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)

Recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-SCF) is currently being tested in clinical trials for the treatment of acute myeloid leukemias with two main intentions: reduction of neutropenia and recruitment of leukemic blasts into cell cycle to enhance cytarabine (ara-C) mediated cytotoxicity. We report a case of a fatal spleen rupture in a patient with acute monocytic leukemia (AML M5b) who was treated according to a clinical phase I/II protocol with rh GM-CSF priming and standard induction chemotherapy TAD 9 (thioguanine/ara-C/daunorubicin). During treatment we observed rapidly rising peripheral blast counts and the development of an acute abdomen. Ultrasound examination revealed splenomegaly due to diffuse cellular infiltration and spleen rupture. The patient died 17 days later due to pneumonia and renewed spleen hemorrhage. Bone marrow progenitor assays before treatment showed exclusive growth of monocytoid blast cell colonies (CFU-L). Colony growth could be stimulated with rh GM-CSF and blocked dose-dependently by a monoclonal anti-GM-CSF antibody. CFU-L proliferation also increased after stimulation with rh interleukin-3 (rh IL-3) and supra-additively with rh granulocyte colony-stimulating factor (rh G-CSF) combined with rh GM-CSF. Furthermore, rh GM-CSF induced surface marker expression of CDw 65 and CD 11b on isolated CFU-L blasts. After short-term suspension culture, rh GM-CSF enhanced the expression of CD 29- and CD 11b-adhesion molecules on peripheral blast cells. In summary, this case represents a fatal spleen rupture occurring during rh GM-CSF priming and induction chemotherapy for acute monocytic leukemia. Although the etiology of this spleen rupture remains uncertain, in view of our data we suggest special caution, when further testing this therapy protocol in acute leukemias with monocytic subtype and high peripheral blast cell counts.
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PMID:Fatal spleen rupture during induction chemotherapy with rh GM-CSF priming for acute monocytic leukemia. Clinical case report and in vitro studies. 845 Jun 76

Treatment results of advanced soft tissue sarcomas are still suboptimal. To evaluate the clinical effects of a combination therapy (FADIP) with Adriamycin (ADM), ifosfamide (IFO), cisplatin (DDP) plus continuous infusion of 5-fluorouracil (FU) as a synergistic factor for alkylating agents, a phase II study was initiated in patients with advanced soft tissue sarcomas of different histological subtypes. Fifty-six previously untreated patients with advanced soft tissue sarcomas of different histological subtypes (24 females, 31 males, median age 51.3 years, median Karnofsky performance status 80%) were included in this study. Treatment consisted of ADM 50 mg/m2 i.v. on day 1, IFO 4,000 mg/m2 i.v. on day 1, mesna 800 mg/m2 i.v. 3 x with 8-hour intervals on day 1 starting with IFO administration, FU 500 mg/m2 i.v. as 24-hour infusion on days 1 + 2, DDP 100 mg/m2 i.v. on day 2. This regimen was repeated every 4 weeks for at least 2 cycles. Major WHO grade III/IV hematological toxicity was observed in 35/56 patients. One toxic death due to severe neutropenia and fungal pneumonia occurred. Granulocyte colony-stimulating factor was administered in 8/35 neutropenic patients. Time to recovery was significantly reduced and no infectious complication was observed. WHO grade III/IV toxic diarrhea was observed in 8 patients requiring intravenous fluid replacement. WHO grade III/IV nausea occurred in 11 patients, 9/11 responded to symptomatic treatment with ondansetron alone. The overall response rate was 30.3%. The median duration of response (complete/partial response, CR/PR) was 18.1 months, the median progression-free interval was 4.5 months. The median survival time of all patients was 11.8 months, and 18.1 months in responding patients (CR/PR). Tumor-related pain was effectively reduced in 15/31 patients under treatment. FADIP produces comparable response rates to other standard treatment regimens in soft tissue sarcomas. Prolonged duration of response and median survival may be due to the use of continuous infusion of FU as a synergistic factor to alkylating agents. Granulocyte colony-stimulating factor is effective in reducing the otherwise observed high rate of WHO grade III/IV hematological toxicity with severe neutropenia.
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PMID:Combination of 5-fluorouracil, adriamycin, ifosfamide and cisplatin in metastatic adult soft tissue sarcoma: results of a phase II study. 857 Jan 33

