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)

Medically refractory heart failure may be present in children with cardiomyopathy (CMP) or complex congenital heart disease (CHD). In adults, the surgical management of this condition is either heart transplantation or the Batista operation. From March 1995 to January 2000, a total of 6 children, aged from 1 to 16 years, with medically refractory heart failure associated with CMP or complex CHD underwent cardiac transplantation and one of them also had the Batista operation as a bridge to transplantation. One of the 6 patients died of intractable sepsis 17 days after the operation, but the other 5 were discharged with satisfactory hemodynamics. Immunosuppressive agents, including azathioprine, cyclosporin or FK-506, were given. One patient experienced moderate acute rejection, but it was controlled by FK-506, OKT-3 and solumedrol. However, another suffered from lymphoproliferative disease 8 months after transplant, but it was controlled by intravenous immunoglubulin, alpha-interferon and acyclovir. Cardiac function during serial follow-up (range, 1 month to 5 years) revealed normal systolic and diastolic function and none received any anticongestive medications. Almost all patients received an oversized donor heart. The left ventricle (LV) mass was remodeled, initially as an decrease and later as an increase. The patient who underwent the Batista operation was discharged 1 month after the operation with an increased LV ejection fraction (from 10% to 22%). She was successfully bridged to heart transplantation 7 months after the Batista operation. The results of cardiac transplantation in growing children are satisfactory and remain the mainstay of surgical treatment for medically refractory heart failure in these patients. However, with a shortage of donor hearts, the Batista operation may be adopted as a bridge to heart transplant with a fair response.
 ...
PMID:Heart transplantation and the Batista operation for children with refractory heart failure. 1131 25

A 35-year-old man with chronic myeloid leukemia (CML) in blastic crisis (BC) received an allogeneic bone marrow transplant from an unrelated donor in October 1998 after three cycles of chemotherapy. BC relapse developed on day 349 after transplantation. After one cycle of chemotherapy and treatment with interferon, the patient received donor lymphocyte infusion (DLI), and this resulted in a complete cytogenetic response 21 days later. Grade III acute graft-versus-host disease developed on day 25 after DLI, but this was resolved after administration of prednisolone. Disease relapse occurred at extramedullary sites on day 162 after DLI, and the patient died of sepsis after receiving chemotherapy. This case illustrates that unrelated DLI can induce remission successfully in patients with relapse of CML in BC through a graft-versus-leukemia effect.
 ...
PMID:[Complete cytogenetic response obtained with unrelated donor lymphocyte infusion for relapse of chronic myeloid leukemia in blastic crisis after allogeneic bone marrow transplantation]. 1134 83

There is a wealth of clinical and experimental evidence indicating the interaction of cytomegalovirus (CMV) infection and rejection in cardiac and other solid organ allografts. A plausible explanation for this association comes from data showing that therapy with biologicals, sepsis, and rejection, all lead to the release of TNF-alpha which, upon binding to its receptor, activates NF-kB. TNF-alpha is also able to stimulate the activity of the CMV-IE enhancer/promoter region. CMV infection of several cell lines leads to NF-kB activation. NF-kB binding sites are present in regulatory regions of various cellular and viral genes, including the IE enhancer region of CMV. In a reciprocal situation, CMV infection, most likely via gamma-interferon, leads to upregulation of MHC antigens in the transplant and, thereby, to increased transplant immunogenicity. Thus, a vicious circle is induced. We have investigated in detail the pathobiology of CMV and allograft vasculopathy (chronic rejection) in experimental animals, using aortic and cardiac allografts as well as a trachea model. The results may be summarized as follows: Infection of the recipient with rat CMV results in an early inflammatory response in the aortic and cardiac allograft vascular adventitia and intima (endothelialitis) and in the airway wall of tracheal allografts. This early inflammatory response leads to enhanced intimal thickness in aortic and cardiac allografts and enhanced luminal occlusion of tracheal allografts. Timewise, this coincides with early activation of intragraft inflammatory leukocytes and increased mRNA of various growth factors and cytokines. When the recipients receive gancyclovir, the enhanced intimal response in aortic and cardiac allografts and luminal occlusion in tracheal allografts is entirely abolished. Gancyclovir treatment dramatically reduces the inflammatory response in the allograft, and thereby growth factor synthesis in response to injury. However, gancyclovir does not prevent the expression of IE antigen of CMV, suggested to inactivate tumor suppressor protein p53 predisposing smooth muscle cells to increased growth. Taken together, the effect of CMV infection on cardiac allograft dysfunction is bidirectional and biphasic. The bidirectional nature emerges from the observations that acute CMV infection may accelerate acute rejection, and, on the other hand, acute alloimmune response-associated cytokine response may activate latent CMV infection. The biphasic effect of CMV on allograft dysfunction refers to its early and late detrimental effects, i.e. during the time of acute and chronic rejection. These two effects of CMV on allograft dysfunction emphasize the need for precise diagnosis of CMV infection in transplant recipients and pre-emptive or prophylactic anti-viral therapy. The benefits of this strategy may not be evident during the early post-transplant period, but 5-10 years after transplantation they manifest as better graft survival.
 ...
PMID:Cytomegalovirus infection and cardiac allograft vasculopathy. 1142 79

