Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RhGM-CSF is a hematopoietic growth factor which stimulates the proliferation, differentiation and functional activity of neutrophils, monocytes and macrophages. It also stimulates proliferation of endothelial cells and induces the production of other cytokines, such as interleukin (IL-1), tumor necrosis factor (TNF), interferon, prostaglandin E2, and plasminogen activating factor which affects both hematopoietic and non-hematopoietic cell activities. Initial clinical studies in 1987 generally excluded experimental therapy with rhGM-CSF in pediatric patients (age < or = 17 years) unless life threatening illness related to neutropenia and infection developed (i.e., patients with graft failure). Serious complications of patients undergoing autologous bone marrow transplantation (BMT) related to pancytopenia include infection and hemorrhage. Other regimen related complications include venooclusive disease, pneumonitis and mucositis. As a result of these complications, patients require intensive medical support including antibiotics and hyperalimentation. Initial hospital duration following marrow reinfusion is generally 4 to 5 weeks. Hematopoietic growth factors have been administered to patients undergoing autologous BMT as an attempt to reduce regimen related toxicity.
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PMID:RhGM-CSF in bone marrow transplantation: experience in pediatric patients. 130 85

Acute respiratory failure in pregnancy is an important cause of maternal and fetal morbidity and mortality. Causes include: ARDS, venous air embolism, beta-adrenergic tocolytic therapy, asthma, thromboembolic disease, pneumothorax, and pneumomediastinum. The most common predisposing diseases for ARDS complicating pregnancy are sepsis, pneumonia, aspiration of gastric contents, and amniotic fluid embolism. Knowledge of normal maternal-fetal physiology and determinants of fetal oxygen delivery (uterine blood flow, placental transfer, fetal circulation) can help sustain normal fetal development, usually without compromising maternal care. The increased microvascular permeability seen in ARDS is likely mediated by neutrophils, proinflammatory mediators (e.g., tumor necrosis factor, interleukin-1, arachidonic acid metabolites) and activation of the complement cascade. Treatment of respiratory failure in pregnancy is largely supportive, including mechanical ventilation, hemodynamic support, nutrition, and prophylaxis against thromboembolism. No specific therapy has as yet been proven effective for ARDS, other than treating the underlying cause. Respiratory failure from status asthmaticus is treated with vigorous bronchodilator therapy, high-dose glucocorticosteroids, magnesium sulfate, and careful ventilator management. Occasionally, more experimental therapies (e.g., isoproterenol infusion, halothane anesthesia) are indicated. Certain strategies can help prevent respiratory failure from aspiration of gastric contents, beta-adrenergic tocolytic therapy, and thromboembolic disease.
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PMID:Acute respiratory failure in pregnancy. 136 44

To gain further insight into the pathogenesis of the adult respiratory distress syndrome (ARDS), we studied possible relationships among the activation status of circulating polymorphonuclear neutrophils (PMN), cytokine levels, and the severity of lung injury in 31 patients: 15 with ARDS, nine with severe pneumonia uncomplicated by ARDS, and seven mechanically ventilated with neither ARDS nor pneumonia. Nine healthy subjects served as controls. Using flow cytometry, we identified a subpopulation of PMN with an increased capacity to generate hydrogen peroxide after stimulation ex vivo in all three patient groups; significantly higher values were found in those with ARDS. The PMN stimulation index, a reflection of the degree of hyperresponsiveness, correlated with elevated levels of tumor necrosis factor-alpha (TNF alpha) in plasma, and both spontaneous and lipopolysaccharide-induced TNF alpha production by cultured monocytes. These biologic expressions of PMN activation and cytokine generation both correlated with indices of the severity of lung injury, but not with the overall clinical severity. In contrast, IL-6 and IL-1 beta showed little or no relationship with either the degree of lung injury or PMN hyperresponsiveness. We conclude that TNF-alpha-primed PMN may play a major role in the pathogenesis of ARDS-associated lung injury.
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PMID:Subpopulation of hyperresponsive polymorphonuclear neutrophils in patients with adult respiratory distress syndrome. Role of cytokine production. 141 30

Leukemia inhibitory factor (LIF) has many biological actions which parallel those of IL-1, IL-6 and tumor necrosis factor-alpha, but its role in the pathogenesis of human disease is unknown. A specific radioreceptor competition assay capable of detecting LIF at concentrations above 1 ng/ml (45 pM) was developed. To identify disease states in which LIF might be involved, a cross-sectional survey of serum and body fluids from approximately 1,500 subjects with a variety of diseases was performed using the LIF radioreceptor competition assay. Serum LIF concentrations were transiently elevated (2-200 ng/ml) in six subjects with meningococcal or Gram-negative septic shock, and in a subject with idiopathic fulminant hepatic failure. Moderately elevated LIF concentrations (> 10 ng/ml) were detected in cerebrospinal fluid from subjects with bacterial meningitis, in effusions associated with pneumonia and peritonitis, and in amniotic fluid from a woman with chorioamnionitis. Low LIF concentrations (1-10 ng/ml) were present in synovial fluid from subjects with inflammatory arthritis, amniotic fluid from women in labor, and some reactive, chronic inflammatory and malignant effusions and cyst fluids, but rarely in transudates. These initial findings suggest that LIF might be involved in the pathogenesis of inflammation and septic shock.
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PMID:Leukemia inhibitory factor levels are elevated in septic shock and various inflammatory body fluids. 143 Feb 24

