Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mycobacterium avium intracellulare (MAI) infection is a serious opportunistic infection that occurs in children with human immunodeficiency virus (HIV) infection. In MAI the hematologic system is profoundly affected. In the present study the hematologic manifestations of MAI in 37 HIV-infected infants and children were reviewed. Anemia was the predominant feature in all patients, with severe anemia (hemoglobin < 6 g/dL) occurring in 7 of 34 (21%) patients. This was followed by leukopenia (79%), monocytosis (82%), thrombocytopenia (59%), leukoerythroblastic reaction (68%), and neutropenia (41%). Serum tumor necrosis factor (TNF)-alpha was markedly elevated in all patients with MAI with an X +/- SE of 702 +/- 182 pg/mL. There was an association between elevated TNF-alpha and anemia in these patients.
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PMID:Elevated tumor necrosis factor-alpha in association with severe anemia in human immunodeficiency virus infection and Mycobacterium avium intracellulare infection. 764 Jan 75

The influence of pentoxifylline (PTX) on mortality and some important mediators was studied in a model of cecal perforation with fulminant intra-abdominal sepsis in rats. Cumulative mortality was registered in three groups of animals: untreated sepsis (n = 36), sepsis + PTX 20 mg/kg/24 h (n = 24), and sepsis + PTX 80 mg/kg/24 h (n = 24). PTX therapy was started at sepsis induction or after 4 h, and mortality was reduced from 89% in untreated sepsis to 60-66% in the PTX groups. Levels of sepsis mediators were studied in two groups: untreated sepsis and sepsis + PTX 40 mg/kg started 1 h after sepsis induction. In both groups 6-10 animals were sacrificed at 4 and 8 h to measure blood levels of bacteria, endotoxin, tumor necrosis factor (TNF), interleukin-6 (IL-6), endothelin-1, lactate, neutrophils, and packed cell volume. Cecal perforation gave high levels of bacteria, endotoxin, TNF, IL-6, and endothelin-1, leading to dehydration, lactacidosis, neutropenia, and death. Treatment with PTX did not modify dehydration, neutropenia, or concentrations of bacteria and endotoxin. Release of endothelin-1 was delayed, TNF burst was nearly abolished, and levels of IL-6 and lactate were substantially suppressed. In summary, PTX improves survival and reduces blood concentrations of TNF, IL-6, lactate, and endothelin-1 in fulminant intra-abdominal sepsis in rats. The primary effect of PTX in this sequence is probably reduction of TNF.
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PMID:Pentoxifylline improves survival and reduces tumor necrosis factor, interleukin-6, and endothelin-1 in fulminant intra-abdominal sepsis in rats. 777 1

Picryl chloride-induced irritant reaction (IR) was shown to be mediated by tumor necrosis factor (TNF). Anti-TNF monoclonal antibodies, but not interleukin 1 receptor antagonist (IL-1 Ra), had a protective effect. Chlorpromazine (CPZ), an inhibitor of TNF synthesis, protected against IR and inhibited the IR-associated TNF induction in ear homogenates. Investigation of the role of polymorphonuclear leukocyte (PMN) in neutropenic mice showed that neutropenia did not prevent the development of the IR.
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PMID:Protective effect of chlorpromazine on TNF-mediated hapten-induced irritant reaction. 779 76

Previous reports have indicated that immunological priming of animals will result in increased cytokine production and enhanced susceptibility to the toxicity of cytokines. We primed mice with complete Freund's adjuvant and challenged 2 weeks later with 1 mg/mouse of lipopolysaccharide. Primed mice produced less tumor necrosis factor than naive mice (35 +/- 8 vs 108 +/- 20 ng/ml) and also less interleukin-6 (182 +/- 37 vs 6.39 +/- 155 ng/ml). Leukopenia developed only in the naive mice. Although neutropenia and lymphocytosis developed in both groups, the alterations manifested themselves more quickly in primed mice. Primed mice had substantially greater pulmonary neutrophil sequestration determined both enzymatically and histologically but no lung damage. However, primed mice had significantly less small bowel damage than naive mice. Mortality was substantially reduced in primed mice compared with unprimed mice. These results demonstrate that immunological priming in vivo decreases cytokine production in response to lipopolysaccharide challenge, decreases organ injury, and reduces mortality.
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PMID:Immunological priming attenuates the in vivo pathophysiological response to lipopolysaccharide. Comparison of cytokine production, tissue injury, and lethality in complete Freund's adjuvant-primed mice and in unprimed mice. 812 45