To determine the relative contribution of lipopolysaccharide (LPS) and non-LPS components of Neisseria meningitidis to the pathogenesis of meningococcal sepsis, this study quantitatively compared cytokine induction by isolated LPS, wild-type serogroup B meningococci (strain H44/76), and LPS-deficient mutant meningococci (strain H44/76[pLAK33]). Stimulation of human peripheral-blood mononuclear cells with wild-type and LPS-deficient meningococci showed that non-LPS components of meningococci are responsible for a substantial part of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta production and virtually all interferon (IFN)-gamma production. Based on tricine sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of LPS in proteinase K-treated lysates of N. meningitidis H44/76, a quantitative comparison was made between the cytokine-inducing capacity of isolated and purified LPS and LPS-containing meningococci. At concentrations of >10(7) bacteria/mL, intact bacteria were more potent cytokine inductors than equivalent amounts of isolated LPS, and cytokine induction by non-LPS components was additive to that by LPS. Experiments with mice showed that non-LPS components of meningococci were able to induce cytokine production and mortality. The principal conclusion is that non-LPS parts of N. meningitidis may play a role in the pathogenesis of meningococcal sepsis by inducing substantial TNF-alpha, IL-1beta, and IFN-gamma production.
 ...
PMID:Contributions of Neisseria meningitidis LPS and non-LPS to proinflammatory cytokine response. 1149 21

Gram-negative sepsis is related to the activation of interconnected inflammatory cascades in response to bacteria and their products. Recent work showed that flagellin, the monomeric subunit of bacterial flagella, triggers innate immune responses mediated by Toll-like receptor 5. Here, we compared the effects of Salmonella enterica serovar Enteritidis lipopolysaccharide (LPS) and recombinant Salmonella enterica serovar Muenchen flagellin administered intravenously (100 microg) to mice. Flagellin and LPS both elicited a prototypical systemic inflammatory response, with increased levels of tumor necrosis factor alpha, gamma interferon, interleukin 6 and 10, and nitrate in plasma. Flagellin induced a widespread oxidative stress, evidenced by an increase in malondialdehyde and a decrease in reduced glutathione in most organs, as well as liver (increased plasma aminotransferases), but not renal, injury. Alternatively, LPS resulted in a less severe oxidative stress and triggered renal, but not liver, damage. Sequestration of polymorphonuclear neutrophils (increased myeloperoxidase activity) in the lungs was observed with both toxins, while only LPS recruited neutrophils in the gut. In additional experiments, the simultaneous administration of small doses of LPS and flagellin (10 microg) induced a synergistic enhancement of the production of proinflammatory cytokines. Our data support a novel concept implicating flagellin as a mediator of systemic inflammation, oxidant stress, and organ damage induced by gram-negative bacteria.
 ...
PMID:Comparison of inflammation, organ damage, and oxidant stress induced by Salmonella enterica serovar Muenchen flagellin and serovar Enteritidis lipopolysaccharide. 1174 82