Pneumocystis carinii, and the inflammatory response it provokes, together contribute to irreversible lung damage in immunocompromised patients. P. carinii cysts were found to be capable of inducing tumor necrosis factor-alpha (TNF) release from alveolar macrophages in a concentration-dependent manner. At physiologically achievable concentrations, pentamidine isethionate (pentamidine) substantially reduces such production. Pretreatment of alveolar macrophages (AM phi) with interferon-gamma (IFN-gamma) synergizes with P. carinii to produce increased levels of TNF, a condition which pentamidine was also able to antagonize. Pentamidine treatment did not interfere with the phagocytic ability of AM phi. Considering clinical reduction of TNF could lessen P. carinii pneumonia (PCP) induced inflammation, the efficacy of pentamidine in the treatment of PCP may be partially associated with its ability to inhibit the release of inflammatory mediators such as TNF.
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PMID:Pneumocystis carinii induction of tumor necrosis factor-alpha by alveolar macrophages: modulation by pentamidine isethionate. 148 15

Pentamidine isethionate, an antiprotozoal agent with therapeutic value against Pneumocystis carinii pneumonia, has been used for over 30 years without a precise understanding of its mechanism of pharmacologic action. We have previously reported that pentamidine has the capacity to inhibit the release of cytokines from macrophages through a post-translational processing event. The present studies were undertaken to assess the ability of pentamidine to modulate the detrimental effects of murine endotoxemia, a disease with a pathophysiology clearly linked to host-produced cytokines. Under conditions where normal B6C3F1 mice succumbed to the lethal effects of endotoxin, mice pretreated with pentamidine were significantly protected from both mortality and loss of thermoregulatory control. The EC50 for protection from mortality by pentamidine was approximately 11.4 mg/kg. These observations correlated with decreased serum levels of tumor necrosis factor (TNF) and interleukin 6. Inhibition of cytokines was not manifested as part of a generalized inhibition of protein synthesis as demonstrated by the lack of significant modulation of serum albumin in pentamidine-treated animals. In addition to decreased serum concentrations of cytokines, lungs isolated from mice treated with both pentamidine and endotoxin exhibited a decreased release of TNF compared to lungs isolated from mice treated with vehicle and endotoxin. The lower levels of TNF released from lung tissue in pentamidine-treated mice correlated with a lesser degree of alveolar deterioration than was observed in vehicle-treated mice. These data indicate that following endotoxin administration, pentamidine has a protective and antiinflammatory role both systemically and in the lung and suggest that inhibition of inflammatory cytokines may be one mechanism operable in the therapeutic activity of the drug against P carinii pneumonia.
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PMID:Pentamidine blocks the pathophysiologic effects of endotoxemia through inhibition of cytokine release. 153 59

Alveolar macrophages in AIDS patients have a marked increase in tumor necrosis factor release in active Pneumocystis carinii pneumonia. We have demonstrated that pentamidine, an aromatic diamidine currently used to treat AIDS-related P. carinii pneumonia, is an effective inhibitor of cellular tumor necrosis factor release from lipopolysaccharide-stimulated rat alveolar macrophages at concentrations greater than 10(-8) M. Inhibition of release is not dependent upon the continued presence of pentamidine in the culture medium during the release phase. In addition, this blockage occurs at neither the transcriptional level as determined by Northern blot analysis nor the translational level as determined by Western blot analysis. Timed addition studies suggest that pentamidine is targeting relatively early events following lipopolysaccharide administration. Pentamidine appears to alter early lipopolysaccharide-induced cellular processes associated with the release of tumor necrosis factor from macrophages.
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PMID:Modulation of tumor necrosis factor release from alveolar macrophages treated with pentamidine isethionate. 162 13

