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)

We studied the effects of intravenous infusion of recombinant human tumor necrosis factor type alpha (rTNF-alpha; 12 micrograms/kg) on lung fluid balance in sheep prepared with chronic lung lymph fistulas. The role of neutrophils was examined in sheep made neutropenic with hydroxyurea (200 mg/kg for 4 or 5 days) before receiving rTNF-alpha. Infusion of rTNF-alpha resulted in respiratory distress and 3-fold increases in pulmonary arterial pressure and pulmonary vascular resistance within 15 min, indicating intense pulmonary vasoconstriction. Pulmonary lymph flow (i.e., net transvascular fluid filtration rate) and transvascular protein clearance rate (a measure of vascular permeability to protein) increased 2-fold within 30 min. The increased permeability was associated with leukopenia and neutropenia. The pulmonary hypertension and vasoconstriction subsided but fluid filtration and vascular permeability continued to increase. Sheep made neutropenic had similar increases in pulmonary transvascular fluid filtration and vascular permeability. rTNF-alpha also produced concentration-dependent increases in permeability of 125I-labeled albumin across ovine endothelial cell monolayers in the absence of neutrophils or other inflammatory mediators. The results indicate that rTNF-alpha increases pulmonary vascular permeability to protein by an effect on the endothelium.
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PMID:Recombinant tumor necrosis factor increases pulmonary vascular permeability independent of neutrophils. 314 14

Most investigators believe that the pulmonary endothelial damage that is characteristic of the adult respiratory distress syndrome (ARDS) requires the action of neutrophils. In a retrospective review of patients with ARDS, we looked for cases that had developed in patients who already had neutropenia. Four clinical criteria were required for the diagnosis of ARDS: the occurrence of a precipitating event, diffuse bilateral pulmonary infiltrates on a chest x-ray film, a normal intravascular volume (as reflected by a wedge pressure of less than 18 mm Hg), and arterial hypoxemia. During 2 1/2 years, 11 patients fulfilled these clinical criteria, had severe neutropenia that antedated the onset of ARDS, and had pulmonary histologic specimens obtained during the early stages (less than seven days) of clinical respiratory distress. Five of these specimens showed diffuse alveolar damage without evidence of infectious pneumonitis (the histopathological finding characteristic of ARDS), and none had a neutrophil infiltrate. We conclude that ARDS can occur in the setting of severe neutropenia, without pulmonary neutrophil infiltration.
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PMID:Adult respiratory distress syndrome in patients with severe neutropenia. 373 38

38 cases of neonatal group B streptococcal (GBS) sepsis (31 with early onset and 7 with late onset) were observed during the years 1976-1982. Early onset disease showed the following clinical characteristics: 1. frequent lack of risk factors for infection in obstetric history, 2. very early onset of symptoms of respiratory distress, 3. rapid development of shock after only minor or missing clinical signs of infection, and 4. unspecific findings on chest radiography. Neutropenia or marked leukocyte left shift as well as the presence of gram-positive cocci in gastric or tracheal aspirate proved to be useful diagnostic clues. The latex agglutination test for the detection of GBS-antigen in urine yielded in our hands many false positive results and unspecific reactions. Given the big difficulties of early diagnosis of early onset GBS-sepsis, the relatively liberal use of antibiotics in newborns with respiratory distress is probably unavoidable. Hereby prior culturing of blood and early termination of antibiotic therapy with negative cultures (of blood, CSF, tracheal aspirate) seems essential to us. The clinical significance of newer therapeutic (granulocyte transfusions, exchange transfusions, immunoglobulins) and prophylactic (intra-partum antibiotics, vaccination) modalities is according to the current literature still not clear in many respects.
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PMID:[Neonatal Streptococcus group B sepsis: problems of early diagnosis, therapy and prevention]. 639 17