The objective of this study was to investigate mechanisms by which circulating polymorphonuclear neutrophils (PMNs) may contribute to the tolerance to hemorrhagic shock induced by pretreatment with lipopolysaccharides (LPS). Tolerance was developed by daily injections of sublethal doses of LPS for four subsequent days while controls received saline injections. During shock, both groups of rats were maintained for 3 h at 40 mmHg mean arterial pressure and were then observed for survival during a 24-h period. This protocol resulted in 40% survival in the untreated controls and 89% survival in the tolerant group (P < 0.0068). Hypotension caused an initial neutropenia in both groups. The circulating PMN counts remained lower in the tolerant than in the controls rats for most of the low flow period. The number of circulating activated PMNs in whole blood, as assessed by spontaneous nitroblue tetrazolium reduction, was lower in tolerant animals before and during most of the hypotensive period, except immediately after bleeding when both groups have low circulating leukocyte counts. No detectable tumor necrosis factor activity was observed in the plasma of either group. Adhesion of circulating PMNs to nylon fibers in vitro and the number of PMNs adhering to the endothelium in the mesentery in vivo was significantly lower in the tolerant rats. We conclude that LPS pretreatment produces a reduction in the activated circulating PMNs and in the degree of PMN adhesion to endothelium with subsequent improvement of survival after hemorrhagic shock.
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PMID:Circulating neutrophil kinetics during tolerance in hemorrhagic shock using bacterial lipopolysaccharide. 814 42

Cyclophosphamide (CY)-induced neutropenia exacerbates septic shock and acute lung injury during Candida albicans (CA) fungemia in conscious rats. We hypothesized that treatment of such animals with recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF) improves host defense during disseminated candidiasis by increasing peripheral neutrophils (PMNs) and enhancing endogenous production of antifungal cytokines including tumor necrosis factor-alpha (TNF). Naive (neutrophil-replete) or neutropenic rats were infected with 10(7) yeast-phase CA; subgroups received GM-CSF (25 micrograms/kg sc) or sterile 0.9% NaCl (NS) twice a day beginning 3 days before CA infection. Arterial hemodynamics, formed blood elements, bioactive TNF in serum and bronchoalveolar lavage fluid (BALF), and lung histopathology were monitored for up to 72 h after infection. All naive animals receiving GM-CSF (n = 5) and 78% of naive rats given NS (n = 9) remained normotensive through 72 h with no lung injury, differing principally in baseline PMNs before CA infection (8.8 +/- 1.8 x 10(3)/microliters, mean +/- SE, vs. 3.7 +/- 0.4 x 10(3)/microliters, respectively, P < 0.01). Neutropenic rats given NS (baseline PMN = 41 +/- 10/microliters, n = 7) were sensitized to CA, and 100% died of hypothermic shock with severe respiratory distress within 56 h of infection. Pulmonary periarterial and alveolar hemorrhage were prominent. Although GM-CSF did not increase baseline PMNs in CY animals by the outset of infection (162 +/- 58/microliters, n = 8), 62% of these rats remained normotensive and eupneic through 72 h (P < 0.01), and their lungs showed no perivascular hemorrhage, alveolar disruption, or fungi.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recombinant GM-CSF reduces lung injury and mortality during neutropenic Candida sepsis. 820 49

