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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus (HIV) infection and infective endocarditis are serious complications of injection drug use. To determine whether HIV infection may increase the risk of endocarditis beyond that associated with drug injection, we performed a nested case-control study among injecting drug users taking part in an ongoing cohort. We identified 26 participants with infective endocarditis between cohort enrollment (in 1988-1989) and June 1992, through reviews of medical records and death certificates. We matched each endocarditis case with up to five controls (N = 120) on enrollment date, race/ethnicity, and follow-up time. Data were taken from baseline and from the one follow-up visit: the last visit before the endocarditis occurred for cases and the closest visit (+/- 3 months) for controls. We used conditional logistic regression to quantify the association between HIV serostatus at follow-up and subsequent endocarditis, after adjusting for a history of endocarditis or sepsis before enrollment, injection duration, current injection frequency, and a recent history of abscess at injection sites. Among current injectors at follow-up, the adjusted odds ratio (OR) of developing endocarditis for HIV-seropositive subjects with > or = 350 CD4 cells per microliter, compared with HIV-seronegative subjects, was 2.31 [95% confidence interval (CI) = 0.61-8.78]; the corresponding OR for HIV-seropositive subjects with < 350 CD4 cells per microliter was 8.31 (95% CI = 1.23-56.37). These data indicate that HIV-related immunodeficiency may independently increase the risk of infective endocarditis among injecting drug users.
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PMID:Human immunodeficiency virus infection and infective endocarditis among injecting drug users. 889 79

Inflammatory cells, in particular monocytes/macrophages, release pro-inflammatory mediators in response to several infectious and non-infectious stimuli. The excessive release of these mediators, resulting in the development of whole body inflammation, may play an important role in the pathogenesis of sepsis and septic shock. TNF-alpha, acting synergistically with cytokines such as IL-1, GM-CSF and IFN-gamma, is the key mediator in the induction process of septic shock, as shown in several experimental models. Based on this concept and on the encouraging results obtained in several experimental models, a number of clinical sepsis trials targeting the production or action of TNF-alpha or IL-1 have been performed in recent years. Unfortunately, these trials have failed to demonstrate a therapeutic benefit. One reason for this may be the lack of exact immunologic analyses during the course of septic disease. Recently, we demonstrated that there is a biphasic immunologic response in sepsis: an initial hyperinflammatory phase is followed by a hypo-inflammatory one. The latter is associated with immunodeficiency which is characterized by monocytic deactivation, which we have called "immunoparalysis". While anti-inflammatory therapy (e.g. anti-TNF antibodies, IL-1 receptor antagonist, IL-10) makes sense during the initial hyperinflammatory phase, immune stimulation by removing inhibitory factors (plasmapheresis) or the administration of monocyte activating cytokines (IFN-gamma, GM-CSF) may be more useful during "immunoparalysis".
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PMID:Monocyte deactivation--rationale for a new therapeutic strategy in sepsis. 892 92

X-linked agammaglobulinemia (XLA) is usually considered a disorder of B cell development; however, the gene that is defective in XLA encodes a cytoplasmic tyrosine kinase called Btk, that is expressed throughout myeloid as well as B cell differentiation. A review of medical records of patients in whom mutations in Btk had been identified indicated that 13 of 50 patients (26%) had experienced episodes of profound neutropenia. In 12 of the 13 patients, neutropenia was part of the acute illness that precipitated an evaluation for immunodeficiency. These boys were more likely to be less than a year of age at the time of diagnosis and they were less likely to have a family history of immunodeficiency. Neutropenia was associated with staphylococcal or pseudomonas sepsis in 6 of the patients. The duration of neutropenia was variable but was often more than 1 week. Neutropenia was not seen in any patient with XLA receiving intravenous gammaglobulin. Although neutropenia was not associated with any specific mutation in Btk, most of the alterations in this gene in the patients with XLA and neutropenia resulted in the absence of Btk protein or in amino acid substitutions in sites thought to be critical to Btk function. Btk may not be required for neutrophil production under normal circumstances; however, it may play a role in the response to stress.
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PMID:Neutropenia in X-linked agammaglobulinemia. 893 4

High serum levels of procalcitonin (PCT) are observed in patients with sepsis or severe infection. In a prospective study of 122 hospitalised adult medical patients with sepsis, serum PCT was determined on admission and for 9 days thereafter. Patients with no alteration in their immune system showed high PCT values up to day 5, decreasing to normal levels by day 9. Patients with sepsis and immunodeficiency had high values on days 0 to 2, similar to the first group, but showed significantly lower levels on the following 3 days. PCT concentrations fell to base line levels on days 6 to 9 of the sepsis episode in both groups. The observed difference was not significantly related to the kind of causative microorganism or a culture negative sepsis. Leukopenia seemed to go together with lower PCT values after day 2 of the episode, but this could not be proven statistically.
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PMID:Procalcitonin in patients with and without immunosuppression and sepsis. 900 90

Distinct cytokine profiles are clearly associated with and relate to the severity of several types of infections. Cytokine networks are apparent with selected human infectious diseases, such as mycobacterial infections (leprosy, tuberculosis), the parasitic infection leishmaniasis, human immunodeficiency virus (HIV) infection, and gram-negative sepsis. Cytokine profiles are determined to some extent by two functional subsets of T lymphocytes, Th1 and Th2. The Th1 cytokines (interferon gamma, interleukin-2 [IL-2], IL-12) enhance cell-mediated immunity, inhibit humoral immunity, and result in protective effect for pathogens that are removed primarily through cell-mediated immunity (Mycobacterium tuberculosis, Mycobacterium leprae, Leishmania). The Th2 cytokines (IL-4, IL-5, IL-10, IL-13) enhance humoral immunity and inhibit cell-mediated immunity, and result in protective effect for pathogens removed primarily through humoral mechanisms. Progression of HIV infection is associated with a switch from a Th1 to a Th2 profile. For sepsis, uncontrolled activation of proinflammatory cytokines (IL-1, tumor necrosis factor-alpha, interferon-gamma) may be a fundamental defect that promotes the detrimental aspects of inflammation, whereas Th2 cytokines may be beneficial in controlling inflammation. Knowledge of basic cytokine immunopharmacology, networks, and relationships with infectious processes will aid clinicians in determining treatment approaches that are likely to be effective.
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PMID:Cytokine networks with infection: mycobacterial infections, leishmaniasis, human immunodeficiency virus infection, and sepsis. 908 11

