP-16, and 120 mg/kg cyclophosphamide. With a median follow-up of 30.5 months (range, 5-60 months), 25 patients are alive in continuous complete remission. Estimated disease-free survival at 5 years is 80.5%. Death was due to transplant-related toxicity (graft-versus-host disease and cytomegalovirus infection, graft-versus-host disease and pneumonia, sepsis and mucositis, respectively). None of the patients have relapsed. As demonstrated by the results of this analysis, the conditioning regimen busulfan/cyclophosphamide/etoposide is effective and well tolerated in patients with AML in first complete remission. Main nonhematological toxicities were mucositis and hepatotoxicity. The low mortality and relapse rate appears to justify allogeneic bone marrow transplantation for patients with AML in first complete remission who have an HLA-identical donor. Whether this regimen offers a substantial improvement in disease-free and overall survival over presently used regimens warrants further investigation.
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PMID:High dose chemotherapy with busulfan, cyclophosphamide, and etoposide as conditioning regimen for allogeneic bone marrow transplantation for patients with acute myeloid leukemia in first complete remission. 1006 72

Encapsulated bacteria infections (EBI) can cause severe complications after BMT, usually occurring in patients with chronic GVHD (cGVHD) and attributed to functional hyposplenism. Using ultrasound (US) scan, we measured spleen size in 22 patients transplanted from HLA identical siblings, with or without cGVHD. No patient had received TBI, spleen irradiation or penicillin prophylaxis. Results were correlated with occurrence of EBI during a mean follow-up of 55 months (range 7-93). In the group without cGVHD, the difference between pre- and post-BMT spleen longitudinal diameters was not significant, and no patient developed EBI. In the cGVHD group, post-BMT spleen longitudinal diameters were significantly smaller than those pre-BMT (9.1+/-1.6 vs. 12.3+/-2.2; P = 0.0005). Out of four patients with cGVHD who showed a major spleen size reduction, two developed a severe infection (an overwhelming sepsis and a pneumococcal meningitis). In our small series, we found a borderline relationship between spleen size reduction and duration of cGVHD (P = 0.06), as well as an increased risk of life-threatening infection in patients with extensive cGVHD and hyposplenism as detected by US scan. We conclude that US scan may be useful to detect spleen size reduction following allogeneic BMT and that penicillin prophylaxis is to be strongly recommended in patients with extensive cGVHD and spleen size reduction, even in those who have not received total body or spleen irradiation.
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PMID:Spleen sizing by ultrasound scan and risk of pneumococcal infection in patients with chronic GVHD: preliminary observations. 1045 46

In the absence of a donor alternative a stem cell transplantation consisting of two cord blood components originating from the haploidentical brother was performed in a 2-year-old girl with c-ALL, early CNS relapse and 7% of blast cells in the BM 14 days before transplantation. Because of various ongoing infectious complications at that time, 1/8 of the immunogenetically acceptable sibling cord blood was ex vivo expanded 10 days before the transplantation date. The total CB consisting of 1.17 x 10(9) NC was cryopreserved in four separate bags. The one containing 1/8 of the total CB with 1.4 x 10(8) NC CliniMACS selected CD34+ cells was expanded in the presence of 100 ng/ml G-CSF, 100 ng/ml TPO and 100 ng/ml flt3-L in 10% autologous CB plasma and X-VIVO 10 medium at day -10 before transplantation. This expanded cell population was sterile and consisted of about 60% granulocytic cells (CD13+, CD15+), about 30% myelomonocytic cells (CD14, HLA-DR+), 5.2% megakaryocytes (CD61+) and 1.2% CD34+ cells. The proportion of T (CD3+), NK cells (CD56+) as well as dendritic cells (CD83+) was below 0.2%. The unseparated CB infused at day 0 and +1 consisted of a total of thawed 4.4 x 10(7) NC/kg BW, 5.8 x 10(4) CFU-GM/kg BW, 1.54 x 10(5) CD34+cells/kg BW and 7. 73 x 10(2) LTC-IC/kg BW. In addition, the 1 x 10(7) NC/kg BW ex vivo expanded cells representing 1.9 x 10(4) CFU-GM/kg BW, 1.13 x 10(5) CD34 cells/kg BW and 4.37 x 10(2) LTC-IC/kg BW, were infused at day +1. At day +2 after transplantation the patient revealed a focal pneumonia on X-ray with generalized sepsis and became catecholamine dependent. From day +4 the patient received 280 microg/m2 G-CSF. At day +5 she developed an erythroderma, which could not be identified as acute GVHD by biopsy. Early engraftment with leukocyte counts at days 8 and 14 were 350 and 700/microl, ANC 310 and 410/microl, respectively. Donor cells determined by chimerism analysis were 97% and 98% in the periphery at this early time. Most importantly, the pneumonia as well as the septicemia subsided within a few days. Notably, as well is the clearly shortened aplastic phase observed after this simultaneous CB cell component transplantation. The patients T cell and NK cell reconstitution could be detected at day +37 with 330 CD3+ cells/microl and 40 CD56+ cells/microl, respectively. The time to reach an absolute platelet count of 20 000 (50 000)/microl was 75 (103) days. The disease-free survival now exceeds 1 year in complete remission without chronic GVHD or any other health problems. These data show that the applicability of ex vivo expanded committed progenitors and LTC-IC, even in high risk leukemia at the time of transplantation, is feasible and can provide sufficient myeloid progenitors resulting in rapid engraftment able to clear bacterial pneumonia and sepsis. In addition, accelerated hematopoietic reconstitution apparently served as a well functioning platform for definitive graft-versus-leukemia activity. This transplantation of defined ex vivo generated components presents a feasible and generally applicable approach and may open a promising new avenue for cell therapy in malignant diseases.
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PMID:Simultaneous cord blood transplantation of ex vivo expanded together with non-expanded cells for high risk leukemia. 1046 29

