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)

We report on a 67-year-old man with Felty's syndrome (FS) complicated by recurrent pneumonia and an infected wound, which was not healing in spite of maximal antibiotic and local therapy. Encouraged by previous experience, we treated him with granulocyte-macrophage colony-stimulating factor (GM-CSF). His total leukocyte count rose, but the patient's pneumonia deteriorated. In addition, a previously known chronic obstructive lung disease (COLD) was exacerbated acutely. These complications finally led to his death. Postmortem examination revealed widespread pneumonia with invasive aspergillosis and a peripheral adenocarcinoma in his left lung.
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PMID:Treatment of neutropenia in Felty's syndrome with granulocyte-macrophage colony-stimulating factor--hematological response accompanied by pulmonary complications with lethal outcome. 145 82

The expression "immunocompromised host" refers to an individual who has one or more defects in the body's natural defense, which leads to severe, often life-threatening, infections. Alcoholism, diabetes mellitus, advanced age, the use of antacids, and viral infections have immune-modulating effects. The human immunodeficiency virus, cytomegalovirus, Epstein-Barr virus, and Non A, Non B hepatitis virus also contribute to immunosuppression. The lung has a special vulnerability to infection, and pneumonia accounts for more than 40% of deaths in the immunosuppressed population. Diagnostic methods include detection of microbial antigens by monoclonal antibodies, DNA sequences by the polymerase chain-reactions or DNA probes, and unique metabolites of pathogens by gas chromatography. Transtracheal aspiration was used to obtain uncontaminated respiratory secretions, but fiberoptic bronchoscopy with shielded brush and bronchoalveolar lavage (BAL) is a better means of diagnosis because of a 90% sensitivity in diagnosing pneumocystis infection. Percutaneous aspiration and open lung biopsy are reserved for more complicated cases. Empiric treatment is justified in far advanced AIDS or relapsed myelogenous leukemia with limited life expectancy, or when there is uncontrollable bleeding diathesis or impaired pulmonary function as invasion diagnostic procedures will not be tolerated. The most important antiinfective measure is careful hand washing, while prophylactic antibiotics, selective decontamination, and antifungal, antiviral, and antiparasitic agents can be used. Active and passive immunization against specific pathogens, immunological reconstitution with granulocyte-macrophage colony-stimulating factor (GM-CSF) and reducing the dosage of immunosuppression are the other strategies for prevention. In the last several decades there has been substantial progress in the management of chronic diseases which used to be fatal.
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PMID:Pulmonary infections in the immunocompromised host. 166 54

Severe congenital neutropenia (SCN) is a disorder of myelopoiesis characterized by severe neutropenia secondary to a maturational arrest at the level of promyelocytes. We treated five patients with SCN with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for 42 days and subsequently, between 1 and 3 months later, with rhG-CSF for 142 days. The objective was to evaluate the safety and ability of these factors to elicit a neutrophil response. rhGM-CSF was administered at a dose of 3 to 30 micrograms/kg/d (30 to 60 minutes, intravenously). In all patients, a specific, dose-dependent increase in the absolute granulocyte counts was observed. However, in four patients this increase was due to an increase in eosinophils, and in only one patient it was due to an increase in the absolute neutrophil counts (ANC). Subsequently, all patients received rhG-CSF at a dose of 3 to 15 micrograms/kg/d subcutaneously. In contrast to rhGM-CSF treatment, all five patients responded to rhG-CSF during the first 6 weeks of treatment with an increase in the ANC to above 1,000/microL. The level of ANC could be maintained during maintenance treatment. In one patient, the increase in ANC was associated with an improvement of a severe pneumonitis caused by Peptostreptococcus and resistant to antibiotic treatment. No severe bacterial infections occurred in any of the patients during CSF treatment. All patients tolerated rhGM-CSF and rhG-CSF treatment without severe side effects. These results demonstrate the beneficial effect of rhG-CSF in SCN patients.
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PMID:Differential effects of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in children with severe congenital neutropenia. 168 95

A 12-month-old boy with Kostmann's syndrome was admitted with cavitary pulmonary disease. He had also had bacterial conjunctivitis, periorbital cellulitis, pneumonitis, and otitis media since the age of 10 days. His umbilical cord had not fallen off until he was 3 weeks old. Neutropenia was diagnosed at 4 weeks of age. Antineutrophil antibody studies were negative. A bone marrow aspirate showed granulocytic hypoplasia and a maturation arrest at the promyelocyte stage. Hematopoietic cell culture showed normal numbers of colony-forming units-granulocyte macrophage. Serum granulocyte-macrophage colony-stimulating factor level, was 0.24 ng/mL (normal, greater than 0.05 ng/mL). Serum granulocyte colony-stimulating factor levels, measured by enzyme immunoassay, were undetectable. The patient was successfully treated with filgrastim (granulocyte colony-stimulating factor), with an increase in the absolute neutrophil count to 10.0 x 10(9)/L. Thus, our case of Kostmann's syndrome appears to represent a defect in regulation or production of granulocyte colony-stimulating factor.
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PMID:Measurement of serum granulocyte colony-stimulating factor in a patient with congenital agranulocytosis (Kostmann's syndrome). 171 5

