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)

Studies indicate that lymphoid tissue (e.g., thymus, bone marrow, and Peyer's patches) shows evidence of increase apoptosis (Ao, a form of nonnecrotic cell death) during sepsis. However, it is not known if mucosal lymphoid tissue, such as lamina propria (LP), also shows evidence of increased Ao and if so, is this associated with functional changes, i.e., cytokine gene expression in the LP. To examine this, male C3H/HeN mice were subjected to cecal ligation and puncture (CLP) and lamina propria mononuclear cells (LPMC) were harvested at 4 h (early sepsis) or 24 h (late sepsis). Alterations in the cell phenotype as well as Ao (Tunel assay) were determined by three-color flow cytometry. Cytokine gene expression was assessed by multiprobe RNase protection assay. Sham LPMC preparations were found to be 34.4 +/- 2.4% B220(+) (B-cells), while 12.4 +/- 2.1% were CD8(+) (cytotoxic T-cells), 22.0 +/- 0.8% were CD4(+) (helper T-cells), and 6.4 +/- 0.7% were F4/80(+) (macrophages). The frequency of B220(+) (9%* upward arrow) and CD8 (6%* upward arrow) populations increased markedly at 4 h after CLP; however, this increase was not seen at 24 h. The percentage of Ao+ in CD8(+), B220(+), and F4/80(+) cells increased markedly at both 4 and 24 h. CD4(+) cells showed a marked increase in Ao only at 24 h after CLP. When LPMC mRNA expression was examined, a significant increase in IL-2, -10, and -15 gene expression was observed only at 24 h but not 4 h after CLP. Thus, the early phenotypic changes associated with increased Ao may be a reflection of localized immune cell activation in early sepsis contributing to the increased cytokine gene expression seen in late sepsis. This localized activation may contribute to gastrointestinal inflammation and/or immune dysfunction in sepsis.
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PMID:Sepsis induces increased apoptosis in lamina propria mononuclear cells which is associated with altered cytokine gene expression. 969 35

Extracorporeal photochemotherapy (EP) is a therapeutic approach to the treatment of drug-resistant graft-vs.-host disease (GVHD) that uses the known immunosuppressive and immunomodulatory effects of ultraviolet light. In 1990, we initiated a pilot study to evaluate the efficacy and safety of EP in patients with refractory GVHD. Between 1991 and 1996, six patients with acute grade IV liver GVHD, 12 patients with chronic following acute GVHD, and six patients with de novo chronic GVHD were treated with EP. All patients had failed to respond to conventional GVHD immunosuppressive drug therapy of cyclosporine and prednisone. The six patients with acute liver GVHD had also received antithymocyte globulin (ATG); therapy for chronic GVHD included thalidomide in eight patients, psoralen plus ultraviolet A in five patients, and ATG in two patients. All patients with acute liver GVHD had progressive liver failure with short survival despite frequent EP. The response rate with EP treatment was 3 of 6 for patients with de novo chronic GVHD and 3 of 12 for patients with chronic following acute GVHD. Three patients with bronchiolitis obliterans had either no response or no documented disease progression while undergoing EP. Side effects of EP were minor and included gastrointestinal upset frequently, catheter-related sepsis in four patients, increased red blood cell and platelet transfusion requirements in one patient, and leukopenia in two patients. EP was discontinued in three patients because of side effects, including GI upset in one patient and bone marrow suppression in two patients. Side effects were reversible with the discontinuation of EP. We were unable to correlate response to EP with the level of methoxypsoralen, number of lymphocytes treated, or pattern of pre- and posttreatment CD4/CD8 ratio. We concluded that EP has some efficacy in the treatment of drug-resistant chronic GVHD, with minor overall toxicity.
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PMID:Extracorporeal photochemotherapy for treatment of drug-resistant graft-vs.-host disease. 970 89