Reactive arthritis is one of the spondyloarthropathy family of clinical syndromes. The clinical features are those shared by other members of the spondyloarthritis family, though it is distinguished by a clear relationship with a precipitating infection. Susceptibility to reactive arthritis is closely linked with the class 1 HLA allele B27; it is likely that all sub-types pre-dispose to this condition. The link between HLA B27 and infection is mirrored by the development of arthritis in HLA B27-transgenic rats. In this model, arthritis does not develop in animals maintained in a germ-free environment. Infections of the gastrointestinal, genitourinary and respiratory tract appear to provoke reactive arthritis and a wide range of pathogens has now been implicated. Although mechanistic parallels may exist, reactive arthritis is distinguished from Lyme disease, rheumatic fever and Whipple's disease by virtue of the distinct clinical features and the link with HLA B27. As in these conditions both antigens and DNA of several micro-organisms have been detected in joint material from patients with reactive arthritis. The role of such disseminated microbial elements in the provocation or maintenance of arthritis remains unclear. HLA B27-restricted T-cell responses to microbial antigens have been demonstrated and these may be important in disease pathogenesis. The importance of dissemination of bacteria from sites of mucosal infection and their deposition in joints has yet to be fully understood. The role of antibiotic therapy in the treatment of reactive arthritis is being explored; in some circumstances, both the anti-inflammatory and anti-microbial effects of certain antibiotics appear to be valuable. The term reactive arthritis should be seen as a transitory one, reflecting a concept which may itself be on the verge of replacement, as our understanding of the condition develops. Nevertheless it appropriately describes arthritis that is associated with demonstrable infection at a distant site without traditional evidence of sepsis at the affected joint(s). Although several forms of disease could be described as "reactive", particularly acute rheumatic fever, post-meningococcal septicaemia arthritis and Lyme disease, in clinical practice the term is restricted to an acute spondyloarthritis, usually, but not exclusively, linked to acute genitourinary or gastrointestinal infection. A proportion of patients fulfil criteria for Reiter's Syndrome [1].
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PMID:Reactive arthritis. 1059 44

The object of this study was to evaluate the treatment outcome in children with acute lymphoblastic leukemia (ALL) in Chennai. The problems inherent in a developing country which affect outcome are analyzed. The importance of prognostic factors especially immunotyping is assessed. The period of study was from June 1991 to December 1995. A total of 135 children were studied. Pre B CALLA positive (CD10, CD19, HLA, DR) was the dominant immunotype in 75 children (69 per cent). T-cell ALL was seen in 15 (14 per cent), biphenotype in three (2 per cent), and B in one (0.9 per cent). Seventy children (53 per cent) were treated with a high risk protocol, 25 (17 per cent) received an intermediate risk, and 40 patients (30 per cent) received a standard risk protocol. Analyzing the outcome in 135 children, 34 (27 per cent) had event free survival (EFS) at the time of analysis; of these 41 per cent had EFS after 2 years of therapy, 31 per cent after 3 years and 18.7 per cent after 4 years (i.e. 1 year after stopping 3 years of therapy). Fifty-seven children (41 per cent) dropped out; 25 (18 per cent) died due to sepsis. Treatment obstacles included delay in diagnosis, poor health education and facilities, poor supportive care, and socio-economic problems.
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PMID:Survival of childhood acute lymphoblastic leukemia: experience in Chennai. 1066 9