A patient with chronic lymphocytic leukaemia (CLL) and severe persisting neutropenia due to marrow infiltration of his leukaemia, developed bilateral Legionella pneumophila pneumonia for which he was treated with erythromycin, rifampin and ciprofloxacin. To increase the number of circulating polymorphonuclear neutrophils, the patient was treated with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) at a dose of 2 micrograms protein/kg bodyweight s.c./12 h. GM-CSF therapy resulted in a sustained rise of the neutrophil count from the fifth day of treatment onwards, without showing an effect on the number of circulating leukemic cells. The patient completely recovered from his pneumonia. It is suggested that the rise of the neutrophil count, due to GM-CSF, contributed to the improvement of the infection of this patient. Our observation illustrates that GM-CSF can be given safely to CLL-patients and that it can be used effectively in CLL patients with severe bacterial infections to restore neutropenia.
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PMID:Correction of neutropenia associated with chronic lymphocytic leukaemia following treatment with granulocyte-macrophage colony-stimulating factor. 203 65

We administered recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) (120 micrograms/m2/d by continuous intravenous [IV] infusion) to 12 patients with newly diagnosed acute myeloid leukemia (AML) at relatively high risk of early death during remission induction. GM-CSF began 3 days after completion of induction chemotherapy (ara-C 1.5 g/m2 d x 4 days by continuous IV infusion after a 3 g/m2 bolus). Rates of fatal infection (42%), pneumonia and/or sepsis (83%), and CR (50%) did not differ significantly (P less than .05) from those observed after administration of the identical chemotherapy without GM-CSF to 53 historical controls with newly diagnosed AML at similarly high risk of early death. There were no significant differences between the GM-CSF-treated and the historical groups in the time required to reach neutrophil counts of 500 or 1,000/microL after administration of chemotherapy. Four patients died of infection before they could have benefited from the earliest recovery of neutrophil count observed in patients who entered CR. Growth of leukemia after GM-CSF administration was observed in only 1 of the 8 patients who survived long enough for response to induction therapy to be fully evaluated. This observation suggests that it might be safe to undertake larger, randomized studies, perhaps using earlier administration of GM-CSF, to definitively determine the role of GM-CSF added to chemotherapy in patients with newly diagnosed AML.
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PMID:Treatment of poor-prognosis, newly diagnosed acute myeloid leukemia with ara-C and recombinant human granulocyte-macrophage colony-stimulating factor. 218 1

We have studied the hematopoietic system of the immunodeficient mouse mutant, viable motheaten (mev/mev). These mice usually die by 9 weeks of age from severe pneumonitis. The lungs at that time are infiltrated with granulocytes, macrophages, and lymphocytes. Granulocyte and macrophage precursor cells (CFU-GM) are dramatically increased in the spleens of mev/mev mice, whereas the bone marrow population of these precursors is decreased when compared with littermate control animals. The CFU-GM population retained its normal dependence on granulocyte-macrophage colony-stimulating factor (GM-CSF) for proliferation and differentiation. In contrast, the frequency of an erythroid precursor (CFU-E) was dramatically increased in spleen and showed increased sensitivity to erythropoietin (Epo). Moreover, a splenic CFU-E subpopulation formed normally appearing erythroid colonies in the absence of exogenous Epo. The bone marrow CFU-E population was significantly diminished in size when compared with either wildtype C57BL/6J mice or mice heterozygous for the mev allele. Unlike the CFU-E population, erythroid burst-forming unit (BFU-E) frequency in mev/mev mice was diminished both in bone marrow and in spleen, although the total number of splenic BFU-E was increased because of splenomegaly in these animals. BFU-E retained their dependence on the presence of both Epo and a source of interleukin 3 (IL-3) for proliferation and differentiation into erythroid bursts. Spleen cells from mev/mev mice, when stimulated in vitro with pokeweed mitogen, failed to produce significant quantities of IL-3. Comparison with medium or +/mev heterozygotes revealed that mev/mev spleen cell-conditioned medium showed a 40-fold reduction in burst-promoting activity. Thus, in viable motheaten mice, there is a major shift in hematopoiesis from bone marrow to spleen, which is accompanied by a diminished capacity of spleen cells to produce burst-promoting activity. These data and those from other studies suggest that the hematopoietic microenvironment of marrow may be impaired in this mutant.
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PMID:Hematologic abnormalities of the immunodeficient mouse mutant, viable motheaten (mev). 278 74