To understand the etiology and clinical outcome of bacterial and fungal sepsis in patients with advanced human immunodeficiency virus (HIV) infection in Taiwan, we conducted a prospective study of nonmycobacterial bacteremia and fungemia in HIV-infected patients with fever who were admitted to a university hospital in Taiwan during a 42-month period. Of 210 patients, 41 (19.5%) had a total of 52 episodes of sepsis due to nonmycobacterial bacteria or fungi, or both (15.5% of 336 episodes of fever). All but one patient had acquired immunodeficiency syndrome (AIDS), and the mean CD4 lymphocyte count was 29/microL (range, 0-321/microL). A total of 57 pathogens (39 bacteria and 18 fungi) were isolated from blood; polymicrobial sepsis due to both bacteria and fungi occurred in four episodes. Nontyphoid Salmonella (NTS) was the most common cause of community-acquired bacteremia (24/30, 80%). Staphylococcus aureus bacteremia was diagnosed in three episodes while Streptococcus pneumoniae bacteremia was found in only one. Cryptococcus neoformans was the most common cause of fungemia and was responsible for 12 episodes, while fungemia due to Penicillium marneffei and Histoplasma capsulatum, two emerging fungi in Taiwan, were diagnosed in four cases and one case, respectively. Nine episodes, eight of bacteremia and one of candidemia, were nosocomial. The overall in-hospital mortality was 29%, and nosocomial sepsis was associated with a higher mortality rate (56%, p = 0.02). The mean duration of survival after recovery from initial sepsis was 426 days. We conclude that NTS bacteremia was the most common cause of sepsis in patients with advanced HIV infection in Taiwan and clinicians caring for such patients should watch for emerging fungal infections. Nosocomial sepsis was associated with a high mortality rate. The mean survival duration after recovery from sepsis of our patients was short.
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PMID:Bacteremia and fungemia in patients with advanced human immunodeficiency virus (HIV) infection in Taiwan. 983 Feb 79

The task of the immune system is the continuous elimination of endogenous cellular debris and the elimination, when necessary, of exogenous structures. It therefore seems useful and practical to add to the paradigms 'self' and 'not self' the term 'altered self'. The concept of stress, introduced by W. B. Cannon and H. Selye in the 1930s, covers the wide range of aggressive environmental influences which for their part result in a uniform shift of the metabolism in the direction of catabolism. This results from the activation of the neuroendocrine stress axis, hypothalamus-pituitary-adrenals, and causes an increased release of catecholamines and glucocorticoids. These latter substances limit life-threatening acute-phase reactions by endogenous inflammation mediators. The purpose of the shift of the cytokine profiles of the CD4 lymphocytes from Th-1 to Th-2 is, with the return of a raised cortisol level to normal values, to temporarily take over the anti-inflammatory functions of the cortisol. A sustained Th-2 shift is an expression of a persistent hypercortisolism in autoimmune states. The suppression of the anti-inflammatory effects of cortisol as a result of states of excessive stress leads to hypercatabolic diseases such as AIDS, sepsis and toxic shock syndrome and protein calorie malnutrition (NAIDS). In the prevention and treatment of AIDS and NAIDS, besides the elimination of the causes of stress, the prophylactic and therapeutic efforts are based mainly on the activation of the mesenchymal production of anabolic matrix components, mainly glycosaminoglycans, and the neutralization of O2 and NO radicals and inflammation mediators from macrophages by polyanions and polyphenols. In our opinion, in sepsis and toxic shock syndromes, lasting reduction of the mortality rates for these diseases is best achieved through the early administration of high intravenous doses of gammaglobulins.
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PMID:The role of the Th-1 to Th-2 shift of the cytokine profiles of CD4 helper cells in the pathogenesis of autoimmune and hypercatabolic diseases. 988 38

A previously healthy 10-year-old Greek boy born to nonconsanguineous healthy parents developed progressive liver disease after acute infectious mononucleosis. EBV-induced autoimmune hepatitis was suspected and treatment was started with high-dose prednisolone, acyclovir and intravenous immunoglobulins. Despite therapy, his liver function continuously deteriorated and the child died 9 months later in profound immune deficiency from candida septicemia. Flow cytometric analysis of his lymphocytes revealed a major subpopulation of atypical cells (20.3%) which were CD3+, fitted into the lymphocyte gate but showed a very low level of CD4 expression, comparable to that of monocytes. After short-time cell culture, the cells became adherent and developed granules and dendrites. We conclude that these cells may represent strongly activated CD4+ T lymphocytes with downregulated CD4 expression or a subtype of dendritic cells.
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PMID:Atypical CD3+ CD4(low) cell population in a boy with fatal EBV-infection. 992 66