To evaluate the significance of bronchoalveolar lavage fluid, levels of tumor necrosis factor-alpha (TNF), gamma-interferon, interleukin 2, and soluble IL-2 receptor in early detection of canine lung allograft rejection, bronchoalveolar lavages were performed serially in mongrel dogs before and after single lung transplantation. The dogs were divided into three groups. Group 1 (control group) consisted of one in which neither donor nor recipient dogs were treated with cyclosporine. In group 2 (CsA-pretreated group) only donors were treated with CsA orally at a single dose of 20 mg/kg/day for 3 days prior to single lung transplantation. In group 3 only recipients were treated with CsA orally at a single dose of 20 mg/kg/day for a short period of 9 days after single-lung transplantation. Marked elevation was found of TNF, IFN-gamma, IL-2, and IL-2R in BALF obtained from the grafted lungs in group 1 and group 2 dogs. The levels of these markers were significantly higher than those obtained from the normal, native lungs (P less than 0.05). Two of three recipients in group 2 had pneumonia in the native lungs on day 10 after single-lung transplantation. All markers except IFN-gamma in BALF obtained from the infected native lungs were also increased, but the titers were less than those obtained from the grafted lungs at the same time. There were significantly higher levels of TNF, IL-2, and IL-2R present in the BALF of grafted lungs of dogs in group 1 than group 2 (P less than 0.05). In group 3, BALF levels of these markers from the grafted lungs were not significantly different from those of the normal and native lungs during the period of CsA treatment after single-lung transplantation. On various days after discontinuation of CsA treatment, BALF levels of all markers began to rise. Abnormal levels of BALF markers obtained from the grafted lungs heralded the appearance of abnormalities detected by chest x-ray films. Our study suggests that serially measuring BALF levels of TNF, IFN-gamma, IL-2, and IL-2R may serve as a useful means in monitoring the immunologic status of canine lung allografts and in the early detection of lung allograft rejection. The role of BALF IFN-gamma in distinguishing lung allograft rejection from pulmonary infection needs further studies.
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PMID:Significance of biochemical markers in early detection of canine lung allograft rejection. 190 Sep 61

Animal studies implicate gut bacterial translocation via the portal vein as a major factor in the pathogenesis of postinjury multiple organ failure (MOF). We therefore inserted portal vein catheters for sequential blood sampling in the operating room, at 6, 12, 24, and 48 hours, and 5 days postoperatively in 20 injured patients (13 blunt, seven penetrating; mean age, 34 years) requiring emergent laparotomy and who were at known risk for MOF. The mean Revised Trauma Score was 6.4 +/- 0.4, and the Injury Severity Score, 29.3 +/- 2.3. Twelve (60%) patients arrived in shock (SBP less than 90 torr). Eight (2%) of 212 portal blood cultures were positive; seven were presumed contaminants. The only positive systemic culture (total, 212) was a Staphylococcus aureus on day 5 in a patient with a concurrent staphyloccal pneumonia. In the first 48 hours, we could not detect endotoxin in portal or systemic blood. Additionally, simultaneous portal and systemic blood levels of complement fragment C3a, tumor necrosis factor, and interleukin-6 were nearly identical and, specifically, were not different in those patients who developed MOF. In summary, this prospective clinical study has not confirmed portal or systemic bacteremia within the first 5 days postinjury, despite an eventual 30% incidence of MOF.
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PMID:Gut bacterial translocation via the portal vein: a clinical perspective with major torso trauma. 203 May 9

Systemic sepsis and pneumonia are common predisposing factors for ARDS, which can serve as the initial manifestation of the multisystem organ failure syndrome. Primary pneumonia that necessitates ICU admission leads to ARDS in approximately 10% of patients. Systemic infection can also lead to ARDS, but when bacteremia alone is present, the risk is low (probably less than 5%). If the septic syndrome with a hemodynamic and end-organ response develops, the ARDS may follow in as many as 40% of patients. When multiple risk factors for acute lung injury are present, the risk of developing ARDS rises dramatically. The septic syndrome, acute lung injury, and multiorgan failure are closely tied to one another because bacterial cell walls can activate inflammatory mediators, such as interleukin-1 and tumor necrosis factor, which can in turn lead to the septic syndrome and inflammatory injury to the lung. Clinical features, more than serum markers, have been the best predictors of whether lung injury will follow sepsis, indicating that the mere presence of mediators alone cannot cause ARDS and that there are individual susceptibility factors in the effects of these mediators. With the advent of monoclonal antibodies and new anti-inflammatory drugs, prevention of progression from sepsis to multiorgan failure may become possible. Pneumonia is the most common infection that complicates ARDS once it is established, and the mortality rate may approach 90%. The existence of acute lung injury, its predisposing conditions, coexisting illnesses, and the therapeutic interventions used for patients with lung injury all can interfere with lung host defenses and set the stage for bacterial infection of the already-injured lung. This infection appears to add to the propagation of the multiple system organ failure that has already begun. In the future, it may become possible to prevent this infection, which would be a welcome development, because currently, we are stymied in our efforts to diagnose and treat pneumonia in the setting of acute lung injury. Preventive efforts will follow from an understanding of the pathogenesis of pneumonia and in the future may include topical antibiotics, selective digestive decontamination, and prophylactic passive immunotherapy.
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PMID:Sepsis syndrome, the adult respiratory distress syndrome, and nosocomial pneumonia. A common clinical sequence. 226 94


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