Chemoattractants such as N-formylmethionyl leucyl phenylalanine (FMLP) cause neutropenia in vivo. The sequestered neutrophils may block the microvasculature and contribute to respiratory distress. Neutrophils from humans receiving 1600 units vitamin E per day have reduced oxidative activity. To test whether vitamin E attenuates the responses of neutrophils to FMLP in vivo we gave rabbits four daily intramuscular injections of 100 mg vitamin E. Serum levels of the vitamin were 2.34 +/- 0.15 mg% compared to 0.19 +/- 0.04 mg% in control rabbits receiving placebo injections. On the fifth day testing was done before and after injecting FMLP. Variables monitored were the absolute granulocyte count (AGC), systolic, diastolic and mean blood pressures (MBP), heart rate, PO2, PCO2, pH and respiratory rate. When 0.5 microgram FMLP was injected intravenously the AGC decreased (at 2.5 min the percentage change was -89.7 +/- 8.0 with vitamin E and -97.0 +/- 2.7 without vitamin E; P = 0.2). MBP decreased also (% change, -29.0 +/- 13.0 with vitamin E and -36.3 +/- 16.0, without vitamin E). By 15 min recovery was seen (AGC % change, -26.0 +/- 17 with vitamin E and -78.7 +/- 10.5, without vitamin E; P = 0.01; MBP % change, -9.3 +/- 3.8 with vitamin E and -52.3 +/- 10.1 without vitamin E). Chromatographic analysis of serum extracts revealed increases in 6-keto-PGF1 alpha after stimulation. Studies with [3h]thymidine-labelled neutrophils showed that the sequestered cells return to the circulation. Vitamin E might facilitate this return by altering the adherence of neutrophils to endothelium. This possibility was tested by measuring the adherence to cultivated rabbit aorta endothelial monolayers of FMLP-stimulated neutrophils from vitamin E-treated rabbits. The percentage of neutrophils adhering was 32.5 +/- 3.5 with vitamin E and 60.0 +/- 7.1, without vitamin E. Thus vitamin E promotes the return of neutrophils to the circulation after chemotactic challenge and may do so by reducing their adherence to endothelium.
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PMID:The effect of vitamin E on rabbit neutrophil activation. 655 3

Phorbol myristate acetate is a potent aggregator of platelets. It was found that it was similarly potent in aggregating neutrophils and in producing striking thrombocytopenia and neutropenia when infused intravenously into rabbits. Aggregation and cytopenia were further correlated in that both types of responses developed abruptly and persisted for more than 90 minutes. Animals infused with 40 microgram/kg of the phorbol ester exhibited moderately severe respiratory distress. Their respiratory rate doubled shortly after the infusion, and this tachypnea persisted for more than 2 hours. At necroscopic examination, the lungs of these rabbits contained two outstanding abnormalities: numerous foci of alveolar hemorrhage and extensive intravascular accumulations of platelets and neutrophils. Thus, these animals had evidence of increased permeability and potential occlusion of the pulmonary microvasculature. Increased permeability, occlusion of lung blood vessels, or the occurrence of both processes was further indicated in studies on animals pre-infused with the plasma protein marker 125I-albumin: animals infused with the phorbol ester had a significantly increased amount of this label in their lungs in spite of thorough postmortem perfusion of their pulmonary vasculature with saline and fixative. We conclude that phorbol myristate acetate has actions in vivo that resemble those of a variety of other platelet (eg, arachidonic acid) and neutrophil (eg, chemotactic factors) aggregating agents that cause cytopenia and lung dysfunction. However, compared with these other agents, the phorbol ester produces respiratory distress of intermediate severity and greater duration. The drug, therefore, induces a syndrome that more closely resembles that seen in a variety of clinical and experimental conditions that associate shocklike states with cytopenia and lung dysfunction. It may serve as a useful tool in the study of the pathophysiology of these states as well as in those produced by other aggregating agents.
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PMID:Phorbol myristate acetate: in vivo effects upon neutrophils, platelets, and lung. 744 4

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

Neonatal sepsis caused by Haemophilus influenzae is characterized by an early onset syndrome associated with pneumonia, shock and neutropenia. Over a 30-month period 13 infants referred to this hospital had early onset H. influenzae sepsis. Obstetric complications included preterm labor (92%), prolonged rupture of membranes > 12 hours (63%), maternal fever (64%), chorioamnionitis (43%), vaginal discharge (44%) and premature rupture of membranes (15%). All 13 infants were symptomatic at delivery and 7 required immediate intubation. Pneumonia and respiratory distress were the prominent clinical findings. H. influenzae was isolated from infant blood, maternal blood, placenta and genital tract. Isolates were predominantly non-type b, beta-lactamase-negative. A study to determine the prevalence of H. influenzae colonization of the genital tract among women attending clinic at the hospital with the most cases showed a rate of 0.3%. Perinatal risk factors and clinical findings in the infants are similar to disease caused by other organisms associated with early onset sepsis.
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PMID:Early onset Haemophilus influenzae sepsis in the newborn infant. 801 85