We compared physiological and ultrastructural indices of acute lung injury (ALI) during septic shock caused by taxonomically diverse pathogens to distinguish ALI due to endogenous inflammatory mediators vs. microbial exotoxins or other factors. Conscious rats were infected i.v. with gram-negative Escherichia coli (EC, serotype 055:B5), exotoxin-C producing gram-positive Staphylococcus aureus (SA), or yeast-phase Candida albicans (CA, a clinical isolate). Viable inocula of 10(10) EC, 10(10) SA, or 10(9) CA caused lethal shock in < 24 h, but distinct types of ALI were noted after bacteria vs. fungi. Within 0.5 h of EC infection, leukocytes marginated in the lung vasculature; by death at 6-14 h, animals were hyperoxemic but not acidemic, and showed slight interstitial edema with increased wet/dry weight ratios (W/D = 5.22 +/- 0.10, mean +/- SE, vs. 4.86 +/- 0.07 in controls, P < 0.05). Similarly mild ALI occurred after 10(10) SA. In contrast, within 0.5 h of CA infection, yeast were visible within lung intravascular leukocytes. By death at 6-12 h, CA animals showed hyperoxic acidemia and moderate ALI with capillary obstruction, interstitial hemorrhage, and elevated lung W/D (5.52 +/- 0.13, P < 0.01 vs. controls) associated with yeast-mycelial transformation. Prior neutropenia accelerated mortality and worsened ALI after CA, with hypoxemic acidemia, increased lung W/D (7.23 +/- 0.34, P < 0.05 vs. other groups), capillary occlusion, perivascular and alveolar hemorrhage, and septal disruption by mycelia. Bacteremia induced large increases in serum tumor necrosis factor-alpha (TNF) and interleukin-1 alpha within 1.5 h, but these cytokines remained low in CA animals, even at death. Neither survival nor ALI after EC or CA was altered by pentoxifylline, which attentuated TNF production, or by cyclooxygenase inhibition with ibuprofen. Thus, overall ALI severity correlated with physiological indices of pulmonary function, but ultrastructural changes correlated better with pathogen type than circulating cytokine or eicosanoid mediators. Whereas lethal bacteremia induced early cytokinemia and mild ALI with or without bacterial exotoxins, moderate ALI apparently was mediated by fungal exotoxins during lethal candidemia, which worsened during neutropenia due to enhanced mycelial proliferation.
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PMID:Acute lung injury during bacterial or fungal sepsis. 828 90

A reconstituted lipoprotein, containing human apolipoprotein A-I and phosphatidylcholine (1:200, molar ratio), referred to as ApoLipo, was used prophylactically in an endotoxin shock model in anesthetized rabbits. ApoLipo was administered at a dose of 75 mg protein/kg body weight 15 min before the beginning of a slow, continuous lipopolysaccharide (LPS, endotoxin) infusion (4.17 micrograms LPS/kg/hr). During the 6 hr LPS infusion, the Control-LPS group manifested a marked increase in serum tumor necrosis factor (TNF, peak value 7.82 [2.7-11.2] ng/ml at 1 hr), and many of the pathophysiologic sequelae of endotoxin shock, including hypotension (MAP: 59 +/- 7 mmHg) and metabolic acidosis (BE: -9.9 +/- 2.7) at 3 hr, and a severe neutropenia developed rapidly (PMN count: 5 +/- 3% of baseline at 30 min). In the ApoLipo treated group, serum TNF levels did not rise during the course of LPS infusion (0.1 [0.06-0.64] ng/ml at 1 hr). Hypotension (77 +/- 2 mmHg) and acidosis (-2.7 +/- 0.4) were also significantly attenuated, and the appearance of leukopenia was delayed by 1 hr (110 +/- 12% at 30 min, but 9 +/- 2% at 2 hr). Endotoxemia in the ApoLipo treated group was reduced in comparison to controls, albeit nonsignificantly. The infusion of the same dose of phosphatidylcholine without apoA-I was significantly less efficacious.
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PMID:A reconstituted, apolipoprotein A-I containing lipoprotein reduces tumor necrosis factor release and attenuates shock in endotoxemic rabbits. 832 86