Approximately 150 human immunodeficiency virus (HIV)-infected patients with a thrombotic microangiopathy (TMA)-like syndrome have been reported in the literature since the early 1980s. The prevalence of a TMA-like syndrome in our hospitalized patients was determined to discern whether it is a more common occurrence than previously recognized and, if possible, to delineate risk factors for its occurrence. A total of 350 patients admitted consecutively to the Johns Hopkins Hospital HIV inpatient service were assessed from May 1, 1996 through February 1, 1997. These patients were evaluated for the presence of anemia, thrombocytopenia, fragmented erythrocytes on peripheral blood smear (schistocytosis), renal dysfunction, neurologic dysfunction, and fever. The association of a TMA-like syndrome with demographic and clinical factors was analyzed. Schistocytosis was present in 24% of the patients and a TMA-like syndrome (anemia, thrombocytopenia, schistocytosis + renal dysfunction or neurologic dysfunction, and fever) was present in 7% of the patients. The patients who had a TMA-like syndrome were more likely to have a low CD4 lymphocyte count or CD4 percentage, Centers for Disease Control and Prevention stage C disease, and have bacterial sepsis. Age, race, HIV risk group, other diagnoses, and prescribed drugs were not associated. Patients were more likely to die if they had a TMA-like syndrome, independently of level of immunosuppression. Schistocytosis and a TMA-like syndrome are relatively common in hospitalized HIV-infected patients. This syndrome may contribute to mortality and morbidity, particularly in patients with more advanced disease.
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PMID:Schistocytosis and a thrombotic microangiopathy-like syndrome in hospitalized HIV-infected patients. 992 2

When compared to controls (n = 30), human immunodeficiency virus type-1 (HIV-1)-positive individuals, either asymptomatic (n = 10) or diagnosed with acquired immunodeficiency syndrome (AIDS) (n = 10), showed a statistically significant decrease in the percentage and absolute number of CD4 ( + ) T-lymphocyte cells (flow cytometry, Becton Dickinson FACScan; mean +/- SD of 42.6 +/- 6.9 and 948.5 +/- 393.3, 19.5 +/- 8.7 and 269.8 +/- 174.3, 4.6 +/- 4.1 and 60.1 +/- 134.3, respectively; Student's t- test, p < 0.05). However, this decrease was less marked in asymptomatic patients; in fact, the percentage and number of the above cells in this group of subjects was significantly higher than in the AIDS patients (Student's t-test, p < 0.05). However, we failed to find significant differences in the percentage of natural killer cells (NKCs; CD15 ( + ) CD56 ( + ) ) between the HIV-1-infected asymptomatic or AIDS groups of patients, or when compared with the controls (mean +/- SD of 10.4% +/- 9.4%, 14.3% +/- 9.7%, and 14.8% +/- 6.4%, respectively). Whereas either group of patients had a lower number of NKCs per microliter than the control group (mean +/- SD of 137.8 +/- 87.6, 91.1 +/- 98.3, and 331. 5 +/- 266.5, respectively), this decrease only reached statistical significance for the AIDS patients (Student's t-test, p < 0.05). Healthy controls showed statistically significantly higher NKC activity than either the HIV-1-infected asymptomatic or AIDS group of patients (K-562 target cell; mean +/- SD and range values as percentage of specific lysis of 19.1% +/- 15.6% and 2.4%-58.2%, 3.4% +/- 3.2% and less than 0.1% [non-detectable]-10.3%, and 6.4% +/- 5. 5% and less than 0.1%-19.5%, respectively; Student's t-test, p < 0. 05). Challenge of samples from the control group with either interleukin-2, alpha-interferon, or with a mixture of the calcium ionophore A23187 (Io) plus the 12-O-tetradecanoylphorbol-13-acetate ester (TPA) resulted in every case in a statistically significant increase in NKC lytic function (mean +/- SD and range values as percentage of specific lysis of 19.1% +/- 15.6% and 2.4%-58.2%, 27. 6% +/- 17.4% and less than 0.1%-56.0%, 32.1% +/- 20.9% and 2.1%-76. 4%, and 62.6% +/- 24.0% and 16.7%-95.0%, respectively; Student's t-test, p < 0.05). A similar challenge for samples from the HIV-1-positive subjects, either asymptomatic or with AIDS, resulted in most cases in an enhanced NKC activity; however, this increase in NKC lytic function reached statistical significance only for the group of Io + TPA-incubated samples (Student's t-test, p < 0.05). These results indicate that control or patient baseline NKC activity, and the response of this cellular immune function to a challenge with different immunomodulators, are phenotype-independent. They also suggest an association between HIV-1 infection and alterations in the initial mechanisms responsible for NKC activation; a similar general explanation has been suggested to account for the abnormal NKC lytic function observed in various severe pathological conditions, e.g., extensive burns, polytrauma, and sepsis. Understanding the molecular mechanism involved in regulating initial NKC activation could provide the rational basis for the design of newer pharmacological strategies to treat these conditions.
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PMID:Enhancement of natural killer cell activity in HIV-1-infected subjects by a mixture of the calcium ionophore A23187 and the phorbol ester TPA: lack of response to a similar challenge with interleukin-2 or alpha-interferon. 1042 40