Host defense mechanisms preventing bacterial invasion are particularly important in the gastrointestinal tract, since most gram-negative infections originate from there. Intraepithelial lymphocytes (IEL) seem to play an important role in this immune surveillance of the intestine, although their function in sepsis is not fully understood. To evaluate the characteristics of IEL in sepsis, C57BL/6 mice received a non-lethal dose of LPS and IEL were harvested at various time points thereafter. Although IEL displayed no phenotypic changes after endotoxemia, they displayed enhanced cytolytic activity and increased proliferation after LPS injection In addition, IEL from septic mice showed enhanced gamma interferon (IFN-gamma) production after LPS administration. The production of IFN-gamma may have induced the increased intestinal NOS-2 mRNA expression which was observed after endotoxemia. In conclusion, endotoxemia leads to functional activation of IEL without phenotypic changes. The activation of IEL and the subsequently increased NOS-2 expression may be important mechanisms in maintaining the mucosal barrier after sublethal LPS challenge.
 ...
PMID:Upregulation of intraepithelial lymphocyte (IEL) function in the small intestinal mucosa in sepsis. 1177 44

Invasive fungal infections (IFI) parallel the explosive increase in the immunocompromized patient population, and are characterized by diagnostic difficulties and extreme mortality. Candidemia in a tertiary referral hospital in the Middle East confirms the current epidemiologic shift in this common blood stream pathogen towards non-malignancy cases (38%) and antifungal prophylaxis failure (20%), high presentation sepsis scores and attributable mortality (32%). Invasive aspergillosis (IA) is also associated with high mortality. Use of non-invasive computerized tomographic (CT) radiologic scanning linked to early administration of high dose liposomal amphotericin B (LAB) is associated with a reduced mortality of 9.5% compared to historical experience of 28%.Life threatening invasive aspergillosis also occurs in patients who are less obviously immunocompromized. Investigations may reveal subtle immune deficits which could place the patient at some risk for an invasive mycosis. Antifungal treatment used in combination with progenitor cell growth factors and gamma-interferon has proved successful in such situations of progressive fungal disease unresponsive to antifungal therapy alone. Pharmacologic remodeling of existing compounds by lipidisation reduces both the toxicity denominator and the efficacy numerator of the therapeutic index when compared to the parent drug. A comparative dose study of liposomal amphotericin B in aspergillosis has demonstrated equi-efficacy, generated debate over the ability of the controlled clinical trial to be capable of assessing antifungal efficacy, and illustrated that recovery from an invasive fungal infection may require maximum tolerated doses and immunomanipulation. Several new antifungal strategies are under clinical investigation. These include reformulating existing antifungals, exploitation of the growing knowledge of virulence factors to synthesize antagonists, immune reconstitution and immunoprotection. An interim analysis of an ongoing placebo controlled study of recombinant interleukin-11 to assess its efficacy in reducing sepsis in leukemia patients through prevention of chemotherapy induced gut epithelial cell apoptosis, has demonstrated a difference in the two study arms in sepsis rates and preservation of gastrointestinal epithelial cell integrity. The unique and special challenges presented by the dynamic epidemiologics of invasive fungal infections are demanding and attracting considerable responses, in the fields of diagnosis and therapeutics. Current strategies need considerable improvement, yet ongoing collaborative efforts will have a positive impact on our understanding of the fungus-host interaction and ultimately our ability to offer better care for our patients with invasive mycoses.
 ...
PMID:Invasive fungal infections: evolving challenges for diagnosis and therapeutics. 1200 73