A 41-year-old woman with follicular lymphoma developed sporadic respiratory syncytial virus (RSV) pneumonia shortly after allogeneic bone marrow transplantation from an HLA-matched sibling. RSV pneumonia is potentially fatal in immunosuppressed patients, but she improved along with the recovery of bone marrow function without specific treatment. Early recovery of myelosuppression supported by granulocyte colony-stimulating factor may have helped to control RSV pneumonia.
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PMID:Early-onset respiratory syncytial virus pneumonia after allogeneic bone marrow transplantation. 858 64

We evaluated the efficacy and adverse effects of biweekly COP-BLAM (cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin and procarbazine) therapy combined with granulocyte colony-stimulating factor (G-CSF) for treating non-Hodgkin's lymphoma (NHL). A complete remission was achieved in 65 (90.3%) of the 72 patients. THe median follow-up period was 28 months, and 64 patients were alive at the time of writing. Treatment was delivered as scheduled to 61 patients. G-CSF made it possible to shorten the interval between courses of chemotherapy. One of the 72 patients died of granulocytopenia and pneumonia; no other severe infections were noted. Further studies regarding adverse effects on organs other than the bone marrow are required to improve the long-term results of combination therapy on NHL.
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PMID:Biweekly COP-BLAM (cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin and procarbazine) regimen combined with granulocyte colony stimulating factor (G-CSF) for intermediate-grade non-Hodgkin's lymphoma. 859 36

A rat model was used to study the effects of granulocyte colony-stimulating factor (G-CSF) on the pathogenesis of pneumococcal pneumonia in cirrhosis. G-CSF or 5% dextrose in water was administered subcutaneously to cirrhotic and control rats before or after transtracheal infection with type 3 Streptococcus pneumoniae. In both groups, G-CSF significantly increased the total number and percentage of polymorphonuclear leukocytes (PMNL) in peripheral blood (P < .002) and bronchoalveolar lavage fluid (P < .01). An in vivo phagocytosis assay revealed no increase in uptake of pneumococci by PMNL within the lungs of cirrhotic or control rats receiving G-CSF. G-CSF administered before infection did not protect cirrhotic or control rats, but G-CSF treatment after infection significantly reduced mortality in control (P = .04) but not cirrhotic rats. These data suggest that despite increasing numbers of circulating and pulmonary PMNL, G-CSF does not protect against fatal pneumococcal pneumonia in cirrhotic rats.
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PMID:Effects of granulocyte colony-stimulating factor in cirrhotic rats with pneumococcal pneumonia. 865 1

A 67-year-old female was admitted with fatigue. Peripheral blood examination showed severe pancytopenia. Bone marrow biopsy revealed hypoplastic marrow. She was diagnosed as having aplastic anemia. Steroid pulse therapy was not effective. After treatment with erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF), blasts which were positive for CD13, CD33, CD34 and HLA-DR and negative for myeloperoxidase appeared in the peripheral blood. At this time, bone marrow biopsy revealed myelofibrosis with increased blasts. Chromosome analysis showed 46XX, add (1) (p36), add (1) (q44), -2, -5, del (7) (q11), -12, +3mar. She died of pneumonia despite chemotherapy with etoposide. Administration of EPO and G-CSF may have led to the rapid development of leukemia and myelofibrosis.
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PMID:[Transformation of aplastic anemia to acute myeloid leukemia with myelofibrosis following treatment with granulocyte colony-stimulating factor and erythropoietin]. 877 84

We studied the effects of inhibiting and augmenting neutrophil function by using an immunocompetent rat model of infectious and hyperoxic lung injury. After intrabronchial Escherichia coli challenge at all fractional inspired O2 (FIO2) values studied (FIO2 = 0.21, 0.60, and 0.95) and after lethal O2 exposure alone (FIO2 = 0.90), lung injury, as measured by histological and physiological changes, was reduced by a CD11b/CD18-directed monoclonal antibody (MAb 1B6, P < 0.05 vs. controls) but was increased by recombinant granulocyte colony-stimulating factor (rG-CSF; P < 0.05 vs. control; MAb 1B6 vs. rG-CSF, P < 0.004). Pulmonary neutrophil counts were reduced by MAb 1B6 (P < 0.04) and increased by rG-CSF (P < 0.0004) compared with control animals. However, despite antibiotics, MAb 1B6 and rG-CSF both significantly increased the relative risk of death, independent of O2 concentration, during E. coli pneumonia (1.74 [symbol: see text] 1.20 and 2.39 [symbol: see text] 1.19, respectively, each P < 0.01). During lethal hyperoxia, MAb 1B6 increased the relative risk of death (1.76 [symbol: see text] 1.28, P < 0.16), whereas rG-CSF had no effect on survival (0.97 [symbol: see text] 1.28, P = 0.89). Thus inhibition of neutrophil function attenuated and enhancement worsened lung injury in response to infectious and hyperoxic challenges, supporting a pathophysiological role of the neutrophil in these processes. However, it is problematic that MAb 1B6 therapy, despite preventing lung damage, ultimately worsened host defenses and survival. Furthermore, rG-CSF also adversely affected survival during infectious lung injury, demonstrating the inherent risks of inhibiting or augmenting neutrophil function in an immunocompetent host during infection.
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PMID:Controlled trials of rG-CSF and CD11b-directed MAb during hyperoxia and E. coli pneumonia in rats. 880 15