Lethal circulatory shock during microbial sepsis is thought to be initiated by early molecular events, including production of tumor necrosis factor (TNF) and cytokine-mediated upregulation of neutrophil (PMN) function, irrespective of the causative organism. The phosphodiesterase inhibitor pentoxifylline (PTX) inhibits TNF gene transcription and modulates PMN function, and has been shown to improve outcome in experimental sepsis. We hypothesized that PTX would attenuate gram-negative and fungal septic shock by different mechanisms: reduced TNF production in Escherichia coli (EC) sepsis vs. enhanced PMN-mediated defense during Candida albicans (CA) fungemia. Conscious chronically catheterized rats received PTX (25 mg/kg, i.v.) before i.v. challenge with 10(10) viable EC (serotype 055:B5), 10(9) viable serotype A yeast-phase CA (each the LD100 in < 24 hr in naive rats), or normal sterile saline (NSS), and then PTX posttreatment (6.5 mg/hr x 4.5 hr). Treatment controls received NSS before and after challenge. Serum TNF peaked 1.5 hr after EC infection in NSS-treated animals (1654 +/- 390 U/ml, mean +/- SE), and was significantly reduced by PTX (120 +/- 32 U/ml, P < 0.01), but PTX did not improve 24 hr survival. PTX also aggravated systemic hypotension after EC, and did not modify neutropenia, thrombocytopenia, or microvascular permeability assessed by organ wet/dry weight (W/D) ratios. Peak serum TNF in CA + NSS animals (130 +/- 45 U/ml) was delayed 8 hr compared to EC animals, and were not reduced by PTX (67 +/- 25 U/ml, P = NS). Moreover, PTX did not alter CA-induced mortality, hypothermia, hypotension, neutropenia, increased lung W/D, or interstitial and alveolar hemorrhage. We conclude that PTX-induced suppression of endogenous TNF production does not prevent gram-negative shock in this model, possibly due to impaired TNF-mediated antibacterial host defense. Since fungal septic shock with acute disseminated candidiasis evolves prior to significant increases in circulating TNF, PTX also appears ineffective in its treatment.
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PMID:Effects of pentoxifylline on tumor necrosis factor production and survival during lethal E. coli sepsis vs. disseminated candidiasis with fungal septic shock. 848 22

Cyclophosphamide-induced neutropenia exacerbates septic shock and multiple organ injury in conscious rats during Escherichia coli (EC) bacteremia despite antibiotics and fluid administration. We hypothesized that such shock and inflammatory organ injury would be mitigated by rBPI23's microbicidal activity and/or binding of EC endotoxins. Four days after 100 mg cyclophosphamide/kg, catheterized rats with < 300 PMNs/microL were pretreated with rBPI23 or the irrelevant 22 kDa protein thaumatin [3.3-6.6 mg/kg, i.v. in 0.9% NaCl (NS)] 5 min before graded i.v. infection with 5 x 10(9) or 1 x 10(10) cfu of EC serotype 055:B5 ending at t = 0. Posttreatment with each protein continued (3.3-6.6 mg/kg in 1 mL NS/h) through 8 h, in addition to penicillin plus amikacin sulfate at t = 1.5 and 8 h. Arterial samples were obtained before pretreatment and at t = 1.5, 4.5, 8, and 24 h when animals were necropsied. One of eight thaumatin + 5 x 10(9) EC rats and none of six thaumatin + 10(10) EC rats survived 24 h. In contrast, rBPI23 significantly reduced mortality after either inoculum, improved bacterial clearance, and led to renormalization of early EC-induced hypotension, hypothermia, tachypnea, hyperoxemia, and hypocarbia. Compared with thaumatin, however, rBPI23 did not reduce circulating endotoxin or bioactive and antigenic tumor necrosis factor-alpha. Sepsis-induced severe neutropenia (< 50 PMNs/microL) evident in all EC rats by t = 1.5 h was reversed with rBPI23 by t = 8 h, but thrombocytopenia (< 5 x 10(4) platelets/microL) evident in all groups by t = 4.5 h was not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The recombinant 23-kDa N-terminal fragment of bactericidal/permeability-increasing protein (rBPI23) decreases Escherichia coli-induced mortality and organ injury during immunosuppression-related neutropenia. 856 60


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