Immunotherapy can be defined as treatment directed at augmenting host immune defence mechanisms. Non-antimicrobial therapies and immunoprophylaxis in bone marrow transplantation (BMT) can be subdivided into three broad categories: passive immunotherapy with intravenous immunoglobulin (IVIG); cytokine therapy; and anti-endotoxin-directed treatments. Most studies using IVIG in BMT are prophylactic and suffer from variability in study design, type of IVIG and dosing regimens. Various effects on viral and bacterial infections and graft-versus-host disease (GVHD) have been reported but few if any have shown benefit in terms of improved patient survival. Moreover the immunomodulatory effect of immunoglobulin G preparations is frequently overlooked. With the exception of cytomegalovirus (CMV) pneumonitis, there is little evidence of benefit in the treatment of established infections and the relative benefits of hyperimmune preparations are poorly established. The development of haemopoietic growth factors has led to the widespread use of cytokines in BMT. The benefits of these agents both in the prevention of fever and infection and as adjuvants to standard antimicrobial therapy in established infection (e.g. invasive mycoses) are rapidly becoming apparent. Both human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and granulocyte colony-stimulating factor (rhG-CSF) have been shown to accelerate granulocyte recovery following BMT and reduce fever days, antibiotic usage and hospitalization. RhGM-CSF appears superior in these respects. The roles of interleukin 1 (IL1), IL3, IL6 and interferons are also under evaluation. As with the much publicised studies using anti-endotoxin antibodies as therapy in sepsis, there is little evidence of benefit in the few studies performed in BMT patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunotherapy and immunoprophylaxis in bone marrow transplantation. 756 Sep 54

Treatment of myelodysplastic syndromes (MDS) with recombinant human erythropoietin (Epo) is successful in only 10% to 25% of patients. We performed a pilot study in 10 anaemic patients with MDS to examine whether sequentially applied recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and Epo improves haemoglobin levels and/or reduces red blood cell transfusion requirements. Morphological diagnoses of patients were refractory anaemia (RA) in 3 cases, RA with ring sideroblasts in 3 cases and RA with excess blasts in 4 cases. GM-CSF was given subcutaneously at a dose of 150 micrograms/m2/d during the initial 10 days. From day 11, Epo was administered by subcutaneous injections for 8 weeks at a dose of 100 U/kg/d and subsequently at an escalated dose of 200 U/kg/d in 3 patients. Changes in reticulocyte counts, haemoglobin levels, RBC support and ferrokinetic parameters were compared with pretreatment values. Two out of 8 evaluable patients showed a rise in haemoglobin levels at week 8 and 10, respectively, and lost their transfusion dependency for a period of 13 and 27 weeks. In 1 patient, haemoglobin level increased only after dose escalation of Epo (200 U/kg/d). Leukocyte counts remained uneffected by treatment with Epo, while 1 patient showed a 4-fold increase in platelet numbers. Toxicity was mild. Two patients died of pneumonia and global heart failure, respectively, unrelated to growth factor therapy. Based on this pilot study, we conclude that sequential treatment with GM-CSF and Epo does not increase erythroid responses in anaemic patients with MDS. Because of the delayed increase in haemoglobin in both responders, we surmise that the beneficial effects were induced by Epo alone.
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PMID:Sequential administration of recombinant human granulocyte-macrophage colony-stimulating factor and human erythropoietin for treatment of myelodysplastic syndromes. 785 74

Mice deficient in granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF, CSF-1) were generated by interbreeding GM-CSF-deficient mice generated by gene targeting (genotype GM-/-) with M-CSF-deficient osteopetrotic mice (genotype M-/-, op/op). Mice deficient in both GM-CSF and M-CSF (genotype GM-/-M-/-) are viable and have coexistent features corresponding to mice deficient in either factor alone. Like M-CSF-deficient mice, they have osteopetrosis and are toothless because of failure of incisor eruption. Like GM-CSF-deficient mice, they have a characteristic alveolar-proteinosis-like lung pathology, but it is more severe than that of GM-CSF-deficient mice and is often fatal. In particular, in GM-/-M-/- mice the accumulation of lipo-proteinaceous alveolar material is more marked, and bacterial pneumonic infections are more prevalent and more extensive, particularly involving Gram-negative bacteria. Neutrophilia consistently accompanies pulmonary infections, and some older GM-/-M-/- mice have polycythemia. Survival of GM-/-M-/- mice is significantly reduced compared with mice deficient in either factor alone, and all GM-/-M-/- mice have broncho- or lobar-pneumonia at death. These observations indicate that in vivo, M-CSF is involved in modulating the consequences of GM-CSF deficiency in the lung. Interestingly, GM-/-M-/- mice have circulating monocytes at levels comparable with those in M-CSF-deficient mice and the diseased lungs of all GM-/-M-/- mice contain numerous phagocytically active macrophages, indicating that in addition to GM-CSF and M-CSF, other factors can be used for macrophage production and function in vivo.
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PMID:Mice lacking both macrophage- and granulocyte-macrophage colony-stimulating factor have macrophages and coexistent osteopetrosis and severe lung disease. 801 21


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