Febrile episodes occurring in 29 elderly patients (mean age 75 years) with leukemia, from 1988 to 1993, were reviewed. A febrile episode was defined as a temperature of 38 degrees C or greater for at least 6 hours. The number of febrile episodes was 64. The average was 2.2 febrile episodes per patient. Seventy-two percent of febrile episodes occurred when the patients had neutropenia below 100/microliters, while 16% occurred with neutropenia of 101/microliters to 500/microliters. Causative microorganisms were identified in 48% of total febrile episodes. The most common infectious site was the urinary tract which accounted for 25% of total episodes. Pneumonia and septicemia accounted for 22% of total episodes, respectively. Gram-positive cocci were responsible for 66% of microbiologically documented febrile episodes, while 21% were caused by gram-negative bacilli. Gram-positive cocci, particularly staphylococcus aureus, coagulae-negative staphylococcus and enterococci increased compared with a decade ago in our department. Granulocyte colony-stimulating factor (G-CSF) was used 12 times for infection. No significant difference in fever amelioration was seen between G-CSF and non-G-CFS cases.
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PMID:[Infection in elderly leukemic patients]. 886 21

It has been well documented that the immune function declines with age; however, little is known about the monocyte/macrophage function of age. In the present study, we measured the concentrations of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), IL-8 and monocyte inflammatory protein-1 alpha (MIP-1 alpha) in sera from 15 elderly patients and 22 young patients with pneumonia, in the acute phase and after recovery, by ELISA. In addition, we measured the concentrations of these cytokines in culture supernatants from lipopolysaccharide (LPS)-stimulated peripheral blood monocytes from normal healthy elderly subjects and young subjects in order to clarify the ability of the elderly to produce these cytokines. The concentrations of these cytokines in sera from old patients and in those from young patients obtained in the acute phase were higher than those in sera obtained after recovery phase. However, the concentrations of these cytokines in the acute phase were lower in elderly patients compared with those in young patients. Serum concentrations of cytokines did not appear to be associated with clinical outcome. In the production of these cytokines by monocytes, LPS-stimulated monocytes from healthy normal elderly subjects produced smaller amounts of G-CSF, GM-CSF, IL-1 beta, TNF-alpha, IL-8 and MIP-1 alpha than those from healthy normal young subjects. These results with the impaired production of these cytokines in the elderly may prove, at least in part, the characteristic features of host defence mechanisms of the elderly.
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PMID:Lower serum concentrations of cytokines in elderly patients with pneumonia and the impaired production of cytokines by peripheral blood monocytes in the elderly. 887 Jul 9

Clinical trials of new therapeutics for community-acquired pneumonia (CAP) have typically used a subjective endpoint of clinical response. However, as this endpoint is not quantitative, it is subject to observer bias and renders the conduct of multicenter trials difficult. For the purposes of conducting a clinical trial of filgrastim, as an adjunct to antibiotics for the treatment of CAP, a set of clinical criteria were developed prospectively to determine the time when a clinical cure was achieved, based on respiratory rate, temperature, oxygenation and roentgenographic findings, which was termed the time to resolution of morbidity (TRM). The TRM was evaluated on the first 100 patients entered in this clinical trial. As no clear reference standard exists, the predictive value for the duration of parenteral antibiotics (AB) and the length of hospital stay (LOS) was compared with that provided by a widely used classification system for severity of disease, APACHE II. The TRM was found to correlate significantly better with AB or LOS than APACHE II (P < 0.001). Furthermore, TRM offers the benefit over the endpoints of LOS and AB of being specifically designed to measure the patient's response to therapy, and, in fact, may aid physicians in determining the duration of parenteral antibiotic therapy. Hence, TRM is relevant to the clinician and is a useful tool to ensure uniformity in the assessment of the response to a new therapeutic in a multicenter clinical trial.
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PMID:Time to resolution of morbidity: an endpoint for assessing the clinical cure of community-acquired pneumonia. 895 15


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