Alterations in protein kinase C (PKC) activity have been implied in the pathogenesis of common variable immunodeficiency (CVID). We analyzed amiloride-sensitive red blood cell Na+/H+ exchange (sodium-proton antiport, SPA) and its response to protein kinase stimulation in a patient with CVID. Compared with healthy subjects or patients with sepsis, a unique pattern of SPA activation has been shown. The patient's SPA was decreased and unresponsive to PKC stimulation, whereas stimulation by insulin, a tyrosine kinase activator, restored SPA activity. An alteration of serine-threonine phosphorylation is suggested as a possible mechanism for the immune failure.
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PMID:Common variable immunodeficiency associated with myelocathexis and altered membrane sodium-proton antiport. 920 Jan 89

An 8-month-old child with an immunodeficiency disorder characterized by abnormal lymphocyte function and by low IgG and IgA levels had combined liver and small bowel transplantation under tacrolimus and steroid immunosuppression for the treatment of short gut syndrome and hepatic cirrhosis. The patient developed an early postoperative episode of Pneumocystis carinii pneumonia, and a subsequent surgical complication, prompting discontinuance of tacrolimus. A skin rash eventually shown to be graft-versus-host disease (GVHD) developed in the flank on the 12th post-transplant day and gradually became generalized. Peritonitis, sepsis, multisystem organ failure including the liver allograft led to death on the 23rd post-operative day. The mechanisms leading to post-transplant GVHD under the specific circumstances in this case are discussed.
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PMID:Graft-versus-host disease after liver and small bowel transplantation in a child. 936 21

Neonatal sepsis is a major cause of morbidity and mortality in newborn infants. Hematopoiesis and host defense in the neonate is developmentally immature compared with the adult. Defects in both the quantitative and qualitative aspects of the phagocytic system contribute significantly to a relative state of immunodeficiency in the neonate. Dysregulation of neonatal hematopoiesis and the immune response is a significant contributing factor to the increased susceptibility of the neonate to infection. A relatively small set of pluripotent stem cells gives rise to large numbers of functionally diverse mature effector cells. Cell proliferation and differentiation are regulated and controlled by highly specific protein factors, affecting single and multiple lineage hematopoiesis. Reduced neonatal rat myeloid progenitor pools, accelerated myeloid progenitor proliferative rates and decreased total body neutrophil storage pools predispose the newborn rat to depletion of mature effector neutrophils and a tendency to develop neutropenia during states of increased demand such as overwhelming bacterial infection. We review here the multifactorial complex biological process involved in the regulation of hematopoietic growth factors. We also review the biological effects of various non-lineage-committed and lineage-committed growth factors as reported in in vitro investigations and in vivo neonatal animal experiments. We also review our results of phase I/II clinical studies utilizing rhuG-CSF in neonates with presumed sepsis, and of rhuGM-CSF in very low birth weight neonates.
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PMID:The role of cytokines in modulating neonatal myelopoiesis and host defense. 938 73

Neonatal sepsis remains a major clinical problem in neonatology, with high morbidity and mortality rates. The host defence against infections is immature in the newborn infant, and this makes the child more susceptible to invasive infection. The neutrophil storage pool and various granulocyte functions are impaired. In addition, the levels of immunoglobulins and complement are low. The detection of raised levels of complement activation products and cytokines may be of diagnostic help at an early stage of neonatal infection. Rapid treatment with antibiotics is essential for a favourable outcome. Possible adjuvant treatment may be to reduce the relative immunodeficiency by giving immunoglobulins or colony-stimulating factors which increase the production of leukocytes. Further, the potent inflammatory reaction initiated by the microorganisms may be suppressed by various therapies. In spite of much research in this field, no such adjuvant treatment has so far been shown to improve the outcome of neonatal sepsis.
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PMID:[New diagnostic and therapeutic possibilities in neonatal sepsis]. 944 23

The use of intravenous immunoglobulin (IVIG) for the prevention and treatment of sepsis in neonates is appealing because of the relative immunodeficiency of the neonate and the desire to improve the relatively poor outcome even with optimal antimicrobial treatment. The effectiveness of IVIG for these uses has been studied in numerous prospective as well as retrospective small and large trials that have had discordant conclusions. Meta-analysis demonstrates the marginal but significant benefit of prophylactic IVIG administered shortly after birth in preventing early onset sepsis in premature low birth weight newborns (P = .0193, two-sided). The expense of prophylactic use of IVIG administration for the relatively large premature newborn population given the minimal benefit as demonstrated by original studies and by meta-analysis is not justified. In contrast, meta-analysis of studies of IVIG for the treatment of neonates with sepsis shows a significant and unequivocal sixfold decrease in the mortality rate (P = .007, two-sided) when IVIG is administered in addition to standard therapies. The additional benefit of decreasing the risk for acute mortality indicates that the inclusion of IVIG should be considered a part of the routine therapy of neonatal sepsis.
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PMID:The role of intravenous immunoglobulin for the prevention and treatment of neonatal sepsis. 952 99


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