Virus infections induce changes in the expression of host cell genes. A global knowledge of these modifications should help to better understand the virus/host cell interactions. To obtain a more comprehensive view of the rainbow trout response to a viral infection, we used the subtractive suppressive hybridization methodology in the viral hemorrhagic septicemia model of infection. We infected rainbow trout leukocytes with viral hemorrhagic septicemia virus (VHSV), and total RNA from infected and mock-infected cells was compared at 40 h postinfection. Twenty-four virus-induced genes were ultimately retrieved from the subtracted cDNA library, and their differential expression was further confirmed by semiquantitative reverse transcription-PCR and Northern blot analysis. Among these sequences, three were already described as VHSV-induced genes. Eight sequences with known homologs were extended to full-length cDNA using 5' and 3' rapid amplification of cDNA ends, and they were subsequently divided into three functional subsets. Four genes were homologous to mammalian interferon responsive genes, three were similar to chemo-attractant molecules (CXC chemokine, galectin), and two had nucleic acid binding domains. All of the virus-induced genes were also induced by rainbow trout interferon, indicating that the interferon pathway is the predominant component of the anti-VHSV response. They were also expressed in vivo in experimentally infected fish, indicating their biological relevance in natural infection.
 ...
PMID:Survey of transcript expression in rainbow trout leukocytes reveals a major contribution of interferon-responsive genes in the early response to a rhabdovirus infection. 1213 9

Necrotizing fasciitis is a soft tissue infection with a lethality ranging up to 80%. Infection causes the activation of interleukin, tumor necrosis factor alpha, and gamma-interferon through a triggering mechanism. This results in a capillary thrombosis with necrosis of the fascia, cutis, and subcutis. The patient's history often reveals a triggering event in the form of a recent minimal trauma or operative procedure. In a fulminant necrotizing fasciitis, the development of sepsis with consecutive multiple-organ failure mainly determines the outcome of the disease. Diagnosis is made initially upon clinical findings with a rapid progression of the disease and confirmed later by histologic and microbiologic findings. Radical surgical debridement within the first 24 h with postoperative treatment in an intensive care unit represents the cornerstone of therapy. Between January 1992 and March 2001, we treated 15 patients with necrotizing fasciitis. Lethality was 33%. There was a significant correlation between risk factors (present in 86% of the patients) and morbidity. Diagnosis and therapy should be performed by an experienced surgeon. In this contribution, we discuss the most important criteria that lead to the diagnosis and the therapeutic consequences.
 ...
PMID:[Diagnosis and therapy of necrotizing fasciitis]. 1214 26

The objective of this study was to investigate the efficacy of our treatment regimen in metastatic melanoma. Thirty patients entered the study after undergoing a thorough metastatic workup. Treatment protocol included carmustine (BCNU) (150 mg/m(2) IV, day 1) every 6 weeks, dacarbazine (DTIC) (220 mg/m(2) IV, days 1-3), and cisplatin (25 mg/m(2) IV, days 1-3) every 3 weeks, interferon A-2B (6 x 10(6) U/m daily s.c. on days 4-8 and 16-20) and tamoxifen 20 mg/day for 6 weeks. Among 29 evaluable patients, overall response was seen in 15 (52%) and complete response in 5 (17%) patients. Median duration of partial response was 4 months (range, 1-12 months); of complete response was 8 months (range, 2-14 months). Complete response continues in two patients with lung metastases. Median survival time was 8.7 months. Side effects were tolerable. Four (13%) patients developed neutropenic fever, and platelet transfusions were required in five (17%) patients. One patient died of neutropenic sepsis. Thrombocytopenia caused prolongation of the median interval between the first and second courses, and drug doses were reduced in the second course in 8 of 26 (31%) patients. Our chemoimmunohormonal regimen is efficient in metastatic malignant melanoma and can induce durable remission. Severe thrombocytopenia leads to a reduction of carmustine dose in a new protocol.
 ...
PMID:Chemoimmunohormonal therapy with carmustine, dacarbazine, cisplatin, tamoxifen, and interferon for metastatic melanoma: a prospective phase II study. 1239 84


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