The systemic inflammatory response (SIRS) results from various types of injuries such as severe infection, trauma, ischemia-reperfusion and major surgery including cardiac surgery with cardio-pulmonary bypass. This response involves immune cell activation and a complex network of proinflammatory cytokines, which may induce multiple organ failure when uncontrolled. The monocyte plays a central role in the response to infection with the release of TNF, IL-1, and IL-12. In addition, monocytes present antigens to T lymphocytes. An optimal antigen presentation requires the expression of MHC class II HLA-DR on monocytes surface and of co-stimulatory molecules such as CD54 on monocytes and LFA-1 on lymphocytes. It has become increasingly apparent that the pro-inflammatory response is balanced by concomitant anti-inflammatory mechanisms that results in monocyte deactivation, characterized by a decrease in HLA-DR expression and the release of anti-inflammatory cytokines such as IL-10. This counterregulatory response, if prolonged or predominant, may predispose the patient to a higher risk of infection. Further studies need to be conducted to precise: 1) the intensity of depression of the surface molecule expression assessing monocyte function, such as HLA DR and CD54; 2) the level of IL-10 and IL-12 release in patients with severe sepsis; 3) the immunomodulating effects of frequently used treatments in these patients with severe sepsis and in surgical patients; 4) the time course of recovery; 5) if the monitoring of HLA-DR, CD54, IL-10 and IL-12 will better predict the clinical outcome than clinical parameters.
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PMID:Assessment of immunological status in the critically ill. 1096 15

Acquired, idiosyncratic aplastic anaemia (AA) is a rare but potentially fatal haematological disorder. Severe AA constitutes an acute medical emergency, and supportive therapy is needed to prevent overwhelming sepsis or a life threatening haemorrhage. Specific therapy for the disease includes the choice between allogeneic stem cell transplantation (SCT) from an HLA-identical sibling or immunosuppressive therapy with anti-thymocyte globulin (ATG) and cyclosporin A (CSA). Long-term cure rates of 75-90% are now achieved following HLA (human leukocyte antigen) identical sibling bone marrow transplant. The use of donors other than HLA-id siblings for transplantation in AA remains experimental. Transplantation offers the patient a chance of cure, whilst treatment with immunosuppressive therapy carries a long-term risk of relapse and clonal transformation. The haemopoietic growth factors, apart from granulocyte colony stimulating factor (G-CSF), have been shown to be potentially toxic when given to patients with AA. A short course of G-CSF may be useful to help treat severe infection, but its longer-term use with ATG and CSA remains controversial. Results from immunosuppressive treatment continue to improve with time, as a result of the additional use of CSA with ATG, the use of repeat courses of ATG for non-responders and improvements in the supportive care of patients.
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PMID:Aplastic anaemia: management. 1098 51

A 56-year-old dairy farmer received a fully HLA matched unrelated donor marrow transplant for high risk CML in chronic phase. His early post-transplant course was complicated by a series of massive intracerebral bleeds and by sepsis related to a malignant otitis externa. The microbial pathogen isolated from ear swabs was found to be Absidia corymbifera, but CT scan at the time showed no intracerebral extension. Despite neutrophil engraftment and aggressive antifungal management he succumbed. Autopsy revealed invasion of Absidia into the brain from the ear. We speculate that colonisation by Absidia resulted from occupational exposure.
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PMID:Fatal invasive cerebral Absidia corymbifera infection following bone marrow transplantation. 1104 74

Acute rejection of hepatic allografts does not show consistent association with the number of mismatches of HLA classes I and II. Therefore, we investigated the relation between specific donor or recipient HLA antigens and the occurrence of acute rejection. HLA typing of 35 liver transplant recipients and donors was performed by serological standard technique, with confirmation and subtyping by polymerase chain reaction with sequence-specific primers. HLA class I antigens were not associated with the occurrence of acute rejection. The graft was positive for HLA-DR13 in 8 of 13 transplant recipients (62%) with acute rejection, but only 4 of 22 recipients (18%; P =.024; P(Bonferroni-corrected) =.33, not significant) without rejection. The graft was positive for DRB1*1301 in 7 of 13 recipients (54%) with acute rejection, but only 1 of 22 recipients (5%) without rejection (P =.002; P(Bonferroni-corrected )=.028). This patient had experienced long-lasting bacterial sepsis, which markedly reduced the risk for acute rejection. We speculate that the expression of donor DRB1*1301 (if mismatched) may increase the risk for acute hepatic allograft rejection.
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PMID:Acute rejection of hepatic allografts from HLA-DR13 (Allele DRB1(*)1301)-positive donors. 1108 59


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