Ticlopidine is an antiplatelet agent that has been proven efficacious in preventing vascular events in patients with a history of vasculopathy. Neutropenia is a significant adverse effect and pancytopenia is rarely reported. A fatal case of pancytopenia associated with unmonitored use of ticlopidine is presented. A 59-year-old woman presented with severe pneumonia and profound neutropenia (absolute neutrophil count 0%). She deteriorated with development of acute respiratory distress syndrome and a marked reduction in trilineage hematopoiesis. Despite prompt marrow response to granulocyte macrophage colony-stimulating factor (GM-CSF) and cessation of ticlopidine, appropriate antibiotics and other supportive therapy, she died 17 days after admission. Hematological monitoring is imperative to identify potential complications: if discovered late, there may be a role for GM-CSF for marrow support. Ticlopidine is indicated for patients intolerant of or nonresponsive to acetylsalicylic acid therapy. As the use of ticlopidine increases, clinicians must be aware of potential life-threatening complications associated with its use and monitor appropriately.
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PMID:Ticlopidine-associated pancytopenia: implications of an acetylsalicylic acid alternative. 937 46

Invasive pulmonary aspergillosis is an opportunistic infection occurring in a background of severe immune depression. The majority of cases occur in patients who have malignant hematologic disease, particularly during chemotherapy induction or consolidations phases for acute non-lymphocytic leukemia. The principal risk factors are profound (PN < 500 per mm3) and prolonged (very high risk beyond 20 days) neutropenia, perturbed phagocyte function and cellular immune deficiency (AIDS, immunosuppressive treatment in organ and bone marrow recipients). Clinically, invasive pulmonary aspergillosis presents as acute non-specific pneumonia with cough, chest pain and fever. The severe infection rapidly becomes life-threatening. The development of massive hemoptysis is a major risk. We report four cases of invasive pulmonary aspergillosis in patients who had hemoptysis. All four patients developed non-specific pneumonia resistant to broad-spectrum antibiotics during post-chemotherapy aplasia. Computed tomography of the thorax and bronchoscopy with bronchoalveolar lavage was performed due to the occurrence of hemoptysis. In the first two cases, the patients were recovering from aplasia. The thoracic CT scan showed evidence of a cavitating mass with peripheral vessels. Bronchoscopy findings suggested mucosal lesions. The patients were managed surgically. Pathology confirmed the diagnosis of invasive pulmonary aspergillosis with the presence of ischemic necrosis of the pulmonary parenchyma harboring numerous aspergillus filaments. Outcome was favorable and chemotherapy was re-initiated in one case. These two patient died from their hematological disease a few months later. The other two patients remained in aplasia. A CT of the thorax showed multifocal infiltration with vascular contact. Bronchoscopy was again suggestive. One patient developed massive hemoptysis with respiratory distress. Embolization was performed but the patient died two days after onset of hemoptysis. In the last case, embolization was successful and outcome was favorable enabling a bone marrow allograft; the patient died a few months later from the hematological disease. The potential gravity of hemoptysis in the course of invasive pulmonary aspergillosis should lead to early treatment with emergency CT scan and, if possible, bronchoscopy with bronchoalveolar lavage to establish the therapeutic strategy based on surgical excision or embolization of the pulmonary or bronchial arteries.
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PMID:[Management of hemoptysis in invasive pulmonary aspergillosis]. 992 34

Critically ill cancer patients constitute a large percentage of admissions to tertiary care medical intensive care units (ICUs). We sought to describe outcomes of such patients, and to evaluate how conditions commonly seen in these patients impact mortality. A total of 348 consecutive medical ICU cancer patients were evaluated. Subgroup comparisons included the three most common cancer types (leukemia, lymphoma, lung cancer), as well as three different treatments/conditions (bone marrow transplant [BMT] versus non-BMT, mechanical ventilation [MV] versus non-MV, neutropenic versus non-neutropenic). There were no mortality differences between patients with leukemia, lymphoma, or lung cancer. By logistic regression, mortality predictors were: MV, hepatic failure, and cardiovascular failure for the group as a whole (41% overall mortality); MV and allogeneic (as compared with autologous) BMT for the BMT group (39% overall mortality); hepatic failure, cardiovascular failure, and persistent acute respiratory distress syndrome (ARDS) for the MV group (67% overall mortality); and MV for the neutropenic group (53% overall mortality). Neutropenia showed no independent association with mortality in the group as a whole or any subgroup analyzed. We conclude that respiratory, hepatic, and cardiovascular failure predict mortality, whereas neutropenia does not. Additionally, we have noted an encouraging improvement in survival in many groups of critically ill cancer patients.
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PMID:Outcomes of critically ill cancer patients in a university hospital setting. 1058 13


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