We conducted a retrospective study to assess the reasons for admission to the intensive care unit, and subsequent outcome, in patients infected with the human immunodeficiency virus (HIV). Four hospitals in the south of England participated, all with specialist HIV units. Data were collected on 127 patients admitted to ICU on 133 separate occasions between June 1993 and October 1997. The mean age on admission was 38 years (range 23-60 years). Ninety-four patients (70.7%) were documented HIV-positive before admission and 36 (27%) were diagnosed HIV-positive for the first time during admission; 36.1% were admitted with Pneumocystis carinii pneumonia. Overall ICU mortality was 33%, in-hospital mortality was 56% and the eventual mortality at the end of follow-up (March 1998) was 72%. Survival was highest in those admitted with respiratory HIV-related disease or HIV-unrelated illness. Associations with poor outcome included a prior AIDS-defining illness, a CD4 cell count of less than 100 cells.ml-1 and admission secondary to sepsis.
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PMID:ICU admission in patients infected with the human immunodeficiency virus - a multicentre survey. 1046 May 23

Thymomas are often associated with autoimmune disorders. We report on a 45-year-old female patient with thymoma and hypogammaglobulinemia (Good's syndrome) who developed symptomatic macrocytic anemia (Hb 4.4 g/dl, MCV 112 fl) and thrombocytosis (Plt 442 G/l). Besides hypogammaglobulinemia (IgG 589 mg/dl), an inverted ratio of CD4(+)/CD8(+) cells was seen. The bone marrow biopsy showed a slightly hypercellular bone marrow with normal granulopoiesis, normal megakaryopoiesis and a mild dyserythropoiesis without any ring-sideroblasts. The in-vitro stem cell culture from the bone marrow revealed an atypical growth of macroclusters, reduced BFU-E and CFU-GEMM colony growth, whereas the CFU-GM colony growth was within the normal range. The chromosomal analysis showed a normal karyotype. The plasma vitamin B(12) and folate levels were within normal ranges, and we could not detect any autoantibodies. These findings excluded the differential diagnoses pure red cell aplasia (PRCA) and pernicious anemia. After resection of the thymoma of mixed cell type, the macrocytic anemia and thrombocytosis disappeared. The clinical course was complicated by a cerebral palsy and a life-threatening fungal septicemia after surgery. In the third year after thymectomy, hyporegenerative macrocytic anemia and thrombocytosis reappeared and an immunosuppressive treatment with prednisolone (1 mg/kg BW) was started. After initiation of the prednisolone therapy, reticulocyte counts increased and macrocytic anemia as well as thrombocytosis disappeared. The normalization of these laboratory parameters during glucocorticoid therapy suggests that in rare cases the constellation of macrocytic anemia, thrombocytosis and hypogammaglobulinemia may be due to an underlying immunologic mechanism.
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PMID:Macrocytic anemia and thrombocytosis associated with thymoma: a case report. 1060 67

Several pathogenetic processes are involved in the progression to AIDS in HIV-infected individuals. These include a gradual, but ultimately profound, depletion in CD4 lymphocytes, defects in B lymphocytes, neutrophil dysfunction and the breakdown of the integument as a consequence of AIDS-related dermatological conditions such as bacterial and fungal dermatoses and Kaposi's sarcoma. Each of these factors has important implications regarding host susceptibility to nosocomial infections. This review deals with some of the difficulties that are encountered in precisely defining the interrelationships between HIV infection/AIDS and nosocomial sepsis, and some of the controversies that surround respiratory, bloodstream (including central venous catheter-related infections) and gastrointestinal infections that may be acquired within healthcare centres. Because of the lack of accurate, detailed information on this subject, parallels will sometimes be drawn from observations made in other immunologically impaired patient groups and from data examining the rates of community-acquired infections in HIV-infected patients compared to controls. Appropriate and rational infection practice to minimize the risk of acquisition of nosocomial infection is highlighted. Finally, some of the common methodological problems commonly encountered in the current literature regarding nosocomial infections in this population group, and future challenges in the study of these infections, are reviewed.
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PMID:Nosocomial infections in HIV-infected/AIDS patients. 1065 79


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